Age- and gender-based comorbidity categories in general practitioner and pulmonology patients with COPD.

Chronic obstructive pulmonary disease (COPD) is a debilitating medical condition often accompanied by multiple chronic conditions. COPD is more frequent among older adults and affects both genders. The aim of the current cross-sectional survey was to characterize chronic comorbidities stratified by gender and age among patients with COPD under the care of general practitioners (GP) and pulmonologists, using real-world patient data. A total of 7966 COPD patients (women: 45%) with more than 5 years of the observation period in the practice were examined using 60 different Chronic comorbid conditions (CCC) and Elixhauser measures. More than 9 in 10 patients had at least one, and 51.7% had more than three comorbidities. No gender difference was found in the number of comorbidities. However, men had higher Elixhauser-van Walraven index scores than women, and the types of comorbidities differed by gender. An increasing number of comorbidities was seen with aging but the patients in their 30s and 40s also had a high number of comorbidities. Moreover, GP patients had a higher number and a wider array of documented comorbidities than pulmonology patients did. Psychological comorbidities were common in all patients, but particularly among younger patients. These findings around gender- and age-stratified comorbidities under the care of GPs and pulmonologists have implications for the choice of data provenience for decision-making analysis and treatment selection and success.

Introduction

Chronic obstructive pulmonary disease (COPD), characterized by chronic obstruction of lung airflow that interferes with normal breathing, claims millions of lives each year and is the fourth leading cause of mortality worldwide[1,2]. COPD used to be more common in men; however, because of increased tobacco use and the higher risk of exposure to indoor air pollution among women, the disease now affects both men and women almost equally[2]. Additionally, COPD is more common among the elderly population as COPD symptoms develop slowly and become apparent during middle age[2,3]. Considering one in six people will be over the age of 65 by 2050[4], the aging of the general population may further increase the burden of COPD.

COPD patients often have a multitude of other chronic conditions that can influence the prognosis of COPD and complicate the disease management[5]. Patients with COPD often die prematurely after suffering for many years due to COPD or its comorbid conditions[1]. These comorbid conditions increase economic burdens by directly increasing medical costs associated with hospitalization and service utilization and indirectly via early retirement or inability to work[6,7]. Recently, multiple studies have further enhanced our understanding of COPD and associated comorbidities[8-12], and some highlighted the potential underlying pathophysiology of COPD, the mechanism of systemic inflammation[13,14]. These studies of comorbidities are crucial because thoroughly understanding the nature and pattern of comorbidity is the foundation for physicians to provide broad yet appropriately targeted and prioritized treatments to enhance the COPD treatment outcome.

While past comorbidity studies have revealed invaluable information about the association and potential mechanism of comorbidities, thorough documentation of COPD comorbidities using routine real-world data in primary care settings is still scarce. Moreover, previous studies either have examined a small number of chronic conditions or did not examine gender differences[8-12]. Therefore, our study aimed to examine the comorbidities stratified by gender and age among primary care patients with COPD using routine care data from the electronic patient records of general practice and pulmonology settings. Our goal is to contribute to the creation of a road map of personalized holistic treatment choices, by outlining the gender- and age-specific comorbidities among patients with COPD.

Methods

Study design

The current study was a cross-sectional survey using primary care data of the German BeoNet Register-Database (BNR). The BNR is a compilation of all routinely documented information from primary care electronic patient records from general practitioners (GPs) and pulmonologists participating in the network. It comprises a retrospective dataset since the practice used electronic files and the database is updated weekly. Only completely anonymized data are available for research purposes. In Germany, all physicians in outpatient practices are considered primary care physicians because patients have direct access to any physician without a referral and regardless of their specialty[15]. Therefore, the patient records from both GP and pulmonology practices were included in the study. Written informed consent from patients was not required, as the analyses were performed on a de-identified dataset out of the Registry database. The study was approved by the Medizinische Hochschule Hannover (MHH) ethics committee.

Study patients

Female and male patients aged 20 years and older with physician-diagnosed COPD were included in the analyses. Physician-diagnosed COPD was identified by having two documented diagnostic codes of J44 following the International Statistical Classification of Diseases (ICD-10)[16,17], and one of which was a permanent diagnosis of COPD. Moreover, patients must have been under observation at least for 5 years, so that the cumulated comorbidities reflect their overall health status. Exclusion criteria were age <20 years old, and/or missing data on major variables such as gender and age. The detailed patient selection process is presented as a flowchart in the Supplementary Document (Supplementary Fig. 1). The patients were stratified into seven age groups based on their age at their last visit: 20s, 30s, 40s, 50s, 60s, 70s, and 80s+ group. Overall comorbidity is stratified and examined by gender and age group.

The 10-year index period analysis

We examined comorbidity occurrence during a 10-year index period, 5 years before and 5 years after the index date. The index date was defined as the time of the first office visit with documented COPD. Based on the age of the patients at the index date, three groups were formed and examined: the <45, 45–64, and ≥65 years of index age groups. For this analysis, the patients who had not been with the practice for more than 10 years (5 years before and after the index date) were excluded.

Comorbidity measures

All ICD codes of each patient entered in the database were examined. Sixty chronic comorbid conditions (CCC) were created by searching and re-coding individual ICD-10 codes into different disease categories corresponding to the classification of Calderón-Larrañaga et al.[18]. Disease category names and codes were retained without any alterations according to the original publication. However, for the purposes of this study, ICD-10 code J44 was excluded from the category named “COPD, emphysema, chronic bronchitis.” The total number of CCC and frequency of 60 categories were examined. In addition, 30 Elixhauser comorbid conditions were generated[19,20]. Although Elixhauser comorbidity includes a smaller number of comorbidity than CCC, the Elixhauser measure was included for its summation scores and index scores based on the van Walraven (vW) algorithm. Elixhauser-vW index scores have been linked to mortality rates and provide additional information, which cannot be assessed using summation scores of each disease category alone[21-27]. Elixhauser-vW index scores were calculated by weighting individual comorbidity categories[21]. The J44 diagnosis was excluded from the total number of comorbidity but not from the Elixhauser-vW index score to adhere to the original algorithm. For the 10-year index period analyses, only the first documentation of each comorbidity was considered.

Data and statistical analyses

The BNR-database was accessed in September 2020. All available medical records of patients with permanent COPD diagnoses were extracted along with patient demographic information and the documented dates of their practice visits. In the first data processing step, the formats were standardized. Subsequently, the variables needed for the inclusion and exclusion criteria were created. Finally, the diagnosis data were reduced to the ICD codes required by the employed methods. The software R (R Core Team, 2020) was used for this process.

Descriptive statistics are presented as means and standard deviations (SD) or absolute numbers and percentages. Given the robustness of parametric tests with large sample sizes, independent t-tests were used to compare demographic gender differences (χ2 test for categorical variables) and analysis of variance (ANOVA) was used to compare the group differences. The Bonferroni post hoc tests were conducted to follow-up on age group differences. The statistical significance level was set at p < 0.05 (two-tailed), and all data were analyzed using the SPSS statistical software package (SPSS, version 26); SPSS and Excel (Microsoft Office Professional Plus 2016) were utilized to create figures.

Table 1

Characteristics of 7957 COPD patients by gender.

Variable	n (%) or mean (SD)
	Female (n = 3573, 44.9%)	Male (n = 4384, 55.1%)	p
Age during the last visit (years)	70.1 (11.9)	70.5 (11.3)	0.12
Age group			<0.05
30s	34 (1.0%)	40 (0.9%)
40s	145 (4.1%)	138 (3.1%)
50s	493 (13.8%)	584 (13.3%)
60s	993 (27.8%)	1155 (26.3%)
70s	1048 (29.3%)	1430 (32.6%)
80s+	860 (24.1%)	1037 (23.7%)
GP (%)/pulmonologist (%)	1021 (28.5%)/2558 (71.5%)	1172 (26.7%)/3215 (73.3%)	0.07
Age of 1st COPD documentation	61.2 (12.7)	61.2 (11.8)	0.99
Duration in practice since 1st COPD documentation (years)	8.9 (6.4)	9.3 (6.5)	<0.01
Observation years in practice	13.9 (6.7)	13.7 (6.6)	0.31

P values are based on an independent t-test or a χ2 test.

Table 2

Frequency of chronic comorbid conditions (CCC) by gender.

	Women		Men		All
Categories	n = 3573	%	n = 4384	%	N = 7957	%
Hypertension	1393	38.99	1758	40.10	3151	39.60
(COPD), emphysema, chronic bronchitis* a	1221	34.17	1594	36.36	2815	35.38
Other respiratory diseases***	823	23.03	1202	27.42	2025	25.45
Sleep disorders***	598	16.74	1322	30.16	1920	24.13
Asthma***	988	27.65	732	16.70	1720	21.62
Ischemic heart disease***	544	15.23	1099	25.07	1643	20.65
Allergy***	678	18.98	501	11.43	1179	14.82
Diabetes***	426	11.92	690	15.74	1116	14.03
Other psychiatric and behavioral diseases***	335	9.38	539	12.29	874	10.98
Esophagus, stomach, and duodenum diseases***	442	12.37	410	9.35	852	10.71
Obesity	392	10.97	451	10.29	843	10.59
Heart failure**	322	9.01	475	10.83	797	10.02
Peripheral neuropathy	379	10.61	410	9.35	789	9.92
Dorsopathies	373	10.44	402	9.17	775	9.74
Other musculoskeletal and joint diseases*	335	9.38	354	8.07	689	8.66
Ear, nose, throat diseases***	319	8.93	287	6.55	606	7.62
Other metabolic diseases	259	7.25	313	7.14	572	7.19
Dyslipidemia	248	6.94	322	7.34	570	7.16
Osteoarthritis and other degenerative joint diseases	258	7.22	274	6.25	532	6.69
Inflammatory arthropathies	226	6.33	293	6.68	519	6.52
Neurotic, stress-related and somatoform diseases***	274	7.67	243	5.54	517	6.50
Depression and mood diseases***	282	7.89	197	4.49	479	6.02
Thyroid diseases***	283	7.92	193	4.40	476	5.98
Chronic infectious diseases	195	5.46	273	6.23	468	5.88
Blood and blood forming organ diseases	206	5.77	217	4.95	423	5.32
Anemia	194	5.43	212	4.84	406	5.10
Cerebrovascular disease	176	4.93	229	5.22	405	5.09
Venous and lymphatic diseases***	222	6.21	174	3.97	396	4.98
Other cardiovascular diseases*	150	4.20	237	5.41	387	4.86
Colitis and related diseases	172	4.81	211	4.81	383	4.81
Peripheral vascular disease**	126	3.53	225	5.13	351	4.41
Atrial fibrillation**	125	3.50	208	4.74	333	4.18
Osteoporosis***	195	5.46	89	2.03	284	3.57
Cataract and other lens diseases	103	2.88	119	2.71	222	2.79
Chronic pancreas, biliary tract and gallbladder diseases**	122	3.41	100	2.28	222	2.79
Deafness, hearing impairment	92	2.57	106	2.42	198	2.49
Other genitourinary diseases**	111	3.11	87	1.98	198	2.49
Other neurological diseases	85	2.38	100	2.28	185	2.32
Chronic kidney diseases	74	2.07	94	2.14	168	2.11
Chronic ulcer of the skin	67	1.88	90	2.05	157	1.97
Cardiac valve diseases	76	2.13	74	1.69	150	1.89
Autoimmune diseases	73	2.04	75	1.71	148	1.86
Dementia	54	1.51	71	1.62	125	1.57
Migraine and facial pain syndromes***	77	2.16	37	0.84	114	1.43
Bradycardias and conduction diseases*	37	1.04	74	1.69	111	1.39
Prostate diseases***	1	0.03	89	2.03	90	1.13
Glaucoma	36	1.01	44	1.00	80	1.01
Parkinson and parkinsonism	28	0.78	45	1.03	73	0.92
Chronic liver diseases	26	0.73	40	0.91	66	0.83
Other eye diseases	34	0.95	32	0.73	66	0.83
Epilepsy	22	0.62	36	0.82	58	0.73
Other digestive diseases	27	0.76	31	0.71	58	0.73
Hermatological neoplasms	19	0.53	38	0.87	57	0.72
Inflammatory bowel diseases	22	0.62	24	0.55	46	0.58
Other skin diseases	26	0.73	20	0.46	46	0.58
Solid neoplasms	14	0.39	12	0.27	26	0.33
Multiple sclerosis	15	0.42	10	0.23	25	0.31
Blindness, visual impairment	6	0.17	9	0.21	15	0.19
Schizophrenia and delusional diseases	5	0.14	5	0.11	10	0.13
Chromosomal abnormalities	0	0	0	0	0	0

Categories are listed in a descending order based on the frequency of each comorbidity in all patients.

*Gender difference significant at p < 0.05, **<0.01, ***<0.001 according to χ2 tests.

a(COPD), emphysema, chronic bronchitis category excludes COPD (J44) diagnoses.

Table 3

Twenty most frequent comorbidities among GP patients and 10 most frequent comorbidities among pulmonology patients using chronic comorbid conditions (CCC) over the three index periods (5 years before, ±5 years during the index date, and 5 years after).

GP patients comorbidity scores, mean (SD)
Index age group	Age < 45: n = 32				45 ≤ Age < 65: n = 218						Age ≥ 65: n = 182
Chronic comorbid conditions	15.13 (8.19)				14.29 (9.09)						16.12 (9.01)
Elixhauser	5.56 (3.42)				5.96 (4.23)						6.22 (3.84)
Elixhauser-vW Index	12.81 (10.47)				14.69 (14.13)						15.92 (12.72)

**Three index age group difference significant at p < 0.01 according to ANOVA.

ad.= diseases.

b(COPD), emphysema, chronic bronchitis—frequency is based on the data excluding J44 diagnosis.