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Severe asthma patients on oral corticosteroid therapy as a distinct phenotype: The european U-BIOPRED cohort

: Chung, Kian F.; Gibeon, David; Sousa, Ana R.; Corfield, Julie; Shaw, Dominick E.; Fowler, Stephen J.; Fleming, Louise J.; Riley, John; Jeyasingham, Elisabeth; Rowe, Anthony; Fichtner, Klaus; Roberts, Graham; Bakke, Per; Garnier, Christophe von; Horvath, Ildiko; Riccardo, Polosa; Krug, Norbert; Dahlen, Barbaro; Musial, Jacek; Pahus, Laurie; Myles, David; Compton, Chris; Higenbottam, Tim W.; Montuschi, Paolo; Larsson, Lars; Sandstrom, Thomas; Wagers, Scott S.; Howarth, Peter H.; Bel, Elisabeth; Bansal, Aruna T.; Djukanovic, Ratko; Sterk, Peter J.

American Journal of Respiratory and Critical Care Medicine 189 (2014), Art. A2424
ISSN: 1073-449X
ISSN: 0003-0805
ISSN: 1535-4970
American Thoracic Society (ATS International Conference) <2014, San Diego/Calif.>
Fraunhofer ITEM ()

Rationale: 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.