Cues such as odours that do not per se evoke bronchoconstriction can become triggers of asthma exacerbations. Despite its clinical significance, the neural basis of this respiratory nocebo effect is unknown.

We investigated this effect in a functional magnetic resonance imaging (fMRI) study involving 36 healthy volunteers. The experiment consisted of an experience phase in which volunteers experienced dyspnoea while being exposed to an odorous gas ("Histarinol"). Volunteers were told that Histarinol induces dyspnoea by bronchoconstriction. This was compared with another odorous gas which did not evoke dyspnoea. Dyspnoea was actually induced by a concealed, resistive load inserted into the breathing system. In a second, expectation phase, Histarinol and the control gas were both followed by an identical, very mild load. Respiration parameters were continuously recorded and participants rated dyspnoea intensity after each trial.

Dyspnoea ratings were significantly higher in Histarinol compared with control conditions, both in the experience and in the expectation phase, despite identical physical resistance in the expectation phase. Insula fMRI signal matched the actual load, i.e. a significant difference between Histarinol and control in the experience phase, but no difference in the expectation phase. The periaqueductal gray showed a significantly higher fMRI signal during the expectation of dyspnoea. Finally, Histarinol-related deactivations during the expectation phase in the rostral anterior cingulate cortex mirrored similar responses for nocebo effects in pain.

These findings highlight the neural basis of expectation effects associated with dyspnoea, which has important consequences for our understanding of the perception of respiratory symptoms.

本身不会引起支气管收缩的气味等线索可成为哮喘发作的诱因。尽管具有临床意义，但这种呼吸反安慰剂效应的神经基础尚不清楚。

我们在一项涉及 36 名健康志愿者的功能性磁共振成像 (fMRI) 研究中调查了这种影响。该实验包括一个体验阶段，其中志愿者在暴露于有气味的气体（“Histarinol”）时会出现呼吸困难。志愿者被告知 Histarinol 通过支气管收缩诱发呼吸困难。这与另一种不会引起呼吸困难的有气味的气体进行了比较。呼吸困难实际上是由插入呼吸系统的隐蔽电阻负载引起的。在第二个预期阶段，Histarinol 和对照气体都跟随相同的、非常温和的负载。持续记录呼吸参数，参与者在每次试验后评定呼吸困难强度。

尽管在预期阶段具有相同的物理阻力，但在体验阶段和预期阶段，与对照条件相比，Histarinol 的呼吸困难评级显着更高。Insula fMRI 信号与实际负荷相匹配，即在体验阶段 Histarinol 和对照之间存在显着差异，但在预期阶段没有差异。在预期呼吸困难期间，导水管周围灰质显示出明显更高的 fMRI 信号。最后，在喙前扣带回皮层的预期阶段，与 Histarinol 相关的失活反映了对疼痛中 nocebo 效应的类似反应。

这些发现强调了与呼吸困难相关的预期效应的神经基础，这对我们理解呼吸系统症状的感知具有重要意义。