Background: Patients suffering from fibrotic interstitial lung diseases (fILD) have a poor prognosis and a high symptom burden. Palliative treatment includes relief of symptoms such as breathlessness. There is no evidencebased treatment for chronic breathlessness but opioids are often used despite concerns due to the hypothetical risk of respiratory depression. This study investigated the effect of oral morphine drops in patients with fILD on chronic breathlessness and safety. Methods: In a double-blinded placebo-controlled study, 36 patients with fILD were randomised to either four daily doses of 5 mg of oral morphine drops or placebo for 1 week. Endpoints and safety parameters were obtained at baseline, at follow-up after 1 h and 1 week. Results: The primary endpoint, the visual analogue score (VAS) of dyspnea was reduced by 1.1 ± 0.33 cm in the morphine group at follow-up compared to baseline (P < 0.01), whereas the reduction was 0.35 ± 0.47 cm in the placebo group. However, the difference between the two groups was not statistically significant (p = 0.2). Oral morphine drops did not affect respiratory frequency, pulse rate, blood pressure, peripheral saturation or the 6-min walk test. More patients treated with morphine reported constipation, nausea and confusion. Conclusion: Oral administration of morphine drops, 20 mg a day, in patients with fILD did not significantly reduce dyspnea VAS score during 1 week compared to placebo. Oral morphine did not induce respiratory depression, but was related to an increased risk of constipation, nausea and confusion. Trial registration: The trial is registered in clinicaltrials.gov (Identifier: NCT02622022). Registered 4 December 2015.

BackgroundIdiopathic pulmonary fibrosis (IPF) is the most common among the idiopathic interstitial pneumonias and has the worst prognosis, with a median survival of 3–5 years. The most common symptom in IPF is dyspnea, impacting on the patient's quality of life and life expectancy. Morphine in the treatment of dyspnea has been investigated but with conflicting results. This review aims to clarify the role of opioids in the treatment of dyspnea in patients with IPF.MethodsA literature search was performed using the MeSH and PubMed databases. As only very few studies included patients with IPF, studies conducted primarily with patients with chronic obstructive pulmonary disease were also included. In total, 14 articles were found.ResultsSeven studies reported use of systemic morphine and seven studies of inhaled morphine. Five of the seven studies investigating systemic administration detected an improvement in either dyspnea or exercise capacity, whereas no beneficial effect on dyspnea was detected in any study using inhaled morphine. No severe adverse effects such as respiratory depression were reported in any study, although constipation was reported as a notable adverse effect.ConclusionsResults were inconsistent, but in some studies systemic morphine administration showed a significant improvement in the dyspnea score on a visual analog scale without observation of severe side effects. Nebulized morphine had no effect on dyspnea.