Nonuniformity of Diffusing Capacity From Small Alveolar Gas Samples Is Increased in Smokers
Authors: Cotton DJ , Mink JT , Graham BL 
Published: March 2016

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 (SBWSM) manoeuvres improve the detection of abnormalities in ventilation inhomogeneity in the lung periphery in smokers compared with traditional vital capacity manoeuvres, SBWSM 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 (DLcoSB‐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 SBWSM 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 (SBWVC) manoeuvres consisting of slow inhalation of test gas from RV to total lung capacity and, without breath holding, slow exhalation to RV. DLcoSB‐3EQ was calculated from the total alveolar gas sample. DLcoSB‐3EQ was also calculated from four equal sequential, simulated aliquots of the total alveolar gas sample. DLcoSB‐3EQ values from the four alveolar samples were normalized by expressing each as a percentge of DLcoSB‐3EQ from the entire alveolar gas sample. An index of variation (DI) among the small‐sample DLcoSB‐3EQ values was correlated with the normalized phase III helium slope (Sn) and the mixing efficiency (Emix).

RESULTS: For SBWSM, DI was increased in smokers at 0 s of breath holding compared with nonsmokers, and correlated with age, smoking pack‐years and Sn. The decrease in DI with breath holding was greater in smokers and correlated with the change in Sn with breath holding. For SBWVC manoeuvres, there were no differences due to smoking in Sn or Emix, but DI was increased in smokers and correlated with age and smoking pack‐years, but not with Sn.

CONCLUSIONS: For SBWSM manoeuvres the increase in DI in smokers correlated with breath hold time‐dependent increases in Sn, suggesting that the changes in DI reflected the same structural alterations that caused increases in peripheral ventilation inhomogeneity. For SBWVC manoeuvres, the increase in DI in smokers was not associated with changes in ventilation inhomogeneity, suggesting that the effect of smoking on DI during this manoeuvre was due to smoke‐related changes in alveolar capillary diffusion, rather than due solely to alterations in the distribution of ventilation.