COPD

Definition (GOLD)
• 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(GOLD, 2017-
2021)
• Most frequent respiratory symptoms include dyspnea, cough and/or
sputum production. But these symptoms may be underestimated and
under-reported by patients
• Main risk factor – smoking, but other extrinsic factors play the role
(biomass use as a fuel, air pollution etc)
• During the course of the disease may be acute worsening episodes of
respiratory symptoms called exacerbations
• In most of patients COPD is associated with significant comorbidities which
influence on morbidity and mortality
 Prevalence

►В 2010 г - 384 mln cases

►Mostly 40+ of age

►Prevalence about 11.7% (95% CI 8.4%–15.0%); GOLD 2022 report

variation between 7.9% in Mexico and 19% in Urugway
►3 mln people die annually from COPD and related conditions

►Due to aging and increase of smokers there is expected the

increase of COPD prevalence in the world

© 2017 Global Initiative for Chronic Obstructive Lung Disease

The Lancet Respiratory Medicine 2020 8585-596DOI:
(10.1016/S2213-2600(20)30105-3
The Lancet Respiratory Medicine 2020 8585-596DOI:
(10.1016/S2213-2600(20)30105-3
Age-related prevalence
European Respiratory Review 2009 18: 213-221;
Risk factors: proved
• 1. Smoking: active and passive
• 2. Biomass use as a fuel in rural regions of some hot countries
• 3. Occupational factors
• 4. Alpha-1-antitrypsin deficiency
Genetic factors
• Hereditary:
• Proven link between homozygote SERPINA1*Z of alpha-1-antitrispine
gene (absolute deficiency of alpha-1-antitrypsine as a COPD phenotype )
• Compared to general population of smokers, in smoking first degree
relatives of patients with severe COPD there is 3-fold increase of the COPD
risk; in non-smoking relatives the risk is compared to general risk in non-
smoking population
• Heterozigotes SERPINA1*Z , other mutations of alpha-1-antitrypsine gene
• In GWAS (genome-wide-associated studies) investigations large number
of genes were revealed which are related with COPD presence and its
different peculiarities (including presence of emphysema)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193187/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193187/
The genes which can be regulated by
different factors including the tobacco smoke

https://news.weill.cornell.edu/news/2014/02/researchers-
reveal-link-between-copd-risk-genes-and-lung-cells
 • Incompleted phagocytosis of particles
Pathogenesis of tobacco smoke by
macrophages/neutrophils, death of the
phagocytes with deliberation of
cytokines and chemokines of Тh-1 and
Тh17 pathways including the IL- 8
• Deliberation of lots of proteases and
free radicals which injury the tissues
• Suppression of the cilia by tobacco
smoke (direct and through action on
the genes encoding the particles of
ciliae
• Relative deficiency of endogenous
antiproteases leads to bronchi and
alveoli injury and development of
remodeling of bronchi (fibrosis) and
parenchyma (emphysema)
• Viral and bacterial infection leads to
progression of inflammation and
increase of proteinases and prooxidants
burden and this to progression of the
https://link.springer.com/chapter/10.1007/164_2016_61 disease
1.Monocytes migrate to lungs and differentiate
to M2-macrophages by the action of
growth-related oncogene (GRO)/CXCL1 and
neutrophil-activating peptide (NAP)-2/CXCL7
2. In lung the extract of tobacco smoke (CSE)
causes production of IL-8/CXCL8 by
alveolar macrophages
3. IL-8/CXCL8 recruits neutrophils
4. Neutrophils produce the neutrophilic
elastase which suppress maturation of the
dendritic cells
5. AM-induced BAFF leads to development of
B-cells and recruiting by peripheral B cells by
BLC/CXCL13 or SDF1/CXCR1 pathways
6. Activated B-cells produce lots of antibodies
which aggravate COPD
7. AM promote granzyme B secretion and
perforin-expressing TC1 response, which
aggravate COPD
8. Epithelial cells secrete MIP-3α/CCL20, so
the recruiting of dendritic cells is promoted
and Th17 IL-17F increased, which leads to
secretion by epithelial cells of CCL20
9. Neutrophilic serine protease induces the
epithelial cells to secrete mucin and aggravate
COPD
 COPD vs Asthma: airways limitation degree
• 1. Domination of irreversible changes (fibrosis and
narrowing of lumen of airways, loss of elastic function due
to alveolar destruction, loss of alveolar support of airways)
• 2. Then – partial reversible changes (edema,
hypersecretion)
• 3. Minimal presence of reversible changes (bronchospasm)
• For asthma 3 is maximal, 1 is minimal
Pulmonary hyperinflation
• Unfavorable factor in pathogenesis
• Present due to chronic irreversible obstruction
Results in:
• Flattening of the diaphragm, which worsens its function as well
as function of other respiratory muscles
• Limitation of possibility to increase the respiratory volume
during physical exercise;
• Increase of hypercapnia at physical exercise
• Intrinsic positive pressure at the end of expiration;
• Increase of the elastic burden on the respiratory system
Other unfavorable pathogenetic factors
• Gas exchange changes: hypoxemia and hypercapnia
• Pulmonary arterial hypertension: spasm of small branches of
PA with their subsequent remodelling
• Systemic manifestations etc: systemic inflammation,
Th=1 mediated = TNF

cachexia, skeletal muscles dysfunction, osteoporosis,

cardiovascular events, anemia, depression

• One more comorbidity is lung cancer, but it is directly related

to same pathogenetic factors (smoking)
© 2022 Global Initiative for Chronic Obstructive Lung Disease
Main syndromes: Bronchial obstruction
• Expiratory/mixed dyspnea, persisting and progressive in time
• Barrel shaped chest (classic emphysema), horizontal ribs,
percussion – bandbox sound
• Decrease of respiratory mobility of lower border of lungs
• Harsh breath, prolonged respiration
• Auscultation may reveals some wheezes
Bronchial inflammatory syndrome
• Cough, sputum expectoration (in non-complicated COPD – small amount, free
discharge, whitish-yellowish; in exacerbations caused by infection – greenish-
yellowish), typically sputum is expectorated in the morning without cough (after
smoking)
• Changes of cough and sputum in complications development:
• Paroxysmal cough, dry (especially after previously it was with sputum) – lung
cancer?
• Increase of sputum amount, (10-50 ml daily), especially when it is purulent –
bronchoectases?
• Hemopthisis – lung cancer? Bronchoectases? Pulm. Embolism also

• Rhonchi (due to sputum in bronchi)

Respiratory failure, cor pulmonale
• Cyanosis
• Clubbing
• Neck veins distension
• PII accent, epigastric pulsation, cardiac beat of RV palpated
COPD diagnosis
• FEV1/FVC less than 0.7
© 2022 Global Initiative for Chronic Obstructive Lung Disease
© 2022 Global Initiative for Chronic Obstructive Lung Disease
© 2020 Global Initiative for Chronic Obstructive Lung Disease
© 2022 Global Initiative for Chronic Obstructive Lung Disease
© 2022 Global Initiative for Chronic Obstructive Lung Disease
© 2022 Global Initiative for Chronic Obstructive Lung Disease
© 2022 Global Initiative for Chronic Obstructive Lung Disease
https://www.grepmed.com/images/2764/bluebloaters-
pinkpuffers-comparison-phenotypes-diagnosis
New COPD phenotypes

https://erj.ersjournals.com/content/46/suppl_59/PA3937
https://radiopaedia.org/cases/emphysema-on-chest-x-ray
Minimal changes: trace centrilobular emphysema (circle),
which involved less than 0.5% of the lung zone.

https://pubs.rsna.org/doi/full/10.1148/radiol.2018172294
Severe confluent emphysema

https://pubs.rsna.org/doi/full/10.1148/radiol.2018172294
Severe emphysema with vascular distortion

https://pubs.rsna.org/doi/full/10.1148/radiol.2018172294
Centrilobular emphysema

https://radiopaedia.org/articles/centrilobular-pulmonary-
emphysema
 Panlobular emphysema

https://www.grepmed.com/images/817/panlobularemphysemhttps://radiopaedia.org/articles/centrilobular-pulmonary-
a-radiologyassistant-panlobular-radiology-emphysema emphysema
Peripheral bullae
Localized bulla
Right atrium and right ventricle hypertrophy
Severe right ventricle hypertrophy example
(more typical for PE than for COPD)
Right bundle branch block
© 2022 Global Initiative for Chronic Obstructive Lung Disease
Indications to steroid treatment
• In addition to long acting bronchodilators (obligatory) in patients
with asthma-COPD overlap or in patients with blood
eosinophilia (eosinophils in blood in remission more than 300
cells in 1 mcl)
• Patients with COPD and frequent exacerbations (2 and more
midsevere or severe exacerbations per year or at least 1 severe
exacerbation leading to hospitalization – group D)
• Prolonged (> 6 mo) inhaled GCS treatment combination with
long acting broncholytics decrease frequency of COPD
exacerbations and improve life quality
• Not recommended as a start treatment in GOLD1-2 (risk of
pneumonias)
Roflumilast: indications
• Supresses the inflammation by inhibiting of PDE-4 and increase
of intracellular cyclic adenosin monophosphate .
• Recommended in case of FEV1 < 50%, with frequent
exacerbations in spite of long acting bronchodilators to
decrease frequency of exacerbations
• Not recommended for decrease of COPD symptoms, it is not
bronchodilator and its influence on life quality is not wekk
lnowin; however during the long time treatment in patient taking
salmeterol or tiotropium was proven that adding of roflumilast
increases FEV1 50-80 ml additionally
© 2020 Global Initiative for Chronic Obstructive Lung Disease
Antibiotics
• Macrolides (azithromycin) as long time treatment – in COPD
with bronchoectases and frequent infectious exacerbations
Long time oxygen treatment
• Chronic respiratory failure symptoms and signs
• SaO2 < 88%
• In long term oxygen treatment You should have a target to
reach PaO2 > 60 mm Hg and SaO2 > 90%
• Not recommended for current smokers, for patients who are not
receiving adequate treatment; with not enough motivation
• Most of patients are recommended to have treatment no less
than 15 hrs daily with maximum breaks not exceeding 2
subsequent hrs with oxygen flow 1-2 l/min
Long-time home lungs ventilation
• Chronic respiratory failure: weakness, dyspnea, morning
headache
• - One or several of following:
• PaCO2 > 55 mm Hg;
• PaCO2 50 - 54 mm Hg and episodes of nocturnal desaturation
(SaO2 < 88% during more than 5 min during oxygen treatment
2 l/min),
• PaCO2 50 - 54 mm Hg and frequent hospitalizations due to
repeated exacerbations (2 and more hospitalizations per 12
mo)
 Plan of examination
Physical examination
Smoking index
mMRC or CAT
Frequency of exacerbations
Oxygen saturation
Spirometry

Chest X-ray

Hemogram with WBC differential count

Stable COPD treatment
Recommendations for smoking cessation should be given

Patient should be instructed to use inhaler correctly

Long acting bronchodilator should be administered, in mMRC>=2 or CAT>=10 –

combination LABA+LAMA

In SaO2<88% - long time home ventilation given

Recommended annual vaccination against influenza and pneumococcal

infection and COVID-2019 pneumococcal in 65+
Evaluation should be performed in 3 months with clinical examination and
spirometry
Exacerbations
• Oral prednisolone 30 - 40 mg/daily – 5-7 days.
• As more safe alternative – inhaled steroids in nebulizer
• Patients with exacerbation and blood eosinophils > 2% have
the best response on systemic GCS
Antibiotics
• - Recommended in case of worsening of dyspnea, increase of
volume and purulence of sputum or if 2 of 3 mentioned signs
present
• Recommended in severe exacerbation if patient need non-
invasive or invasive lungs ventilation
• Recommended if exacerbation is accompanied by CRP >= 10
mg/l
 Severity of COPD FEV1 Most frequent organisms Antibiotics

Haemophilus influenzae
Mild and moderate Moraxella catarrhalis Amoxycillin, macrolides (azitro or
COPD without risk > 50% Streptococcus pneumoniae clarithromycin), cephalosporines
factors Chlamydia pneumoniae 3rd generation (cefexime etc)
Mycoplasma pneumoniae
Haemophilus influenzae
Moraxella catarrhalis Amoxiclav, respiratory
Mild and moderate
COPD with risk factors
> 50% PRSP(пенициллин- fluoroquinolones (levo- or
резистентные Streptococcus moxifloxacin)
pneumoniae)
Haemophilus influenzae
Moraxella catarrhalis
Severe COPD 30 - 50% PRSP
Энтеробактерии,
грамотрицательные
Haemophilus influenzae
PRSP
Ciprofloxacin and other drugs with
Very severe COPD < 30% Энтеробактерии,
antipseudomonas activity
грамотрицательные
Risk factors
• <*> Risk factors: age >= 65 yrs old, concomitant cardiovascular
diseases, frequent exacerbations (>= 2 times ayear )
• <**> Predictors of P.aeruginosa:
• - frequent antibiotics use (> 4 courses per year);
• - FEV1 < 30%;
• - P.aeruginosa in frequent exacerbations or currently
• - frequent systemic GCS use (> 10 mg prednisolone last 10
days);
• - Bronchoectases
Indications to non-invasive lungs ventilations
• Acute respiratory failure:
• - Marked rest dyspnea
• - respiratory rate > 24 per min, accessory muscles
participation :
• - PaCO2 > 45 mm Hg., pH < 7,35;
• PaO2/FiO2 < 200 mm Hg
• no indications to invasive lung ventilaiton
Invasive lung ventilation

• Absolute indications:
• - apnea
• - marked central changes – sopor, coma
• - unstable hemodynamics (SBP < 70 mmHg, heart rate < 50/min or
> 160/min);
• - Tiredness of respiratory muscles
• Relative indications
• - Respiratory rate > 35/min;
• - pH arterial blood < 7,25;
• - PaO2 < 45 mm Hg in spite of oxygen treatment
 At examination
Examination by pulmonologist or general physician no later 30 min from admission
Oxygen saturation no later than 30 min
ICU specialist in SaO2 < 75% no later than in 30 min from admission
Hemogram with WBC formula
Xray
ECG
Spirometry with bronchodilator
mMRC and orCAT
Short acting bronchodilators
Systemic GCS
Antibacterial treatment given if infection signs (purulent sputum or CRP > 10 mg/l) and/ or
in severe examination
Inhaled oxygen given in saturation < 90%
CRP should be decreased up to 50% from initial on antibacterial treatment
As a result of treatment mMRC should decrease min 1 point and CAT min 2 points
Alpha=1 AT
• TO CHECK IN PANLOBULAR EMPHYSEMA IN PATIENTS LESS THAN 40
bibasic
• If less than 10% activity – replacement treatment by i.v. alpha-1
antitrypsin
© 2020 Global Initiative for Chronic Obstructive Lung Disease