The physiologic function of cough is to remove foreign substances and mucus from the respiratory tract. It is a three-phase mechanical process that involves a deep inspiration, increasing lung volume and muscular contraction against a closed glottis and sudden opening of the glottis. The maneuver produces and sustains a high linear air velocity to expel material from the respiratory tree.

Cough is a reflex response that is mediated by the medulla but is subject to voluntary control. The afferent limb may involve receptors in the larynx, respiratory tree, pleura, acoustic duct, nose, sinuses, pharynx, stomach, or diaphragm. The receptors respond to mechanical, inflammatory, or irritant stimuli. The trigeminal, glossopharyngeal, phrenic, and vagus nerves can carry the afferent signal. The efferent limb of the cough reflex involves the recurrent laryngeal, phrenic, and spinal motor nerves, which innervate the respiratory muscles.

Cigarette smoking is the most common cause of chronic cough and may trigger the cough reflex by direct bronchial irritation; alternatively, smoking may induce inflammatory changes and the production of mucus, which stimulates a self-propagating productive cough. Chronic bronchitis may ensue. Chronic cough and decreased flow rates have been observed in adolescents after only 3 to 5 years of smoking. Pipe and cigar smoking cause lesser degrees of difficulty.

Environmental irritants play a major role in the production of cough in patients living in industrialized urban areas. Pollutants that are frequently involved are heavy smog, sulfur dioxide, nitrous oxide, and industrial gases such as ammonia. In Great Britain, the relationship between air quality and the production of cough has been documented. The dusts and particulate matter that are capable of producing pneumoconioses contribute to the problem (see Chapter 39). The excessive drying of normal airway moisture that takes place in centrally heated homes (humidity may fall to <10% unless a humidifier is used) can result in a persistent dry cough during the winter months.

Inflammation anywhere along the upper or lower respiratory tract is capable of producing cough; receptors capable of transmitting impulses that stimulate cough are believed to be distributed throughout the respiratory system. The greater the inflammatory stimulus, the greater is the white cell response and the more purulent is the sputum. (The green coloration of very purulent sputum is caused by the degeneration of white cells.) A number of patients experience a dry, persistent cough after an URI; these postinfectious coughs commonly last more than 3 weeks and may last more than 8 weeks. The pathophysiology may be unrelated to postnasal drip or airway hyperactivity and is believed to be related to airway epithelial damage. In some populations, infection with Bordetella species has proven to be a relatively common explanation for highly prolonged cough associated with infection.

Asthma due to airway hyperreactivity may present as cough. Most patients with classical asthma complain of cough and, in some cases, cough is the symptom that predominates in the clinical picture. Studies of asthmatic patients have emphasized that cough can occur in the absence of wheezing or abnormalities on routine pulmonary function testing. The cough is characteristically worse at night and can be triggered or exacerbated by exposure to environmental irritants, allergens, or cold. Exercise is a common stimulant. In such cases, the bronchorrheal component
of asthma predominates, but methacholine or carbachol challenge will often unmask the obstructive manifestations (see Chapter 48).

Eosinophilic bronchitis is a less well-understood cause of subacute cough that resembles asthma but, although the cough is accompanied by sputum containing eosinophils, there is no wheezing, dyspnea, or demonstrable airway hyperreactivity.

Pertussis represents an important source of subacute cough, with estimates of up to a third of cases in adolescents and adults due to acute infection with Bordetella pertussis. Childhood immunity wears off within 12 years, leaving patients vulnerable. Transmission is by droplet and followed by 7 to 10 days of incubation. The first 2 weeks are designated the catarrhal phase and resemble other causes of an upper respiratory illness (rhinorrhea, mild cough, malaise), but the subsequent paroxysmal phase is heralded by onset of paroxysms of coughing (coughing spells) occurring both during the day and night, interspersed with asymptomatic periods. The spells may be severe enough to cause posttussive emesis or syncope, classic features, but often absent. Such coughing may persist for 2 to 3 months followed by a convalescent phase of gradual improvement and eventually full recovery.

Chronic bronchitis due to smoking is among the most common causes of chronic cough and sputum production. The condition is defined clinically as the presence of a productive cough that persists for at least 3 months for 2 consecutive years. A morning cough is often prominent, and bronchospasm is a frequent accompaniment (see Chapter 47). Bronchiectasis is also characterized by cough and sputum production, but it differs clinically from bronchitis in that repeated bouts of hemoptysis and pneumonia are more likely to occur. Copious amounts of purulent sputum are often produced. Chronic cough and sputum production commonly persist between episodes of pneumonia. Focal destruction of supporting lung tissue leads to dilation of bronchi and focal findings of rhonchi and wheezes on physical examination. A history of suppurative pneumonia in childhood is sometimes elicited. Eosinophilic bronchitis in the absence of asthma has also been associated with chronic cough in 10% to 15% of cases in both primary care and specialist clinics. Its pathophysiology is largely undefined, although the cough does respond to inhaled corticosteroids.

Carcinoma of the lung, more often than not in the smoker, may present with cough in its early stages, particularly when an endobronchial lesion is present. Often, the cigarette smoker notes a change in the pattern of a chronic “cigarette cough.” Hemoptysis is noted in about 5% to 10% of early cases. Other clues are localized wheezing and purulent sputum suggestive of obstruction. In later stages, cough is present in conjunction with weight loss, anorexia, and dyspnea. In some instances, a systemic syndrome (e.g., inappropriate secretion of antidiuretic hormone, hypertrophic pulmonary osteoarthropathy, dermatomyositis, peripheral neuropathy) may precede the appearance of tumor.

Interstitial fibrosis, sarcoidosis (see Chapter 51), and pulmonary edema may stimulate pulmonary interstitial mechanoreceptors and result in a nonproductive cough. Congestive heart failure with chronic interstitial pulmonary edema is associated with nocturnal cough because venous return is increased at night, which worsens heart failure (see Chapter 32). When failure is severe, frothy pink or blood-tinged sputum may be noted. Extraluminal compression of bronchi also stimulates mechanical receptors; examples of compressing lesions include hilar adenopathy, aortic aneurysm, and neoplasm.

Chronic allergic rhinitis (see Chapter 222) with resultant postnasal drip ranks as one of the leading causes of chronic cough in specialty clinic populations. Because receptors of the afferent limb of the cough reflex are found in the nose, pharynx, sinuses, and acoustic ducts, common afflictions in these areas have been found to be common causes of cough. The nasal mucosa may be edematous and the pharyngeal mucosal “cobblestoned” in appearance. Similarly, sinusitis (see Chapter 219) may be associated with a persistent cough and sputum production secondary to excessive retropharyngeal drainage of mucus. It accounts for up to one third of patients with postnasal drip syndrome. Even impacted cerumen and external otitis have been implicated in stimulating the cough reflex (see Chapter 218).

Gastroesophageal reflux is associated with chronic cough, believed related to stimulation of afferent limb receptors for the cough reflex in the stomach and lower esophagus. In fact, it is among the three most common causes identified in case series of patients with persistent chronic cough. Additional mechanisms include esophageal irritation with stimulation of an esophageal-tracheobronchial reflex and nocturnal aspiration of gastric juices. Cough may be the only presenting symptom.

The use of angiotensin-converting enzyme (ACE) inhibitors has been associated with an unexpectedly high incidence of dry nocturnal cough, with reports of 10% to 15% of patients being affected, with the incidence higher among women than men. First reported with use of enalapril, the cough has been associated with most long-acting ACE inhibitor preparations. Patients complain of an irritated feeling. The cough usually does not respond to a switch to another ACE inhibitor, although reducing the dose may help. In about 50% of instances, the cough is so annoying that ACE inhibitor therapy must be terminated. The pathophysiology of ACE inhibitor-induced cough is not entirely understood, but it appears to be an increase in sensitivity to the cough reflex. Therefore, ACE inhibitors may be unmasking subclinical cough associated with one of the aforementioned mechanisms.

Psychogenic cough has been described as more prevalent in children, but it may occur in adults; characteristically, it is nonproductive, occurs at times of emotional stress, and ceases during the night. The prevalence of psychogenic cough in reported series varies inversely with the attention to systematic evaluation and the search for the foregoing mechanisms.

The common causes of chronic cough are listed in Table 41-1. In an often-cited series of 139 consecutive cases of chronic cough encountered in the community setting, the cause was
hyperactive airway disease in 21%, postnasal drip in 19%, postinfectious status in 9%, chronic bronchitis in 4%, gastroesophageal reflux in 4%, and, in a few cases, occupational lung disease and psychiatric illness. In one referral setting study, a postnasal drip syndrome accounted for 41% of cases, asthma for 24%, esophageal reflux for 21%, and chronic bronchitis for 5%. Cough was the sole presentation of asthma in 28% of asthmatic patients and of reflux in 43% of patients with reflux. In one fourth of cases, more than one cause was identified. Sinusitis accounted for 38% of cases of postnasal drip. Insight from a growing number of series of patients from specialty cough clinics using systematic approaches to diagnosis suggests that when a patient who is not a smoker and not taking ACE inhibitors presents with chronic cough and has a normal chest radiograph, it is highly likely that the etiology will be related to asthma, gastroesophageal reflux disease (GERD), a postnasal drip syndrome (recently designated more generally upper airway cough syndrome [UACS]), or some combination of these three entities. This has been termed the pathogenetic triad of chronic cough of relatively obscure origin. Nonasthmatic eosinophilic bronchitis is less common but noteworthy because of its ease of diagnosis in the referral settings that are the source of most published series and its responsiveness to therapy. Rare but noteworthy causes of chronic cough include irritation of the pleura, diaphragm, or pericardium. Osteophytes of the cervical spine and pacemaker malfunction have been reported as truly rare causes of cough.