Eleven asthmatic subjects inhaled doubling concentrations of histamine until a near sixfold increase in total pulmonary flow resistance had been reached. This last concentration (C6) of histamine and methacholine was administered on two subsequent separate visits. Specific lung conductance (sGL) dropped to 18.6 +/- 7.9 (SD) and 19.1 +/- 10.3% of initial value after histamine and methacholine, respectively (NS). Whereas the peak action occurred in a similar interval (1-4 min), the mean duration of the subsequent plateau, defined as values of sGL within 20% of the maximum fall was 16.8 +/- 9.8 min for histamine and 74.6 +/- 53.7 min for methacholine (P less than 0.01). The recovery phase from the end of the plateau to base line lasted 25.5 +/- 14.4 min for histamine and 56.7 +/- 38.3 min for methacholine (P less than 0.01). The duration of plateau and recovery phases were not linked with base-line sGL, maximum fall in sGL, or C6. We conclude that for the same induced bronchoconstriction methacholine has a more prolonged action than histamine.

Purpose of Review The purpose of this review is to summarize the epidemiology, mechanisms, and management of cardiovascular complications of Bruton’s Tyrosine Kinase inhibitors (BTKIs). Recent Findings Ibrutinib increases the risk of atrial fibrillation, bleeding, and hypertension compared with non-BTKI therapies. The evidence to support an association between ibrutinib and other cardiovascular complications including ventricular tachyarrhythmias or cardiomyopathy is limited. Ibrutinib metabolism can be inhibited by some medications used to treat cardiovascular complications. The cardiovascular effects of more selective BTKIs, such as acalabrutinib, remain to be determined. Summary Future research should address the mechanisms underlying the cardiovascular complications of BTKIs and how best to manage them. The risks and benefits of more selective BTKIs as compared with ibrutinib require further evaluation.

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Eight asthmatic and six normal subjects had methacholine chloride inhalation tests on two visits. On first assessment the provocative concentration causing a 20% fall in forced expiratory volume in 1 s (PC20FEV1) was measured. On the second visit the provocative concentration causing a 35% fall in specific lung conductance (PC35sGL) was obtained in addition to the PC20FEV1. Lung resistance was continuously monitored to evaluate the bronchomotor effect of FEV1 maneuver. Results of PC20FEV1 were within one single twofold concentration on the two visits. In all subjects but one PC35sGL was lower than PC20FEV1, and in 10 instances this difference was superior to a single twofold concentration. The bronchodilator effect of FEV1 maneuver was significantly although loosely related to base-line airway caliber and excitability. However, we were unable to show a significant relationship between the differences between PC20FEV1 and PC35sGL and this bronchodilator effect. This suggests that other factors may explain the greater sensitivity of PC35sGL compared with PC20FEV1.

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