DOI: 10.25934/pr00010735
title: Exploration of change in forced expiratory volume:forced vital capacity (FEV1:FVC) ratio from baseline to prognosticate clinical outcomes in idiopathic pulmonary fibrosis and predict treatment response to Nintedanib

description: Idiopathic Pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease that exclusively affects the lungs. It is characterised by the irreversible formation of scar tissue (fibrosis) which gradually replaces normal functioning lung. As the disease progresses patients experience breathlessness. Sadly, this disease carries poor prognosis (likely outcome of the patient’s disease). Average survival time from diagnosis is 3-5 years – which is worse than some cancers. Although once classified as a rare disease it is now considered fairly common. IPF is more common in men and median age of diagnosis is 65 years. Latest UK Interstitial Lung Disease (ILD) registry data suggests there are 30,000 cases in the UK, with an estimated 5000 new cases of IPF diagnosed each year. Currently in the UK, National institute for health and clinical (NICE) guidelines, two antifibrotic drugs are available for treatment of this condition - Nintedanib and Pirfenidone - these work by slowing down the build-up of scar tissue. Although these give benefit in many cases, there are some cases that continue to progress despite treatment. 

Changes in Forced Vital Capacity (FVC) - the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible, gas transfer measurement - where oxygen moves from the lungs into the blood and carbon dioxide from the blood moves into the lungs, computed tomography (CT) scan image appearance and symptoms are classically used for monitoring of disease status. Change from time of diagnosis and year-to-year reduction in FVC and gas transfer are established measures used to guide prognosis and antifibrotic therapy, yet these are not without limitation.

Spirometry, which measures the amount and/or speed of air that can be inhaled or exhaled, such as FVC, or forced expiratory volume (FEV1) which measures how much air a person can exhale in the first second after a full breath in, can be affected by patient effort and other coexistent lung disease. 

The FEV1:FVC ratio measures the proportion of a person's maximum air capacity that they are able to forcibly push out of their lungs in the first second of measurement. FEV1:FVC ratio of less than 80% is commonly used to indicate IPF, but change in FEV1:FVC ratio to predict the likely outcomes in IPF is relatively unknown.

We would like to explore if change in FEV1:FVC ratio is predictive of mortality (death), and evaluate how this compares with FVC decline to predict outcomes in IPF. We would like to explore this using existing data obtained from a previous clinical trials called INPULSIS-1 (NCT01335464) and INPULSIS-2 (NCT01335477), which demonstrated that Nintedanib was effective at reducing the progression of disease in IPF compared to placebo. If an association is observed, it could identify a potential biomarker predictive of treatment response. In turn this preliminary data could provide an early signal to help identify which patients are might be more likely to respond to antifibrotic therapy and those at greater risk of progression of disease.