The impact of regular bisoprolol on the response to salbutamol in asthma: A double-blind randomized placebo-controlled crossover trial.

BACKGROUND AND OBJECTIVE: Non-selective beta-blockers impair the bronchodilator response to beta2 -agonists. Cardio-selective beta1 -blockers are less likely to cause this effect, yet they remain relatively contraindicated in asthma. We investigated whether the response to salbutamol is impaired during cardio-selective beta1 -blocker treatment in people with asthma. METHODS: A random-order, double-blind, placebo-controlled, non-inferiority, crossover study was conducted comparing up to 5 mg bisoprolol daily for 2 weeks with matching placebo, with an open-label extension of up to 10 mg bisoprolol daily. After each treatment period, mannitol was inhaled to induce bronchoconstriction with a 15% fall in forced expiratory volume in 1 s (FEV1 ). Immediately after mannitol challenge, salbutamol (100, 100 and 200 µg) was administered via spacer at 5-min intervals with repeated FEV1 measures. The FEV1 recovery with salbutamol was measured as an area under recovery curve (AUC). Based on earlier research, a clinically relevant non-inferiority limit of a 30% reduction in the AUC was set. RESULTS: A total of 19 adults with mild asthma and positive inhaled mannitol challenge completed the study. Adjusting for the FEV1 fall induced by mannitol and treatment sequence, the mean AUC response to salbutamol after bisoprolol was 5% lower than after placebo, with a one-sided 95% confidence interval (CI) of 26% lower. Thirteen participants completed the open-label extension up to 10 mg bisoprolol daily with mean AUC 11% higher after bisoprolol with a 95% CI of 5% lower. CONCLUSION: The bronchodilator response to rescue salbutamol after mannitol-induced bronchoconstriction is non-inferior during regular treatment with the cardio-selective beta1 -blocker, bisoprolol, compared to placebo. CLINICAL TRIAL REGISTRATION: ACTRN12618000306213 at https://www.anzctr.org.au.

Influences of breath sample re-use on the accuracy of lung cancer detection dogs.

Evaluations of dogs as lung cancer detectors using breath samples have produced a variety of results, some quite promising. Breath samples are typically collected onto a substrate and stored in a sealed container when not in use, but volatile compounds dissipate when the substrate is exposed during training and evaluation sessions. Collection of appropriate samples for training and testing dogs requires significant resources and strict control of recruitment and sample collection processes. Therefore, some researchers re-use samples while training dogs. No systematic evaluation of the effect of sample re-use on dogs' training performance has been conducted, so the influence of this potentially important training factor is not known. We trained seven dogs to indicate the presence of lung cancer positive breath samples using an automated apparatus. The samples were stored at -60 °C or -80 °C. Samples from 460 individuals who were classified as positive or negative for lung cancer were used for training samples. Individual samples were presented to dogs up to four times over a period of 2 years. As sample re-use increased, sensitivity declined (-6.65,p= < .001, 95% CI [-10.56, -2.76]), specificity increased (2.87,p= .036, 95% CI [.19, 5.55]), and the dogs' bias shifted in the direction of a negative indication bias (-.094,p= < .001, 95% CI [-.149, -.39]). However, there were no significant changes in the measure associated with the detectability of the target (-0.30,p= .285, 95% CI [-.087, .26]). All observed changes in performance across sample re-use were small. Therefore, these findings suggest that sample re-use may be appropriate for training, but additional research is required to determine which factors underly changes in performance as breath samples are re-used.

Changes in biomarkers of cardiac dysfunction during exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Cardiac dysfunction is associated with a higher mortality in exacerbations of chronic obstructive pulmonary disease (COPD). It is unknown how the heart responds to treatment of COPD exacerbations. We followed cardiac biomarker levels during hospital admissions for exacerbations of COPD and hypothesised that these biochemical markers of cardiac dysfunction might be affected the severity and treatment of exacerbations of COPD. METHODS: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin T were measured at admission, 12 h, 72 h, and clinical stability in 176 patients. In a second cohort (n = 93), associations between blood salbutamol concentrations and biomarker changes at 12 h were analysed. RESULTS: NT-proBNP increased from a geometric mean of 43 pmol/L at admission to 56 pmol/L at 12 h (p < 0.001), 53 pmol/L at 72 h (p = 0.045), and decreased to 25 pmol/L (p < 0.001) at stability. Troponin T levels decreased at 12 h (p < 0.001), but 15/174 (9%) patients had a clinically significant rise. Nebulised bronchodilator treatment and blood salbutamol concentrations were associated with greater increases in NT-proBNP rise at 12 h independently of baseline COPD or exacerbation severity and other treatments (p < 0.05). Nebulised bronchodilator and blood salbutamol concentrations also predicted rises in troponin T in univariate analyses (p < 0.05). CONCLUSIONS: NT-proBNP continues to rise after admission to hospital for COPD exacerbations and a minority of patients have clinically significant rises in cardiac troponins. These rises were associated with nebulised beta2-agonist treatment. These findings suggest that high doses of beta2-agonists may exacerbate cardiac dysfunction in COPD.