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Prevalence and phenotypic characteristics of severe adult-onset asthma in the U-Biopred cohort

: Hekking, Pieter-Paul; Wagener, Ariane H.; Sousa, Ana R.; Fowler, Stephen J.; Bakke, Per; Frey, Urs; Krug, Norbert; Hashimoto, Simone; Woodcock, Ashley; Chanez, Pascal; Montuschi, Paolo; Bisgaard, Hans; Corfield, Julie; Howarth, Peter H.; Djukanovic, Ratko; Chung, Kian Fan; Fleming, Louise; Riley, John; Jeyasingham, Elisabeth; Fichtner, Klaus; Rowe, Anthony; Roberts, Graham; Singer, Florian; Geiser, Thomas; Horvath, Ildiko; Riccardo, Polosa; Vissing, Nadja H.; Dahlen, Babro; Musial, Jacek; Murray, Clare S.; Myles, David; Compton, Chris; Higenbottam, Tim W.; Vestbo, J.; Pahus, Laurie; Larsson, Lars; Sandstrom, Thomas; Shaw, Dominic; Wagers, Scott S.; Sterk, Peter J.; Bansal, Aruna T.; Bel, Elisabeth

American Journal of Respiratory and Critical Care Medicine 189 (2014), Art. A3697
ISSN: 1073-449X
ISSN: 0003-0805
ISSN: 1535-4970
American Thoracic Society (ATS International Conference) <2014, San Diego/Calif.>
Fraunhofer ITEM ()

Rationale: A recent study has shown that severe adult-onset asthma is a distinct clinical phenotype, characterized by absence of atopy, nasal polyposis, higher FeNO, persistent eosinophilic airway inflammation and higher blood neutrophil counts [Amelink et al, JACI 2013].
The aim of the present study was to assess the prevalence and phenotypic characteristics of adult-onset disease amongst patients with severe asthma.
Methods: This was a cross-sectional analysis of the U-BIOPRED severe asthma cohort. Patients were recruited from tertiary pulmonary outpatient clinics. Asthma diagnosis was confirmed by a history of typical symptoms and one of the following criteria: reversibility in FEV1 of >=12% and 200ml after 400mcg inhaled salbutamol OR airway hyper-responsiveness (PC20 <8 mg/ml) OR diurnal PEF variation OR a decrease in FEV1 of 12% within four weeks after treatment tapering. A diagnosis of severe asthma was based on international IMI-criteria (Bel et al. Thorax 2011). All patients had either uncontrolled asthma as defined by the GINA guidelines AND/OR two or more severe exacerbations in the past 12 months, despite the use of maximal doses of inhaled corticosteroids and long-acting beta-2-agonists. Patients were classified as severe adult-onset asthma (asthma diagnosed >18 years) or as severe childhood-onset asthma. (Ex)smokers (143 patients, 37.1%) were included. Clinical and functional characteristics and inflammatory markers were collected and independent T-test, Mann Whitney U test and Chi-square test were used for group comparisons. Univariate and multivariate logistic regression analyses were performed to determine factors associated with severe adult-onset asthma.
Results: 216 out of 385 (56.1%) patients with severe asthma had adult-onset disease. Compared with patients with severe childhood-onset asthma, patients with severe adult-onset asthma had higher prevalence of male gender (43% vs 30%, p=0.01), were heavier smokers (8.3 (0-108) vs 2.9 (0-67.5) pack-years, p<0.001), had higher FeNO levels (geometric-mean±gsd 29±2.3 vs 23±2.1ppb, p =0.018), higher rate of positive reversibility test (20±19.2 vs 15%±14.8, p=0.02), and higher blood and sputum eosinophil counts (geometric-mean±gsd 3.27%±0.04 vs 2.11%±0.98, p<0.001; 14% (0-74.15) vs 6.4% (0-58.0), p<0.001). Multiple logistic regression analysis showed that a higher number of pack-years and higher blood eosinophil counts were independently associated with adult-onset of the disease (Table 1).
Conclusions: These results show that more than half of patients with severe asthma in tertiary care have adult-onset asthma. A higher number of pack-years and higher blood and sputum eosinophil counts are independently associated with severe adult-onset asthma. This suggests a distinct phenotype, characterized by eosinophilia and/or positive smoking history.