Exons 1-3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome.

BACKGROUND: The pathogenic variants responsible for Birt-Hogg-Dubé syndrome (BHDS) in folliculin (FLCN) gene mostly consist of point mutations. Although large intragenic deletions/duplications have been reported in several case reports, the relationship between large intragenic deletions/duplications and phenotype in BHDS remains unclear. METHODS: We retrospectively identified and reviewed patients with a large intragenic deletion spanning exons 1-3 and analyzed their phenotypic features to compare with those of point mutation carriers in our hospital from January 1, 2017 to August 31, 2022. RESULTS: Twenty unique point mutations (including 4 novel mutations) were detected in 62 patients from 45 families (90%). Exons 1-3 deletion were identified in 8 patients from 5 families (10%) that resided in the same region, Feidong County of Anhui Province, China. Breakpoint analysis indicated that all the deletion breakpoints were flanked by Alu repeats. The prevalence of exons 1-3 deletion carriers in Feidong County was 8.1-times higher than that for BHDS in Anhui Province, suggesting a clustered phenomenon of exons 1-3 deletion. Significantly increased risk of pneumothorax was observed in those with exons 1-3 deletion compared with point mutations (91% vs. 58%, p value 0.047). The risk of renal cancer may be higher in those with exons 1-3 deletion than for those with point mutations (18% vs. 4%, p > 0.05). CONCLUSIONS: Large intragenic deletion of exons 1-3 in FLCN was identified as a local aggregation phenomenon in Feidong County, China, and was associated with a significantly higher risk of pneumothorax compared to those with point mutations.

Smoking related attention alteration in chronic obstructive pulmonary disease-smoking comorbidity.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a respiratory disease that causes a wide range of cognitive impairments. Although COPD-Smoking comorbidity is common, the relationship between smoking and cognitive function in COPD-Smoking comorbidity remains unclear. This study aimed to investigate the effect of smoking on cognitive function like attention in COPD-Smoking patients. METHODS: In this study, we used the Montreal Cognitive Assessment (MoCA) scale and resting-state functional magnetic resonance imaging (fMRI) to explore the effect of smoking on attention in patients with COPD. RESULTS: Behavioral analysis revealed that among patients with COPD the smokers had a shorter course of COPD and showed a worse attention performance than the non-smokers. Resting-state fMRI analysis revealed that among patients with COPD smokers showed lower regional homogeneity (ReHo) value of the fusiform gyrus than non-smokers. Importantly, the ReHo of the fusiform gyrus is positively associated with attention and mediates the effect of smoking on attention in COPD. CONCLUSIONS: In summary, our study provides behavioral and neurobiological evidence supporting the positive effect of smoking on attention in COPD. This may be helpful for understanding and treating COPD and even other diseases comorbid with smoking.

Role of Anti-inflammatory Cytokines IL-35 and IL-37 in Asthma.

Asthma is a chronic airway inflammation that is characterized by intense eosinophil infiltrates, mucus hypersecretion, airway remodeling, and airway hyperresponsiveness. Interleukin (IL)-35 and IL-37 are two cytokines with anti-inflammatory effects found in immune response. Recent findings suggested that expressions of IL-35 and IL-37 are abnormal in asthma. Functional analysis further confirmed the important roles of them in the pathogenesis of asthma. The present study reviewed the updated evidence indicating the roles of IL-35 and IL-37 in asthma. Hopefully, the information obtained may lead to a better understanding of the pathogenesis of the disease.