Regular, low-dose, sustained-release morphine for persisting breathlessness in interstitial lung disease: a randomised, double-blind, placebo-controlled, crossover trial

To the Editor:

People with interstitial lung disease (ILD) often have persistent breathlessness that worsens over months or years, despite optimal disease modifying therapies and non-pharmacological interventions [1]. Regular, low-dose, systemic morphine is recommended as treatment for persistent breathlessness [2, 3], but the majority of participants in studies of this therapy have COPD as the most prevalent aetiology [4, 5]; evidence in ILD is scant. One parallel-arm randomised controlled trial in people with fibrotic ILD suggested that immediate-release oral morphine 5 mg every 6 h was ineffective for breathlessness reduction compared to placebo after 1 week; the direction of signal favoured morphine but not at statistically significant or clinically relevant levels. Morphine produced more harms.