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RATIONALE: Interstitial lung diseases (ILD) are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the lung. There have been few prior descriptions of the clinical ...

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...

Longitudinal monitoring of patients with fibrotic interstitial lung disease (ILD) is essential to identifying disease progression and guiding management decisions. There are no evidence-based clini...

Mortality risk assessment in interstitial lung disease (ILD) is challenging. Our objective was to determine the prognostic significance of BMI and change in weight in the most common fibrotic ILD subtypes.Could BMI and weight loss over time be reliable prognostic indicators in patients with fibrotic ILD?This observational retrospective multicenter cohort study enrolled patients with fibrotic ILD from the six-center CAnadian REgistry for Pulmonary Fibrosis (CARE-PF, derivation) and the ILD registry at the University of California, San Francisco (UCSF, validation). Patients were subcategorized as underweight (BMI 18.5), normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), or obese (BMI30). Annual change in weight was calculated for all years of follow-up as the slope of best fit using the least square method based on every available measurement. Separate multivariable analyses evaluated the associations of BMI and change in weight with mortality, adjusting for common prognostic variables.The derivation and validation cohorts included 1,786 and 1,779 patients, respectively. Compared with patients with normal BMI, mortality was highest in patients who were underweight (hazard ratio [HR], 3.19; 95% CI, 1.88-5.43; P .001) and was lowest in those who were overweight (HR, 0.52; 95% CI, 0.36-0.75; P .001) or obese (HR, 0.55; 95%CI, 0.37-0.83; P .001) in the analysis adjusted for the ILD-GAP (gender, age, physiology) Index. Patients who had a weight loss of at least 2 kg within 1 year had increased risk of death in the subsequent year (HR, 1.41; 95% CI, 1.01-1.97; P = .04) after adjustment for the ILD-GAP Index and baseline BMI category, with a plateau in risk for patients with greater weight loss. Consistent results were observed in the validation cohort.Both BMI and weight loss are independently associated with 1-year mortality in fibrotic ILD. BMI and weight loss may be clinically useful prognostic indicators in fibrotic ILD.

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 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.

Introduction A proportion of patients with idiopathic pulmonary fibrosis (IPF) have autoantibodies directed against intracellular targets. This study aimed to determine the relationship between serologic status, lung function decline and survival. Methods IPF patients assessed for antinuclear antibody (ANA) and related antigen-specific serology detected by addressable laser bead immunoassay (ALBIA) were included. Demographics, serial pulmonary function tests and survival were compared between patients with and without autoantibodies. Linear mixed models were used to estimate changes in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) over time. Cox-proportional hazards models were used to compare survival, adjusted for a composite score including age, sex and baseline lung function. Results Of 61 included patients, the mean baseline age was 70 years (SD = 9), 77% were male, and 87% were Caucasian. Either ANA or antigen-specific serology by ALBIA was positive in 25 (41%) during follow-up. ANA was detected in 23 (38%), and specific autoantibodies by ALBIA in 6 (10%). There was no difference in age, sex, race, smoking status, anti-fibrotic use or baseline FVC or DLCO in patients with and without autoantibodies. There was no association between autoantibody status and survival (HR = 1.18, 95% CI 0.61, 2.29), rate of decline in FVC or DLCO (difference in FVC = 4.2 mL/year, p = 0.82; difference in DLCO = 4.6*10−4 mL/min/mmHg/year, p = 0.20). Conclusion These data suggest that autoantibodies are common in IPF and that patients with a subset of autoantibodies, but without features of autoimmunity, demonstrate similar disease behaviour to those without autoantibodies.

RATIONALE: INSPIRATION PLUS (NCT02552849) was a prospective, observational registry of Canadian patients with idiopathic pulmonary fibrosis (IPF) treated with the oral antifibrotic agent pirfenidon...

Rationale: Early access to subspecialty care is associated with improved outcomes for patients with fibrotic interstitial lung disease (ILD). Access to ILD care may be limited for patients living f...

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 ...

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.

RationaleThe 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).MethodsPatients 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.Results1816 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.ConclusionWe 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.

The evaluation of a patient with fibrotic interstitial lung disease (ILD) includes assessment of clinical, radiological, and often histopathological data. There are currently no specific recommenda...

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis. Physician practice patterns on the diagnosis and management of IPF in Canada have not been described.OBJECTIVE: To describe the practice patterns of Canadian respirologists on the diagnosis and management of IPF and to determine if these patterns reflect current guidelines.METHODS: We conducted surveys of Canadian physicians and fellows-in-training in 2009 and 2013. Questions addressed the diagnosis of IPF, screening for comorbidities, treatment of IPF, and acute exacerbations of IPF.MEASUREMENTS AND MAIN RESULTS: Response rates in the 2009 and 2013 surveys were 22% and 17%, respectively. Most respondents felt that high resolution CT scan can diagnose IPF in most cases, with lung biopsy rarely performed. The majority screened for hypoxemia, pulmonary hypertension, gastroesophageal reflux, and autoimmune disease. In 2013, more respondents used no pharmacologic therapy to treat IPF (2009, 36% vs. 2013...

The treatment of chronic hypersensitivity pneumonitis (cHP) often includes systemic oral corticosteroids, but the optimal pharmacologic management remains unclear. The morbidity associated with prednisone has motivated the search for alternative therapies. We aimed to determine the effect of treatment with mycophenolate mofetil (MMF) or azathioprine (AZA) on lung function in patients with cHP.Patients with cHP treated with either MMF or AZA were retrospectively identified from four interstitial lung disease centers. Change in lung function before and after treatment initiation was analyzed using linear mixed-effects modeling (LMM), adjusting for age, sex, smoking history, and prednisone use.Seventy patients were included: 51 were treated with MMF and 19 with AZA. Median follow-up after treatment initiation was 11 months. Prior to treatment initiation, FVC and diffusion capacity of the lung for carbon monoxide (Dlco) % predicted were declining at a mean rate of 0.12% (P .001) and 0.10% (P .001) per month, respectively. Treatment with either MMF or AZA was not associated with improved FVC (0.5% at 1 year; P = .46) but was associated with a statistically significant improvement in Dlco of 4.2% (P .001) after 1 year of treatment. Results were similar in the subgroup of patients treated with MMF for 1 year; the FVC increased nonsignificantly by 1.3% (P = .103) and Dlco increased by 3.9% (P .001).Treatment with MMF or AZA is associated with improvements in Dlco in patients with cHP. Prospective randomized trials are needed to validate their effectiveness for cHP.

Background The CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) is a multi-center, prospective registry designed to study the natural history of fibrotic interstitial lung disease (ILD) in adults. The aim of this cross-sectional sub-study was to describe the baseline characteristics, risk factors, and comorbidities of patients enrolled in CARE-PF to date. Methods Patients completed study questionnaires and clinical measurements at enrollment and each follow-up visit. Environmental exposures were assessed by patient self-report and comorbidities by the Charlson Comorbidity Index (CCI). Baseline characteristics, exposures, and comorbidities were described for the overall study population and for incident cases, and were compared across ILD subtypes. Results The full cohort included 1285 patients with ILD (961 incident cases (74.8%)). Diagnoses included connective tissue disease-associated ILD (33.3%), idiopathic pulmonary fibrosis (IPF) (24.7%), unclassifiable ILD (22.3%), chronic hypersensitivity pneumonitis (HP) (7.5%), sarcoidosis (3.2%), non-IPF idiopathic interstitial pneumonias (3.0%, including idiopathic nonspecific interstitial pneumonia (NSIP) in 0.9%), and other ILDs (6.0%). Patient-reported exposures were most frequent amongst chronic HP, but common across all ILD subtypes. The CCI was ≤2 in 81% of patients, with a narrow distribution and range of values. Conclusions CTD-ILD, IPF, and unclassifiable ILD made up 80% of ILD diagnoses at ILD referral centers in Canada, while idiopathic NSIP was rare when adhering to recommended diagnostic criteria. CCI had a very narrow distribution across our cohort suggesting it may be a poor discriminator in assessing the impact of comorbidities on patients with ILD.

Fibrotic interstitial lung diseases (ILDs) are highly morbid chronic disorders that frequently occur in working age individuals. The goal of this study was to determine workplace productivity loss, its determinants, and its estimated costs in patients with fibrotic ILD.Patients with idiopathic pulmonary fibrosis, chronic hypersensitivity pneumonitis, idiopathic nonspecific interstitial pneumonia, or unclassifiable ILD were identified from the six-center Canadian Registry for Pulmonary Fibrosis (CARE-PF). The Work Productivity and Activity Impairment questionnaire was used to determine health-related productivity loss. Independent predictors of low workplace productivity were identified by using multivariate regression. Patient data were compared with Canadian population census data. The average productivity loss (hours per week) and the individual's hourly wage were used to estimate the costs of productivity loss.Of 650 eligible patients, 148 (23%) were employed. Productivity loss was reported by 55% of employed patients with an average productivity loss of 7.8 ± 0.9 h per week (2.3 ± 0.6 h per week related to absenteeism and 5.5 ± 0.6 h per week related to presenteeism). Employment among patients with ILD aged 25 to 54 years was 23% lower than the age- and sex-matched general Canadian population (60% vs 83%; P .001). Employment among patients with ILD aged ≥ 55 years was 18% lower than in the age- and sex-matched population (20% vs 38%; P .001). Dyspnea and cough were independent predictors of workplace productivity loss. Estimated annual costs of productivity loss were 11,610 Canadian dollars per employee with ILD.Workplace productivity loss is common in fibrotic ILD, strongly correlated with symptom severity, and associated with significant cost.

Multidisciplinary team (MDT) diagnosis of interstitial lung disease (ILD) has been proposed as a gold standard, but there are no formal recommendations for MDT process or composition and limited knowledge regarding prevalence in routine practice. We performed a systematic evaluation of ILD diagnostic practice across a range of healthcare settings around the world. Electronic questionnaires were distributed across all global regions via society and collaborators networks. Responses from 457 unique centres across 64 countries were included in the analysis. Of the 350 (76.6%) centres holding formal meetings, the majority held face-to-face MDT meetings (80%), for a minimum of 30 min (93%), and discussed diagnosis (96.9%) and patient management (94.9%) at the meetings. Compared with non-academic and academic non-ILD centres, ILD academic centres reported a higher ILD caseload, held more formal MDT meetings, and were more likely to include histopathology and rheumatology specialists in their diagnostic team. Of the centres holding MDT meetings, 5.5% routinely discussed all new cases at such meetings. An MDT approach to ILD diagnosis is consistently interpreted and widely implemented across a range of routine care settings around the world. This observation will inform future ILD diagnostic agreement studies and diagnostic pathway recommendations., In real-world practice, ILD diagnosis uses a multidisciplinary team approach, irrespective of country or healthcare setting http://ow.ly/I1Di30nMNTX

Pulmonary rehabilitation improves dyspnea and exercise capacity in idiopathic pulmonary fibrosis (IPF); however, it is unknown whether breathing high amounts of oxygen during exercise training leads to further benefits.Herein, we describe the design of the High Oxygen Delivery to Preserve Exercise Capacity in IPF Patients Treated with Nintedanib study (the HOPE-IPF study). The primary objective of this study is to determine the physiological and perceptual impact of breathing high levels of oxygen during exercise training in patients with IPF who are receiving antifibrotic therapy.HOPE-IPF is a two-arm double-blind multicenter randomized placebo-controlled trial of 88 patients with IPF treated with nintedanib. Patients will undergo 8 weeks of three times weekly aerobic cycle exercise training, breathing a hyperoxic gas mixture with a constant fraction of 60% inhaled oxygen, or breathing up to 40% oxygen as required to maintain an oxygen saturation level of at least 88%.End points will be assessed at baseline, postintervention (Week 8), and follow-up (Week 26). The primary analysis will compare the between-group baseline with post-training change in endurance time during constant work rate cycle exercise tests. Additional analyses will evaluate the impact of training with high oxygen delivery on 6-minute walk distance, dyspnea, physical activity, and quality of life.The HOPE-IPF study will lead to a comprehensive understanding of IPF exercise physiology, with the potential to change clinical practice by indicating the need for increased delivery of supplemental oxygen during pulmonary rehabilitation in patients with IPF. Clinical trial registered with www.clinicaltrials.gov (NCT02551068).

Idiopathic pulmonary fibrosis (IPF) is a rare disease, with estimates of prevalence varying considerably across countries due to paucity in data collection. The aim of this study was to investigate the prevalence and incidence of IPF in Canada using administrative data requiring minimal extrapolation.We used mandatory national administrative data from 2007–2011 to identify IPF cases of all ages with an International Classification of Diseases (Version 10, Canadian) diagnosis code of J84.1. We used a broad definition that excluded cases with subsequent diagnosis of other interstitial lung diseases, and a narrow definition that required further diagnostic testing prior to IPF diagnosis. We explored survival and quality of life.For all ages, the broad prevalence of IPF was 41.8 per 100 000 (14 259 cases) and was higher for men. The incidence rate was 18.7 per 100 000 (6390 cases) and was higher for men. The narrow prevalence was 20.0 per 100 000 (6822 cases) and incidence was 9.0 per 100 000 (3057 cases). The 4-year risk of death was 41.0% and the quality of life with IPF after 2 years was lower than for Global Initiative for Chronic Obstructive Lung Disease stage IV chronic obstructive pulmonary disease.Using comprehensive national data, the prevalence of IPF in Canada was higher than other national estimates, suggesting that either IPF may be more common in Canada or that data capture may have been previously limited.

Jean-Eric Tarride,1,2 Robert B Hopkins,1,2 Natasha Burke,1,2 Jason R Guertin,3,4 Daria O’Reilly,1,2 Charlene D Fell,5 Genevieve Dion,6 Martin Kolb7 1Department of Health Research Methods, Evidence and Impact, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada; 2Programs for Assessment of Technology in Health (PATH), The Research Institute of St. Joe’s Hamilton, St. Joseph’s Healthcare Hamilton, Hamilton, ON, Canada; 3Department of Social and Preventive Medicine, Laval University, Quebec City, QC, Canada; 4Centre de recherche du CHU de Québec – Université Laval, Axe Santé des Populations et Pratiques Optimales en Santé, Hôpital du St-Sacrement, Quebec City, QC, Canada; 5Division of Respirology, Department of Medicine, University of Calgary, Calgary, AB, Canada; 6Quebec Heart and Lung Institute, Laval University, Quebec City, QC, Canada; 7Division of Respirology, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada Background: Idiopathic pulmonary fibrosis (IPF), although rare, is a severe and costly disease.Objective: To estimate the clinical and economic burden of IPF over multiple years before and after diagnosis using comprehensive administrative databases for the province of Quebec, Canada.Methods: Several administrative databases from Quebec, providing information on hospital care, community care, and pharmaceuticals, were linked over a 5-year period ending March 31, 2011, which was before approval of antifibrotic drugs in Canada. Prevalent and incident IPF cases were defined using International Classification Disease-10-CA codes and International Classification Disease-9-CM codes. We used a broad definition that excluded cases with subsequent diagnosis of other interstitial lung diseases and a narrow definition that required further diagnostic testing to confirm IPF diagnosis. Incident cases had an IPF code in a particular year without any IPF code in the 2 previous years. Health care resource utilization before and after the index diagnosis date was determined and costs calculated. Costs were expressed in 2016 Canadian dollars.Results: Over 5-years, 10,579 (mean age: 76.4; 58% male) satisfied the broad definition of IPF and 8,683 (mean age: 74.5; 57% male) satisfied the narrow definition (82% of broad). Incidences of IPF overall were 25.8 and 21.7/100,000 population for broad and narrow definitions, respectively. Three-year survival was 40% and 37% in broad and narrow cohorts, respectively. For both cohorts, health care resource utilization and costs increased several years before diagnosis ($2,721 and $7,049/patient 5 years and 2 years prior to diagnosis using a broad definition, respectively) and remained elevated for multiple years post diagnosis ($12,978 and $8,267 at 2 and 3 years postdiagnosis).Conclusion: Health care resource utilization and costs of IPF increase many years prior to diagnosis. Incorporating multiyear annual costs before and after diagnosis results in a higher estimate of the economic burden of IPF than previous studies using a 1-year time frame. Keywords: cost of illness, health care utilization, incidence, idiopathic pulmonary fibrosis, Canada

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and ultimately fatal disease of the lung with an unknown etiology and few treatment options. Recognition of patients who fall into phenotypic subsets may provide earlier opportunities for initiation of therapy or referral to transplant. In addition, identification and management of comorbidities may improve quality of life, and this may be more important to some patients than extending survival. This chapter updates prior summaries of proposed phenotypes and comorbidities in IPF (Fell, 2012).

We assessed safety and tolerability of treatment with pirfenidone (1602–2403 mg·day −1 ) and nintedanib (200–300 mg·day −1 ) in patients with idiopathic pulmonary fibrosis (IPF). This 24-week, single-arm, open-label, phase IV study (ClinicalTrials.gov identifier NCT02598193) enrolled patients with IPF with forced vital capacity % pred ≥50% and diffusing capacity of the lung for carbon monoxide % pred ≥30%. Before initiating nintedanib, patients had received pirfenidone for ≥16 weeks and tolerated a stable dose of ≥1602 mg·day −1 for ≥28 days. The primary end-point was the proportion of patients who completed 24 weeks of combination treatment on pirfenidone (1602–2403 mg·day −1 ) and nintedanib (200–300 mg·day −1 ). Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither. 89 patients were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary end-point) and 16 discontinued treatment prematurely (13 due to TEAEs). 74 patients had 418 treatment-related TEAEs, of which diarrhoea, nausea and vomiting were the most common. Two patients had serious treatment-related TEAEs. Combined pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of patients with IPF and associated with a similar pattern of TEAEs expected for either treatment alone. These results encourage further study of combination treatment with pirfenidone and nintedanib in patients with IPF.

Background Safety data on combined pirfenidone and nintedanib use are limited. Methods A single-arm, open-label study (NCT02598193) assessed safety and tolerability of 24 weeks’ pirfenidone (1602–2403 mg/day) and nintedanib (200–300 mg/day) in patients with idiopathic pulmonary fibrosis (IPF) with forced vital capacity (FVC) ≥50% and diffusing capacity of the lung for carbon monoxide (DLco) ≥30%. Before initiating nintedanib, patients had received pirfenidone for ≥16 weeks and tolerated a stable dose of ≥1602 mg/day pirfenidone for ≥28 days. Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither. Change from baseline FVC, DLco and King’s Brief Interstitial Lung Disease (K-BILD) score were assessed at 24 weeks. The study is monitored by a data monitoring committee. Results Eighty-nine patients were enrolled. A pre-specified interim analysis was conducted once 63 patients (mean age 68.7 years, 85.7% male) completed (n=50) or discontinued (n=13) 24 weeks’ combination treatment. Fifty patients had 330 treatment-related TEAEs (Table); 11 patients discontinued due to TEAEs. Two patients had serious treatment-related TEAEs (Table) but none led to death. Final Results for all 89 patients, including change from baseline FVC, DLco and K-BILD score, will be presented at BTS. Conclusions Combined pirfenidone and nintedanib use for 24 weeks did not reveal a different safety profile to that expected for either treatment alone. Patients had tolerated a stable dose of pirfenidone before initiation of nintedanib, which may explain why investigators attributed more TEAEs to nintedanib than pirfenidone. Funding F. Hoffmann-La Roche, Ltd./Genentech, Inc.

Background: Safety data on combined PFD and NIN use are limited. Methods: A single-arm, open-label study (NCT02598193) assessed safety and tolerability of 24 weeks’ PFD (1602–2403 mg/day) and NIN (200–300 mg/day) in patients with IPF with FVC ≥50% and DLco ≥30%. Before initiating NIN, patients had received PFD for ≥16 weeks and tolerated a stable dose of ≥1602 mg/day PFD for ≥28 days. Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to PFD, NIN, both or neither. Change from baseline FVC, DLco and K-BILD were assessed at 24 weeks. The study is monitored by a data monitoring committee. Results: Eighty-nine patients were enrolled. A pre-specified interim analysis was conducted once 63 patients (mean age 68.7 years, 85.7% male) completed (n=50) or discontinued (n=13) 24 weeks’ combination treatment. Fifty patients had 330 treatment-related TEAEs (Table); 11 patients discontinued due to TEAEs. Two patients had serious treatment-related TEAEs (Table) but none led to death. Final results for all 89 patients, including change from baseline FVC, DLco and K-BILD, will be presented at ERS. Conclusions: Combined PFD and NIN use for 24 weeks did not reveal a different safety profile to that expected for either treatment alone. Patients had tolerated a stable dose of PFD before initiation of NIN, which may explain why investigators attributed more TEAEs to NIN than PFD.

Interstitial lung disease (ILD) comprises a large and heterogeneous group of disorders that often lead to progressive fibrosis and premature death. Oxygen supplementation is typically used in patients with advanced lung disease with resting hypoxemia; however, there is a paucity of evidence guiding the use of supplemental oxygen in ILD, and significant heterogeneity in clinical practice. It remains unclear whether supplemental oxygen improves clinically meaningful outcomes, and the role of ambulatory oxygen supplementation in isolated exertional hypoxemia is particularly controversial. In some regions, the lack of robust data creates barriers to funding support and access to supplemental oxygen for patients with ILD. Further research into the role of oxygen supplementation is needed to optimize the comprehensive care of this patient population.

Systemic lupus erythematosus (SLE) is a systemic inflammatory disease, characterized serologically by an autoantibody response to nucleic antigens, and clinically by injury and/or malfunction in any organ system. During their disease course, up to 50% of SLE patients will develop lung disease. Pulmonary manifestations of SLE include pleuritis (with or without effusion), inflammatory and fibrotic forms of interstitial lung disease, alveolar hemorrhage, shrinking lung syndrome, pulmonary hypertension, airways disease, and thromboembolic disease. Two major themes inform our understanding of SLE-associated pulmonary manifestations: first, the presence of specific autoantibodies correlates with the presence of certain pulmonary manifestations and second, vascular injury marks a common pathophysiologic thread among the various SLE-related lung diseases. This review will focus on the clinical presentation, pathogenesis, pathology, management, and prognosis of these SLE-associated lung conditions.

We thank Moran-Mendoza et al. for their thoughtful comments regarding the recent Canadian Thoracic Society position statement on the evaluation of patients with fibrotic interstitial lung disease (...

Background: The interstitial lung diseases (ILDs) are a large group of disorders with heterogeneous clinical presentations and outcomes. The University of Calgary longitudinal ILD database was established to characterize the clinical characteristics and outcomes of ILD patients from a single center. Methods: Consecutive patients were prospectively …

Background. The relative rarity and diversity of fibrotic interstitial lung disease (ILD) have made it challenging to study these diseases in single-centre cohorts. Here we describe formation of a multicentre Canadian registry that is needed to describe the outcomes of fibrotic ILD and to enable detailed healthcare utilization analyses that will be the cornerstone for future healthcare planning.Methods. The Canadian Registry for Pulmonary Fibrosis (CARE-PF) is a prospective cohort anticipated to consist of at least 2,800 patients with fibrotic ILD. CARE-PF will be used to (1) describe the natural history of fibrotic ILD, specifically determining the incidence and outcomes of acute exacerbations of ILD subtypes and (2) determine the impact of ILD and acute exacerbations of ILD on health services use and healthcare costs in the Canadian population. Consecutive patients with fibrotic ILD will be recruited from five Canadian ILD centres over a period of five years. Patients will be followed up as clinically indicated and will complete standardized questionnaires at each clinic visit. Prespecified outcomes and health services use will be measured based on self-report and linkage to provincial health administrative databases.Conclusion. CARE-PF will be among the largest prospective multicentre ILD registries in the world, providing detailed data on the natural history of fibrotic ILD and the healthcare resources used by these patients. As the largest and most comprehensive cohort of Canadian ILD patients, CARE-PF establishes a network for future clinical research and early phase clinical trials and provides a platform for translational and basic science research.

Rationale: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea, impaired gas exchange, and ultimate mortality. Objectives: To test the hypothesis that maximal oxygen uptake during cardiopulmonary exercise testing at baseline and with short-term longitudinal measures would predict mortality in patients with idiopathic pulmonary fibrosis. Methods: Data from 117 patients with IPF and longitudinal cardiopulmonary exercise tests were examined retrospectively. Survival was calculated from the date of the first cardiopulmonary exercise test. Measurements and Main Results: Patients with baseline maximal oxygen uptake less than 8.3 ml/kg/min had an increased risk of death (n = 8; hazard ratio, 3.24; 95% confidence interval, 1.10–9.56; P = 0.03) after adjusting for age, gender, smoking status, baseline forced vital capacity, and baseline diffusion capacity for carbon monoxide. We were unable to define a unit change in maximal oxygen uptake that predicted survival in our cohort. Conclusions: We conclude that a threshold maximal oxygen uptake of 8.3 ml/kg/min during cardiopulmonary exercise testing at baseline adds prognostic information for patients with IPF.

In idiopathic pulmonary fibrosis, incidence is higher in males, and females may have better survival. The aim of the present study was to determine whether the rate of increase in desaturation during serial 6-min walk testing would be greater, and survival worse, for males versus females. Serial changes in the percentage of maximum desaturation area (DA) over 1 yr were estimated using mixed models in 215 patients. DA was defined as the total area above the curve created using desaturation percentage values observed during each minute of the 6-min walk test. Multivariate Cox regression assessed survival differences. Adjusting for baseline DA, 6-min walk distance, change in 6-min walk distance over time and smoking history, the percentage of maximum DA increased by an average of 2.83 and 1.37% per month for males and females, respectively. Females demonstrated better survival overall, which was more pronounced in patients who did not desaturate below 88% on ambulation at baseline and after additionally adjusting for 6-month relative changes in DA and forced vital capacity. These data suggest that differences in disease progression contribute to, but do not completely explain, better survival of females with idiopathic pulmonary fibrosis.

Pulmonary fibrosis occurs in up to 30% of patients with pulmonary alveolar proteinosis, and pulmonary hypertension is rarely identified. A previously healthy, highly active, asymptomatic 59-year-old male was diagnosed with autoimmune pulmonary alveolar proteinosis. He was followed clinically for five years until he developed disease progression with dyspnea on exertion. In the interim, he had developed pulmonary fibrosis, and was later found to have pulmonary hypertension. He continued to decline despite aggressive treatment with whole-lung lavage, inhaled granulocyte-macrophage colony-stimulating factor, and rituximab and now has very limited activity, despite use of supplemental oxygen. Pulmonary fibrosis and pulmonary hypertension are uncommon and unpredictable complications of pulmonary alveolar proteinosis. Current treatment regimens for pulmonary alveolar proteinosis may not benefit patients once fibrosis is established. It is not known whether early aggressive treatment can stabilize or delay disease progression.

Rationale: Idiopathic pulmonary fibrosis (IPF) and other idiopathic interstitial pneumonias (IIPs) have similar clinical and radiographic features, but their histopathology, response to therapy, and natural history differ. A surgical lung biopsy is often required to distinguish between these entities. Objectives: We sought to determine if clinical variables could predict a histopathologic diagnosis of IPF in patients without honeycomb change on high-resolution computed tomography (HRCT). Methods: Data from 97 patients with biopsy-proven IPF and 38 patients with other IIPs were examined. Logistic regression models were built to identify the clinical variables that predict histopathologic diagnosis of IPF. Measurements and Main Results: Increasing age and average total HRCT interstitial score on HRCT scan of the chest may predict a biopsy confirmation of IPF. Sex, pulmonary function, presence of desaturation, or distance walked during a 6-minute walk test did not help discriminate pulmonary fibrosis from other IIPs. Conclusions: Clinical data may be used to predict a diagnosis of IPF over other IIPs. Validation of these data with a prospective study is needed.