Harold H. Newball

Collateral Ventilation in Man

To determine whether collateral ventilation (defined as the ventilation of alveolar structures through passages or channels that bypass the normal airways) changes with age or emphysema, we compared the mechanics of collateral ventilation in seven young normal subjects, three old normal subjects and five patients with emphysema. In supine normal subjects at the end of a quiet expiration, resistance to airflow was greater through collateral channels than through bronchi and bronchioles. In emphysema, airways resistance could exceed collateral resistance, causing air to flow preferentially through collateral pathways. We conclude that high collateral resistance minimizes collateral airflow in supine normal subjects. When peripheral airways become obstructed or obliterated in emphysema, collateral channels may provide for more even distribution of ventilation.

Release of leukocyte kallikrein mediated by IgE

BRADYKININ is a vasoactive nonapeptide believed to mediate various acute inflammatory conditions1. Although its production in plasma is well defined1, an understanding of its role in disease is hampered by the lack of information about the mechanism by which it can be generated by an immune process or by any stimulus other than clotting. Immune release of a kinin-generating factor from perfused sensitised guinea pig lung has been reported2,3. The release is not, however, calcium-dependent and the factor may be a product not of the primary allergic reaction, but of a secondary event4. Substantial information is available, however, about the release of other mediators of inflammatory or allergic reactions—histamine, SRS-A, and ECF-A5. These are secreted after antigen challenge of basophils and mast cells sensitised with IgE antibody6–7. The release depends on calcium and temperature, requires energy and is controlled by hormone-receptor interactions which influence the intracellular level of cyclic nucleotides10–13. We have now demonstrated the immune release of an enzyme from human leukocytes that hydrolyses p-toluene sulphonyl-L-arginine methyl ester (TAMe) and generates bradykinin from citrated human plasma. The release is initiated by the interaction of antigen or anti-IgE with cell-bound IgE6,14 and seems to be similar in mechanism to the release of histamine and the other mediators of the allergic response.