Tests of small airway disease. Final report on CEC Contract 7246-21/8/001

A comparison has been made of the relationship between indices of the distribution of fine inhaled particles and the results of a number of tests of small airway dysfunction. It was intended to compare the relative merits of these tests against an index that was firmly associated with ventilation inequalities in the lung periphery.Measurements of lung function (FEV1, Vmax25, Vmax50, FET, PET 50-100, MTT V isoV) and standard lung volumes were performed on a total of 27 subjects who were either patients (7) with chronic obstructive lung disease (COLD) or healthy non-smokers (9) and asymptomatic smokers (11, inclusive of one ex-smoker). On the same day each subject inhaled an aerosol of 99m labelled particles of diameter 2 um and measurements were made using a gamma- cam era to assess their regional distribution. Additional measurements of the lung distribution of 81m gas were made in 20 of these subjects, in order to assess whether complete peripheral aerosol penetrance had been achieved.The aerosol and 81m lung images were quantitatively compared by subdividing the lung regions into inner, central and peripheral zones. For smokers and non-smokers a good correlation between these images was obtained (r = 0.93) with no significant differences in the proportion of total 99mTc or 8lmkr counts in any region. From these same data an aerosol penetrance index (API) was derived, normalised by 81mKr penetrance, and for smokers and non-smokers the mean API was 0.97 (SD, 0.17), indicating effective peripheral penetrance. For COLD patients the mean API was 0.69 (SD, 0.17), which is significantly lower than for the combined smoker and non-smoker group.An aerosol distribution index (ADl) was devised, derived from the ratio of the variance to the same counts from the gamma-camera, and was applied to the lung images of smokers and non-smokers. It was discovered that although their images lookedsimilar to the naked eye and had the same overall distribution, the detailed distributions as measured by mean ADI were significantly different. The ADI was found to correlate with tests of small airway dysfunction (Vmax25 (r = 0.7l) and Vmax50(r =0.59)) but only poorly with FET, PET 50-100 and MTT, and not significantly with V isoV. It was also found to correlate well with FEV1 (r = 0.67). The ADI was worse for smokers than non-smokers, and was well correlated with amount smoked. These results indicate that some of the so-called small airway tests are indeed associated with disease in the periphery of the lung, and that both ventilatory small airway tests and aerosol deposition tests were sensitive to lung’abnormalities in subjects whose FEVj, in most cases were still within the normal range. However, for the latter four tests mentioned above, only a poor correlation was demonstrated with evidence of peripheral lung abnormality. We discuss the future potential of the aerosol test.A comparison was also made of the detailed distribution of activity in the 81mKr images using the same method of analysis as was used to obtain the ADI. A gas distribution index (GDI) was calculated from the 1mKr images and the results compared with the ADI in the smoker and non-smoker groups. The 81mKr and aerosol images looked similar to the naked eye and were quantitatively similar in terms of the overall distribution of activity. The GDI results generally indicated much less inhomogeneity than the ADI. Statistically significant differences in the GDI between smokers and non-smokers were not found, but there were significant differences between the GDI and ADI within both the smoker and non-smoker groups. We have performed a small additional study to test one possible cause of these differences, namely, gaseous diffusion, but found evidence against this hypothesis. We discuss this result and the further hypothesis that collateral ventilation may be responsible.