COPD Revision Notes


According to GOLD, COPD is a common preventable and treatable disease characterized by:

  1. Persistent airflow limitation (Post-bronchodilator FEV1/FVC < 0.7), usually progressive (excludes Asthma)
  2. Associated with enhanced chronic inflammatory response in airways and the lung to noxious particles or gases
  3. With Extrapulmonary manifestations

Chronic bronchitis, defined as the presence of cough and sputum production for atleast 3 months in each of 2 consecutive years, is not necessarily associated with airflow limitation.

Emphysema is defined as a distension of airspaces distal to the terminal bronchiole (i.e. acinus) with destruction of the alveolar septa but without obvious fibrosis.

Acute Exacerbation of COPD  (AECOPD) is defined as an acute event characterized by worsening of patient’s respiratory symptoms (dyspnea, cough, sputum production) that is beyond normal day-to-day variation and leads to change in medication. They present with increased respiratory rate, increased wheezes and diffuse non-localized crackles.

  • Etiology of AECOPD is multifactorial – both infectious and non-infectious; most common infectious cause is viral (influenza, parvovirus, etc.)

Other obstructive airway diseases are:

  1. Reversible: Bronchial Asthma
  2. Poorly reversible: Bronchiectasis, Cystic fibrosis, Obliterative bronchiolitis


1. Cigarette Smoking: Smoking is associated with a variety of abnormalities of respiratory system, predisposing to COPD –

  • Sluggish ciliary movement
  • Bronchoconstriction
  • Hypertrophy and hyperplasia of mucus-secreting glands (Ratio of thickness of submucosal glands to that of bronchial wall is expressed as Reid index; normal 0.44 +/- 0.09; >0.51 in chronic bronchitis)
  • Release of inflammatory mediators in lungs (Inflammatory response is initiated by NF-Κß and Activator Protein-1 (AP-1)
  • Produces high concentration of ROS (superoxide, hydrogen peroxide, hypochlorous acid) which is responsible for tissue damage and activation neutrophils and eosinophils
  • Release of proteolytic enzymes from PMN leucocytes
  • Inhibition of function of alveolar macrophages

Passive smoking and Maternal smoking plays important role in the development of COPD.

smoking copd

2. Air Pollution and Occupational exposure:

  • Dust, smoke and fumes, suphur dioxide and particulate matter, toulene diisocyanate (plastic industry)
  • Includes indoor air pollution from natural gas used for cooking

3. Genetic: α1 antitrypsin deficiency

  • Alpha-1 antitrypsin is a serine protease inhibitor (SERPIN) secreted by the liver into the blood which inhibits the enzyme neutrophil elastase from damaging the lung tissue.
  • Protease-antiprotease hypothesis: Deficiency of this alpha-1 antitrypsin leads to unopposed elasteolysis (destruction of the elastin fibers in alveolar walls) and development of early emphysema.

4. Other factors: Male gender, Mid and Late adult life, Recurrent respiratory tract infections and Pre-existing asthma

Unilateral emphysema or McLeod’s syndrome occurs as a complication of severe childhood infections caused by rubella or adenovirus, and congenital lobar emphysema is a developmental abnormality affecting newborn children.

COPD pathogenesis


copd pathophysiology


1. Centriacinar (Centrilobular): associated with smoking – limited to respiratory bronchioles (spares alveoli); more prominent in upper lung zones

2. Panacinar: associated with alpha-1 antitrypsin deficiency; both central and peripheral portion of acinus involved (including alveoli); more prominent in lower lung zones

3. Paraseptal: involves only distal acinus; found near the pleura and may cause spontaneous pneumothorax


EmphysemaChronic bronchitis
  1. Neutrophils, macrophages and CD8+ T-cells, release inflammatory mediators and enzymes
  2. Released Proteases like elastase and MMPs break down the connective tissue of the alveolar walls and the septae.
  3. Results in:
    • Loss of elastic recoil
    • Diminished expiratory flow rates
    • Air trapping
    • Airway collapsing
  1. Luminal obstruction by excessive mucus secretion resulting from:
    • Mucous gland enlargement
    • Goblet cell hyperplasia
    • Mucociliary dysfunction
  2. Major site of increased airway resistance is the small airways (≤ 2mm).
  3. Fibrosis and smooth muscle hypertrophy may also occur
PathophysiologyParenchymal destruction and Matched V/Q defect: Alveolar septa destruction along with capillary walls resulting in Matched V/Q defect (areas of low ventilation are also the areas of low perfusion).

Despite Matched V/Q defect mild hypoxia develops: As hyperventilation develops and cardiac output drops – areas of poor blood flow in relatively well oxygenated areas.

Cachexia: At the pulmonary level, the low cardiac output leads to pulmonary cachexia; which induces weight loss and muscle wasting. This gives these patients the characteristic “pink-puffer” appearance.


Small airway inflammation and obstruction: Parenchyma are relatively less damaged.

V/Q mismatch: Obstruction without capillary wall destruction leads to increased perfusion in poorly ventilated areas leading to significant hypoxia with compensator increase in cardiac output and polycythemia.

Severe hypoxia and hypercarbia: Chronic V/Q mismatch leads to decreased oxygenation/deoxygenation of the blood resulting in hypoxemia and increased CO2 retention (respiratory acidosis) – leads to pulmonary artery vasoconstriction resulting in increased right ventricular pressure (pulmonary hypertension) and failure (cor pulmonale)



Emphysema (Pink Puffer – type A)Chronic Bronchitis (Blue bloater – type B)
DyspneaEarly onset progressive dyspnea (“puffing”): Air trapping makes each breath less efficient which is compensated by:

  • Tripod position: use accessory muscles
  • Hyperventilation: Tachypnea

This inturn, leads to respiratory muscle fatigue and flattening of the diaphragm impairing it’s function – which adds to dyspnea

Late in onset – it is due to airflow obstruction
CoughMild cough (after dyspnea starts) – due to irritation of smaller airwayBefore dyspnea starts – “morning cough” that progresses in frequency, severity and duration (all round the year)
SputumScanty and mucoidCopious sputum (produced by goblet cells)
CyanosisNo (Pink) – Matched V/Q defect; no hypoxemiaCyanotic (Blue) – Mismatched V/Q defect; hypoxemia
AppearanceCachectic – Wasting due to loss of skeletal muscle and subcutaneous fat (inflammatory cytokines and anorexia)Bloaters – Edematous due to right ventricular failure (cor pulmonale)
Inspection and PalpationRespiratory distress – tripod position, tachypnea, use of accessory muscles


Prevent collapse by maintaining high intra-bronchial pressure: Prolonged expiration through “pursed lips”, Expiratory grunt


Due to chronic use of accessory muscles (sternocleidomastoid and scalene which are hypertrophied and pulls thorax in AP and upward direction):

·         Barrel-shaped chest (Normal AP to transverse diameter of chest is 5:7; increased AP diameter in barrel-shaped chest)

·         Prominent angle of louis

·         Horizontally and widely placed ribs

·         Widened subcostal angle (normal is 70⁰)

Hoover’s sign: Flattened diaphragm which contracts inwards instead of downwards, thereby paradoxically pulling the inferior ribs inwards with its movement (instead of outwards during normal respiration)

Campbell’s sign: exaggerated tracheal descent during inspiration (increased work of breathing where movements of chest wall, diaphragm and muscles is transmitted to trachea)

Dahl’s sign: Symmetric, slanting regions of hyperpigmentation the thighs – from patients with COPD resting in the tripod position (elbows on thighs)

Apical impulse – invisible or feeble (may be felt at subxiphoid region because heart is vertical and rotated
Chest expansion – symmetrically diminished


Tactile fremitus – Diminished

At rest, no respiratory distress – no tachypnea, no use of respiratory muscle


Usually, no deviation from expected findings


Tactile fremitus – Normal

PercussionHyper-resonant over lungs

Cardiac dullness reduced or obliterated

Liver dullness pushed down or absent

Normally resonant over lungs

Liver dullness and cardiac dullness in normal position

AuscultationDiminished intensity of breath sound bilaterally

Vesicular breath sound with prolonged expiration (>6 seconds)

Scattered, faint, high-pitched, end-expiratory rhonchi

Dimished audibility of heart sounds

Vesicular breath sound with prolonged expiration

Wheezes – airway obstruction

Crepitation – gurgling sound due to mucus hypersecretion in airways (disappear or change in intensity or location after coughing)

Pulmonary hypertension (RVH)Late and mildEarly and severe (Visible and palpable pulmonary artery pulsations, sustained left parasternal heave, Epigastric pulsations, palpable and loud P2)
Right ventricular failure (Cor pulmonale)Late and often terminalRepeated episodes (Peripheral edema, raised JVP, tender hepatomegaly, S3 of right ventricular origin), Functional Tricuspid regurgitation (TR – distended neck veins, pansystolic murmur accentuated during inspiration)
Respiratory failureLate and often terminalRepeated episodes (Type I or Type II); CO2 narcosis manifest as clouding of consciousness, altered behavious, drowsiness, headache, papilledema, bounding pulse and asterexis (flapping tremor)
Mucopurulent relapses (S.pneumoniae, H.influenzae, M.catarrhalis)Less frequentMore frequent (fever and frankly purulent copious sputum)
SpecificPulmonary bullae (from ruptured alveolar walls) – usually located subpleurally along anterior border of lungs which can rupture causing spontaneous pneumothoraxSecondary polycythemia – stimulated by hypoxemia
Non-specific Anemia, Osteoporosis, Depression, Increased Cardiovascular risk
HematocritNormalIncreased (Polycythemia)
PaO2 (ABG)Normal to lowLow (Hypoxia)
PaCO2 (ABG)NormalHigh (Hypercarbia)
PFT↓FEV1 (<12% post-bronchodilator reversibility), ↓FVC, ↓FEV1/FVC, ↓PEF, ↑TLC, ↑FRC, ↑RV
Diffusing lung capacity (DLCO) – PFTReducedNormal
Chest X-rayHyperinflation (low set diaphragm, translucency increased, loss of peripheral vascular markings, widely placed and horizontal ribs) , Bullae and tubular heart, prominent pulmonary artery shadow at hilumIncreased broncho-vascular markings and cardiomegaly
ECGECG changes in COPD


Based on post-bronchodilator FEV1 in patients with FEV1/FVC < 0.7

  1. GOLD 1 (Mild): FEV1 ≥ 80% predicted
  2. GOLD 2 (Moderate): 50% ≤ FEV1 < 80% predicted
  3. GOLD 3 (Severe): 30% ≤ FEV1 < 50% predicted
  4. GOLD 4 (Very severe): FEV1 <30% predicted


combined assessment of copd

CAT (COPD Assessment Test) Questionnaire:

Assessment of severity of symptoms with 8 questions – each scored in the range of 0 to 5 (O being no symptoms to 5 being maximum symptoms)

Mnemonic: COPD

  1. Cough
  2. Chest constriction (tightness)
  3. Confidence in leaving home
  4. Occupation (Activity) limitation at home
  5. Phlegm (mucus)
  6. Psyche (Energy)
  7. Disturbed sleep
  8. Dyspnea on walking uphill or 1 flight of stairs

mMRC (modified Medical Research Council) Dyspnea scale:

0 – Breathless only on exertion

1 – Breathless on hurrying on level ground or walking slight uphill

2 – Walk slower on level ground (compared to those of same age) because of breathlessness OR Have to stop on walking on own pace on level ground

3 – Breathless after walking ~ 100 m or after few minutes on level ground

4 – Too breathless to leave house or Breathless on dressing/undressing


1. Treatment of Acute Exacerbation of COPD (AECOPD) if present


  • PEF measurement
  • Oxygen saturation with or without ABG (in moderate to severe cases)

Sputum cultures are not routinely recommended as these patients are often colonized with respiratory pathogens. It may be helpful in end-stage COPD, frequent exacerbations or bronchiectasis to determine colonizations with gram negative organisms like Pseudomonas aeruginosa.

a. Oxygen:

  • Aim: Oxygen saturation of 88-92%
  • Be careful – high flow rates can worsen hypercapnia
    • Increased dead-space due to aggravation of V/Q mismatch due to release of hypoxic pulmonary vasoconstriction
    • Loss of hypoxic respiratory drive
    • Co2 binding capacity decreases as hemoglobin oxygen saturation increases (Haldane effect)

b. Bronchodilators:

  • Nebulized Short Acting Beta-Adrenergics/SABAs (Salbutamol 2.5 mg i.e. 0.5 ml) and Anticholinergics (Ipratropium 0.5 mg i.e. 2.5 ml) every 20 minutes for initial 1-2 hours
    • SABAs: fast onset of action but short-lived
    • Anticholinergics: delayed onset of action but prolonged effect

c. Antibiotics: Indicated if 2 out of 3 symptoms of exacerbation

aecopd antibiotic algorithm

  • Commonest organisms are: Viral (Influenza, Parainfluenza), Bacterial (S.pneumoniae, H.influenzae, M.catarrhalis), Atypical organisms (Mycoplasma and Chlamydia pneumoniae), Recent hospitalizations and frequent exacerbations i.e. 4 or more in last 1 year and severe exacerbation (P.aeruginosa)
  • Agents not recommended in AECOPD are:
    • Cephalexin (poor activity against penicillin intermediate/resistant S.pneumoniae, no activity against hemophilus and moraxella)
    • Cefaclor (no activity against penicillin intermediate/resistant S.pneumoniae, marginal activity against hemophilus)
    • Cefixime (no activity against penicillin intermediate/resistant S.pneumoniae, excellent activity against hemophilus)
    • Ceftriaxone (not recommended for routine use due to potential for increased resistance to 3rd generation cephalosporins)
    • Erythromycin (poor activity against hemophilus and moraxella)
    • Clindamycin (no activity against hemophilus and moraxella)
  • No antibiotics in <6 wks and no frequent exacerbation (<4/year):
    • Amoxicillin 500 mg PO TID for 7-10 days OR
    • Doxycycline 200 mg PO stat then 100 PO OD daily for 7-10 days OR
    • TMP/SMX 1 DS tablet PO BD for 7-10 days
  • Antibiotics in <6 wks and/or frequent exacerbations:
    • Cefuroxime 250-500 mg PO BD for 7-10 days OR
    • Amoxicillin-Clavulanate 500 mg PO TID for 7-10 days OR
    • Clarithromycin 250-500 mg PO BD for 7-10 days OR
    • Azithromycin 500 mg PO stat then 250 mg PO OD for 4 days
  • Treatment failure or advanced lung disease with severe exacerbation:
    • Levofloxacin 500 mg PO OD for 5-10 days OR
    • Moxifloxacin 400 mg PO OD for 5-10 days OR
    • Gatifloxacin 400 mg PO OD for 5-10 days

Treatment failure – Clinical deterioration after 72 hours of antibiotic therapy or no improvement after 7-10 days of antibiotic therapy

For severe lung disease – Levofloxacin, Moxifloxacin or Gatifloxacin for 10 days (reserved also for treatment failure to minimize development of antibiotic resistance)

Ciprofloxacinsuboptimal coverage for S.pneumoniae; for documented P.aeruginosa infection Ciprofloxacin 750 mg BD for 10 days can be used

d. Corticosteroids:

For patients with advanced lung disease of less severe lung disease with severe exacerbation:

  • Oral prednisolone: start at 0.5-1 mg/kg/day and taper slowly OR
  • IV methylprednisolone: 40-125 mg every 8-12 hours OR
  • IV hydrocortisone: 100 mg every 6-8 hours

They shorten the recovery time and improve lung function (FEV1) and hypoxemia.

e. Methylxanthines:

Aminophylline or Doxophylline (better cardiovascular profile not requiring measurement of drug levels) must be added if the patient fails to respond to initial treatment:

  • Bolus: 5 mg/kg IV in NS over 20 min followed by
  • Infusion: 0.6 mg/kg/hr for 24 hours

f. Diuretics: in patients with gross right ventricular failure (cor-pulmonale)

g. Respiratory stimulants: If not responding to conventional agents – Doxapram 1.5-4 mg/min infusion

h. Non-invasive positive pressure ventilation or Invasive ventilation (if NIPPV fails)

2. Management of Stable COPD

drug treatment of copd
Based on combined assessment of COPD

a. Bronchodilators:

  • Short-acting (4-6 hours for ß2 adrenergics and 6-8 hours for anticholinergics ): Inhaled ß2 adrenergics (salbutamol 100-200 mcg e.g. ventolin, terbutaline 400-500 mcg), Inhaled anticholinergics (ipratropium 20-40 mcg), Oral ß2 adrenergics (salbutamol 2 or 4 mg e.g. ventolin, terbutaline 2.5 or 5 mg); Combination of salbutamol/ipratropium (100/20 mcg)
  • Long-acting (12 hours for ß2 adrenergics and 24 hours for anticholinergics: Inhaled ß2 adrenergics (salmeterol 25-50 mcg, formoterol 4.5-12 mcg), Inhaled anticholinergics (tiotropium 18 mcg e.g. tiova)

Other medications:

  1. Short acting beta adrenergics: Fenoterol, Levalbuterol
  2. Short acting anticholinergics: Oxitropium
  3. Long acting beta adrenergics: Arformoterol, Indacaterol, Oladaterol, Tulabuterol
  4. Long acting anticholinergics: Aclidinium, Glycopyrronium, Umeclidinium

b. Inhaled corticosteroids:

  • Beclomethasone 50-400 mcg
  • Budesonide 100, 200, 400 mcg
  • Fluticasone 50-500 mcg

Foracort is a combination of formoterol (fixed 6 mcg) and budesonide (100, 200 or 400 mcg)

c. Oral methylxanthines:

  • Aminophylline 200-600 mg pill
  • Theophylline 100-600 mg pill
  • Doxofylline 400 mg (PO BD)

d. Systemic steroids: Prednisolone 5-60 mg (pill), Methylprednisolone 4, 8, 16 mg (pill)

  • Long term use of systemic steroids is not recommended

e. Phosphodiesterase-4 inhibitor (new class): roflumilast 500 mcg (duration 24 hours)

f. Symptomatic measures:

  • Hot drinks or steam inhalation to liquefy sputum
  • Mucolytics: bromhexine, N-acetylcysteine, carbocysteine, ambroxol, erdosteine

g. Non-pharmacological interventions:

  • Regular physical activity
  • Pulmonary rehabilitation: patient assessment, exercise training, education, behaviour change, nutritional intervention and psychosocial support
  • Chest physiotherapy: for chronic bronchitis, those with co-existent bronchiectasis and some patients during an acute exacerbation
  • Smoking cessation:
    • 5 A’s of Intervention: Ask (about smoking status), Advise, Assess (willingness to attempt quit within 30 days), Assist (Refer pharmacotherapy – nicotine replacement therapy, buprobion, varenicline; Refer community cessation service), Arrange (assess smoking status every visit)
    • 5 R’s of Motivation: Relevance (benefits of quiting), Risks, Rewards, Roadblocks, Repetition

h. Long-term domiciliary oxygen therapy:

Low dose (2 l/min) oxygen therapy through nasal cannula for atleast 15 hours per day, indicated for (2 X ABG ≥ 3 weeks apart) :

  • PaO2 ≤ 55 mmHg
  • PaO2 55-59 mmHg in the presence of pulmonary hypertension (PAP > 25 mmHg), right heart failure or polycythemia

Hypoxaemia is best screened for using pulse oximetry, however should be confirmed using arterial blood gas (ABG) measurement.

i.  Treatment of pulmonary hypertension:

  • Long term oxygen therapy (hypoxia is a potent pulmonary vasoconstrictor)
  • Synthetic prostacyclins (epoprostenol, iloprost, treprostinil)
  • Endothelin-1 receptor antagonists (bosentan)
  • Phosphodiesterase-5 inhibitors (sildenafil, tadalafil)

j. Surgeries:

  • Bullectomy: resection of large bulla (> 5 cm); giant bulla can be defined as those occupying ≥ 30% of hemithorax with definite displacement of adjacent lung tissue
  • Lung volume reduction surgery (LVRS): resection of most severely affected areas of non-emphysematous, non-bullous lungs
  • Lung transplantation: Recommended for –
    • BODE index 7-10 OR ≥1 of the following:
    • History of hospitalisation for exacerbations associated with acute hypercapnia
    • Pulmonary hypertension or cor pulmonale or both, despite oxygen therapy
    • FEV1 < 20% and either DLCO < 20% or homogeneous emphysema

BODE Index for COPD

Scoring: Add all the 4 parameters and calculate score out of 10:

  1. Body Mass Index (BMI)
    1. Points 0: BMI >21
    2. Points 1: BMI 21 or less
  2. Obstructive airway disease (FEV1)
    1. Points 0: FEV1 >64%
    2. Points 1: FEV1 50-64%
    3. Points 2: FEV1 36-49%
    4. Points 3: FEV1 <36%
  3. Dyspnea Index (mMRC)
    1. Points 0: 0-1
    2. Points 1: 2
    3. Points 2: 3
    4. Points 3: 4
  4. Exercise (Six-Minute Walk Test)
    1. Points 0: Walks >349 meters
    2. Points 1: Walks 250-349 meters
    3. Points 2: Walks 150-249 meters
    4. Points 3: Walks <150 meters

Interpretation: 4 year survival –

  • 0-2: 80%
  • 3-4: 67%
  • 5-6: 57%
  • 7-10: 18%

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