Interstitial Features at Chest CT Enhance the Deleterious Effects of Emphysema in the COPDGene Cohort

Abstract

Purpose To determine if interstitial features at chest CT enhance the effect of emphysema on clinical disease severity in smokers without clinical pulmonary fibrosis. Materials and Methods In this retrospective cohort study, an objective CT analysis tool was used to measure interstitial features (reticular changes, honeycombing, centrilobular nodules, linear scar, nodular changes, subpleural lines, and ground-glass opacities) and emphysema in 8266 participants in a study of chronic obstructive pulmonary disease (COPD) called COPDGene (recruited between October 2006 and January 2011). Additive differences in patients with emphysema with interstitial features and in those without interstitial features were analyzed by using t tests, multivariable linear regression, and Kaplan-Meier analysis. Multivariable linear and Cox regression were used to determine if interstitial features modified the effect of continuously measured emphysema on clinical measures of disease severity and mortality. Results Compared with individuals with emphysema alone, those with emphysema and interstitial features had a higher percentage predicted forced expiratory volume in 1 second (absolute difference, 6.4%; P < .001), a lower percentage predicted diffusing capacity of lung for carbon monoxide (DLCO) (absolute difference, 7.4%; P = .034), a 0.019 higher right ventricular-to-left ventricular (RVLV) volume ratio (P = .029), a 43.2-m shorter 6-minute walk distance (6MWD) (P < .001), a 5.9-point higher St George's Respiratory Questionnaire (SGRQ) score (P < .001), and 82% higher mortality (P < .001). In addition, interstitial features modified the effect of emphysema on percentage predicted DLCO, RVLV volume ratio, 6WMD, SGRQ score, and mortality (P for interaction < .05 for all). Conclusion In smokers, the combined presence of interstitial features and emphysema was associated with worse clinical disease severity and higher mortality than was emphysema alone. In addition, interstitial features enhanced the deleterious effects of emphysema on clinical disease severity and mortality.

Trial registration: ClinicalTrials.gov NCT00608764.

© RSNA, 2018 Online supplemental material is available for this article.

Figures

Figure 1:

A–D, Representative axial CT images in individuals with and those without interstitial features but with similar percentages of lung occupied by emphysema show the effects of the presence of interstitial features. A, B, Images in a 74-year-old man with interstitial features (percentage interstitial = 14.3%). The percentage of his lung occupied by emphysema was 20.7%. His St George’s Respiratory Questionnaire (SGRQ) score was 48. His 6-minute walk distance was 225 m. His right ventricular–to–left ventricular volume ratio was 0.75. He died during follow-up. C, D, Images in a 73-year-old man without interstitial features (percentage interstitial = 6.1%). The percentage of his lung occupied by emphysema was 20.5%. His SGRQ score was 53. His 6-minute walk distance was 480 m. His right ventricular–to–left ventricular volume ratio was 0.61. He did not die during follow-up.

Figure 2a:

Plots show association between percentage predicted forced expiratory volume in 1 second (FEV1) and emphysema in individuals with and those without interstitial features. (a) Univariable additive effect of interstitial features and emphysema. SD = standard deviation. (b) Interaction between interstitial features and emphysema. Interstitial features were defined as present if more than 10% of the lung was occupied by interstitial features. Fora, emphysema was defined as present if more than 15% of the lung was occupied by emphysematous features. Units for β are (percentage predicted forced expiratory volume in 1 second)/(percentage emphysema). * = P for interaction given for multivariable analysis, which was additionally adjusted for age, sex, race, clinical center, current smoking status, number of pack-years smoked, and body mass index.

Figure 2b:

Plots show association between percentage predicted forced expiratory volume in 1 second (FEV1) and emphysema in individuals with and those without interstitial features. (a) Univariable additive effect of interstitial features and emphysema. SD = standard deviation. (b) Interaction between interstitial features and emphysema. Interstitial features were defined as present if more than 10% of the lung was occupied by interstitial features. Fora, emphysema was defined as present if more than 15% of the lung was occupied by emphysematous features. Units for β are (percentage predicted forced expiratory volume in 1 second)/(percentage emphysema). * = P for interaction given for multivariable analysis, which was additionally adjusted for age, sex, race, clinical center, current smoking status, number of pack-years smoked, and body mass index.

Figure 3a:

Plots show association between percentage predicted forced vital capacity(FVC) and emphysema in individuals with and those without interstitial features. (a) Univariable additive effect of interstitial features and emphysema. SD = standard deviation. (b) Interaction between interstitial features and emphysema. Interstitial features were defined as present if more than 10% of the lung was occupied by interstitial features. For a, emphysema was defined as present if more than 15% of the lung was occupied by emphysematous features. Units for β are (percentage predicted forced vital capacity)/(percentage emphysema). * =P for interaction given for multivariable analysis, which was additionally adjusted for age, sex, race, clinical center, current smoking status, number of pack-years smoked, and body mass index.

Figure 3b:

Plots show association between percentage predicted forced vital capacity(FVC) and emphysema in individuals with and those without interstitial features. (a) Univariable additive effect of interstitial features and emphysema. SD = standard deviation. (b) Interaction between interstitial features and emphysema. Interstitial features were defined as present if more than 10% of the lung was occupied by interstitial features. For a, emphysema was defined as present if more than 15% of the lung was occupied by emphysematous features. Units for β are (percentage predicted forced vital capacity)/(percentage emphysema). * =P for interaction given for multivariable analysis, which was additionally adjusted for age, sex, race, clinical center, current smoking status, number of pack-years smoked, and body mass index.

Figure 4a:

Plots show association between percentage predicted diffusing capacity of lung for carbon monoxide and emphysema in individuals with and those without interstitial features. (a) Univariable additive effect of interstitial features and emphysema. SD = standard deviation. (b) Interaction between interstitial features and emphysema. Interstitial features were defined as present if more than 10% of the lung was occupied by interstitial features. For a, emphysema was defined as present if more than 15% of the lung was occupied by emphysematous features. Units for β are (percentage predicted diffusing capacity of lung for carbon monoxide)/(percentage emphysema). * = P for interaction given for multivariable analysis, which was additionally adjusted for age, sex, race, clinical center, current smoking status, number of pack-years smoked, body mass index, and percentage predicted forced expiratory volume in 1 second. There were 352 data points available for diffusing capacity analysis.

Figure 4b:

Plots show association between percentage predicted diffusing capacity of lung for carbon monoxide and emphysema in individuals with and those without interstitial features. (a) Univariable additive effect of interstitial features and emphysema. SD = standard deviation. (b) Interaction between interstitial features and emphysema. Interstitial features were defined as present if more than 10% of the lung was occupied by interstitial features. For a, emphysema was defined as present if more than 15% of the lung was occupied by emphysematous features. Units for β are (percentage predicted diffusing capacity of lung for carbon monoxide)/(percentage emphysema). * = P for interaction given for multivariable analysis, which was additionally adjusted for age, sex, race, clinical center, current smoking status, number of pack-years smoked, body mass index, and percentage predicted forced expiratory volume in 1 second. There were 352 data points available for diffusing capacity analysis.

Figure 5a:

Plots show association between right ventricular–to–left ventricular volume ratio in individuals with and those without interstitial features. (a) Univariable additive effect of interstitial features and emphysema. SD = standard deviation.(b) Interaction between interstitial features and emphysema. Interstitial features were defined as present if more than 10% of the lung was occupied by interstitial features. For a, emphysema was defined as present if more than 15% of the lung was occupied by emphysematous features. Units for β are (right ventricular–to–left ventricular volume ratio)/(percentage emphysema). * = P for interaction given for multivariable analysis, which was additionally adjusted for age, sex, race, clinical center, current smoking status, number of pack-years smoked, body mass index, and percentage predicted forced expiratory volume in 1 second. There were 7407 data points available for right ventricular–to–left ventricular volume ratio analysis.

Figure 5b:

Plots show association between right ventricular–to–left ventricular volume ratio in individuals with and those without interstitial features. (a) Univariable additive effect of interstitial features and emphysema. SD = standard deviation.(b) Interaction between interstitial features and emphysema. Interstitial features were defined as present if more than 10% of the lung was occupied by interstitial features. For a, emphysema was defined as present if more than 15% of the lung was occupied by emphysematous features. Units for β are (right ventricular–to–left ventricular volume ratio)/(percentage emphysema). * = P for interaction given for multivariable analysis, which was additionally adjusted for age, sex, race, clinical center, current smoking status, number of pack-years smoked, body mass index, and percentage predicted forced expiratory volume in 1 second. There were 7407 data points available for right ventricular–to–left ventricular volume ratio analysis.

Figure 6a:

Plots show association between 6-minute walk distance in individuals with and those without interstitial features. (a) Univariable additive effect of interstitial features and emphysema. SD = standard deviation. (b) Interaction between interstitial features and emphysema. Interstitial features were defined as present if more than 10% of the lung was occupied by interstitial features. Fora, emphysema was defined as present if more than 15% of the lung was occupied by emphysematous features. Units for β are (meters)/(percentage emphysema). * = P for interaction given for multivariable analysis, which was additionally adjusted for age, sex, race, clinical center, current smoking status, number of pack-years smoked, body mass index, and percentage predicted forced expiratory volume in 1 second.

Figure 6b:

Plots show association between 6-minute walk distance in individuals with and those without interstitial features. (a) Univariable additive effect of interstitial features and emphysema. SD = standard deviation. (b) Interaction between interstitial features and emphysema. Interstitial features were defined as present if more than 10% of the lung was occupied by interstitial features. Fora, emphysema was defined as present if more than 15% of the lung was occupied by emphysematous features. Units for β are (meters)/(percentage emphysema). * = P for interaction given for multivariable analysis, which was additionally adjusted for age, sex, race, clinical center, current smoking status, number of pack-years smoked, body mass index, and percentage predicted forced expiratory volume in 1 second.

Figure 7a:

Plots show association between St George’s Respiratory Questionnaire total score in individuals with and those without interstitial features.(a) Univariable additive effect of interstitial features and emphysema. SD = standard deviation.(b) Interaction between interstitial features and emphysema. Interstitial features were defined as present if more than 10% of the lung was occupied by interstitial features. For a, emphysema was defined as present if more than 15% of the lung was occupied by emphysematous features. Units for β are (St George’s Respiratory Questionnaire total score)/(percentage emphysema). * =P for interaction given for multivariable analysis, which was additionally adjusted for age, sex, race, clinical center, current smoking status, number of pack-years smoked, body mass index, and percentage predicted forced expiratory volume in 1 second.

Figure 7b:

Plots show association between St George’s Respiratory Questionnaire total score in individuals with and those without interstitial features.(a) Univariable additive effect of interstitial features and emphysema. SD = standard deviation.(b) Interaction between interstitial features and emphysema. Interstitial features were defined as present if more than 10% of the lung was occupied by interstitial features. For a, emphysema was defined as present if more than 15% of the lung was occupied by emphysematous features. Units for β are (St George’s Respiratory Questionnaire total score)/(percentage emphysema). * =P for interaction given for multivariable analysis, which was additionally adjusted for age, sex, race, clinical center, current smoking status, number of pack-years smoked, body mass index, and percentage predicted forced expiratory volume in 1 second.

Figure 8:

Graph shows survival in individuals with emphysema only compared with that in those with both emphysema and interstitial features. Numbers on x-axis = number surviving at each time point.