Asthma, Rhinitis, Other Respiratory Diseases
Exhaled leukotrienes and prostaglandins in asthma,☆☆

https://doi.org/10.1067/mai.2002.122461Get rights and content

Abstract

Background: Most of the studies investigating the role of leukotrienes (LTs) and prostaglandins (PGs) in asthma have used invasive (eg, bronchoalveolar lavage fluid) or semi-invasive (eg, sputum induction) techniques. Others have measured eicosanoids in plasma or urine, probably reflecting systemic rather than lung inflammation. Collection of exhaled breath condensate (EBC) is a noninvasive method to collect airway secretions. Objective: We sought to investigate whether eicosanoids are measurable in EBC, to show possible differences in their concentrations in asthmatic patients and healthy subjects, and to investigate whether exhaled eicosanoids correlate with exhaled nitric oxide (NO), a marker of airway inflammation. Methods: Twelve healthy nonsmokers and 15 steroid-naive patients with mild asthma were studied. Subjects attended on one occasion for pulmonary function tests, collection of EBC, and exhaled NO measurements. Exhaled LTB4-like immunoreactivity, LTE4-like immunoreactivity, PGE2-like immunoreactivity, PGD2-methoxime, PGF2α-like immunoreactivity, and thromboxane B2-like immunoreactivity were measured by means of enzyme immunoassays. Results: LTE4-like immunoreactivity and LTB4-like immunoreactivity were detectable in EBC in healthy subjects, and their levels in asthmatic patients were increased about 3-fold (P < .0001) and 2-fold (P < .0005), respectively. Exhaled NO was increased in asthmatic patients compared with healthy subjects (P < .0001). There was a correlation between exhaled LTB4 and exhaled NO (r = 0.56, P < .04) in patients with asthma. When measurable, prostanoid levels were similar in asthmatic patients and control subjects. Conclusions: Exhaled LTE4 and LTB4 are increased in steroid-naive patients with mild asthma. EBC may be proved to be a novel method to monitor airway inflammation in asthma. (J Allergy Clin Immunol 2002;109:615-20.)

Section snippets

Study subjects

Two groups of subjects were studied: 12 healthy nonsmokers and 15 patients with mild asthma who were nonsmokers (Table I)

. Subject characteristics*

Empty CellHealthy subjectsAsthmatic patients
No.1215
Age (y)30 ± 334 ± 2
Sex (F/M)7/58/7
SmokingNoNo
FEV1 (L)4.45 ± 0.273.56 ± 0.29
FVC (L)4.62 ± 0.303.89 ± 0.24
FEV1 (% predicted)93.7 ± 3.788.7 ± 3.9
FVC (% predicted)97.4 ± 2.893.8 ± 3.1
AtopyNo12
PC20 (mg/mL)>81.6 ± 0.5†
*Data are expressed as numbers or means ± SEM. †P < .01 compared with healthy subjects.

FVC , Forced

Results

LTE4-like immunoreactivity was increased in EBC in asthmatic patients (33.0 ± 3.8 pg; P < .0001; 95% confidence interval [CI], 24.9-41.0) compared with that in healthy subjects (13.0 ± 1.6 pg; 95% CI, 9.4-16.6; Fig 1, A ).

. A , LTE4-like immunoreactivity (LI) in EBC in healthy subjects (open squares) and asthmatic patients (filled squares) . B , LTB4-like immunoreactivity (LI) in EBC in healthy subjects (open squares) and asthmatic patients (filled squares) . LTE4-like immunoreactivity and LTB4

Discussion

In this study we have shown that LTE4-like immunoreactivity is increased in EBC in steroid-naive patients with mild asthma, who have about 3-fold higher levels than healthy subjects. Increased LTE4-like immunoreactivity levels in patients with asthma are consistent with a role for cysLTs in the pathophysiology of this disease. Most of the previous studies failed to show any increase in LTE4 levels in patients with mild asthma.10 However, LTE4 concentrations were generally measured in plasma or

References (29)

  • AA Mathe et al.

    Effect of prostaglandin F and E2 on airway conductance in healthy subjects and asthmatic patients

    Am Rev Respir Dis

    (1975)
  • GM Gauvreau et al.

    Protective effects of inhaled PGE2 on allergen-induced airway responses and inflammation

    Am J Respir Crit Care Med

    (1999)
  • JP Noveral et al.

    Role and mechanism of thromboxane-induced proliferation of cultured airway smooth muscle cells

    Am J Physiol

    (1992)
  • M. Kumlin

    Measurement of leukotrienes in humans

    Am J Respir Crit Care Med

    (2000)
  • Cited by (212)

    View all citing articles on Scopus

    Supported by the National Heart and Lung Institute.

    ☆☆

    Reprint requests: Paolo Montuschi, MD, Department of Pharmacology, Catholic University of the Sacred Heart, L.go F. Vito, 1, 00168 Rome, Italy.

    View full text