Pharmacological smoking cessation of adults aged 30-50 years with COPD.

The prevalence of active smokers has remained relatively stable around 20% for several years in Denmark despite knowledge of the harmful effects. Smoking cessation is the most effective way to limit progression and reduce mortality of chronic obstructive pulmonary disease (COPD). Therefore, smoking cessation is particularly important among adults with COPD. The aim of this study was to determine the extent to which adults 30-50 years of age with COPD redeem pharmacotherapy for smoking cessation, and to identify demographic factors that influence the use of smoking cessation medication. We conducted a national retrospective non-interventional registry study, including all Danish patients with COPD (ICD-10 code J.44: chronic obstructive pulmonary disease) aged 30-50 years in the period 2009-2015. We identified 7734 cases, who were matched with controls (15,307) 1:2 on age, sex, and geography. Smoking status was not registered. We found that 18% of cases (with an estimated smoking prevalence at 33-50%) redeemed pharmacological smoking cessation medication in the study period compared to 3% of the controls (with an estimated smoking prevalence at 23%). The OR for cases collecting pharmacological smoking cessation medication was 5.92 [95% CI 5.24-6.70]. Male sex, being unemployed, and receiving social benefits were factors associated with less probability of redeeming pharmacological smoking cessation medication. Our study indicates that attention is needed on smoking cessation in adults aged 30-50 years with COPD, especially if unemployed or receiving social benefits, as these individuals are less likely to redeem pharmacological smoking cessation medication.

Introduction

Tobacco smoking is the leading cause of preventable death in the western world[1]. The overall mortality for people who smoke is three times higher than for people who have never smoked[2]. According to the Danish Health Authorities, tobacco smoking is the most influential factor for inequalities in health and mortality in Denmark[3]. Smoking is known to cause multiple diseases, e.g., lung cancer, cardiovascular disease, and chronic obstructive pulmonary disease (COPD)[4,5]. Without smoking cessation, the lifetime risk of developing COPD is one out of two[6].

Due to extensive cigarette use, the prevalence and mortality of COPD in Denmark are among the highest in Europe[7]. Danish women have a 3.7 times higher risk of dying from COPD than the general European population[7]. Therefore, there is a great need to improve treatment and reduce the mortality of Danish patients with COPD.

COPD can be treated through pharmacological and non-pharmacological interventions[8,9]. The most effective way to inhibit disease progression is smoking cessation[10-12]. Smoking cessation in patients with COPD is associated with decreased dyspnea, fewer exacerbations and hospitalizations, better lung function, increased quality of life, and increased survival[13,14]. Despite the positive effects of smoking cessation, ~33% of Danish patients with moderate or severe COPD are smoking[15,16]. Smoking cessation is essential in young adults since their lungs are more vulnerable to the harmful effects of smoking[17]. Hospitalization and mortality rates are increased in patients diagnosed with COPD at an early age (before 50 years of age) compared to patients who are diagnosed with COPD after 50 years of age[18]. Even though smoking cessation is the most effective way to inhibit disease progression, a recent study found that up to 50% of Danish patients with COPD under 50 years of age are active smokers[18]. One reason for the extensive tobacco use among young patients could be that they are more nicotine dependent and thus face more difficulties with smoking cessation than older patients with COPD[16].

Three main strategies exist for smoking cessation: quitting without external aid, quitting by the help of professional counseling (e.g., motivational therapy), or quitting by means of smoking cessation medication[19]. In recent years smoking cessation by means of electronic cigarettes has been promoted, but the products have not been approved as pharmacological treatment, and the effect on smoking cessation rates is not well established[20]. Pharmacological treatment has proved to be more efficient than the other strategies, although successful smoking cessation is best achieved through a combination of counseling and pharmacological treatment[19,21]. Three main types of smoking cessation medication are available: nicotine replacement therapy (NRT), bupropion, and varenicline. Quitting rates varies between studies, but are ~20–30% for varenicline, 15–40% for NRT, and 10–20% for bupropion[22-26].

COPD is a disease with a heavy socioeconomic gradient and socioeconomic status is considered an independent risk factor for the development of COPD[27]. The cost of the recommended 12-week treatment varies but is approximately EUR 120 for bupropion (Zyban®, GlaxoSmithKline Pharma) and EUR 360 for varenicline (Champix®, Pfizer). The price of NRT varies, depending on the dosage and duration of the treatment. In Denmark, as in several other European countries, smoking cessation medication is not covered by the national reimbursement system, and other means of financial support is limited[28]. In some municipalities in Denmark (including our study period 2009–2015), smoking cessation medication has experimentally been offered, for various time periods, free of charge to specific groups, e.g., heavy smokers, economically challenged individuals, and pregnant women, if they participated in smoking cessation programs offered by the Danish municipalities[29]. These programs have been a success but smoking cessation medication is still not part of the national reimbursement system[30].

It is of great importance to increase focus on smoking cessation among young adults. A study from 2019 by Tibuakuu et al. showed that tobacco-dependent adults (18–39 years of age) in the United States received less smoking cessation advice from physicians than the rest of the population[31]. Although pharmacological smoking cessation has been proven effective there is still limited knowledge on the degree to which smoking cessation medication is offered to patients with COPD, particularly in young patients[32,33].

The aim of this study was to determine the extent to which adults aged 30–50 years with COPD redeem pharmacotherapy for smoking cessation, and to explore how the use of smoking cessation medication is correlated to different demographic factors.

Methods

Study design

The study was designed as a national, retrospective, non-interventional, registry study.

Data collection

The Danish Civil Registration System (CPR) is a national register that contains information on all Danish citizens. All residents in Denmark receive a unique 10-digit (CPR) number which is recorded in the Danish Civil Registration System. The CPR number enabled us to link data at an individual level across different registries[34].

We included all Danish patients 30–50 years of age who were diagnosed with COPD in the period 2009–2015. Data were collected from the Danish National Patient Registry, which is a complete nationwide registry covering all non-psychiatric contacts to the secondary healthcare sector in Denmark[34]. We used code J44.x of the International Classification of Diseases 10th revision (ICD-10) to identify patients with COPD. Cases and controls were included regardless of smoking status, since this information was not available from any national registry. We excluded patients who died in 2009 to allow for at least one year of eligibility to collect pharmacological smoking cessation medication.

Each case was matched with two controls without a COPD diagnosis in the period 1998–2015. We matched cases and controls on age, sex, and geography. We used descriptive statistics from the index year (2009).

We extracted data on age, sex, and geography from the Danish Civil Registration System[35]. Information about socioeconomic status, educational level, and marital status was obtained from Statistics Denmark. All redeemed prescriptions are registered in the Danish National Prescription Registry and can be linked to the individual CPR number[36]. We included all redeemed prescriptions with codes N07BA01 (NRT), N06AX12 (bupropion), and N07BA03 (varenicline) of the Anatomical Therapeutic Chemical (ATC) Classification System[37]. NRT can be bought as over-the-counter medicine in Denmark. All medication sold as over-the counter medicine is not recorded in the national registries and therefore not included in the study. This applies only for NRT and not for varenicline or bupropion.

Figure 1 shows the inclusion process. A total of 142,273 cases with a COPD diagnosis in 2009–2015 were identified. A total of 721 were excluded due to missing demographic information, and 2698 cases were excluded because we were unable to identify at least one control. An additional 5756 cases were excluded because they died in the index year, and 123,063 cases were excluded due to age above 50 years. The remaining 7734 cases were individually matched with two controls. In total, we included 15,307 controls because we were able to identify only one control in 161 cases.

Fig. 1

Inclusion process.

Statistics

We used a conditional logistic regression model, with case = 1, control = 0, to compare socioeconomic factors for cases and controls. In the model we corrected for socioeconomic factors by using a variable (SOCIO13) from Statistic Denmark for the labor market affiliation status. The variable is based on information about the most important source of income or employment for the person in the year[38]. We used SAS 9.4 TS1M5 (SAS, Inc., Cary, NC, USA) to perform the statistical analyses.

A smoking cessation attempt was defined as the redemption of a prescription for smoking cessation medication. If the period between the redemption of two prescriptions on smoking cessation medication exceeded six month plus the number of treatment days of the previous prescription (measured as defined daily dosage (DDD)) it was categorized as a new smoking cessation attempt.

Outcome

The outcome was the number of redeemed prescriptions for smoking cessation medicine with ATC code N07BA01 (NRT), N06AX12 (bupropion), or N07BA03 (varenicline).

Ethics

The study was approved by the Danish Data Protection Agency. The design was a register-based study, which was based on anonymized data with no identifiable personal information. Therefore, approval was not required by the Danish health research ethics committee system and consent from patients not necessary according to Danish Law. The study complied with the ethical principles outlined by the World Medical Association in the Declaration of Helsinki.

Table 1

Basic characteristics.

Number of people	Case		Control
	7734		15,307
Age	Mean	Std.	Mean	Std.
	44	5	44	5
	N	%-share	N	%-share
Gender
Male	3777	48.8	7460	48.7
Female	3957	51.2	7847	51.3
Civil status
Married/co-living	3711	48.0	10,823	70.7
Single	4023	52.0	4484	29.3
Socioeconomy
Disability pension	2350	30.4	1011	6.6
Educational support	175	2.3	449	2.9
Employed	3315	42.9	12,570	82.1
Sickpay/leave	321	4.2	244	1.6
Social security	1374	17.8	675	4.4
Unemployment benefit	199	2.6	358	2.3
Education
Primary	3610	46.7	3064	20.0
Secondary	278	3.6	926	6.0
Vocational	2642	34.2	6113	39.9
Short college	191	2.5	862	5.6
Bachelor	548	7.1	2681	17.5
Master/PhD	161	2.1	1398	9.1
Unknown	304	3.9	263	1,7

Table 2

Number (n) of cases and controls who redeemed at least one prescription for smoking cessation medication.

	All types			Nicotine Replacement Therapy (NRT)			Varenicline			Bupropion
	Case	Control		Case	Control		Case	Control		Case	Control
	n (n/N, %)	n (n/N, %)	P-value	n (n/N, %)	n (n/N, %)	P-value	n (n/N, %)	n (n/N, %)	P-value	n (n/N, %)	n (n/N, %)	P-value
Number of persons	1441 (18.3)	504 (3.3)		454 (5.9)	61 (0.4)		906 (11.7)	371 (2.4)		287 (3.7)	102 (0.7)
Age
30–39 years	215 (14.3)	78 (2.6)	<0.001	68 (4.5)	10 (0.3)	<0.001	125 (8.3)	59 (2.0)	<0.001	48 (3.2)	14 (0.5)	<0.001
40–50 years	1226 (19.7)	426 (3.4)	<0.001	386 (6.2)	51 (0.4)	<0.001	781 (12.5)	312 (2.5)	<0.001	239 (3.8)	88 (0.7)	<0.001
Sex
Male	613 (16.2)	245 (3.3)	<0.001	206 (5.5)	32 (0.4)	<0.001	374 (9.9)	173 (2.3)	<0.001	116 (3.1)	52 (0.7)	<0.001
Female	828 (20.9)	259 (3.3)	<0.001	248 6.3)	29 (0.4)	<0.001	532 (13.4)	198 (2.5)	<0.001	171 (4.3)	50 (0.6)	<0.001
Civil status
Married/co-living	667 (18.0)	338 (3.1)	<0.001	133 (3.6)	27 (0.2)	<0.001	483 (13.0)	253 (2.3)	<0.001	129 (3.5)	75 (0.7)	<0.001
Single	774 (19.2)	166 (3.7)	<0.001	321 (8.0)	34 (0.8)	<0.001	423 (10.5)	118 (2.6)	<0.001	158 (3.9)	27 (0.6)	<0.001
Socioeconomy
Disability pension	547 (23.3)	57 (5.6)	<0.001	305 (13.0)	22 (2.2)	<0.001	254 (10.8)	33 (3.3)	<0.001	86 (3.7)	9 (0.9)	<0.001
Educational support	28 (16.0)	7 (1.6)	<0.001	4 (2.3)	3 (0.7)	0.085	22 (12.6)	4 (0.9)	<0.001	5 (2.9)	0 (0.0)	<0.001
Employed	588 (17.7)	399 (3.2)	<0.001	62 (1.9)	31 (0.2)	<0.001	459 (13.8)	306 (2.4)	<0.001	140 (4.2)	84 (0.7)	<0.001
Sickpay/leave	62 (19,3)	8 (3.3)	<0.001	20 (6.2)	0 (0)	<0.001	39 (12.1)	6 (2.5)	<0.001	11 (3.4)	–	–
Social security	193 (14.0)	21 (3.1)	<0.001	56 (4.1)	3 (0.4)	<0.001	114 (8.3)	14 (2.1)	<0.001	42 (3.1)	5 (0.7)	0.001
Unemployment benefit	23 (11.6)	12 (3.4)	<0.001	7 (3.5)	0 (0)	0.002	18 (9.0)	8 (2.2)	<0.001	3 (1.5)	3 (0.8)	0.463
Education
Primary	729 (20.2)	146 (4.8)	<0.001	286 (7.9)	24 (0.8)	<0.001	419 (11.6)	106 (3.5)	<0.001	137 (3.8)	26 (0.8)	<0.001
Secondary	37 (13.3)	22 (2.4)	<0.001	14 (5.0)	4 (0.4)	0.112	21 (7.6)	12 (1.3)	<0.001	6 (2.2)	6 (0.6)	<0.001
Vocational	493 (18.7)	226 (3.7)	<0.001	103 (3.9)	19 (0.3)	<0.001	351 (13.3)	171 (2.8)	<0.001	106 (4.0)	49 (0.8)	<0.001
Short college	31 (16.2)	25 (2.9)	<0.001	8 (4.2)	3 (0.3)	<0.001	23 (12.0)	22 (2.6)	<0.001	7 (3.7)	0 (0.0)	<0.001
Bachelor	87 (15.9)	59 (2.2)	<0.001	14 (2.6)	3 (0.1)	<0.001	62 (11.3)	46 (1.7)	<0.001	19 (3.5)	14 (0.5)	0.026
Master/PhD	13 (8.1)	15 (1.1)	<0.001	0 (0.0)	5 (0.4)	<0.001	8 (5.0)	10 (0.7)	0.001	5 (3.1)	0 (0.0)	0.501
Unknown	51 (16.8)	11 (4.2)	<0.001	27 (8.9)	3 (1.1)	<0.001	22 (7.2)	4 (1.5)	<0.001	7 (2.3)	4 (1.5)	<0.001

Table 3

Logistic regression for cases redeeming af prescription on smoking cessation medication.

	All types		NRT		Varenicline		Bupropion
	Odds ratio	P-value	Odds ratio	P-value	Odds ratio	P-value	Odds ratio	P-value
Age	1.02 (1.01–1.04)	<0.001	1.00 (0.98–1.02)	0.715	1.04 (1.02–1.05)	<0.001	1.01 (0.99–1.04)	0.391
Sex
Male	0.73 (0.65–0.82)	<0.001	0.85 (0.69–1.03)	0.096	0.71 (0.61–0.82)	<0.001	0.69 (0.54–0.88)	0.003
Female	–	–	–	–	–	–	–	–
Civil status
Married/co-habiting	0.90 (0.79–1.02)	0.088	0.62 (0.50–0.77)	<0.001	1.07 (0.92–1.24)	0.388	0.77 (0.60–0.99)	0.038
Single	–	–	–	–	–	–	–	–
Socioeconomy
Disability pension	1.27 (1.11–1.46)	0.001	6.51 (4.88–8.69)	<0.001	0.70 (0.59–0.83)	<0.001	0.76 (0.57–1.01)	0.059
Educational support	0.91 (0.60–1.38)	0.650	1.22 (0.44–3.41)	0.702	0.94 (0.59–1.50)	0.806	0.65 (0.26–1.62)	0.357
Employed	–	–	–	–	–	–	–	–
Sickpay/leave	1.10 (0.82–1.48)	0.526	3.23 (1.92–5.45)	0.120	0.87 (0.61–1.24)	0.445	0.79 (0.42–1.47)	0.453
Social security	0.75 (0.63–0.90)	0.002	1.97 (1.35–2.86)	<0.001	0.59 (0.48–0.74)	<0.001	0.67 (0.47–0.96)	0.027
Unemployment benefit	0.65 (0.41–1.01)	0.054	1.88 (0.85–4.17)	0.120	0.68 (0.41–1.12)	0.128	0.37 (0.12–1.16)	0.088

Table 4

Logistic regression showing attempts to quit smoking.

Attempts to quit	Case (n)	Control (n)	Odds ratio	P-value
0	6293	14,803	–	–
1	1008	377	5.59 (4.86–6.44)	<0.001
2	282	93	6.43 (4.90–8.43)	<0.001
3	104	20	10.00 (2.87–11.06)	<0.001
4	47	14	5.63 (2.87–11.06)	<0.001