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Risk of COPD in smokers with low transfer factor

We are concerned that the paper by Harvey et al. [1] in a recent issue of the European Respiratory Journal and its accompanying editorial [2] are misleading the readership with regard to the possible association between gas transfer (TLCO), referred to in the paper as diffusion capacity, and the subsequent risk of developing chronic obstructive pulmonary disease (COPD) in smokers. The authors selected two small groups of subjects (n=59 and 46) from within a larger dataset to compare what happened to their forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio over time. Both groups at baseline had FEV1 >80% of predicted and FEV1/FVC >0.7, but one group had TLCO >80% of predicted, and the other group had TLCO <80% of predicted and also below a lower 95% confidence limit of TLCO per cent of predicted as derived by the authors from the data of a separate set of 405 healthy nonsmokers (whose data were not disclosed). This latter extra criterion is only evident from reading the online supplement and it does not readily relate to a true population lower limit as it is based on per cent of predicted values (vide infra). When comparing these two groups the authors found more subjects in their “low TLCO group” had developed airflow obstruction on follow-up. The article and editorial suggest that TLCO <80% of predicted is a marker of susceptibility for developing airflow limitation and COPD in smokers. However, the authors have not assessed what happened to their subjects whose TLCO is below 80% of predicted but is also above the authors' 95% confidence limit. From figure 1 it can be seen that the true population lower 95% confidence limit in older and smaller subjects can be a long way below 80% of predicted. So it is misleading to suggest that a threshold of 80% of predicted for TLCO has any particular merit in predicting future airflow obstruction when the authors have not assessed what happened to the many subjects who will have a value below this level but above the authors' lower 95% confidence limit that defined their low TLCO group. Furthermore they claim they find a predictor of COPD and yet no evidence is offered with regard to the symptoms required for making this diagnosis. The subsequent development of COPD has not yet been proven to relate to a particular threshold value of TLCO http://ow.ly/XAlx1