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Background The efficacy profile of roflumilast, a phosphodiesterase-4 inhibitor used for the treatment of chronic obstructive pulmonary disease (COPD), is well known. In asthma treatment, much less is understood about the role of roflumilast, particularly its mechanism of action and potential bronchodilatory effects. Aim To evaluate the therapeutic efficacy and mechanism of action of roflumilast in patients with asthma using data from eight placebo-controlled, double-blind phase I–III studies. Methods The studies were conducted at 14 sites in Europe, North America and South Africa from 1997 to 2005. The effect of treatment with 250 μg, 500 μg or 1000 μg roflumilast was compared with placebo in seven cross-over studies and one parallel-group study in 197 patients 18–70 years of age. Primary endpoints focused on the extent of the late allergic response after an allergen challenge, change in sputum cell eosinophil counts or exhaled nitric oxide (eNO), forced expiratory volume in 1 s (FEV 1 ) and exercise-induced bronchoconstriction. Secondary endpoints included the extent of the early allergic response and measurements of tumour necrosis factor α (TNFα), sputum cells and inflammatory markers. Results Roflumilast attenuated allergen-induced bronchoconstriction (FEV 1 ) in patients with asthma. Significant reductions in allergen-induced airway inflammation, including a reduction in both eosinophil and neutrophil counts were also observed and physiologic responses to allergen-induced challenge were confirmed by a significant reduction in TNFα. Side effects were similar to COPD, but did not include weight loss. Conclusions The results from these studies indicate that the anti-inflammatory effects of roflumilast observed in COPD are also seen in asthma and advance our understanding of its mechanism of action. All studies were funded by Takeda. Trial registration numbers available on ClinicalTrials.gov : NCT01365533 . [ABSTRACT FROM AUTHOR]

Background The combination of airway hyper-responsiveness, eosinophilic airway inflammation, and lung function impairment is considered as a hallmark of bronchial asthma. Since airway function might change with time in chronic asthma, the association between parameters which are characteristic of asthma could be different in subjects with different durations of the disease. Objective We assessed whether in patients with asthma the relationship between airway hyper-responsiveness, non-invasive markers of airway inflammation, and baseline lung function depended on the duration of the disease. Methods Sixty-six non-smoking patients with mild to moderate allergic asthma without corticosteroids were assigned to two groups, according to a duration of the disease (time interval since doctor's diagnosis) of either ≤ 16 years (median 8 years; mean FEV1 , 92.6% pred.; n = 34) or > 16 year (median 25 years; mean FEV1 , 87.9% pred.; n = 32). Results Groups did not differ statistically in PC20 FEV1 of methacholine, sputum composition, levels of exhaled nitric oxide (NO), lung function parameters, or history of treatment. There were significant correlations between PC20 FEV1 , eosinophils and NO in patients with a duration of the disease ≤ 16 year, but no relation to lung function. In contrast, patients with a duration > 16 year showed a correlation between PC20 FEV1 of methacholine and lung function but not eosinophils or NO. In both groups, eosinophils and NO were associated with each other. These results were corroborated by the statistical procedure of factor analysis that revealed ‘inflammation’ and ‘lung function’ as major entities and found ‘responsiveness’ to be associated with only one of them in each group. Conclusion Our data demonstrate that with a shorter duration of the asthmatic disease airway... [ABSTRACT FROM AUTHOR]

Indirect assessments have shown a superior lung deposition of HFA–BDP (Ventolair®/Qvar®) compared to CFC–BDP (Aerobec®). The aim of this study was to assess the concentrations of BDP and its metabolite 17-BMP in airways and peripheral tissue from resected lung specimens after inhalation of these BDP formulations.Immediately prior to surgery for lung cancer, 10 patients inhaled 1000 μg of either CFC–BDP (n=5) or HFA–BDP (n=5). Mouthwash was collected after inhalation, and serum before, during, and after surgery.There was no significant difference between CFC and HFA in the concentration of 17-BMP in bronchi (median, 4365 vs 4121 pg/g tissue). After CFC, concentrations of 17-BMP were lower in peripheral tissue (1424 vs 2089 pg/g; ANCOVA, p=0.001) and in serum taken immediately after inhalation (688 vs 1219 pg/ml, p<0.01). Furthermore, the CFC group showed a higher concentration of BDP in the mouthwash (17,660 vs 1320 ng/ml, p<0.05), but the concentration of 17-BMP was lower (452 vs 1028 ng/ml, n.s.).These findings indicate a predominantly peripheral deposition of HFA–BDP, in line with previous data. They also provide evidence for a faster uptake and metabolism of HFA–BDP, probably because BDP is dissolved in HFA and has a smaller particle size distribution than the CFC suspensions. [Copyright &y& Elsevier]