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Table 1 Characteristics of 32 included studies in this meta-analysis

From: The role of viral and bacterial infections in the pathogenesis of IPF: a systematic review and meta-analysis

First author

Country

Year

Sex

Age

Total

Viral genotypes

N

Bacterial species

N

Diagnosis

Method

Sample type

Smoking

Drugs

Ueda

[39]

Japan

1992

46 M/20 F

61.5

66

HCV

19

NA

NA

Clinical, radiologica, physiological, and histological grounds

ELISA, RIBA

Serum

NA

CS

Meliconi

[40]

Italy

1996

43 M/18 F

61

60

HCV

8

NA

NA

Clinical, radiological, physiological, and histological grounds

RT-PCR, ELISA, RIBA

Serum

NA

Immunosuppressive treatment

Kuwano

[41]

Japan

1997

8 M/11 F

62

19

Adenovirus

3

NA

NA

Clinical, radiological, physiological, and histological grounds

Nested PCR,ISH

Lung

Yes

CS

Yonemaru

[10]

Japan

1997

30 M/13 F

63

43

CMV,Adenovirus, EBV, HSV, Parainfluenza

42 CMV,Adeno, EBV, HSV /43Parainfluenza 3

NA

NA

Clinical, radiological, physiological, and histological grounds

EIA,CF, HI

Serum

NA

NA

Stewart

[42]

United Kingdom

1999

19 M/8 F

57

27

EBV

13

NA

NA

UIP pattern at histopathologic examination

and HRCT

PCR

Lung

Yes

CyA, Az, Pred, cyclophosphamide

Tsukamoto

[43]

Japan

2000

22 M/7 F

57.33

25

EBV

24

NA

NA

UIP pattern at histopathologic examination

PCR

Lung

Yes

None

Tang

[44]

United States

2001

NA

NA

23

EBV,CMV, HHV, HSV/VZV/HHV

7CMV,15EBV,19HHV

NA

NA

UIP pattern at histopathologic examination

PCR

Lung

NA

NA

Lok

[45]

United Kingdom

2001

10 M/4 F

59

14

EBV

8

NA

NA

UIP pattern at histopathologic examination

and HRCT

PCR,

IHC

Lung

NA

NA

Kelly

[46]

United Kingdom

2002

15 M/11 F

52.2

27

EBV

23

NA

NA

UIP pattern at histopathologic examination

and HRCT

PCR

Serum

NA

CsA/prednisolone/azathioprine

Magro

[47]

United States

2003

11 M/8 F

50.9

19

CMV, Parvovirus B19

9 CMV, 9B19

NA

NA

UIP pattern at histopathologic examination

IndirectImmunofluorescentRodent Lung Assay

Serum- lung biopsy

NA

NA

Tang

[48]

United States

2003

23 M/10 F

55.27

33

CM, HHV, EBV

21EBV, 7CMV, 29HHV

NA

NA

UIP pattern at histopathologic examination

PCR

Lung

NA

Prednisone,CytoxanImuran,CytoxaNeoralActimmune

Dworniczak[49]

Poland

2004

9 M/7 F

40.9

16

CMV

12

NA

NA

ATS/ERS statement 2000

Q-PCR

BALFBlood-Serum

Yes

Never treated

Miyake

[50]

Japan

2005

94 M/10 F

NA

104

HCV

7

NA

NA

ATS/ERS statement 2002

NA

Medicalhistory

Yes

NA

Lawson

[32]

United States

2008

NA

NA

23

EBV-KSHV- CMV

8EBC, 8CMV, 2KSHV

NA

NA

ATS/ERS statement2000, ATS/ERS

statement 2002

IHC

Lung

NA

NA

Bando

[51]

Japan

2008

43 M/14 F

NA

57

TTV

55

NA

NA

ATS/ERS statement 2000

PCR

Serum

yes

NA

Pozharskaya[52]

United States

2009

NA

NA

13

EBV

9

NA

NA

UIP pattern at histopathologic examination

PCR

Lung

NA

NA

Song

[21]

South Korea

2011

358 M/103 F

63.4

461

CMV, Influenza, RSV

7CMV, 1Influenza, 1RSV

S. pneumoniae, MRSA,

H. influenzae, Legionella, K

pneumonia,M. tuberculosis

2S.pneumoniae,1MRSA,4H.influenzae,1Legionella, 1 K.Pneumoniae, 1 M. tuberculosis

ATS/ERS statement 2001

Retrospective review

BALF

Yes

Steroid with or without cytotoxic therapy

Wootton

[9]

Korea

2011

68 M/15 F

64.06

83

TTV

12

NA

NA

ATS/ERS statement 2000

Collard et al. 2007

PCR

BALF

Yes

CS with or without immunomodulator therapy

Lasithiotaki

[53]

Greece

2011

NA

NA

11 and 13

HHV, HSV

1HSV, 5HHV

NA

NA

ATS/ERS statement 2000

PCR

Lung, BALF

Yes

NA

Pulkkinen

[54]

Finland

2012

11 M/1 F

57.3

12

EBV, HHV,HSV,CMV

11EBV,12HHV,2HSV,2CMV

NA

NA

ATS/ERS statement 2000, ATS/ERS

statement 2002

PCR

Lung

Yes

Prednisolone; cyclosporin A

Calabrese

[55]

Canada

2013

39 M/16 F

55.2

55

HHV-6, PV B19, CM, EBV

7HHV, 4CMV, 13EBV

NA

NA

ATS/ERS statement 2002

PCR, IHC

Lung tissues

Yes

NA

dos Santos

[56]

Brazil

2013

7 M/6 F

65

13

MV, CMV

2MV, 1CMV

NA

NA

ATS/ERS statement 2002

IHC

Surgical lung biopsy

NA

NA

Folcik

[57]

USA

2013

14 M/7 F

60.6

21

HVS

21

NA

NA

ATS/ERS/JRS/ALAT statement, Raghu et al

2011

ISH, IHC

Lung

NA

NA

Bando

[58]

Japan

2014

5 M/4 F

71.4

9

TTV

9

Nontuberculus mycobacterium, Streptococcus pneumoniae, Haemophilus influenzae

3

ATS/ERS/JRS/ALAT statement, Raghu et al.

2012

Real-Time PCR, culture

Serum-sputum

Yes

Steroids/immunosuppressants/

PFD

Ushiki

[59]

Japan

2014

11 M/3 F

69.5

14

RSV,CMV

1RSV, 0CMV

NA

NA

Collard et al. 2007

PCR

BAL

NA

Not treated

Rabea

[60]

Egypt

2015

13 M/17 F

52.4

30

HCV

9

NA

NA

ATS/ERS statement2002

ELISA

Serum

Yes

NA

Keyvani

[24]

Iran

2017

22 M/18 F

66.62

40

RSV,

Parainfluenza, Rhino, Corona, Influenza

1RSV, 3 parainfluenza,4 rhino,1corona,0 influenza

NA

NA

CT scan

DNA array assay

Nasopharyngeal, BAL

NA

NA

Saraya

[61]

Japan

2018

18 M/9 F

74

27

HHV,HPIV,CMV

3 HHV, 2CMV, 1HPIV

NA

NA

Collard et al. 2007, Collard et al. 2016

PCR

Nasal swab, sputu, BALF

Yes

Antifibroticagent/CS oral /CSpulseintravenous CY/oral + CsA/CY

Weng

[62]

China

2019

NA

NA

149

CMV, Adenovirus, Influenza B, RSV

2CMV, Adenovirus, 4Influenza B, 6RSV

Mycoplasma, Legionella, Chlamydia

11,Mycoplasma, 8Legionella, 1Chlamydia

ATS/ERS/JRS/ALAT statement, Raghu et al.

2011

IgM ELISA

Serum

Yes

Glucocorticoids, antibiotics, glutathione, immune support therapy

Weng

[62]

China

2019

AEIPF48M/0 F

StableIPF110M/12 F

AE-IPF = 65

stable IPF = 64

170

NA

NA

Klebsiella pneumoniae, Acinetobacter baumannii, Mycobacterium

tuberculosis, Pseudomonas aeruginosa, Serratia marcescense, Raoultella

10 K. pneumoniae,4A.baumannii, 8 M

tuberculosis,3P.aeruginosa, 1S.marcescen, 1Raoultella

ATS/ERS/JRS/ALAT statement, Raghu et al.

2011

Culture

Sputum

Yes

Glucocorticoids, antibiotics, glutathione, immune support therapy

Le Hingrat

[63]

France

2020

17 M/2 F

58

19

HHV,CMV,EBV,TTV

15HHV,2CMV,12EBV,12TTV

NA

NA

ATS/ERS/JRS/ALAT statement, Raghu et al.

2011

Real-Time PCR

Lung

Yes

PFD, nintedanib, prednisone

Odashima

[22]

Japan

2020

497 M/162 F

70.2

659

NA

NA

NTM, M. tuberculosis

35NTM, 23 M.tuberculosis

ATS/ERS/JRS/ALATstatement, Raghu et al.

2011

Retrospective cohort

Retrospective cohort

Yes

Steroid,Immunosuppressant

Jafarian

[64]

Iran

2020

16 M/13 F

58

29

EBV, HHV

6EBV,3HHV

NA

NA

ATS/ERS/JRS/ALAT statement, Wells et al.

2013

PCR

Lung

NA

NA

  1. CS corticosteroid, AZ azathioprine, PFD pirfenidone, CY cyclophosphamide