Measurement of Exhaled Nitric Oxide (NO) and Bronchial Provocation Test With Mannitol as a Predictor of Response to Inhaled Corticosteroids in Chronic Cough (MANOTOUX)

Measurement of Exhaled Nitric Oxide (NO) and Bronchial Provocation Test With Mannitol as a Predictor of Response to Inhaled Corticosteroids in Chronic Cough

Measurement of Exhaled NO and Bronchial Provocation Test With Mannitol as a Predictor of Response to Inhaled Corticosteroids in Chronic Cough

Chronic cough is defined by its persistence beyond 8 weeks. Many conditions can explain the existence of a bronchial inflammation. In the management of chronic cough, the search for bronchial hyperreactivity (HRB) is recommended. The treatment relies primarily on the prescription of inhaled corticosteroids. It has been shown recently that the existence of an HRB with Methacholine (bronchial provocation test used in routine) does predict the effectiveness of inhaled corticosteroid treatment in no more than 50% of cases. It is now possible to assess the bronchial inflammation by rapid, non-invasive and reproducible tests such that the fraction of exhaled nitric oxide (FeNO) and bronchial provocation test with mannitol. In a retrospective study, it was shown that an increased value of FeNO (cut-off > 35 ppb) predicts a positive response to treatment with a sensitivity of 90% and a specificity of 80%.

The purpose of this study is to show that the use of the prospective value of exhaled NO can predict response to treatment with inhaled corticosteroids in adult with chronic cough. In addition we will assess the interest of the prognosis of bronchial provocation test with mannitol in this indication.

Chronic cough, Inhaled corticosteroid treatment, Bronchial provocation test with mannitol, Methacholine

Patients referred for evaluation of a chronic cough (without treatment or after stopping inhaled corticosteroids for 2 weeks) will perform a measure of FeNO, a bronchial provocation test with mannitol, will fill out a questionnaire of quality of life for the cough (Leicester Cough Questionnaire) and the intensity of coughing on a 10-cm visual scale. After 6 weeks after treatment with inhaled corticosteroids patients will perform the same tests.

Bronchial provocation test with mannitol: Aridol is supplied in kit form containing sufficient capsules to complete one complete challenge, and the inhalation device. Apply nose clip and subject should be directed to breathe through the mouth Insert 0 mg capsule into inhalation device. Puncture capsule by depressing buttons on side of device slowly, and once only (a second puncture may fragment the capsules) The patient should exhale completely, before inhaling from device in a controlled rapid deep inspiration At the end of deep inspiration, start 60 second timer, subject should hold breath for 5 seconds and exhale through mouth before removal of nose clip At the end of 60 seconds, measure the FEV1 in duplicate (this becomes baseline FEV1) Insert 5 mg capsule into inhalation device, and proceed as above Repeat steps 1 - 4 following the dose steps in the table below until the patient has a positive response or 635 mg has been administered.

Sensitivity, specificity, positive predictive value and negative predictive value of the threshold value of 35 ppb FeNo to the clinical response seen as positive if the EVA reduces cough of at least 2 cm

Sensitivity, specificity, positive predictive value and negative predictive value of response to bronchial provocation test with mannitol on the clinical response seen as positive if the EVA reduces cough of at least 2 cm

Correlation between the value of FeNo and dose of mannitol causing a fall of 15% of maximum volume expired second (PD15)

Inclusion Criteria: Chronic Cough during 2 months Social Security regimen affiliated Consent form signed Exclusion Criteria: Smoking active Treatment with angiotensin converting enzyme inhibitor Clinical signs of obvious gastroesophageal reflux Clinical rhinosinusitis Recent respiratory infection (< 1 month) Corticosteroid Treatment(oral or inhaled) within 2 weeks VEMS < 1 L or < 80% of the theoretical value Existence of an obstructive ventilatory disorder defined as a report (FEV/FVC) < 90% of the theoretical value