Nasal nitric oxide (nNO) concentrations are low in patients with primary ciliary dyskinesia (PCD) providing a noninvasive screening test.We conducted a systematic review of the literature to examine the utility of nNO in screening for PCD, in particular 1) different respiratory manoeuvres during sampling (velum closure, tidal breathing, etc.), 2) accuracy in screening young/uncooperative children, 3) stationary versus portable analysers, and 4) nNO in ''atypical'' PCD.96 papers were assessed according to modified PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and 22 were included in this review.Meta-analysis of 11 studies comparing nNO during a velum closure breath hold gave a mean¡SD nNO of 19.4¡18.6 nL?min -1 in PCD (n5478) and 265.0¡118.9 nL?min -1 in healthy controls (n5338). Weighted mean difference for PCD versus healthy controls was 231.1 nL?min -1 (95% CI 193.3-268.9; n5338) and 114.1 nL?min -1 (95% CI 101.5-126.8; n5415) for PCD versus cystic fibrosis. Five studies of nNO measurement during tidal breathing demonstrated that this is an acceptable manoeuvre in young children where velum closure is not possible, but the discriminatory value was reduced. Four small studies of portable NO analysers suggest these are reliable tools for screening for PCD. However, nNO must be interpreted alongside clinical suspicion. Future studies should focus on standardising sampling techniques and reporting. @ERSpublications Nasal nitric oxide is a useful and increasingly versatile screening tool in primary ciliary dyskinesia at all ages http://ow.ly/AR5mqThis article has supplementary material available from erj.ersjournals.com
Previous publications have highlighted the disparity between research trial populations and those in clinical practice, but it has not been established how this relates to randomised controlled trials (RCTs) of phenotype-targeted biological therapies in severe asthma.Detailed characterisation data for 342 severe asthma patients within the Wessex Severe Asthma Cohort (WSAC) was compared against comprehensive trial eligibility criteria for published phase IIB and phase III RCTs evaluating biological therapies in severe asthma since 2000.37 RCTs evaluating 20 biological therapies were identified. Only a median of 9.8% (range 3.5–17.5%) of severe asthma patients were found to be eligible for enrolment in the phase III trials. Stipulations for airflow obstruction, bronchodilator reversibility and smoking history excluded significant numbers of patients. A median of 78.9% (range 73.2–86.6%) of patients with severe eosinophilic asthma would have been excluded from participation in the phase III licensing trials of interleukin (IL)-5/IL-5R targeted therapies.Despite including only well characterised and optimally treated severe asthmatics under specialist care within the WSAC study, the vast majority were excluded from trial participation by criteria designed to re-confirm diagnostic labels rather than by biomarker criteria that predict the characteristic addressed by the treatment.
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