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Comprehensive care integrates individual patient needs and is highly valued for patients with pulmonary fibrosis (PF). The importance of a patient-centered care approach is rooted in the unpredictable progressiveness of the disease course in PF. The respiratory impairment associated with PF has a major impact on the quality of life for both patients and their caregivers. We believe that prioritizing patient preferences could improve the shared decision making process and may ultimately lead to better health outcomes. Despite the growing emphasis for this approach, it remains challenging to adopt it in clinical practice. In this review, we propose the comprehensive Triple A Care Model, consisting of the domains Access, Anticipate, and Act, which emphasizes core elements of patient-centered care for patients with PF. We will provide an overview of the unmet needs in care for patients with PF and elaborate on the current methods for delivering patient-centered care. The latest insights into symptom management and supportive measures and several approaches to improving access to care are discussed, in line with the most recent guidelines., (© 2024. The Author(s).)

Purpose of Review: In chronic pulmonary sarcoidosis, the transition from the inflammatory to the fibrotic stage of the lungs occurs in about 10-20% of cases, eventually causing end-stage fibrotic disease. To date, pathogenetic mechanisms and clinical management remain challenging; thus, we highlight the recent evidence in pulmonary fibrotic processes, clinical signs for an early detection and the potential role of the current investigated antifibrotic agents and promising targeted therapies., Recent Findings: Recent findings of relevant key cellular pathways can be considered as a glimmer of light in the complexity of sarcoidosis. In some patients, granulomas persist and serve as a nidus for fibrosis growth, sustained by several fibrosis-stimulating cytokines. Preclinical studies have detected profibrotic, antifibrotic and pleiotropic T cells as promoters of fibrosis. Epigenetics, genetics and transcriptomics research can lead to new target therapies. Antifibrotic drug nintedanib has shown a positive effect on non-idiopathic pulmonary fibrosis fibrotic lung diseases including fibrotic sarcoidosis; other antifibrotic drugs are under investigation., Summary: Pulmonary fibrosis strongly impacts the outcome of sarcoidosis, and a better understanding of the underlying pathogenic mechanisms can facilitate the development of novel treatments, improving clinical care and life expectancy of these patients. The greatest challenge is to investigate effective antifibrotic therapies once fibrosis develops. The role of these findings in fibrotic sarcoidosis can be translated into other interstitial lung diseases characterized by the coexistence of inflammatory and fibrotic processes., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Extracellular matrix (ECM) stiffening with downstream activation of mechanosensitive pathways is strongly implicated in fibrosis. We previously reported that altered collagen nanoarchitecture is a key determinant of pathogenetic ECM structure-function in human fibrosis (Jones et al., 2018). Here, through human tissue, bioinformatic and ex vivo studies we provide evidence that hypoxia-inducible factor (HIF) pathway activation is a critical pathway for this process regardless of the oxygen status (pseudohypoxia). Whilst TGFβ increased the rate of fibrillar collagen synthesis, HIF pathway activation was required to dysregulate post-translational modification of fibrillar collagen, promoting pyridinoline cross-linking, altering collagen nanostructure, and increasing tissue stiffness. In vitro, knockdown of Factor Inhibiting HIF (FIH), which modulates HIF activity, or oxidative stress caused pseudohypoxic HIF activation in the normal fibroblasts. By contrast, endogenous FIH activity was reduced in fibroblasts from patients with lung fibrosis in association with significantly increased normoxic HIF pathway activation. In human lung fibrosis tissue, HIF-mediated signalling was increased at sites of active fibrogenesis whilst subpopulations of human lung fibrosis mesenchymal cells had increases in both HIF and oxidative stress scores. Our data demonstrate that oxidative stress can drive pseudohypoxic HIF pathway activation which is a critical regulator of pathogenetic collagen structure-function in fibrosis., Competing Interests: CB, LY, ED, YZ, MV, JB, SW, RR, LD, OA, FC, LB, SM, TW, AT, RE, AA, BM, SF, PT, AF, NK, LR, AB, CS, ML, DD, YW, MJ No competing interests declared, (© 2022, Brereton et al.)

Introduction: Lung injury in severe COVID-19 pneumonia can rapidly evolve to established pulmonary fibrosis, with prognostic implications in the acute phase of the disease and long-lasting impact on the quality of life of COVID-19 survivors. This is an emerging medical need, and it has been hypothesized that antifibrotic treatments could have a role in ameliorating the fibrotic process in the lungs of these patients., Areas Covered: The safety and efficacy of available antifibrotic drugs (nintedanib and pirfenidone) and novel promising agents are being assessed in several ongoing clinical trials that were performed either in critically ill patients admitted to intensive care, or in discharged patients presenting fibrotic sequalae from COVID-19. Literature search was performed using Medline and Clinicaltrials.org databases (2001-2021)., Expert Opinion: Despite the strong rationale support the use of antifibrotic therapies in COVID-related fibrosis, there are several uncertainties regarding the timing for their introduction and the real risks/benefits ratio of antifibrotic treatment in the acute and the chronic phases of the disease. The findings of ongoing clinical trials and the long-term observation of longitudinal cohorts will eventually clarify the best management approach for these patients.

To date, more than 100 million people worldwide have recovered from COVID-19. Unfortunately, although the virus is eradicated in such patients, fibrotic irreversible interstitial lung disease (pulmonary fibrosis, PF) is clinically evident. Given the vast numbers of individuals affected, it is urgent to design a strategy to prevent a second wave of late mortality associated with COVID-19 PF as a long-term consequence of such a devastating pandemic. Available antifibrotic therapies, namely nintedanib and pirfenidone, might have a role in attenuating profibrotic pathways in SARS-CoV-2 infection but are not economically sustainable by national health systems and have critical adverse effects. It is our opinion that the mesenchymal stem cell secretome could offer a new therapeutic approach in treating COVID-19 fibrotic lungs through its anti-inflammatory and antifibrotic factors.

Background and Objective: Temporal trends of healthcare use in the period before a diagnosis of pulmonary fibrosis are poorly understood. We investigated trends in respiratory symptoms and LR HRU in the 10 years prior to diagnosis., Methods: We analysed a primary care clinical cohort database (UK OPCRD) and assessed patients aged ≥40 years who had an electronically coded diagnosis of pulmonary fibrosis between 2005 and 2015 and a minimum 2 years of continuous medical records prior to diagnosis. Exclusion criteria consisted of electronic codes for recognized causes of pulmonary fibrosis such as CTD, sarcoidosis or EAA., Results: Data for 2223 patients were assessed. Over the 10 years prior to diagnosis of pulmonary fibrosis, there was a progressive increase in HRU across multiple LR-related domains. Five years before diagnosis, 18% of patients had multiple healthcare contacts for LR complaints; this increased to 79% in the year before diagnosis, with 38% of patients having five or more healthcare contacts., Conclusion: There are opportunities to diagnose pulmonary fibrosis at an earlier stage; research into case-finding algorithms and strategies to educate primary care physicians is required., (© 2020 Asian Pacific Society of Respirology.)

A proportion of patients with interstitial lung diseases (ILDs) are at risk of developing a progressive-fibrosing phenotype, which is associated with a deterioration in lung function and early mortality. In addition to idiopathic pulmonary fibrosis (IPF), fibrosing ILDs that may present a progressive phenotype include idiopathic nonspecific interstitial pneumonia, connective tissue disease-associated ILDs, hypersensitivity pneumonitis, unclassifiable idiopathic interstitial pneumonia, ILDs related to other occupational exposures and sarcoidosis. Corticosteroids and/or immunosuppressive therapies are sometimes prescribed to patients with these diseases. However, this treatment regimen may not be effective, adequate on its own or well tolerated, suggesting that there is a pressing need for efficacious and better tolerated therapies. Currently, the only approved treatments to slow disease progression in patients with IPF are nintedanib and pirfenidone. Similarities in pathobiological mechanisms leading to fibrosis between IPF and other ILDs that may present a progressive-fibrosing phenotype provide a rationale to suggest that nintedanib and pirfenidone may be therapeutic options for patients with the latter diseases.This review provides an overview of the therapeutic options currently available for patients with fibrosing ILDs, including fibrosing ILDs that may present a progressive phenotype, and explores the status of the randomised controlled trials that are underway to determine the efficacy and safety of nintedanib and pirfenidone., Competing Interests: Conflict of interest: L. Richeldi reports grants and personal fees from InterMune, personal fees from Sanofi-Aventis, Roche, ImmuneWorks, Shionogi, Boehringer Ingelheim, Celgene, Nitto, Fibrogen, Promedior, Bristol Myers Squibb and DynaMed, outside the submitted work. Conflict of interest: F. Varone reports personal fees from Boehringer Ingelheim and Hoffmann-La Roche, outside the submitted work. Conflict of interest: M. Bergna received research grants from Novartis, GSK, Boehringer Ingelheim, Roche, AstraZeneca and Sanofi, and advisory and investigator fees from GSK, AstraZeneca and Novartis. Conflict of interest: J. de Andrade reports grants from NIH/NHLBI, grants and personal fees from Boehringer Ingelheim and Genentech, and grants from Fibrogen and GBT, outside the submitted work. Conflict of interest: J. Falk has nothing to disclose. Conflict of interest: R. Hallowell has nothing to disclose. Conflict of interest: S. Jouneau reports grants from AIRB, Boehringer Ingelheim, LVL, Novartis and Roche, and personal fees from Actelion, AIRB, AstraZeneca, BMS, Boehringer Ingelheim, Chiesi, GSK, LVL, Mundipharma, Novartis, Pfizer and Roche, outside the submitted work. Conflict of interest: Y. Kondoh reports personal lecture fees from Boehringer Ingelheim Co. which is relevant to the presentation work. Y. Kondoh also reports advisory board fees and personal fees from Asahi Kasei Pharma Corp., Ltd, and personal fees from Eisai Inc., Kyorin Pharmaceutical Co., Ltd, Novartis Pharma K.K., Shionogi & Co., Ltd and Teijin Pharma Ltd outside the submitted work. Conflict of interest: L. Morrow reports grants from Boehringer Ingelheim and Genentech, outside the submitted work. Conflict of interest: W. Randerath reports nonfinancial support from Boehringer, during the conduct of the study; and grants from Boehringer Ingelheim and Roche Pharma, outside the submitted work. Conflict of interest: M. Strek reports grants from Boehringer and Roche; and personal fees from Boehringer Ingelheim, outside the submitted work. Conflict of interest: G. Tabaj has nothing to disclose., (Copyright ©ERS 2018.)

Heart failure with preserved ejection fraction (HFpEF) has a poor prognosis, and an effective treatment is currently lacking. Increasing evidence suggests a prevailing pathogenic role of cardiac fibrosis in HFpEF, which generates the possibility of a mechanistic overlap with pulmonary fibrosis. Indeed, cardiac and pulmonary fibrosis share some characteristics and molecular pathways, such as that of transforming growth factor-β. If pulmonary and cardiac fibrosis share common pathways, we can hypothesize a beneficial effect of anti-fibrotic drugs used in idiopathic pulmonary fibrosis on cardiac outcomes. Of note, pirfenidone has been tested in animal models of cardiac fibrosis and was found to be effective in reducing ventricular remodelling. Yet, no results are hitherto available for humans. In this review article, we discuss the potential benefit of anti-fibrotic treatment in HFpEF. In particular, we propose to reappraise safety data collected in placebo-controlled trials of anti-fibrotic drugs in idiopathic pulmonary fibrosis, to explore the hypothesis that these might reduce cardiac fibrosis., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Matrix stiffening with downstream activation of mechanosensitive pathways is strongly implicated in progressive fibrosis; however, pathologic changes in extracellular matrix (ECM) that initiate mechano-homeostasis dysregulation are not defined in human disease. By integrated multiscale biomechanical and biological analyses of idiopathic pulmonary fibrosis lung tissue, we identify that increased tissue stiffness is a function of dysregulated post-translational collagen cross-linking rather than any collagen concentration increase whilst at the nanometre-scale collagen fibrils are structurally and functionally abnormal with increased stiffness, reduced swelling ratio, and reduced diameter. In ex vivo and animal models of lung fibrosis, dual inhibition of lysyl oxidase-like (LOXL) 2 and LOXL3 was sufficient to normalise collagen fibrillogenesis, reduce tissue stiffness, and improve lung function in vivo. Thus, in human fibrosis, altered collagen architecture is a key determinant of abnormal ECM structure-function, and inhibition of pyridinoline cross-linking can maintain mechano-homeostasis to limit the self-sustaining effects of ECM on progressive fibrosis., Competing Interests: MJ, OA, KA, DS, AB, PJ, AA, FC, RD, CL, BJ, KB, SF, BM, SJ, CB, SC, CO, PS, JG, MK, SM, AF, AB, LR, KO, PT No competing interests declared, JR As a current employee of Synairgen Research Ltd, J.J.W.R has share options in the company. KL As a current employee of Synairgen Research Ltd, K.L has share options in the company. VT As a current employee of Synairgen Research Ltd, V.J.T has share options in the company. LC As a former or current employee of Pharmaxis Pharmaceuticals Ltd, L.C. has an equity stake in the company. WJ As a current employee of Pharmaxis Pharmaceuticals Ltd, W.J. has an equity stake in the company. PM As a current employee of Synairgen Research Ltd, P.D.M has share options and is a share-holder in the company. DD D.E.D is co-founder of, share-holder in and consultant to Synairgen Research Ltd., (© 2018, Jones et al.)

Background: Idiopathic pulmonary fibrosis is a chronic progressive lung disease with poor outcome and no effective treatment to date. This is an update of a Cochrane Review first published in 2003., Objectives: To assess the efficacy of non-steroid agents in adults with idiopathic pulmonary fibrosis., Search Strategy: We searched the Cochrane Airways Group Register (30 March 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2010), Ovid MEDLINE to March week 5, 2010, EMBASE to week 13, 2010 and PubMed to April 2010, with additional handsearching, including abstracts of international conferences. We also contacted pharmaceutical companies and researchers in the field., Selection Criteria: Randomised studies comparing non-steroid drugs with placebo or steroids in adults with idiopathic pulmonary fibrosis., Data Collection and Analysis: Two authors independently assessed trial quality, extracted data and assessed risk of bias. We contacted pharmaceutical companies to obtain missing information, if any. We combined survival outcomes using Peto odds ratios or hazard ratios (HR)., Main Results: Fifteen trials involving 10 different drugs were included. Two trials enrolling 1156 patients compared interferon gamma-1beta with placebo: interferon gamma-1beta did not significantly improve survival (HR 0.88, 95% CI 0.47 to 1.64; P = 0.68). Four trials involving 1155 patients compared pirfenidone with placebo. Three trials, conducted in 1046 patients, provided data on progression-free survival: pirfenidone significantly reduced the risk of disease progression by 30% (HR 0.70, 95% CI 0.56 to 0.88, P = 0.002). Data on the effect of pirfenidone on pulmonary function could only be assessed for two studies analysing 314 patients. Forced vital capacity or vital capacity was significantly improved by pirfenidone (mean difference 0.08 L, 95% CI 0.03 to 0.13, P = 0.0006)., Authors' Conclusions: Based on available data, partly still unpublished, pirfenidone appears to improve progression-free survival and, to a lesser extent, pulmonary function in patients with idiopathic pulmonary fibrosis. More data are needed on overall survival and quality of life on treatment. From the studies in this review, interferon gamma-1beta has not been shown to affect survival. Other agents evaluated in single studies either failed to provide evidence for a benefit or need to be assessed in larger randomised controlled trials.

Objectives: Systemic sclerosis (SSc) is characterized by abnormal fibrosis of the skin and internal organs, particularly the lungs. Recent reports have revealed a lack of correlation between bronchoalveolar lavage (BAL) variations and response to cyclophosphamide (CYC) in patients with scleroderma-related alveolitis. Our study aimed to evaluate whether the normalization of BAL cellularity correlates with long-term response to CYC., Methods: We retrospectively studied 26 consecutive SSc patients with alveolitis diagnosed by BAL and treated with CYC therapy (cumulative dosage 26.5 +/- 11.7 g; 21.1 +/- 8.9 months of treatment). We evaluated high-resolution computed tomography (HRCT), forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLCO) variations before and after CYC. Radiological and functional parameters were re-evaluated in 23 patients after 1-year follow-up., Results: BAL cellularity normalized after CYC therapy in 12/26 (46.2%) patients (group 1), while it remained abnormal in 14/26 (53.8%) (group 2). FVC and DLCO of group 1 slightly increased after CYC (p = 0.014 and p = 0.07, respectively) and remained stable at follow-up, whereas in group 2 they did not change after CYC and at follow-up (p = not significant). Moreover, at the end of CYC, FVC and/or DLCO showed a clinical improvement/stabilization in all patients of group 1 versus 8/14 of group 2, while at the re-evaluation 1 year after completing CYC, 2/11 patients of group 1 worsened versus 5/12 of group 2. HRCT progression was observed in 1/11 of group 1 and 8/12 of group 2 (p = 0.009)., Conclusions: BAL fluid normalization after CYC therapy correlated with long-term response to treatment, contrary to what is observed in individuals with persistent alveolitis.

The idiopathic interstitial pneumonias (IIPs) comprise a number of clinico-pathological entities of unknown origin, which are sufficiently different from one another to be designated as separate disease entities. The aim of this review is to describe the level of evidence available on the efficacy of corticosteroids and immunosuppressive, antifibrotic, or immunomodulatory therapies in the treatment of different IIPs.

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary disease leading to death within a few years of diagnosis despite medical therapy. On the basis of methodologies of the Cochrane collaboration, this overview discusses the evidence for IPF therapy. Good-quality studies on oral corticosteroids, the most common medical therapy in use for IPF, are lacking. A few small studies have been carried out on the efficacy of many non-steroid immunosuppressive agents, and the results have been generally disappointing. The most extensively studied medical therapy, gamma interferon, showed a significant effect in a small randomized study, but its efficacy was not confirmed in a larger randomized-controlled trial. The long-awaited good news for patients affected by this deadly disease, and for their physicians, could come in the near future from large randomized-controlled trials with gamma interferon or other immunomodulatory agents.

Background: Idiopathic pulmonary fibrosis (IPF), also called cryptogenic fibrosing alveolitis (CFA), is a lethal form of diffuse lung disorder of unknown origin; the mean survival being two to four years. Currently recommended and most prescribed therapy for IPF is based on the use of systemic corticosteroids, even if no formal demonstration of efficacy of this treatment of IPF is available. Furthermore, new insights from pathological studies have produced a new hypothesis, based upon the central role played by aberrant wound healing following repeated lung injury, weakening the rationale basis of the use of corticosteroids in IPF, previously considered simply a chronic inflammatory disease., Objectives: The objective of the review was to determine the efficacy of corticosteroids in the treatment of adults with IPF., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2002), MEDLINE (January 1966 to May 2002) and EMBASE (January 1985 to December 2002) and reference lists of articles. We searched reference lists of published articles to identify trials., Selection Criteria: Randomised controlled trials (RCT) and controlled clinical trials (CCT) using corticosteroids alone for the treatment of adults with IPF., Data Collection and Analysis: Abstracts of identified articles were retrieved and articles possibly fulfilling inclusion criteria were retrieved in full. Two reviewers would have independently assessed trial quality if there had been any included studies., Main Results: Fifteen studies were selected as potentially eligible for meta-analysis. After further analysis of full text papers, no RCTs or CCTs were identified as suitable and therefore no data was available for inclusion in any meta-analysis. All studies were excluded due to inadequate methodologies., Reviewer's Conclusions: At present, there is no evidence for an effect of corticosteroid treatment in patients with Idiopathic pulmonary fibrosis(IPF)/usual interstitial pneumonia (UIP). Given developments in understanding of the pathogenesis of IPF, randomised controlled trials designed to test the efficacy of corticosteroids will probably never be designed. As other forms of pulmonary fibrosis such as non-specific interstitial pneumonia are reported to show a better response to corticosteroids, it is crucial to make an accurate diagnosis in each patient. Moreover, therapies with immunomodulatory rather than anti-inflammatory or immunosuppressive effects may be more promising for the effective treatment of IPF/UIP.

Background: Idiopathic Pulmonary Fibrosis (IPF) or Usual Interstitial Pneumonia (UIP) is a form of chronic fibrosing interstitial pneumonia of unknown aetiology, with progressively deteriorating respiratory function and ultimately death from respiratory failure. Most treatments are intended to suppress inflammation but none has been proven to alter this process. The most widespread approach uses oral corticosteroids; others use immunosuppressive, immunomodulatory or anti-fibrotic agents, alone or with corticosteroids. A Cochrane review of corticosteroids in IPF has found no evidence that they are of benefit., Objectives: To determine the effect of non-corticosteroid immunosuppressive, anti-fibrotic and immunomodulatory agents in the treatment of IPF(UIP)., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library, Issue 2 2003), MEDLINE (January 1966 to April 2003), EMBASE (January 1985 to April 2003) and with additional handsearching., Selection Criteria: RCTs/CCTs utilising non-corticosteroid immunosuppressive, anti-fibrotic or immunomodulatory agents versus either placebo or corticosteroids alone in adult patients with histological evidence of IPF(UIP) or with a diagnosis consistent with published American Thoracic Society guidelines were included., Data Collection and Analysis: We retrieved abstracts of identified articles and reviewed those possibly fulfilling inclusion criteria and included or excluded. Two reviewers assessed the studies for inclusion in the review. Where doubt existed a third reviewer re-assessed the article and consensus was obtained. Methodological quality was assessed using the Jadad scale and the Cochrane assessment of allocation of concealment., Main Results: 59 studies were identified. Quality was generally poor. Only three RCT/CCTs were suitable for meta-analysis, two lesser quality RCTs were included in discussion only, 52 studies were excluded and two ongoing trials were identified. Each high quality trial used a different agent (azathioprine, colchicine, interferon-gamma 1b) and meaningful comparisons are not possible. Azathioprine and Interferon were studied as additional therapy, whilst colchicine was compared with oral corticosteroids. Only interferon was shown to produce any significant improvement in pulmonary function and arterial oxygenation. There may be a small (but undefined) long term survival advantage for azathioprine. One of the lower quality studies showed a marginal benefit for cyclophosphamide and prednisone over prednisone alone; the other showed no benefit for azathioprine and prednisone over prednisone alone. There are no high quality studies utilising cyclophosphamide., Reviewer's Conclusions: There is little good quality information regarding the efficacy of non-corticosteroid agents in IPF(UIP). The older agents have generally not been well evaluated. A number of new agents require further evaluation. Currently there is little to justify the routine use of any non-corticosteroid agent in the management of IPF(UIP).

Idiopathic pulmonary fibrosis (IPF) is a chronic condition of unknown etiology with an unfavorable outcome from progressively deteriorating respiratory function, leading ultimately to death from respiratory failure. It is characterized by sequential acute lung injury resulting in progressive fixed tissue fibrosis, architectural distortion and loss of function. An excess of profibrotic cytokines and/or a deficiency in antifibrotic cytokines have been implicated in the pathological process as has excessive oxidation. IPF is distinguished from other forms of diffuse pulmonary fibrosis by the presence of the specific histological pattern of usual interstitial pneumonitis. Oral corticosteroids are the usual treatment, but objective response rates are poor and good quality studies do not exist. Other therapies either alone or in combination with corticosteroids are widely used, including azathioprine, colchicine, cyclophosphamide and penicillamine. There is a paucity of good quality information regarding the effectiveness of most noncorticosteroid immunosuppressive agents. Older studies of lesser methodological quality have shown benefits from these drugs, generally when added to corticosteroids. Many were retrospective reviews or uncontrolled, nonrandomized, open-label, prospective studies and often included other histological patterns of disease which are now thought to respond better to immunosuppressive agents. The results of intervention with colchicine and azathioprine have been disappointing when assessed by good quality trials using modern diagnostic criteria. Modern high quality studies are lacking for several agents, notably cyclophosphamide and penicillamine. The older agents may yet prove to be effective but further good quality trials will be necessary to assess these agents adequately. Other new anti-inflammatory, antioxidant, antifibrotic or anticytokine compounds are largely untried or unreported. One trial using interferon-gamma-1b showed a significant improvement in pulmonary function but there are concerns regarding the generalizability of this study. Pirfenidone, cyclosporine and acetylcysteine may also prove to be of benefit but current studies are of insufficient quality to allow for any conclusions to be drawn. Currently there is no good evidence to support the routine use of oral corticosteroids, azathioprine, cyclophosphamide, penicillamine, colchicine, cyclosporine or any other immunosuppressive, antifibrotic or immunomodulatory agent in the management of IPF. Interferon, pirfenidone and other new agents may be of benefit but further studies are required. Any recommendations for treatment must therefore be made on an individual and empiric basis. As some other forms of pulmonary fibrosis may respond better to immunosuppressive agents, it remains important to make an accurate diagnosis, by open lung biopsy if necessary.

The article focuses on updates on guidelines and therapeutics regarding Idiopathic pulmonary fibrosis (IPF) in 2011. It mentions IPF receiving a currently used triple-drug therapy consisting of prednisone, azathioprine, and N-acetylcysteine (NAC) had worse outcomes than those who received matching placebo. It also mentions need to determine the effect of treatments used in the management of IPF.

Background: Preclinical data have suggested that nintedanib, an intracellular inhibitor of tyrosine kinases, inhibits processes involved in the progression of lung fibrosis. Although the efficacy of nintedanib has been shown in idiopathic pulmonary fibrosis, its efficacy across a broad range of fibrosing lung diseases is unknown.Methods: In this double-blind, placebo-controlled, phase 3 trial conducted in 15 countries, we randomly assigned patients with fibrosing lung disease affecting more than 10% of lung volume on high-resolution computed tomography (CT) to receive nintedanib at a dose of 150 mg twice daily or placebo. All the patients met criteria for progression of interstitial lung disease in the past 24 months despite treatment and had a forced vital capacity (FVC) of at least 45% of the predicted value and a diffusing capacity of the lung for carbon monoxide ranging from 30 to less than 80% of the predicted value. Randomization was stratified according to the fibrotic pattern (a pattern of usual interstitial pneumonia [UIP] or other fibrotic patterns) on high-resolution CT. The primary end point was the annual rate of decline in the FVC, as assessed over a 52-week period. The two primary populations for analysis were the overall population and patients with a UIP-like fibrotic pattern.Results: A total of 663 patients were treated. In the overall population, the adjusted rate of decline in the FVC was -80.8 ml per year with nintedanib and -187.8 ml per year with placebo, for a between-group difference of 107.0 ml per year (95% confidence interval [CI], 65.4 to 148.5; P<0.001). In patients with a UIP-like fibrotic pattern, the adjusted rate of decline in the FVC was -82.9 ml per year with nintedanib and -211.1 ml per year with placebo, for a difference of 128.2 ml (95% CI, 70.8 to 185.6; P<0.001). Diarrhea was the most common adverse event, as reported in 66.9% and 23.9% of patients treated with nintedanib and placebo, respectively. Abnormalities on liver-function testing were more common in the nintedanib group than in the placebo group.Conclusions: In patients with progressive fibrosing interstitial lung diseases, the annual rate of decline in the FVC was significantly lower among patients who received nintedanib than among those who received placebo. Diarrhea was a common adverse event. (Funded by Boehringer Ingelheim; INBUILD ClinicalTrials.gov number, NCT02999178.). [ABSTRACT FROM AUTHOR]