A cough is a symptom and a reflex action that is an essential protective and defensive act which secures the removal of mucus, noxious substances, and infections from the larynx, trachea, and larger bronchi. Impairment or absence of the coughing mechanism can be dangerous and even fatal in disease. Women tend to have a chronic cough more often and to have heightened cough reflex sensitivity compared to men. Nocturnal cough is distressing and may cause disturbances in sleep.
Causes of a nocturnal cough can be categorized as respiratory, non-respiratory, and systemic. The most common respiratory causes of a chronic cough include postnasal drip, postinfectious, and asthma. Environmental factors include smoking, both active and passive; this is the most frequent environmental factor. Drugs include ACEIs, beta-blockers, and NSAIDs. Drugs causing pulmonary fibrosis are bleomycin, busulphan, methotrexate, carmustine, amiodarone, cyclophosphamide, and hydralazine. Other respiratory causes include bronchiectasis, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, interstitial lung disease (ILD), primary or secondary lung tumors, sarcoidosis, and tuberculosis. Other upper airway conditions to be ruled out are chronic tonsillar enlargement, obstructive sleep apnea, gastroesophageal reflux disease (GERD), laryngeal problems, and foreign bodies in the large airways. Non-respiratory causes are GERD, recurrent aspiration, left ventricular failure, mitral stenosis, pulmonary infarction, and psychogenic cough, which is a diagnosis of exclusion. Very rare conditions include cardiac arrhythmias, aortic aneurysm, cough only when supine (due to a collapse of large airways), following complex involuntary tics (Tourette syndrome), and vitamin B12 deficiency (probably due to sensory neuropathy). Of all these conditions, cough variant asthma, GERD, and upper airway cough syndrome (UACS) are called the pathogenic triad, and they constitute 90% cases.
A worldwide study from 16 countries has shown that a nocturnal cough was present in 30%, productive cough in 10%, and non-productive cough in 10%. Conditions such as chronic bronchitis are therefore grossly underrepresented, even though they cause considerable morbidity within the population. Similarly, such tertiary referral clinics are unlikely to represent the true prevalence of conditions such as asthma as a cause of a chronic cough, since at least in European practice, a therapeutic trial of anti-asthma medication is usually performed by the primary physician.
Cough receptors are present in the pharynx and larynx, up to the segmental bronchi. Many types of sensory receptors respond to mechanical, inflammatory, thermal, and chemical stimuli. These are connected to the vagal afferent nerves. The cough center located in the medulla and receives signals from these cough receptors. The efferent fibers reach the various muscles that produce the forced expiratory effort. Since the higher cortical centers influence the cough center, it is possible to produce or suppress a cough voluntarily. The stimulation of a complex reflex arc is needed for each cough.
A nocturnal cough needs to be assessed by intensity, severity, frequency, and sensitivity. Some clues in the assessment of a nocturnal cough:
General examination should evaluate clubbing (may be indicative of vasculitis, sarcoidosis, and malignancies), pedal edema, and lymphadenopathy. Physical examination includes:
A chest x-ray is mandatory in all cases. A chronic cough with a normal chest x-ray occurs with ACE inhibitor therapy, postnasal drip, GERD, and asthma. These account for 90% of the cases. Diseases causing chronic cough but missed on chest x-ray include tumors, early ILD, bronchiectasis, and atypical mycobacterial pulmonary infection. Sputum examination is essential, whenever possible. Bacterial culture is needed if the sputum is purulent. When feasible and in case of doubt, mycobacterial culture is also necessary. A cytological examination is to identify malignant cells and to rule out eosinophilic bronchitis. ESR and CRP may give a clue to the presence of infection, malignancy, and connective tissue disorders. Cold agglutinin titer for M.pneumoniae, in suspected cases. HIV Elisa for AIDS. Possible further investigations include: B.pertussis can be detected from the nasopharyngeal secretions. Induced sputum analysis when sputum is not easily available, and it is mandatory to examine the sputum. Bronchial provocation testing with methacholine or histamine is positive in bronchial asthma. Bronchoscopy should be performed after excluding all common causes if foreign body inhalation is suspected. Bronchoscopy is also indicated whenever there is abnormal chest x-ray, hemoptysis, obstructive lesions, and infiltrates, that otherwise elude diagnosis. Echocardiography for cardiac ailments. 24hour ambulatory oesophageal PH or oesophageal manometry for diagnosing GERD. Radiology of the sinuses. HRCT – when no other diagnosis can be made. Patients who have isolated chronic nocturnal cough, with a normal physical examination, chest x-ray, and spirogram, are unlikely to have serious pulmonary conditions.
Encourage smokers to cease smoking. A cough should improve within eight weeks of smoking cessation. In the case of ACEI therapy, to stop the therapy. Improvement occurs within four weeks. Persistence of a cough after the withdrawal of ACEIs raises the possibility of other causes of a cough. The onset of asthma has been linked to its use. Advise the patient to keep away from known environmental and occupational pollutants and irritants.
Treatment of UACS depends on a presumed etiology (infection, allergy, or vasomotor rhinitis). So treatment includes first-generation antihistaminics, antibiotics, nasal saline irrigation, nasal pump sprays with glucocorticoids with or without decongestants like pseudoephedrine. Beta 2 agonists with inhaled corticosteroids give relief within a week’s time in case of proven asthma. A negative response to a bronchoprovocation test, e.g., methacholine, rules out cough variant asthma. Peak expiratory flow meter can be used as a cost-effective method to assess therapeutic response. A course of oral steroids for two weeks, or inhaled steroids, gives relief in the case of NAEB. A postinfectious cough can be treated with inhaled ipratropium, inhaled corticosteroids. Macrolide antibiotics with or without antitussives may be needed. GERD therapy includes prokinetic agents, H2 antagonists, and proton pump inhibitors (PPIs). Appropriate dietary therapy and proper positioning of the patient in bed are important aspects of management. PPIs should be tried for 8 to 12 weeks.
The most common cause of an acute/subacute cough is a viral respiratory tract infection. In adults with a cough longer than eight weeks, most of the cases are due to post-nasal drip, asthma, eosinophilic bronchitis, and GERD. Causes of chronic cough are the same in children with the addition of bacterial bronchitis.
The prognosis of nocturnal cough is dependent on the cause. A cough should improve within eight weeks of smoking cessation. In the case of ACEI therapy, improvement occurs within four weeks. Cough caused by GERD only improves after the underlying condition is treated. However, the cough of asthma may be present for years.
Nocturnal cough cause disturbed sleep, which may cause neuropsychiatric disorders in patients.
Nocturnal cough is a common and distressing symptom. It is important to identify and treat the cause of proper management.
In the case of cigarette smoking or use of tobacco products, patients should be encouraged to quit in order to improve their symptoms and prevent other complications. They should be educated on the importance of smoking cessation and how nocturnal cough could be caused or exacerbated by smoking.
Patients who develop a cough after the use of ACEI should be switched to another medication.
An empiric approach is needed to evaluate and effectively treat patients with chronic cough.
Nocturnal cough is a common presentation with diverse etiology. When a patient presents with this symptom, it is best managed by an interprofessional team, including primary care providers, pulmonologists, immunologists, or addiction specialists. In case the nocturnal cough is caused by GERD, a gastroenterologist may need to be consulted to treat the underlying condition. There may also be a need to involve the respiratory therapists, physician assistants, and nurse practitioners to more appropriately manage the patient.
To improve outcomes of nocturnal cough, prompt consultation with an interprofessional group of specialists is recommended.
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