We thank Drs. Kinoshita and Matsuda for their interest in our study.1In that work, we did not seek to determine whether propofol protects against irritant-induced bronchoconstriction in the clinical situation established by previous clinical studies2,3and clinical experience. In contrast, we sought to identify signaling pathways of irritant-induced bronchoconstriction against which propofol might be effective.

We demonstrated that, at the same concentration, propofol was more effective at attenuating contractions induced by nonadrenergic, noncholinergic nerve stimulation or tachykinins compared with contractions induced by cholinergic nerve stimulation or acetylcholine.1This focus was selected because previous clinical studies4–6suggested that propofol's protective airway effects were via  blockade of cholinergic mechanisms.

Drs. Kinoshita and Matsuda are concerned about our comparison of in vitro  bath concentrations of propofol with those measured in plasma. Comparing clinically measured plasma concentrations of a drug with concentrations achieved at a cellular level in vitro  remains challenging. In vivo , although the majority of propofol is bound to serum proteins, extensive lung extraction of propofol has been demonstrated.7 In vitro , drug concentrations at the level of the airway smooth muscle cell rely on tissue diffusion, and there is no benefit from microvascular delivery of the drug to the tissue as occurs in vivo . Thus, different factors in vitro  and in vivo  dictate the drug concentrations achieved at the level of the airway smooth muscle cell. A direct comparison cannot be made until airway smooth muscle cellular concentrations are measured during in vivo  and in vitro  deliveries of propofol—a study that has yet to be done.

*Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. neil.r.gleason@hitchcock.org

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