Among adolescents and adults with predominantly moderate-to-severe asthma, treatment with budesonide-formoterol was associated with a lower risk of asthma exacerbations than budesonide and a similar risk of serious asthma-related events. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01444430 .).

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Bacille Calmette-Guérin (BCG) vaccination generally leads to scar formation and tuberculin skin test (TST) reactivity. This study aimed at analysing these 2 parameters and their correlation in a setting with a low prevalence of tuberculosis. Retrospectively, we analysed 314 children and 390 adults living in Sweden and known from records or individual recall to have undergone BCG vaccination. A BCG scar was present in 161 (51%) of the children and in 340 (87%) of the adults. Among children with a scar, 94 (58%) were TST-positive (>or=6 mm) compared to 23 (15%) of 154 children lacking a visible scar. Among adults with a scar, 258 (76%) were TST- positive compared to 23 (46%) of 50 with no scar. Out of 152 non-vaccinated adults, 142 (94.4%) were TST-negative. When 175 TST-negative health care students were BCG-vaccinated in a prospective part of the study, 174 (99%) were found to develop a scar. In essence, the study showed a positive correlation between scar presence and TST reactivity. Furthermore, BCG vaccination of adults in the present setting resulted in consistent scar formation, while scar prevalence in previously vaccinated children was low.

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Questions have been raised about the effectiveness of Bacille Calmette-Guérin (BCG) vaccination against tuberculosis (TB) in adults. We therefore analysed the immune response after BCG vaccination in primary-vaccinated and revaccinated young adults. 31 tuberculin skin test (TST) negative healthy students were BCG-vaccinated; 15 were primary-vaccinated and 16 revaccinated. Tuberculin-induced lymphocyte transformation (LT) and cytokine production of peripheral blood mononuclear cells were studied before BCG vaccination, as well as after 2 months and 1 y. In the primary-vaccinated as well as the revaccinated group the LT response increased after 2 months and remained significantly higher than baseline values after 1 y. In both groups the interferon-gamma (IFN-gamma) levels increased significantly after 2 months and the increase was maintained after 1 y. LT increased more in the revaccinated group than in the primary-vaccinated group, while the increase in IFN-gamma response did not differ between the 2 groups. Both primary vaccination and revaccination of TST negative young adults caused a significant increase in the T-helper 1-type immune response, suggesting a protective effect against TB. The present in vitro results thus support the policy in several low-endemic countries of primary vaccination as well as revaccination of young adults at risk of TB exposure.

The aim was to study the tuberculin skin test in relation to immunological in vitro reactions in bacille Calmette-Guérin (BCG)-vaccinated healthcare workers.The present study was performed in Sweden, a country with a low incidence of tuberculosis, a high BCG vaccination efficacy and high tuberculin conversion rates. BCG-vaccinated healthcare workers (n~381) were tuberculin skin tested. From these, 11 subjects with negative tuberculin reactions (v6 mm) were matched for age and sex with 11 subjects with large positive reactions (¢15 mm). Lymphocyte transformation and the production of interferon-gamma (IFN-c) were analysed after stimulation in vitro of peripheral blood mononuclear cells with tuberculin purified protein derivative, heatkilled tubercle bacilli and a culture filtrate from tubercle bacilli.In the tuberculin-positive group the lymphocyte transformation response was 2-3 times larger, and IFN-c production was 7-10 times larger, than in the tuberculinnegative group (pv0.001).The present results suggest that a positive tuberculin skin test in bacille CalmetteGuérin-vaccinated subjects indicates a stronger immune response of the protective T-helper 1-type than does a negative test. In similar settings, the study supports the traditional practice of regarding the tuberculin skin test in bacille CalmetteGuérin-vaccinated subjects as an indicator of a protective immune response against tuberculosis.

Objective: To evaluate the efficacy and safety of three doses of glycopyrrolate metered dose inhaler (GP MDI) in patients with uncontrolled asthma despite treatment with inhaled corticosteroid/long-acting β 2 -agonists (ICS/LABA) with or without tiotropium, to characterize the benefit of triple therapy. Method: This phase II/III, double-blind study randomized patients to 24 weeks' treatment with twice-daily GP MDI 36 µg, 18 µg, 9 µg, or placebo MDI (all delivered via Aerosphere inhalers), or once-daily open-label tiotropium 2.5 µg. Patients continued their own ICS/LABA regimen throughout the study. The primary endpoint was change from baseline in forced expiratory volume in 1 s (FEV 1 ) area under the curve from 0 − 4 h (AUC 0 − 4 ) at Week 24. Secondary endpoints included patient questionnaires to measure asthma control or symptoms. Safety was also assessed. Results: The primary analysis (modified intent-to-treat) population included 1066 patients. The primary study endpoint was not met (changes from baseline in FEV 1 AUC 0 − 4 at Week 24 were 294 mL, 284 mL, 308 mL, 240 mL, and 347 mL for GP MDI 36 µg, GP MDI 18 µg, GP MDI 9 µg, placebo, and open-label tiotropium, respectively). There were no significant differences between treatment and placebo in secondary endpoints at Week 24. Post-hoc analyses using post-bronchodilator FEV 1 as the baseline measurement, or averaging values across multiple baseline visits, showed a dose-related response to GP MDI. The incidence of adverse events was low and similar across treatments. Conclusion: Although this study did not meet its primary endpoint, post hoc analyses identified a dose-related response to GP MDI when alternative definitions of baseline FEV 1 were used in the analyses.

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