Arch Bronconeumol. 2023 Dec 18:S0300-2896(23)00403-9. doi: 10.1016/j.arbres.2023.12.002. Online ahead of print.

ABSTRACT

INTRODUCTION: Most patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotics (AF) have progressive disease despite treatment. A switch of AF may improve survival, but evidence from randomised controlled trials is missing. We aimed to evaluate the efficacy of an AF switch on survival and FVC decline in patients from the European MultiPartner IPF registry (EMPIRE).

METHODS: The study included 612 patients who discontinued the first antifibrotic therapy. Patients were grouped and analysed from two perspectives: (1) whether they had received a second antifibrotic treatment after the discontinuation of the first therapy, and (2) a reason for discontinuation of the first AF - "lack of efficacy" (LE) and "intolerance" (INT).

RESULTS: While 263 (43%) of 612 patients received no second AF ("non-switched"), 349 (57%) patients switched. Overall survival was higher in patients who received a second AF (median 50 vs. 29 months; adjusted HR 0.64, P=0.023). Similarly, the annual FVC decline was significantly reduced in switched patients: -98ml/y in switched and -172ml/y in non-switched patients (P=0.023), respectively. The switched patients had similar risk for mortality in both LE and INT groups (adjusted HR 0.95, P=0.85). The high impact of switching on survival was demonstrated in LE patients (adjusted HR 0.27, P<0.001).

CONCLUSION: The patients without a second AF had significantly shorter overall survival. Our analysis suggests the importance of switching patients with an ineffective first AF therapy to a second AF therapy.

PMID:38160169 | DOI:10.1016/j.arbres.2023.12.002

BMJ Open Respir Res. 2023 Dec 30;10(1):e002008. doi: 10.1136/bmjresp-2023-002008.

ABSTRACT

OBJECTIVES: We aimed to assess the available evidence for corticosteroids in fibrotic interstitial lung disease (fILD) to inform the randomised embedded multifactorial adaptive platform ILD.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: We searched Embase, Medline, Cochrane CENTRAL and Web of Science databases from inception to April 17 2023.

ELIGIBILITY CRITERIA: We included studies that compared corticosteroids with standard care, placebo or no treatment in adult patients with fILD.

DATA EXTRACTION AND SYNTHESIS: We report on the change in forced vital capacity (FVC) and mortality. We used random-effects meta-analysis to estimate relative risk (RR) for dichotomous outcomes, and mean difference (MD) and standardised MDs for continuous outcomes, with 95% CIs.

RESULTS: Of the 13 229 unique citations identified, we included 10 observational studies comprising 1639 patients. Corticosteroids had an uncertain effect on mortality compared with no treatment (RR 1.03 (95% CI 0.85 to 1.25); very low certainty evidence). The effect of corticosteroids on the rate of decline in FVC (% predicted) was uncertain when compared with no treatment (MD 4.29% (95% CI -8.26% to 16.83%); very low certainty evidence). However, corticosteroids might reduce the rate of decline in FVC in patients with non-idiopathic pulmonary fibrosis (IPF) fILD (MD 10.89% (95% CI 5.25% to 16.53%); low certainty evidence), while an uncertain effect was observed in patients with IPF (MD -3.80% (95% CI -8.94% to 1.34%); very low certainty evidence).

CONCLUSIONS: The current evidence on the efficacy and safety of corticosteroids in fILD is limited and of low certainty. Randomised trials are needed to address this significant research gap.

PMID:38160015 | DOI:10.1136/bmjresp-2023-002008

Int Immunopharmacol. 2023 Dec 29;127:111456. doi: 10.1016/j.intimp.2023.111456. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is an age-related inflammatory disease with no cure up till now.It is accompanied by neutrophils infiltration as the main responders to inflammation and fibrosis. Importantly, neutrophils release neutrophil extracellular traps (NETs) through NETosis process. The function of microRNAs during inflammation became of great biological attention. Owing to microRNAs' central role in immune system, microRNA-155-5p (miR-155-5p) is intensely involved in the inflammatory response. Capsaicin (Cap) is a bioactive compound that exhibits antioxidative and anti-inflammatory functions. Recent studies have shown its role in regulation of certain microRNAs' expressions. Accordingly, the present study aims to investigate the effect of miR-155-5p regulation in suppressing NETs production via ameliorating its target inflammatory cytokines, IL-1ß, TNF-α and TGF-ß1, in bleomycin (BLM)-induced pulmonary fibrosis rat model treated by Cap. The obtained results demonstrated that miR-155-5p downregulation was associated with significant decrease in IL-1ß, TNF-α, TGF-β1, which consequently, reduced hydroxyproline (HYP), NETs activity markers as NE and PAD-4, and alleviated CTGF levels in lung tissues of animals treated by Cap. Furthermore, NETosis ultrastructure examination by transmission electron microscope (TEM), MPO immunohistochemical staining and histopathological studies confirmed an abolishment in NETs formation and an improvement in lung tissue architecture in Cap-treated rats. This study concluded that Cap quenched the inflammatory response through interrupting IL-1β, TNF-α and TGF-β1 pathway via modulating miR-155-5p expression. In addition, Cap was able to alleviate pulmonary NETosis markers by restraining NETs activity markers. These findings provide novel insight into the application of Cap-based treatment in ameliorating pulmonary damage in IPF.

PMID:38159555 | DOI:10.1016/j.intimp.2023.111456

Expert Rev Respir Med. 2023 Dec 30:1-14. doi: 10.1080/17476348.2023.2299751. Online ahead of print.

ABSTRACT

INTRODUCTION: Many patients with interstitial lung diseases (ILDs), especially fibrotic ILDs, experience chronic cough. It negatively impacts both physical and psychological well-being. Effective treatment options are limited.

AREAS COVERED: The pathophysiology of chronic cough in IPF is complex and involves multiple mechanisms, including mechanical distortion of airways, parenchyma, and nerve fibers. The pathophysiology of cough in other fibrosing ILDs is poorly understood and involves various pathways. The purpose of this review is to highlight mechanisms of chronic cough and to present therapeutic evidence for its management in the most commonly occurring diffuse fibrosing lung diseases including idiopathic pulmonary fibrosis (IPF), connective tissue disease-related interstitial lung disease (CTD-ILD), sarcoidosis-related ILD (Sc-ILD), chronic hypersensitivity pneumonitis-related ILD (CHP-ILD), and post-COVID-19-related interstitial lung disease (PC-ILD).

EXPERT OPINION: This review guides the management of chronic cough in fibrosing ILDs. In this era of precision medicine, chronic cough management should be individualized in each interstitial lung disease.

PMID:38159067 | DOI:10.1080/17476348.2023.2299751

J Cell Mol Med. 2023 Dec 30. doi: 10.1111/jcmm.18098. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is considered as a chronic, fibrosing interstitial pneumonia with unknown mechanism. The present work aimed to explore the function, biogenesis and regulatory mechanism of circELP2 in pulmonary fibrosis and evaluate the value of blocking circELP2-medicated signal pathway for IPF treatment. The results showed that heterogeneous nuclear ribonucleoprotein L initiated reverse splicing of circELP2 resulting in the increase of circELP2 generation. The biogenetic circELP2 activated the abnormal proliferation and migration of fibroblast and extracellular matrix deposition to promote pulmonary fibrogenesis. Mechanistic studies demonstrated that cytoplasmic circELP2 sponged miR-630 to increase transcriptional co-activators Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ). Then, YAP1/TAZ bound to the promoter regions of their target genes, such as mTOR, Raptor and mLST8, which in turn activated or inhibited the genes expression in mitochondrial quality control pathway. Finally, the overexpressed circELP2 and miR-630 mimic were packaged into adenovirus vector for spraying into the mice lung to evaluate therapeutic effect of blocking circELP2-miR-630-YAP1/TAZ-mitochondrial quality control pathway in vivo. In conclusion, blocking circELP2-medicated pathway can alleviate pulmonary fibrosis, and circELP2 may be a potential target to treat lung fibrosis.

PMID:38159063 | DOI:10.1111/jcmm.18098

Eur J Pharmacol. 2023 Dec 27;964:176293. doi: 10.1016/j.ejphar.2023.176293. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with no cure. Bufotalin (BT), an active component extracted from Venenum Bufonis, has been prescribed as a treatment for chronic inflammatory diseases. However, whether BT has antifibrotic properties has never been investigated. In this study, we report on the potential therapeutic effect and mechanism of BT on IPF. BT was shown to attenuate lung injury, inflammation, and fibrosis as well as preserve pulmonary function in bleomycin (BLM)-induced pulmonary fibrosis model. We next confirmed BT's ability to inhibit TGF-β1-induced epithelial-mesenchymal transition (EMT) and myofibroblast activation (including differentiation, proliferation, migration, and extracellular matrix production) in vitro. Furthermore, transcriptional profile analysis indicated the Wnt signaling pathway as a potential target of BT. Mechanistically, BT effectively prevented β-catenin from translocating into the nucleus to activate transcription of profibrotic genes. This was achieved by blunting TGF-β1-induced increases in phosphorylated Akt Ser437 (p-Akt S437) and phosphorylated glycogen synthase kinase (GSK)-3β Ser9 (p-GSK-3β S9), thereby reactivating GSK-3β. Additionally, the antifibrotic effects of BT were further validated in another in vivo model of radiation-induced pulmonary fibrosis. Collectively, these data demonstrated the potent antifibrotic actions of BT through inhibition of Akt/GSK-3β/β-catenin axis downstream of TGF-β1. Thus, BT could be a potential option to be further explored in IPF treatment.

PMID:38158113 | DOI:10.1016/j.ejphar.2023.176293

Cell Mol Life Sci. 2023 Dec 29;81(1):13. doi: 10.1007/s00018-023-05080-4.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal and devastating lung disease of unknown etiology, described as the result of multiple cycles of epithelial cell injury and fibroblast activation. Despite this impressive increase in understanding, a therapy that reverses this form of fibrosis remains elusive. In our previous study, we found that miR-29b has a therapeutic effect on pulmonary fibrosis. However, its anti-fibrotic mechanism is not yet clear. Recently, our study identified that F-Actin Binding Protein (TRIOBP) is one of the target genes of miR-29b and found that deficiency of TRIOBP increases resistance to lung fibrosis in vivo. TRIOBP knockdown inhibited the proliferation of epithelial cells and attenuated the activation of fibroblasts. In addition, deficiency of Trio Rho Guanine Nucleotide Exchange Factor (TRIO) in epithelial cells and fibroblasts decreases susceptibility to lung fibrosis. TRIOBP interacting with TRIO promoted abnormal epithelial-mesenchymal crosstalk and modulated the nucleocytoplasmic translocation of β-catenin. We concluded that the miR-29b‒TRIOBP-TRIO-β-catenin axis might be a key anti-fibrotic axis in IPF to regulate lung regeneration and fibrosis, which may provide a promising treatment strategy for lung fibrosis.

PMID:38157020 | DOI:10.1007/s00018-023-05080-4

Respir Med. 2023 Dec 26:107515. doi: 10.1016/j.rmed.2023.107515. Online ahead of print.

ABSTRACT

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) increases mortality risk, but which factors increase mortality is unknown. We aimed to perform a prognostic review of factors associated with mortality in patients with IPF.

STUDY DESIGN: and methods: We searched MEDLINE, EMBASE, and CINAHL for studies that reported on the association between any prognostic factor and AE-IPF. We assessed risk of bias using the QUIPS tool. We conduced pairwise meta-analyses using REML heterogeneity estimator, and GRADE approach to assess the certainty of the evidence.

RESULTS: We included 35 studies in our analysis. We found that long-term supplemental oxygen at baseline (aHR 2.52 [95 % CI 1.68 to 3.80]; moderate certainty) and a diagnosis of IPF compared to non-IPF ILD (aHR 2.19 [95 % CI 1.22 to 3.92]; moderate certainty) is associated with a higher risk of death in patients with AE-IPF. A diffuse pattern on high resolution computed tomography (HRCT) compared to a non-diffuse pattern (aHR 2.61 [95 % CI 1.32 to 2.90]; moderate certainty) is associated with a higher risk of death in patients with AE-IPF. We found that using corticosteroids prior to hospital admission (aHR 2.19 [95 % CI 1.26 to 3.82]; moderate certainty) and those with increased neutrophils (by % increase) in bronchoalveolar lavage (BAL) during the exacerbation is associated with a higher risk of death (aHR 1.02 [1.01 to 1.04]; moderate certainty).

INTERPRETATION: Our results have implications for healthcare providers in making treatment decisions and prognosticating the clinical trajectory of patients, for researchers to design future interventions to improve patient trajectory, and for guideline developers in making decisions about resource allocation.

PMID:38154738 | DOI:10.1016/j.rmed.2023.107515

Environ Res. 2023 Dec 26:117984. doi: 10.1016/j.envres.2023.117984. Online ahead of print.

ABSTRACT

BACKGROUND: The impact of residential greenness on incident idiopathic pulmonary fibrosis (IPF) is unknown. We aimed to assess the association between residential greenness and incident IPF, identify underlying pathways, and further evaluate the effect among different genetic subgroups.

METHODS: 469,348 participants in the UK Biobank were included and followed until December 2020. Normalized difference vegetation index (NDVI) within 300-, 500-, 1000-, and 1500-m buffers (NDVI300m, NDVI500m, NDVI1000m, and NDVI1500m) was employed as indicators of greenness. The polygenic risk score (PRS) was constructed based on 13 independent SNPs. Cox models were fitted to assess the association of residential greenness with incident IPF. Casual mediation analyses were applied to evaluate potential mediators.

FINDINGS: After a median follow-up of 11.85 years, 1574 IPF cases were identified. We found residential greenness inversely associated with incident IPF. The HRs (95%CIs) for each interquartile increase of NDVI300m, NDVI500m, NDVI1000m, NDVI1500m were 0.93 (0.87, 0.99), 0.92 (0.86, 0.98), 0.89 (0.83, 0.95), and 0.89 (0.83, 0.95), respectively. The association was stronger among individuals with intermediate or high genetic risk. In mediation analyses, the main mediators identified were PM2.5 and NO2, with proportion mediated estimated to be 31.92% and 40.61% respectively for NDVI300m.

INTERPRETATION: Residential greenness was associated with reduced risk of incident IPF.

PMID:38154569 | DOI:10.1016/j.envres.2023.117984

Int J Gen Med. 2023 Dec 23;16:6099-6113. doi: 10.2147/IJGM.S438297. eCollection 2023.

ABSTRACT

OBJECTIVE: To summarize the contents and assess the methodological quality and measurement properties of the patient-reported outcome (PRO) scales featured with Traditional Chinese Medicine (TCM) for respiratory diseases based on the guideline of COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN).

METHODS: PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, and China Biology Medicine (CBM) were searched for studies on PRO scales featured with TCM for respiratory diseases from their inception until December 2022. The characteristics of the PRO scales were qualitatively summarized. Following the COSMIN guideline, the risk of bias was assessed according to the checklist, and different measurement properties (content validity, structural validity, internal consistency, reliability, criterion validity, and responsiveness) were evaluated. Finally, the evidence's overall quality was assessed, and the recommendation was formulated using the modified GRADE approach.

RESULTS: A total of 13 scales were included, with 6 for chronic obstructive pulmonary disease (COPD), 3 for lung cancer, 2 for idiopathic pulmonary fibrosis (IPF), 1 for community-acquired pneumonia (CAP), and 1 for bronchiectasis. All 13 scales are disease-specific scales and were developed based on Chinese cultural background to measure the efficacy of TCM. The study did not provide information on measurement error, cross-cultural validity, and hypothesis testing for the construct validity of these measures. No scale was rated as sufficient in content validity and responsiveness. Two scales showed sufficient structural validity, while 11 scales exhibited sufficient internal consistency. Three scales demonstrated sufficient reliability, and 7 scales showed sufficient criterion validity. All 13 scales have a recommendation level of B.

CONCLUSION: The 13 scales could reflect the clinical efficacy of TCM and are suitable for the Chinese population. Nevertheless, the validation of these scales was not comprehensive enough, and the methodological quality of their studies needs to be further strengthened.

PMID:38152077 | PMC:PMC10752031 | DOI:10.2147/IJGM.S438297

Tuberk Toraks. 2023 Dec;71(4):347-355. doi: 10.5578/tt.20239603.

ABSTRACT

INTRODUCTION: The aim of this study was to evaluate the real-life treatment and follow-up data of patients with idiopathic pulmonary fibrosis (IPF) in a singlecenter setting.

MATERIALS AND METHODS: The study included consecutive patients diagnosed with IPF who were followed up at the Akdeniz University, between January 1, 2014 and December 31, 2022. Patient information was obtained from the hospital automation system.

RESULT: A total of 227 patients with a mean age of 72.0 ± 8.2 years were included in the study. One hundred sixty-seven patients (73.6%) received pirfenidone while 60 patients (26.4%) received nintedanib treatment. Radiological findings were used to diagnose IPF in 79.3% (n= 180) of cases. Mean duration of antifibrotic treatment was 26.3 ± 19.9 months. Of the patients, 49.8% experienced hospital admissions during the treatment course, with respiratory reasons accounting for a majority of these admissions (33.6%). Disease exacerbation was detected in 26.6% of the patients during the treatment period. At least one side effect was observed in 126 patients (55.5%), with a significant portion of these side effects being mild to moderate (n= 79, 34.8%). Disease progression was observed in 21.6% of the patients under antifibrotic treatment. Dose reduction was necessary in 22.9% of the patients, with an average duration of dose reduction of 29 months. Antifibrotic treatment was switched to another medication in 24.2% of the patients. There were no statistically significant differences in baseline forced vital capacity (FVC) levels between the two groups (p= 0.314) while the diffusing capacity of the lungs for carbon monoxide (DLCO) level was higher in the nintedanib group (p= 0.024), and the six-minute walk distance was shorter (p= 0.049).

CONCLUSIONS: In this study evaluating patients with IPF under follow-up in our hospital, it was observed that the majority of patients consisted of elderly male individuals, frequent hospitalizations were due to respiratory reasons, and both antifibrotic medications were well tolerated with a similar side effect profile.

PMID:38152005 | DOI:10.5578/tt.20239603

Sci Rep. 2023 Dec 27;13(1):22977. doi: 10.1038/s41598-023-49180-4.

ABSTRACT

This study investigated the utility of periostin, a matricellular protein, as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) who received nintedanib. Monomeric and total periostin levels were measured by enzyme-linked immunosorbent assay in 87 eligible patients who participated in a multicenter prospective study. Forty-three antifibrotic drug-naive patients with IPF described in previous studies were set as historical controls. Monomeric and total periostin levels were not significantly associated with the change in forced vital capacity (FVC) or diffusing capacity of the lungs for carbon monoxide (DLCO) during any follow-up period. Higher monomeric and total periostin levels were independent risk factors for overall survival in the Cox proportional hazard model. In the analysis of nintedanib effectiveness, higher binarized monomeric periostin levels were associated with more favorable suppressive effects on decreased vital capacity (VC) and DLCO in the treatment group compared with historical controls. Higher binarized levels of total periostin were associated with more favorable suppressive effects on decreased DLCO but not VC. In conclusion, higher periostin levels were independently associated with survival and better therapeutic effectiveness in patients with IPF treated with nintedanib. Periostin assessments may contribute to determining therapeutic strategies for patients with IPF.

PMID:38151520 | DOI:10.1038/s41598-023-49180-4

Aging (Albany NY). 2023 Dec 22;15(24):15382-15401. doi: 10.18632/aging.205355. Epub 2023 Dec 22.

ABSTRACT

Aging usually causes lung-function decline and susceptibility to chronic lung diseases, such as pulmonary fibrosis. However, how aging affects the lung-fibrosis pathways and leads to the occurrence of pulmonary fibrosis is not completely understood. Here, mass spectrometry-based proteomics was used to chart the lung proteome of young and old mice. Micro computed tomography imaging, RNA immunoprecipitation, dual-fluorescence mRFP-GFP-LC3 adenovirus monitoring, transmission electron microscopy, and other experiments were performed to explore the screened differentially expressed proteins related to abnormal ferroptosis, autophagy, mitochondria, and mechanical force in vivo, in vitro, and in healthy people. Combined with our previous studies on pulmonary fibrosis, we further demonstrated that these biological processes and underlying molecular players were also involved in the aging process. Our work depicted a comprehensive cellular and molecular atlas of the aging lung and attempted to explain why aging is a risk factor for pulmonary fibrosis and the role that aging plays in the progression of pulmonary fibrosis. The abnormalities of aging triggered an increase in mechanical force and ferroptosis, autophagy blockade, and mitochondrial dysfunction, which often appear during pulmonary fibrogenesis. We hope that the elucidation of these anomalies will help to enhance our understanding of senescence-inducing pulmonary fibrosis, thereby guiding the use of anti-senescence as an entry point for early intervention in pulmonary fibrosis and age-related diseases.

PMID:38147026 | DOI:10.18632/aging.205355

Am J Med Sci. 2023 Dec 24:S0002-9629(23)01475-1. doi: 10.1016/j.amjms.2023.12.009. Online ahead of print.

ABSTRACT

BACKGROUND: Previous work has shown the ability of Fibresolve, a machine learning system, to non-invasively classify idiopathic pulmonary fibrosis (IPF) with a sensitivity of 41% and specificity of 87% versus other types of interstitial lung disease. Further external validation for the use of Fibresolve to classify IPF in patients with non-definite usual interstitial pneumonia (UIP) is needed. The aim of this study is to assess the sensitivity for Fibresolve to positively classify IPF in an external cohort of patients with a non-definite UIP radiographic pattern.

METHODS: This is a retrospective analysis of patients (n=193) enrolled in two prospective phase two clinical trials that enrolled patients with IPF. We retrospectively identified patients with non-definite UIP on HRCT (n=51), 47 of whom required surgical lung biopsy for diagnosis. Fibresolve was used to analyze the HRCT chest imaging which was obtained prior to invasive biopsy and sensitivity for final diagnosis of IPF was calculated.

RESULTS: The sensitivity of Fibresolve for the non-invasive classification of IPF in patients with a non-definite UIP radiographic pattern by HRCT was 76.5% (95% CI 66.5-83.7). For the subgroup of 47 patients who required surgical biopsy to aid in final diagnosis of IPF, Fibresolve had a sensitivity of 74.5% (95% CI 60.5-84.7).

CONCLUSION: In patients with suspected IPF with non-definite UIP on HRCT, Fibresolve can positively identify cases of IPF with high sensitivity. These results suggest that in combination with standard clinical assessment, Fibresolve has the potential to serve as a low-cost adjunct in the non-invasive diagnosis of IPF.

PMID:38147938 | DOI:10.1016/j.amjms.2023.12.009

Front Med (Lausanne). 2023 Dec 7;10:1280651. doi: 10.3389/fmed.2023.1280651. eCollection 2023.

ABSTRACT

BACKGROUND: Whether the airway is involved in the pathogenesis of interstitial lung abnormalities (ILA) is not well understood. Also the impact of ILA on lung function in COPD patients remains controversial. We aimed to assess the quantitative CT measurements of airway wall thickness (AWT) and lung function according to ILA status in COPD patients.

METHODS: 157 COPD patients discharged from our hospital from August 1, 2019 through August 31, 2022 who underwent chest CT imagings and pulmonary function tests were retrospectively enrolled. Linear regression analysis and multiple models were used to analyze associations between quantitative assessment of airway wall changes and the presence of ILA.

RESULTS: In 157 COPD patients, 23 patients (14.6%) had equivocal ILA, 42 patients (26.8%) had definite ILA. The definite ILA group had the highest measurements of Pi10 (square root of theoretical airway wall area with a lumen perimeter of 10 mm), segmental AWT and segmental WA% (percentage of wall area), whereas the no ILA group had the lowest measurements of Pi10, segmental AWT and segmental WA%. In the adjusted analyses (adjusted by age, sex, body mass index, smoking intensity, COPD GOLD stage, lung function, slice thickness and scanner type), compared to COPD patients without ILA, the measurements of Pi10, segmental AWT and segmental WA% were higher in definite ILA group with differences of 0.225 mm (p = 0.012), 0.152 mm (p < 0.001), 4.8% (p < 0.001) respectively. COPD patients with definite ILA tended to have higher FEV1% predicted, FVC% predicted and lower MMEF75/25% predicted, but there were no statistically differences among the three groups.

CONCLUSION: Our study demonstrates the higher AWT measures in COPD patients with ILA compared to the patients without ILA. These findings suggest that the airway may be involved in the pathogenesis of ILA.

PMID:38146423 | PMC:PMC10749311 | DOI:10.3389/fmed.2023.1280651

Oxf Med Case Reports. 2023 Dec 19;2023(12):omad091. doi: 10.1093/omcr/omad091. eCollection 2023 Dec.

ABSTRACT

Idiopathic pulmonary hemosiderosis (IPH) is a rare entity with no known underlying etiology. It can be complicated by lung fibrosis. Emphysema is rarely reported as a consequence of IPH. We present a case of a 30-year-old female who presented with recurrent hemoptysis and shortness of breath. Radiographs revealed advanced emphysematous changes of the lower lobes. The diagnosis of IPH was established with an open lung biopsy. She was treated with systemic steroids, underwent bullectomy and was subsequently maintained on inhaled steroids.

PMID:38145263 | PMC:PMC10735625 | DOI:10.1093/omcr/omad091

Avicenna J Med. 2023 Nov 1;13(4):230-236. doi: 10.1055/s-0043-1776063. eCollection 2023 Oct.

ABSTRACT

Background Decisions on the management of interstitial lung diseases (ILD) and prognostication require an accurate diagnosis. It has been proposed that multidisciplinary team (MDT) meetings for ILD (ILD-MDT) improve these decisions in challenging cases of ILD. However, most studies in this field have been based on the decisions of individual clinicians and there are few reports on the outcomes of the ILD-MDT approach. We therefore describe the experience of the ILD-MDT meetings at our institution. Methods A single-center retrospective review of the electronic health care records of patients discussed in the ILD-MDT meetings at our institution from February 2016 to January 2021 was performed. At out institution, at each ILD-MDT meeting, the referring pulmonologist presents the clinical history and the results of all relevant investigations including serology, blood gas analyses, lung function tests, bronchoscopy, and bronchoalveolar lavage. A radiologist then describes the imaging including serial computed tomography (CT) scans. When available, the findings on lung biopsy are presented by a pathologist. Subsequent discussions lead to a consensus on the diagnosis and further management. Results The study included 121 patients, comprising 71 (57%) males and 76 nonsmokers (62.8%), with a mean age of 65 years (range: 25-93 years). The average number of comorbidities was 2.4 (range: 0-7). Imaging-based diagnoses were usual interstitial pneumonia (UIP)/chronic hypersensitivity pneumonitis (CHP) in 32 (26%) patients, UIP in 20 (17%) patients, probable UIP in 27 (22%) patients, nonspecific interstitial pneumonia in 11 (9%) patients, and indeterminate interstitial lung abnormalities (ILA) in 10 (8%) patients. The most common consensus clinical diagnosis after an ILD-MDT discussion was chronic hypersensitivity pneumonitis/idiopathic pulmonary fibrosis in 17 patients (14%), followed by idiopathic pulmonary fibrosis and connective tissue disease associated interstitial lung disease in 16 patients (13%), CHP in 11 patients (9.1%), and ILA in 10 patients (8.4%). Only a 42 patients (35%) required surgical lung biopsy for confirmation of the diagnosis. Conclusion This study describes the characteristics of the patients discussed in the ILD-MDT meetings with emphasis on their clinical, radiological, and laboratory data to reach a diagnosis and management plan. The decisions on commencement of antifibrotics or immunosuppressive therapy for patients with various ILDs are also made during these ILD-MDT meetings. This descriptive study could help other health care professionals regarding the structure of their ILD-MDT meetings and with discussions about diagnostic and care decisions for diffused parenchymal lung disease patients.

PMID:38144909 | PMC:PMC10736212 | DOI:10.1055/s-0043-1776063

Reprod Toxicol. 2023 Dec 21:108526. doi: 10.1016/j.reprotox.2023.108526. Online ahead of print.

ABSTRACT

Zinpentraxin alfa is a recombinant human pentraxin-2 (PTX-2) developed for the treatment of various fibrotic diseases with the hypothesis that supplementing endogenous PTX-2 levels through intravenous administration should increase its regulatory capacity in circulation and at the site of disease, thereby promoting healing and reducing fibrosis. Zinpentraxin alfa has been studied in various clinical trials, particularly in patients with idiopathic pulmonary fibrosis, where it has demonstrated efficacy in slowing decline in lung function in a phase 2 study. In the present investigation, we summarize findings from 14-day repeat-dose toxicity studies in rats and cynomolgus monkeys supporting early clinical development of zinpentraxin alfa. In addition, we also describe the findings from the embryo-fetal developmental (EFD) studies conducted in rats and rabbits, since the intended fibrosis patient population may include patients of childbearing potential. Zinpentraxin alfa was well tolerated by rats and monkeys in general toxicity studies with no treatment-related adverse effects, as well as by pregnant rats over the same dose range in a definitive EFD study. In contrast, substantial toxicity was observed in a rabbit dose-range-finder EFD study. Zinpentraxin alfa was poorly tolerated by pregnant rabbits and effects on the dams correlated with post-implantation fetal losses. The disparate effects of zinpentraxin alfa on embryo-fetal development between the two species suggests a potential unknown biological function of PTX-2 in pregnancy in the rabbit, which may be relevant to humans. Our findings warrant the consideration for highly effective contraceptive measures to avoid pregnancy in patients enrolled in clinical studies with zinpentraxin alfa.

PMID:38141866 | DOI:10.1016/j.reprotox.2023.108526

Respir Med Res. 2023 Nov 2;85:101058. doi: 10.1016/j.resmer.2023.101058. Online ahead of print.

ABSTRACT

BACKGROUND: Computational advances in artificial intelligence have led to the recent emergence of U-Net convolutional neural networks (CNNs) applied to medical imaging. Our objectives were to assess the progression of fibrotic interstitial lung disease (ILD) using routine CT scans processed by a U-Net CNN developed by our research team, and to identify a progression threshold indicative of poor prognosis.

METHODS: CT scans and clinical history of 32 patients with idiopathic fibrotic ILDs were retrospectively reviewed. Successive CT scans were processed by the U-Net CNN and ILD quantification was obtained. Correlation between ILD and FVC changes was assessed. ROC curve was used to define a threshold of ILD progression rate (PR) to predict poor prognostic (mortality or lung transplantation). The PR threshold was used to compare the cohort survival with Kaplan Mayer curves and log-rank test.

RESULTS: The follow-up was 3.8 ± 1.5 years encompassing 105 CT scans, with 3.3 ± 1.1 CT scans per patient. A significant correlation between ILD and FVC changes was obtained (p = 0.004, ρ = -0.30 [95% CI: -0.16 to -0.45]). Sixteen patients (50%) experienced unfavorable outcome including 13 deaths and 3 lung transplantations. ROC curve analysis showed an aera under curve of 0.83 (p < 0.001), with an optimal cut-off PR value of 4%/year. Patients exhibiting a PR ≥ 4%/year during the first two years had a poorer prognosis (p = 0.001).

CONCLUSIONS: Applying a U-Net CNN to routine CT scan allowed identifying patients with a rapid progression and unfavorable outcome.

PMID:38141579 | DOI:10.1016/j.resmer.2023.101058

J Clin Med. 2023 Dec 8;12(24):7589. doi: 10.3390/jcm12247589.

ABSTRACT

Neutrophil activation can release neutrophil extracellular traps (NETs) in acute inflammation. NETs result in the release of human neutrophil elastase (HNE) and calprotectin, where the former can degrade the latter and generate protein fragments associated with neutrophil activity. We investigated this in chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) using the novel neoepitope biomarker CPa9-HNE, quantifying a specific HNE-mediated fragment of calprotectin in serum. CPa9-HNE was compared to total calprotectin. Initially, CPa9-HNE was measured in healthy (n = 39), COPD (n = 67), and IPF (n = 16) serum using a neoepitope-specific competitive enzyme-linked immunosorbent assay. Then, a head-to-head comparison of CPa9-HNE and total calprotectin, a non-neoepitope, was conducted in healthy (n = 19), COPD (n = 25), and IPF (n = 19) participants. CPa9-HNE levels were significantly increased in COPD (p < 0.0001) and IPF subjects (p = 0.0001) when compared to healthy participants. Additionally, CPa9-HNE distinguished IPF (p < 0.0001) and COPD (p < 0.0001) from healthy participants more effectively than total calprotectin for IPF (p = 0.0051) and COPD (p = 0.0069). Here, CPa9-HNE also distinguished IPF from COPD (p = 0.045) participants, which was not observed for total calprotectin (p = 0.98). Neutrophil activity was significantly higher, as assessed via serum CPa9-HNE, for COPD and IPF compared to healthy participants. Additionally, CPa9-HNE exceeded the ability of non-neoepitope calprotectin serum measurements to separate healthy from lung disease and even COPD from IPF participants, indicating that neutrophil activity is essential for both COPD and IPF.

PMID:38137658 | DOI:10.3390/jcm12247589