Am. J. Respir. Crit. Care Med., Volume 164, Number 2, July 2001, 202-206

Pulmonary Gas Exchange and Sputum Cellular Responses to Inhaled Leukotriene D₄ in Asthma

ANDRÉS L. ECHAZARRETA, BARBRO DAHLÉN, GABRIEL GARCÍA, CARLOS AGUSTÍ, JOAN ALBERT BARBERÀ, JOSEP ROCA, SVEN-ERIK DAHLÉN, and ROBERT RODRIGUEZ-ROISIN

Servei de Pneumologia i Al·lèrgia Respiratòria, Departament de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; and Department of Internal Medicine at Karolinska Hospital and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

Inhalational challenges with inflammatory mediators may provoke lung function disturbances similar to those shown in spontaneous acute asthma. Cysteinyl leukotrienes (CysLTs) have recently been established as mediators of bronchoconstriction in asthma but their effects on pulmonary gas exchange in asthma have not been assessed. We therefore investigated the effects of leukotriene D₄ (LTD₄) challenge resulting in a significant decrease in FEV₁ (mean ± SE, by 32 ± 3%) in 13 nonsmoking, mild asthmatics. Respiratory system resistance (Rrs), and respiratory and inert gases were measured before and immediately after, and at 15 and 45 min after challenge. After bronchoprovocation, Rrs increased (by 106 ± 12%), Pa_O2 decreased (by 25 ± 4 mm Hg), and ventilation-perfusion distributions moderately to severely deteriorated, as shown by increases in the dispersions of pulmonary blood flow (Log SDQ, by 59 ± 12%) and alveolar ventilation (Log SDV, by 65 ± 20%) (p < 0.05 each). Sputum eosinophils (p < 0.05) and urinary LTE₄ (p < 0.005) increased after challenge. Despite the lack of mathematical correlations between spirometric and Rrs changes and gas exchange indices, the pattern of improvement of the functional variables after challenge ran in parallel. These findings support the evidence that CysLTs, in addition to being potent bronchoconstrictors, also provoke profound disturbances of pulmonary gas exchange in asthma.

Keywords: airway inflammation; bronchial challenge; cysteinyl leukotrienes; induced sputum; ventilation-perfusion relationships

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