title: Problematic severe asthma: a proposed approach to identifying children who are severely resistant to therapy.
abstract: Children with problematic severe asthma (PA) are either difficult to treat because of the presence of aggravating factors or else severely resistant to therapy. We investigated a cohort of school-aged children with PA and compared these children to age-matched peers with controlled persistent asthma (CA). The aims were to characterize features of children suffering from PA and identify children who were severely resistant to therapy. In this cross-sectional, multicenter comparison of children with different manifestations of persistent asthma, PA was defined as insufficient asthma control despite level 4 treatment, according to GINA. The protocol included questionnaires, spirometry, methacholine provocation, measurement of fraction of nitric oxide in exhaled (FE(NO) ) and nasal air, blood sampling for inflammatory biomarkers and atopy, and computerized tomography of sinuses and lungs (in the PA group only). Of the 54 children with PA, 61% had therapy-resistant asthma, with the remaining being difficult to treat because of identified aggravating factors. Children with PA more often had parents with asthma (p=0.003), came from families with a lower socioeconomic status (p=0.01), were less physically active (p=0.04), and had more comorbidity with rhinoconjunctivitis (p=0.01) than did the 39 children with CA. The former also exhibited lower FEV(1) values (p=0.02) and increased bronchial hyper-responsiveness (p=0.01), but there were no differences in atopy (p=0.81) or FE(NO) (p=0.16). A non-invasive protocol, involving a standardized and detailed clinical characterization, revealed distinguishing features of children with PA and enabled the identification of children with therapy-resistant asthma.
authors.affiliation: Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jon R
authors.initials: JR
authors.lastname: Konradsen
authors.forename: Björn
authors.initials: B
authors.lastname: Nordlund
authors.forename: Marika
authors.initials: M
authors.lastname: Lidegran
authors.forename: Christophe
authors.initials: C
authors.lastname: Pedroletti
authors.forename: Hans
authors.initials: H
authors.lastname: Grönlund
authors.forename: Marianne
authors.initials: M
authors.lastname: van Hage
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlen
authors.forename: Gunilla
authors.initials: G
authors.lastname: Hedlin
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity; D001985:Bronchial Provocation Tests; D002648:Child; D003430:Cross-Sectional Studies; D045853:Exhalation; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000502:physiology; D008297:Male; D016210:Methacholine Chloride / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D012129:Respiratory Function Tests; D012220:Rhinitis / Q000150:complications*; D012720:Severity of Illness Index; D013147:Spirometry; D011795:Surveys and Questionnaires
chemical_list: D016210:Methacholine Chloride; D009569:Nitric Oxide