Assessing the Stability of the Healthy Never-smoking Subgroup Over 12 Years and Its Effect on Reference Equations for Lung Function in a Prospective Cohort Study: The Multi-ethnic Study of Atherosclerosis Lung Study

Abstract Rationale. Reference ranges for tests of pulmonary function have been defined upon their distribution in cross-sectional samples of “healthy” participants since the mid-Nineteenth Century. Currently, “healthy” participants are defined as participants recruited from the general population without respiratory symptoms or diseases and without a smoking history. However, reporting of all these factors is known to be imprecise. To better understand the variability of this approach, we investigated the stability of a “healthy” sample over 12 years in a prospective, population-based cohort study. Methods. The Multi-Ethnic Study of Atherosclerosis (MESA) recruited a multiethnic sample of participants ages 45-84 free of clinical cardiovascular disease in 2000-02. The MESA Lung Study performed standardized spirometry in 2004-07, 2010-11, and 2016-18. We defined subpopulations of healthy normal never-smoking participants at each exam in which spirometry was measured according to: self-reported history of never smoking; self-reported absence of respiratory diseases; and self-reported absence of respiratory symptoms (wheezing, persistent cough, phlegm production, and breathless walking on level ground). Stability of the sample over time was assessed with the Kappa statistic. For each exam, we used the healthy never-smoking group to derive sex-stratified reference equations for pre-bronchodilator forced expiratory volume in 1 second (FEV1) by linear regression with predictors of age and height2. Lower limits of normal (LLN) FEV1 were calculated as predicted FEV1-1.645[asterisk]standard error of the estimate, with age=70 years and height=158 cm and 172 cm for female and male, respectively. Results. There were 1,101 (26%) healthy normals of 4,272 participants at baseline (28% White, 20% Black, 22% Hispanic, 30% Asian), 1,075 (34%) of 3,200 at first follow-up, and 614 (24%) of 2,597 at second follow-up. Of 1,863 participants who participated in all three exams, 299 were labeled healthy normal in all exams, 278 were healthy normal in two of three exams, and 188 were healthy normal in only one exam (κ=0.60 across the three exams). Of the 1,129 who reported no symptoms at second follow-up, 32% had reported at least one symptom in at least one previous exam. The different healthy normal groups led to estimates of LLN FEV1 that varied across exams by 60-90 mL (female: 1,356-1,419mL, SD=34; male: 1,963-2,053mL, SD=29). Conclusions. The healthy normal never-smoking sample in a longitudinal cohort study was only moderately stable over time, with modest implications for the estimation of the LLN. These findings raise further questions about the current, cross-sectional approach to the definition of normal pulmonary function.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.