Screening for Lung Cancer in India: Expert Opinion Statement.

Lung cancer (LC) has the highest rate of disability-adjusted life years (DALY) of all cancers in India. A large majority of patients with LC present with advanced disease, resulting in poor survival rates. Early diagnosis can improve survival outcomes as the patients can be treated with curative intent. The National Lung Screening Trial (NLST), in 53,454 persons at high risk for LC in the US, showed a 20% (95% confidence interval of 6.8-26.7; p = 0.004) relative reduction in LC-specific mortality in the patients screened with low-dose computed tomography (LDCT) compared with chest X-ray. To date, India does not have a formal LC screening (LCS) program. As a panel of experts, we reviewed a synthesis of a targeted literature search on the burden of LC, the current status of diagnosis of LC, barriers to early diagnosis, current referral pathways, LC risk patterns, use of artificial intelligence (AI) and risk calculators for risk assessment, and a multidisciplinary team (MDT) approach to diagnosis LC. We used the existing international LCS guidelines, data from published literature, and clinical experience to depict the characteristics of the population at risk of LC in India-young age (<40 years), smoking, especially the predominance of bidi smoking (an indigenous form of tobacco smoking), exposure to biomass fuel smoke, especially in rural women, and air pollution being the prominent features. LC in India is characterized by a higher rate of driver mutations and adenocarcinomatous histology. Here, we present the expert opinion on risk-based LCS in India and discuss the challenges, facilitators, and research priorities for the effective rollout of LCS in India.

Pleural effusion guidelines from ICS and NCCP Section 1: Basic principles, laboratory tests and pleural procedures.

Pleural effusion is a common problem in our country, and most of these patients need invasive tests as they can't be evaluated by blood tests alone. The simplest of them is diagnostic pleural aspiration, and diagnostic techniques such as medical thoracoscopy are being performed more frequently than ever before. However, most physicians in India treat pleural effusion empirically, leading to delays in diagnosis, misdiagnosis and complications from wrong treatments. This situation must change, and the adoption of evidence-based protocols is urgently needed. Furthermore, the spectrum of pleural disease in India is different from that in the West, and yet Western guidelines and algorithms are used by Indian physicians. Therefore, India-specific consensus guidelines are needed. To fulfil this need, the Indian Chest Society and the National College of Chest Physicians; the premier societies for pulmonary physicians came together to create this National guideline. This document aims to provide evidence based recommendations on basic principles, initial assessment, diagnostic modalities and management of pleural effusions.

Prevention of relapse in drug sensitive pulmonary tuberculosis patients with and without vitamin D3 supplementation: A double blinded randomized control clinical trial.

BACKGROUND: The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. METHODS: This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. RESULTS: A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. CONCLUSIONS: The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. TRIAL REGISTRATION: CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).

[68Ga]Ga-Pentixafor PET/CT imaging for in vivo CXCR4 receptor mapping in different lung cancer histologic sub-types: correlation with quantitative receptors' density by immunochemistry techniques.

PURPOSE: In vivo CXCR4 receptor quantification in different lung cancer (LC) sub-types using [68Ga]Ga-Pentixafor PET/CT and to study correlation with quantitative CXCR4 receptors' tissue density by immunochemistry analyses. METHODS: [68Ga]Ga-Pentixafor PET/CT imaging was performed prospectively in 94 (77 M: 17F, mean age 60.1 ± 10.1 years) LC patients. CXCR4 receptors' expression on lung mass in all the patients was estimated by immunohistochemistry (IHC) and fluorescence-activated cell sorting (FACS) analyses. SUVmax on PET, intensity score on IHC, and mean fluorescence index (MFI) on FACS analyses were measured. RESULTS: A total of 75/94 (79.8%) cases had non-small cell lung cancer (NSCLC), 14 (14.9%) had small cell lung cancer (SCLC), and 5 (5.3%) had lung neuroendocrine neoplasm (NEN). All LC types showed increased CXCR4 expression on PET (SUVmax) and FACS (MFI). However, both these parameters (mean SUVmax = 10.3 ± 5.0; mean MFI = 349.0 ± 99.0) were significantly (p = 0.005) higher in SCLC as compared to those in NSCLC and lung NEN. The mean SUVmax in adenocarcinoma (n = 16) was 8.0 ± 1.9 which was significantly (p = 0.003) higher than in squamous cell carcinoma (n = 54; 6.2 ± 2.1) and in not-otherwise specified (NOS) sub-types (n = 5; 5.8 ± 1.5) of NSCLC. A significant correlation (r = 0.697; p = 001) was seen between SUVmax and MFI values in squamous cell NSCLC as well as in NSCLC adenocarcinoma (r = 0.538, p = 0.031) which supports the specific in vivo uptake of [68Ga]Ga-Pentixafor by CXCR4 receptors. However, this correlation was not significant in SCLC (r = 0.435, p = 0.121) and NEN (r = 0.747, p = 0.147) which may be due to the small sample size. [68Ga]Ga-Pentixafor PET/CT provided good sensitivity (85.7%) and specificity (78.1%) for differentiating SCLC from NSCLC (ROC cutoff SUVmax = 7.2). This technique presented similar sensitivity (87.5%) and specificity (71.4%) (ROC cutoff SUVmax = 6.7) for differentiating adenocarcinoma and squamous cell variants of NSCLC. CONCLUSION: The high sensitivity and specificity of [68Ga]Ga-Pentixafor PET/CT for in vivo targeting of CXCR4 receptors in lung cancer can thus be used effectively for the response assessment and development of CXCR4-based radioligand therapies in LC.

A study on the effect of mobile phone use on sleep.

Background & objectives: Several studies have been conducted globally to assess the impact of usage of mobile phones on quality and duration of sleep as also on day time sleepiness. The objective of the present study was to assess the effect of mobile phone usage on the quality and composition of sleep in a sample from Indian population. Methods: The study was conducted at two tertiary care hospitals in north India from July 2014 to September 2019. A total of 566 participants were recruited in this study from both the centres. Sleep quality was assessed with the help of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Subsequently, actigraphy was done in 96 participants and polysomnography in 95 participants. Results: Of the 566 participants, 128 (22.61%) had PSQI ≥5, reflecting poor sleep quality. A higher use of mobile phone was significantly associated with a poor sleep quality as a component of PSQI questionnaire (P=0.01) and higher overall PSQI score (P=0.01). The latency from sleep onset to N2 and N3 sleep stages was significantly shorter in participants having a higher mobile phone usage as compared to those with a lower usage [Median (range): 13.5 min (1.5-109) vs. 6.5 min (0-89); P=0.02] and [Median (range): 49 min (8.5-220.5) vs. 28.75 min (0-141); P=0.03], respectively. Interpretation & conclusions: This study focused on the maladaptive changes brought on by mobile phone usage on sleep. More studies with larger sample sizes need to be done that may serve to confirm the hypothesis generating findings of our study.

Incidence, prevalence, and national burden of interstitial lung diseases in India: Estimates from two studies of 3089 subjects.

BACKGROUND AND OBJECTIVE: The epidemiology of interstitial lung diseases (ILDs) in developing countries remains unknown. The objective of this study was to estimate the incidence, prevalence, and national burden of ILDs in India. METHODS: Data of consecutive subjects (aged >12 years) with ILDs included in a registry between March 2015 and February 2020 were analyzed retrospectively. The proportion of each ILD subtype was determined. The crude annual incidence and prevalence of ILDs for our region were estimated. Subsequently, the primary estimates of the national annual incident and prevalent burden of ILD and its subtypes were calculated. Alternative estimates for each ILD subtype were calculated using the current and a large, previous Indian study (n = 1,084). Data were analyzed using SPSS version 22 and are presented descriptively. RESULTS: A total of 2,005 subjects (mean age, 50.7 years; 47% men) were enrolled. Sarcoidosis (37.3%) was the most common ILD subtype followed by connective tissue disease (CTD)-related ILDs (19.3%), idiopathic pulmonary fibrosis (IPF, 17.0%), and hypersensitivity pneumonitis (HP, 14.4%). The crude annual incidence and prevalence of ILDs were 10.1-20.2 and 49.0-98.1, respectively per 100,000 population. The best primary estimates for the crude national burden of all ILDs, sarcoidosis, CTD-ILD, IPF, HP, and other ILDs (in thousands) were 433-867, 213-427, 75-150, 51-102, 54-109, and 39-78. The respective alternative estimates (in thousands) were sarcoidosis, 127-254; CTD-ILD, 81-162; IPF, 46-91; HP, 130-261; other ILDs, 49-98. CONCLUSION: In contrast to developed countries, sarcoidosis and HP are the ILDs with the highest burden in India.

A multicenter survey study of antifibrotic use for symptomatic patients with post-COVID-19 interstitial lung abnormalities.

Background: Little data exist on antifibrotic drugs for treating symptomatic patients with persistent interstitial lung abnormalities in the postacute phase of coronavirus disease 2019 (COVID-19). Herein, we describe the physician practices of prescribing pirfenidone and nintedanib for these patients and the physician-assessed response. Materials and Methods: This was a multicenter, retrospective survey study of subjects administered pirfenidone or nintedanib for post-COVID-19 interstitial lung abnormalities. Data on the demographic details, comorbidities, abnormalities on the computed tomography (CT) of the chest, treatment, antifibrotic drug use, and physician-assessed response were collected on a standard case record pro forma. We explored physician practices of prescribing antifibrotics (primary objective) and the physician-assessed response (secondary objective). Results: We included 142 subjects (mean age, 55.9 years; 16.2% women) at eight centers. The most common abnormalities on CT chest included ground glass opacities (75.7%), consolidation (49.5%), reticulation (43.9%), and parenchymal bands (16.8%). Of the 5701 patients discharged after hospitalization at six centers, 115 (2.0%) received antifibrotics. The drugs were prescribed an average of 26 days after symptom onset. One hundred and sixteen subjects were administered pirfenidone; 11 (9.5%) received the full dose (2400 mg/day). Thirty subjects were prescribed nintedanib; 23 (76.7%) received the full dose (300 mg/day). Of 76 subjects with available information, 27 (35.6%) and 26 (34.2%) had significant or partial radiologic improvement, respectively, according to the physician's assessment. Conclusions: Antifibrotic agents were administered to a minority of patients discharged after recovery from acute COVID-19 pneumonia. Larger, randomized studies on the efficacy and safety of these agents are required.

Prevalence of Antineutrophil Cytoplasmic Antibodies and Antinuclear Antibodies in Patients with Pulmonary Tuberculosis: A Tertiary Care Center Experience from North India.

BACKGROUND: Tuberculosis (TB) can have manifestations closely mimicking autoimmune diseases. The prevalence of autoantibodies in TB varies among different populations. OBJECTIVES: To study the prevalence of anti-neutrophilic cytoplasmic antibodies (ANCA) and antinuclear antibodies (ANA) in pulmonary tuberculosis (PTB). METHODS: This was a cross-sectional, observational study. Subjects with microbiologically confirmed PTB, either via smear or culture positivity on sputum or bronchoalveolar lavage (BAL) fluid, or positive rapid diagnostic tests were included. ANCA against proteinase-3 (PR3), myeloperoxidase (MPO), lactoferrin, and elastase were tested using an enzyme-linked immunosorbent assay (ELISA). ANA was detected using indirect immunofluorescence (IIF). RESULTS: Eighty-nine subjects with a median [interquartile range (IQR)] age of 28 (20-46) years, 67.4% males, were recruited. Eighty-one subjects had microbiological confirmation on sputum examination, and eight required examination of BAL fluid. Sera were drawn from 62 treatment-naïve subjects, the rest (27) were on antitubercular therapy (ATT). Eighty-six (96.6%) subjects tested positive for anti-elastase antibody, seven of which were also positive for anti-PR3. None were positive for anti-MPO and anti-lactoferrin. Six (6.7%) subjects tested positive for ANA. None of the subjects had features of underlying connective tissue disease or vasculitis. CONCLUSION: PTB patients showed a high prevalence of anti-elastase and a low prevalence of ANA and anti-PR3 antibodies. ANCA positivity should be interpreted with caution in TB endemic areas. The role of anti-elastase antibodies in differentiating TB from ANCA-associated vasculitis (AAV) needs further research.

Long-term Survival and Quality of Life among Survivors Discharged from a Respiratory ICU in North India: A Prospective Study.

Background: Advancements in the intensive care unit (ICU) have improved critically ill subjects' short-term outcomes. However, there is a need to understand the long-term outcomes of these subjects. Herein, we study the long-term outcomes and factors associated with poor outcomes in critically ill subjects with medical illnesses. Materials and methods: All subjects (≥12 years) discharged after an ICU stay of at least 48 hours were included. We evaluated the subjects at 3 and 6 months after ICU discharge. At each visit, subjects were administered the World Health Organization Quality of Life Instrument (WHO-QOL-BREF) questionnaire. The primary outcome was mortality at 6 months after ICU discharge. The key secondary outcome was quality of life (QOL) at 6 months. Results: In total, 265 subjects were admitted to the ICU, of whom 53 subjects (20%) died in the ICU, and 54 were excluded. Finally, 158 subjects were included: 10 (6.3%) subjects were lost to follow-up. The mortality at 6 months was 17.7% (28/158). Most subjects [16.5% (26/158)] died within the initial 3 months after ICU discharge. Quality of life scores were low in all the domains of WHO-QOL-BREF. About 12% (n = 14) of subjects could not perform the activity of daily living at 6 months. After adjusting for covariates, ICU-acquired weakness at the time of discharge (OR 15.12; 95% CI, 2.08-109.81, p <0.01) and requirement for home ventilation (OR 22; 95% CI, 3.1-155, p <0.01) were associated with mortality at 6 months. Conclusion: Intensive care unit survivors have a high risk of death and a poor QOL during the initial 6 months following discharge. How to cite this article: Kodati R, Muthu V, Agarwal R, Dhooria S, Aggarwal AN, Prasad KT, et al. Long-term Survival and Quality of Life among Survivors Discharged from a Respiratory ICU in North India: A Prospective Study. Indian J Crit Care Med 2022;26(10):1078-1085.

Feasibility and impact of screening for venous thromboembolism in treatment-naive lung cancer patients-Results of a prospective cohort study.

Background: Venous thromboembolism (VTE) in cancer remains underdiagnosed. This prospective study aimed to evaluate the feasibility of screening for VTE in lung cancer (LC) patients. We assess the incidence of VTE, its risk factors, and effects on overall survival (OS). Methods: Consecutive treatment-naive LC patients were screened for deep venous thrombosis (DVT) with compression ultrasonography and pulmonary thromboembolism (PTE) with computed tomography pulmonary angiography (CTPA) at diagnosis and after 3 months of treatment. The incidence rate of VTE (DVT and/or PTE) was calculated. Risk factors associated with VTE were assessed using logistic regression analysis. All participants were followed-up to 1 year after enrollment. OS was compared in LC subjects with and without VTE, using the Cox proportional hazard analysis. Results: Around 301 subjects with LC (stages IIIB-IV accounted for 83.1%) were enrolled, of which 16 had VTE (5.3%). The incidence rate of VTE was 90 per 1000 person-years (PY). PTE was asymptomatic in 27.3% of cases while all DVT episodes were symptomatic. The incidence rate of asymptomatic PTE identified during the screening was 17 per 1000 PY. The median duration from LC diagnosis to the VTE event was 96.5 days. Median OS was significantly less in VTE patients [161 versus 311 days; P = 0.007] and death was attributable to VTE in 50%. After adjusting for covariates, VTE (hazard ratio [HR] = 2.1), smoking (HR = 1.7), and Eastern cooperative oncology group performance status ≥2 (HR = 1.6) were independently associated with poor OS in LC. Conclusions: VTE occurs in approximately 1 in 20 newly-diagnosed patients with LC and is associated with decreased OS. Screening for PTE may be considered even in resource-limited settings.

UGT1A1 Gene Polymorphisms in Patients with Small Cell Lung Cancer Treated with Irinotecan-Platinum Doublet Chemotherapy and Their Association with Gastrointestinal Toxicity and Overall Survival.

BACKGROUND: Irinotecan (CPT11) is an important drug for small cell lung cancer (SCLC) chemotherapy (CTx). UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms can influence CPT11-related toxicity. This study aimed to assess prevalence of UGT1A1 polymorphisms and their association with clinical outcomes in patients with SCLC on CPT11-CTx. METHODS: An observational cohort of treatment-naïve patients with SCLC was given CPT11-platinum doublet at a referral center in North India over 3 years. Clinical outcomes assessed were hematological and gastrointestinal toxicity (Common Terminology Criteria for Adverse Events, version 3.0), response rates (RECIST), and overall survival (OS). Peripheral blood was drawn from all enrolled patients just prior to CPT11-CTx initiation, and genomic DNA was isolated. Genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism for UGT1A1*7, UGT1A1*6, and UGT1A1*27 and by PCR-DNA sequencing for UGT1A1*28. Patients were classified as homozygous wild-type (WT/WT), heterozygous mutant (WT/M), or homozygous mutant (M/M) for each polymorphism assessed. RESULTS: Of 140 patients enrolled, no mutant alleles were found for UGT1A1*27 or UGT1A1*7. Frequency of UGT1A1*6 polymorphisms (n = 111) was 89.2% for WT/WT, 8.1% for WT/M, and 2.7% for M/M. For UGT1A1*28 (n = 102), this was 41.2% for WT/WT, 43.1% for WT/M, and 15.7% for M/M. UGT1A1*6 WT/WT patients tolerated >95% predicted CPT11 dose more frequently (59.6% vs. 25.0% in WT/M-M/M combined group; p = .026). The UGT1A1*6 WT/M-M/M group also experienced severe (grade ≥3) diarrhea (41.7% vs. 17.2% in WT/WT; p = .044) and mucositis (41.7% vs. 8.1% in WT/WT; p = .005) more frequently. On multivariate logistic regression analysis, UGT1A1*6 WT/M-M/M status was the only variable associated with occurrence of both mucositis (odds ratio [OR], 10.4) and severe diarrhea (OR, 4.8). UGT1A1*28 WT/M-M/M patients had better OS (320 days [95% confidence interval, 203-437] vs. 216 days [95% confidence interval, 140-292] in WT/WT group; p = .047). On multivariate Cox proportional hazards analysis, UGT1A1*28 WT/M-M/M status was independently associated with better OS (hazard ratio, 0.35), whereas lack of objective radiological response, moderate/heavy smoking, and increasing age were associated with worse OS. CONCLUSION: UGT1A1*6 and UGT1A1*28 polymorphisms were associated with increased gastrointestinal toxicity and improved OS, respectively, in North Indian patients with SCLC receiving CPT11-CTx. IMPLICATIONS FOR PRACTICE: UGT1A1 gene polymorphisms are known to influence irinotecan-related toxicity. In this prospective cohort study of patients with small cell lung cancer receiving first-line irinotecan-platinum chemotherapy, the prevalence of UGT1A1*6 polymorphisms was found to be 10.8% UGT1A1*6 and 58.8% UGT1A1*28 homo/heterozygous mutant, respectively. UGT1A1*6 homo/heterozygous mutant status was associated with severe diarrhea and mucositis. UGT1A1*28 homo/heterozygous mutant status was independently associated with improved overall survival.

Thyroid dysfunction in non-small cell lung cancer patients treated with epidermal growth factor receptor and anaplastic lymphoma kinase inhibitors: Results of a prospective cohort.

OBJECTIVES: Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitors (TKIs) are the preferred treatment option for patients with advanced/metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations and ALK rearrangements respectively. TKIs can theoretically induce thyroid dysfunction via actions on many levels of the hypothalamic-pituitary-thyroid axis. However, there are no published studies on occurrence of thyroid dysfunction related to use of EGFR/ALK TKIs in lung cancer. The current study aimed to prospectively and comprehensively evaluate incidence of thyroid dysfunction in NSCLC patients treated with EGFR and ALK inhibitors. METHODS: This prospective observational study at a tertiary care referral hospital included histologically/cytologically proven advanced/metastatic NSCLC patients treated with EGFR and ALK inhibitors over a period of 15 months. Thyroid function tests (including anti-TPO antibody) were done at baseline and repeated every month for first three months and then every three monthly for 12 months. RESULTS: Six different drugs (EGFR and ALK inhibitors) were used for treatment of 50 NSCLC patients enrolled. Of these, four drugs caused thyroid dysfunction (EGFR inhibitors erlotinib, gefitinib and ALK inhibitors ceritinib, crizotinib). Thyroid dysfunction typically occurred at 1 month following start of TKI treatment. Prevalence of thyroid dysfunction was 8%. Distribution of subclinical (not requiring treatment) and overt thyroid dysfunction (requiring specific treatment) was 4% each. All patients were asymptomatic. Both patients with overt thyroid dysfunction had hypothyroidism while subclinical dysfunction was equally distributed between hypo- and hyper- thyroidism. All patients who developed thyroid dysfunction derived expected clinical benefit and none required TKI dose interruption or stoppage. CONCLUSIONS: NSCLC patients may need to be monitored for occurrence of thyroid dysfunction during treatment with EGFR and ALK TKIs.

Efficacy and safety of nintedanib in Asian patients with systemic sclerosis-associated interstitial lung disease: Subgroup analysis of the SENSCIS trial.

BACKGROUND AND OBJECTIVE: In the SENSCIS trial in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) (mL/year) over 52 weeks by 44% in comparison with placebo, with manageable adverse events in most patients. We analyzed the efficacy and safety of nintedanib in patients of Asian race. METHODS: Patients with SSc-ILD were randomized to receive nintedanib or placebo. The outcomes over 52 weeks were analyzed in Asian versus non-Asian patients. RESULTS: Of the 288 patients in each treatment group, 62 (21.5%) in the nintedanib group and 81 (28.1%) in the placebo group were Asian; 90.2% of the Asian patients were enrolled in Asian countries. In the placebo group, the rate of FVC decline over 52 weeks was consistent between Asian and non-Asian patients (-99.9 and -90.6 mL/year, respectively). The effect of nintedanib on reducing the rate of FVC decline over 52 weeks was consistent between Asian (difference, 44.3 mL/year [95% CI: -32.8, 121.4]) and non-Asian patients (difference, 39.0 mL/year [95% CI: -5.1, 83.1]) (treatment-by-time-by-subgroup interaction, p = 0.91). Diarrhea was the most frequent adverse event and was reported in similar proportions of Asian and non-Asian patients in the nintedanib group (80.6% and 74.3%, respectively) and placebo group (28.4% and 32.9%, respectively). CONCLUSIONS: In patients with SSc-ILD, nintedanib had a consistent benefit on slowing the progression of SSc-ILD in Asian and non-Asian patients, with a similar adverse event profile. TRIAL REGISTRATION: ClinicalTrials.gov NCT02597933.

A real-world study of the dosing and tolerability of pirfenidone and its effect on survival in idiopathic pulmonary fibrosis.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) often do not tolerate pirfenidone in the recommended dose of 2400 mg/day. The proportion of patients requiring dose reduction and its impact on survival in the real-world remain unclear. METHODS: Consecutive subjects with IPF were enrolled between March 2017 and June 2019. The maximum tolerated dose of pirfenidone (primary outcome) and adverse drug reactions (ADRs) were recorded. A post hoc logistic regression analysis was performed to evaluate the predictors of drug discontinuation due to ADRs. We also compared survival between the full-dose (2400 mg/day), reduced-dose (< 2400 mg/day), and the no-pirfenidone groups, with age and percentage of the predicted forced vital capacity (%pred FVC) as covariates. RESULTS: Of the 128 subjects (mean age, 67.4 years; 77.3% men) included, 115 were initiated on pirfenidone. Forty-nine (42.6%) and 51 (44.3%) subjects tolerated the full dose and reduced doses, respectively. Ninety-six (83.5%) subjects developed at least one ADR; anorexia dyspepsia, and nausea being the most common. Twenty-two subjects discontinued the drug; 15 of them due to ADRs. Body mass index < 20 kg/m2 was the only predictor of drug discontinuation due to ADRs. Among subjects newly initiated on treatment during the study period (n = 80), survival was longer (hazard ratio [interquartile range], 0.19 [0.04-0.96]; p = 0.045) in the full-dose but not the reduced-dose group (p = 0.08) compared with the no-pirfenidone group, after adjusting for covariates. CONCLUSION: Pirfenidone was tolerated in the full dose in a minority of patients with IPF and appears to improve survival only with the full dose. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 148-157).

Management of interstitial lung diseases: A consensus statement of the Indian Chest Society (ICS) and National College of Chest Physicians (NCCP).

BACKGROUND: Interstitial lung disease (ILD) is a complex and heterogeneous group of acute and chronic lung diseases of several known and unknown causes. While clinical practice guidelines (CPG) for idiopathic pulmonary fibrosis (IPF) have been recently updated, CPG for ILD other than IPF are needed. METHODS: A working group of multidisciplinary clinicians familiar with clinical management of ILD (pulmonologists, radiologist, pathologist, and rheumatologist) and three epidemiologists selected by the leaderships of Indian Chest Society and National College of Chest Physicians, India, posed questions to address the clinically relevant situation. A systematic search was performed on PubMed, Embase, and Cochrane databases. A modified GRADE approach was used to grade the evidence. The working group discussed the evidence and reached a consensus of opinions for each question following face-to-face discussions. RESULTS: Statements have been made for each specific question and the grade of evidence has been provided after performing a systematic review of literature. For most of the questions addressed, the available evidence was insufficient and of low to very low quality. The consensus of the opinions of the working group has been presented as statements for the questions and not as an evidence-based CPG for the management of ILD. CONCLUSION: This document provides the guidelines made by consensus of opinions among experts following discussion of systematic review of evidence pertaining to the specific questions for management of ILD other than IPF. It is hoped that this document will help the clinician understand the accumulated evidence and help better management of idiopathic and nonidiopathic interstitial pneumonias.

Management of interstitial lung diseases: A consensus statement of the Indian Chest Society (ICS) and National College of Chest Physicians (NCCP)

Interstitial lung disease (ILD) is a complex and heterogeneous group of acute and chronic lung diseases of several known and unknown causes. While clinical practice guidelines (CPG) for idiopathic pulmonary fibrosis (IPF) have been recently updated, CPG for ILD other than IPF are needed. Methods: A working group of multidisciplinary clinicians familiar with clinical management of ILD (pulmonologists, radiologist, pathologist, and rheumatologist) and three epidemiologists selected by the leaderships of Indian Chest Society and National College of Chest Physicians, India, posed questions to address the clinically relevant situation. A systematic search was performed on PubMed, Embase, and Cochrane databases. A modified GRADE approach was used to grade the evidence. The working group discussed the evidence and reached a consensus of opinions for each question following face-to-face discussions. Results: Statements have been made for each specific question and the grade of evidence has been provided after performing a systematic review of literature. For most of the questions addressed, the available evidence was insufficient and of low to very low quality. The consensus of the opinions of the working group has been presented as statements for the questions and not as an evidence-based CPG for the management of ILD. Conclusion: This document provides the guidelines made by consensus of opinions among experts following discussion of systematic review of evidence pertaining to the specific questions for management of ILD other than IPF. It is hoped that this document will help the clinician understand the accumulated evidence and help better management of idiopathic and nonidiopathic interstitial pneumonias.