Autoimmune Connective Tissue Disease Following Carbon Monoxide Poisoning: A Nationwide Population-Based Cohort Study

Figures & data

Figure 1 Flowchart of this study.

Abbreviation: CO, carbon monoxide.

Table 1 Age, Sex, Underlying Comorbidities, and Monthly Income in Participants with and without CO Poisoning

Variables	With CO Poisoning n = 23,877	Without CO Poisoning n = 71,631	p-value
Age (years)	36.4 ± 15.5	36.4 ± 15.5	>0.999
Age (years)
< 20	2680 (11.2)	8043 (11.2)	>0.999
20–34	9366 (39.2)	28,096 (39.2)
35–49	7566 (31.7)	22,698 (31.7)
50–64	2974 (12.5)	8920 (12.5)
≥ 65	1291 (5.4)	3874 (5.4)
Sex
Female	11,905 (49.9)	36,878 (51.5)	<0.001
Male	11,972 (50.1)	34,753 (48.5)
Underlying comorbidity
Diabetes	1439 (6.0)	3460 (4.8)	<0.001
Alcohol abuse	873 (3.7)	661 (0.9)	<0.001
Lyme disease	0 (0)	3 (<0.1)	0.317
Herpes zoster	274 (1.2)	876 (1.2)	0.355
Infectious mononucleosis	6 (<0.1)	22 (<0.1)	0.663
Hepatitis	55 (0.2)	2185 (3.1)	<0.001
HIV infection	64 (0.3)	54 (0.1)	<0.001
Liver disease	3272 (13.7)	8372 (11.7)	<0.001
Renal disease	2336 (9.8)	5120 (7.2)	<0.001
Non-CO poisoning or drug abuse	2122 (8.9)	1064 (1.5)	<0.001
Malignancy	596 (2.5)	1426 (2.0)	<0.001
Hypertension	2730 (11.4)	7404 (10.3)	<0.001
Hyperlipidemia	1893 (7.9)	5168 (7.2)	<0.001
Coronary artery disease	1289 (5.4)	2931 (4.1)	<0.001
Congestive heart failure	343 (1.4)	690 (1.0)	<0.001
Chronic obstructive pulmonary disease	362 (1.5)	723 (1.0)	<0.001
Monthly income (NTD)
<19,999	17,273 (72.3)	44,649 (62.3)	<0.001
20,000–39,999	5292 (22.2)	19,929 (27.8)
≥ 40,000	1312 (5.5)	7053 (9.9)

Note: Data are expressed as mean ± SD or n (%).

Abbreviations: CO, carbon monoxide; NTD, new Taiwan dollars.

Figure 2 Comparison of the risk of autoimmune connective tissue disease between participants with and without CO poisoning during follow-up by Kaplan–Meier’s method and the Log rank test.

Abbreviation: CO, carbon monoxide.

Table 2 Comparison of the Risk for Autoimmune Connective Tissue Disease Between Participants with and without CO Poisoning Using Cox Proportional Hazard Regression Analysis

Variables	With CO Poisoning			Without CO Poisoning (Reference)			Crude HR (95% CI)	AHR* (95% CI)	AHR^competing (95% CI)*
	Autoimmune Connective Tissue Disease (%)	PY	Incidence Rate	Autoimmune Connective Tissue Disease (%)	PY	Incidence Rate
Overall analysis	625 (2.6)	114,194.1	5.5	598 (0.8)	379,829.2	1.6	3.5 (3.1–3.9)	3.5 (3.1–3.9)	3.2 (2.8–3.6)
Stratified analysis
Type of autoimmune connective tissue disease
Systemic lupus erythematosus	36 (5.8)	114,337.9	0.3	30 (5.0)	379,981.5	0.1	4.1 (2.5–6.7)	4.1 (2.5–6.8)	3.5 (2.2–5.8)
Rheumatoid arthritis	278 (44.5)	115,347.6	2.4	264 (44.2)	380,924.7	0.7	3.6 (3.0–4.2)	3.5 (2.9–4.2)	3.1 (2.6–3.7)
Sjögren’s syndrome and Scleroderma	229 (36.6)	114,868.28	2.0	247 (41.3)	380,710.8	0.7	3.2 (2.6–3.8)	3.3 (2.7–3.9)	2.9 (2.4–3.4)
Age (years)
< 20	38 (1.4)	16,641.2	2.3	28 (0.4)	51,566.3	0.5	4.2 (2.6–6.8)	4.0 (2.4–6.5)	3.9 (2.4–6.3)
20–34	197 (2.1)	46,515.4	4.2	141 (0.5)	151,031.0	0.9	4.5 (3.7–5.6)	4.5 (3.6–5.6)	4.2 (3.4–5.2)
35–49	237 (3.1)	35,436.6	6.7	225 (1.0)	120,238.8	1.9	3.6 (3.0–4.3)	3.4 (2.8–4.1)	3.1 (2.6–3.8)
50–64	102 (3.4)	11,298.1	9.0	138 (1.6)	40,248.8	3.4	2.6 (2.0–3.4)	2.6 (2.0–3.4)	2.3 (1.8–3.0)
≥ 65	51 (4.0)	4302.8	11.9	66 (1.7)	16,742.4	3.9	3.0 (2.1–4.3)	3.0 (2.1–4.3)	2.4 (1.7–3.6)
Sex
Female	434 (3.7)	58,718.7	7.4	424 (1.2)	197,213.7	2.2	3.4 (3.0–3.9)	3.5 (3.1–4.0)	3.2 (2.8–3.7)
Male	191 (1.6)	55,475.3	3.4	174 (0.5)	182,615.5	1.0	3.6 (2.9–4.4)	3.4 (2.8–4.2)	3.0 (2.4–3.7)
Underlying comorbidity
Diabetes	42 (2.9)	4719.5	8.9	44 (1.3)	13,834.8	3.2	2.8 (1.8–4.2)	2.8 (1.8–4.4)	2.4 (1.6–3.8)
Lyme disease	0 (0)	–	–	0 (0)	–	–	–	–	–
Herpes zoster	6 (2.2)	837.5	7.2	9 (1.0)	3248.6	2.8	2.5 (0.9–7.1)	2.7 (0.9–8.1)	2.2 (0.7–6.9)
Infectious mononucleosis	0 (0)	–	–	0 (0)	–	–	–	–	–
Hepatitis	0 (0)	–	–	21 (1.0)	9074.1	2.3	–	–	–
HIV infection	0 (0)	–	–	1 (1.9)	182.0	5.5	–	–	–
Liver disease	111 (3.4)	12,285.0	9.0	104 (1.2)	36,676.1	2.8	3.2 (2.4–4.1)	2.9 (2.2–3.9)	2.6 (1.9–3.4)
Renal disease	78 (3.3)	8862.0	8.8	61 (1.2)	21,954.6	2.8	3.2 (2.3–4.4)	2.9 (2.0–4.1)	2.5 (1.8–3.6)
Non-CO poisoning or drug abuse	67 (3.2)	7877.21	8.5	6 (0.6)	4023.7	1.5	5.8 (2.5–13.3)	5.1 (2.2–11.9)	4.3 (1.9–10.0)
Malignancy	14 (2.4)	1685.3	8.3	15 (1.1)	5512.2	2.7	3.0 (1.5–6.3)	3.4 (1.6–7.4)	2.7 (1.3–5.6)
Hypertension	92 (3.4)	9492.9	9.7	104 (1.4)	31,210.8	3.3	2.9 (2.2–3.9)	2.8 (2.1–3.7)	2.4 (1.8–3.2)
Hyperlipidemia	60 (3.2)	6366.7	9.4	66 (1.3)	19,968.4	3.3	2.8 (2.0–4.0)	2.6 (1.8–3.8)	2.3 (1.6–3.4)
Coronary artery disease	47 (3.7)	4523.3	10.4	57 (1.9)	11,990.4	4.8	2.2 (1.5–3.2)	2.3 (1.5–3.5)	2.0 (1.3–2.9)
Congestive heart failure	11 (3.2)	941.1	11.7	10 (1.5)	2448.7	4.1	2.8 (1.2–6.7)	2.3 (0.9–6.0)	1.8 (0.7–4.2)
Chronic obstructive pulmonary disease	15 (4.1)	1126.2	13.3	7 (1.0)	2880.7	2.4	5.4 (2.2–13.2)	5.3 (2.1–13.4)	4.1 (1.7–10.1)
Follow-up period
< 1 month	15 (0.1)	1918.9	7.8	13(<0.1)	5937.4	2.2	3.6 (1.7–7.5)	3.3 (1.6–7.0)	3.2 (1.5–6.7)
1–6 months	67 (0.3)	9202.4	7.3	46 (0.1)	29,027.4	1.6	4.6 (3.2–6.7)	4.6 (3.1–6.8)	4.5 (3.1–6.6)
7–12 months	53 (0.3)	10,388.2	5.1	65 (0.1)	33,235.3	2.0	2.6 (1.8–3.8)	2.5 (1.7–3.6)	2.5 (1.7–3.6)
1–2 years	98 (0.5)	18,832.0	5.2	97 (0.2)	61,189.7	1.6	3.3 (2.5–4.4)	3.1 (2.3–4.1)	3.0 (2.3–4.1)
2–4 years	167 (1.0)	29,963.5	5.6	153 (0.3)	99,706.7	1.5	3.6 (2.9–4.5)	3.8 (3.0–4.7)	3.7 (3.0–4.7)
≥ 4 years	225 (1.8)	43,889.2	5.1	224 (0.5)	150,732.8	1.5	3.5 (2.9–4.2)	3.6 (3.0–4.4)	3.5 (2.9–4.3)

Note: *Adjusted for sex, diabetes, Lyme disease, herpes zoster, infectious mononucleosis, hepatitis, HIV infection, liver disease, renal disease, non-CO poisoning or drug abuse, malignancy, hypertension, hyperlipidemia, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and monthly income.

Abbreviations: CO, carbon monoxide; AHR, adjusted hazard ratio; AHR^competing, risk estimated by competing risk survival analysis; CI, confidence interval; PY, person-year.

Table 3 Independent Predictors for Autoimmune Connective Tissue Disease in the All Participants by Cox Proportional Hazard Regression Analysis

Variables	Crude HR (95% CI)	AHR (95% CI) *	p-value†
Cohort
With CO poisoning	3.5 (3.1–3.9)	3.5 (3.1–3.9)	<0.001
Without CO poisoning	1 (reference)	1 (reference)	–
Age (years)
< 20	1 (reference)	1 (reference)	–
20–34	1.8 (1.4–2.3)	1.7 (1.3–2.2)	<0.001
35–49	3.1 (2.4–3.9)	2.9 (2.2–3.7)	<0.001
50–64	4.8 (3.6–6.3)	4.3 (3.3–5.7)	<0.001
≥ 65	5.7 (4.2–7.7)	5.0 (3.6–7.0)	<0.001
Sex
Female	2 (2–2.5)	2.5 (2–2.5)	<0.001
Male	1 (reference)	1 (reference)	–
Underlying comorbidity
Diabetes	1.9 (1.5–2.4)	0.9 (0.7–1.2)	0.441
Lyme disease	–	–	–
Herpes zoster	1.5 (0.9–2.4)	1.0 (0.6–1.7)	0.948
Infectious mononucleosis	–	–	–
Hepatitis	0.9 (0.6–1.4)	1.0 (0.6–1.5)	0.832
HIV infection	1.1 (0.2–7.5)	1.1 (0.2–7.5)	0.965
Liver disease	1.9 (1.7–2.2)	1.4 (1.2–1.6)	<0.001
Renal disease	1.9 (1.6–2.3)	1.2 (1.0–1.5)	0.032
Non-CO poisoning or drug abuse	2.5 (2.0–3.2)	1.3 (1.0–1.6)	0.063
Malignancy	1.6 (1.1–2.3)	0.9 (0.6–1.3)	0.655
Hypertension	2.1 (1.8–2.4)	1.0 (0.9–1.3)	0.727
Hyperlipidemia	2.0 (1.7–2.4)	1.1 (0.9–1.3)	0.566
Coronary artery disease	2.7 (2.2–3.2)	1.3 (1.0–1.6)	0.047
Congestive heart failure	2.5 (1.6–3.8)	1.0 (0.6–1.6)	0.973
Chronic obstructive pulmonary disease	2.2 (1.4–3.4)	1.1 (0.7–1.6)	0.815
Monthly income (NTD)
<19,999	1.2 (1.0–1.5)	0.9 (0.7–1.1)	0.396
20,000–39,999	1.0 (0.8–1.3)	0.9 (0.7–1.2)	0.468
≥ 40,000	1 (reference)	1 (reference)	–

Notes: *Adjusted for age, sex, diabetes, Lyme disease, herpes zoster, infectious mononucleosis, hepatitis, HIV infection, liver disease, renal disease, non-CO poisoning or drug abuse, malignancy, hypertension, hyperlipidemia, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and monthly income. †For AHR.

Abbreviations: AHR, adjusted hazard ratio; CO, carbon monoxide; CI, confidence interval; ARF, acute respiratory failure; HBOT, hyperbaric oxygen therapy; NTD, new Taiwan dollars.