Vitamin D deficiency is associated with impaired disease control in asthma–COPD overlap syndrome patients

Figures & data

Table 1 Clinical characteristics and sample collection data of the four study groups

	Control	Asthma	COPD	ACOS
Number of patients (n)	21	44	21	20
Female/male	12/9	36/8	10/11	12/8
Age (years)	38.00±3.34	44.84±2.38	66.33±2.63	65.45±1.86
BMI (kg/m^2)	–	26.80±1.31	24.33±0.95	29.12±1.45
Smoking habits, n (%)
Current smoker	0 (0)	1 (2.25)	4 (19)	5 (25)
Ex-smoker	1 (4.75)	2 (4.5)	15 (71.25)	14 (70)
Never-smoker	20 (95)	41 (93.25)	2 (9.5)	1 (5)
GOLD category, n (%)	–	–	II–IV	I–IV
A			0 (0)	3 (15)
B			2 (9.5)	9 (45)
C			0 (0)	0 (0)
D			19 (90.5)	8 (40)
Allergic rhinitis or atopic nature, n (%)	0 (0)	34 (77)	0 (0)	10 (50)
Number of comorbidities, mean [range]	0 [0]	0.34 [0–4]a	2.19 [0–4]	0.70 [0–2]
Sample collected in summer season, n (%)	2 (9.5)	3 (6.75)	5 (24)	0 (0)

Notes: Data expressed as mean ± SEM if not stated otherwise.

a Only one asthmatic patient had four comorbidities.

Abbreviations: ACOS, asthma–COPD overlap syndrome; BMI, body mass index; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; SEM, standard error of mean.

Table 2 Medications and dose of ICS for patients with asthma, COPD, and ACOS

	Asthma	COPD	ACOS
SABA/SAMA, n (%)	31 (70)	18 (85)	20 (100)
LAMA, n (%)	0 (0)	19 (90)	18 (90)
LABA, n (%)	34 (77)	20 (95)	20 (100)
Leukotriene inhibitors, n (%)	21 (47)	0 (0)	8 (40)
Total ICS use, n (%)	39 (88)	21 (100)	20 (100)
Daily dose of ICS (beclomethasone equivalent,	µg)
Low dose, n (%), 200–500 µg	11 (25)	0 (0)	1 (5)
Medium dose, n (%), >500–1,000 µg	27 (61)	3 (14)	14 (70)
High dose, n (%), >1,000 µg	1 (2.25)	18 (85)	5 (25)

Abbreviations: ACOS, asthma–COPD overlap syndrome; COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; SABA, short-acting beta agonist; SAMA, short-acting muscarinic antagonist.

Figure 1 25(OH)D levels in different patient groups and in OLD patients using different ICS doses.

Notes: (A) 25(OH)D levels measured in healthy individuals, asthma, ACOS, and COPD patients. (B) 25(OH)D levels in OLD patients using different doses of ICS. No significant differences were found between the study groups. *P<0.05 vs control. ^#P<0.05 vs asthma.
Abbreviations: ACOS, asthma–COPD overlap syndrome; COPD, chronic obstructive pulmonary disease; 25(OH)D, 25-hydroxyvitamin D; ICS, inhaled corticosteroid; OLD, obstructive lung disease.

Table 3 Lung function parameters, ACT, CAT, and mMRC tests of patients with asthma, COPD, and ACOS

	Asthma	ACOS	COPD	P-value
				Asthma vs ACOS	COPD vs ACOS
FEV1 (% pred)	87.61±2.70	56.25±4.26	32.67±3.93	<0.0001	<0.0001
FVC (% pred)	98.34±2.43	77.15±3.42	56.05±3.69	<0.0001	0.0002
FEF25–75 (% pred)	63.49±3.95	28.85±3.51	13.76±1.26	<0.0001	0.0002
PEF (% pred)	83.41±3.09	48.75±3.87	28.86±2.12	<0.0001	<0.0001
Raw (% pred)	150.6±9.08	171.1±20.95	267.9±20.27	0.29	0.0024
mMRC total score, mean [range]	–	1.80 [1–3]	3.57 [2–4]	–	<0.0001
ACT total score, mean [range]	20.95 [9–25]	15.60 [8–24]	–	<0.0001	–
CAT total score, mean [range]	–	17.95 [6–30]	21.14 [12–31]	–	0.11

Notes: Data expressed as mean ± SEM if not stated otherwise. Significant differences are highlighted in bold.

Abbreviations: ACOS, asthma–COPD overlap syndrome; ACT, asthma control test; CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; FEF25–75, forced expiratory flow between 25% and 75% of FVC; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; mMRC, modified Medical Research Council; % pred, % predicted; Raw, airway resistance; SEM, standard error of mean.

Figure 2 Correlations between 25(OH)D levels and lung function parameters in OLD patients.

Notes: Positive correlation between 25(OH)D levels to FEV₁ (% pred) (A), FVC (% pred) (B), FEF25–75 (% pred) (C), and PEF (% pred) (D).
Abbreviations: FEF25–75, forced expiratory flow between 25% and 75% of FVC; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; 25(OH)D, 25-hydroxyvitamin D; % pred, % predicted; OLD, obstructive lung disease; PEF, peak expiratory flow.

Figure 3 Correlation between 25(OH)D levels and ACT total score.

Notes: (A) Positive correlation between ACT total score and 25(OH)D levels in ACOS and asthma study groups. (B) Positive correlation between ACT total score and 25(OH)D levels in ACOS group.
Abbreviations: ACT, asthma control test; ACOS, asthma–COPD overlap syndrome; COPD, chronic obstructive pulmonary disease; 25(OH)D, 25-hydroxyvitamin D.

Figure 4 Correlation between 25(OH)D levels and CAT total score.

Notes: (A) No association between CAT total score and 25(OH)D levels in ACOS and COPD groups. (B) Negative correlation between CAT total score and 25(OH)D levels in ACOS group.
Abbreviations: ACOS, asthma–COPD overlap syndrome; CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; 25(OH)D, 25-hydroxyvitamin D.

Table 4 Univariate and multivariate logistic regressions showing the risk factors associated with vitamin D deficiency

	Vitamin D deficiency
	OR	95% CI (Ref)	P-value
Univariate
Obstructive pulmonary disease
COPD	3.406	(1.114–10.414)	0.032
ACOS	3.094	(1.007–9.509)	0.049
Bronchial asthma	0.184	(0.072–0.472)	<0.0001
ICS use
Low-dose ICS use	0.22	(0.055–0.880)	0.032
Medium-dose ICS use	0.792	(0.336–1.865)	0.594
High-dose ICS use	2.753	(0.953–7.948)	0.061
Clinical parameters
Sample collected in summer season	1.265	(0.295–5.430)	0.752
Age	1.035	(1.007–1.063)	0.014
Sex	1.016	(0.405–2.545)	0.0974
BMI	1.018	(0.942–1.101)	0.645
FEV1 (% pred) <80%	4.01	(1.600–10.053)	0.003
PEF (% pred) <80%	3.273	(1.294–8.274)	0.012
ACT total score	0.859	(0.766–0.963)	0.009
ACT ≤20 points	2.746	(0.967–7.795)	0.058
CAT total score	1.028	(0.921–1.148)	0.618
CAT ≥20 points	1.214	(0.291–5.060)	0.79
CAT ≥17 points	1.232	(0.255–5.944)	0.715
CAT ≥10 points	1.611	(0.130–19.909)	0.71
mMRC	1.214	(0.641–2.300)	0.551
mMRC ≥2 points	3.467	(0.709–16.938)	0.125
Atopic nature	4.511	(1.778–11.448)	0.002
Eosinophil cell count (G/L)	0.322	(0.053–1.942)	0.216
Eosinophil cell count >0.2 (G/L)	0.662	(0.270–1.621)	0.366
Multivariate
Clinical parameters
Age	1.001	(0.954–1.049)	0.98
FEV1 (% pred) <80%	0.659	(0.099–4.375)	0.666
PEF (% pred) <80%	3.505	(0.497–24.705)	0.208
ACT total score	1.107	(0.951–1.290)	0.19
Atopic nature	0.176	(0.036–0.862)	0.032
Low-dose ICS use	4.77	(0.550–41.400)	0.156
OLD diagnosis	1.618	(0.880–2.978)	0.122

Note: Significant differences are highlighted in bold.

Abbreviations: ACOS, asthma–COPD overlap syndrome; ACT, asthma control test; BMI, body mass index; CAT, COPD assessment test; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; mMRC, modified Medical Research Council; OLD, obstructive lung disease; OR, odds ratio; % pred, % predicted; Ref, reference; PEF, peak expiratory flow.