Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, attenuates allergen-induced asthmatic reactions.

BACKGROUND: Asthma is a chronic inflammatory disease with increasing incidence worldwide. Roflumilast is an oral, once-daily inhibitor of phosphodiesterase type 4 that prevents the breakdown of cyclic adenosine monophosphate levels, leading to inhibition of proinflammatory signaling. OBJECTIVE: The objective of this study was to investigate the effects of repeated doses of 250 or 500 microg of roflumilast on asthmatic airway responses to allergen. METHODS: Twenty-three patients with mild asthma with an FEV1 of 70% of predicted value or greater were enrolled in a randomized, double-blind, placebo-controlled, 3-period crossover study. Patients participated in 3 treatment periods (7-10 days) separated by washout periods (2-5 weeks). Patients received 250 microg of oral roflumilast, 500 microg of roflumilast, or placebo once daily. Allergen challenge was performed at the end of each treatment period, followed by FEV1 measurements over the ensuing 24 hours. RESULTS: Late asthmatic reactions (LARs) were reduced by 27% (P = .0110) and 43% (P = .0009) in patients treated with 250 and 500 microg of roflumilast, respectively, versus placebo. Roflumilast, 250 and 500 microg, also attenuated early asthmatic reactions by 25% (P = .0038) and 28% (P = .0046), although not to the same extent as LAR attenuation. Roflumilast was well tolerated. No serious adverse events or discontinuations caused by adverse events were reported. CONCLUSION: Once-daily oral roflumilast modestly attenuated early asthmatic reactions and, to a greater extent, LARs to allergen in patients with mild allergic asthma. Pronounced suppression of late responses in an allergen challenge model suggests that roflumilast might have anti-inflammatory activity, which could provide clinical efficacy in chronic inflammatory pulmonary diseases, such as asthma.

Rhinovirus is associated with severe asthma exacerbations and raised nasal interleukin-12.

BACKGROUND: Rhinovirus (RV) is associated with asthma exacerbations in longitudinal studies, but the role in patients with acute severe asthma who require admission to a hospital emergency room remains to be fully defined. The cytokines interleukin-10 (IL-10) and IL-12 may be elevated or suppressed by viral infections and contribute to a worsening of airway inflammation in asthmatics. OBJECTIVES: We assessed the association of RV with acute severe asthma and nasal IL-10 and IL-12. METHODS: Patients admitted to a hospital emergency asthma service had nasal aspirates (NAs) taken and peak expiratory flow (PEF) measured on admission and again 7, 28 and 56 days after admission. RV was sought in all NAs using a validated polymerase chain reaction assay and IL-10 and IL-12 were measured on admission and after 56 days in a subgroup of 22 asthmatics and 6 normal controls. RESULTS: Thirty-seven asthmatics with a reduced PEF (% predicted) of 50.4 +/- 2.5% (mean +/- SEM) on admission were studied. RV was detected in NAs of 13 patients (35%) on admission, in 6 of the 13 patients after 7 days (16%), in 1 patient after 28 and 56 days and was absent in controls. IL-10 was not increased on admission or after 56 days. Measurements of IL-12 were raised on admission compared to 56 days later in asthmatics with RV detectable (p = 0.04). In asthmatics without RV, nasal IL-12 levels were correlated with PEF measurements over this period (r = 0.5, p < 0.05). CONCLUSIONS: A temporal relationship between the presence of nasal RV and emergency room admission for acute severe asthma was found in one third of patients. Low levels of IL-10 during RV infections could contribute to unopposed synthesis of pro-inflammatory cytokines whilst increases in IL-12 may amplify nasal and endobronchial inflammation.

Risk factors for near-fatal asthma--a case-control study in a Western Cape teaching hospital.

BACKGROUND AND OBJECTIVES: To evaluate risk factors for asthma death such as access to health care, over-use of beta 2-agonists or under-use of inhaled corticosteroids in the Western Cape (WC) population, using near-fatal asthma (NFA) as a surrogate marker. SUBJECTS AND METHODS: Patients with NFA (cases) admitted to a WC teaching hospital were compared with patients with acute asthma in a case-control study using a structured questionnaire, clinical examination, arterial blood gas measurements, chest radiograph and pulmonary function measurements. RESULTS: Sixteen patients with NFA (cases) and 55 with acute asthma (controls) were prospectively enrolled. Duration of asthma, gender, smoking status and ethnicity were similar. Cases had significantly more previous mechanical ventilation (P < 0.05) and a trend towards more previous intensive care unit (ICU) admissions. No significant differences were found in primary health care variables. CONCLUSION: Our study demonstrates that patients with NFA constitute a significant number of emergency room (ER) admissions for acute asthma (30%) in our population. Similar to other studies, there was a trend for NFA toward more previous ICU admissions and mechanical ventilation. Relative under-use of beta 2-agonists the day before admission and fewer ER visits during the previous year in the NFA group, suggests an impaired perception of the severity of disease or a more rapid onset of symptoms. Negative factors such as inability to access health care or lack of medication supply were similar in both groups. The challenge remains to identify and manage high-risk patients effectively.