Chronic Bronchitis Phenotype COPD

COPD in which chronic productive cough on most days for at least 3 months in each of 2 consecutive years is the dominant feature, with mucus hypersecretion, airway inflammation and airflow obstruction (post-bronchodilator FEV1/FVC less than 0.70). Chronic bronchitis is present in about 15 to 35% of people with COPD, and associated with more frequent exacerbations, faster decline in lung function and higher mortality.

• Cause: tobacco smoking (the main cause), biomass fuel smoke (an important cause in women and rural populations in Africa and Asia), occupational dusts and fumes, air pollution, and recurrent childhood infection.
• Mechanism: goblet cell and submucosal gland hyperplasia, mucus plugging, ciliary dysfunction, airway wall thickening and neutrophilic inflammation, with chronic bacterial colonisation. The "blue bloater" picture (obesity, cyanosis, hypercapnia, polycythaemia, cor pulmonale) is a severe form.
• Prognosis depends on lung function, exacerbation frequency, hypoxaemia and smoking status; smoking cessation is the only intervention proven to slow the loss of lung function.

• Productive cough (often morning sputum), progressive breathlessness, wheeze, frequent chest infections, weight gain, morning headache and sleepiness (hypercapnia), ankle swelling (cor pulmonale).
• Signs: central cyanosis, rhonchi and coarse crackles, wheeze, hyperinflated chest in advanced disease, raised jugular venous pressure, peripheral oedema, flapping tremor and warm hands in hypercapnia, plethoric facies.
• Differential diagnosis: asthma, bronchiectasis (large volume purulent sputum), cystic fibrosis, tuberculosis, lung cancer, heart failure, interstitial lung disease, obstructive sleep apnoea obesity hypoventilation syndrome, and chronic aspiration.
• Complications: frequent exacerbations, chronic respiratory failure, cor pulmonale, secondary polycythaemia, pulmonary hypertension, pneumothorax, venous thromboembolism, lung cancer, osteoporosis, depression, and death.

• Spirometry after a bronchodilator: FEV1/FVC less than 0.70 confirms obstruction; grade severity by FEV1 (mild 80% or more, moderate 50 to 79%, severe 30 to 49%, very severe less than 30% predicted). Lung volumes and diffusing capacity (usually relatively preserved compared with emphysema).
• Chest X-ray: increased bronchovascular markings, cardiomegaly with cor pulmonale; CT chest: airway wall thickening, mucus plugging, bronchiectasis, emphysema extent.
• Blood tests: full blood count (haemoglobin and haematocrit greater than 55% suggests secondary polycythaemia), eosinophil count (300 per microlitre or more predicts response to inhaled corticosteroid), alpha-1 antitrypsin level once in all patients with COPD, urea and electrolytes, bicarbonate.
• Arterial blood gas when SpO2 is 92% or less or hypercapnia is suspected; overnight oximetry or polysomnography for sleep disordered breathing. Echocardiography for pulmonary hypertension and right ventricular function. Sputum culture during stable and exacerbation periods in frequent exacerbators. Xpert MTB/RIF where tuberculosis is possible. Assess breathlessness grade, COPD Assessment Test score, exacerbation history, walking test, BMI.

• Smoking and exposure control (the most important step): brief advice at every visit, behavioural support, and drug therapy: varenicline 0.5 mg daily for 3 days, 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks; nicotine patch 21 mg/24 h (14 mg for under 10 cigarettes a day) with gum or lozenge; bupropion 150 mg daily for 3 days then twice daily. Clean cooking fuels and ventilation for biomass exposure.
• Bronchodilator and anti-inflammatory therapy by symptoms and exacerbation risk:
  • Long acting muscarinic antagonist: tiotropium 18 micrograms inhaled once daily (or 5 micrograms by soft mist inhaler); or umeclidinium 62.5 micrograms daily.
  • Long acting beta agonist and muscarinic antagonist combination for persistent breathlessness: indacaterol/glycopyrronium 110/50 micrograms once daily, or umeclidinium/vilanterol 62.5/25 micrograms once daily, or tiotropium/olodaterol 5/5 micrograms 2 puffs once daily.
  • Triple therapy (adds an inhaled corticosteroid) for patients with two or more moderate exacerbations or one admission a year despite dual therapy, particularly with eosinophils of 300 per microlitre or more: fluticasone furoate/umeclidinium/vilanterol 100/62.5/25 micrograms once daily, or beclometasone/formoterol/glycopyrronium 87/5/9 micrograms 2 puffs twice daily. Inhaled corticosteroid raises the risk of pneumonia, so withdraw it when eosinophils are less than 100 per microlitre and there is no exacerbation benefit.
  • Salbutamol 100 to 200 micrograms as needed for rescue.
• Mucus and exacerbation reduction:
  • Carbocisteine 750 mg orally three times daily, then 500 mg three times daily, or N-acetylcysteine 600 mg twice daily, for frequent exacerbators (evidence is moderate).
  • Roflumilast 500 micrograms once daily for FEV1 less than 50% with chronic bronchitis and a history of admissions or two or more exacerbations a year; monitor weight (loss of 2 kg or more), mood, insomnia and gastrointestinal effects; avoid in depression, suicidal thoughts, low BMI and with theophylline.
  • Azithromycin 250 mg daily or 500 mg three times weekly for ex smokers with frequent exacerbations on optimal inhaled therapy, after sputum for non-tuberculous mycobacteria, an ECG for QT interval, and an audiogram; stop with hearing loss, QT prolongation or bacterial resistance concerns.
  • Dupilumab 300 mg SC every 2 weeks for eosinophils of 300 per microlitre or more with exacerbations despite triple therapy.
  • Airway clearance: huff cough, active cycle of breathing and positive expiratory pressure devices; nebulised hypertonic saline 7% twice daily when sputum is thick (evidence is limited).
• Management of exacerbation: prednisolone 30 to 40 mg daily for 5 days; antibiotic for purulent sputum (amoxicillin 500 mg to 1 g three times daily, doxycycline 200 mg then 100 mg daily, or co-amoxiclav 625 mg three times daily) for 5 days; non-invasive ventilation for acidosis; controlled oxygen at 88 to 92%.
• Chronic respiratory failure and cor pulmonale:
  • Long term oxygen therapy for at least 15 hours daily when PaO2 is 7.3 kPa or less, or 8.0 kPa or less with cor pulmonale, haematocrit greater than 55% or nocturnal hypoxaemia (stable, non-smoking, after 3 weeks of optimal therapy); check for CO2 retention.
  • Home non-invasive ventilation for persistent hypercapnia (PaCO2 greater than 7 kPa) after an acute acidotic admission.
  • Diuretics for oedema: furosemide 20 to 80 mg daily with spironolactone 25 to 50 mg daily; avoid over diuresis.
  • Phlebotomy for symptomatic polycythaemia with haematocrit greater than 60%, with isovolaemic fluid replacement.
  • Avoid sedatives, opioids at high doses, and beta blockers that are non-selective.
• Non-drug care: pulmonary rehabilitation (6 to 8 weeks, twice weekly), nutrition and weight management, treatment of obstructive sleep apnoea with continuous positive airway pressure, vaccination (yearly influenza, pneumococcal conjugate, COVID-19, respiratory syncytial virus in older adults), treatment of anxiety and depression, palliative support, and advance care planning for advanced disease.
• Surgery: lung transplantation is considered for very severe disease (FEV1 less than 25% with frequent admissions, hypercapnia or pulmonary hypertension) in patients under 65 to 70 who have stopped smoking.
• Special groups:
  • Women and biomass exposed patients: clean fuel use, early spirometry, and exclusion of tuberculosis.
  • Pregnancy: rare; continue long acting bronchodilators and inhaled corticosteroid as needed; avoid roflumilast and azithromycin where possible.
  • Elderly: simplify inhaler regimens, check technique, review polypharmacy, and assess frailty.
  • Renal or hepatic impairment: adjust theophylline, azithromycin and roflumilast.
• Red flags: haemoptysis, weight loss, hypercapnic drowsiness, new oedema, syncope, fever with purulent sputum, SpO2 less than 88%, frequent exacerbations.
• Follow up: review every 3 to 6 months with symptoms, exacerbations, inhaler technique, weight and SpO2; yearly spirometry; blood gas and sleep review for hypoxaemia or hypercapnia; reinforce smoking cessation at every visit.