@article{3001909,
    title = "Frequent exacerbators - a distinct phenotype of severe asthma",
    author = "Kupczyk, M. and ten Brinke, A. and Sterk, P.J. and Bel, E.H. and Papi, A. and Chanez, P. and Nizankowska-Mogilnicka, E. and Gjomarkaj, M. and Gaga, M. and Brusselle, G. and Dahlén, B. and Dahlén, S.-E. and Weersink, E. and Papadopoulos, N. and Oikonomidou, E. and Zervas, E. and Contoli, M. and Pauwels, R.A. and Joos, G.F. and de Rudder, I. and Schelfhout, V. and Richter, K. and Gerding, D. and Magnussen, H. and Siafakas, N.M. and Tzortzaki, E. and Samara, K. and Plataki, M. and Papadopouli, E. and Szczeklik, A. and Ziolkowska-Graca, B. and Kania, A. and Gawlewicz-Mroczka, A. and Duplaga, M. and Figiel, E. and Rabe, K.F. and Hiemstra, P.S. and Gauw, S. and van Veen, I. and Kips, J.C. and Johnston, S.L. and Mallia, P. and Campbell, D.A. and Robinson, D.S. and Kanniess, F. and Fabbri, L.M. and Romagnoli, M. and Vachier, I. and Devautour, C. and Meziane, L. and Vignola, A.M. and Pace, E. and Profita, M. and Holgate, S.T. and Howarth, P.H. and Wilson, S.J. and Hewitt, L. and Holoway, J.",
    journal = "Clinical and Experimental Allergy",
    year = "2014",
    volume = "44",
    number = "2",
    pages = "212-221",
    doi = "10.1111/cea.12179",
    keywords = "biological marker;  budesonide, adult;  aged;  article;  asthma;  clinical practice;  clinical study;  controlled study;  disease exacerbation;  drug megadose;  eosinophil;  female;  follow up;  forced expiratory volume;  forced vital capacity;  human;  lung function;  major clinical study;  male;  medical history;  middle aged;  morbidity;  mortality;  neutrophil;  onset age;  patient monitoring;  phenotype;  priority journal;  prospective study;  quality of life;  risk assessment;  risk factor;  severe asthma;  smoking;  sputum analysis;  young adult, asthma exacerbation;  risk factors for exacerbations;  severe asthma, Administration, Inhalation;  Administration, Oral;  Adolescent;  Adult;  Aged;  Asthma;  Eosinophils;  Female;  Follow-Up Studies;  Glucocorticoids;  Humans;  Male;  Middle Aged;  Monitoring, Physiologic;  Severity of Illness Index;  Sputum",
    abstract = "Background: Exacerbations represent a major source of morbidity and mortality in asthma and are a prominent feature of poorly controlled, difficult-to-treat disease. Objective: The goal of our study was to provide a detailed characterization of the frequent exacerbator phenotype and to identify risk factors associated with frequent and seasonal exacerbations. Methods: Ninety-three severe asthmatics (SA) and 76 mild-to-moderate patients (MA) were screened and prospectively followed up for 1 year (NCT00555607). Medical history, baseline clinical data and biomarkers were used to assess risk factors for frequent exacerbations. Results: During the study, 104 exacerbations were recorded in the SA group and 18 in the MA. Frequent exacerbators were characterized by use of higher doses of inhaled (1700 vs. 800 μg) and oral (6.7 vs. 1.7 mg) glucocorticosteroids, worse asthma control (ACQ score 2.3 vs. 1.4), lower quality of life (SGRQ score 48.5 vs. 33.3), higher sputum eosinophils (25.7% vs. 8.2%) and a more rapid decline in FEV1/FVC ratio (-0.07 vs. -0.01 ΔFEV1/FVC, frequent vs. non-frequent, respectively, P < 0.05). Exhaled NO > 45 p.p.b. and a history of smoking were associated with an increased risk of frequent exacerbations (odds ratios: 4.32 and 2.90 respectively). Conclusion and Clinical Relevance: We were able to distinguish and characterize a subphenotype of asthma subjects - frequent exacerbators - who are significantly more prone to exacerbations. Patients with FeNO > 45 p.p.b. and a history of smoking are at increased risk of frequent exacerbations and require careful monitoring in clinical practice. © 2013 John Wiley & Sons Ltd."
}