Characteristics of COPD Phenotypes in Serbia

Figures & data

Figure 1 The study flowchart.

Table 1 Demographic and Clinical Characteristics of Patients from the Serbian COPD Registry

Characteristics	Value (Mean ± Standard Deviation, Range in Parentheses)
Number of the patients	5102
Age when included in the Registry (years) (mean ± SD, range)	67.1 ± 9.2 [26–97]
Age when COPD first diagnosed (years) (mean ± SD, range)	61.3 ± 9.8 [15–97]
Sex (m/f), n (%)	3225/1877 (63.2%/36.8%)
Duration of school education (years) (mean ± SD, range)	10.8 ± 2.9 [1–32]
Absolute value of postbronchodilator FEV1 (L) (mean ±SD, range)	1.44 ± 2.6 [0.6–4.1]
Relative value of postbronchodilator FEV1 (% of predicted) (mean ± SD, range)	52.4 ± 18.6 [21.4 −100.0]
Absolute value of postbronchodilator FVC (L) (mean ± SD, range)	2.6 ± 0.9 [1.0–6.9]
Relative value of postbronchodilator FEV1 (% of predicted) (mean ± SD, range)	74.5 ± 21.5 [20.0–100.0]
FEV1/FVC (%) (mean ± SD, range)	55.3 ± 11.4 [30.1–99.2]
BMI (kg/m^2) (mean ± SD, range)	26.1 ± 4.9 [12.6–39.9]
Number of moderate exacerbations per year (mean ±SD, range)	1.1 ± 1.3 [0–12]
Number of severe exacerbations per year (mean ±SD, range)	0.5 ± 0.8 [0–8]
Living at urban/rural region	3324/1778 (65.2%/34.8%)
Smoking status, n (%)
Never smoking	485 (9.5%)
Passive smoking	66 (1.3%)
Ex-smoker	2327 (45.6%)
Current smoker	2224 (43.6%)
Charlson co-morbidity index, n (%)
1	2760 (54.1%)
2	1174 (23.0%)
3	653 (12.8%)
≥ 4	515 (10.1%)
GOLD group according to mMRC or CAT, n (%)
GOLD A	71 (1.4%)
GOLD B	2311 (45.3%)
GOLD C	398 (7.8%)
GOLD D	2327 (45.6%)
GOLD group according to mMRC, n (%)
GOLD A	128 (2.5%)
GOLD B	2250 (44.1%)
GOLD C	408 (8.0%)
GOLD D	2311 (45.3%)
GOLD group according to CAT, n (%)
GOLD A	352 (6.9%)
GOLD B	2031 (39.8%)
GOLD C	571 (11.2%)
GOLD D	2148 (42.1%)
COPD Phenotype, n (%)
NON-AE	2519 (49.4%)
AE NON-CB	1510 (29.6%)
AE-CB	625 (12.2%)
ACOS	448 (8.8%)

Abbreviations: NON-AE, non-exacerbator; AE NON-CB, frequent exacerbator without chronic bronchitis; AE-CB, frequent exacerbator with chronic bronchitis; ACOS, asthma-COPD overlap; FEV1, forced expiratory volume in 1^st second; FVC, forced vital capacity; BMI, body mass index; CAT, COPD Assessment Test; mMRC, Modified Medical Research Council Dyspnea Scale.

Table 2 Characteristics of COPD Patients According to Phenotype

Characteristics	NON-AE	AE NON-CB	AE-CB	ACOS	Value of a Statistic Test
Number of patients (%)	2519 (49.3%)	1510 (29.7%)	625 (12.3%)	448 (8.7%)
Age when included in the Registry (years) (mean ± SD, range)	67.3 ± 9.1 [26–97]	67.1 ± 8.8 [33–94]	68.1 ± 8.9 [38–92]	64.7 ± 10.7 [33–88]	p ≤ 0.001^#
Age when COPD first diagnosed (years) (mean ± SD, range)	62.3 ± 9.2 [16–97]	61.2 ± 9.9 [15–87]	60.0 ± 9.9 [20–84]	58.3 ± 11.4 [15–87]	p ≤ 0.001^#
Sex (m/f), n (%)	1630/889 (64.7%/35.3%)	939/571 (62.2%/37.8%)	409/216 (65.5%/34.5%)	248/200 (55.3%/44.7%)	p ≤ 0.001**
Duration of school education (years) (mean ± SD, range)	10.6 ± 2.9 [1 −32]	11.2 ± 2.8 [1 −22]	10.1 ± 3.0 [2 −21]	10.8 ± 2.8 [1 −23]	p ≤ 0.001^#
Absolute value of postbronchodilator FEV1 (L) (mean ± SD, range)	1.5 ± 0.6 [0.6 −4.1]	1.3 ± 0.6 [0.6 −4.1]	1.1 ± 0.7 [0.6 −4.1]	1.5 ± 0.6 [0.6 −4.1]	p ≤ 0.001^#
Relative value of postbronchodilator FEV1 (%) (mean ± SD, range)	56.2 ± 17.7 [20.4 −100.0]	49.3 ± 19.9 [22.4 −100.0]	43.6 ± 15.4 [22.5 −121.0]	54.4 ± 17.5 [20.0 −120.0]	p ≤ 0.001^#
Absolute value of postbronchodilator FVC (L) (mean ± SD, range)	2.7 ± 0.9 [1.0 −6.7]	2.5 ± 0.9 [1.0 −6.9]	2.2 ± 0.7 [1.0 −6.9]	2.7 ± 1.0 [1.1 −6.9]	p ≤ 0.001^#
Relative value pf postbronchodilator FVC (%) (mean ± SD, range)	76.8 ± 20.6 [23.6 −100.0]	74.8 ± 22.9 [24.0 −100.0]	63.3 ± 18.0 [20.0 −120.0]	77.0 ± 21.5 [25.0 −100.0]	p ≤ 0.001^#
FEV1/FVC (%) (mean ± SD, range)	57.1 ± 10.7 [30.1 −98.0]	52.6 ± 11.5 [30.3 −99.2]	54.1 ± 12.9 [30.3 −99.0]	56.4 ± 10.9 [30.1 −95.0]	p ≤ 0.001^#
BMI (kg/m^2) (mean ± SD, range)	26.2 ± 4.9 [13.4 −39.9]	25.8 ± 4.9 [14.3 −39.5]	26.1 ± 5.0 [12.7 −39.8]	26.9 ± 4.8 [16.0 −39.8]	p ≤ 0.001^#
Number of moderate exacerbations (mean ± SD, range)	0.3 ± 0.4 [0.0 −1.0]	1.8 ± 1.1 [0.0 −12.0]	2.3 ± 1.7 [0.0 −12.0]	1.4 ± 1.5 [0.0 −10.0]	p ≤ 0.001^#
Number of severe exacerbations (mean ± SD, range)	0.1 ± 0.3 [0.0 −1.0]	1.0 ± 0.9 [0.0 −8.0]	0.9 ± 1.1 [0.0 −8.0]	0.4 ± 0.8 [0.0 −6.0]	p ≤ 0.001^#
Living at urban/rural region, n (%)	1700/819 (67.5%/32.5%)	1056/454 (69.9%/30.1%)	359/266 (55.8%/44.2%)	282/166 (62.9%/37.1%)	p ≤ 0.001**
Smoking status (including non-smokers), n (%)
• never smoking	247 (9,8%)	116 (7,7%)	50 (8,0%)	73 (16,4%)	p ≤ 0.001**
• passive smoking	45 (1,8%)	6 (0,4%)	13 (2,1%)	5 (1,1%)
• ex-smoker	1088 (43,2%)	750 (49,7%)	296 (47,4%)	190 (42,3%)
• current smoker	1139 (45,2%)	637 (42,2%)	266 (42,6%)	180 (40,2%)
Smoking status (excluding non-smokers), n (%)
• passive smoking	45 (1,9%)	6 (0,4%)	13 (2,3%)	5 (1,4%)	p ≤ 0.001**
• ex-smoker	1088 (47,9%)	750 (53,8%)	296 (51,5%)	190 (50,5%)
• current smoker	1139 (50,2%)	637 (45,8%)	266 (46,3%)	180 (48,1%)
Charlson co-morbidity index, n (%)
• 1	1383 (54,9%)	778 (51,5%)	333 (53,3%)	256 (57,1%)	p = 0.144**
• 2	562 (22,3%)	365 (24,2%)	151 (24,1%)	100 (22,4%)
• 3	338 (13,4%)	187 (12,4%)	75 (12,0%)	52 (11,7%)
• ≥ 4	236 (9.4%)	180 (11.9%)	66 (10.6%)	40 (8.9%)
GOLD classification according to mMRC or CAT, n (%)
GOLD A	60 (2,4%)	0 (0,0%)	0 (0,0%)	12 (2,6%)	p ≤ 0.001*
GOLD B	2222 (88,2%)	0 (0,0%)	0 (0,0%)	186 (41,6%)
GOLD C	0 (0,0%)	366 (24,2%)	4 (0,7%)	5 (1,0%)
GOLD D	237 (9,4%)	1144 (75,8%)	621 (99,3%)	246 (54,8%)
GOLD classification according to mMRC, n (%)
GOLD A	113 (4,5%)	0 (0,0%)	0 (0,0%)	20 (4,6%)	p ≤ 0.001*
GOLD B	2169 (86,1%)	0 (0,0%)	0 (0,0%)	178 (39,7%)
GOLD C	8 (0,3%)	368 (24,4%)	9 (1,5%)	5 (1,0%)
GOLD D	229 (9,1%)	1142 (75,6%)	616 (98,5%)	245 (54,8%)
GOLD classification according to CAT, n (%)
GOLD A	333 (13,2%)	0 (0,0%)	0 (0,0%)	34 (7,5%)	p ≤ 0.001*
GOLD B	1950 (77,4%)	0 (0,0%)	0 (0,0%)	165 (36,8%)
GOLD C	10 (0,4%)	506 (33,5%)	13 (2,0%)	14 (3,1%)
GOLD D	227 (9,0%)	1004 (66,5%)	612 (98,0%)	235 (52,6%)

Notes: #Kruskal-Wallis; *Fisher’s exact test with the Freeman-Halton extension; **Chi-square.

Abbreviations: NON-AE, non-exacerbator; AE NON-CB, frequent exacerbator without chronic bronchitis; AE-CB, frequent exacerbator with chronic bronchitis; ACOS, asthma-COPD overlap; FEV1, forced expiratory volume in 1^st second; FVC, forced vital capacity; BMI, body mass index; CAT, COPD Assessment Test; mMRC, Modified Medical Research Council Dyspnea Scale.

Table 3 COPD Phenotype-Specific Rates of the Most Frequent Comorbidities Occurring Among Patients from the Serbian COPD Registry

Comorbidity	NON-AE	AE NON-CB	AE-CB	ACOS	The Test Value
Number of patients, n (%)	2519 (49.3%)	1510 (29.7%)	625 (12.3%)	448 (8.7%)
Myocardial infarction, n (%)	5.5%	5.5%	6.1%	5.6%	p = 0.955**
Congestive heart failure, n (%)	10.7%	11.7%	17.1%	13.2%	p ≤ 0.001**
Atrial fibrillation, n (%)	9.5%	8.6%	11.2%	8.3%	p = 0.238**
Coronary arteries disease, n (%)	7.7%	12.1%	15.0%	11.8%	p ≤ 0.001**
Pulmonary embolism, n (%)	0.8%	0.9%	0.6%	0.7%	p = 0.975*
Peripheral vascular disease, n (%)	8.7%	5.6%	9.4%	10.7%	p ≤ 0.001**
Cerebrovascular disease, n (%)	2.6%	3.4%	5.3%	4.0%	p = 0.007**
Hypertension, n (%)	59.8%	54.6%	75.0%	65.4%	p ≤ 0.001**
Hyperlipidemia, n (%)	9.4%	3.2%	6.4%	10.9%	p ≤ 0.001**
Dementia, n (%)	0.6%	1.4%	2.1%	1.3%	p = 0.008**
Depression, n (%)	4.4%	5.7%	14.9%	8.5%	p ≤ 0.001**
Anxiety, n (%)	3.6%	4.0%	9.6%	6.3%	p ≤ 0.001**
Insomnia, n (%)	5.2%	3.4%	14.1%	8.0%	p ≤ 0.001**
Connective tissue disease, n (%)	2.3%	1.1%	1.8%	2.9%	p = 0.018**
Peptic ulcer disease, n (%)	4.0%	2.9%	4.6%	4.9%	p = 0.106**
Gastro-esophageal reflux disease, n (%)	2.7%	1.2%	5.3%	4.2%	p ≤ 0.001**
Diabetes mellitus without complications, n (%)	10.7%	7.0%	12.8%	9.6%	p ≤ 0.001**
Diabetes mellitus with complications, n (%)	2.6%	3.4%	4.5%	3.8%
Mild to moderate liver disease, n (%)	1.0%	0.5%	0.8%	0.9%	p = 0.816**
Severe liver disease, n (%)	0.2%	0.2%	0.3%	0.2%
Hemiplegia, n (%)	0.0%	0.0%	0.3%	0.0%	p = 0.083*
Moderate or severe renal failure, n (%)	2.9%	2.1%	2.1%	2.2%	p = 0.300**
Leukemia, n (%)	0.2%	0.3%	0.0%	0.2%	p = 0.565*
Lymphoma, n (%)	0.1%	0.1%	0.5%	0.2%	p = 0.071*
Solid tumor without metastases, n (%)	8.0%	4.8%	3.0%	5.6%	p ≤ 0.001**
Metastatic solid tumor, n (%)	2.2%	0.9%	1.0%	0.2%	p ≤ 0.001*
Osteoporosis, n (%)	2.1%	2.3%	4.3%	5.1%	p ≤ 0.001**
Anemia, n (%)	4.0%	1.6%	2.1%	4.7%	p ≤ 0.001**

Notes: *Fisher’s exact test with the Freeman-Halton extension; **Chi-square.

Abbreviations: NON-AE, non-exacerbator; AE NON-CB, frequent exacerbator without chronic bronchitis; AE-CB, frequent exacerbator with chronic bronchitis; ACOS, asthma-COPD overlap.

Table 4 COPD Phenotype-Specific Inhalation and Oral Therapy Prescribed to Patients from the Serbian COPD Registry

Inhalation or Oral Therapy	NON-AE	AE NON-CB	AE-CB	ACOS	The Test Value
Number of patients	2519 (49.3%)	1510 (29.7%)	625 (12.3%)	448 (8.7%)
SAMA monotherapy, (%)	0.9%	1.8%	3.7%	1.8%	p ≤ 0.001**
SABA monotherapy, (%)	10.1%	2.4%	5.5%	7.0%	p ≤ 0.001**
SABA + SAMA, (%)	81.5%	64.7%	87.7%	84.5%	p ≤ 0.001**
LABA monotherapy, (%)	13.4%	3.4%	6.0%	7.0%	p ≤ 0.001**
LAMA + LABA, (%)	16.3%	14.2%	14.0%	14.3%	p = 0.218**
ICS monotherapy, (%)	1.9%	1.9%	2.5%	3.4%	p = 0.207**
ICS + LABA, (%)	43.4%	40.8%	69.2%	64.3%	p ≤ 0.001**
ICS + LABA + LAMA, (%)	30.9%	31.9%	57.1%	45.0%	p ≤ 0.001**
Roflumilast, (%)	0.2%	0.7%	0.8%	0.2%	p = 0.044*
Theophylline, (%)	26.8%	25.5%	56.1%	27.0%	p ≤ 0.001**

Notes: *Fisher’s exact test with the Freeman-Halton extension; **Chi-square.

Abbreviations: NON-AE, non-exacerbator; AE NON-CB, frequent exacerbator without chronic bronchitis; AE-CB, frequent exacerbator with chronic bronchitis; ACOS, asthma-COPD overlap; SAMA, short-acting muscarinic antagonists; SABA, short-acting beta agonists; LAMA, long-acting muscarinic antagonists; LABA, long-acting beta agonists; ICS, inhalational corticosteroids.