Assessment of the Patient With Chronic Cough

Abstract

Chronic cough, defined as cough that persists for 3 weeks or longer, is one of the most common symptoms evaluated by a primary-care physician. With the exclusion of cigarette smoking, postnasal drip, asthma, and gastroesophageal reflux are responsible for more than 80% of the causes of chronic cough. Elicitation of a thorough history and performance of a physical examination will usually provide clues about the cause of chronic cough. The use of diagnostic tests including methacholine challenge, gastroesophageal reflux studies, and sinus imaging is based on clinical suspicion. Treatment of chronic cough is aimed at the underlying cause. Chronic cough, defined as cough that persists for 3 weeks or longer, is one of the most common symptoms evaluated by a primary-care physician. With the exclusion of cigarette smoking, postnasal drip, asthma, and gastroesophageal reflux are responsible for more than 80% of the causes of chronic cough. Elicitation of a thorough history and performance of a physical examination will usually provide clues about the cause of chronic cough. The use of diagnostic tests including methacholine challenge, gastroesophageal reflux studies, and sinus imaging is based on clinical suspicion. Treatment of chronic cough is aimed at the underlying cause. Cough, an explosive expiration that clears and protects the airway, is the fifth most common symptom encountered by physicians who treat outpatients. Clinicians must be aware, however, that some patients who complain of persistent coughing may in fact be experiencing frequent throat clearing, “hawking,” or symptoms of the upper respiratory tract other than cough. When the clinician is unsure whether the patient is truly describing cough, having the patient reproduce the “cough” in the office is helpful. Cough reflex has five components: cough receptors, afferent nerves, cough center (medulla), efferent nerves, and effector organs (respiratory muscles and muscles in the upper airway and tracheobronchial tree). Triggering of cough receptors by chemical or mechanical factors results in stimulation of the cough center. Impulse for the cough is then transmitted through the efferent pathways to the expiratory and laryngotracheobronchial musculature. Cough receptors predominate along the laryngotracheobronchial tree; however, they are also thought to exist in the nose, paranasal sinuses, ear canals and drums, pleura, stomach, pericardium, and diaphragm.1Irwin RS Rosen MJ Braman SS Cough: a comprehensive review.Arch Intern Med. 1977; 137: 1186-1191Crossref PubMed Scopus (144) Google Scholar Any process that stimulates a cough receptor may cause a person to cough. Cough is under both voluntary and involuntary control. Acute and self-limited episodes of cough commonly stem from viral infections of the respiratory tract and usually do not pose a diagnostic problem. Chronic cough is generally defined as cough persisting for 3 weeks or longer.2Patrick H Patrick F Chronic cough.Med Clin North Am. 1995 Mar; 79: 361-372PubMed Scopus (23) Google Scholar, 3Irwin 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: 640-647Crossref PubMed Scopus (719) Google Scholar, 4Pratter MR Bartter T Akers S DuBois J An algorithmic approach to chronic cough.Ann Intern Med. 1993; 119: 977-983Crossref PubMed Scopus (271) Google Scholar In this article, we discuss the diagnostic approach to patients with chronic cough in the absence of hemoptysis, a previously known chronic respiratory disease, or obvious clues detected on a chest roentgenogram. Because a chronic cough in an immunocompromised host has a more serious connotation, it will not be discussed herein. Cigarette smoking is the most common cause of chronic cough in the general population. Cigarette smokers, however, usually do not seek medical attention for their persistent cough, which likely represents chronic bronchitis. Aside from smoking, the most common causes of chronic cough are postnasal drip, asthma, and gastroesophageal reflux.2Patrick H Patrick F Chronic cough.Med Clin North Am. 1995 Mar; 79: 361-372PubMed Scopus (23) Google Scholar,3 These three conditions together account for 80 to 90% of the cases of chronic cough evaluated at outpatient clinics (Table 1).3Irwin 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: 640-647Crossref PubMed Scopus (719) Google ScholarTable 1Causes of Chronic CoughCause% of patients (N = 102)Postnasal drip41Asthma24Gastroesophageal reflux21Chronic bronchitis5Bronchiectasis4Miscellaneous5Data from Irwin and associates.3Irwin 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: 640-647Crossref PubMed Scopus (719) Google Scholar Open table in a new tab Data from Irwin and associates.3Irwin 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: 640-647Crossref PubMed Scopus (719) Google Scholar Postnasal drip is probably the most common cause of chronic cough and is diagnosed in the presence of suggestive symptoms with or without mucoid secretions visualized in the posterior pharynx. Some patients with asthma have chronic cough as a sole manifestation, and the diagnosis is based on results of spirometry with and without a bronchodilator. If the results are normal, a methacholine inhalation challenge test is performed. The diagnosis of asthma is suggested by a history of cough aggravated by exercise or exposure to cold air, irritants, or allergens. A history of intermittent wheeze or dyspnea accompanying a chronic cough is also suggestive of asthma. Similarly, in patients with gastroesophageal reflux, cough may be the sole symptom, the cause of which is the presence of acid in the distal esophagus resulting in an esophageal-tracheobronchial reflex.5Harding SM Richter JE The role of gastroesophageal reflux in chronic cough and asthma.Chest. 1997; 111: 1389-1402Crossref PubMed Scopus (228) Google Scholar Microaspiration of stomach contents may have a minor role in this manifestation. Up to one-half of patients may have more than one cause for their chronic cough.3Irwin 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: 640-647Crossref PubMed Scopus (719) Google Scholar Lung cancer is a rare cause of chronic cough in the absence of suggestive abnormalities on chest radiographs. The term “postinfectious cough” has been used to refer to cough that persists after respiratory tract infections. In some patients, transient bronchial hyperreactivity may be demonstrated. This type of cough generally fades over a period of a few months. Chronic sinusitis, interstitial lung disease, environmental agents, bronchial carcinoid, and drugs may occasionally be implicated as causes of chronic cough.2Patrick H Patrick F Chronic cough.Med Clin North Am. 1995 Mar; 79: 361-372PubMed Scopus (23) Google Scholar, 3Irwin 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: 640-647Crossref PubMed Scopus (719) Google Scholar, 4Pratter MR Bartter T Akers S DuBois J An algorithmic approach to chronic cough.Ann Intern Med. 1993; 119: 977-983Crossref PubMed Scopus (271) Google Scholar In particular, 5 to 20% of patients who take angiotensin-converting enzyme inhibitors have development of cough.6Israili ZH Hall WD Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy: a review of the literature and pathophysiology.Ann Intem Med. 1992; 117: 234-242Crossref PubMed Scopus (888) Google Scholar All commercially available angiotensin-converting enzyme inhibitors have been associated with cough. Such cough usually diminishes within 1 to 4 days after the medication has been discontinued. Occasionally, weeks may pass before improvement is noted. Angiotensin II receptor antagonists are much less likely to cause cough. Psychogenic cough is a diagnosis of exclusion but seems to exist.7Poe RH Harder RV Israel RH Kallay MC Chronic persistent cough: experience in diagnosis and outcome using an anatomic diagnostic protocol.Chest. 1989; 95: 723-728Crossref PubMed Scopus (202) Google Scholar In a recent article, pertussis was diagnosed on the basis of serologic criteria in 21% of 75 adults who had a persistent cough (defined as a cough lasting 2 weeks or longer).8Wright SW Edwards KM Decker MD Zelden MH Pertussis infection in adults with persistent cough.JAMA. 1995; 273: 1044-1046Crossref PubMed Scopus (247) Google Scholar In children, aspiration, foreign body, recurrent viral or atypical infections, cystic fibrosis, and passive exposure to cigarette smoke are additional considerations. The patient's history and findings on physical examination provide a basis for the diagnostic evaluation of chronic cough. The physician should question the patient about production of phlegm, character of phlegm produced, exacerbating factors, time relationships, and associated symptoms. Examination of the patient with special attention to the lungs, ears, nose, and mouth may yield useful clues. A forced exhalation maneuver may produce a localized wheeze or diffuse wheezes suggestive of a localized airway lesion or bronchospasm, respectively. Having the patient breathe in slowly will help in auscultation of fine crackles of pulmonary fibrosis. Standard anteroposterior and lateral chest roentgenograms are usually obtained. Spirometry with or without the use of a bronchodilator may confirm the presence of asthma if reversible obstructive airway disease is present. A methacholine inhalation challenge test can be performed if the baseline spirometry value is normal. A positive methacholine inhalation challenge test result is defined as a decrease of 20% or more from the baseline value of forced expiratory volume in 1 second after inhalation of aerosolized methacholine. A positive methacholine challenge, however, indicates bronchial hyperreactivity and not necessarily asthma. For example, transient bronchial hyperreactivity may be evident after a viral infection of the upper respiratory tract. Thus, a positive methacholine challenge test result must be correlated with the clinical context and subsequent course. Prolonged (usually 24 hours) ambulatory monitoring of esophageal pH is the most sensitive diagnostic test for detecting gastroesophageal reflux.2Patrick H Patrick F Chronic cough.Med Clin North Am. 1995 Mar; 79: 361-372PubMed Scopus (23) Google Scholar3Irwin 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: 640-647Crossref PubMed Scopus (719) Google Scholar5Harding SM Richter JE The role of gastroesophageal reflux in chronic cough and asthma.Chest. 1997; 111: 1389-1402Crossref PubMed Scopus (228) Google Scholar Radiographic examination with a barium swallow or esophagoscopy is less sensitive in diagnosing reflux. Bronchoscopy is of limited value when the chest roentgenogram shows no abnormalities and thus is rarely used in this setting. If a sinus or upper airway problem is suspected, sinus imaging and otolaryngologic consultation may be helpful. Some investigators4Pratter MR Bartter T Akers S DuBois J An algorithmic approach to chronic cough.Ann Intern Med. 1993; 119: 977-983Crossref PubMed Scopus (271) Google Scholar suggest an algorithmic approach to the treatment of chronic cough that incorporates empiric therapy with an antihistamine-decongestant preparation before laboratory tests are performed. The rationale for this strategy is to treat postnasal drip, which seems to be the most common cause of chronic cough in this setting, and to minimize the cost of laboratory testing. This approach includes weekly follow-up visits; thus, the physician can assess the patient's response to empiric therapy and perform sequential diagnostic and therapeutic procedures. Our initial approach is to obtain a chest roentgenogram in most patients, along with elicitation of the history and performance of a physical examination. A chest roentgenogram may be unnecessary in younger nonsmoking patients, especially if the cause of chronic cough is apparent on the initial clinical examination. If one or more causes are identified or suspected, we treat empirically with simple measures. For postnasal drip, we prescribe an antihistamine-decongestant combination drug or nasal corticosteroid spray. Nasal ipratropium bromide spray is now available. For a patient suspected of having gastroesophageal reflux, a trial of antireflux measures (including elevation of the head of the bed, low-fat foods, avoidance of chocolate and peppermint, avoidance of recumbency at least 3 hours after the evening meal, avoidance of bedtime drinks and snacks, weight control, smoking cessation, and reduction of alcohol intake) and drug therapy with an H2 receptor antagonist or proton pump inhibitor is reasonable. For a patient with suspected asthma, we prefer to confirm the presence of bronchial hyperreactivity by spirometry and, if needed, methacholine challenge testing. Treatment of asthma must be tailored to its severity. In the presence of relatively mild impairment, regular use of a corticosteroid inhaler supplemented with a short-acting β2- agonist inhaler as needed generally controls the symptoms. The clinician must remember that several months of therapy may be necessary in some cases.3Irwin 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: 640-647Crossref PubMed Scopus (719) Google Scholar4Pratter MR Bartter T Akers S DuBois J An algorithmic approach to chronic cough.Ann Intern Med. 1993; 119: 977-983Crossref PubMed Scopus (271) Google Scholar If the cause of chronic cough is not apparent or the patient has no response to empiric treatment, further testing is performed based on clinical suspicion. Pulmonary function testing is usually done first, followed by evaluation for gastroesophageal reflux if bronchial hyperreactivity is not demonstrated. Additional evaluation including sinus imaging, otolaryngologic consultation, computed tomography of the chest, pulmonary consultation, and bronchoscopy may be considered in difficult cases. For patients with refractory cough and no apparent cause, cough suppressants such as codeine, ipratropium or corticosteroid inhaler, brief course of orally administered corticosteroids, nebulized lidocaine, or behavioral modification therapy may be helpful.9Irwin RS Curley FJ The treatment of cough: a comprehensive review.Chest. 1991; 99: 1477-1484Crossref PubMed Scopus (66) Google Scholar, 10Trochtenberg S Nebulized lidocaine in the treatment of refractory cough.Chest. 1994; 105: 1592-1593Crossref PubMed Scopus (37) Google Scholar, 11Poe RH Israel RH Chronic cough: a strategy for work-up and therapy.J Respir Dis. 1997; 18: 629-641Google Scholar