Chronic ObstructivePulmonary Disease(COPD)By Dr. Ahmed AzhadModerator: Dr. Mariyam Niyaz15th October 2012
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.
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
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
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
Diagnosis of COPD• Spirometry is required to make a clinical diagnosis of COPD• Post bronchodilator FEV1/FVC < 0.70
Assesment of COPD• Symptoms• Degree of airflow limitations• Risk of exacerbations• Comorbidities
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.
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
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/]
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
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
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%
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.
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
Therapeutic options• Prevention• Pharmacological• Other treatment
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)
Strategies to help patients willingto 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
Other treatments• Rehabilitation• Oxygen therapy• Ventilatory support• Surgical treatment
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
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)
• 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)
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.
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.
Combination bronchodilatortherapy • 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.
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.
Combination inhaledcorticosteroid/bronchodilatortherapy • 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).
• 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).
• 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.
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
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.
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).
Alpha-1 Antitrpsin Augmentationtherapy • 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
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).
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).
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
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
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
• 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).
• 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).
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.
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
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
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
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.
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)
References• Global strategy for the diagnosis, management, and prevention of Chronic Obstructive Pulmonary disease (2011 Revision) – http://www.goldcopd.org/• http://www.uptodate.com/