Dynamics of respiratory symptoms during infancy and associations with wheezing at school age.

Usemann, Jakob; Xu, Binbin; Delgado-Eckert, Edgar; Korten, Insa Christina Severine; Anagnostopoulou, Pinelopi; Gorlanova, Olga; Kuehni, Claudia; Röösli, Martin; Latzin, Philipp; Frey, Urs; study group, BILD (2018). Dynamics of respiratory symptoms during infancy and associations with wheezing at school age. ERJ Open Research, 4(4), 00037. European Respiratory Society 10.1183/23120541.00037-2018

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Children with frequent respiratory symptoms in infancy have an increased risk for later wheezing, but the association with symptom dynamics is unknown. We developed an observer-independent method to characterise symptom dynamics and tested their association with subsequent respiratory morbidity. In this birth-cohort of healthy neonates, we prospectively assessed weekly respiratory symptoms during infancy, resulting in a time series of 52 symptom scores. For each infant, we calculated the transition probability between two consecutive symptom scores. We used these transition probabilities to construct a Markov matrix, which characterised symptom dynamics quantitatively using an entropy parameter. Using this parameter, we determined phenotypes by hierarchical clustering. We then studied the association between phenotypes and wheezing at 6 years. In 322 children with complete data for symptom scores during infancy (16 864 observations), we identified three dynamic phenotypes. Compared to the low-risk phenotype, the high-risk phenotype, defined by the highest entropy parameter, was associated with an increased risk of wheezing (odds ratio (OR) 3.01, 95% CI 1.15-7.88) at 6 years. In this phenotype, infants were more often male (64%) and had been exposed to environmental tobacco smoke (31%). In addition, more infants had siblings (67%) and attended childcare (38%). We describe a novel method to objectively characterise dynamics of respiratory symptoms in infancy, which helps identify abnormal clinical susceptibility and recovery patterns of infant airways associated with persistent wheezing.

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