Table 2. Studies on breath analysis for MPM, asbestosis and asbestos-exposed persons, according to breath source.
| Article (ref) | Study design | Exclusion criteria | Technique(s) | Background correction | Study population (n, median age) | Statistics | Validation | Results | VOCs |
|---|---|---|---|---|---|---|---|---|---|
| EBC + FENO | |||||||||
| Lehtonen et al., 2007 (67) | Case-control study | Acute respiratory symptoms; asthma; chronic bronchitis; COPD; current smoking; other pulmonary diseases | NOA (Sievers NOA 280) | No | Asbestosis (n=15, 67 y); HC (n=15, 63 y) | Kolmogorov-Smirnov test; Student’s t-test | NA | ↑ FENO (P=0.008); ↑ LT B4 (P=0.002); ↑ 8-isoprostane (P=0.048); ↑ CRP (P=0.003); ↑ IL-6 (P=0.007); ↑ Myeloperoxidase (P=0.034) |
NA |
| Pelclová et al., 2008 (32) | Case-control study | No exclusion criteria. Only inclusion criteria: lifestyle similar to the asbestos-exposed group | LC-ESI-MS | No | AEx (n=92, 69 y); HC (n=46, 65 y) | Student’s t-test; F-test; ANOVA; Chi2-test; Linear regression | NA | ↑ 8-isoprostane (P≤0.001) | NA |
| Chow et al., 2009 (68) | Case-control study | Asthma; COPD; Current smoking (<1 y) inhaled corticosteroids | Ecoscreen® | No | Asbestosis (n=18, 75y) HC (n=26, 71y) | ANOVA; Post hoc tests; Pearson’s correlation coefficient | NA | ↑ 8-isoprostane (P≤0.001); ↑ H2O2 (P≤0.05); ↑ FENO (P≤0.05) |
NA |
| Syslová et al., 2010 (69) | Case-control study | NA | LC-ESI-MS/MS | No | Asbestosis/silicosis (n=10, 69 y); HC (n=10, 67 y) | Student’s t-test | Internal validation | ↑ 8-iso-PGF2α (P=0.05); ↑ o-Tyr (P=0.05); ↑ 8-OHdG (P=0.01) |
NA |
| Lehtimäki et al., 2010 (70) | Case-control study | Asthma; asthma medication; bronchiectasis or signs of emphysema; FEV1/FVC <70%; other pulmonary diseases; HC: respiratory symptoms | NOA (Sievers NOA 280) | No | AEx with borderline parenchymal changes (AExborderline) (n=31, 67 y) AEx with normal parenchymal changes (AExnormal) (n=35, 62 y); HC (n=41, 63 y) | Kolmogorov-Smirnov test; Student’s t-test; Chi2-test; Pearson’s correlation coefficient; LSD post-test | NA | (I) AExborderline
vs. HC: ↑ FENO (P=0.009); ↑ LT B4 (P≤0.001); ↑ 8-isoprostane (P=0.021). (II) AExnormal vs. HC: ↑ FENO (P=0.687); ↑ LT B4 (P≤0.001); ↑ 8-isoprostane (P=0.269) |
NA |
| Sandrini et al., 2006 (71) | Case-control study | Alcohol; asthma; inhaled glucocorticosteroids other medications; lung diseases; recent upper RTI; sinusitis; smoking (active or passive) | Rapid-response chemiluminescence NO and CO analyzer | No | Asbestosis (n=12, 66 y); PP (n=32, 66 y); HC (n=35, 68 y) | ANOVA; Post hoc test; Spearman’s correlation coefficient | NA | ↑ FENO (P=0.006) | NA |
| VOCs | |||||||||
| de Gennaro et al., 2010 (72) | Cross-sectional, case-control study | Asthma; cancer; COPD; current smokers; no current treatment of MPM; systemic disease; upper or lower RTI (<4 weeks); HC: drug usage and any known disease | TD-GC-MS | Yes | MPM (n=13, 61 y); AEx (n=13, 52 y); HC (n=13, 67 y) | ANOVA; PCA; DFA; F-test | Internal validation (cross-validation) | MPM vs. AEx vs. HC: acc =0.95 | Cyclopentane, cyclohexane, dodecane, xylene, toluene, decane, methylcyclohexane, dimethylnonane, benzaldehyde, limonene, α-Pinene, β-Pinene, 1,2-pentadiene, methyl-octane, styrene, trimethylbenzene, acetophenone |
| Chapman et al., 2012 (73) | Cross-sectional, case-control study | Acute exacerbation of any underlying respiratory disease (<4 weeks); any uncontrolled medical condition; recent RTI; HC: abnormal spirometry; current respiratory symptoms; lung disease | CPA eNose (Cyranose 320°) | No | MPM (n=20, 69 y); HC (n=42, 67 y); ARD (n=18, 70 y), of which 5 with asbestosis | PCA | External validation | (I) MPM vs. HC: training: acc =0.95; Test: acc =0.90, se =0.90, sP =0.91. (II) MPM vs. ARD: sP =0.83. (III) MPM vs. asbestosis: sP =0.60. (IV) MPM vs. ARD vs. HC: Se =0.90; sP =0.88, PPV =0.60, NPV =0.98 |
NA |
| Dragonieri et al., 2012 (74) | Cross-sectional, case-control study | Cardiovascular disease; diabetes; pulmonary disease; respiratory or systemic infection (<4 weeks); HC: any known disease and a history of smoking | eNose (Cyranose 320°) | No | MPM (n=13, 61 y); HC (n=13, 52 y); ARD (n=13, 76 y) | Student’s t-test; PCA; CDA | Internal validation (LOOCV, bootstrapping) | (I) MPM vs. ARD vs. HC: acc =0.80. (II) MPM vs. ARD: acc =0.81, se =0.92, sP =0.86, PPV =0.83, NPV =0.80. (III) MPM vs. HC: acc =0.85, se =0.92, sP =0.69, PPV =0.91, NPV =0.80 |
NA |
| Lamote et al. 2016 (52) | Multicentre, cross-sectional, case-control study | MPM: anti-tumour treatment before breath sampling; HC: presence of other asbestos-related diseases | MCC-IMS | Yes | MPM (n=23, 66 y); AEx (n=22, 56 y); HC (n=21, 56 y) | Lasso regression | Internal validation (LOOCV) | (I) MPM vs. HC + AEx: acc =0.76, se =0.87, sP =0.70, PPV =0.61, NPV =0.91 | P3, P5, P50, P71 |
| (II) MPM vs. AEx: acc =0.87, se =0.87, sP =0.86, PPV =0.87, NPV =0.86 | P3, P5, P30, P50, P54, P71 | ||||||||
| (III) AEx vs. HC: acc =0.91, se =0.95, sP =0.86, PPV =0.88, NPV =0.95 | P5, P8, P13, P25 | ||||||||
| (IV) MPM vs. HC: acc =0.82, se =0.96, sP =0.67, PPV =0.76, NPV =0.93 | P50, P84 | ||||||||
| Lamote et al., 2017 (75) | Multicenter, cross-sectional, case-control study | MPM: anti-tumour treatment before breath sampling; HC: presence of other asbestos-related diseases | MCC-IMS | Yes | MPM (n=52, 67 y); ARD (n=41, 58 y); AEx (n=59, 53 y); HC (n=52, 51 y) |
Lasso regression | Internal validation (LOOCV) | (I) MPM vs. HC: acc =0.65, se =0.89, sP =0.42, PPV =0.61, NPV =0.79 | P0, P4, P10, P15, P99, P103, P104, P108, P114, P119, P203, P207, P208 |
| (II) MPM vs. AEx: acc =0.88, se =0.87, sP =0.90, PPV =0.88, NPV =0.88 | P1, P3, P9, P21, P26, P66, P84, P101, P110, P112, P114, P120, P126 | ||||||||
| (III) MPM vs. ARD: acc =0.82, se =0.89, sP =0.73, PPV =0.81, NPV =0.83 | P1, P9, P21, P26, P34, P83, P92, P94, P102, P114, P119, P127, P176, P185 | ||||||||
| (IV) MPM vs. Aex + ARD: acc =0.85, se =0.94, sP =0.80, PPV =0.71, NPV =0.96 | P1, P7, P9, P15, P21, P26, P84, P88, P101, P122, P151, P153, P159, P161 | ||||||||
| Lamote et al., 2017 (31) | Multicenter, cross-sectional, case-control study | Start of any anti-tumour treatment HC: presence of non-asbestos-related disease | GC-MS; eNose platform (Cyranose C320°, Tor Vergata eNose, Common Invent eNose, and Owlstone Lonestar) | Yes | MPM (n=14, 69 y); ARD (n=15, 60 y); AEx (n=19, 50 y); HC (n=16, 56 y) | Lasso regression; PCA; Shapiro-Wilk test; Chi2-test | Internal validation (LOOCV) | eNose | |
| (I) MPM vs. HC: acc =0.65, se =0.67, sP =0.64, PPV =0.67, NPV =0.64 | |||||||||
| (II) MPM vs. AEx:acc =0.73, se =0.80, sP =0.64, PPV =0.75, NPV =0.70 | |||||||||
| (III) MPM vs. ARD: acc =0.70, se =0.75, sP =0.64, PPV =0.69, NPV =0.70 | |||||||||
| (IV) MPM vs. Aex + ARD: acc =0.74, se =0.82, sP =0.55, PPV =0.82, NPV =0.55 | |||||||||
| GC-MS | |||||||||
| (I) MPM vs. HC: acc =0.71, se =0.64, sP =0.79, PPV =0.75, NPV =0.69 | Nonane, VOC IK 1349, Benzonitrile, Isoprene, Limonene, Propylbenzene, 1,3-dichlorobenzene, 3-methylpentane | ||||||||
| (II) MPM vs. AEx: acc =0.97, se =0.93, sP =1.00, PPV =1.00, NPV =0.95 | Ethanol, Diethyl ether, 2-ethyl-1-hexanol, Limonene, Nonanal, 2-methyl-1-propanol, Methyl-cyclopentane, 1,2,4-trichlorobenzene, Cyclohexane, VOC IK 679, Chloroform, naphthalene, VOC IK 1287, Phenol, Linalole, Furfural, Bromobenzene | ||||||||
| (III) MPM vs. ARD: acc =0.79, se =0.79, sP =0.80, PPV =0.79, NPV =0.80 | VOC IK 931, VOC IK 1493, β-Pinene, Diethyl ether, 1,2-dichlorobenzene, Limonene, Hexane | ||||||||
| (IV) MPM vs. Aex + ARD: acc =0.94, se =1.00, sP =0.91, PPV =0.82, NPV =1.00 | Ethanol, Diethyl ether, xylene, Isothiocyanato-cyclohexane, VOC IK 1233, VOC IK 1287, VOC IK 1309, n-Butylbenzene, 1,2-dichlorobenzene, Methylbenzoate, 1,2,3-trichloro-benzene, Limonene, Bromobenzene, VOC IK 1100, Tert-butylbenzene, m/p-2,2,4-trimethyl-pentane, VOC IK 1493, VOC IK 720, Hexamethyldisiloxane | ||||||||
8-iso-PGF2α, 8-iso-prostaglandin F2α; 8-OHdG, 8-hydroxy-2’-deoxy-guanosine; acc, accuracy; AEx, asymptomatic asbestos exposed persons; ARD, patients with benign asbestos related disease; CDA, Canonical Discriminant Analysis; COPD, chronic obstructive pulmonary disease; CPA, carbon polymer array; DFA, Discriminant Function Analysis; EBC, exhaled breath condensate; eNose, electronic nose; FENO: fractional exhaled nitric oxide; FEV1/FVC, forced expiratory volume in one second/forced vital capacity; H2O2, hydrogen peroxide; HC, healthy controls; IL, interleukin; LC-ESI-MS(/MS), liquid chromatography-electrospray ionization-mass spectrometry(-tandem mass); LOOCV, leave-one-out cross-validation, LT, leukotriene; MCC-IMS, multicapillary column-ion mobility spectrometry; MPM, malignant pleural mesothelioma; NA, not applicable; NO, nitric oxide; NOA, nitric oxide analyzer; NPV, negative predictive value; O-Tyr, o-tyrosine, PCA, Principal Component Analysis; PP, pleural plaques; PPV, positive predictive value; ref, reference; RTI, respiratory tract infection; se, sensitivity; sp, specificity; TD-GC-MS, thermal desorption gas chromatography-mass spectrometry; VOCs, volatile organic compounds; y, years; ↑, level increased in first group.