Mechanical tissue stretch contributes to the development of pulmonary fibrosis via mechanotransduced activation of TGF-β1 in rodent and human pulmonary fibrosis.

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Objective Higher self‐reported disability (high Health Assessment Questionnaire [HAQ] score) has been associated with hospitalizations and mortality in established rheumatoid arthritis (RA), but associations in early RA are unknown. Methods Patients with early RA (symptom duration <1 year) enrolled in the Canadian Early Arthritis Cohort who initiated disease‐modifying antirheumatic drugs and had completed HAQ data at baseline and 1 year were included in the study. Discrete‐time proportional hazards models were used to estimate crude and multi‐adjusted associations of baseline HAQ and HAQ at 1 year with all‐cause mortality in each year of follow‐up. Results A total of 1,724 patients with early RA were included. The mean age was 55 years, and 72% were women. Over 10 years, 62 deaths (3.6%) were recorded. Deceased patients had higher HAQ scores at baseline (mean ± SD 1.2 ± 0.7) and at 1 year (0.9 ± 0.7) than living patients (1.0 ± 0.7 and 0.5 ± 0.6, respectively; P < 0.001). Disease Activity Score in 28 joints (DAS28) was higher in deceased versus living patients at baseline (mean ± SD 5.4 ± 1.3 versus 4.9 ± 1.4) and at 1 year (mean ± SD 3.6 ± 1.4 versus 2.8 ± 1.4) (P < 0.001). Older age, male sex, lower education level, smoking, more comorbidities, higher baseline DAS28, and glucocorticoid use were associated with mortality. Contrary to HAQ score at baseline, the association between all‐cause mortality and HAQ score at 1 year remained significant even after adjustment for confounders. For baseline HAQ score, the unadjusted hazard ratio (HR) was 1.46 (95% confidence interval [95% CI] 1.02–2.09), and the adjusted HR was 1.25 (95% CI 0.81–1.94). For HAQ score at 1 year, the unadjusted HR was 2.58 (95% CI 1.78–3.72), and the adjusted HR was 1.75 (95% CI 1.10–2.77). Conclusion Our findings indicate that higher HAQ score and DAS28 at 1 year are significantly associated with all‐cause mortality in a large early RA cohort.

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Background:Patients with RA are at greater risk of mortality than the general population. Higher HAQ disability has been associated with hospitalizations and mortality in established RA; whether HAQ disability predicts mortality in early RA (ERA) is unknown.Objectives:The objective of this study is to analyze how well the HAQ can predict future mortality in patients with early RA.Methods:Data were from adult early RA patients (symptoms <1 year) enrolled in the Canadian Early Arthritis Cohort (CATCH) between 2007 and 2017; who initiated treatment with 1 or more DMARDs and had completed HAQ data at baseline and 1 year. Descriptive statistics, t-tests and chi-square tests were used to summarize and compare baseline patient characteristics including sociodemographic variables, RA characteristics and comorbidities amongst deceased and non-deceased patients. Discrete-time proportional hazards models were used to estimate crude and multi-adjusted associations between HAQ at baseline and 1 year, respectively, with all-cause mortality in each year of follow up.Results:This study included 1724 patients with early RA; mean age was 55 years and 72% were female. In 10 years of follow up, 62 deaths (2.4%) occurred. Deceased patients had higher HAQ scores and DAS28 scores at baseline and at 1 year versus the non-deceased group. Age, male sex, lower education, smoking, more comorbidities, higher baseline disease activity and steroid use were associated with mortality in unadjusted survival models (Table 1). Contrary to HAQ at baseline, the association between all-cause mortality and HAQ at 1 year remained significant even after adjusting for age, gender, comorbidities, disease activity, smoking, education, seropositivity, symptom duration and steroid use in adjusted survival models (Table 2).Table 1.Unadjusted survival model: Association of each variable with all-cause mortalityBaseline VariableUnadjustedHazard OR95% CISocio-DemographicAge (years)1.101.07 – 1.13Female0.370.22 – 0.62Caucasian (white or European)1.010.46 – 2.24Aboriginal1.710.61 – 4.76Education > high school degree0.480.28 – 0.82Current Smoker1.811.01 – 3.24Rheumatic Disease Comorbidity Index (0-9)1.601.36 – 1.87RA CharacteristicsSymptom duration (months)0.990.91 – 1.08Seropositivity in first year1.110.55 – 2.23DAS28 ESR or CRP if ESR is missing1.261.06 – 1.51Oral Steroid use1.751.03 – 2.98Table 2.Multivariable discrete-time survival models: HAQ baseline vs 1 yearModelModel 1:Crude(Time + HAQ-DI)Model 2:Adjusted for age + sexModel 3:Adjusted for Model 2 + DAS28 + RDCIModel 4:Adjusted for Model 3 + education, smoking, seropositivity, symptom duration and oral steroids useModel 5:Adjusted for Model 3 + smoking, symptom duration onlyHAQ-DI (0-3) (at baseline)1.461.02 – 2.091.370.96 – 1.951.250.81 – 1.941.320.85 – 2.041.300.84 – 2.00HAQ-DI (0-3) (at 1 year)2.581.78 – 3.722.401.63 – 3.521.751.10 – 2.771.871.16 – 3.021.731.09 – 2.74*Hazard OR, 95% CI~HAQ-DI: (Health Assessment Questionnaire Disability Index); RDCI: Rheumatic Disease Comorbidity Index; DAS28: Disease Activity ScoreConclusion:Higher HAQ at 1 year was significantly associated with all-cause mortality in a large early RA cohort suggesting that poorer disease control and function in the first year of RA contributes to higher mortality.Disclosure of Interests:Safoora Fatima: None declared, Orit Schieir: None declared, Marie-France Valois: None declared, Susan J. Bartlett Consultant of: Pfizer, UCB, Lilly, Novartis, Merck, Janssen, Abbvie, Speakers bureau: Pfizer, UCB, Lilly, Novartis, Merck, Janssen, Abbvie, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Gilles Boire Grant/research support from: Merck Canada (Registry of biologices, Improvement of comorbidity surveillance)Amgen Canada (CATCH, clinical nurse)Abbvie (CATCH, clinical nurse)Pfizer (CATCH, Registry of biologics, Clinical nurse)Hoffman-LaRoche (CATCH)UCB Canada (CATCH, Clinical nurse)BMS (CATCH, Clinical nurse, Observational Study Protocol IM101664. SEROPOSITIVITY IN A LARGE CANADIAN OBSERVATIONAL COHORT)Janssen (CATCH)Celgene (Clinical nurse)Eli Lilly (Registry of biologics, Clinical nurse), Consultant of: Eli Lilly, Janssen, Novartis, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Glen Hazlewood: None declared, Carol Hitchon Grant/research support from: UCB Canada; Pfizer Canada, Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant of: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion,Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, LillyPharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Diane Tin: None declared, Carter Thorne Consultant of: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Vivian Bykerk: None declared, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB