Cobalt exposure via skin alters lung immune cells and enhances pulmonary responses to cobalt in mice.

Cobalt has been associated with allergic contact dermatitis and occupational asthma. However, the link between skin exposure and lung responses to cobalt is currently unknown. We investigated the effect of prior dermal sensitization to cobalt on pulmonary physiological and immunological responses after subsequent challenge with cobalt via the airways. BALB/c mice received epicutaneous applications (25 µL/ear) with 5% CoCl2*6H2O (Co) or the vehicle (Veh) dimethyl sulfoxide (DMSO) twice; they then received oropharyngeal challenges with 0.05% CoCl2*6H2O or saline five times, thereby obtaining four groups: Veh/Veh, Co/Veh, Veh/Co, and Co/Co. To detect early respiratory responses noninvasively, we performed sequential in vivo microcomputed tomography (µCT). One day after the last challenge, we assessed airway hyperreactivity (AHR) to methacholine, inflammation in bronchoalveolar lavage (BAL), innate lymphoid cells (ILCs) and dendritic cells (DCs) in the lungs, and serum IgE. Compared with the Veh/Veh group, the Co/Co group showed increased µCT-derived lung response, increased AHR to methacholine, mixed neutrophilic and eosinophilic inflammation, elevated monocyte chemoattractant protein-1 (MCP-1), and elevated keratinocyte chemoattractant (KC) in BAL. Flow cytometry in the Co/Co group demonstrated increased DC, type 1 and type 2 conventional DC (cDC1/cDC2), monocyte-derived DC, increased ILC group 2, and natural cytotoxicity receptor-ILC group 3. The Veh/Co group showed only increased AHR to methacholine and elevated MCP-1 in BAL, whereas the Co/Veh group showed increased cDC1 and ILC2 in lung. We conclude that dermal sensitization to cobalt may increase the susceptibility of the lungs to inhaling cobalt. Mechanistically, this enhanced susceptibility involves changes in pulmonary DCs and ILCs.

Occupational Asthma Caused by Low-Molecular-Weight Chemicals Associated With Contact Dermatitis: A Retrospective Study.

BACKGROUND: Occupational asthma (OA) may have different etiologies, but it is not clear whether the etiologic agents influence the clinical presentation, especially the co-occurrence of skin lesions. OBJECTIVE: To determine the impact of different asthmagens on the characteristics of OA, with a focus on the occurrence of prior or concomitant skin disorders. METHODS: In a retrospective analysis of patients who visited the Occupational and Environmental Disease Clinic of a tertiary referral hospital from 2009 to 2019, we classified patients into definite, probable, or possible OA according to prespecified diagnostic guidelines. In multivariate logistic regression with sensitivity analysis, we examined the relation of high- and low-molecular-weight (HMW and LMW) agents with the clinical presentation. RESULTS: Of 209 cases of OA, 66 were caused by HMW agents and 143 by LMW agents. Patients with OA exposed to LMW agents had higher odds of having (had) allergic contact dermatitis (odds ratio, 5.45 [1.80-23.70]; P < .01), compared with patients exposed to HMW agents. Conversely, HMW agents were associated with higher odds of rhinitis symptoms (odds ratio of LMW/HMW, 0.33 [0.17-0.63]; P < .001) and high total IgE (odds ratio of LMW/HMW, 0.35 [0.17-0.70]; P < .01). Risk factors for having coexisting contact dermatitis included construction work, hairdressing, and exposure to metals or epoxy resins. CONCLUSIONS: Among patients with OA, exposure to specific LMW agents was associated with a high frequency of contact dermatitis. Different types of asthmagens within HMW or LMW agents appear to determine the phenotype and comorbidity of OA.

Skin Exposure Contributes to Chemical-Induced Asthma: What is the Evidence? A Systematic Review of Animal Models.

It is generally assumed that allergic asthma originates primarily through sensitization via the respiratory mucosa, but emerging clinical observations and experimental studies indicate that skin exposure to low molecular weight (LMW) agents, i.e. "chemicals," may lead to systemic sensitization and subsequently develop asthma when the chemical is inhaled. This review aims to evaluate the accumulating experimental evidence that adverse respiratory responses can be elicited upon inhalation of an LMW chemical sensitizer after previous sensitization by dermal exposure. We systematically searched the PubMed and Embase databases up to April 15, 2017, and conducted forward and backward reference tracking. Animal studies involving both skin and airway exposure to LMW agents were included. We extracted 6 indicators of "selective airway hyper-responsiveness" (SAHR)-i.e. respiratory responses that only occurred in previously sensitized animals-and synthesized the evidence level for each indicator into strong, moderate or limited strength. The summarized evidence weight for each chemical agent was graded into high, middle, low or "not possible to assess." We identified 144 relevant animal studies. These studies involved 29 LMW agents, with 107 (74%) studies investigating the occurrence of SAHR. Indicators of SAHR included physiological, cytological/histological and immunological responses in bronchoalveolar lavage, lung tissue and airway-draining lymph nodes. Evidence for skin exposure-induced SAHR was present for 22 agents; for 7 agents the evidence for SAHR was inconclusive, but could not be excluded. The ability of a chemical to cause sensitization via skin exposure should be regarded as constituting a risk of adverse respiratory reactions.

Lifetime exposure to particulate air pollutants is negatively associated with lung function in non-asthmatic children.

BACKGROUND: Pulmonary function is known to be affected by acute and subacute exposure to ambient air pollution. However, the impacts of lifetime exposure to air pollution on the pulmonary function of children have been inconsistent. The present study investigated the impact of lifetime residential exposure to intermediate levels of air pollution on the pulmonary function of schoolchildren. METHODS: In 2011, a survey of children aged 6-15 years was conducted in 44 schools in Taiwan. Atopic history, residential history, and environmental factors were recorded. Spirograms were obtained from a random sample of children without asthma. A total of 535 girls and 481 boys without a history of asthma were enrolled. Lifetime residential exposure to air pollutants, including particulate matter with an aerodynamic diameter less than 10 µm (PM10), ozone (O3), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO), was estimated using the kriging method, based on monitored data from the Taiwan Environmental Protection Administration. Multiple linear regression was used to analyze the association between lifetime air pollution exposure and pulmonary function, after adjustment for potential confounders and recent exposure. RESULTS: After adjustment for 7-day average air pollutant levels, a 10 µg/m3 increase in PM10 was related to reductions in the forced expiratory volume in 1 s (-2.00%; 95% confidence interval [CI] -3.09% to -0.90%), forced vital capacity (-1.86%; CI: -2.96% to -0.75%), and maximal midexpiratory flow (-2.28%; CI: -4.04% to -0.51%). These associations were independent of the other pollutants. CONCLUSION: Lifetime exposure to 25-85 µg/m3 of PM10 has negative impacts on the pulmonary function of children.

Effects of long-term exposure to CO and PM2.5 on microalbuminuria in type 2 diabetes.

OBJECTIVE: No study has examined the effects of air pollutants on albuminuria in type 2 diabetes. Therefore, the present study investigated this association. METHODS: This follow-up study enrolled 812 patients with type 2 diabetes between 2003 and 2012. The urinary albumin-to-creatinine ratio (ACR) was recorded annually. Exposure to the air pollutants CO, NO2, O3, SO2, and PM2.5 was interpolated from 72 air-quality monitoring stations to residences by using the kriging method. The association between air pollutants and ACR increase was assessed using mixed-effect model with random intercepts for 36 clinics. RESULTS: The study objects (mean age: 55.4 years) were followed for 3 or more years (average period: 5.4 years). ACR increase was found to be positively associated with the male sex, baseline hemoglobin A1c, and exposure to CO and PM2.5, and negatively associated with waist circumference through multiple linear regression. Annually urine albumin/creatinine ratio increase was estimated by the final model, Patients exposed to higher levels of CO (e.g., third quartile, 1025 ppb) and lower levels of CO (e.g., first quartile, 850 ppb) had an annual ACR increase of 3.73 and 3.54 mg/g, respectively. Patients exposed to higher levels of PM2.5 (e.g., third quartile, 38.8 µg/M3) and lower levels of PM2.5 (e.g., first quartile, 27.7 µg/M3) had an annual ACR increase of 3.96 and 3.17 mg/g, respectively. CONCLUSIONS: Exposure to high CO and PM2.5 levels increased albuminuria in type 2 diabetes.

Tumor size matters differently in pulmonary adenocarcinoma and squamous cell carcinoma.

Little about primary tumor size and nodal/distant metastases among different cell types in non-small cell lung cancer (NSCLC) was discussed. This study aimed to investigate distinct associations between tumor size and nodal/distant metastases in pulmonary adenocarcinoma and squamous cell carcinoma. The study also aimed to clarify the cutoff size relating to a higher likelihood of metastases. We retrospectively evaluated 932 NSCLC patients over a 3-year period and focused on cases with primary tumors less than 4.0 cm in size. Our data showed that 2.5 cm was the critical cutoff size regarding increased nodal/distant metastases in adenocarcinoma (p<0.001), but not in squamous cell carcinoma (p>0.05). In addition, the incidence of nodal/distant metastases reached a plateau of more than 80% in adenocarcinoma when the tumor size exceeded 2.5 cm. In contrast, there was no such correlation observed in squamous cell carcinoma. This study showed that tumor size mattered differently in pulmonary adenocarcinoma and squamous cell carcinoma.