Comparison of a portable, pneumotach flow-sensor-based spirometer (Spirofy™) with the vitalograph alpha Touch™ spirometer in evaluating lung function in healthy individuals, asthmatics, and COPD patients-a randomized, crossover study.

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 < 0.7 was used to compare the diagnostic accuracies of the Spirofy™ with Vitalograph™ Alpha Touch™ spirometers. RESULTS: Ninety subjects participated in this study. The mean ± SD FVC values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 2.60 ± 1.05 L, 2.64 ± 1.04 L, and 2.67 ± 1.04 L, respectively. The mean ± SD FEV1 values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 1.87 ± 0.92 (L), 1.88 ± 0.92 (L), and 1.93 ± 0.93 (L), respectively. A significant positive correlation was found between the FVC and FEV1 values recorded by Vitalograph Alpha Touch™, Spirofy™ 1, and Spirofy™ 2. As compared to Vitalograph Alpha Touch™, the Spirofy™ device showed good sensitivity (97%), specificity (90%), and overall accuracy (93.3%) at an FEV1/FVC ratio < 0.7. No inter-device variability was observed between the two Spirofy™ devices. CONCLUSION: Spirofy™ is a portable and easy-to-use device and is as accurate as the standard Vitalograph Alpha Touch™ spirometer for the diagnosis of COPD and asthma. TRIAL REGISTRATION: CTRI/2021/09/036492 (Clinical Trials Registry - India).

Interpreting lung oscillometry results: Z-scores or fixed cut-off values?

Instead of using % predicted values or Z-scores to define and quantify respiratory abnormality in oscillometry, fixed cut-off values will likely give more accurate discrimination https://bit.ly/3vVmIyE.

Is underuse of Inhaled Corticosteroids for Asthma in India contributing to 42% of global asthma deaths?

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.

Global Asthma Network Phase I, India: Results for allergic rhinitis and eczema in 127,309 children and adults.

Background: The Global Asthma Network phase I study in India aimed to study the prevalence, time trends, and associated risk factors of allergic rhinitis and eczema among 6-7-year-old, and 13-14-year-old school children and their parents. Objectives: The objective of the study was to understand the current prevalence and associated risk factors of Allergic Rhinitis and Eczema in India among 6-7-year-olds, 13-14-year-olds and in their parents/guardians for newer directions to health care providers, policy makers and academicians. Methods: Cross-sectional, multicenter study using self- and parent-administered questionnaire among randomly selected school children aged 6 to 7 years from 8 centers and 13 to 14 years from 9 centers and their respective parents/guardians across India. Results: Prevalence of allergic rhinitis (AR) (%, 95% CI) among 20,084 6-7-year-olds (children), 25,887 13-14-year-olds (adolescents), and 81,296 adults/parents was 7.7% (7.4%-8.1%), 23.5% (23.0%-24.1%), and 9.8% (9.55%-9.96%) and that of eczema was 2.5% (2.3%-2.7%), 3.5% (3.27%-3.71%), and 9.9% (9.7%-10.1%), respectively. Among 6-7-year-olds, AR and eczema showed a significantly (P < .001) declining time trend since the International Study of Asthma and Allergies in school children phase III in 2002-2003. Among 13-14-year-olds, AR (P < .01) but not eczema showed a significant temporal decline. Coexisting atopic condition, parental history of atopy, and some environmental factors consistent with previous studies were significant risk factors among children and adolescents. AR or eczema in either parent strongly predicted the same atopic condition among their adolescent offspring. Among adults, coexisting atopic condition was the strongest predictor of either AR or eczema. Conclusions: There is a slight declining time trend of AR and eczema in India over 2 decades among children and adolescents. Nearly 10% of Indian adults suffer from AR and eczema. Although genetic factors had the strongest association for AR and eczema among all age groups, certain early-life and environmental exposures need consideration to devise preventative strategies.

Association between air pollution, body mass index, respiratory symptoms, and asthma among adolescent school children living in Delhi, India.

BACKGROUND: Delhi is one of the most polluted cities in the world with annual average ambient PM10 and PM2.5 levels exceeding the World Health Organization standards by over 15 fold. We aimed to study the prevalence of respiratory and allergic symptoms and asthma among adolescent children living in Delhi (D) and compare it with children living in lesser polluted cities of Kottayam (K) and Mysore (M) located in Southern India. METHODS: 4361 boys and girls between the age group of 13-14 and 16-17 years from 12 randomly selected private schools from D, K, and M were invited to participate. Modified and expanded International Study for Asthma and Allergies in Children (ISAAC) questionnaires (Q) were filled by the students who also performed spirometry using the ultrasonic flow-sensor-based nDD Spirometer. RESULTS: 3157 students (50.4% boys) completed the Q and performed good quality spirometry. The prevalence of asthma and airflow obstruction among children living in Delhi was 21.7% using the ISAAC Q and 29.4% on spirometry, respectively. This was accompanied by significantly higher rates of self-reported cough, shortness of breath, chest tightness, sneezing, itchy and watery eyes, itchy skin, and eczema among Delhi children (vs. K-M, all P < 0.05). Delhi children were more overweight and obese (39.8% vs. 16.4%, P < 0.0001), and this was the only risk factor that was strongly associated with asthma (odds ratio [OR]: 1.79; confidence interval: 1.49-2.14), with a more pronounced effect in Delhi children (P = 0.04). Forced expiratory volume1 and Forced vital capacity values were significantly higher in Delhi children (vs. K-M P < 0.0001). Preserved ratio impaired spirometry was more common in K-M children (P < 0.0001). CONCLUSION: Adolescent children living in the polluted city of Delhi had a high prevalence of asthma, respiratory symptoms, allergic rhinitis, and eczema that was strongly associated with a high body mass index (BMI). Our study suggests an association between air pollution, high BMI, and asthma/allergic diseases, which needs to be explored further.

COPD awareness in the urban slums and rural areas around Pune city in India.

COPD is the second leading cause of death and disability adjusted life years (DALYs) in India, yet, it remains poorly recognized. We aimed to study the level of awareness of COPD in urban slums of Pune city in India and its neighboring rural areas. All male and female subjects above the age of 30 years residing in 13 randomly selected slums of Pune city (total population of 3000) and 7 randomly selected neighboring rural villages (total population of 3000) were invited to participate in this cross-sectional community survey. After obtaining written informed consent, 13 trained community health workers (CHWs) administered a questionnaire that captured their level of awareness of COPD. Of the 6000 subjects approached, 5420 residents (mean age ± SD = 48.0 ± 13.5 years; 38% males) consented and answered all questions. The number of people who had ever heard the word COPD was 49/5420 [0.9% (0.6-1.1%); 0.7% (0.5-1.3%) of the urban slum dwellers and 1.15% (0.5-1.3%) of rural residents]. Among those who had never heard the word COPD (n = 5371), when asked what was the name of the disease caused by long-term tobacco smoking, 38% said cancer, 16.7% said asthma, and 4.4% said TB. Among those who had heard the word COPD (n = 49), 6.1% said it was a disease of the heart, and 61% attributed COPD to smoke and dust pollution and 20% to tobacco smoking. The level of awareness of COPD in the Indian community is extremely low, highlighting the need to have nationwide mass awareness programs in India.

Monitoring of inhaler use at home with a smartphone video application in a pilot study.

Inhalation therapy is the basis of the pharmacological management of asthma and COPD. Most patients are trained on the correct use of inhalers by health professionals but after that do patients continue to take them correctly at home remains largely unknown. Video recording of the inhalation technique using a smartphone can be used to evaluate the inhaler technique at home. Through this pilot study, we aimed to understand whether inhaler training given to patients in the outpatient clinic translates into good inhalation practices at home by a video application platform using a smartphone. We recruited 70 newly diagnosed asthma and COPD patients and a pulmonologist trained them to use their inhaler until they were able to use it correctly. Videos of inhaler use were captured by a relative or a friend at home and then sent to an independent reviewer via WhatsApp on Days 1, 7, 14 and 28 (±2). Each step of the inhaler technique was evaluated based on a predetermined checklist with a rating scale of 0 to 10 (10 for all steps done correctly). Out of 70 patients recruited, 30 (42%) sent all videos. We found that, although all patients performed all the steps correctly in the clinic, none of them performed all steps correctly at home even on Day 1 itself of the inhaler use. On Day 1, the steps score reduced from 10 to 6.9 with a downward trend until Day 28. The most common mistakes from Day 1 onwards were incorrect inspiratory flow rates and not gargling after the inhaler use. Also, most patients showed partially effective inhalation as per our scoring method. Remote video monitoring of inhaler use in the home environment is possible with a mobile video application that gives us a better insight into the most common inhaler mistakes performed by patients at home. Inhaler errors start appearing immediately on Day 1 after the training, and incorrect inspiratory flow rates and forgetting to do gargles are common errors. Early detection of inhaler errors at home may be possible through this method.

Phenotypic comparison between smoking and non-smoking chronic obstructive pulmonary disease.

BACKGROUND: Although COPD among non-smokers (NS-COPD) is common, little is known about this phenotype. We compared NS-COPD subjects with smoking COPD (S-COPD) patients in a rural Indian population using a variety of clinical, physiological, radiological, sputum cellular and blood biomarkers. METHODS: Two hundred ninety subjects (118 healthy, 79 S-COPD, 93 NS-COPD) performed pre- and post-bronchodilator spirometry and were followed for 2 years to study the annual rate of decline in lung function. Body plethysmography, impulse oscillometry, inspiratory-expiratory HRCT, induced sputum cellular profile and blood biomarkers were compared between 49 healthy, 45 S-COPD and 55 NS-COPD subjects using standardized methods. Spirometric response to oral corticosteroids was measured in 30 female NS-COPD patients. RESULTS: Compared to all male S-COPD subjects, 47% of NS-COPD subjects were female, were younger by 3.2 years, had greater body mass index, a slower rate of decline in lung function (80 vs 130 mL/year), more small airways obstruction measured by impulse oscillometry (p < 0.001), significantly less emphysema (29% vs 11%) on CT scans, lower values in lung diffusion parameters, significantly less neutrophils in induced sputum (p < 0.05) and tended to have more sputum eosinophils. Hemoglobin and red cell volume were higher and serum insulin lower in S-COPD compared to NS-COPD. Spirometric indices, symptoms and quality of life were similar between S-COPD and NS-COPD. There was no improvement in spirometry in NS-COPD patients after 2 weeks of an oral corticosteroid. CONCLUSIONS: Compared to S-COPD, NS-COPD is seen in younger subjects with equal male-female predominance, is predominantly a small-airway disease phenotype with less emphysema, preserved lung diffusion and a slower rate of decline in lung function.

Systemic Immuno-metabolic alterations in chronic obstructive pulmonary disease (COPD).

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 (ß-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 < 0.05) and FVC (r = 0.79, p < 0.05) values in HS was observed. The metabolic shift towards fatty acid metabolism in healthy smokers promoted an inflammatory cytokine response with a greater increase in the levels of IL-5, IL-9 and IFN-α as compared to IFN-γ, IL-17 and TNF-α. In-vitro experiments with RAW 264.7 cells showed similar metabolic alterations and a reduced ability to phagocytose Streptococcus pneumonia and Haemophilus influenza after cigarette smoke exposure in the presence of glucose or palmitate. CONCLUSIONS: These findings indicate a metabolic basis for the inflammatory response in COPD and could suggest a new therapeutic target for controlling the immune response and delaying the onset of disease. TRIAL REGISTRATION: This observational study was retrospectively registered in the Clinical Trails Registry - India (ICMR - NIMS) on 19th January 2018 with the registration number CTRI/2018/01/011441 .

Personal exposures to particulate matter <2.5 µm in mass median aerodynamic diameter (PM2.5) pollution during the burning of six most commonly used firecrackers in India.

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 <2.5 µm in mass median aerodynamic diameter (PM2.5) during burning of six of the most commonly used firecracker types in India. METHODS: Sparklers, ground spinners, flower pots, pulpuls, a garland of 1000 sounding crackers, and snake tablets were burnt outdoors in an open area during the late evening hours. Minute by minute PM2.5levels were measured at a distance and height from where they are normally burnt using Thermo pDR 1200, USA, and a set of five such experiments were conducted to examine the variability between the firecrackers. RESULTS: When measured at a distance and height from where they are normally burnt, the burning of snake tablets produced the highest peak level of PM2.5 (64,500 mcg/m3), followed by a garland of 1000 sounding crackers (38,540 mcg/m3), pulpuls (28,950 mcg/m3), sparklers (10,390 mcg/m3), ground spinners (9490 mcg/m3) and flower pots (4860 mcg/m3). CONCLUSION: Burning of firecrackers produce extremely high levels of personal exposure to PM2.5 levels that are likely to have significant short-term and long-term adverse health effects. The initiative taken by the Supreme Court of India in 2017 to ban the sale of firecrackers seems to be a step in the right direction to reduce the adverse health impacts in the community.

Prevalence, risk factors and clinical correlates of COPD in a rural setting in Tanzania.

Chronic obstructive pulmonary disease (COPD) causes substantial burden of disease in developed countries, but there are limited data from Africa. We aimed to estimate the prevalence of COPD in Tanzania and identify the risk factors associated with it.This was a cross-sectional descriptive survey involving adults aged ≥35 years. We collected data on symptoms and risk factors using the Burden of Obstructive Lung Diseases questionnaire. Spirometry was performed and COPD diagnosed based on post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <70%. We also measured indoor and outdoor carbon monoxide (CO) levels.A total of 869 participants (49.1% females) completed the questionnaires. Of these, 57.1% completed post-bronchodilator spirometry. Of the 25.2% ever-smokers, only 5.4% were current smokers. COPD prevalence was estimated at 17.5% (21.7% in males and 12.9% in females). COPD was associated with a history of cough, phlegm production and wheezing. 51.7% of COPD patients reported cough and 85% had mild to moderate airway limitation. Females had a higher rate of exacerbation. Pulmonary tuberculosis (TB) was reported in 10% of patients. Only 1.7% of patients who were diagnosed as COPD had ever received any medication, with only one female COPD patient having received an inhaler. 99.5% of the population used biomass fuels for cooking. The majority of households had CO levels up to 20 ppm.The prevalence of COPD in Tanzania is high, with a peak at a relatively young age and a preponderance in males. A history of TB, cigarette smoking and male sex are important risk factors. Indoor air pollution coupled with use of biomass fuel for cooking and heating may be an important risk factor for developing COPD in rural Tanzania. However, these factors need to be studied further.

Use of spirometry among chest physicians and primary care physicians in India.

Although spirometry is the gold-standard diagnostic test for obstructive airways diseases, it remains poorly utilised in clinical practice. We aimed to investigate the use of spirometry across India, the change in its usage over a period of time and to understand the reasons for its under-utilisation. Two nationwide surveys were conducted in the years 2005 and 2013, among four groups of doctors: chest physicians (CPs), general physicians (GenPs), general practitioners (GPs) and paediatricians (Ps). A total of 1,000 physicians from each of the four groups were randomly selected from our database in the years 2005 and 2013. These surveys were conducted in 52 cities and towns across 15 states in India. A questionnaire was administered to the physicians, which captured information about their demographic details, type of practice and use of spirometry. The overall response rates of the physicians in 2005 and 2013 were 42.8% and 54.9%, respectively. Spirometry was reported to be used by 55% CPs, 20% GenPs, 10% GPs and 5% Ps in 2005, and this increased by 30.9% among CPs (P value <0.01), 18% among GenPs (P value=0.01), 20% among GPs (P value: not significant) and 224% among Ps (P value <0.01). The reasons for not using spirometry varied between 2005 and 2013. In all, 32.2% of physicians were unaware of which predicted equation they were using. The use of spirometry in India is low, although it seems to have improved over the years. The reasons identified in this study for under-utilisation should be used to address initiatives to improve the use of spirometry in clinical practice.

Challenges in recruitment and retention of clinical trial subjects.

BACKGROUND: Successful recruitment of patients is known to be one of the most challenging aspects in conduct of randomized controlled trials. Inadequate patient retention during conduct of trial affects conclusive results. OBJECTIVE: To assess the level of challenges faced by Indian investigators in recruitment and retention of trial subjects. METHODS: We developed a survey questionnaire on challenges encountered by investigators in subject recruitment and retention which was hosted on a web portal. RESULTS: Seventy-three investigators from India participated in the survey. The frequently encountered challenges in subject recruitment were complexity of study protocol (38%), lack of awareness about clinical trials in patients (37%), and sociocultural issues related to trial participation (37%). About 63% of participants strongly agreed that creating a positive awareness about clinical trials among people through press and media, having a dedicated clinical research coordinator for trial (50.7%), and designing a recruitment strategy prior to study initiation (46.6%) would enhance recruitment. Almost 50.7% of participants agreed that interacting with medical community in vicinity of the study site and educating patients about clinical trials during routine outpatient department visits (46.6%) would enhance recruitment. Experiencing a serious adverse event, subject's fear for study procedures (47%) and side effects (44%) were thought to have a moderate effect on subject retention. CONCLUSION: Our survey has put forth factors related to negative publicity by media, lack of patient education about clinical trials; complex study designs are barriers to clinical trial recruitment in India. It is essential to devise innovative and effective strategies focusing on education of public and mass media about clinical research in India.

Opinions and perceptions regarding the impact of new regulatory guidelines: A survey in Indian Clinical Trial Investigators.

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.

Indoor Particulate Matter < 2.5 µm in Mean Aerodynamic Diameter and Carbon Monoxide Levels During the Burning of Mosquito Coils and Their Association With Respiratory Health.

BACKGROUND: An estimated 700 million people suffer from mosquito-borne diseases worldwide. Various types of mosquito repellents are widely used to prevent mosquito bites. The objectives of this study were (1) to measure the indoor levels of particulate matter < 2.5 µm in mean aerodynamic diameter (PM2.5) and carbon monoxide (CO) during the burning of mosquito coils (MCs) and study the impact of indoor ventilation patterns; and (2) to study and compare the prevalence of respiratory ailments in homes using different types of mosquito repellents. METHODS: Indoor PM2.5 and CO levels were measured inside a bedroom during the burning of MCs keeping the window and/or door open/closed over a 6-h duration. A cross-sectional survey was conducted in three villages where 465 individuals were administered a questionnaire that captured demographic details, type and duration of mosquito repellents used, and prevalence of respiratory symptoms and diseases. RESULTS: Fifty-three percent of the subjects burned MCs on most days of the week, and 63% did so with their doors and windows closed. Burning of MCs produced very high levels of PM2.5 (1,031 µg/m(3) mean, 1,613 µg/m(3) peak) and CO (6.50 parts per million (ppm) mean, 10.27 ppm peak) when both the door and window were closed. These levels reduced by around 50% when the window was opened and > 95% when both the window and the door were opened. The prevalence rates of respiratory symptoms and diseases were higher in subjects using MCs, although not statistically significant. Those living in smaller homes and using MCs had significantly greater morbidity. CONCLUSIONS: Burning of MCs produces indoor levels of PM2.5 and CO that are higher than those reported during the burning of biomass fuels for cooking purposes and may be associated with respiratory morbidity.

Symptoms and medical conditions in 204 912 patients visiting primary health-care practitioners in India: a 1-day point prevalence study (the POSEIDON study).

BACKGROUND: India has one of the highest disease burdens in the world. A better understanding of what ails India will help policy makers plan appropriate health-care services and infrastructure development, design medical education curricula, and identify health research priorities that are relevant to the needs of the country. The POSEIDON study aimed to record the prevalence of symptoms and medical conditions for which patients visit a primary health-care practitioner in India. METHODS: We randomly selected 12 000 general practitioners, general physicians, and paediatricians from 880 cities and towns and invited them to record demographic details, symptoms, and medical conditions for every patient they saw on Feb 1, 2011. A further 1225 practitioners volunteered to participate and their responses were included. We did simple descriptive analyses of prevalence rates and used χ(2) tests to study comorbid associations. Through application of systems biology methods, we visualised inter-relations between organ involvement of diseases and symptoms and deciphered how these associations change with age and gender. FINDINGS: We included responses from 7400 health-care practitioners, which represented data for 204 912 patients, who presented with 554 146 reasons for visit. Fever (35·5%) was the most common presenting symptom. More than half of all patients presented with respiratory symptoms across all age groups and regions of India. Other common presentations were digestive system symptoms (25%), circulatory symptoms (12·5%), skin complaints (9%), and endocrine disorders (6·6%). Hypertension (14·52%), obstructive airways diseases (14·51%), and upper respiratory tract infections (12·9%) were the most common diagnoses reported. Of note was that 21·4% of all patients with hypertension reported by the primary health-care practitioners were younger than 40 years. Anaemia was the fourth most common disease reported by these health-care practitioners and was most common in women of menstrual age living outside metro cities. INTERPRETATION: The POSEIDON study provides insight into the reasons that patients visit primary health-care practitioners in India; our results highlight important social and medical challenges in the developing world. FUNDING: Chest Research Foundation, Council of Scientific and Industrial Research-Institute of Genomics and Integrated Biology (CSIR-IGIB), and Cipla Ltd.

Priming of beta-2 agonist and antimuscarinic induced physiological responses induced by 1200mg/day NAC in moderate to severe COPD patients: A pilot study.

UNLABELLED: This study evaluated antioxidant modulations of lung physiological-responses to beta-2-agonist and antimuscarinic bronchodilators with 1200mg/day n-acetyl-cysteine (NAC) in a placebo-controlled, randomised, double-blind, parallel-group study, in moderate-very severe COPD patients. METHODS: 15 COPD patients received NAC treatment, while 9 COPD patients received placebo treatment, for 15 days. Pre-and-post salbutamol and ipratopium-bromide lung-physiology responses were measured using body-plethysmography, impulse-oscillometry (IOS) and spirometry before-and-after study treatments. RESULTS: Compared to pre-treatment, the NAC-treatment significantly enhanced the potential of ipratopium-bromide to reduce functional-residual-capacity (FRC) by nearly 3-folds (mean% FRC-response: pre-NAC: -5.51%±10.42% versus post-NAC: -17.89%±12.94%, p=0.02; mean-absolute FRC-response: pre-NAC: -300ml±450ml versus post-NAC: -770ml±550ml, p=0.02), which was superior to placebo-treatment. The increase in total-lung-capacity response to ipratopium-bromide, although insignificant, was superior with post-NAC treatment versus post-placebo treatment (p=0.049). The salbutamol-response remained unaltered with either treatment. CONCLUSION: The treatment with 1200mg/day NAC has potential to enhance the bronchodilator ability of antimuscarinic-agents but not beta-2-agonist. However, its clinical application has to be established in large sample-size studies for longer-duration.

Bronchodilator efficacy of tiotropium-formoterol via single pressurized meter dose inhaler (pMDI) versus tiotropium alone in COPD.

BACKGROUND: Bronchodilators form the main stay of treatment for COPD. When symptoms are not adequately controlled with one bronchodilator, addition of another bronchodilator is recommended. We have recently developed a combination of tiotropium and formoterol in a single pressurized metered dose inhaler (pMDI) (Cipla Ltd., India). The aim of this study was to compare the bronchodilator effects of a single dose of 18 mcg of tiotropium versus a single dose of a combination of 18 mcg tiotropium plus 12 mcg formoterol administered via a pMDI in subjects with moderate-to-severe COPD. STUDY DESIGN: 44 COPD subjects were enrolled in this randomized, double-blind, multi-centre, cross-over study. 18 mcg tiotropium and 18 mcg tiotropium plus 12 mcg formoterol were administered via pressurized metered dose inhalers on two separate days. FEV(1), FVC and Inspiratory capacity (IC) were measured before, 15, 30 min, 1, 2, 3, 4, 6, 8, 12 and 24 h after the study drugs were administered. RESULTS: Compared with tiotropium alone, a combination of tiotropium plus formoterol showed a faster onset of bronchodilator response (p < 0.01 for FEV(1) and FVC), a greater mean maximum change in FEV(1) (p = 0.01) and FVC (p = 0.008) and greater AUC(0-24h) values for FEV(1), FVC and IC. Trough FEV(1) and FVC values were also greater in the combination group. CONCLUSION: A combination of tiotropium plus formoterol administered via a single inhaler produced a superior bronchodilator response than tiotropium alone over a period of 24 h.