C. Chronic Cough

man coughing Cough is an important defense mechanism that plays a major role in maintaining the integrity of the airways and can be voluntary or involuntary.

Introduction

Cough is one of the most common symptoms prompting a visit to the primary care physician’s office. Apart from smoking, most coughs are caused by acute viral upper respiratory tract infections and are self-limiting. Some coughs persist for weeks to years, and cause patients to go from one physician to another seeking relief from incessant coughing which may rob them of sleep, cause urinary incontinence, chest pain, or syncope, and interfere with work and life style. Cough can be a vexing problem for the patient and the physician alike. Successful treatment depends on making an accurate diagnosis and giving specific therapy. This presentation will focus on establishing the causes of chronic cough, which has been defined as a cough that persists for more than three weeks.

Cough is an important defense mechanism that plays a major role in maintaining the integrity of the airways and can be voluntary or involuntary. The pathophysiology of cough is incompletely understood. Cough is commonly triggered by mechanical or chemical stimulation of receptors in the pharynx, larynx, trachea and bronchi. Cough receptors also exist in the nose, paranasal sinuses, external auditory ear canals, tympanic membranes, parietal pleura, esophagus, stomach, pericardium and diaphragm.

Causes of Chronic Cough

Causes of chronic cough range from the common (Table 5) to the obscure (Table 6). Chronic bronchitis secondary to cigarette smoking is probably the most common cause of chronic cough, but most smokers do not acknowledge “cigarette cough” and do not seek medical advice until the onset of other serious complaints such as dyspnea . A change in the pattern of a smoker’s cough may herald associated complications such as bronchogenic neoplasm.

In non-smokers with normal chest x-rays the most likely causes of chronic cough are: post-viral respiratory tract infections, post-nasal drip, asthma, gastroesophageal reflux disease and drug-related (angiotensin converting enzyme inhibitors) (Table 5). Multiple causes are frequently encountered in the same patient. For example, in a study of 102 outpatients (Table 7) with chronic cough at the University of Massachusetts School of Medicine, Irwin and colleagues found a single cause in only 38%, whereas two or more causes were felt to be responsible in 59%. Assessment of the patient with chronic cough begins with a comprehensive history, physical examination, chest x-ray and spirometry.

History

The cause(s) of chronic cough may become apparent after taking a careful history. Is the symptom a cough or “hawking” or clearing the throat? It helps to have the patient act out the cough to distinguish true cough from throat clearing. Is the cough dry or productive? If so, what is produced? Are systemic symptoms such as fever, night sweats or weight loss present? A detailed history of the work and home environment should be taken with emphasis on possible exposure to noxious inhalants or allergens. The history should include the time and circumstances of onset, frequency, and aggravating and relieving factors. Patients with asthma may note worsening of cough on exposure to cold air, irritants or allergens. Is there an allergic history? Does the patient wheeze with cough? Is the cough accompanied by dyspnea? If so, congestive heart failure or interstitial lung disease may be suspected. Is the cough related to time of day, eating or position? A nocturnal cough may be associated with asthma, post-nasal drip, congestive heart failure or gastroesophageal reflux disease (GERD). Half of the patients with GERD have none of the classic symptoms. Does the patient cough while eating? Chronic aspiration is common in the elderly patient, especially following stroke. Is the patient on angiotensin converting enzyme inhibitors or other drugs that may predispose to cough or asthma? Do not overlook ophthalmic preparations. Beta blocker eye drops may precipitate asthma.

Physical Examination

The physical examination may provide clues to the causes of cough. Examination of the upper airways may show nasal mucous membrane swelling, post-nasal drip or nasal polyps. Hairs impinging on the tympanic membrane is a rare cause of cough but is easily treated. The finding of wheezes, rhonchi or crackles may indicate asthma, bronchitis, COPD, interstitial lung disease or congestive heart failure. The finding of unilateral wheezing may be due to an endobronchial lesion or foreign body. Masses in the neck, including thyroid enlargement, can compress the trachea and cause cough.

Dianostic Studies

The work-up for chronic cough should begin with standard posterior- anterior and lateral chest x-rays; these often reveal the presence of underlying infectious or neoplastic causes of chronic cough. Spirometric studies before and after bronchodilator administration may reveal reversible airways obstruction (asthma). In patients with normal base-line spirometry, methacholine inhalation challenge (MIC) is indicated to rule out asthma that presents primarily with cough. Computerized tomograms (CT) of the sinuses are superior to plain x-rays in identifying sinusitis. High-resolution or spiral CT scans of the thorax may reveal subtle changes consistent with cough due to chronic interstitial pneumonia or bronchiectasis. The finding of a reduced single breath diffusing capacity may suggest interstitial lung disease. Barium esophagograms and upper gastrointestinal endoscopy have a low sensitivity (48%) and specificity (76% ) for identifying GERD as the culprit in chronic cough; monitoring the esophageal pH for 24 hours is the gold standard. In patients suspected of having chronic aspiration, a video swallowing study with a speech therapist in attendance should be performed. A systematic approach to the work-up of a patient with nondrug-related chronic cough is presented in Figure 2.

Post-nasal Drip Syndrome

Post-nasal drip syndrome is said to be one of the most common causes of chronic cough and is caused by a variety of conditions including vasomotor rhinitis, allergic rhinitis, nasal polyps and chronic sinusitis. The diagnosis is made on clinical grounds. Patients may complain of a tickle or drainage of liquid in the back of the throat. On examination, cobblestoning of the nasal or oropharygeal mucosa may be observed. In many patients cough may be the only symptom of post-nasal drip syndrome. Confirmation of the diagnosis may depend on the resolution of symptoms after treatment with antihistamines and intranasal or systemic corticosteroids.

Asthma

Typically, asthma patients complain of episodic wheezing, cough, chest tightness and dyspnea and demonstrate reversible obstructive air flow. In so called cough-variant asthma, a dry cough, particularly at night, is the only symptom and routine spirometry is normal. The diagnosis is often made on the basis of a favorable clinical response to empirically administered beta2-agonist bronchodilators and inhaled corticosteroids, and a positive bronchoprovocation test using methacholine inhalation challenge (MIC). A positive MIC test, defined as a 20% or greater decrease in the FEV1 after MIC, indicates bronchial hyperreactivity but not necessarily asthma. For example, bronchial hyperreactivity may follow viral respiratory tract infections and persist for as long as 6 weeks. Because MIC has a positive predictive value of from 60% to 80%, Irwin and colleagues advise that a positive test must be correlated with favorable response to therapy before concluding that a patient has cough-variant asthma.

Gastroesophageal Reflux-related Chronic Cough

GERD is a very common problem. Surveys of the general population have led to estimates that 10% of the adult population of the United States have daily heartburn and a third have intermittent symptoms; moreover, GERD has been shown to cause 10% to 40% of cases of chronic cough. Cough in GERD is triggered by reflux of acid into the distal esophagus and stimulation of an esophageal-tracheobronchial reflex. Cough is not dependent on aspiration into the larynx or tracheobronchial tree.

Proving the relationship of chronic cough to GERD can be difficult. The lack of typical symptoms of reflux and negative endoscopic and radiographic studies do not rule it out. The 24-hour esophageal pH monitoring test has become the gold standard for diagnosis and has both a sensitivity and specificity approaching 90%. Correlation of the results of pH monitoring with response to therapy adds to the reliability of the test. If GERD is the sole cause of chronic cough, aggressive anti-reflux therapy should eliminate the cough in nearly all cases. One study reported 100% success. Treatment involves the use of dietary, mechanical and drug therapy. Drug therapy should be initiated with proton pump inhibitors and prokinetic agents. H2-antagonist can be substituted for the proton pump inhibitor after 3 months.

Post-infectious Cough

Patients who have had recent viral respiratory tract infections may have prolonged cough that is refractory to treatment. Airway hyperresponsiveness can be demonstrated by MIC testing in some cases. Treatment with bronchodilators and inhaled or systemic corticosteroids in moderate to high doses may help relieve symptoms. The cough can be self-perpetuating and cause continuing trauma to the airways, and in these cases, prolonged suppression with narcotics may eventually allow resolution.

Bordetella pertussis (the cause of whooping cough) infection in adults should be included in the differential diagnosis of chronic cough. In one series of 75 patients with chronic cough lasting longer than 2 weeks, 21% had pertussis.

Angiotensin Converting Enzyme Inhibitor Cough

Angiotensin converting enzyme inhibitor (ACEI) drugs are frequently used in the treatment of hypertension, congestive heart failure and myocardial infarction. The generic and brand names of most commonly used drugs are listed in Table 8. Ten to 20% of patents taking ACEI drugs develop cough. There is no evidence at this time that any one ACEI drug is less likely to cause cough than another. In spite of this well-documented side effect, referrals to a specialist for evaluation of chronic cough still occur frequently. Many of these patients have had extensive and costly work-ups and treatment with a variety of medications, including antihistamines, antibiotics, cough suppressants and corticosteroids, without relief.

The pathophysiology of ACEI-induced cough remains an enigma. Clinically, the cough may begin from as early as 3 weeks to as long as a year after starting treatment. The severity of the cough can vary from a mild tickle in the throat to a severe hacking, debilitating cough that interferes with sleep, work and social function. It is frequently worse at night and in the supine position. When the ACEI drug is discontinued, the cough usually abates in 2 weeks but may persist for months. Angiotensin ll receptor antagonists, a new class of antihypertensive agents, have not been associated with an increased incidence of cough.

Less Common Causes of Cough

Chronic cough may be the presenting complaint in patients who ultimately prove to have tumors, both benign and malignant, sarcoidosis or other infiltrating lung diseases; all these conditions require special investigations to make the diagnosis. Psychogenic or habitual cough does exist but patients should not be put in this category without an exhaustive work-up, failure of empirical therapy and prolonged follow up.

Symptomatic Treatment

The treatment of cough is effective only if directed at the cause, but patients should be offered symptomatic relief while awaiting the results of specific therapy. Expectorants such as iodides and guaifenesin, hydration, inhaled steam, cough lozenges and hard candies are helpful. Dextromethorphan and codeine are effective cough suppressants. In the future a better understanding of the cough reflex may allow the development of more effective cough remedies.

When to Refer

When the patient with chronic cough remains symptomatic despite evaluation and treatment for 6 to 8 weeks, the primary care physician should consider referral to a specialist. In difficult cases referral to a pulmonologist for evaluation, therapy and for specific testing such as fiberoptic bronchoscopy and MIC is recommended. Referral for upper gastrointestinal endoscopy and 24-hour pH monitoring may be indicated to rule out cough due to GERD. Referral to an allergist may be indicated for allergy testing and subsequently for immunotherapy if the patient is sensitive to an unavoidable antigen.

Medicolegal Issues

One of the most common reasons patients file suit is for failure to diagnose cancer. Even though bronchogenic carcinoma is an uncommon cause of chronic cough in the context of a normal chest x-ray, it must not be overlooked . Failure to diagnose tuberculosis is another cause of litigation but again would be an unlikely cause of chronic cough with normal chest roentgenograms .

Summary

Cough is a common presenting complaint in the frontline physician’s office, but in most patients the symptom is self limiting. In others, symptoms may persist from weeks to years and are associated with significant morbidity. Successful treatment depends on finding the cause and initiating specific therapy. The most common causes are cigarette smoking, post-nasal drip, asthma, GERD, or post-viral respiratory tract infection. Multiple causes in the same patient are common. When the cough persists in spite of specific or empiric therapy and either the physician or the patient is dissatisfied with the diagnosis or treatment, referral to a specialist should be considered.

References

Yu, ML, Ryu, JH. Assessment of the patient with chronic cough. Mayo Clin Proc 1997; 72:957-959. A concise review of chronic cough for primary care physicians.

Patrick, H, Patrick, F. Chronic cough. Med Clin N Am 1995; 79: 361-372. An excellent , concise review of the pathophysiology, diagnosis and treatment of chronic cough.

Irwin RS, Curley FJ, French CL. Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. Am Rev Respir Dis 1990;141:640-647. Irwin and associates have set the standards in the research into the causes and treatment of chronic cough.

Harding SM, Richter ER. The role of gastroesophageal reflux in chronic cough and asthma. Chest 1997; 111:1389-1402. Comprehensive review of the association of GERD in chronic cough and asthma.

Irwin RS, Frech CT, Smyrnios NA, Curley FJ. Interpretation of positive results of a methacholine inhalation challenge and 1 week of inhaled bronchodialator use in diagnosing and treating cough-variant asthma. Arch Intern Med 1997; 157:1981-1987. Emphasizes the importance of correlating results of methacholine challenge testing with clinical response to bronchodilators.

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