Systematic review of pleural plaques and lung function

Figures & data

Figure 1. Literature identification and screening process.

Figure 2. Risk of bias evaluation process.

Table 1. HRCT study characteristics.

					Detection of plaques			Lung function tests		Statistical analysis
References	Study design	Study size	Participation rate	Appropriate controls	Multiple readers	Extent of plaques	Exposure assessment	Standards	Multiple parameters	Model type	Adjustment for BMI	Adjustment for smoking	Adjustment for exposure
Staples et al. (1989)	Cross-sectional	133	NR	Yes	2	No	Yes	NR	Yes	t-test	No	No	No
Valkila et al. (1995)	Cross-sectional	59	NR	Yes	1	No	Yes	Dawson (1982); Knudson et al. (1976)	Yes	Multiple regression	No	Yes	No
Kee et al. (1996)	Cross-sectional	106	NR	Yes	1	No	Yes	ATS	Yes	ANOVA	No	No	No
Neri et al. (1996)	Cross-sectional	119	NR	Yes	2	No	Yes	ATS	Yes	ANOVA, multiple regression	No	Yes	No
Soulat et al. (1999)	Cross-sectional	170	67%	Yes	1	No	Yes	Quanjer et al. (1993)	Yes	Student's t-test	No	No	No
Copley et al. (2001)	Cross-sectional	50	NR	None^a	2	Yes	No	European Respiratory Society	Yes	Multivariate analysis	No	No	No
Oldenburg  et al. (2001)	Cross-sectional	43	NR	Yes	NR	Yes	Yes	NR	Yes	Wilcoxon rank sum test; Jonckheere–Terpstra test for effect of number of plaques	No	Yes	No
Van Cleemput  et al. (2001)	Cross-sectional	94	95%	Yes	3	Yes	Yes	Quanjer et al. (1993); European Community for Steel and Coal	Yes	Unpaired t-test; multiple regression for effect of plaque size	No	Yes	Yes
Mazziotti  et al. (2004)	Cross-sectional	31	NR	Yes	2	No	Yes	ATS	Yes	ANOVA	No	No	No
Rui et al. (2004)	Longitudinal, mean 3.7 year follow-up	103	NR	Yes	1	No	Yes	European Respiratory Society	Yes	t-test, Χ^2 test, GEE, regression	Yes	Yes	Yes
Sette et al. (2004)	Cross-sectional	82	NR	Yes	3	Yes	Yes	ATS	No	Logistic regression	No	No	No
Sandrini et al. (2006)	Cross-sectional	91	NR	No	NR	No	No	ATS	Yes	ANOVA followed by Scheffe multiple comparison post hoc test	No	Yes	No
Damian et al. (2007)	Longitudinal (mean 5 years)	305	NR	Yes	NR	No	Yes	NR	Yes	Paired t-test	No	Yes	No
Clin et al. (2011)	Cross-sectional	2743	NA	Yes	2–3	Yes	Yes	European Respiratory Society	Yes	Multilevel unconditional logistic models; multilevel generalized linear models (for effect of extent of LPT)	Yes	Yes	Yes
Spyratos et al. (2012)	Cross-sectional	112	42%	Yes	2–3	No	Yes	ATS	Yes	ANOVA & multivariate linear regression	No	Yes	Yes
Clark et al. (2014)	Cross-sectional	166	NR	Yes	NR	Yes	Yes	ATS	Yes	Multivariate regression analyses with Tukey adjustment for multiple comparisons	Yes	Yes	Yes

ANOVA = analysis of variance; ATS = American Thoracic Society; BMI = body mass index; GEE = generalized estimating equations; HRCT = high-resolution computed tomography; LPT = localized pleural thickening; NA = not applicable; NR = not reported.

^aRegression analysis to identify independent effect of pleural plaques; no control group used.

Table 2. X-ray study characteristics.

					Detection of plaques			Lung function tests		Statistical analysis
References	Study design	Study size	Participation rate	Appropriate controls	Multiple readers	Extent of plaques	Exposure assessment	Standards	Multiple parameters	Model type	Adjustment for BMI	Adjustment for smoking	Adjustment for exposure
Lumley (1977)	Cross-sectional	194	NR	Yes	3	No	No	NR	Yes	Not specified	No	No	No
Fridriksson et al. (1981)	Cross-sectional	45	90%	No	NR	Yes	Yes	NR	Yes	Simple linear regression, partial regression, ANOVA, analysis of covariance	Yes	Yes	No
Hedenstierna et al. (1981)	Cross-sectional	162	NR	Yes	NR	No	Yes	NR	Yes	t-test	No	Yes	No
Ohlson et al. (1984)	Cross-sectional	201	96%	Yes	1	No	Yes	ATS	Yes	Analysis of Covariance and multiple regression	No	Yes	No
Neuberger & Ambrosch (1985)	Cross-sectional	182	14%	Yes	2	No	No	NR	Yes	t-test	No	Yes	No
Ohlson et al. (1985)	Longitudinal (4-year follow up to Ohlson et al., 1984)	131	86% (exposed) 86% (referents)	Yes	1	No	Yes	NR	Yes	Regression equations; lung volume changes over 4 years analyzed with ANOVA	No	Yes	Yes
Järvholm & Sanden (1986)	Cross-sectional	202	NR	Yes	1	No	Yes	NR	Yes	t-test	No	Yes	No
Hilt et al. (1987)	Cross-sectional	634	NR	Yes	2	No	Yes	NR	Yes	Mantel Haenszel test	No	Yes	No
Sider et al. (1987)	Cross-sectional	93	NR	Yes	1–2	No	Yes	NR	Yes	Not specified	No	No	No
Hjortsberg et al. (1988a)	Cross-sectional	87	NR	No	2	No	Yes	NR	Yes	t-test	No	Yes	No
Hjortsberg et al. (1988b)	Cross-sectional	87	NR	No	2	No	Yes	NR	Yes	t-test	No	Yes	No
Järvholm & Larsson (1988)	Cross-sectional	1233	NR	Yes	1	No	No	NR	Yes	t-test, Χ^2 test	No	Yes	No
Oliver et al. (1988)	Cross-sectional	383	NR	Yes	2	Yes	Yes	ATS	Yes	Stratified and multivariate analyses; logistic regression	No	Yes	Yes
Rosenstock et al. (1988)	Cross-sectional	681	97%	Yes	2	No	Yes	NR	No	Student t-test	No	No	No
Britton et al. (1989)	Cross-sectional	34	NR	Yes	2	No	Yes	Methods of Hughes and Empey	Yes	NR	No	Yes	No
Bourbeau et al. (1990)	Cross-sectional	110	85%	Yes	2	No	Yes	ATS	Yes	ANOVA	No	Yes	Yes
Hillerdal et al. (1990)	Cross-sectional	23	NR	No	1	Yes	Yes	NR	Yes	t-test	No	Yes	No
Kilburn & Warshaw (1990)	Cross-sectional	64	NR	No	NR	No	No	ATS	Yes	t-test	No	Yes	No
Schwartz et al. (1990a)	Cross-sectional	1211	46%	Yes	1 (3 on 10%  of films)	No	Yes	ATS	Yes	ANOVA and multivariate linear regression	No	Yes	No
Schwartz et al. (1990b)	Cross-sectional	24	3.4%	Yes	1	No	Yes	ATS	Yes	Student t-test and linear regression	No	Yes	Yes
Kouris et al. (1991)	Cross-sectional	913	NR	Yes	2	No	Yes	NR	Yes	t-test and logistic regression	No	No	No
Kennedy et al. (1991)	Cross-sectional	88	77%	Yes	2	No	Yes	ATS	Yes	Linear regression and logistic regression	No	Yes	No
Broderick et al. (1992)	Cross-sectional (same population as Schwartz 1990)	1211	46%	Yes	1 (3 on 10% of films)	Yes (did not separate LPT versus DPT)	Yes	ATS	No	Stepwise multiple linear regression	No	Yes	Yes
Dujić et al. (1993)	Cross-sectional	307	82%	Yes	2	Yes	Yes	ATS	Yes	Mann–Whitney and Χ^2 tests	No	Yes (logistic regression only)	Yes (logistic regression only)
Zavalic & Bogadi-Sare (1993)	Cross-sectional	299	NR	Yes	3	Yes	Yes	NR	Yes	t-test, Mann–Whitney test	No	No	No
Schwartz et al. (1994)	Longitudinal (mean 2 years)	117	NR	Yes	3	No	Yes	ATS	Yes	GEE	No	Yes	No
Ostiguy et al. (1995)	Cross-sectional/Longitudinal (7 years)	494	NR	Yes	2	Yes	Yes	ATS	Yes	ANOVA	Yes	Yes	Yes
Di Lorenzo et al. (1996)	Cross-sectional	39	86%	Yes	2	No	Yes	ATS	Yes	ANOVA	No	Yes	Yes
Glencross et al. (1997)	Longitudinal (10 years)	122	23% (initial study) 38% (follow-up)	Yes	2–3	No	Yes	ATS	No	GEE approach	No	Yes	Yes
Singh et al. (1999)	Cross-sectional	26	NR	Yes	1	No	No	NR	Yes	t-test	No	No	No
Weill et al. (2011)	Cross-sectional	4524	NR	Yes	3	No	Yes	NR	No	t-test, Χ^2 tests, multiple linear regression	Yes	Yes	Yes
Larson et al. (2012)	Cross-sectional	6476	79%	Yes	2	Yes	Yes	ATS	Yes	Logistic regression	Yes	Yes	Yes
Miller et al. (2013)	Cross-sectional	5003	NR	Yes	1	No	Yes	ATS	Yes	ANOVA	Yes	Yes	No
Garcia-Closas & Christiani (1995)	Cross-sectional	631	NR	Yes	2	No	Yes	ATS	Yes	t-test, Χ^2 tests, multiple linear regression, logistic regression	No	Yes	Yes
Miller et al. (1992)	Cross-sectional	2611	40%	Yes	1	No	Yes	ATS	Yes	t-test, ANOVA, Duncan's multiple-range test, multiple linear regression	No	No^a	No
Bresnitz et al.(1993)	Cross-sectional	91	NR	Yes	2–3	No	Yes	ATS	Yes	Two-tailed t-test, Χ^2 tests, ANOVA	Yes	Yes	Yes

ANOVA = analysis of variance; ATS = American Thoracic Society; BMI = body mass index; DPT = diffuse pleural thickening; GEE = generalized estimating equations; HRCT = high-resolution computed tomography; LPT = localized pleural thickening; NR = not reported; PP = pleural plaques.

^aNot considered when analyzing the pleural plaque versus control data.

Table 3. HCRT study results for pleural plaques and lung function.

									Result
References	Asbestos-exposed population	No. with pleural plaques only	Reference population	No. of Referents	Location	Asbestos exposure measure	Avg. estimated exposure	Measure of lung function^a	Unexposed control	Exposed control	Pleural plaques only	p Value^b	Extent of plaques effect
Staples et al. (1989)	Asbestos-exposed workers	NR	Asbestos-exposed workers	76	US	Duration (mean years)	Normal: 14.5 PP: 20.8	VC, %		NR	NR	>0.05	Not assessed
								FEV1, %		NR	NR	>0.05
								FEV1/FVC%		NR	NR	>0.05
								TLC, %		NR	NR	>0.05
								RV, %		NR	NR	>0.05
								DLCO, %		NR	NR	>0.05
								DL/VA, %		NR	NR	>0.05
Valkila et al. (1995)	Construction workers	23	NA (regression analysis)	NA	Finland	Duration (mean years)	30	FVC	NR	NR	NR	0.444	Not assessed
								FEV1	NR	NR	NR	0.224
								DLCO	NR	NR	NR	0.03
								Cst	NR	NR	NR	0.065
								Cdyn	NR	NR	NR	0.78
Kee et al. (1996)	Shipyard and construction workers	44	Shipyard and construction workers	9	US	Duration (mean years)	26.5 ± 12	FVC %		74 ± 17	78 ± 14	>0.05	Not assessed
								FEV1/FVC %		77 ± 8	74 ± 10
								DLCO %		80 ± 22	88 ± 20
Neri et al. (1996)	Shipyard factory workers	50	Shipyard factory workers	31	Italy	Duration (mean years)	Normal: 4.8 ± 4.4 PP: 9.1 ± 5.5	FVC		NR	NR	>0.05	Not assessed
								FEV1		NR	NR
								FEV1/FVC		NR	NR
								TLC		NR	NR
								DLCO		NR	NR
								MEF25–75		NR	NR
Soulat et al. (1999)	Asbestos-exposed workers	84	Asbestos-exposed workers	51	France	Duration (mean years)	12.9 ± 0.6	FVC, %		108.9 ± 2.60 (SE)	110.2 ± 2.03 (SE)	NS	Not assessed
								FEV1, %		108.4 ± 3.15 (SE)	112.6 ± 2.40 (SE)	NS
								MEF, %		111.1 ± 3.66 (SE)	116.1 ± 2.96 (SE)	NS
								MMEF, %		76.9 ± 4.53 (SE)	81.1 ± 4.02 (SE)	NS
Copley et al. (2001)	Patients with benign pleural disease	NR	NA (regression analysis)	NA	England	NR	NR	FVC			NR	>0.05	No effect
								FEV1			NR
								TLC			NR
								RV			NR
								DCO			NR
Oldenburg et al. (2001)	Asbestos workers	22	Asbestos workers	21	Germany	Duration (mean years)	30.7	FVC, %		89.89 ± 11.86	88.8 ± 13.89	>0.05	No relationship between number of plaques and lung function
								FEV1, %		86.58 ± 28.09	91.67 ± 20.25
								FEV1/VC %		94.9 ± 19.48	98.58 ± 13.48
								MEF25, %		106.74 ± 54.27	101.37 ± 48.24
								MEF50, %		93.07 ± 37.69	90.14 ± 36.79
								MEF75, %		84.9 ± 29.93	82.64 ± 32.58
Van Cleemput et al. (2001)	Asbestos cement workers	44	Asbestos cement workers	21	Belgium	CEI (f-years/ml)	26.3 ± 12.6	VC, %		109.8 ± 14.9	110.5 ± 13.4	0.24	No effect
								FEV1, %		103.8 ± 13.7	104.1 ± 12.9	0.24
								FEV1/VC		0.78 ± 0.07	0.78 ± 0.07	1
								PEF, %		108.7 ± 21.5	100.5 ± 23.3	0.48
								MEF75, %		108.8 ± 28.3	99.2 ± 26.1	0.48
								MEF50, %		103.0 ± 35.7	109.2 ± 25.02	0.27
								MEF25, %		80.9 ± 28.0	84.8 ± 30.3	0.54
								TLCO, %		97.2 ± 15.5	102.0 ± 16.5	0.93
Mazziotti et al. (2004)	Workers exposed to siliceous dust	6	Workers exposed to siliceous dust	22	Italy	Duration (mean years)	Normal: 15.0 ± 7.4 PP: 31.2 ± 3.0	FVC, %		90.6 ± 9.1	83.5 ± 10.4	0.17^c	Not assessed
								FEV1, %		94.6 ± 15.4	77.8 ± 9.1	0.004^c
								FEF25–75, %		111.1 ± 30.7	80.0 ± 5.5	0.0001^c
Rui et al. (2004)	Asbestos workers	36	Asbestos workers	67	Italy	Duration (mean years)	Normal: 22 ± 6 PP: 30 ± 6	VC, % (baseline)		97 ± 10	91 ± 10	<0.05	Not assessed
								FEV1, % (baseline)		103 ± 12	97 ± 13	NS
								FEV1/VC (baseline) %		79 ± 6	78 ± 6	NS
								TLC, % (baseline)		98 ± 8	93 ± 7	<0.05
								VC, % (follow-up)		96 ± 11	90 ± 10	<0.05
								FEV1, % (follow-up)		102 ± 13	95 ± 14	<0.05
								FEV1/VC (follow-up) %		78 ± 6	77 ± 7	NS
								TLC, % (follow-up)		97 ± 9	91 ± 9	<0.05
								ΔVC, %/year (95% CI)		Reference	−3.4 (−7.9 to 1.0)	>0.05
								ΔFEV1, %/year (95% CI)		Reference	−1.5 (−7.1 to 4.0)	>0.05
								ΔFEV1/VC, %/year (95% CI)		Reference	0.3 (−2.7 to 3.2)	>0.05
								ΔTLC, %/year (95% CI)		Reference	−3.6 (−7.4 to 0.2)	>0.05
Sette et al. (2004)	Asbestos-cement workers and chrysotile miners	NR	Asbestos-cement workers and chrysotile miners	21	Brazil	Duration (mean years)	13.8 ± 10.1	Gas exchange impairment			Not associated with gas exchange impairment	>0.05	# Of plaques not associated with gas exchange impairment
Sandrini et al. (2006)	Patients with asbestos-related disorders	32	Normal controls	35	Australia	NR	NR	FVC %	94 ± 13.5		95 ± 2.4	>0.05	Not assessed
								FEV1, %	92 ± 16.9		93 ± 13.2	>0.05
Damian et al. (2007)	Shipbuilding workers	49	Shipbuilding workers	147	Italy	Duration (mean years)	Normal: 28.45 ± 5.84 PP: 34.43 ±  5.37	VC, %, baseline	95.56 ± 10.78	97.83 ± 9.55	92.79 ± 9.65	≤0.01	Not assessed
								FEV1, %, baseline	99.34 ± 12.7	104.4 ± 11.4	99.98 ± 12.58	NS
								FEV1/VC, %, baseline	78.02 ± 6.40	79.83 ± 5.37	78.66 ± 6.35	NS
								TLC, %, baseline	NR	98.77 ± 7.67	94.49 ± 6.80	≤0.01
								VC, %, follow-up	94.6 ± 11.52	96.72 ± 10.22	91.2 ± 10.27	≤0.01
								FEV1, %, follow-up	97.38 ± 13.93	102.72 ± 12.35	97.42 ± 13.51	<0.05
								FEV1/VC, %, follow-up	76.05 ± 7.60	78.13 ± 5.68	76.67 ± 6.53	NS
								TLC, %, follow-up	NR	97.37 ± 8.63	91.24 ± 7.87	≤0.001
								ΔVC, ml/year	−36.36 ± 79.43	−28.69 ± 66.26	−37.16 ± 85.24	NS
								ΔFEV1, ml/year	−46.59 ± 71.11	−41.00 ± 65.32	−44.18 ± 67.81	NS
								ΔTLC, ml/year	NR	−16.96 ± 80.11	−30.77 ± 114.00	NS
Clin et al. (2011)	Asbestos workers	403	Asbestos workers	1802	France	CEI (exposure units × years)	Normal: 47.9 ± 83.1 PP: 112.6 ± 128.6	FVC, %		100.4 ± 16.6	96.6 ± 16.6	<0.0001	Significant trend for FVC and TLC
								FEV1, %		101.9 ± 19.2	97.9 ± 19.4	0.0032
								FEV1/FVC		80.0 ± 7.9	79.2 ± 9.0	0.27
								TLC, %		101.2 ± 16.0	98.1 ± 14.2	0.0494
								RV, %		109.1 ± 35.4	106.5 ± 28.9	0.8838
								FEF25–75, %		95.9 ± 35.5	91.8 ± 36.2	0.53
								FEF25, %		92.4 ± 60.5	88.5 ± 53.7	0.5
								FEF50, %		93.9 ± 34.2	89.3 ± 34.5	0.42
								FEF75, %		91.8 ± 28.7	87.5 ± 29.4	0.2
Spyratos et al. (2012)	Asbestos-exposed cement workers	29	Asbestos-exposed cement workers	37	Greece	Duration (mean years)	Normal: 20.3 ± 7.1 PP: 25.7 ± 5.2	FVC, %, mean difference (95% CI)		Reference	3.04 (−6.66 to 12.73)	0.536	Not assessed
								FEV1, %, mean difference (95% CI)		Reference	3.18 (−5.35 to 11.70)	0.461
								FEV1/FVC, mean difference (95% CI)		Reference	−2.96 (−8.52 to 2.60)	0.294
								TLC, %, mean difference (95% CI)		Reference	−0.08 (−7.28 to 7.12)	0.983
								DLCO, %, mean difference (95% CI)		Reference	−1.09 (−12.09 to 9.90)	0.844
								MMEF, %, mean difference (95% CI)		Reference	−3.23 (−19.96 to 13.51)	0.703
Clark et al. (2014)	Libby vermiculite miners	89	Libby vermiculite miners	16	Libby, Montana	Duration (mean years)	Normal: 4.95 ± 6.6 PP: 5.94 ± 7.36	FVC, %		90.77 ± 11.66	85.48 ± 16.49	0.3	No effect
								FEV1, %		89.45 ± 17.09	83.73 ± 20.58	0.5
								FEV1/FVC, %		73.38 ± 8.97	73.24 ± 10.50	0.7
								TLC, %		98.63 ± 16.24	94.49 ± 18.8	0.2
								RV, %		107.81 ± 32.28	113.70 ± 40.79	0.8
								DLCO, %		97.09 ± 23.67	91.11 ± 21.83	0.2
								ERV, %		55.47 ± 31.25	100.64 ± 89.26	0.08
								DLCO/VA, %		98.77 ± 15.20	98.38 ± 23.78	0.51

Cdyn = dynamic lung compliance; CEI = cumulative exposure index; CI = confidence interval; Cst = static lung compliance; D_CO = single breath carbon monoxide; DL = diffusing capacity of the lung; DL_CO = diffusing capacity of carbon monoxide; ERV = expiratory reserve volume; FEF₂₅ = forced expiratory flow at 25% of the forced vital capacity; FEF_25–75 = forced expiratory flow at 25–75% of the FVC; FEF₅₀ = forced expiratory flow at 50% of the forced vital capacity; FEF₇₅ = forced expiratory flow at 75% of the FVC; FEV₁ = forced expiratory volume in 1 s; FVC = forced vital capacity; HRCT = high-resolution computed tomography; MEF₂₅ = maximal expiratory flow; MEF_25-75 = mid-expiratory flow between 25 and 75% of FVC; MEF₅₀ = mid-expiratory flow at 50% FVC; MEF₇₅ = MEF at 75% of FVC; MMEF = maximum mid-expiratory flow; NA = not applicable; NR = not reported; NS = not significant; PEF = peak expiratory flow; PP = pleural plaques; RV = residual volume; SE = standard error; TLC = total lung capacity; TL_CO = carbon monoxide transfer factor; V_A = alveolar volume; VC = vital capacity.

^aAll results are presented as mean % predicted (with the exception of the FEV₁/FVC ratio which is either unitless or presented as a %) ± standard deviation unless otherwise noted.

^bBolded values are statistically significant.

^cp Value was calculated by the present authors using the t test and assuming the variances of the two groups are unequal.

Table 4. X-ray study results for pleural plaques and lung function.

									Result
References	Asbestos-exposed population	No. with pleural plaques only	Reference population	No. of Referents	Location	Asbestos exposure measure	Avg. estimated exposure	Measure of lung function^a	Unexposed control	Exposed control	Pleural plaques only	p Value^b	Extent of plaques effect
Lumley (1977)	Dockyard employees and Royal Naval personnel	86 (46 for non-calcified pleural plaques, 40 for calcified pleural plaques)	Dockyard employees and Royal Naval personnel	41	England	Not assessed	NA	FVC, liters		4.41	Non-calcified pleural plaques: 4.07 Calcified PP: 4.37	Non-calcified PP: <0.01 Calcified PP: NS	Not assessed
								FEV1, liters		3.39	Non-calcified PP: 3.06 Calcified PP: 3.31	Non-calcified PP: <0.01 Calcified PP: NS
								FEV/FVC %		77	Non-calcified PP: 75 Calcified PP: 76	Non-calcified PP: NS Calcified PP: NS
								TLC, liters		6.35	Non-calcified PP: 6.07 Calcified PP: 6.22	Non-calcified PP: <0.05 Calcified PP: NS
								DCO, mmol/min kPa		9.85	Non-calcified PP: 9.08 Calcified PP: 9.41	Non-calcified PP: <0.05 Calcified PP: NS
								VE1, liters/min		24.4	Non-calcified PP: 26.4 Calcified PP: 24.3	Non-calcified PP: <0.05 Calcified PP: NS
								Vt30, liters		1.53	Non-calcified PP: 1.35 Calcified PP: 1.48	Non-calcified PP: <0.001 Calcified PP: NS
								Dyspnoeic Index at VE1 %		20	Non-calcified PP: 26 Calcified PP: 24	Non-calcified PP: <0.01 Calcified PP: NS
Fridriksson et al. (1981)	People who fulfilled the radiographic criteria of pleural plaques in the health survey at Uppsala	45	Healthy men	263	Sweden	Duration (mean years)	22 ± 14.4	VC, % deviation	Reference		−15 ± 15.9	<0.001	Correlated with TLC, RV, Raw, Gaw/V, Pst(max), Cst/TLC
								FEV1, % deviation	Reference		−14 ± 18.6	<0.001
								FEV1/VC, % deviation	Reference		−3 ± 9.56	<0.05
								TLC, % deviation	Reference		−16 ± 12.8	<0.001
								RV, % deviation	Reference		−15 ± 24.2	<0.001
								MEF, % deviation	Reference		−15 ± 19.3	<0.001
								FEF0.50, % deviation	Reference		−14 ± 34.5	<0.01
								Raw, % deviation	Reference		+72 ± 148	<0.001
								MVV40, % deviation	Reference		−23 ± 21.1	<0.001
								Gaw/V, % deviation	Reference		−6 ± 74.6	>0.05
								Phase III, % deviation	Reference		+50 ± 61.6	<0.001
								CV, % deviation	Reference		−6 ± 30.0	>0.05
								CV/VC, % deviation	Reference		+14 ± 34.7	<0.001
								CC/TLC, % deviation	Reference		+1 ± 13.2	>0.05
								Pst(max), % deviation	Reference		+22 ± 27.8	<0.001
								Cst, % deviation	Reference		−40 ± 20.0	<0.001
								Cst/TLC, % deviation	Reference		−30 ± 23.8	<0.001
								TI, % deviation	Reference		−24 ± 14.0	<0.001
Hedenstierna et al. (1981)^c	Construction workers registered as exposed to asbestos	55	Construction workers and unexposed workers	55	Sweden	Duration (mean years)	Normal: 14.3 PP: 17.9	FVC (L)	4.66 ± 0.78	4.41 ± 0.71	4.25 ± 0.84	<0.01	Not assessed
								FEV1 (L)	3.54 ± 0.73	3.27 ± 0.68	3.11 ± 0.65	<0.01
								FEV %	75.9 ± 6.5	73.9 ± 8.9	73.1 ± 9.3	>0.05
								TLCO (ml/min/mm Hg)	29.4 ± 6.8	26.3 ± 7.5	25.6 ± 7.0	<0.01
								MEF75 (l/sec)	7.71 ± 1.77	7.35 ± 1.86	7.02 ± 2.36	>0.05
								MEF50 (l/sec)	4.34 ± 1.34	4.09 ± 1.16	3.55 ± 1.25	<0.01
								MEF25 (l/sec)	1.81 ± 0.68	1.52 ± 0.47	1.39 ± 0.55	<0.001
								CV (L)	1.08 ± 0.25	1.18 ± 0.24	1.33 ± 0.42	<0.001
Ohlson et al. (1984)	Asbestos cement plant workers	42	Asbestos cement workers and unexposed workers	76	Sweden	Cumulative exposure (fiber-years)	NR	FVC, %	NR	NR	NR	NS	Not assessed
								FEV1, %	NR	NR	NR	NS
Neuberger & Ambrosch (1985)	Residents of a town with environmental asbestos	24	Residents of a town with environmental asbestos	75	Austria	Age	Normal: 49.8 PP: 59.9	FEV1, %		82.6	76	>0.05	Not assessed
								PEF, %		83	71.6
								MEF25, %		89	69.7
								MEF50, %		85.3	63.9
								MEF75, %		84.8	70.9
Ohlson et al. (1985)	Asbestos workers	24	Asbestos workers and unexposed workers	56	Sweden	Cumulative exposure (fiber-years)	≤14	FVC, %		98.9	97.3	NR	Not assessed
							15–22			91.9	105.2
							≥23			85.9	91.2
							≤14	FEV1, %		100.8	98.3	NR
							15–22			91	99.8
							≥23			81	92.5
							Overall mean 19.7	ΔFVC over 4 yrs, %		6.74	6.34	>0.05
								ΔFEV1 over 4 yrs, %		7.39	6.43	>0.05
Järvholm & Sanden (1986)	Shipyard workers	87	Shipyard workers	115	Sweden	Duration (mean years)	Normal: 22.9 PP: 26.0	FVC, %		99.6 ± 12.8	92.7 ± 13.0	<0.001	Not assessed
								FEV1, %		110.5 ± 14.4	102.9 ± 15.8	<0.001
Hilt et al. (1987)	Members of the general population with suspected asbestos-related X-ray findings	363	Subjects with previous asbestos exposure and no abnormal findings and subjects with no previous exposure	98	Norway	Duration (mean years)	3.6 ± 3.8	FVC, %	104.5	97.8	95.2	>0.05	Not assessed
								FEV1, %	97.1	94.3	93.5	>0.05
								FEV1/FVC	71.7	73.3	72.5	>0.05
Sider et al. (1987)	Wives of asbestos-exposed workers	18^d	Wives of asbestos-exposed workers	75	US	Duration (mean years)	Normal: 27.8 ± 10.0 PP: 32.3 ± 6.6	FVC, %		101.7 ± 14.0	92.0 ± 13.2	<0.011	Not assessed
								FEV1, %		99.8 ± 15.4	90.7 ± 14.0	<0.028
								FEF25–75, %		95.5 ± 29.7	89.4 ± 31.8	<0.456
Hjortsberg et al. (1988a)	Railroad workers	87 (Results shown are for 22 never-smokers)	Healthy non-smokers from other workplaces	200	Sweden	Duration (mean years)	30 (median)	VC, %	NR		94 ± 10	0.011	Not assessed
								FEV1/VC	NR		106 ± 7	<0.001
								RV	NR		99 ± 24	>0.05
Hjortsberg et al. (1988b)	Railroad workers	87 (Results shown are for 22 never-smokers)	Healthy non-smokers from other workplaces	62	Sweden	Duration (mean years)	30 (median)	WOV	NR		28.0 ± 8.9	>0.05	Not assessed
								VTG	NR		133 ± 45	<0.01
								VTG:TLC	NR		2.0 ± 0.8	<0.05
Järvholm & Larsson (1988)	Asbestos-exposed workers	124	Asbestos-exposed workers	1091	Sweden	Not assessed	N/A	VC, % (nonsmokers)		98.6 ± 11.8	96.4 ± 8.4	<0.05	Not assessed
								VC, % (former smokers)		98.8 ± 12.1	93.0 ± 9.9	<0.01
								VC, % (smokers)		96.7 ± 12.0	94.4 ± 10.5	<0.05
								FEV1, % (nonsmokers)		109.4 ± 14.3	107.8 ± 15.3	>0.05
								FEV1, % (former smokers)		108.2 ± 14.5	102.2 ± 14.4	<0.01
								FEV1, % (smokers)		102.6 ± 14.6	103.1 ± 13.4	>0.05
Oliver et al. (1988)	Railroad workers	81	Railroad workers	278	Pennsylvania, US	Duration (mean years)	Normal: 27.4 PP: 35.4	FVC, %		92.7 ± 0.14	86.0 ± 0.17	0.0001	Associated with decrements in FVC and restriction
								FEV1, %		87.3 ± 0.19	80.3 ± 21.3	0.0049
								DLCO, %		101.9 ± 19.7	97.0 ± 21.3	0.055
								Restriction (% of subjects)		9.0	18.5	0.017
Rosenstock et al. (1988)	Plumbers and pipefitters	48	Plumbers and pipefitters	480	Washington, US	Duration (mean years)	17.1	FVC, %		98.1^e	93.2^e	NS	Not assessed
Britton et al. (1989)	Asbestos workers	4	Asbestos workers	11	London, UK	Duration (years)	23.3	VC, %	114 ± 17	104 ± 13.5	101.3 ± 7.8	NS	Not assessed
								DLCO, %	104 ± 20.4	102 ± 21.5	104 ± 22.7	NS
								KCO, %	101 ± 15.2	104 ± 24.8	108.8 ± 27.7	NS
Bourbeau et al. (1990)	Insulators	49	Insulators	46	Canada	Duration (mean years)	Normal: 18.5 ± 10.2 PP: 17.3 ± 7.4	FVC, liters, standardized mean difference^f		Reference	−0.35 ± 0.10 (SE)	<0.05	Not assessed
								FEV1, liters, standardized mean difference^f		Reference	−0.20 ± 0.09 (SE)	<0.05
Hillerdal et al. (1990)	Hospital pulmonary patients with occupational asbestos exposure	13	Healthy, unexposed people	NR	Sweden	Duration (mean years)	Normal: 0 PP: 15–29	VC, %	NR		97 ± 11	>0.05	No effect
								FEV1, %	NR		98 ± 10	>0.05
								FEV1/VC	NR		98 ± 7	>0.05
								TLC, %	NR		96 ± 8	>0.05
								FEF50, %	NR		95 ± 22	>0.05
								MEF/FEF50, %	NR		118 ± 27	<0.05
								MVV, %	NR		91 ± 11	<0.05
Kilburn & Warshaw (1990)	Asbestos-exposed union workers - smokers	43	Random population sample of Michigan - smokers	167	US	Not assessed	N/A	FVC, %	95.8		93.5	0.4	Not assessed
								FEV1, %	95.2		93.1	0.2
								FEV1/FVC%	77.4		72.3	0.0001
								FEF25–75, %	95.1		82.7	0.0013
								FEF75–85, %	106.8		83.2	0.0001
								TGV, %	101.3		108.0	0.0001
								RV/TGV%	34.0		46.0	0.0001
	Asbestos-exposed union workers – non-smokers	21	Random population sample of Michigan – non-smokers	119				FVC, %	99.0		96.0	0.3
								FEV1, %	99.2		92.1	0.015
								FEV1/FVC%	80.0		76.5	0.018
								FEF25–75, %	100.1		92.1	0.4
								FEF75–85, %	102.1		72.3	0.0014
								TGV, %	100.1		110.8	0.0009
								RV/TGV%	30.3		46.8	0.0001
Schwartz et al. (1990a)	Sheet metal workers	260	Sheet metal workers	877	Midwestern US	Duration (mean years)	32.7 ± 6.7	FVC, %		94.7 ± 16.8	90.3 ± 13.4 (SE)	0.0002^g	Not assessed
								FVC, regression coefficient		Reference	−0.14 ± 0.05 (SE)	0.007
								FEV1, regression coefficient		Reference	−0.06 ± 0.05 (SE)	0.12
								FEV1/FVC%, regression coefficient		Reference	1.34 ± 0.62 (SE)	0.03
Schwartz et al. (1990b)	Sheet metal workers	9	Sheet metal workers	7	Midwestern US	Duration (mean years)	Normal: 33.3 ± 6.6 PP: 30.3 ± 7.2	FVC, %		104.9 ± 6.7	96.0 ± 11.8	NS	Not assessed
								FEV1, %		110.4 ± 9.1	100.1 ± 17.2	NS
								FEV1/FVC, %		76.1 ± 6.4	75.1 ± 7.9	NS
								TLC, %		121.9 ± 12.5	116.7 ± 13.9	NS
								RV, %		120.7 ± 21.9	121.6 ± 42.5	NS
								DLCO, %		111.6 ± 23.2	111.8 ± 16.3	NS
								FVC, regression coefficient		Reference	−11.0 ± 5.3 (SE)	0.06
								TLC, regression coefficient		Reference	−1.5 ± 6.6 (SE)	NS
								DLCO, regression coefficient		Reference	−7.3 ± 8.6 (SE)	NS
Kennedy et al. (1991)	Construction insulators	23	Construction insulators	39	Canada	Duration (mean years)	Normal: 27.6 ± 7.1 PP: 29.5 ± 6.9	FVC, regression coefficient		Reference	0.07	0.7	Not assessed
								FEV1/FVC%, regression coefficient		Reference	−4.21	0.1
								Obstruction, OR (95% CI)		Reference	2.59 (0.7–10.0)	NS
								Restriction, OR (95% CI)		Reference	1.61 (0.4–7.5)	NS
Kouris et al. (1991)	Asbestos-exposed workers	146	Asbestos-exposed workers	745	Minnesota, US	Duration of employment during 1958–1974 (mean years)	Normal: 7.5 ± 6.0 PP: 12.7 ± 4.8	FVC <80%, OR (95% CI)		Reference	1.5 (1.0–2.2)	NS	Not assessed
								FEV1 <80%, OR (95% CI)		Reference	1.5 (1.0–2.2)	NS
								FEV% <90%, OR (95% CI)		Reference	0.9 (0.6–1.5)	NS
Broderick et al. (1992)	Sheet metal workers	260	Sheet metal workers	877	Midwest US	Duration (mean years)	34.0 ± 5.4	FVC, regression coefficient	Not applicable	Reference	−0.14 ± 0.05 (SE)	<0.05	Not assessed for PP alone
Miller et al. (1992)	Asbestos-exposed workers	885	Asbestos-exposed workers	722	19 cities in US and Canada	Duration (mean years)	Never smokers: 36.2 ± 7.7 Positive smoking history: 34.8 ± 7.0	FVC, %		88.9	82.4	NR	Not assessed
Bresnitz et al. (1993)	Asbestos-exposed workers	20	Asbestos-exposed workers	71	Philadelphia, Pennsylvania, US	Duration (mean years)	27.1 ± 5.8	FVC, %		89.4 ± 16.2	85.8 ± 10.6	NS	Not assessed
								FEV1, %		86.1 ± 19.7	86.3 ± 11.8	NS
								FEV1/FVC%		76.4 ± 11.6	79.5 ± 7.7	NS
								FEF25–75, %		79.5 ± 32.1	90.7 ± 40.0	NS
Dujić et al. (1993)	Workers in an asbestos cement factory	55	Workers in an asbestos cement factory	252	Croatia	Cumulative exposure (fiber-years)	Normal: 31.2 ± 17.8 PP: 39.6 ± 12.3	FVC, %		92.2 ± 9.9	75.8 ± 12.7	<10^−^6	Not assessed
								Decrement in FVC			Yes	0.03
								FEV1, %		89.0 ± 12.0	86.8 ± 10.6	0.14
								Decrement in FEV1			No	NS
								FEV1/FVC, %		96.5 ± 8.8	114.5 ± 9.7	<10^−^6
								Increment in FEV1/FVC, %			Yes	0.04
								TLC, %		97.2 ± 12.1	89.3 ± 10.8	0.00002
								Decrement in TLC			Yes	0.08
								RV, %		95.7 ± 13.8	91.9 ± 12.8	0.062
								DLCO, %		98.8 ± 12.6	89.9 ± 11.6	<10^−^6
								Decrement in DLCO			Yes	0.04
								DLCO corrected, %		96.8 ± 12.7	90.6 ± 11.8	0.003
								Decrement in DLCO corrected			No	0.07
								DLCO:VA, %		102.2 ± 16.8	95.5 ± 15.8	0.002
								FEF25–75, %		97.1 ± 10.2	88.2 ± 15.2	0.0001
								Restriction, percentage		16.2	41.9	0.0002
								Obstruction, percentage		9.2	7.2	0.062
Zavalić & Bogadi-Šare (1993)	Shipyard workers	67	Shipyard workers	101	Croatia	Duration (mean years)	Normal: 17.3 ± 11.1 PP: 21.5 ± 14.1	FVC, %		90.9 ± 21.2	87.5 ± 18.4^h	>0.05	Slight, non-significant trend toward reduction in FVC, FEV1, MEF25
								FEV1, %		86.0 ± 17.2	86.3 ± 14.8
								FEV1/FVC		94.6 ± 17.6	93.4 ± 11.2
								DLCO		90.1 ± 16.2	91.2 ± 11.0
								MEF25, %		75.3 ± 28.2	71.2 ± 13.2
								MEF50, %		81.8 ± 22.1	82.3 ± 17.3
								MEF75, %		83.3 ± 17.6	80.1 ± 11.2
Schwartz et al. (1994)	Asbestos-exposed workers	NR	Asbestos-exposed workers	31	US	Duration (mean years)	31.7 ± 11.3	ΔTLC, regression coefficient		Reference	−0.26 ± 0.18 (SE)	0.15	Not assessed
								ΔDLCO, regression coefficient		Reference	1.25 ± 1.08 (SE)	0.25
Garcia-Closas & Christiani (1995)	Asbestos-exposed workers	64	Asbestos-exposed workers	457	Eastern Massachusetts, US	Duration (mean years)	Normal: 18.4 ± 9.8 PP: 28.0 ± 8.5	FVC, %		99.1 ± 12.0	94.2 ± 14.7	<0.01	Not assessed
								FEV1, %		94.4 ± 13.6	87.3 ± 16.4	<0.01
								FEV1/FVC%		77.9 ± 7.2	74.1 ± 8.2	<0.01
								Obstructive Pattern [n (%)]		42 (9.2)	10 (15.6)	>0.05
								Restrictive Pattern [n (%)]		18 (3.9)	5 (7.8)	>0.05
								Mixed Pattern [n (%)]		6 (1.3)	4 (6.5)	<0.05
Ostiguy et al. (1995)	Asbestos-exposed workers	54	Asbestos-exposed workers	247	Canada	Duration (mean years)	20.6 ± 0.5	FVC, %		106 ± 1 (SE)	104 ± 2 (SE)	NS	Not significant with pleural score
								FEV1, %		111 ± 1 (SE)	107 ± 2 (SE)	NS
								MMEF, %		114 ± 2 (SE)	106 ± 5 (SE)	NS
								Loss of FVC, ml/year		15 ± 6 (SE)	31 ± 12 (SE)	NS	Not assessed
Di Lorenzo et al. (1996)	Former workers of an asbestos cement factory	10	Unexposed volunteers	9	Italy	Duration (mean years)	Normal: 21.9 ± 7.9 PP: 23.5 ± 7.4	FVC, %	94.2 ± 10.6	92.4 ± 13.4	83.2 ± 12.2	NS	Not assessed
								FEV1, %	89.9 ± 8.3	86.9 ± 9.6	76.5 ± 14.3	<0.05^i
								FEV1/FVC%	77.6 ± 5.0	77.9 ± 5.7	74.4 ± 10.8	NS
								TLCOsb, %	101.9 ± 5.1	86.0 ± 10.7	83.2 ± 17.9	NS
								PEF, %	96.7 ± 6.1	86.9 ± 4.0	75.5 ± 18.4	NS
								FEF75, %	85.1 ± 17.6	79.8 ± 16.8	66.6 ± 27.8	NS
								FEF50, %	73.3 ± 13.9	67.6 ± 16.1	59.3 ± 29.7	NS
								FEF25, %	65.9 ± 7.6	56.2 ± 24.5	48.3 ± 25.9	NS
								PaO2, mm Hg	94.9 ± 1.4	83.4 ± 4.6	83.1 ± 6.2	NS
								PaCO2,S mm Hg	40.1 ± 1.2	40.7 ± 1.4	40.4 ± 2.0	NS
								DuO2, %	105.0 ± 7.0	86.0 ± 14.5	84.5 ± 19.3	NS
								DuCO2, %	93.0 ± 7.6	90.3 ± 14.6	86.7 ± 12.3	NS
Glencross et al. (1997)	Sheet metal workers	60	Sheet metal workers w/o PP	62	US	Duration (mean years)	35 ± 8.6	FVC		NR	NR (R = −0.084)	0.17	Not assessed
Singh et al. (1999)	Asbestos-exposed individuals	12	Asbestos-exposed individuals	7	Australia	Not assessed	NR	VC, %		101.2 ± 4.0 (SE)	98.0 ± 4.5 (SE)	NS	Not assessed
								TLC, %		93.6 ± 5.4 (SE)	96.2 ± 3.3 (SE)	NS
								RV, %		95.9 ± 7.1 (SE)	106.5 ± 7.6 (SE)	NS
								TLCO, %		96.1 ± 5.2 (SE)	102.7 ± 4.8 (SE)	NS
								TLCO/VA, %		108.1 ± 2.8 (SE)	111.2 ± 5.4 (SE)	NS
								MIP, cm H2O		94.3 ± 6.5 (SE)	91.3 ± 10.4 (SE)	NS
								MEP, cm H2O		152.4 ± 22.5 (SE)	153.0 ± 16.7 (SE)	NS
Weill et al. (2011)	Residents of Libby, Montana	482	Residents with no lung abnormalities	4065	Libby, Montana, US	Age	Normal: 49.12 ± 0.76 PP: 60.07 ± 0.53	FVC, %		103.15 ± 0.25 (SE)	95.63 ± 0.76 (SE)	<0.05	Not assessed
Larson et al. (2012)	Libby community residents	708	Libby community residents	NA	Libby, Montana, US	Number of exposure pathways	0 – ≥6	Restriction, OR (95% CI)		Reference	1.4 (1.1–1.8)	Significant	OR = 1.9 (1.5–2.5) for index > median versus index = 0
								Obstruction, OR (95% CI)		Reference	0.8 (0.5 to 1.0)	NS	No association
								Mixed, OR (95% CI)		Reference	1.1 (0.7 to 1.7)	NS	Not assessed
Miller et al. (2013)	Asbestos-exposed workers	290	Asbestos-exposed workers	1096	US	Duration (mean years)	28.0 ± 10.6	FVC, %		96.6 ± 15.87	90.5 ± 15.65	<0.01	Not assessed
								DLCO, %		98.6 ± 19.09	91.0 ± 20.69	<0.01

CC = closing capacity; CI = confidence interval; Cst = static lung compliance; CV = closing volume; D_CO = single breath carbon monoxide; DL_CO = diffusing capacity of carbon monoxide; DL_{CO corrected} = DL_CO corrected for carboxyhemoglobin; DL_CO:VA = ratio of DL_CO to alveolar volume; DuCO₂ = carbon dioxide ductance; DuO₂ = oxygen ductance; FEF_0.50 = forced expiratory flow at 50% of the forced vital capacity; FEF₂₅ = forced expiratory flow at 25% of the forced vital capacity; FEF_25–75 = forced expiratory flow at 25–75% of the FVC; FEF₅₀ = forced expiratory flow at 50% of the forced vital capacity; FEF₇₅ = forced expiratory flow at 75% of the FVC; FEF_75–85 = forced expiratory flow at 75–85% of the FVC; FEV = forced expiratory volume; FEV₁ = forced expiratory volume in 1 s; FVC = forced vital capacity; Gaw/V = volumic airways conductance; KCO = % predicted diffusing coefficient; kPa = kilopascal; MEF₂₅ = maximal expiratory flow; MEF₅₀ = mid-expiratory flow at 50% FVC; MEF₇₅ = MEF at 75% of FVC; MEP = maximal expiratory mouth pressure; min = minute; MIP = maximal inspiratory mouth pressure; MMEF = maximum mid-expiratory flow; mmol = millimoles; MVV = maximum voluntary ventilation; MVV₄₀ = maximal voluntary ventilation at breathing frequency 40 breaths/min; n = number; NA = not applicable; NR = not reported; NS = not significant; OR = odds ratio; PaCO₂ = mean arterial carbon dioxide tension; PaO₂ = arterial oxygen tension; PEF = peak expiratory flow; Phase III = slope of the alveolar plateau of the single breath nitrogen test; PP = pleural plaques; Pst(max) = maximal elastic recoil pressure; Raw = airways resistance; RV = residual volume; SE = standard error; TGV = thoracic gas volume; Tl = transfer factor for carbon monoxide; TLC = total lung capacity; TL_CO = carbon monoxide transfer factor; TL_COsb = carbon monoxide transfer factor; VA = alveolar volume; VC = vital capacity; VE₁ = minute volume expired at oxygen uptake of 1.0 l/min.; V_t30 = minute ventilation of 30 l/min.; VTG = vol trapped gas; WOV = washout vol.

^aAll results are presented as mean % predicted (with the exception of the FEV₁/FVC ratio which is either unitless or presented as a %) ± standard deviation unless otherwise noted.

^bBolded values are statistically significant.

^cPP only group described as having “no complicating diseases”, but this group had more reported chronic bronchitis (at least three months for two consecutive years) than control group (21/55 versus 5/55, respectively). p Values are for comparison to unexposed controls.

^dOne of the 18 with pleural abnormality has DPT.

^eOnly graphs available in the publication, values read from a graph digitizer software.

^fFrom ANOVA, adjusted for age, height, smoking and parenchymal disease.

^gp Value was calculated by the present authors using the t test and assuming the variances of the two groups are unequal.

^hData taken from Table 5, group A (67/68 subjects) because stats for all 68 are not given. Inclusion of the one subject in group C did not change any of the mean values by more than 0.1.

ⁱp Value for PP compared to exposed, no PP.

Table 5. Risk of bias.

		No adjustment for
References	No asbestos -exposed controls	Smoking	Asbestos exposure	Cross- sectional study design	Small study size	Single reader for imaging	Single pulmonary function test parameter	Inappropriate statistical approach	No adjustment for BMI	Risk of bias
HRCT studies
Staples et al. (1989)		√	√	√					√	High
Valkila et al. (1995)			√	√	√	√			√	High
Kee et al. (1996)		√	√	√	√	√			√	High
Neri et al. (1996)			√	√	√				√	High
Soulat et al. (1999)		√	√	√		√			√	High
Copley et al. (2001)	√	√	√	√	√				√	High
Oldenburg et al. (2001)			√	√	√	√			√	High
Van Cleemput et al. (2001)				√	√				√	Low
Mazziotti et al. (2004)		√	√	√	√				√	High
Rui et al. (2004)						√				Low
Sette et al. (2004)		√	√	√	√		√		√	High
Sandrini et al. (2006)	√		√	√	√	√			√	High
Damian et al. (2007)			√			√			√	Low
Clin et al. (2011)				√						Low
Spyratos et al. (2012)				√	√				√	Low
Clark et al. (2014)				√	√	√				Low
X-ray studies
Lumley (1977)		√	√	√				√	√	High
Fridriksson et al. (1981)	√		√	√		√				High
Hedenstierna et al. (1981)			√	√	√	√			√	High
Sider et al. (1981)		√	√	√	√	√		√	√	High
Ohlson et al. (1984)			√		√	√			√	High
Neuberger & Ambrosch (1985)			√	√	√				√	High
Ohlson et al. (1985)				√	√	√			√	Low
Jarvholm & Sanden (1986)			√	√		√			√	High
Hilt et al. (1987)			√	√					√	Low
Hjortsberg et al. (1988)	√		√	√					√	High
Hjortsberg et al. (1988)	√		√	√					√	High
Järvholm & Larsson (1988)			√	√		√			√	High
Oliver et al. (1988)				√					√	Low
Rosenstock et al. (1988)		√	√	√			√		√	High
Britton et al. (1989)			√	√	√			√	√	High
Bourbeau et al. (1990)				√	√				√	Low
Hillerdal et al. (1990)	√		√	√	√	√			√	High
Kilburn & Warshaw (1990)	√		√	√		√			√	High
Schwartz et al. (1990a)			√	v		√			√	High
Schwartz et al. (1990b)				√	√	√			√	Low
Kouris et al. (1991)		√	√	√					√	High
Kennedy et al. (1991)			√	√	√				√	High
Bresnitz et al. (1992)				√	√					Low
Broderick et al. (1992)				√		√	√		√	Low
Miller et al. (2012)		√	√	√		√			√	High
Dujic et al. (1993)				√					√	Low
Zavalic & Bogadi-Sare (1993)		√	√	√					√	High
Schwartz et al. (1994)			√		√				√	Low
Garcia-Closas & Christiani (1995)				√					√	Low
Ostiguy et al. (1995)				√						Low
Di Lorenzo et al. (1996)				√	√				√	Low
Glencross et al. (1997)							√		√	Low
Singh et al. (1999)		√	√	√	√	√			√	High
Weill et al. (2011)				√			√			Low
Larson et al. (2012)				√						Low
Miller et al. (2013)			√	√		√				Low

Each study was assessed for characteristics that could lead to bias.

Table 6. Differences in spirometry, gas diffusion, and lung volume in participants with pleural plauqes compared to controls in higher quality HRCT and X-ray studies^a.

References	FVC or VC mean difference (95% CI)	FEV1 mean difference (95% CI)	FEV1/FVC or FEV1/VC mean difference (95% CI)	TLC mean difference (95% CI)	RV mean difference (95% CI)	DLCO (TLCO) mean difference (95% CI)
HRCT
Van Cleemput et al. (2001)	+0.7 (−7.6, 9.0)	+0.3 (−7.6, 8.2)	0 (−4.2, 4.2)			+4.8 (−4.9, 14.5)
Rui et al. (2004)^b	−6 (−10.7, −1.3)	−7 (−13.2, −0.8)	−1 (−4.0, 2.0)	−6 (−10.2, −1.8)
Damian et al. (2007)^b	−5 (−8.6, −1.5)	−5.3 (−10.0, −0.6)	−1.5 (−3.6, 0.7)	−6.1 (−9.3, −3.0)
Clin et al. (2011)	−3.8 (−5.9, −1.7)	−4 (−6.4, −1.6)	−0.8 (−1.8, 0.2)	−3.1 (−5.0, −1.2)	−2.6 (−6.8, 1.6)
Spyratos et al. (2012)	+3 (−6.7, 12.7)	+3.2 (−5.4, 11.7)	−3 (−8.5, 2.6)	−0.1 (−7.3, 7.1)		−1.1 (−12.1, 9.9)
Clark et al. (2014)	−5.3 (−15.0, 4.4)	−5.7 (−18.0, 6.6)	−0.1 (−6.4, 6.2)	−4.1 (−15.4, 7.1)	+5.9 (−18.4, 30.2)	−6 (19.5, 7.5)
X-ray
Ohlson et al. (1985)
Avg. exposure ≤14 fiber-years	−1.6	−2.5
Avg. exposure 15–22 fiber-years	+13.3	+8.8
Avg. exposure ≥23 fiber-years	+5.3	+11.5
Hilt et al. (1987)	−2.6	−0.8	−0.8
Oliver et al. (1988)	−6.7 (−6.7, −6.7)	−7 (−9.9, −4.1)				−4.9 (−10.6, 0.8)
Bourbeau et al. (1990)	−0.35^c	−0.2^c
Schwartz et al. (1990b)	−8.9 (−20.7, 2.9)	−10.3 (−27.2, 6.6)	−1 (−9.6, 7.6)	−5.2 (−21, 10.6)	+0.9 (−40.7, 42.5)	+0.2 (−22.9, 23.3)
Bresnitz et al. (1992)	−3.6 (−12.3, 5.1)	+0.2 (−10.2, 10.6)	+3.1 (−3.1, 9.3)
Broderick et al. (1992)	−0.14^d
Dujic et al. (1993)	−16.4 (−19.9, 12.9)	−2.2 (−6.1, 1.7)	+18 (15, 21)	−7.9 (−11.9, −3.9)	−3.8 (−8.4, 0.8)	−8.9 (−13.1, −4.7)
Schwartz et al. (1994)				−0.26^d		+1.25^d
Garcia-Closas & Christiani (1995)	−4.9 (−8.6, −1.2)	−7.1 (−11.3, −2.9)	−3.8 (−6.0, −1.6)
Ostiguy et al. (1995)	−2 (−7.2,3.2)	−4 (−9.2, 1.2)
Di Lorenzo et al. (1996)	−9.2 (−22.9, 4.5)	−10.4 (−23.6, 2.8)	−3.5 (−12.9, 5.9)			−2.8 (−18.8, 13.2)
Glencross et al. (1997)	−0.084^d
Weill et al. (2011)	−7.5 (−9.2, −5.8)
Larson et al. (2012)	Not reported	Not reported
Miller et al. (2013)	−6.1 (−8.4, −3.8)					−7.6 (−10.5, −4.7)

CI = confidence interval; DL_CO = diffusing capacity of carbon monoxide; FEV₁ = forced expiratory volume in 1 second; FVC = forced vital capacity; HRCT = high resolution computed tomography; RV = residual volume; TLC = total lung capacity; TL_CO = diffusing capacity of carbon monoxide; VC = vital capacity.

^aStatistically significant results are in bold type; high quality studies are defined in text. For studies that did not report the 95% CI of the mean difference, the 95% CI was calculated by the present authors.

^bDirection of effect was consistent for baseline and follow-up.

^cChanges in liters.

^dEstimates of regression coefficients.

Table 7. Differences in lung function in participants with pleural plaques compared to those with no abnormalities in higher quality longitudinal HRCT and X-ray studies.

References	Follow-up (Mean Years)	Units	FVC	VC	FEV1	FEV1/VC	TLC	DLCO
HRCT
Rui et al. (2004)	3.7	%/year (95% CI)	–	−3.4 (−7.9, 1.0)	−1.5 (−7.4, 4.0)	+0.3 (−2.7, 3.2)	−3.6 (−7.4, 0.2)	–
Damian et al. (2007)	5	ml/year	–	−8.47	−3.18	–	−13.81	–
X-ray
Ohlson et al. (1985)	4	%/4 years	+0.4	–	+0.96	–	–	–
Schwartz et al. (1994)	2	Regression coefficient for change over 2 years ± SE			–	–	−0.26 ± 0.18	+1.25 ± 1.08
Ostiguy et al. (1995)	7	ml/year	−16	–	–	–	–	–
Glencross et al. (1997)	10	Regression coefficient for change over 10 years	−0.084	–	–	–	–	–

– = Parameters not measured; CI = confidence interval; DL_CO = diffusing capacity of carbon monoxide; FEV₁ = forced expiratory volume in 1 s; FVC = forced vital capacity; HRCT = high resolution computed tomography; SE = standard error; TLC = total lung capacity; VC = vital capacity.

None of the results are significant at p < 0.05. Results reported in % or ml/time are presented as change over time in group with pleural plaques compared to exposed referents.

Figure 3 Spirometry results in high quality HRCT and X-ray studies. Percent predicted FVC and FEV₁, and FVC/FEV₁ ratio, among individuals with no lung lesions (light gray bars) or pleural plaques (dark gray bars). Error bars indicate standard deviations, except for Hilt et al. (1987), where no standard deviations were reported. (A, B and C) show the results of higher quality HRCT studies and (D, E and F) show the results of the higher quality X-ray studies.

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