Chronic Cough Evaluation
Clear the red flags, remove the culprits, then treat the big four in sequence
Definitions and the first visit
Duration sorts the differential. In adults, cough under 3 weeks is acute (viral URI; also pneumonia, an asthma or COPD exacerbation, heart failure, pulmonary embolism), 3–8 weeks is subacute (usually post-infectious; do not miss pertussis), and beyond 8 weeks is chronic. In children the chronic threshold is 4 weeks and the causes differ (asthma, protracted bacterial bronchitis, foreign body).
Red flags. Image before any empiric trial—chest radiograph first, then chest CT if the film is unrevealing:
- Hemoptysis; unintentional weight loss, fever or night sweats
- Smoker older than 45 with a new cough or a change in a long-standing cough
- Dysphagia, choking or vomiting with cough; hoarseness
- Prominent dyspnea, recurrent pneumonia, or an abnormal lung examination
Baseline evaluation. Every patient gets a focused history, an examination and a chest radiograph:
- History and examinationScreen for red flags; ask about ACE inhibitors, tobacco, occupational exposures, and nasal, reflux and wheeze symptoms.
- Remove triggersStop the ACE inhibitor (switch to an ARB) and help the patient quit smoking.
- Chest radiographAbnormal film or red flags → CT and targeted workup.
- Sequential, additive empiric therapyNormal film: treat the common causes empirically rather than testing for everything—UACS first, then asthma and NAEB, then GERD.
- Refractory coughObjective testing (spirometry, methacholine, sputum eosinophils, pH-impedance, HRCT, bronchoscopy), then gabapentin and speech therapy.
ACE inhibitors and tobacco
ACE-inhibitor cough. Angiotensin-converting enzyme is also kininase II; blocking it lets bradykinin and substance P accumulate and sensitizes the cough reflex. The dry, tickling cough affects roughly 5–35% of users (more often women and East Asian patients), is unrelated to dose, and usually begins within weeks of starting but sometimes months later. As a class effect, it does not improve with a lower dose or a different ACE inhibitor. After the drug is stopped the cough resolves within 1–4 weeks, occasionally up to 3 months. ARBs do not block bradykinin breakdown and cause cough at about placebo rates, so they are the natural substitute.
Bradykinin also mediates ACE-inhibitor angioedema. Cough is a nuisance; angioedema means an ACE inhibitor should never be prescribed again.
Smoking. Chronic bronchitis—productive cough on most days for at least 3 months in each of 2 consecutive years—is the usual cause of cough in smokers and typically improves within weeks of quitting. A new or changed cough in a long-term smoker is a lung-cancer red flag; hemoptysis in a high-risk smoker warrants CT, and often bronchoscopy, even when the chest film is normal.
Normal chest film: the four common causes
The big four. In a nonsmoker off ACE inhibitors with a normal chest radiograph, upper-airway cough syndrome (the most common single cause), asthma, GERD and nonasthmatic eosinophilic bronchitis account for about 90% of chronic cough. Two or more often coexist, so therapy is sequential and additive: keep a therapy that gave partial relief while adding the next trial.
| Cause | Clues | Confirming test | Treatment |
|---|---|---|---|
| Upper-airway cough syndrome | Drainage sensation, throat clearing, congestion; cobblestoned, mucus-coated pharynx | Response to empiric therapy | First-generation antihistamine + decongestant; intranasal steroid for allergic rhinitis |
| Cough-variant asthma | Dry cough at night, with exercise, cold air or allergens | Spirometry with bronchodilator; methacholine challenge (negative excludes) | Inhaled corticosteroid ± bronchodilator; montelukast alternative |
| Nonasthmatic eosinophilic bronchitis | Cough without wheeze; occupational or allergen exposure | Sputum eosinophils ≥3%; normal spirometry and methacholine | Inhaled corticosteroid; avoid the exposure |
| GERD | Cough with meals, talking or lying down; hoarseness; heartburn often absent | Response to therapy; pH-impedance if refractory | High-dose PPI twice daily for 8–12 weeks + lifestyle |
Upper-airway cough syndrome. Formerly called postnasal drip, UACS arises from allergic, nonallergic or post-infectious rhinitis and chronic sinusitis. A first-generation antihistamine plus decongestant (chlorpheniramine or brompheniramine with pseudoephedrine) usually helps within 1–2 weeks. Nonsedating second-generation antihistamines work less well unless allergy is the driver, because much of the older agents' benefit is anticholinergic drying; add an intranasal corticosteroid for allergic rhinitis. Watch for sedation and urinary retention in older adults.
Cough-variant asthma. Cough may be asthma's only symptom, and spirometry is often normal. A bronchodilator response (FEV1 rise ≥12% and ≥200 mL) confirms reversible obstruction; with normal spirometry, methacholine challenge detects hyperresponsiveness. A negative test essentially excludes asthma, whereas a positive test is confirmed only by response to an inhaled corticosteroid (± bronchodilator) over several weeks. Montelukast is an alternative.
Nonasthmatic eosinophilic bronchitis. NAEB shares asthma's eosinophilic inflammation (sputum eosinophils ≥3%) but lacks variable obstruction and hyperresponsiveness, so spirometry and methacholine challenge are normal. It often follows occupational or allergen exposure and responds to inhaled corticosteroids plus avoidance.
GERD-related cough. Reflux triggers cough through an esophageal–bronchial reflex and microaspiration, and many patients have no heartburn. Give a high-dose PPI twice daily with weight loss, no late meals and head-of-bed elevation. Response is the slowest of the four—often 2–3 months—so continue 8–12 weeks before judging failure; refractory cases get pH-impedance monitoring, and surgery is reserved for documented reflux.
Pertussis and post-infectious cough
Pertussis in adults. Bordetella pertussis is a gram-negative coccobacillus whose toxin raises intracellular cAMP. Vaccine immunity wanes, so adults are infected and can pass it to unvaccinated infants, in whom it is most dangerous. Adults have paroxysms of cough, post-tussive emesis and gasping, sometimes syncope or rib fracture; fever is minimal and the whoop is often absent.
| Stage | Duration | Features |
|---|---|---|
| Catarrhal | 1–2 weeks | Cold-like symptoms; most contagious |
| Paroxysmal | 1–6 weeks (up to 10) | Coughing fits, post-tussive emesis, ± whoop |
| Convalescent | Weeks to months | Fits gradually fade ("100-day cough") |
Diagnosis and treatment. Nasopharyngeal PCR is the test of choice, most sensitive in the first 3–4 weeks; culture is specific but insensitive. Azithromycin for 5 days is first-line (TMP-SMX if macrolides cannot be used) and mainly shortens infectiousness. Give the same regimen to all household and high-risk close contacts (infants, pregnant women, infant caregivers) regardless of vaccination, and keep droplet precautions until 5 days of therapy are complete. Prevention: Tdap once for every adult and in every pregnancy at 27–36 weeks.
Post-infectious cough. Cough lasting 3–8 weeks after a respiratory infection, with a normal chest film, reflects transient airway inflammation and hyperresponsiveness. It resolves on its own; inhaled ipratropium helps troublesome cases. Beyond 8 weeks, evaluate it as chronic cough.
Other causes and refractory cough
When clues point elsewhere. An abnormal film or atypical features direct targeted testing:
- Bronchiectasis—copious purulent sputum, recurrent infections; HRCT
- Interstitial lung disease—progressive dyspnea, Velcro crackles, clubbing; HRCT
- Lung cancer—smoker with hemoptysis, weight loss or a changed cough; CT ± bronchoscopy
- Heart failure—nocturnal cough, orthopnea, edema; BNP and echocardiography
- Tuberculosis—fever, night sweats, weight loss, exposure; sputum acid-fast testing
Refractory chronic cough. Cough persisting despite objective testing and adequate trials for each common cause reflects cough-reflex hypersensitivity, often a throat tickle triggered by talking, cold air or scents. First confirm adherence, adequate dose and duration of each trial, and that ACE inhibitors and tobacco are truly gone. Then use a neuromodulator (gabapentin or pregabalin) plus speech-language therapy teaching cough-suppression and breathing techniques.
Stopping a partially effective therapy before adding the next is a common reason cough only looks refractory.