Aspirin causes bronchoconstriction in aspirin-intolerant asthma (AIA) patients by triggering cysteinyl-leukotriene (cys-LT) production, probably by removing PGE2-dependent inhibition. To investigate why aspirin does not cause bronchoconstriction in all individuals, we immunostained enzymes of the leukotriene and prostanoid pathways in bronchial biopsies from AIA patients, aspirin-tolerant asthma (ATA) patients, and normal (N) subjects. Counts of cells expressing the terminal enzyme for cys-LT synthesis, LTC4 synthase, were fivefold higher in AIA biopsies (11.5+/-2.2 cells/mm2, n = 10) than in ATA biopsies (2.2+/-0.7, n = 10; P = 0. 0006) and 18-fold higher than in N biopsies (0.6+/-0.4, n = 9; P = 0. 0002). Immunostaining for 5-lipoxygenase, its activating protein (FLAP), LTA4 hydrolase, cyclooxygenase (COX)-1, and COX-2 did not differ. Enhanced baseline cys-LT levels in bronchoalveolar lavage (BAL) fluid of AIA patients correlated uniquely with bronchial counts of LTC4 synthase+ cells (rho = 0.83, P = 0.01). Lysine-aspirin challenge released additional cys-LTs into BAL fluid in AIA patients (200+/-120 pg/ml, n = 8) but not in ATA patients (0. 7+/-5.1, n = 5; P = 0.007). Bronchial responsiveness to lysine-aspirin correlated exclusively with LTC4 synthase+ cell counts (rho = -0.63, P = 0.049, n = 10). Aspirin may remove PGE2-dependent suppression in all subjects, but only in AIA patients does increased bronchial expression of LTC4 synthase allow marked overproduction of cys-LTs leading to bronchoconstriction.

A short, easy-to-use health status questionnaire is needed in the multidimensional assessment of chronic obstructive pulmonary disease (COPD) in routine practice.

Pan-European data on health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) are lacking. This cross-sectional epidemiological study evaluated health status in 1817 COPD patients from an 'all-comers' primary care population in seven European countries (87% stable disease; 13% with current exacerbation) using: St George's Respiratory Questionnaire-COPD specific (SGRQ-C), the short form health survey (SF-12) and the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale. Mean total score for SGRQ was 44.7 ± 19.4 showing marked impairment of HRQL. Scores differed little between countries (range 39.2-50.1). Impairment was associated with the severity of airway obstruction, but within each GOLD stage the variation (SD) was wide [Stage I: 38.5 ± 19.3 (n = 223); Stage II: 40.4 ± 18.1 (n = 868); Stage III: 50.2 ± 18.6 (n = 551); Stage IV: 58.6 ± 17.7 (n = 144)]. Patients suffering an exacerbation had a worse SGRQ score (54.9 ± 19.3) than those with stable disease (43.3 ± 19.0). The presence of ≥3 co-morbidities (CM) was also associated with a significantly worse score (49.9 ± 19.1) vs. 1-2 CM (42.1 ± 19.1) or no CM (42.3 ± 18.6). Findings with the SF-12 and FACIT-F results were consistent with those from the SGRQ-C. This large observational primary care study shows that health status is significantly impaired in COPD patients of all severities, even in those with mild airway obstruction. Within each GOLD stage of severity there is considerable heterogeneity in HRQL impairment among patients. (Study number: 111749).

Although the main goal of asthma management guidelines is to achieve and maintain clinical control, reported levels of not well-controlled asthma remain high. The aim of this analysis was to compare the levels of asthma control and the associated impact on patients' health status in Europe in 2006, 2008 and 2010. An additional outcome was the comparison of the burden of asthma with diabetes. Data were obtained from the cross-sectional, self-reported, European National Health and Wellness Surveys conducted in France, Germany, Italy, Spain and the UK. Asthma control (Asthma Control Test™; QualityMetric, Inc., Lincoln, RI, USA) and health status (Short Form (SF)-12 health survey and the Work Productivity Loss and Activity Impairment questionnaire) were assessed. In 2010, the proportion of treated asthma patients assessed as having not well-controlled asthma was 53.5%, compared with 56.6% and 55.0% in 2008 and 2006, respectively. A significant reduction in not well-controlled asthma was observed in Germany between 2006 (72.3%) and 2010 (62.5%; p=0.005). Fluctuations in control levels were observed in other countries. For all surveys, having at least well-controlled asthma was associated with a significantly lower number of healthcare contacts in the previous 6 months, better mean±(SD) SF-12 scores for the physical (data for 2010: not well controlled 39.9±11.38, at least well-controlled 48.0±9.89; p<0.001) and mental (data for 2010: not well-controlled 40.6±10.95, at least well-controlled 45.0±10.91; p<0.001) components, and significantly less impact on Work Productivity Loss and Activity Impairment. Asthma and diabetes were associated with a similar overall negative impact on health status. A substantial proportion of asthmatics remain not well-controlled across five European countries, resulting in a significant impact on health resources and patients' health status. The overall burden of asthma appears to be similar to that of diabetes.