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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-O2 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 Interpretation Patients with IPF have higher cumulative incidence of exertional and resting hypoxemia than patients without IPF. The extended ILD-GAP-O2 model provides additional risk stratification for 1-year prognosis in fibrotic ILD.

BackgroundThe impact of pulmonary rehabilitation (PR) on survival in patients with fibrotic interstitial lung disease (ILD) is unknown. Given the challenges conducting a large randomised controlled trial, we aimed to determine whether improvement in 6-minute walk distance (6MWD) was associated with better survival.MethodsThis retrospective, international cohort study included patients with fibrotic ILD participating in either inpatient or outpatient PR at 12 sites in 5 countries. Multivariable models were used to estimate the association between change in 6MWD and time to death or lung transplantation accounting for clustering by centre and other confounders.Results701 participants (445 men and 256 women) with fibrotic ILD were included. The mean±SD ages of the 196 inpatients and 505 outpatients were 70±11 and 69±12 years, respectively. Baseline/changes in 6MWD were 262±128/55±83 m for inpatients and 358±125/34±65 m for outpatients. Improvement in 6MWD during PR was associated with lower hazard rates for death or lung transplant on adjusted analysis for both inpatient (HR per 10 m 0.94, 95% CI 0.91 to 0.97, pConclusionsPatients with fibrotic ILD who improved physical performance during PR had better survival compared with those who did not improve performance. Confirmation of these hypothesis-generating findings in a randomised controlled trial would be required to definitely change clinical practice, and would further support efforts to improve availability of PR for patients with fibrotic ILD.

Interstitial lung diseases (ILDs) are heterogenous and complex chronic lung diseases that even today are challenging to diagnose and classify. The terminology and mechanistic understanding of specific ILDs have evolved substantially over the last centuries and decades, and clinicians, pathologists, radiologists, and researchers are continuously working to untangle the various ILDs of differing causes. Despite many drawbacks and negative clinical trials, the unremitting work of ILD researchers have resulted in great therapeutic successes over the last decade. In this chapter, the authors present historical aspects of ILD and build a foundation to understand current and emerging concepts in ILD.

The purpose of this study was to determine the association between sleep measurements by wrist actigraphy and patient self-report and assess the impact of physical activity and extrapulmonary sympt...

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 CT...

Background: Lung function impairment persists in some patients for months after acute coronavirus disease 2019 (COVID-19). Long-term lung function, radiological features, and their association remain to be clarified. Objectives: We aimed to prospectively investigate lung function and radiological abnormalities over 12 months after severe and non-severe COVID-19. Methods: 584 patients were included in the Swiss COVID-19 lung study. We assessed lung function at 3, 6, and 12 months after acute COVID-19 and compared chest computed tomography (CT) imaging to lung functional abnormalities. Results: At 12 months, diffusion capacity for carbon monoxide (DLCOcorr) was lower after severe COVID-19 compared to non-severe COVID-19 (74.9% vs. 85.2% predicted, p < 0.001). Similarly, minimal oxygen saturation on 6-min walk test and total lung capacity were lower after severe COVID-19 (89.6% vs. 92.2%, p = 0.004, respectively, 88.2% vs. 95.1% predicted, p = 0.011). The difference for forced vital capacity (91.6% vs. 96.3% predicted, p = 0.082) was not statistically significant. Between 3 and 12 months, lung function improved in both groups and differences in DLCO between non-severe and severe COVID-19 patients decreased. In patients with chest CT scans at 12 months, we observed a correlation between radiological abnormalities and reduced lung function. While the overall extent of radiological abnormalities diminished over time, the frequency of mosaic attenuation and curvilinear patterns increased. Conclusions: In this prospective cohort study, patients who had severe COVID-19 had diminished lung function over the first year compared to those after non-severe COVID-19, albeit with a greater extent of recovery in the severe disease group.

RATIONALE Patients with idiopathic pulmonary fibrosis (IPF) frequently suffer from difficult to treat chronic cough, which substantially affects their quality of life. Azithromycin has been demonstrated to relieve chronic cough in some populations, however this has not been investigated in IPF. OBJECTIVES To determine the safety and efficacy of azithromycin for the treatment of chronic cough in patients with IPF. METHODS In a double-blind randomized controlled cross-over trial, patients with IPF underwent two 12-week intervention periods (azithromycin 500mg or placebo 3 times per week). The primary outcome was change in cough-related quality of life measured by the Leicester cough questionnaire (LCQ). Secondary outcomes included cough severity measured using Visual Analog Scale (VAS), health-related quality of life assessed by the St. George's Respiratory Questionnaire (SGRQ), and objective cough frequency using audiovisual readings from 24h respiratory polygraphy. RESULTS 25 patients were randomized (23 men, 2 women), 20 patients completed the study. Mean (standard deviation, SD) age was 67 (8) years, mean (SD) forced vital capacity (FVC) was 65 (16) %-predicted, and diffusion capacity (DLCO) 43 (16) %-predicted. Mean (SD) baseline LCQ was 11.7 (3.7) and 11.3 (3.3) for the azithromycin and the placebo period, respectively, and the corresponding mean (SD) cough VAS 5.6 (2.3) and 5.8 (2.1). There was no significant change in LCQ and VAS with azithromycin or placebo. Similarly, there was no significant difference in change in polygraphy measured cough frequency between the azithromycin and placebo periods. Gastrointestinal adverse effects were more frequent with azithromycin than with placebo (diarrhea 43% vs 5%, p=0.03). CONCLUSIONS This randomized controlled trial does not support the use of low dose azithromycin for chronic cough in patients with IPF. Clinical trial registered with ClinicalTrials.gov (NCT02173145).

Fibrotic interstitial lung diseases (ILDs) are often challenging to diagnose and classify, but an accurate diagnosis has significant implications for both treatment and prognosis. A subset of patients with fibrotic ILD experience progressive deterioration in lung function, physical performance, and quality of life. Several risk factors for ILD progression have been reported, such as male sex, older age, lower baseline pulmonary function, and a radiological or pathological pattern of usual interstitial pneumonia. Morphological similarities, common underlying pathobiologic mechanisms, and the consistently progressive worsening of these patients support the concept of a progressive fibrosing (PF)-ILD phenotype that can be applied to a variety of ILD subtypes. The conventional approach has been to use antifibrotic medications in patients with idiopathic pulmonary fibrosis (IPF) and immunosuppressive medications in patients with other fibrotic ILD subtypes; however, recent clinical trials have suggested a favourable treatment response to antifibrotic therapy in a wider variety of fibrotic ILDs. This review summarizes the literature on the evaluation and management of patients with PF-ILD, and discusses questions relevant to applying recent clinicial trial findings to real-world practice.

PURPOSE The impact of psychological deficits and pain on physical activity has not been adequately studied in patients with fibrotic interstitial lung disease (ILD). We aimed to determine the association of depression, anxiety, sleep quality, and pain with physical activity in fibrotic ILD. METHODS Waist ActiGraph activity monitors were worn for seven consecutive days to track step counts and moderate-to-vigorous physical activity (MVPA) minutes at baseline and 6-month follow-up. Psychological deficits and pain were assessed using the Hospital Anxiety and Depression Scale, the Pittsburgh Sleep Quality Index, and the Brief Pain Inventory. Multivariable linear regression was used to determine if each deficit independently predicted physical activity when adjusted for potential confounders. RESULTS A total of 111 patients were recruited, with 91 of these patients completing the 6-month follow-up. Median step count and MVPA minutes were 3853 steps/day (interquartile range 2236-6805) and 87 (17-225) min/week at baseline, respectively, with no significant changes at follow-up. Borderline or abnormal depression and anxiety scores were present in 19% and 22% of patients, respectively. Poor sleep quality and moderate-to-severe pain were present in 61% and 9% of patients. Higher depression scores were associated with fewer baseline and follow-up step counts and lower MVPA minutes at follow-up on unadjusted analysis; higher pain severity scores were associated with fewer baseline step count. Pain severity remained an independent predictor of reduced step count after adjusting for patient's age, smoking status, ILD severity, and weather variables. CONCLUSIONS Pain severity may be a potentially modifiable determinant of physical activity in patients with fibrotic ILD.

Interstitial lung diseases (ILDs) are heterogenous and complex chronic lung diseases that even today are challenging to diagnose and classify. The terminology and mechanistic understanding of specific ILDs have evolved substantially over the last centuries and decades, and clinicians, pathologists, radiologists, and researchers are continuously working to untangle the various ILDs of differing causes. Despite many drawbacks and negative clinical trials, the unremitting work of ILD researchers have resulted in great therapeutic successes over the last decade. In this chapter, the authors present historical aspects of ILD and build a foundation to understand current and emerging concepts in ILD.

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.

Background The differential diagnosis fibrotic hypersensitivity pneumonitis (HP) versus idiopathic pulmonary fibrosis (IPF) is important but challenging. Recent diagnostic guidelines for HP emphasize including multidisciplinary discussion (MDD) in the diagnostic process, however MDD is not comprehensively available. We aimed to establish the diagnostic accuracy and prognostic validity of a previously proposed HP diagnostic algorithm that foregoes MDD. Methods We tested the algorithm in patients with an MDD diagnosis of fibrotic HP or IPF (case control study) and determined diagnostic test performances for diagnostic confidences of ≥ 90% and ≥ 70%. Prognostic validity was established using Cox proportional hazards models. Results Thirty-one patients with fibrotic HP and 50 IPF patients were included. The algorithm-derived ≥ 90% confidence level for HP had high specificity (0.94, 95% confidence interval [CI] 0.83–0.99), but low sensitivity (0.35 [95%CI 0.19–0.55], J-index 0.29). Test performance was improved for the ≥ 70% confidence level (J-index 0.64) with a specificity of 0.90 (95%CI 0.78–0.97), and a sensitivity of 0.74 (95%CI 0.55–0.88). MDD fibrotic HP diagnosis was strongly associated with lower risk of death (adjusted hazard ratio [HR] 0.10 [0.01–0.92], p = 0.04), whereas the algorithm-derived ≥ 70% and ≥ 90% confidence diagnoses were not significantly associated with survival (adjusted HR 0.37 [0.07–1.80], p = 0.22, and adjusted HR 0.41 [0.05–3.25], p = 0.39, respectively). Conclusion The algorithm-derived ≥ 70% diagnostic confidence had satisfactory test performance for MDD-HP diagnosis, with insufficient sensitivity for ≥ 90% confidence. The lowest risk of death in the MDD-derived HP diagnosis validates the reference standard and suggests that a diagnostic algorithm not including MDD, might not replace the latter.

Background The infectious coronavirus disease 2019 (COVID-19) pandemic is an ongoing global healthcare challenge. Up to one-third of hospitalised patients develop severe pulmonary complications and acute respiratory distress syndrome. Pulmonary outcomes following COVID-19 are unknown. Methods The Swiss COVID-19 lung study is a multicentre prospective cohort investigating pulmonary sequelae of COVID-19. We report on initial follow-up 4 months after mild/moderate or severe/critical COVID-19 according to the World Health Organization severity classification. Results 113 COVID-19 survivors were included (mild/moderate n=47, severe/critical n=66). We confirmed several comorbidities as risk factors for severe/critical disease. Severe/critical disease was associated with impaired pulmonary function, i.e. diffusing capacity of the lung for carbon monoxide (DLCO) % predicted, reduced 6-min walk distance (6MWD) and exercise-induced oxygen desaturation. After adjustment for potential confounding by age, sex and body mass index (BMI), patients after severe/critical COVID-19 had a DLCO 20.9% pred (95% CI 12.4–29.4% pred, p=0.01) lower at follow-up. DLCO % pred was the strongest independent factor associated with previous severe/critical disease when age, sex, BMI, 6MWD and minimal peripheral oxygen saturation at exercise were included in the multivariable model (adjusted odds ratio per 10% predicted 0.59, 95% CI 0. 37–0.87; p=0.01). Mosaic hypoattenuation on chest computed tomography at follow-up was significantly associated with previous severe/critical COVID-19 including adjustment for age and sex (adjusted OR 11.7, 95% CI 1.7–239; p=0.03). Conclusions 4 months after severe acute respiratory syndrome coronavirus 2 infection, severe/critical COVID-19 was associated with significant functional and radiological abnormalities, potentially due to small-airway and lung parenchymal disease. A systematic follow-up for survivors needs to be evaluated to optimise care for patients recovering from COVID-19., COVID-19 pulmonary sequelae are unknown. The Swiss COVID-19 lung study reports on initial follow-up findings. Severe or critical COVID-19 was associated with significant functional impairment and radiological abnormalities after 4 months. https://bit.ly/34sNVvi

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 (SpO2), 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 0.05). The annual negative PMA slope was associated with annual negative slopes in FVC, FEV1, and DLCO (all p 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.

Diverses pneumopathies interstitielles peuvent avoir une evolution fibrosante progressive. Elles se manifestent par des symptomes croissants, une perte de fonction pulmonaire et la progression des alterations radiologiques.

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.

Fibrotic interstitial lung diseases (ILDs) frequently have nonspecific and overlapping clinical and radiological features, resulting in ∼10–20% of patients with ILD lacking a clear diagnosis and thus being labelled with unclassifiable ILD. The objective of this review is to describe how patients with unclassifiable ILD should be evaluated, and what impact specific clinical, radiological and histopathological features may have on management decisions, focusing on patients with a predominantly fibrotic phenotype. We highlight recent data that have suggested an increasing role for antifibrotic medications in a variety of fibrotic ILDs, but justify the ongoing importance of making an accurate ILD diagnosis given the benefit of immunomodulatory therapies in many patient populations. We provide a practical approach to support management decisions that can be used by clinicians and tested by clinical researchers, and further identify the need for additional research to support a rational and standardised approach to the management of patients with unclassifiable ILD., This review describes how patients with unclassifiable ILD should be evaluated and what impact specific clinical, radiological and histopathological features may have on management decisions, focusing on patients with a predominantly fibrotic phenotype https://bit.ly/3o43nqr

BackgroundNon-invasive biomarkers for the assessment of disease severity in idiopathic pulmonary fibrosis (IPF) are urgently needed. Calprotectin belongs to the S-100 proteins produced by neutrophils, which likely contribute to IPF pathogenesis. Calprotectin is a well-established biomarker in inflammatory bowel diseases. In this cross-sectional study, we aimed to establish the potential role of calprotectin as a biomarker in IPF. Specifically, we hypothesised that patients with IPF have higher serum calprotectin levels compared with healthy controls, and that calprotectin levels are associated with disease severity.MethodsBlood samples were obtained from healthy volunteers (n=26) and from two independent IPF cohorts (derivation cohort n=26, validation cohort n=66). Serum calprotectin levels were measured with a commercial kit adapted for that purpose and compared between healthy controls and patients with IPF. Clinical parameters, including forced vital capacity, diffusing capacity for carbon monoxide (DLCO) and the Composite Physiologic Index (CPI), were correlated with calprotectin serum levels.ResultsThe IPF derivation cohort showed increased serum calprotectin levels compared with healthy controls (2.47±1.67 vs 0.97±0.53 µg/mL, pConclusionSerum calprotectin levels are significantly increased in patients with IPF compared with healthy controls and correlate with DLCO and CPI. Calprotectin might be a potential new biomarker for disease severity in IPF.

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.What are the epidemiologic features of hypoxemia and its additive prognostic value in a current risk prediction model of fibrotic ILD?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-OThe 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-OPatients with IPF have higher cumulative incidence of exertional and resting hypoxemia than patients without IPF. The extended ILD-GAP-O

Background: Fibrotic hypersensitivity pneumonitis (fHP) diagnosis is challenging with idiopathic pulmonary fibrosis (IPF) as important differential diagnosis. Recently proposed diagnostic criteria are not validated.[Morisset J, et al. AJRCCM. 2018;197(8):1036-44] Objectives: We aimed to determine the diagnostic test performance of the proposed algorithm with our multidisciplinary team (MDT) diagnosis as reference standard. Methods: Diagnostic criteria were retrospectively tested in fHP or IPF patients. Cases were allocated a confident fHP diagnosis, a ≥70% or >50% diagnostic confidence for fHP. Radiological evaluation was blinded to the MDT diagnosis. Test characteristics and risk of death (Cox proportional hazard) were estimated. Results: We included 31 fHP and 50 IPF patients (78% men). Sensitivity and specificity were 35% (95%CI 19-55%) and 94% (83-99%) for confident fHP, and 74% [55-88%] and 90% [78-97%]) for ≥ 70% confidence level, respectively. Median observation time was 16 (IQR 6-30) months. A confident algorithm fHP diagnosis showed a non-significant association with risk of death (HR 0.16 [95%CI 0.02-1.20], p=0.07), whereas patients diagnosed with ≥70% confidence had a lower and patients with a MDT-diagnosed fHP the lowest risk of death (HR 0.14 [0.03-0.59], p=0.007 and HR 0.06 [0.01-0.45], p=0.006, respectively). Conclusion: In our cohort the algorithm derived diagnostic confidence of ≥70% had satisfactory test performance for MDT-fHP diagnosis, with insufficient sensitivity for confident fHP. The lowest risk of death for the MDT-fHP diagnosis validates the reference standard and suggests that a diagnostic algorithm might not replace MDT for challenging cases.

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.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.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.

The optimal method of physical activity measurement has not been determined in patients with fibrotic interstitial lung disease (ILD).To assess the validity, internal consistency, and responsiveness of the International Physical Activity Questionnaire long form (IPAQ-LF) and to estimate the minimal important difference (MID) for moderate to vigorous physical activity (MVPA) in patients with fibrotic ILD.This two-center prospective cohort study included a convenience sample of 111 outpatients with fibrotic ILD who wore waist and wrist ActiGraph accelerometers for 7 consecutive days, followed by self-administration of the IPAQ-LF. Both measurements were performed at baseline and 6-month follow-up. Spearman rank correlations were used to evaluate the IPAQ-LF validity in comparison to activity monitor data, lung function, step count, and quality of life. The internal consistency of the IPAQ-LF was determined using Cronbach's α. Self-reported changes in IPAQ-LF parameters were compared among tertiles of change measured by the waist activity monitor to assess the responsiveness of the IPAQ-LF after 6 months. Anchor- and distribution-based methods were used to estimate the MID for MVPA.Self-reported MVPA minutes, activity-related energy expenditure, sedentary time, and inactive time of the IPAQ-LF generally showed moderate to strong correlations with corresponding waist activity monitor data, step count, lung function, and quality of life. The Cronbach's α of the IPAQ-LF was 0.78. The IPAQ-LF was responsive at detecting increases in weekly MVPA and energy expenditure. The MIDs for MVPA were 8 to 26 and 13 to 58 min/wk using the anchor-based method for waist activity monitor and IPAQ-LF data, respectively. The distribution-based MID estimate for MVPA was 104 to 242 min/wk.The IPAQ-LF has acceptable validity and internal consistency for measuring daily physical activity in patients with fibrotic ILD. The IPAQ-LF was responsive at detecting increases in physical activity but limited in its ability to detect declines or changes in inactivity. Using an anchor-based approach, the MID for MVPA measured by a waist activity monitor is approximately 26 min/wk.

Previous studies have suggested that interstitial lung disease (ILD) progresses most rapidly early in the course of systemic sclerosis-associated (SSc)-ILD, and that SSc-ILD is often more stable or even "burned out" after the first 4 years following diagnosis.Our objectives were to determine whether an apparent plateau in pulmonary function decline is due to survival bias and to identify distinct prognostic phenotypes of ILD progression.Consecutive patients with SSc-ILD from a single center were included. Pulmonary function measurements were typically performed every 6 months. Study participants were categorized into long-term survivors (8 yr survival from diagnosis), and those with medium-term and short-term mortality (4-8 and4 yr survival, respectively). We excluded those censored with less than 8 years of follow-up. Subject-specific slopes for change in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DlThe cohort included 171 study participants with SSc-ILD. A plateau in the progression of FVC was apparent in the full cohort analysis but disappeared with stratification into prognostic subgroups to account for survival bias. Those with short-term mortality had a higher annual rate of decline in FVC (-4.10 [95% confidence interval (CI), -7.92 to -0.28] vs. -2.14 [95% CI, -3.31 to -0.97] and -0.94 [-1.46 to -0.42]; P = 0.003) and DlAdults with SSc-ILD have distinct patterns of physiological progression that remain relatively consistent during long-term follow-up; however, recent change in FVC cannot be used to predict future change in FVC within shorter follow-up intervals. The findings of this study provide important information on the course of disease in SSc-ILD and identify specific phenotypes of progression that may improve clinical decision-making and design of future therapeutic trials.

Accurate diagnosis of interstitial lung disease is necessary to identify the most appropriate management strategy and to inform prognosis. Many patients cannot be provided a confident diagnosis, despite an exhaustive search for potential etiologies and review in a multidisciplinary conference, and are consequently labeled with unclassifiable interstitial lung disease.To systematically review and meta-analyze previous studies reporting on the diagnostic criteria, prevalence, clinical features, and outcome of unclassifiable interstitial lung disease.MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials databases were systematically searched for all studies related to unclassifiable interstitial lung disease published before September 1, 2017. Two authors independently screened each citation for eligibility criteria, serially reviewing the title, abstract, and full-text manuscript, and then abstracted data pertaining to the study objectives from eligible studies. Articles were stratified by risk of selection bias, whether the publication stated that patients were reviewed in a multidisciplinary discussion, and by the frequency of surgical lung biopsy. Meta-analyses and meta-regression were performed to calculate the pooled prevalence of unclassifiable interstitial lung disease within an interstitial lung disease population and within specific subgroups to identify reasons for across-study heterogeneity.The search identified 10,130 unique citations, 313 articles underwent full-text review, and eligibility criteria were met in 88 articles. Twenty-two studies were deemed low risk of selection bias, including 1,060 patients with unclassifiable interstitial lung disease from a total of 10,174 patients with interstitial lung disease. The terminology and definition of unclassifiable interstitial lung disease varied substantially across publications, with inconsistent diagnostic criteria and evaluation processes. The prevalence of unclassifiable interstitial lung disease was 11.9% (95% confidence interval, 8.5-15.6%), with lower prevalence in centers that reported use of a formal multidisciplinary discussion of cases (9.5% vs. 14.5%). Four articles reported survival of unclassifiable interstitial lung disease, with 1-year, 2-year, and 5-year survival of 84% to 89%, 70% to 76%, and 46% to 70%, respectively.This systematic review and meta-analysis shows that unclassifiable interstitial lung disease is common but has substantial heterogeneity and inconsistent definitions across interstitial lung disease cohorts. These findings highlight important limitations in multicenter studies of fibrotic interstitial lung disease and the need for a standardized approach to interstitial lung disease diagnostic classification.

Current oxygen delivery modes lack monitoring and can be cumbersome for patients with chronic respiratory diseases. Integrating a pulse oximeter and nasal oxygen cannulas into eyeglasses would reduce the burden of current solutions. An ear pulse oximeter (OxyFrame) was evaluated on 16 healthy volunteers and 20 hypoxemic patients with chronic respiratory diseases undergoing a prespecified protocol simulating daily activities. Correlation, error, and accuracy root mean square error (ARMS) were calculated to compare SpO2 measured by OxyFrame, a standard pulse oximeter (MASIMO), and arterial blood gas analysis (aBGA). SpO2 measured by OxyFrame and MASIMO correlated strongly in volunteers, with low error and high accuracy (r = 0.85, error = 0.2 ± 2.9%, ARMS = 2.88%). Performances were similar in patients (r = 0.87, error 0 ± 2.5%, ARMS = 2.49% compared with MASIMO; and r = 0.93, error = 0.4 ± 1.9%, ARMS = 1.94% compared with aBGA). However, the percentage of rejected measurements was high (volunteers 77.2%, patients 46.9%). The OxyFrame cavum conchae pulse oximeter was successfully evaluated, and demonstrated accurate SpO2 measurements, compliant with ISO 80601-2-61:2017. Several reasons for the high rejection rate were identified, and potential solutions were proposed, which might be valuable for optimization of the sensor hardware.

The ATS/ERS/JRS/ALAT recently released a new clinical practice guideline (ATS/ERS/JRS/ALAT2018) for idiopathic pulmonary fibrosis (IPF) with simultaneously proposed diagnostic criteria by the Fleischner Society. [1, 2] Both diagnostic algorithms agree on most diagnostic steps, with divergent recommendations on the position of surgical lung biopsy (SLB): ATS/ERS/JRS/ALAT2018 recommends SLB in most patients with probable usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) (conditional recommendation), whereas the Fleischner society proposes to forgo SLB in patients with definite or probable UIP HRCT pattern, presenting in the right clinical context. [3, 4] We aimed to quantify the impact of the previous (ATS/ERS/JRS/ALAT2011) [5] and the two new diagnostic approaches [1, 2] on real-life clinical practice, with assessment of radiological inter-rater agreement, diagnostic test characteristics, and prognostic validity of the diverging radiological diagnoses for a multidisciplinary IPF diagnosis in our cohort. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Funke-Chambour reports grants from Roche, grants from Boehringer Ingelheim, grants from Intermune, during the conduct of the study. Conflict of interest: Dr. Guler has nothing to disclose. Conflict of interest: Dr. Geiser has nothing to disclose. Conflict of interest: Dr. Christe has nothing to disclose. Conflict of interest: Dr. Heverhagen has nothing to disclose. Conflict of interest: Alexander Pollinger Conflict of interest: Dr. Huber has nothing to disclose. Conflict of interest: Dr. Ebner has nothing to disclose. Conflict of interest: Dr. Poellinger has nothing to disclose.

Background: Dehydroepiandrosterone sulfate (DHEAS) has antifibrotic properties in vitro and DHEAS plasma levels in patients with idiopathic pulmonary fibrosis (IPF) are low. Objective: To determine the association of DHEAS plasma levels with pulmonary function in patients with fibrotic interstitial lung disease (ILD). Methods: Blood samples were acquired from two distinct ILD cohorts. DHEAS plasma levels were measured by ELISA and tested for their associations with forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO). The primary analysis was performed in a Canadian fibrotic ILD cohort and then validated in a male Swiss IPF cohort. Results: In the derivation cohort mean (SD) age was 68 (10) years, FVC% 76 (18), and DLCO% 50 (16). Median (IQR) DHEAS plasma levels were 0.39 (0.23-0.63) mcg/ml in 76 men and 0.41 (0.23-0.60) mcg/ml in 53 women. The validation cohort (32 men) had a mean (SD) age of 68 (9) years, FVC% 62 (15), DLCO% 44 (12), and median (IQR) DHEAS of 0.33 (0.20-0.61) mcg/ml. In the derivation cohort, DHEAS correlated with FVC% in men (r=0.43, p Conclusion: We identified an age-independent association of DHEAS with FVC and DLCO in a diverse cohort of patients with fibrotic ILD with confirmation in a well-characterized cohort of men with IPF.