Chronic cough

Chronic cough is cough lasting more than 8 weeks in adults (over 4 weeks in children). It affects about 10% of adults, is more frequent in women and in the fifth to sixth decades, and can cause major impairment: sleep loss, stress incontinence, rib fracture, syncope, hoarseness, and social avoidance.

Clinical relevance. In non smokers with a normal chest radiograph who take no ACE inhibitor, over 90% of chronic cough comes from:

• upper airway cough syndrome (postnasal drip)
• asthma (including cough variant asthma and eosinophilic bronchitis)
• gastro-oesophageal reflux disease

They often act together.

A significant minority have refractory chronic cough (cough hypersensitivity syndrome) after other causes are treated.

A persistent cough in a smoker, with weight loss, haemoptysis or abnormal radiograph, needs urgent exclusion of lung cancer and tuberculosis.

Classification.

• Chest radiograph abnormal: suspect lung cancer, tuberculosis, bronchiectasis, interstitial lung disease, sarcoidosis, heart failure, chronic infection, mediastinal mass, pleural disease, foreign body.
• Chest radiograph normal: upper airway cough syndrome, asthma, eosinophilic bronchitis, gastro-oesophageal reflux disease, drug induced (ACE inhibitor), chronic obstructive pulmonary disease and smoker's cough, post infectious cough, pertussis, obstructive sleep apnoea, vocal cord dysfunction, habit cough, refractory (unexplained) chronic cough, early interstitial lung disease, bronchiectasis.
• By duration: chronic over 8 weeks; subacute 3 to 8 weeks (post infectious).
• By character: dry, productive (chronic bronchitis over 3 months in 2 years, bronchiectasis with daily purulent sputum), paroxysmal.

Mechanism. Persistent inflammation or irritation of cough receptors and central sensitisation of the cough reflex (cough hypersensitivity) cause cough with low triggers such as talking, laughing, cold air, strong smells and perfumes.

History.

• Duration, onset (after a viral illness, after starting a drug, after exposure), character (dry or productive), time of day (night, on waking, after meals, on lying down), triggers (talking, laughing, cold air, perfume, exercise, food), frequency, paroxysms, impact (urinary incontinence, sleep loss, rib pain, syncope, voice change), efforts to treat.
• Upper airway: nasal obstruction, rhinorrhoea, sneezing, throat clearing, sensation of mucus dripping, hoarseness, sinus pain.
• Lower airway: wheeze, breathlessness, chest tightness, sputum volume and colour, haemoptysis, recurrent chest infections, childhood chest problems.
• Gastro-oesophageal: heartburn, regurgitation, sour taste, dysphagia, cough after meals, with silent reflux possible with no symptoms.
• Systemic: weight loss, fever, night sweats, tuberculosis contact, foreign travel, immunosuppression, HIV risk, cancer history, joint pain, rash, dry eyes.
• Smoking (pack years), vaping, occupational and environmental exposures (asbestos, silica, mould, birds), alcohol, atopy, family history.
• Drugs: ACE inhibitors (cough may start weeks to months after beginning and persist weeks after stopping), amiodarone, nitrofurantoin, methotrexate, beta blockers, checkpoint inhibitors, inhaled drugs, sitagliptin.
• Cardiac: breathlessness, orthopnoea, oedema, palpitations.
• Sleep: snoring, witnessed apnoeas, daytime sleepiness.
• Mood and anxiety, habit cough (disappears during sleep and distraction).

Examination.

• Vital signs, weight, body mass index, oxygen saturation, respiratory rate.
• Nose and throat: rhinitis, polyps, postnasal discharge, cobblestone pharynx, tonsils, larynx.
• Chest: wheeze, crackles (basal fine inspiratory crackles in fibrosis, coarse in bronchiectasis), reduced breath sounds, dullness, hyperinflation.
• Clubbing (lung cancer, bronchiectasis, interstitial lung disease, cystic fibrosis), cyanosis, lymphadenopathy (cervical, supraclavicular), hoarse voice.
• Heart: signs of failure, murmurs, atrial fibrillation.
• Skin and joints: connective tissue disease signs, erythema nodosum.
• Observe the cough (honking in habit cough, wet in bronchiectasis, paroxysmal with whoop).

Red flags.

• Haemoptysis, weight loss, night sweats, fever, anorexia.
• Smoker over 40 with new or changed cough, hoarseness, chest pain, clubbing, supraclavicular nodes (lung cancer).
• Abnormal chest radiograph.
• Breathlessness, inspiratory crackles or clubbing (interstitial lung disease).
• Dysphagia, choking or cough on eating (aspiration, oesophageal disease).
• Recurrent pneumonia, daily purulent sputum (bronchiectasis, cystic fibrosis, immune deficiency).
• Tuberculosis contact, residence or travel in endemic areas, HIV, immunosuppression.
• Stridor, voice change or neck mass.
• Fever with night sweats and lymphadenopathy (lymphoma, tuberculosis).
• Cough with heart failure signs, or on an ACE inhibitor.

Common non smoker triad.

• Upper airway cough syndrome (allergic and non allergic rhinitis, chronic rhinosinusitis, adenoid disease)
• Asthma (cough variant)
• Non asthmatic eosinophilic bronchitis
• Gastro-oesophageal reflux disease (with or without laryngopharyngeal reflux)

Drug induced. ACE inhibitors (about 10% to 15%), amiodarone, nitrofurantoin, methotrexate, beta blockers, checkpoint inhibitors.

Airway and parenchymal disease.

• Chronic obstructive pulmonary disease and chronic bronchitis, bronchiectasis, cystic fibrosis
• Interstitial lung disease (idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis, connective tissue disease associated)
• Chronic infection (tuberculosis, nontuberculous mycobacteria, fungal infection, chronic pertussis), post infectious cough
• Lung cancer, carcinoid, endobronchial tumour, foreign body
• Tracheobronchomalacia, tracheal stenosis, mediastinal masses, pleural disease

Cardiac. Chronic left heart failure, mitral stenosis, pulmonary hypertension.

Upper airway and vocal. Vocal cord dysfunction and paradoxical vocal fold motion, laryngeal sensory neuropathy, laryngitis, laryngeal tumour, elongated uvula, tonsillar disease, Eustachian tube dysfunction, elongated styloid process, Arnold nerve reflex (wax).

Sleep and neurological. Obstructive sleep apnoea, aspiration from bulbar disease (stroke, Parkinson disease, motor neurone disease), post stroke dysphagia.

Others. Tic and habit cough, psychogenic cough, refractory chronic cough (cough hypersensitivity syndrome), pertussis like illness, congestive cough in renal disease, bronchial carcinoid.

1. Take a full history and examination; review all drugs; stop ACE inhibitors for 4 weeks as a diagnostic step.
2. Chest radiograph in all patients with chronic cough; if abnormal, proceed to CT chest and targeted tests.
3. Spirometry with bronchodilator reversibility (FEV1 increase of 12% and 200 mL or more), peak flow diary (variability over 20%), fractional exhaled nitric oxide (FeNO over 40 ppb suggests eosinophilic airway inflammation and steroid response), blood eosinophil count (0.3 x 10^9/L or more), IgE and specific allergy tests; methacholine or mannitol challenge when asthma is possible but spirometry is normal.
4. Sputum: induced sputum eosinophil count (3% or more suggests eosinophilic bronchitis), culture, acid fast bacilli smear, culture and nucleic acid amplification for tuberculosis (3 samples), cytology.
5. Full blood count, ESR, C reactive protein, urea, creatinine, liver function, HIV test, immunoglobulins, autoimmune serology (antinuclear antibody, rheumatoid factor, anti cyclic citrullinated peptide, myositis antibodies) where interstitial disease is suspected, alpha 1 antitrypsin level when emphysema is present at a young age, natriuretic peptide for heart failure, interferon gamma release assay for tuberculosis.
6. High resolution CT chest for interstitial lung disease, bronchiectasis and unexplained cough with normal radiograph in smokers or with risk; bronchoscopy for endobronchial lesions, haemoptysis, foreign body or unexplained abnormality.
7. Upper airway evaluation: nasal endoscopy, sinus CT, and laryngoscopy for chronic rhinosinusitis, laryngeal pathology, voice change and vocal cord dysfunction.
8. Reflux assessment: empirical proton pump inhibitor therapy (8 to 12 weeks), ambulatory oesophageal pH and impedance monitoring (for non acid and extraoesophageal reflux), oesophageal manometry, endoscopy, barium swallow for dysphagia, and video fluoroscopic swallow study for aspiration.
9. Echocardiography and ECG for suspected heart disease; sleep study for sleep apnoea; pertussis serology (IgG to pertussis toxin) for cough of 2 to 8 weeks.
10. Structured cough assessment (cough severity visual analogue scale, Leicester Cough Questionnaire) for follow up; cough monitoring where available.
11. Test therapy by cause in sequence while keeping one change at a time; reassess response at 4 to 8 weeks for each step.

Limits. Multiple causes coexist in 20% to 40%, so all triggers need treatment. Diagnostic tests such as reflux monitoring have limited specificity. Spirometry is normal in cough variant asthma and eosinophilic bronchitis. Response to treatment is the final diagnostic test, and cough may persist for weeks after the cause is treated. Chest radiograph misses early cancer and interstitial lung disease; CT is needed if suspicion persists.

General measures.

• Stop smoking and avoid irritants.
• Stop ACE inhibitors (replace with angiotensin receptor blocker, for example losartan 50 mg daily) and other culprit drugs.
• Treat the specific cause, and reassure.
• Advise hydration, avoid throat clearing, humidify air, sip water, and use cough suppression techniques (swallowing, sipping, breathing exercises).
• Explain that cough hypersensitivity needs time and patience.

Upper airway cough syndrome.

• Intranasal corticosteroid (fluticasone propionate 2 sprays in each nostril once daily, or mometasone 2 sprays in each nostril once daily) for at least 4 weeks.
• Saline nasal irrigation twice daily.
• First generation antihistamine with decongestant at night (chlorphenamine 4 mg at night, short courses), or second generation antihistamine (loratadine 10 mg daily, cetirizine 10 mg daily) for allergic rhinitis.
• Intranasal azelastine 1 spray in each nostril twice daily.
• Intranasal ipratropium 2 sprays in each nostril three times daily for rhinorrhoea.
• Avoid oral decongestants in hypertension.
• Antibiotics for bacterial sinusitis (amoxicillin 500 mg three times daily for 5 to 7 days, or doxycycline 200 mg then 100 mg daily).
• ENT referral for polyps and chronic sinusitis.

Asthma and cough variant asthma and eosinophilic bronchitis.

• Inhaled corticosteroid: beclometasone 200 to 400 micrograms twice daily or budesonide 200 to 400 micrograms twice daily (increase to 800 micrograms twice daily if needed) for 4 to 8 weeks.
• Combine with long acting beta agonist (budesonide with formoterol 200/6 micrograms 1 to 2 puffs twice daily) if asthma is confirmed.
• Montelukast 10 mg at night.
• Short acting beta agonist as needed (salbutamol 100 to 200 micrograms).
• Short course prednisolone 30 to 40 mg daily for 5 to 7 days for severe or unresponsive cough.
• Allergen avoidance and treat rhinitis.
• Review inhaler technique and use a spacer.

Gastro-oesophageal reflux related cough.

• Lifestyle: weight loss, avoid late meals, raise the head of the bed 15 to 20 cm, avoid alcohol, caffeine, chocolate, fatty and spicy food, stop smoking.
• Proton pump inhibitor: omeprazole 20 to 40 mg twice daily (30 to 60 minutes before meals) for 8 to 12 weeks. Cough improvement may take 2 to 3 months.
• Add alginate (sodium alginate and potassium bicarbonate 10 to 20 mL after meals and at bedtime) or famotidine 20 to 40 mg at night.
• Prokinetic metoclopramide 10 mg three times daily before meals for 2 weeks if dysmotility.
• Antireflux surgery or endoscopic therapy for confirmed refractory reflux with objective evidence.
• Stop treatment if no response at 12 weeks (long term proton pump inhibitor use carries risk).

Bronchiectasis.

• Airway clearance (physiotherapy, active cycle of breathing, oscillating positive expiratory pressure device).
• Mucolytics (hypertonic saline 7% nebulised twice daily after salbutamol).
• Treat exacerbations (amoxicillin 500 mg to 1 g three times daily, or doxycycline 200 mg then 100 mg daily, or ciprofloxacin 500 to 750 mg twice daily for 14 days if Pseudomonas).
• Long term macrolide (azithromycin 250 mg daily or 500 mg three times weekly) for 3 or more exacerbations a year. Check ECG QTc, hearing and exclude nontuberculous mycobacteria.
• Inhaled antibiotics for chronic Pseudomonas infection (colistin or tobramycin).
• Vaccinations and pulmonary rehabilitation.
• Treat the cause: immunoglobulin replacement for antibody deficiency; allergic bronchopulmonary aspergillosis with prednisolone 0.5 mg/kg and itraconazole 200 mg twice daily.

Chronic obstructive pulmonary disease and chronic bronchitis.

• Smoking cessation: nicotine replacement patch 21 mg daily for 6 weeks, 14 mg for 2 weeks, 7 mg for 2 weeks, plus gum or lozenge; varenicline 0.5 mg daily for 3 days, 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks; bupropion 150 mg daily for 3 days then 150 mg twice daily.
• Long acting bronchodilators: tiotropium 18 micrograms inhaled daily, or umeclidinium 62.5 micrograms daily, with formoterol 12 micrograms twice daily or indacaterol 150 micrograms daily.
• Inhaled corticosteroid for frequent exacerbations and eosinophils over 0.3 x 10^9/L.
• Pulmonary rehabilitation and vaccinations.
• Long term oxygen when saturation is 88% or less.
• Roflumilast 500 micrograms daily or azithromycin for frequent exacerbations.

Interstitial lung disease.

• Specialist assessment.
• Antifibrotic therapy (nintedanib 150 mg twice daily or pirfenidone 801 mg three times daily with food) for idiopathic pulmonary fibrosis.
• Immunosuppression for hypersensitivity pneumonitis, sarcoidosis (prednisolone 20 to 40 mg daily, tapering) and connective tissue disease (mycophenolate mofetil 1 to 1.5 g twice daily).
• Avoid triggers, and give oxygen.
• Low dose morphine slow release for intractable cough and breathlessness.

Lung cancer. Urgent CT and referral (urgent suspected cancer referral with a 2 week appointment), bronchoscopy, staging and multidisciplinary treatment.

Tuberculosis. Isoniazid 5 mg/kg (maximum 300 mg), rifampicin 10 mg/kg (maximum 600 mg), pyrazinamide 25 mg/kg (maximum 2 g) and ethambutol 15 mg/kg for 2 months. Then give isoniazid and rifampicin for 4 months, with pyridoxine 10 mg daily. Check liver function at baseline and 2 weeks. Use directly observed therapy, contact tracing and HIV test.

Heart failure. Diuretics (furosemide 20 to 80 mg daily), ACE inhibitor or angiotensin receptor blocker with cough review, beta blocker, mineralocorticoid antagonist and sodium glucose co-transporter 2 inhibitor.

Pertussis. Azithromycin 500 mg on day 1 then 250 mg daily for 4 days (only effective in the first 3 weeks). Give symptomatic therapy. The cough lasts weeks to months.

Sleep apnoea. Weight loss and continuous positive airway pressure.

Vocal cord dysfunction and habit cough. Speech and language therapy (cough suppression therapy, voice hygiene, vocal cord relaxation breathing exercises), cognitive behavioural therapy, and reassurance.

Refractory chronic cough (after treatable causes are excluded and treated).

• Speech and language therapy (cough control therapy; effective in 50% to 70%).
• Neuromodulators: gabapentin 100 mg at night increasing every 3 to 7 days to 300 mg three times daily and up to 1,800 mg daily as tolerated (drowsiness, dizziness; adjust for renal function), or pregabalin 25 mg twice daily increasing to 150 mg twice daily; amitriptyline 10 mg at night increasing to 25 to 50 mg (anticholinergic effects). Review at 4 weeks and stop if no response.
• Low dose slow release morphine 5 mg twice daily (increase to 10 mg twice daily) for severe cough with careful counselling about opioid risks (constipation, sedation, dependence), under specialist supervision.
• P2X3 receptor antagonist gefapixant 45 mg twice daily where licensed (taste disturbance in 60% to 70%).
• Inhaled lidocaine or other nerve modulating therapy in specialist centres; botulinum toxin for laryngeal causes.
• Address stress, mood and sleep; avoid unnecessary repeated antibiotics and steroids.

Monitoring. Review at 4 weeks and 8 weeks after each treatment step using a cough severity score. Assess adherence and inhaler technique. Reassess the diagnosis if no response after the full course of therapy for a given cause (do not add drugs indefinitely). Repeat imaging for persisting cough in smokers. Monitor liver function and blood pressure on relevant drugs, and check ECG on azithromycin. Provide long term review for cough with hypersensitivity.

Referral and escalation.

• Urgent respiratory referral for suspected cancer, haemoptysis, abnormal imaging, weight loss, interstitial lung disease or tuberculosis.
• Specialist cough clinic for refractory cough.
• ENT for upper airway and laryngeal disease.
• Gastroenterology for dysphagia and refractory reflux.
• Allergy and immunology for allergic and immune deficiency.
• Cardiology for heart failure; sleep medicine; speech and language therapy; psychology.

Admission. Massive haemoptysis, respiratory failure, suspected superior vena cava obstruction or large airway tumour, severe pneumonia, cough syncope with injury, or need for urgent bronchoscopy.

Safety netting. Return urgently for coughing blood, breathlessness, chest pain, weight loss, fever and night sweats, hoarseness over 3 weeks, difficulty swallowing, or syncope. Report any new cough after starting an ACE inhibitor. Review if cough changes character.

Special groups.

• Children: chronic cough over 4 weeks needs evaluation (protracted bacterial bronchitis, asthma, foreign body, cystic fibrosis, pertussis, tuberculosis, habit cough). Avoid opioids and cough suppressants.
• Pregnancy: avoid ACE inhibitors, angiotensin receptor blockers, gabapentin and pregabalin where possible. Reflux and rhinitis are common. Treat with alginates, intranasal steroid and omeprazole 20 mg.
• Older adults: aspiration, heart failure and malignancy; review drug list.
• Smokers: smoker's cough and cancer; screen.
• Women in perimenopause: higher prevalence of refractory cough.
• Endemic regions: tuberculosis, chronic fungal infection, strongyloides and ascaris migration, schistosomiasis, paragonimiasis, HIV related lung disease, and biomass fuel exposure are common causes.