The Evaluation of FeNO for Predicting Response to ICS in Subjects With Non-specific Respiratory Symptoms
The Evaluation of FeNO for Predicting Response to ICS in Subjects With Non-specific Respiratory Symptoms
Nitric Oxide is recognized as a biological marker for many chronic airway diseases. It has
 been standardised for clinical use indicating airway inflammation.

 In clinical practice, FeNO can aid confirmation of an asthma diagnosis and can indicate the
 degree of steroid-responsiveness. This can help guide physician decisions on the initiation
 of inhaled corticosteroid (ICS) therapy, or adjustment of ICS therapy.

 Therefore, FeNO measurement could be particularly useful to confirm an asthma diagnosis in
 patients with non-specific respiratory symptoms (≥ 6 weeks of cough and/or wheezing and/or
 chronic dyspnoea) and to assess how likely they are to benefit from corticosteroid treatment.

 This study will assess the suitability of FeNO to predict ICS responsiveness in patients with
 non-specific respiratory symptoms.

 Additionally, we would like to determine the suitability of FeNO as a diagnostic tool for
 asthma in comparison to conventional predictors, e.g. spirometry.
Randomised, double-blind, placebo-controlled trial with planned enrolment of 264 patients
 from the UK and Singapore. Eligible patients are 18-80 years old with ≥6 weeks' duration of
 non-specific respiratory symptoms defined as cough and/or wheeze and/or dyspnoea. Patients
 with FEV1 <90% predicted at visit 1 must show reversibility of <20% at visit 1 or within the
 prior year. Key exclusion criteria are prior diagnosis of asthma; evidence of concomitant
 chronic respiratory disease, respiratory tract infection; or known significant risk factor
 for cough or wheeze.

 Baseline assessments will include spirometry (FEV1, forced vital capacity) and FeNO
 measurement. Patients will be provided with a peak flow meter for twice daily measurement
 throughout the study. At 2 weeks, a clinical assessment and spirometry will be performed to
 confirm eligibility, and patients will complete four validated questionnaires to assess
 quality of life, asthma control, and asthma symptoms, including a visual analog scale for
 bother from asthma symptoms. Eligible patients will then be stratified by baseline FeNO level
 (normal ≤25, intermediate >25 to ≤50, or high >50 ppb); each group will be randomised to
 receive beclometasone 400 mcg daily or placebo for 6 weeks. An optional blood sample will be
 collected from consenting patients to assess blood eosinophils.

 At visit 3, final assessments will include spirometry, FeNO measurement, and all
 questionnaires. Interaction analysis will be used to determine whether a differential effect
 exists in response to ICS between FeNO groups.
Inclusion Criteria:

 -  Written informed consent is obtained before conducting any study-related procedures

 -  The patient is a man or woman aged 18 to 80 years as of the screening visit

 -  The patient is experiencing non-specific respiratory symptoms defined as follows:
 Cough and/or wheeze and/or chronic dyspnoea for ≥ 6 weeks prior to visit 1

 -  Patients displaying an FEV1< 90% predicted at visit 1, will also need to show a
 reversibility to a short-acting beta-agonist of < 20% at visit 1 or within the
 previous year

 -  Women of childbearing potential (post-menarche or less than 2 years post-menopausal or
 not surgically sterile) must be willing to commit to using a medically accepted method
 of contraception for the duration of the study. Accepted methods of contraception
 include: intrauterine devices (IUD), systemic contraception e.g. steroidal
 contraceptives (oral, implanted transdermal or injected), barrier methods with
 spermicide, and partner vasectomy

 Exclusion Criteria:

 -  The patient has ever been diagnosed with asthma as evidenced by the UK quality outcome
 framework approved Read code as well as a reversibility of ≥ 20% predicted

 -  The patient has received oral, inhaled or systemic corticosteroids, a leukotriene
 modifier or long-acting-beta-agonist within four weeks prior to visit 1. All therapy
 and treatment other than those outlined are permitted during the study

 -  The patient has a significant chronic respiratory disorder other than asthma, e.g.
 COPD (fixed obstruction, post-bronchodilator) cystic fibrosis, severe and untreated
 bronchiectasis or interstitial lung disease

 -  The patient has a significant medical condition that would make it unlikely for the
 patient to complete the study

 -  The patient has a known significant risk factor for cough or wheeze, including but not
 limited to: taking an ACE inhibitor, severe untreated rhinitis, or significant
 gastroesophageal reflux disease

 -  The patient is asymptomatic (ACQ < 1) after the initial 2-week assessment

 -  The patient has had a respiratory tract infection as judged clinically, within four
 weeks prior to visit 1, or displays an acute respiratory tract infection at the time
 of the study

 -  The patient is a pregnant woman or intends to get pregnant (Any woman becoming
 pregnant during the study will be withdrawn from the study)