• Malgorzata Krajnik, Ewa Jassem, and Piotr Sobanski.
• aChair of Palliative Care, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Poland bDepartment of Allergology, University of Medical Sciences in Gdansk, Poland cPalliativzentrum Hildegard, Basel, Switzerland.
• Curr Opin Support Palliat Care. 2014 Sep 1;8(3):191-9.

Purpose Of ReviewSystemic opioids have the evidence to support their use in refractory dyspnea; however, the mechanisms of how they exert their effects are not fully understood. The relevance of peripheral mechanisms, in part, is still questioned, especially as a meta-analysis demonstrated no benefit from nebulized opioids. This might be related to the lack of standardization of the inhalation methods. There is a need to clarify whether peripheral opioid receptors may serve as the target for inhaled treatment and what are the potential peripheral mechanisms of opioids.Recent FindingsOpioidergic systems are present in structures important for the regulation of bronchial and pulmonary vascular responses, as well as breathlessness perception in the human respiratory system. Opioid receptors located in the pulmonary neuroendocrine cells (PNECs) and sensory C-fibers within the bronchial epithelium are easily accessible for inhaled treatment. Morphine administrated by a pneumodosimetric method shows a different pharmacokinetic profile to those described for systemic routes, suggesting local metabolism in lung.SummaryResearch suggests that peripheral opioid receptors in lungs may be utilized as a target for therapeutic interventions. According to this hypothesis, to achieve breathlessness relief, opioids should be administered in close proximity to their receptors in the PNECs and sensory C-fibers of the bronchial epithelium.

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