Prospective Single-centre, Double Blind Randomised Trial of Montelukast in Patients With Chronic Cough and Bronchial Hyperreactivity

Chronic cough is a frequent problem in general practice and one of the most common reasons for referral to a respiratory clinic. Prospective studies have shown that the vast majority of cases of chronic cough are due to one or more of three conditions: rhinitis/postnasal drip syndrome, asthma and gastro-oesophageal reflux disease. Other significant causes of chronic cough include postviral (post-infectious) cough, and eosinophilic bronchitis. In only a minority of the patients with a chronic cough no cause can be found. This is called idiopathic cough.

Analysis and treatment of patients with chronic cough often proved to be difficult and disappointing. Nevertheless, centers in which a comprehensive diagnostic and therapeutic protocol was implemented reported excellent results. Therefore the first cough clinic is started in The Isala Klinieken, Zwolle/The Netherlands in 2004.

Asthmatic cough is often accompanied by the more typical symptoms of dyspnoea and wheezing. In a subgroup of asthmatics, however, cough is the sole or predominant symptom. This condition is termed cough-variant asthma (CVA). Cough due to CVA usually improves within the first week of inhaled bronchodilator therapy, however, complete resolution of cough may require up to 8 weeks of combination therapy with inhaled bronchodilators and corticosteroids. A subgroup of CVA patients with severe, refractory cough may require systemic (oral) steroids, alone or followed by inhaled therapy.

Leukotrienes are contributing significantly to the pathobiology of asthma. These 'pathways of asthma' could be suppressed by leukotriene inhibitors. Multiple clinical trials have demonstrated the ability of the leukotriene modifiers to improve symptoms, pulmonary function and bronchial hyperresponsiveness in chronic asthma, as well as in exercise-induced and aspirin-induced asthma. Until recently, the antitussive effects of this drug class had not been investigated properly. Spector and Tan concluded in a pilot trial with only 14 patients that 10 mg montelukast seems to be effective in CVA. However, nowadays in care of asthma, montelukast is widely used in a dosage of 10 mg. Therefore we intend to study the effects of montelukast on chronic cough (VAS-cough-score) on a wider patient population; is montelukast superior to placebo in the treatment of patients with chronic cough and a demonstrated bronchial hyperreactivity?

Aim of the study: