Chung, Kian F.Kian F.ChungGibeon, DavidDavidGibeonSousa, Ana R.Ana R.SousaCorfield, JulieJulieCorfieldShaw, Dominick E.Dominick E.ShawFowler, Stephen J.Stephen J.FowlerFleming, Louise J.Louise J.FlemingRiley, JohnJohnRileyJeyasingham, ElisabethElisabethJeyasinghamRowe, AnthonyAnthonyRoweFichtner, KlausKlausFichtnerRoberts, GrahamGrahamRobertsBakke, PerPerBakkeGarnier, Christophe vonChristophe vonGarnierHorvath, IldikoIldikoHorvathRiccardo, PolosaPolosaRiccardoKrug, NorbertNorbertKrugDahlen, BarbaroBarbaroDahlenMusial, JacekJacekMusialPahus, LaurieLauriePahusMyles, DavidDavidMylesCompton, ChrisChrisComptonHigenbottam, Tim W.Tim W.HigenbottamMontuschi, PaoloPaoloMontuschiLarsson, LarsLarsLarssonSandstrom, ThomasThomasSandstromWagers, Scott S.Scott S.WagersHowarth, Peter H.Peter H.HowarthBel, ElisabethElisabethBelBansal, Aruna T.Aruna T.BansalDjukanovic, RatkoRatkoDjukanovicSterk, Peter J.Peter J.Sterk2022-03-042022-03-042014https://publica.fraunhofer.de/handle/publica/238555Rationale: A relatively important proportion of patients with severe asthma end up using a daily dose of oral corticosteroids (OCS) in addition to their high dose of inhaled corticosteroids (ICS). We have determined whether oral CS-dependent severe asthma is a distinct phenotype from those only on ICS. Methods: Participants were recruited from adult pulmonary clinics across Europe and severe asthma diagnosed according to IMI-criteria (Bel et al. Thorax 2011). They had either uncontrolled asthma as defined by the GINA guidelines AND/OR two or more severe exacerbations in the past 12 months. Asthma diagnosis was confirmed by a history of typical symptoms and either reversibility in FEV1 of >=12% and 200ml after 400 T-test, Mann Whitney U test and Chi-square test were used. Results: In the 374 severe asthma participants, 167 (44%) were on oral prednisolone. The oral prednisolone group was older but had similar FEV1 (% predicted) and BMI. There was a lower rate of cigarette smoking with lower proportion of current smokers and never-smokers, but a higher percentage with nasal polyps. There was no difference in atopy as measured by skin prick tests or RAST IgE. A higher proportion of patients had 2 or more exacerbations per year (68.3% vs 56.4%; p=0.02). A greater proportion of patients were using MDI and nebulised short-acting b-agonists and theophylline. Exhaled NO was raised (31 ppb vs 22 ppb; p<0.0001). In the 182 participants with sputum data (49%), there was a higher proportion of eosinophils in sputum of CS-dependent severe asthma (4.8% vs 1.6%; p<0.007), with no differences in neutrophils. Using a cut-off point of eosinophils >=3% and neutrophils>=65%, there was a greater proportion of eosinophilic (38% vs 30%) and of mixed granulocytic (23% vs 5%), at the expense of lower paucigranulocytic (14% vs 41%)(Chi-square: p<0.0001). Conclusions: CS-dependent severe asthma patients represent a more severe group of asthmatics compared to those not on oral steroids, characterised by higher inflammatory markers. This group may represent a CS-insensitive group. Analysis of associated lipidomic, transcriptomic and proteomic data may provide further support. Grant Support: Innovative Medicines Initiative.en616journal article