Young 1989.

Methods	Cross‐over study Exercise study Cycle endurance test Nebulised opioid
Participants	COPD (9) or idiopathic pulmonary fibrosis (2) Mean age 58.4 years (39 to 74) Exercise tolerance limited by dyspnoea FEV1 0.4 to 1
Interventions	Morphine 5 mg or placebo neb 15 mins before exercise test Tests on separate days 100% O2 inhaled during exercise test
Outcomes	Cycle ergometer exercise test at 80% of pre‐determined Emax Endurance time Ventilation during last minute of exercise FEV1
Notes	The study authors did not use dyspnoea as an outcome measure, although they selected participants because exercise was limited by dyspnoea. They initially studied 18 participants and 7 excluded on run‐in day because exercise was limited by other factors: the participants were excluded from the study authors’ and from this review analysis Mean endurance time increased by 64 seconds: 1 participant had an increase of 400 seconds. If the study authors had excluded that participant from their analysis, the mean increase would have been approximately 25 seconds and not statistically significant. The study authors concluded that morphine had a significant effect on exercise endurance time vs placebo
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The study authors did not state the methods of random sequence generation.
Allocation concealment (selection bias)	Unclear risk	The hospital pharmacist performed allocation, but the study authors did not further describe the method used to conceal allocation.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	The study authors did not state whether they performed blinding of participants and personnel.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	The study authors did not state whether they performed blinding of outcome assessment.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	The study authors did not clearly report complete participant data and dropouts.
Selective reporting (reporting bias)	Low risk	We did not detect any evidence of selective reporting bias.
Other bias	Low risk	We judged that this trial appeared to be free of other sources of bias.
Size bias	High risk	This study had a small sample size, and was at high risk of bias; there were < 50 participants per arm.

Chronic obstructive pulmonary disease (COPD), three times daily (TDS), six‐minute walking test (6MWT), standard deviation (SD), minimental state exam (MMSE), left ventricular ejection fraction (LVEF), New York Heart Association (NYHA), angiotensin‐converting‐enzyme (ACE), blood pressure (BP), partial pressure of oxygen (PaO₂), ventilation to carbon dioxide output (VE‐VCO₂ slope), mean forced expiratory volume in one second (FEV1), mean partial pressure of carbon dioxide (paCO₂), A‐aPO₂ (alveolar‐arterial oxygen tension difference), interstitial lung disease (ILD), oxygen saturations (SaO₂), O₂ uptake (VO₂), CO₂ output (VCO₂), end‐tidal CO₂ minute ventilation (VI), visual analogue scale (VAS), numeric rating scale (NRS), glomerular filtration rate (eGFR), four times a day (QID or QDS), twice daily (BD).