Prevalence and characteristics of progressive fibrosing interstitial lung disease in a prospective registry

Rationale Progressive fibrosing interstitial lung disease (PF-ILD) is characterized by progressive physiologic, symptomatic, and/or radiographic worsening. The real-world prevalence and characteristics of PF-ILD remain uncertain. Methods Patients were enrolled from the Canadian Registry for Pulmonary Fibrosis between 2015-2020. PF-ILD was defined as a relative forced vital capacity (FVC) decline ≥10%, death, lung transplantation, or any 2 of: relative FVC decline ≥5 and <10%, worsening respiratory symptoms, or worsening fibrosis on computed tomography of the chest, all within 24 months of diagnosis. Time-to-event analysis compared progression between key diagnostic subgroups. Characteristics associated with progression were determined by multivariable regression. Results Of 2,746 patients with fibrotic ILD (mean age 65±12 years, 51% female), 1,376 (50%) met PFILD 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 diseaseassociated ILD (CTD-ILD). Compared to IPF, time to progression was similar in patients with HP (hazard ratio [HR] 0.96, 95% confidence interval, 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 utilized in 49%, 61%, and 37% of patients with CHP, CTD-ILD, and U-ILD respectively. Increasing age, male sex, gastroesophageal reflux disease, and lower baseline pulmonary function were independently associated with progression. Interpretation 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 strategie

Risk and safety perception on urban and rural roads: Effects of environmental features, driver age and risk sensitivity

Objective: The ability to detect changing visual information is a vital component of safe driving. In addition to detecting changing visual information, drivers must also interpret its relevance to safety. Environmental changes considered to have high safety relevance will likely demand greater attention and more timely responses than those considered to have lower safety relevance. The aim of the present study was to explore factors that are likely to influence perceptions of risk and safety regarding changing visual information in the driving environment. Factors explored were the environment in which the change occurs (i.e., urban versus rural), the type of object that changes, and the driver's age, experience and risk sensitivity.\ud \ud Methods: 63 licensed drivers aged 18–70 years completed a hazard rating task, which required them to rate the perceived hazardousness of changing specific elements within urban and rural driving environments. Three attributes of potential hazards were systematically manipulated: the environment (urban, rural); the type of object changed (road sign, car, motorcycle, pedestrian, traffic light, animal, tree); and its inherent safety risk (low-risk, high-risk). Inherent safety risk was manipulated by either varying the object's placement, on/near or away from the road, or altering an infrastructure element which would require a change to driver behaviour. Participants also completed two driving-related risk perception tasks, rating their relative crash risk and perceived risk of aberrant driving behaviours.\ud \ud Results: Driver age was not significantly associated with hazard ratings, but individual differences in perceived risk of aberrant driving behaviours predicted hazard ratings, suggesting that general driving-related risk sensitivity plays a strong role in safety perception. In both urban and rural scenes there were significant associations between hazard ratings and inherent safety risk, with low-risk changes perceived as consistently less hazardous than high-risk impact changes; however, the effect was larger for urban environments. There were also effects of object type, with certain objects rated as consistently more safety relevant. In urban scenes, changes involving pedestrians were rated significantly more hazardous than all other objects, and in rural scenes, changes involving animals were rated as significantly more hazardous. Notably, hazard ratings were found to be higher in urban compared with rural driving environments, even when changes were matched between environments.\ud \ud Conclusion: The present study demonstrates that drivers perceive rural roads as less risky than urban roads, even when similar scenarios occur in both environments. Age did not affect hazard ratings. Instead, the findings suggest that the assessment of risk posed by hazards is influenced more by individual differences in risk sensitivity. This highlights the need for driver education to account for appraisal of hazards' risk and relevance, in addition to hazard detection, when considering factors which promote road safety

The clinical frailty scale for risk stratification in patients with fibrotic interstitial lung disease.

BACKGROUND Previous studies have shown the importance of frailty in patients with fibrotic interstitial lung disease (ILD). RESEARCH QUESTION Is the Clinical Frailty Scale (CFS) a valid tool to improve risk stratification in patients with fibrotic ILD? STUDY DESIGN AND METHODS Patients with fibrotic ILD were included from the prospective multicenter Canadian Registry for Pulmonary Fibrosis. The CFS was assessed using available information from initial ILD clinic visits. Patients were stratified into fit (CFS 1-3), vulnerable (CFS 4), and frail (CFS 5-9) subgroups. Cox proportional hazards and logistic regression models with mixed effects were used to estimate time to death or lung transplantation. A derivation and validation cohort were used to establish prognostic performance. Trajectories of functional tests were compared using joint models. RESULTS Of the 1587 patients with fibrotic ILD, 858 (54%) were fit, 400 (25%) vulnerable and 329 (21%) frail. Frailty was a risk factor for early mortality (HR 5.58, 95%CI 3.64-5.76, p<0.001) in the entire cohort, in individual ILD diagnoses, and after adjustment for potential confounders. Adding frailty to established risk prediction parameters improved the prognostic performance in derivation and validation cohorts. Frail patients had larger annual declines in forced vital capacity (FVC) %-predicted compared to fit patients (-2.32 (95%CI -3.39 to -1.17) vs. -1.55 (95%CI -2.04 to -1.15); p=0.02, respectively). INTERPRETATION The simple and practical CFS is associated with pulmonary and physical function decline in patients with fibrotic ILD and provides additional prognostic accuracy in clinical practice

Costs of Workplace Productivity Loss in Patients with Connective Tissue Disease Associated Interstitial Lung Disease.

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

A cluster-based analysis evaluating the impact of comorbidities in fibrotic interstitial lung disease

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.Medicine, Faculty ofPharmaceutical Sciences, Faculty ofNon UBCMedicine, Department ofReviewedFacult

Mapping EQ5D utilities from forced vital capacity and diffusing capacity in fibrotic interstitial lung disease.

ObjectivesFibrotic interstitial lung disease (ILD) includes a large group of conditions that lead to scarring of the lungs. The lack of available 5-level EuroQol 5D (EQ5D) data has limited the ability to conduct economic evaluations in ILD. The purpose of this study was to develop and validate a mapping algorithm that predicts EQ5D utilities from commonly collected pulmonary function measurements (forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide [DLCO]) in fibrotic ILDs.MethodsEQ5D utility and pulmonary function measurements from the Canadian Registry for Pulmonary Fibrosis were included. Ordinary least squares (OLS), beta regression, two-part, and tobit models were used to map EQ5D utilities from FVC or DLCO. Model performance was assessed by comparing the predicted and observed utilities. Subgroup analyses were also conducted to test how well models performed across different patient characteristics. The models were then externally validated in the Australian Idiopathic Pulmonary Fibrosis Registry.ResultsThe OLS model performed as well as other more complex models (root mean squared error: 0.17 for FVC and 0.16 for DLCO). As with the other models, the OLS algorithm performed well across the different subgroups (except for EQ5D utilities ConclusionWe developed a mapping algorithm that predicts EQ5D utilities from FVC and DLCO, with the intent that this algorithm can be applied to clinical trial populations and real-world cohorts that have not prioritized collection of health-related utilities. The mapping algorithm can be used in future economic evaluations of potential ILD therapies

Validation and minimum important difference of the UCSD Shortness of Breath Questionnaire in fibrotic interstitial lung disease

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