Prolonged cough in adults

Essentials

• A cough that lasts more than 8 weeks is defined as prolonged.
• Most important causes: mucus in the nasopharynx for various reasons, asthma and gastro-oesophageal reflux disease. Cough may be the only symptom in all of these.
• Cough may be prolonged after a respiratory tract infection due to bronchial hyperreactivity but it may also be a symptom caused by maxillary sinusitis or new-onset asthma.
• In smokers, the most common cause of cough is COPD or chronic bronchitis.
• ACE inhibitors are the most common drugs associated with cough, but beta blockers in asthmatic patients, nitrofurantoin and methotrexate should also be considered.
• The cause should be treated, ex juvantibus as necessary (asthma, gastro-oesophageal reflux disease). If causal treatment is not possible and the cough interferes significantly with the patient's life, antitussives can be used for symptomatic treatment.

Causes

• The cough reflex is stimulated by various mechanical, chemical and temperature-based stimuli, as well as by local mediators.
• Cough may originate in various organs. There are cough receptors in the nose, sinuses, pharynx, larynx, ear, trachea, bronchi, pleura, pericardium, diaphragm, oesophagus and stomach but not in pulmonary tissue.
• Causes of prolonged cough are listed in table .

• In non-smokers who are not taking ACE inhibitors and whose lung x-ray is normal, the most common causes of chronic cough (in even more than 90% of cases) are
  • upper airway cough syndrome (mucus draining down the back of the throat)
  • asthma
  • gastro-oesophageal reflux disease.
• Patient with atopy or allergy
  • Probable diagnosis: asthma or allergic rhinitis
• Smoker
  • Most probable diagnoses: prolonged acute bronchitis or incipient chronic obstructive pulmonary disease (COPD)
  • The possibility of lung cancer should always be considered in middle-aged and older patients.
• Occupational cough
  • Often associated with unspecific airborne stimuli.
  • Asbestosis requires exposure to asbestos to develop .
  • A farmer may develop farmer's lung or asthma as occupational diseases.
  • Occupational asthma that begins with a cough is possible in various workplaces where the patient is exposed to chemicals, solvents (isocyanates, formaldehyde, acrylates, etc.) (e.g. car repair shops, plastics industry, commercial cleaning companies, dental laboratories and dentists' offices, etc.).
  • These cases should normally be examined in a special clinic for pulmonary diseases or for occupational health.

Examination

• History, clinical examination, chest x-ray, spirometry as necessary, PEF monitoring
  • In patients with dry chronic cough in the absence of other symptoms and normal basic examinations listed above, serious lung disease is unlikely.
  • Abundant or bloody sputum, general symptoms, significant dyspnoea, wheezing or abnormal findings on clinical examination increase the probability of lung disease.
  • Examinations such as high resolution computed tomography and bronchoscopy can be considered as further examinations in specialized care.

Upper airway cough syndrome (mucus draining down the back of the throat)

• Typically caused by inflammatory disease of the nose, sinuses or nasopharynx (chronic sinusitis, allergic, non-allergic or vasomotor rhinitis).
  • Previously called postnasal drip, today preferably upper airway cough syndrome, UACS.
  • Caused by direct irritation by mucus or an inflammatory reaction in cough receptors.
  • No clear diagnostic criteria
• Symptoms
  • Rhinitis, feeling of mucus draining down the back of the throat, need to clear the throat, but symptoms may also be totally absent.
  • In allergic rhinitis, itchy and runny nose, sneezing, nasal congestion, eye symptoms
• The patient may have nasal polyposis .
• On clinical examination, there may be cobblestoning of the pharyngeal mucosa and mucus at the back of the throat.
• Ultrasound or x-ray examination of the sinuses may show horizontal fluid levels or mucosal oedema.
• Response to therapeutic trial will confirm the diagnosis.
  • Combination of antihistamine and decongestant; must not be used for more than 10 days
  • Nasal corticosteroid spray, anticholinergic drug or antihistamine, as necessary
  • Topically administered combination of antihistamine and corticosteroid
  • Nasal saline irrigation is also often helpful .
• Sinusitis: see ; allergic rhinitis: see

Asthma

• Prolonged cough may be the only symptom of incipient asthma but usually there is also occasional dyspnoea and wheezing.
• Symptoms of asthma often appear in connection with viral respiratory tract infection, exposure to allergens, exertion or respiratory tract stimulation (cold or dry air, dust, mould, perfumes).
• The patients are often atopic, and there is often a family history of asthma.
• The diagnosis can be confirmed by showing transient bronchial obstruction.
  • In primary health care PEF monitoring at home, spirometry, bronchodilation test, and therapeutic trial with an inhaled corticosteroid should be performed as necessary .
• For the treatment of asthma, see .

Gastro-oesophageal reflux disease

• Gastro-oesophageal reflux disease may be the cause of cough even in the absence of typical symptoms (such as heartburn, gastro-oesophageal reflux).
• Cough is caused by stimulation of cough receptors in the upper respiratory tract and oesophagus and possible aspiration.
• The symptoms of laryngopharyngeal reflux (LPR) include hoarseness, slight difficulty swallowing and dry cough.
  • The symptoms typically occur when the patient is in the vertical position and in connection with straining, for example, whereas actual gastro-oesophageal reflux disease causes more symptoms in the supine position.
• A trial of 2 to 3 months' treatment with proton pump inhibitors can be made. However, pronounced symptoms of gastro-oesophageal reflux always require endoscopic examination.
• For the examination and treatment of gastro-oesophageal reflux disease, see .

Cough associated with medication

• ACE inhibitors cause dry cough in as many as 15% of users.
  • The cough usually begins within a week from the institution of treatment but may appear as late as several months later.
  • Cough usually resolves within a few days after withdrawing the medication.
• Beta blockers (incl. beta1-selective ones) may cause cough particularly in atopic patients and in patients with tendency to bronchial hyperreactivity.
• Certain drugs may cause a lung parenchyma reaction causing cough (for a comprehensive list of causes of drug reactions, see www.pneumotox.com 1).
  • Amiodarone
  • Nitrofurantoin (picture )
  • Methotrexate
  • Cyclophosphamide
  • Bleomycin
  • Gold

Cough beginning with symptoms of respiratory tract infection

• Prolonged cough after an infection may be due to the upper airway cough syndrome and associated with mucus in the nasopharynx, or a sign of incipient asthma (see above).
• It may also be due to bronchial hyperreactivity after an infection or to an extended inflammatory reaction in the airways, both resolving spontaneously with time.
• It is not uncommon for cough to continue for as long as a few months if caused by mycoplasma, chlamydia or bordetella. These are usually readily suspected if there is a local epidemic.
  • Pertussis is associated with typical "whooping", very troublesome coughing at night and vomiting.
• Examinations should be performed as considered appropriate: basic blood tests (CRP, complete blood count with differential), chest x-ray, ultrasound examination or x-ray of maxillary sinuses.
• If cough is associated with fever and purulent sputum, more extensive differential diagnostic alternatives need to be considered.
  • Pulmonary tuberculosis
  • Pulmonary infection caused by atypical mycobacteria
  • Bronchiectasis
  • Vasculitis (e.g. polyarteritis nodosa, Wegener's granulomatosis )
  • Eosinophilic pneumonia
• If a patient with pneumonia has multiple other diseases or is elderly, recovery may take more time for several reasons .
  • Primary tests
    • Chest x-ray
    • Staining and culture of sputum for tuberculosis
    • Complete blood count with differential, sedimentation rate, CRP (infection parameters may also be elevated in vasculitis)
  • If symptoms continue, consult a clinic specializing in pulmonary diseases.
• The most probable diagnosis is either prolonged respiratory tract infection (sinusitis!) or incipient asthma.

Chronic bronchitis and COPD

• In chronic bronchitis the patient has had cough and mucus production lasting at least 3 months in two consecutive years (typically in the morning).
• The diagnosis is based on the symptoms after other diseases causing similar symptoms have been excluded.
• Every fifth patient with symptoms of chronic bronchitis develops chronic obstructive pulmonary disease (COPD ). The diagnosis of COPD is primarily based on spirometric detection of irreversible bronchial obstruction.

Eosinophilic bronchitis

• Non-asthmatic eosinophilic bronchitis (NAEB) may be a far more common cause of prolonged cough than assumed.
• Most of the patients are atopic. Some of them later develop asthma.
• Diagnosis
  • Eosinophilia in sputum specimen
  • Normal spirometry, no bronchial hyperreactivity
  • Fractional exhaled nitric oxide (FeNO) can also be used as a measure of inflammation.
  • Therapeutic trial: both cough and eosinophilia are corrected by an inhaled corticosteroid.

Other respiratory diseases

• Bronchiectasis
  • In some cases, the only symptom is dry cough but usually there is mucopurulent – during exacerbations purulent – sputum.
• Lung cancer
  • The possibility of lung cancer should always be considered in middle-aged and older patients. Ask if the patient has had haemoptysis.
  • Prolonged cough is the main symptom of lung cancer usually only if the tumour is located in the large bronchial tubes.
  • A chest x-ray should be taken especially if the patient is over 40 years of age, unless one has been taken during the past 6 months.
  • If pneumonia infiltration is found and the cough is treated as pneumonia , take a follow-up chest x-ray after 6–8 weeks.
• Parenchymal lung diseases (incl. carcinosis, sarcoidosis, extrinsic allergic alveolitis, fibrosing alveolitis, lymphangioleiomyomatosis, Pneumocystis jirovecii infection)
  • In incipient or mild diffuse lung parenchymal diseases, the finding on an ordinary chest x-ray may be normal.
  • If there is reason to suspect parenchymal disease based on the history (exposure to mould spores, patient with immunosuppression), auscultation of the lungs (inspiratory fine rales), lung function tests (reduced volume, reduced diffusion capacity) or general symptoms (fever, weight loss) or for other reasons, high resolution computed tomography of the lungs should be performed.
  • Interstitial pulmonary disease causing cough and dyspnoea may be associated with a connective tissue disorder such as rheumatoid arthritis or scleroderma, or the drugs used to treat such disorders (gold, sulfasalazine, penicillamine, methotrexate).
  • A unit specializing in internal medicine or pulmonary diseases should always be consulted in these cases.
• Foreign body
  • A foreign body is very rarely the reason for prolonged cough because it can normally be suspected in the acute phase, already, based on the history (cough starting acutely, often in connection with biting or swallowing, without symptoms of infection).
  • A hair in the ear or residual stitches after respiratory tract surgery are examples of very rare causes of cough of the foreign body type.
• Aspiration
  • If coughing occurs in connection with eating or drinking, aspiration should be suspected.
  • This is always associated with a neurological disturbance that is usually already known.
  • The diagnosis can be confirmed by an examination using a contrast medium.

Other causes

• Heart failure
  • The first sign of mild heart failure is often a cough at night.
  • Peribronchial oedema causes narrowing of small airways, cough and dyspnoea.
  • Cardiac enlargement seen in the chest x-ray often suggests heart failure even in the absence of any signs of venous congestion.
• A cough may be the only sign of pleural effusion .
• Conditions of the thyroid gland (goitre, thyroiditis)
• Large soft palate or large tonsils
• Habit cough
  • Usually does not occur during sleep.
  • Diagnosis is based on careful history and the exclusion of other diseases.
• Irritable larynx
  • In addition to cough, the patient has a feeling of a lump in the throat and increased need for coughing and clearing the throat.

Symptomatic treatment

• The treatment of cough is always primarily determined by the cause.
• If no cause can be identified for a prolonged cough and therapeutic trials remain ineffective, the patient probably has an idiopathic cough. Its prevalence varies between 7 and 46 % in different reports.
• If the cough is severe, symptomatic medication can temporarily be used to suppress the cough reflex.
• If this type of a patient has signs suggesting a functional voice disorder, speech therapy may be beneficial.
• In patients with severe symptoms that are refractory to other treatments, short-term use of antitussive agents can be tried, e.g. dextromethorphan (90–120 mg/day in adults) or codeine (60 mg/day).
• Gabapentin may reduce the sensitization of the cough reflex, and its use in the treatment of a chronic cough that does not respond well to other treatments is under research.
• There is little evidence that mucolytic agents which thin the mucus and facilitate its excretion are effective in symptomatic relief of cough. They may be useful in patients with COPD exacerbation.

Related resources

• Cochrane reviews
• Other evidence summaries
• Clinical guidelines
• Literature

Ədəbiyyat

1. Pavord ID, Chung KF. Management of chronic cough. Lancet 2008;371(9621):1375-84.
2. Irwin RS, Baumann MH, Bolser DC et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest 2006;129(1 Suppl):1S-23S.
3. Pratter MR. Overview of common causes of chronic cough: ACCP evidence-based clinical practice guidelines. Chest 2006;129(1 Suppl):59S-62S.
4. Ryan NM, Birring SS, Gibson PG. Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial. Lancet 2012;380(9853):1583-9.
5. Ryan NM, Gibson PG. Recent additions in the treatment of cough. J Thorac Dis 2014;6(Suppl 7):S739-47.
6. Birring SS, Kavanagh J, Lai K et al. Adult and paediatric cough guidelines: Ready for an overhaul? Pulm Pharmacol Ther 2015;():.