Letters to the Editor

	ABSTRACT

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The following is the abstract of the article discussed in the subsequent letter:

Verbanck, S., D. Schuermans, A. Van Muylem, M. Paiva, M. Noppen, and W. Vincken. Ventilation distribution during histamine provocation. J. Appl. Physiol. 83(6):1907-1916, 1997.We investigated ventilation inhomogeneity during provocation with inhaled histamine in 20 asymptomatic nonsmoking subjects. We used N₂ multiple-breath washout (MBW) to derive parameters S_cond and S_acin as a measurement of ventilation inhomogeneity in conductive and acinar zones of the lungs, respectively. A 20% decrease of forced expiratory volume in 1 s (FEV₁) was used to distinguish responders from nonresponders. In the responder group, average FEV₁ decreased by 26%, whereas S_cond increased by 390% with no significant change in S_acin. In the nonresponder group, FEV₁ decreased by 11%, whereas S_cond increased by 198% with no significant S_acin change. Despite the absence of change in S_acin during provocation, baseline S_acin was significantly larger in the responder vs. the nonresponder group. The main findings of our study are that during provocation large ventilation inhomogeneities occur, that the small airways affected by the provocation process are situated proximal to the acinar zone where the diffusion front stands, and that, in addition to overall decrease in airway caliber, there is inhomogeneous narrowing of parallel airways.

	LETTER

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Histamine-Induced Ventilation Distribution: Epithelial Factors or NO?

To the Editor: A recent article published in your journal (3) showed that, in otherwise asymptomatic subjects with airway hyperresponsiveness to inhaled histamine, airway narrowing occurs predominantly in airways proximal to the acini.

Inhibitory nonadrenergic noncholinergic (iNANC) nerves constitute a major pathway inhibiting excessive bronchoconstriction in humans. Recent investigations suggest that nitric oxide (NO) is one of the neurotransmitters released from iNANC. NO derived from the sympathetic nervous system regulates airway responsiveness to histamine in guinea pigs (1). Histamine also increases the release of NO from the epithelium three- to fourfold, compared with basal levels (2). Epithelial NO influences the airway smooth muscles, activates guanylate cyclase, produces cGMP, and induces relaxation of muscles. NO may have a number of other effects in addition to smooth muscle relaxation, including neurotransmission and enzyme activities. However, the type of epithelial layer varies in cellular structure and function depending on anatomic location. The proximal airway is characterized by increased thickness of the epithelial cell layer, taller cells, and a pseudostratified appearance. The epithelium becomes progressively thinner distally until, at the level of the bronchioles, it is composed of low cuboidal cells.

Consequently, the homeostatic role of epithelial NO in normal subjects after histamine-provocation test is different between trachea and airways proximal to the acini. This may be an additional mechanism for the ventilation distribution during histamine provocation.

	REFERENCES

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1.   Matsumoto, K., H. Aizawa, S. Takata, H. Inoue, N. Takahashi, and N. Hara. Nitric oxide derived from sympathetic nerves regulates airway responsiveness to histamine in guinea pigs. J. Appl. Physiol. 83: 1432-1437, 1997[Abstract/Free Full Text].

2.   Sadeghi-Hashjin, G., P. A. Henricks, G. Folkerts, A. K. Verheyen, H. J. van der Linde, and F. P. Nijkamp. Bovine tracheal responsiveness in vitro: role of the epithelium and nitric oxide. Eur. Respir. J. 9: 2286-2293, 1996[Abstract].

3.   Verbanck, S., D. Schuermans, A. Van Muylem, M. Paiva, M. Noppen, and W. Vincken. Ventilation distribution during histamine provocation. J. Appl. Physiol. 83: 1907-1916, 1997[Abstract/Free Full Text].

K. I. Gourgoulianis P. A. Molyvdas Department of Physiology University of Thessaly Medical School Larissa, 412 22, Greece

	REPLY

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To the Editor: Gourgoulianis and Molyvdas suggest that ventilation distribution in the conductive airways could in part be influenced by density differences in production of epithelium-derived NO through an inhibitory effect on bronchoconstriction within the conductive airway tree. However, it is very unlikely that phase III slopes could be attributed to serial differences (i.e., between successive airway generations) in degree of airway constriction within the conductive airway tree, where convective transport predominates. By contrast, parallel differences (i.e., between any two daughter branches within an airway generation) in degree of airway constriction can, indeed, lead to phase III slopes. Within the context of conductive airway narrowing, such as during histamine provocation, this points to the interest of verifying in situ whether parallel differences exist in density of airway constrictors (e.g., muscarinic receptors or cholinergic innervation) or, indeed, inhibitory NO.