Pulmonológy Merge

Bronchial asthma
Dr. habil. Gabor Horvath, Ph.D.

Associate professor
Department of Pulmonology
Semmelweis University
2019-2020
Asthma quiz
What do you think...

how many people suffer asthma worldwide?
A./ ~ 30 million (~ Canada)

B./ ~ 100 million (~ Japan)
C./ ~ 300 million (~ USA)
Global Initiative for Asthma
(GINA)
ginasthma.org
Global burden of asthma
 Asthma is one of the most common chronic

diseases in the world (~ 300 million people).
 Asthma prevalence increases…
 in most countries
 especially in children
 by „western lifestyles”
 by urbanisation
 There will be an additional 100 million patients with
asthma by 2025.
 Asthma accounts for 1 in every 250 deaths.
Prevalence in children (13-14 yrs)
Asthma morbidity and mortality
in Hungary
300000 Asthma patients 3,0%
250000 Mortality %
2,5%
200000 2,0%
150000 1,5%
100000 1,0%
50000 0,5%
0 0%
80
90
94
96
98
00
02
04
06
08
10
19
19
19
19
19
20
20
20
20
20
20
Definition of asthma
 A chronic inflammatory disorder of the airway

 Infiltration of mast cells, eosinophils and
lymphocytes in the airwaw
 Recurrent episodes of wheezing, coughing
and shortness of breath
 Widespread, variable and often reversible
airflow limitation
 Airway hyperresponsiveness
Airway inflammation in asthma
Normal airways Mild asthma
Busse et al., N Engl J Med 2001;344(5):350-362

Airway inflammation in asthma
Busse et al., N Engl J Med

2001;344(5):350-362
Asthma: pathological changes
Normal airway Asthma

Asthma pathomechanism I.
Airflow limitation
 Caused primarily by bronchoconstriction
 Bronchoconstriction caused by inflammatory
mediators (histamine, leukotrienes, prostaglandins)
 Inhaled allergens
 Other triggers: exercise, cold air, airborne
irritants, infections, stress, GERD, aspirin, etc.
 Reversible by bronchodilators!
Asthma pathomechanism II.
Other factors contribute airflow limitation

 Edema formation - secondary to inflammatory
hyperpermeability
 Mucus hypersecretion
 Structural changes such as hypertrophy and
hyperplasia of bronchial smooth muscle,
tissue fibrosis (as part of remodeling)
Asthma pathomechanism III.
Airway hyperresponsiveness
 Exaggerated bronchoconstrictor response to
triggers such as exercise, cold air, stress
 Measured by responsiveness to inhaled
methacholine, adenosine, mannitol
 Anti-inflammatory therapy reduces airway
hyperresponsiveness
Airway „remodelling”
in chronic asthma
• Bronchial smooth muscle hypertrophy

and hyperplasia
• Collagen deposition
• Increased mucous glands and mucus
production
• Increased vascularity
Asthma classification
 Severity
(intermittent, mild, moderate, severe)
 Control level
(controlled, partly controlled, uncontrolled)
 Etiology
(extrinsic = allergic, intrinsic = non-allergic)
Asthma control levels
Asthma diagnosis
 History and patterns of symptoms

 Lung function measurements
 Measurement of airway responsiveness
(reversibility and/or hyperreactivity)
 Measurements of allergic status to identify
risk factors
Asthma symptoms
Symtoms can be permanent, intermittent, seasonal:

 Wheezing: intermittent, prolonged exspiration,
improves after bronchodilator inhalation
 Coughing
 Chest tightness
 Dyspnea, tachypnea
 Increased sputum production
 Prodromal symptoms may precede asthma attack,
such chest dyscomfort, itching, unexplained fear
Asthma symptoms
Exacerbation
Exacerbation
Asthma
symptom
intensity
Time (days, weeks, months)

Lung function measurements
• Spirometry
• Peek exspiratory flow measurement
• Body plethysmography
• Airway hyperreactivity testing:
− bronchial challenge tests
− exercise challenge test
• Airflow limitation reversibility testing
(pharmacodynamic test)
Spirometry
Expired
volume
Healthy subject
FEV1 Asthmatic (after bronchodilator)
Asthmatic (before bronchodilator)
Time (sec)
1 2 3 4 5
Spirometry quiz
What do you think...

decreased FEV1 proves the diagnosis of asthma?
A./ Yes
B./ No
C./ I don’t know
Peak exspiratory flow (PEF)
 Peak flow meter

 PEF unit: l/min
 Normal range: 400-600 l/min
 Asthmatics: 200-400 l/min
 Severe asthma attack: < 100
l/min
 Daily PEF variability is normal
 Daily PEF variablity > 20%
suggests asthma
Body plethysmography
Raw , TGV 
Measuring airway responsiveness:
the bronchial challenge test
Decrease in FEV1 after

methacholine inhalation
Asthma results in
increased sensitivity
Allergy tests in asthma
In vivo tests
• Allergy skin (prick) test
• Bronchial challenge test (specific)
In vitro tests
• Serum total/specific IgE levels
• Others: eosinophilic cationic protein,
histamine, triptase etc.
Allergy skin (prick) test
Markers of airway inflammation
 Exhaled NO: produced by epithelial

and alveolar cells.
 Elevated exhaled NO reflects well
eosinophilic airway inflammation.
 May be used as a compliance
check with anti-infallamtory drugs.
 Sputum eosinophils: correlates with

the inflammatory response, but not
practical.
Quiz: asthma or COPD?
Asthma COPD
 Dyspnea, wheezing, coughing  

 History of smoking

 History of allergy

 Reversible airflow obstruction

 Airway hyperreactivity

 Progressive disease

Therapy: identify and reduce
exposure to risk factors
 Reduce exposure to indoor allergens

 Avoid tobacco smoke
 Identify irritants in the workplace
 Avoid vehicle emission
 Explore role of infections on asthma
development, especially in children and
young infants
Inhaled medications
Oral drugs:
Slow onset
Larger dosage
Greater side effects
Less expensive
Inhaled drugs:
Rapid onset
Less amount of drug
Better tolerated
More expensive
Rescue medications
Bronchodilators
 Short-acting inhaled β2-agonists (SABA)
 Anticholinergics
 Theophyllines (iv.)
2-agonist bronchodilators
K+
2-receptor K+ channel
Gs Gs
AC
ATP  cAMP
Hyperpolarization
 MLCK
 Na+/Ca2+ transport
PKA Smooth muscle
 Na+/K+ ATPase
activation relaxation
 PI-hidrolysis
 Bronchodilation
Improve airway airflow by relaxation of bronchial
smooth muscle.
 Mast cell degranulation 
 Vascular permeability  Anti-inflammatory

 Neutrophilic inflammation  effects
 Mucociliary clearance 
 Rescue medications
 Used during acute attacks
 Quick relief of symptoms can be achieved
 Action lasts 4-6 hrs
 Drugs:
 Salbutamol
 Terbutaline
 Fenoterol
Controller medications
Anti-inflammatory drugs
 Corticosteroids
 Leukotriene modifiers
 Anti-IgE
Long-acting bronchodilators
 Long-acting β2-agonists (LABA)
 Theophyllines (per os)
Cellular actions of corticosteroids
Anti-inflammatory
effect
Protein synthesis
GR receptor
mRNA
NF-B
AP-1
DNA
Inhaled corticosteroids
BECLOMETASONE BUDESONIDE
FLUTICASONE CICLESONIDE
Leukotriene modifiers
Arachidonic acid
5-LO 5-LO- and FLAP-
inhibitors
FLAP
5-HPETE
LTA4
LTB4 LTC4
CysLT1-receptor-
LTD4 antagonists
LTE4
Chemotaxis and immun- Mediators of mucus secretion,
modulation edema, eosinophilia and
bronchoconstriction
5-LO = 5-lipoxigenase; FLAP = 5-lipoxigenase-activating protein;

5-HPETE = 5-hidroperoxi-ikozatetraenic acid; CysLT1 receptor = type 1. cisteinil-leukotriene-receptor
Leukotriene modifiers
5-LO inhibitor: CysLT1 antagonists:

Zileuton (Zyflo) Pranlukast (Pranlukast)
Zafirlukast (Accolate)
Montelukast (Singulair)
Anti-IgE: Omalizumab (Xolair®)
Anti-IL-5: Mepolizumab (Nucala®)
Reslizumab (Cinqaero®)
Anti-IL-5R: Benralizumab (Fasenra®)
Recommended „stepwise”
approach to asthma therapy
Thank you for your attention!
COPD – Chronic Obstructive
Pulmonary Disease
Dr. Noémi Eszes
2020
Faculty of Medicine
Definition (source: www.goldcopd.org; Pocket
Guideline)
► Chronic Obstructive Pulmonary Disease (COPD) is a common,

preventable and treatable disease that is characterized by
persistent respiratory symptoms and airflow limitation that is
due to airway and/or alveolar abnormalities usually caused by
significant exposure to noxious particles or gases.
► The most common respiratory symptoms include dyspnea,

cough and/or sputum production.
► The main risk factor for COPD is tobacco smoking but other
environmental exposures such as biomass fuel exposure and
air pollution may contribute.
►Besides exposures, host factors predispose individuals
to develop COPD. These include genetic abnormalities,
abnormal lung development and accelerated aging.
►COPD may be punctuated by periods of acute

worsening of respiratory symptoms, called
exacerbations.
►In most patients, COPD is associated with significant

concomitant chronic diseases, which increase its
morbidity and mortality.
Pathology, pathogenesis & pathophysiology
► Pathology
 Chronic inflammation
 Structural changes
► Pathogenesis
 Oxidative stress
 Protease-antiprotease imbalance
 Inflammatory cells
 Inflammatory mediators
 Peribronchiolar and interstitial fibrosis
► Pathophysiology
 Airflow limitation and gas trapping
 Gas exchange abnormalities
 Mucus hypersecretion
 Pulmonary hypertension
Diagnosis
► COPD should be considered in any patient who has dyspnea,

chronic cough or sputum production, and/or a history of
exposure to risk factors for the disease.
► Spirometry is required to make the diagnosis; the presence of a

post-bronchodilator FEV1/FVC < 0.70 confirms the presence of
persistent airflow limitation.
► The goals of COPD assessment are to determine the level of

airflow limitation, the impact of disease on the patient’s health
status, and the risk of future events (such as exacerbations,
hospital admissions, or death), in order to guide therapy.
Diagnosis and Initial Assessment
Diagnosis
► Symptoms of COPD
 Chronic and progressive dyspnea

 Cough
 Sputum production
 Wheezing and chest tightness
 Others – including fatigue, weight loss,
anorexia, syncope, rib fractures, ankle
swelling, depression, anxiety.
© 2017 Global Initiative for Chronic Obstructive Lung Disease

Differential diagnosis
Spirometry

Classification of severity of airflow
limitation
Symptom assessment
► COPD Assessment Test (CAT TM )
► Chronic Respiratory Questionnaire (CCQ® )
► St George’s Respiratory Questionnaire (SGRQ)
► Chronic Respiratory Questionnaire (CRQ)
► Modified Medical Research Council (mMRC) questionnaire
COPD Assessment Test (CATTM)

Modified MRC dyspnea scale

Assessment of Exacerbation Risk
► COPD exacerbations are defined as an acute worsening of respiratory

symptoms that result in additional therapy.
► Classified as:
 Mild (treated with SABDs only)
 Moderate (treated with SABDs plus antibiotics and/or oral
corticosteroids) or
 Severe (patient requires hospitalization or visits the emergency room).
Severe exacerbations may also be associated with acute respiratory
failure.
► Blood eosinophil count may also predict exacerbation rates (in patients
treated with LABA without ICS).
ABCD Assessment Tool
Prevention & Maintenance Therapy
► Smoking cessation is the first step

► Influenza vaccination decreases the incidence of lower respiratory tract
infections.
► Pneumococcal vaccination decreases lower respiratory tract infections.
► Pulmonary rehabilitation improves symptoms, quality of life, and physical
and emotional participation in everyday activities.
► In patients with severe resting chronic hypoxemia, long-term oxygen therapy
improves survival.
► In patients with stable COPD and resting or exercise-induced moderate
desaturation, long-term oxygen treatment should not be prescribed
routinely. However, individual patient factors must be considered when
evaluating the patient’s need for supplemental oxygen.
Előadás főcíme Minta Péter
Előadás
© 2020 Global Initiative for Chronic Obstructive Lungalcíme
Disease igazgató
Prevention & Maintenance Therapy
► In patients with severe chronic hypercapnia and a history of hospitalization

for acute respiratory failure, long-term non-invasive ventilation may
decrease mortality and prevent re-hospitalization.
► In select patients with advanced emphysema refractory to optimized

medical care, surgical or bronchoscopic interventional treatments may be
beneficial.
► Palliative approaches are effective in controlling symptoms in advanced

COPD.
Pharmacologic Therapy
The Inhaled Route

Management of Stable COPD
► Once COPD has been diagnosed, effective management should be

based on an individualized assessment to reduce both current
symptoms and future risks of exacerbations.
Treatment of stable COPD
► Following implementation of therapy, patients should be reassessed for

attainment of treatment goals and identification of any barriers for
successful treatment (Figure 4.2).
► Following review of the patient response to treatment initiation,
adjustments in pharmacological treatment may be needed.

Treatment of stable COPD
Definition of abbreviations: eos: blood eosinophil count in cells per microliter; mMRC: modified Medical Research Council dyspnea
questionnaire; CAT™: COPD Assessment Test™.

Non-Pharmacologic Treatment
► Education and self-management

► Physical activity
► Pulmonary rehabilitation programs
► Exercise training
► Self-management education
► End of life and palliative care
► Nutritional support
► Vaccination
► Oxygen therapy
Management of Exacerbations
► An exacerbation of COPD is defined as an acute worsening of respiratory

symptoms that results in additional therapy.
► Exacerbations of COPD can be precipitated by several factors. The most

common causes are respiratory tract infections.
► The goal for treatment of COPD exacerbations is to minimize the negative

impact of the current exacerbation and to prevent subsequent events.
► Short-acting inhaled beta2-agonists, with or without short-acting

anticholinergics, are recommended as the initial bronchodilators to treat an
acute exacerbation.
► Maintenance therapy with long-acting bronchodilators should be initiated as

soon as possible before hospital discharge.
► Systemic corticosteroids can improve lung function (FEV1), oxygenation and

shorten recovery time and hospitalization duration. Duration of therapy
should not be more than 5-7 days.
► Antibiotics, when indicated, can shorten recovery time, reduce the risk of
early relapse, treatment failure, and hospitalization duration. Duration of
therapy should be 5-7 days.
► Methylxanthines are not recommended due to increased side effect profiles.

► Non-invasive mechanical ventilation should be the first mode of ventilation

used in COPD patients with acute respiratory failure who have no absolute
contraindication because it improves gas exchange, reduces work of
breathing and the need for intubation, decreases hospitalization duration
and improves survival.
COPD and Comorbidities
Some common comorbidities occurring in patients with COPD with stable

disease include:
► Cardiovascular disease (CVD)
► Heart failure
► Ischaemic heart disease (IHD)
► Arrhythmias
► Peripheral vascular disease
► Hypertension
► Osteoporosis
► Anxiety and depression
► COPD and lung cancer
► Metabolic syndrome and diabetes
► Gastroesophageal reflux (GERD)
► Bronchiectasis
► Obstructive sleep apnea

Thank you very much for the
attention!
COVID-19
Treatment of SARS-COV2 infection
Zoltán Süttő M.D., Ph.D.

Epidemiology in Hungary: new cases
3rd Wave 4th Wave 5th Wave

(omicron)
2nd Wave
1st „Wave”
vaccination started
Zoltán Süttő,
COVID-19
Epidemiology in Hungary: death rate
3rd Wave 4th Wave 5th Wave

(omicron)
2nd Wave
1st „Wave”
vaccination started
Zoltán Süttő,
COVID-19
Immunomodulant/
Anti-viral treatment? Immunosuppressive
https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.5
treatment
Zoltán Süttő,
COVID-19
Drugs used in COVID
• antiviral drugs
• neutralizing monoclonal antibodies
• corticosteroids and other immunomodulatory drugs
• mixed mechansim
• non-specific medication (anticoagulation etc.)
Zoltán Süttő,
COVID-19
Drugs used in COVID
• antiviral drugs
• mixed mechansim
Zoltán Süttő,
COVID-19
Antiviral drugs for COVID
Drug Maker Mechanism of action Route of
administration
remdesivir Gilead RTP competes with ATP  chain termination iv.

(Veklury)
nirmatlervir + Pfizer nirmatlervir: inhibiton of protease (Mpro)  inhib. of cleavage of oral

ritonavir polyprotein precursors
(Paxlovid) ritonavir: inhib. of nirmatlervir’s metabolism  plasmaconcentration 
molnupiravir MSD competes with CTP during RNA synthesis  error in viral genome (C- oral
(Lagevrio) to-U transition)  lethal mutagenesis of the virus
Possible side effects:
• emergence of new virus variants?
• carcinogenesis?
• mutagenic effect on spermatogenesis?
favipiravir EGIS, Inhib. of entry and exit of the virus from cells. oral, iv.
etc. Inhib. of RNA polymerase  inhib. of viral replication
Zoltán Süttő,
COVID-19
Drugs used in COVID
• antiviral drugs
• mixed mechansim
Zoltán Süttő,
COVID-19
Zoltán Süttő,
COVID-19
Neutralizing monoclonal antibodies (mAbs)
lack of
efficacy
against
Omicron
BA1
reduced
activity
against
Omicron
BA2
Zoltán Süttő,
COVID-19
Hwang Y-C, J Biomed Sci, 2022 Jan 4;29(1):1.
Neutralizing monoclonal antibodies (mAbs)
Casirivimab/Imdevimab Bamlanivimab/Etesevimab Sotrovimab
(REGEN-COV™)
Mechanism of action mAbs against spike protein; blocks viral attachment and entry
Reduction in hosp./deaths 70% 87% 79%
Authorized use lab-confirmed mild-moderate COVID-19 (outpatients, w/o O2-therapy)
post-exposure prophylaxis yes yes no
Eligible populations patients at high risk for progressing to severe COVID-19
age, body weight >12 years, >40 kg all (incl. neonates) >12 years, >40 kg
Prescribing window within 10 days of symptom onset
Administration route(s) IV or SC IV IV
Bebtelovimab is active in vitro against all circulating Omicron (B.1.1.529) subvariants, but there are no clinical
efficacy data from placebo-controlled trials
Zoltán Süttő,
COVID-19
Drugs used in COVID
• antiviral drugs
• mixed mechansim
Zoltán Süttő,
COVID-19
IL-1 pathway
anakinra
(Kineret sc. inj.)
van de Veerdonk and Netea Critical Care (2020) 24:445
Zoltán Süttő,
COVID-19
IL-6 pathway Janus kinase
inhibiton
tocilizumab (TCZ)
(Roactemra sc. inj.)
sarilumab
(Kevzara sc. Inj.)
baricitinib
(Olumiant tbl.)
Kaye A.G., PeerJ, 2020 Nov 2;8:e10322.
Zoltán Süttő,
COVID-19
Drugs used in COVID
• antiviral drugs
• mixed mechansim
Zoltán Süttő,
COVID-19
COVID-19 Drug Repurposing: a Drug-wide Association Study (DWAS)
Association between drug exposure (from 3-months prior to the pandemic until the COVID-19 diagnosis)
and all-cause of death
Database of 9748
symptomatic COVID-
poz patients:
• 667 hospitalized
• 105 ICU-admitted
• 84 on ventilator
• 138 dead
Bejan CA et al; Clin Pharmacol Ther, 2021 Dec;110(6):1537-46

Zoltán Süttő,
COVID-19
COVID-19 Drug Repurposing: a Drug-wide Association Study (DWAS)
Association between drug exposure (from 3-months prior to the pandemic until the COVID-19 diagnosis)
and all-cause of death
Bejan CA et al; Clin Pharmacol Ther, 2021 Dec;110(6):1537-46

Zoltán Süttő,
COVID-19
Proposed model for antiviral mechanisms of antihistamines
1 Antihistamine ( )  off-target interaction with

ACE2  conformational change  inhibition of
1 binding of SARS-CoV2 spike receptor binding
domain (RBD, ) to ACE2.
2 Antihistamine ( ) binds the sigma-1

receptor  blocking protein-protein
2 interactions with NSP6  potential
inhibition of virus life cycle by the
inhibition of binding of SARS-CoV-2
replicase/transcriptase complex to
the endoplasmic reticulum.
Reznikov LR et al, Biochem Biophys Res Commun, 2021 Jan; 538:173-9
Zoltán Süttő,
COVID-19
The mechanisms of action
of ivermectin against
SARS-CoV-2
Zaidi AK et al, The Journal of Antibiotics

(2022) 75:60–71
Zoltán Süttő,
COVID-19
Zoltán Süttő,
COVID-19
Zoltán Süttő,
COVID-19
Evidence base used for other COVID 19 approvals -
compared with ivermectin evidence base




- pending
https://ivmmeta.com/
Zoltán Süttő,
COVID-19
Zoltán Süttő,
COVID-19
Zoltán Süttő,
COVID-19
Recommendations
in favour
Zoltán Süttő,
COVID-19
Recommendations
against
Zoltán Süttő,
COVID-19
COVID-19
treatment:
home
treatment
https://www.covid19treatmentguidelines.nih.gov/
NIH, September 30, 2022
Zoltán Süttő,
COVID-19
COVID-19
treatment:
home
treatment
Zoltán Süttő,
COVID-19
COVID-19
treatment:
home
treatment
Zoltán Süttő,
COVID-19
COVID-19
treatment:
hospitalized
patients
NIH, Septemner 30, 2022
Zoltán Süttő,
COVID-19
COVID-19
treatment:
hospitalized
patients
Zoltán Süttő,
COVID-19
COVID-19
treatment:
hospitalized
patients
Zoltán Süttő,
COVID-19
Interstitial lung disease (ILD)
Prof. Veronika Müller
2019/2020 II semester
Case
• 67 year old man. Engineer, just retired. He was working
in a big car construction enterprise. Excellent familiar
support.
• Main complain: he is exhausted too quickly. This is a
major problem as he wants to spend more time with his
grandson playing soccer.
• He had several specialist consultations, however no
treatment so far resulted in an increase of his physical
activity capacity. His main goal is to walk for 15-20
minutes and running for some minutes without getting
tired.
• Exercising some minutes he experiences tachypnea,
sometimes dry „unstoppable” cough.
Previous results
• Anamnesis:
• Hypertension Q:
• IHD What specific questions would you ask
• Atherosclerosis from your patients regarding interstitial
– Non smoker since 5 year, lung disuse about:
• Medications?
previously 35PY
• Organic and an organic dust
• Since years treated with exposure?
• Signs of autoimmune disease?
„lung fibrosis”
• On chest CT enlarged
lymph nodes
3
Diagnostic tests performed due to
persisting exercise induced dyspnea
• ECHO: sPAP 32 mmHg,
normal ventricular functions,
EF62% Q:
• Can spirometry give you sufficient data
• Immune serology: ANA 1:40+ about lung function?
• Nucleolar • What pulmonary diagnostic procedures
• Anti –chromatin positive would you do to get closer to diagnosis?
• Spirometry:
– FVC: 3.74 L (88%)
– FEV1: 3.24 L (88%)
4
Diagnostic tests performed due to
persisting exercise induced dyspnea
• ECHO: sPAP 32 mmHg,
normal ventricular functions, ABG:
pH: 7,39
EF62% pCO2: 37 mmHg
pO2: 67 mmHg
• Immune serology: ANA 1:40+
• Nucleolar
• Anti –chromatin positive
6 MWT:
Distance: 489 m
Pulse: 91-117 /min
• Spirometry: Sat: 91-84%
– FVC: 3.74 L (88%) BORG: 0-3
– FEV1: 3.24 L (88%)
• TLC: 4.82 L (67%) Q:

• DLco: 46 % • What of these diagnostic possibilities
can be performed in all GP practices?
5
ILD
 Heterogeneous group of entities (>150) with similar
clinical presentation
 Diseases affect the distal airspaces and parenchyma
What happened after 4 months?
100
90
80
70
60 FVC: -15%
Referencia %
FVC
TLC: -11%
50 TLco: -4%
TLC
Dlco
40
30
20
10
0
Február Június Szeptember
8
What can we expect in 1 year?
100
90
80
70
60
Referencia %
FVC
FEV1
50
TLC
Dlco
40
30
20
10
0
FVC: -15% 1 year: -45%

TLC: -11% 1 year: -33%
TLco: -4% 1 year: -12% 9
ILD and NOT fibrosis!!
ILD: injury and/or aberrant repair
Effects of interstitial enlargement
capillaris alveolus capillaris alveolus
O2 O2
CO2 CO2
 ILD classification
 Diagnostic approach
 Therapeutic options
ILD
40% 40% ~15% ~5%
ILD known etiology

Granulomatosus ILD Other ILD
(eg. drug, CTD, organic and IIP (pl. sarcoisosis) (pl. LSG, LAM)
anorganic exposure)
Major IIP
Rare IIP
Unclassifiable IIP
Rövidítések: IIP=idiopathiás interstitialis pneumonia, IPF= idiopathiás pulmonalis fibrosis, UIP=usual intestitialis pneumonia, DIP=desquamatív intestitialis pneumonia, AIP=acut interstitialis
pneumonia, NSIP=nem specifikus interstitialis pneumonia, RB-ILD=respiratórikus bronchiolitis okozta interstitialis tüdőbetegség, COP=cryptogen szervülő pneumonia, LIP=lymphocytás
interstitialis pneumonia, LAM= lymphangioleiomyomatosis, LSG=Langerhans sejtes granulomatosis
Symptoms and diagnostics
Underlying disease:
symptoms:
» Exercise induced dyspnea
» Dry cough
fatigue, exhaustion
clubbing, cor pulmonale
 Physical examination
No change/velco like cracles
 Chest X-ray
Diffuse or nodular bronchovascular, reticulonodular or
infiltrative pattern
Lung function and CO diffusion
HRCT pattern
Bronchoscopy and BAL
6 MWT and ABG
Immune serology
Echocardiography
Diagnostic procedures
 Lung function
With progression of the disease dominantly
restrictive ventilatory disorder
» FVC, FEV1, TLC, RV↓, but FEV1/FVC →
CO diffusion impairment (DLco and KLco)
 HRCT
Description of pattern
(usual intersitial pneumonia =UIP!)
Chest X-ray
HRCT
≤1 mm slices, in and expiratory scan, prone position
pUIP pattern
HRCT
NSIP
pattern
RB-ILD DIP
smoking!
AIP LIP
Bronchoscopy
Should be performed in all ILD patients
Increased risk if extensive disease(FEV1<1.5 L, pO2<60 mmHG) due
to lung tissue rigidity
Trasbronchial lung biopsy is diagnostic:
Sarcoidois
Cancer
TB
Eosinophil lung disease
Histiocytosis C
» In all other ILD cryobiopsy or VATS!!
BAL
Diagnostic in eosinophil lung diseases
High cell numbers are indicative for worse prognosis, might indicate
HP, drug induced ILD or infection etc.
» >10% neutrophils, >28%lymphocyts
 Labs
Underlying disease
Inflammatory markers (BSR, haematology)
Elektroforesis
Autoimmun serology
SACE, Ca
 Blood gases
Progressive hypoxaemia (later partial respiratory insufficiency)
Blood gas examination following exercise
 6 MWT
Distance
Desaturation
Pulse
BORG Dyspnoe scale VAS (0-10)
 ECHO: SPAP measurement
ILD
ILD known etiology

anorganic exposure)
Major IIP
Diagnosis: Rare IIP

ILD-team!
Unclassifiable IIP
IPF and CTD-ILDs
Autoimmun features
Other
Other ILD IPF U-ILD IPAF U-CTD CTD autoimmune
disease
Lung involvement
Ferri C et al: Interstitial pneumonia with autoimmune features and undifferentiated connective tissue disease. Our
interdisciplinary rheumatology–pneumology experience, and review of the literature. Autoimmunity reviews 2015.
Chronic fibrosing ILDs
20% IPF
20% non fibrosing
Ahmad K et al: Interstitial pneumonia with autoimmune features: Clinical, radiologic,and histological characteristics and
outcome in a series of 57 patients. Respir Med 2017; 123: 56-2.
Examination Yes No
Anamnesis Lung fibrosis in the family? □ □
Lung fibrosis inducing drug? Cordarone □ □

Bleomicin □ □
Methotrexate □ □
Other □ □
Dust (an organic) exposure? Asbest □ □
Wood dust □ □
Metal dust □ □
Organic dust exposure? Mould □ □
Earth □ □
Bir/feather □ □
Other organic dust □ □
Actual smoking Daily cigarettes……. PY….. □ □
Former smoking PY….. □ □
Physical examination Bibasilar basal velcro crackles □ □
Signs of systemic autoimmune disease Arthralgia □ □
Raynaud □ □
Skin changes □ □
Photosensitivity □ □
Spirometry FEV1/FVC >80% □ □
FVC severity? >80% □ □
50-80% □ □
<50% □ □
Saturation >92% □ □
Saturation changes after Decrease □ □
exercise
Expert center
Examination Yes No
CO diffusion DLCO<80% □ □
KLCO<80% □ □
Blood gases Hypoxaemia □ □
HRCT (in and UIP patternt □ □

exspiration) Possible UIP □ □
6 MWT Distance…….m BORG Before After

Saturation
Pulse
Immunpanel positiviy ANA □ □

ENA □ □
RF □ □
aCCP □ □
(ANCA) □ □
Echocardiography Pulmonary hypertension (systolic pulmonális □ □

artery pressrure >35 Hgmm)
Bronchoscopy Pathogen (aerob, anaerob, fungi, □ □

Mycobacterium) □ □
Cytology (malignancy) □ □
BAL cells
Raghu et al. AJRCCM 2018
ILD
40% 40% ~15% ~5%
ILD known etiology

anorganic dust exposure)
HP
IPF
CTD
Clinical course of IPF
Raghu G et al.; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based
guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824.
IPF= shorter survival than cancer!
Pirfenidone in the treatment of Idiopathic Pulmonary Fibrosis – A Canadian therapeutic position statement
IPF therapy
Time
Pharmacological Disease progression

•Control every 4-6 months
Non pharmacological
•O2
IPF •Rehabilitation Evaluate for
Dg LUTX
Comorbidities Acute exacerbation
•Pulmonary hypertension •Corticosteroids
•GOR
Respiratory failure
Symptomatic treatment •IPF progression
Clinical trials
Raghu G et al. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management.
Am J Respir Crit Care Med 2011; 183:788–824.
Breakthrough in IPF therapy:
pirfenidone & nintedanib
King TE et al. NEJM 2014 Richeldi L et al. NEJM 2014

IPF therapy
Nintedanib start
100
90
80
70
60
Referencia %
FVC
FEV1
50
TLC
Dlco
40
30
20
10
0
2015 …..2017 November
34
ILD survival
U-ILD= CTD-ILD, HP, idiopathias NSIP Korra, nemre, FVC-re és DLco-ra korrigált
Ryerson C et al: Prevalence and prognosis of unclassifiable interstitial lung disease. Eur Respir J 2013; 42: 750–757
Progressive fibrosing ILDs
non IPF
Possible UIP
pUIP
IPAF IPF fNSIP

CTD-ILD
fHP (-Ag)
fHP
(+Ag) RA-ILD
Sarcoidosis
Athol Wells ERS 2017

Future therapeutic options
Idiopathic UIP CTD-ILD

(IPF) (any pattern)
Idiopathic non-UIP
Chronic HP
Clinical trial Non classifiable ILD
LuTX
Non fibrosing Fibrosing

Nintedanib
Pirfenidone
ISU ISU
+/-
Nintedanib
Pirfenidone
or
Other antifibrotic therapy
IPF AEx
IPF EAx
Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, Lee JS, Maher TM, Wells AU, Antoniou KM, Behr J, Brown KK, Cottin V, Flaherty KR, Fukuoka J, Hansell DM, Johkoh T,
Kaminski N, Kim DS, Kolb M, Lynch DA, Myers JL, Raghu G, Richeldi L, Taniguchi H, Martinez FJ. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report.
Am J Respir Crit Care Med. 2016 Aug 1;194(3):265-75.
IPF AEx and mortality
Mortalitás 52 hét alatt (%)
Severe AEx Mild AEx IPF patients wo AEx

(n=49) (n=14) (n=998)
Efficacy of nintedanib on acute exacerbations reported as serious adverse events in the INPULSIS® trials in idiopathic pulmonary fibrosis (IPF)
Data presented at American Thoracic Society (ATS) International Conference, San Francisco, California, USA, 13–18 May 2016 [Kreuter et al]
ILD
 Diagnostics: interdisciplinary approach
 Pulmonary specialist:
Detailed LF+ CO diffusion measurement (+ABG+6MWT)
HRCT
Bronchoscopy
Consultation (cardiologist, rheumatologist, medical oncologist…)
 Diagnosis: ILD-team (pulmonologist, radiologist, pathologist)
 Therapy
Dependent on underlying condition
Antifibrotic therapy
AEx and comorbidity treatment, oxygen supplementation
Interstitial lung diseases (ILD)
Lung transplantation (LuTx)
Cystic fibrosis (CF)
Anikó Bohács M.D., PhD., associate professor

Semmelweis University Department of Pulmonology
Interstitial lung diseases
 Heterogeneous group of entities
(>150) with similar clinical
presentation
 Diseases affect the distal
airspaces and lung parenchyma
ILD
40% 40% ~15% ~5%
ILD known etiology

Idiopathic interstitial Granulomatosus ILD Other ILD
(eg. Drug induced ILD
CTD-ILD pneumoniaa IIP (pl. sarcoisosis) (pl. LSG, LAM)
organic and
anorganic exposure
(hypersensitive HP Major IIP
pneumoconiosis)
Rare IIP
Unclassifiable IIP
Rövidítések: IIP=idiopathiás interstitialis pneumonia, IPF= idiopathiás pulmonalis fibrosis, UIP=usual intestitialis pneumonia, DIP=desquamatív intestitialis pneumonia, AIP=acut
interstitialis pneumonia, NSIP=nem specifikus interstitialis pneumonia, RB-ILD=respiratórikus bronchiolitis okozta interstitialis tüdőbetegség, COP=cryptogen szervülő pneumonia,
LIP=lymphocytás interstitialis pneumonia, LAM= lymphangioleiomyomatosis, LSG=Langerhans sejtes granulomatosis
Clinical symptoms and diagnostic tools of ILD
Symptoms:
• exercise induced dyspnea
Check list • dry cough
Anamnestic information: fatigue Bronchoalveolar
working-dust expos. , clubbing, cor pulmonale lavage+ lung biopsy
animal husbandry (birds),
drug exp.
Physical examination
HRCT
pattern
Immunserology Functional parameters:

autoimmunity • Restrictive lung function
• Decreased diffusion
VELCRO crakles capasity
Clubbing fingers • Hypoxaemia in blood
gas,
• Desaturation on 6
minutes walking test
High resolution computer tomography (HRCT)
1 mm slices, in and expiratory scan, prone position
- Extension and severity of ILD
pUIP pattern
The role of the multidisciplinary team (MDT) in ILD
Raghu G, Remy-Jardin M, Richeldi L, Thomson CC, Inoue Y, Johkoh T, Kreuter M, Lynch DA, Maher TM, Martinez FJ, Molina-Molina M, Myers JL, Nicholson AG, Ryerson CJ, Strek ME, Troy LK, Wijsenbeek
M, Mammen MJ, Hossain T, Bissell BD, Herman DD, Hon SM, Kheir F, Khor YH, Macrea M, Antoniou KM, Bouros D, Buendia-Roldan I, Caro F, Crestani B, Ho L, Morisset J, Olson AL, Podolanczuk A, Poletti
V, Selman M, Ewing T, Jones S, Knight SL, Ghazipura M, Wilson KC. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice
Guideline. Am J Respir Crit Care Med. 2022 May 1;205(9):e18-e47. doi: 10.1164/rccm.202202-0399ST. PMID: 35486072.
Raghu G et al.; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and
management. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824.
Known origin ILD-s
Types:
 Occupational ILD: mineworkers, dental techician, polischer
 Drug induced (DI-ILD): amiodarone, bleomycin, check-point
inhibitors (https://www.pneumotox.com/drug/index)
 Connective tissue disease-ILD: Scleroderma, Rheumatoid
arthritis (RA), Sjögren sy, Myositis,
 Hypersensitive pneumonitis: acute, subacute, chronic (CHP)
Clinical symptoms: improductive coughing, dyspnoe on exertion.
RA-ILD
CHP: ground glass
opacity,
reticulation, fibrotic
changes
Major IIP: Idiopathic pulmonary fibrosis (IPF)
 Chronic, progressive, high mortality ILD
 Pathology: Scars in the lung parenchyma (stiffness,
thickness)
 Risk for IPF: older age (> 63 years), family history of IPF
 Typical HRCT pattern: honey combing, traction
bronchiactasis, bilateral basal dominant. UIP-usual
interstitial pneumonitis pattern.
Restrictive lung function

Tiffeneu index (FEV1/FVC): 105%
Diffusion capacity ↓: Dlco: 56%.
Raghu G et al.; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-
based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824.
pirfenidone (ESBRIET) & nintedanib (OFEV)
Both drugs slow down the progression of IPF,

decrease the risk of acute exacerbation.

Granulomatosus ILD: Sarcoidosis
 Hystology: non necrotizing granulomatosus disease.
 Epidemiology: younger age (25-45 yr)
 General symtoms: fatigue, swollen lymph nodes, pain and
swelling in joints, weight loss.
 Lung symptoms: asymptomatic,dry cough, shortness of
breath,
 Multiorgan involvement:
• eyes-uveitis, CNS-neurosarcoidosis 5%
• skin (Löfgren syndrome-erythema nodosum, fever, arthritis)
• heart-arrythmias,
• liver, spleen, kidney involvement
• affect calcium metabolism (serum Ca2+↑)
• SACE-serum angiotensin converting enzyme ↑)
Radiologic stages of sarcoidosis
0.Stage: no changes in chest X-ray (extrapulmonary manifestation)
I. Stage
BHL: bilateral hilar

lymphadenopathie
III.Stage
Parenchymal changes: noduls, reticulation)
II.Stage:
BHL+parenchymal involvement
(galaxy sign:nodules) IV. Stage:
Fibrosis in upper lobes
Department of Pulmonology 2022-2023

Other, rare cystic ILD:
lymphangioleiomyomatosis (LAM)
• Younger ladies with obstructive ventilation

disorder
• Cystic changes on HRCT
• Angiomyolipomas on abdominal US
• Histology typical
• VEGF↑
Complication: pneumothorax (ptx), Chylothorax
Treatment: mTOR inhibitors, lung transplantation
Department of Pulmonology Aniko Bohacs MD.,2022-2023

PhD
Dep. Of Pulmonology Semmelweis University
Progressive fibrotizing (PF)-ILD
Progressive pulmonary fibrosis (PPF)
Diagnostic criteria (2 from 3):
 Progression on clinical symptoms
 Progression on lung function:
• Absolute FVC ↓ >= 5% in 1 yr
• Abszolute DlCO ↓ >=10% 1 yr
 Progression on HRCT (extension,
severity)
Wells AU et al.; What is in a name? That which we call IPF, by any other name would act the same. ERJ 2018;51:1800692
LUNG TRANSPLANTATION
Donor and recipient match:

• Size maching
• Main blood group mathing
• No HLA matching
Chlamshell thoracotomy
Aim of lung transplantation (LuTx)
Lung transplantation may be the only intervention

that can prolong survival and improve quality of life
for those patients with advanced, end stage lung
disease:
• who are refractory for conventional therapies
• who are acceptable candidates for the procedure.
Indication of lung transplantation
General criteria: High (>50%) risk of death due to lung disease
within 2 years if lung transplantation is not performed.
Disease specific candidate recommendation (ISHLT 2014,2021)
Main causes:
• Progressive pulmonary diseases (etc: idiopathic pulmonary
fibrosis (IPF)
• Cystic fibrosis (CF)
• Chronic obstructive lung disease (COPD)
• α1-antitrypsin deficiency emphysema
• Idiopathic artherial hypertension (iPAH)
Weill D.J Thorac Dis. 2018 Jul;10(7):4574-4587.

Weill et al. A consensus document for the selection of lung transplant candidates. The Journal of
Heart and Lung Transplantation, Vol 34, No 1, January 2015
Less frequent causes:

• Non CF bronchiectasis
• Chonic thromboembolism with pulmonary
hypertension (CPTE)
• Other, rare interstitial lung diseases [Boeck-
sarcoidosis, Lymphangioleiomyomatosis (LAM),
eosinophil granulomatosis (histiocytosis)]
• Eisenmenger-syndrome
Adult Lung Transplants
Major Diagnoses by Year (%)
2018
JHLT. 2018 Oct; 37(10): 1155-1206
Number of Transplants by Year and Procedure Type
NOTE: This figure includes only the adult lung

transplants that are reported to the ISHLT Transplant
Registry. As such, this should not be construed as
2017 representing changes in the number of adult lung
transplants performed worldwide.
JHLT. 2017 Oct; 36(10): 1037-1079
Absolute contraindication of LuTx
• Malignancy (5 year).
• Severe systemic comorbidity (coronary disease, renal function
impairment. Bleeding susceptibility.
• Septicaemia, uncontrolled infection
• Panrezistant MRSA, Pseudomonas, HIV
• Grade II or III obesity (BMI ≥35.0 kg/m2)
• Psychiatric disorder, non-compliance.
• Addiction (smoking, drug, alcohol)
• No social supportation
• Low chance for rehabilitation.
Checkup before transplantation
• Coronarography, echocardiography
• Chemistry
• Serology (HIV, hepatitis, treponema pallidum)
• Osteodensitometry (ODM)
• HLA fenotyping
• Chest CT and lungscintigraphy
• Exclusion of inflammatory focuses
• PET CT for exclude occult tumors (age>40y)
Lung transplantation in Hungary, special
condition.
• 1996 LuTx available for Hungarian patients in Wienna

• Refer LuTx candidate to the center
• Post LuTx was Wienna
• Hungarian LuTx waiting list comittee:
3 pulmonologist, 1 surgeon, 1 anesthesiologist
• Posttransplant follow up:
• Adults: 2008-Semmelweis University Dep. of Pulmonology
• Child: 1st. Pediatric Clinic of SE
• LuTx surgical procedure in Budapest from 2015.12.
• Prof. Gy. Lang and dr Rényi-Vámos Ferenc
• 173 patient undervent the procedure
Surveillance controll after transplantation
• In the first 3 month every week: lung function,

chest Xray, ECG, labory chemistry,
immunosuppressive drug serum level, CMV
antigenic,
• Bronchoscopy, lavage for microbiology,
transbronchial biopsy at week 2. 4. 8., at 3. 6. 12.
month.
• Chest CT at every 6. month, after every year
Bronchoscopy need, when progression in lung

function or new radiologic sign is observed .
Bronchial complications
Frequency: 2-33%
• Sloughing of the airways 50%
• Anastomotic dehiscence 1-10%

20%
• Exophytic granulation
• Bronchial stenosis 4-24%
• Vanishing airway syndroma 1%
• Tracheobronchomalacia 1-40%
• Bronchial fistulas 1%
• Anastomotic infections 1-25%
01 4 8 12 26 52 hét
postLuTx idő
Chest 2017; 152(3):627-638; J Heart Lung Transplant 2018;37:548–563

Bronchial complication
Exophytic granulation
Anastomosis
dehiscence
Normal anastomosis
Bronchial
fistula
stenosis
Surweilance bronchoscopy:
samples from the lower respiratory tract.
 Microbiology/TB (Mycobact. Tuberculosis)
 Virology (adeno-, Repiratory syntitial-, Corona- , Rhino., influenza, parainfluenza)
 Micology (candida sp., Aspergillus, Mucor, Rhizopus)
 CMV PCR/copies, EBV

 Histology (rejection grading, infection)
 BAL propotion of neutrophil/lymphocyte/eosinophil
Lung function and immunosuppression
• Imbalance between the immunosuppression and

host defence is important:
o Prevent from graft rejection
o Eligible immun response against the
infection
• This point is important in the lung transplanted

patient, because of the Iung is the entrance of the
infective agent. (viruses, bacterials,….)
Induction treatment
 Inhibition of the lymphocyte

migration to the donor lung.
 Peripherial immuntolerance.
Reactive
• ATG(anti-thymocyte globulin) T lymph.
• Alemtuzumab (CD52
monoclonal antibody)
• Inhibition of reactive T
• Daclizumab (Il-2 blocker) lymphocytes
• Decrease of T cell number
Immunszuppressive therapy after LuTx
• Traditional ”triple drug combination” ± induction

1. Calcineurin inhibitor (CNI)
(tacrolimus, cyclosporin)
2. Antimetabolite (mycofenolate)
3. Steroid
omTOR inhibitors (everolimus, rapamycine)

indication: BOS or posttransplant malignancy.
Atimicrobiological profilaxis after the lung
transplantation
 Inhalation of Amphotericin B
 For 3 month.
 Against the colonization of Aspergillus specieses.
 Trimethoprim/sulfomethoxazole (tmp/smx):
 Long life
 Against the Pneumocystis jirovecii and Nocardia
 Valgancyclovir:
 For 3 month
 In high risk patient (CMV+donor/CMV–recip) 6-12 month)
 Against the Cytomegalovírus (CMV) infection
Opportunistic infection in LuTx patients
• Usually harmless microorganism that can
become pathogenic when the host's
resistance is impaired.
• Opportunistic agents:
• Nocardia
• Pneumocystis jiroveci
• Fungus (aspergillus, mucor)
• Cytomegalovirus (CMv)
• Herpes zoster
• High mortality without effective treatment
on time
Kaplan-Meier Survival by Diagnosis
(Transplants: January 1990 – June 2015)
Median survival (years):

A1ATD: 6.7; CF: 9.2; COPD: 5.8; IIP: 4.9; ILD-
not IIP: 6.0; Retransplant: 2.9
All pair-wise comparisons were

significant at p < 0.05 except
A1ATD vs. ILD-non IIP and COPD
vs. ILD-non IIP
2017
JHLT. 2017 Oct; 36(10): 1037-1079
Nataraju Angaswamy:Interplay between Immune responses to HLA and Non-HLA self-
antigens in allograft rejection. Hum Immunol. 2013 Nov; 74(11): 10.1016
Type of graft failure.
• Acute graft failure (3,6% cause of death 1 month

after LuTx)
• Subacut
• Chronic Lung Allograft Dysfunction-CLAD:
1. Bronchiolitis obliterans syndroma (BOS)
2. Restrictív allograft syndroma (RAS)
J Heart Lung Transplant 2014; 33: 1009

Two form of CLAD
Bronchiolitis obliterans Restrictiv allograft
syndrom (BOS) dysfunction (RAS)
CT: mozaic attenuation CT: fibrotic changes

LF: obstructive ventilation LF: restrictive ventilation
disorder disorder
Slow progression Rapid progression, high
mortality
Donor specific antibodies (DSA)
Relative Incidence of Leading Causes of Death
(Deaths: January 1990 – June 2016)
2017
JHLT. 2017 Oct; 36(10): 1037-1079
CYSTIC FIBROSIS
• Epidemiology: rare disease ‚1:3600 newborns.
• Genetic disorder (autosomal recessive inharitance)
ΔF508 mutation (CFTR Cystic fibrosis transmembrane
conductance regulator) gene mutation . Eu population
70%.
• CFTR protein is not working correctly, it’s unable to
help move chloride to the cell surface. The mucus in
various organs becomes thick and sticky.
Multiorgan involvement
Cystic fibrosis in chest CT scans
Bronchiectasis, mucus impactation,

peribronchial inflammation
Sweat chloride testing and genetic testing
Malnutrion in CF
• GI manifestation (pancreatitis,
liver fibrosis, worst intestine
absorption).
• AE: lost appetite
• Progressive decline of lung

function
BMI:13kg/m2 • Lost repiratory muscles
Aim of treatment
• Diminisches
the decline of
lung function
• Better nutrition
• Better quality of
life
Pulmonary threatment opions I.
• Expectoration: physiotherapy important, hypertonic
salin, pulmozyme.
• Treat colonization:
 Antibiotic: target therapy against Haemophilus inf.,
staphylococcus aureus, pseudomonas aeruginosa (per
os, i.v., inhalation), stenotrophomonas maltophilia,
Burkholderia cepacia.
 Antimycotic agent: against Aspergillus spp.
(Voriconazol)
 Antituberculotic agents: Mycobacteria tub.
Pulmonary threatment opions II.
• Bronchodilators: nebulised ẞ2-agonists

• Treat pulmonary complication:
 Chest drainage in ptx
 Selective embolism of pulm. art. In
haemoptysis
• Pulmonary rehabilitation
When refer to transplant center?
 FEV1 ≤ 30%, or progressive decline in lung function, non
tuberculotic mycobacterium (NTM) infection or Burkholdeia
cepacia complex infectionand/or DM.
 6MWT < 400 m.
 Pulmonalis hypertension estimated PAP> 25 Hgmm at
echocardiograph.
 Frequent exacerbations:
• Need NIV
• Antibiotic resistance widening, recovery from AE longer.
• malnutrition
• Pneumothorax (PTX).
• Critical haemoptisis
The Journal of Heart and Lung Transplantation, Vol 34, No 1, January 2015
Interstitial lung diseases (ILD)
Anikó Bohács M.D., PhD., associate professor

Semmelweis University Department of Pulmonology
Interstitial lung diseases
 Heterogeneous group of entities
(>150) with similar clinical
presentation
 Diseases affect the distal
airspaces and lung parenchyma
ILD
40% 40% ~15% ~5%
ILD known etiology

Idiopathic interstitial Granulomatosus ILD Other ILD
(eg. Drug induced ILD
CTD-ILD pneumoniaa IIP (pl. sarcoisosis) (pl. LSG, LAM)
organic and
anorganic exposure
(hypersensitive HP Major IIP
pneumoconiosis)
Rare IIP
Unclassifiable IIP
Rövidítések: IIP=idiopathiás interstitialis pneumonia, IPF= idiopathiás pulmonalis fibrosis, UIP=usual intestitialis pneumonia, DIP=desquamatív intestitialis pneumonia, AIP=acut
interstitialis pneumonia, NSIP=nem specifikus interstitialis pneumonia, RB-ILD=respiratórikus bronchiolitis okozta interstitialis tüdőbetegség, COP=cryptogen szervülő pneumonia,
LIP=lymphocytás interstitialis pneumonia, LAM= lymphangioleiomyomatosis, LSG=Langerhans sejtes granulomatosis
Clinical symptoms and diagnostic tools of ILD
Symptoms:
• exercise induced dyspnea
Check list • dry cough
Anamnestic information: fatigue Bronchoalveolar
working-dust expos. , clubbing, cor pulmonale lavage+ lung biopsy
animal husbandry (birds),
drug exp.
HRCT
pattern
Immunserology Functional parameters:

autoimmunity • Restrictive lung function
• Decreased diffusion
VELCRO crakles capasity
Clubbing fingers • Hypoxaemia in blood
gas,
• Desaturation on 6
minutes walking test
High resolution computer tomography (HRCT)
1 mm slices, in and expiratory scan, prone position
- Extension and severity of ILD
pUIP pattern
The role of the multidisciplinary team (MDT) in ILD
Raghu G, Remy-Jardin M, Richeldi L, Thomson CC, Inoue Y, Johkoh T, Kreuter M, Lynch DA, Maher TM, Martinez FJ, Molina-Molina M, Myers JL, Nicholson AG, Ryerson CJ, Strek ME, Troy LK, Wijsenbeek
M, Mammen MJ, Hossain T, Bissell BD, Herman DD, Hon SM, Kheir F, Khor YH, Macrea M, Antoniou KM, Bouros D, Buendia-Roldan I, Caro F, Crestani B, Ho L, Morisset J, Olson AL, Podolanczuk A, Poletti
V, Selman M, Ewing T, Jones S, Knight SL, Ghazipura M, Wilson KC. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice
Guideline. Am J Respir Crit Care Med. 2022 May 1;205(9):e18-e47. doi: 10.1164/rccm.202202-0399ST. PMID: 35486072.
Raghu G et al.; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and
management. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824.
Known origin ILD-s
Types:
 Occupational ILD: mineworkers, dental techician, polischer
 Drug induced (DI-ILD): amiodarone, bleomycin, check-point
inhibitors (https://www.pneumotox.com/drug/index)
 Connective tissue disease-ILD: Scleroderma, Rheumatoid
arthritis (RA), Sjögren sy, Myositis,
 Hypersensitive pneumonitis: acute, subacute, chronic (CHP)
Clinical symptoms: improductive coughing, dyspnoe on exertion.
RA-ILD
CHP: ground glass
opacity,
reticulation, fibrotic
changes
Major IIP: Idiopathic pulmonary fibrosis (IPF)
 Chronic, progressive, high mortality ILD
 Pathology: Scars in the lung parenchyma (stiffness,
thickness)
 Risk for IPF: older age (> 63 years), family history of IPF
 Typical HRCT pattern: honey combing, traction
bronchiactasis, bilateral basal dominant. UIP-usual
interstitial pneumonitis pattern.
Restrictive lung function

Tiffeneu index (FEV1/FVC): 105%
Diffusion capacity ↓: Dlco: 56%.
Raghu G et al.; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-
based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824.
pirfenidone (ESBRIET) & nintedanib (OFEV)
Both drugs slow down the progression of IPF,

decrease the risk of acute exacerbation.

Granulomatosus ILD: Sarcoidosis
 Hystology: non necrotizing granulomatosus disease.
 Epidemiology: younger age (25-45 yr)
 General symtoms: fatigue, swollen lymph nodes, pain and
swelling in joints, weight loss.
 Lung symptoms: asymptomatic,dry cough, shortness of
breath,
 Multiorgan involvement:
• eyes-uveitis, CNS-neurosarcoidosis 5%
• skin (Löfgren syndrome-erythema nodosum, fever, arthritis)
• heart-arrythmias,
• liver, spleen, kidney involvement
• affect calcium metabolism (serum Ca2+↑)
• SACE-serum angiotensin converting enzyme ↑)
Radiologic stages of sarcoidosis
0.Stage: no changes in chest X-ray (extrapulmonary manifestation)
I. Stage
BHL: bilateral hilar

lymphadenopathie
III.Stage
Parenchymal changes: noduls, reticulation)
II.Stage:
BHL+parenchymal involvement
(galaxy sign:nodules) IV. Stage:
Fibrosis in upper lobes
Department of Pulmonology 2022-2023

Other, rare cystic ILD:
lymphangioleiomyomatosis (LAM)
• Younger ladies with obstructive ventilation

disorder
• Cystic changes on HRCT
• Angiomyolipomas on abdominal US
• Histology typical
• VEGF↑
Complication: pneumothorax (ptx), Chylothorax
Treatment: mTOR inhibitors, lung transplantation
Department of Pulmonology Aniko Bohacs MD.,2022-2023

PhD
Dep. Of Pulmonology Semmelweis University
Progressive fibrotizing (PF)-ILD
Progressive pulmonary fibrosis (PPF)
Diagnostic criteria (2 from 3):
 Progression on clinical symptoms
 Progression on lung function:
• Absolute FVC ↓ >= 5% in 1 yr
• Abszolute DlCO ↓ >=10% 1 yr
 Progression on HRCT (extension,
severity)
Wells AU et al.; What is in a name? That which we call IPF, by any other name would act the same. ERJ 2018;51:1800692
LUNG TRANSPLANTATION
Donor and recipient match:

• Size maching
• No HLA matching
Lung transplantation may be the only intervention

that can prolong survival and improve quality of life
for those patients with advanced, end stage lung
disease:
General criteria: High (>50%) risk of death due to lung disease
within 2 years if lung transplantation is not performed.
Disease specific candidate recommendation (ISHLT 2014,2021)
Main causes:
• Progressive pulmonary diseases (etc: idiopathic pulmonary
fibrosis (IPF)


• Non CF bronchiectasis
hypertension (CPTE)
• Other, rare interstitial lung diseases [Boeck-
sarcoidosis, Lymphangioleiomyomatosis (LAM),
eosinophil granulomatosis (histiocytosis)]
2018
JHLT. 2018 Oct; 37(10): 1155-1206

JHLT. 2017 Oct; 36(10): 1037-1079
• Severe systemic comorbidity (coronary disease, renal function
impairment. Bleeding susceptibility.
• Chemistry
• Serology (HIV, hepatitis, treponema pallidum)
• Osteodensitometry (ODM)
• HLA fenotyping
• Chest CT and lungscintigraphy
• Exclusion of inflammatory focuses
condition.

3 pulmonologist, 1 surgeon, 1 anesthesiologist
• Posttransplant follow up:
• Adults: 2008-Semmelweis University Dep. of Pulmonology
• Child: 1st. Pediatric Clinic of SE

antigenic,
month.

Bronchial complications
Frequency: 2-33%
• Sloughing of the airways 50%
• Anastomotic dehiscence 1-10%

20%
• Exophytic granulation
• Bronchial stenosis 4-24%
• Vanishing airway syndroma 1%
• Tracheobronchomalacia 1-40%
• Bronchial fistulas 1%
• Anastomotic infections 1-25%
01 4 8 12 26 52 hét
postLuTx idő
Chest 2017; 152(3):627-638; J Heart Lung Transplant 2018;37:548–563

Bronchial complication
Exophytic granulation
Anastomosis
dehiscence
Normal anastomosis
Bronchial
fistula
stenosis
Surweilance bronchoscopy:
samples from the lower respiratory tract.
 Microbiology/TB (Mycobact. Tuberculosis)
 Virology (adeno-, Repiratory syntitial-, Corona- , Rhino., influenza, parainfluenza)
 Micology (candida sp., Aspergillus, Mucor, Rhizopus)

 Histology (rejection grading, infection)
 BAL propotion of neutrophil/lymphocyte/eosinophil

infection
• This point is important in the lung transplanted

Induction treatment

Reactive
• ATG(anti-thymocyte globulin) T lymph.
• Inhibition of reactive T
• Daclizumab (Il-2 blocker) lymphocytes

3. Steroid

Atimicrobiological profilaxis after the lung
transplantation
 For 3 month.
 Long life
 Against the Pneumocystis jirovecii and Nocardia
 Valgancyclovir:
 For 3 month
Opportunistic infection in LuTx patients
• Usually harmless microorganism that can
become pathogenic when the host's
resistance is impaired.
• Opportunistic agents:
• Nocardia
• Pneumocystis jiroveci
• Fungus (aspergillus, mucor)
• Cytomegalovirus (CMv)
• Herpes zoster
• High mortality without effective treatment
on time


vs. ILD-non IIP
2017
JHLT. 2017 Oct; 36(10): 1037-1079

after LuTx)
• Subacut

Two form of CLAD
Bronchiolitis obliterans Restrictiv allograft
syndrom (BOS) dysfunction (RAS)
CT: mozaic attenuation CT: fibrotic changes

LF: obstructive ventilation LF: restrictive ventilation
disorder disorder
Slow progression Rapid progression, high
mortality
Donor specific antibodies (DSA)
2017
JHLT. 2017 Oct; 36(10): 1037-1079
CYSTIC FIBROSIS
70%.
Multiorgan involvement
Bronchiectasis, mucus impactation,

peribronchial inflammation
Sweat chloride testing and genetic testing
Malnutrion in CF
absorption).

function
Aim of treatment
• Diminisches
the decline of
lung function
life
salin, pulmozyme.
(Voriconazol)

haemoptysis
 6MWT < 400 m.
 Pulmonalis hypertension estimated PAP> 25 Hgmm at
echocardiograph.
• Need NIV
• malnutrition
Lung cancer
Prof. Dr. Tamási Lilla

Tószegi Fanni demonstrátor
Semmelweis Egyetem, Pulmonológiai Klinika
2022
Pulmonológiai Klinika
Blokkoktatás 2019-2020
Pulmonológiai Klinika 2019-2020
Etiology
• smoking (packyear=pack of cigarettes per day x years spent smoking)

• Air pollution
• Radon, asbetos(mesothelioma) nickel, other carcinogenic substances, genetics
• Mutations in tumorsuppressor genes and proto-oncogenesincreased

proliferation, inhibition of apoptosis clonal expansion of tumor cells

Histological classification of lung
cancer
Epithelial tumors
Small cell lung cancer (SCLC)
Non-small cell lung cancer( NSCLC)
Soft tissue sarcoma
Mesothelial tumors
metastases…

Two main histological types of lung cc
1. Small-cell lung cancer (SCLC) 2. Non-small-cell lung cancer (NSCLC) –
• agressive but chemosensitive • In early stages (I-IIIA) surgery is the first
choice – it can lead to complete remission
• caused by smoking • IIIB és IV: chemo- and radiotherapy to
slow the progression
• it is treated as a systemic disease from • Targeted and immune therapy
the beginning( micro-metastases are Adenocarcinoma
present at the time of diagnosis) • most commom histological type
• Especially in non-smokers, women and
young patients (50’>)
• Often peripheral
• most important modality of treatment Squamosus cell carcinoma
is chemotherapy • More common in men, after many years of
smoking
• radiation therapy is often applied • Rather central, locally spreading form
besides chemo – especially in cases when Large cell carcinoma és neuroendocrine large
there are no distant metastases cell carcinoma
• surgery is never part of the treatment
protocol as it does’t increase survival

Diagnosis
 symptoms
 screening
 Imaging methods
 histology
 molecular pathology

Symptoms
LOCAL SYMPTOMS SYMPTOMS CAUSED BY METASTASES
• Cough, with sputum • Bone metastasespain, pathological fracture
• Coughing up blood (hemoptoe ) • brain confusion, epileptiform seizures,

paresis, other neurological symptoms
• If the tumor causes pleural fluid or obstructs a
bigger bronchusdyspnoe • Liver enlarged liver
• If the tumor invades the pleurachest pain PARANEOPLASTIC SYMPTOMS
• (in the apex of the lung)Pancoast- • SIADH

tumorHorner’s syndrome: myosis, ptosis, • thromboembolic diseases e.g. DIC,
enophtalmus thrombophlebitis migrans
• If the tumor compresses SVCsuperior vena • PTHrP productionHypercalcemia
cava syndrome (swelling of face, neck and arm,
dyspnoe) • ACTH productionCushing’s syndrome…
GENERAL SYMPTOMS OF CANCER

• Loss of apetite
• Weight loss
• fatigue
Screening
• Lung cancer often has few or no symptoms at all-->this often leads to a late
diagnosis
• Complete remission is only possible if it is diagnosed in early stages and
surgery is executed
• Screening would increase the chance of early diagnosis thus would
improve survival rate
• Low-dose CT would be the best for screening
• In Hungary screening with low-dose CT is under clinical trial

Imaging methods
Tumnor causing atelectasia in the right upper lobe
 Chest x-ray

Imaging methods
 CT with contrast material
Tumor reaches chest wall

Imaging methods
 Staging--> PET CT and head CT or
chest+abdomen+head CT and bone
scintigraphy

Bronchoscopy
collecting sample, histology, molecular pathology
The diagnosis of lung cancer

needs to be confirmed by the
pathologist
Sample for histology can be

collected using
• Bronchoscopy
• CT-guided trans-thoracic core
biopsy
• Pleural biopsy, pleuroscopy
• VATS
• Mediastinoscopy surgeries

Bronchoscopy

Molecular pathology
• samplehistologic examination
• Immunohistochemistry is used to
determine the origin of the
tumor(primer/metastatic) and
the histological type ( SCLC or
NSCLC)
• If it is adenocarcinoma we
look for mutations in ALK,
ROS1, PDL-1, BRAF, KRAS,
EGFR genes  method: NGS
• If it is squamosus cell cc only
PDL-1 is examined
Targeted therapy

Treatment
• Based on our aim, the chosen treatment can be
• curative: our aim is to remove the tumor completely from the patient 
full recovery
• palliative: our aim is to slow the progress by decreasing the size of the
tumoractive oncotherapy, but we are not expecting complete remission
• supportive: our aim is to treat the symptoms of the disease and to reduce
the side effects of oncotherapy, thus providing a better quality of life- not
active oncotherapy. E.g. painkillers, oxygen, antiemetics

Treatment
• TERÁPIÁS MODALITÁSOK Our choice depends on
• Surgery
• overall condition of the patient
 Lobectomy
• histological type of the tumor, in
 Bilobectomy
case of adenocarcinoma the
 Pulmonectomy
presence of molecular targets
 In some cases atypical resection
• The stage of the disease
• Chemotherapy
• Immune therapy
• Targeted therapy
• radiation

Staging of lung cancer
 Based on the 8th TNM
 T: size of the primer tumor
 N: spread of cancer to nearby lymph nodes
 M: distant metastases

 T2a: 3cm <primer tumor <4cm
 T2b: 4cm < primer tumor < 5cm

T3: the tumor is between 5 and 7 cm or…

T4: the tumor is > 7cm or…

N: spread of cancer to
nearby lymph nodes

M: distant metastases

Staging

Detailed treatment
SCLC
First line:
stages I-III:
• 6 cycles of cisplatin/carboplatin+etoposide chemotherapy
• Radiation of the chest a after the 3rd cycle
stage IV:
• 4-6 cycles of the same chemotherapy
Second line:
• Topotecan OR
• Epirubicine-Cyclophosphamid-Vincristine (4 cycles)
• SCLC is sensitive to chemo but it always returns…

Case of a patient

65 years old male patient, dyspnoe,
cough, swollen face
• smoker, 60py
• Hypertonia

Bronchoscopy, biopsy–SCLC

3 months after chemo-radiotherapy–
almost complete remission

Before treatment After treatment

Kezelés részletesen
NSCLC – Major contraindications for
NSCLC 1. surgery (IA-IIIA - inoperability)
stages IA-IIIA surgery • Advanced biological age
• Adjuvant chemo: after the • MI within past 3 months

surgery– from stage IB • Major arrhythmias
• Neo-adjuvant chemo: before • Severe pulmonary hypertension
surgery to ease resecability (pl. • Severe or very severe COPD
IIIA)
Pre-op severe hypoxia
Stages IIIB-IVpalliative chemo
Pre-op FEV1 < 1L
Targeted, immune therapy

Detailed treatment
Chemotherapy in NSCLC
In stages IIIB-IV. (palliative indication) and IB-IIIA (neo-adjuvant/adjuvant
indication) we apply the same combinations of drugs
First line: platine-based chemo
cisplatin/carboplatin
• +
• gemcitabin / paclitaxel / docetaxel / vinorelbin / pemetrexed (3rd
generation drugs)
Second, third line
• docetaxel/pemetrexed monotherapy

Targeted therapy in adenocarcinoma
If the histology says it is adenocarcinomawe examine the mutations
Most common mutations

Targeted therapy in adenocarcinoma-st. IIIB, IV
Most common mutations in NSCLC and the drugs used against them
EGFR hyperfunctiontyrosin kinase

inhibitorsthese inhibit the function of the
tyrosin kinase domain of the receptor
• First generation drugs: gefitinib,
erlotinib
• Second generation drug: afatinib
• Third generation drug: osimertinib
If EGFR mutatipn is present, we can
apply these in any line
Side effects:
• Skin issues, rash
• Constipation
• Nausea

• 2. anti-VEGF
drugBevacizumab
• VEGF is a molecule that the tumor
secretes and it helps the
angiogenesis thus supplies the
tumor with oxygen and nutrients
• besides first line chemo
• contraindictions: diseases of the
vessels, hemoptoe at the time of
diagnosis
• Side effects
• bleeding, hemoptoe
• Hypertonia

3. KRAS
It is a molecule with GTP-ase activity, the
downstream element of pathways starting
with EGFR and MET receptors
• If mutation is present in KRAS, it
causes EGFR TKI drug resistance
• Bad prognosis
• sotorasib is a drug we use as a target
therapy

4. BRAF:
• It is a proto-oncogene, a Serin-Treonin kinase
• It's mutation leads to the constant activation of RAS/RAF/MEK/ERK
pathwayproliferation
• drugs: combination of trametinib (MEK-inhibitor) and dabrafenib (RAF-inhibitor)

• 5. ALK-positive lung cancer– an important category of NSCLC

• Mutation in anaplastic lymphoma kinase gene
• a the fusion of mutated ALK protein and EML4 causes the
proliferation of tumor cells
• It is usually impossible to have mutations in KRAS, ALK and EGFR genes
at the same time
• drugs
• First generation: crizotinib
• Second generation: alectinib, brigatinib
• Third generation: lorlatinib
Patients are often
 Young
 Women
 Non-smokers

Immunotherapy
 Tumor cells secrete PD-L1 molecules(programmed death receptor ligand 1) that
bind to the PD-1 (programmed cell death protein 1) receptors of T lymphocytes
 this connection inhibits the anti-tumor activity of CD8+ citotoxic T cells.
 treatment: immune checkpoint inhibitor drugsdisinhibition=they enhance the
response of the immune system against the tumor
• Anti-PD-1 antibodies : nivolumab, pembrolizumab
• Anti-PD-L1 antibodies : atezolizumab, durvalumab
• CTLA-4 inhibitor drugs (ipilimumab) it helps the maturation of T lymphocytes

and promotes the invasion of tumor by them

Immunotherapy

Immunotherapy
 First, second line, in case of relapse
 Monotherapy or combined with chemo
 Not only in adenocc but also in squamosus cell cc
 Exept for patients with EGFR and ALK mutations
 Patients with smoking in their anamnesis react bettermore
mutationsthe tumor is more immunogenic
 Side effects are autoimmune reactions (because of the increased
T cell activity ) e.g. thyroiditis, hypophysitis…(inflammation of
organs)
 If this happens, we stop the therapy and give
immunosuppressant drugs to the patient
 Relative contraindication: the patient has autoimmune disease
or takes immunosuppressants

and Cystic Fibrosis (CF)
Anikó Bohács M.D. Ph.D., associate professor,
Pulmonologist, clinical immunologist and allegologist
Dep. of Pulmonology of Semmelweis University
2019/2020 II semester
Faculty of Medicine
Lung transplantation may be the only intervention that

can prolong survival and improve quality of life for
those patients with advanced, end stage lung disease:
High (>50%) risk of death due to lung disease within 2 years
if lung transplantation is not performed.
Main causes:
• Idiopathic pulmonary fibrosis (IPF)

• Bronchiectasis
hypertension (CPTE)
• Interstitial lung diseases [Boeck-sarcoidosis,
Lymphangioleiomyomatosis (LAM), eosinophil
granulomatosis (histiocytosis)]
2018
JHLT. 2018 Oct; 37(10): 1155-1206
• Severe systemic comorbidity (coronary disease, renal
function impairment. Bleeding susceptibility.
condition.

Prof. Klepetko,
3 pulmonologist, 1 surgeon, 1 anesthesiologist Prof. Gy. Lang
• Posttransplant follow up: Prof. P. Jaksch
• 2005-2008 National Koranyi Instittute of Pulmonology

• 2008-2018 Semmelweis University Dep. of Pulmonology
Surgery procedure of the lung transplantation
Donor and recipient
match:
• Size maching
• No HLA matching
LuTx has got high perioperative morbidity and mortality.


JHLT. 2017 Oct; 36(10): 1037-1079

antigenic,
month.


infection
• This point is impontant in the lung trasplanted

Lung transplanted patient for pulmonary fibrosis
CASE RIPORT
Idiopathic pulmonary fibrosis (IPF)
 IPF came from histology (VATS)
 Despite the cyclophophamide and steroid treatment
progression.
RestrictÍv Ventillation
pattern
Descreased diffusion
capacity
Flow-volume curve
• Chemistry
• Serology (HIV, hepatitis, lues)
• Osteodensitometry
• HLA fenotyping
• Lungscintigraphy
• Exclusion of inflammatory focus
6 month after the bilateral LuTx.
Chest X-ray after LuTx
Induction treatment

Reactive
T lymph.
• Inhibition of reaktív T
• ATG(anti-thymocyte globulin)
lymphocytes
• Daclizumab (Il-2 blocker)

3. Steroid

Atimicrobiological treatment after the
lung transplantation
 For 3 month.
 Long life
 Against the Pneumocystis jirovecii
 Valgancyclovir:
 For 3 month
Risk factors for infections after luTx
 Frequent antimicrobic therapy before the LuTx,
colonization (e.g. CF).
 Poliresistant agent because of ICU treatment
(donor and recipient).
 Decreased mucociliar clearence because of
denervation.
 Anatomic changes of the anastomosis of
bronchus..
 break of continuity of lymphatic drainage.
 Immunosuppression.
Infection can make an active immun responce or initiates

acut rejection in the graft.
What can we do under infection?
 Empiric therapy.
 Target therapy against the organism according to

the lates result of micobiology (antibiotic
resistance).
 Immediately invazive airway sample

„bronchioloalveolare lavage, BAL”. Microbiology!!!
Samples from the lower respiratory tract.
 Mycrobiology/TB (Mycobact.
tuberculosis9
 Virology
 Micology
 + from transplanted patient:

 Hystology
 BAL propotion of
neutrophil/lymphocyte/eosinophil
Infections cronology after LuTx
Donor
ICU, personal
flora
idő
operation 4 week 3 month 6 month TB, Nocardia, Aspergillus, repiratory viruses
bacterias, fungus
HSV, VZV, Pneumocystis, Toxoplasma
CMV EBV
Candida, Aspergillus, Pseudomonas
Mattner et al. Post-operative nosocomial infections after lung and heart transplantation.
J Heart Lung Transplant, 2007, 26, 241-249.
Kovats Zs et al. Airway pathogens during the first year after lung transplantation: a single center experience.
Transplant Proc 2011 May;43(4):1290-1.
Diagnostic algoritm of pulmonary infiltrations in Lung
trasplanted patient
Infiltration
Diffuse Multifocal focal
Wide spectrum antibiotic

BAL
therapy ( 48-72 h)
Targeted
Diagnosis diagnostics
No diagnosis
Treatment
Needle biopsy
BAL or lung biopsy Bronchoscopy
again recovery Surgery biopsy
Müller V, Kováts Zs, Horváth G. Szervtranszplantációt kísérő pulmonalis infekciók. Orvosi Hetilap 2012(23):899-903.
1. case: early infection after LuTx (4. week).
2. case: 4.month after LuTx (CMV pneumonitis)
3. case: herpes zoster infections
4. case: fungal infections
INFECTIVE COMPLICATION AFTER

LUTX CASE REPORTS
Pseudomonas aeruginosa(PA) infection is more
frequent in LuTx for cystic fibrosis.
• Causes
 PA colonization is more frequent before lung transplantation.
 The paranasalis sinusis and trachea are reservoare after LuTX.
 Induction therapy before lung Tx (antithymocita globulin
(ATG®) vagy anti-CD52 alemtuzumab (Campath®).
 Immunosppression.
 Decreassed mucociliare clearance in the denervated lung .
(nerves were cutted under Tx operation).
Colonization of pseudomonas aeruginosa is an
independ risk factor of bronchiolitis obliterans
syndrome (BOS) in LuTx patients.
LuTx for non CF
• In a center of lung Tx pseudomonas aeruginosa colonization was
observed in 50% of patients1.
• Colonization of pseudomonas aeruginosa elevate of risk for
bronchiolitis obliterans, which can lead to chronic graft
LuTx for CF2.
insufficiency
Inhalation of profilactic antibiotic

(colistin, brulamycin, tobramycin)!
1ZeglenS. et al. Frequency

All LuTx recip. of Pseudomonas aeruginosa colonizations/infections in lung transplant
recipients. Transplant Proc. 2009., 41(8):3222-4.
2 Vos R. Pseudomonal airway colonisation: risk factor for bronchiolitis obliterans syndrome after
lung transplantation? Eur. Respir J2008 May;31(5):1037-45.

1. case: 23 years man with cystic fibrosis
• CF was knowledged for postnatal 8

month.
• Complications:
 Pneumothorax (ptx)-4x
 haemoptoe-6x → intervention:
embolism of. art. bronchialis
 Colonisation of PA
 Decreased lung function→
Before LuTX noninvazíve ventillation.
2012.02.
bilateral lung transplantation
4 weeks surveillance bronchoscopy
Immunosuppression: - tacrolimus (15-18ng/mL)
- prednisolon (0,2mg/ttkg)
- mycophenolate mofetil (2000mg/nap).
• chest dyskomfort and retention of mucus

in the right side.
• Decreased lung function: FVC: 500ml-t,
FEV1: 600ml-t decrease, a MEF50:83%-ról
13%-ra ↓.
• Physical examination: bronchial wheezing
in the right lower lob.
• Chest x-ray
• Elevated inflammation parameters
(CRP:57 mg/l, 92% Neu).
Result of bronchoscopy and the transbronchial lung
biopsy:
• Endobroncial sign: purulent sputum in the trachea 1/3.

• Cytology of lavage: purulent exudatation.
• Mycrobiology of lavage: Achromobacter xylosoxidans +
Pseudomonas aeruginosa + Stenotrophomonas maltophilia.
• Hystology: no rejection, A0B0
Parenteral colistin+ imipenem cilastatin and
physicotherapy.
Antibiotic susceptibility Pseudomonas Stenotrophomonas Achromobacter
aeruginosa maltophilia xylosoxidans
Time: 03.21 05.17 03.21 05.17 03.21
Imipenem M R R R R
Meropenem E R R R E
Piperacillin/Tazobactam R R NV NV E
Ceftazidim R R NV NV R
Ciprofloxacin R R R R R
Amikacin R R R R R
Tobramycin R R R R R
Gentamicin R R R R R
Cefepime R R NV NV NV
Colistin E E R NV R
Sulfamethoxasole/trimethoprim NV NV E E NV
Change for target antibiotic therapy: I.v. colistin + meropenem

+ oral sulfametoxasole/trimetoprin
A laboratory parameters under the target
antibiotic treatment.
i.v. Colomycin +
i.v.Meropenem + 2x1MNE Colomycin inhalation
per os summetrolim oral Sumetrolim
4. Month after LuTx.
CASE REPORT 3.
CMV infection after Alemtuzumab induction.
 Cs.Cs. 26 years old man, cystic

fibrosis
 2012.06.07. bilateral
lungtransplantation in wien,
CMV status: D+/R+
 Normal postoperatíve care,
good physical conditions.
 In 4.month after Tx decreased
lung functions, small infiltration
WBC: 3.44 G/l (Neu 70%), CMV
antigenaemia positive
Treatment
 Valgancyclovir 2x450mg for
2 weeks.
 CMV antigenaemia
discontinued.
Virus infection after 6 month of LuTx.
CASE REPORT 4.
Itching skin lesion 6. month after
the LuTX.
Indication of LuTx: COPD
HERPES ZOSTER
Treatment of Herpes Zoster in Tx patients
 Dosis of acyclovir: 5x800mg .

Fungal infections in LuTx patients
CASE REPORTS
Candida pleuritis in a LuTx patients for COPD.
2012. jan: bilateralis LuTx
4 month
• CRP:41mg/l,
• Pleurapunctation: exudates
• Pleural biopsy: chr. pleuritis
• Mikrobiológy Candida albicans:
fluconasol:E, itraconasole:E, Amph.B:E,
Voriconazole:E
Antimyotic treatment + chest drainage
desinficiant lavages
i.v. 2x400mg
Fluconazole, majd
2x200mg per os
Problem:
Under antimycotic treatment need to change
CRP:11 mg/l
the dosis of the immunosuppressant (hepatic
metabolism).
Infection in the upper lobe
• Tuberculosis?
• Fungal infection?
• Malignancy?
1. Bronchoscopy, BAL for

mycobiology
2. Transzbronchial biopsy


vs. ILD-non IIP
2017
JHLT. 2017 Oct; 36(10): 1037-1079

after LuTx)
• Subacut

BOS RAS
v.s.
14 month after LuTx A0-1B1 rejection

FVC és FEV1 1,06L , Hasimoto
FVC: 2,54L(60%) thyreoiditis.
FEV1:1,28L (35%)
DSA 11500 MFI (both donor)
Tiffeneux: 50,2% DQ 7(3)~DQA1*05 antigénnel
Klco:81% No DSA . After the plasmaferesis DSA 2000 MFI ↓
Irrevezibile graft loss, NIV dependency.

2017
JHLT. 2017 Oct; 36(10): 1037-1079
CYSTIC FIBROSIS
70%.
Multiorgan
involvement
LUNG
MANIFESTATIONS:
• Mucus impactation
• Bronchiectasis
• Pneumothorax
• Haemoptisis
• Cor plmonale
Association between genotype and fenotype.
I-IIIclass
Serious state
IV-V. class
Mild
fenomenome
Sweat chloride testing
Malnutrion in CF
absorption).

function
Aim of treatment
• Diminisches
the decline of
lung function
life
salin, pulmozyme.
(Voriconazol)

haemoptysis
 6MWT < 400 m.
 Pulmonalis hypertensionEstimated PAP> 25 Hgmm at
echocardiograph.
• Need NIV
• malnutrition
Lung transplantation in CF patient
Before LuTx After LuTx

Postoperative care of solid organ
transplanted patient and treat the CF
patients is a multidisciplinar problem!
PNEUMONIA
Dr. György Losonczy

professor of pulmonology
2020
Faculty of Medicine
Definition
Pneumonia: Inflammation of the distal small
airways, alveoli and the interstitium which
is associated with exudate accumulation in
the alveolar space.
Pneumonitis: pneumonia induced by
irradiation or chemical agents.
Interstitial pneumonia: inflammation
affecting primarily the interstitium.
HISTOLOGY OF BRONCHOPNEUMONIA
SEVERE ACUTE RESPIRASTORY SYNDROME (SARS, Coronavirus).
Hyalin membrane (arrows), alveolar edema
CLASSIFICATION
• Community acquired pneumonia (CAP);
• Nosocomial (hospital acquired) pneumonia
(HAP); ventilator associated pneumonia
(VAP);
CAP and HAP (or VAP):different

pathogens,different group of patients
(considering underlying condition), different
prognosis.
Pneumonia incidence and mortality
Community acquired p; Hungary 150 000/year, 1% mortality
(1500/year)
1. 20-50% Streptococcus pneumoniae
2-3. Mycoplasma pn., Chlamydia pn.
4-5. Hemophilus inf., Klebsiella pn.
6. Viruses
Nosocomial pneumonia (NP):

0.5-1.0% of all hospitalized patients suffers from NP.
Letality: 20-70%; 1. Enterobacteriaceae (E. coli) ; 2.
Pseudom. ae; 3.Staphy. au.; 4. Acinetobakter spp.; 5. Haemoph.
inf.;
MAJOR SYMPTOMS AND SIGNS OF
PNEUMONIA
-fever
-cough, sputum
-dyspnea
-chest pain
-shortened sound with percussion
-auscultation: fine crepitation (temporary), rales
-X-ray shadow
Real challange: etiology?!

Pneumonia is curable, but only with adequately
selected antibiotics. Inadequately treated
pneumonia may be lethal.
Lobar pneumonia (upper lobe)
(e.g. Streptococcus pneumoniae)
Bilateral pneumonia with multiplex cavitation. Patient first
had bacterial endocarditis. (Hematogen dissemination)
Bilateral, diffuse, reticulonodular
infiltration: typical, but not
specific for influenza pneumonia
Test results in pneumonia
Laboratory: CRP ↑, neutrophil granulocytes ↑, ESR
(erythr. sed. rate) ↑, LDH ↑, GOT ↑, renal
function↓, … , procalcitonin in severe sepsis↑
Blood gas: hypoxaemia, hypocapnia, respiratory

alkalosis
ECG: sinus tachycardia (fever)
Lung function tests: not very informative in

pneumonia
Etiological diagnosis in pneumonia
-sputum from lower airway; bronchofiberoscopy: protected brush
specimen, bronchoalveolar lavage; bacteriology: Gram-
staining (microscopy, rapid), culture and antibiotic sensitivity
(3-4 days)
-Viruses (including Coronavirus): DNA based testing of nasal
and pharyngeal excretions (and feces)
-serology: Mycoplasma, Chlamydia, Legionella, Coronavirus IgA,
IgM;
-urinary Streptococcus pneumoniae and Legionella pneumophila
antigen detection ;
-Mycobacterium tuberculosis: Mantoux, direct Koch, culture,
PCR, Quantiferon test;
Lower airway sputum Gram staining
(Gram-positive diplococci)
Testing of antibiotic sensitivity

Quantitative estimation of risks of patients suffering from
pneumonia
man Age in years
woman Age in years - 10
Malignant disease +30

Liver disease +20
Cardiovascular disease +10
Cerebrovascular disease +10
Kidney disease +10
Disordered mental status +20
Tachypnoe 30/min +20
Systolic blood pressure90 mmHg +20
Temperature ( 35oC or 40oC) +15
Heart rate 125/min +10
Arterial pH 7.35 +30
BUN 11 mmol/l +20
Sodium 130 mmol/l +10
Glucose 14 mmol/l +10
Hematocrit 30% +10
pO2 60 mmHg +10
Pleural fluid +10
PORT* (Pneumonia Outcome Research Team) points
correlate with risks of pneumonia patients (n=14 000)
Needed Needed Death Lethality Total

PORT later while in within
later lethality
intensive
group hospitaliza- care
ambulato- hospitalized
%
tion % ry care %
%
%
I. < 40 5,1 4,3 0,0 0,5 0,1
II. < 70 8,2 4,3 0,4 0,9 0,6
III. 71-90 16,7 5,9 0,0 1,2 0,9

IV. 91-130 20,0 11,4 12,5 9,0 9,3
V. > 130 0 17,3 0,0 27,1 27,0
•PORT points increase with age, comorbidity and severity of pneumonia

symptoms
Risks: treatment at home or
hospitalization?
PORT I: at home, per os antibiotics (AB)
PORT II-III: at home, per os AB, some will

need later hospitalization
PORT III-IV: iv AB, hospitalization
PORT IV-V: iv AB, respiratory intensive care

Principles of antibiotic treatment
____________________________
Dose large enough
Treatment time long enough
Adequate (effective) but narrowest

spectrum, less expensive
EMPIRICAL ANTIBIOTIC (AB) SELECTION in
PORT I.
Possible pathogens:
Strept. pn., Mycopl. pn., vírusok, Chlam. pn.,
Hemoph. inf., Staph. au.
AB: -amoxicillin-clavulanic acid (Augmentin, <3

g) p.o., or
-macrolids (Klacid, Sumamed) p.o.,
or
-their combination
Letality: below 1%
EMPIRICAL ANTIBIOTIC (AB) SELECTION IN
PORT II-III.
Possible pathogens:
Strept. pn., vírusok, Hemoph. inf., Enterobacteriaceae, Staph.
au., Chlam. pn., Morax. catarr., Legionella spp.
AB: -amoxicillin-clavulanic (Augmentin) p.o.

+
macrolids (Klacid, Sumamed) p.o.,
or
-levofloxacin (Tavanic) p.o., or moxifloxacin (Avelox) p.o.
5-20% will be hospitalized later; letality: 1-5%

PORT III-IV.
HOSPITALIZATION NEEDED
Possible pathogens:
Strept. pn., Hemoph. inf., polymicrobial infection with anaerobs,
Enterobacteriaceae, Legionella spp, Staph. au., Chlam. pn.,
Morax. catarr., viruses
AB: -amoxicillin-clavulanic (Augmentin) iv., or

cefriaxon (Rocephin) iv., or
-cefotaxim (Claforan) iv.
+
-macrolids (Klacid, Sumamed) iv., or
-levofloxacin (Tavanic) iv.
Letality: 5-25%
PORT IV-V.
RESPIRATORY INTENSIVE CARE
Possible pathogens:
Strept. pn., Legionella spp., Staph. au., aerob Gram negative bacilli, Hemoph.
inf., viruses
AB: -cefriaxon (Rocephin) iv.

-cefotaxim (Claforan) iv.
-imipenem/cilastatin (Tienam) iv.
-meropenem (Meronem) iv.
-piperacillin+tasobactam (Tazocin) iv
+
-macrolids (Klacid, Sumamed) iv., or
-levofloxacin (Tavanic) iv.
-aminoglycosid (Amikin) iv.
Letality: 25-50%
SUPPORTIVE THERAPY IN
PNEUMONIA
Oxygen
Fluids and electrolytes
Antipyretics
Insulin
Antiarrhythmic treatment
Anticoagulation (low molecular weight heparin)
Low dose steroid (antifibrogen)
Bronchodilatative treatment
TUBERCULOSIS
Definition
Tuberculosis is an infectious disease caused
by Mycobacterium tuberculosis.
Features:
-Prolonged latency period between initial
infection and overt disease.
-85% of tuberculotic diseases are manifested
in the lungs.
Etiologic agent I.
-Genus: Mycobacterium
-Most important strain: Mycobacterium
tuberculosis.
-Other strains of the tuberculosis complex:
M. tub.,
M. bovis,
cause similar disease
M. africanum,
M. microti
Epidemiology
-Globally, tuberculosis is the leading infectious
cause of morbidity and mortality.
-Within industrialized nations selected groups
are afflicted.
-One third of the world,s population is infected.
-From these 8-10 million people become
diseased.
-Annual death rate is 2-3 million.
-Reason: delayed, inadequate or unavailable
therapy.
High-Risk Groups
1. HIV
2. Close contacts (within 3 months), if remain
negative with PPD for 8 weeks, no infection
occurred
3. Recent converters (PPD has increased >10 mm
within 2 years
4. Patients with old healed apical fibronodular
lesions
5. Iv. drug users
6. Immigrants from high prevalence countries
7. Medically underserved, low-income pop.-s
8. Correctional inst-s, nursing homes, mental inst-s
Spreading and transmission I.
Obligate aerob (mostly upper lobes), facultative
intracellular parasite. Spreading depends on
survival and proliferation within mononuclear
phagocytes.
Infection spreads almost exclusively by
aerosolization of contaminated respiratory
secretions. Cough of cavitary lung diseased
patients! Sputum may consist 1-100 million
bacilli/ml, and even 1 single M. tub. can cause
disease.
Pathogenesis and immunity
In 95% of infections the host prevails (no or mild
disease symptoms). However, few live bacteria
may remain in lung, bone, kidneys, meninges,
which are potential foci of subsequent reactivation
tuberculosis.
During these processes the organism becomes
sensitized against antigens of M. tub., including
„pure protein derivate (PPD)”, with other words, a
delayed type, or cell mediated hypersensitivity
develops.
Clinical presentations
When immunity is competent: disease is mostly
localized to lung (85% of adults).
Less robust defense: lung + dissemination (15%).
Skin test is negative in 20% of cases.
Fever may be absent although patients feel
„feverish”.
Pulmonary disease I.
-Cough, initially dry, later purulent from blood
streaking to gross hemoptysis
-Fever
-Sweating, drenching night sweats
-Malaise, fatigue
-Weight loss
-Non-pleuritic chest pain
-Dyspnea
Pulmonary disease II.
Auscultation:
-Rales, course rhonchi as secretions become
voluminous and tenacious
-Lung consolidation is rare
-Wheezing as peribronchial and endobronchial
airway obstruction develops
Pulmonary disease III.
Chest X-ray:
-main rule: tuberculosis can induce any pattern of
X-ray shadowing
-upper lung zone fibronodular pattern
-upper lung zone fluffy coalescence
-upper lung zone cavitation
Lung zones involved in descending order: segment

2 (left), segment 2 (right), segments 6 (both
sides)
Multilobar
tuberculotic
bronchopneumonia
Right upper
lobe cavity
with fluid niveau
Right upper
lobe cavity
healed
Pulmonary disease IV.
Lower zone <15%. More common in diabetics, and
with peribronchial, endobronchial involvement.
Pleural effusions are uncommon in reactivation-type
pulmonary disease.
Sputum:
Microscopy: Ziehl-Neelsen, important, very useful,
but not very sensitive or specific.
50-60% of tuberculotics have acid-fast positive
sputum.
Microscopy of acid-fast bacilli. Ziehl-Neelsen carbol-fuchsin staining
Mycobacteriological diagnosis
Culture: 6-8 weeks on solid medium, 2 weeks on
liquid media.
Nucleic acid techniques (PCR): 1-2 days, but do not

replace older techniques. Useful in pleural fluid,
liquor.
About 15% of patients are treated by antituberculotic

drugs without bacteriological diagnosis, purely
based on clinical criteria.
Treatment minimum of 6 months
Drug daily dose side effect
Isoniacid (INH) 300 mg po. Hepatitis/neuritis

Rifampin (RIF) 600 mg po. Hepatitis,
thrombopenia
Pyrazinamide (PZA) 1.5 g po. Hepatitis, arthralgia
Ethambutol (EMB) 2.0 g po. Optic neuritis
Pulmonary embolism
Dr. habil. Gabor Horvath, Ph.D.
Associate professor
2019-2020
Definition
Pulmonary embolism is a blockage

of an artery in the lungs by a
substance that has moved from
elsewhere in the body through the
bloodstream (embolus).
Thromboembolism is a
consequence of thrombus formation
within a deep vein of the body.
Pulmonary
embolus
Pathological
preparations
Incidence Mortality
Epidemiology
Morbidity:
 Incidence: 150-200 per 100.000 inhabitants/year
 USA: 600.000 patients/year
Mortality:
 10% mortality in the very first hour after
pulmonary embolism
 USA: 100.000 patients/year
 mortality without treatment: 25-30%
 mortality with treatment: 2-8%
 diagnostics success rate ~ 16-30%
Origin of the thrombus
- Lower extremity veins

- Pelvic veins
- Abdominal veins Question:
- Upper extremity veins Which one is diagnosed as the
most common source?
- Head and cervical veins
- Right heart
- Left heart
(septal defect or patent foramen ovale)
Thrombus formation:
Virchow’s triad
 Venous stasis
 Hypercoagulability
 Vascular wall injury

Risk factors
Inherited (primary): Acquired (secondary):

- Antithrombin III deficiency* - Immobilization
- Protein C deficiency* - Trauma
- Protein S deficiency* - Chronic venous insufficiency
- Factor V. Leiden mutation* - Malignancy  chemotherapy
- Congenital dysfibrinogenaemia - Surgery
- Plazminogen deficiency - Oral contraceptives
- Hyperhomocysteinaemia - Obesity
- Dysplasminogenaemia - Stroke
- Anticardiolipin antibodies - Age > 40 years
- Excessive plasminogen activator inhibitor - Venous catheter
- Factor XII. deficiency - Heart failure
- Prothrombin 20210A mutation - Smoking
- Pregnancy
- Crohn disease
- Nephrosis
* relatively frequent types
Vascular pathology
Thromboembolism occurring in the

pulmonary system causes partial or
complete termination of peripheral
pulmonary blood flow.
In contrast to other parenchymal

organs (brain, heart), necrosis of the
lung parenchyma is infrequent!
Question:
Why pulmonary infarction has a relatively
uncommon occurence (~20%)?
Blood supply
to the lungs
Peripheral pulmonary
vessels
E
A
E: thrombus in the pulmonary
artery
A: broncho-pulmonary arterial
anastomosis
Haemodynamics
Ventilation/perfusion (V/Q)
Affected regions of the lung:

 hypoperfusion  V/Q  (alveolar dead space )
 hypocapnic bronchoconstriction
 atelectasis/necrosis due to reduced production of
surfactant
Normal regions of the lung:
 hyperperfusion  V/Q  (= functional shunt )

Hypoxemia (PaO2 )
Clinical
forms
Symptoms, signs
Symptoms % Signs %
Dyspnea* 84 Tachypnea 92
Pleuritic chest pain* 74 Rales 58
Fear of death 59 Increased pulmonary 2nd 53
Cough 53 heart sound
Hemoptysis* 30 Tachycardia 44
Sweating 27 Fever 43
Atypical chest pain 14 Sweating 36
Syncope 13 3rd or 4th heart sound 34
Edema of lower extremity 24
* classic triad of symptoms Cyanosis 19
Diagnostic algorithm
Clinical prediction rules:
Wells score
Wells-score calculation
(http://mdcalc.com)
Chest x-ray
 Normal chest x-ray

 Abnormal findings (nonspecific):
 atelectasis/infiltrate
 Fleischner’s line or atelectasis
 enlarged pulmonary artery
 local oligemia (Westermark’s sign)
 pleural effusion
 elevated hemidiaphragm
Chest x-ray Line atelectasis
Atelectasis
Chest x-ray Elevated hemidiaphragm
Pleural effusion
ECG
 Normal ECG
 Abnormal findings (nonspecific):
 ST depression 50%
 sinus tachycardia 44%
 negative T in V1-V2 23%
 supraventricular arrhythmias 17%
 SI, QIII, negative TIII 16%
 right bundle brach block 13%
 P-pulmonale 6%
Laboratory parameters
 Nonspecific changes
 D-dimer  (non-diagnostic, but excludes pulmonary
embolism with 90% confidence)
 Blood gas analysis:
 PaO2 
 PaCO2  (due to hyperventilation)
 pH  (respiratory alkalosis)
 In pulmonary infarction: We , FVS  és CRP 

 Others: Troponin , LDH , SeBi , SGOT 
CT angiography
 CT angiography is the method of choice for imaging

the pulmonary vasculature in patients with suspected
pulmonary embolism.
 It allows adequate visualization of the pulmonary
arteries down to at least the segmental level.
 Sensitivity: 86–96%
 Specificity: 92–98%
CT angiography
Contrast material
filling defect in
pulmonary
embolism
Ventilation-perfusion scintigraphy
Perfusion scintigraphy

99Tc-labeled microspheres iv.
 detects occlusion in vessels > 3 mm
 normal perfusion excludes pulmonary embolism
 specificity: tumor, pneumonia, hypoxic
vasoconstriction may also cause abnormal findings

 to be evaluated only with chest x-ray
Ventilation scintigraphy

133Xe iv.
Combined: sensitivity ~ 91%, specificity ~ 87%

Perfusion scintigraphy
Normal Pulmonary embolism

Pulmonary angiography
 Reference method - definitive diagnosis!

 Indications:
 failure of other studies, and
 thrombolytic or anticoagulant therapy is contraindicated
 Relative contraindications:
 contrast material hypersensitivity
 severe congestive heart failure, pulmonary hypertension
 Mortality: ~ 0.1-1.5%
 Sensitivity: ~ 98%, specificity: ~ 95-98%
Contrast material filling
defect in pulmonary
embolism
Case study
 24 years old, physically active athlete

 His right chest pain started 3 days age after training. Intensity of chest pain reduced in
the last 2 days. He has some difficulties with breathing. He has no history of lung or
other significant disease. But 2 weeks ago, he had upper airway infection symptoms
and some hemoptysis.
 Vital parameters: RR=124/82 Hgmm, P=64/min, breathing=16/min, T=36,2C
 Physical examination: Normal breathing sounds.
 Others: Normal chest x-ray and ecg. Blood gas analysis: pH=7,41, PaO2=94 Hgmm,
PaCO2=41 Hgmm, Sat=99%
 Wells score 0-1
 D-dimer: 0,23 (norm. <0,5 µg/ml)
Question:
Are futher studies or treatment required for pulmonary embolism?
Therapeutic algorithm I.
Instable Stable
hemodynamics hemodynamics
Contraindication of Contraindication of
thrombolysis? anticoagulation?
no yes no yes
Thrombolysis Inferior vena

cava filter?
Embolectomy? Anticoagulation
Severity classification
Thrombolytic therapy
 Mechanism: with the activation of endogenous

thrombolytic mechanisms, thrombus dissolves and
improves the perfusion of the occluded vessels
 Indication: acute, massive pulmonary embolism with
hemodynamic instability
 Advantages: faster and more complete
revascularization, pulmonary hypertension , mortality
, recurrence 
Plazminogen activators
 Streptokinase, urokinase, alteplase,

reteplase, tenekteplase
 There is no significant difference between the
pharmacological actions of these drugs.
 Drug selections is performed based on mostly
local, institutional protocols.
Thrombolytic therapy
Before 24 hours after

Contraindications
Absolute contraindications: Relative contraindications:

 active gastrointestinal bleeding  „major” surgery
 intracranial haemorrhage  delivery
 ischemic stroke in 2 months
 gastrointestinal bleeding within 10 days
 severe trauma within 15 days
 neurosurgical, ophthalmic surgery within 1
month
 untreated hypertension (systolic value > 180,
diastolic > 110 mmHg)
 platelet count <100 000/mm3, anticoagulation
 pregnancy
 infectious endocarditis
 diabetic haemorrhagic retinopathy
Catheter embolectomy
1. 2. 3.
Surgical embolectomy
 Rarely performed intervention

 Indications:
 acute, massive pulmonary embolism
 contraindication of thrombolytic therapy
 cases not responding to thrombolysis
 High mortality rates (~ 50%)
Therapeutic algorithm II.
Instable Stable
hemodynamics hemodynamics
Contraindication of Contraindication of
thrombolysis? anticoagulation?
no yes no yes
Thrombolysis Inferior vena

cava filter?
Embolectomy? Anticoagulation
Na-heparin
 Treatment is required for suspected cases already!

 Mechanism: among others, inactivates thrombin, and
factors IXa and Xa by binding to antithrombin-III
 Administration:
 iv. 5000-10000 NE, followed by
 1250 NE/hour for 5-6 days
 control of aPTI is required (1,5 – 2,5x)
 Complications: bleeding, thrombocytopenia, osteoporosis
 Antidote: protamine sulphate
Low molecular weigth (LMW) heparin
 Equivalent to Na-heparin
 Administration: daily 2x s.c., 100 NE/kg
 Advantages:
 doesn’t require lab controls
 suitable for home anticoagulant treatment
 local bleeding complications , thrombocytopenia ,
osteoporosis 
 Antidote: protamine sulphate (partial antagonist)
Vitamin K antagonists:
acenocoumarol, warfarin
 Oral, long-term anticoagulant therapy
 Mechanism: inhibits the synthesis of the vitamin K-
dependent factors II., VII., IX. and X.
 Its actions takes 3-5 days - coagulation may increase
during this period (protein-C , protein-S )
 Recommended for at least 3 months
 Lab control: INR = 2-3
 Antidote: vitamin K in 8-24 hours
 Not allowed in pregnancy because of embryotoxicity!
Inferior vena cava filters
 Rarely performed intervention

 Indications:
 contraindication of anticoagulant therapy
 recurrent embolism despite anticoagulant therapy
 prophylactically after surgical embolectomy
 Contraindications :
 highly enlarged (> 3 cm) inferior vena cava
 septic vena cava thrombosis
Inferior vena cava filters
Other forms
Fat embolism
 after the fractures of long, tubular bones or
orthopedic surgeries
Septic embolism
 due to osteomyelitis, otitis, or endocarditis
Air embolism
 after traumatic injury to large veins
Amniotic fluid embolism
 during delivery, amniotic fluids can reach the
maternal circulation through the uterine veins
Thank you!
Pulmonary Rehabilitation
János Varga MD, PhD

Budapest
2021
What is the Next Step in the
Treatment of COPD Therapy?
• New bronchodilator therapy ?

• New anti-inflammatory therapy ?
Time to renew
• Reduction the number of
exacerbations?
conception ?
• Alveolar grow factor ?
• Stem cells ?
Courtesy of
• Care ? Casaburi R
Troosters T et al. Am J Crit Care Med, 2005
Physical Activity in COPD
Chance to Survive (COPD)
Mortality (Survival rate%)
1.0 Garcia-Aymerich Thorax 2006
0.75
0.50
High
Average
0.25 Low
Very low
0.0
0 5 10 15 20
Time (Years)
Very low: Mainly sedentery, no physical activity in freetime
Low: < 2 hours/week low intensity physical activity
Peripherial Muscle Dysfunction in
COPD
Lactate increment
• Low muscle mass during exercise
• Abnormality in capilarisation
• Low oxidative enzime activity
• Low ratio of type I muscle fibers
• Inflammation in muscles
• Corticosteroid myopathy
• Low level of anabolic hormones
• Abnormality in vasoregulation
VO2 (L/min)
Thorax, 2010
Maltais F, et al. Am J Respir Crit Care Med. 1996;153:288-293.

Physical Inactivity in COPD
Correlation between physical activity and lung
function, muscle force and walking distance
1.0
12000
 EELV (l)
10000 0.5
Steps.day-1 ( n )
8000
6000 0.0
4000
2000 N=50 R -0.5
0
FEV1 1 2 3 4
Ctrl I II III IV %pred 0.28* Daily activity (Quartile VMU)
TL,CO
%pred 0.38*
QF
%pred 0.45*
Courtesy of 6MWD
Troosters T %pred 0.76*
Troosters ERS 2007
Watz AJRCCM 2008 Pitta AJRCCM 2005 Garcia-Rio AJRCCM 2009
The Effect of Metabolic Syndrome on Physical Activity
No Metabol syndrome
1.9
Physical activity level

Metabolic syndrome
12000
1.7
10000
Steps.day-1 ( n )
8000
1.5
6000
4000 1.3
2000
0 1.1
Ctrl I II III IV CB I II III IV
Severity
Physical inactivity
Courtesy of
enchances the chance of
Troosters T
development of co-
Troosters ERS 2007
Watz AJRCCM 2008 morbidities Watz Chest 2009
Physical Inactivity in COPD Acute
Exacerbation
Low physical activity enchances

the risk of new exacerbation.
The importance of early

pulmonary rehabilitation after
exacerbation.
Day 2 Day 7 Month 1
Pitta Chest 2006 Seymour JM Thorax

Garcia-Aymerich Thorax 2010
2003
Limiting Factors in Exercise
Tolerance in COPD
• Abnormal lung mechanics

• Respiratory muscle dysfunction
• Peripherial muscle dysfunction
• Limitation in gas exchange, oxygen delivery
• Cardiac dysfunction
Controlled breathing techniques
• Perth lip breathing (PLB)
• Diaphragmatic breathing
• Turn the trunc to 45 degrees

Respiratory Endurance Training
COPD (n=11)
FEV1: 36±14 %pred
3x10 minutes respiratory
endurance training
MIP: 47±16 vs. 59±20

H2Ocm
MEP:90±45 vs.
123±72 H2Ocm
Respiratory Muscle Training-
Strength Training-
Powerbreathe
Tolerance in COPD

Exercise training has favourable effect in
COPD. High intensity continous training is
more effective compared to low intensity
training.
•Casaburi R, Patessio A, Ioli F et al.: Reduction in exercise lactic

acidosis and ventilation as a result of exercise training in patients with
chronic obstructive lung disease. Am Rev Respir Dis 1991; 143:9-18.
•Casaburi R, Porszasz J, Burns MR et al.: Physiologic benefits of exercise

training in rehabilitation of patients with severe chronic obstructive
pulmonary disease. Am J Respir Crit Care Med 1997;155(5):1541-51.
The Effectivity of Training in COPD
Casaburi, ARRD 1991

The Role of Peroxisome Proliferator-
Activated Receptor-Gamma Coactivator 1α
(PGC-1α) on Muscle Function
Handschin C
Nature 2008
Reduction of Exercise-induced Dynamic
Hyperinflation with Exercise Training at
Submaximal Intensity
Porszasz J, Emtner M, Goto S, Somfay A, Whipp BJ and Casaburi R.

Exercise Training Decreases Ventilatory Requirements and Exercise-
Induced Hyperinflation at Submaximal Intensities in Patients with
COPD.
Chest 2005;128;2025-2034
Interval vs. High Intensity
Continous Training
Varga J et al. Resp. Med. 2007

Continous Training

„Nordic
walking”:
Maximal exercise
capacity and physical
activity
New Technique for Lung Transplant
Patient- Whole Body Vibration
Gloeckl R et al. 2012

Daily activity
monitoring
Tolerance in COPD

• Limitation in gas exchange and oxygen
delivery
Oxygen Favourable Effect
during Exercise in Non-
hypoxemic Patients with COPD
Somfay A, Porszasz J, Lee SM and Casaburi R. Effect of

Hyperoxia on Gas Exchange and Lactate Kinetics Following
Exercise Onset in Nonhypoxemic COPD Patients.
Chest 2002;121;393-400
Emtner M, Porszasz J, Burns M, Somfay A, Casaburi R.

Benefits of supplemental oxygen in exercise training in
nonhypoxemic chronic obstructive pulmonary disease patients.
Am J Respir Crit Care Med 2003;168(9):1034-42.
Exercise training with oxygen have superior effect in
selected exercise physiologic parameters in
respiratory failure in COPD.
Cognitive
function
Hypoxia,
hypercapnia,
smoking,
comorbidities COPD itself
(vascular
disorders) had
influence on
cognitive function
in COPD
Measurement of
Feeding State:
•Determination of body
composition
•Body weight
•Calory intake
•Gastrointestinal symptoms
•Functional capacity
•Physical examination
Age-dependent PAP change in
Healthy Subjects
Kovacs G
<30 év 30-50 >50 year <30 év 30-50 >50 year
year year et al. ERJ
2009;
34(4):888-
94.
Pulmonary Arterial Pressure Increment during
Exercise in COPD
Terhelés indukálta pulmonális artériás nyomásemelkedés
100
* #
80
#;p<0,05 csoportok között
*
PAP (Hgmm)
60
40
20
0
Kontroll csoport COPD Varga J et al. ERS
Nyugalomban
2009, P3259
Csúcsteljesitménynél
Sleep Apnea Monitoring
Saturation
Heart rate
AHI
Thank you for
your attention!
E-mail:
varga.janos_tama
s@med.semmelwe
is-univ.hu
PULMONARY
REHABILITATION
2019/2020
Zsuzsanna Kováts MD PhD
SEMMELWEIS UNIVERSITY
Faculty of Medicine Department of Pulmonology
http://semmelweis.hu
Consequences of disease
• Impairment of organ function and structure interferes with
• independence in activities of daily life (ADL) and with
• participation in family, social and occupational life,
• influenced by personal and enviromental factors.

SEMMELWEIS UNIVERSITY © Zsuzsanna Kováts: Pulmonary rehabilitation
Relationship between somatic, psychic and social effects
of chronic lung diseases ( GOLD )
Deconditioning
COPD Dyspnoe Immobility

(ILD, Asztma)
Depression Social isolation
Numerous consequemces of disease are not (enough)

influenced by the traditional medication, thus an
ndependent, complex and interdisciplinartreatment
conception is needed: pulmonary rehabilitation.
Interventions in rehabilitation
• Recovery of competence: Recovery or prevention
of loss of physical or psychycal function which
was lost because of disease or disability –
mobilisation, improvement of condition.
• Prevention: Prevention and postive influence of
the secunder impairments e.g. depression, social
isolation, deconditioning.
• Reintegration: to warrant or restore the
partitipation of patients in occupational,family
and social life.
Basic components of pulmonary
rehabilitation
• Breathing exercises and lower limb dynamic endurance
training, strength training:
– Improvement of ventilatory mechanic, reduced hyperinflation, improved V/Q ratio.
– More efective muscle metabolism, lower metabolic load on respiratory system.
– Diminished dyspnea (physiological adaptation + desenibility)
– Prevention/improvement of osteoporosis
• Dietetics: optimal body weight and composition, energy-

uptake with lowest respiratiry load.
• Psychology: depression, anxiety, coping, smoking
cessation.
• Social workers: job oppurtunities, social and financial
support.
RESPIRATORY FAILURE
Dr. György Losonczy

Professor of pulmonology
2021.
Blood gas in partial and global respiratory
insufficiency
Pneumonia: most frequently hypoxaemia and hypocapnia

Definition and classification of respiratory failures
Type 1 or partial: induced by pulmonary diseases,

arterial pO2< 60 mmHg, pCO2< 46 mmHg
Type 2 or global: induced by pump failure (global hypoventilation),

arterial pO2< 60 mmHg, pCO2> 46 mmHg (numerical reduction of pO2
is close to numerical increase of pCO2
Type 3 or mixed: induced by pulmonary disease plus pump failure

(e.g. respiratory muscle exertion),
arterial pO2< < 60 mmHg, pCO2> 46 mmHg, hypoxaemia is
numerically more severe than hypercapnia
Physiology of pulmonary hypoxaemias
• 1.Ventilation-perfusion (V/Q) mismatch (V/Q↓, VA*)

• 2. Disturbed diffusion (VA )
• 3. Right-left shunt (Qshunt/Qtotal, VA )
• 4. Total hypoventilation (VA)
• In lung diseases mostly mechanisms 1-3 contribute to hypoxaemia.

Mechanism 4 frequently associated with severe or terminal stage
pulmonary, cardiac or neurologic patients.
* VA: total alveolar ventilation (normal value: ~4 liter/min)

Bilateral pneumonia with multiplex cavitation. Arterial pO2=50 mmHg
(partial respiratory failure)
V/Q mismatch
V/Q less than 0.8 decreases O2 content of arterialized pulmonary
capillary blood but greater than 1 – e.g. in compensatory
hyperventilation – does not increase it
Increased V/Q increases alveolar gas pO2 but arterial O2 content
will not increase over the physiological 20 ml/100 ml blood.
Relationship of partial pressure and content of O2 in blood: over
60 mmHg O2 content will not be further increased
Alveolar or arterial
Effect of V/Q mismatch on pulmonary
O2 uptake
• Compensatory hyperventilation of healthy
regions does not replace decreased O2 uptake
of diseased regions, because pO2 over ~70
mmHg will not increase O2 content of blood.
Effect of V/Q mismatch on pulmonary
CO2 removal
Compensatory hyperventilation of healthy

regions effectively removes CO2 retained by
diseased regions. Moreover,
overcompensation is frequently observed.
Pulmonary hypoxaemias are frequently
associated with respiratory alkalosis.
An increase of total alveolar ventilation will decrease alveolar
(=arterial) pCO2 irrespective of V/Q conditions
Evaluation of the relative importance of V/Q
mismatch in the development of pulmonary
hypoxaemia
• Alveolo-arterial pO2 difference widened

• Increased FiO2 (O2 therapy) will increase
arterial pO2
• Increased venous pO2 will increase
arterial pO2
Reduced diffusion: does not impair oxygenation at rest.
Exercise induces impaired oxygenation due to reduced transit time
Evaluation of the relative importance of
impaired diffusion
• Not important in dyspnoe at rest.

• May be major cause of effort
dyspnoe/syncope.
• Increased FiO2 lessens diffusion impairement
related hypoxaemia.
Effect of exercise on arterial blood gases and pH
(K.A., 36 years old female patient)
_________________________________________________________
climbing two stairs
before after *
_________________________________________________________
pO2 63 mmHg  35
pCO2 33 mmHg  40
lactate 1 mmol/L  9.4
BE 3.0 mmol/L  -2.5
pH 7.49  7.36
*nausea, tachycardia, tachypnoe, hypertension, paleness, cyanosis,

sweating
Treatment of acute partial respiratory
failure
• 1. Increase FiO2, O2 saturation 90%, pCO2

should not increase over 46 mmHg;
• 2. Support cardiac output (systemic arterial
pressure, heart rate)
• 3. Substitute hemoglobin (transfusion if
needed in severe anaemia)
• 4. Treat airway obstruction, infection,
thromboembolism, edema, pneumothorax,
etc.
Treatment of chronic respiratory
failure *
• Long-term home oxygen therapy may increase

5 years survival to 70% (otherwise <30%).
• 16 hours a day, 1 liter/min O2
(liquid oxygen, oxygen concentrator)
* 3-4% of the population aged over 50 years

Effect of reduced total alveolar ventilation on
arterial gas tensions (global respiratory failure)
Reduction of pO2
is equal with
increase of pCO2.
Physiologic features of total alveolar
hypoventilations
• High pCO2
• Normal alveolo-arterial pO2 difference
• Increased FiO2 increases arterial pO2
• Increased alveolar ventilation increases
arterial pO2
Causes of global respiratory failure – pump failure
or total alveolar hypoventilation
Location of disease disease
Central drugs, trauma,
hypothermia
pr. hypovent. sy.
Brain stem encephalitis,
bleeding,trauma
Spine/myelon high cervical
trauma, poliomyelitis
Peripheral nerves Guillain-Barré-sy.
crit. illness polyneur.
Upper airway stenosis trachea stenosis
Chest deformity kyphoscoliosis
Respiratory muscle myasthenia,
disease/fatigue chronic/severe resp.dis.
Signs of respiratory muscle fatigue
• Weakened cough
• Dyspnoe more severe
• Orthopnoe
• Rapid, shallow breathing
• Alternating thoracic or abdominal breathing
• Paradox abdominal movement (abdominal wall
flattens during inspiration in the supine patient)
• Parcial global respiratory failure
• Dyspnoe decreases, sleepiness
Treatment of respiratory muscle
fatigue
• Decrease inspiratory load: decrease airway
resistance, increase compliance, decreased
hyperventilation, decrease respiratory
demand
• Increase inspiratory muscle strength: O2
therapy, normalize pH, increase cardiac output
• Mechanical support of breathing
Treatment of acute global respiratory
insufficiency I.
• O2 supplementation
• If normal lung and chest and
suspicion of
- opiate overdose: antidote - Naloxon 0.4 mg iv,
may be repeated
- other respiratory depressant drugs – antidote
Doxapram 0.2-0.4 mg/min iv. infusion
Artificial ventilation
• Artificial ventilation is defined as the provision of the minute

volume of respiration (ca. 6 L/min) by external forces.
• This is usually required when there is impaired action of the
patient’s respiratory muscles (or respiratory neuromuscular
activity).
• Artificial ventilation can be performed through intubation of
the trachea (invasive ventilation) or via clinically acceptable
tight-fitting facemasks (non-invasive ventilation).
insufficiency II.
Assisted mechanical ventilation:

-noninvasive assisted ventilation (continous
positive airway pressure – CPAP or biphasic
positive airway pressure - BiPAP)
-invasive mechanical ventilation after
intratracheal intubation (emergency or
intensive care)
Noninvasive, positive pressure assisted
ventilation (NIV)
Indications
-Acute increase of pCO2 over 50 mmHg
-Acute fall of pH below 7.30
-long-standing tachypnoe35/min
-With FiO2 40%: pO2 stays below 60 mmHg, a
SaO2 below 90%, P(A-a)O2 greater than 300
-Clinical instability
Indications of invasive mechanical
ventilation
Oxygen refractory hypoxaemia (ARDS, SARS – severe cases
of Coronavirus pneumonia)
Worsening hypercapnia, acidosis pH<7.25
confusion
Instabil hemodinamics
With NIV: falling pH, increasing pCO2 (after 30 min),
mental state not improving
Horovitz-index below 200 (pO2/FiO2)
Severe retention of airway mucus
Other complications, co-morbidities
Respiratory failure, non-invasive
ventilation
Dr. Horváth Péter

Semmelweis Egyetem
Respiratory failure
(severely impaired gas transfer)
Type I, partial: a consequence of lung tissue disease
arterial pO2< 60 Hgmm, pCO2< 46 Hgmm
Type II, global, a consequence of alveolar hypoventilation:

arterial pO2< 60 Hgmm, pCO2> 46 Hgmm
Type III, mixed, both pathology:

arterial pO2< 60 Hgmm, pCO2> 46 Hgmm, however hypoxia is more severe than we would expect
based on the pCO2
Mixed respiratory failure
• Normal pCO2 = 40 Hgmm

• If patient has pCO2 of 60 and pO2 of 55:
• Actual pCO2-normal pCO2 = 20 Hgmm
pO2 corrected = pO2 actual + pCO2 diff = 55+20 = 75 Hgmm →
corrected pO2 is above 60, Type II
• If patient has pCO2 of 50 and pO2 of 50:

• Actual pCO2-normal pCO2 = 5 Hgmm
pO2 corrected = pO2 actual + pCO2 diff = 50 + 5 = 55 Hgmm →
corrected pO2 below 60, Type III
Main symptoms:
Dyspnea, tachypnoe, tachycardy, increased
respiratory work
hypoxaemia hypercapnia
Cyanosis Warm, wet skin
Tachycardia Tachycardia
Increased blood pressure Increased blood pressure
Headache Headache
- Narrow pupils,
Agitation Agitation
Desorientation Desorientation
Loss of consciousness tremor
Atrial fibrillation Impaired reflexes
Convulsion Loss of consciousness
Brain injury Coma
Causes of respiratory failure
• Airway diseases I. II.

• Alveolar/interst. diseases I.
• ARDS I.
• Pulmonary embolism I.
• Hydrothorax I. II.
• Chest deformity I. II.
• Neuromusc. disease II.
• Decreased respiratory drive(centralis
hypopnoe-apnoe II.
Physiology of respiratory failure
 1.Ventilation-perfusion mismatch (V/Q) (VA*)
 2. Impaired diffusion(VA )
 3. Right-left shunt (V/Q=0, VA )
 4. Total hypoventilation (VA)
 In lung diseases usually 1., 2., and 3. are dominant.
* VA: total alveolar ventilation

Arterial pO2 and pCO2 in V/Q mismatch after increased Va
Pneumonia: Usually hypoxaemia and hypercapnia

V/Q mismatch and oxygen uptake
• Compensatoric hyperventilation will not correct hypoxaemia as
low ventilation areas have higher perfusion
• V/Q mismatch hypoxaemia will respond to increased FiO2 while
shunt hypoxaemia will not
• In V/Q mismatch there is no hypercapnia
• In V/Q mismatch we encounter hypercapnia if alveolar
ventilation increases due to respiratory muscle fatigue (due to
compensatory hyperventilation
Assessing the role of diffusion impairment
in hypoxaemia
•It does not cause dyspnea at rest
•It might be a major cause of exertional
dyspnea (effort dyspnoe/syncope).
•Increasing FiO2 will correct diffusion related
hypoxemia
The effect of physical exertion on the ABG in impaired
diffusion (pulmonary fibrosis)
____________________________________________________________
Climbing stairs
Before After *
____________________________________________________________
pO2 63 mmHg  35
pCO2 33 mmHg  40
lactate 1 mmol/L  9.4
BE 3.0 mmol/L  -2.5
pH 7.49  7.36
*nausea, tachycardia, tachypnoe, hypertonia, paleness, cyanosis, sweating

Treatment of acute partial respiratory
failure
•1. Increase FiO2 to increase SpO2 but look out
for pCO2!;
•2. Increase cardiac output
•3. increase erythrocyte count
•4. Treat underlying lung/respiratory drive/chest
wall problems
Signs of respiratory muscle fatigue
• Weak cough
• Increased dyspnea
• orthopnoe
• Quick, shalloe breath
• Periodical changes in abdominal and chest wall movements
• Paradoxic abdominal movement (abdomen will be flat during
inspiration, therefore decreased movement of diaphragm)
• Partial respiratory failure → Global respiratory failure
• Decreased dyspnoe, loss of consciousness
failure
Main methods of mechanical ventilation
-non-invasive assisted ventilation (eg. CPAP, BiPAP)
-invasive ventilation after endotracheal intubation
Indication: respiratory failure
Invasive ventilation
Mechanical • There is an invasive connection between the
patient and the ventilator
ventilation
Non-invasive ventilation
• There is a noninvasive interface between
the patient and the ventilator (eg. Mask)
Helmet
Total face mask
Mask
Full face maszk
types
Nose maszk
Nose cushion
• CPAP
• Continous positive airway pressure
• Same pressure in expiration and inspiration
• It provides a patent airway (preventing collapse)
• BiPAP
• Bilevel positive airway pressure
• Different pressure profiles in inspiration and
exspiration
• It provides a patent airway AND helps ventilation
Types of NIV
ventilation
• Pressure controlled modes:
• T-mode
• S-mode
• S/T mode
• iVAPS/AVAPS
• Volume controlled modes
• CM-V (controll mode – volume) ventilation
Types of NIV
ventilation
Pressure and flow profile during
ventilation
Dr. habil. Gábor Horváth, Ph.D.
Associate professor
Dept. of Pulmonology
Semmelweis University Budapest
Classification of sleep disorders
(ICSD-3; AASM 2014)
1. Sleep-related breathing disorders
2. Sleep-related movement disorders
3. Central disorders of hypersomnolence
4. Insomnia
5. Circadian rhythm sleep-wake disorders
6. Parasomnias
Sleep-related breathing disorders:
significance
• The most common sleep disorders, affecting ~25% of the total
adult population
• Severe acute consequences: intermittent hypoxia, negative
intrathoracic pressure, arrhythmias, sleep fragmentation,
excessive daytime sleepiness, cognitive impairment, decreased
vigilance, driving and workplace accidents
• Severe chronic consequences: hypertension, arrhythmias, left
ventricular hypertrophy, left ventricular dysfunction and
damage, heart failure, cerebrovascular disease, metabolic
disorders , increased platelet aggregability and blood
coagulability
• Highly underdiagnosed medical disorders.
Sleep-related breathing disorders:
definitions
Hypopnea – reduction of oronasal airflow
• peak signal drop ≥ 30%
• duration ≥ 10 s
• reduction of O2-saturation ≥ 4% OR the event is associated with an arousal
Apnea – cessation of oronasal airflow
• peak signal drop ≥ 90%
• duration ≥ 10 s
Obstructive apnea – ineffective thoracic/abdominal movements
Central apnea – no thoracic/abdominal movements
Apnea-hypopnea index (AHI) – number of apnea/hypopnea events per hour of sleep
Most common patients in the sleep laboratory:
sleep-related breathing disorders
1. Obstructive sleep apnea (OSA)
• OSA, upper airway resistance syndrome (UARS)
2. Central sleep apnea
• Cheyne-Stokes breathing (CSB), due to medical disorders, medication- or drug-
induced, high- altitude periodic respiration, therapy-induced, primary/ idiopathic
3. Sleep-related hypoventilation
• obesity-hypoventilation syndrome (OHS), simultaneously with other diseases
(OSA: Pickwickian syndrome, COPD: overlap syndrome), drug-induced, congenital,
late form with hypothalamic dysfunction, primary/idiopathic (Ondine’s curse)
4. Sleep-related hypoxaemia
5. Others
• snoring, catathrenia
Obstructive sleep apnea
Airway collapse typically occurs behind the palate
(velopharynx), the tongue (oropharynx), or both
Mechanism of upper airway obstruction
in OSA
Morphological factors: Functional factors:
- obesity - chronic upper airway inflammation

- short neck - alcohol use
- retrognathia, micrognathia - smoking
- macroglossia - sedatives with muscle relaxing effect
- large uvula - central nervous system diseases
- tonsil hypertrophy - pharyngeal neuropathy/myopathy
- nasal septum deviation - generalized neuropathy/myopathy
Obstructive sleep apnea (OSA)
Definition: recurrent episodes of complete or partial
obstruction of the upper airway leading to reduced
or absent breathing during sleep
Main features:
− lack of ventilation is associated with a decrease in PaO2
(intermittent hypoxia) +/− an increase in PaCO2
− episodes are terminated by different levels of arousal
(sleep fragmentation) and a sudden increase in
sympathetic activity
Severity index, prevalence:
− mild (AHI = 5-15) ♂: 24%, ♀: 9%
− moderate (AHI = 15-30) ♂: 4%, ♀: 2%
− severe (AHI > 30) ~ 1%
Events of obstructive apnea and
apnea termination
During apnea: Apnea termination:

- hypoxia - arousal
- hypercapnia 30-300x - stress reaction
- vagotonia episodes - sympathetic tone 
- bradycardia per night - tachycardia
- blood pressure  - blood pressure 
- cardiac output  -cessation of hypoxia
Obstructive hypopnea/apnea
(cardiorespiratory polygraphy)
Sleep fragmentation by respiratory event induced
arousals in OSA (polysomnography)
Hypnograms and sleep stages of a healthy
individual (top) and a patient with OSA (bottom)
OSA disrupts sleep

architecture with loss
of REM and SWS.
Lavrentaki A, et al. Eur J Endocrinol. 2019 Mar;180(3):R91-R125

Sleep fragmentation vs. sleep deprivation
Common symptoms:
- excessive daytime sleepiness (EDS)
- decreased psychomotor performance
- degraded mood
Symptomatic differences are more related to the degree

of sleep loss or fragmentation rather than to the type
of sleep disturbance.
Both can exacerbate sleep pathology by increasing the

length and pathophysiology of sleep apnea!
Driving accidents and OSA
• OSA is the confirmed cause in 30-35% of drowsy
driving crashes.
• Untreated OSA patients are 5-8x more likely to
cause driving accidents.
• OSA incidence of 15-20% among professional
drivers.
• OSA screening of drivers is mandatory (from 2015).
Pathophysiological pathways involved in OSA
and systemic consequences
Systemic complications & comorbidities of
Hypertension
- hypertension patients: OSA incidence ~30%
- therapy resistant cases: OSA incidence ~80%
- moderate-severe OSA  2-4 odds ratio of hypertension
- „non-dipper” type
Arrhythmias
- OSA patients: incidence ~50% (SVES, VES, AV-block, atrial fibrillation)
Heart failure
- severe OSA: 2-4 odds ratio of heart failure
Pulmonary hypertension (PH)
- OSA patients: incidence 20-52%
Systemic complications & comorbidities of
Atherosclerosis
- moderate-severe OSA: independent risk factor for coronary atherosclerosis
- strong correlation between the progression of coronary atherosclerosis and
the O2 desaturation index (ODI)
Diabetes
- OSA is a independent risk factor for type 2 diabetes
GERD
- mechanisms underlying GERD in OSA patients remains unclear, however, recent
studies suggest a role for obesity, rather than OSA per se
Nocturnal enuresis
Impotence
Disease severity and survival rates in OSA patients
(the Wisconsin Sleep Cohort)
n = 1396
Young T, et al. Sleep. 2008 Aug;31(8):1071-8.

Diagnostics of sleep-related
breathing disorders
1. Signs & symptoms
2. Standardized sleep questionnaires
3. Sleep studies (PG, PSG)
Daytime and nighttime symptoms
in OSA
Nighttime: - snoring
- observed apneas
- poor sleep quality
- night sweating
- enuresis
Daytime: - sleepiness
- morning headache
- morning dry mouth
- poor short term memory
- poor mood, depression
- GERD symptoms
- impotence, decreased libido
Epworth Sleepiness Scale (ESS)
ApneaLink home sleep testing devices
Sleep laboratory & polysomnography
Polysomnography: to study multiple physiological
parameters and the sleep-wake rhythm
- EEG
- EMG (chin + legs)
- EOG
- Nasal airflow/thermistor
- Respiratory effort
(thoracic/abd. movements)
- O2 saturation
- ECG
- Microphone (snoring)
- Body position
- Night vision camera
- Trained technician
- Somnologist specialist
Central sleep apnea
Cheyne-Stokes breathing (CSB)
Definition: cyclic episodes of central apnea and
hyperventilation with a crescendo-decrescendo
breathing pattern
Polysomnographic characteristics:
• At least 3 consecutive central apneas
separated by crescendo-decrescendo
pattern of breathing
• Episode duration > 40 s (45-90 s)
• Episode frequency > 5/hour
• Arousal at peak phase of breathing
• Cyclic episodes appear primarily in NREM
(Stage 2: reduced PaCO2 sensitivity)
Epidemiology and pathomechanism
Predisposing factors:
• Congestive heart failure (LVEF < 40%: 50%), atrial fibrillation (25-40%), increased
ventricular filling pressure, advanced ventricular remodeling
• Neurological (mainly vascular) diseases with midline, brainstem involvement
• Others: older age (> 80 év), renal failure, increased intracranial pressure
Complex pathomechanism (still not fully explored) :

• Slow circulation time  PaCO2 change arrives late at chemoreceptors
• Hypersensitive ventilation response to PaCO2
• Increased pulmonary resistance and pressure
• Pulmonary congestion induced tachypnoe  decreased PaCO2 levels and CO2 reserve
• DecreasedPaCO2 - apnea threshold difference
Sleep-related hypoventilation
Dual mechanism:
• deterioration of respiratory pump function
during sleep
• abnormal regulation of breathing (CO2 drive )
Characteristics:
• abnormally elevated PaCO2 and/or reduced
PaO2 during sleep
• desaturation periods of up to 1 minute
• not caused by apnea/hypopnea
Serious consequences due to chronic hypoxia:
• erythrocytosis
• pulmonary hypertension
• cor pulmonale
• heart failure
• Obesity-hypoventilation syndrome (OHS)
Obesity (BMI > 30 kg/m2) and abdominal adipose tissue accumulation severely interfere
with the function of diaphram that has a central role in breathing activity in REM.
• Pickwickian syndrome
coexistence of OHS and OSA
• Overlap syndrome
coexistence of OHS and COPD
• Due to chest deformity, neuromuscular diseases
• Ondine’s curse syndrome
Congenital or acquired disease of the central nervous system (e.g. inflammation, tumor,
surgery of the central nervous system). During sleep, especially in SWS, breathing
frequency is abnormally low. Breathing pattern returns to normal after sleep.
Therapy
1. Weight loss
2. PAP therapy
3. Position therapy
4. Intraoral devices
5. Surgery
6. Others
Weight loss
• Appr. 60% of OSA patients are obes (BMI > 30 kg/m2)
• Significance of obesity:
- increases the collapsibility of the pharynx  obstruction
- impairs breathing during sleep  hypoventilation
• Type of obesity:
Pharyngeal (neck) and abdominal adipose tissue
accumulation are the most dangerous forms.
• Significance of weight loss:
10-15% weight loss reduces the severity of
OSA by 20-30%
• Dieting, weight loss surgery
Positive airway pressure (PAP)
therapy
PAP modes, devices:
• CPAP
• AutoCPAP
• BiPAP S
• BiPAP S/T
• BiPAP AVAPS
• ASV
Mask types for PAP therapy
Manual/autoCPAP titration (raw data)
 CPAP + CPAP
Effects of CPAP therapy
• Proven to improve:
- quality of life related to sleep
- mood
- anxiety
- depressive symptoms
- daytime sleepiness
- hypertension
- risk of traffic accidents
• Likely to improve:
- cardiovascular complications/mortality
- mortality in general
- neurocognitive functions
Position therapy
• Recommended in (primarily supine) position-dependent breathing problems
• Position pad prevents sleeping in supine position
• Long-term compliance is poor
Intraoral devices
• Intraoral protrusion devices prevent the jaw and thus
the tongue from sliding backwards
• Made based on the unique individual pattern of teeth
and jaws
• Recommended for snorers and mild to moderate OSA
• Effectiveness is 50-80% and tolerance ranges from 40-
80% in mild to moderate OSA
• Discomfort complains are common during prolonged
use: hypersalivation, dry mouth, jaw pain, tooth
sensitivity, permanent tooth retention, occlusion
abnormalities
ENT surgical procedures
UPPP
• Nose
septo-rhinoplasty, septum resection, FESS
• Nasopharynx
adenotomy
• Oropharynx, soft palate
tonsillectomy, uvulo-palato-pharyngoplastica (UPPP), laser-assisted uvulo-
pharyngoplastica (LAUP), RF-assisted uvulo-pharyngoplastica (RAUP)
• Hypopharynx MMA
tonsillectomy, mandibular osteotomy (MMA), maxillo-
mandibular osteotomy and anteposition surgery
• Larynx
epiglottopexy, tracheotomy
Take home message
• OSA is an underrecognized and underdiagnosed disease that
usually affects middle-aged, overweight adults with serious
consequences on patients' health and society as a whole.
• OSA has many negative effects on sleep and daytime functioning, such as poor
mood, performance, accidents, hypertension, heart disease, stroke, and insulin
resistance.
• The disease can be diagnosed by a visit to the sleep lab (polysomnography).
• CPAP and oral devices work well, but they are not cures for sleep apnea. OSA can
also be improved by losing weight or ENT surgery.
• Effective treatment improves a person’s overall health and quality of sleep.

Department of Pulmonogy
Tömő str. 25-29.
1083 Budapest

Chemo- and radiotherapy
of lung cancer
Professor Lilla Tamási

DSc.
Semmelweis University, Department of
Pulmonology
2020
Blokkoktatás 2019-2020
Introduction – Everyday practice,
clinical manifestations of lung cancer

Bronchoscopy

65 yr male pt, breathlessness, cough,
- 2012
• Presenting symptoms
cough, breathlessness
and facial swelling
• Smoker, 60py
• Arterial hypertension
treated with a calcium
channel blocker

Bronchoscopy, biopsies – Small cell
lung cancer

3 months after chemoradiotherapy –
nearly complete regression

Before therapy After therapy

Generally, two main types of lung
cancer: SCLC and NSCLC
1. Small-cell lung cancer (SCLC)
• agressive but sensitive to chemotherapy
• closely linked to smoking
• almost always a systemic disease from the
beginning
• chemotherapy is the mainstay of the treatment
• radiation therapy is often used along with
chemotherapy to treat lung tumors that have not
spread beyond the chest or other organs
• surgery is not commonly used in SCLC due to its
tendency to spread quickly
• surgery*European
has no demonstrable influence on survival
Respiratory Society Handbook: Respiratory Medicine 2013, 374-380.
2. Non-small-cell lung cancer (NSCLC)
• patients diagnosed as having NSCLC in

its early stages (until stage IIIA) are
candidates for surgical resection with a
realistic hope of curing the disease
• Stages IIIB and IV: chemotherapy and
radiation therapy is used to slow tumor
growth and relieve symptoms.
*European Respiratory Society Handbook: Respiratory Medicine 2013, 374-380.

Adenocarcinoma
 Most common form in women, probably in men too
 Predominant type in non-smokers and former smokers,
and in young (<50 ys old)
 Frequently peripheral
Squamous Cell Carcinoma

 More often found in men, usually associated with long
smoking history
 Centrally located lesions and spread locally
Large Cell Carcinoma and Large cell neuroendocrine

carcinoma
Staging of lung cancer
 T- tumor (size, invasion etc.)

 N- lymph nodes
 M- metastases
UyBico S J et al. Radiographics 2010;30:1163-1181

T1a – T2b

T3 – T4

Lymph nodes
N1 - ipsilateral hilar
N2 - ipsilateral mediastinal and / or

- subcarinal
N3 - contralateral mediastinal/hilar
- supraclavicular bilateral
- scalenus lymph node bil.

M1a/b

7th edition of the TNM staging system for lung
cancer

Staging – Stage I.
 Stage IA: T1a/T1b N0 M0 (T<3cm)
 Stage IB: T2a N0 M0 (T=3-5cm)

Stage II.
 Stage IIA: T1a/1b/2a N1 M0 (<5 cm)
 Stage IIA: T2b N0 M0 (5-7 cm)
 Stage IIB: T2b N1 M0

 Stage IIB: T3 N0 M0 (>7 cm)
Stage III.
 Stage IIIA: T4 N0-N1 M0 or
T3 N1 M0
T1-3 N2 M0
 Stage IIIB: Any T N3 M0

T4 N2 M0

Stage IV - Any T Any N M1a or M1b

Treatment options
 Surgery:
 Lobectomy
 Bilobectomy
 Pulmonectomy
 Atypical resection in some cases
 Chemotherapy
 Radiation therapy
 Supportive treatment
Good performance status – Required
condition of active oncological
treatment

SCLC
 Stages I-III:
First line: cisplatin/carboplatin+etoposide
chemotherapy 6 cycles
Thoracic radiation is given after the 3rd
course, mostly 50 Grays
 Stage IV:
4-6 cycles of the same chemotherapy
 Second line treatment (if first line fails or
progression occurs earlier than 6 months after
the first line):
Topotecan OR
Epirubicine-Cyclophosphamid-Vincristine (4
cycles).*European Respiratory Society Handbook: Respiratory Medicine 2013, 374-380.
NSCLC
 Surgical treatment: stage IA- stage IIIA
• Adjuvant chemotherapy:
– use of chemotherapy after surgery to improve the
outcome
– for patients with stage IB cancer or more advanced (IB-
IIIA)
• Neo-adjuvant chemotherapy
– use of chemotherapy before surgery to make the lesion
resecable (e.g. IIIA)
• Palliative / definitive chemotherapy:
– stage IIIB-IV Pulmonológiai Klinika 2019-2020
NSCLC – Major contraindications for
surgery (IA-IIIA - inoperability)
 Advanced biological age

 MI within past 3 months
 Major arrhythmias
 Severe pulmonary hypertension
 Severe or very severe COPD
 Pre-op severe hypoxia
 Pre-op FEV1 < 1L

Treatment options and 5-year
survivals in NSCLC
Group Stage Treatment 5-year
survival
Early stages Stage I •Surgical resection 60-70%
•Adjuvant chemotherapy
from stage IB
SURGERY
Stage II WITH OR WITHOUT CHEMOTHERAPY
35-45%
(ADJUVANT OR NEOADJUVANT)
Locally Stage IIIA •Surgical resection 25%
advanced •Adjuvant chemotherapy
disease
Stage IIIB •Chemotherapy
PALLIATIVE+ CHEMOTHERAPY
radiation 10%
Metastatic Stage IV WITH OR WITHOUT
Chemotherapy RADIATION
and targeted <5%
disease THERAPY OR TARGETED THERAPY
agents
*European Respiratory Society Handbook: Respiratory Medicine 2013, 374-380
NSCLC IIIB-IV.
First line platinum based chemotherapy
 cisplatin or carboplatin
+
 gemcitabin / paclitaxel / docetaxel /
vinorelbin / pemetrexed (3rd generation
agents)
These combinations can be used in stages IB-IIIA
before or after surgery as well (neo-adjuvant/adjuvant
settings)
NSCLC – second/third line
chemotherapy
 If first line fails, or progression occurs within 6
months after the previous line
 Chemotherapy:
Docetaxel or pemetrexed monotherapy
 Targeted therapy (EGFR blockers)

Possible side effects of chemotherapy
 Chemotherapy acts by killing cells that divide rapidly
 It may also harm cells that divide rapidly under normal
circumstances:
 bone marrow
 digestive tract
 hair follicles.
 This results in the most common side effects of chemotherapy:
 Myelosuppression:
 Neutropenia
 Anaemia
 Thrombocytopenia
 Mucositis of the digestive tract
 Nausea, vomiting
 Alopecia
 Fatigue
 Neuropathy
 Renal impariment.

Supportive treatment – prevention or
therapy of side effects
 Colony stimulating factors
 Erythropoietins
 Transfusions
 Steroids
 Serotonine antagonists as central anti-
emetics (e.g. ondansetron)
 Proper hidration (especially with platinum)

Targeted therapy in adenocarcinoma - Driver
Mutations NSCLC
http://www.discoverymedicine.com/Tim-
Harris/files/2010/08/discovery_medicine_harris_no51_figure_1.jpg
http://www.discoverymedicine.com/Tim-
Harris/files/2010/08/discovery_medicine_harris_no51_figure_1.jpg
Molecular targeted therapy in locally
advanced (IIIB) and metastatic (IV)
adenocarcinoma
The angiogenesis inhibitor – VEGF-blocker -
bevacizumab (in combination with first line
chemotherapy)
Gefitinib or erlotinib are tyrosin-kinase

inhibitors (EGFR antagonists) which improve
survival in IIIB-IV adenocarcinomas
They may be used in first/second/third
line treatment as monotherapy.
Bevacizumab Blocks Angiogenesis

Rosell & Karachaliou. Nat.Rev.Clin.Oncol. 2013
Activating mutation (+):

predicts good response to
tyrosin-kinase blockers

CELL DIVISION AND PROLIFERATION
Possible side effects of targeted
therapy
 EGFR antagonists:
Skin problems, rush
Constipation or diarrhea
Nausea
 VEGF blockers:
 Bleedings, haemoptysis
 Hypertension.

The picture of lung cancer has
changed…
Reck M, Heigener DF, Mok T, Soria JC, Rabe KF, Lancet 2013; 382: 709-19.
ALK+ disease is a distinct subset
of NSCLC
Histological classification of lung cancer6
ALK+ disease occurs in ~5% of
patients with advanced NSCLC1–5
More than 75,000 patients per

year diagnosed7
The incidence of ALK+ NSCLC

is higher in
• Patients with non-squamous
histology2,8
• Never or former smokers2,8
• Younger patients2,8
• Females2
• Patients who do not have EGFR
or KRAS mutations2,8
Clinical characteristics do not always predict the presence of ALK+ NSCLC9,10

ALK = anaplastic lymphoma kinase 1. Dearden, et al. Ann Oncol 2013; 2. Gridelli, et al. Cancer Treat Rev 2014
EGFR = epidermal growth factor receptor 3. Hallberg, et al. Nat Rev Cancer 2013; 4. Rikova, et al. Cell 2007
5. Soda, et al. Nature 2007; 6. American Cancer Society 2013
NSCLC = non-small cell lung cancer 7. Torre, et al. CA Cancer J Clin 2015; 8. Perez, et al. Lung Cancer 2014
9. Lindeman, et al. J Thorac Oncol 2013; 10. Leighl, et al. J Clin Oncol 2014

Ultimately, relapse occurs following crizotinib
treatment – Second line: alectinib – Third line:
lorlatinib Disease response in
Initial diagnosis Acquired resistance
some patients
Brain metastasis
Local recurrence
Continue treatment
Systemic
Treatment disease
ALK+ patients treated with crizotinib typically relapse within 1 year, with approximately half of patients
experiencing disease progression in the CNS1–6
1. Katayama, et al. Sci Transl Med 2012; 2. Weickhardt, et al. J Thorac Oncol 2012; 3. Shaw, et al. N Engl J Med 2013
4. Crizotinib US PI 2015; 5. Crizotinib EU SmPC 2014; 6. Solomon, et al. N Engl J Med 2014
Immunetherapy – Rationale (CTLA-
4 and PD-1 pathway inhibition)
Lymph nodes Microenvironment of the tumor
Activation
(Cytokines, lysis, proliferation,
migration to the tumor)
TCR
TCR MHC
MHC
+++ +++
Dendritic B7 CD28 T cell T cell PD-1 PD-L1 Tumor cell
Cell
+++ ---
B7 CTLA-4
--- Anti-PD-1/PD-L1
PD-1 PD-L2
Anti-CTLA-4 ---
Anti-PD-1
CTLA-4 signaling pathway PD-1 signaling pathway
CTLA-4 regulates the amplitude of the earlier PD-1 limits the T-cell activation in the
activation of naive and memory T cells. periphery during an inflammatory reaction.
Wolchock et al, J Clin Oncol 2013 ASCO Annual Meeting Abstracts 31:15_suppl

Nivolumab and pembrolizumab -
immune checkpoint inhibitors
(Sundar. Ther Adv Med Oncol 2015)

Radiation therapy
 Radiation therapy is the delivery of focused high-
energy x-rays
 it affects cells that are rapidly dividing—such as cancer
cells.
• External irradiation
 greater volume of tumor irradiated
 more normal tissue irradiated
 easier to perform
• Endoluminal brachytherapy
 higher radiation dose to the tumor
 decrease the dose to normal tissues
Possible side effects of radiation
therapy
 Fatigue
 Hair loss in the area of the chest wall
included in the radiation field
 Skin irritation
 Loss of appetite
 Esophagitis
 Radiation pneumonitis or fibrosis

Palliative Radiotherapy
 Palliative radiotherapy is aiming to
relieve or prevent symptoms related
to the disease.
 Indications:
Primary lung tumor
Superior vena cava syndrom
Brain metastases
Spinal cord compression
Bone metastasis…
SVC SYNDROM : CLINICAL
PRESENTATION
 Eyelid edema
 Neck edema
 Upper arm edema
 Collateral circulation
Therapy:
Radiation
Requires 1 to 2 weeks to achieve a relief
of symptoms
Steroids and furosemide
Vena cava stent implantation

Spinal cord compression
 A true emergency in
selected cases
 Diagnosis by CT or MR
 Treatment:
steroids+furosemide
surgery and/or
radiotherapy (10x3Gy)
depending on
prognostic factors and
patient life expectancy
Brain metastasis
 A very common problem for lung cancer
 Treatment decision:
no active treatment, just steroids and
dehidration (e.g. more than 5 metastases or
very poor life expectancy)…
……radiotherapy or surgery based on different
prognostic factors including performance status,
other systemic disease, the primary disease.
Questions ?
Tuberculosis
Posztgraduális oktatás
ÁOK IV. évfolyam
Mycobacterium tuberculosis complex
• Bacteria belonging to the Mycobacteriaceae family of the Actynomycetia
class
• Clinically very similar disease. Members:
• M. tuberculosis
• M. africanum
• M. bovis (cows)
• M. canetti
• M. microti (rodents)
• M. pinnipedis (seals)
• M. capreum (goats)
• Gram neg. acid fast bacilli
Pulmonary TB in Hungary
TB in Hungary
14 000
12 000
10 000
8 000
6 000
4 000
2 000
0
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020
Új tbc-s beteg Nyilvántartott tbc-s beteg

Patomechanism
• MTBC antigens activate

lymphocytes and NK-
cells to produce IFN-
gamma
• As a consequence
macrophages
differentiate
• Epitheloid cells, and
multinucleated giant cells
form
• They enclose the
bacteria in a palisade like
manner
Peter D O Davies, Ajit Lalvani ,Muhunthan Thillai:
Clinical tuberculosis
Route of infection
• Usually by inhalation of aerosols containing MTBC
• MTBC deposits in terminal bronchiols
• Immune system might get rid of it, but latent infection can also develop
• Prolonged exposition increases the risk of infection. 30-50% chance of
infection in people living in the same household
• Other routes:
• Intestines (usually unpasteurised milk)
• Skin (open wound, tuberculosis verrucosa cutis – butchers, pathologists)
Primary TB
• After infection macrophages phagocyte the bacteria and transport them to
the local lymph nodes
• Gohn-complex develops:
• Primary granuloma
• Enlarged hilar lymph node
• The lymphatic vessel connecting the two
• Usually TB heals and the grenuloma will heal by scarring -> Gohn-focus
• Memory T-cells of the patient will keep the bacteria at bay for a long time
(years-decades-lifelong)
Primary TB in the upper left lobe
Post primary TB
• Reactivation of latent infection or reinfection of
sensitized patient
• Inflammation with upper lobe dominance (the bacteria
prefer high pO2)
• Compared to primary TB more pronounced destruction
of the lung parenchyma with cavitation
Lobar right upper lobe TB and
TB bronchopneumonia in left lung
TB bronchopneumonia affecting
more than one lobe
Right upper lobe pneumonia with
cavitation and air-fluid nivo
RUL caverna after healing
Right sided tuberculoma
Focal nodular shadows
in the left S6
Miliary TB. Blizzard-like
X-ray image
Bilateral post primary TB
Bilateral TB. The
left lung is
shrinked and it
„pulls” the
mediastinum to the
left
Post primary TB on CT and PET/CT
Symptoms
• Cough
• Productive cough
• Fatigue
• Weight loss
• Chest pain
• Dyspnea
• Night sweats
Diagnostic follow up in suspected TB
• History
• Physical examination
• Chest X-ray
• General lab tests
• Bacteriology
Lab signs
• ESR
• CRP
• Neutrophilia, lymphopenia
• Hypalbuminaemia
• Anaemia
• Impaired liver function
• Hyponatraemia
• Low iron, increased ferritine
Mycobacteriology
• Test specimen:
Morning sputum. It can be stored at room temperature for 1-2 hours, for
longer periods it should be stored at 2-8 degrees.
Induced sputum, gastric lavage.
Samples should be obtained on 3 consecutive days!
Bronchial wash, BAL, pleural, pericardial fluid, ascites, urine.
Blood samples should be collected into special haemoculture containers for
TB.
Microscopic examination of sputum smear after Ziehl-Neelsen staining
Culture
• Gold standard: Löwenstein-Jensen (solid medium); It is more
sensitive than direct microscopic examination, however it takes
8 weeks
• Liquid medium (pl. BACTEC, MGIT) good sensitivity (90%) , it
is prone to contamination. 2-3 weeks
• Every newly diagnosed patient has to be tested for drug
resistance via culture!
Tuberculin skin test
(Mantoux)
• Intracutaneous injection of MTB antigene (0.1 mg) PPD = purified protein
derivative
• After 72 hours of incubation we measure the edema at the site of
inoculation:
• If ≤ 10 mm - normergic
• If >10 mm – hyperegic (TB or NTM)
• If no edema – anergic (susceptible to TB or immunocompromised)
• The interpretation depends on a number of factors (BCG vaccination, prior

infection, immune system etc)
Interferon-gamma tests
• Eg. Quantiferon TB test:
• We isolate the mononuclear cells from the patients
blood sample. If they are sensitized to TB they produce
IFN-gamma in the presence of MTBC anitigenes
• Advantages:
• More sensitive and specific than TST
• It is not positive in NTMs
Identification
Methods for specific identificaton:
• Nuclein acid hybridization
• HPLC
• PCR és RFLP
• DNA sequencing
• DNA chip
DNA fingerprint
It has an epidemiologic significance, we can identify the exact route of the
bacteria from one patient to the other.
Direct nuclein acid amplification methods
• It might show the presence of a single bacterium

• Quick: 6-8 h
• Sensitivity: 80%
• Specificity: 93%
Pharmacotherapy
Aim:
• Elimination of the actively dividing bacteria and the cure of the patient
• Interruption of the chain of infection
• Prevent the development of resistance against TB drugs
• To sterilize the lung tissue (dormant and intermittantly active bacteria)
First line anti-TB agents in different metabolic state
First line treatment
INH:
• 300 mg/day
• Hepatotoxic, neurotoxic, MAO inhibitor
• It can be administered in pregnancy and renal failure
Rifampicin:
• 600 mg/day
• Toxicity: hepatotoxic (especially in combination with isoniazide).
• Prurity, exanthemas, nausea, aemolytic anaemia, renal insuff., it colors secretions
to orange (saliva, tear, urine)
• It can be administered in pregnancy and renal failure
First line treatment
• Pirazinamide (PZA): 1.5 g/day
• Toxicity: hepatotoxicity, nausea, hyperuricaemia (jaundice!). Fotosensitive
dermatitis, Polyarthralgy
• Should be avoided in pregnancy, in renal failure it should be administered
every other day
• Ethambutol (Sural): 1.5 g/day
• Toxicitás: retrobulbar neuritis (problems with vision), peripheral neuritis
• Can be given in pregnancy
Usual 6 month 2 month of 4 drugs
treatment plan of TB
(intensive phase)
• If the therapeutic
response is not
adequate it can be
prolonged to 12
months Followed by 4 month of
INH and rifampicine
(continuation phase)
Second line anti TB agents
• Streptomycin, capreomycin, amikacin, kanamycin (oto-, nephro- és
neurotoxicity)
Cycloserin: 1 g/day, toxicity: neuropsychiatric symptoms
• Ethionamid (Trecator): 1 g/day); Toxicity: nausea, hepatotpxicity
• PAS: 12-15 g/day iv.; Toxicitás: GI symptoms, liver, coagulopathy,
hypothyreosis.
• Levofloxacine (or moxifloxacine), levo: 500-1000 mg/day.
Resistent TB
• Drug resistent TB: If TB is resistent to one first-line
agent
• Multidrug resistent (MDR) TB: resistent to INH and RMP
• XDR-TB: MDR + resistance against fluoroquinolones
and one second line IV drug (amikacin, capreomycin,
kanamycin)
MDR TB
• It develops after early discontinuation of effective TB treatment
• Globally:
2.9% of new TB cases are MDR-TB
15.3% of previously treated TB patients are MDR-TB
10% of WHO registered MDR-TB patients receive adequate therapy
• Former USSR: 50% monoresistent, 20% MDR. (similar in China)
• Western countries: 7-10% monoresistent and MDR cases
Prevalence of multidrug resistance among new cases of tuberculosis globally,
1994-2007. Adapted from World Heath Organization
Grant, A. et al. BMJ 2008;337:a1110 Copyright ©2008 BMJ Publishing Group Ltd.
MDR-(XDR)-TBC treatment
• If there is no clinical improvement after one to two
months of treatment we can presume resistance even
before the culture results
• We have to administer 4 effective drugs for at least 18-
24 months, preferably with DOT (directly observed
therapy)
• Effective first line drug + fluoroquinolone + daily
administered iv drug + effective second line agent
Thank you for attendance!
Case Reports
Janos T. Varga MD, PhD, Prof. Gyorgy

Losonczy, MD, DSc.
Department of Pulmonology,
Semmelweis University, Budapest
2021
I. 33 years woman with breathlessness and fever
Anamnesis:
High temperature for 2 weeks, coughing, dyspnoea for 3 days,
fatigue. Combined oral antibiotics because of pneumonia, but
clinical progression in 2 days, chest X-ray progression, ARDS-
like chest X-ray, PaO2 38 Hgmm, 4 l/min O2 supplementation
PaO2 42 Hgmm, nasal O2 supplementation, than „high flow
nasal oxygen” (HFNO) treatment can not reduce hypoxemia,
FiO2/pO2=280. PaCO2 27 Hgmm. Transmission to ICU.
Signs:
Dyspnoe, cyanosis, choughing, respiratory rate: 40/perc, RR:
100/60 Hgmm, pulse 120/min,
33 years woman with respiratory distress syndrome
Laboratory results
neutrophilia 11 G/l
Hb: 83 g/l
CRP 158 mg/l
Procalc: 0,32 ug/l (normal)
Na 140 mmol/l
K 4,2 mmol/l
pH: 7,49, pO2: 221 Hgmm (FiO2:80%), pCO2 28 Hgmm, BE -1,5
mmol/l, lactate: 1,7 mmol/l (norm.)
Horowitz ratio: pO2 (Hgmm)/FiO2% (phys: 100/0,21=476),
in this case: 221/0,8=276.)
Chest X-ray
Before intensive care after

Pulmonary hypoxemy because of right to left shunt ( ARDS)
Fiziológiás Eltérés a V/Q
gázcsere arányában
physiologic V/Q↓
Jobb-bal shunt
right-left shunt
pl. ARDS
Can not improve
with O2 treatment
Pulmonary circulation with
right-left shunt
Evaluation of ratio
(patient with intubation)
*
In healthy subject 80%-os O2

content in inspired air (FiO2) (red star). A tárgyalt
In this patient PaO2 221 Hgmm
(purple star). 20% shunt in
*
pulmonary circulation
Blood gas and acid-base titration
Treatment:
invasive, biphasic positive pressure ventilation (4 days)
Imipenem-cilastatin + clarithromycin parenteral antibiotics
Five days later:
CRP: 12 mg/l
pH 7,45, pO2 97 Hgmm, pCO2 36 Hgmm, BE 1,5 mmol/l, lactate
0,4 mmol/l, O2 supplementation 2 l/min (FiO2: 27%)
Horowitz quotient: 97/0,27 = 359 (still not physiologic)
II. 69 years man, main symptom is dyspnoea, high temperature,
chest pain
Anamnesis
50 pack year smoking, hyperlipidemia, hypertension, acute
myocardial infarction, coronaria bypass, chronic obstructive
pulmonary disease (COPD), hospitalisation because of acute
exacerbation, non-invasive ventilation (acute, but reversible
type 2 respiratory failure)
Pharmacotherapy
Aspirin, angiotensin con. enzime blokade, Betaloc (non-
selective β-bloccer), inhaled long acting β2-agonist (LABA) and
inhaled long acting musc. antagonist (LAMA)
Symptom
Fever (39.0oC), chest pain, dyspnoea
Signs
Physical findings:
RR: 145/82 Hgmm, P: 90/min
Whistle in the lung, crepitation above the diaphragm on the left side
Lung function:
irreversible big- and small airway obstruction), FVC 1,35 L (34%), FEV1 0,58
L/mp (19%), FEV1/FVC 0,5 (<0,7 can be COPD), Rairway 405%,
Blood gas, acid-base titration:
pO2 66 Hgmm (2 L/min O2 inhalation - FiO2 27%)
pH 7,40
pCO2 43 Hgmm
Chem. Lab.:
CRP 88 mg/L
Elektrolites in normal range
GGT and LDH elevated
Troponin T negative, BNP in normal range
ECG:
no novum sign
K. Z. 69 years old, dyspnoea, chest pain
Flow-volume loop pressure-flow loop
spirometry body pletysmography
Áramlási seb. Áramlási seb.

Kilégzés belégzés
←
←
térfogat nyomás
Belégzés kilégzés
hyperinflation, airway resistance: 4-x

Dynamic compression of the small airways
Chest X-rays
kkkkk
Kezelés előtt kezelés után
Higher level of left side of the diaphragm, left costo-diaphragmatic angle is rounded,
Heart configuration is abnormal (pulm. hypertension?). Sternotomy (coronary bypass).
Treatment and Blood Gas Results
• Treatment
Antibiotics, systemic steroid, inhaled bronchodilators
(like in COPD acute exacerbation)
before after
__________________________________________________
PaO2 66 Hgmm (+2 l/perc O2) 60 (O2 nélkül)
PaO2/FiO2 244 286
pH 7,40 7,43
pCO2 43 47
BE +1,0 mmol/l +6,1 mmol/l
III. 33 years woman, fatigue, fever, dyspnoea, hey
fever
Anamnesis
33 years old, hospitalized before because of astma, but regular maintance astma
treatment, no smoking
Symptom
Fatigue, 39oC fever, coughing, no expectoration, right chest pain (sharp, connection
with breathing, motion), mild dyspnoea
Mild whistle in the end of exspiration, RR 115/78, P: 98/min
Blood gas and laboratory result

PaO2 65 Hgmm, PaCO2 30 Hgmm, pH 7,48, BE -3,0 mmol/l, CRP 300 mg/l, Procalc 1,5
ug/l, electrolites in normal range
Sputum bacteriological examination

negatíve
Lung Function
Áramlás áramlás
kilégzés belégzés
térfogat nyomás
Belégzés kilégzés
Perihilar infiltration on the right side in astmatic
woman
Before tratment After treatment

xxxxxx
ECG (negative)
Treatment and new Results
1. Amoxicillin-clavulonate + clarithromycin per os.

2. Daily 120 mg, than 80 mg systemic steroid iv.
3. Inhaled short acting β2 agonist daily 6x
No improvement in CRP levels in 3 days, change to
4. ceftazidim + clarithromycin iv. antibiotics (anti-pseudomonas
effect).
Fever absent in one week, radiological improvement, CRP 12

mg/l.
No airway obstruction in lung function.
49 years woman anamnesis
• Open lung surgery in 2004: „usual interstitial
pneumonia (UIP)” = idiopathic pulmonary
fibrosis
• 2004-2010 january, Sopron: freqvent systemic
steroid+azathioprin treatment, but clinical
condition is worsening
• 2010. january: Pulmonary Clinic examinations
for lung transplant evaluation
2010. january: main symptoms, physical
findings
• Severe exertional dyspnoe (desaturation,

cyanosis)
• No dyspnoea at rest
• Cushingoid shape
• Crepitatio of the lung in auscultation
• 6 minutes walking distance: 259 m (reference
value>600 m)
Postero-anterior CHEST X-RAY: Diffuse
reticular sign
HONEY COMBING AND TRACTION BRONCHIECTASIS
(2010. january)
FLow-volume loop
2010 summer:
DLCO 62%,
TLC 41%
Blood gas, chemistry
• Art pO2: 40 Hgmm, with 8 l/min O2 55 Hgmm

• Art pCO2: 30 Hgmm (VA = 6 l/perc)
• CRP: 40 mg/l
• Sedimentation: 50 mm/ó
• LDH: 720 U/l
• HbA1c. 9%
• Chol: 6.9 mmol/l
• Trig: 4.1 mmol/l
• Glu: 9.1 mmol/l
• Kidney, liver, blood count in normal range
Invasive cardiology
• Pulm. art. pressure.: 39/19 Hgmm, mean
pressure: 28 Hgmm
• Coronary perfusion: left ventricular
dominancy (physiologic)
2010. january-jul (II.)
• Recurrent bronchopneumonia: Pseudomonas
aeruginosa
• Lung Transplantation Committee: no
indication because of the shape of the patient.
Shape, Lung-mechanics
Condition before Exitus
• High temperature, high CRP, complete exercise

intolerance, circulation is compensated. With
O2 supplementation pO2 55, pCO2 30 Hgmm.
• Cyanosis, syncope at night, circulatory-
ventilatory failure, unsuccesful cardio-
respiratory resustitation.
Lung histology: reduced aircontent, lymphocytic infiltration,
increased interstitium, hyperemia, bronchial lumen with
sputum, weightening in vessel`s wall
Direct cause of death: DILATATION VENTRICULI
DEXTRI CORDIS
Concomittant disease:
bilateral bronchopneumonia
Main disease:
Idiopathic pulmonary fibrosis
Thank you very much for your
attention!
COUGH
Dr. Hidvégi Edit PhD

Upper/lower airways and diseases
Sinuses
sinusitis
Nose
rhinitis Ear
otitis
Pharynx Tonsills
pharyngitis tonsillitis
Trachea
tracheitis
Lung
pneumonia
Bronchii
bronchitis
Cough mechanism
Four phases
irritation – inspiration – contraction – blow out
• Short, deep inspiration, than forced exspiration with closed glottis

• Reflex to clear the airways.
• Reflex circle:
- Receptors (Large airways, auditory canal)
- Afferent fibers (n. vagus, n. laryngeus, n. glossopharyngeus, n. trigeminus)
- Cough center (pons – medulla oblongata)
- Efferent fibers: coordination of larynx – diaphragma – intercostal muscles
Types and causes of cough
Mucus (productive) Dry (improductive)
Acute Bronchitis acuta PNDS (postnasal drip sy.)
Sinobronchitis Pharyngitis, Laryngitis acuta
Tracheitis Atypical pneumonia
Pneumonia Pleuritis
Asthma
Embolism
Irritation of auditory canal
Foreign body
Lung tumor
Chronic Chr. bronchitis (COPD) Emphysema
Lung tumor Cardiac disease
Bronchiectasis Reflux (GERD)
Tuberculosis Pulmonary fibrosis
ACE inhibitor
Tic (psychic)
Acute Bronchitis acuta Atypical pneumonia
Sinobronchitis Pleuritis
Tracheitis Asthma
Pneumonia Embolism
PNDS (postnasal drip sy.) Irritation of auditory canal
Pharyngitis, Laryngitis acuta Lung tumor
Foreign body
Bronchiectasis Pulmonary fibrosis
Tb ACE inhibitor
Reflux disease (GERD) Tic (psychic)
85% of airway infections are viral
Influenza Adenovirus
SARS-CoV2
RSV
Bacterial pathogens
Streptococcus pneum. Moraxella catarrh.

Haemophilus influenzae
Atypical bacteria
• 3 of those:
• Chlamydia pneumoniae
• Mycoplasma pneumoniae
• Legionella pneumophila
• Intracellular pathogens
• Interstitial pneumonia Chlamydia
Mycoplasma
Legionella
Therapy
•Central drugs •Peripheral drugs
- Opioid alkaloids (codein) -Expectorants
- Semi-synthetic: -Secretolytics
dionin = etilmorfin - ipecacuanha
dihidrocodein = hidrocodin - saponin
- synthetic: - guajacol
dextrometorphan - essential oils
noscapin = narcotin - iodine salt
- Non opioid drugs - ammonium salt
butamirat -Mucolytics
pentoxiverin - acetylcystein
- carbocystein
- bromhexin
Local drugs
- ambroxol
Anesthesia of the receptors
lidocain
Surface coatings
honey, sweets
Thank you for your
attention!
COUGH
Dr. Edit Hidvégi PhD

Pulmonologist
Upper/lower airways and diseases
Sinuses
sinusitis
Nose
rhinitis Ear
otitis
Pharynx Tonsills
pharyngitis tonsillitis
Trachea
tracheitis
Lung
pneumonia
Bronchii
bronchitis
Cough mechanism
Four phases
irritation – inspiration – contraction – blow out
• Short, deep inspiration, than forced exspiration with closed glottis

• Reflex to clear the airways.
• Reflex circle:
- Receptors (Large airways, auditory canal)
- Afferent fibers (n. vagus, n. laryngeus, n. glossopharyngeus, n. trigeminus)
- Cough center (pons – medulla oblongata)
- Efferent fibers: coordination of larynx – diaphragma – intercostal muscles
Acute Bronchitis acuta PNDS (postnasal drip sy.)
Sinobronchitis Pharyngitis, Laryngitis acuta
Tracheitis Atypical pneumonia
Pneumonia * Pleuritis
Asthma
Embolism *
Irritation of auditory canal
Foreign body
Lung tumor
Lung tumor * Cardiac disease *
Bronchiectasis * Reflux (GERD) *
Tuberculosis * Pulmonary fibrosis
ACE inhibitor
Tic (psychic)
Acute Bronchitis acuta Atypical pneumonia
Sinobronchitis Pleuritis
Tracheitis Asthma
Pneumonia Embolism
PNDS (postnasal drip sy.) Irritation of auditory canal
Pharyngitis, Laryngitis acuta Lung tumor
Foreign body
Bronchiectasis Pulmonary fibrosis
Tb ACE inhibitor
Reflux disease (GERD) Tic (psychic)
85% of airway infections are viral
Influenza Adenovirus
SARS-CoV2
RSV
Bacterial pathogens
Streptococcus pneum. Moraxella catarrh.

Haemophilus influenzae
Atypical bacteria
• 3 of those:
• Chlamydia pneumoniae
• Mycoplasma pneumoniae
• Legionella pneumophila
• Intracellular pathogens
• Interstitial pneumonia Chlamydia
Mycoplasma
Legionella
Therapy
•Central drugs •Peripheral drugs
- Opioid alkaloids (codein) -Expectorants
- Semi-synthetic: -Secretolytics
dionin = etilmorfin - ipecacuanha
dihidrocodein = hidrocodin - saponin
- synthetic: - guajacol
dextrometorphan - essential oils
noscapin = narcotin - iodine salt
- Non opioid drugs - ammonium salt
butamirat -Mucolytics
pentoxiverin - acetylcystein
- carbocystein
- bromhexin
Local drugs
- ambroxol
Anesthesia of the receptors
lidocain
Surface coatings
honey, sweets
Thank you for your
attention!
Inhalation therapy
Dr. Erdélyi Tamás

SE Pulmonológiai Klinika
2022.09.28.
I. Pharmacokinetics
II. Types of inhalers
III.Further possibles fields of usage
IV.Factors influencing effectiveness
Pharmacokinetics
Primary goals are increasing local
effectivity and reducing side effects.
Reaching the correct concentration at the

appropiate locus.
Inhalative agents:
• Corticosteroids
• β2- agonists
• Muscarinic
• Antibiotics
Weibel 1963
Specific pharmacokinetical
processes of the respiratory system
1. Deposition
2. Dissolution
3. Mucociliariy and macrophage clearance
4. Tissue absorption
5. Tissue retention and metabolization
6. Entering systemic circulation
Specific pharmacokinetical processes I.
Jens Markus Borghardt, Charlotte Kloft, Ashish Sharma, "Inhaled Therapy in Respiratory Disease: The Complex Interplay of Pulmonary Kinetic Processes", Canadian Respiratory Journal, vol. 2018, Article
ID 2732017, 11 pages, 2018. https://doi.org/10.1155/2018/2732017
Specific pharmacokinetical processes II.
Specific pharmacokinetical processes III.
Trachea Small airways Alveoli
Absorption
speed
Systemic
absorption
Mucociliariy
and
macrophage
clearance
Ideal
deposition*
*regarding patients with obstructive airway diseases

Deposition
Influencing factors:
• Agent size
• IVC
• Inhalation flow and PIF
• Inhalation and breath-hold time
• Respiratory anatomy
• Inhaler characteritics
Trachea Small airways Alveoli
Impaction
Sedimentation
Diffusion
Deposition distribution
II. Inhaler types and mechanisms
Nebulizer Pressurized metered-dose inhaler (pMDI)
Dry powder inhaler (DPI) Soft mist inhaler (SMI)

Nebulizer
Advantages: Disadvantages:
• No need for coordination • Inaccurate dosing
• Applicable in emergency situations • Expensive
• Need for maintenance
Jet nebulizer Ultrasound nebulizer Mesh nebulizer

pMDI
• Small particle size • Need for accurate coordination
• Effective deposition (excluded Autohaler®)
• Cheap • Hig particle velocity
Earlier the propellant was

chlorofluorocarbon (CFC) volt, since
the Montreal Protocol
hydrofluroalkane (HFA) is in usage.
HFA leads to slower spray causing a

decrease in impaction.
First pMDI:
1956, Medihaler-epi®
Inner structure
pMDI
Ventolin Evohaler® Symbicort pMDI®
Autohaler® Trimbow pMDI®

DPI
• No need for accurate coordination • Depends on PIF
• A lot of subtypes are available • Influenced by humidity
• Lower effectivity
(Excluded extra-fine particle inhalers)
First DPI:
1967, Spinhaler ®
Multi-dose DPI Capsule DPI

DPI
• Sufficiently strong inhalation is required for proper effectiveness
• Particle size is not constant, it depends on PIF
• PIF defines the mass median aerodynamic diameter (MMAD)
• The carrier is lactose
• Deaggregation is reduced by humidity
The faster the inhalation, the smaller the particles that come out of the
device.
Capsule DPI inhalers:
Spiriva Handihaler® Ultibro Breezhaler® Braltus®

DPI
Multi-dose DPI inhalers
Symbicort Turbuhaler® Bretaris Genuair®
Foster Nexthaler® Trelegy Ellipta®

DPI
Electron microscopic image of lactose and salbutamol.
Stein SW, Thiel CG. The History of Therapeutic Aerosols: A Chronological Review. J Aerosol Med Pulm Drug Deliv. 2017;30(1):20-41. doi:10.1089/jamp.2016.1297
SMI
• Needs less accurate coordination • Expensive
• Effective deposition
Respimat® inner structure and its nebulizer (Uniblock)

Agents in usage
GINA Report 2021
GOLD Report 2022

III. Further possible fields of usage
Medihaler-epi, created in 1956, was recalled

in 1996 for its CFC content, and they could
not guarantee the previously described
warranty period.
In 1957, the preparation containing

epinephrine and isoproterenol appeared
under the name Duo-Medihaler.
Inzulin and iloprost
Afrezza®
Exubera®
The FDA has recalled devices using

inhaled insulin due to hypoglycemia as
a side effect. Breelib® - Iloprost
Mesh nebulizer
Antibiotics
Tobi Podhaler®
Colomyicin®
Colobreathe®
Gentamicin® Fungizone® - amfotericin B

Off-label Off-label
Cayston® - aztreonam
IV. Factors influencing effectiveness
• Age, education, socio-economic status, physical condition,

comorbidities, disease awareness
• Lifestyle, family support
• Psychological status
• Dosage, ease of use, patient education
• Price, appearance, size, taste
• Doctor-patient relationship, communication
ADVANTAGES DISADVANTAGES
 Effective: low dose  Need device
 Rapid effect: drug  Depends from the
directly join to their patient compliance
receptor  Depens from the
 Safety: small side inhalation technic.
effect, local
deposition
1. Meter dose inhalers (MDI)
 with special HFA-suspension (Modulite®)
2. Dry powder inhaler (DPI):
 single dose inhalers (Aeroliser, Handihaler,
Breezhaler)
 Multi dose inhalers (Turbuhaler, Diskus,
Genuair)
3. Soft Mist InhalerTM Respimat
4. Nebulizers work with
 ultrasound
 Compresed air
30 #
good adherance patient
26,4
25 poor adherance patients
#
20 0,3 0,27
0,25
15 n=1232
0,2
11,3 0,15
10 0,15
0,1
5 n=4880
0,05
0 0
mortality admission to hospital with
AE
Vestbo J. Adherence to inhaled therapy, mortality and hospital admission in COPD.

Thorax. 2009 Nov;64(11):939-43. 20
 Older age
 Use of multiple devices
 Co-mobidities (arthritis, stroke, neuropathy)
 Lack of previous education on inhaler

technique.
% 96,8
100
87,4
80
66
60 53 non educated
47 patient
40 34 educated patient
20 12,6
3,2
0
stop tapper dose compliance adherence
treatment
Incorvaia C. 2011. Ann. Thorac. Med 6(4):242-243

n=1305
Which is the good education on inhaler

technique?
 Minimum 6 min.
 Combined
Sestini P. Prescription bias and factors with
associated with practice
improper use of inhalers. J
Aerosol Med 2006;19(2):127-136.  Repeated education
Before trainig After training
37% 53%
RESPIMAT →
Soft Mist inháler
Brand P- Higher lung deposition with Respimat Soft Mist inhaler than HFA-MDI in COPD
patients with poor technique. Int. Chron. Obdstructi pulmon Dis. 2008;3(4):763-70.
1. Insert the cartridge or canister into the base of the inhaler
device.
2. Press down on a hard surface to secure the cartridge into the
device and close the base.
 Breathe out fully  Press your lips around
 Open the cap. the mouthpiece without
covering the air vents.
Begin to breathe in
slowly and deeply
through the mouth.
Hold the inhaler upright
with the cap closed.
Turn the base in the
direction of arrows until
it clicks.
Inhalator is ready Inhalation was succesfull
Signalling of the successfull inhalation

 Clicking when breathing
 After the correct inhalations the chencking
window turn to red.
Audiovisualis kontroll
Open
Breath
in
Close
1. Woepse M et al. 2013. Poster: B29. 2. Riley JH et al. 2013. Poster: P4145.
The theraputic successfull depends from the efficient
molecules and the correct use of inhaler.
 Education the patients
 Regularly check inhalation technique
Lifebelt for the patient

Légzésfunkciós vizsgálatok
Dr. Losonczy György

Egyetemi tanár
General exam of patients suspect of lung disease
history X-ray
physical exam
lung function test blood gas
ECG chemistry
hematology
HEALTHY
OBSTRUCTIVE
RESTRICTIVE (Fibrosis)
FIBROSIS (CT)
Classification of lung diseases according to
mechanics of disordered ventilation
Obstructive
Increased airway resistance (e.g. COPD, bronchial
asthma)
Restrictive
Decreased compliance and diffusion capacity
(e.g. interstitial lung diseases, Boeck-sarcoidosis,
fibrosis)
Mixed
Static lung volumes in health and disease
SPIROMETRY. STATIC LUNG VOLUMES
SPIROMETRY. DYNAMIC PARAMETERS:
Expiratory volume during 1st second of forced expiration:
FEV1
Relationship between lung function (FEV1) and
arterial pO2
THE VOLUME FLOW LOOP
DETERMINATION OF
AIRWAY RESISTANCE (R=P/Q)
Q
Relationship of alv-atm P difference and air flow.
Normal and abnormal pressure-flow loop patterns
insp.
flow↕ i
exp.
↔
pressure
Exp. forced maneuver
THE VOLUME-FLOW
LOOP volume of in-
at rest and expired air
Airflow 

Insp.
THE PRESSURE-FLOW Insp.

LOOP Alveolo-atmos.
pressure difference
Airflow 

Name: SF, 21 years old male,
b.w.:76 kg
TLC: 7,3 L (99%) expir. forced maneuver

RV: 1,91 L (113%)
FVC: 4,99 L (92%) at rest VOLUME
FEV1: 4,32 L (94%) FLOW
PEF: 8.75 L/s (86%)
Raw: 0.20 kPa x s/L (90%) inspir.
PO2: 90 mmHg
pCO2: 35 mmHg
pH: 7,45
BE: 2.0 mmol/L
NORMAL LUNG inspir. Alveolo-

MECHANICS AND atmospheric
FLOW pressure diff.
ALVEOLO-CAPILLARY
GAS EXCHANGE expir.
Name: Gy.S. 26 years old male, bw:60 kg
Dyspnea at rest, long expiration
expiration
before after 2-mimetic
2
TLC: 115% 104%
RV: 140% 114% vol.
FVC: 80% 99% flow
FEV1: 70% 94%
PEF: 71% 97%
Raw: 200% 63% inspiration
pO2: 70 mmHg
pCO2: 30 mmHg
Ph: 7,5
BE: -5 mmol/l inspiration
flow 2
BRONCHIAL ASTHMAREVERSIBLE pres.
OBSTRUCTION
expiration
CHRONIC OBSTRUCTIVE Volume-flow
PULMONARY DISEASE expir.

(COPD)
Name: FL, 76 years old male, b.w.66 kg,
60 p/y, dyspnea at rest
TLC: 7.86 L 129%

RV: 4.02 L 154% inspir.
FVC: 2.88 L 90%
FEV1: 1,22 L 51% Pressure-flow
PEF: 2.98 L/s 42%
Raw: 0.60 kPa x s/L 272 %
inspir.
pO2: 55 mmHg
pCO2: 50 mmHg
pH: 7.40 expir.
BE: 12 mmol/l
HEALTHY
OBSTRUCTIVE
FIBROSIS (CT)
Healthy
Emphysema:
loss of alveo-
lar walls with
consequent
enlargement
of air spaces
and loss of
radial traction on small
airways
Mechanism of large and small airway obstruction* in
chronic obstructive pulmonary disease (COPD)
*irreversible to a large extent

Small airways are kept open during forced expiration
by elastic recoil (elastic fibres) of alveolar septa
Volume, flow and small airway compression
during expiration
small airway compression

flow in expiration during expiration
pleural
space
airways
volume
Volume-flow loop
in COPD.
Compression of
airways during Dynamic compression
forced expiration
flow↕ volume
ACUTE DYNAMIC HYPERINFLATION
DURING
Dynamic EXERSIZE
Hyperinflation IN COPD
with Exercise in COPD
TLC Terhelés
IC IRV IC IC
NORMÁL
Health
EELV
RV
TLC
IC IC IC
COPD
EELV
RV
HEALTHY
OBSTRUCTIVE
FIBROSIS (CT)
Name:
O.K., 36 years old male, bw: 61 kg
tachypnea at rest, severe
dyspnea during mild exersize;
TLC: 3.2 L (47%) volume

flow
RV: 1.42 L (69%)
FVC: 1.55 L (35%)
FEV1: 1.56 L (43%)
PEF: 7.33 L/s (83%)
Raw: 0.11 kPa x s/L (50%)
Diff. cap.: 2.49 mmol/min x kPa) (25%)
pO2: 65 mmHg
pCO2: 32 mmHg
flow pressure
pH: 7.50
BE -3 mmol/l
PULMONARY FIBROSIS
When oxygen diffusion
is impaired*, oxygen up-
take may be sufficient
at rest. During exercise
contact time shortens,
and leads to reduced
uptake of oxygen.
*thickenes alveolo-
capillary membrane
Effect of exercise on arterial pO2
in fibrosis. Case of a 34 years old
female patient
_________________________________________
before after*
climbing 2 floors (stairs)
__________________________________________
pO2 63 mmHg  35
pCO2 33 mmHg  40
Lactate 1 mmol/L  9.4
BE 3.0 mmol/L  -2.5
pH 7.49  7.36
*nausea, tachycardia, tachypnea, hypertension, pallor, profuse sweat
Noninvasive ventilation
Dr. József Lukácsovits

Assistant Professor
SEMMELWEIS UNIVERSITY
FACULTY OF MEDICINE
DEPARTMENT OF PULMONOLOGY
Gas exchange unit
Respiratory failure
The history of non-invasive ventilation
John Dalziel, Scottish physician built the first mechanical ventilator ,

operated by hand, in 1828.
This was the first ventilator functioning with negative pressure.
The history of non-invasive ventilation
-Philipp Drinker built the first ‘iron

lung’ in 1928.
-It was perfected by Emerson in 1931

and widely used during the
polyomielitis epidemic between 1930-
1960.
- The ‘iron lung’ nowadays is used mostly for research.
- New types of negative pressure ventilators are the cuirass

ventilators.
-There were not enough iron lungs during the 1952
Copenhagen polio epidemics, and for this reason,
positive pressure ventilators were also considered and
tested - with very good results.
-Positive pressure ventilators have been routinely

used in the US in rehabilitation centers since the
1960s.
-Since the 1980s technical advances have made home

ventilation of patients with sleep apnea possible.
Modern invasive ventilators
-They are used in ICUs mainly for invasive
ventilation; suitable for non-invasive ventilation as
well
- A central gas source
is used and therefore,
its maximum flow is
about 160 l/min. For
this reason the leakage
can be less
compensated.
Modern non-invasive ventilators
- Small-sized units developed primarily for non-invasive
ventilation.
- They can be used in intensive care, hospital ward and at
home.
- They are usually portable; some models can operate for
several hours on battery.
- Some types can also perform invasive mechanical
ventilation.
- Gas source: electric turbine, creating a flow of about
260 l/min which allows a good leakage compensation.
The structure ofnon-invasive ventilators
Principles of operation
Operating with active

exhalation valve
(closed masc +
separated inspiratory
and expiratory line)
Operating with open

circuit Passive
exhalation valve on the
mask or on the end of
the tube (whisper)
The structure ofnon-invasive ventilators
Non-Invasive ventilator
Ventilation circuit
(flexible tube)
Head strap
Mask
Active humidifier
Components of the mask
Built in
clear plastic
exhalation port
frame Provides continous leak
path in the circuit
soft cuff
Safety valve
allows patient to
breathe in case of Fastners
machine failure for fixing the
head strap
Interfaces
Interface selection
Nasal mask and nasal pillow
• less claustrophobic reaction
• better communication , more effective
cough
• possibility of oral feeding
• less dead space
18
Interface selection
Oronasal mask
• The difficulty breathing in general is
"mouth breathing "
• impedes speech and expectoration
• bigger dead space
• risk of aspiration
19
Interface selection
Full Face Mask
• better fit than the oronasal mask
• its dead space is barely larger than the
oronasal mask
• higher pressures can be used without
sealing problems
20
Interface selection
Helmet
Advantages:
• good insulation , good tolerance
• it improves the oxygenation, but is less
effective in reducing the PaCO2 caused
by larger dead space
• fewer complications (skin ulceration,
eye irritation, stomach bloating)
Disadvantages:
• too noisy
• less efficient triggering, caused by big dead space
21
Ventilator settings
 IPAP (inspiratory positive airway pressure): 8-16 cmH2O
 EPAP (expiratory positive airway pressure): 4-6 cmH2O
 RR (respiratory rate) (in T and S/T modes): 12/min
 Ramp (pressure rising time): 1-4 ms
 I:E ratio (physiological : 1:2)
 individual settings !
Noninvasive mechanical
ventilation modes
 CPAP
 BiPAP
 spontaneous (S),
 timed (T),
 spontaneous/timed (S/T),
 pressure controlled (PC).

CPAP
S mode
T mode
S/T mode
PC mode
Goals of NIV
In acute care settings In chronic care settings
- Relieve symptoms - Improve sleep duration
- Reduce work of and quality
breathing - Prolong survival
- Improve or stabilize gas - Maximize quality of life
exchange
- Optimize patient
comfort
- Avoid intubation
Indications of NPPV
•Hypercapnic respiratory failure: Obstructive diseases,
restrictive diseases
• Hypoxic respiratory failure: acute pulmonary edema,

pneumonia, ARDS, Trauma
• Immunocompromized patients; do not intubate

patients; post operative patients; weaning after early
extubation
Exclusion criteria of NPPV
• Respiratory arrest
• Cardiovascular instability
• Impairment of consciousness
• Insufficient collaboration
• Excessive amount of secretion
• Facial or gastroesophageal operation, craniofacial
trauma, burns
Relative contraindications
• angina pectoris
• recent acute myocardial infarction (<2 weeks )
• large amount of mucus production (the removal of

secretion can be made with bronchoscopy)
• problems with leak
• edentulous patients
• beard
INITIATION OF NIV
- Appropriately monitored location
- Patient in bed or chair sitting at > 30-degree angle
- Select and fit interface
- Apply headgear - avoid excessive strap tension
- Connect interface to ventilator tubing and turn on
ventilator
- Start with low pressures (IPAP: 8-12 cmH2O) in
„S” mode, with backup rate ~ 12-14/min; PEEP:
of 3 to 5 cmH2O
INITIATION OF NIV
- Gradually increase inspiratory pressure (15 to 20
cm H2O) to achieve a tidal volume of 8-10 ml/kg;
- Provide O2 supplementation as needed to keep O2
sat > 90%
- Check for air leaks, readjust straps as needed
- Monitor the blood gases (1/2 h, 1 h, 2h…)
NPPV is to be stopped if
• There is an urgent indication for intubation
- Circulatory or respiratory arrest
- Coma
- Secretion retention
- Airway protection
• No improvement in gas exchange or dyspnea
• Hemodynamic instability (cardiac ischemia,

arrhythmias)
• Mask intolerance
• No improved in mental disorder in agitated hypoxic

patients after 30 minutes use of NPPV
The possible complications of NIV
Complications: Possible therapies:
• Discomfort associated with • Check the fit and straps; use

the mask of water-based gel on contact
points; try different types of
masks
• Skin erythema and nasal • Loosening of the straps;

bridge ulceration application of foam sheets;
creams with local steroid and
antibiotic; try different types
of masks
• Claustrophobia
• Smaller mask, sedation
• Pressure and flow related
complications
- nasal congestion - nose drops; antihistamine;
nasal steroid
- sinus or ear pain - reducing pressure
- dryness of mouth and nose - nasal saline; humidification
- eye irritation - check mask fit; reduction of

leaks
- stomach bloating - Simeticone; sedation;
pressure reduction
• serious complications
- aspiration pneumonia careful patient selection
- hypotension pressure reduction
- pneumothorax pressure reduction

Monitoring
• Patient's comfort and work of breathing
- Bedside observation
- Discomfort, related to the mask or airflow
• Physiologic response
- Monitoring circulatory parameters (RR, HR)
- Synchrony with the ventilator
-Change in accessory muscle activity
- Monitoring of air leaks and Vt
•Gas exchange
- Continuous pulse oximetry
- Arterial blood gas analysis (½, 1, 2 … hours after starting
NPPV)
NPPV in COPD patients
• Reduces Mortality • Goals and priorities:
• Reduces the intubation - Providing adequate gas
rate exchange
• Reduces the length of -disencumber the
ICU stay respiratory muscles
• Improves pulmonary gas
exchange
• Reduces the work of
breathing
COPD patients with acute exacerbations and respiratory acidosis
Use of standard medications and oxygen therapy
pH>7,35 Repeated blood gas analysis Relative

NIV not contraindications :
coma , confusion, need to airway
indicated protection, associated severe
disease , vomiting, intestinal
obstruction , hemodynamic
instability
7.3<pH<7,35
NIV advised pH<7,2
7,2<pH<7,3
80% will get better with NIV advised
conventional treatment. NIV strongly taking into
Only 10% of patients advised account the
need NIV to avoid ETI. In 50% of clinical
NIV leads to more rapid patients ETI conditions of
resolution of dyspnoea. can be avoided the patient !
Thank you for your attention
2020.02.28.
Gas exchange:
introduction
Oxygen therapy Normal metabolism…

 requires O2
 requires elimination of the produced CO2
Gabor Horvath, MD Ph.D. O2 demand:
associate professor  4 ml / min / kg (= 280 ml / min / 70kg)
Normal O2 levels:
Depertment of Pulmonology
Semmelweis University Budapest  Saturation > 95%
 PaO2 = 90-100 mmHg (= 102 – 0,33  age)
Pulse oximetry Arterial blood gas measurement

Measurement of O2 saturation:
 Fraction of O2-saturated hemoglobin
relative to total hemoglobin.
 Normal: > 95%
 Tolerable: 90-95%
 Tissue hypoxia: < 90% Capillary sampling Arterial sampling
 Incorrect readings in poor peripheral  Minimal dyscomfort  Painful, bleeding
blood circulation!
 Less accurate  Accurate
 Less accurate than arterial blood gas
measurement  Normal circulation  Critically ill patient
Correlation of O2 saturation History of O2

and PaO2 therapy
Joseph Priestly (1733-1804)
• English Separatist theologian, natural philosopher,
chemist, innovative grammarian, multi-subject educator,
and liberal political theorist
• credited with the discovery of O2
In 19th century:
• Physicians used atmospheric pressure O2 to „treat” various
health problems
• It was considered meaningless after having demonstrated
that arterial blood was almost saturated with O2
1
2020.02.28.
Respiratory failure Definition of respiratory failure

 Lung diseases: asthma attack, COPD, pneumonia, pulmonary
fibrosis, pulmonary embolism, pneumothorax, ARDS, etc.
 Hypotension (RRsyst < 100 mmHg)
Partial (type 1) = hypoxia
 Abnormal heart function (regardless of specificity)  PaO2 < 60 mmHg
 Metabolic acidosis
 Acute myocardial infarction  (PaCO2 ~ 40 mmHg)
 Severe trauma and/or serious blood loss
 Septicemia
 Any form of acute loss of consciousness Global (type 2) = hypoxia + hypercapnia
 Poisoning
 PaO2 < 60 mmHg
 Smoke, CO, other toxic gas inhalation
 Birth complications  PaCO2 > 50 mmHg  potentially life-threatening!
 Transport of a critically ill patient
 Postoperative status
Hypoxia Hypercapnia When and how much O2

(PaO2 < 60 mmHg) (PaCO2 > 50 mmHg) should be given?
Anxiety Anxiety As soon as possible…
Headache Headache
 Early correction of hypoxia can reduce complications
Confusion Somnolence (circulatory arrest, arrhythmia, etc.).
Pale, cyanotic skin Warm, moist skin As much as needed…
 Target O2 saturation: > 90%, optimal: > 95%.
Bradycardia Tachycardia
Blood pressure  Blood pressure   At least for 14-16 hours!
 High O2 flow can be dangerous!
Tachypnea Tachypnea  Having corrected hypoxia, O2 flow can be reduced.
Methods of O2 supplementation O2 supplementation

Nasal cannula, face mask
• Simple, cheap, safe, comfortable
for the patient
• No moving parts
• Nasal mucosal injury may occur
at high flow rates (> 3 l/min)
• Irritation of nostrils
• High O2 flow rates require
humidification!
2
2020.02.28.
How much is the inhaled O2

O2 supplementation
concentration (FiO2)?
A
Which one is
B the correct
reading?
C
FiO2 = 20% + 4  flow rate (l/min)
Potential problems
Technical problems…
 Poor water tank conditions (poorly fixed tank, low water
level, algae)
 Leaky connectors
 Defective flow meter
Flow adjusment problems…
 Too high/low O2 flow for the patient
 Confused patient may switch the flow meter to dangerous
high/low O2 levels
Long-term oxygen therapy The effect of LTOT (15 hours/day)

(LTOT) on survival in COPD patients
Principles:
 Long-lasting (> 14-16 hours/day) adminstration
 Mostly for night use 5-year survival is 50%
 Humidification higher in the O2 group n : 42 O2 2 L/perc
than in controls.
Forms of O2 supplementation:
 Compressed O2
n: 45
 O2 concentrator
 Liquid (frozen) O2
3
2020.02.28.
LTOT for 15/24 hours a day and Benefits of LTOT

the survival in COPD patients in COPD
 Reduces dyspnea
 Physical capacity increases
3-year mortality 2x lower  Survival improves (by 6-7 years!)
in 24-hour/day group than
 Circulation improves (reduces the
in the 15-hour/day group. n : 203
progression of pulmonary hypertension)
 Reduces polycythemia
 Mental health improves
 Quality of life improves
 Patient mobility improves
Indications of LTOT Compressed

in COPD O2
In clinical remission (≥ 3 months after COPD exacerbation)
After smoking cessation
If PaO2 ≤ 55 mmHg or SaO2 ≤ 88%
If PaO2 55-60 mmHg and...
 polycythemia (htk > 55%) and/or
 cor pulmonale
Requires blood gas analysis
 2x (2 weeks apart), without O2 supplementation
How long does a 20-liter (200 bar)

Compressed O2
O2 tank can last?
O2 tank: 10 or 20 liter volume, 200 bar pressure Flow rate Time
Other part: pressure reducer, humidifier, nasal cannula
1 l/min ~ 66 h
2 l/min ~ 33 h
Advantages Disadvantages 3 l/min ~ 22 h
Quiet Heavy - fixed 6 l/min ~ 11 h
Cheap for patients High costs
Well-organized care Must be replaced frequently 10 l/min ~6h
Risk of explosion
Patient might „economize"
4
2020.02.28.
O2 concentrator O2 concentrator
Produces 90-96% O2 from air, using electricity

Principle: zeolit filter absorbs atmospheric N 2
Advantages Disadvantages
Portable Relatively inexpensive for Electricity bill for the patient
the patient Expensive device
No tank change Cannot produce high flow
Safe Noisy
Maintenance is required
Fixed May broken down
Power outage
Liquid (frozen) Liquid (frozen) O2

O2
Principle: O2 gas is liquid at -183 °C, its volume is reduced
Parts: storage tank + rechargeable unit + demand valve
Advantages Disadvantages
Quiet Expensive device
Lasts long Evaporation loss
Patient mobility is ensured Waiting list
Can produce high flow Maintenance is required
Some noise
Recommendations for LTOT Danger of O2 supplementation

Target: PaO2 = 60-65 mmHg (SaO2 = 88-90%)
• Non-compliant patient
Flow rate: 1-2 l/min
• Smoker patient
During physical activity: +1 l/min • CO2 retention
Danger: hypercapnia
On airplane:
• Cabin FiO2: ~ 15%
• Recommended: +1 l/min
• Not required: PaO2 > 70 mmHg
5
2020.02.28.
Mechanism of CO2 retention

during O2 supplementation
High risk: in patients with chronic hypercapnia
CO2 sensitivity is reduced/missing in these patients.
Drive to breathe is provide by the low O2 level.
Mechanism:
O2 supplementation elevates PaO2
„Normalized” PaO2 reduces drive to breathe
Reduced breathing volume elevates PaCO 2
Loss of consciousness, coma
6
Pulmonary hypertension
Karlócai Kristóf, Györgyi Csósza

Dep of Pulmonology
2021
Definition of pulmonary
hypertension
Epidemiology
• Incidence of PH 2-6% in general population
Lancet Respir Med. 2016 Apr;4

Classification of pulmonary hypertension
4,2% 10%
0,6%
79%
Rosenkranz el al. Circulation. 2020 Feb 25;141(8):678-693.
ECG in PH
back
back
Chest X-ray
2014 11 03
Echocardiography
TR-Vmax 4,1 m/sec
PAPsy (est) 77
mmHg
IVRT 0,124 msec ( > 0,059), Tei index 1,0 ( > 0,4)
Right heart catheter
Pulmonary angiography in PAH
back
VQ scan in
PAH
What kind of disease?
• Normally the lung circulation is a low
pressure, highly distensible system
• Here instead:
– Arterial walls: thickend
– Arterial lumen: narrow
– Pressure: high
– RV work load: increased
Pathology in pulmonary arterial
hypertension
PAH histology
15
PH WHO group 1
• Pulmonary arterial hypertension (2-4 new cases/M/year)
– Idiopathic
– Heritable
– Drug and toxins induced
– Associated with
• CTD - scleroderma
• HIV infection
• Portal hypertension - cirrhosis
• Congenital heart disease
PAH subtype at diagnosis
(French national registry)
HIV, human immunodeficiency virus; PAH, pulmonary arterial hypertension
Humbert et al. Am J Respir Crit Care Med. 2006;173:1023-1030

The diagnosis is late
•From onset of symptoms to the diagnosis the

average time is 2.5 years
•Reasons of late diagnosis

• Nature of symptoms: unspecific
• Difficulty of different diagnosis
• iPAH diagnosis is based on exclusions
Hoeper ERS 2003

Poor prognosis of PAH
Average survival time (without therapy): 2.8 years
100
80
60
Survival %
40
20
0
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
FU time (y)
D’Alonzo et al. Ann Internal Med 1991;115:343

Recommendations of treatment
in pulmonary arterial hypertension (group 1)
Countinuous iv epoprostenol
Treprostinil in PAH
Side effects of iv treatment
Sc Treprostinil in PAH
local side effects
Local SE : (hyperemia, induration,

local pain) in 86%,
stop of treatment in 8%,
preventing dose escalation in 25%.
Few systemic SE
Evidence based treatment algorithm for pulmonary arterial
hypertension patients (for group 1 patients only)
PH WHO group 2
• LV systolic dysfunction
• LV diastolic dysfunction
• Valvular heart disease
• LV outflow tract obstruction
• Pulmonary vein stenosis
Treatment: Treatment of the underlying disease

PH WHO group 3
PH due to lung disease / hypoxia
Chronic respiratory failure:
• COPD
• ILD
• Mixed restrictive and obstructive
• Sleep-disordered breathing
• Alveolar hypoventilation
• Chronic exposure to high altitude
• Developmental lung disease
Treatment:
• Treatment of the underlying disease
• Long-term oxygen terapy (LTOT)
• NIV at home
PH WHO group 4
Chronic ThromboEmbolic PH
• CTEPH
• Other pulmonary artery obstructions
– Angiosarcoma
– Other tumors
– Arteriitis
– Congenital pulmonary arteries stenoses
– Parasites
Treatment:
• Surgical: PEA pulmonary endartherectomy
• Catheterization: BPA- Balloon pulmonary
angioplasty
• Medication: vasodilatator therapy – in special
cases : inadequate hemodynamic response;
inoperable cases
Summary
▪ PAH is a rare, progressive disease

▪ Diagnosis: based on an exclusion algorithm
▪ Specific therapy: Pulmonary vasodilator
▪ In other PH groups: treatment of primary disease
is required
Pulmonary Rehabilitation
János Varga MD, PhD

Budapest
2021
What is the Next Step in the
Treatment of COPD Therapy?
• New bronchodilator therapy ?

• New anti-inflammatory therapy ?
Time to renew
• Reduction the number of
exacerbations?
conception ?
• Alveolar grow factor ?
• Stem cells ?
Courtesy of
• Care ? Casaburi R
Troosters T et al. Am J Crit Care Med, 2005
Physical Activity in COPD
Chance to Survive (COPD)
Mortality (Survival rate%)
1.0 Garcia-Aymerich Thorax 2006
0.75
0.50
High
Average
0.25 Low
Very low
0.0
0 5 10 15 20
Time (Years)
Very low: Mainly sedentery, no physical activity in freetime
Low: < 2 hours/week low intensity physical activity
Peripherial Muscle Dysfunction in
COPD
Lactate increment
• Low muscle mass during exercise
• Abnormality in capilarisation
• Low oxidative enzime activity
• Low ratio of type I muscle fibers
• Inflammation in muscles
• Corticosteroid myopathy
• Low level of anabolic hormones
• Abnormality in vasoregulation
VO2 (L/min)
Thorax, 2010
Maltais F, et al. Am J Respir Crit Care Med. 1996;153:288-293.

Correlation between physical activity and lung
function, muscle force and walking distance
1.0
12000
 EELV (l)
10000 0.5
Steps.day-1 ( n )
8000
6000 0.0
4000
2000 N=50 R -0.5
0
FEV1 1 2 3 4
Ctrl I II III IV %pred 0.28* Daily activity (Quartile VMU)
TL,CO
%pred 0.38*
QF
%pred 0.45*
Courtesy of 6MWD
Troosters T %pred 0.76*
Troosters ERS 2007
Watz AJRCCM 2008 Pitta AJRCCM 2005 Garcia-Rio AJRCCM 2009
The Effect of Metabolic Syndrome on Physical Activity
No Metabol syndrome
1.9
Physical activity level

Metabolic syndrome
12000
1.7
10000
Steps.day-1 ( n )
8000
1.5
6000
4000 1.3
2000
0 1.1
Ctrl I II III IV CB I II III IV
Severity
Physical inactivity
Courtesy of
enchances the chance of
Troosters T
development of co-
Troosters ERS 2007
Watz AJRCCM 2008 morbidities Watz Chest 2009
Physical Inactivity in COPD Acute
Exacerbation
Low physical activity enchances

the risk of new exacerbation.
The importance of early

pulmonary rehabilitation after
exacerbation.
Day 2 Day 7 Month 1
Pitta Chest 2006 Seymour JM Thorax

Garcia-Aymerich Thorax 2010
2003
Tolerance in COPD

Controlled breathing techniques
• Perth lip breathing (PLB)
• Diaphragmatic breathing
• Turn the trunc to 45 degrees

Respiratory Endurance Training
COPD (n=11)
FEV1: 36±14 %pred
3x10 minutes respiratory
endurance training
MIP: 47±16 vs. 59±20

H2Ocm
MEP:90±45 vs.
123±72 H2Ocm
Respiratory Muscle Training-
Strength Training-
Powerbreathe
Tolerance in COPD

Exercise training has favourable effect in
COPD. High intensity continous training is
more effective compared to low intensity
training.
•Casaburi R, Patessio A, Ioli F et al.: Reduction in exercise lactic

acidosis and ventilation as a result of exercise training in patients with
chronic obstructive lung disease. Am Rev Respir Dis 1991; 143:9-18.
•Casaburi R, Porszasz J, Burns MR et al.: Physiologic benefits of exercise

training in rehabilitation of patients with severe chronic obstructive
pulmonary disease. Am J Respir Crit Care Med 1997;155(5):1541-51.
The Effectivity of Training in COPD
Casaburi, ARRD 1991

The Role of Peroxisome Proliferator-
Activated Receptor-Gamma Coactivator 1α
(PGC-1α) on Muscle Function
Handschin C
Nature 2008
Reduction of Exercise-induced Dynamic
Hyperinflation with Exercise Training at
Submaximal Intensity
Porszasz J, Emtner M, Goto S, Somfay A, Whipp BJ and Casaburi R.

Exercise Training Decreases Ventilatory Requirements and Exercise-
Induced Hyperinflation at Submaximal Intensities in Patients with
COPD.
Chest 2005;128;2025-2034
Continous Training

Continous Training

„Nordic
walking”:
Maximal exercise
capacity and physical
activity
New Technique for Lung Transplant
Patient- Whole Body Vibration
Gloeckl R et al. 2012

Daily activity
monitoring
Tolerance in COPD

• Limitation in gas exchange and oxygen
delivery
Oxygen Favourable Effect
during Exercise in Non-
hypoxemic Patients with COPD
Somfay A, Porszasz J, Lee SM and Casaburi R. Effect of

Hyperoxia on Gas Exchange and Lactate Kinetics Following
Exercise Onset in Nonhypoxemic COPD Patients.
Chest 2002;121;393-400
Emtner M, Porszasz J, Burns M, Somfay A, Casaburi R.

Benefits of supplemental oxygen in exercise training in
nonhypoxemic chronic obstructive pulmonary disease patients.
Am J Respir Crit Care Med 2003;168(9):1034-42.
Exercise training with oxygen have superior effect in
selected exercise physiologic parameters in
respiratory failure in COPD.
Cognitive
function
Hypoxia,
hypercapnia,
smoking,
comorbidities COPD itself
(vascular
disorders) had
influence on
cognitive function
in COPD
Measurement of
Feeding State:
•Determination of body
composition
•Body weight
•Calory intake
•Gastrointestinal symptoms
•Functional capacity
•Physical examination
Age-dependent PAP change in
Healthy Subjects
Kovacs G
<30 év 30-50 >50 year <30 év 30-50 >50 year
year year et al. ERJ
2009;
34(4):888-
94.
Pulmonary Arterial Pressure Increment during
Exercise in COPD
Terhelés indukálta pulmonális artériás nyomásemelkedés
100
* #
80
#;p<0,05 csoportok között
*
PAP (Hgmm)
60
40
20
0
Kontroll csoport COPD Varga J et al. ERS
Nyugalomban
2009, P3259
Csúcsteljesitménynél
Sleep Apnea Monitoring
Saturation
Heart rate
AHI
Thank you for
your attention!
E-mail:
varga@koranyi.hu
2019. 10. 09.
Test procedures :
• Chest x-ray /tomography
Pulmonary diagnostics training I. • Fluoroscopy
Indications:
------------------------------------------------ • CT • asymptomatic
(screeing (LDCT), staging…)
(chest x-ray, fluoroscopy) • MR • symptomatic
• US (suspicion of lung disease, abnormal chest x-ray,
diff.dg…)
• Angiography, bronchography • unconscious, polytrauma

…
Dr. Czaller Ibolya • Isotope methods
assistant lecturer
• follow up
• Hibrid techniques
• intervention techniques
Semmelweis University, Department of Pulmonology
Take home m.
Chest x-ray basics Thorax, lung, airway anatomy

PA
• Trachea, lobes, broncho-pulm. segments, and subsegments, sec.lobulus

(Kerley B lines), acinus, primer lobulus (not see at chest x-ray)
• interstitium
• Respiratory, bronchus development anomalies, normal variants, lymph and
blood supply
Lobe’s localization – right lung Lobe’s localization – left lung
RML
1
2019. 10. 09.
Radiogram, X-ray recording Which does not appear on the PA/AP recording:
• Standing stationary,
• deep breathing in Film or
• scapula „rotation out” detector
(from the projection of lung)
• postero-anterior PA or AP recording
targeting
Postero-anterior beam: light
posterior source to anterior detector
Crosshair
X-rays - tube
metal sheath, lead cloak
Bed-side imaging:
(in supine, face up pos.)
PA AP view:
(standing/sitting pos.)
Radiogram, X-ray recording

handrail
Radiogram, X-ray recording
raised arm
• LL projection • Heavy beam technique ~110KeV, ↓mAs

-> (lower radiation exposure),
focus-film distance ~ 2m
• side lying (Friehmann-Dahl recording)
• Summation image, tomography
detector
X-ray film in cassette • central projection (AP, on-site recording)
Lead shield
• Chest x-ray - keyword:

air _ = transparency
• inclined radius direction from X-ray tube – x-ray shot
tissue + liquid
chestwall, diaphragm, „sinuses” (costodiaphragmatic recess/angle),

lungparenchym (apex-basis), hilar region, middle shadow, pleura „Shadow” (intrapulm./extrapulm.)
PA LL
intrapulmonary:
• alveolar
• interstitial
• blood-vessel shade
• bronchial shadow
extrapulmonary:
• pleural
• extrathoracic
In findings (as mentioned):

– nodule shadow
veiled fine lung design: – pulmonary infiltrates
lungparenchym = alveolus + interstitium – line/linear shadows
(elements of interstitium: arteriola, venula, lymphatic-tracts, connective tissue) – coverage
2
2019. 10. 09.
Nodules Regular settling

solitary multiplex TB: apical location Metastasis: on basis
ventilation ↑ perfusion ↑
(several mm or some cm) size, well-defined shadows
Nodules Pulmonary infiltrates

benign:
round, segmented,
sharped edges,
central calcification
(popcorn)
well-defined boundary
Calcareous deviation: granuloma,

hamarthoma, TB, malignancy (carc.:10%)
Other forms:
tiny, grainy, eccentric, amorphous
malign: Several cm, uncertainly bounded, Dg: (atypical) pneumonia l.s. sup.
irregular, or spiculated, homogeneous or inhomogeneous shadow
blurred contour,
eccentric calcification
Pulmonary infiltrates X-ray shadows types and those common causes 1.

1. Atelectasis: lung cc., compression of bigger
Bronchopneumonia: lymphNodes, mucus plugs, foreign body, pleural
spotted structure (patchy) effusion, abdominal diseases (cholecystitis etc.)
(inhomogeneous) 2. Infiltrates (with exudate, caseous necrosis):
multifocal pneumonia, lung cc, TB, pulmonary infarction
3. Scattering (spread/dissemination): coniosis,
granulomatous d., TB, metastasis, sarcoidosis
4. Linear shadow: pulmonary embolism,
lymphangiosis carcinomatosa.
5. Nodular shadows: primary lung cancer,
metastasis, tuberculoma, benignoma,
arteriovenous malformations, echinococcus
6. Hilar-expanding: central lungcc., mediastinal
tumors, sarcoidosis, lymphomas, oesophagus-
Lobar pneumonia:
dilatation, pulmonary circulation’s stagnation
respect the border of lobes,
7. Shadows of vessels: pulm. hypertension,
air bronchogram
dilatation of vessels
not displaced recesses
8. Pleural effusion’s shadow
or surrounding lungs
9. „Barbell” shadow: focal TB + lymphangitis +
enlarged hilar LN
10. Kerley lines: pulmonary oedema
3
2019. 10. 09.
X-ray shadows types and those common causes 2. „Negative shadows”

1. Apical bullous emphysema (thin-walled sacs) Westermark sign: Air bronchogram:
2. Bronchial shadow: thichened bronchial wall: behind the (vessel)obstruction, or if there is no air in the alveoli
„tram track” lines & „signet-ring”; bronchiectasis (surrounding lungs infiltrated)
in valvular bronchoconstriction,
3. Calcificated residual nodules: old „burned
the lungs parenchyma: „brighter” the bronchial lumen outlined (drawn
out” inflammations, TB residuum
4. Comet tail sign: curvilinear opacities, extend or with increased transparency around)
from a subpleural “mass” toward the hilum.
Distortion of vessels and bronchi that lead to an
adjacent area of rounded atelectasis.
(TB, asbestos pleuritis, tumour, Dressler sy)
5. Fissures (horizontal, oblique) (interpleural
recesses) outlined if it thickens, if in pleural
space: air, effusion, other appearing…
6. Basket-handle form: pulmonary abscess
7. Aspergilloma (mycetoma or fungus ball)
8. Cavity (caverna): TB, tumour;
Calcareous tissue: hamarthoma, tumour, TB √
9. Gastric bubble
10. Hiatus hernia
Dark bronchus sign
Volume changes Fluid vs. atelectasis

• intrapulmonary inflammation, haemorrhagia, • Atelectasis, other pushed through pull it
pleural fluid or haematoma, pneumothorax shrinking processes
-> it requires more space than usual, or -> reserve less space
size of the affected lung is unchanged
effusion: push atelectasis: pull

volume increases volume decreases
Fluid: Fluid:
characteristic form of appearance characteristic form of appearance
• Observing the curve of the fluidum – if plane horizon present: search for ptx too!
Hydrothorax (free fluid)
hydro-pneumothorax
4
2019. 10. 09.
Appearance forms of pneumothorax Curve of the fluidum 

Ellis-Damoiseau line vs. X-ray recording
apical
Concave shape with

basal x-ray imaging
Partial Cape-like Total, complete
Tension Sero/hydro-PTX Mediastinal

Convex (domed) with percussion
Chest fluoroscopy:
continuous X-ray image on a monitor
(X-ray movie)
Chest fluoroscopy
• Képerősítő lánc előnye: • Image amplification chain advantages:
– rekeszmozgás megítélése, – shows the respiratory movement of the diaphragm,
– pulzáció, – pulsation of the heart, hilus
– paradox mozgás megítélése, – judgement of paradoxical movement,
– Holzkneckt Jacobson tünet (mediastinum ingamozgása – Holzknecht Jacobson sign (pendulum movement of mediastinum
- kóros oldal felé történő hilus elmozdulás during inspiration and expiration)
belégzéskor) The hilus moves towards the obstructed lung during inspiration, during
– rávetülő vagy kóros képlet lokalizálása expiration it moves in the other direction.
• Hátránya: nagyobb sugárterhelés, rossz felbontás – eliminate superposition, localization of the target lesion
• Csak célzott felvétel készítésekor van • Disadvantage: higher radiation exposure, bad resolution
dokumentum
• Document available only when targeted „shot” is made
Contrast enhanced (BaSO4-, GastrografinR) studies

with fluoroscopic control
Chest tomography:
• Traditional chest tomography: not using nowdays
predetermined plane (55 degrees hilar tomograpy)
• Information content: (PA & LL recording)
– enlargement of the heart, • DTS (digital tomosynthesis) method for performing high-
resolution limited-angle tomography with low radiation dose.
– chest tightness Combines digital image capture and processing with simple
– contrast media passed through or leave… tube/detector motion as used in CT.
– locate/rule out fistula (aspiration) Only uses a limited rotation angle (15-60 degrees) with a
lower number of discrete exposures. Studies in progress ….
– confirm hiatus hernia
Trachea
stenosis
Barium esophagogram
5
2019. 10. 09.
Test procedures :
Imaging diagnostics • Chest x-ray /tomography

Indications:
in pulmonology II. • Fluoroscopy
• CT (spiral-, LD-, MS-, HR-, angio-) • asymptomatic
------------------------------------------------ • MR (chestwall, mediastinal, heart, great vessels)
(screeing (LDCT), staging…)
(CT, MR, US, scintigraphy) • symptomatic

• USonoGraphy (pleural fluid., EBUS) (suspicion of lung disease, abnormal chest x-ray,
diff.dg…)
• Angiography, bronchography • unconscious, polytrauma

…
Dr. Czaller Ibolya • Isotope methods
assistant lecturer (ventilation, perfusion scintigraphy) • follow up
• Hibrid techniques • intervention techniques
(PET-CT…)
Semmelweis University, Department of Pulmonology
Abdomen windowing
CT indications CT scan
• Chest x-ray is a suspicious, inaccurate difference • Narrow beam scanning – absorption profile –> voxel (unique volume
absorbing volume element) – grey scale
(parenchym, pleura, mediastinum, heart, big vessels -> pixel
diseases), nodules table stepping - slice thickness
• Tumor staging (T,N,M), stadium, RECIST (therapeutic effect) • 4000 shade(-1000(air)-3000(bone); 0:water) – HU – characterized by the
compactness of the radiant material
• Interstitial lungdisease
• Lung transplant patients • maximum radiation absorption: white color
• Windowing technics - reduces the number of density values
• Traumatology • Axial slices / series - transverse anatomy
• Negative chest x-ray, +abnormal spirometry, +chronic • Native & contrast agent measurement
• Standard protocol applications (embolism protocol)
coughing
• Postprocessing
• CT guided (core) biopsy, RadioFrekvAbalation controlling – density measurements
– size determination pulmonal
– enlargement windowing
– making secondary reconstructions (sagittal, coronal, 3D )
CT + contrast agent Chest standard reconstructions

• Advantages: Contrast-enhanced,
– no summation,
abdominal / mediastinal
– good contrast resolution windowing
– cross-sectional images make orientation easier
• Tissue resolution can be enhanced by adding contrast
media:
– differentiation of hilar region (lymph n., vessels),
– In case of embolism, thrombosis – free lumen separation
• accumulation dynamics (art-venal phase) shows the
functional characteristics
(increased vascularity - necrosis)
6
2019. 10. 09.
CT-Angiography Virtual bronchoscopy

• Apply appropriate pace contrast agent /reach with injector/ • Essential before intervention of trachea,
• Vessels representation: main bronchi, airway stenosis. (surgical
– norm/abnormal vessels, AVM, VCS sy and other invasive interventions)
– thromboembolic process, • central /peripheral airway expected
– vascularisation of tumor obstruction: -its length? -possibility of
– accurate analysis of liver noduls intervention? -> Planning
• Representation of parenchymal organs
• Create 3D reconstruction in any plane
a. lusoria
• Secondary atelectasis behind

left lower lobe terime (tumor)
LAM
HRCT (high resolution) Lung structure

• Very thin slices (1-2 mm), the finest structure of the
lungs is visible
(acinar structure) – interstitial lung diseases! - ddg • Lobus
• radiation exposure is higher • Bronchopulmonar segment
• native
• morphology reflecting functional information is expected only from • Secunder lobulus
examinations carried out by inhalation and exhalation – eg. air trap /
obstruction • pulmonary acinus
• Judgement of functional position-dependent atelectasia: back / prone • primer lobulus
position exhale inhale
• ILD, TX
Pulm.acinus: the smallest operative unit of the
lung (bronchiolus respiratoricus +branching +
related alveoli)
GGO artefact
Primer lobulus: distal from respiratory
• Classification of CT results by appearance:
bronchiole: (alveolar duct +alveoli)
– Reduced radiation transmission
– Increased radiation transmission
Secunder lobulus: terminal bronchiole and its Sec. lobulus: 1-2,5 cm
– Nodular opacity sized, polyhedron,
branching, contains max 10-12 acinus, +
– Linear opacity bounded with connective
tree in bud 30-50 primer lobulus’s functional unit tissue.
LDCT (low dose) Spiral, multislice MDCT

• reduce lung cancer– screening…
• low radiation dose CT scan
• the difference between the lung parenchyma and nodule • Spiral=helical CT: During the continuous rotation of the x-ray
density allows, setting the test parameters lower than the tube and the detectors, the table moves at a steady speed
conventional CT scan, so small peripheral foci can still be Recording from a full volume is completed between two
detected breaths.
• min.16 slice CT, 1–3 mSv közötti effektive dose, maximal (No cross-sections are made, but the volume of body parts
1 mm slice thickness can be inspected.)
Risk group suggested by international • MS-CT: one or more (4, 8, 16,… 128) slides are made during
literature:
≥50 y.old,
an exposure (1 turn), detects by multiple detectors
≥20 packyear index, smoker, and – the chest can be examined under a respiratory retention
ex smokers (motion artifact ↓)
FEV1/FVC<70% és FEV1<80% (COPD) – large amounts of data collection, no information loss
other malignant disease
pulmonary malignancy in family history – 0.1 mm slice thickness;
workplace exposure (asbestos, radon) – any plane reconstruction can be made
7
2019. 10. 09.
PET-CT, PET-MR PET-CT, PET-MR

• image fusion (morphological-functional information)
• Interference: movement, physical work, diabetes mell.,
• 18F isotope (cyclotron) containing: fluoro-
deoxyglucose-6-phosphate (FDG) uptake exam. before eating, cold (not show osteoplastic metastasis)
(cell: glu-6-Páz not binding) ->„metabolic trapping”-> • False positive: inflammation, postop. irradiation, after
accumulate - prolonged storage pleurodesis, activated brown fatty tissue, aspecific intestinal
• FDG uptake semiquantitative characterization: SUV activity, metformin (OAD)
(for follow up)
• FDG physiologically accumulate: brain, myocardium,
kidney, bladder, physical exercise: muscles, tonsils, • Waiting is recommended:
parotids, vocal cord, chewing muscles – kemoth. 3-6 week
• Viability – vs. scar tissue >5mm-es nodular shadows – radioth. 3 month
(apex: 5mm, basis: 8mm – because of breathing!) – postop. 8 week
• primary lung cancer and metastases also exhibit
increased positron emission – detecting -> Staging
(N,M), operability, SPN, tumor diagnostics • Not suitable for skull testing (staging: cerebral-MR!) /brain-glu/
• Microcell. cc. (NEAK) does not finance (reason: not cumulate)
• Not cumulate well: pulm. mucinosus adenocc, bronchoalveol.cc,
pulm. carcinoid.
MR-imaging features MR imaging

• There are few proton in the lungs, and a lot of motion artifact - ECG gating
• It is predominantly sensitive to the hydrogen-rich water and fat and
the displacements. • We are investigating less sensitive rapid spin echo sequences:
• For the values of each voxel, the corresponding colors of the gray – chest wall and mediastinal structures, /Pancoast tu./
scale are assigned. – information on the tissue composition,
• Images displays proton densities, and the air giving the weakest – hematomas can be well tested
signal is always black. • Diffusion inhibition: lymph node with pathological structure
• White is a high signal intensity.
• Judgment of operability: disappearance of oily border near vasculature ->
• Water-less connective tissue, tendon, cartilage, vocal cords barely refers to infiltration
gives a signal.
• „black” / „white” blood technic: detection of flow in the heart, in vessels, in
• The airborne areas and in minerals rich bones or calcifications,
stones are not / barely measurable. the whole pulmonary vasculature - can be mapped without contrast agents,
tumor invasion to vessels can also be recognized.
MR imaging Isotope methods I.

• „black” / „white” blood technic:
– With flow-sensitive technique, the free lumens of the vessels are depicted (p+ • Bone scintigraphy (part of the staging in pulmonary malignancies)
already left the measured section), the circulating blood will be sign-free, in the – if the activity of osteoblasts increases -> leading to isotopic enrichment
well marked surrounding tissue („black blood”) – non-specific procedure (indicates a lot of bone disease) (benign/malign.)
– If the gradient space is adjusted to the direction of the circulation, blood will
have a high signal intensity in the poor signed environment („white blood”) – a practical method for detecting bone metastases
• For moving organs or for better resolution, blood vessels are tested by contrast – 99mTc labeled phosphate compounds
media.
• Gadolinium administration: inflammation, tumor signal intensity increases Features:
• Oxygen-/ helium-inhalation:
– in emphysema, bronchiolitis obliterans and pulmonary transplants, the airborne
– high sensitivity - for simultaneous representation of the entire bone system
and actually ventured lung portions can be judged - false positives are more common(degeneratio, inflammatory or traumatic
bone, joint changes), than false negativity (diffuse metastasis)
– the detrimental effect of smoking on respiratory dynamics can be detected
• Native image: independent of renal function – 99mTc pyrophosphate or diphosphonate scintigraphy
• not have to starve at it
• Advantage: in the detection of perfusion disorders MR-angio (kids, pregnancy <3T) • Targeted x-ray recordings: if the patient has a well-rounded complaints,
• Disadvantage: linear resolution is limited, greater measurement time, after uncertain result of bone scintigraphy, used for for differential
contraindicated in those who have a metal, electric, magnetisable, or mechanical diagnostic purposes
implant, device, object in their body.
(metal implants eg: pacemaker, defibrillator, brain aneurysma clip, artificial eye, built-in hearing
aid, heart valve, built-in joint prosthesis, arthritis, orthopedic metal material, formerly injured
projectile, shotgun!)
8
2019. 10. 09.
Isotope methods II. Isotope test for pulmonary embolism

• Perfusion lungscintigraphy: (Tc-99m macroaggregate pharmacon)
information on pulmonary circulation
– a by interrupting the particles in the lung capillaries, provides functional and morphological
information on lung circulation, to evaluate the blood supply and blood distribution of the lungs
(before lung surgery (pulmonectomy))
– suitable for detection pulmonary embolism (if CT-angio scan not feasible, renal function decrease
or insuff.)
– Static shots: made of six directions, all segments of two lungs can be judged, at least two
projections
• Ventilation lungscintigraphy: (Tc-99m aerosol (DTPA), or noble gases: Kr-81, Xe-133

inhalation) shows breathing dynamics
– provides functional data on ventilation
– penetration of different molecules (MMAD) into the lungs
– respiratory dynamics data in COPD, asthma br.
– used inhalation lungscintigraphy to reduce the number of false positive perfusion scintigraphy
studies (additional examination)
– (V/Q) scintigráfia („mismatch”) proves or excludes the existence of PE.
• When rating: on both picture lines, or just the perfusion scintigram and chest X-rays ventilation lung-scintigram perfusion lung-scintigram
should also be taken into account! The perfusion lung scintigraphy alone is not specific.
(Several other causes may result in loss of activity – beside embolism) „mismatch effect”
• The result of the test: shows (degree of) the risk of diagnosis.
US USG
Transducer – ultrasound wave -> tissue - acoustic impedance -> ultrasound reflection
• „A” mode (amplitude – used by eye specialists) • Detection of: pleural fluid, thoracal, pleural and pleura close
• „B” mode (brightness) – 2D image - today's devices: real time, grey scale pathological processes (3.5-5Mhz)
• „M” mode (motion based mapping) – echocardiographia • US guided punctures, controlling transthoracal biopsy
• „D” mode – Doppler-effect; color & duplex exam • Ultrasound not see through the air (like normal lung)
• looking for artifacts!
• Advantages:
– non invasive exam
– non ionizing radiation (can be repeated several times) • detection of pneumothx (non moving, non pulsatile lung area draws
– cheap attention) B, M mode! Looking for artefacts!
– preparation not required
– simple, fast, excellent for orientation • monitoring of pneumonia, atelectasis, ILD follow up, pulmonary
edema, position of ETTube
• Disadvantages: • detection of pleural adhesion
– air makes the exam impossible at times - disturbing „shadows" may occur – looking for this!
– dehydration increases the scattering of the ultrasound, • place of drainage (empyems), follow up - efficacy of treatment
– fat can cause strong deflection and increased attenuation , • judgment of diaphragm’s movement
– bone-covered organs can not be tested (it causes sound-shadows)
– accuracy is highly examiner-dependent, requires great practice, it is harder to document • fluid between the plates of the pericardium can be well depicted
• Heart and big vessels abnormalities, measurement of IVC diameter
(refer to: hypo/hypervolaemia)
USG encapsulated fluid - compartments

• pleural fluid + atelectasis of lung septa,
echo-free - transsudate fibrin fibers,
balo.
„organising” fluid
Pl
PE
L H
empyem
(echogenic+debris)
9
2019. 10. 09.
Pneumothorax Lung vs. pneumothorax

M B
• Lung parenchym with air vs. ptx (air in the thorax)
B M B M
lung point
US signs:
M mode (motion imaging): • B-mode: lack of lung sliding
- not moving and pulsatile lung area • M-mode: bar code sign
see shore sign bar code sign
-disturbing US-signals (shadows) are displayed • Granular points („sand”) disappeared
Transversal
US
view:
EBUS(-TBNA)
pneumonia monitoring
• Mediastinal staging vs. mediastinoscopy
Longitudinal
view:
checking of ETT position
„hepatisation”
lymph node:
target laesion
TransBronchial Needle Aspiration

with US guide
benign pleural thickening subpleural pulm. metastasis B lines –
staging with good efficiency like mediastinosc.
pulmonal oedema
Angiographia – DSA Bronchography

(we extract the „mask” from the angio measurement )
• vascular system depicted (selective & superselective) • analysis of the bronchial system with water soluble contrast agent:
• Venal penetration: vessel anomalies, pulmonal angiography - to detect branches of a
small bloodstream. – give in a tacky, iodine contrast agent - through cannula - which draw
the bronchial system
• Arterial penetration: - selective a.bronchiale occlude - attenuation of phtisis, selective
embolisation. – we are not using it today
• Superselective angiography -> intervention!
• Beyond visualization, the high pulmonary pressure can be measured during
catheterization (precapillar, wedge) - diagnosis can be confirmed
• The most reliable method for detecting pulmonary embolism, which is already capable
of detecting small defects or obstructions. Invasive intervention.
• CT scan has recently pushed it out (in diagnosis of acute, massive pulmonal embolism)
Generally performed before embolectomy.
AVMalformation
trifurcatio
BS6 bronchiectasis
10
RADIOLOGY
Dr. Edit Hidvégi PhD

Semmelweis University - Pulmonology
X ray
• Standing position
Film or
• Inspiration detector
• PA – AP + lateral
• Summation targeting
light
Crosshair
X-rays - tube
metal sheath, lead cloak
Bed-side imaging:
(in supine, face up pos.)
PA AP view:
(standing/sitting pos.)
Right lung
RML
Left lung
Emphysema/Chronic Bronchitis
Bronchopneumonia, Lobar pneumonia
Interstitial pneumonia/Lung fibrosis
Lung infarct / Atelectasis
Atelectasis/Hydrothorax
Ellis-Damoiseau-Line
Hydrothorax (bilateral)
Pneumothorax
apical < 2 cm „cape” total

Hydropneumothorax/Pneumomediastinum
Subcutan emphysema
Lung tumor
Lung tumor
Pancoast tumor
Lung tumors (?)/Metastasis ?
Lymphangitis carcinomatosa
BHL/Sarcoidosis Lymphoma
Tuberculosis
(Miliar)
Lung abscess • Staphylococcus
• Tuberculosis
• Tumor
• Fungal infektion
Aspergilloma
Cardiomegalia / Card. decomp.
Pacemaker / Tracheostoma
Foreign body (?)
?
X-ray fluoroscopy
• Pro • Con
• Movement • Radiation exposure is high
• mobility of the diaphragm • Bad resolution
• middle shadow • Documentation is difficult
• heart pulsation
• rotation (covered space)
• Bronchography
• Swallow X-ray
• Reason for aspiration (swallowing
coordination)
• Esophageal compression
• Fistula
• Reflux diagnostics (past!)
Ultrasound
• Pleural fluid
• Pneumonia
• Lung edema
• Pneumothorax
• Metastasis in liver,
Adrenal gland*
• DVT (Doppler)*
• EBUS
* Radiologist
Tumor on the pleura EBUS
(US-guided biopsy)
CT – Radiation exposure is high, except for low dose CT (screening)
CT – native or with contrast
HR CT – fine structure (Interstitium)
Pulmonary embolism - angioCT
MR(I)
Isotope examination (pulmonary embolism)
Ventilation scintigraphy Perfusion scintigraphy
„mismatch effect”
Isotope examination
• Lung scintigraphy
• Ventilation (Xe) - Perfusion (Tc)
• Before the operation
• AngioCT ist contraindicated
(Embolism)
• Sarcoidosis Dg. (Gallium, old)
• Bone isotope
• Tc - Metastasis
• PET CT
PET CT
• Contrast medium: FDG
18 fluoro-dezoxi-glucose
(no allergy, blood sugar)
• Accumulation (>8 mm)
• malignant tumors (not
all!)
• Metastasis, lymphnode
• Inflammation (Tb,
Sarcoidosis)
• Brain, heart, bladder
• Metformin in gut
• Radiation exposure = CT
• Staging before operation
Thank you
for your attention!

Pulmonológy Merge

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Bronchial asthma

Dr. habil. Gabor Horvath, Ph.D.

What do you think...

A./ ~ 30 million (~ Canada)

 Asthma is one of the most common chronic

 A chronic inflammatory disorder of the airway

Normal airways Mild asthma

Busse et al., N Engl J Med 2001;344(5):350-362

Busse et al., N Engl J Med

Normal airway Asthma

Other factors contribute airflow limitation

• Bronchial smooth muscle hypertrophy

 History and patterns of symptoms

Symtoms can be permanent, intermittent, seasonal:

Time (days, weeks, months)

FEV1 Asthmatic (after bronchodilator)

Asthmatic (before bronchodilator)

What do you think...

 Peak flow meter

Decrease in FEV1 after

 Exhaled NO: produced by epithelial

 Sputum eosinophils: correlates with

 Dyspnea, wheezing, coughing  

 Reduce exposure to indoor allergens

 Mast cell degranulation 

 Vascular permeability  Anti-inflammatory

5-LO = 5-lipoxigenase; FLAP = 5-lipoxigenase-activating protein;

5-LO inhibitor: CysLT1 antagonists:

Dr. Noémi Eszes

► Chronic Obstructive Pulmonary Disease (COPD) is a common,

► The most common respiratory symptoms include dyspnea,

►COPD may be punctuated by periods of acute

►In most patients, COPD is associated with significant

► COPD should be considered in any patient who has dyspnea,

► Spirometry is required to make the diagnosis; the presence of a

► The goals of COPD assessment are to determine the level of

 Chronic and progressive dyspnea

© 2017 Global Initiative for Chronic Obstructive Lung Disease

© 2019 Global Initiative for Chronic Obstructive Lung Disease

© 2019 Global Initiative for Chronic Obstructive Lung Disease

© 2019 Global Initiative for Chronic Obstructive Lung Disease

► COPD exacerbations are defined as an acute worsening of respiratory

► Smoking cessation is the first step

► In patients with severe chronic hypercapnia and a history of hospitalization

► In select patients with advanced emphysema refractory to optimized

► Palliative approaches are effective in controlling symptoms in advanced

© 2017 Global Initiative for Chronic Obstructive Lung Disease

► Once COPD has been diagnosed, effective management should be

► Following implementation of therapy, patients should be reassessed for

© 2017 Global Initiative for Chronic Obstructive Lung Disease

© 2017 Global Initiative for Chronic Obstructive Lung Disease

► Education and self-management

► An exacerbation of COPD is defined as an acute worsening of respiratory

► Exacerbations of COPD can be precipitated by several factors. The most

► The goal for treatment of COPD exacerbations is to minimize the negative

► Short-acting inhaled beta2-agonists, with or without short-acting

► Maintenance therapy with long-acting bronchodilators should be initiated as

► Systemic corticosteroids can improve lung function (FEV1), oxygenation and

► Methylxanthines are not recommended due to increased side effect profiles.

► Non-invasive mechanical ventilation should be the first mode of ventilation

Some common comorbidities occurring in patients with COPD with stable

© 2017 Global Initiative for Chronic Obstructive Lung Disease

Zoltán Süttő M.D., Ph.D.

3rd Wave 4th Wave 5th Wave