MCT and Capsaicin Provocation Challenge in Diagnosis of Chronic Cough
Condition: Cough; Cough Variant Asthma; Upper-Airway Cough Syndrome; GERD; Allergic Rhinitis
MeSH terms: Rhinitis; Rhinitis, Allergic; Cough
Study type: Observational

Summary: 
      The aim of the study is to assess the prevalence of bronchial hyperresponsiveness (BHR) in
      non-smoking adults with chronic cough and the prevalence of BHR in patients with upper airway
      cough syndrome (UACS) and gastroesophageal reflux disease (GERD), to evaluate the
      relationship between BHR and cough reflex sensitivity, to assess the diagnostic accuracy of
      methacholine challenge test (MCT) in cough variant asthma (CVA) with special regard to its
      discriminating cut off value between CVA and other causes of chronic cough, particularly
      GERD, to estimate prognostic value of BHR, fractional exhaled nitric oxide (FeNO) and induced
      sputum eosinophil count in predicting response to asthma treatment.

      Patients diagnosed with a chronic cough will undergo the standard diagnostic work-up
      recommended by experts for patients with a chronic cough, including methacholine challenge
      test (MCT) and an at least 4-week period of causal treatment. Patients with BHR in MCT will
      be treated with - in first step B2-agonist and inhaled corticosteroid (ICS) for at least 4
      weeks, if improvement is not significant in next steps with leukotriene receptor antagonist
      (LTRA) or systemic corticosteroid. A good treatment response, evaluated by visual analogue
      scale (VAS), Leicester Cough Questionnaire (LCQ) and cough challenge will confirm the
      diagnosis of the disease. A statistical analysis will consist of the frequency of BHR in a
      chronic cough, correlation between the results of MCT and cough reflex sensitivity in
      capsaicin inhalation test and cut-off point for MCT to discriminate asthma from other causes
      of a chronic cough.
    

Detailed description: 
      The present study has the following objectives:

        1. to assess the prevalence of BHR in non-smoking adults with a chronic cough,

        2. to assess the prevalence of BHR in patients with UACS and GERD,

        3. to evaluate the relationship between BHR and cough reflex sensitivity,

        4. to assess the diagnostic accuracy of MCT in CVA with special regard to its
           discriminating value between CVA and other causes of a chronic cough, particularly GERD,

        5. to estimate prognostic value of BHR, fractional exhaled nitric oxide (FeNO) and induced
           sputum eosinophil count in predicting response to asthma treatment.

      The investigated group will consist of 80 non-smoking adults (18-75 years old), who are not
      treated with angiotensin-converting enzyme inhibitors, with no signs of respiratory infection
      within six weeks prior to enrolment, with a normal chest radiograph and who are referred to
      the hospital due to a cough lasting at least eight weeks.

      After obtaining an informed consent, the diagnostic approach of the most common causes of
      chronic cough will be performed: a medical history, physical examination, chest radiograph,
      in some cases chest computed tomography, pulmonary function tests (spirometry, fractional
      exhaled nitric oxide, methacholine challenge test), laboratory tests (total immunoglobulin E
      concentration, complete blood count), skin prick tests, induced sputum cell count, computed
      tomography of the paranasal sinuses and ENT consultation, 24-hour impedance with pH
      monitoring, videolaryngoscopy and cough challenge with capsaicin.

      The cough severity will be assessed twice (on admission and after six weeks of causal
      treatment) using the Visual Analogue Scale (VAS), the Polish version of the Leicester Cough
      Questionnaire (LCQ) and the capsaicin inhalation cough challenge.

      If MCT result is positive, CVA will be assumed the cause of a chronic cough and treatment
      with an inhaled steroid combined with a long-acting beta-agonist will be administered for at
      least 4 weeks. If no satisfactory response to this treatment is observed, an anti-leukotriene
      agent or in the next step systemic corticosteroid will be applied. Ineffective treatment with
      the above-mentioned medications will indicate an opportunity for a different underlying cause
      of BHR. The estimation the area under a ROC (receiver operating characteristic) curve will be
      used to determine the optimal cut-off point for the differentiation between asthma and
      alternate causes of a chronic cough.

      It is expected to assess the frequency of bronchial hyperresponsiveness in subjects with a
      chronic cough, to confirm a correlation between the results of MCT and the sensitivity of
      cough reflex measured in capsaicin inhalation cough challenge. The investigation will
      probably determine a precise cut-off point for MCT which would allow discriminating asthma
      from other causes of a chronic cough.
    

Intervention name(s): Cough variant asthma treatment
Intervention type(s): Other
Intervention description(s): Evaluation of the treatment response to inhaled corticosteroids, long-acting beta-agonists, montelukast, prednisone.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Non-smoking patients aged 18-75, meeting inclusion criteria.
      
Biospecimen description: 
      blood samples
    
Keywords: Chronic Cough; Upper-Airway Cough Syndrome; GERD; Allergic Rhinitis; Methacholine Challenge Test; Cough Challenge; Capsaicin