A Systematic Evaluation of Mechanisms in Chronic Cough

Abstract

We tested the hypothesis that hyperresponsiveness of the upper airway (UAHR) is present in patients with chronic cough of diverse etiology. We determined the frequency of bronchial hyperresponsiveness (BHR), hyperresponsiveness of the upper airway, sputum eosinophilia, pulmonary aspiration, and psychological symptoms in adults with chronic cough. Consecutive adults (n = 30) presenting to a tertiary referral clinic with chronic cough were compared with a group of 20 asymptomatic adults. Measurements included histamine provocation testing with measurement of flow volume curves to determine inspiratory and expiratory airflow obstruction; hypertonic saline induced sputum for analysis of eosinophils, mast cells and lipid-laden macrophages; and a validated psychological symptom questionnaire. Symptomatic rhinitis and gastroesophageal reflux were common causes of chronic cough. BHR occurred in seven patients (23%) and in no control subjects (p < 0.05). UAHR occurred in 40% of patients with cough and in four (20%) control subjects (p > 0.05). Eosinophils were present in the sputum of more patients with cough than control subjects (50% versus 19%; p < 0.05). High degrees of eosinophilia were present in six patients with cough, including three without BHR. No subject had significant lipid-laden macrophages. There was greater somatization in patients with chronic cough; ten subjects scored in the clinically significant range (p < 0.05). Abnormalities in one or more of these tests were 7.67-fold (95% CI 1.83-34.52) more likely to occur in cough patients than control subjects. We conclude that chronic cough is a nonspecific symptom that is associated with several apparently unrelated mechanisms. These include UAHR, somatization, BHR, and eosinophilic bronchitis. UAHR cannot be implicated as a single unifying mechanism. These findings emphasize the need to systematically evaluate several different causes of cough in patients who present with chronic cough.

Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis

“…Eosinophilic bronchitis is a recently recognized condition, which although a common cause of chronic cough [3,4], is not sufficiently prevalent to easily recruit for placebo controlled studies. Furthermore, the main focus of the current study was not the efficacy of treatment but the relative effects on upper and lower airway inflammation.…”

“…The authors [3] and others [4] have shown that eosinophilic bronchitis is the cause of cough in 10±20% of patients presenting to a respiratory specialist. The reason for the different relationship between eosinophilic airway inflammation and disordered airway function in eosinophilic bronchitis compared with asthma is unknown.…”

Lipid-laden macrophages in induced sputum are a marker of oropharyngeal reflux and possible gastric aspiration

“…Most studies have used relatively crude indicators such as response to therapy, clinically witnessed aspiration, barium oesophagography or conventional single-channel 24-h pH monitoring to detect aspiration [11±13, 15,21]. Some studies have used symptoms alone [17], which are insensitive in the diagnosis of oropharyngeal reflux and GOR. In the present study, dual-channel oesophageal pH recording was used to detect oropharyngeal reflux.…”

“…A number of previous studies have attempted to detect aspiration by examining sputum [15,17], tracheobronchial washings [14] or bronchoalveolar lavage fluid [11±13, 21] for the presence of lipid in macrophages. In those studies that included healthy controls [22], lipid-laden macrophages were seldom found and therefore the lipid index was low (mean SD 1.31.5).…”

“…Demonstration of lipid in alveolar macrophages may be an indicator of aspiration of acidic gastric contents [10], and cytological examination of bronchoalveolar lavage fluid for lipid-laden macrophages has been suggested as a useful diagnostic test for aspiration [11±15]. Determination of cell counts in induced sputum separated from saliva is a reliable noninvasive method of assessing airway inflammation [16], and the use of an index of macrophages in sputum staining positive for intracellular lipid has been reported [17]. In previous studies there have been two difficulties, the lack of a "gold standard" for the diagnosis of aspiration and the inclusion of patients with a variety of chronic respiratory diseases [18].…”