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. 2023 Aug 15;208(4):451-460.
doi: 10.1164/rccm.202210-1887OC.

Causes of and Clinical Features Associated with Death in Tobacco Cigarette Users by Lung Function Impairment

Wassim W Labaki  1 , Tian Gu  2 , Susan Murray  3 , Jeffrey L Curtis  1   4 , J Michael Wells  5 , Surya P Bhatt  5 , Jessica Bon  6   7 , Alejandro A Diaz  8 , Craig P Hersh  8   9 , Emily S Wan  9   10 , Victor Kim  11 , Terri H Beaty  12 , John E Hokanson  13 , Russell P Bowler  14 , Douglas A Arenberg  1 , Ella A Kazerooni  1   15 , Fernando J Martinez  16 , Edwin K Silverman  8   9 , James D Crapo  14 , Barry J Make  14 , Elizabeth A Regan  17 , MeiLan K Han  1 ; COPDGene Investigators – Core Units; COPDGene Investigators – Clinical Centers
Collaborators, Affiliations

Causes of and Clinical Features Associated with Death in Tobacco Cigarette Users by Lung Function Impairment

Wassim W Labaki et al. Am J Respir Crit Care Med. .

Abstract

Rationale: Cigarette smoking contributes to the risk of death through different mechanisms. Objectives: To determine how causes of and clinical features associated with death vary in tobacco cigarette users by lung function impairment. Methods: We stratified current and former tobacco cigarette users enrolled in Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) into normal spirometry, PRISm (Preserved Ratio Impaired Spirometry), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-2 COPD, and GOLD 3-4 COPD. Deaths were identified via longitudinal follow-up and Social Security Death Index search. Causes of death were adjudicated after a review of death certificates, medical records, and next-of-kin interviews. We tested associations between baseline clinical variables and all-cause mortality using multivariable Cox proportional hazards models. Measurements and Main Results: Over a 10.1-year median follow-up, 2,200 deaths occurred among 10,132 participants (age 59.5 ± 9.0 yr; 46.6% women). Death from cardiovascular disease was most frequent in PRISm (31% of deaths). Lung cancer deaths were most frequent in GOLD 1-2 (18% of deaths vs. 9-11% in other groups). Respiratory deaths outpaced competing causes of death in GOLD 3-4, particularly when BODE index ⩾7. St. George's Respiratory Questionnaire score ⩾25 was associated with higher mortality in all groups: Hazard ratio (HR), 1.48 (1.20-1.84) normal spirometry; HR, 1.40 (1.05-1.87) PRISm; HR, 1.80 (1.49-2.17) GOLD 1-2; HR, 1.65 (1.26-2.17) GOLD 3-4. History of respiratory exacerbations was associated with higher mortality in GOLD 1-2 and GOLD 3-4, quantitative emphysema in GOLD 1-2, and airway wall thickness in PRISm and GOLD 3-4. Conclusions: Leading causes of death vary by lung function impairment in tobacco cigarette users. Worse respiratory-related quality of life is associated with all-cause mortality regardless of lung function.

Keywords: exacerbations; mortality; respiratory-related quality of life; smokers; spirometry.

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Figures

Figure 1.
Figure 1.
Distribution of causes of death by baseline lung function category. GOLD = Global Initiative for Chronic Obstructive Lung Disease; PRISm = preserved ratio impaired spirometry.
Figure 2.
Figure 2.
Kaplan-Meier plots of inverse-weighted survival probabilities of respiratory, cardiovascular, and lung cancer deaths in A) all participants by lung function category and B) GOLD 3–4 participants by BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index category. GOLD = Global Initiative for Chronic Obstructive Lung Disease; PRISm = preserved ratio impaired spirometry.
Figure 3.
Figure 3.
Kaplan-Meier plots of survival probabilities by lung function category, stratified by A) the number of respiratory exacerbations in the year before enrollment; and B) the baseline score of St. George’s Respiratory Questionnaire. GOLD = Global Initiative for Chronic Obstructive Lung Disease; PRISm = preserved ratio impaired spirometry.
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