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Rationale: To improve disease outcomes in idiopathic pulmonary fibrosis (IPF), it is essential to understand its early pathophysiology so that it can be targeted therapeutically. Objectives: Perform three-dimensional assessment of the IPF lung microstructure using stereology and multiresolution computed tomography (CT) imaging. Methods: Explanted lungs from patients with IPF ( n  = 8) and donor control subjects ( n  = 8) were inflated with air and frozen. CT scans were used to assess large airways. Unbiased, systematic uniform random samples ( n  = 8/lung) were scanned with microCT for stereological assessment of small airways (count number, and measure airway wall and lumen area) and parenchymal fibrosis (volume fraction of tissue, alveolar surface area, and septal wall thickness). Measurements and Main Results: The total number of airways on clinical CT was greater in IPF lungs than control lungs ( P  < 0.01), owing to an increase in the wall ( P  < 0.05) and lumen area ( P  < 0.05) resulting in more visible airways with a lumen larger than 2 mm. In IPF tissue samples without microscopic fibrosis, assessed by the volume fraction of tissue using microCT, there was a reduction in the number of the terminal ( P  < 0.01) and transitional ( P  < 0.001) bronchioles, and an increase in terminal bronchiole wall area ( P  < 0.001) compared with control lungs. In IPF tissue samples with microscopic parenchymal fibrosis, terminal bronchioles had increased airway wall thickness ( P  < 0.05) and dilated airway lumens ( P  < 0.001) leading to honeycomb cyst formations. Conclusions: This study has important implications for the current thinking on how the lung tissue is remodeled in IPF and highlights small airways as a potential target to modify IPF outcomes.

Rationale: Real-life pharmacological treatment patterns of patients with interstitial lung diseases (ILD) remain elusive. Objectives: To determine how often and with what medications patients with ILD are treated in Canadian tertiary care clinics. Methods: All patients with ILD prospectively enrolled in the Canadian Registry for Pulmonary Fibrosis were included in this observational study. All first instances of medication for each patient were compiled. The time between the diagnosis of ILD and the first initiation of an ILD-related medication was compared across diagnostic categories. Cox proportional hazards models were used to identify variables associated with time-to-treatment initiation, stratified by diagnostic category. Results: Out of 2,652 patients, a total of 1,483 (56%) were treated with an ILD-related medication during the median follow up of 3.0 years (1.4-5.9), including 349/646 (54%) patients with idiopathic pulmonary fibrosis (IPF) who received an antifibrotic. Patients with IPF were treated earlier and in greater proportion than those with non-IPF ILD ( P  = 0.001). Male sex and lower lung function were associated with shorter time-to-treatment initiation in the full cohort. Conclusions: Overall, 56% of patients with ILD seen across seven Canadian specialized ILD clinics received pharmacological treatment over a median follow up of 3 years. Further studies are needed to assess longitudinal patterns of treatment and their influence on key outcomes.

Social media is an increasingly popular source of health information, and the rarity and complexity of interstitial lung disease (ILD) may particularly draw patients with ILD to social media for information and support. The objective of this viewpoint is to provide an overview of social media, explore the benefits and limitations of ILD-related social media use, and discuss future development of healthcare information on social media. We describe the value of integrating social media into the practice of ILD health professionals, including its role in information dissemination, patient engagement, knowledge generation, and formation of health policy. We also describe major challenges to expanded social media use in ILD, including limited access for some individuals and populations, abundance of misinformation, and concerns about patient privacy. Finally, for healthcare professionals looking to join social media, we provide practical guidance and considerations to optimize the potential benefits and minimize the potential pitfalls of social media., (© 2021. The Author(s).)

Objectives: The aim of this study was to compare respiratory and patient-reported outcome measures (PROMs) between 3 and 6 months after symptom onset and to identify features that predict these changes., Methods: This was a consecutive prospective cohort of 73 patients who were hospitalised with coronavirus disease 2019 (COVID-19). We evaluated the changes in pulmonary function tests and PROMs between 3 and 6 months and then investigated the associations between outcomes (change in diffusing capacity of the lung for carbon monoxide ( D LCO ), dyspnoea and quality of life (QoL)) and clinical and radiological features., Results: There was improvement in forced vital capacity, total lung capacity and D LCO between 3 and 6 months by 3.25%, 3.82% and 5.69%, respectively; however, there was no difference in PROMs. Reticulation and total computed tomography (CT) scores were associated with lower D LCO % predicted at 6 months (coefficients; -8.7 and -5.3, respectively). The association between radiological scores and D LCO were modified by time, with the degree of association between ground glass and D LCO having decreased markedly over time. There was no association between other predictors and change in dyspnoea or QoL over time., Conclusions: There is improvement in pulmonary function measurements between 3 and 6 months after COVID-19 symptom onset; however, PROMs did not improve. A higher reticulation and total CT score are negatively associated with D LCO , but this association is attenuated over time. Lastly, there is a considerable proportion of patients with unexplained dyspnoea at 6 months, motivating further research to identify the underlying mechanisms., Competing Interests: Conflict of interest: A.S. Shah has nothing to disclose. Conflict of interest: M.H. Ryu has nothing to disclose. Conflict of interest: C.J. Hague has nothing to disclose. Conflict of interest: D.T. Murphy has nothing to disclose. Conflict of interest: J.C. Johnston has nothing to disclose. Conflict of interest: C.J. Ryerson has nothing to disclose. Conflict of interest: C. Carlsten has nothing to disclose. Conflict of interest: A.W. Wong has nothing to disclose., (Copyright ©The authors 2021.)

Introduction: For the management of patients referred to respiratory triage during the early stages of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic, either chest radiography or computed tomography (CT) were used as first-line diagnostic tools. The aim of this study was to compare the impact on the triage, diagnosis and prognosis of patients with suspected COVID-19 when clinical decisions are derived from reconstructed chest radiography or from CT., Methods: We reconstructed chest radiographs from high-resolution CT (HRCT) scans. Five clinical observers independently reviewed clinical charts of 300 subjects with suspected COVID-19 pneumonia, integrated with either a reconstructed chest radiography or HRCT report in two consecutive blinded and randomised sessions: clinical decisions were recorded for each session. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and prognostic value were compared between reconstructed chest radiography and HRCT. The best radiological integration was also examined to develop an optimised respiratory triage algorithm., Results: Interobserver agreement was fair (Kendall's W =0.365, p<0.001) by the reconstructed chest radiography-based protocol and good (Kendall's W =0.654, p<0.001) by the CT-based protocol. NPV assisted by reconstructed chest radiography (31.4%) was lower than that of HRCT (77.9%). In case of indeterminate or typical radiological appearance for COVID-19 pneumonia, extent of disease on reconstructed chest radiography or HRCT were the only two imaging variables that were similarly linked to mortality by adjusted multivariable models CONCLUSIONS: The present findings suggest that clinical triage is safely assisted by chest radiography. An integrated algorithm using first-line chest radiography and contingent use of HRCT can help optimise management and prognostication of COVID-19., Competing Interests: Conflict of interests: N. Sverzellati has nothing to disclose. Conflict of interests: C.J. Ryerson has nothing to disclose. Conflict of interests: G. Milanese has nothing to disclose. Conflict of interests: E.A. Renzoni has nothing to disclose. Conflict of interests: A. Volpi has nothing to disclose. Conflict of interests: P. Spagnolo reports grants, personal fees and nonfinancial support from Roche, PPM Services and Boehringer Ingelheim, personal fees from Red X Pharma, Galapagos and Chiesi, outside the submitted work; and the author's spouse is an employee of Novartis. Conflict of interests: F. Bonella reports personal fees and nonfinancial support from Boehringer Ingelheim, Roche, Galapagos, Savara Pharma and Bristol Myers Squibb, outside the submitted work. Conflict of interests: I. Comelli has nothing to disclose. Conflict of interests: P. Affanni has nothing to disclose. Conflict of interests: L. Veronesi has nothing to disclose. Conflict of interests: C. Manna has nothing to disclose. Conflict of interests: A. Ciuni has nothing to disclose. Conflict of interests: C. Sartorio has nothing to disclose. Conflict of interests: G. Tringali has nothing to disclose. Conflict of interests: M. Silva has nothing to disclose. Conflict of interests: E. Michieletti has nothing to disclose. Conflict of interests: D. Colombi has nothing to disclose. Conflict of interests: A.U. Wells reports personal fees and other from Roche, Boehringer Ingelheim and Bayer, outside the submitted work., (Copyright ©The authors 2021.)

Rationale: The pathophysiology of interstitial lung disease (ILD) impacts body composition, whereby ILD severity is linked to lower lean mass., Objectives: To determine i) if pectoralis muscle area (PMA) is a surrogate for whole-body lean mass in ILD, ii) whether PMA is associated with ILD severity, and iii) if the longitudinal change in PMA is associated with pulmonary function and mortality in ILD., Methods: Patients with ILD (n = 164) were analyzed retrospectively. PMA was quantified from a chest computed tomography scan. Peripheral oxygen saturation (SpO 2 ), 6-min walk distance (6MWD), and pulmonary function were obtained as part of routine clinical care. Dyspnea and quality of life were assessed using the UCSD Shortness of Breath Questionnaire and European Quality of Life 5 Dimensions questionnaire, respectively., Results: PMA was associated with whole-body lean mass (p < 0.001). After adjusting for age, sex, height, body mass, and prednisone status, PMA was associated with %-predicted forced vital capacity (FVC), %-predicted diffusion capacity (DL CO ), resting and exertional SpO 2 , and dyspnea (all p < 0.05), but not forced expiratory volume in 1 s (FEV 1 ), FEV 1 /FVC, 6MWD, or quality of life (all p > 0.05). The annual negative PMA slope was associated with annual negative slopes in FVC, FEV 1 , and DL CO (all p < 0.05), but not FEV 1 /FVC (p = 0.46). Annual slope in PMA was associated with all-cause mortality (hazard ratio = -0.80, 95% CI:0.889-0.959; p < 0.001)., Conclusion: In patients with ILD, PMA is a suitable surrogate for whole-body lean mass. A lower PMA is associated with indices of ILD severity, which supports the notion that ILD progression may involve sarcopenia., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Many patients with interstitial lung disease (ILD) develop pulmonary fibrosis, which can lead to reduced quality of life and early mortality. Patients with fibrotic ILD often have considerable diagnostic delay, and are exposed to unnecessary and costly diagnostic procedures, and ineffective and potentially harmful treatments. Non-specific and insidious presenting symptoms, along with scarce knowledge of fibrotic ILD among primary care physicians and non-ILD experts, are some of the main causes of diagnostic delay. Here, we outline and discuss the challenges facing both patients and physicians in making an early diagnosis of fibrotic ILD, and explore strategies to facilitate early identification of patients with fibrotic ILD, both in the general population and among individuals at highest risk of developing the disease. Finally, we discuss controversies and key uncertainties in screening programmes for fibrotic ILD. Timely identification and accurate diagnosis of patients with fibrotic ILD poses several substantial clinical challenges, but could potentially improve outcomes through early initiation of appropriate management., Competing Interests: Declaration of interests PS reports grants, personal fees, and non-financial support from Roche, PPM Services, and Boehringer Ingelheim, and personal fees from Galapagos, Chiesi, and Santhera Pharmaceuticals, outside of the submitted work; his wife is an employee of Novartis. CJR reports grants and personal fees from Boehringer Ingelheim and Hoffmann-La Roche, outside of the submitted work. RP reports grants from National Institutes of Health (NIH), during the conduct of the study. JO reports grants from NIH and personal fees from Genentech and Boehringer Ingelheim, outside of the submitted work. MS reports grants from NIH, during the conduct of the study; and personal fees from Boehringer Ingelheim, Orinove, and Roche, outside of the submitted work. NS reports personal fees from Roche and Boehringer Ingelheim, and grants from Chiesi, outside of the submitted work. CV reports personal fees from Boehringer Ingelheim, Hoffmann-La Roche, Galapagos, and BMS, outside of the submitted work. SG reports personal fees from Boehringer Ingelheim and Hoffmann-La Roche, outside of the submitted work. MW reports grants, speaker fees, and consultancy fees from Boehringer Ingelheim and Hoffman la Roche, consultancy fees from Galapagos and Respivant, data safety monitoring fees from Savara, and speaker fees from Novartis, outside of the submitted work; all grants and fees were paid to her institution. VC reports personal fees and non-financial support from Actelion and Roche/Promedior, grants, personal fees, and non-financial support from Boehringer Ingelheim, and personal fees from Bayer/MSD, Novartis, Sanofi, Celgene, Galapagos, Galecto, Shionogi, AstraZeneca, and Fibrogen, outside of the submitted work. SJ declares no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Hypoxemia is a cardinal feature of fibrotic interstitial lung disease (ILD). The incidence, progression, and prognostic significance of hypoxemia in patients with fibrotic ILD currently is unknown., Research Question: What are the epidemiologic features of hypoxemia and its additive prognostic value in a current risk prediction model of fibrotic ILD?, Methods: We identified 848 patients with fibrotic ILD (258 with idiopathic pulmonary fibrosis [IPF]) in five prospective ILD registries from Australia, Canada, and Switzerland. Cumulative incidence of exertional and resting hypoxemia from the time of diagnosis was estimated at 1-year intervals in patients with baseline 6-min walk tests, adjusted for competing risks of death and lung transplantation. Likelihood ratio tests were used to determine the prognostic significance of exertional and resting hypoxemia for 1-year mortality or transplantation when added to the ILD-GAP model. The cohort was divided into derivation and validation subsets to evaluate performance characteristics of the extended model (the ILD-GAP-O 2 model), which included oxygenation status as a predictor., Results: The 1-, 2-, and 5-year overall cumulative incidence was 6.1%, 17.3%, and 40.1%, respectively, for exertional hypoxemia and 2.4%, 5.6%, and 16.5%, respectively, for resting hypoxemia, which were significantly higher in patients with IPF compared with patients without IPF (P < .001 for both). Addition of exertional or resting hypoxemia to the ILD-GAP model improved 1-year mortality and transplantation prediction (P < .001 for both). The ILD-GAP-O 2 model showed improved discrimination (C-index, 0.80 vs 0.75) and model fit (Akaike information criteria, 400 vs 422) in the validation cohort, with comparable calibration., Interpretation: Patients with IPF have higher cumulative incidence of exertional and resting hypoxemia than patients without IPF. The extended ILD-GAP-O 2 model provides additional risk stratification for 1-year prognosis in fibrotic ILD., (Copyright © 2021 American College of Chest Physicians. All rights reserved.)

Obstructive sleep apnea (OSA) is one of the most common comorbidities in patients with interstitial lung disease (ILD). Growing evidence highlights the significance of sleep disturbance on health outcomes in this population. The relationships between ILD and OSA are complex and possibly bidirectional, with multiple mechanisms postulated for the pathogenic and physiologic links. This review synthesizes current evidence and hypotheses regarding different aspects of the relationships between ILD and OSA, emphasizing the interactions between epidemiology, pathogenesis, and pathophysiology., Competing Interests: Conflicts of interest Y.H.K. reports non-financial research support from Air Liquide Healthcare, personal fees from Boehringer Ingelheim and Roche, and grants from Boehringer Ingelheim, outside the submitted work. C.J.R. reports grants and personal fees from Boehringer Ingelheim and Hoffmann-La Roche, outside the submitted work. B.A.E. reports income from Signifier Medical (consulting) and Apnimed (grant support), outside the submitted work. G.S.H reports non-financial research support from Resmed, Philips Respironics and Air Liquide Healthcare, outside the submitted work., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: In the past two decades, many advances have been made to our understanding of interstitial lung disease (ILD) and the way we approach its treatment. Despite this, many questions remain unanswered, particularly those related to how the disease and its therapies impact outcomes that are most important to patients. There is currently a lack of guidance on how to best define and incorporate these patient-centered outcomes in ILD research. Objectives: To summarize the current state of patient-centered outcomes research in ILD, identify gaps in knowledge and research, and highlight opportunities and methods for future patient-centered research agendas in ILD. Methods: An international interdisciplinary group of experts was assembled. The group identified top patient-centered outcomes in ILD, reviewed available literature for each outcome, highlighted important discoveries and knowledge gaps, and formulated research recommendations. Results: The committee identified seven themes around patient-centered outcomes as the focus of the statement. After a review of the literature and expert committee discussion, we developed 28 research recommendations. Conclusions: Patient-centered outcomes are key to ascertaining whether and how ILD and interventions used to treat it affect the way patients feel and function in their daily lives. Ample opportunities exist to conduct additional work dedicated to elevating and incorporating patient-centered outcomes in ILD research.

Rationale: The University of California, San Diego Shortness of Breath Questionnaire (UCSDSOBQ) is a frequently used domain-specific dyspnea questionnaire; however, there is little information available regarding its use and minimum important difference (MID) in fibrotic interstitial lung disease (ILD). We aimed to describe the key performance characteristics of the UCSDSOBQ in this population., Methods: UCSDSOBQ scores and selected anchors were measured in 1933 patients from the prospective multi-center Canadian Registry for Pulmonary Fibrosis. Anchors included the St. George's Respiratory Questionnaire (SGRQ), European Quality of Life 5 Dimensions 5 Levels questionnaire (EQ-5D-5L) and EQ visual analogue scale (EQ-VAS), percent-predicted forced vital capacity (FVC%), diffusing capacity of the lung for carbon monoxide (DLCO%), and 6-min walk distance (6MWD). Concurrent validity, internal consistency, ceiling and floor effects, and responsiveness were assessed, followed by estimation of the MID by anchor-based (linear regression) and distribution-based methods (standard error of measurement)., Results: The UCSDSOBQ had a high level of internal consistency (Cronbach's alpha = 0.97), no obvious floor or ceiling effect, strong correlations with SGRQ, EQ-5D-5L, and EQ-VAS (|r| > 0.5), and moderate correlations with FVC%, DLCO%, and 6MWD (0.3 < |r| < 0.5). The MID estimate for UCSDSOBQ was 5 points (1-8) for the anchor-based method, and 4.5 points for the distribution-based method., Conclusion: This study demonstrates the validity of UCSDSOBQ in a large and heterogeneous population of patients with fibrotic ILD, and provides a robust MID estimate of 5-8 points.

Background and Objective: Physical frailty is associated with increased mortality and hospitalizations in older adults. We describe the prevalence of physical frailty and its prognostic impact in patients with a spectrum of fibrotic interstitial lung disease (ILD)., Methods: Patients with fibrotic ILD at the McMaster University ILD programme were prospectively followed up from November 2015 to March 2020. Baseline data were used to classify patients as non-frail (score = 0), pre-frail (score = 1-2) or frail (score = 3-5) based on modified Fried physical frailty criteria. The association between physical frailty and mortality was assessed using time-to-event models, adjusted for age, sex, lung function and diagnosis using the ILD Gender-Age-Physiology (ILD-GAP) score., Results: We included 463 patients (55% male, mean [SD] age 68 [11] years); 82 (18%) were non-frail, 258 (56%) pre-frail and 123 (26%) frail. The most common ILD diagnoses were idiopathic pulmonary fibrosis (n = 183, 40%) and connective tissue disease-associated-ILD (n = 79, 17%). Mean time since diagnosis was 2.7 ± 4.6 years. There were 56 deaths within the median follow-up of 1.71 (interquartile range [IQR] 1.24, 2.31) years. Both frail and pre-frail individuals had a higher risk of death compared to those categorized as non-frail at baseline (adjusted hazard ratio [aHR] 4.14, 95% CI 1.27-13.5 for pre-frail and aHR 4.41, 95% CI 1.29-15.1 for frail)., Conclusion: Physical frailty is prevalent in patients with ILD and is independently associated with an increased risk of death. Assessment of physical frailty provides additional prognostic value to recognized risk scores such as the ILD-GAP score, and may present a modifiable target for intervention., (© 2021 Asian Pacific Society of Respirology.)

Interstitial lung diseases (ILDs) are challenging to diagnose, requiring integration of multiple complex features that are often difficult to interpret. This article reviews a pragmatic approach to ILD diagnosis and classification, focusing on diagnostic tools and strategies that are used to separate different subtypes and identify the most appropriate management. We discuss the evolution of ILD classification and the contemporary approach that integrates routinely used diagnostic tools in a multidisciplinary discussion. We highlight the increasing importance of taking a multipronged approach to ILD classification that reflects the recent emphasis on disease behavior while also considering etiopathogenesis and morphologic features., Competing Interests: Conflict of Interest Disclosures A. Adegunsoye is supported by a career development award from the National Heart, Lung, and Blood Institute (K23HL146942), and has received speaking and advisory board fees from Boehringer Ingelheim and grant funding for interstitial lung disease research from the Pulmonary Fibrosis Foundation. C.J. Ryerson is supported by a Health Professional Investigator Award from the Michael Smith Foundation for Health Research., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The purpose of this study was to examine the physiological mechanisms of persistent dyspnoea in COVID-19 survivors. Non-critical patients (n = 186) with varying degrees of COVID-19 severity reported persistent symptoms using a standardized questionnaire and underwent pulmonary function and 6-minute walk testing between 30 and 90 days following the onset of acute COVID-19 symptoms. Patients were divided into those with (n = 70) and without (n = 116) persistent dyspnoea. Patients with persistent dyspnoea had significantly lower FVC (p = 0.03), FEV 1 (p = 0.04), D LCO (p = 0.01), 6-minute walk distance (% predicted, p = 0.03), and end-exercise oxygen saturation (p < 0.001), and higher Borg 0-10 ratings of dyspnoea and fatigue (both p < 0.001) compared to patients without persistent dyspnoea. We have shown that dyspnoea is a common persistent symptom across varying degrees of initial COVID-19 severity. Patients with persistent dyspnoea had greater restriction on spirometry, lower D LCO , reduced functional capacity, and increased exertional desaturation and symptoms. This suggests that there is a true physiological mechanism that may explain persistent dyspnoea after COVID-19., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease of unknown cause characterized by relentless scarring of the lung parenchyma leading to reduced quality of life and earlier mortality. IPF is an age-related disorder, and with the population aging worldwide, the economic burden of IPF is expected to steadily increase in the future. The mechanisms of fibrosis in IPF remain elusive, with favored concepts of disease pathogenesis involving recurrent microinjuries to a genetically predisposed alveolar epithelium, followed by an aberrant reparative response characterized by excessive collagen deposition. Pirfenidone and nintedanib are approved for treatment of IPF based on their ability to slow functional decline and disease progression; however, they do not offer a cure and are associated with tolerability issues. In this review, we critically discuss how cutting-edge research in disease pathogenesis may translate into identification of new therapeutic targets, thus facilitate drug discovery. There is a growing portfolio of treatment options for IPF. However, targeting the multitude of profibrotic cytokines and growth factors involved in disease pathogenesis may require a combination of therapeutic strategies with different mechanisms of action., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Pleuroparenchymal fibroelastosis (PPFE) is a progressive and frequently fatal interstitial lung disease that involves the upper lobes. Although its cause remains unknown, the histopathologic evidence underlying PPFE bears striking resemblance to that of the pulmonary apical cap (PAC), a relatively common and benign entity. We describe the case of a patient with PAC that evolved into distinctly asymmetric PPFE over 6 years after unilateral surgical lung injury. Given the histologic similarity between these two conditions, we propose that these two entities underlie common biologic pathways of abnormal response to lung injury, with the presence of a PAC increasing susceptibility to the development of PPFE in the face of ongoing inflammatory insults. This case describes the histopathologic evolution of PAC to PPFE before and after an inciting injury., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Patients use Facebook as a resource for medical information. We analyzed posts on idiopathic pulmonary fibrosis (IPF)-related Facebook groups and pages for the presence of guideline content, user engagement, and usefulness., Objective: The objective of this study was to describe and analyze posts from Facebook groups and pages that primarily focus on IPF-related content., Methods: Cross-sectional analysis was performed on a single date, identifying Facebook groups and pages resulting from separately searching "IPF" and "idiopathic pulmonary fibrosis." For inclusion, groups and pages needed to meet either search term and be in English, publicly available, and relevant to IPF. Every 10th post was assessed for general characteristics, source, focus, and user engagement metrics. Posts were analyzed for presence of IPF guideline content, useful scientific information (eg, scientific publications), useful support information (eg, information about support groups), and potentially harmful information., Results: Eligibility criteria were met by 12 groups and 27 pages, leading to analysis of 523 posts. Of these, 42% contained guideline content, 24% provided useful support, 20% provided useful scientific information, and 5% contained potentially harmful information. The most common post source was nonmedical users (85%). Posts most frequently focused on IPF-related news (29%). Posts containing any guideline content had fewer likes or comments and a higher likelihood of containing potentially harmful content. Posts containing useful supportive information had more likes, shares, and comments., Conclusions: Facebook contains useful information about IPF, but posts with misinformation and less guideline content have higher user engagement, making them more visible. Identifying ways to help patients with IPF discriminate between useful and harmful information on Facebook and other social media platforms is an important task for health care professionals., (©Andrew Kochan, Shaun Ong, Sabina Guler, Kerri A Johannson, Christopher J Ryerson, Gillian C Goobie. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 31.05.2021.)

Background: The transition from normal lung anatomy to minimal and established fibrosis is an important feature of the pathology of idiopathic pulmonary fibrosis (IPF). The purpose of this report is to examine the molecular and cellular mechanisms associated with this transition., Methods: Pre-operative thoracic Multidetector Computed Tomography (MDCT) scans of patients with severe IPF (n = 9) were used to identify regions of minimal(n = 27) and established fibrosis(n = 27). MDCT, Micro-CT, quantitative histology, and next-generation sequencing were used to compare 24 samples from donor controls (n = 4) to minimal and established fibrosis samples., Findings: The present results extended earlier reports about the transition from normal lung anatomy to minimal and established fibrosis by showing that there are activations of TGFBI, T cell co-stimulatory genes, and the down-regulation of inhibitory immune-checkpoint genes compared to controls. The expression patterns of these genes indicated activation of a field immune response, which is further supported by the increased infiltration of inflammatory immune cells dominated by lymphocytes that are capable of forming lymphoid follicles. Moreover, fibrosis pathways, mucin secretion, surfactant, TLRs, and cytokine storm-related genes also participate in the transitions from normal lung anatomy to minimal and established fibrosis., Interpretation: The transition from normal lung anatomy to minimal and established fibrosis is associated with genes that are involved in the tissue repair processes, the activation of immune responses as well as the increased infiltration of CD4, CD8, B cell lymphocytes, and macrophages. These molecular and cellular events correlate with the development of structural abnormality of IPF and probably contribute to its pathogenesis., Competing Interests: Declaration of Competing Interest All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The long-term respiratory morbidity of COVID-19 remains unclear. We describe the clinical, radiological and pulmonary function abnormalities that persist in previously hospitalised patients assessed 12 weeks after COVID-19 symptom onset, and identify clinical predictors of respiratory outcomes. At least one pulmonary function variable was abnormal in 58% of patients and 88% had abnormal imaging on chest CT. There was strong association between days on oxygen supplementation during the acute phase of COVID-19 and both DLCO-% (diffusion capacity of the lung for carbon monoxide) predicted and total CT score. These findings highlight the need to develop treatment strategies and the importance of long-term respiratory follow-up after hospitalisation for COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Dyspnoea is a cardinal symptom of fibrotic interstitial lung disease (ILD), with a lack of proven effective therapies. With emerging evidence of the role of facial and nasal airflow for relieving breathlessness, this pilot study was conducted to examine the feasibility of conducting a clinical trial of a handheld fan (HHF) for dyspnoea management in patients with fibrotic ILD. In this mixed-methods, randomised, assessor-blinded, controlled trial, 30 participants with fibrotic ILD who were dyspnoeic with a modified Medical Research Council Dyspnoea grade ≥ 2 were randomised to a HHF for symptom control or no intervention for 2 weeks. Primary outcomes were trial feasibility, change in Dyspnoea-12 scores at Week 2, and participants' perspectives on using a HHF for dyspnoea management. Study recruitment was completed within nine months at a single site. Successful assessor blinding was achieved in the fan group [Bang's Blinding Index - 0.08 (95% CI - 0.45, 0.30)] but not the control group [0.47 (0.12, 0.81)]. There were no significant between-group differences for the change in Dyspnoea-12 or secondary efficacy outcomes. During qualitative interviews, participants reported that using the HHF relieved breathlessness and provided relaxation, despite initial scepticism about its therapeutic benefit. Oxygen-experienced participants described the HHF being easier to use, but not as effective for symptomatic relief, compared to oxygen therapy. Our results confirmed the feasibility of a clinical trial of a HHF in fibrotic ILD. There was a high level of patient acceptance of a HHF for managing dyspnoea, with patients reporting both symptomatic benefits and ease of use.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mm Hg and classified into five different groups sharing similar pathophysiologic mechanisms, hemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: (a) Is noninvasive imaging capable of identifying PH? (b) What is the role of imaging in establishing the cause of PH? (c) How does imaging determine the severity and complications of PH? (d) How should imaging be used to assess chronic thromboembolic PH before treatment? (e) Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH. This article is a simultaneous joint publication in Radiology and European Respiratory Journal . The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. © 2021 RSNA and the European Respiratory Society. Online supplemental material is available for this article.

Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others. This article is a simultaneous joint publication in Radiology and CHEST . The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Interstitial lung diseases (ILDs), which can arise from a broad spectrum of distinct aetiologies, can manifest as a pulmonary complication of an underlying autoimmune and connective tissue disease (CTD-ILD), such as rheumatoid arthritis-ILD and systemic sclerosis (SSc-ILD). Patients with clinically distinct ILDs, whether CTD-related or not, can exhibit a pattern of common clinical disease behaviour (declining lung function, worsening respiratory symptoms and higher mortality), attributable to progressive fibrosis in the lungs. In recent years, the tyrosine kinase inhibitor nintedanib has demonstrated efficacy and safety in idiopathic pulmonary fibrosis (IPF), SSc-ILD and a broad range of other fibrosing ILDs with a progressive phenotype, including those associated with CTDs. Data from phase II studies also suggest that pirfenidone, which has a different-yet largely unknown-mechanism of action, may also have activity in other fibrosing ILDs with a progressive phenotype, in addition to its known efficacy in IPF. Collectively, these studies add weight to the hypothesis that, irrespective of the original clinical diagnosis of ILD, a progressive fibrosing phenotype may arise from common, underlying pathophysiological mechanisms of fibrosis involving pathways associated with the targets of nintedanib and, potentially, pirfenidone. However, despite the early proof of concept provided by these clinical studies, very little is known about the mechanistic commonalities and differences between ILDs with a progressive phenotype. In this review, we explore the biological and genetic mechanisms that drive fibrosis, and identify the missing evidence needed to provide the rationale for further studies that use the progressive phenotype as a target population., Competing Interests: Competing interests: PS reports grants, personal fees, non-financial support and other from Boehringer Ingelheim, during the conduct of the study; grants, personal fees and non-financial support from Roche and PPM Services; and personal fees from Red X Pharma, Galapagos and Chiesi outside the submitted work. His wife is an employee of Novartis. OD reports personal fees from Boehringer Ingelheim, during the conduct of the study; grants and personal fees from Actelion, Bayer, Boehringer Ingelheim and Mitsubishi; personal fees and non-financial support from Pfizer; and personal fees from Abbvie, Acceleron Pharma, Anamar, Amgen, Catenion, CSL Behring, ChemomAb, Ergonex, GSK, Inventiva, Italfarmaco, iQone, iQvia, Medac, Medscape, Menarini, Mepha, MSD, Lilly, Novartis, Roche, Sanofi, Target BioScience, UCB, Baecon Discovery, Blade Therapeutics, Curzion Pharmaceuticals and Glenmark Pharmaceuticals, outside the submitted work. In addition, OD has a patent US8247389, EP2331143 issued. CJR reports grants and personal fees from Boehringer Ingelheim and Hoffmann-La Roche, outside the submitted work. AT reports grants, personal fees, non-financial support and other from BI Hellas, during the conduct of the study; and other from Roche, outside the submitted work. In addition, AT has a patent for inhaled or aerosolised delivery of thyroid hormone to the lung as a novel therapeutic agent in fibrotic lung diseases issued. JSL reports grants from NIH and Boehringer Ingelheim, and personal fees from Boehringer Ingelheim, Galapagos, Celgene and Genentech, outside the submitted work. FB reports grants, personal fees and non-financial support from Boehringer Ingelheim, during the conduct of the study; grants, personal fees and non-financial support from Boehringer Ingelheim; personal fees and non-financial support from Savara, Bristol Myers Squibb and Roche; and personal fees from Galapagos, outside the submitted work. DB reports grants, personal fees, non-financial support and other from BI Hellas and other from Roche, outside the submitted work. A-MH-V reports personal fees, grants, non-financial support and other from Boehringer Ingelheim, personal fees and non-financial support from Actelion, personal fees from Bayer and Roche, outside the submitted work. BC reports personal fees and non-financial support from AstraZeneca, Sanofi and BMS; grants, personal fees and non-financial support from Boehringer Ingelheim and Roche; and personal fees from Genzyme, outside the submitted work. ELM reports personal fees from Boehringer Ingelheim, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Frailty is a state of increased vulnerability to various health stressors but little information is summarized about frailty in patients with specific chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and asthma., Objective: We aimed to describe the burden of frailty on patients with chronic respiratory disorders and to discuss the need for multidisciplinary care services., Methods: PubMed and Cochrane Central databases were systematically reviewed for studies reporting outcomes associated with frailty in COPD, IPF, and asthma. Electronic databases were searched for relevant articles published in English from 2010 up to July 2020. Appraisal was carried out based on the Hierarchy of Evidence Rating System and the GRADE guidelines., Results: A total of 31 articles met all inclusion criteria with 24 of them at level IV, 1 at level V, and 6 at level VI. Frailty is likely to negatively affect quality of life and to increase the risk of mortality, especially in elderly with COPD, IPF and asthma. Each disease has a particular effect on the balance between health status, respiratory impairment and frailty. A greater understanding of frailty phenotype across different ages, as well as in a range of long-term conditions, is of great necessity in both clinical and research settings. Limited conformity was observed between different methodologies and nature of chronic diseases studied, leading to a further difficulty to extract homogeneous information., Conclusion: Literature shows that frailty is prevalent in COPD, IPF, and asthma, after adjusting for shared risk factors. Our findings suggest that frailty should be approached as an entity per se', in order to assess real mortality risk, alongside respiratory disease severity and the presence of comorbidities. Health care professionals need knowledge, skills and multidisciplinary collaboration to buffer the impact of frailty on everyday practice., Competing Interests: EKS conceived the study idea, invited team members and offered a guidance to search topic. AK performed the literature search and composed results section by appraising findings for the studies included. AK and EKS cross-checked the emerged literature information. KA critically reviewed literature information and offered clinical input when this was necessary. AK, EKS and KA contributed to the first draft preparation. ED and CJR offered intellectual input and contributed in the draft writing and revision based on the field of their expertise. All authors read and approved final manuscriptWe would like to thank Professor Jeffrey J. Swigris for his intellectual input and advice during writing the first draft.Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.) that might pose a conflict of interest in connection with the submitted article., (Copyright: © 2021 SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES.)

Rationale: The European Quality of Life 5-Dimensions 5-Levels questionnaire (EQ-5D-5L) is a multidimensional patient-reported questionnaire that supports calculation of quality-adjusted life-years. Our objectives were to demonstrate feasibility of use and to calculate the minimum important difference (MID) of the EQ-5D-5L and its associated visual analogue scale (EQ-VAS) in patients with fibrotic interstitial lung disease (ILD)., Methods: Patients who completed the EQ-5D-5L were identified from the prospective multicentre CAnadian REgistry for Pulmonary Fibrosis. Validity, internal consistency and responsiveness of the EQ-5D-5L were assessed, followed by calculation of the MID for the EQ-5D-5L and EQ-VAS. Anchor-based methods used an unadjusted linear regression against pulmonary function tests (PFTs) and dyspnoea and other quality of life questionnaires. Distribution-based method used one-half SD and SE measurement (SEM) calculations., Results: 1816 patients were analysed, including 472 (26%) with idiopathic pulmonary fibrosis. EQ-5D-5L scores were strongly correlated with the dyspnoea and other quality of life questionnaires and weakly associated with PFTs. The estimated MID for EQ-5D-5L ranged from 0.0050 to 0.054 and from 0.078 to 0.095 for the anchor-based and distribution-based methods, respectively. The MID for EQ-VAS ranged from 0.5 to 5.0 and from 8.0 to 9.7 for the anchor-based and distribution-based methods. Findings were similar across ILD subtypes, sex and age., Conclusion: We used a large and diverse cohort of patients with a variety of fibrotic ILD subtypes to suggest validity and MID of both the EQ-5D-5L and EQ-VAS. These findings will assist in designing future clinical trials and supporting cost-effectiveness analyses of potential treatments for patients with fibrotic ILD., Competing Interests: Competing interests: CJR, MRJK, JM, KF, NH and DA report personal fees and grants from Boehringer Ingelheim and Hoffman La Roche outside the submitted work. HM reports grants from Boehringer Ingelheim. SS reports personal fees and grants from Boehringer Ingelheim and AstraZeneca Canada, and participation in clinical trials as site PI in Prometric Canada, Sanofi-Aventis, Gilead Pharmaceuticals, and Galapagos. KF also reports personal fees and grants from Theravance, Blade Therapeutics, Chest Foundation, University of Calgary School of Medicine, Pulmonary Fibrosis Society of Calgary, UCB Biopharma SPRL. NH also reports personal fees and grants from Actelion, Bayer and Novartis. MK also reports personal fees and grants from GSK, Gilead, Actelion, Respivert, Genoa, Alkermes, Pharmaxis, Prometric, Indalo and Third Pole. DA also reports personal fees and grants from Novartis. APYT, AW, SAH, GC, PGW, JF, MS, AG, CF, NK, AH and TT report no competing interests., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Comorbidities are frequent and have been associated with poor quality of life, increased hospitalizations, and mortality in patients with interstitial lung disease (ILD). However, it is unclear how comorbidities lead to these negative outcomes and whether they could influence ILD disease progression. The goal of this study was to identify clusters of patients based on similar comorbidity profiles and to determine whether these clusters were associated with rate of lung function decline and/or mortality., Methods: Patients with a major fibrotic ILD (idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, connective tissue disease-associated ILD, and unclassifiable ILD) from the CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) were included. Hierarchical agglomerative clustering of comorbidities, age, sex, and smoking pack-years was conducted for each ILD subtype to identify combinations of these features that frequently occurred together in patients. The association between clusters and change in lung function over time was determined using linear mixed effects modeling, with adjustment for age, sex, and smoking pack-years. Kaplan Meier curves were used to assess differences in survival between the clusters., Results: Discrete clusters were identified within each fibrotic ILD. In IPF, males with obstructive sleep apnea (OSA) had more rapid decline in FVC %-predicted (- 11.9% per year [95% CI - 15.3, - 8.5]) compared to females without any comorbidities (- 8.1% per year [95% CI - 13.6, - 2.7]; p = 0.03). Females without comorbidities also had significantly longer survival compared to all other IPF clusters. There were no significant differences in rate of lung function decline or survival between clusters in the other fibrotic ILD subtypes., Conclusions: The combination of male sex and OSA may portend worse outcomes in IPF. Further research is required to elucidate the interplay between sex and comorbidities in ILD, as well as the role of OSA in ILD disease progression.

Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Methods: The multidisciplinary panel created six research questions using a modified Delphi approach. A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations. Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1 ) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2 ) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3 ) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4 ) a conditional recommendation for ambulatory liquid-oxygen use in patients who are mobile outside the home and require >3 L/min of continuous-flow oxygen during exertion (very-low-quality evidence), and 5 ) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (best-practice statement). Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice.

Background: Nintedanib slows disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF) by reducing decline in Forced Vital Capacity (FVC). The effects of nintedanib on abnormalities on high-resolution computed tomography scans have not been previously studied., Objective: We conducted a Phase IIIb trial to assess the effects of nintedanib on changes in Quantitative Lung Fibrosis (QLF) score and other measures of disease progression in patients with IPF., Methods: 113 patients were randomized 1:1 to receive nintedanib 150 mg bid or placebo double-blind for ≥6 months, followed by open-label nintedanib. The primary endpoint was the relative change from baseline in QLF score (%) at month 6. Analyses were descriptive and exploratory., Results: Adjusted mean relative changes from baseline in QLF score at month 6 were 11.4% in the nintedanib group (n=42) and 14.6% in the placebo group (n=45) (difference 3.2% [95% CI: -9.2, 15.6]). Adjusted mean absolute changes from baseline in QLF score at month 6 were 0.98% and 1.33% in these groups, respectively (difference 0.35% [95% CI: -1.27, 1.96]). Adjusted mean absolute changes from baseline in FVC at month 6 were -14.2 mL and -83.2 mL in the nintedanib (n=54) and placebo (n=54) groups, respectively (difference 69.0 mL [95% CI: -8.7, 146.8])., Conclusion: Exploratory data suggest that in patients with IPF, 6 months' treatment with nintedanib was associated with a numerically smaller degree of fibrotic change in the lungs and reduced FVC decline versus placebo. These data support previous findings that nintedanib slows the progression of IPF., (© 2020 Lancaster etal.)

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has affected virtually all aspects of patient care. Health-care systems around the world are trying simultaneously to treat patients with COVID-19, prepare for its long-term impacts, and treat patients with other acute and chronic diseases. There are multiple ways that the COVID-19 pandemic will directly affect patients with fibrotic interstitial lung disease (ILD), particularly given their common risk factors for poor outcomes. Major issues for patients with ILD will include restricted access to key components of the diagnostic process, new uncertainties in the use of common ILD pharmacotherapies, limited ability to monitor both disease severity and the presence of medication adverse effects, and significantly curtailed research activities. The purpose of this review is to summarize how COVID-19 has impacted key components of the diagnosis and management of fibrotic ILD as well as to provide strategies to mitigate these challenges. We further review major obstacles for researchers and identify priority areas for future ILD research related to COVID-19. Our goals are to provide practical considerations to support the care of patients with ILD during the COVID-19 pandemic and to provide a road map for clinicians caring for these patients during future infectious disease outbreaks., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Rationale: Interstitial lung disease (ILD) develops in a large percentage of patients with connective tissue disease (CTD) and is associated with increased morbidity and mortality. Patients with CTD-associated ILD (CTD-ILD) often present at a young age, suggesting that ILD likely impacts workplace productivity. Objectives: We aimed to determine the employment rate and workplace productivity loss, along with its associated factors and estimated costs, in patients with fibrotic CTD-ILD. Methods: Patients with fibrotic CTD-ILD from the six centers of the Canadian Registry for Pulmonary Fibrosis were eligible. Health-related productivity loss was assessed using the Work Productivity and Activity Impairment questionnaire. Proposed factors associated with low workplace productivity were forced into a multivariable regression model. Average productivity loss in hours/week was used to calculate the costs of productivity loss based on hourly wages obtained from national census data matched for age and sex. Workplace productivity loss outcomes were compared between patients with CTD-ILD and patients with a non-CTD fibrotic ILD. Results: Of 375 eligible patients with fibrotic CTD-ILD, 113 (30%) were employed. Productivity loss was reported by 59% of employed patients, with a mean loss of 9.4 ± 1.2 hours/week, including 3.9 ± 0.9 hours/week from absenteeism and 5.5 ± 0.7 hours/week from presenteeism. Employment among patients 25-54 years of age with fibrotic CTD-ILD was 27% lower than that in the matched general Canadian population (56% vs. 83%; P  < 0.001). Employment among patients ≥55 years of age with CTD-ILD was 17% lower than that in the matched population (19% vs. 36%; P  < 0.001). Workplace productivity loss was not associated with respiratory symptoms or lung physiology. Annual costs of productivity loss were calculated at 13,593 Canadian dollars per employee with fibrotic CTD-ILD. Workplace productivity loss was similar in patients with fibrotic CTD-ILD and those with non-CTD fibrotic ILD. Conclusions: Patients with fibrotic CTD-ILD frequently report workplace productivity loss, which is unexplained by respiratory symptoms or lung physiology and is associated with significant costs.

Purpose of Review: The incidence of age-related diseases such as interstitial lung disease (ILD) is rising, and the importance of multimorbidity and accumulation of health deficits in patients with chronic lung diseases is increasingly recognized. There are multiple relationships between aging and ILD on a demographic and a biological level. Frailty conceptualizes the decline of a patient's physiological reserves and complements the chronological and biological aspects of aging., Recent Findings: Frailty affects more than 50% of patients with ILD, with respiratory impairment, accelerated biological aging, comorbidities, medication adverse effects, and social factors collectively playing important roles. Frailty is an independent risk factor for adverse health outcomes such as hospitalizations and early mortality, including before and after lung transplant. Given the multicomponent determinants of frailty, programs such as pulmonary rehabilitation are promising strategies for managing this complex issue., Summary: Frailty is a common risk factor for adverse outcomes in patients with ILD. The multiple pathways leading to frailty are not completely understood, and further studies are needed to determine the optimal tools for assessment and to develop strategies to prevent and counteract frailty in the aging ILD population.

Study Objective: To validate the Vibe actigraph in assessing sleep-wake patterns compared to polysomnography (PSG) in patients with COPD., Methods: Nine stable COPD patients wore actigraphs while undergoing PSG. The correlation between total sleep time (TST), total sleep period (TSP), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency was determined for corresponding measurements from the actigraph and PSG. Sensitivity, specificity, and positive and negative predictive values were calculated for the actigraph, considering PSG the gold standard. Levels of agreement between the variables of PSG and the actigraph were estimated using Bland-Altman plots., Results: A strong and statistically significant correlation was noted between PSG and the actigraph in detecting movement during sleep [mean activity score (counts)], TST and TSP (all r s = 0.83; p = 0.005). The median agreement of sleep and wake counts between PSG and the actigraph was 73% and the Cohen's Kappa value was 0.66. The medians of sensitivity and specificity of the actigraph for detecting sleep versus PSG were 84 and 66%, respectively. The median positive and negative predictive values of the actigraph were 74 and 72%, respectively., Conclusions: This study demonstrated that, under controlled laboratory conditions, the Vibe actigraph in its default settings is a promising tool for the detection of sleep-wake parameters in a small number of ambulatory patients with COPD. Clinical Impact: The actigraph used in this pilot study suggests that these devices could provide clinically relevant information in COPD to better understand the relationship between sleep and health in this population.

Hypersensitivity pneumonitis (HP) is a complex syndrome caused by the inhalation of a variety of antigens in susceptible and sensitized individuals. These antigens are found in the environment, mostly derived from bird proteins and fungi. The prevalence and incidence of HP vary widely depending on the intensity of exposure, the geographical area and the local climate. Immunopathologically, HP is characterized by an exaggerated humoral and cellular immune response affecting the small airways and lung parenchyma. A complex interplay of genetic, host and environmental factors underlies the development and progression of HP. HP can be classified into acute, chronic non-fibrotic and chronic fibrotic forms. Acute HP results from intermittent, high-level exposure to the inducing antigen, usually within a few hours of exposure, whereas chronic HP mostly originates from long-term, low-level exposure (usually to birds or moulds in the home), is not easy to define in terms of time, and may occur within weeks, months or even years of exposure. Some patients with fibrotic HP may evolve to a progressive phenotype, even with complete exposure avoidance. Diagnosis is based on an accurate exposure history, clinical presentation, characteristic high-resolution CT findings, specific IgG antibodies to the offending antigen, bronchoalveolar lavage and pathological features. Complete antigen avoidance is the mainstay of treatment. The pharmacotherapy of chronic HP consists of immunosuppressive drugs such as corticosteroids, with antifibrotic therapy being a potential therapy for patients with progressive disease.

Introduction: Idiopathic pulmonary fibrosis (IPF) is an age-related disease of unknown cause. The disease is characterized by relentless scarring of the lung parenchyma resulting in respiratory failure and death. Two antifibrotic drugs (pirfenidone and nintedanib) are approved for the treatment of IPF worldwide, but they do not offer a cure and are associated with tolerability issues. Owing to its high unmet medical need, IPF is an area of dynamic research activity., Areas Covered: There is a growing portfolio of novel therapies that target different pathways involved in the complex pathogenesis of IPF. In this review, we discuss the mechanisms of action and available data for compounds in the most advanced stages of clinical development. We searched PubMed for articles on this topic published from 1 January 2000, to 6 June 2020., Expert Opinion: The approval of pirfenidone and nintedanib has fueled IPF drug discovery and development. New drugs are likely to reach the clinic in the near future. However, numerous challenges remain; the lack of animal models that reproduce the complexity of human disease and the poor translation of preclinical and early-phase positive effects to late stage clinical trials must be tackled.

Background: This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax. Methods: Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Results: The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions. Conclusions: The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.

Interstitial lung disease (ILD) is a heterogeneous group of conditions characterized by fibrosis and/or inflammation of the lung parenchyma. The pathogenesis of ILD consistently results in exertional dyspnea and exercise intolerance. Cardiopulmonary exercise testing (CPET) provides important information concerning the pathophysiology of ILD that can help inform patient management. Despite the purported benefits of CPET, its clinical utility in ILD is not well defined; however, there is a growing body of evidence that provides insight into the potential value of CPET in ILD. Characteristic responses to CPET in patients with ILD include exercise-induced arterial hypoxemia, an exaggerated ventilatory response, a rapid and shallow breathing pattern, critically low inspiratory reserve volume, and elevated sensations of dyspnea and leg discomfort. CPET is used in ILD to determine cause(s) of symptoms such as exertional dyspnea, evaluate functional capacity, inform exercise prescription, and determine the effects of pharmacological and non-pharmacological interventions on exercise capacity and exertional symptoms. However, preliminary evidence suggests that CPET in ILD may also provide valuable prognostic information and can be used to ascertain the degree of exercise-induced pulmonary hypertension. Despite these recent advances, additional research is required to confirm the utility of CPET in patients with ILD. This brief review outlines the clinical utility of CPET in patients with ILD. Typical patterns of response are described and practical issues concerning CPET interpretation in ILD are addressed. Additionally, important unanswered questions relating to the clinical utility of CPET in the assessment, prognostication, and management of patients with ILD are identified., (Copyright © 2020 Molgat-Seon, Schaeffer, Ryerson and Guenette.)