Cigarette smoking is associated with subclinical parenchymal lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA)-lung study

Abstract

Rationale: Cigarette smoking is a risk factor for diffuse parenchymal lung disease. Risk factors for subclinical parenchymal lung disease have not been described.

Objectives: To determine if cigarette smoking is associated with subclinical parenchymal lung disease, as measured by spirometric restriction and regions of high attenuation on computed tomography (CT) imaging.

Methods: We examined 2,563 adults without airflow obstruction or clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis, a population-based cohort sampled from six communities in the United States. Cumulative and current cigarette smoking were assessed by pack-years and urine cotinine, respectively. Spirometric restriction was defined as a forced vital capacity less than the lower limit of normal. High attenuation areas on the lung fields of cardiac CT scans were defined as regions having an attenuation between -600 and -250 Hounsfield units, reflecting ground-glass and reticular abnormalities. Generalized additive models were used to adjust for age, gender, race/ethnicity, smoking status, anthropometrics, center, and CT scan parameters.

Measurements and main results: The prevalence of spirometric restriction was 10.0% (95% confidence interval [CI], 8.9-11.2%) and increased relatively by 8% (95% CI, 3-12%) for each 10 cigarette pack-years in multivariate analysis. The median volume of high attenuation areas was 119 cm(3) (interquartile range, 100-143 cm(3)). The volume of high attenuation areas increased by 1.6 cm(3) (95% CI, 0.9-2.4 cm(3)) for each 10 cigarette pack-years in multivariate analysis.

Conclusions: Smoking may cause subclinical parenchymal lung disease detectable by spirometry and CT imaging, even among a generally healthy cohort.

Figures

Figure 1.

Participants in the Multi-Ethnic Study of Atherosclerosis–Lung study included in the present analysis.

Figure 2.

(A) Histograms of lung attenuation and (B–D) representative computed tomography images of three study participants at the (B) 50th, (C) 75th, and (D) 95th percentiles of high attenuation area (119, 143, and 202 cm3 of HAAs, respectively). The differences in the number of HAAs (−600 to −250 Hounsfield units) appear small on visual inspection of the histograms in A. However, there are notable differences in the peakedness (kurtosis) and skewness of the three histograms, with lower kurtosis and skewness as the number of HAAs increases. Areas of increased attenuation appear gray and white on the lung windows shown in C and D.

Figure 3.

Continuous relationships of cigarette pack-years to (A) spirometric restriction and (B) the volume of high lung attenuation. Thick dotted lines: smoothed regression lines adjusted for age, gender, race/ethnicity, current smoking status, urine cotinine, height, body mass index, and waist and hip circumferences. B is further adjusted for study site, total volume of imaged lung, and milliampere dose. Thin solid lines: 95% confidence intervals. Neither smoothed curve differed significantly from a straight line (A: P = 0.65; B: P = 0.16), suggesting that the relationships between cigarette pack-years and both measures are linear. Multivariate-adjusted (predicted) probabilities of spirometric restriction were estimated by combining the prevalence of spirometric restriction in the sample with the predicted incremental probabilities of spirometric restriction using a generalized additive model. Multivariate-adjusted (predicted) values of HAA were estimated by adding the sample mean to predicted mean differences using a generalized additive model.