METHODS: We developed mouse models representing three different phenotypes of allergic airway inflammation-eosinophilic, mixed, and neutrophilic asthma via different methods of house dust mite sensitization and challenge. Transcriptomic analysis of the lungs, followed by the RT-PCR, western blot, and confocal microscopy, was performed. Primary human bronchial epithelial cells cultured in air-liquid interface were used to study the mechanisms revealed in the in vivo models.
RESULTS: By whole-genome transcriptome profiling of the lung, we found that airway tight junction (TJ), mucin, and inflammasome-related genes are differentially expressed in these distinct phenotypes. Further analysis of proteins from these families revealed that Zo-1 and Cldn18 were downregulated in all phenotypes, while increased Cldn4 expression was characteristic for neutrophilic airway inflammation. Mucins Clca1 (Gob5) and Muc5ac were upregulated in eosinophilic and even more in neutrophilic phenotype. Increased expression of inflammasome-related molecules such as Nlrp3, Nlrc4, Casp-1, and IL-1β was characteristic for neutrophilic asthma. In addition, we showed that inflammasome/Th17/neutrophilic axis cytokine-IL-1β-may transiently impair epithelial barrier function, while IL-1β and IL-17 increase mucin expressions in primary human bronchial epithelial cells.
CONCLUSION: Our findings suggest that differential expression of TJ, mucin, and inflammasome-related molecules in distinct inflammatory phenotypes of asthma may be linked to pathophysiology and might reflect the differences observed in the clinic.
METHOD: We performed a cross-sectional study using the International Study of Asthma and Allergies in Childhood questionnaire to identify 7-12-year-old Malay children with asthma symptoms from a primary school in central Kuala Lumpur. Sixty-five of 76 children with 'ever wheeze' performed an exercise challenge test successfully in an uncontrolled environment. A random sample of 80 schoolchildren with no history of wheeze were similarly tested as controls. The relative humidity and temperature were recorded. A fall of > 15% was considered as clinically important.
RESULTS: The prevalence of EIB in schoolchildren with 'ever wheeze' was 47.7%. The prevalence of EIB in children with 'current wheeze' was 51.6%. The prevalence of EIB in controls was 7.5%. The relative humidity during the study ranged from 41 to 90%. There was no significant relationship between different humidity levels and EIB (P = 0.58, regression analysis).
CONCLUSION: This study demonstrates that EIB is present in asthmatic children despite the highly humid tropical environment.