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Thorax 2004;59:459-464
© 2004 BMJ Publishing Group Ltd & British Thoracic Society


ASTHMA

Plasma 9{alpha},11ß-PGF2, a PGD2 metabolite, as a sensitive marker of mast cell activation by allergen in bronchial asthma

G Bochenek, E Nizankowska, A Gielicz, M Swierczynska, A Szczeklik

Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland

Correspondence to:
Correspondence to:
Professor A Szczeklik
Department of Medicine, Jagiellonian University School of Medicine, 31-066 Cracow, Skawinska 8, Poland; mmszczek{at}cyf-kr.edu.pl

Background: Prostaglandin D2 (PGD2) is a major cyclooxygenase product generated by activated mast cells during an allergic response. Assessment of PGD2 and its metabolites in patients with asthma has mostly been performed in urine, bronchoalveolar lavage fluid and induced sputum, whereas human plasma determinations have been performed only sporadically.

Methods: In 32 patients with allergic asthma and 50 healthy non-allergic controls, baseline plasma and urinary levels of 9{alpha},11ß-PGF2, a primary PGD2 metabolite, were assessed by gas chromatography/mass spectrometry. Serum tryptase levels were measured by fluoroenzyme immunoassay and urinary leukotriene E4 (LTE4) by ELISA. In a subgroup of 10 asthmatics (randomly selected from the 32 study patients) in whom bronchial allergen challenges with specific allergens (Dermatophagoides pteronyssinus, n = 4, mixed grass pollens, n = 6) were carried out, measurements were taken both before and after provocation.

Results: At baseline no significant differences between mean plasma and urinary levels of the PGD2 metabolite and serum tryptase levels were found in asthmatics or controls. Asthmatic patients had significantly higher urinary LTE4 levels. Allergen challenge resulted in a significant early increase in the mean plasma 9{alpha},11ß-PGF2 level and only a borderline but significant increase in the urinary 9{alpha},11ß-PGF2 level within 2 hours after provocation. The challenge did not produce statistically significant changes in serum tryptase levels. Urinary LTE4 levels remained significantly increased 4 hours after provocation.

Conclusions: PGD2 is actively involved in the early asthmatic response to allergens. Measurement of 9{alpha},11ß-PGF2 release into plasma rather than urine following allergen challenge is a sensitive marker of enhanced PGD2 synthesis, most probably due to mast cell activation.


Keywords: asthma; prostaglandin D2; plasma 9{alpha},11ß-PGF2; leukotriene E4

Abbreviations: EAR, early asthmatic response; FEV1, forced expiratory volume in 1 second; LAR, late asthmatic response; LTE4, leukotriene E4; PGD2, prostaglandin D2




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