Low molecular weight agents heighten inhalation challenge risk

Asthmatic reactions needing drug treatment are more likely to result from specific inhalation challenges (SIC) for occupational asthma with low molecular weight (LMW) agents than high molecular weight (HMW) agents, show the results of a Belgian study.

Olivier Vandenplas (Catholic University of Leuven, Yvoir) and colleagues say the findings could help guide the administration of SIC, which are rarely used - partly due to concerns over safety.

Patients treated at a single center were exposed to a control agent on day one and a suspected occupational agent on day two. The exposures were designed to be as close to real-world exposure as possible, for example, by nebulizing or vaporizing the agent.

The study included 335 patients in whom a fall in forced expiratory volume in 1 second (FEV₁) of at least 20% was observed during the SIC. Of these tests, 206 were with HMW agents and 123 were with LMW agents.

In total, 20% of patients needed an inhaled short-acting beta-agonist (SABA) following the SIC. Multivariate analysis showed that SIC involving a LMW agent increased the odds for needing inhaled SABA 2.5-fold compared with LMW agents (54 vs 32% patients).

In all, 40 asthmatic reactions were graded as moderate, and 10 were graded as severe, including one life-threatening case. SIC involving a LMW agent was the only significant predictor of a moderate or severe reaction, increasing the odds threefold compared with HMW agents (60 vs 33% patients).

Vandenplas and colleagues note that the majority of severe reactions took place within the first hour of exposure, highlighting this as a critical time window for close observation. In addition, half developed after exposures of 5 minutes or less, showing that even short exposures carry the risk for a severe reaction.

The authors say further research is needed to explore why patients react differently to LMW and HMW agents, but say it could be that they act through different pathophysiologic mechanisms.

Writing in Chest, they conclude that their results support prior recommendations to reduce the occurrence of severe reactions, which includes limiting exposure during challenges to very short durations and not exposing patients for more than 15 minutes on the first challenge day.

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