Introduction Idiopathic Pulmonary Fibrosis Research Articles

Sumatriptan mitigates bleomycin-induced lung fibrosis in male rats: Involvement of inflammation, oxidative stress and α-SMA

IntroductionIdiopathic pulmonary fibrosis (IPF) is a fibrotic lung condition that produces symptoms including coughing which may cause by excessive accumulation of scar tissue inflammatory and oxidative stress exacerbation. Sumatriptan, utilized for migraine treatment as a selective 5-HT1B/1D receptor agonist, has demonstrated significant anti-inflammatory and antioxidant properties in multiple preclinical investigations. Operating primarily on serotonin receptors, sumatriptan leverages the diverse physiological functions of serotonin, playing a pivotal role in regulating both inflammation and oxidative stress which is particularly relevant in the context of IPF. Materials & methodsThirty-five male Wistar rats were divided to five group, including: Sham (without IPF induction), control (BLM 5 mg/kg, intraperitoneally), and three fibrosis group with sumatriptan (0.5, 1, and 3 mg/kg, i.p. for 2 weeks) administration. IPF was induced by injection of BLM (single dose, 5 mg/kg intratracheally). Lung tissues were separated for measurement of myeloperoxidase (MPO) as an oxidative stress hallmark, and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-β), and transforming growth factor-β (TGF-β) as inflammatory markers as well as alpha smooth muscle actin (α-SMA). Also, for histological investigations, tissue damages were assessed by Hematoxylin-eosin (H&E) and Masson’s trichrome staining method. ResultsBLM-induced fibrosis could increase α-SMA, MPO, TNF-α, IL-1β, and TGF-β, while treatment with sumatriptan has reversed the α-SMA, MPO, and IL-1β levels. Moreover, the results of H&E and Masson’s trichrome staining indicated that sumatriptan (1 and 3 mg/kg) reduced tissue damages, alveolar wall thickness, collagen accumulation, and pulmonary fibrosis induced by BLM. ConclusionAccording to the data achieved from this study, Sumatriptan appears to have therapeutic benefits in IPF, possibly via reducing α-SMA as well as inflammation and the toxicity caused by oxidative stress.

The gene expression of CALD1, CDH2, and POSTN in fibroblast are related to idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung dysfunction due to excessive collagen production and tissue scarring. Despite recent advancements, the molecular mechanisms remain unclear. RNA sequencing identified 475 differentially expressed genes (DEGs) in the TGF-β1-induced primary lung fibrosis model. Gene expression chips GSE101286 and GSE110147 from NCBI gene expression omnibus (GEO) database were analyzed using GEO2R, revealing 94 DEGs in IPF lung tissue samples. The gene ontology (GO) and pathway enrichment, Protein-protein interaction (PPI) network construction, and Maximal Clique Centrality (MCC) scoring were performed. Experimental validation included RT-qPCR, Immunohistochemistry (IHC), and Western Blot, with siRNA used for gene knockdown. A co-expression network was constructed by GeneMANIA. GO enrichment highlighted significant enrichment of DEGs in TGF-β cellular response, connective tissue development, extracellular matrix components, and signaling pathways such as the AGE-RAGE signaling pathway and ECM-receptor interaction. PPI network analysis identified hub genes, including FN1, COL1A1, POSTN, KIF11, and ECT2. CALD1 (Caldesmon 1), CDH2 (Cadherin 2), and POSTN (Periostin) were identified as dysregulated hub genes in both the RNA sequencing and GEO datasets. Validation experiments confirmed the upregulation of CALD1, CDH2, and POSTN in TGF-β1-treated fibroblasts and IPF lung tissue samples. IHC experiments probed tissue-level expression patterns of these three molecules. Knockdown of CALD1, CDH2, and POSTN attenuated the expression of fibrotic markers (collagen I and α-SMA) in response to TGF-β1 stimulation in primary fibroblasts. Co-expression analysis revealed interactions between hub genes and predicted genes involved in actin cytoskeleton regulation and cell-cell junction organization. CALD1, CDH2, and POSTN, identified as potential contributors to pulmonary fibrosis, present promising therapeutic targets for IPF patients.

Proteomic profiling of formalin-fixed paraffine-embedded tissue reveals key proteins related to lung dysfunction in idiopathic pulmonary fibrosis.

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. 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. 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. 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.

Association study of human leukocyte antigen variants and idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk. We performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case-control studies of IPF (comprising 5159 cases and 27 459 controls, including a prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold of p<4.5×10-4 and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reported HLA-DQB1 association in the subset of studies independent of the original report. The meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. The HLA-DQB1 association was not replicated in the independent IPF studies. Variation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF.

Therapeutic effects of fatty acid binding protein 1 in mice with pulmonary fibrosis by regulating alveolar epithelial regeneration

IntroductionIdiopathic pulmonary fibrosis is a progressive fibrotic lung disease with limited therapeutic options and high lethality, related to alveolar type II epithelial (ATII) cell dysregulation, the abnormal repair of alveolar...

Atractylodin ameliorates bleomycin-induced pulmonary inflammation and fibrosis in mice

IntroductionIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease. The commonly used drugs for the treatment of pulmonary fibrosis can only delay the damage of lung function but cannot prolong the life of patients. Atractylodin (ATR), a kind of herbal medicine that has been proven to protect anti-inflammation and attenuate acute lung injury, was investigated to determine whether it could provide a new idea for the treatment of IPF by reducing the inflammatory reaction and collagen formation in the process of pulmonary fibrosis. MethodsIn vivo experiments, mice were divided into 6 groups, normal group, model, drug group (10 mg/kg, 30 mg/kg, 90 mg/kg) and positive control group (pirfenidone). Mice were given BLM through trachea, and after 24 h, normal saline, different concentrations of atractylodin and pirfenidone were given respectively. On 7 days, 14 days and 21 days, the weight, lung function, alveolar lavage fluid and lung tissue were tested. In vitro experiments to investigate the effect of atractylodin on fibroses, NIH3T3 cells were induced by TGF-β1 to detect the formation of cellular collagen and the phosphorylation level of Smad2/3 at different time points after their fibrosis. ResultsThe results showed that atractylodin could alleviate the lung function damage (FVC, FEV100, Tidal volume, tissue elastance) caused by BLM, reduce the inflammatory factors (IL-1β, IL-6, TNF-α), neutrophils and macrophage infiltration in the alveolar lavage fluid, as well as the formation and deposition of collagen (fibronectin, α-SMA, ColA1). In vitro studies have demonstrated that atractylodin can alleviate TGF-β1-induced pulmonary fibrosis by inhibiting the TGF-β1/Smad2/3 pathway. ConclusionAtractylodin can alleviate the lung function damage and attenuate pulmonary fibrosis induced by BLM through inhibiting the TGF-β1/Smad2/3 pathway. This may provide new ideas for the treatment of IPF.

Idiopathic pulmonary fibrosis - novel approach on future treatment

IntroductionIdiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disease that leads to progressive fibrosis and extremely poor resaults.. Since the etiology is unknown, there are highly limited options of the IPF treatment. The researchers are trying to discover the most valuable targets, leading them to the agents registered in different conditions or not registered as any other treatment. This innovative approach can result in IPF being determined as not fatal. PurposeThe purpose of our review is to present possible future treatment of idiopathic pulmonary fibrosis and point out the promising targets that could lead the researchers to the development of better IPF management. Materials and methodsWe have reviewed the literature from the PubMed database searching for clinical trials, meta analysis and randomized controlled trials from the past 5 years. The keywords we agreed on offered us the most informative articles and made us hope for the further development of our article. ResultsOur review shows that there are new targets that could significantly benefit IPF treatment. However, the means we presented in our review need more research to prove its safeness, effectiveness in slowing down the decline of the FVC, improving patients’ physical efficiency, their saturation level and most importantly their ability to stop the continuous fibrosis of the lungs. ConclusionsThe only treatment registered for IPF are nintedanib and pirfenidone, but the researchers continue the exploration of new possible measures to improve the survival rate and quality of life of the patients suffering from this fatal disease.

Effects of full-body exercise-based pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis protocol

IntroductionIdiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterised by progressive and irreversible fibrosis of the lung parenchyma, resulting in reduced lung function. Since conventional medicines can be associated...

Niclosamide-loaded nanoparticles (Ncl-NPs) reverse pulmonary fibrosis in vivo and in vitro

IntroductionIdiopathic pulmonary fibrosis (IPF), a life-threatening interstitial lung disease, is characterized by excessive activation and proliferation of fibroblasts and epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AEC) accompanied by a large amount of extracellular matrix aggregation. There are no therapies to reverse pulmonary fibrosis, and nintedanib and pirfenidone could only slow down the decline of lung function of IPF patients and delay their survival time. Niclosamide (Ncl) is an antihelminthic drug approved by FDA, which has been reported to have pleiotropic pharmacological activities in recent years, but it’s almost complete insolubility in water limits its clinical application. ObjectivesTo improve the water solubility of Ncl, explore its ability to reverse BLM-induced pulmonary fibrosis and its specific mechanism of action. MethodsThe Niclosamide-loaded nanoparticles (Ncl-NPs) were formed by emulsification solvent evaporation method. A mouse model induced by bleomycin (BLM) was established to evaluate its effects and mechanisms of inhibiting and reversing fibrosis in vivo. The cell models treated by transforming growth factor-β1 (TGF-β1) were used to examine the mechanism of Ncl-NPs inhibiting fibrosis in vitro. Flow cytometry, IHC, IL-4-induced macrophage model and co-culture system were used to assess the effect of Ncl-NPs on M2 polarization of macrophages. ResultsThe Ncl-NPs improved the poor water solubility of Ncl. The lower dose of Ncl-NPs (2.5 mg/kg) showed the same effect of reversing established pulmonary fibrosis as free Ncl (5 mg/kg). Mechanistic studies revealed that Ncl-NPs blocked TGF-β/Smad and signaling transducer and activator of transcription 3 (Stat3) signaling pathways and inhibited the M2 polarization of macrophages. Additionally, H&E staining of the tissues initially showed the safety of Ncl-NPs. ConclusionThese results indicate Ncl-NPs may serve as a new idea for the treatment of pulmonary fibrosis.

Impact of reduction in antifibrotic treatment on mortality in idiopathic pulmonary fibrosis

IntroductionIdiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease for which two effective antifibrotics, nintedanib and pirfenidone, are available. However, many patients receive a reduced dosage or pause treatment due to side effects although the impact of antifibrotic treatment reduction is uncertain. MethodsWe retrospectively investigated the impact of antifibrotic treatment reduction on death in a large real-life IPF cohort. The primary endpoint of the analyses was time until death by any cause. Five patient groups were defined based on treatment intensity (full, reduced or no treatment) and the antifibrotic drug type (pirfenidone or nintedanib). Between group survival was compared using Cox proportional hazards analysis adjusted for age, sex, smoking status, and lung function at baseline. Results375 patients from the Danish PFBIO-cohort were followed from April 2016 until November 2021 with a median follow-up time of 1.84 years. Of patients receiving nintedanib and pirfenidone, 80.19% and 67.42% had reduced treatment, respectively, when considering the entire follow-up period.Treatment with nintedanib and pirfenidone was associated with improved survival compared to no antifibrotic treatment independent of treatment intensity (nintedanib: HR: 0.31, 95%-CI: 0.19–0.53, p < 0.001 & pirfenidone: HR: 0.26, 95%-CI: 0.16–0.42, p < 0.001). Nintedanib and pirfenidone in lower intensities were not associated with worse survival outcomes. ConclusionA substantial proportion of patients with IPF receive reduced antifibrotic treatment to ameliorate the side effects associated with a full dosage regime. Treatment with nintedanib and pirfenidone, independent of treatment intensity, was preferable over no antifibrotic treatment in improving survival and reduced dose appears to be a good alternative if full dose is not tolerated.

Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis.

IntroductionIdiopathic pulmonary fibrosis (IPF) is a progressively fibrotic lung condition with poor prognosis. Matrix metalloproteinase-7 (MMP7) is a protein secreted by epithelial cells in IPF lungs. It is not known if MMP7 expression correlates with fibrotic changes in lung tissue.MethodsTissue samples from lung apices and bases were obtained from 20 IPF patients and 14 non-diseased control (NDC) donors. In formalin-fixed paraffin-embedded sections, histological assessment of fibrosis was performed; overall MMP7 positivity was assessed by immunohistochemistry and MMP7+ cells were quantified using multiplex immunohistochemistry. Protein expression of MMP7 in whole lung lysates was quantified by Western blotting. Bulk tissue transcriptomic profiles of 101 samples were analysed using RNA sequencing technologies.ResultsLung tissue from IPF bases was more fibrotic than in apices. MMP7 protein is elevated in IPF lung base tissue. In IPF whole lung lysates, MMP7 protein levels are increased compared to NDC donors and was increased in IPF lung bases compared to apices. MMP7 protein levels correlated with MMP7 gene expression levels in lung tissue. MMP7 transcript levels were increased in IPF base compared to NDC base lung tissue and increased in IPF base tissue compared to IPF apex tissue.ConclusionsOur cross-sectional study suggests that lung epithelial MMP7 expression increases as the tissue becomes more fibrotic and identifies a potentially nonepithelial or immune-cell source. Mechanisms of disease progression in IPF are still unclear, and our study suggests aberrant MMP7 production may be a histological starting point of lung tissue fibrosis.

Study design and rationale for the TETON phase 3, randomised, controlled clinical trials of inhaled treprostinil in the treatment of idiopathic pulmonary fibrosis

IntroductionIdiopathic pulmonary fibrosis (IPF) greatly impacts quality of life and eventually leads to premature death from respiratory failure. Inhaled treprostinil was associated with improvements in forced vital capacity (FVC) and...

Latin American Registry of Idiopathic Pulmonary Fibrosis (REFIPI): Clinical Characteristics, Evolution and Treatment

IntroductionIdiopathic pulmonary fibrosis (IPF) is a progressive, irreversible and frequently fatal disease. Currently there are national and multinational registries in Europe, United States, Australia and China to better understand the magnitude of the problem and the characteristics of the IPF patients. However, there are no national or regional registries in Latin America, so the objective of this study was to carry out a Latin American registry that would allow the identification of IPF patients in our region. MethodologyA system consisting of 3 levels of control was designed, ensuring that patients met the diagnostic criteria for IPF according to international guidelines ATS/ERS/ALAT/JRS 2011. Demographic, clinical, serological, functional, tomographic, histological and treatment variables were recorded through a digital platform. Results761 IPF patients from 14 Latin American countries were included for analysis, 74.7% were male, with a mean age of 71.9+8.3 years. In general there was a long period of symptoms before definitive diagnosis (median 1 year). In functional tests, an average reduction of FVC (70.9%) and DLCO (53.7%) was detected. 72% received at least one antifibrotic drug (pirfenidone or nintedanib) and 11.2% of the patients had an acute exacerbation, of which 38 (45.2%) died from this cause. ConclusionsLike other registries, we found that there is difficulty in the recognition and excessive delay in the diagnosis of IPF in Latin America. Most of the patients in REFIPI received antifibrotics; these were well tolerated and associated with fewer adverse events than those reported in clinical trials.

CC-90001, a c-Jun N-terminal kinase (JNK) inhibitor, in patients with pulmonary fibrosis: design of a phase 2, randomised, placebo-controlled trial

IntroductionIdiopathic pulmonary fibrosis (IPF) is a progressive and often fatal interstitial lung disease (ILD); other ILDs have a progressive, fibrotic phenotype (PF-ILD). Antifibrotic agents can slow but not stop disease...

Percepción de los pacientes en cuanto al manejo de la fibrosis pulmonar idiopática. Proyecto Explora-IPF

IntroductionIdiopathic pulmonary fibrosis (IPF) impacts the life of patients and their families, so it is necessary to ascertain their perception in the approach to their disease. MethodsObservational study by means of a specific questionnaire that includes socio-demographic and clinical variables, perception of the impact of the disease (5-point Likert scale), preferences regarding the characteristics of the medication (degree of importance/concern 1-10) and satisfaction with treatment (SATMED-Q® scale 0-100). Results69 individuals participated (age: 66.5 ± 7.6 years; time until diagnosis: 16.5 ± 17.4 months; diagnosis time: 49.6 ± 42.3 months). The majority state that IPF limits them physically (90%) and emotionally (75%). The most highly valued features of the treatment were: slowing down progression of the disease (7.4 ± 2.8), stabilising lung capacity (6.9 ± 2.8) and improving quality of life (6.9 ± 2.8), above stabilising/improving symptoms (6.1 ± 2.8/6.3 ± 2.8) or avoiding hospitalisation (6.6 ± 2.7). The principal factors of concern were suffering gastric disorders (7.1 ± 2.9), photosensitivity (6.6 ± 3.0) or interaction with other drugs (6.0 ± 3.0). Overall satisfaction with the current treatment scored 61.1 points, with the highest scores being for medical follow-up (79.5) and overall opinion of the medicine (74.3). ConclusionsA study conducted in Spain on the perspective of IPF patients regarding the disease and its treatment. The results show a high level of awareness in terms of the seriousness of the disease on the part of patients, whose main concern is to slow down its progression. The information provided may help to optimise the management of IPF patients.

Phase 2 trial design of BMS-986278, a lysophosphatidic acid receptor 1 (LPA1) antagonist, in patients with idiopathic pulmonary fibrosis (IPF) or progressive fibrotic interstitial lung disease (PF-ILD)

IntroductionIdiopathic pulmonary fibrosis (IPF) and non-IPF, progressive fibrotic interstitial lung diseases (PF-ILD), are associated with a progressive loss of lung function and a poor prognosis. Treatment with antifibrotic agents can...

Fine crackles on chest auscultation in the early diagnosis of idiopathic pulmonary fibrosis: a prospective cohort study

IntroductionIdiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) with a poor prognosis. Early diagnosis and treatment of IPF may increase lifespan and preserve quality of life. Chest CT...

Esomeprazole attenuates inflammatory and fibrotic response in lung cells through the MAPK/Nrf2/HO1 pathway

IntroductionIdiopathic pulmonary fibrosis (IPF) is an orphan disease characterized by progressive loss of lung function resulting in shortness of breath and often death within 3–4 years of diagnosis. Repetitive lung injury in susceptible individuals is believed to promote chronic oxidative stress, inflammation, and uncontrolled collagen deposition. Several preclinical and retrospective clinical studies in IPF have reported beneficial outcomes associated with the use of proton pump inhibitors (PPIs) such as esomeprazole. Accordingly, we sought to investigate molecular mechanism(s) by which PPIs favorably regulate the disease process.MethodsWe stimulated oxidative stress, pro-inflammatory and profibrotic phenotypes in primary human lung epithelial cells and fibroblasts upon treatment with bleomycin or transforming growth factor β (TGFβ) and assessed the effect of a prototype PPI, esomeprazole, in regulating these processes.ResultsOur study shows that esomeprazole controls pro-inflammatory and profibrotic molecules through nuclear translocation of the transcription factor nuclear factor-like 2 (Nrf2) and induction of the cytoprotective molecule heme oxygenase 1 (HO1). Genetic deletion of Nrf2 or pharmacological inhibition of HO1 impaired esomeprazole-mediated regulation of proinflammatory and profibrotic molecules. Additional studies indicate that activation of Mitogen Activated Protein Kinase (MAPK) pathway is involved in the process. Our experimental data was corroborated by bioinformatics studies of an NIH chemical library which hosts gene expression profiles of IPF lung fibroblasts treated with over 20,000 compounds including esomeprazole. Intriguingly, we found 45 genes that are upregulated in IPF but downregulated by esomeprazole. Pathway analysis showed that these genes are enriched for profibrotic processes. Unbiased high throughput RNA-seq study supported antifibrotic effect of esomeprazole and revealed several novel targets.ConclusionsTaken together, PPIs may play antifibrotic role in IPF through direct regulation of the MAPK/Nrf2/HO1 pathway to favorably influence the disease process in IPF.

Antithrombin III as predictive indicator of survival in idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib: a preliminary study.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease often managed with nintedanib, a tyrosine kinase inhibitor targeting several profibrotic pathways. Although clotting processes are involved in wound healing and repair in the lung, there are no data on the role of antithrombin III (ATIII) in IPF patients treated with nintedanib. A previous proteomic analysis of serum of IPF patients before and after 1 year of nintedanib treatment showed differential protein expression of ATIII. Here we used quantitative methods to evaluate differential ATIII concentrations in IPF patients before and after 1 year of nintedanib treatment and to assess the potential of ATIII as a prognostic biomarker in IPF patients. Serum levels of ATIII were measured by enzyme-linked immunosorbent assay in 14 IPF patients before and after 1 year of nintedanib treatment. A statistically significant inverse correlation was found between serum ATIII concentrations and pulmonary function test parameters in all patients at baseline and follow up. Baseline serum ATIII and bronchoalveolar lavage (BAL) neutrophils proved to be reliable predictors of poor prognosis. A baseline ATIII threshold of 126.5 μg/mL discriminated survivors from non-survivors. After 12 months of antifibrotic treatment, IPF patients with high serum ATIII concentrations and high BAL neutrophil percentages had a poor prognosis and increased survival risk. The results of this preliminary study suggest that ATIII has potential as a biomarker of IPF severity and in predicting response to nintedanib therapy. As a marker, ATIII showed several advantages over BAL neutrophil percentage.

Different Faces of Idiopathic Pulmonary Fibrosis With Preserved Forced Vital Capacity

IntroductionIdiopathic pulmonary fibrosis (IPF) is progressive and irreversible. Some discrepancies about IPF staging exists, especially in mild phases. Forced vital capacity (FVC) higher than 80% has been considered early or mild IPF even for the design of clinical trials. MethodsSpanish multicentre, observational, retrospective study of IPF patients diagnosed between 2012 and 2016, based on the ATS/ERS criteria, which presented FVC greater or equal 80% at diagnosis. Clinical and demographic characteristics, lung function, radiological pattern, treatment, and follow-up were analyzed. Results225 IPF patients were included, 72.9% were men. The mean age was 69.5 years. The predominant high-resolution computed tomography (HRCT) pattern was consistent usual interstitial pneumonia (UIP) (51.6%). 84.7% of patients presented respiratory symptoms (exertional dyspnea and/or cough) and 33.33% showed oxygen desaturation below 90% in the 6min walking test (6MWT). Anti-fibrotic treatment was initiated at diagnosis in 55.11% of patients. Median FVC was 89.6% (IQR 17) and 58.7% of patients had a decrease of diffusion lung capacity for carbon monoxide (DLCO) below 60% of theoretical value; most of them presented functional progression (61.4%) and higher mortality at 3 years (20.45%). A statistically significant correlation with the 3-years mortality was observed between DLCO <60% and consistent UIP radiological pattern. ConclusionsPatients with preserved FVC but presenting UIP radiological pattern and moderate–severe DLCO decrease at diagnosis associate an increased risk of progression, death or lung transplantation. Therefore, in these cases, preserved FVC would not be representative of early or mild IPF.