Nonuniformity of Diffusing Capacity From Small Alveolar Gas Samples Is Increased in Smokers

Abstract

BACKGROUND: Although centrilobular emphysema, and small airway, interstitial and alveoli inflammation can be detected pathologically in the lungs of smokers with relatively well preserved lung function, these changes are difficult to assess using available physiological tests. Because submaximal single breath washout (SBW_SM) manoeuvres improve the detection of abnormalities in ventilation inhomogeneity in the lung periphery in smokers compared with traditional vital capacity manoeuvres, SBW_SM manoeuvres were used in this study to measure temporal differences in diffusing capacity using a rapid response carbon monoxide analyzer.OBJECTIVE: To determine whether abnormalities in the lung periphery can be detected in smokers with normal forced expired volumes in 1 s using the three-equation diffusing capacity (DLco^SB-3EQ) among small alveolar gas samples and whether the abnormalities correlate with increases in peripheral ventilation inhomogeneity.PARTICIPANTS AND DESIGN: Cross-sectional study in 21 smokers and 21 nonsmokers all with normal forced exhaled flow rates.METHODS: Both smokers and nonsmokers performed SBW_SM manoeuvres consisting of slow inhalation of test gas from functional residual capacity to one-half inspiratory capacity with either 0 or 10 s of breath holding and slow exhalation to residual volume (RV). They also performed conventional vital capacity single breath (SBW_VC) manoeuvres consisting of slow inhalation of test gas from RV to total lung capacity and, without breath holding, slow exhalation to RV. DLco^SB-3EQ was calculated from the total alveolar gas sample. DLco^SB-3EQ was also calculated from four equal sequential, simulated aliquots of the total alveolar gas sample. DLco^SB-3EQ values from the four alveolar samples were normalized by expressing each as a percentge of DLco^SB-3EQ from the entire alveolar gas sample. An index of variation (D_I) among the small-sample DLco^SB-3EQ values was correlated with the normalized phase III helium slope (S_n) and the mixing efficiency (E_mix).RESULTS: For SBW_SM, D_I was increased in smokers at 0 s of breath holding compared with nonsmokers, and correlated with age, smoking pack-years and S_n. The decrease in D_I with breath holding was greater in smokers and correlated with the change in Sn with breath holding. For SBW_VC manoeuvres, there were no differences due to smoking in Sn or E_mix, but D_I was increased in smokers and correlated with age and smoking pack-years, but not with S_n.CONCLUSIONS: For SBW_SM manoeuvres the increase in D_I in smokers correlated with breath hold time-dependent increases in S_n, suggesting that the changes in D_I reflected the same structural alterations that caused increases in peripheral ventilation inhomogeneity. For SBW_VC manoeuvres, the increase in D_I in smokers was not associated with changes in ventilation inhomogeneity, suggesting that the effect of smoking on D_I during this manoeuvre was due to smoke-related changes in alveolar capillary diffusion, rather than due solely to alterations in the distribution of ventilation.