Chronic Cough

Chronic cough is cough lasting more than 8 weeks in adults (more than 4 weeks in children). It affects about 10% of adults, is commoner in women (peak between ages 50 and 70), and has a major effect on quality of life, with stress incontinence, sleep loss, hoarseness, rib fracture and social isolation.

• Common causes in adults with a normal chest X-ray:
  • Upper airway cough syndrome (postnasal drip from rhinitis or rhinosinusitis).
  • Asthma, including cough variant asthma, and eosinophilic bronchitis without airflow obstruction.
  • Gastro oesophageal reflux disease, including laryngopharyngeal reflux.
  • These three account for about 80% of cases, and more than one cause often coexists.
• Other causes: ACE inhibitor therapy (resolves in 1 to 4 weeks after stopping, sometimes up to 3 months), smoking and chronic bronchitis, chronic obstructive pulmonary disease, bronchiectasis, post-infectious cough, interstitial lung disease, lung cancer, tuberculosis, heart failure, sarcoidosis, obstructive sleep apnoea, pertussis, aspiration, foreign body, habit or somatic cough, and refractory (unexplained) chronic cough.
• Refractory chronic cough, or unexplained chronic cough, describes cough that persists despite investigation and treatment of potential causes. It is thought to arise from cough hypersensitivity syndrome, with neural sensitisation of the vagal afferent pathways. It affects about 10 to 20% of patients attending a cough clinic and is more common in women after the menopause.
• Cough hypersensitivity: coughing triggered by low level thermal, mechanical or chemical stimuli (cold air, talking, laughing, perfume, smoke, eating).
• In children, the commonest causes are protracted bacterial bronchitis, asthma, upper airway cough syndrome, post-infectious cough, foreign body, bronchiectasis, tuberculosis and habit cough.

• A daily cough for more than 8 weeks, dry or productive, with a persistent tickle in the throat, frequent throat clearing, hoarseness, a sensation of postnasal drip, and cough worse with talking, laughing, change of air temperature, or lying flat.
• Complications reported: stress urinary incontinence (in up to 50% of women), cough syncope, sleep disruption, chest wall and rib pain, headache, hoarseness, anxiety, depression, and social avoidance.
• Features pointing to the cause:
  • Postnasal drip, nasal obstruction, rhinorrhoea and throat clearing: upper airway cough syndrome.
  • Wheeze, breathlessness, nocturnal cough, atopy and exercise induced symptoms: asthma. Dry cough without wheeze in cough variant asthma.
  • Heartburn, regurgitation, a cough after meals or on lying, hoarseness: reflux. About 50% of reflux related cough occurs without typical reflux symptoms.
  • A dry cough starting within weeks of an ACE inhibitor.
  • Sputum production most days: chronic bronchitis or bronchiectasis.
  • Haemoptysis, weight loss, night sweats, clubbing: cancer, tuberculosis, bronchiectasis.
  • Orthopnoea, oedema, and exertional breathlessness: heart failure.
  • Snoring and daytime sleepiness: obstructive sleep apnoea.
  • Cough with eating or drinking, a wet voice, or recurrent chest infection: aspiration.
• Differential diagnosis: upper airway cough syndrome, asthma, eosinophilic bronchitis, reflux disease, ACE inhibitor cough, smoking related disease, chronic obstructive pulmonary disease, bronchiectasis, interstitial lung disease, lung cancer, tuberculosis, heart failure, sarcoidosis, obstructive sleep apnoea, pertussis, aspiration, habit cough, and also pulmonary embolism (chronic thromboembolic disease), recurrent aspiration, tracheobronchomalacia, laryngeal disorders (vocal cord dysfunction, laryngeal tumour), an enlarged thyroid, cervical osteophytes, and an elongated uvula.
• Red flags: haemoptysis; age above 45 and a smoker with a change in cough; hoarseness lasting more than 3 weeks; weight loss; fever or night sweats; breathlessness out of proportion; chest pain; clubbing; recurrent pneumonia; difficulty swallowing; dyspnoea at rest; a neck mass; a history of cancer or tuberculosis; immunosuppression; and an abnormal chest X-ray.

• A systematic assessment: history (duration, character, timing, triggers, sputum, associated symptoms, smoking, occupational and environmental exposure, family history, all medicines, especially ACE inhibitors), examination (chest, nose, throat, oropharynx, lymph nodes, clubbing, cardiovascular system, weight, body mass index), and a review of earlier investigations.
• First line tests in all patients:
  • Chest X-ray (posteroanterior and lateral) to exclude lung cancer, tuberculosis, interstitial disease, heart failure and bronchiectasis.
  • Spirometry with bronchodilator reversibility testing (forced expiratory volume in 1 second increase of 12% and 200 mL or more).
  • Peak flow diary for 2 weeks if asthma is suspected (variability above 20%).
  • Full blood count with eosinophil count, plus glucose and, when relevant, B-type natriuretic peptide.
  • Smoking status (cotinine test if uncertain), and a review of medicines.
• Further tests, directed by the findings:
  • Fractional exhaled nitric oxide (above 40 ppb in adults suggests eosinophilic airway disease) and sputum eosinophil count (above 3%).
  • Methacholine or mannitol bronchial provocation testing for cough variant asthma, when spirometry is normal.
  • High resolution CT of the chest for persistent unexplained cough, abnormal spirometry, suspected bronchiectasis or interstitial lung disease, or unresolved X-ray findings.
  • Nasal endoscopy and CT of the sinuses for chronic rhinosinusitis or persistent upper airway symptoms.
  • Laryngoscopy for hoarseness, throat symptoms or suspected laryngeal causes.
  • Reflux assessment: a course of acid suppression, or 24 hour oesophageal pH-impedance monitoring and upper endoscopy for alarm symptoms or refractory symptoms.
  • Sputum tests for acid fast bacilli or a molecular assay, and culture, in suspected infection.
  • Bronchoscopy for haemoptysis, suspected foreign body, tumour, or an unexplained abnormal chest X-ray.
  • Sleep study when sleep apnoea is suspected.
  • Swallow assessment (videofluoroscopy) for suspected aspiration.
• A response to treatment is part of the diagnosis: an improvement in cough with a specific treatment supports that cause. Allow 2 to 4 weeks for nasal therapy, 4 to 8 weeks for inhaled steroids, and 8 to 12 weeks for acid suppression.
• Screen for depression, anxiety and sleep disturbance, and measure the effect of the cough using a validated cough score or a visual analogue scale from 0 to 10.

• General measures for every patient:
  • Stop smoking and avoid triggers (fumes, dust, perfumes). Offer nicotine replacement (patch 21 mg per 24 hours for those smoking more than 10 cigarettes daily) or varenicline 0.5 mg daily for 3 days, then 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks.
  • Stop ACE inhibitors and replace with an angiotensin receptor blocker (for example losartan 50 mg once daily). Expect improvement within 1 to 4 weeks, and up to 3 months.
  • Treat obesity, avoid late meals, and raise the head of the bed 10 to 15 cm if reflux is suspected.
  • Reduce throat clearing and caffeine, and sip water.
• Upper airway cough syndrome: fluticasone propionate nasal spray 50 micrograms per spray, 2 sprays each nostril once daily (or mometasone furoate 50 micrograms per spray, 2 sprays each nostril once daily), with saline irrigation. Add azelastine nasal spray 137 micrograms per spray, 1 to 2 sprays each nostril twice daily, for allergic or non-allergic rhinitis. A first generation antihistamine, such as chlorphenamine 4 mg orally every 4 to 6 hours (maximum 24 mg per day), can help non-allergic postnasal drip at night for 1 to 2 weeks, with drowsiness as a limiting factor. For bacterial rhinosinusitis, amoxicillin 500 mg orally 8 hourly for 5 to 7 days (or doxycycline 200 mg on day 1, then 100 mg daily for 5 to 7 days). Review in 2 to 4 weeks.
• Asthma and eosinophilic bronchitis: inhaled corticosteroid, for example beclometasone 200 to 400 micrograms twice daily or budesonide 200 to 400 micrograms twice daily by spacer or dry powder inhaler, for at least 4 to 8 weeks. Add a long acting beta agonist (formoterol 12 micrograms twice daily, as budesonide formoterol) for asthma with symptoms. Montelukast 10 mg orally once daily at night is an alternative for cough variant asthma (monitor mood changes). For severe exacerbations or disabling cough, prednisolone 30 to 40 mg once daily for 5 to 7 days.
• Gastro oesophageal reflux: omeprazole 20 to 40 mg orally once daily 30 to 60 minutes before breakfast (or esomeprazole 40 mg), for 8 to 12 weeks, with lifestyle advice. Add an evening dose or alginate (sodium alginate and potassium bicarbonate 10 to 20 mL after meals and at bedtime) if reflux symptoms persist. Cough improves slowly, and 2 to 3 months may be needed. Stop the proton pump inhibitor if no improvement, rather than continuing indefinitely.
• Chronic bronchitis and COPD: smoking cessation, inhaled bronchodilators (tiotropium 18 micrograms once daily by inhalation, or salbutamol 100 to 200 micrograms as needed), and pulmonary rehabilitation. Mucolytic carbocisteine 750 mg orally 3 times daily for 1 month, reduced to 750 mg twice daily, when sputum is troublesome. Review at 4 to 8 weeks.
• Bronchiectasis: airway clearance physiotherapy, hypertonic saline nebulised, and antibiotics for exacerbations (amoxicillin 500 mg to 1 g 8 hourly, or ciprofloxacin 500 to 750 mg 12 hourly for Pseudomonas, for 14 days).
• Tuberculosis: treat with isoniazid, rifampicin, pyrazinamide and ethambutol for 2 months, then isoniazid and rifampicin for 4 months, as weight based fixed dose combinations.
• Heart failure: treat with diuretics (furosemide 20 to 40 mg orally once daily), ACE inhibitor or alternative (an angiotensin receptor blocker, if cough), beta blocker and mineralocorticoid antagonist, under specialist cardiology care.
• Obstructive sleep apnoea: weight loss, positional therapy, and continuous positive airway pressure.
• Refractory or unexplained chronic cough (after a thorough review and treatment courses for the common causes):
  • Speech and language therapy (cough suppression therapy, education, vocal hygiene, breathing exercises, 4 to 6 sessions), which reduces cough frequency by 30 to 50%. This is the first line non-drug option.
  • Gabapentin 100 mg orally at night, increased every 3 to 7 days to 300 mg 3 times daily, and, if tolerated, to a maximum of 1800 mg daily in divided doses, for 8 to 12 weeks. Common adverse effects are drowsiness, dizziness and confusion. Reduce the dose in renal impairment (creatinine clearance below 60 mL/min), and avoid abrupt cessation. Pregabalin 25 to 75 mg orally twice daily is an alternative.
  • Low dose slow release morphine 5 mg orally 12 hourly, increased to 10 mg 12 hourly after 1 week if tolerated, for severe, disabling cough in specialist care, with laxatives and monitoring for sedation and dependence. It reduces cough by about 40% in some studies.
  • Amitriptyline 10 mg orally at night, increased by 10 mg every 1 to 2 weeks to 25 to 50 mg, in specialist care, with the usual cautions (anticholinergic effects, arrhythmia in older patients).
  • Peripherally acting P2X3 receptor antagonists are available in some countries for refractory chronic cough, taken as a tablet twice daily, and cause taste changes as the main adverse effect. Availability varies.
  • Inhaled lidocaine and botulinum toxin have been used experimentally, and are not routine.
• Habit (psychogenic or somatic) cough: a loud, honking, barking cough that disappears during sleep or distraction. Treat with reassurance, cough suppression therapy, and cognitive behavioural therapy, avoiding antitussives and antibiotics.
• Chronic cough in lung cancer or other serious cause: treat the cause, and refer to oncology for palliation, which may include codeine 15 to 30 mg orally 4 to 6 hourly, nebulised sodium cromoglicate, or morphine.
• Special groups:
  • Children: avoid cough suppressants and codeine. Investigate with a chest X-ray and spirometry, treat protracted bacterial bronchitis with amoxicillin clavulanate 22.5 mg/kg of amoxicillin 12 hourly for 2 weeks, and review in 2 to 4 weeks. Specific treatment of asthma (inhaled budesonide 100 to 200 micrograms twice daily by spacer), and removal of environmental smoke exposure. Refer for a persistent cough beyond 8 weeks, a wet cough, failure to thrive, clubbing or abnormal chest X-ray.
  • Pregnancy: use saline, intranasal steroids (budesonide or fluticasone), inhaled asthma treatment, alginates and omeprazole if needed, and avoid codeine, gabapentin and montelukast unless benefits outweigh risks.
  • Elderly: review polypharmacy, give lower doses of gabapentin and amitriptyline, and consider falls risk and swallowing.
  • Renal impairment: reduce gabapentin and pregabalin, and avoid NSAIDs.
  • Hepatic impairment: reduce morphine and avoid high dose paracetamol.
  • Women with stress incontinence: pelvic floor exercises and referral if persistent.
• Follow up: review at 4 to 8 weeks after each therapeutic course, and stop treatments that have not helped. Refer to a respiratory or cough clinic if cough persists beyond 3 months despite empirical treatment, or earlier for red flags (haemoptysis, abnormal chest X-ray, weight loss, voice change, age above 45 and a smoker).