Treatment of idiopathic pulmonary fibrosis: an update on emerging drugs in phase II & III clinical trials.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating lung disease with poor prognosis. Although two antifibrotics have been approved in the past decade there are no curative therapies. AREAS COVERED: This review highlights the current landscape of IPF research in the development of novel compounds for the treatment of IPF while also evaluating repurposed medications and their role in the management of IPF. The literature search includes studies found on PubMed, conference abstracts, and press releases until March 2024. EXPERT OPINION: Disease progression in IPF is driven by a dysregulated cycle of microinjury, aberrant wound healing, and propagating fibrosis. Current drug development focuses on attenuating fibrotic responses via multiple pathways. Phosphodiesterase 4 inhibitors (PDE4i), lysophosphatidic acid (LPA) antagonists, dual-selective inhibitor of αvß6 and αvß1 integrins, and the prostacyclin agonist Treprostinil have had supportive phase II clinical trial results in slowing decline in forced vital capacity (FVC) in IPF. Barriers to drug development specific to IPF include the lack of a rodent model that mimics IPF pathology, the nascent understanding of the role of genetics affecting development of IPF and response to treatment, and the lack of a validated biomarker to monitor therapeutic response in patients with IPF. Successful treatment of IPF will likely include a multi-targeted approach anchored in precision medicine.

Disseminated coinfection with Mycobacterium Avium complex and Mycobacterium Kansasii in a patient with idiopathic CD4+ lymphocytopenia: A case report.

Simultaneously disseminated coinfection with two species of nontuberculous mycobacteria (NTM) is extremely rare and had been reported only in immunocompromised individuals. Here, we report a 59-year-old Thai man, previously healthy. He presented with a 2-month history of prolonged fever, constitutional symptoms, and hepatosplenomegaly. His chest and abdomen computed tomography illustrated multiple enlarged mediastinal lymph nodes accompanied with multifocal crazy-paving appearance in both lungs and hepatosplenomegaly. Endobronchial ultrasound-guided transbronchial needle aspiration was performed on the mediastinal nodes. The pathologic findings were necrotizing granulomatous lymphadenitis with numerous AFB-positive bacilli. Blood culture subsequently isolated M. intracellulare, while BAL and lymph node culture isolated M. intracellulare and M. kansasii, which confirmed species by multiplex PCR and 16s rRNA sequencing. Idiopathic CD4+ lymphocytopenia (ICL) was diagnosed as the cause of secondary immune deficiency. Intravenous imipenem, amikacin, and azithromycin were administered as an empirical antibiotic regimen for 4 weeks, then substituted to oral rifampicin, clarithromycin, moxifloxacin, and ethambutol as definitive regimen. Unfortunately, it was found that he had died unexpectedly at home after 4 months of treatment, possibly related to this illness. In our view, patients with severe disseminated NTM disease should be evaluated to explore a secondary immune deficiency disorder. An ICL is a rare heterogenous syndrome but should be considered.

Comparative efficacy of peptide-based versus standard polymeric enteral nutrition in ICU patients at high nutritional risk: a multicenter randomized controlled trial.

Within intensive care units (ICU), the administration of peptide-based formulas (PBF) may confer nutritional advantages for critically ill patients identified with heightened nutritional risk. This investigation aimed to ascertain the efficacy of PBF in comparison to standard polymeric formulas (SPF) among this patient cohort. A double-blind, randomized controlled trial was conducted across three ICUs, encompassing 63 adult patients characterized by elevated modified Nutrition Risk in Critically Ill (mNUTRIC) scores. Enrollment occurred promptly subsequent to ICU admission, with participants allocated to receive either PBF or SPF. Primary outcome was the duration to achieve caloric targets. Secondary outcomes involved the evaluation of mean daily gastric residual volume, mechanical ventilation period, infection rates within the ICU, length of hospitalization, mortality rates, nutritional status and inflammatory markers, specifically serum albumin and interleukin-6 levels. Patients in the PBF group reached their caloric targets more expeditiously compared to the SPF group (2.06 ± 0.43 days versus 2.39 ± 0.79 days; p = 0.03). No significant differences were discernible between the groups regarding gastric residual volume, duration of mechanical ventilation, ICU length of stay, mortality, or infection rates. Both cohorts exhibited minimal adverse effects and were devoid of any instances of abdominal distension. While not reaching statistical significance, the observed trends in albumin and interleukin-6 levels suggest a potential advantage of PBF utilization. The implementation of PBF enabled swifter attainment of caloric goals in ICU patients at high nutritional risk without adversely impacting other clinical parameters. Given its favorable tolerance profile and potential immunomodulatory properties, PBF may be considered a valuable nutritional intervention in this setting.Thai Clinical Trials Registry TCTR20220221006. Registered 21 February 2022, https://www.thaiclinicaltrials.org/show/TCTR20220221006 .

Prevalence and Risk Factors of Burnout Syndrome during COVID-19 Pandemic among Healthcare Providers in Thailand.

Objective: To study prevalence, risk factors, and consequences of the COVID-19 pandemic related to Burnout syndrome (BOS) among Thai healthcare providers (HCPs) during the COVID-19 pandemic. Methods: We performed a cross-sectional study among HCPs, involved in caring for patients during the pandemic in two periods (1st period, May-Jun 2021, and 2nd period, Sep-Oct 2021). Data were distributed using electronic questionnaires. BOS was defined if respondents exhibited a high level of at least one domain in the Maslach Burnout Inventory criteria. The primary outcome was prevalence of BOS. Results: Altogether, 2,027 and 1,146 respondents were enrolled in the 1st and 2nd periods, respectively. Most respondents were female (73.3, 68.2%). The top three job positions were physicians (49.2, 58.9%), nurses (41.2, 30.6%), and nursing assistants (4.8, 6.5%), respectively. No difference was found in overall prevalence of Burnout syndrome during the 1st and 2nd periods (73 vs. 73.5%, p=0.80). Using multivariate analysis, significant risk factors for Burnout syndrome in both periods were (1) living with family (odds ratio (OR) 1.3 and 1.5), (2) tertiary care hospital (OR 1.92 and 2.13), (3) nurse (OR 1.38 and 2.29), (4) nursing assistant (OR 0.92 and 4.81), (5) salary ≤40,000 THB (OR 1.53 and 1.53), (6) >20 patients per shift (OR 1.55 and 1.88), (7) >6 shifts after hours monthly (OR 1.26 and 1.49), and (8) ≤1 rest day weekly (OR 1.3 and 1.4). Conclusion: We found a high prevalence of Burnout syndrome among Thai HCPs during the pandemic. Knowing those risk factors may provide a strategy to BOS during the pandemic.

Pulmonary pseudoaneurysm presented as a lung nodule after recovering from Covid-19 pneumonia.

Pulmonary pseudoaneurysms (PAPs) are an uncommon complication of severe acute respiratory syndrome coronavirus 2 infection, although they are a potentially life-threatening condition. We present this interesting condition of severe coronavirus disease 2019 (Covid-19) pneumonia. The patient presented with abnormal lung nodule and developed massive haemoptysis after recovering from Covid-19 pneumonia. PAP was diagnosed by computed tomography angiography. Endovascular embolization was performed and the bleeding was stopped.

Effects of Farinelli Breating Exercise on Respiratory Function and Symptoms in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Farinelli breathing (FB) exercise is a typical breathing exercise used by singers. This study aimed to compare effects of FB exercise and diaphragmatic breathing (DB) exercise on respiratory function and symptoms in patients with chronic obstructive pulmonary disease (COPD). METHODS: Sixteen patients aged 51-80 years with mild or moderate COPD were recruited for this study. They were divided into two groups: DB group (n=8) and FB group (n=8). Both groups received complete breathing exercise training five times per week for 8 weeks. Their respiratory functions, COPD symptoms, cytokine levels, and oxidative stress variables were analyzed during pre- and post-tests. Dependent variables were compared between pre- and post-tests using paired t-tests. An independent t-test was used to compare variables between the groups. Differences were considered significant at p-lt;0.05. RESULTS: The maximal expiratory pressure (MEP), maximum oxygen consumption (VO2max), and COPD Assessment Test (CAT) scores changed significantly in the DB group after the 8-week intervention compared to those at pre-test, whereas force vital capacity, forced expiratory volume in the first second, maximum voluntary ventilation, maximal inspiratory pressure (MIP), MEP, VO2max, CAT score, tumor necrosis factor-α, and malondialdehyde level changed significantly in the FB group at post-test compared to those at pre-test. Moreover, both MIP and MEP in the FB group were significantly higher than those in the DB group. CONCLUSION: FB exercise improved respiratory functions and COPD symptoms of patients with COPD. It might be an alternative breathing exercise in pulmonary rehabilitation programs for patients with COPD.

Sarcoidosis developing after COVID-19: A case report.

COVID-19 has been implicated in the development of a range of autoimmune diseases and medical consequences. Sarcoidosis is an inflammatory disease with sustained granulomatous inflammation. The possible main pathogenesis of sarcoidosis is a dysregulation between immune response and certain environmental antigens. We present a case of sarcoidosis as an interesting sequela of COVID-19. The patient was hospitalized due to SARS-CoV-2 without complication. Ten weeks after the illness, his chest computed tomography (CT) showed bilateral hilar, paratracheal and subcarinal lymph node enlargement. Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) was performed; pathologic findings were that of well-formed non-necrotizing granulomas. Complete eye examination reported panuveitis and papillitis in both eyes. On the basis of these findings, sarcoidosis was diagnosed. Therefore, sarcoidosis developing after COVID-19 was suggested as a possible link between the viral infection and dysregulation of the inflammation process. However, further studies are needed to confirm this association.