Serum cytokine levels related to exposure to volatile organic compounds and PM_2.5 in dwellings and workplaces in French farmers – a mechanism to explain nonsmoking COPD

Figures & data

Table 1 Descriptive characteristics of the study population

Population characteristics (n=72)	n	%
Sex (male)	46	63.8
Sex (female)	26	36.1
Age (years)
Mean =47.02 years ±10.1 SD
Smoking status
Current smokers	9	12.5
Former smokers	26	36.1
Nonsmokers	63	87.5
Education level
<High school	9	12.5
High school	42	58.33
>High school	10	13.89
Others	11	15.28
Lived on a farm as a child	66	91.6
Farm characteristics
Presence of pets	64	88.8
Presence of mold, fungi	4	5.6
Month of visit
January	16	22.2
February	10	13.8
May	3	4.2
October	13	18.1
November	30	41.6
Location
Riom-ès-Montagnes	28	38.8
Saugues	15	20.8
St-Sauveur	29	40.3

Figure 1 Distribution of VOCs according to the residence type.

Abbreviation: VOCs, volatile organic compounds.

Figure 2 Distribution of the global VOC scores in the farms.

Abbreviation: VOCs, volatile organic compounds.

Figure 3 Distribution of PM_2.5 according to the residence type.

Note: PM_2.5, particles with an aerodynamic diameter <2.5 µm.

Figure 4 Distribution rate of each cytokine and ILs.

Table 2 Association between IL/cytokine concentrations and respiratory symptoms and diseases

Symptoms	IL4		IL5		IL6		IL8		IL10		IL13		IL17		IFNγ		TNFα
	Mean (pg/mL)	P-value*	Mean (pg/mL)	P-value*	Mean (pg/mL)	P-value*	Mean (pg/mL)	P-value*	Mean (pg/mL)	P-value*	Mean (pg/mL)	P-value*	Mean (pg/mL)	P-value*	Mean (pg/mL)	P-value*	Mean (pg/mL)	P-value*
Morning cough in the past 12 months
No (n=61)	6.4	0.65	7.1	0.08	14.3	0.41	21.5	0.14	8.8	0.09	1.6	0.55	22.6	0.76	221.6	0.24	90.0	0.44
Yes (n=11)	5.5		3.3		7.2		13.2		2.4		1.0		28.9		139.4		61.1
Phlegm in the past 12 months
No (n=57)	5.5	0.39	6.7	0.65	10.3	0.35	16.5	0.29	6.6	0.59	1.3	0.56	19.0	0.42	194.0	0.56	70.4	0.30
Yes (n=15)	9.6		5.9		23.5		32.7		12.8		2.3		40.0		239.0		143.7
Shortness of breath in the past 12 months
No (n=61)	5.8	0.59	6.2	0.20	12.3	0.45	18.1	0.29	7.9	0.26	1.1	0.18	22.5	0.50	186.3	0.67	74.8	0.45
Yes (n=11)	8.0		8.1		14.2		24.1		7.9		2.7		28.2		261.2		114.7
Wheezing in the past 12 months
No (n=62)	5.8	0.76	6.4	0.70	10.5	0.60	17.7	0.65	6.6	0.91	1.4	0.34	22.2	0.95	194.7	0.65	75.4	0.84
Yes (n=10)	7.5		6.9		20.6		24.5		12.9		1.8		28.2		224.2		106.9
Shortness of breath after intense effort in the past 12 months
No (n=56)	6.1	0.36	6.6	0.65	11.1	0.62	18.4	0.18	6.5	0.71	1.4	0.95	21.8	0.48	206.6	0.33	79.0	0.39
Yes (n=16)	6.7		6.2		19.8		23.1		12.1		1.7		28.4		183.5		98.6
Woken by an attack of shortness of breath in the past 12 months
No (n=64)	6.5	0.28	7.5	0.009	13.3	0.52	20.8	0.08	8.7	0.28	1.5	0.49	25.5	0.60	213.5	0.25	88.0	0.39
Yes (n=8)	3.8		2.3		5.9		7.9		4.1		0.4		14.4		100.0		40.0
Asthma
No (n=63)	6.4	0.15	6.6	0.66	13.1	0.37	19.8	0.35	8.0	0.86	1.5	0.66	24.7	0.55	207.2	0.12	85.2	0.19
Yes (n=9)	1.9		5.6		3.4		8.3		6.4		0.2		7.5		50.5		21.8
COPD
No (n=67)	6.6	0.13	7.2	0.008	13.8	0.49	20.8	0.19	8.6	0.10	1.5	0.70	26.2	0.10	217.0	0.16	90.5	0.16
Yes (n=5)	3.6		1.1		6.4		10.8		2.2		0.7		0.8		106.8		36.6
SAD**
No (n=49)	6.4	0.66	6.7	0.58	14.3	0.96	21.3	0.68	9.1	0.51	1.6	0.83	24.5	0.51	204.9	0.97	91.0	0.90
Yes (n=23)	6.0		6.4		10.4		16.8		6.4		1.3		22.1		198.0		73.2

Notes: Bold indicates significant values.

* P-values were calculated by the Mann–Whitney U test relative to the healthy controls;

** SAD, small airways disease (FEF25–75 <80% of the predicted level and FEV/FVC >70%, after bronchodilation during the reversibility test.

Table 3 Association between exposure to VOC and cytokine levels

Log (cytokines)	VOCs
	Exposure level	Unadjusted			Adjusted#
		β	95% CI	P-value	β	95% CI	P-value
IL4	1 vs 0	−0.13	−0.49 to −0.2	0.45	−0.10	−0.46 to −0.2	0.57
IL5	1 vs 0	−0.18	−0.5 to −0.21	0.36	−0.23	−0.5 to −0.12	0.19
IL6	1 vs 0	−0.29	−0.7 to −0.19	0.23	−0.30	−0.7 to −0.10	0.14
IL8	1 vs 0	−0.21	−0.5 to −0.13	0.2	−0.18	−0.5 to −0.18	0.31
IL10	1 vs 0	−0.04	−0.4 to −0.35	0.8	−0.17	−0.5 to −0.2	0.37
IL13	1 vs 0	−0.42	−1.0 to −0.2	0.19	−0.51	−0.9 to −0.1	0.01*
IL17	1 vs 0	−0.50	−1.19 to −0.17	0.14	−0.46	−1.14 to −0.2	0.17
TNFα	1 vs 0	−0.18	−0.6 to −0.2	0.38	−0.18	−0.6 to −0.2	0.4
IFNγ	1 vs 0	−0.19	−0.5 to −0.2	0.34	−0.16	−0.5 to −0.2	0.4

Notes: β, regression coefficient.

# Adjusted for age, sex, smoking (classified as: never, former or current smoking), the presence of pets, mold in the home and childhood in a farm.

* P<0.05.

Abbreviations: VOCs, volatile organic compounds; CI, confidence interval.

Table 4 Results of linear regression models before and after adjustment for potential cofounders of the association between exposure to PM_2.5 and cytokine levels

Log (cytokines)	PM2.5
	Exposure level	Unadjusted			Adjusted#
		β	CI (95%)	P-value	β	CI (95%)	P-value
IL4	1 vs 0	−0.62	−1.14 to −0.11	0.01	−0.64	−1.19 to −0.08	0.02*
IL5	1 vs 0	−0.60	−1.3 to −0.1	0.10	−0.49	−1.12 to 0.14	0.13
IL6	1 vs 0	−1.26	−1.9 to −0.60	0.0002	−0.79	−1.4 to −0.13	0.01*
IL8	1 vs 0	−0.78	−1.3 to −0.2	0.003	−0.82	−1.4 to −0.2	0.005**
IL10	1 vs 0	−0.24	−1.06 to −0.5	0.55	−0.12	−0.9 to −0.6	0.75
IL13	1 vs 0	−0.86	−1.8 to −0.07	0.07	−0.94	−1.5 to −0.2	0.004**
IL17	1 vs 0	−1.03	−2.6 to −0.5	0.21	−1.3	−2.8 to −0.2	0.10
TNFα	1 vs 0	−0.86	−1.4 to −0.2	0.005	−0.85	−1.5 to −0.2	0.01*
IFNγ	1 vs 0	−0.94	−1.5 to −0.3	0.001	−0.79	−1.3 to −0.1	0.009**

Notes: β, regression coefficient.

# Adjusted for age, sex, smoking (classified as: never, former or current smoking), the presence of pets, mold in the home and childhood in a farm.

*P<0.05;

**P<0.01.

Abbreviation: CI, confidence interval.

Table S1 Distribution of volatile organic compounds in all farms

Variable	Mean (µg/m^3)	Min (µg/m^3)	Median (µg/m^3)	Third quartile (µg/m^3)	Max (µg/m^3)
Stable
Hexane	1.6	0.2	0.4	1.7	11.5
Benzene	1.3	0.6	1.1	1.5	2.7
Trichloroethylene	0.0	0.0	0.0	0.0	0.7
Toluene	2.1	0.4	1.3	2.2	11.2
Tetrachloroethylene	0.1	0.1	0.1	0.1	0.2
Ethylbenzene	0.8	0.1	0.3	0.4	6.5
n-Decane	10.6	2.2	5.0	6.8	96.9
2-Butoxyethylacetate	0.1	0.0	0.0	0.2	0.7
n-Undecane	14.6	1.7	8.0	10.8	132.3
Granary
Hexane	0.9	0.2	0.8	1.4	3.6
Benzene	1.7	0.8	1.2	1.6	10.6
Trichloroethylene	0.3	0.0	0.0	0.0	3.2
Toluene	5.9	0.5	3.2	5.3	28.26
Tetrachloroethylene	0.1	0.1	0.1	0.1	0.2
Ethylbenzene	1.3	0.1	0.7	1.8	5.7
n-Decane	10.3	2.9	9.0	12.4	30.7
2-Butoxyethylacetate	0.0	0.0	0.0	0.0	0.0
n-Undecane	12.5	1.9	9.9	16.6	33.6
Living
Hexane	1.2	0.2	0.5	1.1	11.0
Benzene	1.5	0.5	1.2	1.9	4.9
Trichloroethylene	0.1	0.0	0.0	0.0	2.1
Toluene	12.1	0.4	6.1	13.4	105.8
Tetrachloroethylene	0.1	0.0	0.1	0.1	0.5
Ethylbenzene	3.8	0.1	1.5	5.1	25.1
n-Decane	35.4	2.3	14.7	38.3	252.9
2-Butoxyethylacetate	0.1	0.0	0.0	0.3	1.1
n-Undecane	42.4	3.5	24.3	47.0	248.5

Abbreviations: min, minimum; max, maximum.

Table S2 Distribution of PM_2.5 in all farms

Variable	Mean (µg/m^3)	Min (µg/m^3)	Median (µg/m^3)	Third quartile (µg/m^3)	Max (µg/m^3)
Living
PM2.5 (µg/m^3)	3.8	1.0	2.0	4.5	40.0
Stable/granary
PM2.5 (µg/m^3)	11.0	0.0	3.0	8.0	327.0
Bedroom
PM2.5 (µg/m^3)	3.3	0.0	1.0	3.0	46.0

Note: PM_2.5, particles with an aerodynamic diameter <2.5 µm.

Abbreviations: min, minimum; max, maximum.