Semin Respir Crit Care Med. 2023 Apr 18. doi: 10.1055/s-0043-1766117. Online ahead of print.

ABSTRACT

Lung diseases caused by workplace exposure are too often mis- or underdiagnosed due in part to nonexistent or inadequate health surveillance programs for workers. Many of these diseases are indistinguishable from those that occur in the general population and are not recognized as being caused at least in part by occupational exposures. More than 10% of all lung diseases are estimated to result from workplace exposures. This study reviews recent estimates of the burden of the most important occupational lung diseases using data published by United Nations specialized agencies as well as the Global Burden of Disease studies. We focus on occupational chronic respiratory disease of which chronic obstructive lung disease and asthma are the most significant. Among occupational cancers, lung cancer is the most common, and is associated with more than 10 important workplace carcinogens. Classic occupational interstitial lung diseases such as asbestosis, silicosis, and coal workers' pneumoconiosis still comprise a substantial burden of disease in modern industrial societies, while other occupational causes of pulmonary fibrosis and granulomatous inflammation are frequently misclassified as idiopathic. Occupational respiratory infections gained prominence during the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic, eclipsing influenza and tuberculosis and other less common workplace infectious agents. The most significant risks are workplace exposures to particulate matter, gases, and fumes as well as occupational carcinogens and asthmagens. We present data on the burden of disease measured by deaths attributable to occupational respiratory disease as well as disability-adjusted years of life lost. Where available, prevalence and incidence data are also presented. These diseases are unique in that they are theoretically 100% preventable if appropriate exposure controls and workplace medical surveillance are implemented. This remains a continuing challenge globally and requires steadfast commitment on the part of government, industry, organized labor, and the medical profession.

PMID:37072021 | DOI:10.1055/s-0043-1766117

Eur Rev Med Pharmacol Sci. 2023 Apr;27(7):3045-3052. doi: 10.26355/eurrev_202304_31938.

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate New York Heart Association (NYHA) class and systolic pulmonary artery pressure (sPAP) as survival predictors in major interstitial lung diseases (ILD) including idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP) and hypersensitivity pneumonitis (HP) and in other ILD like granulomatosis with polyangiitis (GPA).

PATIENTS AND METHODS: We analyzed survival, NYHA class, sPAP, and Octreoscan uptake index (UI) in 104 ILD patients (59 IPF, 19 NSIP, 10 HP and 16 GPA; median age 60.5 years) all referred to a single centre.

RESULTS: Median survival was 68 months, with 1- and 2-year survival of 91% and 78%, respectively. Survival was lower among IPF and NSIP vs. HP and GPA patients (p=0.01). NYHA class 3-4 was more frequent among IPF (76.3%) vs. NSIP patients (31.6%; p<0.001). HP and GPA had NYHA class 1-2. NYHA class was negatively associated with survival (class 1=90.3 months vs. class 3=18.3 months and class 4=5.1 months; p=0.001). sPAP was >55 mmHg in 76.3% of patients with IPF and 35-55 mmHg in 63.2% of patients with NSIP. Patients with HP and GPA had sPAP < 55 mmHg. Among patients with IPF, NYHA and sPAP were negatively associated with survival (p<0.01) both showed a parallel trend. High-resolution computed tomography and survival were worse among IPF and NSIP vs. HP and GPA patients (p<0.001). Octreoscan UI was <10, 10-12, and >12 in IPF, NSIP, HP and GPA, respectively. Octreoscan UI was negatively associated with survival (p=0.002).

CONCLUSIONS: NYHA class and sPAP are comparable ILD survival predictors. NYHA class is correlated with worse prognosis for IPF and NSIP vs. HP and GPA patients.

PMID:37070907 | DOI:10.26355/eurrev_202304_31938

Eur Rev Med Pharmacol Sci. 2023 Apr;27(7):3033-3044. doi: 10.26355/eurrev_202304_31937.

ABSTRACT

OBJECTIVE: Small airway dysfunction is a pathological component of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), and impulse oscillometry is an easy-to-administer, effort-independent non-invasive test reflecting small airway dysfunction. We aimed to compare the impulse oscillometry (IOS) measurements between COPD and IPF patients and investigate their correlation with severity of both diseases and other conventional parameters.

PATIENTS AND METHODS: This was a prospective, longitudinal study. We longitudinally evaluated the baseline demographic characteristics, COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scale, Pulmonary Function Test (PFT), Carbon Monoxide Diffusing Capacity (DLCO), Hemogram and Impulse Oscillometry measurements of the patients diagnosed with COPD and IPF.

RESULTS: The study included 60 IPF patients and 48 COPD patients. The CAT and mMRC scores were higher in COPD patients. The majority of COPD patients were classified into Category B (46%), while 68% of IPF patients had Stage 1 GAP. The mean FEF 25-75%, which is typically considered to reflect small airway disease, was 93% in IPF patients, while it was significantly lower in COPD patients (29%). Impulse oscillometry measurements were consistent with spirometry parameters. IOS resistance and reactance values were significantly higher in COPD patients than in IPF patients.

CONCLUSIONS: IOS is advantageous in COPD and IPF patients who cannot exhale due to severe dyspnea, as it is easy to administer and reflects small airway resistance better. Diagnosis of small airway dysfunction may be beneficial in the management of patients with IPF and COPD.

PMID:37070906 | DOI:10.26355/eurrev_202304_31937

BMC Pulm Med. 2023 Apr 17;23(1):123. doi: 10.1186/s12890-023-02409-4.

ABSTRACT

INTRODUCTION: In Pakistan, chronic respiratory conditions contribute a large burden of morbidity and mortality. A major reason for this is the lack of availability of local evidence-based clinical practice guidelines (EBCPGs) in Pakistan, particularly at the primary care level. Thus, we developed EBCPGs and created clinical diagnosis and referral pathways for the primary care management of chronic respiratory conditions in Pakistan.

METHODS: The source guidelines were selected by two local expert pulmonologists after a thorough literature review on PubMed and Google Scholar from 2010 to December 2021. The source guidelines covered idiopathic pulmonary fibrosis, asthma, chronic obstructive pulmonary disorders, and bronchiectasis. The GRADE-ADOLOPMENT process consists of three key elements: adoption (using recommendations as is or with minor changes), adaptation (effective context-specific changes to recommendations) or additions (including new recommendations to fill a gap in the EBCPG). We employed the GRADE-ADOLOPMENT process to adopt, adapt, adopt with minor changes, or exclude recommendations from a source guideline. Additional recommendations were added to the clinical pathways based on a best-evidence review process.

RESULTS: 46 recommendations were excluded mainly due to the unavailability of recommended management in Pakistan and scope beyond the practice of general physicians. Clinical diagnosis and referral pathways were designed for the four chronic respiratory conditions, explicitly delineating the role of primary care practitioners in the diagnosis, basic management, and timely referral of patients. Across the four conditions, 18 recommendations were added (seven for IPF, three for bronchiectasis, four for COPD, and four for asthma).

CONCLUSION: The widespread use of the newly created EBCPGs and clinical pathways in the primary healthcare system of Pakistan can help alleviate the morbidity and mortality related to chronic respiratory conditions disease in the country.

PMID:37069600 | DOI:10.1186/s12890-023-02409-4

ERJ Open Res. 2023 Apr 17;9(2):00487-2022. doi: 10.1183/23120541.00487-2022. eCollection 2023 Mar.

ABSTRACT

BACKGROUND: We have previously reported arterial remodelling in patients with idiopathic pulmonary fibrosis (IPF) and suggested that endothelial-to-mesenchymal transition (EndMT) might be central to these changes. This study aims to provide evidence for active EndMT in IPF patients.

METHODS: Lung resections from 13 patients with IPF and 15 normal controls (NCs) were immunostained for EndMT biomarkers: vascular endothelial cadherin (VE-cadherin), neural cadherin (N-cadherin), S100A4 and vimentin. Pulmonary arteries were analysed for EndMT markers by using computer- and microscope-assisted image analysis software Image ProPlus7.0. All the analysis was done with observer blinded to subject and diagnosis.

RESULTS: Increased expression of mesenchymal markers N-cadherin (p<0.0001), vimentin (p<0.0001) and S100A4 (p<0.05) was noted with downregulation of junctional endothelial VE-cadherin (p<0.01) in the intimal layer of the arteries from patients with IPF compared to NCs. Cadherin switch was observed in IPF patients, showing increase in endothelial N-cadherin and decrease in VE-cadherin (p<0.01). There was also VE-cadherin shift from junctions to cytoplasm (p<0.01), effecting endothelial cell integrity in patients with IPF. In IPF, individual mesenchymal markers vimentin and N-cadherin negatively correlated with diffusing capacity of the lungs for carbon monoxide (r'= -0.63, p=0.03 and r'= -0.66, p=0.01). Further, N-cadherin positively correlated with arterial thickness (r'=0.58, p=0.03).

CONCLUSION: This is the first study to demonstrate active EndMT in size-based classified pulmonary arteries from IPF patients and potential role in driving remodelling changes. The mesenchymal markers had a negative impact on the diffusing capacity of the lungs for carbon monoxide. This work also informs early origins of pulmonary hypertension in patients with IPF.

PMID:37077555 | PMC:PMC10107070 | DOI:10.1183/23120541.00487-2022

ERJ Open Res. 2023 Apr 17;9(2):00584-2022. doi: 10.1183/23120541.00584-2022. eCollection 2023 Mar.

ABSTRACT

This article contains a selection of scientific highlights in the field of interstitial lung diseases (ILDs) presented at the hybrid European Respiratory Society International Congress 2022. Early Career Members of Assembly 12 summarise recent advances in translational and clinical research in idiopathic interstitial pneumonias, ILDs of known origin, sarcoidosis and other granulomatous diseases, and rare ILDs. Many studies focused on evaluation of diagnostic and prognostic (bio)markers, and novel pharmacological and nonpharmacological treatment options for different ILDs. In addition, new insights in clinical, physiological and radiological features of various rare ILDs were presented.

PMID:37077550 | PMC:PMC10107062 | DOI:10.1183/23120541.00584-2022

Respir Physiol Neurobiol. 2023 Apr 17:104064. doi: 10.1016/j.resp.2023.104064. Online ahead of print.

ABSTRACT

This study aimed to investigate the physical functioning predictors for health-related quality of life (HRQL) decline in patients with idiopathic interstitial fibrosis (IPF), sarcoidosis and other interstitial lung disease (ILD). The study enrolled 52 patients with ILD and 16 healthy individuals. Participants' HRQL was assessed using the 36-item Short-Form Health Survey questionnaire. Spirometry, physical performance, and daily physical activity (PA) were monitored. Patients with IPF showed significantly lower PA compared to patients with other ILD (p =0.002)and sarcoidosis (p =0.01). The type of disease aetiology had no significant effect on aerobic capacity, HRQL and fatigue. Patients with ILD showed significant greater fatigue, lower physical functioning and greater physical aspects scores compared to the control group (F=6.0; p=0.018; F=12.64; p=0.001, respectively). A significant positive correlation was observed between 6-minute walking distance (6MWD) and the physical domain of HRQL (r=0.35, p=0.012) and PA and the physical aspects of HRQL (r=0.37, p=0.007). This study revealed that the key predictors for HRQL decline were lower lung function, lower PA and physical performance.

PMID:37076026 | DOI:10.1016/j.resp.2023.104064

J Lipid Res. 2023 Apr 17:100375. doi: 10.1016/j.jlr.2023.100375. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with significant mortality. Prognostic biomarkers to identify rapid progressors are urgently needed to improve patient management. Since the lysophosphatidic acid (LPA) pathway has been implicated in lung fibrosis in preclinical models and identified as a potential therapeutic target, we aimed to investigate if bioactive lipid LPA species could be prognostic biomarkers that predict disease progression in IPF. LPAs and lipidomics were measured in baseline placebo plasma of a randomized IPF controlled trial using a quantitative LPA assay and LipidyzerTM, respectively. The association of lipids with disease indices including lung function decline, exacerbation, death and radiographic progression were assessed using statistical models. Compared to healthy, IPF patients had significantly higher levels of five LPAs (LPA16:0, 16:1, 18:1, 18:2, 20:4) and reduced levels of two triglycerides (TAG) species (TAG48:4-FA12:0 and -FA18:2) (FDR<0·05, fold change>2). Patients with higher levels of LPAs had greater declines in DLCO over 52 weeks (p<0·01); additionally, LPA20:4-high patients (≥median) had earlier time to exacerbation compared to LPA20:4-low (<median) subgroup (hazard ratio (95% CI)): LPA20:4-high=5·71 (1·17-27·72) (p=0·031). Higher baseline LPAs were associated with greater increases in fibrosis in lower lungs as quantified by high-resolution computed tomography at week 72 (p<0·05). Some of these LPAs were positively associated with biomarkers of profibrotic macrophages (CCL17, CCL18, OPN, and YKL40) and of lung epithelial damage (sRAGE and SPD) (p<0·05). Our study established the association of LPAs with disease progression in IPF patients, further supporting the role of the LPA pathway in IPF pathobiology.

PMID:37075981 | DOI:10.1016/j.jlr.2023.100375

Intern Emerg Med. 2023 Apr 17. doi: 10.1007/s11739-023-03267-y. Online ahead of print.

ABSTRACT

Retrospective study comparing pulmonary hypertension risk in systemic sclerosis (SSc) and non-SSc interstitial lung disease patients with usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Retrospective analysis of 144 interstitial lung disease patients, 53 SSc (32 UIP and 21 NSIP) and 91 non-SSc (47 UIP and 44 NSIP). Pulmonary hypertension was diagnosed as pulmonary systolic artery pressure (PAPs) > 25 mmHg. All SSc and non-SSc patients with pulmonary hypertension were classified WHO Group 3. Pulmonary hypertension was identified in 21/32 (65.6%), 9/21 (42.8%), 14/47 (29.7%), and 28/44 (45.4%) SSc-UIP, SSc-NSIP, control-UIP, and control-NSIP groups, respectively. PAPs mean of SSc-UIP group was higher than control-UIP group (32.6 ± 9.8 vs 28.5 ± 6.6, p-value = 0.02). PAPs mean of SSc-NSIP group was lower than control-NSIP group (27.0 ± 7.1 vs 33.9 ± 8.8, p = 0.002). Frequency of patients with PAP > 25 mmHg in SSc-UIP group was 60% higher in comparison to control-UIP (OR = 1.62, 95% CI 0.51-5.16) and SSc-NSIP (OR = 1.60, 95% CI 0.45-5.70) groups. Logistic regression analysis estimating the linear trend per ten-unit increase in PAPs levels demonstrated an increment for the SSc-UIP group compared to the control-UIP (OR = 2.64, 95% CI 1.25-5.58, p = 0.01) and the control-NSIP (OR = 6.34, 95% CI 2.82-14.3, p < 0.001) groups. The case-control study confirms that pulmonary hypertension is frequently found in SSc patients and demonstrates, for the first time, a significant increased risk of pulmonary hypertension among SSc-UIP patients.

PMID:37069417 | DOI:10.1007/s11739-023-03267-y

Curr Comput Aided Drug Des. 2023 Apr 17. doi: 10.2174/1573409919666230417080832. Online ahead of print.

ABSTRACT

AIM: Idiopathic pulmonary fibrosis is a chronic progressive disorder and is diagnosed as post-COVID fibrosis. Idiopathic pulmonary fibrosis has no effective treatment because of the low therapeutic effects and side effects of currently available drugs.

INTRODUCTION: The aim is to screen new inhibitors against idiopathic pulmonary fibrosis from traditional Chinese medicines.

METHODS: Few-shot-based machine learning and molecule docking were used to predict the potential activities of candidates and calculate the ligand-receptor interactions. In vitro A549 cell model was taken to verify the effects of the selected leads on idiopathic pulmonary fibrosis.

RESULTS AND DISCUSSION: A logistic regression classifier model with an accuracy of 0.82 was built and, combined with molecule docking, used to predict the activities of candidates. 6 leads were finally screened out and 5 of them were in vitro experimentally verified as effective inhibitors against idiopathic pulmonary fibrosis.

CONCLUSION: Herbacetin, morusin, swertiamarin, vicenin-2, and vitexin were active inhibitors against idiopathic pulmonary fibrosis. Swertiamarin exhibited the highest anti-idiopathic pulmonary fibrosis effect and should be further in vivo investigated for its activity.

PMID:37066777 | DOI:10.2174/1573409919666230417080832

J Thorac Dis. 2023 Mar 31;15(3):1486-1493. doi: 10.21037/jtd-22-535. Epub 2023 Mar 6.

ABSTRACT

BACKGROUND: Radical treatment for non-small cell lung cancer (NSCLC) combined with idiopathic pulmonary fibrosis (IPF) is challenging to plan due to the invasiveness of lung cancer and an acute exacerbation (AE) of IPF that is sometimes lethal.

METHODS: We intend to conduct the PIII-PEOPLE study (NEJ034), which is a phase III multicenter prospective randomized controlled clinical trial, to validate the effect of perioperative pirfenidone therapy (PPT), involving oral pirfenidone (600 mg) administration for 14 days after registration followed by oral pirfenidone (1,200 mg) for more than 14 days before surgery, with additional oral pirfenidone resumed and continued after surgery. Another group (control) will be allowed to perform any AE preventative treatment, excluding anti-fibrotic agents. Surgery without any preventative measures is also allowed in the control group. The primary endpoint is the IPF exacerbation rate within 30 days postoperatively. The data analysis will be performed in 2023-2024.

DISCUSSION: This trial will validate the perioperative AE suppression effect of PPT, and survival benefits including overall, cancer-free, and IP progression free survival due to PPT. It leads to the establishment of an optimized therapeutic strategy for NSCLC combined with IPF.

TRIAL REGISTRATION: This trial has been registered at the UMIN Clinical Trials Registry as UMIN000029411 (http://www.umin.ac.jp/ctr/).

PMID:37065585 | PMC:PMC10089862 | DOI:10.21037/jtd-22-535

Front Immunol. 2023 Mar 29;14:1146904. doi: 10.3389/fimmu.2023.1146904. eCollection 2023.

ABSTRACT

Interstitial lung disease (ILD) is one of the most serious lung complications of connective tissue disease (CTD). The application of proteomics in the past decade has revealed that various proteins are involved in the pathogenesis of each subtype of CTD-ILD through different pathways, providing novel ideas to study pathological mechanisms and clinical biomarkers. On this basis, a multidimensional diagnosis or prediction model is established. This paper reviews the results of proteomic detection of different subtypes of CTD-ILD and discusses the role of some differentially expressed proteins in the development of pulmonary fibrosis and their potential clinical applications.

PMID:37063894 | PMC:PMC10090492 | DOI:10.3389/fimmu.2023.1146904

JTCVS Open. 2022 Dec 10;13:389-410. doi: 10.1016/j.xjon.2022.11.018. eCollection 2023 Mar.

ABSTRACT

OBJECTIVE: Sputum is a source of exfoliated respiratory epithelial cells transformed early in lung carcinogenesis. Malignant cells are hypomethylated and contain less genomic 5-methylcytosine (5mC). Validating a test that recognizes and quantifies aberrantly hypomethylated cells in sputum, we assessed its potential as a screening tool for detecting early-stage non-small cell lung cancer.

METHODS: Cells extracted from sputum were immunofluorescence labeled with an anti-5-methylcytosine antibody and counterstained with 4',6-diamidino-2-phenylindole (DAPI) delineating global nuclear DNA (gDNA). Via confocal scanning and 3-dimensional image analysis, fluorescence 5mC and DAPI signals were measured in segmented cell nuclei, and a 5mC/DAPI co-distribution map was generated for each imaged cell. Cells were classified as hypomethylated based on 5mC load and 5mC/DAPI co-distribution. The proportion of hypomethylated epithelial cells in the sputum determines whether a patient has lung cancer.

RESULTS: A total of 88 subjects were enrolled: 12 healthy subjects; 34 high-risk subjects with benign chronic lung disorders (10 with chronic obstructive pulmonary disease, 24 with idiopathic pulmonary fibrosis), and 43 subjects with non-small cell lung cancer (27 with stage I-II and 16 with stage III-IV). The test identified early-stage non-small cell lung cancer and distinguished it from the high-risk group with 95.8% (95% confidence interval, 78.9-99.9) sensitivity and 41.2% (95% confidence interval, 24.6-59.3) specificity applying only 5mC, 95.8% (95% confidence interval, 78.9-99.9) sensitivity and 26.5% (95% confidence interval, 12.9-44.4) specificity using solely 5mC/DAPI index, and 100% (95% confidence interval, 98.7-100) sensitivity and 26.1% (95% confidence interval, 26.2-27.8) specificity with the combined parameters.

CONCLUSIONS: We tested and validated a novel, noninvasive, highly sensitive screening test for non-small cell lung cancer. With the use of sputum, our test may impact lung cancer screening, evaluation of pulmonary nodules, and cancer surveillance algorithms.

PMID:37063144 | PMC:PMC10091303 | DOI:10.1016/j.xjon.2022.11.018

Mod Rheumatol Case Rep. 2023 Apr 15:rxad021. doi: 10.1093/mrcr/rxad021. Online ahead of print.

ABSTRACT

Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA). Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis. Herein, we described the case of an 87-year-old woman treated with Janus kinase inhibitor (JAKi). Chest computed tomography revealed increased honeycombing; she was administered nitedanib while continuing RA treatment. The combination treatment (JAKi and nintedanib) controlled the RA disease activity, without ILD deterioration. This case shows the potential of combination treatment with JAKi and nintedanib for prevention of worsening of disease activity in RA and ILD.

PMID:37061836 | DOI:10.1093/mrcr/rxad021

Respir Res. 2023 Apr 15;24(1):112. doi: 10.1186/s12931-023-02413-6.

ABSTRACT

BACKGROUND: Pulmonary fibrosis is an emerging complication of SARS-CoV-2 infection. In this study, we speculate that patients with COVID-19 and idiopathic pulmonary fibrosis (IPF) may share aberrant expressed microRNAs (miRNAs) associated to the progression of lung fibrosis.

OBJECTIVE: To identify miRNAs presenting similar alteration in COVID-19 and IPF, and describe their impact on fibrogenesis.

METHODS: A systematic review of the literature published between 2010 and January 2022 (PROSPERO, CRD42022341016) was conducted using the key words (COVID-19 OR SARS-CoV-2) AND (microRNA OR miRNA) or (idiopathic pulmonary fibrosis OR IPF) AND (microRNA OR miRNA) in Title/Abstract.

RESULTS: Of the 1988 references considered, 70 original articles were appropriate for data extraction: 27 studies focused on miRNAs in COVID-19, and 43 on miRNAs in IPF. 34 miRNAs were overlapping in COVID-19 and IPF, 7 miRNAs presenting an upregulation (miR-19a-3p, miR-200c-3p, miR-21-5p, miR-145-5p, miR-199a-5p, miR-23b and miR-424) and 9 miRNAs a downregulation (miR-17-5p, miR-20a-5p, miR-92a-3p, miR-141-3p, miR-16-5p, miR-142-5p, miR-486-5p, miR-708-3p and miR-150-5p).

CONCLUSION: Several studies reported elevated levels of profibrotic miRNAs in COVID-19 context. In addition, the balance of antifibrotic miRNAs responsible of the modulation of fibrotic processes is impaired in COVID-19. This evidence suggests that the deregulation of fibrotic-related miRNAs participates in the development of fibrotic lesions in the lung of post-COVID-19 patients.

PMID:37061683 | DOI:10.1186/s12931-023-02413-6

Life Sci. 2023 Apr 13:121692. doi: 10.1016/j.lfs.2023.121692. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is the most widely studied interstitial lung disease. IPF eventually leads to respiratory insufficiency, lung cancer, and death. Carvedilol (CAR) is a third-generation β-adrenergic receptor antagonist with α1-blocking effect. CAR demonstrates antifibrotic activities in various experimental models of organ fibrosis.

AIMS: This work is designed to explore the possible alleviating effects of CAR on bleomycin (BLM)-induced lung fibrosis in rats.

MAIN METHODS: The BLM rat model of lung fibrosis was achieved by intratracheal delivery of a single dose of 5 mg/kg of BLM. Seven days following BLM injection, either prednisolone or CAR was orally administered at doses of 10 mg/kg once daily for 21 days to rats. The actions of CAR were evaluated by lung oxidant/antioxidant parameters, protein concentration and total leucocyte count (TLC) in bronchoalveolar lavage fluid (BALF), fibrosis regulator-related genes along with the coexistent lung histological changes.

KEY FINDINGS: CAR effectively decreased lung malondialdehyde level, increased superoxide dismutase activity, declined both protein concentration and TLC in BALF, downregulated TGF-β1/α-SMA/Smad2/3 and STAT3 gene expressions, and repaired the damaged lung tissues.

SIGNIFICANCE: CAR conferred therapeutic potential against BLM-induced lung fibrosis in rats, at least in part, to its antioxidant, anti-inflammatory, and antifibrotic activities. CAR could be utilized as a prospective therapeutic option in patients with lung fibrosis in clinical practice.

PMID:37061127 | DOI:10.1016/j.lfs.2023.121692

Expert Opin Emerg Drugs. 2023 Apr 15. doi: 10.1080/14728214.2023.2203912. Online ahead of print.

ABSTRACT

INTRODUCTION: Chronic cough is a debilitating condition that is among the most common reasons for seeking medical attention yet remains challenging to manage. Identifying an underlying respiratory, nasal or upper gastrointestinal disease triggering cough is the first step in assessment, but once this has been ruled out or adequately treated, many patients remain troubled with chronic cough.

AREAS COVERED: This narrative review discusses the role of existing treatments and describes the current research landscape for the development of new therapies for chronic cough greater than 8 weeks that is refractory (RCC) or unexplained (UCC). The literature search includes published studies found on pubmed and conference abstracts until 2023.

EXPERT OPINION: RCC/UCC can occur due to neuronal dysregulation of the vagus nerve or central nervous system. Hence, novel anti-tussives have targeted ion channels involved in the neuronal signaling which triggers cough. Although some therapies targeting receptors such as TRPV1 have failed to show efficacy, P2X3 antagonists have emerged as the most promising therapy for patients impacted by chronic cough. Disease specific therapies such as for idiopathic pulmonary fibrosis are in early development.

PMID:37060576 | DOI:10.1080/14728214.2023.2203912

Chest. 2023 Apr 12:S0012-3692(23)00504-4. doi: 10.1016/j.chest.2023.04.008. Online ahead of print.

ABSTRACT

BACKGROUND: Lifestyle is thought to be an important contributor of age-related chronic disease, but the association between lifestyle and the risk of idiopathic pulmonary fibrosis (IPF) remains unknown. Also, the extent to which genetic susceptibility modifies the effects of lifestyle on IPF remains unclear.

RESEARCH QUESTION: Whether there is joint effect or interaction of lifestyle and genetic susceptibility on the risk of developing IPF?

STUDY DESIGN AND METHODS: Our study included 407615 participants from the UK Biobank. We constructed a lifestyle score and a polygenic risk score (PRS) for each participant, separately. Participants were then classified into 3 lifestyle categories and 3 genetic risk categories based on the corresponding score. Cox models were fitted to assess the association of lifestyle and genetic risk with the risk of incident IPF.

RESULTS: With favorable lifestyle as the reference group, intermediate lifestyle (hazard ratio (HR): 1.384, 95% confidence interval (CI): 1.218-1.574) and unfavorable lifestyle (HR: 2.271, 95% CI: 1.852-2.785) were significantly associated with increased risk of IPF. For the combined effect of lifestyle and PRS, participants with unfavorable lifestyle and high genetic risk had the highest risk of IPF (HR: 7.796, 95% CI: 5.482-11.086) compared to those with favorable lifestyle and low genetic risk. Moreover, approximately 32.7% (11.3%, 54.1%) of IPF risk could be attributed to the interaction of an unfavorable lifestyle and high genetic risk.

INTERPRETATION: Exposure to unfavorable lifestyle significantly increased the risk of IPF, particularly in those with high genetic risk.

PMID:37059176 | DOI:10.1016/j.chest.2023.04.008

Immunol Allergy Clin North Am. 2023 May;43(2):229-244. doi: 10.1016/j.iac.2023.01.005. Epub 2023 Mar 3.

ABSTRACT

Connective tissue disease associated interstitial lung disease (CTD-ILD) is a heterogenous collection of conditions with a diverse spectrum of interstitial lung disease (ILD) manifestations. Currently, clinical practice of lung-directed immunosuppression in CTD-ILD is supported by several randomized, placebo-controlled trials (RCTs) in patients with scleroderma and several observational, retrospective studies in other autoimmune conditions. However, given the harm of immunosuppression in idiopathic pulmonary fibrosis, there is an urgent need for RCTs of immunosuppression and antifibrotic agents in fibrotic CTD-ILD populations as well as the study of intervention in patients with subclinical CTD-ILD.

PMID:37055086 | DOI:10.1016/j.iac.2023.01.005

Immunol Allergy Clin North Am. 2023 May;43(2):209-228. doi: 10.1016/j.iac.2023.01.010. Epub 2023 Mar 3.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF), a common interstitial lung disease (ILD), is a chronic, progressive fibrosing interstitial pneumonia, with an unknown cause. IPF has been linked to several genetic and environmental risk factors. Disease progression is common and associated with worse outcomes. Management often encompasses pharmacotherapy, supportive interventions, addressing comorbidities when present, and treating hypoxia with ambulatory O2. Consideration for antifibrotic therapy and lung transplantation evaluation should occur early. Patients with ILD other than IPF, and who have radiological evidence of pulmonary fibrosis, may have progressive pulmonary fibrosis.

PMID:37055085 | DOI:10.1016/j.iac.2023.01.010