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Prediction and stratification of longitudinal risk for chronic obstructive pulmonary disease across smoking behaviors.

ABSTRACT: Smoking is the leading risk factor for chronic obstructive pulmonary disease (COPD) worldwide, yet many people who never smoke develop COPD. We perform a longitudinal analysis of COPD in the UK Biobank to derive and validate the Socioeconomic and Environmental Risk Score which captures additive and cumulative environmental, behavioral, and socioeconomic exposure risks beyond tobacco smoking. The Socioeconomic and Environmental Risk Score is more predictive of COPD than smoking status and pack-years. Individuals in the highest decile of the risk score have a greater risk for incident COPD compared to the remaining population. Never smokers in the highest decile of exposure risk are more likely to develop COPD than previous and current smokers in the lowest decile. In general, the prediction accuracy of the Social and Environmental Risk Score is lower in non-European populations. While smoking status is often considered in screening COPD, our finding highlights the importance of other non-smoking environmental and socioeconomic variables.

SUBMITTER: He Y

PROVIDER: S-EPMC10721891 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Prediction and stratification of longitudinal risk for chronic obstructive pulmonary disease across smoking behaviors.

He Yixuan Y Qian David C DC Diao James A JA Cho Michael H MH Silverman Edwin K EK Gusev Alexander A Manrai Arjun K AK Martin Alicia R AR Patel Chirag J CJ

Nature communications 20231214 1

Smoking is the leading risk factor for chronic obstructive pulmonary disease (COPD) worldwide, yet many people who never smoke develop COPD. We perform a longitudinal analysis of COPD in the UK Biobank to derive and validate the Socioeconomic and Environmental Risk Score which captures additive and cumulative environmental, behavioral, and socioeconomic exposure risks beyond tobacco smoking. The Socioeconomic and Environmental Risk Score is more predictive of COPD than smoking status and pack-ye ...[more]

PMID: 38097585

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Project description:BACKGROUND AND HYPOTHESIS: Heterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management. Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease. Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics. OBJECTIVE AND METHOD: To explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management. To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people). Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena. RESULTS: (1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering. CONCLUSIONS: The results indicate the high potential of a systems approach to address COPD heterogeneity. Significant knowledge gaps were identified that are relevant to shape strategies aiming at fostering 4P Medicine for patients with COPD.

Project description:BACKGROUND:Cigarette smoking is the strongest risk factor for COPD. Smoking burden is frequently measured in pack-years, but the relative contribution of cigarettes smoked per day versus duration towards the development of structural lung disease, airflow obstruction and functional outcomes is not known. METHODS:We analysed cross-sectional data from a large multicentre cohort (COPDGene) of current and former smokers. Primary outcome was airflow obstruction (FEV1/FVC); secondary outcomes included five additional measures of disease: FEV1, CT emphysema, CT gas trapping, functional capacity (6 min walk distance, 6MWD) and respiratory morbidity (St George's Respiratory Questionnaire, SGRQ). Generalised linear models were estimated to compare the relative contribution of each smoking variable with the outcomes, after adjustment for age, race, sex, body mass index, CT scanner, centre, age of smoking onset and current smoking status. We also estimated adjusted means of each outcome by categories of pack-years and combined groups of categorised smoking duration and cigarettes/day, and estimated linear trends of adjusted means for each outcome by categorised cigarettes/day, smoking duration and pack-years. RESULTS:10 187 subjects were included. For FEV1/FVC, standardised beta coefficient for smoking duration was greater than for cigarettes/day and pack-years (P<0.001). After categorisation, there was a linear increase in adjusted means FEV1/FVC with increase in pack-years (regression coefficient β=-0.023±SE0.003; P=0.003) and duration over all ranges of smoking cigarettes/day (β=-0.041±0.004; P<0.001) but a relatively flat slope for cigarettes/day across all ranges of smoking duration (β=-0.009±0.0.009; P=0.34). Strength of association of duration was similarly greater than pack-years for emphysema, gas trapping, FEV1, 6MWD and SGRQ. CONCLUSION:Smoking duration alone provides stronger risk estimates of COPD than the composite index of pack-years. TRIAL REGISTRATION NUMBER:Post-results; NCT00608764.

Dataset Information

Prediction and stratification of longitudinal risk for chronic obstructive pulmonary disease across smoking behaviors.

Publications

Prediction and stratification of longitudinal risk for chronic obstructive pulmonary disease across smoking behaviors.

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