Open Access Study protocol

Inflammatory phenotypes underlying uncontrolled childhood asthma despite inhaled corticosteroid treatment: rationale and design of the PACMAN2 study

Susanne JH Vijverberg12, Leo Koenderman2, Francine C van Erp3, Cornelis K van der Ent3, Dirkje S Postma4, Paul Brinkman5, Peter J Sterk5, Jan AM Raaijmakers1 and Anke-Hilse Maitland-van der Zee1*

Author Affiliations

1 Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, Utrecht 3508 TB, the Netherlands

2 Department of Respiratory Medicine, University Medical Centre Utrecht, Heidelberglaan 100, Utrecht 3584 CX, the Netherlands

3 Department of Paediatric Respiratory Medicine, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Lundlaan 6, Utrecht 3584 EA, the Netherlands

4 Department of Pulmonology, Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen 9713 GZ, the Netherlands

5 Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands

For all author emails, please log on.

BMC Pediatrics 2013, 13:94  doi:10.1186/1471-2431-13-94

Published: 15 June 2013



The 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.


The 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).


Asthmatic 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.

Asthma; Child; Phenotypes; Inflammation; Proteomics; Volatile organic compounds; Corticosteroids