Asthma

Definition
• Asthma is heterogenous disease characterized by
• chronic airways inflammation
• respiratory symptoms as wheezing, dyspnena, chest tightness or
discomphort, cough
• which vary by time and intensity
• and manifested together with variable airways obstruction
• Heterogentiy of asthma is manifested by different phenotypes,
which could be identified in routine clincal practice
Variants of preceding years definitions
■ Chronic inflammation of airways
■ In pathogenesis of which participate numerous cells and cellular
elements (in more early definitions only eosinophils and mast cells
were mentioned )
■ Presence of chronic inflammation is associated with bronchial
hyperresponsiveness, which leads to dyspnea, respiratory
dyscomphort, chest tightness and cough (in more early ones -
suffocation only)
Characterized by variable, wide-spread, often reversible obstruction
So, what changed:
• 1. Inflammation in airways and variable obstruction are the
pathogenetic base of the disease but currently:
• 2. Underlined the pathogenetic and clinical heterogenity and
presence of phenotypes
• 3. Key points of diagnosis are not depending on phenotype:
variability of respiratory symptoms in time and intensity +
variable (not obligatory reversible) airways obstruction
Key difference with COPD
• COPD: persisting progressive airways limitation

• Asthma: variability of symptoms and obstruction by time

and intensity
Epidemiology
• 300 mln patients over the world
•
Prevalence by countries
 Япония:
https://www.sciencedirect.com/science/articl
e/pii/S1323893020301015
, но согласуется с данными других стран
Difficult to treat asthma
• 20–30% - severe atopic asthma, asthma in obesity, asthma in
smokers, late onset asthma, asthma with fixed obstruction
• In emergency care units asthma exacerbations are up to 12% visits,
from them 20–30% need hospitalization to specialized departments
and 4-7% – to ICU
• About 5% of all patients with asthma exacerbations require tracheal
intubation and invasive lungs ventilation, in case of invasive lung
ventilation mortality is up to 7%
.Factors influencing the onset and
development of asthma
• genetic predisposition to atopy
• genetic predisposition to bronchial hyperresponsiveness
• In young age in males more frequent, in adolescents and adults in
females
• obesity
Outdoor factors:
• Allergens: domestic (house dust mites), pollen, epidermal
(epidermal of pets and other animals), food, drug,
cockroach, fungal, latex
• Infection related factors (viral and bacterial)
• Occupational factors
• Aeropollutants: ozone, sulfur and nitric dioxides, diezel fuel
products, tobacco smoke (active and passive smoking)
• Dietary: increased digestion of highly processed products,
increased omega-6 and decreased omega-3 and antioxidants
indigestion
Interaction between genetic and epigenetic
factors
 Epigenetic factors
• DNA methylation - non-
methylated CpGs induce gene
expression (e.g. KRT5), and
methylated supress (e.g.
STAT5A).
• Acethylated histones stimulate
gene expression (e.g. ΔNp63) a
nd non acetylated supress
• Micro RNA influence on gene
expression through degradation
https://www.researchgate.net/figure/Epigenetic-regulatory- or transitory supressing  
factors-in-airway-epithelium-a-DNA-methylation-white-
circles_fig1_308547864
 Asthma pathogenesis:
1. Eosinophilic (IgE-mast cells-
eosinophils - IL5, IL13, IL4 )
2. Non-allergic eosinophilic
3. Neutrophilic (Тh1, Тh17)
4. Mixed granulocytic
5. Oligogranulocytic

https://www.researchgate.net/figure/The-heterogeneity-of-
asthma-immunopathology-segmented-into-eosinophilic-
allergic-and_fig1_322694561
 Тх-2 – asthma -
allergens, mast
cells, eosinophils,
IL-5 and 13

https://www.thelancet.com/journals/lancet/
article/PIIS0140-6736(13)61536-6/fulltext
 Non-allergic eosinophilic :

Pollutants, microbes, glycolipids

lead to deliberation of cytokines by
epithelial cells (IL33, IL25, thymic
stromal lymphopoietin(TSLP),
this leads to activation of innate
lymphoid cells (ILCs) by antigen-
independent mechanism through
receptors (IL-17 receptor B (IL-
17RB), ST2 and TSLP receptor
(TSLPR)).

Activated ILC2s produce lots of

IL-5 and IL-13
This leads to eosinophilia,
hypersecretion of mucus and
hyperresponsiveness of airways
CRTH2: chemoattractant receptor homologous molecule expressed on
Th2 cells; ALX/FPR2: receptor for lipoxin A4; FcεRI: high-affinity
receptor for IgE; GATA3: GATA-binding protein 3; PG: prostaglandin;
ROR: retinoic acid receptor-related orphan receptor; NK: natural killer;
MHC: major histocompatibility complex; TCR: T-cell receptor.

https://openres.ersjournals.com/content/1/1/00024-2015
 Aspirine-exacerbated respiratory disease

Same mechanism - alarmins, IL 33

and IL 25, TSLP

 NSAIDs lead to shift from cyclooxigenase to

lipooxygenase way and disappearance of supressive
influence of  PGE2 on massive secretion of histamin and
generation of cystenil leucotriens by mast cells
https://www.nejm.org/doi/full/10.1056/NEJMra1712125
 Non Тh-2 аsthma - role of neutrophils, Th-1, Th-17, IL-8, smooth
muscles cells, infection, tobacco smoke and pollutants

Mechanisms of non‐T2 asthma, including neutrophilic inflammation and airway

hyperresponsiveness. ASM, airway smooth muscle; CXCL1, C‐X‐C Motif chemokine
ligand 1; DAMPs, damage‐associated molecular patterns; IFN‐γ, interferon gamma;
IL, interleukin; LTB4, leukotriene B4; MMP, metallopeptidase; MPO,
myeloperoxidase; PAMPs, pathogen‐associated molecular patterns; Th1, T helper 1
https://www.researchgate.net/
cell; Th17, T helper 17 cell; TLR, Toll‐like receptor; TNF‐α, tissue necrosis factor
alpha
figure/Pathophysiological-
mechanisms-of-T2-hi-and-T2-lo-
https://onlinelibrary.wiley.com/doi/10.1111/all.13985
asthma-and-the-current-biologics-
that_fig1_328516228
Role of infection - lipoproteins, peptidoglycanes, LPS, flagellin, RNA of
respiratory viruses activate neutrophilic mechanism of pathogenesis
Infection and lung microbiome
• Inflammation leads to changing
in lung microbiome

https://respiratory-research.biomedcentral.com/articles/
10.1186/s12931-016-0479-4
Non-Th-2 asthma - olygogranulocytic variant

• trigger factor lead to disorder in

structural cells (miofibroblasts, epithelial
smooth muscular and mast cells)
• This leads to hyperresponsiveness
• In most cases low sensitivity to GCS
treatment

• . MUC5AC: Mucin 5AC Oligomeric

Mucus/Gel-Forming; Ach:
Acetylcholine; M2R: Muscarinic Receptor
2; M3R: Muscarinic Receptor 3; IL:
Interleukin; MCP-1: Monocyte
Chemoattractant Protein 1; TGFb:
Transforming growth factor beta; ECM:
extracellular matrix.
Sever asthma - complex mechanism with Тh1-2-17, GERD, obesity and protease-
antiprotease equilibrum disorder
 Тh-2-asthma: «hygienic hypothese»
https://www.nature.com/articles/nm0304-232
• Worked out basing on long time observation of
patients from newborn to 30+ (Tuscon, USA)
• Confirmed by significant increase of asthma
prevalence in African countries last 20 yrs
during the advanced westernisation
• Early (<6 mo) contact with environmental
allergens (animals, farm, microbes) lead to
dominationof Th-1 response, which is
protective to Th-2 asthma
• Sterile conditions in age < 6 mo and late (>6
mo) contact with outdoor factors leads to
formation of Th-2 response and asthma
development
• Currently this hypothesis is discussed basing on
the new data
Main clinical syndromes
• Bronchial obstruction
• Variable, manifested by paroxismal cough, wheezing, tightness of
chest, expiratory discomphort or suffocation
• Obstructive episodes appear or increase during allergens contact, at
cold air inspiration, during respiratory viral, less bacterial infection, at
physical activity (running mostly), laughter
• Physical examination reveals harsh breath with prolonged expiration,
wheezing, which sometimes can be auscultated only at forced
expiration
• Other signs (including emphysema) can be seen in severe asthma or
severe exacerbaiton
Bronchial inflammatory syndrome
• Cough - dry or with small amount of viscous sputum, difficult to
expectorate
• In viral and especially bacterial infections sputum color may change to
greenish yellowish, in allergic bronchopulmonary aspergillosis - black
particles in sputum
Intoxication
• Rare (if infection is significant)
Extrapulmonary allergy (atopy) manifestations
in patient and relatives родственников
• Atopic dermatitis (mostly in infancy)
• Rhinoconjunctivitis (mostly pollen dependent)
Complications in severe course
• Respiratory failure
• Cor pulmonale
Increase probability of asthma diagnosis
• presence of more than one bronchial obstruction syndrome
• symptoms worsen at night and early morning
• symptoms vary by time and intensity
• triggers are viral infection, allergens contact, weather changes,
laughter, irritant including the car motor gases, tobacco smoke, strong
smells
 Decrease probability of asthma diagnosis
• Isolated cough without other respiratory symptoms (GERD?)
• Chronic sputum production (COPD? Bronchoectases?)
• Dyspnea associated with dizziness and presyncopes (arrhythmias? other
heart problems?)
• Chest pain (angina? MI? pleura or pericardium affection? pulmonary
embolism?)
• Dyspnea caused by physical exercise with loud expiration (stridor)
Confirmation of asthma diagnosis
• FEV/FVC decrease (at least once), normal values for adults >0.75 –
0.80; for children
>0.90
• Variability of respiratory indices higher than in healthy individuals
• FEV1 after bronchodilator increase >12% or >200mL
• in PEF - significant variability during the day (2 times minimum daily during 1-
2 weeks - daily amplitude x 100/median daily)
• Significant increase of FEV1 or PEF after 4 wks of treatment by controller
drugs
• If variability not detected
• Repeat if patient becomes symptomatic or after cessation of bronchodilators
• Metacholine test if needed
PEF measuring
Typical spirometric tracings
Volume Flow
Normal

FEV1
Asthma
(after BD)
Normal
Asthma
(before BD) Asthma
(after BD)

Asthma
(before BD)

1 2 3 4 5 6 Volume
Time (seconds)
Note: Each FEV1 represents the highest of
three reproducible measurements

GINA 2017 © Global Initiative for Asthma

Diagnosis of asthma includes
• Asthma
• Phenotype
• Severity (different scales for new onset and on
treatment situations)
• Levels of control
New onset astma severity evaluation: evaluate as more severe if
at least one criterion of more severe group present

© Global Initiative for Asthma

© Global Initiative for Asthma
Levels of asthma control: evaluation during last 4 wks
Asthma control test questionnaire (Elizabeth F. Juniper)

https://www.thoracic.org/
members/assemblies/
assemblies/srn/questionaires/
acq.php
Severity of exacerbations: mild to moderate

•  PEF  50-75% of best or predicted

•  Increase of frequency of emergency drugs ≥ 50% or use of

nebulizer

•  Breaks of the nocturnal sleep due to asthma symptoms which

require the emergency drugs
Severe exacerbation
•  PEF  33-50% of best
•  respiratory rate >  25 per min 
• Pulse >  110 min
• Impossible to tell one phrase at one inspiration
Life threatening asthma
•  PEF < 33%of best
•  SрO2 < 92%
•  PaO2 < 60 mm Hg
•  Normocapnia (РаСО2 35-45 mm Hg.)
•  "Silent" lung syndrome
•  Cyanosis
•  Weak respiratory efforst
•  Bradycardia
•  Hypotension
•  Tiredness
• Sopor
•  Coma
Asthma close to fatal
•  Hypercapnia (РаСО2 > 45 mm Hg.) and/or
•  Need to mechanic lungs ventilation
Allergic asthma
• Most easily recognised
• Usually starts in childhood
• Extrapulmonary conditions usually present (atopic dermatitis,
allergic rhinitis, food allergy) in patient or relatives
• Eosinophilic inflammation
• Mostly no severe changes of pulmonary function test
• Usually good response in inhaled GCS
• Early onset allergic asthma (classical) and late onset allergic
asthma (more frequent severe, may be steroid-resistant)
Aspirine exacerbated respiratory disease
(AERD)
• late-onset (mostly females 40-45-55)
• COX-1 inhibitor-induced respiratory reactions (exacerbations at
aspirine and NSAIDS intake and tartrazine stain indigestion;
tartrazine is the yellow pigment present in some drinks like
Fanta, some drugs etc)
• Usually severe course
• Nasal poliposis typical
• Typical is severe course with frequent exacerbations
 Phenotypes and endotypes: Th2 high
Clinical Molecular
Endotype Phenotype Biomarkers Natural history
characteristics mechanism

Blood/sputum
eosinophil count, Identifiable and
Allergic serum specific treatable,
T2 high Atopic
Well defined, sensitization allergen IgE, high preserved lung
early onset, FeNO, high total function
steroid sensitive IgE

Severe from
± concomitant Staphylococcus Blood/sputum
onset, more
Late onset CRSwNP, steroid aureus enterotoxi eosinophil count,
frequent
refractory n high FeNO
exacerbation

Severe from
Dysregulated Blood/sputum
onset, more
AERD Adult onset arachidonic acid eosinophil count,
frequent
metabolism urinary LTE4
exacerbation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411459/#:~:text=The
%20term%20asthma%20is%20now,inherent%20therapeutic%20and
%20prognostic%20implications.
Laboratory markers of Th2 response

• Sputum eosinophilia
• Blood eosinophilia – seen not in all
cases
• Total and specific IgE
• Skin allergic tests positive
• (FeNO) elevated – nitric oxide in
exhaled air
New markers of Th-2 responce
• Periostin: extracellular matrix protein with expression
related IL-4 and IL-13 activity; stimulates eosinophil
degranulation, superoxide generation, and cysLTs
production from eosinophils as well as TGF-β.
• Dipeptidyl Peptidase 4 (DPP-4) – role unclear but serum
DPP-4 can predict responses to anti–IL-13 therapy
• urinary LTE4 - marker of aspirin exacerbated respiratory
disease
Non allergic asthma:
• occurs in adults
• not relate to allergy
• Inflammation in airways can be eosinophilic,
neutrophilic, mixed or paucigranulocytic
• Basing on type of inflammation patients may
respond or not on GCS treatment
Late onset asthma

• In some patients, mostly females

• Mostly no allergy
• Usually steroid refractory or higher doses of
steroids needed
Very Late Onset asthma

• > 65 yrs old onset of the disease

• Mechanisms suggest Th1 and Th17
inflammation in patients with age related
loss of elastic recoil and mechanical
disadvantages
• increased sputum neutrophilia typical
Asthma with fixed airways obstruction

•in some patients with long anamnesis

due to remodeling of airways
Asthma with obesity
• Obesity biases CD4 cells toward Th1 differentiation,
which is associated with steroid refractory asthma
• Pathogenetically important are IL-17, IL-22, and IL-6
• mostly marked respiratory symptoms
• no allergy

• Classical phenotype is non-atopic, middle-aged woman

with severe symptoms despite a moderately preserved
lung function.
Asthma-COPD overslap (smoking-related
asthma)
• Mostly steroid-resistant phenotype
• Neutrophilic type of inflammation; oxidative
stress mediates epigenetic modifications
causing neutrophil and macrophage
activation
• smoking increases risk of sensitization to
allergens and increases total IgE
 АCO – asthma+ COPD
• Not disease but association of 2 different diseases
•
• The aim of the ACO introduction
• Asthma: never treated by bronchodilators only (risk of
death, hospitalizations, severe exacerbations)
• COPD at onset of the diseases inhaled GCS not to be given
• Patients with ACO have risk of death or hospitalization if
inhaled GCS not used
• High doses of inhaled GCS necessary for asthma but are
not to be used in COPD
Criteria of ACO (asthma-COPD overlap
syndrome)
• Major criteria:
• persistent airflow limitation in patients > 40 years of age with at
least 10 pack-years of tobacco smoking
• onset of asthma at < 40 years of age
• Minor criteria
• history of atopy
• significant bronchodilator reversibility
• peripheral eosinophilia. .
 Phenotypes and endotypes: non Th-2
Clinical Molecular
Endotype Phenotype Biomarkers Natural history
characteristics mechanism
Adult onset— NLRP3/1L-1 β, Induced sputum
Variable course
Non-T2 Non-atopic paucigranulocytic or altered micro-RNA neutrophil count,
and lung function
neutrophilic expression, Thl7 MMP-9 in BAL
More frequent
Oxidative stress,
Induced sputum exacerbation,
Smokers Older adults mixed Th2
neutrophil count lower
high/Th2 low
lung function
Oxidative stress, Severe
neutrophils, symptoms,
Obesity related Female sex Serum IL-6
increased innate preserved lung
immune activation function
Immunosenescenc
> 50 to > 65 years Induced sputum
Elderly e, Thl/Thl7 Steroid resistant
at onset neutrophil count
inflammation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411459/#:~:text=The%20term%20asthma%20is%20now,inherent%20therapeutic
%20and%20prognostic%20implications.
Markers of non-Th-2 responce
• Increased sputum neutrophils count
• Absence of sputum and blood eosinophilia, low
total and specific IgE
• Low FENO
New markers of non-Th-2 responce
• Th1 inflammatory signature: high IFN-γ in about 50% of patients
with severe asthma
• Th17-high inflammatory signature: cytokines and chemokines of
Th17 pathway: neutrophilic inflammation, severe course and
steroid resistance are associated with IL-17A and IL-17F;
increased smooth muscles proliferation and irreversibility of
obstruction with IL-17A/IL-22 (IL17A – also collagen
deposition) and frequent exacerbations with IL-17F
Modern goals of asthma treatment
• Long-time control of symptoms
• Maximal decrease the risk of exacerbations,
fixed obstruction and adverse effects in future
• In every patient symptoms control, risk of
exacerbations, risk of irreversible obstruction
and adverse effects to be evaluated
• GINA 2020-2022:
• At level step 1 – low doses inhaled ICS-formoterol is the
GCS+LABA; short acting beta 2 preferred reliever for
agonists not recommended
patients prescribed
maintenance and reliever
therapy. For other
ICS-LABAs, the reliever
is SABA

GINA 2020, Box 3-5A © Global Initiative for Asthma, www.ginasthma.org

1-2 steps – mild asthma
• 1 step:
• Low doses of inhaled steroids +
formoterol (including at demand
mode)
• 2 step
• Low doses inhaled GCS
(alternative – leukotrien
antagonists)
• At demand - low doses of
inhaled steroids + formoterol
Moderate/severe asthma – 3-4 steps
• 3 step – moderate asthma
• Low doses of inhaled GCS + LABA
• Alternative – moderate dose
inhaled GCS
• Alternative – low doses inhaled
GCS+ leukotriens antagonists
• At demand - low doses of inhaled
steroids + formoterol
• 4 step – severe asthma
• Median doses inhaled GCS + LABA
• Alternative – high doses of inhaled
GCS
• Add tiotropium
• Add leukotriene antagonist
• At demand - low doses of inhaled
steroids + formoterol
• For adults on the 4-th step
• if disease is not controlled
• and/or frequent or severe exacerbations are
present (≥2 exacerbations per year)
• and/or at least one exacerbation per year
leading to hospitalization or systemic steroids
administration:

• Tiotropium bromide is recommended in liquid

inhaler
5 step – severe asthma
• High dose inhaled GCS + LABA • Alternative – to add low dose of
• Phenotype specific treatment oral GCS

• At demand - low doses of

inhaled steroids + formoterol
5 step of asthma variants
• Additionally to LABA + inhaled GCS in dose 1000
mcg of beclometazone dipropionate or
equivalent:
• tiotropium bromide
• Omalizumab
• Mepolizumab
• Reslizumab
• Minimal possible dose of oral GCS
 Isolated use of short-acting beta2-agonists
lead to:
• Down regulation of beta receptors, increased
hyperresponsiveness, decrease of receptors reaction
• Increase of allergic response, increase of eosinophilic
inflammation
High doses of SABA are associated with following adverse
effects:
• In case if ≥3 inhaler bottles per year (average 1.7
inhalation per day ) with high risk of ICU admission
• ≥12 inhaler bottles per year – high risk of asthma related
death
As alternative to SABA combination
“formoterol + small doses of inhaled GCS”
recommended
GINA 2020, Box 3-4A © Global Initiative for Asthma, www.ginasthma.org
 Inhaled GCS doses in patients 12 yrs and
older

This is NOT a table of equivalence. These are suggested total daily doses for the ‘low’, ‘medium’ and
‘high’ dose treatment options with different ICS.
DPI: dry powder inhaler; HFA: hydrofluoroalkane propellant; pMDI: pressurized metered dose inhaler (non-CFC); * see product information

GINA 2020, Box 3-6A

Montelucast: neuropsychiatric adverse effect
• Increased risk of suicidality
• In children – nightmares and behavioral problems
• Patients and parents should be informed about these adverse effects
Omalizumab
• Recommended for adults, adolescents and children older than 6 yrs of
age
• Not controlled by treatment of 4th step

• Indicated when:

• clinically significant atopy,

• confirmed link between allergens exposure and
symptoms/exacerbations of asthma,
• total IgE before biologic treatment 30-1500 МЕ/ml;
• moderate blood eosinophilia
Mepolizimab (anti- IL-5) for adult patients

• Adult patients with severe exacerbating

eosinophilic asthma (blood eosinophils
≥150 cells/mcl at the start of biological
treatment or ≥300 cells/mcl during last 12
months
• 100 mg once 4 wks
Reslizimab (anti-IL-5)

• Adult patients (≥18 yrs old)

• Severe asthma
• Eosinophilic inflamation (persistent blood
eosinophilia ≥400 cells/mcl)
Indications for anti-IL-5
• Mostly late onset of asthma
• Chronic rhinosinusitis, polyps
• Fixed obstructions
• Air traps and mucous obstruction of small airways
• Adult patients on oral steroids, who didn’t
receive any inhaled treatment:
• gradual decrease of oral steroids
• with inhaled steroids up to 2000 mcg daily
if needed
© Global Initiative for Asthma, www.ginasthma.org
 Allergen-specific immune therapy
• In patients older than 5 yrs old, if allergy plays the
important role in pathogenesis
• Expected is moderate clinical effect, steroid sparing,
quality of life improvement, possibility of step down
treatment
• Subcutaneous and sublingual modes
• Recommended in mild to moderate asthma, associated
with allergic conjunctivitis, if asthma is controlled by drug
therapy
 АCO – asthma+ COPD
• Not disease but association of 2 different diseases
•
• The aim of the ACO introduction
• Asthma: never treated by bronchodilators only (risk of
death, hospitalizations, severe exacerbations)
• COPD at onset of the diseases inhaled GCS not to be given
• Patients with ACO have risk of death or hospitalization if
inhaled GCS not used
• High doses of inhaled GCS necessary for asthma but are
not to be used in COPD
GINA 2020, Box 5-2
Asthma exacerbations
• Episodes of increasing:
• dyspnea
• Cough
• Wheezings
• Chest tightness
• Which make necessary the changes of
normal treatment regimen
• decrease of PEF and FEV1 is typical
• Can be in patients with known asthma diagnosis or be
the first asthma manifestation
• May develop in any patient independently on disease
severity, but mostly appear in difficult to control
asthma
• Exacerbation can develop rapidly or slowly – from
minutes to hour or 10-14 days gradually; the cessation
of the exacerbation is from 5 to 14 days usually
Patients with high risk of death from asthma criteria
should apply to physician at any worsening of the disease

• Episodes of life threatening asthma exacerbations in case history

• Episodes if invasive lungs ventilation due to asthma exacerbations
• Pneumothorax or pneumomediastinum in case history
• Hospitalization due asthma last year
• Psychological problems (patient rejects the fact of the disease)
• Social economical factors (low income, inavailability of drugs)
• Recent decrease the dose or cessation of steroids
• Low treatment compliance
• Decrease of dyspnea perception
 Factors of risk of exacerbations
• Symptoms of uncontrolled asthma
• Inhaled GCS not administered, low adherence to treatment
• Increased use of SABA
• Low FEV1, especially < 60% of predicted values
• Significant psychological or social and economical problems
• Smoking, allergen exposures and other extrinsic factors
• Concomitant diseases – rhinosinusitis, GERB, food allergy,
obesity
• Sputum or blood eosinophilia
• Pregnancy
• One or more severe exacerbation last 12 months
In treatment of asthma exacerbation regular evaluation
of criteria of severity of exacerbation should be done
• Respiratory rate
• Heart rate
• PEF
• Oxygen saturation
Clinical signs of severe exacerbation
• Prolonged air insufficiency including insufficiency
of air to finish the phrase at one respiration
• Tachypnoe
• Absence of respiratory sounds (silent lung)
• Cyanosis
• Decrease levels of consciousness
 Life threatening asthma
•Consciousness disorder (decreased consciousness, somnolence, sopor, coma)
•Tiredness
•Cyanosis
•Weak respiratory efforts
•Bradycardia
•Hypotension
•Absence of respiratory sounds
•PEF <33%.
•SpO2 ≤92%

•For patients with low saturation (SpO₂)≤92% and/or other signs of life
threating asthma blood gases should be evaluated
Chest X ray

• Should be done in patients with asthma

• To exclude mediastinal emphysema or
pneumothorax
• If pneumonia is suspected
• In clinical signs of life threatening
exacerbation
• If invasive lung ventilation needed
 Treatment: systemic GCS
• Should be used for all exacerbation except the mildest
• Indicated if initial treatment with beta2 agonists didn’t
lead to improving or exacerbation developed in patient
taking oral steroids, also if the preceding exacerbations
already required oral GCS
• Oral steroids are recommended more than intravenous
• The dose at exacerbation is 40-50 mg once daily – 5-7 days
• Parenteral use indications are inability to use oral drugs
due to dyspnea or other reasons
Oxygen treatment

•Asthma exacerbation + SрО2 less than

90
• 1-4 liters per min through nasal canulae
•Targeted SрО2 is 93-95%.
SABA and LABA at exacerbation
• First line treatment are SABA or SABA +
ipratropium
• In nebulizer usually 2.5 mg of salbutamol
per 1 inhalation
Non-invasive lung ventilation

• Severe dyspnea
• Hypercapnia
• Clinical signs of overstrain of respiratory
muscles without tiredness
• Absence of conscious disorders
Invasive lung ventilation indications
•  apnoe
•  conscious disorders – sopor, coma
•  unstable hemodynamics
•  general tiredness, exhaustion
•  respiratory muscles tiredness
•  refractory hypoxemia (РаО2) < 60 mm Hg, (FiO2) >
60%).