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Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease characterised by worsening respiratory symptoms and physiological impairment. Increasing awareness of the clinical manifestations of IPF, more widespread use of computed tomography scans and other potential factors have contributed to a rising prevalence of IPF over the last two decades, especially among people over the age of 65 years. Significant advances in the understanding of the pathobiology of IPF have emerged, and multiple genetic and nongenetic contributors have been identified. The individual patient course and the rate of disease progression in IPF are often unpredictable and heterogeneous. The rate of lung function decline is further modified by treatment with antifibrotic therapies, which have been shown to slow down disease progression. The presence of comorbid conditions may increase symptom burden and impact survival. Clinical monitoring at regular intervals to assess for disease progression by worsening symptoms, physiological parameters and/or radiological features is essential to assess the natural disease course and to guide further management, including prompt detection of complications and comorbid conditions that warrant additional treatment considerations, and timely consideration of referral to palliative care and lung transplantation for the appropriate patient. More studies are needed to determine whether early detection of IPF might improve patient outcomes. The purpose of this concise clinical review is to provide an update on IPF diagnosis, epidemiology, natural history and treatment in the context of new knowledge and latest clinical practice guidelines., Competing Interests: Conflict of interest: A.J. Podolanczuk reports grants from the American Lung Association and NHLBI, consulting fees from Regeneron, Roche and Imvaria, lecture honoraria from National Association for Continuing Education and EBSCO/DynaMed, and advisory board participation with Boehringer Ingelheim, outside the submitted work. L. Richeldi reports grants from Roche, Boehringer Ingelheim and the Italian Drug Agency, consulting fees from Biogen, Celgene, Nitto, Pliant Therapeutics, Toray, BMS, RespiVant and CSL Behring, lecture honoraria from Boehringer Ingelheim, Zambon and Cipla, travel support from Boehringer Ingelheim and Roche, advisory board participation with Roche, Boehringer Ingelheim, FibroGen and Promedior, and steering committee membership with Boehringer Ingelheim and Roche, outside the submitted work. F.J. Martinez reports steering committee membership with Afferent/Merck, Bayer, Biogen, Nitto, Novartis, Patara/Respivant, Promedior/Roche and Veracyte, consulting fees from Abvie, Boehringer Ingelheim, BMS, Bridge Biotherapeutics, CSL Behring, DevPro, Genentech, IQVIA, Sanofi, Shionogi, twoXAR and Veracyte, travel support from Boehringer Ingelheim, CSL Behring and Patara/Respivant, and advisory board membership with Biogen and Boehringer Ingelheim, outside the submitted work. M. Kolb reports grants from Boehringer Ingelheim, Pieris and Roche, consulting fees from Boehringer Ingelheim, Roche, Horizon, Cipla, AbbVie, Belerophon, Algernon, CSL Behring and United Therapeutics, lecture honoraria from Roche, Novartis and Boehringer Ingelheim, payment for expert testimony from Roche, advisory board membership with United Therapeutics and LabCorp, and has been remunerated for Chief Editorship of the European Respiratory Journal. G. Raghu reports personal fees from Boehringer Ingelheim, BMS, United Therapeutics and Veracyte, consulting fees and/or advisory board membership from Boehringer Ingelheim, Biogen, Bellerophan, Fibrogen, Nitto, Roche Genentech, Novartis, Zambon, Avalyn and Blade Therapeutics, and research grants from the National Institutes of Health, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Progressive fibrosing interstitial lung disease (PF-ILD) is characterised by progressive physiological, symptomatic and/or radiographic worsening. The real-world prevalence and characteristics of PF-ILD remain uncertain., Methods: Patients were enrolled from the Canadian Registry for Pulmonary Fibrosis between 2015 and 2020. PF-ILD was defined as a relative forced vital capacity (FVC) decline ≥10%, death, lung transplantation or any two of: relative FVC decline ≥5% and <10%, worsening respiratory symptoms or worsening fibrosis on computed tomography of the chest, all within 24 months of diagnosis. Time-to-event analysis compared progression between key diagnostic subgroups. Characteristics associated with progression were determined by multivariable regression., Results: Of 2746 patients with fibrotic ILD (mean±sd age 65±12 years; 51% female), 1376 (50%) met PF-ILD criteria in the first 24 months of follow-up. PF-ILD occurred in 427 (59%) patients with idiopathic pulmonary fibrosis (IPF), 125 (58%) with fibrotic hypersensitivity pneumonitis (HP), 281 (51%) with unclassifiable ILD (U-ILD) and 402 (45%) with connective tissue disease-associated ILD (CTD-ILD). Compared with IPF, time to progression was similar in patients with HP (hazard ratio (HR) 0.96, 95% CI 0.79-1.17), but was delayed in patients with U-ILD (HR 0.82, 95% CI 0.71-0.96) and CTD-ILD (HR 0.65, 95% CI 0.56-0.74). Background treatment varied across diagnostic subtypes, with 66% of IPF patients receiving antifibrotic therapy, while immunomodulatory therapy was utilised in 49%, 61% and 37% of patients with CHP, CTD-ILD and U-ILD, respectively. Increasing age, male sex, gastro-oesophageal reflux disease and lower baseline pulmonary function were independently associated with progression., Conclusions: Progression is common in patients with fibrotic ILD, and is similarly prevalent in HP and IPF. Routinely collected variables help identify patients at risk for progression and may guide therapeutic strategies., Competing Interests: Conflict of interest: M.M. Farooqi reports no conflicts of interest relevant to this manuscript. Conflict of interest: A. Dvorkin-Gheva reports no conflicts of interest relevant to this manuscript. Conflict of interest: K. Donohoe reports no conflicts of interest relevant to this manuscript. Conflict of interest: K. Garlick was an employee for the medical department of Boehringer Ingelheim at the time of the preparation of this manuscript. Conflict of interest: C. Scallan reports personal fees from Boehringer Ingelheim. Conflict of interest: S.G. Chong reports no conflicts of interest relevant to this manuscript. Conflict of interest: S. MacIsaac reports no conflicts of interest relevant to this manuscript. Conflict of interest: D. Assayag reports personal fees from Roche and Boehringer Ingelheim. Conflict of interest: K.A. Johannson reports grants from Boehringer Ingelheim, Pulmonary Fibrosis Society of Calgary and University of Calgary School of Medicine; personal fees from Boehringer Ingelheim, Roche, Three Lakes Foundation, Pliant Therapeutics, Theravance and Blade Therapeutics. Conflict of interest: C.D. Fell reports educational grants and research grants from Boehringer Ingelheim, Roche and the Canadian Pulmonary Fibrosis Foundation; personal fees from Roche and Boehringer Ingelheim; Chair of the Boards for the Canadian Pulmonary Fibrosis Foundation. Conflict of interest: V. Marcoux reports grants from Boehringer Ingelheim, AstraZeneca and Roche; personal fees from Boehringer Ingelheim and Roche. Conflict of interest: H. Manganas reports grants from Boehringer Ingelheim and Gilead. Conflict of interest: J. Morisset reports personal fees from Boehringer Ingelheim and Roche. Conflict of interest: A. Comes reports no conflicts of interest relevant to this manuscript. Conflict of interest: J.H. Fisher reports no conflicts of interest relevant to this manuscript. Conflict of interest: S. Shapera reports educational grants and research grants from Boehringer Ingelheim, Roche and the Canadian Pulmonary Fibrosis Foundation; personal fees from AstraZeneca, Boehringer Ingelheim Canada and Hoffman La-Roche Canada; served on the medical advisory board for the Canadian Pulmonary Fibrosis Foundation. Conflict of interest: A.S. Gershon reports a research grant from the Canadian Pulmonary Fibrosis Foundation. Conflict of interest: T. To reports no conflicts of interest relevant to this manuscript. Conflict of interest: A.W. Wong reports personal fees from AstraZeneca and Boehringer Ingelheim. Conflict of interest: M. Sadatsafavi reports grants from Boehringer Ingelheim; personal fees from Boehringer Ingelheim. Conflict of interest: P.G. Wilcox reports personal fees from Boehringer Ingelheim. Conflict of interest: A.J. Halayko reports no conflicts of interest relevant to this manuscript. Conflict of interest: N. Khalil reports no conflicts of interest relevant to this manuscript. Conflict of interest: G. Cox reports personal fees from Boehringer Ingelheim and Roche. Conflict of interest: L. Richeldi reports grants and personal fees from Boehringer Ingelheim; personal fees from Biogen, Sanofi-Aventis, Celgene, RespiVant, CSL Behring, Nitto, Pliant Therapeutics, Cipla, Zambon, Promedior, Boehringer Ingelheim, Roche and Fibrogen. Conflict of interest: C.J. Ryerson reports grants from Boehringer Ingelheim; personal fees from Boehringer Ingelheim, Roche, Pliant Therapeutics, Cipla and Veracyte. Conflict of interest: M. Kolb reports grants from the Canadian Institute for Health Research, Roche, Boehringer Ingelheim, Pieris and Prometic; personal fees from Boehringer Ingelheim, Roche, European Respiratory Journal, Belerophon, United Therapeutics, Nitto Denko, MitoImmune, Pieris, AbbVie, DevPro Biopharma, Horizon, Algernon and CSL Behring. Conflict of interest: N. Hambly reports grants from Roche and Boehringer Ingelheim; personal fees from Roche, Boehringer Ingelheim and Janssen., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: The primary analysis of the INBUILD trial showed that in subjects with progressive fibrosing interstitial lung diseases (ILDs), nintedanib slowed the decline in forced vital capacity (FVC) over 52 weeks. We report the effects of nintedanib on ILD progression over the whole trial., Methods: Subjects with fibrosing ILDs other than idiopathic pulmonary fibrosis, who had ILD progression within the 24 months before screening despite management deemed appropriate in clinical practice, were randomised to receive nintedanib or placebo. Subjects continued on blinded randomised treatment until all subjects had completed the trial. Over the whole trial, mean±sd exposure to trial medication was 15.6±7.2 and 16.8±5.8 months in the nintedanib and placebo groups, respectively., Results: In the nintedanib (n=332) and placebo (n=331) groups, respectively, the proportions of subjects who had ILD progression (absolute decline in FVC ≥10% predicted) or died were 40.4% and 54.7% in the overall population (hazard ratio (HR) 0.66, 95% CI 0.53-0.83; p=0.0003) and 43.7% and 55.8% among subjects with a usual interstitial pneumonia (UIP)-like fibrotic pattern on high-resolution computed tomography (HRCT) (HR 0.69, 95% CI 0.53-0.91; p=0.009). In the nintedanib and placebo groups, respectively, the proportions who had an acute exacerbation of ILD or died were 13.9% and 19.6% in the overall population (HR 0.67, 95% CI 0.46-0.98; p=0.04) and 15.0% and 22.8% among subjects with a UIP-like fibrotic pattern on HRCT (HR 0.62, 95% CI 0.39-0.97; p=0.03)., Conclusion: Based on data from the whole INBUILD trial, nintedanib reduced the risk of events indicating ILD progression., Competing Interests: Conflict of interest: K.R. Flaherty reports grants and personal fees from Boehringer Ingelheim and Roche/Genentech; and personal fees from Bellerophon, Blade Therapeutics, Celgene, FibroGen, Respivant, Sanofi Genzyme and Veracyte. Conflict of interest: A.U. Wells reports personal fees from Blade Therapeutics, Boehringer Ingelheim and Roche. Conflict of interest: V. Cottin reports personal fees and nonfinancial support from Actelion and Roche/Promedior; grants, personal fees and nonfinancial support from Boehringer Ingelheim; and personal fees from AstraZeneca, Bayer/MSD, Bristol-Myers Squibb, Celgene, Fibrogen, Galapagos, Galecto, Novartis, Sanofi and Shionogi. Conflict of interest: A. Devaraj reports personal fees from Boehringer Ingelheim, Galapagos, Galecto, GlaxoSmithKline and Roche. Conflict of interest: Y. Inoue reports other from Asahi Kasei, Boehringer Ingelheim, Galapagos, Roche, Savara, Inc., Shionogi and Taiho; and grants from the Japan Agency for Medical Research and Development and Ministry of Health, Labour and Welfare of Japan. Conflict of interest: L. Richeldi reports grants and personal fees from Boehringer Ingelheim and Roche; and personal fees from Asahi Kasei, Biogen, Bristol-Myers Squibb, Celgene, CSL Behring, FibroGen, ImmuneWorks, Nitto, Pliant Therapeutics, Promedior, Respivant and Toray. Conflict of interest: S.L.F. Walsh reports grants and personal fees from Boehringer Ingelheim; and personal fees from Bracco, Galapagos, Open Source Imaging Consortium, Roche and Sanofi. Conflict of interest: M. Kolb reports grants and personal fees from Boehringer Ingelheim, Pieris, Prometic, Roche; personal fees from Algernon, AstraZeneca, GlaxoSmithKline, Indalo and Third Pole, Inc.; and other from the European Respiratory Society. Conflict of interest: D. Koschel reports personal fees and nonfinancial support from Boehringer Ingelheim; and personal fees from Roche. Conflict of interest: T. Moua has nothing to disclose. Conflict of interest: S. Stowasser is an employee of Boehringer Ingelheim International GmbH. Conflict of interest: R-G. Goeldner is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG. Conflict of interest: R. Schlenker-Herceg is an employee of Boehringer Ingelheim Pharmaceuticals, Inc. Conflict of interest: K.K. Brown reports personal fees and nonfinancial support from Boehringer Ingelheim; grants from the National Heart, Lung, and Blood Institute; personal fees from Biogen, Blade Therapeutics, DevPro Biopharma, Dispersol, Galapagos, Galecto, Huitai Biomedicine, Humanetics, Lifemax, Lilly, Pliant, Third Pole Therapeutics and Theravance; and other from the Open Source Imaging Consortium., (Copyright ©The authors 2022.)

For patients with IPF, length of time in healthcare systems prior to review in an ILD clinic reflects disease severity and may impact upon patient outcome https://bit.ly/2TkO26r., Competing Interests: Conflict of interest: C.J. Brereton reports nonfinancial support from Boehringer Ingelheim outside the submitted work. Conflict of interest: T. Wallis has nothing to disclose. Conflict of interest: M. Casey has nothing to disclose. Conflict of interest: L. Fox reports nonfinancial support from Roche for a study day in Manchester and nonfinancial support from Boehinger Ingelheim to attend ILD INN, outside the submitted work. Conflict of interest: K. Pontoppidan reports personal fees for conference attendance from Bayer outside the submitted work. Conflict of interest: D. Laws has nothing to disclose. Conflict of interest: J. Graves reports personal fees from GSK for an asthma talk to practice nurses and personal fees for a Pfizer-funded smoking cessation webinar, outside the submitted work. Conflict of interest: V. Titmuss has nothing to disclose. Conflict of interest: S. Kearney has nothing to disclose. Conflict of interest: S. Evans has nothing to disclose. Conflict of interest: A. Grove has nothing to disclose. Conflict of interest: S. Hamid has nothing to disclose. Conflict of interest: L. Richeldi reports personal fees from Biogen for consulting activity; grants and personal fees for membership of an advisory board from Roche; personal fees for consulting activity from ImmuneWorks; grants, and personal fees for membership of a steering committee and an advisory board from Boehringer Ingelheim; personal fees for consulting activity from Celgene and Nitto; personal fees for membership of advisory boards from FibroGen and Promedior; and personal fees for consulting activity from Pliant Therapeutics, Asahi Kasei, Toray, BMS, RespiVant and CSL Behring, all outside the submitted work. Conflict of interest: K.M.A. O'Reilly reports grants and personal fees for an advisory board from Boehringer Ingelheim, and personal fees for talks and advisory work from Roche, outside the submitted work. Conflict of interest: S.V. Fletcher reports personal fees and nonfinancial support from Boehringer Ingelheim and Roche/Intermune, outside the submitted work Conflict of interest: M.G. Jones has nothing to disclose., (Copyright ©ERS 2020.)

We conducted a post hoc analysis to assess the potential impact of GAP (gender, age, physiology) stage on the treatment effect of nintedanib in patients with idiopathic pulmonary fibrosis. Outcomes were compared in patients at GAP stage I versus II/III at baseline in the INPULSIS® trials. At baseline, 500 patients were at GAP stage I (nintedanib 304, placebo 196), 489 were at GAP stage II (nintedanib 296, placebo 193) and 71 were at GAP stage III (nintedanib 38, placebo 33). In nintedanib-treated patients, the annual rate of decline in forced vital capacity (FVC) was similar in patients at GAP stage I and GAP stage II/III at baseline (-110.1 and -116.6 mL·year -1 , respectively), and in both subgroups was lower than in placebo-treated patients (-218.5 and -227.6 mL·year -1 , respectively) (treatment-by-time-by-subgroup interaction p=0.92). In the nintedanib group, the number of deaths was 43.8% of those predicted based on GAP stage (35 versus 79.9). In the placebo group, the number of deaths was 59.8% of those predicted based on GAP stage (33 versus 55.2). In conclusion, data from the INPULSIS® trials suggest that nintedanib has a similar beneficial effect on the rate of FVC decline in patients at GAP stage I versus II/III at baseline., Competing Interests: Conflict of interest: C.J. Ryerson reports grants and personal fees from Boehringer Ingelheim and Hoffmann-La Roche, outside the submitted work. Conflict of interest: M. Kolb reports research funding from the Canadian Pulmonary Fibrosis Foundation and the Canadian Institute for Health Research, acting as a site principal investigator in industry-sponsored clinical trials for Roche, Sanofi and Boehringer Ingelheim, grants from and service on an advisory board for the Pulmonary Fibrosis Foundation, advisory board fees from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Vertex, Genoa, Gilead and Alkermes, and grants and advisory board fees from Roche Canada and Janssen, personal fees from Prometic, outside the submitted work. Conflict of interest: L. Richeldi reports grants and personal fees from Boehringer Ingelheim during the conduct of the study; and grants and personal fees from InterMune, and personal fees from Medimmune, Biogen-Idec, Sanofi-Aventis Roche, Takeda, ImmuneWorks and Shionogi, outside the submitted work. Conflict of interest: J. Lee reports grants from the NIH, and personal fees from Genentech and Celgene, outside the submitted work. Conflict of interest: D. Wachtlin is an employee of Boehringer Ingelheim Conflict of interest: S. Stowasser is an employee of Boehringer Ingelheim. Conflict of interest: V. Poletti reports personal fees from Boehringer Ingelheim during the conduct of the study.

Multidisciplinary team (MDT) diagnosis of interstitial lung disease (ILD) has been proposed as a gold standard, but there are no formal recommendations for MDT process or composition and limited knowledge regarding prevalence in routine practice. We performed a systematic evaluation of ILD diagnostic practice across a range of healthcare settings around the world. Electronic questionnaires were distributed across all global regions via society and collaborators networks. Responses from 457 unique centres across 64 countries were included in the analysis. Of the 350 (76.6%) centres holding formal meetings, the majority held face-to-face MDT meetings (80%), for a minimum of 30 min (93%), and discussed diagnosis (96.9%) and patient management (94.9%) at the meetings. Compared with non-academic and academic non-ILD centres, ILD academic centres reported a higher ILD caseload, held more formal MDT meetings, and were more likely to include histopathology and rheumatology specialists in their diagnostic team. Of the centres holding MDT meetings, 5.5% routinely discussed all new cases at such meetings. An MDT approach to ILD diagnosis is consistently interpreted and widely implemented across a range of routine care settings around the world. This observation will inform future ILD diagnostic agreement studies and diagnostic pathway recommendations., Competing Interests: Conflict of interest: L. Richeldi reports personal fees for consulting activity from Sanofi-Aventis, ImmuneWorks, Celgene, Nitto, Bristol-Myers Squibb and Pliant Therapeutics, personal fees for membership of an advisory board from Roche, Fibrogen and Promedior, speaker fees from Shionogi, grants and personal fees for membership of a steering committee from Boehringer Ingelheim, and personal fees for editorial activity from DynaMed, outside the submitted work. Conflict of interest: N. Launders reports that the Respiratory Effectiveness Group received grants from Roche, Boehringer Ingelheim and Three Lakes Partners, and nonfinancial support from Veracyte, during the conduct of the study. Conflict of interest: F. Martinez reports personal fees, nonfinancial support and other support from Boehringer Ingelheim during the conduct of the study; personal fees and nonfinancial support from the American College of Chest Physicians, AstraZeneca, Boehringer Ingelheim, Continuing Education, ConCert, Genentech, GlaxoSmithKline, Miller Communications, the National Association for Continuing Education, Novartis, Pearl Pharmaceuticals, PeerView Communications, Prime Communications, the Puerto Rican Respiratory Society, Chiesi, Roche, Sunovion, Theravance, Potomac, the University of Alabama Birmingham, the Physicians Education Resource, the Canadian Respiratory Network and Teva, nonfinancial support from ProterrixBio, the Inova Fairfax Health System, Gilead, Nitto, Patara and Zambon, personal fees from Columbia University, Integritas, MD Magazine, Methodist Hospital Brooklyn, New York University, Unity, UpToDate, WebMD/MedScape, the Western Connecticut Health Network, Academic CME, PlatformIQ, the American Thoracic Society and Rockpointe, other support from Afferent/Merck, Biogen, Veracyte, Prometic, Bayer and Bridge Biotherapeutics, and grants from the NIH, Rare Disease Healthcare Communications and ProMedior, outside the submitted work. Conflict of interest: S.L.F. Walsh has nothing to disclose. Conflict of interest: J. Myers has nothing to disclose. Conflict of interest: B. Wang has nothing to disclose. Conflict of interest: M. Jones has nothing to disclose. Conflict of interest: A. Chisholm reports she worked for the Respiratory Effectiveness Group during the design and data capture stages of the study; she now works for Syneos Health. She has no conflicts of interest to declare in relation to this study. Conflict of interest: K.R. Flaherty reports grants and personal fees from Boehringer Ingelheim and Roche/Genentech, personal fees from Veracyte, Aeolus, Pharmakea, Sanofi-Genzyme and Fibrogen, outside the submitted work.

Nintedanib and pirfenidone are approved treatments for idiopathic pulmonary fibrosis (IPF). This open-label, two-group trial investigated the pharmacokinetic drug-drug interaction between these two drugs in patients with IPF.Subjects not treated with antifibrotics at screening (group 1, n=20) received a single nintedanib dose (150 mg) followed by pirfenidone (titrated to 801 mg thrice daily) for 3 weeks, with a further single nintedanib dose (150 mg) on the last day (day 23). Subjects treated with pirfenidone at screening (group 2, n=17) continued to receive pirfenidone alone (801 mg thrice daily) for 7 days, then co-administered with nintedanib (150 mg twice daily) for a further 7 days, before single doses of both treatments on day 16.In group 1, adjusted geometric mean (gMean) ratios (with/without pirfenidone) were 88.6% and 80.6% for nintedanib area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C max ), respectively. In group 2, gMean ratios (with/without nintedanib) were 97.2% and 99.5% for pirfenidone AUC and C max , respectively. For all parameters, the 90% confidence intervals included 100%, suggesting similar exposure for administration alone and when co-administered. Both treatments were well tolerated.These data indicate there is no relevant pharmacokinetic drug-drug interaction between nintedanib and pirfenidone when co-administered in IPF patients., Competing Interests: Conflict of interest: L. Richeldi reports grants and personal fees (member of an advisory board) from InterMune, personal fees for consultancy from Sanofi-Aventis, ImmuneWorks, Celgene, Nitto and Bristol Myers Squibb, personal fees as member of an advisory board from Roche, Fibrogen and Promedior, personal fees for speaking from Shionogi, personal fees as a member of a steering committee from Boehringer Ingelheim, personal fees for editorial activity from DynaMed, outside the submitted work. Conflict of interest: S. Fletcher has nothing to disclose. Conflict of interest: H. Adamali has nothing to disclose. Conflict of interest: N. Chaudhuri reports grants (for a project) from Boehringer Ingelheim, personal fees (for speakers fees) from Boehringer Ingelheim, other funding for educational sponsorship from Roche and Boehringer Ingelheim, and personal fees (for advisory boards) from Roche, outside the submitted work. Conflict of interest: S. Wiebe is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG. Conflict of interest: S. Wind is an employee of Boehringer Ingelheim Pharma GmbH & Co KG. Conflict of interest: K. Hohl has nothing to disclose. Conflict of interest: A. Baker is an employee of Boehringer Ingelheim. Conflict of interest: R. Schlenker-Herceg has nothing to disclose. Conflict of interest: S. Stowasser is an employee of Boehringer Ingelheim International GmbH. Conflict of interest: T.M. Maher has, via his institution, received industry-academic funding from GlaxoSmithKline R&D and UCB and has received consultancy or speakers fees from Apellis, AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Cipla, GlaxoSmithKline R&D, ProMetic, Roche, Sanumed and UCB., (Copyright ©ERS 2019.)

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.)

A phase 2b trial (NCT02345070) was conducted to evaluate the efficacy and safety of two dose levels/regimens of SAR156597 (a bispecific IgG4 antibody that binds and neutralises both circulating interleukin-4 and interleukin-13), in comparison with placebo, administered to patients with idiopathic pulmonary fibrosis (IPF) over 52 weeks.DRI11772 was a multinational randomised double-blind placebo-controlled phase 2b trial. Patients aged >40 years with a documented diagnosis of IPF received SAR156597 200 mg once every week (QW), SAR156597 200 mg once every 2 weeks (Q2W) or placebo, over 52 weeks. The primary efficacy end-point was absolute change from baseline in forced vital capacity (FVC) % predicted at 52 weeks.Of 327 randomised patients, 325 received treatment with placebo (n=109), SAR156597 Q2W (n=108) or SAR156597 QW (n=108). The mean change from baseline in FVC % pred at 52 weeks was -5.8%, -5.2% and -6.3% for the placebo, Q2W and QW arms, respectively (Q2W versus placebo, p=0.59; QW versus placebo, p=0.63). The safety profile observed in the three treatment arms was generally similar, although serious adverse events were more common in the QW arm than in the other arms.The DRI11772 study failed to demonstrate benefit of SAR156597 in the treatment of IPF., Competing Interests: Conflict of interest: G. Raghu reports consultant and advisor fees from Sanofi during the conduct of the study, and consultant and advisor fees from Bellerophan, Boehringer Ingelheim, BMS, FibroGen, Gilead, Nitto, Parata, Promedior and Veracyte, outside the submitted work. Conflict of interest: L. Richeldi reports grants and personal fees from InterMune, personal fees (for advisory board membership) from Medimmune, Roche and Takeda, personal fees (for consultancy) from Biogen, Sanofi-Aventis, ImmuneWorks and Pliants Therapeutics, speakers fees from Shionogi and Cipla, and fees from Boehringer Ingelheim as a member of a steering committee, outside the submitted work. Conflict of interest: B. Crestani reports personal fees from Sanofi, grants, personal fees and non-financial support (for speaking, travel and research) from Boehringer Ingelheim and Roche, grants for research from CARDIF and LVL, personal fees and non-financial support (for speaking and travel) from AstraZeneca, and grants and non-financial support (for research and travel) from Medlmmune, outside the submitted work. Conflict of interest: P. Wung has nothing to disclose. Conflict of interest: R. Bejuit reports personal fees (salary) from Sanofi, during the conduct of the study and outside the submitted work. Conflict of interest: C. Esperet reports personal fees (salary) from Sanofi, during the conduct of the study and outside the submitted work. Conflict of interest: C. Antoni reports personal fees (salary) from Sanofi, during the conduct of the study and outside the submitted work. Conflict of interest: C. Soubrane reports personal fees (salary) from Sanofi, during the conduct of the study and outside the submitted work., (Copyright ©ERS 2018.)

In IPF, commencement of antifibrotic therapy in patients with preserved lung volume may increase the duration of therapy http://ow.ly/4HeM30lFS67., Competing Interests: Conflict of interest: S.V. Fletcher reports receiving funding to attend conferences, speaker fees and fees for advisory boards from Roche and Boehringer Ingelheim. Conflict of interest: M.G. Jones has nothing to disclose. Conflict of interest: E.A. Renzoni reports receiving lecture fees from Boehringer, Roche and Takeda outside the submitted work. Conflict of interest: H. Parfrey reports receiving personal fees for consultancy work from Boehringer Ingelheim and Roche, and nonfinancial support for conference attendance from Boehringer Ingelheim and Roche. Conflict of interest: R.K. Hoyles reports receiving support for a specialist interstitial lung disease nurse (part time) for 1 year outside the submitted work. Conflict of interest: K. Spinks reports receiving advisory board fees and conference sponsorship from Boehringer Ingelheim, and educational meeting sponsorship from Roche, outside the submitted work. Conflict of interest: M. Kokosi has nothing to disclose. Conflict of interest: A. Kwok has nothing to disclose. Conflict of interest: C. Warburton has nothing to disclose. Conflict of interest: V. Titmuss reports receiving personal fees for discussion on the new formulary of pirfenidone and its new patient information leaflet from the Roche Nurse Advisory Board outside the submitted work. Conflict of interest: M. Thillai has received travel scholarships and consultancy fees from Boehringer Ingelheim and Roche. Conflict of interest: N. Simler has nothing to disclose. Conflict of interest: T.M. Maher reports receiving grant funding to his institution and personal fees for service on a clinical trial advisory board from GSK; personal fees from Boehringer Ingelheim, InterMune, Sanofi Aventis, AstraZeneca, Roche, Biogen Idec, Cipla, Prometic and Sanumed; research fees to his institution, personal fees and nonfinancial support from UCB; and holds stock options in Apellis, all outside the submitted work. Conflict of interest: C.J. Brereton reports receiving support to attend a conference from Boehringer Ingelheim outside the submitted work. Conflict of interest: F. Chua has nothing to disclose. Conflict of interest: A.U. Wells reports receiving fees for consulting and speaking from Intermune/Roche, Boehringer Ingelheim and Bayer, fees for consulting from Gilead, outside the submitted work. Conflict of interest: L. Richeldi reports grants and personal fees for service on an advisory board from InterMune, personal fees for service on an advisory board from Medimmune, Roche and FibroGen, personal fees for consulting activity from Biogen, Sanofi-Aventis, ImmuneWorks, Celgene and Nitton, a speaker fee from Shionogi, and personal fees for service on a steering committee from Boehringer Ingelheim, outside the submitted work. Conflict of interest: L.G. Spencer has received payments for advisory boards and travel support to attend respiratory conferences from both Boehringer Ingelheim and Roche, and speaker fees from Boehringer Ingelheim in the last 36 months.

In the Phase III INPULSIS® trials, nintedanib reduced the annual rate of decline in forced vital capacity (FVC) versus placebo in patients with idiopathic pulmonary fibrosis (IPF).We conducted post hoc analyses of the distribution of changes in FVC in the INPULSIS® trials and FVC changes in the open-label extension trial INPULSIS®-ON in subgroups of patients based on whether patients had shown an improvement or no decline in FVC in INPULSIS®. Analyses were descriptive.Based on the annual rate of change in FVC, 158 of 638 patients (24.8%) treated with nintedanib and 38 of 423 patients (9.0%) treated with placebo had an improvement/no decline in FVC in the INPULSIS® trials. In patients whose FVC improved/did not decline, median (interquartile range) improvements in FVC at week 52 were 76.5 (31-152) mL and 57.5 (31-103) mL in the nintedanib and placebo groups, respectively. Changes in FVC from baseline to week 48 of INPULSIS®-ON were similar in patients whose FVC improved or declined in the preceding INPULSIS® trial.In the INPULSIS® trials, treatment with nintedanib resulted in a greater proportion of patients with IPF showing an improvement/no decline in FVC compared to taking placebo. Mechanisms underlying improvement in FVC in patients with IPF are unknown., Competing Interests: Conflict of interest: K.R. Flaherty reports grants and personal fees for consultancy from Boehringer Ingelheim and Roche/Genentech; personal fees for consultancy from Veracyte, Biogen, Aeolus, Pharmakea, Fibrogen and Sanofi-Genzyme; and grants from Afferent; outside the submitted work. Conflict of interest: M. Kolb reports grants from Canadian Pulmonary Fibrosis Foundation and Canadian Institute for Health Research; grants and personal fees for advisory board work from Pulmonary Fibrosis Foundation, Roche Canada and Janssen; personal fees for advisory board work from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Vertex, Genoa, Gilead, Prometic and Alkermes; and has been site principal investigator in industry-sponsored clinical trials for Roche, Sanofi and Boehringer Ingelheim; outside the submitted work. Conflict of interest: C. Vancheri reports grants and personal fees from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: W. Tang is an employee of Boehringer Ingelheim Pharmaceuticals, Inc. Conflict of interest: C.S. Conoscenti is an employee of Boehringer Ingelheim Pharmaceuticals, Inc. Conflict of interest: L. Richeldi reports grants and personal fees for advisory board work from InterMune; personal fees for advisory board work from Medimmune, Roche and Takeda; personal fees for consultancy from Biogen-Idec, Sanofi-Aventis and ImmuneWorks; personal fees for lecturing from Shionogi; personal fees for steering committee work from Boehringer Ingelheim; and personal fees from Pliant Therapeutics; outside the submitted work., (Copyright ©ERS 2018.)

Experimental models are critical for the understanding of lung health and disease and are indispensable for drug development. However, the pathogenetic and clinical relevance of the models is often unclear. Further, the use of animals in biomedical research is controversial from an ethical perspective.The objective of this task force was to issue a statement with research recommendations about lung disease models by facilitating in-depth discussions between respiratory scientists, and to provide an overview of the literature on the available models. Focus was put on their specific benefits and limitations. This will result in more efficient use of resources and greater reduction in the numbers of animals employed, thereby enhancing the ethical standards and translational capacity of experimental research.The task force statement addresses general issues of experimental research (ethics, species, sex, age, ex vivo and in vitro models, gene editing). The statement also includes research recommendations on modelling asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung infections, acute lung injury and pulmonary hypertension.The task force stressed the importance of using multiple models to strengthen validity of results, the need to increase the availability of human tissues and the importance of standard operating procedures and data quality., Competing Interests: Conflict of interest: P. Bonniaud reports personal fees (board/advice) from Roche, Boehringer, Novartis, TEVA and AstraZeneca, and travel reimbursement (ERS meetings) from Chiesi, outside the submitted work. Conflict of interest: A. Fabre reports grants from Pfizer, reagents from Roche, and personal fees from MSD (Merck Sharp & Dohme Corp.), outside the submitted work. Conflict of interest: T. Maes reports grants from Belgian Science Policy (Federal Government Belgium-Interuniversity attraction Poles), Ghent University (Concerted Research Action and Spearhead Immunology) and Novartis, and personal fees (GSK Clinical Science award: prize for best abstract presentation at Belgian Pulmonology Society Meeting 2015) and non-financial support (travel/accommodation/meeting expenses) from GlaxoSmithKline, outside the submitted work; and is shareholder of Oryzon Genomics. Conflict of interest: W. Shi reports grants from National Institute of Health and Department of Defense, outside the submitted work. Conflict of interest: M. Stampfli reports grants from RespiVert and MedImmune, and personal fees from AstraZeneca and Boehringer Ingelheim, outside the submitted work. Conflict of interest: S. Uhlig reports grants from Germany Research Foundation (DFG), during the conduct of the study. Conflict of interest: E. White reports grants and other support from NIH, personal fees for consulting from Akcea Therapeutics and Kadmon Pharmaceuticals, and research grants and personal fees for consulting from Boehringer-Ingelheim, outside the submitted work. Conflict of interest: M. Witzenrath reports grants and personal fees from Bayer Health Care, Boehringer Ingelheim, Biotest and Vaxxilon, and personal fees from Actelion, Berlin Chemie, AstraZeneca, GlaxoSmithKline and Novartis, outside the submitted work. Conflict of interest: B. Crestani has receieved an honorarium for speaking from Aventis, honoraria for speaking, grants for research and congress travel support grants from Boehringer Ingelheim and Roche, grants for research from CARDIF and LVL, an honorarium for speaking and congress travel support from AstraZeneca, and a grant for research and congress travel support from MedImmune, outside the submitted work. Conflict of interest: O. Eickelberg reports grants from the Helmholtz Association, the German Center of Lung Research, Roche, and Bayer and consultancy/lecture fees from BMS, Novartis, Bayer, Intermune, McKinsey, and MorphoSys. Conflict of interest: A. Guenther reports research funding, and compensation for lectures and consulting from Roche, compensation for lectures and consulting from Boehringer Ingelheim and Teva, and research funding from Sanofi, outside the submitted work. Conflict of interest: G. Jenkins reports grants from GlaxoSmithKline (institutional funding for the PROFILE study) and the Medical Research Council (co-funder of the PROFILE study with GSK through MICA award), during the conduct of the study; grants from Biogen (SRA for work on integrins in IPF), personal fees (consulting and data monitoring committees on lung fibrosis) from Boehringer Ingelheim, grants (PhD studentship) from Galecto, personal fees (advisory board on IPF) from GlaxoSmithKline and Intermune, grants and personal fees (consulting on IPF, PhD studentship) from MedImmune, personal fees (consulting on IPF) from PharmAkea, personal fees (advisory board on IPF and lecture fees) from Roche, consulting on IPF (with no payment received to date) for Pliant Therapeutics, participating in scientific advisory boards (with no payment received to date) for NuMedii, and personal fees from Pulmatrix, outside the submitted work; and is a trustee for the charities Action for Pulmonary Fibrosis and the British Thoracic Society. Conflict of interest: G. Joos reports grants, personal fees and non-financial support from AstraZeneca, grants and personal fees from Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Novartis, and personal fees from Mundipharma, Sandoz and Teva, outside the submitted work. Conflict of interest: U.A. Maus reports grants from Federal Ministry of Education and Research, German Research Foundation and Lower Saxony Society for the Control of Tuberculosis and Bronchial Diseases, outside the submitted work. Conflict of interest: L. Richeldi reports grants and personal fees (for advisory board membership) from InterMune, personal fees (for advisory board membership) from Medimmune, Roche and FibroGen, personal fees (for consulting activity) from Biogen, Sanofi-Aventis, ImmuneWorks, Celgene and Nitto, personal fees (for speaking) from Shionogi, and personal fees (for membership of steering committee) from Boehringer Ingelheim, outside the submitted work. Conflict of interest: M. Kolb reports grants and personal fees from Roche, Boehringer Ingelheim, GSK, Gilead, Prometic and Alkermes, grants from Actelion, Respivert and Synairgen, and personal fees from AstraZeneca and Genoa, outside the submitted work., (Copyright ©ERS 2018.)

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts.A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (κ w ). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the C-index.A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (κ w =0.65, IQR 0.53-0.72, p<0.0001) than academic physicians (κ w =0.56, IQR 0.45-0.65, p<0.0001) or physicians with access to multidisciplinary team (MDT) meetings (κ w =0.54, IQR 0.45-0.64, p<0.0001). The prognostic accuracy of academic physicians with >20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75).Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Time to first investigator-reported acute exacerbation was a key secondary end-point in the INPULSIS trials of nintedanib in patients with idiopathic pulmonary fibrosis (IPF).We used the INPULSIS trial data to investigate risk factors for acute exacerbation of IPF and to explore the impact of nintedanib on risk and outcome of investigator-reported and adjudicated confirmed/suspected acute exacerbations. Mortality following these events and events adjudicated as not acute exacerbations was analysed using the log rank test.Risk of acute exacerbations was most strongly associated with the following variables: baseline forced vital capacity (higher risk with lower value), baseline supplemental oxygen (higher risk with use), baseline antacid medication (higher risk with use), treatment (higher risk with placebo), and for confirmed/suspected acute exacerbations, cigarette smoking. Mortality was similar following investigator-reported and adjudicated confirmed/suspected acute exacerbations. Nintedanib had no significant effect on risk of mortality post-exacerbation.Investigator-reported acute exacerbations of IPF are associated with similar risk factors and outcomes as adjudicated confirmed/suspected acute exacerbations., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Many patients with an idiopathic interstitial pneumonia (IIP) have clinical features that suggest an underlying autoimmune process but do not meet established criteria for a connective tissue disease (CTD). Researchers have proposed differing criteria and terms to describe these patients, and lack of consensus over nomenclature and classification limits the ability to conduct prospective studies of a uniform cohort.The "European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease" was formed to create consensus regarding the nomenclature and classification criteria for patients with IIP and features of autoimmunity.The task force proposes the term "interstitial pneumonia with autoimmune features" (IPAF) and offers classification criteria organised around the presence of a combination of features from three domains: a clinical domain consisting of specific extra-thoracic features, a serologic domain consisting of specific autoantibodies, and a morphologic domain consisting of specific chest imaging, histopathologic or pulmonary physiologic features.A designation of IPAF should be used to identify individuals with IIP and features suggestive of, but not definitive for, a CTD. With IPAF, a sound platform has been provided from which to launch the requisite future research investigations of a more uniform cohort., (Copyright ©ERS 2015.)

The aim of the present study was to define the prevalence, characteristics, risk factors and impact on clinical outcomes of acute myocardial infarction (AMI) versus other cardiovascular events (CVEs) in patients with community-acquired pneumonia (CAP). This was an international, multicentre, observational, prospective study of CAP patients hospitalised in eight hospitals in Italy and Switzerland. Three groups were identified: those without CVEs, those with AMI and those with other CVEs. Among 905 patients, 21 (2.3%) patients experienced at least one AMI, while 107 (11.7%) patients experienced at least one other CVE. Patients with CAP and either AMI or other CVEs showed a higher severity of the disease than patients with CAP alone. Female sex, liver disease and the presence of severe sepsis were independent predictors for the occurrence of AMI, while female sex, age >65 years, neurological disease and the presence of pleural effusion predicted other CVEs. In-hospital mortality was significantly higher among those who experienced AMI in comparison to those experiencing other CVEs (43% versus 21%, p=0.039). The presence of AMI showed an adjusted odds ratio for in-hospital mortality of 3.57 (p=0.012) and for other CVEs of 2.63 (p=0.002). These findings on AMI versus other CVEs as complications of CAP may be important when planning interventional studies on cardioprotective medications., Competing Interests: can be found alongside this article at openres.ersjournals.com

The past decade has seen substantial progress in understanding the pathobiology, natural history, and clinical significance of idiopathic pulmonary fibrosis (IPF), culminating in the establishment of two effective medical therapies. Now seems an important time to reconsider the design and conduct of future IPF clinical trials. Building on lessons learned over the past decade, we use this perspective to lay out four key considerations for moving forward effectively and efficiently with the next generation of clinical trials in IPF. These are: development of a coordinated IPF clinical trials network; establishment of expectations for early phase proof of concept studies; adaptation of late-phase efficacy trial designs to the emergence of approved therapies, and; agreement on primary end-points for late phase clinical trials. Continued progress in the field of IPF will require creativity and collaboration on the part of all stakeholders. We believe that addressing these four considerations will encourage and enable investment in this new era of drug development in IPF, and will lead to more rapid development of effective therapies., (Copyright ©ERS 2015.)

In idiopathic pulmonary fibrosis (IPF), some facts or concepts based on substantial evidence, whilst implicit for learned subspecialists, have previously been neglected and/or not explicitly formulated or made accessible to a wider audience. IPF is strongly associated with cigarette smoking and is predominantly a disease of ageing. However, its cause(s) remain elusive and, thus, it is one of the most challenging diseases for the development of novel effective and safe therapies. With the approval of pirfenidone for patients with mild-to-moderate IPF, an earlier diagnosis of IPF is a prerequisite for earlier treatment and, potentially, improvement of the long-term clinical outcome of this progressive and ultimately fatal disease. An earlier diagnosis may be achieved in IPF by promoting thin-slice chest high-resolution computed tomography screening of interstitial lung disease as a "by-product" of large-scale lung cancer screening strategies in smokers, but other techniques, which have been neglected in the past, are now available. Lung auscultation and early identification of "velcro" crackles has been proposed as a key component of early diagnosis of IPF. An ongoing study is exploring correlations between lung sounds on auscultation obtained using electronic stethoscopes and high-resolution computed tomography patterns.

The aim of this study was to determine the prevalence, characteristics and outcomes of patients with unclassifiable interstitial lung disease (ILD) and to develop a simple method of predicting disease behaviour. Unclassifiable ILD patients were identified from an ongoing longitudinal cohort. Unclassifiable ILD was diagnosed after a multidisciplinary review did not secure a specific ILD diagnosis. Clinical characteristics and outcomes were compared with idiopathic pulmonary fibrosis (IPF) and non-IPF ILDs. Independent predictors of mortality were determined using Cox proportional-hazards analysis to identify subgroups with distinct disease behaviour. Unclassifiable ILD was diagnosed in 10% of the ILD cohort (132 out of 1370 patients). The most common reason for being unclassifiable was missing histopathological assessment due to a high risk of surgical lung biopsy. Demographic and physiological features of unclassifiable ILD were intermediate between IPF and non-IPF disease controls. Unclassifiable ILD had longer survival rates when compared to IPF on adjusted analysis (hazard ratio 0.62, p = 0.04) and similar survival compared to non-IPF ILDs (hazard ratio 1.54, p = 0.12). Independent predictors of survival in unclassifiable ILD included diffusion capacity of the lung for carbon monoxide (p = 0.001) and a radiological fibrosis score (p = 0.02). Unclassifiable ILD represents approximately 10% of ILD cases and has a heterogeneous clinical course, which can be predicted using clinical and radiological variables.

The magnitude of treatment effect can be assessed by a number of methods. One method of collectively analysing data is that used by the Cochrane Collaboration. Their systematic reviews identify, analyse and present research-based evidence in an accessible format. These reviews may contain meta-analyses combining data from multiple studies to provide robust evaluations of overall treatment effects. In 2003, Cochrane reviews of data for treatment with corticosteroids in idiopathic pulmonary fibrosis (IPF) found no evidence supporting their use; similarly, reviews of immunomodulatory agents found very little evidence to support their use. A recent update of these Cochrane reviews failed to identify any evidence supporting the use of corticosteroids in IPF; however, a review of non-steroid agents in the treatment of IPF identified 15 clinical trials suitable for analysis. Two trials of interferon-γ-1b were combined, and no treatment effect was observed in terms of survival. Two Japanese trials of treatment with pirfenidone were combined, and a positive effect of pirfenidone on pulmonary function decline was observed. Meta-analysis of three phase III studies suggested that pirfenidone significantly increased progression-free survival by 30%. The findings of this systematic review, although not presenting new original data, together with an acceptable safety profile, suggest that pirfenidone may have a role in IPF treatment.

The diagnosis of pleural tuberculosis (plTB) by the analysis of pleural effusions (PEs) with standard diagnostic tools is difficult. In routine clinical practice, the present authors evaluated the performance of a commercially available Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunospot assay on peripheral blood mononuclear cells (PBMCs) and pleural effusion mononuclear cells (PEMCs) in patients with suspect plTB. The T-SPOT.TB test (Oxford Immunotec Ltd, Abingdon, UK) was performed on PBMCs and PEMCs in 20 patients with a clinical and radiological suspect of plTB and in 21 control subjects with a diagnosis of PE of nontuberculous origin at four centres participating in the European Tuberculosis Network. In total, 18 (90%) out of 20 patients with plTB tested T-SPOT.TB-positive on PBMCs and 19 (95%) out of 20 on PEMCs. Among controls, T-SPOT.TB was positive in seven out of 21 (33%) patients when performed on PBMCs (these patients were assumed to be latently infected with MTB) and five (23%) out of 21 when performed on PEMCs. Sensitivity and specificity of T-SPOT.TB for the diagnosis of active plTB when performed on PEMCs were 95 and 76%, respectively. Enumerating Mycobacterium tuberculosis-specific T-cells in pleural effusion mononuclear cells by ELISPOT is feasible in routine clinical practice and may be useful for a rapid and accurate diagnosis of pleural tuberculosis.

The triggering receptor expressed on myeloid cells (TREM)-1 is a recently described molecule, which plays an important role in myeloid cell-activated inflammatory responses. TREM-1 is expressed on blood neutrophils and monocytes, and also on alveolar macrophages, thus suggesting a potential role in lung inflammatory responses against infections. To investigate the differential expression of TREM-1 in lung infections, its levels were assessed in bronchoalveolar lavage specimens from patients with community-acquired pneumonia or tuberculosis. TREM-1 was also investigated in patients with interstitial lung diseases, as a model of noninfectious inflammatory disease of the lung. TREM-1 expression was significantly increased in lung neutrophils and in lung macrophages of patients with pneumonia (n=7; 387.9+/-61.4 and 660.5+/-18.3, respectively) compared with patients with pulmonary tuberculosis (n=7; 59.2+/-13.1 and 80.6+/-291.2) and patients with interstitial lung diseases (n=10; 91.8+/-23.3 and 123.9+/-22.8). In contrast, TREM-1 expression on peripheral blood neutrophils was no different among the three groups. In conclusion, these data suggest that triggering receptor expressed on myeloid cells-1 is selectively expressed in the lungs of patients with pneumonia caused by extracellular bacteria and not in patients with tuberculosis, providing a potential marker for differential diagnosis.