Page 72 - ADULT-ONSET ASTHMA PREDICTORS OF CLINICAL COURSE AND SEVERITY
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ADULT-ONSET ASTHMA – PREDICTORS OF CLINICAL COURSE AND SEVERITY
METHODS
ELIGIBILITY CRITERIA
Studies were included if they had evaluated the diagnos c accuracy of one or more blood, serum, nasal lavage, or exhaled breath markers9 (index test) in detec ng airway eosinophilia (target condi on) in pa ents with (suspected) asthma. Direct airway sampling methods (induced sputum, BAL, and/or EBB) were considered as acceptable reference standards, independent of the threshold for posi vity used. We excluded review ar cles.
SEARCH AND SELECTION
A medical informa on specialist (RS) developed searches in MEDLINE, Embase, and PubMed without date or language restric ons (Appendix 1). The searches were updated in August 2014. Two independent reviewers (DAK, GAW) examined  tles and abstracts of all search results. Full reports of studies that were considered poten ally eligible by at least one of them were obtained and independently assessed for inclusion. Disagreements were resolved by consensus. One reviewer (DAK) also scanned reference lists of included ar cles, and searched trial registries (ClinicalTrials.gov, Current Controlled Trials, Netherlands Trial Register, Australian New Zealand Clinical Trials Registry) for unpublished or ongoing studies.
DATA EXTRACTION AND QUALITY ASSESSMENT
One reviewer (DAK) performed data extrac on, which was veri ed by a second reviewer (GAW). We iden  ed the  rst author, country, journal, year of publica on, recruitment se ng, sample size and characteris cs of included pa ents (age, gender, body mass index, atopy status, asthma severity, FEV1 % predicted, smoking status, cor costeroid treatment status). We also extracted the index test(s), reference standard(s), test posi vity thresholds, disease prevalence, accuracy es mates, and data for 2x2 tables presen ng index test results by reference standard results for each reported threshold. If 2x2 tables were not reported, we a empted to reconstruct them from summary es mates or by contac ng corresponding authors through email. If it appeared from an ar cle that mul ple markers had been assessed, but diagnos c accuracy data were not reported for all of them, we contacted authors to obtain these data. Two authors (DAK, GAW) independently assessed risk of bias and applicability concerns using QUADAS-210.
ENRICHMENT SAMPLE
To enrich the number of included studies, we tried to iden fy unpublished data by contac ng authors of published studies that had not reported on the diagnos c accuracy of a marker to detect airway eosinophilia, but seemed to have data from which accuracy es mates could be calculated. Studies were selected if they had performed at least one index test and one reference standard, as de ned above. Such studies were only eligible if they explicitly
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