Last word on viewpoint: unresolved mysteries.

TO THE EDITOR: We thank those colleagues (see Ref. 1) who have taken the time to comment on our Viewpoint. Our interpretation of these comments is that there is general agreement that there remain uncertainties about how peripheral lung structure changes with lung inflation and deflation. We focused on a simple experiment that measured a mean linear dimension in the peripheral lung, and although only Dr. Frazer found problems with the interpretation of these published data, we will briefly comment on the other letters with specific issues. We agree with Dr. Woods and Dr. Nieman, that our studies have more similarities than differences, but that the essential question remains unresolved. Dr. Weibel emphasizes the important point (with which we agree) that proper acinar inflation and deflation requires a structural and surface continuum from airways to the visceral pleura. Indeed, this fact likely will make attempts to regenerate parenchymal regions in destroyed regions of emphysematous lungs impossible. Dr. Frazer focuses on the potential role of air trapping and menisci in the recruitment process and the potential problems with inflation from very low volumes. However, in our experiments, there was no gas trapping and we observed the same results when lungs were inflated from FRC. Dr. Schittny focuses on lung development, suggesting that alveolar folding can explain recruitment in mature lungs and that opening and closing of units is a phenomenon defined by surfactant and surface tension. As we have not attempted to provide a mechanistic explanation, we are comfortable with his speculations. Finally, we hope that our Viewpoint and these letters will help stimulate further mechanistic research to explain in anatomic detail how the acinar structure expands and contracts in health and disease.