Influence of light at night on allergic diseases: a systematic review and meta-analysis.

BACKGROUND: Allergic diseases impose a significant global disease burden, however, the influence of light at night exposure on these diseases in humans has not been comprehensively assessed. We aimed to summarize available evidence considering the association between light at night exposure and major allergic diseases through a systematic review and meta-analysis. METHODS: We completed a search of six databases, two registries, and Google Scholar from inception until December 15, 2023, and included studies that investigated the influence of artificial light at night (ALAN, high vs. low exposure), chronotype (evening vs. morning chronotype), or shift work (night vs. day shift work) on allergic disease outcomes (asthma, allergic rhinitis, and skin allergies). We performed inverse-variance random-effects meta-analyses to examine the association between the exposures (ALAN exposure, chronotype, or shiftwork) and these allergic outcomes. Stratification analyses were conducted by exposure type, disease type, participant age, and geographical location along with sensitivity analyses to assess publication bias. RESULTS: We included 12 publications in our review. We found that exposure to light at night was associated with higher odds of allergic diseases, with the strongest association observed for ALAN exposure (OR: 1.88; 95% CI: 1.04 to 3.39), followed by evening chronotype (OR: 1.35; 95% CI: 0.98 to 1.87) and exposure to night shift work (OR: 1.33; 95% CI: 1.06 to 1.67). When analyses were stratified by disease types, light at night exposure was significantly associated with asthma (OR: 1.62; 95% CI: 1.19 to 2.20), allergic rhinitis (OR: 1.89; 95% CI: 1.60 to 2.24), and skin allergies (OR: 1.11; 95% CI: 1.09 to 1.91). We also found that the association between light at night exposure and allergic diseases was more profound in youth (OR: 1.63; 95% CI: 1.07 to 2.48) than adults (OR: 1.30; 95% CI: 1.03 to 1.63). Additionally, we observed significant geographical variations in the association between light at night exposure and allergic diseases. CONCLUSIONS: Light at night exposure was associated with a higher prevalence of allergic diseases, both in youth and adults. More long-term epidemiological and mechanistic research is required to understand the possible interactions between light at night and allergic diseases.

Long-term effect of asthma on the development of obesity among adults: an international cohort study, ECRHS.

INTRODUCTION: Obesity is a known risk factor for asthma. Although some evidence showed asthma causing obesity in children, the link between asthma and obesity has not been investigated in adults. METHODS: We used data from the European Community Respiratory Health Survey (ECRHS), a cohort study in 11 European countries and Australia in 3 waves between 1990 and 2014, at intervals of approximately 10 years. We considered two study periods: from ECRHS I (t) to ECRHS II (t+1), and from ECRHS II (t) to ECRHS III (t+1). We excluded obese (body mass index≥30 kg/m2) individuals at visit t. The relative risk (RR) of obesity at t+1 associated with asthma at t was estimated by multivariable modified Poisson regression (lag) with repeated measurements. Additionally, we examined the association of atopy and asthma medication on the development of obesity. RESULTS: We included 7576 participants in the period ECRHS I-II (51.5% female, mean (SD) age of 34 (7) years) and 4976 in ECRHS II-III (51.3% female, 42 (8) years). 9% of participants became obese in ECRHS I-II and 15% in ECRHS II-III. The risk of developing obesity was higher among asthmatics than non-asthmatics (RR 1.22, 95% CI 1.07 to 1.38), and particularly higher among non-atopic than atopic (1.47; 1.17 to 1.86 vs 1.04; 0.86 to 1.27), those with longer disease duration (1.32; 1.10 to 1.59 in >20 years vs 1.12; 0.87 to 1.43 in ≤20 years) and those on oral corticosteroids (1.99; 1.26 to 3.15 vs 1.15; 1.03 to 1.28). Physical activity was not a mediator of this association. CONCLUSION: This is the first study showing that adult asthmatics have a higher risk of developing obesity than non-asthmatics, particularly those non-atopic, of longer disease duration or on oral corticosteroids.

Allergic rhinitis in India.

India is the home of nearly 20% of the global population with 1.35 billion people. Of all non-communicable diseases, allergic diseases such as allergic rhinitis (AR) and asthma appear to have increased in India over the past decades. Approximately 22% of adolescents currently suffer from AR in India. However, owing to the lack of adequate epidemiological studies in India, particularly in rural and suburban areas, this number may misrepresent the true burden of this disease. While the risk factors for AR are mainly environmental exposures or genetic factors, several new environmental, social, and behavioural risk factors such as the presence of dumpsters near residences, movement of vehicles near homes, and exposure to artificial light at night have been found to be associated with AR. However, despite international guidelines, the diagnosis and management of AR in India are often suboptimal, for multiple reasons such as the lack of specialized training in allergy and immunology among Indian clinicians, the lack of diagnostic facilities, and the high cost of medications. This review aims at highlighting the current scenario of AR in India and how it differs from the rest of the world. It also highlights the need for developing a strategic approach to enhance the quality of care for allergic diseases by upgrading education and training for healthcare professionals, creating awareness among clinicians and patients, and involving stakeholders and policymakers in making treatments accessible and affordable to patients.

Metabolomics of Respiratory Diseases.

Metabolomics is an expanding field of systems biology that is gaining significant attention in respiratory research. As a unique approach to understanding and diagnosing diseases, metabolomics provides a snapshot of all metabolites present in biological samples such as exhaled breath condensate, bronchoalveolar lavage, plasma, serum, urine, and other specimens that may be obtained from patients with respiratory diseases. In this article, we review the rapidly expanding field of metabolomics in its application to respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), pneumonia, and acute lung injury, along with its more severe form, adult respiratory disease syndrome. We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized occupational and environmental materials. With the latest advances in our understanding of the microbiome, we discuss microbiome-derived metabolites that arise from the gut and lung in asthma and COPD that have mechanistic implications for these diseases. Recent literature has suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe diseases which may be fatal for many patients each year.

Roles of the physical environment in health-related quality of life in patients with chronic obstructive pulmonary disease.

RATIONALE: Many clinical and psychological factors are known to influence the health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD). However, research on whether environmental factors, such as air pollution, noise, temperature, and blue/green spaces also influence HRQL in COPD has not been systematically investigated. OBJECTIVE: To assess the relationship between air pollution, road traffic noise, temperature, and distance to blue/green spaces and respiratory-specific HRQL in COPD. METHODS: We used cross-sectional data from a multicenter study in 407 stable mild-to-very severe COPD patients from Barcelona (Catalonia). Patients answered the COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ). Individual residential exposure to air pollutants (nitrogen dioxide [NO2] and particulate matters of varying aerodynamic diameters [PM2.5, PM10, and PM2.5absorbance]), road traffic noise (Lden), and land surface temperature were estimated using long-term averages from land-use regression models, 24-h noise maps, and land surface temperature maps, respectively. We measured residential distances to blue/green spaces from the Urban Atlas. We used mixed-effect negative binomial (for CAT) and linear (for CCQ) regression models, adjusted for potential confounders, with a random effect by center. RESULTS: Of those patients, 85 % were male and had a mean (SD) age of 69 (9) years, CAT score of 12 (7), CCQ-total score of 1.4 (1.0), and post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57 (18) %predicted. We found that NO2 and PM2.5absorbance were associated with worsened CAT and CCQ-mental scores, e.g., 0.15-unit change in CAT score [regression coefficient (ß) = 0.15; 95 % confidence interval (CI) = 0.03, 0.26] per interquartile range in NO2 [13.7 µg/m3]. Greater distances to blue/green spaces were associated with worsened CCQ-mental scores [0.08; 0.002, 0.15]. CONCLUSIONS: Our study showed that increased air pollution, particularly NO2 and PM2.5absorbance and greater distances to blue/green spaces negatively influence HRQL in COPD patients. These findings have important implications for the WHO promotion to develop healthy cities for our future.

Club cell protein (CC16) in plasma, bronchial brushes, BAL and urine following an inhaled allergen challenge in allergic asthmatics.

BACKGROUND: Club cell protein (CC16) is a pneumoprotein secreted by epithelial club cells. CC16 possesses anti-inflammatory properties and is a potential biomarker for airway epithelial damage. We studied the effect of inhaled allergen on pulmonary and systemic CC16 levels. METHODS: Thirty-four subjects with allergic asthma underwent an inhaled allergen challenge. Bronchoscopy with bronchoalveolar lavage (BAL) and brushings was performed before and 24 h after the challenge. CC16 was quantified in BAL and CC16 positive cells and CC16 mRNA in bronchial brushings. CC16 was measured in plasma and urine before and repeatedly after the challenge. Thirty subjects performed a mannitol inhalation challenge prior to the allergen challenge. RESULTS: Compared to baseline, CC16 in plasma was significantly increased in all subjects 0-1 h after the allergen challenge, while CC16 in BAL was only increased in subjects without a late allergic response. Levels of CC16 in plasma and in the alveolar fraction of BAL correlated significantly after the challenge. There was no increase in urinary levels of CC16 post-challenge. Mannitol responsiveness was greater in subjects with lower baseline levels of CC16 in plasma. CONCLUSIONS: The increase in plasma CC16 following inhaled allergen supports the notion of CC16 as a biomarker of epithelial dysfunction.

Exposure to heavy metals alters the surface topology of alveolar macrophages and induces respiratory dysfunction among Indian metal arc-welders.

BACKGROUND: Despite the available clinico-epidemiological evidence of heavy metal-associated respiratory health hazards among metal arc-welders, experimental confirmation of such an association is lacking. METHODS: In this study, we recruited 15 metal arc-welders and 10 referent workers without direct exposure. We assessed respiratory health through a questionnaire and spirometry; estimated manganese, nickel and cadmium levels in blood, urine and induced sputum; performed differential counts of sputum leucocytes and measured plasma malondialdehyde (MDA). We used atomic force and scanning electron microscopy to assess the physical property of the alveolar macrophages (AMs) obtained from induced sputum and analysed cell surface deposition of heavy metals using energy dispersion X-ray analysis (EDX). Sputum cellular DNA damage was assessed by DNA-laddering assay. RESULTS: There was a higher body burden of manganese and nickel in the metal arc-welders than the referents. Among major spirometric indices, only the forced mid-expiratory flow rates (FEF25-75) were reduced in the welders compared with the referents (63.4 ± 14.7 vs. 89.2 ± 26.7, p < 0.01); this reduction was associated with both heavy metal levels (ß: -41.8, 95% CI: -78.5% to -5.1%) and plasma MDA (-0.37; -0.68 to -0.06). In metal arc-welders, significant physical and morphological changes were observed in AMs through microscopic evaluation while EDX analyses demonstrated higher deposition of heavy metals on the AM cell surface than the referents. We also observed a higher degree of DNA damage in the sputum cells of the exposed workers than the referents. CONCLUSION: Heavy metal exposure-induced adverse respiratory effects among metal arc-welders are mediated through haematological and cytological interactions.

Evaluating the role of leukotriene-modifying drugs in asthma management: Are their benefits 'losing in translation'?

Leukotrienes (LTs) initiate a cascade of reactions that cause bronchoconstriction and inflammation in asthma. LT-modifying drugs have been proved very effective to reduce inflammation and associated exacerbation however despite some illustrious clinical trials the usage of these drugs remains overlooked because the evidence to support their utility in asthma management has been mixed and varied between studies. Although, there are plenty of evidences which suggest that the leukotriene-modifying drugs provide consistent improvement even after just the first oral dose and reduce asthma exacerbations, the beneficial effect of these drugs has remained sparse and widely debated. And these beneficial effects are often overlooked because most of the clinical studies include a mixed population of asthmatics who do not respond to LT-modifiers equally. Therefore, in the present era of personalized medicine, it is important to properly stratify the patients and non-invasive measurements of biomarkers may warrant the possibility to characterize biological/pathological pathway to direct treatment to those who will benefit from it. Endotyping based on individual's leukotriene levels should probably ascertain a subgroup of patients that would clearly benefit from the treatment even though the trial fails to show overall significance. In this article, we have methodically evaluated contemporary literature describing the efficacy of LT-modifying drugs in the management of asthma and highlighted the importance of phenotyping the asthmatics for better treatment outcomes.

Global perspectives of emerging occupational and environmental lung diseases.

PURPOSE OF REVIEW: New technologies continue to be introduced into the workplace and the environment. These novel technologies also bring in new hazards leading to evolving patterns of established occupational and environmental diseases, as well as novel conditions never before encountered. RECENT FINDINGS: Many of these emerging conditions have appeared in media outlets or in the literature as case reports. These sentinel cases often serve as a warning sign for subsequent outbreaks. This review will discuss environmental and occupational lung diseases and exposures from a global perspective. These diseases and exposures include environmental exposure to asbestos and lung diseases, accelerated silicosis in sandblasting jean workers, coal worker's pneumoconiosis in surface coal miners, health effects of indoor air pollution from burning of biomass fuels and exposures to heavy metals and potential health effects from hydraulic fracturing (fracking). Other emerging conditions are also discussed, including smog in developing countries, sand storms in Asia and the Middle East and respiratory illnesses from nanoparticles and man-made fibres. SUMMARY: Clinicians must remain vigilant for potential occupational and environmental exposures, especially when evaluating patients with unusual and unique presentation, so that occupational and environmental risk factors may be identified, and monitoring and preventive measures can be implemented early.

Impact of occupational cadmium exposure on spirometry, sputum leukocyte count, and lung cell DNA damage among Indian goldsmiths.

BACKGROUND: Cadmium is frequently used in manual jewelry industries. Although its toxicity on lung function is well-known, the mechanism is not well-understood. METHODS: Among 26 goldsmiths exposed to cadmium (mean age 35.9 ± 5.0 years) and 17 referent workers without direct exposure (36.6 ± 6.6 years), we measured blood and urinary cadmium concentration and performed spirometry and quantified leukocytes and comet formation in the cells from spontaneously expectorated sputum samples. RESULTS: The goldsmiths had higher cadmium concentration in urine (mean 6.14 ± 1.63 vs. 0.47 ± 0.17 µg/dl) and blood (0.90 ± 0.23 vs. 0.02 ± 0.007 µg/dl) than the referents, which were inversely associated with FEV1 /FVC. Cadmium exposure also resulted in higher neutrophils (%) and lower macrophage (%) prevalence in the sputum and also caused substantial DNA damage in the lung cells among the goldsmiths than the referents (69 vs. 14%). CONCLUSION: Altered lung function among cadmium-exposed goldsmiths was associated with enhanced inflammatory response and increased cellular DNA damage in the lungs.

Occupational cadmium exposure-associated oxidative stress and erythrocyte fragility among jewelry workers in India.

BACKGROUND: Cadmium-induced pulmonary and renal target organ effects are well-established although its association with oxidative stress and associated hematological effects for human toxicity remain understudied. METHODS: In a population of cadmium-exposed male jewelry manufacturing workers (n = 32) and referents without direct exposure (n = 21), all with urinary cadmium quantification, we measured plasma antioxidant enzymes (catalase, superoxide dismutase), lipid peroxidation (malondialdehyde), erythrocyte fragility, and surface irregularity of the erythrocyte membrane. RESULTS: Compared to referents, exposed workers manifested significantly lower plasma antioxidant enzymes, and increased malondialdehyde and erythrocyte fragility (for all, P < 0.01). Consistent with the exposure subcategories, activities of superoxide dismutase and catalase were reduced and lipid peroxidation and erythrocyte fragility were enhanced (P < 0.01 for all) in terms of Cd-effect indicating a strong impact on hematological system and oxidative stress. CONCLUSION: Cd exposure contributes to oxidative stress and related erythrocyte effects thus making the hematological system another end-organ target for chronic Cd toxicity.

Comparison of race-specific and race-neutral GLI spirometric reference equations with an Indian reference equation.

BACKGROUND: Despite the increasing popularity and use of Global Lung Function Initiative (GLI) spirometric reference equations, the appropriateness of the race-specific and race-neutral GLI spirometric reference models among the Indian population has not been systematically investigated. METHODS: In this cross-sectional analysis, we used spirometric measurements of 1123 healthy Indian adults (≥18 years of age). We computed reference values and z-scores for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC from race-specific and race-neutral GLI reference equations as well as from a widely used Indian reference equation. We studied heterogeneity between GLI equations and the Indian equations using Bland-Altman analysis, and the differences between the reference and observed values were compared using the Friedman test. RESULTS: In Bland-Altman analysis, significant heterogeneity in FVC and FEV1 between race-specific and Indian equations was observed (bias: 10.4 % and 14.1 %, respectively), with less bias for FEV1/FVC (3.76 %). The race-neutral equations showed almost similar bias (9.8 %, 13.8 %, and 3.8 % for FVC, FEV1, and FEV1/FVC, respectively). Median differences in race-specific reference values from observed values for FVC and FEV1 were 0.49L and 0.44L, respectively, decreasing slightly with race-neutral equations (0.46L and 0.43L) whereas Indian models showed minimal differences (FVC: 0.10L, FEV1: 0.05L). Z-scores for FVC and FEV1 were significantly different between race-specific and race-neutral GLI equations, and both differed from Indian equations. CONCLUSION: Both race-specific and race-neutral GLI reference equations are significantly different from the Indian equations, which underscores the importance of determining the suitability of global reference models before being used indiscriminately.

Comorbidity Profiling in Rural and Urban Population of West Bengal, India: Report From a Community-Based Primary Healthcare System.

Introduction The burden of non-communicable diseases (NCDs) is fast changing across the world, especially in the context of rapid urbanization, adoption of Western lifestyles, and an aging multi-morbid population. Over the last three decades, India has undergone a significant demographic and socioeconomic transition. For effective targeting of health system resources and services, it is essential to understand how the prevalence of NCDs varies among population groups across India. We set out to understand the distribution of NCDs and co-morbidities in urban and rural West Bengal. Methods As part of a service improvement project, data was collected from four urban and four rural community-based clinics across West Bengal, India. The reason for visiting the healthcare center was recorded as the primary diagnosis and co-morbidities were recorded per the Elixhauser comorbidity scoring criteria. Associations between all the demographic variables and NCDs were studied using the Poisson regression model and multivariate analysis. Demographic profile, co-morbidities, and Elixhauser comorbidity index were expressed as frequency (%), mean (standard deviation, SD), or median (interquartile range, IQR) as appropriate. Results We obtained data from 1244 patients of which 886 (71%) were from urban areas and 358 (29%) were from rural areas. Patients were mostly female (61%) and had a mean (SD) age of 53 (11) years. There was a positive correlation between living in an urban residence and age, body mass index (BMI), hypertension, cardiovascular disease (CVD), and respiratory disease. There was a positive correlation between CVD and age, male sex, living in an urban residence, and hypertension but did not correlate positively with diabetes. BMI positively correlated with living in an urban residence, hypertension, diabetes, and musculoskeletal disorders. We observed a significantly higher prevalence of musculoskeletal (p=0.002) and psychological diseases (p<0.001) in the rural population, while the prevalence of hypertension (p<0.001) and respiratory diseases among the participants living in urban areas was higher (p<0.001). There was no statistically significant difference in the prevalence of diabetes between urban and rural areas (p=0.38). In the multivariable analyses, we observed that increased age, being overweight, and living in urban areas were associated with hypertension (prevalence ratio (PR): 1.40, 1.30, and 1.30, respectively; all p-values <0.05). An interaction between sex and living area was associated with a lower prevalence of musculoskeletal diseases (PR: 0.34; 95%CI: 0.18-0.66), i.e., musculoskeletal diseases were less prevalent in males living in urban areas (p=0.002). Conclusion There is a rise in multimorbidity with changing demographic patterns and a narrowing of the urban-rural gap in disease distribution. More investment is required in risk factor prevention, screening, and treatment, with greater accessibility of healthcare resources for those in rural areas. Further work needs to be done to study the trends and distribution of NCDs in West Bengal to inform healthcare policy.

Upper Airway Alarmin Cytokine Expression in Asthma of Different Severities.

Background: The secretion of alarmin cytokines by epithelial cells, including thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33, initiates inflammatory cascades in asthma. However, alarmin cytokine expression in the upper airways in asthma remains largely unknown. Methods: We recruited 40 participants with asthma into four groups as per the Global Initiative for Asthma (GINA) steps (10 in each group of GINA 1/2, 3, 4, and 5). Cells were derived from nasal, buccal, and throat brushings. Intracellular cytokine expression (TSLP, IL-25, and IL-33) was assessed by flow cytometry in cytokeratin 8+ (Ck8+) epithelial cells immediately following collection. Results: TSLP was significantly increased (p < 0.001) in GINA 5 patients across nasal, buccal, and throat Ck8+ epithelial cells, while IL-25 was elevated in nasal and throat samples (p < 0.003), and IL-33 levels were variable, compared with GINA 1-4 patients. Individual GINA subgroup comparison showed that TSLP levels in nasal samples from GINA 5 patients were significantly (p = 0.03) elevated but did not differ between patients with and without nasal comorbidities. IL-25 and IL-33 (obtained from nasal, buccal, and throat samples) were not significantly different in individual groups. Conclusions: Our study demonstrates for the first time that Ck8+ nasal epithelial cells from GINA 5 asthma patients express elevated levels of TSLP.

Adverse respiratory effects associated with cadmium exposure in small-scale jewellery workshops in India.

BACKGROUND: Cadmium (Cd) is an important metal with both common occupational and environmental sources of exposure. Although it is likely to cause adverse respiratory effects, relevant human data are relatively sparse. METHODS: A cross-sectional study of 133 workers in jewellery workshops using Cd under poor hygienic conditions and 54 referent jewellery sales staffs was performed. We assessed symptoms, performed spirometry, measured urinary Cd levels in all study subjects and quantified airborne total oxidant contents for 35 job areas in which the studied workforce was employed. We tested the association of symptoms with exposure relative to the unexposed referents using logistic regression analysis, and tested the association between urinary Cd levels and lung function using multiple regression analysis, adjusting for demographics, smoking and area-level airborne oxidants. RESULTS: Exposed workers had 10 times higher urinary Cd values than referents (geometric mean 5.8 vs 0.41 µg/dl; p<0.01). Of the exposed subjects, 75% reported respiratory tract symptoms compared with 33% of the referents (OR=3.1, 95% CI 1.4 to 7.3). Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were also lower among the exposed workers than the referents (>600 ml decrement for each, p<0.001). For every 1 µg increase in urinary Cd there was a 34 ml decrement in FVC and a 39 ml decrement in FEV1 (p<0.01), taking into account other covariates including workplace airborne oxidant concentrations. CONCLUSIONS: This cohort of heavily exposed jewellery workers experienced frequent respiratory symptoms and manifested a marked deficit in lung function, demonstrating a strong response to Cd exposure.

A comparative ergonomics postural assessment of potters and sculptors in the unorganized sector in West Bengal, India.

Potters and sculptors perform their work in very awkward postures. The purpose of this study was to analyse these postures. The modified Nordic questionnaire was used to analyse musculoskeletal discomfort. Rapid entire body assessment (REBA) and rapid upper limb assessment (RULA) were used to evaluate the subjects' postures. There were no significant differences between times of discomfort and the group of subjects. However, there were significant differences in discomfort in different body parts. The analysis indicated that various body postures were harmful to the subjects and that there were profound deviations from natural curvature of various body parts due to awkward body postures. Ergonomics intervention was required to improve the quality of life.