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Title: Gait speed and prognosis in idiopathic pulmonary fibrosis
Author: Nolan, Claire
ISNI:       0000 0004 7658 3273
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Background: Idiopathic Pulmonary Fibrosis (IPF) is a progressive disease of the lungs with a median life expectancy of three years. Surrogate endpoints that can predict adverse outcomes are required to help develop and evaluate new treatments for IPF, but existing options have limitations. The four metre gait speed (4MGS) test measures usual walking speed, which in older people is a consistently strong predictor of adverse outcomes and has been described as a 'marker of global well-being'. Aims: To evaluate the reliability, concurrent validity, responsiveness, minimum clinically important difference (MCID) and predictive validity of the 4MGS test in patients with IPF. Methods and results: 4MGS was reliable (n=46) and showed concurrent validity with established IPF measures in two independent cohorts (n=65 and n=62). Stratification according to slow gait speed phenotype (4MGS < 0.80ms-1) identified significant impairments in exercise capacity, dyspnoea, quality of life and prognostic index. The 4MGS test was responsive to pulmonary rehabilitation (n=90) with an MCID of 0.08 to 0.18ms-1 calculated using distribution- and anchor-based methods. In a separate cohort of patients newly diagnosed with IPF (n=130), 4MGS was associated with a significantly increased risk of all-cause mortality (hazard ratio (HR) (95% confidence interval (95% CI)): 0.03 (0.01 to 0.25) and non-elective hospitalisation (HR (95% CI): 0.03 (0.01 to 0.18) at one year. Multivariable models that included 4MGS had higher discrimination for predicting adverse outcomes (c-statistic: 0.78-0.81) than established prognostic indices (c-statistic: 0.65-0.73). Improvement in 4MGS following rehabilitation was associated with longer survival but not time to non-elective hospitalisation. A 4MGS change cut-point of ≥0.09ms-1 provided the best sensitivity and specificity to identify survival at one year. Conclusion: The 4MGS test is a reliable, valid and responsive objective measure of physical performance that has prognostic ability and potential utility as a simple assessment tool and surrogate endpoint in IPF.
Supervisor: Man, William D.-C. ; Maher, Toby M. ; Cullinan, Paul Sponsor: National Institute for Health Research
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral