ASTHMA

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

G Bochenek, E Niankowska, A Gielicz, M wierczyska, 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, Skawiska 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 9,11ß-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 9,11ß-PGF₂ level and only a borderline but significant increase in the urinary 9,11ß-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 9,11ß-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 9,11ß-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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