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).

Retrospective Observational Study to Assess Safety and Tolerability of Nebulized Colistin for the Treatment of Patients With Pneumonia in Real-World Settings in Respiratory ICU.

INTRODUCTION: Colistin is used to treat hospital-acquired pneumonia and ventilator-associated pneumonia. However, direct drug deposition at the site of infection may improve its efficacy and reduce systemic exposure. The aim of this study was to assess the safety and tolerability of nebulized colistin among Indian patients diagnosed with pneumonia caused by multidrug-resistant gram-negative bacilli in real-world settings. METHODOLOGY: We retrospectively reviewed the medical records of patients treated with nebulized colistin for pneumonia. We assessed the adverse events and relevant abnormal laboratory findings of nebulized colistin therapy. RESULTS: All enrolled patients (N=30, males: 22, females: 8; average age: 71.06 years) were treated for 13.36 days. Almost 80% of patients had a history of shortness of breath, which was a major symptom when they were admitted to the hospital. The patients were administered nebulized colistin for an average of six days (8 hours per day). The most common dosing schedule was 1 million international units (MIU)/8 hours. No serious adverse event was observed, and only one patient died while on the treatment but the death was not related to colistin treatment. The average sequential organ failure assessment score for all patients was 6.5. CONCLUSION: Our study demonstrated the efficient clinical utility and well-tolerated safety profile of nebulized colistin in the treatment of patients with pneumonia. Neurotoxicity and nephrotoxicity were not reported. Since a significant percentage of patients were with chronic respiratory diseases, our study further indicates the safety and effectiveness of nebulized colistin in chronic obstructive pulmonary disease (COPD) patients too.

Impact of comorbidities and inflammatory markers on mortality of COVID-19 patients.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes coronavirus disease 2019 (COVID-19) is a serious global health concern. The severity of the disease can be determined by serologic indicators such as C-reactive protein, lactate dehydrogenase, D-dimer, ferritin, and interleukin-6. (IL-6). Patients with preexisting conditions such as respiratory, cardiovascular, and pulmonary disease could be at risk of adverse outcomes. It is crucial to provide adequate medical care to manage these patients and increase their chances of survival. AIM: The study examined the impact of comorbidity and inflammatory markers on the severity and mortality of hospitalised COVID-19 patients. MATERIALS AND METHODS: This retrospective study included 101 COVID-19 patients who had comorbidities and were hospitalised from April 2021 to April 2022. RESULTS: Patients with a severe COVID-19 infection could be anticipated to have higher levels of inflammatory markers in their blood. Patients with chronic kidney and coronary artery disease have a worse prognosis than those with other comorbidities (P value <0.001). However, tuberculosis had no statistically significant effect on mortality and showed a minimal chance of death (P value = 0.303). In addition, tocilizumab performed poorly and was ineffective against the COVID-19 treatment. However, ivermectin exhibited a statistically significant probability of survival in COVID-19 patients. CONCLUSION: The inflammatory markers D-dimer, ferritin, and IL-6 were identified as valuable indicators of disease severity. Further, chronic kidney disease and coronary artery disease were identified as risk factors for mortality, while tuberculosis showed potential protective effects. The study showed that higher neutrophil levels were linked to mortality in tocilizumab-treated patients, while ivermectin showed promise in increasing survival rates.

Genomic revolution: Transforming tuberculosis diagnosis and treatment with the use of Whole Genome Sequencing - A consensus statement.

Tuberculosis (TB) is a preventable, treatable, and curable disease. However, in 2020, 9∙9 million people were estimated to have developed tuberculosis, and 1.5 million people were estimated to have died from it. Whereas in India, 2.6 million were diagnosed with TB and 436,000 succumbed to TB in 2019. India (26%) is the major contributor to the global drop in TB cases. The COVID-19 pandemic has substantially reduced access to services for the diagnosis and treatment of TB, resulting in an increase in deaths and a reversal in global progress. [1] Presently, TB incidence is falling at a rate of 2% per year, obstructed mainly by the rearing pandemic of drug-resistant tuberculosis (DRTB). Particularly concerning is multi-drug resistant TB (MDRTB), defined as resistance towards isoniazid (INH) and rifampicin (RIF). [2] The World Health Organization (WHO) targeted to reduce worldwide TB incidence by 90% until 2035. (1) Early initiation of effective treatment based on susceptibility patterns of the Mycobacterium tuberculosis complex (MTBC) is considered key to successful TB control in countries with high DRTB incidence. Worldwide MDRTB treatment outcomes are poor, with cure rates less than 60% (2) due to the lack of comprehensive Drug Susceptibility Testing (DST) in most high MDRTB burden countries. This is leading to the inadequate anti-TB activity of the provided regimens (3-5), unlike regimens advised for DST assure optimal results. (6) In addition to resistances to the established regimens, the resistance to the newer DRTB drugs is increasing. On World TB Day 2022, Academy of Advanced Medical Education, Thyrocare Technologies Limited and HyastackAnalytics - IITB along with expert pulmonologist and renowned physicians from India convened for an advisory board meeting in Delhi on 20th March 2022 to discuss the role of Whole Genome Sequencing (WGS) in the diagnosis and management of TB. Objectives and specific topics relating to WGS in MDRTB were discussed, each expert shared their views, which led to a group discussion with a commitment to putting the patient first, and increasing their collective efforts, the organizations recognized that it is possible to make this goal a reality. The organizations involved in the discussion have declared their commitment to engaging in collaborative efforts to tackle DRTB detection efficiently. They advocate for strengthening access to WGS TB services, controlling and preventing TB, improving surveillance and drug resistance management, and investing in research and development. This Round Table serves as a framework to build on and ensure that the goal of ending TB is achievable with WGS services wherever needed. Post discussion, a uniform consensus was said to be arrived if more than 80% board members agreed to the statement. The present paper is the outcome of aspects presented and discussed in the advisory board meeting.

Expert Opinion on the Management of Acute and Chronic Cough: An Indian Perspective in Primary Care Setting.

Cough is the body's reflex when the throat or airway is irritated by a foreign body, such as irritants, microbes, and fluids. Cough caused due to a disorder or infection can last for a few days to a couple of weeks and is usually self-limiting and self-resolving. However, in certain cases, cough can persist for months, disrupting everyday activities, affecting the patient's mental health, and causing pain and fatigue. There are a number of different therapeutic strategies to manage acute and chronic cough, depending on the cause. Dry cough can be treated using opioids, nonopioids, antitussives, and antihistamines. Expectorants and mucolytics are widely used in the management of productive cough. The underlying cause of cough should be appropriately managed with specific therapy. The choice of treatment regimen is dependent on the patient's medical history, symptoms, and preexisting conditions. Based on the literature review and clinical practice, a comprehensive approach to the management of cough as a symptom has been proposed.

Scoring System for the Use of Nebulizers in the Primary Care Settings: An Expert Consensus Statement.

BACKGROUND: The use of nebulizers is an important and useful method for delivering drugs to the lungs in patients with various airway and lung parenchymal disorders. They are primarily used in patients with acute symptoms and in a selected group of patients for maintenance treatment. Its use has increased, especially during the coronavirus disease 2019 (COVID-19) pandemic. To ensure the appropriate use of nebulizers by primary care physicians and to guide them, we aimed to develop a simple nebulizer use score. METHODS: An expert working group (EWG) of pulmonologists were formed who using a semi- Delphi method, developed a list of variables and a cut-off score to decide when to use nebulizers. We started with a total of 55 variables that were developed through an exhaustive review of the literature. These were further reduced to smaller numbers that had the maximum score as well as concordance with the EWG. The scores ranged from 1 to 10 (completely disagree to completely agree), and only those above 7.5 were selected. RESULTS: A total of 8 variables with the highest scores were selected (Table 1), which had a total maximum score of 40. A score of <15 was suggested to indicate no use of nebulizer and >20 to suggest definite use of nebulizer. A score between 15 and 20 was suggested for physician judgment. A separate table of 12 conditions was made where the use of nebulizers was mandatory. CONCLUSION: This first-of-its-kind nebulizer score can be used by primary care physicians to decide which patients should be put on nebulizer treatment.

Navigating patient journey in early diagnosis of lung cancer in India.

Lung cancer (LC) is one of the leading causes of cancer deaths worldwide. In India, the incidence of LC is increasing rapidly, and a majority of the patients are diagnosed at advanced stages of the disease when treatment is less likely to be effective. Recent therapeutic developments have significantly improved survival outcomes in patients with LC. Prompt specialist referral remains critical for early diagnosis for improved patient survival. In the Indian scenario, distinguishing LC from benign and endemic medical conditions such as tuberculosis can pose a challenge. Hence, awareness regarding the red flags-signs and symptoms that warrant further investigations and referral-is vital. This review is an effort toward encouraging general physicians to maintain a high index of clinical suspicion for those at risk of developing LC and assisting them in refering patients with concerning symptoms to specialists or multidisciplinary teams as early as possible.

Validation of the Sarcoidosis Diagnostic Score in a Multicontinental Study.

Rationale: The Sarcoidosis Diagnostic Score (SDS) has been established to quantitate the clinical features consistent with sarcoidosis in a monocentric study. Objectives: We aimed to confirm the diagnostic value of SDS in a large, multicontinental study and to assess the utility of SDS in differentiating sarcoidosis from alternative diagnoses, including infectious and noninfectious granulomatous diseases. Methods: We included patients with biopsy-confirmed sarcoidosis at nine centers across the world. Patients without sarcoidosis seen at the same sites served as control patients. Using a modified World Association of Sarcoidosis and Other Granulomatous Disorders organ assessment instrument, we scored all patients for the presence of granuloma on biopsy, highly probable symptoms, and least probable symptoms for each area. Two sarcoidosis scores were generated: SDS Biopsy (with biopsy) and SDS Clinical (without biopsy). SDS Clinical and Biopsy were calculated for all patients. We calculated and compared the area under the curve (AUC) for SDS Clinical and Biopsy according to different diagnosis scenarios. Results: A total of 1,041 patients with sarcoidosis and 1,035 without sarcoidosis were included. The results for SDS Clinical (AUC, 0.888; 95% confidence interval [CI], 0.874-0.902) and SDS Biopsy (AUC, 0.979; 95% CI, 0.973-0.985) according to AUC were good to excellent for differentiating sarcoidosis from alternative diagnosis. SDS Clinical was less discriminatory in males (P = 0.01) and in high tuberculosis prevalence centers (P < 0.001). However, SDS Clinical (AUC, 0.684; 95% CI, 0.602-0.766) and SDS Biopsy (AUC, 0.754; 95% CI, 0.673-0.835) were not sufficiently discriminative for noninfectious granulomatous diseases, but both SDSs could differentiate sarcoidosis from infectious granulomatous diseases. Algorithms were proposed for the SDS Clinical and SDS Biopsy to assist the clinician in the diagnostic process, and cutoff values were proposed for the SDS Clinical and SDS Biopsy, allowing the diagnosis of sarcoidosis to be safely confirmed or rejected in most cases except for noninfectious granulomatous disease. Conclusions: This multicontinental study confirms that both SDS Clinical and SDS Biopsy have good to excellent performance in discriminating sarcoidosis from alternative diagnoses. Differences in the AUC were seen for high tuberculosis prevalence versus low tuberculosis prevalence centers and for males versus females. Both SDSs had good discriminatory function for infectious granulomatous disease but failed in cases of noninfectious granulomatous disease such as berylliosis.

Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Does inspiratory muscle training provide additional benefits during pulmonary rehabilitation in people with interstitial lung disease? A randomized control trial.

BACKGROUND: Interstitial lung disease (ILD) encompasses a diverse group of chronic lung conditions which is often characterized by inspiratory muscle weakness (IMW). Despite the potential importance of inspiratory muscle dysfunction in ILD, the effect of inspiratory muscle training (IMT) added to pulmonary rehabilitation (PR) in ILD largely remains unknown. OBJECTIVE: The primary objective of the present study was to evaluate the benefits of IMT added to PR on inspiratory muscle strength and secondary objectives were to assess its effects on functional capacity, health-related quality of life (HRQoL), pulmonary function test (PFT) and dyspnea in ILD along with IMW. METHODS: Fifty-one participants were randomly allocated into two groups; PR + IMT (n = 26) or PR alone (n = 25). The primary outcome [maximal inspiratory pressure (PImax)] and secondary outcomes [6-min walk distance (6MWD), St. George's Respiratory Questionnaire (SGRQ), PFT and modified Medical Research Council dyspnea scale (mMRC)] were evaluated before and after the 8-weeks intervention. Independent t-test or Mann Whitney-U test was applied for between-group comparisons while for within-group comparison Wilcoxon's Sign Rank test or paired t test was performed. RESULTS: At the end of 8 weeks exercise intervention inspiratory muscle strength (PImax + 11.10 cm H2O, p< .001), functional capacity (6MWD, + 47.90 m, p= .001), HRQoL (SGRQ-total - 4 points, p= .038) and dyspnea (mMRC dyspnea scale, -1.27, p< .001) improved significantly in PR+IMT group alone. CONCLUSION: Inclusion of IMT to PR may have superior benefits as compared to PR alone in ILD accompanied with IMW.

An early Indian experience with benralizumab - A compendium on severe asthma cases: a case series.

Background: Severe eosinophilic asthma (SEA), one of the phenotypes of asthma that is characterized by elevated blood eosinophil counts, is a common cause of uncontrolled asthma. Patients with SEA often experience severe persistent symptoms and have frequent exacerbations despite optimal inhaler therapy. They also have poor lung function and quality of life (QoL). Benralizumab (Fasenra), a monoclonal antibody, has been approved for managing cases of SEA. This series of six cases, the first of its kind from India, aims to add to the real-world evidence of benralizumab in India. Methods: Benralizumab 30 mg (once in four weeks for the first three doses followed by a dose every eight weeks for two years) was administered in six patients with symptoms of cough, breathlessness on exertion, and wheezing, diagnosed with SEA. The following were the endpoints assessed: (i) overlap between high immunoglobulin E (IgE) and eosinophilic asthma; (ii) reduction of exacerbations; (iii) withdrawal of oral corticosteroids; and (iv) improvement in lung function and QoL. Results: In all cases, management with benralizumab resulted in optimal clinical and functional improvement, a decline in systemic steroid use, and improved QoL. Conclusions: The cases presented here are the first of their kind in the Indian asthmatic population with all SEA patients demonstrating significant improvement in symptoms with the use of benralizumab.

Indian Guidelines on Nebulization Therapy.

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for its use, and the widening scope of this therapy; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including their disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection, and other adverse outcomes. Thus, it is imperative to have a proper national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in this practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997 which have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in various settings such as inpatient, out-patient, emergency room, critical care, and domiciliary use in India in a wide variety of indications to standardize nebulization practices and to address many other related issues; National College of Chest Physicians (India), commissioned a National task force consisting of eminent experts in the field of Pulmonary Medicine from different backgrounds and different parts of the country to review the available evidence from the medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines on it. The guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies, position papers, consensus reports, and recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts comprising of advisors, chairpersons, convenor and members, and such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions, followed by point-wise evidence statements based on the existing knowledge, and recommendations have been formulated.

ICS/Ultra LABA in the Treatment of Obstructive Airway Diseases: A Consensus of Indian Experts.

Inhaled corticosteroid and ultra-long-acting beta-agonist (ICS/uLABA) combination is a recent advancement in the armamentarium against obstructive airways diseases (OADs). The combination of ICS/uLABA has several advantages, creating a favorable landscape for its utilization. Fluticasone furoate/vilanterol trifenatate (FF/Vi) is one such example of an ICS/uLABA. It offers several benefits from both drugs, such as a convenient once daily dosing schedule; high lipophilicity; high receptor affinity of fluticasone furoate along with high functional selectivity and a quick onset of action of vilanterol. However, the Global Initiative for Asthma (GINA) as well as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines do not clearly define the positioning of ICS/uLABA compared to conventional ICS/LABAs. There are a few areas of uncertainty especially around the appropriate reliever strategy with ICS/uLABA in Asthma. The current consensus was planned with a group of Indian pulmonology experts to provide more clarity on the potential use of FF/Vi in Asthma and COPD. The clinical statements highlighted in this consensus manuscript address crucial clinical questions revolving around the efficacy and safety of FF/Vi as compared to conventional ICS/LABAs and identify the ideal patient profile for its use. This consensus paper also sheds light upon the appropriate reliever to be used along with FF/Vi in Asthma and the utilization of FF/Vi-based triple therapy in OADs. Expert recommendations mentioned in this paper will serve as guidance to pulmonologists as well as consultant physicians who are involved in providing care to OAD patients and will help them weigh the various factors that need to be taken into account while prescribing ICS/uLABA combination.

Vanishing lung syndrome masquerading as pneumothorax in a smoker: Now you see me, now you do not.

A rare clinical syndrome, giant bullous emphysema, also known by the name of vanishing lung syndrome (VLS), is characterized by an X-ray of the chest showing disappearance of the lung. VLS is a chronic disease that progresses gradually and is usually seen in young male smokers, with other risk factors being alpha-1 antitrypsin deficiency and marijuana abuse. Giant emphysematous bullae are a pathognomonic presentation with a preference towards the upper lobe of the lungs. These emphysematous bullae may remain dormant for a long duration before presenting as worsening dyspnoea. Computed tomography is an essential tool to diagnose VLS. The treatment modalities include surgical and thoracoscopic resection of the bullae. We have reported a rare case of VLS in a 58-year-old chronic smoker managed conservatively.

Paradoxical cause of weaning failure: Post tracheostomy foreign body causing non-resolving pneumonia with worsening failure to wean.

The Percutaneous technique for tracheostomy has become the standard procedure, due to its ease in placement, minimal complications, and has almost replaced the traditional open (surgical) tracheostomy in intensive care units. We describe a case of broken tracheal cartilage which slipped into the tracheobronchial tree following percutaneous tracheostomy (PCT), impinging and causing collapse of medial basal segment of right lower lobe.

Acute Exacerbation of Idiopathic Pulmonary Fibrosis With Pirfenidone and Nintedanib: A Friend or Foe.

Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) is unfortunate a deadly event with a very high mortality rate. Its occurrence is highly unpredictable, though few baseline risk factors have been identified. The revised definition of AE is more precise with clarity on defined parameters. However, no clear guidelines exist on treatment, with most therapies showing inconsistent benefits. Both the approved anti-fibrotic (pirfenidone and nintedanib) have shown equal efficacy in reducing the decline in lung functions, with few studies suggesting a drop in AE. We report a case of a patient with IPF with mildly impaired lung functions who was initiated on pirfenidone with dose titrated on a weekly basis but developed AE-IPF on day 10 of starting pirfenidone and after four days of doubling the dose from 600 mg/day to 1,200 mg/day. This raised the suspicion of whether pirfenidone played any role in this unfortunate event. With no response to conventional therapy of steroids and non-invasive ventilation for AE-IPF, initialization of nintedanib led to recovery with discharge of the patient in two weeks of hospitalization. This case highlights inadequacy in knowledge about the effects of these anti-fibrotics in IPF and recommends close monitoring in the future.

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.

Use of single-inhaler triple therapy in the management of obstructive airway disease: Indian medical experts' review.

Obstructive airway disease (OAD), which includes COPD and asthma, is the leading cause of morbidity and mortality in India. Long-acting bronchodilators (long-acting ß2 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.

Pulmonary-Renal Syndrome: A Real-World Experience From a Tertiary Care Pulmonary Center in North India.

BACKGROUND: Pulmonary renal syndrome (PRS) is a simultaneous occurrence of diffuse alveolar hemorrhage (DAH) and glomerulonephritis (GN). The diagnosis of PRS not only requires a high index of clinical suspicion and prompt management, but it is often fatal due to rapidly progressive clinical deterioration despite aggressive treatment. The authors, therefore, share the real-world experience of PRS presenting to tertiary care pulmonary center in north India. AIMS: The objectives of the study were to identify etiology, clinical manifestations, treatment modalities and outcomes of patients presenting with PRS. MATERIALS & METHODS: This was a retrospective observational study undertaken at Metro Centre for Respiratory Diseases of patients diagnosed with PRS during the last two years between 2019 and 2021. The patients diagnosed with PRS based on clinical manifestations, serology and biopsies were included in the study. All cases of non-immunological causes of PRS were excluded from the study. Chi-square and Mann-Whitney U tests were done to look for associations obtained between survivors and non-survivors. Cox regression analysis was done to estimate the hazard ratios of clinical variables on survival in PRS patients. RESULTS: A total of 12 patients of PRS were included in the study and diagnosis was made based on clinical manifestations, serology as well as biopsies. The mean age of presentation was 45.4 (± 17.8) years and 66.7% of the patients were females. The most common etiology was anti-nuclear cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) seen in 83.3% of the cases. The most common symptoms were coughing and fever (80%) followed by dyspnea and hemoptysis (70%) with the mean duration of symptoms being 17.1 (±8.9) days. The mortality of PRS patients in our study was 41.6% and these patients had a higher acute physiology and chronic health evaluation (APACHE) score (median-26) compared to those patients who survived (median - 15.8). CONCLUSION: The occurrence of PRS, although rare, presents with rapid clinical deterioration leading to a high mortality rate. AAV was the most common cause of PRS as observed in our study. Early recognition and prompt aggressive management strategies with immunosuppressant therapies are essential for better outcomes for the patients.