BMC Pulm Med. 2023 Oct 26;23(1):407. doi: 10.1186/s12890-023-02714-y.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with unknown etiology. To date, the identification of new diagnostic, prognostic and progression biomarkers of IPF turns out to be necessary. MicroRNA (miRNA) are small non-coding RNAs which negatively regulate gene expression at the post-transcriptional level in several biological and pathological processes. An aberrant regulation of gene expression by miRNA is often associated with various diseases, including IPF. As result, miRNAs have emerged as potential biomarkers with relevance to pulmonary fibrosis. Several reports suggested that miRNAs are secreted as microvesicles or exosome, and hance they are stable and can be readily detected in the circulation. In the contest of miRNAs as circulating biomarkers, different studies show their role in various types of interstitial lung diseases and suggest that these small molecules could be used as prognostic markers of the disease. Exosomes are small, lipid-bound vesicles able to carry various elements of the naïve cells such as proteins, lipids, mRNAs and miRNA to facilitate cell communication under normal and diseases condition. Exosomal miRNAs (exo-miRNA) have been studied in relation to many diseases. However, there is little or no knowledge regarding exo-miRNA in bronchoalveolar lavage (BAL) in IPF. Our study's aim is to evaluate the changes in the expression of two exo-miRNAs in BAL, respectively miR-21 and miR-92a, through highlighting the differences between IPF, progressive pulmonary fibrosis (PPF) and not-progressive pulmonary fibrosis (nPPF).

METHODS: Exosomes were characterized by Western Blot and Multiplex Surface Marker Analysis. Exosomal miRNA expression was performed by qRT-PCR. ANOVA or Kruskal-Wallis test, based on data normality, was used to compare the differential expression between groups.

RESULTS: MiR-21 expression was significantly higher in the nPPF group than in both IPF and PPF. A result that could point above a possible role of miR-21, as a biomarker in the differential diagnosis between PPF and nPPF. MiR-92a, indeed, was down regulated in PPF compared to IPF and down regulated in PPF compared to nPPF.

CONCLUSIONS: This study demonstrated the putative role of both miR-21 and miR-92a as possible biomarkers of pulmonary fibrosis progression. Moreover, the role of exo-miRNAs is examined as a possible future direction that could lead to new therapeutic strategies for the treatment of progressive and non-progressive pulmonary fibrosis.

PMID:37884953 | DOI:10.1186/s12890-023-02714-y

Drugs Real World Outcomes. 2023 Oct 26. doi: 10.1007/s40801-023-00396-w. Online ahead of print.

ABSTRACT

BACKGROUND: The antifibrotic drugs, nintedanib and pirfenidone, inhibit the decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib also inhibits the onset of acute exacerbation and reduces the risk of all-cause mortality. However, their effectiveness in real-world practice remains unclear. Our study aimed to investigate the changes in forced vital capacity, survival period, causes of death, and risk factors for mortality in patients with IPF receiving antifibrotic drugs.

METHODS: This retrospective study enrolled Japanese patients who visited Toho University Sakura Medical Center who were diagnosed with IPF and received antifibrotic drugs.

RESULTS: We included 102 patients [mean age ± standard deviation (SD): 71.8 ± 7.5 years], of whom 76 were males. The decline in forced vital capacity (mean ± SD) during the antifibrotic therapy period was - 154 ± 259 mL/year, which was significantly lower than before the antifibrotic therapy period (- 484 ± 589 mL/year; n = 80, p = 0.003). Altogether, 52 deaths were confirmed, and the median survival time from antifibrotic therapy initiation was 38.0 months (95% confidence interval: 25.9-50.1 months). Acute exacerbation accounted for 9.6% of all deaths (95% confidence interval: 1.6-17.6). The decline in forced vital capacity during antifibrotic therapy was a risk factor for mortality.

CONCLUSIONS: In actual clinical practice in Japan, antifibrotic drugs suppressed the gradual decline in forced vital capacity, which is a risk factor for mortality. However, the median survival period remained poor at 38 months.

PMID:37883007 | DOI:10.1007/s40801-023-00396-w

Drugs. 2023 Oct 26. doi: 10.1007/s40265-023-01950-0. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) remains a disease with poor survival. The pathogenesis is complex and encompasses multiple molecular pathways. The first-generation antifibrotics pirfenidone and nintedanib, approved more than 10 years ago, have been shown to reduce the rate of progression, increase the length of life for patients with IPF, and work for other fibrotic lung diseases. In the last two decades, most clinical trials on IPF have failed to meet the primary endpoint and an urgent unmet need remains to identify agents or treatment strategies that can stop disease progression. The pharmacotherapeutic landscape for IPF is moving forward with a number of new drugs currently in clinical development, mostly in phase I and II trials, while only a few phase III trials are running. Since our understanding of IPF pathogenesis is still limited, we should keep focusing our efforts to deeper understand the mechanisms underlying this complex disease and their reflection on clinical phenotypes. This review discusses the key pathogenetic concepts for the development of new antifibrotic agents, presents the newest data on approved therapies, and summarizes new compounds currently in clinical development. Finally, future directions in antifibrotics development are discussed.

PMID:37882943 | DOI:10.1007/s40265-023-01950-0

Chest. 2023 Oct 23:S0012-3692(23)05666-0. doi: 10.1016/j.chest.2023.10.021. Online ahead of print.

ABSTRACT

BACKGROUND: Different patterns of fibrosis on high resolution computer tomography scans (HRCT) have been associated with reduced survival in some interstitial lung diseases. Nothing is known about HRCT patterns and survival in sarcoidosis.

RESEARCH QUESTION: Will a detailed description of the extent and pattern of HRCT fibrosis in patients with Stage IV pulmonary sarcoidosis impact pulmonary function and survival ?

STUDY DESIGN AND METHODS: 240 stage IV sarcoidosis patients at two large tertiary institutions were studied. The earliest HRCT with fibrosis was reviewed for extent of fibrosis (<10%, 10-20% and >20%) and presence of bronchiectasis, upper lobe fibrocystic changes, basal subpleural honeycombing, ground glass opacities (GGOs), large bullae and mycetomas. Presence of sarcoidosis associated pulmonary hypertension (SAPH) and PFTs performed within one year of HRCT were recorded. Patients were followed until last clinic visit, death, or lung transplant (LT).

RESULTS: The mean age was 58.4 years. 74% were African American, 63% were female, and mean follow-up was 7.4 years. Death or LT occurred in 53 patients (22%). 31% had >20% fibrosis, 25% had 10-20% fibrosis and 44% had <10% fibrosis. The most common HRCT abnormalities were bronchiectasis (76%), upper lobe fibrocystic changes (36%), and GGOs (28%). 12% had basal subpleural honeycombing and 32% had SAPH. Patients with >20% fibrosis had more severe pulmonary impairment, were more likely to have SAPH(53%) and had worse survival (44% mortality; p<0.001). Upper lobe fibrocystic changes, basal subpleural honeycombing, and large bullae were associated with worse pulmonary function and worse survival. Patients with basal subpleural honeycombing had the worst pulmonary function and survival (55% mortality, p<0.001). GGOs were associated with worse pulmonary function but not worse survival while mycetomas were associated with worse survival but not worse pulmonary function. A Cox-proportional hazards model revealed that basal subpleural honeycombing (HR 7.95), DLCO<40% (HR 5.67) and White Race (HR 2.61) were independent predictors of reduced survival.

INTERPRETATION: HRCT features of fibrotic pulmonary sarcoidosis had an impact on pulmonary function and survival. Presence of >20% fibrosis and basal subpleural honeycombing are predictive of worse pulmonary function and worse survival in patients with stage IV pulmonary sarcoidosis.

PMID:37879560 | DOI:10.1016/j.chest.2023.10.021

Respir Res. 2023 Oct 25;24(1):254. doi: 10.1186/s12931-023-02556-6.

ABSTRACT

BACKGROUND: Fibroblast activation protein-α (FAPα) is a marker of activated fibroblasts that can be selectively targeted by an inhibitor (FAPI) and visualised by PET/CT imaging. We evaluated whether the measurement of FAPα in bronchoalveolar lavage fluids (BALF) and the uptake of FAPI by PET/CT could be used as biomarkers of fibrogenesis.

METHODS: The dynamics of lung uptake of 18F-labeled FAPI ([18F]FAPI-74) was assessed in the bleomycin mouse model at various time points and using different concentrations of bleomycin by PET/CT. FAPα was measured in BALFs from these bleomycin-treated and control mice. FAPα levels were also assessed in BALFs from controls and patients with idiopathic pulmonary fibrosis (IPF).

RESULTS: Bleomycin-treated mice presented a significantly higher uptake of [18F]FAPI-74 during lung fibrinogenesis (days 10 and 16 after instillation) compared to control mice. No significant difference was observed at initial inflammatory phase (3 days) and when fibrosis was already established (28 days). [18F]FAPI-74 tracer was unable to show a dose-response to bleomycin treatment. On the other hand, BALF FAPα levels were steeply higher in bleomycin-treated mice at day 10 and a significant dose-response effect was observed. Moreover, FAPα levels were strongly correlated with lung fibrosis as measured by the modified Aschroft histological analysis, hydroxyproline and the percentage of weight loss. Importantly, higher levels of FAPα were observed in IPF patients where the disease was progressing as compared to stable patients and controls. Moreover, patients with FAPα BALF levels higher than 192.5 pg/mL presented a higher risk of progression, transplantation or death compared to patients with lower levels.

CONCLUSIONS: Our preclinical data highlight a specific increase of [18F]FAPI-74 lung uptake during the fibrotic phase of the bleomycin murine model. The measurement of FAPα in BALF appears to be a promising marker of the fibrotic activity in preclinical models of lung fibrosis and in IPF patients. Further studies are required to confirm the role of FAPα in BALF as biomarker of IPF activity and assess the relationship between FAPα levels in BALF and [18F]FAPI-74 uptake on PET/CT in patients with fibrotic lung disease.

PMID:37880678 | DOI:10.1186/s12931-023-02556-6

BMC Pulm Med. 2023 Oct 26;23(1):404. doi: 10.1186/s12890-023-02724-w.

ABSTRACT

INTRODUCTION: Antigen identification impacts diagnosis as well as prognosis in patients with hypersensitivity pneumonitis. An antigen may also be present in other etiologies of interstitial lung disease, however it is unknown whether identification impacts survival.

METHODS: We evaluated a retrospective cohort in order to determine if antigen identification affects transplant free survival in patients with hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, connective tissue disease interstitial lung disease, and interstitial pneumonia with autoimmune features. Only patients with definite or high probability of hypersensitivity pneumonitis by American Thoracic Society guidelines were included in the analysis.

RESULTS: Transplant free survival was improved with antigen identification in patients with hypersensitivity pneumonitis but not in patients with idiopathic pulmonary fibrosis, connective tissue disease interstitial lung disease, and interstitial pneumonia with autoimmune features.

CONCLUSION: Our study suggests that removal of identified antigen in interstitial lung diseases other than hypersensitivity pneumonitis may not be impactful. Additionally, it further suggests that definitive diagnosis of hypersensitivity pneumonitis with bronchoalveolar lavage and transbronchial biopsy may be beneficial prior to recommending antigen removal.

PMID:37880637 | DOI:10.1186/s12890-023-02724-w

Circ J. 2023 Oct 26. doi: 10.1253/circj.CJ-23-0657. Online ahead of print.

ABSTRACT

Aging is a major risk factor for cardiovascular diseases (CVDs) and accumulating evidence indicates that biological aging has a significant effect on the onset and progression of CVDs. In recent years, therapies targeting senescent cells (senotherapies), particularly senolytics that selectively eliminate senescent cells, have been developed and show promise for treating geriatric syndromes and age-associated diseases, including CVDs. In 2 pilot studies published in 2019 the senolytic combination, dasatinib plus quercetin, improved physical function in patients with idiopathic pulmonary fibrosis and eliminated senescent cells from adipose tissue in patients with diabetic kidney disease. More than 30 clinical trials using senolytics are currently underway or planned. In preclinical CVD models, senolytics appear to improve heart failure, ischemic heart disease, valvular heart disease, atherosclerosis, aortic aneurysm, vascular dysfunction, dialysis arteriovenous fistula patency, and pre-eclampsia. Because senotherapies are completely different strategies from existing treatment paradigms, they might alleviate diseases for which there are no current effective treatments or they could be used in addition to current therapies to enhance efficacy. Moreover, senotherapies might delay, prevent, alleviate or treat multiple diseases in the elderly and reduce polypharmacy, because senotherapies target fundamental aging mechanisms. We comprehensively summarize the preclinical evidence about senotherapies for CVDs and discuss future prospects for their clinical application.

PMID:37880106 | DOI:10.1253/circj.CJ-23-0657

Ann Am Thorac Soc. 2023 Oct 25. doi: 10.1513/AnnalsATS.202308-697RL. Online ahead of print.

NO ABSTRACT

PMID:37879035 | DOI:10.1513/AnnalsATS.202308-697RL

J Mol Histol. 2023 Oct 25. doi: 10.1007/s10735-023-10169-y. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic lung disease characterized by abnormal proliferation and activation of fibroblasts, excessive accumulation of extracellular matrix (ECM), inflammatory damage, and disrupted alveolar structure. Despite its increasing morbidity and mortality rates, effective clinical treatments for IPF remain elusive. Osteopontin (OPN), a multifunctional ECM protein found in various tissues, has been implicated in numerous biological processes such as bone remodeling, innate immunity, acute and chronic inflammation, and cancer. Recent studies have highlighted the pivotal role of OPN in the pathogenesis of IPF. This review aims to delve into the involvement of OPN in the inflammatory response, ECM deposition, and epithelial-mesenchymal transition (EMT) during IPF, and intends to lay a solid theoretical groundwork for the development of therapeutic strategies for IPF.

PMID:37878112 | DOI:10.1007/s10735-023-10169-y

bioRxiv. 2023 Oct 10:2023.10.07.561349. doi: 10.1101/2023.10.07.561349. Preprint.

ABSTRACT

BACKGROUND: Mast-Cell Expressed Membrane Protein-1 (MCEMP1) is higher in Idiopathic Pulmonary Fibrosis (IPF) patients with increased risk of death and poor outcomes. Here we seek to establish the mechanistic role of MCEMP1 in pulmonary fibrosis.

METHODS: MCEMP1 expression was analyzed by single-cell RNA sequencing, immunofluorescence in Peripheral Blood Mononuclear Cells (PBMC) as well as in lung tissues from IPF patients and controls. Chromatin Immunoprecipitation (ChiP) and Proximity Ligation Assay (PLA) were used to study the transcriptional regulation of MCEMP1 . Transient RNA interference and lentivirus transduction were used to knockdown and knock-in MCEMP1 in THP-1 cells to study chemotaxis, adhesion, and migration. Bulk RNA sequencing was used to identify the mechanisms by which MCEMP1 participates in monocyte function. Active RHO pull-down assay was used to validate bulk RNA sequencing results.

RESULTS: We identified increased MCEMP1 expression in classical monocytes and alveolar macrophages in IPF compared to controls. MCEMP1 was upregulated by TGFβ at the mRNA and protein levels in THP-1. TGFβ-mediated MCEMP1 upregulation results from the cooperation of SMAD3 and SP1 via concomitant binding to SMAD3/SP1 cis -regulatory elements within the MCEMP1 promoter. In terms of its function, we found that MCEMP1 regulates TGFβ-mediated monocyte chemotaxis, adhesion, and migration. 400 differentially expressed genes were found to increase after TGFβ stimulation of THP-1, further increased in MCEMP1 knock-in cells treated with TGFβ and decreased in MCEMP1 knockdown cells treated with TGFβ. GO annotation analysis of these genes showed enrichment for positive regulation of RHO GTPase activity and signal transduction. While TGFβ enhanced RHO GTPase activity in THP-1 cells, this effect was attenuated following MCEMP1 knockdown.

CONCLUSION: MCEMP1 is highly expressed in circulating classical monocytes and alveolar macrophages in IPF. MCEMP1 is regulated by TGFβ and participates in the chemotaxis, adhesion, and migration of circulating monocytes by modulating the effect of TGFβ in RHO activity. Our results suggest that MCEMP1 may regulate the migration and transition of monocytes to monocyte-derived alveolar macrophages during pulmonary fibrosis development and progression.

PMID:37873485 | PMC:PMC10592658 | DOI:10.1101/2023.10.07.561349

Acta Clin Croat. 2022 Dec;61(4):722-726. doi: 10.20471/acc.2022.61.04.21.

ABSTRACT

Acute interstitial pneumonia (AIP) is a rare idiopathic interstitial pneumonia with histology finding of diffuse alveolar damage (DAD). It is characterized by progressive hypoxic respiratory failure, high mortality rate, and absence of guidelines for its treatment. Here we present a case of a 64-year-old woman with progressive dyspnea, acute respiratory failure, diffuse bilateral reticulonodular opacities on standard chest radiograph, diffuse ground-glass opacities on computed tomography, and biopsy proven DAD. Diagnosis of AIP was established after extensive work-up that excluded the known risk factors for acute respiratory distress syndrome. Oxygen therapy and high-dose parenteral corticosteroids led to gradual improvement and resulted in complete respiratory recovery. Since there are no existing guidelines for treating AIP, more case reports and case series if not randomized control trials are warranted in order to define the most effective therapeutic modality.

PMID:37868166 | PMC:PMC10588378 | DOI:10.20471/acc.2022.61.04.21

QJM. 2023 Oct 23;116(10):891. doi: 10.1093/qjmed/hcad231.

NO ABSTRACT

PMID:37871308 | DOI:10.1093/qjmed/hcad231

ERJ Open Res. 2023 Oct 2;9(5):00210-2023. doi: 10.1183/23120541.00210-2023. eCollection 2023 Sep.

ABSTRACT

BACKGROUND: Identifying systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients at risk of more rapid forced vital capacity (FVC) decline could improve trial design. The purpose of the present study was to explore the prognostic value of quantitative high-resolution computed tomography (HRCT) metrics derived by Imbio lung texture analysis (LTA) tool in predicting FVC slope.

METHODS: This retrospective study used data from patients who were not treated with investigational drugs with and without background antifibrotic therapies in tocilizumab phase 3 SSc, lebrikizumab phase 2 IPF, and zinpentraxin alfa phase 2 IPF studies conducted from 2015 to 2021. Controlled HRCT axial volumetric multidetector computed tomography scans were evaluated using the Imbio LTA tool. Associations between HRCT metrics and FVC slope were assessed through the Spearman correlation coefficient and adjusted R2 in a linear regression model adjusted by demographics and baseline clinical characteristics.

RESULTS: A total of 271 SSc and IPF patients were analysed. Correlation coefficients of highest magnitude were observed in the SSc study between the extent of ground glass, normal volume, quantification of interstitial lung disease, reticular pattern, and FVC slope (-0.25, 0.28, -0.28, and -0.33, respectively), while the correlation coefficients observed in IPF studies were in general <0.2. The incremental prognostic value of the baseline HRCT metrics was marginal after adjusting baseline characteristics and was inconsistent across study arms.

CONCLUSION: Data from the SSc and IPF studies suggested weak to no and inconsistent correlation between quantitative HRCT metrics derived by the Imbio LTA tool and FVC slope in the studied SSc and IPF population.

PMID:37868144 | PMC:PMC10588799 | DOI:10.1183/23120541.00210-2023

Chest. 2023 Oct 20:S0012-3692(23)05645-3. doi: 10.1016/j.chest.2023.09.035. Online ahead of print.

ABSTRACT

BACKGROUND: Preclinical experiments suggest protective effects of omega-3 fatty acids and their metabolites in lung injury and fibrosis. Whether higher intake of omega-3 fatty acids is associated with disease progression and survival in humans with pulmonary fibrosis is unknown.

RESEARCH QUESTION: What are the associations of plasma omega-3 fatty acid levels (a validated marker of omega-3 nutritional intake) with disease progression and transplant-free survival in pulmonary fibrosis?.

STUDY DESIGN AND METHODS: Omega-3 fatty acid levels were measured from plasma samples of patients with clinically diagnosed pulmonary fibrosis from the Pulmonary Fibrosis Foundation (PFF) Patient Registry (n = 150), University of Virginia (UVA) (n = 58), and University of Chicago (UC) (n = 101) cohorts. The N-3 index (docosahexaenoic acid [DHA] + eicosapentaenoic acid [EPA]) was the primary exposure variable of interest. Linear-mixed effects models with random intercept and slope were used to examine associations of plasma omega-3 fatty acid levels with changes in FVC and diffusing capacity for carbon monoxide (Dlco) over a period of 12 months. Cox proportional hazards models were used to examine transplant-free survival. Stratified analyses by telomere length were performed in the UC cohort.

RESULTS: Most of the cohort were patients with idiopathic pulmonary fibrosis (IPF) (88%) and men (74%). One-unit increment in log-transformed N-3 index plasma level was associated with a change in Dlco of 1.43 mL/min/mm Hg per 12 months (95% CI, 0.46-2.41) and a hazard ratio for transplant-free survival of 0.44 (95% CI, 0.24-0.83). Cardiovascular disease history, smoking, and antifibrotic usage did not significantly modify associations. Omega-3 fatty acid levels were not significantly associated with changes in FVC. Higher EPA plasma levels were associated with longer transplant-free survival among UC participants with shorter telomere length (P-value for interaction = .02).

INTERPRETATION: Further research is needed to investigate underlying biological mechanisms and whether omega-3 fatty acids are a potential disease-modifying therapy.

PMID:37866772 | DOI:10.1016/j.chest.2023.09.035

Farm Hosp. 2023 Oct 19:S1130-6343(23)00885-1. doi: 10.1016/j.farma.2023.09.004. Online ahead of print.

ABSTRACT

OBJECTIVE: To develop a checklist to facilitate pharmaceutical care for patients with interstitial lung disease who require or are undergoing treatment with antifibrotic drugs.

METHOD: Five hospital pharmacists developed an initial list of 37 items divided into 4 blocks: (1) First visit, which included general patient data and data from the first treatment; (2) follow-up visits, assessing aspects of the follow-up of the treatment with nintedanib or pirfenidone; (3) telepharmacy, consisting of the evaluation of the inclusion of patients in a program of this type, course of the disease, and identification of the contact with the pharmacy service; (4) non-pharmacological treatment and patient information. To decide its potential inclusion in the checklist, 2 rounds of the Delphi were carried out in which the panelists had to assess the degree of agreement of each proposed item according to its "utility", which was the determining criterion for its inclusion, and its "applicability".

RESULTS: Forty-eight hospital pharmacists were contacted, 30 (63%) agreed in writing to participate, 28 (58%) completed the first round of the Delphi, and 27 (56%) completed the second round. After the first round of the Delphi, the questionnaire was amended and comprised 40 items. Of the 40 items evaluated after the 2 rounds of the Delphi, there were 2 that, based on utility, the participants did not reach consensus for inclusion in the checklist: the one referring to "History of surgical intervention, specifically abdominal surgery in the last 4 weeks" (finally kept on the checklist due to its involvement in the indication of nintedanib) and to make recommendations on "Relaxation". No consensus was reached on their applicability for 2 of the items: "Patient stratification according to the Spanish Society of Hospital Pharmacy (SEFH) chronic patient model" and "Collection of Results Reported by the Patient".

CONCLUSIONS: The management of patients with ILD and/or pulmonary fibrosis is complex and requires a multidisciplinary approach where the hospital pharmacist plays a key role, especially, although not only, in monitoring drug treatment. We believe that this checklist can contribute from pharmaceutical care to improving the integrated care of patients with ILD who require or are undergoing treatment with antifibrotic drugs.

PMID:37865593 | DOI:10.1016/j.farma.2023.09.004

Clin Exp Med. 2023 Oct 21. doi: 10.1007/s10238-023-01214-x. Online ahead of print.

ABSTRACT

Few biomarkers distinguish connective tissue disease-associated interstitial lung disease (CTD-ILD) from idiopathic pulmonary fibrosis (IPF). Latent transforming growth factor-β binding protein-2 (LTBP2), a secreted extracellular matrix protein, is involved in pulmonary fibrosis. However, the role of LTBP2 in differentially diagnosing CTD-ILD and IPF is unclear. In this study, enzyme-linked immunosorbent assays quantified plasma LTBP2 concentrations in 200 individuals (35 healthy controls, 42 CTD patients without ILD, 89 CTD-ILD patients, and 34 IPF patients). CTD-ILD and IPF were further classified based on chest imaging pattern and pulmonary function test results. Plasma LTBP2 levels were significantly elevated in the IPF group compared with the CTD-ILD group. ROC analysis further suggested the possible value of LTBP2 in differentially diagnosing CTD-ILD and IPF. Additionally, CTD-ILD patients with progressive lung fibrosis had higher plasma LTBP2 concentrations than those who did not. Similarly, patients with IPF developing acute exacerbation showed higher plasma LTBP2 levels than those with stable IPF. This is the first study showing that LTBP2 was closely associated with the usual interstitial pneumonia (UIP) pattern in rheumatoid arthritis-associated ILD (RA-ILD). Moreover, the optimal cutoff values of LTBP2 for distinguishing IPF from CTD-UIP/RA-UIP were 33.75 and 38.33 ng/mL with an AUC of 0.682 and 0.681, respectively. Our findings suggest that plasma LTBP2 levels may differentially diagnose CTD-ILD and IPF, and assess their fibrotic activity. Additionally, clinical LTBP2 evaluation may be a great aid to identifying the presence of the UIP pattern in RA-ILD and to discriminating IPF from CTD-UIP, particularly RA-UIP.

PMID:37864077 | DOI:10.1007/s10238-023-01214-x

Respir Med. 2023 Oct 18:107433. doi: 10.1016/j.rmed.2023.107433. Online ahead of print.

ABSTRACT

BACKGROUND: Interstitial lung diseases (ILDs) cause fibrosis of lung parenchyma, leading to impaired quality of life, dyspnea, and functional decline. Individuals with ILD experience a high prevalence of anxiety and depression. Recent research has demonstrated pulmonary rehabilitation (PR) alleviates symptoms of anxiety and depression in those with COPD.

RESEARCH QUESTION: What is the influence of PR on symptoms of anxiety and depression in individuals with ILD?

STUDY DESIGN: and Methods: We conducted a PRISMA-2020-compliant systematic review of randomized controlled trials (RCTs) investigating PR's effect on anxiety and depression in patients with ILD. We searched MEDLINE, EMBASE, Cochrane, and PsycINFO from inception until April 3, 2023. A narrative synthesis was conducted where a quantitative approach was not feasible.

RESULTS: Five RCTs (n = 281) were included. Idiopathic pulmonary fibrosis (IPF) was the most common type of ILD (k = 3). One study reported clinically-significant improvements in symptoms of anxiety among patients with IPF, and two studies for symptoms of depression among patients with sarcoidosis. Dropout rates were similar between intervention and control groups. All studies were at a high risk of bias.

INTERPRETATION: Pulmonary rehabilitation is not detrimental to anxiety or depression for patients with ILD, and may improve symptoms of anxiety in IPF and depression in sarcoidosis. However, no conclusion can be drawn from available evidence, which is limited by heterogeneous populations/interventions, sample sizes and low prevalences of clinically-significant anxiety or depression. Further adequately powered RCTs that focus on anxiety and depressive symptoms as primary outcomes are needed.

PMID:37863339 | DOI:10.1016/j.rmed.2023.107433

Curr Rheumatol Rev. 2023 Oct 9. doi: 10.2174/0115733971262676230920102922. Online ahead of print.

ABSTRACT

Autoimmune diseases can express pathologies in specific organs (e.g. thyroid, pancreas, skin) or generate systemic pathologies (generalized lupus erythematosus, rheumatoid arthritis, systemic sclerosis), the latter usually present systemic inflammatory phenomena. Some studies have reported alterations in right ventricular contractility in patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and juvenile idiopathic arthritis, which may contribute to the known outcome of increased cardiovascular risk. However, there is not much information available on the causes that generate these alterations, the most likely being small vessel damage and fibrosis due to subclinical inflammation.1-5 In this sense, the disease in which the alterations of the right ventricle have been more studied is systemic sclerosis, specifically at the changes induced due to pulmonary arterial hypertension, this being one of the main causes of death in this group of patients after the significant decrease in mortality associated with the sclerodermic renal crisis with the treatment of angiotensin-converting enzyme inhibitors. In this review, we will focus on explaining the structural and functional changes that occur in the right ventricle of patients with systemic sclerosis, from early alterations to late complications. In this context, it is necessary to distinguish between right heart alterations that occur in patients with systemic sclerosis and pulmonary arterial hypertension and those that occur without pulmonary arterial hypertension and that can be attributed to other causes such as microvascular damage or myocardial fibrosis.

PMID:37861019 | DOI:10.2174/0115733971262676230920102922

Eur Respir J. 2023 Oct 19;62(4):2300262. doi: 10.1183/13993003.00262-2023. Print 2023 Oct.

NO ABSTRACT

PMID:37857429 | DOI:10.1183/13993003.00262-2023

Eur Respir J. 2023 Oct 19:2300323. doi: 10.1183/13993003.00323-2023. Online ahead of print.

NO ABSTRACT

PMID:37857422 | DOI:10.1183/13993003.00323-2023