Asthma and lower airway diseaseExhaled breath condensate eicosanoid levels associate with asthma and its severity
Section snippets
Participants
All participants provided written informed consent that was approved by the institutional review board. We recruited adults with mild intermittent, moderate, and severe asthma to participate in a phenotypic characterization study as part of the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. Severe asthma was defined per the criteria developed by the American Thoracic Society Workshop on Refractory Asthma.22 Patients with moderate asthma were required to be taking
Participants' characteristics
Table I, Table II describe the demographic and phenotypic characteristics of the participants. Patients with severe asthma were the oldest among the 4 groups. Groups were similar with respect to the distribution of sex, race, and ethnicity. As expected, patients with severe asthma received much higher doses of ICSs and had lower lung function. There were no other significant differences between the patients with moderate and those with severe asthma, similar to what has been seen in the entire
Discussion
Using direct in vivo measurements from the airways, we demonstrate that the lipoxin and leukotriene pathways are upregulated in patients with asthma of all severities. Our data also provide in vivo confirmation that relative underproduction of lipoxins occurs with increasing asthma severity. Lastly, our data suggest that noninvasively obtained EBC measurements of representative eicosanoids from these pathways distinguish asthmatic from nonasthmatic patients with high sensitivity and
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Supported by NIH/NLHBI grants HL069349, HL107166, and HL109172; NIH/NIAID grant AI068084; and NIH/NCRR grants RR022292, RR025757, and RR025758.
Disclosure of potential conflict of interest: S. Kazani has received research and travel support from the National Institutes of Health (National Heart Lung and Blood Institute's Severe Asthma Research Program and Asthma Clinical Research Network) and the American Lung Institute. The work was conducted with the support of a KL2 Medical Research Investigator Training (MeRIT) award from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8KL2TR000168-05). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. M. E. Wechsler has consultant arrangements with GlaxoSmithKline, Novartis, Cephalon/TEVA, Sepracor/SUNOVION, Schering-Plough, NKT Therapeutics, Asthmatx/BSCI, Genzyme, MapPharma, Genentech, Boehringer Ingelheim, Merck, and Cytos and has received payment for lectures from Merck. B. D. Levy has received research support from the National Institutes of Health; has consultant arrangements with Novartis, Eisai, and Fresenius; and is coinventor on patents issued on lipoxins in airway diseases that were outlicensed by Brigham and Women's Hospital for clinical development. E. Israel has consultant arrangements with Abbott, Amgen, Cowen & Co, Infinity Pharmaceuticals, MedImmune (now AstraZeneca), Merck, newMentor, NKT Therapeutics, Ono Pharmaceuticals, Regeneron Pharmaceuticals, Schering Plough, TEVA Specialty Pharmaceuticals, Gilead Sciences, Johnson & Johnson, and Agenzia Italiana del Farmico; has provided expert testimony for Campbell, Campbell, Edwards & Conroy, Diedrich & Donohue, Ficksman & Conley, Ryan Ryan Deluca LLP, and Sullway & Hollis; has received grants from Aerovance, Amgen, i3 Research (Biota), Genentech, MedImmune, and Novartis; has received payment for lectures from Merck, the Spanish Society of Allergy & Immunology (SEAIC Congress-Madrid), Western Society of Allergy, Asthma & Immunology (WSAAI-Maui), and the World Allergy Congress (WAC-Cancun and WAC-India); and has received royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest.