Chest

Background:Previously healthy firefighters with World Trade Center (WTC) dust exposure developed airway disease. Risk factors for irritant-associated asthma/COPD overlap are poorly defined.Methods:The study included 2,137 WTC-exposed firefighters who received a clinically-indicated bronchodilator pulmonary function test (BD-PFT) between 9/11/2001\u20139/10/2017. A post-BD FEV1 increase of >12% and 200 ml from baseline defined asthma, and post-BD FEV1/FVC ratio<0.7 identified COPD cases. Participants who met both criteria had asthma/COPD overlap. Eosinophil levels were measured on screening blood tests performed shortly after 9/11/2001 and prior to BD-PFT; a subgroup of participants also had serum IgE and 21 cytokines measured (N=215). Marginal Cox regression models for multiple events assessed the associations of eosinophil levels or serum biomarkers with subsequent diagnosis, with age, race, smoking, WTC-exposure, first post-9/11 FEV1/FVC ratio, and BMI included as covariates.Results:BD-PFT diagnosed asthma/COPD overlap in 99 individuals (4.6%), isolated-asthma in 202 (9.5%), and isolated-COPD in 215 (10.1%). Eosinophil concentration 65300 cells/\u3bcl was associated with increased risk of asthma/COPD overlap (HR: 1.85, 95% CI: 1.16\u20132.95), but not with isolated-asthma or isolated-COPD. Serum IL-4 also predicted asthma/COPD overlap (HR: 1.51 per doubling of cytokine concentration, 95% CI: 1.17\u20131.95). Greater IL-21 concentration was associated with both isolated-asthma and isolated-COPD (HR: 1.73, 95% CI: 1.27\u20132.35 and HR: 2.06, 95% CI: 1.31\u20133.23, respectively).Conclusions:In WTC-exposed firefighters, elevated blood eosinophils and IL-4 levels are associated with subsequent asthma/COPD overlap. Disease-specific Th-2 biomarkers present years before diagnosis suggest patient-intrinsic predisposition to irritant-associated asthma/COPD overlap.R01 HL119326/HL/NHLBI NIH HHS/United StatesU01 OH011300/OH/NIOSH CDC HHS/United StatesU01 OH011302/OH/NIOSH CDC HHS/United States2019-12-01T00:00:00Z30028968PMC6289858696

Preventive effects of vitamin E against oxidative damage in aged diabetic rat bladders.

OBJECTIVES: To examine the effects of aging and/or diabetes mellitus on oxidative stress and the protective effect of vitamin E in the bladder. It was proposed that the balance between oxidant and antioxidant species is important regarding the aging process and prevention of diabetic complications. METHODS: Young and aged rats were randomly allotted into six experimental groups: aged control, aged diabetic, aged diabetic and vitamin E-treated, young control, young diabetic, young diabetic and vitamin E-treated. Diabetes was induced by streptozotocin. Vitamin E was administered to the treated groups. Malondialdehyde and reduced glutathione levels were measured in all rat bladders, and histological changes were examined by electron microscopy. RESULTS: We found increased malondialdehyde and decreased glutathione levels in the young and aged diabetic groups compared with the nondiabetic control groups. Elevated malondialdehyde and reduced glutathione levels were observed in the aged compared with the young control groups. There were no significant differences in the malondialdehyde and glutathione levels between young and aged diabetic vitamin E-treated groups compared with the related control groups. Degeneration was greatest in the aged diabetic group. The protective effects of vitamin E were seen in young and aged diabetic groups, especially in the young diabetic group. CONCLUSIONS: Our results suggest that vitamin E supplementation prevents free radical damage in bladders of young and aged diabetic rats

LID - 10.1007/s00345-019-03046-5 [doi]

PURPOSE: Adrenergic and cholinergic pathways play an important role in contraction-relaxation harmony in human bladder. Functional changes in any proteins in these pathways may result in overactive bladder. We aimed to investigate whether single gene polymorphisms affecting adrenergic and cholinergic pathways are associated with OAB syndrome. METHODS: 60 patients with idiopathic OAB and 60 healthy controls were included in the study. A validated OAB-V8 questionnaire was given to all patients. Polymorphisms of ADRB3, ROCK2, and GEF gene were detected by PCR from whole blood samples. Genotypic structures of patients and controls were compared. The relationship between genotypic structures and OAB symptom scores were investigated. RESULTS: We found no significant difference in the genotype and allele frequencies between the patients and controls for all three SNP. While there was no relationship between ADRB3 and GEF gene polymorphisms and OAB scores in OAB patients, the OAB score in heterozygous polymorphic individuals was significantly higher than in homozygous polymorphic individuals in the ROCK2 gene (p = 0.039). CONCLUSION: The polymorphisms of the ADRB3, ROCK2, and GEF genes were present in both OAB group and healthy controls, but were not associated with OAB syndrome

Relation of ADRB3, GEF, ROCK2 gene polymorphisms to clinical findings in overactive bladder.

PURPOSE: Adrenergic and cholinergic pathways play an important role in contraction-relaxation harmony in human bladder. Functional changes in any proteins in these pathways may result in overactive bladder. We aimed to investigate whether single gene polymorphisms affecting adrenergic and cholinergic pathways are associated with OAB syndrome. METHODS: 60 patients with idiopathic OAB and 60 healthy controls were included in the study. A validated OAB-V8 questionnaire was given to all patients. Polymorphisms of ADRB3, ROCK2, and GEF gene were detected by PCR from whole blood samples. Genotypic structures of patients and controls were compared. The relationship between genotypic structures and OAB symptom scores were investigated. RESULTS: We found no significant difference in the genotype and allele frequencies between the patients and controls for all three SNP. While there was no relationship between ADRB3 and GEF gene polymorphisms and OAB scores in OAB patients, the OAB score in heterozygous polymorphic individuals was significantly higher than in homozygous polymorphic individuals in the ROCK2 gene (p = 0.039). CONCLUSION: The polymorphisms of the ADRB3, ROCK2, and GEF genes were present in both OAB group and healthy controls, but were not associated with OAB syndrome