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Abstract Background Spirofy™ is India’s first portable, pneumotach flow-sensor-based digital spirometer developed to diagnose asthma and chronic obstructive pulmonary disease (COPD). In this study, we compared the performance of the Spirofy™ device with that of the Vitalograph Alpha Touch™ spirometer in measuring the lung capacities of healthy individuals, asthmatics, and COPD patients. We also assessed the inter-device variability between two Spirofy™ devices. Methods In a randomized, three-way crossover, open-label study, we measured the differences in forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) between the Spirofy™ and Vitalograph Alpha Touch™ spirometers. A proportion of the FEV1/FVC ratio distribution of

BackgroundTo date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.AimTo elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.MethodsThis was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.ResultsOverall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and

Summary: Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Funding: Wellcome Trust.

Abstract Background Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown. Methods Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN). Results Almost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77–2.70), chronic cough (OR = 2.56, 95% CI 2.08–3.15), chronic phlegm (OR = 2.29, 95% CI 1.77–4.05), wheeze (OR = 2.87, 95% CI 2.50–3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11–1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease. Conclusion Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters.

BackgroundChronic respiratory diseases (CRDs) contribute significantly to morbidity and mortality worldwide and in India. Access to nonpharmacological options, such as pulmonary rehabilitation (PR), are, however, limited. Given the difference between need and availability, exploring PR, specifically remotely delivered PR, in a resource-poor setting, will help inform future work. ObjectiveThis study explored the perceptions, experiences, needs, and challenges of patients with CRDs and the potential of and the need for PR from the perspective of patients as well as medical professionals involved in the referral (doctors) and delivery (physiotherapists) of PR. MethodsIn-depth qualitative semistructured interviews were conducted among 20 individuals diagnosed with CRDs and 9 medical professionals. An inductive thematic analysis approach was used as we sought to identify the meanings shared both within and across the 2 participant groups. ResultsThe 20 patients considered lifestyle choices (smoking and drinking), a lack of physical activity, mental stress, and heredity as the triggering factors for their CRDs. All of them equated the disease with breathlessness and a lack of physical strength, consulting multiple doctors about their physical symptoms. The most commonly cited treatment choice was an inhaler. Most of them believed that yoga and exercise are good self-management strategies, and some were performing yoga postures and breathing exercises, as advised by friends or family members or learned from a televised program or YouTube videos. None of them identified with the term “pulmonary rehabilitation,” but many were aware of the exercise component and its benefits. Despite being naive to smartphone technology or having difficulty in reading, most of them were enthusiastic about enrolling in an application-based remotely delivered digital PR program. The 9 medical professionals were, however, reluctant to depend on a PR program delivered entirely online. They recommended that patients with CRDs be supported by their family to use technology, with some time spent with a medical professional during the program. ConclusionsPatients with CRDs in India currently manage their disease with nonguided strategies but are eager to improve and would benefit from a guided PR program to feel better. A home-based PR program, with delivery facilitated by digital solutions, would be welcomed by patients and health care professionals involved in their care, as it would reduce the need for travel, specialist equipment, and setup. However, low digital literacy, low resource availability, and a lack of expertise are of concern to health care professionals. For India, including yoga could be a way of making PR “culturally congruent” and more successful. The digital PR intervention should be flexible to individual patient needs and should be complemented with physical sessions and a feedback mechanism for both practitioners as well as patients for better uptake and adherence.

Background: Total lung capacity (TLC) is the volume of air in the lungs at the end of a maximal inhalation. TLC mainly depends on various factors/predictors such as height, age, gender, and ethnicity, and therefore, population-specific reference equations should be used. Currently, in India, we use the (European committee for coal and steel [ECCS], published in the year 1993) reference equation with no correction factor for TLC. It is recommended that the reference equation should be tested on a sample of local healthy participants, differences between the measured values and the predicted values are determined to see if the reference equation is a suitable/good fit for the population. Aim: The aim of this study was to compare the actual values of TLC from the healthy male and female volunteers from Pune city with the reference values obtained from the ECCS equations in these participants and determine the correction factor/percent differences between the mean values for different age and height groups. Design and Setting: A prospective, cross-sectional study of lung function measurements (TLC) by body plethysmography was carried out in a research center. Methodology: TLC was measured by Jaeger's Body Plethysmograph (model: Master scope) according to the recommendation of the American Thoracic Society's/European Respiratory Society's standards 2005 in a sample of 241 healthy nonsmoking volunteers (150 men and 82 women) aged 20–70 years, living in Pune city of Maharashtra, India. Statistical Analysis: The mean of actual TLC and the reference TLC were plotted against the different age groups and height groups and percentage difference was determined. Multiple linear regression was carried out to find the predictive equations for TLC parameter measured by the body plethysmography. Age, height, and weight were used as the predictors (independent variables) in the multiple regression analysis. Since sex is also a predictor of TLC, separate models were run for men and women. Results: There were statistically significant differences between the measured TLC and the reference TLC obtained from the ECCS equation in both males (5.05 L ± 0.69 vs. 6.3 L ± 0.50) and females (3.69 L ± 0.54 vs. 4.39 L ± 0.36), respectively. Males have higher TLC as compared to females of the same age and height. The mean of actual TLC and the reference TLC was plotted against different age groups and height groups, and percentage difference was determined. The percentage differences ranged from 17% to 21% in males and 13%–17% in females. Conclusion: The ECCS equation is not suitable for Pune population and may lead to misinterpretation of restrictive lung diseases and hyperinflation. A correction factor of 18.5% in males and 15% in females may be used for the ECCS equation for TLC in Pune population.

Background: The Indian traditional medicinal system, Ayurveda, describes several lifestyle practices, processes and medicines as an intervention to treat asthma. Rasayana therapy is one of them and although these treatment modules show improvement in bronchial asthma, their mechanism of action, particularly the effect on DNA methylation, is largely understudied. Objectives: Our study aimed at identifying the contribution of DNA methylation changes in modulating bronchial asthma phenotype upon Ayurveda intervention. Materials and methods: In this study, genome-wide methylation profiling in peripheral blood DNA of healthy controls and bronchial asthmatics before (BT) and after (AT) Ayurveda treatment was performed using array-based profiling of reference-independent methylation status (aPRIMES) coupled to microarray technique. Results: We identified 4820 treatment-associated DNA methylation signatures (TADS) and 11,643 asthma-associated DNA methylation signatures (AADS), differentially methylated [FDR (≤0.1) adjusted p-values] in AT and HC groups respectively, compared to BT group. Neurotrophin TRK receptor signaling pathway was significantly enriched for differentially methylated genes in bronchial asthmatics, compared to AT and HC subjects. Additionally, we identified over 100 differentially methylated immune-related genes located in the promoter/5′-UTR regions of TADS and AADS. Various immediate-early response and immune regulatory genes with functions such as transcription factor activity (FOXD1, FOXD2, GATA6, HOXA3, HOXA5, MZF1, NFATC1, NKX2-2, NKX2-3, RUNX1, KLF11), G-protein coupled receptor activity (CXCR4, PTGER4), G-protein coupled receptor binding (UCN), DNA binding (JARID2, EBF2, SOX9), SNARE binding (CAPN10), transmembrane signaling receptor activity (GP1BB), integrin binding (ITGA6), calcium ion binding (PCDHGA12), actin binding (TRPM7, PANX1, TPM1), receptor tyrosine kinase binding (PIK3R2), receptor activity (GDNF), histone methyltransferase activity (MLL5), and catalytic activity (TSTA3) were found to show consistent methylation status between AT and HC group in microarray data. Conclusions: Our study reports the DNA methylation-regulated genes in bronchial asthmatics showing improvement in symptoms after Ayurveda intervention. DNA methylation regulation in the identified genes and pathways represents the Ayurveda intervention responsive genes and may be further explored as diagnostic, prognostic, and therapeutic biomarkers for bronchial asthma in peripheral blood.

Background: The safety and efficacy of fixed-dose combination (FDC) of glycopyrronium bromide 12.5 μg/formoterol fumarate 12 μg (GB/FF) twice daily as dry powder inhalers (DPIs) compared to glycopyrronium 50 μg monotherapy (GLY) once daily as DPI in subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD) were evaluated. Methods: This was a phase-3, randomized, double-blind, active-controlled, parallel-group, superiority study conducted in India. COPD patients aged ≥40 to ≤65 years, current or ex-smokers with FEV1/FVC

COVID-19 pandemic has been a global health concern since the beginning of 2020. Many individuals suffered and lost their lives, making it a considerable burden on the healthcare systems in their countries. Healthcare professionals worked beyond their limits to cater to the needs of the patients, working against the constraints of a workforce shortage. Many doctors and other allied health professionals also lost their lives. Although the medical and allied health education suffered during the pandemic, it has also provided respiratory therapists (RTs) several opportunities to prove themselves. There was a huge demand for RTs, and they were able to help inpatient management and save lives. RTs were also able to contribute to the capacity building of their juniors and other healthcare professionals. Hands-on work and the use of blended learning strategies during the pandemic proved to be a boon for respiratory therapy education and training. Ongoing updates on innovation, research, and new knowledge generated by the international community enhanced the learning of RTs. RTs became a recognized workforce during the pandemic, and their demand grew substantially. Overall, the COVID-19 pandemic offered the RTs opportunities to grow and evolve. This narrative review highlights the opportunities presented by the COVID-19 pandemic and its impact on the evolution of RT in India.

Background: According to the 2019 Global Burden of Disease (GBD) report, India contributes to an estimated 12.9% of global asthma cases (34.3 million) but a disproportionate 42.3% of all global asthma deaths. Also, asthma causes 4.83 million disability-adjusted life years (DALYs) annually in India, four times more than China, which ranks second. Hypothesis: We hypothesised that this disproportionate increase in asthma deaths and suffering in India could be due to the under-use of inhaled corticosteroids. Methods: Using the estimated number of asthma cases in each state and union territory in India (34.3 million) from the 2019 GBD data, we calculated the expected sales of inhaled corticosteroids (ICS) for asthmatics in India. We assumed that 10% of asthmatics have mild intermitted disease and thus need only 4 units of ICS pMDI per year. The remaining 90% should ideally use 12 units of ICS pMDI or equivalent DPI. We also assumed that 30% of ICS sales in India would be accounted for by the 38 million COPD patients. State-wise actual sales of ICS in India were obtained from IQVIA. Results: The total amount of ICS sales in India for asthma obtained from IQVIA was 26.4 million versus the 384.16 million expected sales, which is only 6.8% of the required estimated sales. Moreover, when we correlated state-wise actual sales of ICS in India versus asthma mortality and DALYs (per 100,000 population), we found a significant negative correlation (R = −0.56; P < 0.001 for asthma deaths and R = −0.61; P < 0.001 for asthma DALYs). Impact and Future Direction: Policy-makers, health care providers, public health researchers, asthma sufferers and the people at large need to take cognizance of our findings and undertake appropriate measures, such as creating awareness and ensuring availability and regular use of ICS by asthmatics in India.

# Introduction Chronic respiratory diseases are the most common causes of morbidity and mortality globally. Pulmonary rehabilitation (PR) is a low-cost, high-impact intervention with patient education and exercise at its core. Although supported by a well-established evidence base, demand greatly exceeds capacity in low- and middle-income countries (LMIC), including limited workforce training opportunities to support PR development and implementation. The International Primary Care Respiratory Group's (IPCRG) Teach the Teacher (TtT) is an established education programme designed to build sustainable local clinical teaching and delivery capacity. # Methods A collaboration between the National Institute for Health and Care Research (NIHR) funded Global RECHARGE Group for PR and IPCRG to deliver a 'Teach the Teacher' (TtT) programme for PR capacity building. Our Tier 1 TtT programme combined educational and PR service development concepts with core clinical content adapted for RECHARGE partners in India (Pune and Delhi), Sri Lanka, Kyrgyzstan and Uganda. Due to the severe acute respiratory syndrome coronavirus-2 (SARS‑CoV‑2) pandemic, the programme was adapted to a digital environment using online platforms such as Zoom video conferencing and Google Classroom. We used an adapted framework to evaluate professional learning and its impact. # Findings Fifteen Tier 1/local leader participants attended a sixteen-hour online programme in September-October 2021. Participants included nurses, physiotherapists, doctors and early career health professionals/researchers. As local leaders in PR, participants created a tiered teaching programme for developing a critical mass of PR expert teachers, contextualised to their local healthcare systems and cultures. Participants also explored how to engage and influence multiple professional groups and stakeholders to support the widespread sustainable implementation of PR. # Conclusions The RECHARGE-IPCRG TtT programme provided a clear education and service development framework to support PR capacity development in LMIC. We address a lack of empirical evidence concerning capacity-building initiatives by being explicit about the programme's learning design, management and evaluation. A whole system perspective to PR allowed consideration of health systems, culture, referral pathways and scalability. Sustainable national PR education programmes will require additional resources and a long-term strategy, potentially aligning with the TtT three-tier cascade model.

Summary: Background: Asthma and chronic obstructive pulmonary disease (COPD) cause a considerable burden of morbidity and mortality in low-income and middle-income countries (LMICs). Access to safe, effective, quality-assured, and affordable essential medicines is variable. We aimed to review the existing literature relating to the availability, cost, and affordability of WHO's essential medicines for asthma and COPD in LMICs. Methods: A systematic review of the literature was done by searching seven databases to identify research articles published between Jan 1, 2010, and June 30, 2022. Studies on named essential medicines for asthma and COPD in LMICs were included and review articles were excluded. Two authors (MS and HT) screened and extracted data independently, and assessed bias using Joanna Briggs Institute appraisal tools. The main outcome measures were availability (WHO target of 80%), cost (compared with median price ratio [MPR]), and affordability (number of days of work of the lowest paid government worker). The study was registered with PROSPERO, CRD42021281069. Findings: Of 4742 studies identified, 29 met the inclusion criteria providing data from 60 LMICs. All studies had a low risk of bias. Six of 58 countries met the 80% availability target for short-acting beta-agonists (SABAs), three of 48 countries for inhaled corticosteroids (ICSs), and zero of four for inhaled corticosteroid–long-acting beta-agonist (ICS–LABA) combination inhalers. Costs were reported by 12 studies: the range of MPRs was 1·1–351 for SABAs, 2·6–340 for ICSs, and 24 for ICS–LABAs in the single study reporting this. Affordability was calculated in ten studies: SABA inhalers typically cost around 1–4 days’ wages, ICSs 2–7 days, and ICS–LABAs at least 6 days. The included studies showed heterogeneity. Interpretation: Essential medicines for treating asthma and COPD were largely unavailable and unaffordable in LMICs. This was particularly true for inhalers containing corticosteroids. Funding: WHO and Wellcome Trust.

Objective The objective of this subanalysis of data from centres across urban areas in India of the Global Asthma Network (GAN) was to study 1) the prevalence of symptoms of asthma in children and adults, 2) the change in prevalence of asthma and its trigger factors since the International Study of Asthma and Allergies in Childhood (ISAAC), and 3) current asthma treatment practice. Methods In this cross-sectional, multicentre, school-based and self-administered questionnaire, responses from children aged 6–7 years and 13–14 years, and their respective parents, were analysed. Results The GAN Phase I study included 20 084 children in the 6–7-year age group, 25 887 children in the 13–14-year age group and 81 296 parents. The prevalence of wheeze in the previous 12 months was 3.16%, 3.63% and 3.30% in the three groups, respectively. In comparison to the ISAAC studies, there was a significant reduction in the prevalence of current wheeze (p

Obstructive airway disease (OAD), which includes COPD and asthma, is the leading cause of morbidity and mortality in India. Long-acting bronchodilators (long-acting β2 agonists (LABAs) and/or long-acting muscarinic antagonists (LAMAs)) and inhaled corticosteroids (ICS) have a vital role in the management of patients with OAD. While symptom burden and exacerbations are common amongst treated patients, poor adherence to inhaler therapy is a frequent challenge. Better treatment options that optimise symptom control, improve quality of life, reduce exacerbation risk and improve adherence are desired. Triple therapy (ICS/LABA/LAMA) is recommended in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2021 guidelines for symptomatic COPD patients on ICS/LABA or LABA/LAMA, and who are at increased risk for frequent or severe exacerbations. Similarly, add-on LAMA is recommended in uncontrolled asthma patients on medium- to high-dose ICS/LABA by the Global Initiative for Asthma (GINA) 2021 guideline. In the real world, high-risk and overlapping phenotypes exist, which necessitate early initiation of triple therapy. We aim to provide an expert review on the use of single-inhaler triple therapy (SITT) for OAD management in global and Indian settings, knowledge from which can be extrapolated for appropriate treatment of Indian patients. The OAD population in India may benefit from early optimisation to SITT characterised by a high burden of exacerbating OAD, nonsmoker COPD and asthma–COPD overlap.

Background: Respiratory disorders are important contributors to disease burden across the world. The aim is to assess the proportionate burden of types of respiratory diseases and their seasonal patterns in India we are performing a field study. The present report describes methodological aspects of a respiratory disease point prevalence survey from India. Methods: A total of 4108 chest physicians were invited. Acceptance was received from 420 sites. Chest physicians were classified according to location of practice one as medical college, district government hospital, private hospital, and private clinics. Qualifications of practicing chest physicians were postgraduate in chest medicine, including Doctorate of Medicine (68.4%), diploma in chest medicine (22.1%), and Postgraduate in Medicine (9.5%). The study questionnaire was designed to record demographic data, comorbidities, risk factors, and respiratory conditions based on ICD-10. Results: A total of 366 sites provided baseline data, and the response rate of recruitment of the study sites was 8.9% in the baseline phase. However, government and private medical colleges, as well as government and private hospitals across India, were part of recruitment of respiratory patients for this survey. Conclusions: It is feasible to conduct a large multisite study to assess respiratory disease burden. Challenges include low response rate and logistic issues.

BackgroundThe Global Burden of Disease data suggest that respiratory diseases contribute to high morbidity in India. However, the factors responsible for high morbidity are not quite clear. Therefore, the Seasonal Waves Of Respiratory Disorders (SWORD) study was planned to estimate the point prevalence due to respiratory diseases in Indian OPD services and its association with risk factors and change in seasons.MethodsIn this point prevalence observational multicenter study conducted during 2017-18, participating physicians recorded information of consecutive patients in response to a questionnaire. The study was conducted on four predetermined days representing transition of Indian seasons i.e., February (winter), May (summer), August (monsoon), and November (autumn).ResultsThe eligible number of patients from across 302 sites in India was 25,177. The mean age of study population was 46.1±18.1 years, 14102(56.0%) were males and 11075(44.0%) females. The common diagnoses were: asthma(29.8%), chronic obstructive pulmonary disease (COPD),15.6%, respiratory tract infections (RTIs),11.3%, and tuberculosis(8.7%). All these conditions showed significant seasonal trends (Asthma 31.4% autumn vs. 26.5% summer, COPD 21.1% winter vs. 8.1% summer, RTIs 13.3% winter vs. 4.3% summer, and tuberculosis 12.5% autumn vs. 4.1% summer, pConclusionsThe SWORD study showed wide seasonal variations in outpatient attendance of patients with common respiratory conditions. Novel risk-factors associated with respiratory diseases were also identified.

Background The aim of this work was to investigate the safety and efficacy of single-inhaler triple therapy with 12.5 μg glycopyrronium (GB)/12 μg formoterol fumarate (FF)/250 μg fluticasone propionate (FP), compared to 50 μg GB co-administered with a fixed dose of 12 μg FF/250 μg FP in subjects with COPD. Methods This was a phase 3, randomised, double-blind, active-control, parallel-group, noninferiority study conducted at 20 sites across India. COPD patients aged ≥40 to ≤75 years, with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)

Abstract Background Metabolic adaptation in immune cells is necessary to modulate immune cell function as it is intricately coupled with intracellular metabolism. We aimed to characterize the metabolic state of human peripheral blood mononuclear cells (PBMCs) after long-term exposure to tobacco smoke in smokers with preserved lung function and COPD subjects. Methods PBMCs were isolated from healthy non-smokers (HNS), healthy smokers (HS) and COPD subjects, cultured and the mitochondrial respiration while utilizing glucose (glycolysis), fatty acids (β-oxidation) or pyruvate (direct Krebs’ cycle substrate) was measured using the XFp Extracellular Flux Analyzer. Plasma levels of inflammatory cytokines IFN-γ, IL-17, TNF-α, IL-5, IL-9 and IFN-α were measured using flow cytometry. RAW264.7 cells were exposed to cigarette smoke condensate (CSC) for 1 h and its effect on cell viability, cellular metabolism and phagocytosis ability were also studied. Patient’s data was analyzed using the Mann Whitney U test, whereas Student’s t test was performed to analyze the in-vitro data. Results PBMCs from COPD subjects showed a significant decrease in extracellular acidification rate (ECAR) while utilizing glucose as compared to HNS (151.9 Vs 215%). Mitochondrial oxygen consumption rate (OCR) on palmitate or pyruvate was also found to be significantly lower in COPD subjects as compared to HS and a strong positive correlation between palmitate OCR in PBMCs and FEV1 (r = 0.74, p

Background: Skeletal muscle dysfunction is well known in chronic obstructive pulmonary disease (COPD). The muscle strength is altered in various muscles variedly. Lower-limb muscle strength is very important for walking distance. Reduced lower-limb strength can affect the physical quality of life. Objectives: The aim of the study was to assess and compare the quadriceps strength in COPD patients and age-matched healthy controls and to study the correlation between lung function parameters and the quadriceps strength in patients with COPD. Methodology: Thirty nonsmoker male patients; thirty nonsmoker female patients with COPD; and sixty age-, BMI-, and gender-matched healthy controls were studied. Quadriceps muscle strength was measured using a quadriceps dynamometer. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEF 25–75, and peak expiratory flow rate were measured using Helios 702 Spirometer. The quadriceps muscle strength between the two groups was compared using the unpaired Student's t-test. Correlations between FVC and FEV1with muscle strength were analyzed using the Pearson's coefficient. Results: The mean unilateral and bilateral quadriceps strength in both male and female COPD patients was significantly lesser than the healthy controls (P < 0.05). There was a significant positive correlation between muscle strength and FVC and muscle strength and FEV1in patients with COPD. Conclusion: The study shows that there is quadriceps weakness in COPD patients, and pulmonary functions have a direct impact on skeletal muscle strength. Identifying those patients who have reduced strength will allow early interventions targeted at improving the quality of life of the patient.

Introduction: Diwali or the festival of lights is the most popular festival celebrated in India when firecrackers are burnt by almost every household for 3 days. Levels of ambient air pollution are reported to be very high during the Diwali festival in India. In this study, we aimed to measure and compare the personal exposure levels to particulate matter

Summary: Background: The association of air pollution with multiple adverse health outcomes is becoming well established, but its negative economic impact is less well appreciated. It is important to elucidate this impact for the states of India. Methods: We estimated exposure to ambient particulate matter pollution, household air pollution, and ambient ozone pollution, and their attributable deaths and disability-adjusted life-years in every state of India as part of the Global Burden of Disease Study (GBD) 2019. We estimated the economic impact of air pollution as the cost of lost output due to premature deaths and morbidity attributable to air pollution for every state of India, using the cost-of-illness method. Findings: 1·67 million (95% uncertainty interval 1·42–1·92) deaths were attributable to air pollution in India in 2019, accounting for 17·8% (15·8–19·5) of the total deaths in the country. The majority of these deaths were from ambient particulate matter pollution (0·98 million [0·77–1·19]) and household air pollution (0·61 million [0·39–0·86]). The death rate due to household air pollution decreased by 64·2% (52·2–74·2) from 1990 to 2019, while that due to ambient particulate matter pollution increased by 115·3% (28·3–344·4) and that due to ambient ozone pollution increased by 139·2% (96·5–195·8). Lost output from premature deaths and morbidity attributable to air pollution accounted for economic losses of US$28·8 billion (21·4–37·4) and $8·0 billion (5·9–10·3), respectively, in India in 2019. This total loss of $36·8 billion (27·4–47·7) was 1·36% of India's gross domestic product (GDP). The economic loss as a proportion of the state GDP varied 3·2 times between the states, ranging from 0·67% (0·47–0·91) to 2·15% (1·60–2·77), and was highest in the low per-capita GDP states of Uttar Pradesh, Bihar, Rajasthan, Madhya Pradesh, and Chhattisgarh. Delhi had the highest per-capita economic loss due to air pollution, followed by Haryana in 2019, with 5·4 times variation across all states. Interpretation: The high burden of death and disease due to air pollution and its associated substantial adverse economic impact from loss of output could impede India's aspiration to be a $5 trillion economy by 2024. Successful reduction of air pollution in India through state-specific strategies would lead to substantial benefits for both the health of the population and the economy. Funding: UN Environment Programme; Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.

Background: Low vital capacity, one of the consequences of restricted lung growth, is a strong predictor of cardiovascular mortality. Vital capacity is lower in the developing world than the developed world, even after adjusting for height, weight and gender. This difference is typically dismissed as ethnic variation, adjusted for by redefining normal. Whether this is a consequence of stunted lung growth, rather than just genetically smaller lungs, has not been investigated in detail. Therefore, we sought to compare factors implicated in both stunting and lung development, particularly in the developing world. Methods: We conducted a manual screen of articles identified through Google Scholar and assessed risk of bias. No language restrictions were applied, so long as there was an associated English abstract. We queried VizHub (Global Burden of Disease Visualization Tool) and Google Dataset search engines for disease burden and genome wide association studies. The scope of the article and the heterogeneity of the outcome measures reported required a narrative review of available evidence. To the extent possible, the review follows PRISMA reporting guidelines. Results: Early life influences operate in synergism with genetic, environmental and nutritional factors to influence lung growth and development in children. Low lung function and stunting have common anthropometric, environmental and nutritional correlates originating during early development. Similar anthropometric correlates shared chronic inflammatory pathways, indicated that the two conditions were analogous. Conclusion: The analogy between poor lung function and stunting is conspicuous in the developing world, with malnutrition at the center of non -achievement of growth potential, susceptibility to infectious diseases and intrauterine programming for metabolic syndrome. This counter the idea of redefining the normal for lung function measurements, since observed inter-ethnic variations are likely a mix of natural genetic differences as well as differences in nurture such that reduced lung function reflects early life adversities.

Summary: Background: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. Methods: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients (≥18 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. Findings: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41–66] vs the European and US registries; p

[This corrects the article DOI: 10.1371/journal.pone.0217289.].

BackgroundBurden, phenotype and risk-factors of lung function defects in successfully treated tuberculosis cases are unclear.MethodsWe performed spirometry with bronchodilators in new drug-sensitive adult (≥18 years) pulmonary tuberculosis cases during the 12 months following successful treatment in India. Airflow obstruction was defined as pre-bronchodilator FEV1/FVCResultsOf the 172 participants included in the analysis, 82 (48%) were female, 22 (13%) had diabetes and 34 (20%) ever-smoked with a median (IQR) exposure of 3.5 (0.2-9.9) pack-years. Median (IQR) age and body-mass index (BMI) at enrollment was 32 (23-39) years and 18.1 (16.0-20.5) kg/m2 respectively. Airflow obstruction was detected in 42 (24%) participants; of whom 9 (21%) responded to short-acting bronchodilators and 25 (56%) had COPD; and was associated with duration of illness prior to treatment (aOR = 1.32 per 30-days, 95%CI 1.04-1.68, p = 0.02). A restrictive spirometry pattern was detected in 89 (52%) participants and was associated with female sex (aOR = 3.73, 95%CI 1.51-9.17, p = 0.004) and diabetes (aOR = 4.06, 95%CI 1.14-14.42, p = 0.03). Higher HbA1c at treatment initiation was associated with greater odds of a restrictive spirometry pattern (aOR = 1.29 per unit higher HbA1c, 95%CI 1.04 to 1.60, p = 0.02).ConclusionWe found a high burden of lung function defects and COPD in tuberculosis cases who successfully completed treatment. Screening for chronic lung diseases following treatment and linkage to respiratory health clinics should be included in the routine management plan of all tuberculosis cases in India, regardless of conventional COPD risk-factors such as older age and smoking.

Summary: Background: Air pollution is a major planetary health risk, with India estimated to have some of the worst levels globally. To inform action at subnational levels in India, we estimated the exposure to air pollution and its impact on deaths, disease burden, and life expectancy in every state of India in 2017. Methods: We estimated exposure to air pollution, including ambient particulate matter pollution, defined as the annual average gridded concentration of PM2.5, and household air pollution, defined as percentage of households using solid cooking fuels and the corresponding exposure to PM2.5, across the states of India using accessible data from multiple sources as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. The states were categorised into three Socio-demographic Index (SDI) levels as calculated by GBD 2017 on the basis of lag-distributed per-capita income, mean education in people aged 15 years or older, and total fertility rate in people younger than 25 years. We estimated deaths and disability-adjusted life-years (DALYs) attributable to air pollution exposure, on the basis of exposure–response relationships from the published literature, as assessed in GBD 2017; the proportion of total global air pollution DALYs in India; and what the life expectancy would have been in each state of India if air pollution levels had been less than the minimum level causing health loss. Findings: The annual population-weighted mean exposure to ambient particulate matter PM2·5 in India was 89·9 μg/m3 (95% uncertainty interval [UI] 67·0–112·0) in 2017. Most states, and 76·8% of the population of India, were exposed to annual population-weighted mean PM2·5 greater than 40 μg/m3, which is the limit recommended by the National Ambient Air Quality Standards in India. Delhi had the highest annual population-weighted mean PM2·5 in 2017, followed by Uttar Pradesh, Bihar, and Haryana in north India, all with mean values greater than 125 μg/m3. The proportion of population using solid fuels in India was 55·5% (54·8–56·2) in 2017, which exceeded 75% in the low SDI states of Bihar, Jharkhand, and Odisha. 1·24 million (1·09–1·39) deaths in India in 2017, which were 12·5% of the total deaths, were attributable to air pollution, including 0·67 million (0·55–0·79) from ambient particulate matter pollution and 0·48 million (0·39–0·58) from household air pollution. Of these deaths attributable to air pollution, 51·4% were in people younger than 70 years. India contributed 18·1% of the global population but had 26·2% of the global air pollution DALYs in 2017. The ambient particulate matter pollution DALY rate was highest in the north Indian states of Uttar Pradesh, Haryana, Delhi, Punjab, and Rajasthan, spread across the three SDI state groups, and the household air pollution DALY rate was highest in the low SDI states of Chhattisgarh, Rajasthan, Madhya Pradesh, and Assam in north and northeast India. We estimated that if the air pollution level in India were less than the minimum causing health loss, the average life expectancy in 2017 would have been higher by 1·7 years (1·6–1·9), with this increase exceeding 2 years in the north Indian states of Rajasthan, Uttar Pradesh, and Haryana. Interpretation: India has disproportionately high mortality and disease burden due to air pollution. This burden is generally highest in the low SDI states of north India. Reducing the substantial avoidable deaths and disease burden from this major environmental risk is dependent on rapid deployment of effective multisectoral policies throughout India that are commensurate with the magnitude of air pollution in each state. Funding: Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.

Summary: Background: India has 18% of the global population and an increasing burden of chronic respiratory diseases. However, a systematic understanding of the distribution of chronic respiratory diseases and their trends over time is not readily available for all of the states of India. Our aim was to report the trends in the burden of chronic respiratory diseases and the heterogeneity in their distribution in all states of India between 1990 and 2016. Methods: Using all accessible data from multiple sources, we estimated the prevalence of major chronic respiratory diseases and the deaths and disability-adjusted life-years (DALYs) caused by them for every state of India from 1990 to 2016 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016. We assessed heterogeneity in the burden of chronic obstructive pulmonary disease (COPD) and asthma across the states of India. The states were categorised into four groups based on their epidemiological transition level (ETL). ETL was defined as the ratio of DALYs from communicable diseases to those from non-communicable diseases and injuries combined, with a low ratio denoting high ETL and vice versa. We also assessed the contribution of risk factors to DALYs due to COPD. We compared the burden of chronic respiratory diseases in India against the global average in GBD 2016. We calculated 95% uncertainty intervals (UIs) for the point estimates. Findings: The contribution of chronic respiratory diseases to the total DALYs in India increased from 4·5% (95% UI 4·0–4·9) in 1990 to 6·4% (5·8–7·0) in 2016. Of the total global DALYs due to chronic respiratory diseases in 2016, 32·0% occurred in India. COPD and asthma were responsible for 75·6% and 20·0% of the chronic respiratory disease DALYs, respectively, in India in 2016. The number of cases of COPD in India increased from 28·1 million (27·0–29·2) in 1990 to 55·3 million (53·1–57·6) in 2016, an increase in prevalence from 3·3% (3·1–3·4) to 4·2% (4·0–4·4). The age-standardised COPD prevalence and DALY rates in 2016 were highest in the less developed low ETL state group. There were 37·9 million (35·7–40·2) cases of asthma in India in 2016, with similar prevalence in the four ETL state groups, but the highest DALY rate was in the low ETL state group. The highest DALY rates for both COPD and asthma in 2016 were in the low ETL states of Rajasthan and Uttar Pradesh. The DALYs per case of COPD and asthma were 1·7 and 2·4 times higher in India than the global average in 2016, respectively; most states had higher rates compared with other locations worldwide at similar levels of Socio-demographic Index. Of the DALYs due to COPD in India in 2016, 53·7% (43·1–65·0) were attributable to air pollution, 25·4% (19·5–31·7) to tobacco use, and 16·5% (14·1–19·2) to occupational risks, making these the leading risk factors for COPD. Interpretation: India has a disproportionately high burden of chronic respiratory diseases. The increasing contribution of these diseases to the overall disease burden across India and the high rate of health loss from them, especially in the less developed low ETL states, highlights the need for focused policy interventions to address this significant cause of disease burden in India. Funding: Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.

Background: Clinical research in India experienced dramatic changes with series of stringent guidelines introduced by regulatory authorities. These guidelines posed significant challenges for the clinical trial industry. Objective: To assess the perceptions and opinion of Indian Investigators about the new regulatory guidelines. Methods: We developed a survey questionnaire on recent regulatory guidelines which was hosted on a web portal. Seventy-three investigators from India participated in the survey. Results: Central registration of Ethics Committees (ECs) was agreed by 90.1% participants, 76.8% participants agreed to compensation of subjects for study related Serious Adverse Events (SAE's). The compulsion to include government sites in clinical trials was not agreed by 49.3% participants while 21.2% agreed to it. Restriction on a number of trials per investigator was agreed by 49.3% of participants while 40.9% disagreed. Participants (50.7%) disagreed to the introduction of audio-video (AV) recording of informed consent, 36.6% agreed and 12.7% were neutral. Discussion: Participants observed that post central registration; ECs have improved systems with adequate member composition, functional Standard Operating Procedures, and timely approvals. Participants agreed that compensation of study related SAE's would assure subject protection and safety. The introduction of AV consenting was strongly debated sighting sociocultural issues in the implementation of the same. Conclusion: Participants endorsed guidelines pertaining to the central registration of ECs, SAE related compensation. Restrictions on a number of trials per investigator and AV consenting were debated ardently. The response of the survey participants who are clinical trial investigators in India showed general acceptance, effectiveness and anticipated compliance to the new regulatory guidelines.

This study aimed to describe real-life microbiological testing of adults hospitalised with community-acquired pneumonia (CAP) and to assess concordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) and 2011 European Respiratory Society (ERS) CAP guidelines. This was a cohort study based on the Global Initiative for Methicillin-resistant Staphylococcus aureus Pneumonia (GLIMP) database, which contains point-prevalence data on adults hospitalised with CAP across 54 countries during 2015. In total, 3702 patients were included. Testing was performed in 3217 patients, and included blood culture (71.1%), sputum culture (61.8%), Legionella urinary antigen test (30.1%), pneumococcal urinary antigen test (30.0%), viral testing (14.9%), acute-phase serology (8.8%), bronchoalveolar lavage culture (8.4%) and pleural fluid culture (3.2%). A pathogen was detected in 1173 (36.5%) patients. Testing attitudes varied significantly according to geography and disease severity. Testing was concordant with IDSA/ATS and ERS guidelines in 16.7% and 23.9% of patients, respectively. IDSA/ATS concordance was higher in Europe than in North America (21.5% versus 9.8%; p

Health and demographic surveillance system (HDSS) is a population-based health and vital event registration system that monitors demographic and health events in a geographically defined population at regular intervals. Human microbiome research in the past decade has been the field of increasingly intense research much due to its demonstrated impact upon various health conditions including human chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Many confounding factors have been revealed to play a role in shaping the microbiome in chronic airway diseases. Asthma and COPD follows a typical pattern of disease progression, which includes stable and exacerbation state in which the microbiota is known to vary. However, many such studies lack extensive and longitudinal sampling with inadequate metadata, which has resulted in the inconsistencies in the observations. HDSS provides such a platform, which can offer a deeper understanding of the role of the microbiome in human health. In this review, we highlight opportunities and limitations in microbiome research with the help of studies conducted on chronic airway diseases like asthma and COPD. In addition, we also emphasize on the benefits of HDSS and future directions in lung microbiome research.

Background: Pulmonary complications of diabetes mellitus (DM) have been poorly characterized. Some authors have reported normal pulmonary functions and even concluded that spirometry is not at all necessary in diabetic patients. Some studies have shown abnormal respiratory parameters in patients of DM. Moreover, the duration of DM and glycemic control have varied impact on the pulmonary functions. Aims and Objectives: The study was undertaken to analyze the pulmonary function parameters in diabetic patients and compare them with age and gender matched healthy subjects. We correlated forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV 1 ) in diabetic patients with duration of the disease and glycosylated hemoglobin (HbA1c). Materials and Methods: Pulmonary function tests (PFTs) were recorded in 60 type 2 diabetic male patients and 60 normal healthy male controls aged 40-60 years by using Helios 702 spirometer. The PFTs recorded were - FVC, FEV 1 , FEV 1 /FVC, FEF 25 , FEF 50 , FEF 75 , FEF 25-75 , FEF 0.2-1.2 , and peak expiratory flow rate (PEFR). HbA1c of all the patients was estimated by ion exchange resin method, which is a very standard method of estimation. PFTs of diabetic patients and controls were compared by applying Student′s unpaired t test. Associations between FVC and FEV 1 and HbA1c and duration of illness in diabetic patients were analyzed by applying Pearson′s coefficient. Results: The PFTs were significantly decreased in diabetic patients compared with the healthy controls except FEV 1 /FVC. There was no correlation found between FVC and FEV 1 and duration of illness as well as HbA1c. Conclusion: DM being a systemic disease, which also affects lungs causing restrictive type of ventilatory changes probably because of glycosylation of connective tissues, reduced pulmonary elastic recoil and inflammatory changes in lungs. We found glycemic levels and duration of disease are probably not the major determinants of lung pathology, which requires further research.

Household air pollution is a leading cause of disability-adjusted life years in Southeast Asia and the third leading cause of disability-adjusted life years globally. There are at least sixty sources of household air pollution, and these vary from country to country. Indoor tobacco smoking, construction material used in building houses, fuel used for cooking, heating and lighting, use of incense and various forms of mosquito repellents, use of pesticides and chemicals used for cleaning at home, and use of artificial fragrances are some of the various sources that contribute to household air pollution. Household air pollution affects all stages of life with multi-systemic health effects, and its effects are evident right from pre-conception to old age. In utero exposure to household air pollutants has been shown to have health effects which resonate over the entire lifetime. Exposures to indoor air pollutants in early childhood also tend to have repercussions throughout life. The respiratory system bears the maximum brunt, but effects on the cardiovascular system, endocrine system, and nervous system are largely underplayed. Household air pollutants have also been implicated in the development of various types of cancers. Identifying household air pollutants and their health implications helps us prepare for various health-related issues. However, the real challenge is adopting changes to reduce the health effects of household air pollution and designing innovative interventions to minimize the risk of further exposure. This review is an attempt to understand the various sources of household air pollution, the effects on health, and strategies to deal with this emergent risk factor of global mortality and morbidity.

Air pollution generated from motor vehicle exhaust has become a major cause for scientific and public concern worldwide over recent years. The rapid and marked increase in the motor vehicle traffic and its associated emissions in urban areas have paralleled a sharp increase in the prevalence of allergic diseases such as asthma and rhinitis. Epidemiological studies have demonstrated a strong association between people living in close proximity to roads with high traffic density and increased allergic symptoms, reduced lung function and increased sensitization to common aeroallergens. Several laboratory-based studies have demonstrated that pollutants emitted from motor vehicles can induce allergic inflammation and increase airway hyperresponsiveness, which may provide an underlying mechanism for the increasing prevalence of allergic diseases. Although the detrimental effects of air pollution on human health have been brought to public attention, it appears that less attention has been given to the potential role of road traffic fumes in the induction of the allergic state. Legislators should consider pollutants emitted from motor vehicle exhausts as a potential pro-allergic hazard, before making important changes in environmental policy.