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

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