Proportionate clinical burden of respiratory diseases in Indian outdoor services and its relationship with seasonal transitions and risk factors: The results of SWORD survey.

BACKGROUND: The 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. METHODS: In 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). RESULTS: The 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, p<0.001 for each respectively). After adjustment for risk factors, asthma was significantly associated with exposure to molds (OR:1.12,CI:1.03-1.22), pet animals (OR:1.07,CI:1.01-1.14), recent-travel (OR:1.22,CI:1.13-1.32), and rain-wetting (OR:1.27,CI:1.15-1.40); and RTIs with rain-wetting (OR:1.53,CI:1.34-1.74), and recent-travel (OR:1.17,CI:1.05-1.30). CONCLUSIONS: The 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.

Fixed-dose combination of three drugs, i.e. LABA/LAMA/ICS for COPD: Results of a real-world study from India.

BACKGROUND: The use of triple therapy with inhaled corticosteroids, long-acting beta-agonist and long-acting antimuscarinics has been shown to be beneficial in COPD patients who continue to have symptoms and exacerbations, despite receiving dual bronchodilator combinations. This study assessed the real-world effectiveness and safety of once-daily, fixed-dose combination of Tiotropium/Formoterol/Ciclesonide (TFC) (18 mcg/12 mcg/400 mcg) via dry powder inhaler (DPI) or metered dose inhaler (MDI) in patients with COPD. PATIENTS AND METHODS: In this 24-week, open-label, prospective, non-comparative, multicentre, real-world study, COPD patients requiring triple therapy as judged by their physician, were enrolled. The primary endpoint was mean change from baseline in pre-dose Forced Expiratory Volume in 1 s (FEV1) at week 24. Pre and post-dose (30 min) FEV1, Forced Vital capacity (FVC), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) score and safety were also evaluated. A post-hoc analysis was conducted to evaluate the efficacy of the triple drug combination among smoker and non-smoker COPD patients. RESULTS: Out of the 297 patients enrolled [mean age 61 ± 10 years; 84.8% males; 55.2% smokers and post-dose FEV1 (% predicted) 39 ± 16%], 253 completed the study. Mean change in pre-dose FEV1 from baseline to week 24 increased significantly after administering the triple drug combination [580 ± 600 mL, 95% CI (510, 650 mL), p < 0.0001]. The increase in the pre-dose FEV1 was significant at all time points (p < 0.0001). Similar improvements were seen in pre-dose FVC, post-dose FEV1 and post-dose FVC across all time points. CAT scores and the proportion of patients with improved mMRC score improved at all visits. The post-hoc analysis showed that TFC significantly increased pre-dose FEV1 both among smokers [mean change 200 ± 430 mL, 95% CI (130, 270 mL), p < 0.0001] as well as non-smokers [990 ± 470 mL, 95% CI (900, 1070 mL), p < 0.0001] at week 24. This difference was significant from week 12 onwards. Mean change in pre and post-dose FEV1 and FVC was significant across all visits between the two groups. At week 24, CAT score reduced significantly from baseline (overall: -6.6 ± 6.07; smokers: -5.17 + 6.96; non-smokers: 8.06 ± 4.44; all p < 0.0001). The mean difference between the two groups was 2.88 (p < 0.0001) at week 24. TFC was well tolerated. CONCLUSION: In this real world, multicentre study in India, TFC significantly improved lung function, symptoms and quality of life among all patients with COPD, but the effect was more pronounced among non-smoker COPD patients.

Dissecting an Outbreak: A Clinico-epidemiological Study of Nipah Virus Infection in Kerala, India, 2018.

BACKGROUND: An outbreak of Nipah virus infection was confirmed in Kerala, India in May 2018. Five out of 23 cases including the first laboratory-confirmed case were treated at Baby Memorial Hospital (BMH), Kozhikode. The study describes the clinical characteristics and epidemiology of the Nipah virus outbreak at Kozhikode during May 2018. OBJECTIVE: To study the clinical and epidemiological profile of Nipah virus epidemic that occurred in Kerala in May 2018. METHODS: A collaborative team of physicians and epidemiologists from BMH, Medical College Hospital (MCH) Kozhikode and from the Indian Medical Association (IMA) conducted this study. The clinical and exposure history and the data on outbreak response were gathered from hospital medical records and through interviewing patient relatives and health workers using questionnaires. RESULTS: It was identified that out of the 23 patients with Nipah virus infection, 21 (91.3%) expired. Out of the 21 patients, 18 tested positive for Nipah virus by Real Time polymerase chain reaction (RT-PCR). It has been found that only the index case was infected in the community from fruit bats. Rest of the cases were due to transmission of the virus at three public hospitals. Median age was 45 years. 65% of them were males. Median incubation period was 9.5 days. Fever (100%), altered sensorium (84.2%), tachycardia (63.1%), hypertension (36.8%), segmental myoclonus (15.7%), segmental sweating (15.7%) and shortness of breath (73.6%) were common features. Mean duration of illness was 6.4 days. CONCLUSION: The rapid spread of infection uncovered the miserable state of health care system in implementing infection control measures. The case fatality and the socio-economic burden warrant developing appropriate treatments, vaccines and diagnostics.

Methodology of Seasonal Waves of Respiratory Disorders survey conducted at respiratory outpatient clinics across India.

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.

Clinical Manifestations of Nipah Virus-Infected Patients Who Presented to the Emergency Department During an Outbreak in Kerala State in India, May 2018.

BACKGROUND: An outbreak of Nipah virus (NiV) disease occurred in the Kozhikode district of Kerala State in India in May 2018. Several cases were treated at the emergency medicine department (ED) of the Government Medical College, Kozhikode (GMCK). The clinical manifestations and outcome of these cases are described. METHODS: The study included 12 cases treated in the ED of GMCK. Detailed clinical examination, laboratory investigations, and molecular testing for etiological diagnosis were performed. RESULTS: The median age of the patients was 30 years and the male to female ratio was 1.4:1.0. All the cases except the index case contracted the infection from hospitals. The median incubation period was 10 days, and the case fatality ratio was 83.3%. Ten (83.3%) patients had encephalitis and 9 out of 11 patients whose chest X-rays were obtained had bilateral infiltrates. Three patients had bradycardia and intractable hypotension requiring inotropes. Encephalitis, acute respiratory distress syndrome, and myocarditis were the clinical prototypes, but there were large overlaps between these. Ribavirin therapy was given to a subset of the patients. Although there was a 20% reduction in NiV encephalitis cases treated with the drug, the difference was not statistically significant. The outbreak ended soon after the introduction of total isolation of patients and barrier nursing. CONCLUSION: The outbreak of NiV disease in Kozhikode in May 2018 presented as encephalitis, acute respiratory distress and myocarditis or combinations of these. The CFR was high. Ribavirin therapy was tried but no evidence for its benefit could be obtained.

Role of Domiciliary Noninvasive Ventilation in Chronic Obstructive Pulmonary Disease Patients Requiring Repeated Admissions with Acute Type II Respiratory Failure: A Prospective Cohort Study.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with acute hypercapnic respiratory failure (AHRF) is associated with high mortality and increased risk for further exacerbations and hospitalization. While there is ample evidence regarding the benefit of noninvasive ventilation (NIV) during AECOPD, evidence supporting long-term noninvasive ventilation (LTNIV) for more stable COPD patients is limited. OBJECTIVE: The aim of this study is to assess the effectiveness of LTNIV in COPD patients requiring frequent hospital admissions and NIV support for AHRF. MATERIALS AND METHODS: A prospective cohort study including 120 patients having survived an admission requiring NIV support for AHRF due to COPD, with a history of ≥3 similar episodes in the past year. Patients were advised LTNIV (30) with standard treatment, or (90) standard treatment alone. Both groups were followed up for 1 year. Among non-NIV group 10 died, and 8 lost follow-up, whereas two died in NIV group. The primary endpoint was death. Data of remaining 100 patients were analyzed for other objectives-number of readmissions, AHRF, Intensive Care Unit (ICU)/ventilator requirement, dyspnea, quality of life, exercise tolerance, lung function, and arterial blood gases. RESULTS: LTNIV group had 40% reduction in mortality (6.6% vs. 11.1%). There was significant reduction in number of hospital admissions (28.6% vs. 84.7%: P <0.05), ICU admissions (7.1% vs. 56.9%: P = 0.01), ventilator requirement (3.6% vs. 30.6%: P = 0.003), AHRF (7.1% vs. 48.6%: P = 0.000) and improvement in partial arterial CO2 pressure (39.8 ± 2.1 vs. 57.03 ± 3.7 mmHg) and severe respiratory insufficiency score (P < 0.05) among LTNIV group, but no significant change in lung function and exercise tolerance. CONCLUSION: Patients tolerated LTNIV well and had a better outcome compared to those without NIV. LTNIV may be considered in patients with recurrent AHRF.

Role of Pirfenidone in Idiopathic Pulmonary Fibrosis - A Longitudinal Cohort Study.

BACKGROUND: But so far there is no proven pharmacological treatment for Idiopathic pulmonary fibrosis (IPF). As trials investigating different agents with different mechanisms of actions are going on, encouraging results have led to the licensing of the first IPF-specific drug, Pirfenidone. OBJECTIVE: To assess the proportion of IPF among interstitial lung disease patients and to assess their treatment response to Pirfenidone. MATERIAL AND METHODS: All consecutive patients attending the outpatient department from 1st January 2012 to 30th June 2012 with a proven diagnosis of Interstitial lung Disease (ILD) were included in this longitudinal cohort study. Out of the total ILDs, patients with IPF were identified. The disease, its natural course, available treatment options and the risks and benefits of drugs were discussed with each IPF patient along with their family members. After obtaining their consent, we started 23 patients on a combination of Pirfenidone, N-acetyl cysteine (NAC) and proton pump inhibitors (PPI). Patients were followed up for 52 weeks. Pirfenidone was discontinued in one patient due to an adverse effect 1 month after onset of treatment. Anova test using SPSS software and independent T test was used to analyse the data. RESULTS: During the study period 69 patients with ILD attended our OPD which included 24 IPF patients representing 34.8% and 23 of these patients received treatment with Pirfenidone, NAC and PPI. One patient discontinued Pirfenidone due to adverse effects. After 12 months, 8 patients had worsening of FVC ≥10%, the FVC of 7 patients remained stable, 8 patients could not repeat the tests and none of them had improvement. There was less than 15% decline in DLCO for 9 patients, 7 patients could not repeat the test and none improved. 8 patients had stable dyspnoea on exertion and 11 had worsening. Three patients died. Combining all the above parameters, only 4 patients had stable disease with the rest having no improvement. CONCLUSIONS: The present study does not show any significant beneficial effect for Pirfenidone. Only four patients remained stable which cannot be attributed to the effect of any particular management strategy.

Diffuse Parenchymal Lung Diseases with Clinicoradiological Discordance: Role of Transbronchial Lung Biopsy as a Diagnostic Tool - An Observational Study.

INTRODUCTION: The diagnosis of Diffuse Parenchymal Lung Disease (DPLD) requires a multidisciplinary approach with reconciliation of clinicoradiological and histopathological data. But when the preliminary clinicoradiological profile fails to suggest a diagnosis, an adequate lung biopsy specimen with meticulous histological examination and a multidisciplinary approach usually yields results. There is also a high chance of sampling error due to patchy and heterogeneous involvement of the disease process and due to the small volume of tissue taken. As seen in our study, Trans-Bronchial Lung Biopsy (TBLB) if performed by an experienced bronchoscopist can be done as an outpatient procedure yielding adequate specimens for diagnosis and guide effective treatment in these patients. AIM: To study the utility and diagnostic yield of TBLB in DPLD patients when there is clinicoradiological discordance. MATERIALS AND METHODS: The current retrospective observational study was undertaken in the Institute of Chest Diseases, Government Medical College, Kozhikode, Kerala, India, from January 2012 to December 2014. Out of 169 DPLD patients who attended the tertiary care centre, 66 patients without a definite diagnosis by clinicoradiological assessment were included in the study. They underwent TBLB using a fibre-optic video bronchoscope. An open lung biopsy was advised if the TBLB did not yield a definite diagnosis. RESULTS: Among the 66 patients, histopathological confirmation was obtained in 51 patients, 39 of which were by TBLB (59%). Few diagnoses like invasive adenocarcinoma, Pneumocystis jirovecii pneumonia and Aspergillus infection were least expected. CONCLUSION: TBLB if performed correctly can be an effective intervening modality in establishing the diagnosis of DPLD before going for an invasive surgical biopsy.

Basidiobolus: An unusual cause of lung abscess.

Non-resolving pneumonia leading to lung abscess is always a challenge to the treating physician especially in a diabetic patient. Atypical radiological features of lung abscess should raise the suspicion of unusual organisms. This is a case report of a 42 year old diabetic male presented with features suggestive of lung abscess and multiple target organ damage. Subsequent work up revealed that the etiological agent is a rare fungus - Basidiobolus. To the best of our knowledge this is the first case of Basidiobolus lung abscess reported from India.