A presentation on Chronic Obstructive Pulmonary Disease based on GOLD Guidelines.

1. Chronic Obstructive
Pulmonary Disease
(COPD)
By Dr. Ahmed Azhad
Moderator: Dr. Mariyam Niyaz
15th October 2012

2. COPD - Definition
• common preventable and treatable disease,
• is characterized by persistent airflow limitation that is usually
progressive, not fully reversible
• and associated with an enhanced chronic inflammatory
response in the airways in the lung to noxious gases and
particles.

3. COPD – Key Points
• Exacerbations and comorbidities – contribute to overall
severity in individual patients
• Fourth leading cause of death worldwide
• Risk factors: tobacco smoke, smoke from biomass fuels →
modified inflammatory response

4. COPD – Mechanism
Small airways disease Parenchymal destruction
Airway inflammation Loss of alveolar attachments
Airway fibrosis; luminal plugs Decrease of elastic recoil
Increased airway resistance
AIRFLOW LIMITATION

6. Diagnosis of COPD
• COPD to be considered when clinically:
• Dyspnea (progressive, worsening on exercise, persistent)
• Chronic cough (maybe intermittent, maybe unproductive)
• Sputum production (no particular pattern)
• And/ or history of exposure to risk factor
• Family history

7. Diagnosis of COPD
• Spirometry is required to make a clinical diagnosis of COPD
• Post bronchodilator FEV1/FVC < 0.70

8. Assesment of COPD
• Symptoms
• Degree of airflow limitations
• Risk of exacerbations
• Comorbidities

9. Grading of breathlessness
mMRC Grade 0 In only get breathless with strenuous exercise.
mMRC Grade 1 I get short of breath when hurrying on the level or
walking up a slight hill.
mMRC Grade 2 I walk slower than people of the same age on the level
because of breathlessness, or I have to stop for breath
when walking on my own pace on the level.
mMRC Grade 3 I stop for breath after walking about 100 meters or
after a few minutes on the level.
mMRC Grade 4 I am too breathless to leave the house or I am
breathless when dressing or undressing.

10. Spirometry
• In patients with FEV1/FEV < 0.70
GOLD 1 Mild FEV1 ≥ 80% predicted
GOLD 2 Moderate 50% ≤ FEV1 < 80% predicted
GOLD 3 Severe 30% ≤ FEV1 < 50% predicted
GOLD 4 Very Severe FEV1 < 30% predicted

11. Spirometry

12. Combined COPD assessment
Gold classification of airflow limitation
4
C D ≥2
Exacerbation history
3
RISK
RISK
2 1
A B
1 0
mmRC 0-1 mmRC ≥ 2
CAT < 10 CAT ≥ 10
Symptoms
(mMRC or CAT score)
[CAT Score -
http://www.catestonline.org/]

13. Combined COPD assessment
• Group A – Low risk, less symptoms
• Group B – Low risk, more symptoms
• Group C – High risk, less symptoms
• Group D – High risk, more symptoms

14. Other investigations
• Chest X-ray
• Not useful in diagnosis of COPD, but useful in excluding other
differentials and finding co-morbidities
(fibrosis, bronchiectasis, pleural disease)
• Signs on X-ray: lung hyperinflation – flattened diaphragm on
lateral chest radiograph, increased volume in retrosternal lung.
• CT Scan – not routinely recommended

15. Other investigations
• DLCO – to assess functional impact of emphysema
• Pulse oximetry – to assess need of supplemental oxygen
therapy
• Should be used for patients with:
• FEV1 < 35% predicted
• Clinical signs of respiratory failure or right heart failure
• ABG – in patients whose sPO2 < 92%

16. Other investigations
• Alpha-1 Antitrypsin deficiency
• WHO recommended in areas of high prevalence
• Patient’s presenting with lower lobe emphysema with age < 45
yrs.
• In such cases family member screening advisable
• A serum conc. < 15-20% of normal value is suggestive of
homozygous Alpha-1 Antitrypsin deficiency
• Exercise testing – for prognosis.

17. Differential Diagnosis
• COPD – midlife, progressive, h/o exposure to smoke
• Asthma – early, symptom variability day-day, worse at
night, atopy, family history
• Congestive Heart failure – X-ray: dilated heart, pulmonary
edema, volumetric deficiency (not obstructive)

18. Differential Diagnosis
• Bronchiectasis – purulent sputum (large volume), bacterial
infections, CXR: bronchial dilation/wall thickening
• TB – all ages, Xray: lung infiltrates, AFB, high local prevalence
• Obliterative bronchiolitis – younger age, non-
smokers, RA, exposure to fumes, post-lung transplant, CT:
hypodense areas on inspiration
• Diffuse panbronchiolitis: Asians, male, non-smokers, +chronic
sinusitis, Xray/HRCT: diffuse, small, centrilobular nodular
opacities + hyperinflation

19. Therapeutic options
• Prevention
• Pharmacological
• Other treatment

20. Treatment
• Smoking cessation
• Nicotine replacement therapy: contraindications unstable
CAD, untreated PUD, recent MI/stroke
• Pharmacologic: Varenicline, bupropion, nortriptyline
• “Counselling delivered by physicians and other health
professionals significantly increases quit rates over self-initiated
strategies”. (Evidence A)

21. Strategies to help patients willing
to quit smoking
• ASK: Systemic identification: EVERY patient, EVERY clinic visit
• ADVISE: Strongly urge all tobacco users to quit
• ASSESS: Determine willingness to make a quit attempt.
• ASSIST: Aid the patient – quit plan, social
support, pharmacotherapy
• ARRANGE: Followup

22. Pharmacological
• Bronchodilators
• Inhaled corticosteroids (ICS)
• Combination inhaled corticosteroid/ bronchodilator
• Oral corticosteroids
• Phosphodiesterase-4 inhibitors
• Methylxanthines
• Other
• Vaccines
• Alpha 1 antitrypsin augmentation therapy
• Antibiotics
• Mucolytics

23. Other treatments
• Rehabilitation
• Oxygen therapy
• Ventilatory support
• Surgical treatment

24. Bronchodilators
• Increase FEV1
• Use of nebulisers useful in exacerbations
• Given SOS / regular basis (Evidence A)
• Central to symptom management
• Inhaled therapy preferred
• Long-acting more convenient
• Combination of various classes improves efficacy and reduces
side effects

25. Beta2-agonists
• Regular and as-needed use of short-acting beta2-agonists
improve FEV1 and symptoms (Evidence B)
• Formetrol and salmetrol significantly improve FEV1, lung
volumes, dyspnoea, health-related quality of life and
exacerbation rate (Evidence A)
• Salmetrol reduces the rate of hospitalisation (Evidence B)

26. • Indacaterol is a novel long-acting beta2-agonist with a duration of
action of 24 hours. It significantly improves FEV1, dyspnoea and
health-related quality of life (Evidence A)
• Adverse effects: somatic tremor, hypokalemia and oxygen
consumption (latter two showing tachyphylaxis unlike
bronchodilator action), mild fall in PaO2 (clinical significance not
known)

27. Anticholinergics
• Tiotropium reduces exacerbations and related
hospitalisations, improves symptoms and health status (Evidence
A) and improves the effectiveness of pulmonary rehabilitation
(Evidence B).
• Adverse effects: dryness of mouth, bitter metallic taste.

28. Methylxanthines
• Theophylline: modest bronchodilator effect compared with
placebo in stable COPD (Evidence A).
• Addition of theophylline to salmeterol produced a greater
improvement in FEV1 and breathlessness than salmeterol alone
(Evidence B).
• Low-dose theophylline reduces exacerbations but does not
improve post-bronchodilator lung function (Evidence B).
• Adverse effects: toxicity, small therapeutic ratio, arrhythmias.

29. Combination bronchodilator
therapy
• Shortness-term combination therapy using formoterol and
tiotropium has been shown to have a bigger impact on FEV1 than
the single components (Evidence B).
• Combinations of short-acting beta2-agonists and anticholinergics
are also superior compared to either medication alone in
improving FEV1 and symptoms.

30. Inhaled corticosteroids
• Regular treatment with inhaled corticosteroids improves
symptoms, lung function and quality of life, and reduces
frequency of exacerbations in COPD patients with an FEV1 < 60%
predicted (Evidence A).
• Regular treatment with inhaled corticosteroids does not modify
the long-term decline of FEV1 nor mortality in patients with COPD
(Evidence A).
• Adverse effects: oral candidiasis, hoarse voice, skin
bruising, increased risk of pneumonia.

31. Combination inhaled
corticosteroid/bronchodilator
therapy
• An inhaled corticosteroid combined with a long-acting beta2-
agonist is more effective than the individual components in
improving lung function and health status and reducing
exacerbations in patients with moderate (Evidence B) to very
severe COPD (Evidence A).

32. • A large prospective clinical trial failed to demonstrate a
statistically significant effect of combination therapy on mortality
but a subsequent meta-analysis found that combination therapy
may reduce mortality with a number needed to treat of 36
(Evidence B).
• Combination therapy is associated with an increased risk of
pneumonia but no other significant side effect (Evidence A).

33. • The addition of long-acting beta2-agonist/inhaled corticosteroid
combination to tiotropium improves lung function and quality of
life and may further reduce exacerbations (Evidence B) but more
studies of triple therapy are needed.

34. Oral corticosteroids
• No role of long term oral corticosteroid
• Used only in exacerbations
• Improve symptoms and lung function, and decrease the length of
hospital stay
• Oral glucocorticoids appear equally efficacious as intravenous
glucocorticoids for treating most exacerbations of COPD.
• Numerous side effects – steroid myopathy, respiratory failure in
patients with very severe COPD

35. Phosphodiesterase-4 inhibitors
• Reduces inflammation by inhibiting breakdown of intracellular cyclic
AMP
• Once daily oral medication
• Roflumilast reduces moderate and severe exacerbations treated with
corticosteroids by 15-20% in patients with chronic bronchitis, severe
to very severe COPD and a history of exacerbations (Evidence A).
• The effects of lung function are also seen when roflumilast is added
to long-acting bronchodilators (Evidence A).
• Adverse effects: nausea, reduced appetite, abdominal
pain, diarrhoea, sleep disturbances, headache, weight loss. Should
be used with caution in depression. Cannot be given with
theophylline.

36. Vaccines
• Influenza vaccine can reduce serious illness and death in COPD
patients (Evidence A).
• Pneumococcal polysaccharide vaccine is recommended for
patients older than 65 yrs of age
• In addition, this vaccine has been shown to reduce the incidence
of community-acquired pneumonia in COPD patients younger
than age 65 with an FEV1 < 40% predicted (Evidence B).

37. Alpha-1 Antitrpsin Augmentation
therapy
• Young patients with severe hereditary alpha-1 antitrypsin
defeciency and established emphysema may be candidates for
alpha-1 antitrypsin augmentation therapy (Evidence C).
• Expensive
• Not available in most countries

38. Other Pharmacological treatments
• Antibiotics
• Use of antibiotics, other than for treating exacerbations of COPD
and other bacterial infections is currently not indicated (Evidence
B).
• Mucolytic and antioxidant agents:
• Although a few patients with viscous sputum may benefit from
mucolytics, the overall benefits seem to be very small; the
widespread use of these agents cannot be recommended at
present (Evidence D).

39. Other Pharmacological treatments
• Mucolytic and antioxidant agents:
• Drugs like N-acetylcysteine may have antioxidant effects, leading
to speculation that these medications could have a role in the
treatment of patients with recurrent exacerbations (Evidence B).
• There is some evidence that in COPD patient not receiving
inhaled corticosteroids, treatment with mucolytics such as
carbocysteine and N-acetylcysteine may reduce exacerbations
(Evidence B).

40. Other Pharmacological treatments
• Immune-regulators
• Reports of decrease in severity and frequency of
exacerbations, additional studies required
• Antitussives
• The regular use of antitussives is not recommended in stable
COPD (Evidence D).
• Vasodilators
• Contraindicated in stable COPD

41. Other Treatments
• Narcotics (morphine) – insufficient data, limited benefit
• Others: Nedocromil and leukotriene modifiers – not
adequately tested
• Non-pharmacologic:
• Pulmonary rehabilitation which includes exercise training
• Nutritional counselling

42. Oxygen Therapy
• The long term administration of oxygen (>15 hours per day) to
patients with chronic respiratory failure has been shown to
increase survival in patients with severe resting hypoxemia
(Evidence B).
• Indicated for:
• PaO2 ≤ 7.3 kPa (55 mm Hg) or SaO2 ≤ 88 with or without hypercapnia
confirmed twice over a three week period (Evidence B); or

43. • PaO2 between 7.3 kPa (55 mmHg) and 8.0 kPa (60mm Hg), or
SaO2 of 88%, if there is evidence of pulmonary
hypertension, peripheral edema suggesting congestive cardiac
failure, or polycythemia (hematocrit > 55%) (Evidence D).

44. • Air travel – safe for most patients with COPD
• Patients should be able to maintain an in-flight PaO2 of 6.7 kPa (50
mm Hg) – requiring O2 3LPM or Venturi 31% by facemask
• PaO2 > 9.3 (70mm Hg) are likely to be safe to fly without
supplemental O2, althought it does not exclude development of
severe hypoxemia when travelling by air (Evidence C).
• Other comorbidities to be considered (cardiac impairment, anemia).

45. Ventilatory support
• NIV +LTOT
• Combination of non invasive ventilation and long term oxygen
maybe useful in patients with pronounced daytime
hypercapnia.
• Improve survival but does not increase quality of life.
• Clear benefits of CPAP on both survival and risk of hospital
admission.

46. Surgical treatments
• Lung Volume Reduction Surgery
• In contrast to medical treatment, LVRS had been demonstrated to
result in improved survival (54% vs. 39.7%) in severe emphysema
patients with upper lobe emphysema and low post-rehabilitation
exercise capacity (Evidence A).
• Higher mortality than medical management in severe
emphysema patients with FEV1 < 20% predicted
• Lung transplantation
• Bullectomy

47. Stable COPD
• Goal: To reduce symptoms, reduce risk
• Smoking cessation

48. Stable COPD: Pharmacotherapy
Patient Group First Choice Second Choice Alternative choice
A (less Short-acting anti-chol. SOS
Long-acting anti-chol. OR
Long-acting β2 agonist OR
risk, less OR
Short-acting β2 agonist and
Theophylline
Short-acting β2-agonist SOS
sym) short-acting anti-chol.
Short-acting β2 agonist
B (less and/or short-acting
Long-acting anti-chol. OR Long-acting anti-chol. AND
risk, more Long-acting β2-agonist long-acting β2-agonist
anticholinergic
sym) Theophylline
Phosphodiesterase-4
inhibitor
C (more Inhaled corticosteroid +
Long-acting anti-chol and Short-acting β2 agonist
risk, less long-acting β2 agonist OR
long acting β2 agonist and/or short-acting
long-acting anti-chol.
sym) anticholinergic
Theophylline
ICS + long-acting anti-chol
or
ICS + long-acting β2 agonist
and long-acting antichol
or Carbocysteine
ICS + long-acting β2 agonist
D (more Inhaled corticosteroid + and phosphodiesterase-4 Short-acting β2 agonist
risk, more long-acting β2 agonist OR inhibitor and/or short-acting
long-acting anti-chol. or anticholinergic
sym) Long-acting anti-chol. And
long-acting β2-agonist Theophylline
or
Long-acting anti-chol. And
phosphodiesterase-4
inhibitor

49. Exacerbations of COPD
• Mostly due to viral URTI
• Acute worsening of symptoms beyond day-day variation
• Goal: Minimise impact of exacerbation and to prevent
subsequent exacerbations
• Short-acting inhaler bronchodilators + systemic corticosteroids
• Oxygen therapy (target sPO2 88-92%), using Venturi if
tolerated, ABG every 30-60 mins to check for CO2 retention
• Can be prevented by smoking cessation, influenza and
pneumococcal vaccination, correct use of inhalers, and use of
long-acting bronchodilators ± corticosteroids

50. Exacerbations of COPD
• GOLD: Antibiotics to be given to patients with three cardinal
symptoms: increase in dyspnoea, sputum volume, and sputum
purulence (Evidence B); have two cardinal symptoms if
increase of purulence of sputum is one of them (Evidence C);
or require mechanical or non-invasive ventilation (Evidence B).
Recommended Length: 5-10 days.
• Uptodate: Antibiotics given in moderate to severe COPD
exacerbation which is defined by having atleast two of three
symptoms — increased dyspnea, increased sputum volume, or
increased sputum purulence — or requiring hospitalization.
• Antibiotic therapy not initiated in patients whose exacerbation is
mild, which is defined as having only one of these three
symptoms and not requiring hospitalization or ventilatory
assistance.

51. Exacerbations of COPD
• Mechanical ventilation to prevent respiratory acidosis
• Indications for NIV:
• pH < 7.35 or pCO2 > 45mm Hg
• severe dyspnoea with clinical signs of respiratory muscle fatigue,
increased work of breathing or both (use of resp. muscles, paradoxical
movement of abdomen, retraction of intercostal spaces).
• Indications for invasive ventilation:
• Not tolerating NIV, resp./cardiac arrest, respiratory pauses/gasping,
diminished consciousness, psychomotor agitation not controlled by
sedation, massive aspiration, persistent inability to remove respiratory
secretions, HR < 50 with loss of alertness, severe hemodynamic
instability without response to fluids/vasoactive drugs, severe ventricular
arrythmias, life-threatening hypoxemia in patients undergoing NIV
• Systemic corticosteroids to be used in exacerbations (Evidence A)
• Dose: Prednisolone 30-40 mg, x 10-14 days (Evidence D)

52. References
• Global strategy for the diagnosis, management, and
prevention of Chronic Obstructive Pulmonary disease (2011
Revision) – http://www.goldcopd.org/
• http://www.uptodate.com/

53. Thank You