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.
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.
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.
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.
Idiopathic pulmonary fibrosis is a progressive, fatal disease. This prospective, randomised, double-blind, multicentre, parallel-group, placebo-controlled phase II trial (NCT00903331) investigated ...the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis. Eligible subjects were adults with idiopathic pulmonary fibrosis of <3 years duration and a histological pattern of usual interstitial pneumonia on surgical lung biopsy. The primary objective was to demonstrate that macitentan (10 mg once daily) positively affected forced vital capacity versus placebo. Using a centralised system, 178 subjects were randomised (2:1) to macitentan (n=119) or placebo (n=59). The median change from baseline up to month 12 in forced vital capacity was -0.20 L in the macitentan arm and -0.20 L in the placebo arm. Overall, no differences between treatments were observed in pulmonary function tests or time to disease worsening or death. Median exposures to macitentan and placebo were 14.5 months and 15.0 months, respectively. Alanine and/or aspartate aminotransferase elevations over three times upper limit of normal arose in 3.4% of macitentan-treated subjects and 5.1% of placebo recipients. In conclusion, the primary objective was not met. Long-term exposure to macitentan was well tolerated with a similar, low incidence of elevated hepatic aminotransferases in each treatment group.
Progressive fibrosing interstitial lung disease (PF-ILD) is characterised by progressive physiological, symptomatic and/or radiographic worsening. The real-world prevalence and characteristics of ...PF-ILD remain uncertain.
Patients were enrolled from the Canadian Registry for Pulmonary Fibrosis between 2015 and 2020. PF-ILD was defined as a relative forced vital capacity (FVC) decline ≥10%, death, lung transplantation or any two of: relative FVC decline ≥5% and <10%, worsening respiratory symptoms or worsening fibrosis on computed tomography of the chest, all within 24 months of diagnosis. Time-to-event analysis compared progression between key diagnostic subgroups. Characteristics associated with progression were determined by multivariable regression.
Of 2746 patients with fibrotic ILD (mean±sd age 65±12 years; 51% female), 1376 (50%) met PF-ILD criteria in the first 24 months of follow-up. PF-ILD occurred in 427 (59%) patients with idiopathic pulmonary fibrosis (IPF), 125 (58%) with fibrotic hypersensitivity pneumonitis (HP), 281 (51%) with unclassifiable ILD (U-ILD) and 402 (45%) with connective tissue disease-associated ILD (CTD-ILD). Compared with IPF, time to progression was similar in patients with HP (hazard ratio (HR) 0.96, 95% CI 0.79-1.17), but was delayed in patients with U-ILD (HR 0.82, 95% CI 0.71-0.96) and CTD-ILD (HR 0.65, 95% CI 0.56-0.74). Background treatment varied across diagnostic subtypes, with 66% of IPF patients receiving antifibrotic therapy, while immunomodulatory therapy was utilised in 49%, 61% and 37% of patients with CHP, CTD-ILD and U-ILD, respectively. Increasing age, male sex, gastro-oesophageal reflux disease and lower baseline pulmonary function were independently associated with progression.
Progression is common in patients with fibrotic ILD, and is similarly prevalent in HP and IPF. Routinely collected variables help identify patients at risk for progression and may guide therapeutic strategies.
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 (BMI > 30). 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.
Display omitted
Particulate matter 2.5 μm or less in diameter (PM2.5) is associated with adverse outcomes for patients with idiopathic pulmonary fibrosis, but its association with other fibrotic interstitial lung ...diseases (fILDs) and the association of PM2.5 composition with adverse outcomes remain unclear.
To investigate the association of PM2.5 exposure with mortality and lung function among patients with fILD.
In this multicenter, international, prospective cohort study, patients were enrolled in the Simmons Center for Interstitial Lung Disease Registry at the University of Pittsburgh in Pittsburgh, Pennsylvania; 42 sites of the Pulmonary Fibrosis Foundation Registry; and 8 sites of the Canadian Registry for Pulmonary Fibrosis. A total of 6683 patients with fILD were included (Simmons, 1424; Pulmonary Fibrosis Foundation, 1870; and Canadian Registry for Pulmonary Fibrosis, 3389). Data were analyzed from June 1, 2021, to August 2, 2022.
Exposure to PM2.5 and its constituents was estimated with hybrid models, combining satellite-derived aerosol optical depth with chemical transport models and ground-based PM2.5 measurements.
Multivariable linear regression was used to test associations of exposures 5 years before enrollment with baseline forced vital capacity and diffusion capacity for carbon monoxide. Multivariable Cox models were used to test associations of exposure in the 5 years before censoring with mortality, and linear mixed models were used to test associations of exposure with a decrease in lung function. Multiconstituent analyses were performed with quantile-based g-computation. Cohort effect estimates were meta-analyzed. Models were adjusted for age, sex, smoking history, race, a socioeconomic variable, and site (only for Pulmonary Fibrosis Foundation and Canadian Registry for Pulmonary Fibrosis cohorts).
Median follow-up across the 3 cohorts was 2.9 years (IQR, 1.5-4.5 years), with death for 28% of patients and lung transplant for 10% of patients. Of the 6683 patients in the cohort, 3653 were men (55%), 205 were Black (3.1%), and 5609 were White (84.0%). Median (IQR) age at enrollment across all cohorts was 66 (58-73) years. A PM2.5 exposure of 8 μg/m3 or more was associated with a hazard ratio for mortality of 4.40 (95% CI, 3.51-5.51) in the Simmons cohort, 1.71 (95% CI, 1.32-2.21) in the Pulmonary Fibrosis Foundation cohort, and 1.45 (95% CI, 1.18-1.79) in the Canadian Registry for Pulmonary Fibrosis cohort. Increasing exposure to sulfate, nitrate, and ammonium PM2.5 constituents was associated with increased mortality across all cohorts, and multiconstituent models demonstrated that these constituents tended to be associated with the most adverse outcomes with regard to mortality and baseline lung function. Meta-analyses revealed consistent associations of exposure to sulfate and ammonium with mortality and with the rate of decrease in forced vital capacity and diffusion capacity of carbon monoxide and an association of increasing levels of PM2.5 multiconstituent mixture with all outcomes.
This cohort study found that exposure to PM2.5 was associated with baseline severity, disease progression, and mortality among patients with fILD and that sulfate, ammonium, and nitrate constituents were associated with the most harm, highlighting the need for reductions in human-derived sources of pollution.
Fibrotic interstitial lung disease (fILD) is a group of pathologic entities characterized by scarring of the lungs and high morbidity and mortality. Research investigating how socioeconomic and ...residential factors impact outcomes in patients with fILD is lacking.
To determine the association between neighborhood-level disadvantage and presentation severity, disease progression, lung transplantation, and mortality in patients with fILD from the United States and Canada.
We performed a multicenter, international, prospective cohort study of 4,729 patients with fILD from one U.S. and eight Canadian ILD registry sites. Neighborhood-level disadvantage was measured by the area deprivation index in the United States and the Canadian Index of Multiple Deprivation in Canada.
In the U.S. but not in the Canadian cohort, patients with fILD living in neighborhoods with the greatest disadvantage (top quartile) experience the highest risk of mortality (hazard ratio = 1.51,
= 0.002), and in subgroups of patients with idiopathic pulmonary fibrosis, the top quartile of disadvantage experienced the lowest odds of lung transplantation (odds ratio = 0.46,
= 0.04). Greater disadvantage was associated with reduced baseline DL
in both cohorts, but it was not associated with baseline FVC or FVC or DL
decline in either cohort.
Patients with fILD who live in areas with greater neighborhood-level disadvantage in the United States experience higher mortality, and patients with idiopathic pulmonary fibrosis experience lower odds of lung transplantation. These disparities are not seen in Canadian patients, which may indicate differences in access to care between the United States and Canada.
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.
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).
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.
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.
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.
PDF
