From the Authors

From the authors:

We thank D‐J. Slebos and colleagues for their comments relating to our paper on the imbalance between haem oxygenase (HO)‐1 and inducible nitric oxide synthase (iNOS) in the lungs of severe chronic obstructive pulmonary disease (COPD) patients 1.

Our data showed that expression of HO‐1 was decreased in alveolar macrophages in severe COPD, whereas iNOS expression in type‐2 pneumocytes was increased. It is of great interest to see that the results provided by Slebos and colleagues confirm the part of our findings related to HO‐1 expression in alveolar macrophages. Since the origin of macrophages retrieved by bronchoalveolar lavage is undetermined, the findings of Slebos and colleagues might indicate that the altered expression of HO‐1 in COPD is not limited to the alveolar compartment, but extends to macrophages from the bronchial lumen.

We believe that the presence of current smokers among our patients was a negligible confounding factor for the different expression of HO‐1 in severe COPD as compared with control smokers without impairment of lung function 1. In fact, it was shown in our previous paper 2 that upregulation of HO‐1 in alveolar macrophages of subjects with smoking history was irrespective of the fact they were current or ex-smokers. The data provided by Slebos and colleagues support the interpretation that HO‐1 expression is not influenced directly by cigarette smoke.

We are aware of the potential bias in studies performed on surgically resected specimens, due to the presence of cancer itself or to the selection of the worst part of the lungs in patients who underwent lung volume reduction surgery. However, surgical specimens are precious tissue because they allow direct examination of lung pathology in living patients, which would be otherwise impossible for obvious ethical reasons. This opportunity is particularly relevant in COPD, as peripheral lung is the site where most of the pathological processes take place. This compartment of the lungs cannot be explored using bronchial biopsies. The alternative would be performing post-mortem studies, but in this case clinical and functional characterisation of the subjects is problematic.

One real limitation of immunohistological studies is that they are not suitable for quantitative evaluation of an enzyme such as HO‐1. We assumed that the number of positively stained cells is related to enzyme activity, but this may not be true. The attempt to express the results of immunostaining as a score of intensity does not appear to overcome such limitation unless this score is validated by other measurements.