SummaryThis is the first multi-centre retrospective survey from the United Kingdom to evaluate the aetiology and diagnostic performance of tryptase in anaphylaxis during general anaesthesia (GA). Data were collected retrospectively (2005-12) from 161 patients [mean ± standard deviation (s.d.), 50 ± 15 years] referred to four regional UK centres. Receiver operating characteristic curves (ROC) were constructed to assess the utility of tryptase measurements in the diagnosis of immunoglobulin (Ig)E-mediated anaphylaxis and the performance of percentage change from baseline [percentage change (PC)] and absolute tryptase (AT) quantitation. An IgE-mediated cause was identified in 103 patients (64%); neuromuscular blocking agents (NMBA) constituted the leading cause (38%) followed by antibiotics (8%), patent blue dye (6%), chlorhexidine (5%) and other agents (7%). In contrast to previous reports, latex-induced anaphylaxis was rare (0·6%). A non-IgE-mediated cause was attributed in 10 patients (6%) and no cause could be established in 48 cases (30%). Three serial tryptase measurements were available in 34% of patients and a ROC analysis of area under the curve (AUC) showed comparable performance for PC and AT. A ≥ 80% PPV for identifying an IgEmediated anaphylaxis was achieved with a PC of >141% or an AT of >15·7 mg/l. NMBAs were the leading cause of anaphylaxis, followed by antibiotics, with latex allergy being uncommon. Chlorhexidine and patent blue dye are emerging important health-care-associated allergens that may lead to anaphylaxis. An elevated acute serum tryptase (PC >141%, AT >15·7 mg/l) is highly predictive of IgE-mediated anaphylaxis, and both methods of interpretation are comparable.

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Allergic asthma and rhinitis imposes a huge burden in terms of treatment costs, productivity loss and hospital admissions. IgE plays a significant role in the manifestation of these conditions and the identification of a monoclonal antibody that binds to IgE provides clinicians another therapeutic strategy in the management of these conditions. Blocking the effects of IgE by omalizumab, a recombinant humanized monoclonal antibody that selectively binds to IgE has been shown to be a useful adjunct in the treatment of allergic asthma and rhinitis. Omalizumab is effective as a steroid reducing agent in patients with severe asthma and is successful in decreasing asthma exacerbations. Omalizumab was well tolerated in clinical trials, however, the potential long-term side effects need careful monitoring. The high cost of the molecule could make this a therapeutic option in a small proportion of patients in whom there is a large unmet need.

Interaction among mediators such as bradykinin (BK), histamine (H), and prostaglandin (PG) D2 may contribute to reduction in airway caliber in asthma. Ten stable asthmatic subjects took part in a study to investigate possible mediator interaction. The provocative concentration of mediator required to reduce forced expiratory volume in 1 s (FEV1) by 12.5% from the starting baseline value (PC12.5) and that required to reduce the fall in FEV1 from 12.5 to 25% (PC25-12.5) of H, BK, and PGD2 were determined. On three subsequent occasions, subjects inhaled either the vehicle plus BK PC12.5 or the vehicle plus H or PGD2 PC25-12.5, and FEV1 was measured at regular time intervals up to 40 min. Predicted time course curves were calculated from these results. On two additional occasions, interactive time course studies were undertaken when the subject inhaled BK PC12.5 followed by H or PGD2 PC25-12.5. On a further three visits, the time courses of individual mediators were studied. When BK was combined with H and PGD2, the maximum fall in FEV1 and the rate of recovery after inhalation of the second mediator were not significantly different from those values of predicted time course responses for the same combination of mediator. Thus, by employing pharmacologically active concentrations of inhaled BK, H, and PGD2, which act through separate receptor mechanisms, we were unable to demonstrate any pharmacological interaction on airway caliber in asthma.