NEW YORK CITY—Three well-known respiratory medicine experts addressed a common but perplexing problem—chronic cough—at the recent annual meeting of the American Academy of Allergy, Asthma, and Immunology.[1] Postnasal drip, gastroesophageal reflux disease (GERD), and asthma are the most common causes of chronic cough, together accounting for about 80% of cases, reported William W. Busse, MD, Head of the Division of Allergy and Clinical Immunology at the University of Wisconsin in Madison.

UPPER RESPIRATORY CAUSES

Although upper airway disorders are a common cause of chronic cough, clinicians frequently have difficulty in diagnosing the underlying disorder. The many causes of rhinitis are often chronic and can lead to cough; of the various forms of the condition, allergic rhinitis is the most prevalent, especially in younger age-groups. In addition, post-infectious and vasomotor, as well as drug abuse–related rhinitis, should be considered.

Other potential upper respiratory causes of chronic cough include sinusitis, cystic fibrosis, sarcoidosis, hypothyroidism, pregnancy, connective tissue diseases (eg, Wegener’s granulomatosis), and immune function abnormalities, such as immunoglobulin A or G deficiency. In as many as 40% of cases, chronic cough has more than one cause.

The problem with diagnosing chronic cough of nasal origin, said Dr. Busse, is that there is no established testing algorithm. Sinus imaging, preferably with computed tomography (CT) instead of the usual chest film, is crucial for excluding sinusitis and for overall diagnostic accuracy, he stressed. “Skin testing is imperative” to diagnose allergic rhinitis, he added. Often, patients with perennial allergies do not present with classic symptoms of episodic coughing events and sneezing. In addition, pulmonary and immune function tests can be performed.

One common presenting symptom is that patients with chronic cough often report a postnasal drip sensation. “They are constantly clearing their throat,” Dr. Busse remarked. These patients may also report snoring or other sleep disorders, hoarseness, and nasal congestion or secretions. During the physical examination, posterior pharyngeal cobblestoning may be seen.

Treatment of upper airway chronic cough may include antihistamines, decongestants, and intranasal corticosteroids and anticholinergics. Unfortunately, however, there are few published clinical trials to evaluate the effectiveness of these treatments. “One would anticipate that nasal corticosteroids are going to be the most effective because they are the most potent,” Dr. Busse speculated.

GERD AS A CAUSE OF COUGH

Cough is often thought of as an atypical presentation of GERD, but it is really a typical presentation, asserted Christopher J. Allen, MD, Associate Professor of Medicine in the Firestone Institute for Respiratory Health at McMaster University in Hamilton, Ontario. “When we look systematically at patients who present primarily with reflux symptoms … we find that 62% of them have cough,” Dr. Allen pointed out.

GERD is associated with increased cough sensitivity that can be reproduced through inhaled capsaicin challenge. Such challenge typically reveals a much lower PD5—the dose of capsaicin that produces five coughs—in patients with GERD than in those without the disorder. Cough in GERD patients may also be due to reflux-related aspiration or to an esophagobronchial reflex whereby acid reflux into the esophagus triggers bronchospasm.

Cough and other GERD symptoms correlate closely with the esophageal pH, which is measured for 24 hours with an electrode that is inserted through the nose and positioned 5 cm above the lower esophageal sphincter. Reflux episodes usually occur when the esophageal pH dips below 4.0.

Although the 24-hour esophageal pH measurement is the diagnostic gold standard for GERD, the diagnosis can be truly confirmed only by a response to appropriate therapy, Dr. Allen said.[2] GERD patients with eosinophilic esophagitis tend to have greater esophageal damage and do not respond as well to treatment, he noted.

Three months’ prescription of a double-dose proton-pump inhibitor or another established treatment is generally accepted for typical GERD; an H2-receptor antagonist in the evening may also be appropriate in these cases to prevent nighttime breakthrough symptoms. Patients with atypical GERD should undergo a 24-hour esophageal pH test if available; otherwise, a three-month trial of treatment is acceptable.

Anti-reflux surgery may be indicated for GERD that does not respond to medical treatment. “Ninety-four percent [of these patients] will have long-term improvement in reflux, and 65% will have long-term improvement in cough,” Dr. Allen estimated.

COUGH IN ASTHMA AND BRONCHITIS

Because they are common conditions, asthma and bronchitis should be considered in patients with chronic cough. Because symptoms are nonspecific, objective measurements are necessary to make the correct diagnosis.

Methacholine challenge is probably the most sensitive and relevant test to confirm the presence of asthma. It is indicated when the baseline forced expiratory volume in one second (FEV1) is normal in a symptomatic patient. The patient is considered asthmatic if the methacholine dose that causes the FEV1 to drop by 20% is in the asthmatic range, related Frederick E. Hargreave, MD, Professor of Medicine at McMaster University. Although exercise testing is more specific for asthma than is the methacholine challenge, it is not as sensitive.

Either eosinophilic or non-eosinophilic bronchitis can occur in patients with or without asthma. When eosinophilic bronchitis is associated with normal spirometric results and airway responsiveness to methacholine, there are no features of asthma, Dr. Hargreave stressed. Eosinophilic bronchitis can occur with or without rhinitis, nasal polyps, or atopy. The condition usually responds well to 400 µg/d of inhaled budesonide or the equivalent dose of another corticosteroid for four weeks, he said.[3]

Tests for induced sputum cell counts, which are not yet widely available, have improved our understanding of chronic cough in asthma and bronchitis. Sputum induction is successful in about 80% of patients with chronic cough and in more than 90% of those with other airway diseases. Refined methods of examination of sputum can accurately identify the presence, type, and severity of airway inflammation.

Non-eosinophilic bronchitis can also be a cause of chronic cough. In its viral form, sputum testing shows only a modest increase in total cell count of about 15 to 20 million/mL versus 9.7 million/mL, which is normal. In bacterial neutrophilic bronchitis, the neutrophilia is more intense with a total cell count higher than 25 million/mL and neutrophils higher than 80%.

With respect to prognosis, chronic cough caused by eosinophilic bronchitis can be transient or persistent and, if persistent, requires regular treatment with an inhaled corticosteroid (or prednisone in some patients). Asthma features may develop in some cases, particularly if the condition is allowed to progress uncontrolled. In one reported case, chronic airflow limitation developed, Dr. Hargreave said.

—Timothy Begany