Abstract
BackgroundThe diagnosis of childhood asthma covers a broad spectrum of pathological mechanisms that can lead to similarly presenting clinical symptoms, but may nonetheless require different treatment approaches. Distinct underlying inflammatory patterns are thought to influence responsiveness to standard asthma medication.Methods/designThe purpose of the PACMAN2 study is to identify inflammatory phenotypes that can discriminate uncontrolled childhood asthma from controlled childhood asthma by measures in peripheral blood and exhaled air. PACMAN2 is a nested, case–control follow-up study to the ongoing pharmacy-based “Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects” (PACMAN) study. The original PACMAN cohort consists of children aged 4–12 years with reported use of asthma medication. The PACMAN2 study will be conducted within the larger PACMAN cohort, and will focus on detailed phenotyping of a subset of the PACMAN children. The selected participants will be invited to a follow-up visit in a clinical setting at least six months after their baseline visit based on their adherence to usage of inhaled corticosteroids, their asthma symptoms in the past year, and their age (≥ 8 years). During the follow-up visit, current and long-term asthma symptoms, medication use, environmental factors, medication adherence and levels of exhaled nitric oxide will be reassessed. The following measures will also be examined: pulmonary function, exhaled volatile organic compounds, as well as inflammatory markers in peripheral blood and blood plasma. Comparative analysis and cluster-analyses will be used to identify markers that differentiate children with uncontrolled asthma despite their use of inhaled corticosteroids (ICS) (cases) from children whose asthma is controlled by the use of ICS (controls).DiscussionAsthmatic children with distinct inflammatory phenotypes may respond differently to anti-inflammatory therapy. Therefore, by identifying inflammatory phenotypes in children with the PACMAN2 study, we may greatly impact future personalised treatment strategies, uncover new leads for therapeutic targets and improve the design of future clinical studies in the assessment of the efficacy of novel therapeutics.
Highlights
The diagnosis of childhood asthma covers a broad spectrum of pathological mechanisms that can lead to presenting clinical symptoms, but may require different treatment approaches
Since we aim to identify a fingerprint of markers that are differentially expressed, we will further explore the data using principal component analysis and other clusteringanalyses on the entire data set with adequatevalidation according to recent recommendation in order to limit false-discovery [39,40]
Based on a preliminary analysis of 744 children included in the PACMAN cohort, we found that 86.4% of the children use Inhaled corticosteroids (ICS) and 60.2% are adherent to ICS treatment
Summary
The diagnosis of childhood asthma covers a broad spectrum of pathological mechanisms that can lead to presenting clinical symptoms, but may require different treatment approaches. Inhaled corticosteroids (ICS) have become the first-line controller therapy for asthma, and the standard treatment of persistent asthma is generally guided by symptom control [1]. Most children with persistent asthma symptoms will have a beneficial response to ICS. There is large inter-individual variability [3] and a portion of children with asthma will remain uncontrolled despite intensive treatment with high dosages of inhaled corticosteroids and/or oral corticosteroids. It is essential to identify asthmatic children with a high risk of poor response to standard asthma medication at an early stage
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