Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 132, Issue 3, Pages 547-553Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2013.01.058
Keywords
Asthma; biomarkers; breath tests; eicosanoids; leukotriene B-4; lipoxin A(4)
Categories
Funding
- NIH/NLHBI [HL069349, HL107166, HL109172]
- NIH/NIAID [AI068084]
- NIH/NCRR [RR022292, RR025757, RR025758]
- National Institutes of Health (National Heart Lung and Blood Institute's Severe Asthma Research Program and Asthma Clinical Research Network)
- American Lung Institute
- KL2 Medical Research Investigator Training (MeRIT) award from Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources
- KL2 Medical Research Investigator Training (MeRIT) award from National Center for Advancing Translational Sciences, National Institutes of Health Award [8KL2TR000168-05]
- Merck
- National Institutes of Health
- Aerovance
- Amgen
- i3 Research (Biota)
- Genentech
- MedImmune
- Novartis
- Spanish Society of Allergy & Immunology (SEAIC Congress-Madrid)
- Western Society of Allergy, Asthma & Immunology (WSAAI-Maui)
- World Allergy Congress (WAC-Cancun)
- World Allergy Congress (WAC-India)
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Background: The relationship between anti-inflammatory lipoxins and proinflammatory leukotrienes might be important in the pathobiology and severity of asthma. Objective: We sought to investigate whether exhaled breath condensate (EBC) lipoxin and leukotriene measurements can noninvasively characterize the asthmatic diathesis and its severity. Methods: We measured lipoxin A(4) (LXA(4)) and leukotriene B-4 (LTB4) levels in EBC collected from patients with asthma of different severities and from healthy control subjects. Results: EBC LXA(4) and LTB4 levels are increased in asthmatic patients compared with those seen in healthy control subjects (LXA(4): 31.40 vs 2.41 pg/mL EBC, respectively [P < .001]; LTB4: 45.62 vs 3.82 pg/mL EBC, respectively [P < .001]). Although levels of both eicosanoids are increased in asthmatic patients, the LXA(4)/LTB4 ratio decreases with increasing asthma severity. It is 41% lower in patients with severe versus moderate asthma (0.52 vs 0.88, P = .034). EBC LXA(4) levels correlate with the degree of airflow obstruction measured by using FEV1 (r = 0.28, P = .018). An LXA(4) cutoff value of 7 pg/mL EBC provides 90% sensitivity and 92% specificity for the diagnosis of asthma (area under the curve, 0.96; P < .001). An LTB4 cutoff value of 11 pg/mL EBC provides 100% sensitivity and 100% specificity for the diagnosis of asthma (area under the curve, 1; P < .001). Conclusions: Proresolving and proinflammatory eicosanoids are generated in the airways of all asthmatic patients. The proportion of proresolving compounds decreases with asthma severity. These findings support the role for EBC eicosanoid measurements in the noninvasive diagnosis of asthma and suggest that proresolving eicosanoid pathways are dysregulated in patients with severe asthma.
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