Purpose of the Conference The purpose of the Transatlantic Airway Conference is to bring together investigators interested in basic and applied research directed at various aspects of airway physiology and pathophysiology. The Seventh Conference was held in Lucerne, Switzerland in January 1992.The theme of this year's meeting was the bronchial circulation. Under the experienced and skillful guidance of Adam Wanner, chairman ofthe meeting, the participants, who are acknowledged leaders in their respective scientific areas of research, identified the basic processes involved in the physiologic control of the bronchial circulation, the function of the microvascular circulation, and the biology of the endothelial cells.The free exchange of ideas also raised relevant new questions to be answered by future investigations. In this supplement are published the formal presentations that served as the basis for a productive interchange between experts coming from inside and outside the pulmonary scientific community. The Scientific Committee thanks the following speakers and discussants who made this conference so successful: S. Anderson, P. Barnes, J. Butler, S. J. Feinmark, G. Kaley, N. Granger, L. Laitinen, J. Lundberg, T. F. Luscher, A. Lockhart,..R. Matran, D. M. McDonald, E. R. McFadden, Jr., C. C. Michel, R. Michel, W. Mitzner, S. T. O'Rourke, P. Pare, G. Parsons, C. Persson, E. M. Renkin, R. K. Reed, B. Rippe, U. Ryan, J. Solway,A.E. Taylor, D. L. Traber, J. Widdicombe, and T. J. Williams. In addition, the Scientific Committee would like to thank G. Krick, M. T. Lopez-Vidreiro, and the Boehringer Ingelheim Company for their support and professionalskill.Without their help, the Transatlantic Airway Conferences would not be possible.

Scientific Committee: HOMER A. BOUSHEY University of California San Francisco, CA, USA ALAIN JUNOD

University of Geneva Geneva, Switzerland ANDRE ~ PERRUCHOUD

University of Basel Basel, Switzerland

Chairman's Summary Airway inflammation is considered to have a pivotal role in the pathogenesis of bronchial asthma and other forms of airway disease. Because the blood circulation typically participates in the inflammatory response at the AM REV RESPIR DIS 1992; 146:S1-S2

tissue level, the vasculature of the tracheobronchial tree can be expected to undergo structural and functional changes in these conditions. Based on observations made in other systemic vascular beds, the changes may include hyperemia, endothelial hyperpermeability, and new vessel formation. In addition, the vasculature must be critically involved in the recruitment of inflammatory cells to the airway, and in heat and water exchange, phenomena that pertain to bronchial asthma. During the past 10 yr, a considerable amount of new information has been generated on the morphology and the physiology of the airway circulation, a previously neglected vascular bed (1). This was paralleled by significant new observations in endothelial cell biology (2). The scientific committee of the Transatlantic Airway Conference therefore chose to devote its seventh annual meeting to the airway circulation. The objectives of the meeting wereto review what is currently known about the structure and function of the airway circulation, to relate them to relevant information on vascular biology in general, and to speculate on the possible role of the airway circulation in airway disease. It was recognized at the outset that only a minority of the data has been obtained in human subjects for technical reasons and that extrapolation of animal findings to human disease should be met with caution. The first session addressed the physiologic control of the airwaycirculation. Widdicombe pointed out that the subepithelial microvasculature receives a considerably greater fraction of total airway blood flowthan do deeper layers of the airway wall, that in large airways there is an additional peribronchial vascular bed, and that in some species there are venous sinusoids (severalhundred micrometers in diameter) whose roles remain elusive. He also discussed the fact that most non-neural and neural inflammatory mediators are vasodilators in the airway circulation, and one can conclude from these studiesthat there are multiple mechanisms underlying inflammatory vasodilation, in analogy to the mechanisms of bronchoconstriction. This has therapeutic implications if the prevention or reversal of bronchial hyperperfusion and hyperemia is a treatment goal. The neural regulation of bronchial vascular tone was studied by O'Rourke in dogs. By comparing bronchial artery rings with coronary artery rings in vitro, he found similarities between the two with respect to sympathetic and parasympathetic contraction and relaxation and the importance of the endothelium in mediating acetylcholine-induced relaxation. The vascular rings that were obtained near the root of the bronchial artery are unlikelyto represent resistance vesselsthat are probably at the arteriolar level and may exhibit different responses to autonomic agonists. This will have to be clarified with different experimental approaches. Another physiologic function that relates indirectly to the microvascular exchange vessels is lymphatic drainage. The methodology

required to study this function in the conducting airway has only recently been developed. Traber and coworkers have succeeded in cannulating a lymph duct in the trachea, and they found that the responses of the flow and protein concentration of lymph to hydrostaticand permeability edema are similar to those in the pulmonary circulation. These investigators also made the interesting observation that the maximal attainable lymph flow is greater in permeability edema than in hydrostaticedema, suggesting that the flow of lymph is not a passive phenomenon and that inflammatory mediators influence the dynamics of the lymphatic circulation by an as yet unknown mechanism. There was an enthusiastic discussion about the role of the airway circulation in heat and water exchange and in exercise- and hyperventilation-induced bronchoconstriction. McFadden reported the results of sophisticated physical measurements in the bronchi of intact human subjects, and he suggested that asthmatics have an exaggerated vasodilator response to airway cooling caused by hyperventilation, and that the vasomotor response is an important pathogenetic factor in hyperventilation-induced bronchial obstruction. The accentuated blood flow response in asthmatics could narrow the airway directly by the mechanical effect of hyperemia or indirectly by an as yet unknown mechanism. This viewwas challenged by Anderson who argued that neither a rapid rewarming nor an abnormal temperature gradient are prerequisites for the airways to narrow in response to hyperpnea. Instead, she suggested that the surface liquid loss during hyperventilation and its effect on the osmolality of airway tissue and surface liquid could be sufficient to trigger mediator secretion by inflammatory cells (present in the airway of asthmatic patients) and neurons, and that the airway obstruction could result from airway smooth muscle contraction and microvascular hyperpermeability produced by those mediators (3). The increased vascular response would also be related to mediator release but constitute an epiphenomenon rather than the cause of airway narrowing. Clearly, more experimental data are needed to resolve this controversy. The session addressing physiologic control was closed out by a review of the effects of blood flow on airflow. Specifically,Lockhart wished to answer the question if alterations in the airway circulation narrow the bronchial lumen. He concluded from his own observations and from those made by others in animals and in humans that hyperemia,hyperpermeability leading to fluid accumulation in the airwaywall and lumen, and hydrostaticpressure-dependent autonomic reflexescausing an increase in bronchomotor tone can all increase airflow resistance, but that these processes make only a minor contribution to baseline airflow obstruction in airwaydisease. However, although prenarrowing of the airway caused by hyperemia and hyperpermeability per se may increase airflow resistance 81

Airway Circulation. Proceedings from the 7th Transatlantic Airway Conference. Lucerne, Switzerland, January 1992.

Purpose of the Conference The purpose of the Transatlantic Airway Conference is to bring together investigators interested in basic and applied resear...
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