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The effect of inhaled leukotriene D4 and methacholine on sputum cell differentials in asthma. 1997

Z Diamant, and J T Hiltermann, and E L van Rensen, and P M Callenbach, and M Veselic-Charvat, and H van der Veen, and J K Sont, and P J Sterk
Department of Pulmonology, Leiden University Medical Centre, The Netherlands.

The cysteinyl leukotriene LTE4 has been shown to induce airway eosinophilia in asthmatics in vivo. This phenomenon has not yet been reported for LTD4. Hence, we examined the effect of inhaled LTD4 and a control bronchoconstrictor agent, methacholine, on cell differentials in hypertonic saline-induced whole sputum samples of 12 nonsmoking atopic asthmatic subjects (three women, nine men; 21 to 29 yr of age; FEV1, 74 to 120% pred; PC20FEV1 methacholine < 9.6 mg/ml). The study had a cross-over, placebo-controlled design consisting of 4 d separated by > or = 1 wk. On each randomized study day, the subjects inhaled five serial doses of either LTD4 (mean cumulative concentration: 95.7 microM) or methacholine (mean cumulative concentration: 542 mM) or five doses of their respective diluents (PBS/ethanol or PBS). The airway response was measured by FEV1, followed by sputum induction with 4.5% NaCl, 4 h postchallenge. Inflammatory cells (> or = 250) were counted twice on coded cytospins and expressed as percentages of nonsquamous cells. There was no significant difference in the maximal percent fall in FEV1 from baseline between LTD4 (mean +/- SEM, 49.5 +/- 4.4% fall) and methacholine (mean +/- SEM, 55.9 +/- 3.4% fall) (p = 0.11). LTD4 induced a significant increase in the percentage of sputum eosinophils as compared with its diluent (mean +/- SD, 26.6 +/- 21.3% and 10.2 +/- 8.8%, respectively; p = 0.025), whereas a similar trend for methacholine failed to reach significance (mean +/- SD, 19.1 +/- 22.9% and 7.8 +/- 5.8%, respectively; p = 0.11). There was no significant difference in the changes in the percentage of sputum eosinophils between LTD4 and methacholine (mean difference +/- SD, 7.5 +/- 12.5% eosinophils; p = 0.09). We conclude that LTD4 induces eosinophilia in sputum of asthmatic subjects 4 h after inhalation. Our data suggest that LTD4 recruits eosinophils into the airways of asthmatics in vivo, possibly by virtue of direct or indirect chemotactic properties, whereas an additional effect of vigourous airway narrowing per se cannot be excluded.

UI MeSH Term Description Entries
D008297 Male Males
D011657 Pulmonary Eosinophilia A condition characterized by infiltration of the lung with EOSINOPHILS due to inflammation or other disease processes. Major eosinophilic lung diseases are the eosinophilic pneumonias caused by infections, allergens, or toxic agents. Eosinophilia, Pulmonary,Eosinophilic Pneumonia,Loeffler Syndrome,Pneumonia, Eosinophilic,Eosinophilias, Pulmonary,Pulmonary Eosinophilias,Simple Pulmonary Eosinophilia,Tropical Eosinophilic Pneumonia,Eosinophilic Pneumonia, Tropical,Eosinophilic Pneumonias,Eosinophilic Pneumonias, Tropical,Pneumonias, Eosinophilic,Pulmonary Eosinophilia, Simple,Simple Pulmonary Eosinophilias,Syndrome, Loeffler,Tropical Eosinophilic Pneumonias
D001985 Bronchial Provocation Tests Tests involving inhalation of allergens (nebulized or in dust form), nebulized pharmacologically active solutions (e.g., histamine, methacholine), or control solutions, followed by assessment of respiratory function. These tests are used in the diagnosis of asthma. Allergen Bronchial Provocation Tests,Allergen Challenge, Endobronchial,Antigen Bronchial Provocation Tests,Bronchial Allergen Challenge,Bronchial Challenge Tests,Inhalation Provocation Tests,Provocation Tests, Bronchial,Endobronchial Challenge Tests,Allergen Challenge, Bronchial,Allergen Challenges, Bronchial,Allergen Challenges, Endobronchial,Bronchial Allergen Challenges,Bronchial Challenge Test,Bronchial Provocation Test,Challenge Test, Bronchial,Challenge Test, Endobronchial,Challenge Tests, Bronchial,Challenge Tests, Endobronchial,Challenge, Bronchial Allergen,Challenge, Endobronchial Allergen,Challenges, Bronchial Allergen,Challenges, Endobronchial Allergen,Endobronchial Allergen Challenge,Endobronchial Allergen Challenges,Endobronchial Challenge Test,Inhalation Provocation Test,Provocation Test, Bronchial,Provocation Test, Inhalation,Provocation Tests, Inhalation,Test, Bronchial Challenge,Test, Bronchial Provocation,Test, Endobronchial Challenge,Test, Inhalation Provocation,Tests, Bronchial Challenge,Tests, Bronchial Provocation,Tests, Endobronchial Challenge,Tests, Inhalation Provocation
D002452 Cell Count The number of CELLS of a specific kind, usually measured per unit volume or area of sample. Cell Density,Cell Number,Cell Counts,Cell Densities,Cell Numbers,Count, Cell,Counts, Cell,Densities, Cell,Density, Cell,Number, Cell,Numbers, Cell
D004804 Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Eosinophil
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000280 Administration, Inhalation The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract. Drug Administration, Inhalation,Drug Administration, Respiratory,Drug Aerosol Therapy,Inhalation Drug Administration,Inhalation of Drugs,Respiratory Drug Administration,Aerosol Drug Therapy,Aerosol Therapy, Drug,Drug Therapy, Aerosol,Inhalation Administration,Administration, Inhalation Drug,Administration, Respiratory Drug,Therapy, Aerosol Drug,Therapy, Drug Aerosol
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D001249 Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). Asthma, Bronchial,Bronchial Asthma,Asthmas

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