Management of cough in adults

Acute, self limiting viral infections of the upper and lower airways

Common cold is the most common cause of cough and usually subsides spontaneously, in otherwise healthy persons, after 2–3 weeks [11].

Upper airways allergic disease

Hay fever, and intermittent or persistent allergic rhinitis, often in combination with sinusitis, conjunctivitis, pharyngitis and laryngitis, can also trigger acute cough. Itchy eyes and throat are usually characteristic of these diseases [12].

Intermittent asthma

Intermittent asthma, either allergic or due to infection, can cause acute cough.

Aspiration

Aspiration of a foreign body, most commonly in 1–3-yr-old children, as well as in elderly, fragile patients, triggers acute cough with expectoration of the foreign body, or permanent bronchial obstruction with consecutive chronic cough.

Acute inhalative intoxication

Workplace accidents, fires, and solvent or glue sniffing can lead to a toxic lung oedema, acute interstitial pneumonia and bronchiolitis with re-emergence of cough, often after a discomfort- and cough-free interval of 6–48 h. Immediate high-dose inhaled corticosteroid treatment should be initiated (≤100 puffs in 24 h).

Post-infectious cough

Post-infectious cough persists >3 weeks after an acute, often viral airway infection and resolves after <8 weeks. Epithelial damage after B. pertussis or M. pneumoniae infection, or a transient increase in bronchial hyperresponsiveness (BHR), later subsiding spontaneously, are responsible for post-infectious cough. In the latter case, a short course of asthma treatment (inhaled corticosteroids or β₂-adrenergics [4]) is effective.

Persistent BHR with consequent chronic cough without airflow obstruction is described as cough-variant asthma (see later). In this case, long-term inhaled corticosteroid treatment is required.

Pneumonia

Pneumonia should be considered as a cause of acute cough.

Pleurisy

Pleurisy is also a possible cause of acute cough.

Pulmonary embolism

50% of patients with acute pulmonary embolism present with a cough [13].

Pneumothorax

All forms of pneumothorax can be accompanied by a dry cough.

Acute heart failure with pulmonary congestion

Acute left heart failure (including lung oedema) can trigger both cough and bronchial obstruction [14, 15]. Bradycardia associated with acute emerging atrioventricular (AV) block II–III can greatly reduce stroke volume, eliciting pulmonary congestion and cough. Atrial premature beats can elicit acute cough [16].

Chronic bronchitis

The World Health Organization defines chronic (nonobstructive) bronchitis as the presence of cough and phlegm on most days over a period of ≥3 months during two consecutive years without other causes. Many patients suffering from chronic cough meet these criteria. From a therapeutic point of view, this diagnosis is only useful if an obvious cause (i.e. smoking or work-related exposures) can be identified, cessation is possible and other causes of chronic cough have thoroughly been excluded. Though long-standing smokers frequently suffer from, but rarely complain of, cough and phlegm, chronic bronchitis is seldom a reason to attend a cough clinic.

Chronic obstructive pulmonary disease

By definition, patients with the chronic obstructive bronchitis phenotype of chronic obstructive pulmonary disease (COPD) are suffering from cough and phlegm. Chronic cough is a common symptom of COPD. In contrast to simple chronic bronchitis (see earlier), not fully reversible airflow limitation, as measured by spirometry, is the condition sine qua non for the diagnosis of COPD.

Asthma and other eosinophilic respiratory disease

Asthma is often responsible for chronic cough [17]. Dry cough can elicit or worsen an asthma attack.

Cough-variant asthma is characterised by dry cough and BHR. Wheezing, dyspnoea and bronchial obstruction are absent. Chronic cough with proven BHR can only be confirmed as variant asthma if asthma treatment (inhaled corticosteroids or β₂-adrenergics) eliminates the cough [10, 18–24].

Eosinophilic bronchitis is characterised by chronic cough and sputum eosinophilia in the absence of BHR. It is responsive to inhaled corticosteroid treatment [25, 26].

Lung tumours

Cough is the most common presenting symptom of lung tumours [27]. If a patient presenting with chronic cough (i.e. lasting >8 weeks) is not taking an angiotensin-converting enzyme (ACE) inhibitor, chest radiography should be performed immediately. Furthermore, in order to exclude a lung tumour, each patient with unexplained chronic cough should have a bronchoscopy at the end of the diagnostic algorithm (fig. 2).

Cough due to upper airway disease

Chronic rhinitis and sinusitis (rhino-sinusitis) [28] are often associated with posterior (i.e. postnasal drip) and/or anterior mucopurulent drainage, nasal stuffiness, facial pain, pressure, and/or fullness and decreased sense of smell. Chronic rhino-sinusitis can occur with or without nasal polyposis and allergic fungal rhinosinusitis, respectively.

Chronic pharyngitis and laryngitis [29] and chronic affections of the external auditory canal [30] can also cause chronic cough.

Vocal cord dysfunction

Recurrent voluntary inspiratory (sometimes also expiratory) adduction of the vocal cords can elicit throat clearing, dry cough, wheezing and dyspnoea. Vocal cord dysfunction can mimic asthma and often affects younger women [31].

Gastro-oesophageal reflux disease

Cough is triggered either by reflex, through reflux to the pharynx and larynx (laryngo-pharyngeal reflux), or microaspirations [32] of aerosolised gastric juice. Cough due to reflux can occur with or without heartburn [9] and does not necessarily coincide with reflux oesophagitis (nonerosive reflux disease). Thus, the gold standard of the reflux diagnosis is a triple-sensor, 24-h pH probe and impedance pH probe. The latter allows diagnosis of both acid and weakly acid reflux. Thus, aerosolised gastric juice, which probably plays a crucial role, can be measured directly by pharyngeal pH probe. Since pH probes are of limited sensitivity, frequently not available and poorly tolerated, high dose (2×40 mg) proton pump inhibitor treatment over the course of ≤3 months can be carried out as an alternative, thereby confirming or excluding the diagnosis of reflux cough [33] (fig. 2). However, unequivocal evidence for the efficacy of acid suppression from randomised controlled trials is lacking. In certain cases, surgical treatment (fundoplicatio) can be performed [34, 35], but no evidence-based selection criteria for surgery are yet available.

Drug-induced cough

Approximately 10% of women and 5% of men cough while taking ACE inhibitor medication [36], which increases cough reflex sensitivity. The therapeutic (antihypertensive, cardiac or nephroprotective) effects of an ACE inhibitor treatment can be replaced by angiotensin II receptor antagonists, which do not cause cough more frequently than placebo. For other drugs inducing cough, information is available at www.pneumotox.com

Infections

In adults, pertussis is a rare cause of chronic cough, but has been described even without a preceding phase of acute infection. In particular, patients with recent contact with persons suffering from acute whooping cough should be checked for antibodies. However, interpretation of the results is difficult. After the acute exudative phase of infection (taking ≤10 days) a direct culture of Bordetella is no longer possible and antibiotics will have no effect on cough or on the natural history of the infection.

Chronic cough is a typical symptom of tuberculosis, and was one of its key diagnostic criteria in the pre-radiography era.

Chronic cough due to heart disease

Aside from chronic left heart failure (cough generally occurs upon physical exertion or prone position), AV block II–III, endocarditis [37] and cardiac arrhythmia [38, 39] can cause pulmonary congestion-related chronic cough. Moreover, chronic cough as a side-effect of cardiac drugs, including ACE inhibitors, β-blockers (in patients with BHR) and amiodarone (eliciting alveolitis) has to be considered.

Diffuse parenchymatous lung disease and systemic diseases with diffuse lung involvement

In addition to dyspnoea, dry cough is the most common symptom of diffuse parenchymatous lung disease (DPLD). Some forms of diffuse parenchymatous lung disease cause cough at such an early stage that the DPLD can be missed by conventional chest radiography. Thus, an apparently “normal” chest radiograph and spirometry do not rule out early lung disease with cough. A high-resolution computed tomography (HRCT) scan can establish the diagnosis.

Most systemic autoimmune disease can develop lung involvement and cause cough (e.g. Sjögren’s syndrome, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and vasculitides). Chronic cough in DPLD, however, can also be due to the treatment or infection.⇓]

Cough due to inhalative events

Chronic cough is caused if an aspirated foreign body becomes trapped in the bronchial system (usually in children 1–3 yrs of age), or due to chronic recurrent aspiration of food (liquids) resulting from dysphagia in underlying neurological conditions (e.g. bulbar paralysis, Parkinson disease [40] and myasthenia gravis). Other causes include tracheal−oesophageal fistula, malformations, neck dissection (head and neck cancer) and regurgitation in heavy gastro-oesophageal reflux disease

Reactive airways dysfunction syndrome (RADS) occurs following short-term, intense inhalation of vapours, smoke or gases [41] (usually due to accidents in the workplace) and often develops into difficult asthma.

Non-cystic fibrosis bronchiectasis and tracheobronchomalacia

Bronchiectasis can be missed on chest radiography. The gold standard for diagnosis is HRCT. Bronchiectasis usually causes productive cough with voluminous secretion, and often haemoptysis.

Tracheobronchomalacia elicits chronic cough due to contact between the anterior and posterior wall of the bronchus intermedius or the trachea [42, 43].

Cystic fibrosis

Cystic fibrosis is an autosomal recessive inherited disease. Abortive forms can manifest in adulthood for the first time through cough, bronchial infections and bronchiectasis.

Isolated orphan airways disease

Isolated orphan airways disease usually emerges in patients >40 yrs of age. It can lead to expiratory bronchial collapse and irreversible central obstruction of the airways. Coughing is frequently the main symptom (table 6).

Sleep apnoea

Sleep apnoea patients often complain of chronic cough [44].

Psychogenic (habit) cough

By definition, the sensitivity of the cough reflex is not increased in patients with psychogenic cough, but this is difficult to measure reliably. There is always a risk of misdiagnosis of multicausal or idiopathic cough as psychogenic cough.

Chronic idiopathic cough

Despite extensive diagnostic procedures, underlying causes (e.g. reflux, asthma, etc.) of the increased sensitivity of the cough reflex (as measured by standardised capsaicin or citric acid testing) cannot be determined in ≤18% of patients with chronic persistent cough (females:males = 2:1) [45].

Physiotherapy of cough

Despite being clinical routine in both hospital and outpatient care [47], as well as in rehabilitation, evidence for the efficacy of physiotherapy for cough is lacking. Physiotherapy aims to: 1) increase expectoration using effective coughing techniques for patients with productive but ineffective cough; 2) suppress voluntarily nonproductive cough; and 3) instruct patient in the use of physiotherapeutic equipment improving expectoration, such as Acapella® (DHD Healthcare, Wampsville, NY, USA), Flutter® (Desitin/Scandipharm VarioRaw SA, Birmingham, AL, USA) and RC Cornet® (BoniCur, Eastcote, UK).

Pharmacotherapy

Expectorants reduce irritation of the cough receptors by accumulated mucus through “coughing up”, and represent the most common medication used for respiratory diseases in Germany (e.g. ambroxol and N-acetylcysteine). Because of the lack of appropriate methods, effectiveness is difficult to assess. Regarding relative effectiveness of different expectorants, conflicting or inconsistent evidence exists throughout the published literature [48]. Symptomatic use of expectorants is recommended to ease cough in cases with production of viscous secretions (COPD and bronchiectasis). Many patients also report positive subjective effectiveness using self-medication for acute bronchitis.

Combination phytotherapeutics can reduce the duration of acute cough of the common cold [49, 50].

In cystic fibrosis bronchiectasis, inhaled dornase-α eases cough

Inhalative anticholinergics (i.e. ipratropium and tiotropium) are thought to reduce mucus production; however, their antitussive effect is not consistent [51].

Theophylline and β₂-adrenergics do increase mucociliary clearance, but are not effective relieving cough.

By “coating” cough receptors in the throat, demulcents are thought to have an antitussive effect. Cough syrups, lozenges and drops, and honey share sugar as a common ingredient. Effectiveness, if any, is limited in time to the contact of the sugar with the receptor, which is usually 20–30 min.

Systemic α-adrenergics for nasal decongestion are popular in the US, but are virtually not in use in Germany and other parts of Europe. Fixed combinations with older, anticholinergic and central effective antihistamines (i.e. clorpheniramine or dexbrompheniramine) are not readily available in Europe. Moreover, evidence for their efficacy from randomised controlled trials is lacking.

Antibiotics are only effective against cough caused by a bacterial infection, characterised by purulent phlegm (i.e. suppurative bronchitis, bronchiectasis, exacerbation of COPD, purulent rhinitis and sinusitis). Antibiotics are not indicated in acute bronchitis.

Inhalative and nasal corticosteroids, and oral leukotriene antagonists alleviate cough in asthma, eosinophilic bronchitis, post-infectious cough due to BHR, and rhinitis.

Local anaesthetics disable electrophysiological activity in the receptors and afferent nerves (e.g. during bronchoscopy). They are increasingly used off-label for idiopathic cough and in palliative medicine [52].

Drugs affecting central mechanism for cough (antitussives) include systemically applied morphine or codeine, as well as natural and synthetic derivatives (i.e. dextromethorphan, dihydrocodeine, noscapine and pentoxyverin). Some nonaddictive herbal remedies (thyme, ribwort and sundew) claim central antitussive properties, though this is not proven by clinical studies. Opiates are recommended for effective symptomatic treatment of dry debilitating cough [53]. They have limited efficacy in the treatment of cough resulting from common cold [54].