FEV1 decline across BMI gradient in COPD patients who were part of large randomized controlled trial over at least 3 years.

Proposal
5642

Title of Proposed Research

Lead Researcher

Don D Sin

Affiliation

Centre for Heart Lung Innovation, St Paul's Hospital and Division of Respiratory Medicine, University of British Columbia,Vancouver, BC V6Z 1Y6, Canada

Funding Source

Potential Conflicts of Interest

Data Sharing Agreement Date

13 June 2019

Lay Summary

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable respiratory disease characterized by persistent and progressive airflow limitation in the lungs. Airflow limitation is commonly caused by lung inflammation, the lungs' response to noxious particles or gases, particularly cigarette smoke. COPD is a leading cause of death worldwide and its prevalence is increasing due to continuous exposure to risk factors and aging of the population. It leads to enormous social and economic burdens on individuals and society. Therefore, COPD is a major public health issue that requires great attention.Weight loss and muscle wasting are common in patients with COPD, especially in severe cases. Body mass index (BMI), a measurement of weight to height, is generally recognized as the most useful indicator of health risk among people who are over- or underweight. It is well known that low BMI is predictive of greater risk of death in patients with COPD. However it is unclear whether BMI is a predictor of COPD disease progression. It is widely accepted that COPD disease progression can be assessed using the rate of decline in FEV1 (a measurement of the amount of air a patient can exhale in one second). Some studies suggested that COPD patients with greater BMI showed slower rates of decline in FEV1. In another study, COPD patients with normal BMI had the slowest decline in FEV1, patients with low BMI had the fastest decline in FEV1, and patients with high BMI had the slower decline in FEV1. Another study showed BMI had no relation with the rate of decline in FEV1 in COPD patients. Therefore, the relationship between BMI and the rate of decline in FEV1 in patients with COPD is still uncertain. The objective of the proposed research is to determine whether BMI is a predictor of FEV1 decline and explore the relationship between them. We hypothesize that BMI is a predictor of the decline in FEV1 and that patients with a lower BMI will show a faster decline in lung function. It may be helpful to identify COPD patients with rapid progression who require more intensive treatment, and also provide more theoretical basis for nutritional support treatment for COPD patients.

Study Data Provided

[{ "PostingID": 416, "Title": "GSK-SCO30003", "Description": "A multicentre, randomised, double-blind, parallel group, placebo-controlled study to investigate the long-term effects of salmeterol/fluticasone propionate (SERETIDE® inhaler) 50/500mcg BD, salmeterol 50mcg BD and fluticasone propionate 500mcg BD, all delivered via the DISKUS®/ACCUHALER® inhaler, on mortality and morbidity of subjects with chronic obstructive pulmonary disease (COPD) over 3 years of treatment" },{ "PostingID": 4109, "Title": "GSK-HZC113782", "Description": "A Clinical Outcomes Study to compare the effect of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg with placebo on Survival in Subjects with moderate Chronic Obstructive Pulmonary Disease (COPD) and a history of or at increased risk for cardiovascular disease" }]

Statistical Analysis Plan

All patients enrolled in our project have given the informed consent on the basis of the record of the integrated projects. The traditional randomization procedures of our project have been published before(6). The aim of this project is clarifying the relationships between the loss of lung function, namely the decline of absolute FEV1, and body mass index (BMI). The samples that *** would be selected from the big dataset. The rest of the data would not be included in our analysis. The selected samples would be sub-categorized into *** subgroups. Random coefficients model would be applied to regress the relationship among the decline of lung function and other patient indexes including BMI, age, sex, smoking status, ethnic origin, baseline percentage predicted FEV1, region, previous exacerbation history, the distinct medical treatment etc. At least two FEV1 would be collected for the mathematical analysis. The slope of different BMI categories in the statistical model would be recorded if the adjusted p-value of the index is significant. The FDR<0.1 is planned to be used as the cutoff in our study to estimate the effect of slopes. The relationship between the loss of lung function and BMI would be estimated on the basis of the slope of the regressed random coefficients model. The whole analysis procedure would be run on R, version 3.5.0, on the Unix platform of Compute Canada super server. The function lmer from R package lme4 would be applied to study the relationship between the loss of lung functions and distinct covariates especially BMI in our project.This methodology description should not be limited to a list of tests. It should be a discussion of such items as: • Effect measure of interest (e.g. for inferential studies: odds ratio, risk or rate ratio, risk or rate difference, absolute difference)• Statistical analysis methods (e.g. logistic regression, Kaplan-Meier curves, log-rank test, multiplicity adjustments)• Planned adjustment for covariates• Meta-analysis methods, if applicable (e.g. random effects meta-analysis, stratified meta-analysis, meta-regression)• Power to detect a clinically important effect, or the precision of the effect estimate given the sample size available• Planned sensitivity analyses, if relevant• Planned subgroup analyses [e.g. by age, disease status, ethnicity, socio-economic status, presence or absence of co-morbidities, different types of intervention (e.g. drug dose)]• Handling of missing data6. Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. The New England journal of medicine 2007; 356(8): 775-89.

Publication Citation

Sun, Y., Milne, S., Jaw, J.E. et al. BMI is associated with FEV1 decline in chronic obstructive pulmonary disease: a meta-analysis of clinical trials. Respir Res 20, 236 (2019).

https://doi.org/10.1186/s12931-019-1209-5