Insights, attitudes, and perceptions about asthma and its treatment: a multinational survey of patients from Europe and Canada.

BACKGROUND: Asthma surveys completed within the past 10 years in the Americas and the Asia-Pacific region have shown significant underassessment of asthma severity in addition to undertreatment of asthma and have suggested the need to improve long-term asthma management. In this study, we examined the frequency of asthma symptoms and severe episodes, patients' perceived asthma control, and use of asthma medications in Europe and Canada. METHODS: The Asthma Insight and Management survey (54 questions) was conducted in Europe (Germany, Italy, Spain and the United Kingdom) and Canada from June 14 through July 28, 2010. Telephone interviews were conducted with randomly screened patients or parents of adolescents (aged 12-17 years) with asthma; patients younger than 12 years of age were excluded from the survey. Responses were reported separately for each country and in total for all five countries. RESULTS: Seventy-five thousand three hundered thirty-five households were screened, and 2003 patients were interviewed. The survey respondents represented a wide range of severity. Overall, 26 % of patients reported symptoms daily or most days over the past 4 weeks, but most patients (81 %) perceived their asthma to be well or completely controlled. Over the past year, 41 % of patients had episodes of frequent/severe symptoms, and 50 % reported acute treatment (e.g. hospitalization, emergency visit, unscheduled physician visit) for asthma. Across countries, 52 % of patients reported taking controller medication every day over the past year, 27 % reported not taking any controller medication, and 14 % reported stopping controller treatment for 3 months or longer the last time they stopped. Many patients considered asthma well controlled if each year they had only two urgent doctor visits (50 %), three or four exacerbations (60 %), and/or one emergency room visit (41 %). DISCUSSION: This is the largest survey of patients with asthma in Europe and Canada in more than a decade. CONCLUSION: In 2010, many surveyed patients in Europe and Canada reported features indicating uncontrolled asthma, yet the majority believed they were well controlled, indicating that they had low expectations of long-term asthma management. Use of controller medications was substantially less than recommended in treatment guidelines.

300IR 5-Grass pollen sublingual tablet offers relief from nasal symptoms in patients with allergic rhinitis.

BACKGROUND: 300IR 5-grass pollen sublingual immunotherapy tablets have been approved for the treatment of allergic rhinitis (AR) with or without conjunctivitis in adults and children >5 years with grass pollen allergy. This study was designed to review data on nasal symptoms with 300IR 5-grass pollen sublingual tablets in adults and children. METHODS: We reviewed data from four double-blind, placebo-controlled, randomized clinical trials. Two groups of patients who received a daily dose of either placebo or 300IR 5-grass pollen sublingual tablets starting 4 months before the expected start of the pollen season and continuing through the season were compared (analysis of covariance) for scores of sneezing, rhinorrhea, nasal pruritus, nasal congestion, total nasal symptom score (TNSS), and adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores. RESULTS: Data for 266 children (one pediatric trial) and 1036 adults (three trials) were analyzed. Compared with the placebo groups, mean TNSS in the 300IR groups was lower by 22% in children and 19-36% in adults. Among the four nasal symptoms, the lowest scores relative to placebo were for nasal congestion in children (31%) and adults (43%). Mean adult RQLQ scores were 21-31% lower in the 300IR group than in the placebo group. CONCLUSION: Allergen immunotherapy with 300IR 5-grass pollen sublingual tablets was consistently associated with AR symptom relief in adults and children and provided a clinically meaningful improvement in quality of life.

The endocannabinoid arachidonyl ethanolamide (anandamide) increases pulmonary arterial pressure via cyclooxygenase-2 products in isolated rabbit lungs.

Several cannabinoids elicit systemic vasodilation, mainly via CB1 cannabinoid and vanilloid receptors. However, effects in the pulmonary circulation are unknown. Using the isolated, ventilated, buffer-perfused rabbit lung, we have shown that the endocannabinoids arachidonyl ethanolamide (anandamide) and 2-arachidonyl glycerol (2-AG) dose-dependently increase pulmonary arterial pressure (+19.9 +/- 3.4 mmHg, 5 microM, and +39.5 +/- 10.8 mmHg, 0.4 microM, respectively). 2-AG induced lung edema. The CB1 receptor antagonist AM-251 (0.1 and 5 microM) and the VR1 vanilloid receptor antagonist capsazepine (10 microM) failed to reduce anandamide's effects. The metabolically stable anandamide and 2-AG analogs R-methanandamide and noladin ether, Delta9-tetrahydrocannabinol, and the synthetic cannabinoid HU-210, which is no arachidonic acid product, were without effect. The unspecific cyclooxygenase (COX) inhibitor aspirin (100 microM, P < 0.001) and the specific COX-2 inhibitor nimesulide (10 microM, P < 0.01) completely prevented pulmonary hypertension after 5 microM anandamide. COX-2 RNA was detected in rabbit lungs. The synthetic thromboxane receptor antagonist SQ 29,548 was without effect, but the specific EP1 prostanoid receptor antagonist SC-19220 (100 microM) inhibited the pressure increase after anandamide (P < 0.05). PCR analysis detected fatty acid amidohydrolase (FAAH), an enzyme that degrades endocannabinoids, in rabbit lung tissue. Furthermore, the specific FAAH inhibitor methyl arachidonyl fluorophosphonate (0.1 microM) blocked pressure effects of anandamide (P < 0.01). Finally, anandamide (99 +/- 55 pmol/g) and 2-AG (19.6 +/- 8.4 nmol/g) were found in native lungs. We conclude that anandamide increases pulmonary arterial pressure via COX-2 metabolites following enzymatic degradation by FAAH into arachidonic acid products.

The oxidants hypochlorite and hydrogen peroxide induce distinct patterns of acute lung injury.

Oxidative stress due to activated neutrophils, macrophages and endothelial cells plays a crucial role in acute lung injury. This study compares the effects of the nonradical oxidants hypochlorite (HOCl) and hydrogen peroxide (H2O2) on pulmonary artery pressure [PAPtorr], capillary filtration coefficient (Kf,c), tissue lipid peroxidation (LPO) and reduced glutathione (GSH) depletion. HOCl, H2O2 (1000 nmol min(-1)) or buffer (control) is infused into isolated rabbit lungs. PAP, K(f,c) and lung weight were measured. Experiments were terminated after 105 min or when fluid retention exceeded 50 g. Lung tissue was analyzed for LPO products and GSH. The oxidants induced comparable maximum effects. However, the patterns of lung injury were distinct: H2O2 infusion evoked an early biphasic pressure response (DeltaPAPmax 2.8+/-0.22/4.2+/-0.37 after 5.7+/-1.4/39+/-4.0 min) and a sixfold increase in Kf,c after 90 min. HOCl application caused a late pressure response (DeltaPAPmax 7.6+/-1.7 after 50.6+/-3.7 min) and a sevenfold increase in Kf,c after 60 min. H2O2-induced effects were attenuated by desferal. This may suggest an involvement of transition metal catalysed hydroxyl radical formation. Different oxidants induced distinct patterns of changes in PAP and Kf,c , which are accompanied by a comparable accumulation of LPO products and by a distinct degree of GSH depletion.

Tissue lipid peroxidation and reduced glutathione depletion in hypochlorite-induced lung injury.

STUDY OBJECTIVE: Neutrophils are involved in acute lung injury during ARDS via several mechanisms. This study focuses on neutrophil-derived oxidative stress. Hypochlorite is a major neutrophil-derived oxidant. This study characterizes hypochlorite-induced acute changes in pulmonary circulation and the involvement of tissue lipid peroxidation (LPO) and reduced glutathione (rGSH) depletion. METHODS: Hypochlorite (500, 1,000, and 2,000 nmol/min) or buffer (control) were infused into isolated rabbit lungs. Pulmonary artery pressure (PAP), capillary filtration coefficient (Kf,c) [10(4)/mL/s/cm H(2)O/g], and lung weight were measured. Experiments were terminated after 105 min or when fluid retention was > 50 g. Lung tissue was frozen immediately after termination of the experiments and analyzed for LPO products and rGSH (nanomoles per milligram of protein). RESULTS: Baseline PAP and Kf,c values averaged from 6.1 to 6.5 mm Hg and from 0.97 to 1.23, respectively, in all groups. Hypochlorite infusion of 500, 1,000, and 2,000 nmol/min (n = 5 to 7 per group) evoked an increase (mean +/- SEM) in maximum PAP (PAPmax) [12.9 +/- 2.1, 14.3 +/- 1.7, and 13.3 +/- 2.2 mm Hg], in maximum Kf,c (Kf,cmax) [1.9 +/- 1.2, 6.34 +/- 1.2, and >10.0], and in tissue LPO products (1.7 +/- 0.06, 2.1 +/- 0.06, and 2.3 +/- 0.11 vs 1.4 +/- 0.04 in controls), and a decrease in tissue rGSH (73.4 +/- 8.7, 43.0 +/- 9.6, and 50.4 +/- 7.2 vs 139 +/- 12.6 in controls). Parameters of lung injury (PAPmax and Kf,cmax) of each single experiment were closely correlated with tissue rGSH but did not correlate with tissue LPO products. All changes are significant (p < 0.05) vs control. CONCLUSION: The neutrophil-specific oxidant hypochlorite induces acute lung injury, rGSH depletion, and LPO in isolated rabbit lungs. The lung injury correlates with rGSH depletion, suggesting an important mechanistic role in hypochlorite-induced acute lung injury.