ADDITIONAL FILES
Additional File 1. Search Strategy to Identify Papers Indexed in MEDLINE and EMBASE and Reporting
Data on Post-Transplantation Survival Among Patients with IPF
MEDLINE Search (via PubMed)
1.
“lung transplantation”[MeSH] OR lung transplant* OR lung graft
2.
“idiopathic pulmonary fibrosis”[MeSH] OR “IPF”[tiab] OR “pulmonary fibrosis”[MeSH] OR “pulmonary fibrosis”
OR “lung diseases, interstitial”[MeSH] OR interstitial lung disease* OR “ILD”[tiab] OR “fibrosing alveolitis” OR
“CFA”[tiab] OR “usual interstitial pneumonia” OR “UIP”[tiab] OR idiopathic interstitial pneumonia* OR “IIP”[tiab]
3.
“animals”[MeSH] NOT “humans”[MeSH]
4.
(#1 AND #2) NOT #3
Limits: English, Published from 1990/01/01 to 2013/03/28
Embase Search
1.
‘lung transplant’ OR ‘lung transplants’ OR ‘lung transplantation’ OR ‘lung transplantations’ OR ‘lung graft’ OR ‘lung
grafts’ OR ‘lung grafting’ OR ‘lung graftings’
2.
‘fibrosing alveolitis’/exp OR ‘fibrosing alveolitis’ OR ‘pulmonary fibrosis’ OR ‘interstitial lung disease’ or ‘interstitial
lung diseases’ OR ‘usual interstitial pneumonia’ OR ‘idiopathic interstitial pneumonia’ or ‘idiopathic interstitial
pneumonias’
3.
[animals]/lim NOT [humans]/lim
4.
[cochrane review]/lim OR [systematic review]/lim OR [conference paper]/lim OR [conference abstract]/lim OR
[editorial]/lim OR [erratum]/lim OR [note]/lim OR [review]/lim
5.
(#1 AND #2) NOT (#3 OR #4)
Limits: English, Published from 1990/01/01 to 2013/03/28
Additional File 2. Summary of the 56 sources included in the review
Reference
Sample source
No. of IPF
Mean + SD age
patients
%
females
ISHLT data
ISHLT website[10]
ISHLT data (website)1995 – 2012
8,904
NR
NR
Christie, et al[48]
ISHLT data (2012 annual report), 1995 – 2011
7,925
NR
NR
Trulock, et al[49]
ISHLT data, All adult IPF lung transplant recipients,
2,318
NR
NR
1,271
NR
NR
1994–2004
OPTN data
OPTN website[16]
OPTN data, All adult IPF lung transplant recipients,
1997 – 2004
McCurry, et al[20]
OPTN data, All IPF lung transplant recipients, 2007
NR
NR
NR
Edwards, et al[19]
OPTN data, Adult IPF lung transplant recipients
786
NR
NR
3,860
SLT: 56.5 + 9.5
39.7
1987–2002
Force, et al[51]
OPTN data, All IPF lung transplant recipients,
1987–2008
Freitas, et al[22]
OPTN data, All IPF lung transplant recipients,
BLT: 51.8 + 12.2
4,475
NR
NR
1,241
NR
NR
NR
NR
NR
429
NR
NR
4,190
65.4 ± 10.1
31.9
3,327
SLT: 57.1 + 9.0
32.0
1987–2010
Merlo, et al[58]
OPTN data, All IPF lung transplant recipients, 2002
- 2008
Meyer et al[17]
OPTN data, All IPF lung transplant recipients, 1988
- 1999
Nwakanma, et
OPTN data, All IPF lung transplant recipients, 1998
al[52]
- 2004
Takagishi, et al[23]
OPTN data, All IPF lung transplant recipients, 1991
- 2009
Thabut, et al[18]
OPTN data, Adult IPF lung transplant recipients,
1987 - 2009
BLT: 54.0 + 10.0
Reference
Sample source
No. of IPF
Mean + SD age
patients
Weiss, et al[53]
OPTN data, Adult IPF lung transplant recipients,
%
females
NR
NR
NR
NR
NR
NR
454
56 ± 9
33
2,115
51.4 ± 9.6
39.3
261
NR
NR
104
NR
NR
16
51.4 ± 7.7
18.8
26
52.1 ± 6.0
23.1
231
NR
NR
61
NR
NR
16
45.2 ± 10.5
56.3
45
49.5 ± 10
42.2
1987 – 1997
Chen, et al[21]
OPTN data, IPF lung transplant recipients, 2002 2008
Lederer, et al[63]
OPTN data, IPF patients listed for lung transplant,
2004 - 2005
Shorr, et al[64]
OPTN data, All IPF patients on the waiting list for
lung transplantation, 1995 - 2000
Other registry data or large databases
Coll, et al[24]
IPF lung transplant recipients, Spanish Lung
Transplant Registry, 2006 - 2010
Smits, et al[50]
Adult IPF lung transplant recipients, Eurotransplant
database, 1997-1999
Grossman, et al[44]
IPF single-lung transplant recipients, Toronto Lung
Transplant Group, 1983 - 1989
Kadikar, et al[65]
IPF patients evaluated for lung transplantation,
Toronto Lung Transplant Program, 1991–1995
Teo, et al[25]
Adults with IPF (ICD-9 code) as primary inpatient
diagnosis and inpatient lung transplantation codes,
Nationwide Inpatient Sample database, 1988–2006
Paik, et al[54]
All IPF patients on the lung transplant waiting list,
KONOS registry, 1996–2011
Single center data, North America
Davis, et al[43]
All adult IPF single-lung transplant recipients,
Washington University/Barnes Hospital 1988 - 1993
Meyers et al, [38]
All IPF lung transplant recipients, Washington
University/Barnes Hospital, 1988–1998
Reference
Sample source
No. of IPF
Mean + SD age
patients
De Oliveira, et
Consecutive IPF lung transplant recipients,
al[46]
University of Wisconsin Hospital and Clinics, 1993 -
79
%
females
Pre-LAS: 52.5 ± 9.9
19
Post-LAS: 57.9 ± 6.5
2009
Di Giuseppe, et al
All IPF lung transplant recipients, University of
[35]
Pittsburgh, 1986 - 2007
Mason, et al[45]
All IPF lung transplant recipients, Cleveland Clinic,
79
54.5 ± 10.3
32.9
82
52 ± 11
36.6
32
CMV-: 51 + 6
28.1
1990 - 2005
Milstone et al [40]
IPF lung transplant recipients, Vanderbilt University
Medical Center, 1990–1998
Nathan, et al[28]
IPF lung transplant recipients, Inova Fairfax
CMV+ 54 + 9
23
Hospital, 1996–2002
Patients with PE
39.1
event: 58.7 + 4.3
No PE event: 54.7 +
7.0
Nathan, et al[27]
IPF patients evaluated for lung transplantation,
521
65 + NR
28.3
73
NR
NR
135
58 ± 7
27
38
58.8 + NR
23.7
70
55.7 ± 8.6
40.0
27
NR
NR
48
55.8 ± 7.9
41.7
Inova Fairfax Hospital,2000 - 2009
Nathan, et al[66]
IPF patients listed for lung transplantation, Inova
Fairfax Hospital, US, 2000–2005
Rivera-Lebron, et
IPF patients evaluated for lung transplant with ECG
al[37]
and RHC reported, Hospital of the University of
Pennsylvania, 2005–2010
Saggar, et al[39]
All IPF bilateral lung transplant recipients,
University of California, Los Angeles, 2003–2007
Schachna, et al[36]
All IPF lung transplant recipients, Johns Hopkins
Hospital; University of Pittsburgh Medical Center,
1989–2002
Smith, et al[41]
Adult IPF lung transplant recipients, University of
Virginia, 1995–2005
Wille, et al[42]
All IPF lung transplant recipients, University of
Reference
Sample source
No. of IPF
Mean + SD age
patients
%
females
Alabama at Birmingham, 1994–2004
De Oliveira, et
Consecutive IPF patients who underwent lung
al[47]
transplantation, University of Wisconsin Hospital
79
SLT: 56.8 ± 7.2
19
BLT: 43.4 ± 12.3
and Clinics, 1993–2009
Horai, et al[59]
Consecutive IPF lung transplant patients, University
140
NR
NR
25
NR
NR
55
NR
NR
11
NR
NR
17
53.8 + NR
NR
76
SLT: 53.74 ± 1.15*
43.4
of Pittsburgh Medical Center, 2005–2010
Timmer, et al[67]
Adult lung transplant candidates with a pathological
diagnosis of UIP, University of California San
Diego, 1990–1999
Erasmus, et al[68]
IPF lung transplant recipients with large airway
complications, Mayo Clinic Jacksonville, US, 2001–
2007
Single center data, Europe
McNeil, et al [29]
IPF single-lung transplant recipients, Papworth
Hospital, UK, 1984–1994
Mackay, et al[69]
All IPF lung transplant recipients, Freeman Hospital,
UK, 1999–2004
Neurohr, et al[31]
Consecutive IPF lung transplant recipients, LudwigMaximilians University of Munich, 1997–2008
Thabut, et al[30]
IPF lung transplant recipients, Beaujon Hospital,
BLT: 50.38 ± 1.34*
28
49.3 + NR
28.6
89
51 ± 11
28.1
21
NR
NR
53
NR
NR
Clichy, France, 1988–2001
Algar, et al[32]
IPF lung transplant recipients, University of
Cordoba, Spain, 1993–2009
Burton, et al[26]
All IPF patients receiving deceased donor lung
transplants, Rigshospitalet, Copenhagen University
Hospital, Denmark, 1992–2004
Callegari, et al[56]
IPF patients enrolled at a lung transplant program,
Pulmonary Division Medical Centre of Montescano,
Reference
Sample source
No. of IPF
Mean + SD age
patients
%
females
Italy, 1991–1999
Jastrzebski, et al[55]
Adult IPF lung transplant candidates, Silesian
24
NR
NR
85
NR
NR
51
58 ± 11
43.1
61
61 ± 7
32.8
20
56.3 ± 1.4
35.0
33
NR
NR
53
NR
NR
67
NR
NR
School of Medicine, Zabrze, Poland, 1999–2005
Shitrit, et al[70]
Consecutive IPF patients registered on the waiting
list for lung transplantation, Rabin Medical Center,
Israel, 1997–2006
Shitrit, et al[71]
IPF patients with progressive symptomatic and/or
physiologic deterioration despite treatment with
prednisone ± immunosuppresive agents, Rabin
Medical Center, Israel, 2004
Rusanov, et al[72]
IPF patients with progressive symptomatic and/or
physiologic deterioration despite treatment with
prednisone ± immunosuppresive agents, Rabin
Medical Center, Israel, 2009
Adamali, et al[57]
All Irish citizens with IPF who underwent lung
transplantation at MMUH, Freeman Hospital in
Newcastle, Harefield Hospital in Middlesex, or
Great Ormond Street in London, 2000–2011
Single center data, South America, Australia
Costa da Silva, et
IPF patients at a single institution in Brazil
al[73]
registered on the waiting list from 2001 to June 2008
Machuca, et al [33]
All IPF lung transplant recipients, Santa Casa de
Misericordia de Porto Alegre, Brazil, 2004 - 2009
Keating, et al[34]
IPF lung transplant recipients, Alfred Hospital,
Melbourne, 1990 - 2008
MMUH: Mater Misericordiae University Hospital [Dublin, Ireland]; PE: Pulmonary Embolism; UIP: usual interstitial
pneumonitis; * standard error
Additional File 3. Summary of cause of death in IPF patients
Source
Yr. of
No. of
No. of
transplant
patients
deaths
1987 - 2009
3,327
1,556
Cause of death
OPTN Data
Analysis of
Infection: 23.6%
OPTN data
Primary graft failure: 5.4%
(Thabut et al)
Cancer: 10.2%
[18]
Chronic rejection: 8.4%
Respiratory failure: 11.7%
Other: 30.1%
Missing data: 10.6%
Single Center Studies in Europe
Hopital Beaujon,
1988 - 2001
28
12
Sepsis: 50.0%
France (Thabut, et
Chronic rejection: 33.3%
al) [30]
Carcinoma: 8.3%
Primary graft failure: 8.3%
University of
1997 - 2008
76
33
Technical complications/others: 9.1%
Munich, Germany
CMV: 3.0%
(Neurohr, et al)
Non-CMV pulmonary infection: 18.2%
[31]
BOS ≥ stage 1: 42.4%
Graft failure: 27.3%
Single Center Studies in North America
Two centers
(Johns Hopkins
Hospital and the
University of
Pittsburgh
1989 - 2002
70
23
Primary graft failure and infection were the leading causes of
death
Source
Yr. of
No. of
No. of
transplant
patients
deaths
2003 - 2007
38
11
Cause of death
Medical Center),
US (Schachna, et
al)[36]
University of
BOS complications: 27.3%
California, Los
Sepsis/pneumonia: 36.4%
Angeles, US
Community acquired adenoviral infection: 9.1%
(Saggar, et al)
Perforated bowel: 9.1%
[39]
Air embolus: 9.1%
Thorocosternotomy wound dehiscence: 9.1%
University of
1994 - 2004
48
24
Infection: 25.0%
Alabama, US
BOS: 20.8%
(Wille, et al) [42]
Primary grafit failure: 16.7%
Mulitple orgain failure: 12.5%
Airway dehiscence: 8.3%
Malignancy: 4.2%
Toronto Lung
1983 - 1989
16
6
Perioperative deaths: n=1 gram-negative sepsis; n=1 air
Transplant Group,
embolism; n=1 viral pneumonia. Post-operative deaths, n=1
Canada
viral pneumonia; n=2 chronic rejection
(Grossman, et al)
[44]
Cleveland Clinic,
1990 - 2005
82
40
Respiratory infection 32.5%
US (Mason, et al)
Sepsis or multisystem organ failure: 22.5%
[45]
Malignancy: 12.5%
Other: 32.5%
Source
Papworth hospital
Yr. of
No. of
No. of
Cause of death
transplant
patients
deaths
1984 - 1994
11
6
Death within 3 months: n=4 (67%) infection
2009
20
3
Acute lung rejection: 66.7%
(UK) (Meyers et
al)[38]
Pulmonary
Institute of Rabin
Sepsis: 33.3%
Medical Center,
Israel (Rusanov et
al)[72]
Pulmonary
2004 - 2005
15
3
2 of acute lung rejection and 1 of sepsis.
2001 - 20007
19a
5
Graft failure: 40.0%
Institute of Rabin
Medical Center,
Israel (Shirit et
al)69
Mayo Clinic
Jacksonville Lung
Lymphoma: 20.0%
Transplant
Non small cell lung carcinoma: 20.0%
Database
Sarcoma pleura: 20.0%
(Erasmus et
al)[68]
a
IPF patients with Large airway stenosis, and/or bronchomalacia
Additional File 4. Post-transplant length of stay and adjunct interventions in IPF patients
Days in hospital following transplantation
Davis, et
All adult IPF single-lung transplant
al[43]
recipients, Washington University/Barnes
Hospital 1988 - 1993
16
37.2 ± 35.1
(ICU stay: 12 ± 19.9)
De Oliveira,
Consecutive IPF lung transplant
79
et al[46]
recipients, University of Wisconsin
Pre-LAS: 23
Post-LAS: 11 (p<0.01)
Hospital and Clinics, 1993 - 2009
Pre-LAS: ICU stay 6
Post-LAS: ICU stay 3 (p<0.01)
Meyers et al,
All IPF lung transplant recipients,
45
[38]
Washington University/Barnes Hospital,
22 (14–33)
ICU stay: 5 (4–12)
1988–1998
231
Length of stay ≥14 days: 116 (50.2%);
Teo, et
Adults with IPF (ICD-9 code) as primary
al[25]
inpatient diagnosis and inpatient lung
There was a non-significant trend for shorter length of
transplantation codes, Nationwide
stay in SLT vs BLT (46.2% LOS ≥14 days vs 58.7%,
Inpatient Sample database,1988–2006
Thabut, et
IPF lung transplant recipients, Beaujon
al[30]
Hospital, Clichy, France, 1988–2001
p=0.075).
28
longer median hospital stay (14 days [IQR, 9 to 24
days] vs. 17 days [IQR, 11 to 31 days]; P< 0.001)
Indicators of Inadequate Pulmonary Status
Davis, et
All adult IPF single-lung transplant
al[43]
recipients, Washington University/Barnes
16
25% needed tracheostomy (after ≥7 days on
ventilator)
Hospital 1988 - 1993
De Oliveira,
Consecutive IPF lung transplant
et al[46]
recipients, University of Wisconsin
79
Inhalation of nitric oxide: 45 (57.0%)
≥48 hours of nitric oxide inhalation: 17 (21.5%)
Hospital and Clinics, 1993 - 2009
Reintubation: 16 (20.3%)
≥48 hours of ventilator support: 31 (39.2%)
There were significant differences between Pre-LAS
and LAS IPF patients in terms of postoperative
inhalation of nitric oxide (36.4% vs 71.7%, p<0.01),
48+ hours of inhalation (33.3% vs 13.0%, p=0.03),
length of mechanical ventilation (2.8 days vs 1.1 days,
p<0.01), 48+ hours of ventilation (57.6% vs 26.1%,
p<0.01),
Meyers et al,
All IPF lung transplant recipients,
[38]
Washington University/Barnes Hospital,
45
Mechanical ventilation mean: 3 days (2–10 days)
Tracheostomy: 7/45 (15.6%)
1988–1998
There were no significant differences between SLT
and BLT in terms of tracheostomy, or days of
postoperative hospital stay, mechanical ventilation, or
ICU stay.