Introduction
Methods
Search strategy and data extraction
Results
Study | Study type | Experimental treatment | Country | Sample size1 | Disease duration (mo) mean (SD) | Baseline SGRQ score2 | Baseline spirometric values2 | ||
---|---|---|---|---|---|---|---|---|---|
All | IPF | FVC% predicted | DLCO% predicted | ||||||
Antoniou et al., 2006 [13] | RCT | Interferon gamma b | Greece | 50 | 50 | T = 49.4 (24.3) C = 42.7 (16.8) | -- | T = 71.8 (15.0) C = 70.7 (17.7) | -- |
Berry et al., 2012 [14] | Secondary validation study | n/a | US | 405 | 239 | -- | -- | 66.0 (52–78) | -- |
Chang et al., 1999 [15] | Standalone validation study | n/a | US | 50 | 33 | -- | Total = 38.9 [28.7–55.2] Symptoms domain = 50.5 [31.5–69.8], Activity domain = 54.4 [39.9–72.9], Impact domain = 28.4 [18.8–45.1] | 65.0 (49.0–81.0) | 49.0 (36.5–59.8) |
du Bois et al., 2011 [16] | RCT | Interferon gamma b | Multi-national | 822 | 822 | -- | Total = 41.8 (18) | 72.5 (12.7) | 47.4 (9.2) |
Han et al., 2013 [17] | RCT | Sildenafil | US | 119 | 119 | 20.4 | -- | 56.9 | 26.0 |
Horton et al., 2012 [18] | RCT | Thalidomide | US | 23 | 23 | 20.5 (3–59) | Total = 57.4 (18.8) Symptoms domain = 67.7 (19.7), Activity domain = 64.3 (22.7), Impact domain = 48.1 (20.7) | 70.4 (13.7) | 57.4 (14.4) |
King, Jr. et al., 2008 [19] | RCT | Bosentan | Multi-national | 158 | 158 | T = 12.2 (12.2) C = 12.1 (12.0) | T-Total = 45.7 (18.1), C-Total = 45.2 (19) | T = 65.9 (10.5), C = 69.5 (12.6) | T = 42.3 (9.5), C = 41.4 (9.5) |
King, Jr. et al., 2009 [20] | RCT | Interferon gamma b | Multi-national | 826 | 826 | – | T-Total = 41.6 (17.9), C-Total = 42.4 (18.2) | T = 72.2 (12.3), C = 73.1 (13.4) | T = 47.4 (9.2), C = 47.3 (9.3) |
Lechtzin et al., 2013 [21] | RCT | Thalidomide | US | 24 | 24 | -- | Total = 57.4 (18.8), Symptoms domain = 67.7 (19.7), Activity domain = 64.3 (22.7), Impact domain = 48.1 (20.7) | 70.4 (13.7) | 57.4 (14.4) |
Mishra et al., 2011 [22] | Within-subject trial | Oral doxycycline | India | 6 | 6 | -- | Total = 50.90 (8.38) | n/a | n/a |
Naji et al., 2006 [23] | Within-subject trial | Pulmonary rehabilitation | Ireland | 26 | 19 | -- | Total = 48 (27.6, 67.9) | 66.7 (20.7) | 42.5 (14) |
Nishiyama et al., 2005 [24] | Standalone validation study | n/a | Japan | 41 | 41 | -- | Total = 35.7 (20.6) [range 1.6–77.6], Symptoms domain = 40.1 (24.6) [range 4.4–85.6], Activity domain = 44.5 (26.7) [range 0–93.9], Impact domain = 28.9 (19.8) [range 0–77.0] | n/a | n/a |
Nishiyama et al., 2008 [25] | RCT | Pulmonary rehabilitation | Japan | 28 | 28 | -- | T-Total = 50.2 (16.3), T-Symptoms domain = 56.4 (22.3), T-Activity domain = 64.7 (17.1), T-Impact domain = 39.7 (17.6), C-Total = 37.8 (22.7), C-Symptoms domain = 38.0 (25.8), C-Activity domain = 50.4 (26.2), C-Impact domain = 29.9 (23.7) | T = 66.1 (13.2), C = 68.7 (19.5) | T = 59.4 (16.7), C = 48.6 (16.7) |
Noth et al., 2012 [26] | RCT | Warfarin | US | 145 | 145 | T = 21.6, C = 25.2 | T-Total = 46.2 (18.0), C-Total = 50.1 (17.2) | T = 58.9 (16.2), C = 58.7 (16.1) | T = 33.8 (12.4), C = 34.6 (13.4) |
Patel et al., 2012 [27] | Standalone validation study | n/a | UK | 173 | 49 | 48.0 | -- | 82 (34–143) | -- |
Peng et al., 2008 [28] | Standalone validation study | n/a | China | 68 | 68 | 14.0 (14.0) | Total = 54 (15), Symptoms domain = 65 (16), Activity domain = 56 (15), Impact domain = 49 (19) | 66 (18) | 54 (16) |
Raghu et al., 2004 [29] | RCT | Interferon gamma b | Multi-national | 330 | 330 | -- | -- | T = 63.9 (10.7), C = 64.1 (11.3) | -- |
Raghu et al., 2008 [30] | RCT | Etanercept | Multi-national | 88 | 88 | T = 14.7 (19.8), C = 12.3 (13.6) | T-Total = 40.8 (18.1), C-Total = 42.9 (19.4) | T = 64.7 (14.1), C = 63.0 (12.7) | T = 36.3 (12.6), C = 36.9 (10.8) |
Raghu et al., 2013 [31] | RCT | Ambrisentan | Multi-national | 492 | 492 | T = 13.2, C = 10.8 | T-Total = 44.5 (21.6), C-Total = 40.5 (21.1) | T = 68.7 (13.1), C = 69.9 (13.8) | T = 42.0 (13.8), C = 45.6 (13.3) |
Rammaert et al., 2009 [32] | Within-subject trial | Pulmonary rehabilitation | France | 13 | 13 | -- | -- | 67 (14) | 32 (13) |
Richeldi et al., 2011 [33] | RCT | Nintedanib (BIBF 1120) | Multi-national | 428 | 428 | T, 50 mg qd = 16.8 (15.6), T, 50 mg bid = 13.2 (14.4), T, 100 mg bid = 14.4 (14.4), T, 150 mg bid = 12 (14.4), C = 16.8 (18) | T, 50 mg qd-Total = 43.7 (17.5), T, 50 mg bid-Total = 42.5 (17.0), T, 100 mg bid-Total = 43.7 (16.6), T, 150 mg bid-Total = 40.1 (18.3), C-Total = 41.2 (17.9) | T, 50 mg qd = 80.4 (17.8), T, 50 mg bid = 79.8 (15.8), T, 100 mg bid = 85.5 (19.2), T, 150 mg bid = 79.1 (18.5), C = 81.7 (17.6) | – |
Swigris et al., 2010 [34] | Secondary validation study | Bosentan | Multi-national | 158 | 158 | -- | Total = 44.8 (19.5), Symptoms domain = 50.1 (21.9), Activity domain = 60.6 (22.8), Impact domain = 33.7 (20.6) | 67.0 (12.8) | 40.98 (10.1) |
Swigris et al., 2012 [35] | Secondary validation study | Sildenafil | US | 180 | 180 | 24.0 | Activity domain = 69.6 (17.6) | 56.8 (14.2) | 26.3 (6.1) |
Tzanakis et al., 2005 [36] | Standalone validation study | n/a | Greece | 25 | 25 | 31.2 | Total = 37.7 (18.9), Symptoms domain = 55.9 (25.3), Activity domain = 36.2 (21.4), Impact domain = 29.6 (21) | 68.8 (16) | -- |
Tzouvelekis et al., 2013 [37] | Within-subject trial | Adipose-derived stromal cells | Greece | 14 | 14 | -- | -- | -- | -- |
Verma et al., 2011 [38] | Standalone validation study | n/a | Canada | 137 | 137 | – | Total = 63.4 (3.7–96.3), Symptoms domain = 59.8 (0–97.2), Activity domain = 81.6 (6.0–99.5), Impact domain = 54.1 (0–96.4) | 61.7 (19.8) | 49.5 (17.9) |
Yorke et al., 20103[10] | Secondary validation study | Bosentan | Multi-national | 158 | 158 | -- | -- | 61.0 (12.2) | -- |
Yorke et al., 2011 [39] | Standalone validation study | n/a | Multi-national | 101 | 67 | -- | Total = 53 (24), Symptoms domain = 61 (23), Activity domain = 65 (30), Impact domain = 41 (24) | 77 (19.5) | 51.6 (21) |
Zimmermann et al., 2007 [40] | Standalone validation study | n/a | Brazil | 22 | 22 | -- | Total = 48.4 (17.9), Symptoms domain = 46.4 (20.3), Activity domain = 62.4 (19), Impact domain = 43.6 (20.9) | 70.4 (19.4) | 41.5 (16.2) |
Zisman et al., 2010 [41] | RCT | Sildenafil | US | 180 | 180 | T = 24.4, C = 22.4 | T-Total = 54.55 (16.46), C-Total = 51.72 (15.86) | T = 54.9 (14.00), C = 58.7 (14.12) | -- |
Internal consistency
Convergent validity
Measure | Scale | Correlation with SGRQ symptoms domain score | Correlation with SGRQ activity domain score | Correlation with SGRQ impact domain score | Correlation with SGRQ total score | |
---|---|---|---|---|---|---|
Cross-sectional studies
| ||||||
Chang et al., 1999 [15] | Borg Dyspnea Index | 0.56† | ||||
Lechtzin et al., 2013 [21] | CQLQ | Total | 0.72* | 0.72‡ | 0.81‡ | 0.79‡ |
Physical complaints | 0.50* | 0.72‡ | 0.71‡ | 0.77‡ | ||
Psychological issues | 0.29 | 0.40 | 0.62† | 0.54* | ||
Functional ability | 0.53* | 0.54* | 0.66† | 0.66† | ||
Emotional well-being | 0.19 | 0.42 | 0.57† | 0.50* | ||
Extreme physical complaints | 0.38 | 0.34 | 0.63† | 0.54* | ||
Personal safety fears | 0.05 | 0.23 | 0.45* | 0.34 | ||
Nishiyama et al., 2005 [24] | BDI | −0.55‡ | −0.77§ | −0.53‡ | −0.69§ | |
Patel et al., 2012 [27] | K-BILD | Total | −0.67† | −0.79† | −0.87† | −0.89† |
Psychological | −0.60† | −0.67† | −0.80† | −0.79† | ||
Breathlessness | −0.59† | −0.84† | −0.80† | −0.86† | ||
Chest | −0.65† | −0.64† | −0.79† | −0.78† | ||
Peng et al., 2008 [28] | Dyspnea score | NS | 0.58§ | 0.30† | 0.38‡ | |
Swigris et al., 2012 [35] | UCSD-SOBQ | 0.80§ | ||||
Yorke et al., 20101[10] | BDI | −0.39§ | −0.72§ | −0.61§ | −0.68§ | |
SF-36 PCS | −0.52§ | −0.74§ | −0.63§ | −0.71§ | ||
Borg Dyspnea Index | 0.35§ | 0.45§ | 0.40§ | 0.45§ | ||
Yorke et al., 2011 [39] | D-12 | 0.57‡ | 0.78‡ | 0.75‡ | 0.79‡ | |
Zimmermann et al., 2007 [40] | BDI | −0.62* | −0.75* | −0.63* | −0.72* | |
Longitudinal studies
| ||||||
Nishiyama et al., 2008 [25] | Δ BDI | −0.29 | ||||
Peng et al., 2008 [28] | Δ Dyspnea score | NS | 0.59† | 0.56† | 0.45† |
Measure | Correlation with SGRQ symptoms domain score | Correlation with SGRQ activity domain score | Correlation with SGRQ impact domain score | Correlation with SGRQ total score | |
---|---|---|---|---|---|
Cross-sectional studies
| |||||
Chang et al., 1999 [15] | 6MWD | −0.66† | |||
du Bois et al., 2011 [16] | 6MWD | −0.26‡ | |||
Peng et al., 2008 [28] | 6MWD | −0.32† | −0.43‡ | −0.41‡ | −0.45‡ |
Yorke et al., 20101[10] | 6MWD | −0.14 | −0.32§ | −0.24† | −0.28† |
Yorke et al., 2011 [39] | 6MWD | −0.32† | −0.54† | −0.47† | |
Zimmermann et al., 2007 [40] | 6MWD | −0.41 | −0.72* | −0.63* | −0.72* |
Longitudinal studies
| |||||
du Bois et al., 2011 [16] | Δ 6MWD | −0.231‡ | |||
Nishiyama et al., 2008 [25] | Δ 6MWD | −0.43* | |||
Peng et al., 2008 [28] | Δ 6MWD | NS | −0.43 | −0.46 | −0.41† |
Lung function measure | Correlation with SGRQ symptoms domain score | Correlation with SGRQ activity domain score | Correlation with SGRQ impact domain score | Correlation with SGRQ total score | |
---|---|---|---|---|---|
Chang et al., 1999 [15] | DLCO% predicted | −0.55† | |||
FEV1% predicted | −0.46† | ||||
FVC% predicted | −0.45† | ||||
TLC% predicted | −0.36† | ||||
Nishiyama et al., 2005 [24] | PaO2 | −0.21 | −0.48† | −0.29 | −0.37* |
SpO2 | −0.38* | −0.48† | −0.22 | −0.37* | |
TLC | −0.48† | −0.38* | −0.21 | −0.36* | |
TLCO | −0.32* | −0.45† | −0.27 | −0.39* | |
VC | −0.35* | −0.36* | −0.15 | −0.30 | |
Peng et al., 2008 [28] | DLCO% predicted | −0.46§ | −0.46§ | −0.34† | −0.44‡ |
FEV1% predicted | NS | −0.53§ | −0.34† | −0.42§ | |
PaO2 | NS | −0.54‡ | NS | −0.32† | |
TLC% predicted | −0.50§ | −0.61§ | −0.52§ | −0.62§ | |
VC% predicted | NS | −0.59§ | −0.35† | −0.47§ | |
Tzanakis et al., 2005 [36] | FEV1% predicted | −0.50† | |||
PaO2 (at rest) | −0.51† | ||||
PaO2 (at exertion) | −0.60† | ||||
TLC% predicted | −0.55† | ||||
Yorke et al., 20101[10] | FVC% predicted | −0.27† | −0.31§ | −0.30§ | −0.34§ |
TLCO% predicted | −0.23† | −0.34§ | −0.38§ | −0.38§ | |
Yorke et al., 2011 [39] | DLCO% | −0.16 | −0.37† | −0.28* | |
FVC% | −0.13 | −0.16 | −0.24* | ||
Zimmermann et al., 2007 [40] | DLCO% predicted | −0.41 | −0.32 | −0.39 | −0.47* |
FEV1% predicted | −0.08 | −0.57* | −0.52* | −0.57* | |
TLC% predicted | −0.37 | −0.65* | −0.58* | −0.66* | |
VC% predicted | −0.14 | −0.54* | −0.61* | −0.56* |
Study | HRCT measure | Correlation with SGRQ symptoms domain score | Correlation with SGRQ activity domain score | Correlation with SGRQ impact domain score | Correlation with SGRQ total score |
---|---|---|---|---|---|
Peng et al., 2008 [28] | CT-alv | 0.41† | NS | 0.34* | 0.39† |
CT-fib | NS | 0.37* | NS | NS | |
CT-tot | 0.36* | 0.39† | 0.35* | 0.42† |
Patient-reported outcome measures
Measures of exercise capacity
Pulmonary function tests and arterial blood gas analysis
HRCT
Known groups validity
Test-retest reliability (reproducibility)
Minimal important difference
Responsiveness
SGRQ as an endpoint
Study | Treatment under investigation | Treatment duration | Sample size | SGRQ total score1 | Effect size | p-value2 | ||
---|---|---|---|---|---|---|---|---|
Total | IPF | Baseline | Post-treatment | |||||
Mishra et al., 2011 [22] | Oral doxycycline | 24 weeks | 6 | 6 | 50.90 (8.38) | 18.40 (6.39) | 3.88 | <0.001 |
Naji et al., 2006 [23] | Pulmonary rehabilitation | 8 weeks | 26 | 19 | 48.3 [21.5, 82] | 39.5 [17.4, 69.4] | 0.41 | <0.10 |
Rammaert et al., 2009 [32] | Pulmonary rehabilitation | 8 weeks | 13 | 13 | – | – | – | NS |
Tzouvelekis et al., 2013 [37] | Endobronchial infusion of adipose-derived stromal cells | 6 months | 14 | 14 | 35.1 (6.8) | 27.8 (5.6) | 1.07 | <0.05 |
Study | Treatment duration | Sample size, IPF | Randomized groups | Change from baseline in SGRQ symptoms domain score | Change from baseline in SGRQ activity domain score | Change from baseline in SGRQ impact domain score | Change from baseline in SGRQ total score |
---|---|---|---|---|---|---|---|
Antoniou et al., 2006 [13] | 12 months | 50 | Interferon gamma b | −13.2 [21.4,5.0] | −4.8 [-12.7, 3.0] | −1.9 [-9.2, 5.4] | −4.7 [-11.4, 2.0] |
Colchicine | 7.5 [-4.5, 19.5] | 4.7 [-12.1, 22.0] | 4.1 [-6.4, 14.6] | 4.8 [-5.9, 15.5] | |||
p-value2 | 0.01 | NS | NS | NS | |||
Han et al., 2013 [17] | 12 weeks | 22 | Sildenafil (with RVSD) | – | – | – | – |
Placebo (with RVSD) | – | – | – | – | |||
Difference1 | −28.0 [-41.7, -14.4] | −5.6 [-16.1, 5.0] | −14.0 [-25.6, -2.4] | −13.4 [-22.7, -4.2] | |||
p-value2 | <0.0001 | NS | 0.02 | 0.005 | |||
97 | Sildenafil (without RVSD) | – | – | – | – | ||
Placebo, (without RVSD) | – | – | – | – | |||
Difference1 | −3.8 [-10.7, 3.0] | −4.1 [-9.2, 1.1] | −1.8 [-7.5, 3.9] | −3.0 [-7.6, 1.7] | |||
p-value2 | NS | NS | NS | NS | |||
Horton et al., 2012 [18] | 12 weeks | 23 | Thalidomide | – | – | – | – |
Placebo | – | – | – | – | |||
Difference1 | −12.1 [22.2,2.0] | −3.3 [-9.8, 3.2] | −13.1 [-19.7, -6.6] | −11.7 [-18.6, -4.8] | |||
p-value2 | 0.018 | NS | <0.001 | 0.001 | |||
King, Jr. et al., 2008 [19] | 6 months4 | 158 | Bosentan | – | – | – | – |
Placebo | – | – | – | – | |||
Difference1 | – | – | – | −3.3 (2.6) | |||
p-value2 | – | – | – | 0.034 | |||
King, Jr. et al., 2009 [20] | 77 weeks | 826 | Interferon gamma b | -- | -- | -- | 5.7 (13.5) |
Placebo | – | – | – | 6.2 (14.3) | |||
p-value2 | – | – | – | NS | |||
Nishiyama et al., 2008 [25] | 10 weeks | 28 | Pulmonary rehabilitation | – | – | – | – |
No pulmonary rehabilitation | – | – | – | – | |||
Difference1 | −5.7 [-18.7, 7.2] | −5.8 [-14.7, 3.1] | −6.2 [-12.8, 0.3] | −6.1 [-11.7, 0.5] | |||
p-value2 | NS | NS | NS | <.05 | |||
Noth et al., 2012 [26] | 28 weeks | 145 | Warfarin | – | – | – | – |
Placebo | – | – | – | – | |||
p-value2 | – | – | – | NS | |||
Raghu et al., 2004 [29] | 48 weeks | 330 | Interferon gamma 1b | – | – | – | – |
Placebo | – | – | – | – | |||
p-value2 | – | – | – | NS | |||
Raghu et al., 2008 [30] | 48 weeks | 88 | Etanercept | – | – | – | -- |
Placebo | – | – | – | -- | |||
Difference1 | – | – | – | -- | |||
p-value2 | NS | NS | NS | NS | |||
Raghu et al., 2013 [31] | 48 weeks | 492 | Ambrisentan | – | – | – | 4.7 |
Placebo | – | – | – | 3.0 | |||
p-value2 | – | – | – | NS | |||
Richeldi et al., 2011 [33] | 12 months | 431 | Nintedanib 50 mg qd | 3.39 (2.51) | 7.39 (1.96) | 3.71 (2.04) | 4.67 (1.78) |
Nintedanib 50 mg bid | 2.11 (2.34) | 3.54 (1.82) | 1.73 (1.90) | 2.18 (1.65) | |||
Nintedanib 100 mg bid | 2.33 (2.35) | 3.00 (1.83) | 0.79 (1.91) | 1.48 (1.66) | |||
Nintedanib 150 mg bid | −3.14 (2.40) | 0.32 (1.89) | −0.14 (1.97) | −0.66 (1.71) | |||
Placebo | 6.45 (2.45) | 7.48 (1.91) | 4.21 (1.99) | 5.46 (1.73) | |||
p-value3 | <0.005 | <0.005 | – | <0.01 | |||
Zisman et al., 2010 [41] | 12 weeks | 180 | Sildenafil | −3.58 [-7.02, -0.13] | −1.15 [-3.68, 1.38] | −0.88 [-3.78, 2.02] | −1.64 [-3.91, 0.64] |
Placebo | 2.15 [-1.30, 5.61] | 2.49 [0.00, 4.99] | 2.82 [-0.03, 5.67] | 2.45 [0.17, 4.72] | |||
Difference1 | −5.73 [-10.61, -0.85] | −3.64 [-7.20, -0.09] | −3.70 [-7.76, 0.37] | −4.08 [-7.30, -0.86] | |||
p-value2 | 0.02 | .04 | NS | .01 |