Pathophysiological characterization of asthma transitions across adolescence

Abstract

BackgroundAdolescence is a period of change, which coincides with disease remission in a significant proportion of subjects with childhood asthma. There is incomplete understanding of the changing characteristics underlying different adolescent asthma transitions. We undertook pathophysiological characterization of transitional adolescent asthma phenotypes in a longitudinal birth cohort.MethodsThe Isle of Wight Birth Cohort (N = 1456) was reviewed at 1, 2, 4, 10 and 18-years. Characterization included questionnaires, skin tests, spirometry, exhaled nitric oxide, bronchial challenge and (in a subset of 100 at 18-years) induced sputum. Asthma groups were “never asthma” (no asthma since birth), “persistent asthma” (asthma at age 10 and 18), “remission asthma” (asthma at age 10 but not at 18) and “adolescent-onset asthma” (asthma at age 18 but not at age 10).ResultsParticipants whose asthma remitted during adolescence had lower bronchial reactivity (odds ratio (OR) 0.30; CI 0.10 -0.90; p = 0.03) at age 10 plus greater improvement in lung function (forced expiratory flow 25-75% gain: 1.7 L; 1.0-2.9; p = 0.04) compared to persistent asthma by age 18. Male sex (0.3; 0.1-0.7; p < 0.01) and lower acetaminophen use (0.4; 0.2-0.8; p < 0.01) independently favoured asthma remission, when compared to persistent asthma. Asthma remission had a lower total sputum cell count compared to never asthma (31.5 [25–75 centiles] 12.9-40.4) vs. 47.0 (19.5-181.3); p = 0.03). Sputum examination in adolescent-onset asthma showed eosinophilic airway inflammation (3.0%, 0.7-6.6), not seen in persistent asthma (1.0%, 0–3.9), while remission group had the lowest sputum eosinophil count (0.3%, 0–1.4) and lowest eosinophils/neutrophils ratio of 0.0 (Interquartile range: 0.1).ConclusionAsthma remission during adolescence is associated with lower initial BHR and greater gain in small airways function, while adolescent-onset asthma is primarily eosinophilic.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0153-7) contains supplementary material, which is available to authorized users.

Filaggrin mutations increase allergic airway disease in childhood and adolescence through interactions with eczema and aeroallergen sensitization

“…The documentation of ongoing systemic eosinophilic inflammation in adolescent asthma was observed in a previous report in this cohort. 36 Our study supports this observation whereby aeroallergen sensitization at 4 years leads to asthma at 10 years which in turn strongly predicts asthma persistence into adolescence via a significant direct effect. In contrast, the pathogenesis of early childhood asthma appears to be heterogenous.…”

Seasonality of sputum eosinophilia in adolescents with asthma remission: effects of montelukast

“…However, adequate sputum was obtained only in 16 cases. 6 The results of our study showed a pronounced effect of seasonality on eosinophilic inflammation as determined by the percentage of eosinophils present in the induced sputum. During the autumn-winter period, the placebo group showed a significant increase in eosinophil content, as compared to the summer baseline.…”

NOx in exhaled breath condensate is related to allergic sensitization in young and middle‐aged adults

“…It is possible that some of these participants had prior asthma leading to airway remodelling, 33 ongoing airway inflammation and elevated oxidative stress, 34,35 but quite possibly, atopy may directly influence NO x , without requiring asthma to be intermediary step. It is possible that some of these participants had prior asthma leading to airway remodelling, 33 ongoing airway inflammation and elevated oxidative stress, 34,35 but quite possibly, atopy may directly influence NO x , without requiring asthma to be intermediary step.…”

“…Interestingly, we found that elevated EBC NO x levels were associated with atopic nonasthma in the TAHS participants. It is possible that some of these participants had prior asthma leading to airway remodelling, 33 ongoing airway inflammation and elevated oxidative stress, 34,35 but quite possibly, atopy may directly influence NO x , without requiring asthma to be intermediary step.…”