Assessment of wood smoke induced pulmonary toxicity in normal- and chronic bronchitis-like bronchial and alveolar lung mucosa models at air-liquid interface.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has the highest increased risk due to household air pollution arising from biomass fuel burning. However, knowledge on COPD patho-mechanisms is mainly limited to tobacco smoke exposure. In this study, a repeated direct wood smoke (WS) exposure was performed using normal- (bro-ALI) and chronic bronchitis-like bronchial (bro-ALI-CB), and alveolar (alv-ALI) lung mucosa models at air-liquid interface (ALI) to assess broad toxicological end points. METHODS: The bro-ALI and bro-ALI-CB models were developed using human primary bronchial epithelial cells and the alv-ALI model was developed using a representative type-II pneumocyte cell line. The lung models were exposed to WS (10 min/exposure; 5-exposures over 3-days; n = 6-7 independent experiments). Sham exposed samples served as control. WS composition was analyzed following passive sampling. Cytotoxicity, total cellular reactive oxygen species (ROS) and stress responsive NFkB were assessed by flow cytometry. WS exposure induced changes in gene expression were evaluated by RNA-seq (p ≤ 0.01) followed by pathway enrichment analysis. Secreted levels of proinflammatory cytokines were assessed in the basal media. Non-parametric statistical analysis was performed. RESULTS: 147 unique compounds were annotated in WS of which 42 compounds have inhalation toxicity (9 very high). WS exposure resulted in significantly increased ROS in bro-ALI (11.2%) and bro-ALI-CB (25.7%) along with correspondingly increased NFkB levels (bro-ALI: 35.6%; bro-ALI-CB: 18.1%). A total of 1262 (817-up and 445-down), 329 (141-up and 188-down), and 102 (33-up and 69-down) genes were differentially regulated in the WS-exposed bro-ALI, bro-ALI-CB, and alv-ALI models respectively. The enriched pathways included the terms acute phase response, mitochondrial dysfunction, inflammation, oxidative stress, NFkB, ROS, xenobiotic metabolism of AHR, and chronic respiratory disorder. The enrichment of the 'cilium' related genes was predominant in the WS-exposed bro-ALI (180-up and 7-down). The pathways primary ciliary dyskinesia, ciliopathy, and ciliary movement were enriched in both WS-exposed bro-ALI and bro-ALI-CB. Interleukin-6 and tumor necrosis factor-α were reduced (p < 0.05) in WS-exposed bro-ALI and bro-ALI-CB. CONCLUSION: Findings of this study indicate differential response to WS-exposure in different lung regions and in chronic bronchitis, a condition commonly associated with COPD. Further, the data suggests ciliopathy as a candidate pathway in relation to WS-exposure.

Chronic airflow obstruction attributable to poverty in the multinational Burden of Obstructive Lung Disease (BOLD) study.

Poverty is strongly associated with all-cause and chronic obstructive pulmonary disease (COPD) mortality. Less is known about the contribution of poverty to spirometrically defined chronic airflow obstruction (CAO)-a key characteristic of COPD. Using cross-sectional data from an asset-based questionnaire to define poverty in 21 sites of the Burden of Obstructive Lung Disease study, we estimated the risk of CAO attributable to poverty. Up to 6% of the population over 40 years had CAO attributable to poverty. Understanding the relationship between poverty and CAO might suggest ways to improve lung health, especially in low-income and middle-income countries.

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. METHODS: We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. RESULTS: Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19-1.94), wheeze (OR 1.37, 95% CI 1.16-1.63) and dyspnoea (OR 1.83, 95% CI 1.53-2.20), but not lower FVC (ß=0.02 L, 95% CI -0.02-0.06 L) or lower FEV1/FVC (ß=0.04%, 95% CI -0.49-0.58%). Some findings differed by sex and gross national income. CONCLUSION: At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.

Allergic sensitization to foods in India and other Low-Middle-income countries.

Food allergy is an important cause of morbidity, significantly affecting the quality of life of the sufferer. Most food allergy research has been undertaken in high-income countries. Here, we summarize literature regarding food allergy in India and other low-middle-income countries (LMIC). We provide summaries of self-reported adverse food reactions and food sensitization in these regions by reviewing published community-based studies of prevalence, burden, and risk factors. We identified 2 community-based studies of food allergy prevalence in Karnataka, India, which estimate that food allergy affects just 0.14% of children and 1.2% of adults. The overall prevalence of allergic sensitization to 'any' food was 26.5% in adults and 19.1% in children by serum-specific IgE; but only 4.48% in children by skin prick test. We identified a further 28 studies in other LMICs, mainly from China but also Turkey, South Africa, Ghana, Mexico, Brazil, Thailand, Philippines, and Korea. The overall prevalence of allergic sensitization to 'any' food ranged from 0.11% to 16.8% in children using serum-specific IgE and 0.14% to 9.6% in children by skin prick test. The questionnaires and skin prick testing materials used and number of allergens tested varied significantly between studies. Other than Karnataka, there is no information on prevalence of food sensitization and probable food allergy in the community in India. Similar lack of information is noted among the majority of the 136 LMICs. Where community-based studies have been undertaken, there is wide variation in the prevalence and patterns of food sensitization across different LMICs, at least partly due to variations in study methodology. International collaboration is required in order to formally assess food allergy prevalence and burden across representative samples from multiple LMICs.

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.

Allergic diseases in India - Prevalence, risk factors and current challenges.

Epidemiological studies have shown a rise in the prevalence of allergic diseases in India during the last two decades. However, recent evidence from the Global Asthma Network study has observed a decrease in allergic rhinitis, asthma and atopic dermatitis in children. Still, with a population over 1.3 billion, there is a huge burden of allergic rhinitis, asthma and atopic dermatitis, and this is compounded by an unmet demand for trained allergy specialists and poor health service framework. There is wide variation in the prevalence of allergic diseases between different geographical locations in India, and the reasons are unclear at present. This may at least in part be attributable to considerable heterogeneity in aero-biology, weather, air pollution levels, cultural and religious factors, diet, socioeconomic strata and literacy. At present, factors enhancing risks and those protecting from development of atopy and allergic diseases have not been well delineated, although there is some evidence for the influence of genetic factors alongside cultural and environmental variables such as diet, exposure to tobacco smoke and air pollution and residence in urban areas. This narrative review provides an overview of data from India regarding epidemiology, risk factors and genetics and highlights gaps in evidence as well as areas for future research.

Practical management of suspected hypersensitivity reactions to anti-tuberculosis drugs.

Tuberculosis (TB) is the commonest cause of death by a single infectious agent globally and ranks amongst the top ten causes of global mortality. The incidence of TB is highest in Low-Middle Income countries (LMICs). Prompt institution of, and compliance with, therapy are cornerstones for a favourable outcome in TB and to mitigate the risk of multiple drug resistant (MDR)-TB, which is challenging to treat. There is some evidence that adverse drug reactions (ADRs) and hypersensitivity reactions (HSRs) to anti-TB drugs occur in over 60% and 3%-4% of patients respectively. Both ADRs and HSRs represent significant barriers to treatment adherence and are recognised risk factors for MDR-TB. HSRs to anti-TB drugs are usually cutaneous and benign, occur within few weeks after commencement of therapy and are likely to be T-cell mediated. Severe and systemic T-cell mediated HSRs and IgE mediated anaphylaxis to anti-TB drugs are relatively rare, but important to recognise and treat promptly. T-cell-mediated HSRs are more frequent amongst patients with co-existing HIV infection. Some patients develop multiple sensitisation to anti-TB drugs. Whilst skin tests, patch tests and in vitro diagnostics have been used in the investigation of HSRs to anti-TB drugs, their predictive value is not established, they are onerous, require specialist input of an allergist and are resource-dependent. This is compounded by the global, unmet demand for allergy specialists, particularly in low-income countries (LICs)/LMICs and now the challenging circumstances of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This narrative review provides a critical analysis of the limited published evidence on this topic and proposes a cautious and pragmatic approach to optimise and standardise the management of HSRs to anti-TB drugs. This includes clinical risk stratification and a dual strategy involving sequential re-challenge and rapid drug desensitisation. Furthermore, a concerted international effort is needed to generate real-time data on ADRs, HSRs, safety and clinical outcomes of these interventions.

Chronic airflow obstruction and ambient particulate air pollution.

Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised.

Pediatric allergic diseases in the Indian subcontinent-Epidemiology, risk factors and current challenges.

INTRODUCTION: India is low-middle-income country (LMIC) with a population of 1.3bn, comprising about 20% of the global population. While the high-income Western countries faced an "allergy epidemic" during the last three decades, there has been a gradual rise in prevalence of allergic diseases in India. METHODS: Narrative review. RESULTS AND DISCUSSION: Allergic diseases occur as a consequence of a complex interplay between genetic and environmental factors. There are multiple contrasting determinants that are important to consider in India including high levels of air pollution, in particular PM2.5 due to burning of fossil fuels and biomass fuels, diverse aero-biology, tropical climate, cultural and social diversity, religious beliefs/myths, linguistic diversity, literacy level, breastfeeding and weaning, diet (large proportion vegetarian), and high incidence rates of TB, HIV, malaria, filariasis, parasitic infestations, and others, that not only shape the immune system early in life, but also impact on biomarkers relevant to allergic diseases. India has a relatively weak and heterogeneous healthcare framework, and allergology has not yet been recognized as an independent specialty. There are very few post-graduate training programs, and allergic diseases are managed by primary care physicians, organ-based specialists, and general pediatricians. Adrenaline auto-injectors are not available, there is patient unaffordability for inhalers, nasal sprays, and biologics, and this is compounded by poor compliance leading to 40%-50% of asthmatic children having uncontrolled disease and high rates of oral corticosteroid use. Standardized allergen extracts are not available for skin tests and desensitization. This article provides a critical analysis of pediatric allergic diseases in India.

Unveiling Silent Consequences: Impact of Pulmonary Tuberculosis on Lung Health and Functional Wellbeing after Treatment.

Background: Pulmonary tuberculosis (TB) remains a major public health issue in India, with high incidence and mortality. The current literature on post-TB sequelae functional defects focuses heavily on spirometry, with conflicting obstruction vs. restriction data, lacks advanced statistical analysis, and has insufficient data on diffusion limitation and functional impairment. Objective: This study aimed to thoroughly evaluate post-tubercular sequelae after treatment, assessing chest radiology, spirometry, diffusing capacity, and exercise capacity. Methods: A total of 85 patients were studied at a university teaching hospital in Mysuru. The data collected included characteristics, comorbidities, smoking history, and respiratory symptoms. The investigations included spirometry, DLCO, chest X-rays with scoring, and 6MWT. Results: Of the patients, 70% had abnormal X-rays post-treatment, correlating with reduced lung function. Additionally, 70% had impaired spirometry with obstructive/restrictive patterns, and 62.2% had reduced DLCO, with females at higher risk. Smoking increased the risk of sequelae. Conclusions: Most patients had residual radiological/lung function abnormalities post-treatment. Advanced analyses provide insights into obstructive vs. restrictive defects. Ongoing research should explore pathogenetic mechanisms and therapeutic modalities to minimize long-term post-TB disability.

Exploring the potential of telemedicine for improved primary healthcare in India: a comprehensive review.

Telemedicine is a promising solution to the challenges of delivering equitable and quality primary healthcare, especially in LMICs. This review evaluated peer-reviewed literature on telehealth interventions in Indian primary care published from Jan 1, 2011 to Dec 31, 2021, from PubMed, Scopus, TRIP, Google Scholar, Indian Kanoon, and Cochrane database The majority of Indian studies focus on key health issues like maternal and child health, mental health, diabetes, infectious diseases, and hypertension, mainly through patient education, monitoring, and diagnostics. Yet, there's a lack of research on telemedicine's cost-effectiveness, communication among providers, and the role of leadership in its quality and accessibility. The current research has gaps, including small sample sizes and inconsistent methodologies, which hamper the evaluation of telemedicine's effectiveness. India's varied healthcare landscape, technological limitations, and social factors further challenge telemedicine's adoption. Despite regulatory efforts, issues like the digital divide and data privacy persist. Addressing these challenges with a context-aware, technologically driven approach is crucial for enhancing healthcare through telemedicine in India.

Effects of Ambient Air Pollutants on Hospital Admissions among Children Due to Asthma and Wheezing-Associated Lower Respiratory Infections in Mysore, India: A Time Series Study.

Air pollutants are known to trigger asthma and wheezing-associated lower respiratory infections in children, but evidence regarding their effect on hospital admissions in India is limited. We conducted a time-series study over a period of five years to assess the role of ambient air pollutants in daily asthma-related hospital admissions in children in Mysore, India. Daily asthma and wheeze (associated with lower respiratory infections) admissions were modelled using a generalised additive model (GAM) to examine the non-linear effects and generalised linear models (GLM) for linear effects, if any. Models were adjusted by day of the week and lag days, with smooth terms for time, maximum temperature, and relative humidity, and they were stratified by sex and age group. Of the 362 children admitted, more than 50% were boys, and the mean age was 5.34 years (±4.66). The GAMs showed non-linear associations between NO2, PM2.5, and NH3. For example, a 10 µgm-3 (or 10%) increase in NO2 increased admissions by 2.42. These non-linear effects were more pronounced in boys. A linear effect was detected for PM10 with a relative risk (95% CI) of 1.028, 1.013, and 1.043 with admission. Further research is needed to explore whether these findings can be replicated in different cities in India. Air pollution needs to be controlled, and policies that focus on lower cut-off levels for vulnerable populations are necessary.

The Use of High-Flow Nasal Cannula and Non-Invasive Mechanical Ventilation in the Management of COVID-19 Patients: A Prospective Study.

High-flow nasal cannula (HFNC) and ventilator-delivered non-invasive mechanical ventilation (NIV) were used to treat acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia, especially in low- and middle-income countries (LMICs), due to lack of ventilators and manpower resources despite the paucity of data regarding their efficacy. This prospective study aimed to analyse the efficacy of HFNC versus NIV in the management of COVID-19 ARDS. A total of 88 RT-PCR-confirmed COVID-19 patients with moderate ARDS were recruited. Linear regression and generalized estimating equations (GEEs) were used for trends in vital parameters over time. A total of 37 patients were on HFNC, and 51 were on NIV. Patients in the HFNC group stayed slightly but not significantly longer in the ICU as compared to their NIV counterparts (HFNC vs. NIV: 8.00 (4.0-12.0) days vs. 7.00 (2.0-12.0) days; p = 0.055). Intubation rates, complications, and mortality were similar in both groups. The switch to HFNC from NIV was 5.8%, while 37.8% required a switch to NIV from HFNC. The resolution of respiratory alkalosis was better with NIV. We conclude that in patients with COVID-19 pneumonia with moderate ARDS, the duration of treatment in the ICU, intubation rate, and mortality did not differ significantly with the use of HFNC or NIV for respiratory support.

The Validity of the ROX Index and APACHE II in Predicting Early, Late, and Non-Responses to Non-Invasive Ventilation in Patients with COVID-19 in a Low-Resource Setting.

The use of the Ratio of Oxygen Saturation (ROX) index to predict the success of high-flow nasal oxygenation (HFNO) is well established. The ROX can also predict the need for intubation, mortality, and is easier to calculate compared with APACHE II. In this prospective study, the primary aim is to compare the ROX (easily administered in resource limited setting) to APACHE II for clinically relevant outcomes such as mortality and the need for intubation. Our secondary aim was to identify thresholds for the ROX index in predicting outcomes such as the length of ICU stay and failure of non-invasive respiratory support therapies and to assess the effectiveness of using the ROX (day 1 at admission, day 2, and day 3) versus Acute physiology and chronic health evaluation (APACHE) II scores (at admission) in patients with Coronavirus Disease 2019 (COVID-19) pneumonia and Acute Respiratory Distress Syndrome (ARDS) to predict early, late, and non-responders. After screening 208 intensive care unit patients, a total of 118 COVID-19 patients were enrolled, who were categorized into early (n = 38), late (n = 34), and non-responders (n = 46). Multinomial logistic regression, receiver operating characteristic (ROC), Multivariate Cox regression, and Kaplan-Meier analysis were conducted. Multinomial logistic regressions between late and early responders and between non- and early responders were associated with reduced risk of treatment failures. ROC analysis for early vs. late responders showed that APACHE II on admission had the largest area under the curve (0.847), followed by the ROX index on admission (0.843). For responders vs. non-responders, we found that the ROX index on admission had a slightly better AUC than APACHE II on admission (0.759 vs. 0.751). A higher ROX index on admission [HR (95% CI): 0.29 (0.13-0.52)] and on day 2 [HR (95% CI): 0.55 (0.34-0.89)] were associated with a reduced risk of treatment failure. The ROX index can be used as an independent predictor of early response and mortality outcomes to HFNO and NIV in COVID-19 pneumonia, especially in low-resource settings, and is non-inferior to APACHE II.

Whole-Genome Sequencing of Mycobacterium tuberculosis Isolates from Diabetic and Non-Diabetic Patients with Pulmonary Tuberculosis.

The association of tuberculosis and type 2 diabetes mellitus has been a recognized re-emerging challenge in management of the convergence of the two epidemics. Though much of the literature has studied this association, there is less knowledge in the field of genetic diversities that might occur in strains infecting tuberculosis patients with and without diabetes. Our study focused on determining the extent of diversity of genotypes of Mycobacterium tuberculosis in both these categories of patients. We subjected 55 M. tuberculosis isolates from patients diagnosed with pulmonary TB with and without type 2 diabetes mellitus to whole-genome sequencing on Illumina Hi Seq platform. The most common lineage identified was lineage 1, the Indo-Oceanic lineage (n = 22%), followed by lineage 4, the Euro-American lineage (n = 18, 33%); lineage 3, the East-African Indian lineage (n = 13, 24%); and lineage 2, the East-Asian lineage (n = 1, 2%). There were no significant differences in the distribution of lineages in both diabetics and non-diabetics in the South Indian population, and further studies involving computational analysis and comparative transcriptomics are needed to provide deeper insights.

Unmasking the Silent Threat: Periodontal Health's Impact on COPD Severity and Hospitalization.

OBJECTIVE: This study investigated the relationship between chronic obstructive pulmonary disease (COPD) and periodontitis, focusing on how periodontal health impacts COPD airflow limitation, exacerbations, and hospitalization. BACKGROUND: Periodontitis, a multifactorial inflammatory disease, is characterized by destruction of tooth-supporting structures, while COPD is a global pulmonary disorder with high mortality. METHODS: A total of 199 COPD patients aged over 40 years underwent lung function tests (spirometry), 6 min walk test, and St George's Respiratory Questionnaire-COPD (SGRQ-C) to assess lung health. Periodontal indices such as probing depth (PD), clinical attachment loss (CAL), and plaque index (PI) were assessed. RESULTS: We found a significant negative correlation between periodontal disease severity and lung function (lower FEV1, FVC, and FEV1/FVC ratio) after adjusting for smoking. Likewise, periodontal parameters (PPD, PI, and CAL) exhibited negative correlations with lung function. These periodontal indices were independently associated with airflow limitation severity, exacerbations frequency, and prior-year hospitalization. Linear regression indicated that each unit increase in PPD, PI, and CAL corresponded to estimated increases in GOLD airflow limitation grading (0.288, 0.718, and 0.193, respectively) and number of exacerbations (0.115, 0.041, and 0.109, respectively). In logistic regression, PPD, PI, and CAL adjusted odds ratios (ORs) were estimated to increase by 1.29 (95%CI: 1.03-1.62), 3.04 (95%CI: 1.28-7.2), and 1.26 (95%CI: 1.06-1.49), respectively, for hospitalization in previous year. CONCLUSION: Periodontitis is associated with COPD airflow limitation, exacerbation, and hospitalization, with PI being the most clinically relevant periodontal factor. Dentists and physicians should monitor and increase awareness among COPD patients to maintain oral hygiene for prevention of periodontal diseases and mitigate its effect on COPD progression.

Association between ADAM33 Single-Nucleotide Polymorphisms and Treatment Response to Inhaled Corticosteroids and a Long-Acting Beta-Agonist in Asthma.

ADAM33 has been linked to airway structural changes in patients with asthma, leading to airway hyperresponsiveness, narrowing, and ultimately poor treatment responsiveness. This study aimed to evaluate the genetic association of ADAM33 SNPs with asthma, disease severity, and treatment responsiveness to ICS+LABA in the South Indian population. In this case-control study (486 controls and 503 cases), we performed genotyping using MassArray for six SNPs of ADAM33, namely rs2280091, rs2787094, rs3918396, rs67044, rs2853209, and rs3918392. We studied the association with asthma and treatment responsiveness to ICS+LABA, using genotype, allele frequency distribution, and haplotype analysis. A significant clinical finding of the study was that certain patients in the disease severity group (moderate and mild) showed poor or no improvement after a three-month follow-up of regular ICS+LABA therapy. Of the studied ADAM33 SNPs, rs2853209 showed an association with asthma. The further analysis of asthma patients according to disease severity suggested an association between moderate disease and the minor allele "T" for rs2853209. The homozygous minor allele of SNP rs2787094 was found to be associated with poorer lung function and the least lung-function improvement after three months of ICS+LABA therapy. The haplotype analysis of six SNPs showed a significant association between the rs2853209 and rs3918396 blocks and asthma. ADAM33 gene polymorphism has clinical relevance in terms of disease association and response to treatment. SNP rs2853209 seemed most relevant to asthma, and SNP rs2787094 could be a genetic marker for predicting response to ICS+LABA therapy in the study population.