Abstract
BackgroundSystemic morphine has evidence to support its use for reducing breathlessness in patients with severe chronic obstructive pulmonary disease (COPD). The effectiveness of the nebulized route, however, has not yet been confirmed. Recent studies have shown that opioid receptors are localized within epithelium of human trachea and large bronchi, a target site for a dosimetric nebulizer. The aim of this study was to compare any clinical or statistical differences in breathlessness intensity between nebulized 2.0% morphine and 0,9% NaCl in patients with very severe COPD.MethodsThe study was a double-blind, controlled, cross-over trial. Participants received morphine or NaCl during two 4-day periods. Sequence of periods was randomized. The primary outcome measure was reduction of breathlessness intensity now by ≥20 mm using a 100 mm visual analogue scale (VAS) at baseline, 15, 30, 60, 120, 180 and 240 min after daily administration, during normal activities.ResultsTen of 11 patients included completed the study protocol. All patients experienced clinically and statistically significant (p < 0.0001) breathlessness reduction during morphine nebulization. Mean VAS changes for morphine and 0.9% NaCl periods were 25.4 mm (standard deviation (SD): 9.0; median: 23,0; range: 14.0 to 41,5; confidence interval (CI): 95%) and 6.3 mm (SD: 7.8; median: 6.8; range: −11,5 to 19,5; CI: 95%), respectively. No treatment emergent adverse effects were noted.DiscussionOur study showed superiority of dosimetrically administered nebulized morphine compared to NaCl in reducing breathlessness. This may have been achieved through morphine’s direct action on receptors in large airways, although a systemic effect from absorption through the lungs cannot be excluded.Trial registrationRetrospectively registered (07.03.2017), ISRCTN14865597
Highlights
Systemic morphine has evidence to support its use for reducing breathlessness in patients with severe chronic obstructive pulmonary disease (COPD)
A total of 270 patients were screened, 30 of whom met the following inclusion criteria: (a) age above 50 years; (b) diagnosis of COPD group D, according to 2013 Global Initiative For Chronic Obstructive Lung Disease (GOLD) guidelines [14] which are consistent with their 2017 version [15]; (c) stage IV airflow limitation i.e. forced expiratory volume in one second (FEV1)% < 30%, according to 2011
Out of the 30 patients primary screened for the study, 5 declined participation, and 8 died before entering the trial
Summary
Systemic morphine has evidence to support its use for reducing breathlessness in patients with severe chronic obstructive pulmonary disease (COPD). Recent studies have shown that opioid receptors are localized within epithelium of human trachea and large bronchi, a target site for a dosimetric nebulizer. The aim of this study was to compare any clinical or statistical differences in breathlessness intensity between nebulized 2.0% morphine and 0,9% NaCl in patients with very severe COPD. There is evidence for the use of systemic, oral or parenteral, opioids to reduce the symptom of chronic breathlessness, Janowiak et al BMC Pulmonary Medicine (2017) 17:186 breathlessness was demonstrated only in a few uncontrolled studies and case reports [5,6,7]. Recent studies have shown that opioid receptors are localized within epithelium of human trachea and large bronchi on unmyelinated C nerve fibers and pulmonary neuroendocrine cells (PNEC) [12]. We demonstrated that the large bronchi could be targeted by a dosimetrically operated nebulizer [13]
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