Front Oncol. 2024 Jan 23;13:1275346. doi: 10.3389/fonc.2023.1275346. eCollection 2023.

ABSTRACT

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) severely affects the lung leading to aberrant deposition of extracellular matrix and parenchymal stiffness with progressive functional derangement. The limited availability of fresh tissues represents one of the major limitations to study the molecular profiling of IPF lung tissue. The primary aim of this study was to explore the proteomic profiling yield of archived formalin-fixed paraffin-embedded (FFPE) specimens of IPF lung tissues.

METHODS: We further determined the protein expression according to respiratory functional decline at the time of biopsy. The total proteins isolated from 11 FFPE samples of IPF patients compared to 3 FFPE samples from a non-fibrotic lung defined as controls, were subjected to label-free quantitative proteomic analysis by liquid chromatography-mass spectrometry (LC-MS/MS) and resulted in the detection of about 400 proteins.

RESULTS: After the pairwise comparison between controls and IPF, functional enrichment analysis identified differentially expressed proteins that were involved in extracellular matrix signaling pathways, focal adhesion and transforming growth factor β (TGF-β) signaling pathways strongly associated with IPF onset and progression. Five proteins were significantly over- expressed in the lung of IPF patients with either advanced disease stage (Stage II) or impaired pulmonary function (FVC<75, DLCO<55) compared to controls; these were lymphocyte cytosolic protein 1 (LCP1), peroxiredoxin-2 (PRDX2), transgelin 2 (TAGLN2), lumican (LUM) and mimecan (OGN) that might play a key role in the fibrogenic processes.

DISCUSSION: Our work showed that the analysis of FFPE samples was able to identify key proteins that might be crucial for the IPF pathogenesis. These proteins are correlated with lung carcinogenesis or involved in the immune landscape of lung cancer, thus making possible common mechanisms between lung carcinogenesis and fibrosis progression, two pathological conditions at risk for each other in the real life.

PMID:38322285 | PMC:PMC10844556 | DOI:10.3389/fonc.2023.1275346

Respir Res. 2024 Feb 6;25(1):77. doi: 10.1186/s12931-024-02716-2.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited treatment options. Circular RNAs (circRNAs) have emerged as a novel class of non-coding RNAs with diverse functions in cellular processes. This review paper aims to explore the potential involvement of circRNAs in the pathogenesis of IPF and their diagnostic and therapeutic implications. We begin by providing an overview of the epidemiology and risk factors associated with IPF, followed by a discussion of the pathophysiology underlying this complex disease. Subsequently, we delve into the history, types, biogenesis, and functions of circRNAs and then emphasize their regulatory roles in the pathogenesis of IPF. Furthermore, we examine the current methodologies for detecting circRNAs and explore their diagnostic applications in IPF. Finally, we discuss the potential utility of circRNAs in the treatment of IPF. In conclusion, circRNAs hold great promise as novel biomarkers and therapeutic targets in the management of IPF.

PMID:38321530 | PMC:PMC10848557 | DOI:10.1186/s12931-024-02716-2

Respirology. 2024 Feb 6. doi: 10.1111/resp.14669. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: The identification of progression in patients with fibrosing non-idiopathic pulmonary fibrosis (IPF) interstitial lung diseases (ILDs) represents an ongoing clinical challenge. Lung function decline alone may have significant limitations in the detection of clinically significant progression. We hypothesized that longitudinal changes of 6-min walk distance (6MWD) from baseline, simultaneously considered with measures of lung function, may independently predict survival and identifying clinically significant progression of disease.

METHODS: Forced vital capacity (FVC), diffusing lung capacity (DLCO) and 6MWD were considered both at baseline and at 1 year in a discovery cohort (n = 105) and in a validation cohort (n = 138) from different centres. The primary endpoint was lung transplant (LTx)-free survival.

RESULTS: Average follow-up was 3 years in both cohorts. Combined incidence of deaths and LTx was 29% and 21%, respectively. No collinearity and no strong correlations were observed among FVC, DLCO and 6MWD longitudinal changes. While age, gender and BMI were not significant, 6MWD decline ≥24 m predicted LTx-free-survival significantly and independently from FVC and DLCO declines, with high sensitivity and specificity, in both the discovery and the validation cohorts. Although FVC and DLCO declines remained significant predictors of LTx-free survival, 6MWD decline was more accurate than the proposed ATS/ERS/JRS/ALAT functional criteria. Results were confirmed after stratifying patients by baseline FVC.

CONCLUSION: Longitudinal declines of 6MWD are associated with poor survival in fibrosing ILDs across a wide range of baseline severity, with high accuracy. 6MWD longitudinal decline is largely independent from lung function decline and may be integrated into the routine assessment of progression.

PMID:38320863 | DOI:10.1111/resp.14669

Kidney Int. 2024 Feb 4:S0085-2538(24)00067-X. doi: 10.1016/j.kint.2024.01.011. Online ahead of print.

ABSTRACT

Toxin- and drug-induced tubulointerstitial nephritis (TIN), characterized by interstitial infiltration of immune cells, frequently necessitates dialysis for patients due to irreversible fibrosis. However, agents modulating interstitial immune cells are lacking. Here, we addressed whether the house keeping enzyme glutamyl-prolyl-transfer RNA synthetase 1 (EPRS1), responsible for attaching glutamic acid and proline to transfer RNA, modulates immune cell activity during TIN and whether its pharmacological inhibition abrogates fibrotic transformation. The immunological feature following TIN induction by means of an adenine-mixed diet was infiltration of EPRS1high T cells, particularly proliferating T and γδ T cells. The proliferation capacity of both CD4+ and CD8+ T cells, along with interleukin-17 production of γδ T cells, were higher in the kidneys of TIN-induced Eprs1+/+ mice than in the kidneys of TIN-induced Eprs1+/- mice. This discrepancy contributed to the fibrotic amelioration observed in kidneys of Eprs1+/- mice. TIN-induced fibrosis was also reduced in Rag1-/- mice adoptively transferred with Eprs1+/- T cells compared to the Rag1-/- mice transferred with Eprs1+/+ T cells. The use of an EPRS1-targeting small molecule inhibitor (bersiporocin) under clinical trials to evaluate its therapeutic potential against idiopathic pulmonary fibrosis, alleviated immunofibrotic aggravation in TIN. EPRS1 expression was also observed in human kidney tissues and blood-derived T cells, and high expression was associated with worse patient outcomes. Thus, EPRS1 may emerge as a therapeutic target in toxin- and drug-induced TIN, modulating the proliferation and activity of infiltrated T cells.

PMID:38320721 | DOI:10.1016/j.kint.2024.01.011

NEJM Evid. 2023 Aug;2(8):EVIDe2300126. doi: 10.1056/EVIDe2300126. Epub 2023 Jul 25.

ABSTRACT

In this issue of NEJM Evidence, Maher et al.1 report the results of a randomized, controlled, 22-day treatment crossover trial comparing the antitussive effect of extended-release nalbuphine, an opioid agonist-antagonist, with placebo in a cohort of patients with definite or probable idiopathic pulmonary fibrosis (IPF). In this small, short-term trial of 38 evaluable patients, the active drug was associated with a 75.1% reduction in daytime objective cough frequency (the primary outcome) compared with a 22.6% reduction in placebo-treated patients, yielding a substantial and statistically significant 52.5 percentage point placebo-adjusted change from baseline.

PMID:38320149 | DOI:10.1056/EVIDe2300126

NEJM Evid. 2023 Aug;2(8):EVIDoa2300083. doi: 10.1056/EVIDoa2300083. Epub 2023 May 22.

ABSTRACT

Nalbuphine for Cough with Idiopathic Pulmonary FibrosisIn patients with idiopathic pulmonary fibrosis, cough may have a negative impact on daily life. In a randomized, 22-day treatment period, placebo-controlled, crossover trial, extended-release nalbuphine (NAL ER), an opioid agonist-antagonist, was compared to placebo for cough control and adverse effects. During active treatment there was a 75.1% reduction in daytime objective cough frequency compared with 22.6% in the placebo treatment period. Nausea, fatigue, constipation, and dizziness were more common with NAL ER than with placebo.

PMID:38320144 | DOI:10.1056/EVIDoa2300083

Radiology. 2024 Feb;310(2):e231718. doi: 10.1148/radiol.231718.

ABSTRACT

Background There is clinical need to better quantify lung disease severity in pulmonary hypertension (PH), particularly in idiopathic pulmonary arterial hypertension (IPAH) and PH associated with lung disease (PH-LD). Purpose To quantify fibrosis on CT pulmonary angiograms using an artificial intelligence (AI) model and to assess whether this approach can be used in combination with radiologic scoring to predict survival. Materials and Methods This retrospective multicenter study included adult patients with IPAH or PH-LD who underwent incidental CT imaging between February 2007 and January 2019. Patients were divided into training and test cohorts based on the institution of imaging. The test cohort included imaging examinations performed in 37 external hospitals. Fibrosis was quantified using an established AI model and radiologically scored by radiologists. Multivariable Cox regression adjusted for age, sex, World Health Organization functional class, pulmonary vascular resistance, and diffusing capacity of the lungs for carbon monoxide was performed. The performance of predictive models with or without AI-quantified fibrosis was assessed using the concordance index (C index). Results The training and test cohorts included 275 (median age, 68 years [IQR, 60-75 years]; 128 women) and 246 (median age, 65 years [IQR, 51-72 years]; 142 women) patients, respectively. Multivariable analysis showed that AI-quantified percentage of fibrosis was associated with an increased risk of patient mortality in the training cohort (hazard ratio, 1.01 [95% CI: 1.00, 1.02]; P = .04). This finding was validated in the external test cohort (C index, 0.76). The model combining AI-quantified fibrosis and radiologic scoring showed improved performance for predicting patient mortality compared with a model including radiologic scoring alone (C index, 0.67 vs 0.61; P < .001). Conclusion Percentage of lung fibrosis quantified on CT pulmonary angiograms by an AI model was associated with increased risk of mortality and showed improved performance for predicting patient survival when used in combination with radiologic severity scoring compared with radiologic scoring alone. © RSNA, 2024 Supplemental material is available for this article.

PMID:38319169 | DOI:10.1148/radiol.231718

ACS Nano. 2024 Feb 6. doi: 10.1021/acsnano.3c09852. Online ahead of print.

ABSTRACT

The coexistence of lung adenocarcinoma (LUAD) with idiopathic pulmonary fibrosis (IPF), which has been extensively documented as a prominent risk factor for checkpoint inhibitor-related pneumonitis (CIP) in patients undergoing immunotherapy, has long been considered a restricted domain for the use of immune checkpoint inhibitors (ICIs). To overcome it, an approach was employed herein to specifically target PD-L1 within the cellular interior, surpassing the conventional focus solely on the cytomembrane, thereby facilitating the development of ICIs capable of distinguishing between LUAD cells and noncancerous cells based on their distinctive endocytic propensities. By exploiting the aurophilicity-driven self-assembly of a PD-L1 binding peptide (PDBP) and subsequently encapsulating it within erythrocyte membranes (EM), the resulting biomimetic ICIs protein EMS-PDBP exhibited extraordinary selectivity in internalizing LUAD cells, effectively targeting PD-L1 within cancer cells while hindering its membrane translocation. The EMS-PDBP treatment not only reactivated the antitumor immune response in the LUAD orthotopic allograft mouse model but also demonstrated a favorable safety profile by effectively eliminating any immune-related adverse events (irAEs). Most significantly, EMS-PDBP successfully and safely restored the antitumor immune response in a mouse model of LUAD with coexistent IPF, thus shattering the confines of ICIs immunotherapy. The reported EMS-PDBP collectively offers a potential strategy for immune reactivation to overcome the limitations of immunotherapy in LUAD coexisting with IPF.

PMID:38319028 | DOI:10.1021/acsnano.3c09852

Expert Rev Clin Immunol. 2024 Feb 6:1-15. doi: 10.1080/1744666X.2024.2315218. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to explore the relevance of anoikis in idiopathic pulmonary fibrosis (IPF) and identify associated biomarkers and signaling pathways.

METHOD: Unsupervised consensus cluster analysis was employed to categorize IPF patients into subtypes. We utilized Weighted Gene Co-Expression Network Analysis (WGCNA) and Protein-Protein Interaction network construction to identify anoikis-related modules and key genes. A prognostic signature was developed using Lasso and multivariate Cox regression analysis. Single-cell sequencing assessed hub gene expression in various cell types, and both cell and animal experiments confirmed IPF-related pathways.

RESULTS: We identified two distinct anoikis-associated subtypes with differing prognoses. WGCNA revealed essential hub genes, with SPP1 being prominent in the anoikis-related signature. The anoikis-related signature is effective in determining the prognosis of patients with IPF. Single-cell sequencing highlighted significant differences in SPP1 expression, notably elevated in fibroblasts derived from IPF patients. In vivo and in vitro experiments demonstrated that SPP1 enhances fibrosis in mouse lung fibroblasts by regulating p27 through the PI3K/Akt pathway.

CONCLUSION: Our research demonstrates a robust prognostic signature associated with anoikis and highlights SPP1 as a pivotal regulator of the PI3K/AKT signaling pathway in pulmonary fibrosis.

PMID:38318669 | DOI:10.1080/1744666X.2024.2315218

Thorax. 2024 Feb 5:thorax-2023-220179. doi: 10.1136/thorax-2023-220179. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary hypertension (PH) is defined by elevated mean pulmonary arterial pressure (MPAP), and elevated pulmonary vascular resistance (PVR) reflects pulmonary vascular abnormalities. The clinical significance of non-severe PH in patients with various interstitial lung diseases (ILDs) has not been fully elucidated. We aimed to investigate the clinical significance of MPAP and PVR for mortality in patients with newly diagnosed ILD.

METHODS: We retrospectively analysed consecutive patients with ILD at initial evaluations that included right heart catheterisation from 2007 to 2018. These patients were classified by MPAP and PVR using the 2022 the European Society of Cardiology (ESC)/the European Respiratory Society (ERS) guidelines for PH. The clinical significance of MPAP and PVR for mortality was analysed.

RESULTS: Among 854 patients, 167 (19.6%) had MPAP>20 mm Hg. The proportion of patients with PVR>2 Wood units (WU) among those with MPAP≤20 mm Hg, 20<MPAP<25 mm Hg, and ≥25 mm Hg were 26.2%, 60.4% and 86.4%, respectively. In Cox proportional hazards analyses with adjustment for ILD-Gender, Age and Physiology Index, PVR but not MPAP was associated with a higher mortality rate (HR 1.37, 95% CI 1.23 to 1.52, p<0.0001; HR 0.98, 95% CI 0.96 to 1.01, p=0.1671, respectively). PVR>2 WU was associated with a higher mortality rate (HR 1.61, 95% CI 1.28 to 2.02, p<0.0001) even in a group with MPAP≤20 mm Hg.

CONCLUSIONS: Mild elevation of PVR was associated with a higher mortality rate in patients with newly diagnosed ILD, even in those with MPAP≤20 mm Hg.

PMID:38316550 | DOI:10.1136/thorax-2023-220179

Biomarkers. 2024 Feb 5:1-10. doi: 10.1080/1354750X.2024.2311178. Online ahead of print.

ABSTRACT

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is the most serious form of interstitial lung disease. We aimed to investigate the effect of Phœnix dactylifera, L. seed oil (DSO) on a murine model of IPF induced by bleomycin (BLM).

METHODS: Male Wistar rats were treated with a single intra-tracheal injection of BLM (4 mg/kg) and a daily intraperitoneal injection of DSO (75, 150 and 300 mg/kg) for 4 weeks.

RESULTS: Our phytochemical results showed that DSO has an important antioxidant activity with a high content of polyphenols and flavonoids. High-Performance Liquid Chromatography (HPLC) and Gas chromatography/mass spectrometry (GC-MS) analysis revealed a high amount of oleic and lauric acids and a large quantity of vitamins. Histological examination showed a significant reduction in fibrosis score and collagen bands in the group of rats treated with 75 mg/kg of DSO compared to the BLM group. DSO (75 mg/kg) reversed also the increase in catalase and malondialdehyde (MDA) levels while higher doses (150 and 300 mg/kg) are ineffective against the deleterious effects of BLM. We revealed also that DSO has no renal or hepatic cytotoxic effects.

CONCLUSION: DSO can play antioxidant and antifibrotic effects on rat models of pulmonary fibrosis at the lowest dose administered.

PMID:38314578 | DOI:10.1080/1354750X.2024.2311178

Gen Physiol Biophys. 2024 Jan;43(1):49-55. doi: 10.4149/gpb_2023029.

ABSTRACT

The objective of this article is to describe and classify usual interstitial pneumonia (UIP) changes according to their relevance in the pathology of the idiopathic pulmonary fibrosis (IPF) process. In a cohort of 50 patients (25♀, 25♂) with UIP findings, the percentage ratio between fibrotic and preserved parts of the lungs was quantified. Three quantitative stages of fibrotic involvement of the lung parenchyma and concomitant changes were defined. These are initial (≤20%), advanced (21-40%), and diffuse (≥41%) fibrosis of the lungs. Histologically, temporal heterogeneity is predominant with thickened alveolar septa, interstitial fibrosis, and the presence of fibroblastic foci up to mature diffuse fibrosis with honeycomb changes. The finding is accompanied by variably mature lymphocytic inflammation, presence of macrophages, emphysema, bronchioloectasia of the alveoli, bronchiectasis, bronchial muscle wall hypertrophy, hypertrophy of the vessel walls, alveolar mucosa, focal haemorrhage, and hyalinization of the lungs. Pneumocyte hyperplasia, occasionally atypical in appearance with hobnail changes, as well as squamous metaplasia are observed. In the methodically quantified stages of fibrous involvement, 14 subjects were classified (6♀, 8♂) into the stage of initial fibrosis, 21 subjects (11♀; 10♂) into the stage of advanced fibrosis, and 15 subjects (8♀; 7♂) into the stage of diffuse fibrosis.

PMID:38312034 | DOI:10.4149/gpb_2023029

Biogerontology. 2024 Feb 4. doi: 10.1007/s10522-024-10094-x. Online ahead of print.

ABSTRACT

Telomere Biology Disorders (TBDs) are a group of rare diseases characterized by the presence of short and/or dysfunctional telomeres. They comprise a group of bone marrow failure syndromes, idiopathic pulmonary fibrosis, and liver disease, among other diseases. Genetic alterations (variants) in the genes responsible for telomere homeostasis have been linked to TBDs. Despite the number of variants already identified as pathogenic, an even more significant number must be better understood. The study of TBDs is challenging since identifying these variants is difficult due to their rareness, it is hard to predict their impact on the disease onset, and there are not enough samples to study. Most of our knowledge about pathogenic variants comes from assessing telomerase activity from patients and their relatives affected by a TBD. However, we still lack a cell-based model to identify new variants and to study the long-term impact of such variants on the genes involved in TBDs. Herein, we present a cell-based model using CRISPR base editing to mutagenize the endogenous alleles of 21 genes involved in telomere biology. We identified key residues in the genes encoding 17 different proteins impacting cell growth. We provide functional evidence for variants of uncertain significance in patients with TBDs. We also identified variants resistant to telomerase inhibition that, similar to cells expressing wild-type telomerase, exhibited increased tumorigenic potential using an in vitro tumour growth assay. We believe that such cell-based approaches will significantly advance our understanding of the biology of TBDs and may contribute to the development of new therapies for this group of diseases.

PMID:38310618 | DOI:10.1007/s10522-024-10094-x

Pulmonology. 2024 Feb 2:S2531-0437(24)00007-2. doi: 10.1016/j.pulmoe.2024.01.002. Online ahead of print.

ABSTRACT

INTRODUCTION AND OBJECTIVES: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with diverse clinical features that can present a fibrotic phenotype similar to idiopathic pulmonary fibrosis (IPF) in genetically predisposed individuals. While several single nucleotide polymorphisms (SNPs) have been associated with IPF, the genetic factors contributing to fibrotic HP (fHP) remain poorly understood. This study investigated the association of MUC5B and TOLLIP variants with susceptibility, clinical presentation and survival in Portuguese patients with fHP.

MATERIAL AND METHODS: A case-control study was undertaken with 97 fHP patients and 112 controls. Six SNPs residing in the MUC5B and TOLLIP genes and their haplotypes were analyzed. Associations with risk, survival, and clinical, radiographic, and pathological features of fHP were probed through comparisons among patients and controls.

RESULTS: MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP. Minor allele frequencies were greater among fHP patients than in controls (40.7% vs 12.1%, P<0.0001; 52.6% vs 40.2%, P = 0.011; 22.7% vs 13.4%, P = 0.013; and 23.2% vs 12.9%, P = 0.006, respectively). Haplotypes formed by these variants were also linked to fHP susceptibility. Moreover, carriers of a specific haplotype (G-T-G-C) had a significant decrease in survival (adjusted hazard ratio 6.92, 95% CI 1.73-27.64, P = 0.006). Additional associations were found between TOLLIP rs111521887 and rs5743894 variants and decreased lung function at baseline, and the MUC5B SNP and radiographic features, further highlighting the influence of genetic factors in fHP.

CONCLUSION: These findings suggest that TOLLIP and MUC5B variants and haplotypes may serve as valuable tools for risk assessment and prognosis in fibrotic hypersensitivity pneumonitis, potentially contributing to its patient stratification, and offer insights into the genetic factors influencing the clinical course of the condition.

PMID:38309995 | DOI:10.1016/j.pulmoe.2024.01.002

Zhonghua Jie He He Hu Xi Za Zhi. 2024 Feb 12;47(2):178-182. doi: 10.3760/cma.j.cn112147-20230902-00128.

ABSTRACT

The world's population is ageing at a rate unprecedented in human history. As the number of older people increases, so does the prevalence of lung disease in the elderly, making it essential to understand the pathophysiology of elderly patients with lung disease. Age-related changes in immune system function and lung parenchyma occur throughout a person's life. Immunosenescence refers to the tendency for innate and adaptive immunity to decline in the elderly. As we age, changes in the innate and adaptive immune systems can lead to dysregulation and reduced immune function. A low-level chronic inflammatory state is known as inflamm-aging and is driven by immunosenescence. This review discusses the role of immunosenescence and inflamm-aging in pulmonary diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and lung infections. Understanding the different manifestations of lung diseases between the elderly and the young, finding new therapeutic sites, or improving clinical outcomes in hospitalized patients will provide clinicians with new ideas.

PMID:38309971 | DOI:10.3760/cma.j.cn112147-20230902-00128

J Manag Care Spec Pharm. 2024 Feb 3;30(2):163-174. doi: 10.18553/jmcp.2024.30.2.163.

ABSTRACT

BACKGROUND: Fibrosing interstitial lung disease (ILD) encompasses more than 200 diverse pulmonary disorders, of which up to 40% become progressive. The 4 underlying ILD types most likely to result in progression are unclassified ILD/idiopathic interstitial pneumonia (IIP), autoimmune ILDs, exposure-related ILD/hypersensitivity pneumonitis, and sarcoidosis.

OBJECTIVE: To compare health care resource utilization (HCRU) and costs among patients with fibrosing ILD that has progressed ("progressive" fibrosing cohort) vs patients whose fibrosis did not meet criteria set for progression ("not yet progressed" cohort).

METHODS: This was a noninterventional study of commercial enrollees and Medicare Advantage with Part D beneficiaries, which used administrative claims data for the period from October 1, 2015, through May 31, 2021. Adult patients (aged ≥18 years) with fibrosing ILD and 12 months of continuous health plan enrollment were included. Patients with idiopathic pulmonary fibrosis, baseline ILD diagnoses, or missing demographic data were excluded. Patients were first classified according to the underlying type of fibrosing ILD. For statistical analyses of outcomes, 2 cohorts were compared within each subtype: progressive fibrosing ILD vs not yet progressed ILD. The final study population included propensity score-matched (PSM) patients (1:1) based on pre-ILD baseline demographic and clinical characteristics. HCRU categories included inpatient hospitalization counts and the number of inpatient days and total costs (in 2021 US dollars), analyzed descriptively and weighted by the per-patient-per-month cost. Lin's regression was used to predict 12-month total cost estimates for comparison by cohort.

RESULTS: The distribution by underlying conditions was as follows: autoimmune ILD (n = 4,156), HP (n = 8,181), sarcoidosis (n = 775), and unclassified ILD/IIP (n = 18,635). After PSM, pre-ILD baseline variables were generally well balanced between the progressive and not yet progressed fibrosing ILD cohorts. For all underlying subtypes of ILD, patients in the progressive cohort had significantly more utilization and higher costs compared with patients in the not yet progressed cohort. Progressive cohorts had significantly higher adjusted rates of inpatient days among patients with at least 1 inpatient stay compared with the not yet progressed cohorts (all P < 0.01). In addition, the progressive cohorts had significantly higher adjusted 12-month total costs, with the differences ranging from $24,493 to $55,072 (all comparisons P < 0.001).

CONCLUSIONS: Irrespective of underlying ILD type, patients with progressive fibrosing ILD had significantly increased HCRU and cost relative to those whose fibrosing ILD had not yet progressed.

PMID:38308627 | DOI:10.18553/jmcp.2024.30.2.163

Eur Respir J. 2024 Feb 1;63(2):2400067. doi: 10.1183/13993003.00067-2024. Print 2024 Feb.

NO ABSTRACT

PMID:38302183 | DOI:10.1183/13993003.00067-2024

Respirology. 2024 Feb 1. doi: 10.1111/resp.14668. Online ahead of print.

NO ABSTRACT

PMID:38302099 | DOI:10.1111/resp.14668

Ann Med. 2024 Dec;56(1):2311845. doi: 10.1080/07853890.2024.2311845. Epub 2024 Feb 1.

ABSTRACT

OBJECTIVE: The association between nutritional status and prognosis of idiopathic pulmonary fibrosis (IPF) remains unclear. This systematic review and meta-analysis aimed to explore the effect of body mass index (BMI) and weight loss on the prognosis of IPF patients.

METHODS: We accumulated studies on IPF, BMI, and weight loss from databases including PubMed, Embase, Web of science, Scopus, Ovid and Cochrane Library up to 4 August 2023. Using Cox proportional hazard regression model for subgroup analysis, hazard ratio (HR) and 95% confidence intervals (CI) for BMI in relation to mortality, acute exacerbation (AE), and hospitalization in IPF patients were calculated, and HR, odds ratio (OR), and 95% CI for weight loss corresponding to IPF patient mortality were assessed. Sensitivity analysis was peformed by eliminating every study one by one, and publication bias was judged by Egger's test and trim-and-fill method.

RESULTS: A total of 34 eligible studies involving 18,343 IPF patients were included in the meta-analysis. The pooled results by univariate Cox regression analysis showed that baseline BMI was a predictive factor for IPF mortality (HR = 0.93, 95%CI = [0.91, 0.94]). Furthermore, the results by the multivariable regression model indicated that baseline BMI was an independent risk factor for predicting IPF mortality (HR = 0.94, 95%CI = [0.91, 0.98]). Weight loss was identified as a risk factor for IPF mortality (HR = 2.74, 95% CI = [2.12, 3.54]; OR = 4.51, 95% CI = [1.72, 11.82]) and there was no predictive value of BMI for acute exacerbation (HR = 1.00, 95% CI= [0.93, 1.07]) or hospitalization (HR = 0.95, 95% CI = [0.89, 1.02]).

CONCLUSION: Low baseline BMI and weight loss in the course of IPF may indicate a high risk of mortality in patients with IPF, so it is meaningful to monitor and manage the nutritional status of IPF patients, and early intervention should be conducted for low BMI and weight loss.

PMID:38301276 | PMC:PMC10836485 | DOI:10.1080/07853890.2024.2311845

Am J Respir Crit Care Med. 2024 Feb 1. doi: 10.1164/rccm.202311-2169LE. Online ahead of print.

NO ABSTRACT

PMID:38301238 | DOI:10.1164/rccm.202311-2169LE