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Table 1 Characteristics of included studies on VOCs in pulmonary diseases

From: Clinical use of exhaled volatile organic compounds in pulmonary diseases: a systematic review

Author (year)

Design

Comparison

Sample size

Setting

Technique

Outcome measure

Ref.

Caldeira (2011)

Cross-sectional

Asthma vs. controls

35 children with asthma, 15 healthy controls

Hospital D. Pedro, Aveiro (Portugal)

GC-MS

Set of 44 VOCs

[17]

Caldeira (2012)

Cross-sectional

Asthma vs. controls

32 children with allergic asthma, 27 healthy controls

Hospital D. Pedro, Aveiro (Portugal)

GC-MS

VOCs profile

[18]

Dallinga (2010)

Cross-sectional

Asthma vs. controls

63 children with asthma, 57 healthy controls

Maastricht University MC

GC-MS

VOCs profile

[19]

(the Netherlands)

Dragonieri (2007)

Cross-sectional

Asthma vs. controls

10 patients with mild asthma, 10 patients with severe asthma, 20 healthy controls

Leiden University MC (the Netherlands)

eNose

VOCs profile

[10]

Ibrahim (2011)

Cross-sectional

Asthma vs. controls

35 patients with asthma, 23 healthy controls

Wythenshawe Hospital, Manchester (UK)

GC-MS

VOCs profile

[20]

Lärstad (2007)

Cross-sectional

Asthma vs. controls

13 patients with asthma, 14 healthy controls

Göteborg University (Sweden)

GC-FID

Ethane, Pentane, Isoprene

[21]

Montuschi (2010)

Cross-sectional

Asthma vs. controls

27 patients with asthma, 24 healthy controls

Istituto Dermopatico dell’ Immacolata, Rome (Italy)

eNose, GC-MS

VOCs profile

[22]

Olopade (1997)

Cross-sectional Short follow-up in acute asthma

Asthma vs. controls

12 patients with acute asthma, 11 patients with stable asthma, 17 healthy controls

University of Ilinois Hospital, Chicago (USA)

GC-FID

Pentane

[23]

Paredi (2000)

Cross-sectional

Asthma vs. controls

26 patients with asthma, 14 healthy controls

National Heart and Lung Institute, Imperial College, London (UK)

GC-FID

Ethane

[24]

Basanta (2010)

Cross-sectional

COPD vs. smokers

20 patients with COPD, 6 healthy smokers

Wytenshawe Hospital, Manchester (UK)

GC-DMS

VOCs profile

[25]

Cristescu (2011)

Cross-sectional

Emphysema vs. No emphysema

204 (former) smokers (43 with emphysema/COPD)

Radboud University, Nijmegen (the Netherlands)

PTR-MS

Mass-spectra

[26]

Fens (2009)

Cross-sectional

COPD vs. asthma vs. controls

30 patients with COPD, 20 patients with asthma, 20 non-smoking controls, 20 smoking controls

Academic MC Amsterdam; Haga Teaching Hospital, The Hague; Albert Schweitzer Hospital, Dordrecht (the Netherlands)

eNose

VOCs profile

[15]

Fens (2011)

Cross-sectional

COPD vs. asthma

40 patients with COPD, 21 patients with fixed asthma, 39 patients with classic asthma

Academic MC Amsterdam; Haga Teaching Hospital, The Hague; Albert Schweitzer Hospital, Dordrecht (the Netherlands)

eNose

VOCs profile

[27]

Hattesohl (2011)

Cross-sectional Follow up after treatment

COPD vs. controls

10 patients with COPD with AAT deficiency, 23 patients with COPD without AAT deficiency, 10 healthy controls

Phillipps University, Marburg (Germany)

eNose

VOCs profile

[28]

Hauschild (2012)

Cross-sectional

COPD vs. controls

30 patients with COPD, 54 patients with COPD + BC, 35 healthy controls

Max Planck Institute for Informatics, Saarbrücken (Germany)

IMS

VOCs profile

[29]

Paredi (2000)

Cross-sectional

COPD vs. controls

22 patients with COPD, 14 healthy controls

National Heart and Lung Institute, Imperial College, London (UK)

GC-FID

Ethane

[30]

Phillips (2012)

Cross-sectional

COPD vs. controls

119 patients with COPD, 63 healthy controls

Swansea University, Swansea (UK)

GC-MS

VOCs profile

[31]

Timms (2012)

Cross-sectional

COPD vs. asthma vs. controls

17 patients with COPD, 20 patients with asthma, 7 healthy controls

University of New South Wales, Sydney (Australia)

eNose

VOCs profile

[32]

Van Berkel (2010)

Cross-sectional

COPD vs. controls

66 patients with COPD, 15 steroid naïve COPD patients, 45 healthy controls

Maastricht University MC (the Netherlands)

GC-MS

VOCs profile

[33]

Barker (2006)

Cross-sectional

CF vs. controls

20 patients with CF, 20 healthy controls

Aachen CF center (Germany)

GC-MS

Set of 12 VOCs

[34]

Enderby (2009)

Cross-sectional

CF vs. asthma

16 patients with CF, 21 patients with asthma

University Hospital of North Staffordshire,Stoke-on-Trent (UK)

SIFT-MS

Hydrogen cyanide

[35]

Gilchrist (2012)

Cross-sectional

CF with- vs. CF without Ps. infection

8 CF patients with Ps. infection, 7 CF patients without Ps. infection

University Hospital of North Staffordshire,Stoke-on-Trent (UK)

SIFT-MS

Hydrogen cyanide

[36]

Kamboures (2005)

Cross-sectional

CF vs. controls

20 patients with CF, 23 healthy controls

University of California, Irvine (USA)

GC-MS

Carbonyl sulphide, Dimethyl sulphide, Carbon disulphide

[37]

McGrath (2000)

Cross-sectional Follow up after treatment

CF during- vs. CF after exacerbation vs. controls

12 patients with CF, 12 healthy controls

Queen’s University, Belfast (UK)

GC-MS

Isoprene

[38]

Paredi (2000)

Cross-sectional

CF vs. controls

23 patients with CF, 14 healthy controls

National Heart and Lung Institute, Imperial College, London (UK)

GC-FID

Ethane

[39]

Robroeks (2010)

Cross-sectional

CF vs. controls

48 patients with CF, 57 healthy controls

Maastricht University MC (the Netherlands)

GC-MS

VOCs profile

[14]

Shestivska (2011)

Cross-sectional

CF vs. controls

28 patients with CF, 9 healthy controls

Academy of Science of the Czech Republic, Prague (Czech Republic)

GC-MS

Methyl thiocyanate

[40]

Bajtarevic (2009)

Cross-sectional

LC vs. controls

285 patients with LC, 472 healthy controls

Innsbruck Medical University (Austria)

PTR-MS, GC-MS

VOCs profile

[41]

Buszewski (2012)

Cross-sectional

LC vs. controls

29 patients with LC, 44 healthy controls

Nicolaus Copernicus University, Torun (Poland)

GC-MS

Set of multiple VOCs

[42]

Crohns (2009)

Cross-sectional Follow up after treatment

LC vs. controls

11 patients with LC, 30 healthy controls

Tampere University Hospital (Finland)

GC-MS

Pentane

[43]

D’Amico (2010)

Cross-sectional

LC vs. no LC vs. controls

28 patients with LC, 28 patients with diverse lung diseases (e.g. COPD (n = 16), bronchitis), 36 healthy controls

C. Forlanini Hospital, Rome (Italy)

eNose (GC-MS)

VOCs profile

[44]

Di Natale (2003)

Cross-sectional

LC vs. controls

35 patients with LC, 9 post-surgical LC patients, 18 healthy controls

C. Forlanini Hospital, Rome (Italy)

eNose (GC-MS)

VOCs profile

[11]

Dragonieri (2009)

Cross-sectional

LC vs. COPD vs. controls

10 patients with NSCLC, 10 patients with COPD, 10 healthy controls

Leiden University MC (the Netherlands)

eNose

VOCs profile

[12]

Fuchs (2010)

Cross-sectional

LC vs. controls

12 patients with LC, 12 healthy smokers, 12 healthy controls

University Rostock (Germany)

GC-MS

Set of 10 volatile aliphatic aldehydes

[45]

Gaspar (2009)

Cross-sectional

LC vs. controls

18 patients with LC, 10 healthy controls

University of Lisbon (Portugal)

GC-MS

VOCS profile

[46]

Gordon (1985)

Cross-sectional

LC vs. controls

12 patients with LC, 9 healthy controls

Michael Reese Hospital, Chicago (USA)

GC-MS

Set of 22 VOCs

[47]

Kischkel (2010)

Cross-sectional

LC vs. controls

31 patients with LC, 31 healthy smokers, 31 healthy controls

University of Rostock (Germany)

GC-MS

Set of 42 VOCs

[48]

Ligor (2009)

Cross-sectional

LC vs. controls

65 patients with LC, 31 healthy controls

Innsbruck Medical University (Austria)

GC-MS

Set of 103 VOCs

[49]

Machado (2005)

Cross-sectional

LC vs. no LC vs. controls

28 patients with LC, 57 patients with diverse lung diseases (e.g. COPD (n = 12), asthma (n = 11), CBD), 50 healthy controls

Cleveland Clinic (USA)

eNose (GC-MS)

VOCs profile

[13]

Mazzone (2007)

Cross-sectional

LC vs. no LC vs. controls

49 patients with NSCLC, 73 patients with diverse lung diseases (e.g. COPD (n = 18), sarcoidosis), 21 healthy controls

Cleveland Clinic (USA)

Colorimetric sensor array

VOCs profile

[50]

Mazzone (2012)

Cross-sectional

LC vs. controls

92 patients with LC, 59 healthy smokers, 78 patients with diverse lung diseases (e.g. COPD (n = 8))

Cleveland Clinic (USA)

Colorimetric sensor array

VOCs profile

[51]

Peng (2009)

Cross-sectional

LC vs. controls

40 patients with LC, 56 healthy controls

Rambam Health Care Campus, Haifa (Israel)

GNPs GC-MS

VOCs profile

[52]

Peng (2010)

Cross-sectional

LC vs. controls

30 patients with PLC, 22 healthy controls

Rambam Health Care Campus, Haifa (Israel)

GNPs GC-MS

VOCs profile

[53]

Phillips (1999)

Cross-sectional

LC vs. no LC

108 patients with abnormal chest radiograph (60 patients with LC)

Penn State MC, Hershey (USA); Hammersmith Hospital, London (UK); St. Vincent’s MC, New York (USA)

GC-MS

VOCs profile

[54]

Phillips (2003)

Cross-sectional

LC vs. no LC vs. controls

178 patients with abnormal chest radiograph (87 patients with LC), 41 healthy controls

Charing Cross Hospital, London (UK); Columbia Presbyterian MC/New York University MC/St. Vincent’s MC, New York (USA); Penn State MC, Hershey (USA)

GC-MS

VOCs profile

[7]

Phillips (2007–2008)

Cross-sectional

LC vs. controls

193 patients with PLC, 211 (former) healthy smokers

Harper Hospital, Detroit; New York University MC/Columbia University MC/Weill Medical College of Cornell University, New York (USA); University of California, Los Angeles; Danbury Hospital, Connecticut (USA).

GC-MS

VOCs profile

[55], [56]

Poli (2005)

Cross-sectional Short follow-up in LC

LC vs. COPD vs. controls

36 patients with NSCLC, 25 patients with COPD, 35 healthy smokers, 50 healthy non-smokers

University of Parma (Italy)

GC-MS

Set of 13 VOCs

[57]

Poli (2008)

Follow-up

LC before vs. after surgery

36 patients with NSCLC, 50 healthy controls

University of Parma (Italy)

GC-MS

Set of 12 VOCs

[58]

Poli (2010)

Cross-sectional

LC vs. controls

40 patients with NSCLC, 38 healthy controls

University of Parma (Italy)

GC-MS

Set of 7 aldehydes

[59]

Preti (1988)

Cross-sectional

LC vs. controls

10 patients with LC, 16 healthy controls

University Hospital Pennsylvania, Philadelphia (USA)

GC-MS

Aniline, o-Toluidine

[60]

Rudnicka (2011)

Cross-sectional

LC vs. controls

23 patients with LC, 30 healthy controls

Nicolaus Copernicus University, Torun (Poland)

GC-MS

Set of 55 VOCs

[61]

Skeldon (2006)

Cross-sectional

LC vs. no LC vs. controls

12 patients with LC, 40 patients with diverse lung diseases, 58 healthy controls

Ninewells Hospital, Dundee (UK)

Laser absorption spectroscopy

Ethane

[62]

Song (2010)

Cross-sectional

LC vs. controls

43 patients with NSCLC, 41 healthy controls

Anhui Medical University, Hefei, Anhui (China)

GC-MS

1-butanol, 3-hydroxy-2-butanone

[63]

Steeghs (2007)

Cross-sectional

LC vs. controls

11 patients with LC, 57 healthy smokers

Radboud University, Nijmegen (the Netherlands)

PTR-MS

Mass-spectra

[64]

Ulanowska (2011)

Cross-sectional

LC vs. controls

137 patients with LC, 143 healthy controls

Nicolaus Copernicus University, Torun (Poland)

GC-MS

VOCs profile

[65]

Wehinger (2007)

Cross-sectional

LC vs. controls

17 patients with PLC, 170 healthy controls

Innsbruck Medical University (Austria)

PTR-MS

Mass-spectra

[66]

Westhoff (2009)

Cross-sectional

LC vs. controls

32 patients with LC, 54 healthy controls

Hemer Lung Hospital (Germany)

IMS

VOCs profile

[67]

Chapman (2012)

Cross-sectional

MPM vs. ARD vs. controls

20 patients with MPM, 18 patients with ARD, 42 healthy controls

St Vincent and Prince of Wales Hospital, Sydney (Australia)

eNose

VOCs profile

[68]

Gennaro (2010) Dragonieri (2012)

Cross-sectional

MPM vs. no MPM

13 patients with MPM, 13 subjects with long-term asbestos exposure, 13 healthy controls

University of Bari Aldo Moro, Bari (Italy)

eNose, GC-MS

VOCs profile

[69], [70]

Chambers (2009)

Cross-sectional

A. fumigatus vs. controls

32 patients with diverse lung diseases (e.g. asthma (n = 11), CF (n = 6), COPD (n = 3), 10 neutropenic patients, 14 healthy controls

University of Christchurch (New Zealand)

GC-MS

2-Pentylfuran

[71]

Hanson (2005)

Cross-sectional

VAP vs. no VAP

19 patients with + VAP score, 19 patients with - VAP score

University of Pennsylvania, Philadelphia (USA)

eNose

VOCs profile

[72]

Hockstein (2004)

Cross-sectional

VAP vs. no VAP

13 ventilated patients with VAP, 12 ventilated patients without VAP

University of Pennsylvania, Philadelphia (USA)

eNose

VOCs profile

[73]

Hockstein (2005)

Cross-sectional

VAP vs. no VAP

15 patients with + VAP score, 29 patients with - VAP score

University of Pennsylvania, Philadelphia (USA)

eNose

VOCs profile

[74]

Kanoh (2005)

Cross-sectional Short follow-up in ILD patients

ILD vs. controls

34 patients with ILD, 16 healthy controls

National Defense Medical College, Saitama (Japan)

GC-FID

Ethane

[75]

Kolk (2012)

Cross-sectional

TB vs. no TB

171 patients suspected of TB

Royal Tropical Institute, Amsterdam (the Netherlands); Desmond Tutu TB Centre, Cape Town (South Africa)

GC-MS

VOCs profile

[76]

Phillips (2007)

Cross-sectional

TB vs. no TB vs. controls

42 patients suspected of TB, 59 healthy controls

Bellevue Hospital, New York (USA)

GC-MS

VOCs profile

[77]

Phillips (2010)

Cross-sectional

TB vs. no TB

226 patients suspected of TB

University of California, San Diego (USA); University of Santo Tomas, Manila (Philippines), De La Salle University Hospital, Cavite (Philippines), East London Tuberculosis Service (UK)

GC-MS

VOCs profile

[78]

Phillips (2012)

Cross-sectional

TB vs. controls

130 patients with TB, 121 healthy controls

University of Santo Tomas, Manila (Philippines); De La Salle University Hospital, Cavite (Philippines); Homerton University Hospital, London (UK); Hinduja Hospital, Mumbai (India)

GC-SAW

VOCs profile

[79]

Syhre (2009)

Cross-sectional

TB vs. controls

10 patients with TB, 10 healthy controls

Otago University, Christchurch (New Zealand); Modilon Hospital, Madang (Papua New Guinea)

GC-MS

Methyl nicotinate

[80]

Scholpp (2002)

Cross-sectional

Critically ill patients vs. controls

65 critically ill patients (n = 19 with head injury, n = 13 with ARDS, n = 33 at risk of ARDS), 10 healthy controls

University Hospital of Freiburg (Germany)

GC-FID, GC-MS

Acetone Isoprene, n-Pentane

[81]

Schubert (1998)

Cross-sectional Short follow-up in VAP patients

ARDS vs. no ARDS

19 critically ill patients with ARDS, 18 critically ill patients without ARDS

University Hospital of Freiburg (Germany)

GC-FID, GC-MS

Acetone Isoprene, n-Pentane

[82]

  1. Abbreviations: AAT deficiency = Alpha 1-antitrypsin deficiency; A. fumigatus = Aspergillus fumigatus; ARD = Benign Asbestos-Related Diseases; ARDS = Acute Respiratory Distress Syndrome; BC = Bronchial Carcinoma; CBD = Chronic pulmonary Beryllium Disease; CF = Cystic Fibrosis; Classic asthma = Asthmatics with reversible airway obstruction; COPD = Chronic Obstructive Pulmonary Disease; DMS = Differential Mobility Spectrometry; eNose = electronic Nose; FID = Flame Ionization Detector; Fixed asthma = Asthmatics with fixed airway obstruction; GC = Gas Chromatography; GNPs = Gold Nano Particles sensors; ILD = Interstitial Lung Disease (e.g. sarcoidosis, idiopathic pulmonary fibrosis, cryptogenic organizing pneumonia); IMS = Ion Mobility Spectrometry; LC = Lung Cancer; MC = Medical Centre; MPM = Malignant Pleural Mesothelioma; MS = Mass Spectrometry; NSCLC = Non-Small Cell Lung Cancer; OFD = On-Fiber-Derivatization; P. infection = Pseudomonas aeruginosa infection; PLC = Primary Lung Cancer; PTR-MS = Proton Transfer Reaction Mass Spectrometry; Ref. = Reference; SAW = surface acoustic wave; SIFT-MS = Selected Ion Flow Tube Mass Spectrometry; TB = pulmonary Tuberculosis; VAP = Ventilator Associated-Pneumonia; VOCs = Volatile Organic Compounds.