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Chronic non-specific respiratory symptoms are difficult to manage. This trial aimed to evaluate the association between baseline fractional exhaled nitric oxide (FeNO) and the response to inhaled corticosteroids in patients with non-specific respiratory symptoms.In this double-blind randomised placebo-controlled trial, we enrolled undiagnosed patients, aged 18-80 years, with cough, wheeze, or dyspnoea and less than 20% bronchodilator reversibility across 26 primary care centres and hospitals in the UK and Singapore. Patients were assessed for 2 weeks before being randomly assigned (1:1) to 4 weeks of treatment with extrafine inhaled corticosteroids (QVAR 80 μg, two puffs twice per day, equivalent to 800 μg per day beclomethasone dipropionate) or placebo. Randomisation was stratified by baseline FeNO measurement: normal (≤25 parts per billion [ppb]), intermediate (25 tp40 ppb), and high (≥40 ppb). The primary endpoint was change in Asthma Control Questionnaire (ACQ7) mean score. We used generalised linear modelling to assess FeNO as a predictor of response, estimating an interaction effect between FeNO and treatment on change in ACQ7. We did our primary and secondary analyses in the per-protocol set, which excluded patients with non-completion of the primary endpoint, non-compliance to treatment (ascertained by patient report), and study visits made outside the predefined visit windows. This study is registered on ClinicalTrials.gov, number NCT02294279.Between Feb 4, 2015, and July 12, 2016, we randomly assigned 294 patients to extrafine inhaled corticosteroid treatment (n=148) or placebo (n=146). Following exclusions due to protocol violations, we analysed 214 patients (114 extrafine inhaled corticosteroids and 100 placebo). We observed a significant interaction between baseline FeNO and treatment group for every 10 ppb increase in baseline FeNO, with the change in ACQ7 greater in the extrafine inhaled corticosteroids group than in the placebo group (difference between groups 0·071, 95% CI 0·002 to 0·139; p=0·044). The most common adverse events were nasopharyngitis (18 [12%] patients in the treatment group vs 13 [9%] in the placebo group), infections and infestations (25 [17%] vs 21 [14%]), and respiratory, thoracic, and mediastinal disorders (13 [9%] vs 17 [12%]).FeNO measurement is an easy and non-invasive tool to use in clinical practice in patients with non-specific respiratory symptoms to predict response to inhaled corticosteroids. Further research is needed to examine its role in patients with evidence of other airway diseases, such as chronic obstructive pulmonary disease.Sponsored by OPRI with partial funding by Circassia and study drugs provided by TEVA.

Background: Fractional exhaled nitric oxide (FeNO) can predict treatment response in asthma, but little is known of its utility in patients with non-specific respiratory symptoms (NSRS). Aims and objectives: To evaluate the association between baseline FeNO and response to treatment with inhaled corticosteroids (ICS) in patients with NSRS. Methods: This was a multi-centre randomised, placebo-controlled trial, carried out in UK and Singapore. It consisted of a 2-week assessment period to establish baseline measurements and a 4-week treatment period with either extrafine ICS (200 µ beclomethasone bid) or placebo. NIOX VERO (Circassia) was used to measure baseline FeNO. The primary endpoint was change in ACQ7 score (Asthma Control Questionnaire, 7 questions). Analysis was carried out in a Main Analysis Set (MAS), which contained all randomised patients who complied with their study treatment and completed follow-up within 6 weeks of randomisation, and in a Per Protocol (PP) set, which included all patients in the MAS but excluded protocol violations. Results: In the PP set (n=214), we found that higher baseline FeNO was associated with a greater treatment effect. Improvement of ACQ7 was 0.071 (95% confidence interval [CI], 0.002-0.139) greater in patients receiving extrafine ICS compared to patients receiving placebo, for every 10 ppb increase in baseline FeNO. The equivalent effect was not significant in the MAS set (n=259) (0.049; 95% CI, -0.012-0.110). Conclusions: FeNO measurement is a simple, near patient, quantitative and non-invasive diagnostic tool that could support treatment decisions for patients with NSRS. Further research is needed to establish a treatment paradigm.

Background Fractional exhaled nitric oxide (FeNO) is a surrogate marker of eosinophilic airway inflammation and good predictor of corticosteroid response. Aim To evaluate how FeNO is being used to guide primary care asthma management in the United Kingdom (UK) with a view to devising practical algorithms for the use of FeNO in the diagnosis of steroid-responsive disease and to guide on-going asthma management. Methods Eligible patients (n = 678) were those in the Optimum Patient Care Research Database (OPCRD) aged 4–80 years who, at an index date, had their first FeNO assessment via NIOX MINO® or Flex®. Eligible practices were those using FeNO measurement in at least ten patients during the study period. Patients were characterized over a one-year baseline period immediately before the index date. Outcomes were evaluated in the year immediately following index date for two patient cohorts: (i) those in whom FeNO measurement was being used to identify steroid-responsive disease and (ii) those in whom FeNO monitoring was being used to guide on-going asthma management. Outcomes for cohort (i) were incidence of new ICS initiation at, or within the one-month following, their first FeNO measurement, and ICS dose during the outcome year. Outcomes for cohort (ii) were adherence, change in adherence (from baseline) and ICS dose. Outcomes In cohort (i) (n = 304) the higher the FeNO category, the higher the percentage of patients that initiated ICS at, or in the one month immediately following, their first FeNO measurement: 82%, 46% and 26% of patients with high, intermediate and low FeNO, respectively. In cohort (ii) (n = 374) high FeNO levels were associated with poorer baseline adherence (p = 0.005) but greater improvement in adherence in the outcome year (p = 0.017). Across both cohorts, patients with high FeNO levels were associated with significantly higher ICS dosing (p

These are two cases of cocaine abuse with the following previously unreported cocaine-associated features: 1) biopsy-proven accelerated/malignant hypertension, 2) association of cocaine with persistent hypertension, and 3) renal failure with rapid progression to end-stage renal disease that did not reverse following blood pressure control.

Background Airway inflammation is the fundamental mechanism in asthma and can be measured non-invasively by means of fractional exhaled nitric oxide (FeNO). Both, The National Institute for Health and Care Excellence (NICE) diagnostics guidance 12 and British guideline on the management of asthma, are recommending the inclusion of FeNO testing as part of diagnosis in patients that have an intermediate probability of having asthma. Furthermore, FeNO testing is recommended as an option for monitoring response to corticosteroid treatment in patients with increased FeNO. However, there is a need for establishing routine data predictors for individuals with increased FeNO, to identify those that would benefit from FeNO measurement as a tool for aiding asthma diagnosis and monitoring treatment responsiveness. To provide a real-life predictive model for the identification of individuals at risk of asthma that have increased FeNO.