Expert opinion on diagnosis and management of Severe Asthma in low and middle income countries (LMIC) with focus on India.

OBJECTIVE: In this document, 9 Indian experts have evaluated the factors specific to LMICs when it came to Severe Asthma (SA) diagnosis, evaluation, biologic selection, non-biologic treatment options, and follow-up. DATA SOURCES: A search was performed using 50 keywords, focusing on the Indian/LMICs perspective, in PubMed, Cochrane Library, and Google Scholar. The key areas of the search were focused on diagnosis, phenoendotyping, non-biological therapies, selecting a biologic, assessment of treatment response, and management of exacerbation. STUDY SELECTIONS: The initial search revealed 1826 articles, from these case reports, observational studies, cohort studies, non-English language papers, etc., were excluded and we short-listed 20 articles for each area. Five relevant articles were selected by the experts for review. RESULTS: In LMICs, SA patients may be referred to the specialist for evaluation a little late for Phenoendotyping of SA. While biologic therapy is now a standard of care, pulmonologists in LMICs may not have access to all the investigations to phenoendotype SA patients like fractional exhaled nitric oxide (FeNO), skin prick test (SPT), etc., but phenotyping of SA patients can also be done with simple blood investigations, eosinophil count and serum immunoglobulin E (IgE). Choosing a biologic in the overlapping phenotype of SA and ACO patients is also a challenge in the LMICs. CONCLUSIONS: Given the limitations of LMIC, it is important to select the right patient and explain the potential benefits of biological therapy. Non-biologic add-on therapies can be attempted in a resource-limited setting where biological therapy is not available/feasible for patients.

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).

Understanding the lived experience of idiopathic pulmonary fibrosis and how this shapes views on home-based pulmonary rehabilitation in Delhi, India.

OBJECTIVES: Pulmonary Rehabilitation (PR) is a high-impact intervention for individuals with idiopathic pulmonary fibrosis (IPF) but access is limited in India. PR barriers include distance to travel, lack of service provision and lack of healthcare professionals to deliver PR, thus it is disproportionate to the immense burden of IPF in India. We explored the lived experiences of people living with IPF, family caregivers (CGs) and healthcare workers (HCWs) as well as their views towards home-based PR (HBPR) in Delhi, India. METHODS: A qualitative study using semi-structured interviews with individuals with IPF (n = 20), CGs (n = 10) and HCWs (n = 10) was conducted. Data were analysed using codebook thematic analysis. RESULTS: Three major themes were generated: (i) Health impact, which included pathophysiological changes, range of symptoms experienced, disease consequences and impact of comorbidities; (ii) Disease management, which described strategies to control the progression and overall management of IPF, such as medications and exercises; (iii) Mode of Pulmonary Rehabilitation, which described perceptions regarding HBPR, comparisons with centre-based programmes, and how HBPR may fit as part of a menu of PR delivery options. CONCLUSION: People living with IPF, family caregivers and healthcare workers were positive about the potential implementation of HBPR and suggested the development of a paper-based manual to facilitate HBPR over digital/online approaches. The content of HBPR should be sensitive to the additional impact of non-IPF health issues and challenges of reduced interactions with healthcare professionals.

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.

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.

Real-world Experience with Favipiravir for Treatment of COVID-19 among Indian Healthcare Professionals.

INTRODUCTION: Favipiravir has shown promising results for COVID-19 globally. Though many Indian patients have received favipiravir, there is a lack of realworld data for its clinical use by the practicing physicians. Hence, a qualitative survey was conducted to understand real-world use of favipiravir in management of COVID-19. METHODS: A cross-sectional, web-based, qualitative survey was conducted between September 2020 to October 2020, among Indian physicians from various specialties involved in COVID-19 care and using favipiravir in their practice. Physicians were provided survey link having a structured questionnaire with 32 questions. They were enquired on- 1) demographics,practice information, 2) place of favipiravir in clinical practice, 3) treatment protocol for mild to moderate COVID-19, 4) dosage and duration of favipiravir, 5) effectiveness of favipiravir, 6) tolerability of favipiravir 7) global efficacy and safety assessment of favipiravir. RESULTS: A total of 500 physicians were contacted, of which 50 physicians completed the questionnaire. 25(50.0%) were from south zone followed by 12(24.0%) from west. . Majority physicians (47, 97.9%) stated that favipiravir was used for COVID-19 in outpatient setting. Favipiravir was considered as the current drug of choice for ' mild COVID-19 with fever(86.6%). All physicians agreed that favipiravir was being used as per the recommended dose.. A total of 75% & 62.5% physicians agreed to observed clinical improvement by around 3-5 days & 5-7 days in symptomatic mild & moderate COVID-19 respectively. CONCLUSION: Majority of the physicians considered favipiravir to be safe and effective in treatment of mild to moderate COVID-19.

Improving the optical performance of multi-chip LEDs by using patterned phosphor configurations.

In order to improve the color uniformity of multi-chip LEDs, a patterned phosphor configuration has been proposed by using pulsing spray process. The patterned phosphor has detached yellow and red phosphor regions matching every single LED chip. Optical performances of different phosphor parameters are experimentally investigated. The results show that the yellow central coating (YCC) configuration produces outstanding performance not only in chromatic uniformity but also in luminous. In comparison with the conventional phosphor coating, the YCC patterned phosphor LED can improve the luminous flux by 20.6%, and decrease the difference of the correlated color temperature (CCT) distribution from 1362K to 489K. We believe that the patterned phosphor configuration can be used for improving optical properties of multi-chip LEDs.

Interstitial Lung Disease in India. Results of a Prospective Registry.

RATIONALE: Interstitial lung disease (ILD) is a heterogeneous group of acute and chronic inflammatory and fibrotic lung diseases. Existing ILD registries have had variable findings. Little is known about the clinical profile of ILDs in India. OBJECTIVES: To characterize new-onset ILDs in India by creating a prospective ILD using multidisciplinary discussion (MDD) to validate diagnoses. METHODS: Adult patients of Indian origin living in India with new-onset ILD (27 centers, 19 Indian cities, March 2012-June 2015) without malignancy or infection were included. All had connective tissue disease (CTD) serologies, spirometry, and high-resolution computed tomography chest. ILD pattern was defined by high-resolution computed tomography images. Three groups independently made diagnoses after review of clinical data including that from prompted case report forms: local site investigators, ILD experts at the National Data Coordinating Center (NDCC; Jaipur, India) with MDD, and experienced ILD experts at the Center for ILD (CILD; Seattle, WA) with MDD. Cohen's κ was used to assess reliability of interobserver agreement. MEASUREMENTS AND MAIN RESULTS: A total of 1,084 patients were recruited. Final diagnosis: hypersensitivity pneumonitis in 47.3% (n = 513; exposure, 48.1% air coolers), CTD-ILD in 13.9%, and idiopathic pulmonary fibrosis in 13.7%. Cohen's κ: 0.351 site investigator/CILD, 0.519 site investigator/NDCC, and 0.618 NDCC/CILD. CONCLUSIONS: Hypersensitivity pneumonitis was the most common new-onset ILD in India, followed by CTD-ILD and idiopathic pulmonary fibrosis; diagnoses varied between site investigators and CILD experts, emphasizing the value of MDD in ILD diagnosis. Prompted case report forms including environmental exposures in prospective registries will likely provide further insight into the etiology and management of ILD worldwide.

Tombs of Aspergillus: A missed cause of recurrent respiratory infections in allergic bronchopulmonary aspergillosis.

Broncholithiasis is an often overlooked condition and has been associated with symptoms such as cough, hemoptysis, and recurrent respiratory infections. The most common mechanism of a broncholith formation is the enlargement and subsequent erosion of a lymph node into an adjacent airway. Here, we describe this entity in a patient with advanced allergic bronchopulmonary aspergillosis, with chronic hypercapnic respiratory failure, and with frequent infective exacerbations. These frequent exacerbations were initially attributed to the poor lung function of the patient and the inability to cough out the secretions. The diagnosis of broncholithiasis was eventually established on bronchoscopy, when the patient was intubated and mechanically ventilated. In this patient, the mixed broncholiths were not associated with mediastinal lymphadenopathy and with biopsy showing Aspergillus with no lymph node tissue indicating its bronchial origin. A high index of suspicion should be kept in patients with recurrent infective exacerbations of pulmonary diseases, especially when computed tomography images show calcifications in the vicinity of airways even in the absence of lymphadenopathy, as most of these can be treated with routine bronchoscopic interventions.

Crimean-Congo hemorrhagic fever: An emerging threat for the intensivist.

We present the case of a 55-year-old female, who presented with 15 days of fever with rash, pancytopenia, and altered behavior. She was investigated for routine causes of fever with rash and multi organ dysfunction and treated for the same. As she tested negative for all routine causes of such an illness and did not show improvement to therapy, she was investigated for Crimean-Congo hemorrhagic fever and tested positive for the same. She was started on ribavirin, but eventually succumbed to her illness. This disease has rarely been reported from the Northern India and we need to have high clinical suspicion for this deadly disease so that appropriate therapy can be started in time for the patient and prophylaxis given to all inadvertently exposed.

The effect of a short-term pulmonary rehabilitation on exercise capacity and quality of life in patients hospitalised with acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Recent research shows that pulmonary rehabilitation (PR) programmes in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), reduced dyspnoea, improved exercise capacity, and prevented occurrence of further exacerbations. OBJECTIVE: To evaluate the utility of a 3-week PR programme in patients with AECOPD. METHODS: Patients admitted with AECOPD, following clinical stabilisation in the respiratroy intensive care unit (RICU), were alternately assigned to intervention (n=15); and control groups (n=15), respectively. Baseline assessment included spirometry, six-minute walk test (6MWT), symptom limited cardiopulmonary exercise test (CPET), health-related quality of life (HRQoL) assessment by generic questionnaire medical outcomes study short form (S-F 36) questionnaire and dyspnoea evaluation by Borg score. The intervention group patients were treated with usual care plus PR exercises in the form of 20 minutes each of walking, bicycle ergometry and resistance exercises, thrice-weekly for three weeks. The control group patients were treated with only the usual care. After discharge from hospital the treatment regimens were continued on alternate days on outpatient basis, for a total of three weeks. The assessment was repeated in both the groups after three weeks. RESULTS: Nine sessions of PR exercises produced statistically significant improvement in general well-being, forced expiratory volume in the first second (FEV1), 6MWT parameters, exercise capacity, peak oxygen uptake and volume of oxygen consumption (VO2)/Watts slope on CPET in patients with AECOPD. CONCLUSION: Short duration PR programmes appear to be helpful in the management of AECOPD.

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.

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.

A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation.

OBJECTIVES: To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. DESIGN: Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial. SETTING: Two hundred and thirty-three ICUs in 17 countries. PATIENTS: All adult patients admitted with sepsis and suspected disseminated intravascular coagulation as assessed using a modified International Society on Thrombosis and Hemostasis score. INTERVENTIONS: Patients were randomized to receive IV ART-123 (0.06 mg/kg/d) for 6 days or placebo, in addition to standard of care. The primary endpoint was reduction in mortality. Secondary endpoints included reversal of overt disseminated intravascular coagulation and reduction in disease severity. MEASUREMENTS AND MAIN RESULTS: A total of 750 patients were randomized, nine of whom did not receive the allocated treatment so that 371 patients received ART-123 and 370 received placebo. There were no meaningful differences between the two groups in any of the baseline variables. Twenty-eight-day mortality was 17.8% in the ART-123 group and 21.6% in the placebo group (Cochran-Mantel-Haenszel two-sided p value of 0.273 in favor of ART-123, which met the predefined statistical test for evidence suggestive of efficacy). There were no statistically significant differences in event-free and alive days between the two groups. d-dimer, prothrombin fragment F1.2 and TATc concentrations were lower in the ART-123 group than in the placebo group. There were no differences between the two groups in organ function, inflammatory markers, bleeding or thrombotic events or in the development of new infections. In post hoc analyses, greatest benefit from ART-123 was seen in patients with at least one organ system dysfunction and an international normalized ratio greater than 1.4 at baseline. CONCLUSIONS: ART-123 is a safe intervention in critically ill patients with sepsis and suspected disseminated intravascular coagulation. The study provided evidence suggestive of efficacy supporting further development of this drug in sepsis-associated coagulopathy including disseminated intravascular coagulation. Future study should focus on using ART-123 in the subgroup of patients most likely to respond to this agent.

Intravenous anidulafungin followed optionally by oral voriconazole for the treatment of candidemia in Asian patients: results from an open-label Phase III trial.

BACKGROUND: Candidemia is a significant cause of morbidity and mortality in hospitalized patients, particularly in Asia. Anidulafungin has been reported to be an effective treatment for candidemia in Western populations, but little is known about its efficacy in Asian patients, where the clinical presentation and epidemiology may be different. METHODS: An open-label study of anidulafungin for the treatment of candidemia was recently conducted in several Asian countries. Treatment was initiated with intravenous anidulafungin, given for at least 5 days, with the option to complete treatment with oral voriconazole. The primary endpoint was global (clinical and microbiological) response, and the primary analysis was the proportion of patients in the modified intent-to-treat population with successful global response at the end of therapy. Secondary analyses included proportion with successful global response in clinically relevant patient subgroups. The safety and tolerability profile of anidulafungin and voriconazole in this population was also investigated. RESULTS: Forty-three patients were studied, including 42 in the modified intent-to-treat population. Eighteen patients were > 65 years, the largest age subgroup, and 21 had central venous catheters. The most common Candida species causing infection were C. tropicalis (n = 18) and C. albicans (n = 10). In the primary analysis, 73.8% had a successful global response at end of therapy. Success rates in subgroups were: 72.2% for C. tropicalis and 71.4% for C. albicans infection, 58.8% for patients > 65 years, and 81.0% for patients with central venous catheters. Safety and tolerability were comparable with the known profiles for anidulafungin (and voriconazole). CONCLUSIONS: Although the epidemiology of Candida infections was different in this open-label study, the efficacy of anidulafungin in Asian patients with documented candidemia was consistent with previous studies in Western populations. No new safety concerns were identified. TRIAL REGISTRATION: http://www.clinicaltrials.gov identifier NCT00537329.

Echinocandins in invasive candidiasis.

We summarise a recent meeting, sponsored by Pfizer Inc., where experts in Asia shared their clinical experience in managing IC. The echinocandins have demonstrated good activity against non-albicans infections and also azole-resistant strains, both preclinically and in recent clinical trials. As well as proving efficacious, echinocandins have a favourable safety profile and are well tolerated, including among inpatient subpopulations, such as transplant recipients and those with renal or hepatic dysfunction. In addition the echinocandins generally have minimal drug-drug interactions, unlike the oral azoles, which have multiple effects on cytochrome P450-mediated drug metabolism. Echinocandins are characterised by a good safety profile, few drug-drug interactions and good susceptibilities. With the increase in potentially azole-resistant non-albicans infections, echinocandins may become the first-line treatment of choice for many patients.

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.