Smoking produces a number of pathological lesions in the lung . Recent observations using computed tomography (CT) revealed surprisingly common abnormalities in smokers with relatively normal lung function. The abnormalities consisted of ground glass attenuation, micronodules and diffuse emphysematous changes in smokers, but these changes were not found in nonsmokers . Pathologically, ground glass attenuation correlated with alveolitis and interstitial inflammation; parenchymal micronodules correlated with bronchiolectasis and peribronchial fibrosis, similar to those previously found in smokers ; and emphysema exceeded the extent observed from CT analysis .
For SBWSM at 0 s of breath holding the increase in Di with smoking pack-years could be related to any one or a combination of these abnormalities. Macroscopic emphysema was unlikely to have caused the increase in Di in this group of smokers. Previous postmortem studies in smokers found no relationship between either emphysema grade, or the destructive index, and the single breath phase III slope in the present study. Therefore, inflammation and fibrosis in small airways most likely accounted for the increase in Di in these healthy smokers in the present study. This was supported by the correlation of Di with Sn in smokers (Figure 4) for SBWSM manoeuvres at 0 s of breath holding. Moreover, breath holding dramatically decreased Di for SBWSM manoeuvres (Figure 2), and the decrease in Di with breath holding correlated with the change in Sn with breath holding (Figure 4). This observation further supported the concept that the effects of smoking on Di occurred primarily in the pulmonary parenchyma distal to the membranous bronchioles .
Figure 4) Degree of diffusion nonuniformity (Di) (%) correlates with the normalized phase III helium slope (Sn)for submaximal single breath washout (SBWsm) manoeuvres at0 s of breath holding in both smokers (r2=0.63, P<0.001, solid line) and in nonsmokers (r=0.38, P<0.01, dashed line). For the nonsmokers and smokers combined, (r2=0.69, P<0.001). O Nonsmokers; 0 Smokers