Although we did not measure carboxy-hemoglobin in the smokers in this study, most of whom reported smoking in the 2 h before testing, it would likely have been elevated, accounting for most of the apparent reduction in DLcoSb-3EQ measured from the total sample in smokers compared with nonsmokers . DLcoSb-3EQ measured from the total sample in smokers would have been affected by both carbon monoxide back pressure and carboxy-hemoglobin. However, we found that Di required no corrections because it was not affected by increases in carboxy-hemoglobin in normal subjects .
The present method of measuring DLcoSb-3EQ from four sequential alveolar gas samples has a number of potential limitations. An analyzer with appropriate instrumentation and software is not currently commercially available. We employed a carbon monoxide analyzer that was modified to decrease its response time to 110 ms . The use of mass spectrometry for analysis of helium, while providing excellent signal characteristics, is too expensive for routine implementation. The manoeuvres also required instantaneous biofeedback to ensure reproducibility. This is feasible using available computer technology, and the software has been developed. In our experience, naive subjects are able to complete these manoeuvres with minimal prior coaching, but the reproducibility is less than in trained subjects . Finally, although this report demonstrates clear changes in smokers, the effect of smoking on Di is not necesarily specific. Other pathological processes that lead to small airway obstruction such as bronchiolitis obliterans following lung transplant, could have similar effects.