Cough is a natural defense mechanism that allows clearance of bronchial tree secretions and the elimination of inhaled foreign particles. It is a common respiratory symptom for diseases that are either apparent or covert and can produce significant suffering for patients and a diagnostic dilemma for physicians. An acute cough that is caused by a known cause is dealt with by managing the underlying cause. Here, the discussion will focus only on cough as the only symptom without a clear presence of an etiology. This could be either a subacute (4-8 weeks) or a chronic cough (> 8 weeks). For a sub-acute cough, if it is an extension of a known cause, then it needs to be dealt with accordingly. If the cause is not apparent, then it is managed as a chronic cough.
Upper Airway Cough Syndrome (UACS)
This includes all nasopharyngeal conditions (including allergic rhinitis (AR), rhinosinusitis, and laryngopharyngitis) that may be associated with post-nasal drip and subtle sensation of irritation of secretions in the back of the throat and the upper airways that present with a cough as the only symptom. Throat examination may reveal signs of pharyngitis and cobble-stone appearance. These conditions can be silent (no symptoms besides a cough) in up to 20% of cases. Because of disease chronicity, it is likely that, over time, patients will become tolerant of other symptoms, which are not as bothersome as a cough. The diagnosis of silent UACS can reliably be made only after patients show significant improvement with prescribed treatment directed to suggestive features in history, physical examination, or laboratory testing.
A cough can be the only manifestation of asthma. Unlike silent UACS, the diagnosis of C-VA can be confirmed in most cases with pre and post-bronchodilator spirometry with or without methacholine challenge test (MCT).
Non-asthmatic eosinophilic bronchitis (NAEB)
NAEB shares eosinophilic airway inflammation with asthma, but there is no demonstrable airflow limitation on spirometry, and MCT is negative. A chest x-ray is usually normal. Missing this diagnosis is possible because sputum examination and/or bronchoalveolar lavage to detect airway eosinophilia are not routinely performed during the diagnostic work-up, and NAEB tends to respond to corticosteroids in the same way as asthma.
Gastroesophageal Reflux Disease(GERD)
Reflux triggers cough by a direct effect of acid on the proximal part of the esophagus and the laryngopharyngeal areas or by indirect vagal stimulation through the effect of gastric contents on the distal part of the esophagus. Other symptoms of acid reflux, such as heartburn, may be absent (silent reflux) in as many as 75% of cases of a reflux-induced cough. pH esophageal monitoring may confirm the presence of silent reflux, although anti-reflux therapy does not always resolve a cough.
Cough Hypersensitivity Syndrome (CHS)
Cough hypersensitivity syndrome is defined as “troublesome coughing triggered by a low level of thermal, mechanical, or chemical exposure.” It is characterized by enhancement of the cough reflex through sensitization of afferent neuronal pathways of a cough, both at the peripheral and central levels. Patients with CHS develop a cough in an exaggerated response to stimuli that would not otherwise elicit cough. It is thought that this nerve hypersensitivity is a result of various recurrent triggers, such as URTI or AR. A chronic cough is seen with UACS, asthma, and reflux may be induced by the development of cough hypersensitivity. Pharyngeal and/or laryngeal sensations (irritation, tickle, tightness, throat clearing), which are frequently associated with UACS and reflux-induced cough, may represent a sensory neuronal dysfunction of vagal afferents in the upper airways and a phenotype of cough hypersensitivity syndrome. Symptoms such as dysphonia, dysphagia, dyspnea, and abnormalities of vocal fold motion on laryngoscopy may also be present along with a cough as part of the pharyngeal/laryngeal nerve dysfunction seen with cough hypersensitivity syndrome.
There are 3 phases of a cough: an inhalation phase which generates enough volume for an effective cough, a compression phase with pressure against a closed larynx by the contraction of the chest wall, diaphragm, and abdominal muscles, and an expiratory phase when the glottis opens resulting in high air flow. A cough could be a voluntary or involuntary act. A voluntary cough is manifested by cough inhibition or initiation. An involuntary cough is regulated by the vagal afferent nerves. By stimulating cough receptors that present in the airways and other areas in the upper body, impulses travel through the vagus nerve to the cough center in the medulla, which is controlled by the higher cortical centers. Afferent signals move down via the phrenic and spinal motor nerves to the expiratory muscles producing the cough. A chronic cough may also be brought about by abnormalities of the cough reflex and sensitization of its afferent and central components with exaggerated cough reflex sensitivity to stimuli that normally do not cause a cough (cough hypersensitivity syndrome).
Initial evaluation of a cough of more than eight weeks duration should include a focused history and physical examination, and chest x-ray Patients who are taking an angiotensin-converting enzyme inhibitor should switch to another drug class. The most common causes of chronic cough in adults are asthma, upper airway cough syndrome, and gastroesophageal reflux disease. If upper airway cough syndrome is suspected, a trial of a decongestant and an antihistamine is warranted. The diagnosis of asthma should be confirmed based on clinical response to empiric therapy. Empiric treatment for gastroesophageal reflux disease should be initiated in lieu of testing for patients with chronic cough and reflux. Patients should avoid exposure to cough-evoking irritants.
Further testing, such as high-resolution computed tomography, and referral to a pulmonologist is indicated if the cause of chronic cough is not identified. In children, a cough lasting longer than four weeks is considered chronic. The most common causes in children are asthma, respiratory tract infections, and reflux disease. Evaluation of children with chronic cough should include a chest x-ray and spirometry.
Initial evaluation of the patient with a chronic cough should include a detailed history, a focused physical examination, and CXR. Patients who smoke are advised to quit smoking, and those who are taking an angiotensin-converting enzyme inhibitor should switch to medication from another drug class. Sequential empirical therapy is advised before embarking on extensive workup. The most common causes of chronic cough in adults are UACS, asthma, and GERD, alone or in combination. If UACS is suspected, a trial of nasal saline rinses, a decongestant, a first-generation antihistamine, and nasal steroids is recommended. Further tests like sinus CT scanning and nasopharyngoscopy are spared for non-responders. The diagnosis of asthma should be confirmed based on clinical response to inhaled bronchodilators and/or corticosteroids. Empiric treatment for GERD with diet, lifestyle modification, and proton-pump inhibitors for three months should be prescribed before considering 24-hour esophageal pH monitoring. NAEP is treated with inhaled steroids if sputum or BAL testing is showing greater than 3% eosinophils. After a period of targeted treatment, patients with a persistent cough are subjected to further investigations like chest high-resolution computed tomography (HRCT) scanning, bronchoscopy, and echocardiography. For cases with no clear etiology after an extensive work-up, CHS is the most likely explanation. A trial of antitussive drugs like dextromethorphan or gabapentin that can down-regulate cough reflex sensitivity can be used. Another less common possibility is a psychogenic cough, and it is also a diagnosis of exclusion. 
Management of chronic cough requires an interprofessional team because of the vast number of causes. The primary care provider and nurse practitioner should always be aware of malignancy when evaluating a patient with a chronic cough. When the cough is persistent, it is highly recommended that the patient be referred for appropriate workup. The prognosis depends on the cause.
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