Allergy in chronic airflow obstruction:a community-based population study

CARA is een van de meest voorkomende aandoeningen in geïndustrialiseerde landen. De term CARA (de afkorting voor chronische aspecifieke respiratoire aandoeningen) omvat de klinische aandoeningen astma, chronische bronchitis en emfyseem. De gevolgen van CARA kunnen aanzienlijk zijn, zowel individueel als sociaal-economisch: invaliditeit, school- en werkverzuim, ziekenhuisopname, vroegtijdig overlijden. Onze kennis ten aanzien van de oorzaken van CARA is echter nog beperkt. Het verwerven van meer inzicht, middels wetenschappelijk onderzoek, is daarom noodzakelijk. Het doel van deze studie is om in het bijzonder de rol van allergie bij CARA te onderzoeken, omdat allergie een van de mogelijke oorzaken van CARA kan zijn. Allergie is een overgevoeligheidsreactie die op kan treden na contact met allergenen uit de omgeving (door inademing, voedsel of huidcontact).... Zie: Samenvatting

Non-invasive Biomarkers in Asthma: Promises and Pitfalls

The asthma concept has evolved throughout the years: one major step in asthma management is the recognition of the chronic (airway) inflammation; another major step is further understanding of asthma heterogeneity and subsequent development of targeted therapies. While the concept of chronic inflammation, airway structural changes and their variability over time are widely accepted, their measurement and monitoring have gone through many hardships

Toll-like receptor 3 blockade in rhinovirus-induced experimental asthma exacerbations:A Randomized Controlled Study

BACKGROUND: Human rhinoviruses (HRVs) commonly precipitate asthma exacerbations. Toll-like receptor 3, an innate pattern recognition receptor, is triggered by HRV, driving inflammation that can worsen asthma. OBJECTIVE: We sought to evaluate an inhibitory mAb to Toll-like receptor 3, CNTO3157, on experimental HRV-16 inoculation in healthy subjects and asthmatic patients. METHODS: In this double-blind, multicenter, randomized, parallel-group study in North America and Europe, healthy subjects and patients with mild-to-moderate stable asthma received single or multiple doses of CNTO3157 or placebo, respectively, and were then inoculated with HRV-16 within 72 hours. All subjects were monitored for respiratory symptoms, lung function, and nasal viral load. The primary end point was maximal decrease in FEV1 during 10 days after inoculation. RESULTS: In asthmatic patients (n = 63) CNTO3157 provided no protection against FEV1 decrease (least squares mean: CNTO3157 [n = 30] = -7.08% [SE, 8.15%]; placebo [n = 25] = -5.98% [SE, 8.56%]) or symptoms after inoculation. In healthy subjects (n = 12) CNTO3157 versus placebo significantly attenuated upper (P = .03) and lower (P = .02) airway symptom scores, with area-under-the-curve increases of 9.1 (15.1) versus 34.9 (17.6) and 13.0 (18.4) versus 50.4 (25.9) for the CNTO3157 (n = 8) and placebo (n = 4) groups, respectively, after inoculation. All of the severe and 4 of the nonserious asthma exacerbations occurred while receiving CNTO3157. CONCLUSION: In summary, CNTO3157 was ineffective in attenuating the effect of HRV-16 challenge on lung function, asthma control, and symptoms in asthmatic patients but suppressed cold symptoms in healthy subjects. Other approaches, including blockade of multiple pathways or antiviral agents, need to be sought for this high unmet medical need

Relationship of Skin Test Reactivity and Eosinophilia to Level of Pulmonary Function in a Community-based Population Study

We studied the relationship of skin test reactivity (sumscore greater-than-or-equal-to 3) and eosinophilia(greater-than-or-equal-to 275 cells/mm3 blood), separately and combined, to the level of FEV1 in a community cohort. We used the regression analysis technique, adjusting for age and area of residence, and stratifying by gender and cigarette smoking. Eosinophilia, among men, was associated with lower levels of FEV1 in skin test negative subjects with moderate cigarette smoking (greater-than-or-equal-to 5 to 10 pack-tr: beta = -250 ml, p = 0.02; greater-than-or-equal-to 10 pack-yr: beta = -234 ml, p <0.01) and in skin test positive subjects who either never smoked (beta = -228 ml, p = 0.06) or had only a brief history of smoking (beta = -428 ml, p <0.01). Eosinophilia, among women, was significantly associated with lower levels of FEV1 in never smokers (beta = -95 ml, p <0.01), especially if subjects were skin test positive as well (beta = -289 ml, p <0.01). Moderate cigarette smoking was uncommon in women. These data suggest an association of indices of in-flammation (eosinophilia alone) and allergic inflammation (eosinophilia combined with skin test reactivity) with lower levels of FEV1, independent of the effect of cigarette smoking

Effect of mavoglurant (AFQ056) on the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and levonorgestrel in healthy women

Objective: To compare the pharmacokinetics (PKs) of a combination oral contraceptive (OC) when given alone or concomitantly with the selective metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056). Methods: This open-label, fixed-sequence, two-period study included 30 healthy female subjects aged 18–40 years. In Period 1, a single oral dose of an OC containing 30 μg ethinyl estradiol (EE)/150 μg levonorgestrel (LNG) was administered alone. In Period 2, OC was administered with a clinically relevant multiple-dose of 100 mg b.i.d. mavoglurant under-steady conditions. Plasma concentrations of EE and LNG were measured up to 72 hours post administration and PK parameters Cmax and AUClast were estimated using noncompartmental methods. Results: The geometric mean ratios of EE PK parameters Cmax and AUClast obtained with and without mavoglurant were 0.97 (90% confidence interval [CI]: 0.90-1.06) and 0.94 (90% CI: 0.86-1.03), respectively. The corresponding Cmax and AUClast for LNG were 0.81 (90% CI: 0.75-0.87) and 0.68 (90% CI: 0.63 0.73), respectively. Conclusions: In conclusion, the EE PK was unchanged, whereas Cmax and AUClast of LNG was approximately 19% and 32% lower, respectively, when given with mavoglurant. Further investigation regarding the impact on contraceptive efficacy is warranted