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Table 1 Overview of randomized clinical trials investigating the effect of opioids on dyspnea, quality of life or health status in COPD

From: Opioids in patients with COPD and refractory dyspnea: literature review and design of a multicenter double blind study of low dosed morphine and fentanyl (MoreFoRCOPD)

References Design n (% COPD) Setting Comparison Treatment duration Breathlessness Quality of life or health status
Measurement (scale) Opioid Placebo Measurement (scale) Opioid Placebo
Woodcock et al. [18] Cross-over 12 (100) Outpatient Dihydrocodeine Single dose VAS (0–10 cm)
45 min after med
5.54 ± 1.91 6.33 ± 2.0
Light et al. [19] Cross-over 13 (100) Outpatient Oral morphine 0.8 mg/kg Single dose Borg score (0–10)
Rest
0.29 ± 0.58 0.13 ± 0.23
Jankelson et al. [20] Cross-over 16 (100) Outpatient Nebulized morphine 20/40 mg Single dose Borg score (0–10)
After 6MWT
4.2 ± 2.1/4.3 ± 1.8 4.3 ± 2.2
Noseda et al. [21] Cross-over 14 (79)# Hospitalized Nebulized morphine 10/20 mg ± oxygen Single dose VAS (− 100 to + 100%)  + 33 ± 28/+ 43 ± 27  + 42 ± 27
Jensen et al. [22] Cross-over 12 (100) Outpatient Nebulized fentanyl 50 µg Single dose Borg score (0–10)
Isotime CPET
2.0 ± 0.5 2.6 ± 0.5
Abdallah et al. [13] Cross-over 20 (100) Outpatient Morphine dose up to 10 mg Single dose Borg score (0–10)
Isotime CPET
3.0 ± 1.6* 4.2 ± 2.6
Iupati et al. [23] Cross-over
Multicenter
21 (62) Outpatient Intranasal fentanyl 20 µg as needed 1 day VAS (0–100 mm)
15 min after med
26 ± 21 (Δ29 ± 25) 21 ± 19 (Δ33 ± 24)
Abernethy et al. [7] Cross-over
Multicenter
48 (88)# Outpatient SR morphine 20 mg od 4 days VAS (0–100 mm)
Morning/evening
40.1 ± 24*/40.3 ± 23* 47.7 ± 26
49.9 ± 24
Data not presented Data not presented Data not presented
Janowiak et al. [24] Cross-over 10 (100) Hospitalized Nebulized morphine 3–5 mg qid 4 days VAS (0–100 mm)
Now (2dd)
Δ25.4 ± 9.0$ Δ6.3 ± 7.8
Johnson et al. [8] Cross-over 18 (100) Outpatient Dihydrocodeine 15 mg as needed up to tds 7 days VAS (0–10 cm)
Mean daily
4.6 ± 2.1* 5.6 ± 2.3
Currow et al. [15] Parallel
Multicenter
284 (58)# Outpatient SR morphine 20 mg qd
All arms: morphine 2.5 mg as needed
7 days VAS (0–100 mm)
Now (2dd)
Δ-5.00 ± 2.13 Δ-4.86 ± 2.07 EORTC-QLQ-C15 PAL (0–100) Δ1.8 ± 2.2 Δ1.5 ± 2.2
Ferriera et al. [16] Parallel
Multicenter
155 (60)# Outpatient Oxycodone 5 mg tds
All arms: morphine 2.5 mg as needed
7 days VAS (0–100 mm)
Now
Δ-3.7 ± 2.9 Δ-9.0 ± 2.7 EORTC-QLQ-C15 PAL (0–100) Δ-1.7 ± 3.1 Δ2.82 ± 3.1
Eiser et al. [25] Cross-over 14 (100) Outpatient Diamorphine 2.5/5 mg
qid
14 days VAS (0–10 cm) 7.0 ± 0.7/7.0 ± 0.8 6.5 ± 0.7
Verberkt et al. [17] Parallel
Multicenter
124 (100) Outpatient SR morphine 10 mg 1-tds 28 days NRS (0–10 points)
Mean
Δ-0.60 (− 1.55 to 0.35) CAT (0–40) Δ-2.18 (− 4.14 to − 0.2)*
Poole et al. [9] Cross-over 16 (100) Outpatient SR morphine 10 mg od or bid 42 days DBS (0–5) 2.22 2.26 CRQ (20–140) ∆2.08 ± 4.53 ∆2.94 ± 3.46
  1. Data presented as mean ± SD
  2. od once a day, bid twice daily, tds three times a day, qid four times a day, SR sustained release, VAS visual analogue score, DBS daytime breathlessness score, NRS numeric rating scale, CRQ chronic respiratory questionnaire, EORTC-QLQ-C15 PAL Quality of life questionnaire developed by the European Organisation for Research and Treatment of Cancer, CAT COPD assessment test, CPET cardiopulmonary exercise testing, 6MWT 6-min walking test
  3. *p < 0.05 opioid versus placebo, $p < 0.05 change after treatment. #Data not exclusively on COPD