Epithelial Aryl Hydrocarbon Receptor Protects From Mucus Production by Inhibiting ROS-Triggered NLRP3 Inflammasome in Asthma

BackgroundDespite long-standing recognition in the significance of mucus overproduction in asthma, its etiology remains poorly understood. Muc5ac is a secretory mucin that has been associated with reduced pulmonary function and asthma exacerbations.ObjectivesWe sought to investigate the immunological pathway that controls Muc5ac expression and allergic airway inflammation in asthma.MethodsCockroach allergen-induced Muc5ac expression and aryl hydrocarbon receptor (AhR) signaling activation was examined in the human bronchial epithelial cells (HBECs) and mouse model of asthma. AhR regulation of Muc5ac expression, mitochondrial ROS (Mito-ROS) generation, and NLRP3 inflammasome was determined by AhR knockdown, the antagonist CH223191, and AhR-/- mice. The role of NLRP3 inflammasome in Muc5ac expression and airway inflammation was also investigated.ResultsCockroach allergen induced Muc5ac overexpression in HBECs and airways of asthma mouse model. Increased expression of AhR and its downstream genes CYP1A1 and CYP1B1 was also observed. Mice with AhR deletion showed increased allergic airway inflammation and MUC5AC expression. Moreover, cockroach allergen induced epithelial NLRP3 inflammasome activation (e.g., NLRP3, Caspase-1, and IL-1β), which was enhanced by AhR knockdown or the antagonist CH223191. Furthermore, AhR deletion in HBECs led to enhanced ROS generation, particularly Mito-ROS, and inhibition of ROS or Mito-ROS subsequently suppressed the inflammasome activation. Importantly, inhibition of the inflammasome with MCC950, a NLRP3-specifc inhibitor, attenuated allergic airway inflammation and Muc5ac expression. IL-1β generated by the activated inflammasomes mediated cockroach allergen-induced Muc5ac expression in HBECs.ConclusionsThese results reveal a previously unidentified functional axis of AhR-ROS-NLRP3 inflammasome in regulating Muc5ac expression and airway inflammation.

Knowledge, attitudes, and practices concerning cockroach exposure among caregivers of children with asthma

Background Cockroach allergen is one of the most important asthma triggers for children. There is an extensive body of research on interventions to reduce exposure. However, adherence to these interventions is low. Insight into the knowledge, attitudes, and practices (KAP) associated with cockroach remediation is needed. We assessed KAP using the Health Beliefs Model (HBM) as a framework for predicting behavior. This study aimed to assess the socio-demographic and psycho-social characteristics associated with cockroach KAP and to quantify the relationship between KAP and number of cockroaches in the home. Methods To identify factors associated with cockroach KAP a cross-sectional study was conducted using a structured questionnaire administered to caregivers of children with asthma in New Orleans, Louisiana. Positive scores in each metric of the KAP signified better cockroach knowledge, increased concern about cockroaches’ impact on health (attitudes), and participation in recommended cockroach remediation practices (practices). To evaluate cockroach KAP scores as a predictor of cockroach exposure in the home, a cohort study was conducted among a sub-sample of participants. Results Fifty-six caregivers participated in the study. Participants had positive scores on all subscales of KAP with knowledge having a lower score compared to attitudes and practices. Cockroach knowledge was inversely correlated with age at asthma diagnosis (ρ = − 0.36, p = 0.01). Caregivers identifying as black/African American had higher cockroach knowledge scores compared to other races (Median: 6.0 v 3.0; p = 0.05). Caregivers other than mothers had higher cockroach attitude scores (Median 6.5 v 4.0; p = 0.003) and total KAP scores (Median 18.0 v 14.0; p = 0.05). Twenty-six participants completed the cohort study. Cockroach exposure was not significantly associated with higher cockroach knowledge, cockroach practice, or total KAP score. For attitude scores, participants in the highest quartile had significantly lower exposure (β: -1.96, 95% CI: − 3.50 - 0.42) compared to those in the lowest quartile (p = 0.01). Conclusions Different socio-demographic and psycho-social factors were associated with the components of cockroach KAP. Greater concern about cockroaches (attitude) was significantly associated with reduced cockroach exposure. This highlights the importance of identifying the key elements of caregiver KAP to improve cockroach remediation among caregivers of children with asthma.

Serum allergen spectrum and prevalence of allergic disease in Shenzhen, China

Purpose: Allergen sensitization are common allergic diseases worldwide, with widely varying estimates of prevalence in the population. The characteristics and prevalence of allergens and diseases in Shenzhen. Patients and methods: Allergen-specific IgE results were investigated among 20483 subjects from January 2016 to June 2020 based on by Western blotting, and statistical analysis was performed on sIgE and related diseases in patients with different ages, genders, months, mixed allergens and grade. Results: Among 20483 subjects, 13149 (64.19%) were clinically positive for at least single allergen. Single allergen positive rate (35.42%), double allergen positive rate (23.96%), triple allergen positive rate (16.04%). The positive rate of sIgE in male was higher than that in female (69.15% and 60. 02% respectively, P<0.01). Allergen detection rate varies with age (P<0.05). The cumulative positive results were 35083, grade 1: 16705 items, 47.61%; grade 2: 8003 items, 22.81%; grade 5: 3840 items, 10.94%. The positive rate of sIgE in March was the highest (82.20%), which was statistically significant compared with other months (P<0.05). The probability of cockroach allergen causing atopic dermatitis/urticaria was 67%, and asthma in just 4%. Conclusion: Our findings reveal that the positive rate of allergens was high in Shenzhen. Dust mite was the main allergen. There were differences in age, gender and month, and the probability of allergic diseases such as atopic dermatitis/urticaria aznd rhinitis/sinusitis is high.