Levels of FENO at baseline and after mannitol dry powder challenge.

<p>Abbreviations: SPT, skin prick test; BHR, bronchial hyperresponsiveness; MDP, mannitol dry powder; FENO, fractional exhaled nitric oxide; IQR, interquartile range.</p>*<p>BHR reported as MDP challenge results (provocative dose (in mg) inducing a 15% drop of FEV₁ (PD₁₅)). BHR severity is directly correlated with No of MDP manoeuvres.</p>†<p>Non-parametric test, matched group = Wilcoxon signed rank test comparing medians of FENO at baseline and after MDP challenge.</p

% difference of FENO after MDP challenge by baseline FENO, asthma, atopy and BHR severity.

<p>Abbreviations: FENO, fractional exhaled nitric oxide; MDP, mannitol dry powder; BHR, bronchial hyperresponsiveness; SPT, skin prick test. Baseline FENO defined as tertiles (low levels: <13 ppb; medium levels: 13 ppb–30 ppb; high levels: >30 ppb). Atopy defined as none (negative SPT), mild (1 to 2 positive SPT), moderate (≥3 positive SPT). BHR reported as MDP challenge results (provocative dose (in mg) inducing a 15% drop of FEV₁ (PD₁₅)) and defined as normal (>635 mg, 11 manoeuvres), mild (155–635 mg, 8–10 manoeuvres), moderate to severe (<155 mg, ≤7 manoeuvres).</p

A Disease Model for Wheezing Disorders in Preschool Children Based on Clinicians' Perceptions

Background: Wheezing disorders in childhood vary widely in clinical presentation and disease course. During the last years, several ways to classify wheezing children into different disease phenotypes have been proposed and are increasingly used for clinical guidance, but validation of these hypothetical entities is difficult. Methodology/Principal Findings: The aim of this study was to develop a testable disease model which reflects the full spectrum of wheezing illness in preschool children. We performed a qualitative study among a panel of 7 experienced clinicians from 4 European countries working in primary, secondary and tertiary paediatric care. In a series of questionnaire surveys and structured discussions, we found a general consensus that preschool wheezing disorders consist of several phenotypes, with a great heterogeneity of specific disease concepts between clinicians. Initially, 24 disease entities were described among the 7 physicians. In structured discussions, these could be narrowed down to three entities which were linked to proposed mechanisms: a) allergic wheeze, b) non-allergic wheeze due to structural airway narrowing and c) non-allergic wheeze due to increased immune response to viral infections. This disease model will serve to create an artificial dataset that allows the validation of data-driven multidimensional methods, such as cluster analysis, which have been proposed for identification of wheezing phenotypes in children. Conclusions/Significance: While there appears to be wide agreement among clinicians that wheezing disorders consist of several diseases, there is less agreement regarding their number and nature. A great diversity of disease concepts exist but a unified phenotype classification reflecting underlying disease mechanisms is lacking. We propose a disease model which may help guide future research so that proposed mechanisms are measured at the right time and their role in disease heterogeneity can be studied

Classification of wheezing disorders in children aged 0-5 years as initially suggested by panel members.

<p>Classification of wheezing disorders in children aged 0-5 years as initially suggested by panel members.</p

Disease model for wheezing disorders in children aged 0–5 years as agreed by panel.

<p>Abbreviations: BAL bronchoalveolar lavage; BDR bronchodilator response; BHR bronchial hyperresponsiveness; ETS environmental tobacco smoke; ICS inhaled corticosteroids; LF lung function; NO nitric oxide; SPT skin prick test.</p