Fractional exhaled nitric oxide levels in asthma–COPD overlap syndrome: analysis of the National Health and Nutrition Examination Survey, 2007–2012

Figures & data

Table 1 Characteristics of subjects with asthma–COPD overlap syndrome and those with COPD alone

Characteristicsa	ACOS	COPD alone	P-value
Unweighted sample, n	48	149	–
Weighted estimate, n	662,424	2,165,367	–
Demographics
Age (year), mean (SE)	56 (1.4)	58 (1.1)	0.23
Male sex	75 (53–88)	67 (58–75)	0.47
Race/ethnicity			0.74
Non-Hispanic white	88 (78–94)	91 (85–94)
Non-Hispanic black	8 (4–18)	5 (3–9)
Hispanics	1 (0–3)	1 (0–3)
Others	3 (1–7)	3 (1–8)
Primary health insurance			0.80
Medicare	10 (5–21)	12 (8–19)
Medicaid	3 (1–12)	2 (1–4)
Private	73 (53–86)	68 (59–76)
No insurance	2 (0–10)	5 (3–10)
Others	12 (4–32)	12 (7–20)
Medical history
Body mass index (kg/m^2), mean (SE)	30.1 (1.1)	27.2 (0.5)	0.03
Smoking status
Current smoker	48 (33–64)	59 (47–70)	0.34
Pack-years, mean (SE)	32 (3.3)	36 (2.2)	0.30
≥10 pack-years	79 (63–89)	83 (74–90)	0.58
Symptoms
Cough	33 (17–53)	37 (29–45)	0.72
Sputum	34 (19–53)	31 (22–42)	0.78
Wheezing	72 (48–88)	35 (27–45)	0.01
Shortness of breath on exertion	60 (42–75)	70 (61–78)	0.34
Comorbidities
Coronary heart diseasesb	10 (3–30)	15 (9–24)	0.43
Diabetes	11 (4–25)	11 (7–18)	0.92
Hypertension	36 (22–53)	41 (31–52)	0.62
Renal failure	9 (2–37)	2 (1–6)	0.38
Health care utilization
Having a routine place for health care	91 (79–97)	94 (90–97)	0.55
Number of health care visits in the past year, mean (SE)	2 (0.2)	2 (0.2)	0.51
Number of health care visits for wheezing in the past year, mean (SE)	1 (0.5)	1 (0.3)	0.64
Overnight hospital stay in the past year	9 (3–23)	14 (9–23)	0.37
Medications for wheezing	58 (37–77)	32 (19–49)	0.01
Oral corticosteroids	3 (1–21)	1 (0–5)	0.47
Inhaled corticosteroids	5 (1–19)	0 (0–0)	0.18
Laboratory tests
White blood cell count (cells/μL), mean (SE)
Total	7,349 (297)	7,972 (178)	0.09
Neutrophils	4,538 (256)	4,909 (148)	0.25
Lymphocytes	1,951 (87)	2,194 (79)	0.04
Eosinophils	272 (44)	236 (13)	0.45
Spirometry, mean (SE)
Baseline FVC (L)	3.9 (0.2)	4.0 (0.1)	0.85
Baseline FEV1 (L)	2.4 (0.1)	2.4 (0.1)	0.97
Baseline PEF (L/min)	383 (25)	377 (9)	0.81
Baseline FEV1 % predicted	58 (53–62)	61 (57–64)	0.32
Baseline FEV1/FVC%	60 (58–62)	59 (57–61)	0.54
Post-bronchodilator FVC (L)	4.2 (0.2)	4.0 (0.1)	0.50
Post-bronchodilator FEV1 (L)	2.6 (0.1)	2.5 (0.1)	0.40
Post-bronchodilator PEF (L/min)	430 (27)	402 (10)	0.33
Post-bronchodilator FEV1 % predicted	63 (59–67)	63 (60–67)	0.92
Post-bronchodilator FEV1/FVC%	62 (59–65)	61 (59–63)	0.50
GOLD stage			0.07
I	2 (0–16)	17 (10–25)
II	84 (73–91)	63 (50–74)
III	14 (6–27)	19 (12–30)
IV	0 (0–0)	1 (0–6)

Notes:

a Data are expressed as % (95% confidence interval) unless otherwise indicated.

b Coronary heart diseases include ischemic heart disease, angina, myocardial infarction, and heart failure.

Abbreviations: ACOS, asthma–COPD overlap syndrome; COPD, chronic obstructive pulmonary disease; GOLD, the Global initiative of chronic Obstructive Lung Disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; PEF, peak flow; SE, standard error.

Table 2 Unadjusted and adjusted differences in fractional exhaled nitric oxide level between subjects with asthma–COPD overlap syndrome and those with COPD alone

Models	Primary analysis		Stratified analysis
			Current smokers n=112		Non-current smokers n=85
	β coefficient (95% CI)	P-value	β coefficient (95% CI)	P-value	β coefficient (95% CI)	P-value
Unadjusted model
ACOS (vs COPD alone)	8.2 (0.2 to 16.2)a	0.045	1.1 (−1.9 to 4.2)b	0.46	11.6 (−1.7 to 24.9)c	0.09
Multivariable model
ACOS (vs COPD alone)	8.2 (0.9 to 15.5)	0.03	3.2 (−0.1 to 6.6)	0.06	20.5 (4.4 to 36.6)	0.02
Age	0.2 (−0.2 to 0.6)	0.38	−0.04 (−0.2 to 0.1)	0.52	0.7 (−0.1 to 1.5)	0.08
Female sex	3.2 (−13.5 to 19.9)	0.70	1.1 (−3.6 to 5.8)	0.63	5.4 (−18.1 to 28.9)	0.64
Race/ethnicity
Non-Hispanic white	1 (reference)		1 (reference)		1 (reference)
Non-Hispanic black	−3.0 (−12.4 to 6.4)	0.52	5.3 (−2.0 to 12.6)	0.15	−25.6 (−45.4 to −5.8)	0.01
Mexican–American	2.1 (−5.1 to 9.4)	0.56	2.6 (−1.3 to 6.5)	0.18	11.8 (−0.8 to 24.3)	0.07
Other race	−1.6 (−11.8 to 8.6)	0.75	2.3 (−4.0 to 8.6)	0.46	−7.5 (−17.3 to 2.2)	0.12
Corticosteroid used	−1.9 (−14.7 to 11.0)	0.77	8.2 (5.7 to 10.8)	<0.001	−20.6 (−48.2 to 7.0)	0.14
Medications for wheezing	−4.8 (−12.9 to 3.2)	0.23	−0.5 (−3.2 to 2.2)	0.72	−10.4 (−22.8 to 2.0)	0.10
Current smoking	−15.8 (−23.9 to −7.8)	<0.001

Notes:

a Mean 21.2 ppb in ACOS vs 13.0 ppb in COPD alone.

b Mean 9.6 ppb in ACOS vs 8.5 ppb in COPD alone.

c Mean 31.9 ppb in ACOS vs 20.3 ppb in COPD alone.

d Including oral corticosteroids and inhaled corticosteroids.

Abbreviations: ACOS, asthma–COPD overlap syndrome; CI, confidence interval; COPD, chronic obstructive pulmonary disease.

Table 3 Unadjusted and adjusted differences in fractional exhaled nitric oxide level between subjects with asthma–COPD overlap syndrome (alternative definition) and those with COPD alone

Models	Primary analysis		Stratified analysis
			Current smokers n=112		Non-current smokers n=85
	β coefficient (95% CI)	P-value	β coefficient (95% CI)	P-value	β coefficient (95% CI)	P-value
Unadjusted model
ACOS (vs COPD alone)	6.7 (−0.2 to 13.8)a	0.06	1.6 (−1.4 to 4.7)b	0.29	7.1 (−4.0 to 18.2)c	0.20
Multivariable model
ACOS (vs COPD alone)	7.2 (0.8 to 13.5)	0.03	2.9 (−0.4 to 6.2)	0.08	19.0 (3.8 to 34.1)	0.02
Age	0.2 (−0.2 to 0.6)	0.37	−0.03 (−0.2 to 0.1)	0.63	0.7 (−0.2 to 1.5)	0.11
Female sex	1.6 (−16.7 to 20.0)	0.86	1.0 (−4.0 to 5.9)	0.69	−0.04 (−28.3 to 28.3)	0.99
Race/ethnicity
Non-Hispanic white	1 (reference)		1 (reference)		1 (reference)
Non-Hispanic black	−2.7 (−11.9 to 6.6)	0.57	5.3 (−2.0 to 12.6)	0.15	−24.9 (−43.9 to −5.8)	0.01
Mexican–American	3.3 (−2.9 to 9.6)	0.29	3.1 (0.3 to 6.0)	0.03	13.1 (−1.3 to 27.4)	0.07
Other race	−3.8 (−14.2 to 6.6)	0.47	0.2 (−7.1 to 7.6)	0.95	−8.5 (−19.5 to 2.6)	0.13
Corticosteroid used	−1.2 (−12.9 to 10.5)	0.84	8.0 (5.5 to 10.5)	<0.001	−17.0 (−43.4 to 9.4)	0.20
Medications for wheezing	−5.7 (−14.7 to 3.3)	0.21	−0.5 (−3.2 to 2.3)	0.73	−14.1 (−29.9 to 1.7)	0.08
Current smoking	−15.8 (−24.3 to −7.2)	0.001	–	–	–	–

Notes:

a Mean 19.8 ppb in ACOS vs 13.1 ppb in COPD alone.

b Mean 10.0 ppb in ACOS vs 8.3 ppb in COPD alone.

c Mean 28.3 ppb in ACOS vs 21.2 ppb in COPD alone.

d Including oral corticosteroids and inhaled corticosteroids.

Abbreviations: ACOS, asthma–COPD overlap syndrome; CI, confidence interval; COPD, chronic obstructive pulmonary disease.

Figure 1 Unadjusted differences in mean fractional exhaled nitric oxide level between subjects with asthma–COPD overlap syndrome and those with COPD alone.

Abbreviations: ACOS, asthma–COPD overlap syndrome; COPD, chronic obstructive pulmonary disease.

Figure 2 Receiver operating characteristic curve for fractional exhaled nitric oxide level to discriminate asthma–COPD overlap syndrome from COPD alone.

Abbreviations: COPD, chronic obstructive pulmonary disease; ROC, receiver operating characteristic.