IgG Sensitization to Extracellular Vesicles in Indoor Dust Is Closely Associated With the Prevalence of Non-Eosinophilic Asthma, COPD, and Lung Cancer

Abstract

PurposeRecent experimental evidence shows that extracellular vesicles (EVs) in indoor dust induce neurtrophilic pulmonary inflammation, which is a characteristic pathology in patients with severe asthma and chronic obstructive pulmonary disease (COPD). In addition, COPD is known to be an important risk factor for lung cancer, irrespective of cigarette smoking. Here, we evaluated whether sensitization to indoor dust EVs is a risk for the development of asthma, COPD, or lung cancer.MethodsSerum IgG antibodies against dust EVs were measured in 90 healthy control subjects, 294 asthmatics, 242 COPD patients, and 325 lung cancer patients. Serum anti-dust EV IgG titers were considered high if they exceeded a 95 percentile value of the control subjects. Age-, gender-, and cigarette smoke-adjusted multiple logistic regression analyses were performed to determine odds ratios (ORs) for asthma, COPD, and lung cancer patients vs the control subjects.ResultsIn total, 4.4%, 13.6%, 29.3%, and 54.9% of the control, asthma, COPD, and lung cancer groups, respectively, had high serum anti-dust EV IgG titers. Adjusted multiple logistic regression revealed that sensitization to dust EVs (high serum anti-dust EV IgG titer) was an independent risk factor for asthma (adjusted OR, 3.3; 95% confidence interval [CI], 1.1-10.0), COPD (adjusted OR, 8.0; 95% CI, 2.0-32.5) and lung cancer (adjusted OR, 38.7; 95% CI, 10.4-144.3).ConclusionsIgG sensitization to indoor dust EVs appears to be a major risk for the development of asthma, COPD, and lung cancer.

The impact of bacteria-derived ultrafine dust particles on pulmonary diseases

“…This finding indicates the particularly significant role that EVs in indoor dust play in the development of childhood asthma-associated immune responses 35 . Higher serum anti-dust EV IgG antibody levels were also reported in patients with noneosinophilic asthma, COPD, and lung cancer than in healthy controls 14 . Interestingly, adjusted multiple logistic regression showed that the significant increase in anti-dust EV IgG antibody levels in patients with pulmonary disease compared with those in healthy controls was an independent risk factor for asthma, COPD and lung cancer irrespective of more typically associated factors, such as smoking history, age, and sex 14 .…”

“…Higher serum anti-dust EV IgG antibody levels were also reported in patients with noneosinophilic asthma, COPD, and lung cancer than in healthy controls 14 . Interestingly, adjusted multiple logistic regression showed that the significant increase in anti-dust EV IgG antibody levels in patients with pulmonary disease compared with those in healthy controls was an independent risk factor for asthma, COPD and lung cancer irrespective of more typically associated factors, such as smoking history, age, and sex 14 . Altogether, while research on the impact of bacterial EVs in indoor dust on pulmonary disease is in its early stages, preliminary findings indicate that bacterial EVs pose a serious risk in terms of asthma, COPD, and lung cancer incidence.…”

“…In addition, many COPD and lung cancer patients have no history of cigarette smoking 13 . Interestingly, the relationship between serum anti-dust extracellular vesicle (EV) IgG levels and the risk of asthma, COPD, and lung cancer is stronger than that for cigarette smoking 14 . Pulmonary diseases are a result of chronic inflammation induced by immune dysfunction stemming from the presence of genes conferring susceptibility and environmental factors, including chemical substances and biological factors.…”

“…Moreover, indoor dust, which contains many components of bacteria, has been associated with both Th1 and Th17 responses, which induce neutrophilic pulmonary inflammation 35,56 . As bacteriaderived EVs can affect distal host cell sites 14 , these vesicles might have significant effects throughout the body. These results suggest that the pathogenicity of bacterial EVs is dependent on the substances contained in the EVs.…”

Extracellular Vesicles, a Key Mediator to Link Environmental Microbiota to Airway Immunity

“…Pseudomonas aeruginosa often contributes to lung diseases such as cystic fibrosis, and its EVs increase pulmonary inflammation through Toll-like receptor (TLR)2 and TLR4 pathways 67. Moreover, indoor dust, which contains many components of bacteria, has been associated with both Th1 and Th17 responses, which induce neutrophilic pulmonary inflammation 6869. As bacteria-derived EVs can affect distal host cell sites,70 these vesicles might play significant roles throughout the body.…”