Diffusing Capacity of Carbon Monoxide in Assessment of COPD

Abstract

Background: Diffusing capacity of the lung for carbon monoxide (Dlco) is inconsistently obtained in patients with COPD, and the added benefit of Dlco testing beyond that of more common tools is unknown.

Objective: The goal of this study was to determine whether lower Dlco is associated with increased COPD morbidity independent of emphysema assessed via spirometry and CT imaging.

Methods: Data for 1,806 participants with COPD from the Genetic Epidemiology of COPD (COPDGene) study 5-year visit were analyzed, including pulmonary function testing, quality of life, symptoms, exercise performance, and exacerbation rates. Dlco percent predicted was primarily analyzed as a continuous variable and additionally categorized into four groups: (1) Dlco and FEV1 > 50% (reference); (2) only Dlco ≤ 50%; (3) only FEV1 ≤ 50%; and (4) both ≤ 50% predicted. Outcomes were modeled by using multivariable linear and negative binomial regression, including emphysema and FEV1 percent predicted among other confounders.

Results: In multivariable analyses, every 10% predicted decrease in Dlco was associated with symptoms and quality of life (COPD Assessment Test, 0.53 [P < .001]; St. George's Respiratory Questionnaire, 1.67 [P < .001]; Medical Outcomes Study Short Form 36 Physical Function, -0.89 [P < .001]), exercise performance (6-min walk distance, -45.35 feet; P < .001), and severe exacerbation rate (rate ratio, 1.14; P < .001). When categorized, severe impairment in Dlco alone, FEV1 alone, or both Dlco and FEV1 were associated with significantly worse morbidity compared with the reference group (P < .05 for all outcomes).

Conclusions: Impairment in Dlco was associated with increased COPD symptoms, reduced exercise performance, and severe exacerbation risk even after accounting for spirometry and CT evidence of emphysema. These findings suggest that Dlco should be considered for inclusion in future multidimensional tools assessing COPD.

Trial registration: ClinicalTrials.gov NCT00608764.

Keywords: COPD; pulmonary diffusing capacity; pulmonary gas exchange.

Copyright © 2019. Published by Elsevier Inc.

Figures

Figure 1

Participant selection. Models with and without emphysema (%LAA-950) are presented for all outcomes in Tables 2, 3, and e-Table 2. COPDGene = Genetic Epidemiology of COPD; Dlco = diffusing capacity of the lung for carbon monoxide; GOLD = Global Obstructive Lung Disease; %LAA-950 = percent low attenuation areas at or below –950 Hounsfield units consistent with emphysema.

Figure 2

Severe impairment in Dlco in isolation and in combination with severe impairment in FEV1 is associated with increased COPD morbidity. Association between categories of percent predicted FEV1 and Dlco with (A) COPD Assessment Test score, (B) St. George’s Respiratory Questionnaire score, (C) Medical Outcomes Study Short Form 36 Physical Function, and (D) 6-min walk distance in feet. Groups are defined as reference (FEV1 and Dlco both > 50% predicted), Dlco impaired (FEV1 > 50% and Dlco ≤ 50%), FEV1 impaired (FEV1 ≤ 50% and Dlco > 50%), and both impaired (FEV1 and Dlco ≤ 50%). Models (N = 1,564) are adjusted for age, sex, BMI categories, ethnicity, education, smoking pack-years, smoking status, anemia status, diabetes status, congestive heart failure status, sleep apnea status, and %LAA-950 (emphysema). See Figure 1 legend for expansion of abbreviations.

Figure 3

Severe impairment in Dlco in isolation and in combination with severe impairment in FEV1 is associated with higher severe COPD exacerbation rates. Association between categories of FEV1 and Dlco and self-reported rate of severe exacerbations. Groups are defined as reference (FEV1 and Dlco both > 50% predicted), Dlco impaired (FEV1 > 50% and Dlco ≤ 50%), FEV1 impaired (FEV1 ≤ 50% and Dlco > 50%), and both impaired (FEV1 and Dlco ≤ 50%). Model is adjusted for age, sex, ethnicity, BMI categories, smoking pack-years, smoking status, anemia status, diabetes status, congestive heart failure status, sleep apnea status, and emphysema as a categorical variable (missing, ≤ 5% LAA-950, > 5% LAA-950), with N = 1,806. Severe refers only to those exacerbations requiring an ED visit or hospitalization. RR = rate ratio. See Figure 1 legend for expansion of other abbreviations.