Asthma control level in Finland among asthmatics with smoking history: a cross-sectional study

Surprisingly little is known about asthma control level of smoking asthmatics. The aim of this study was to investigate asthma control level, according to GINA guidelines, among asthmatics with smoking history. One hundred and ninety asthmatics from primary care were investigated. The patients were current or ex-smokers with history of 10 or more pack-years. They completed a questionnaire, with questions set according to the GINA guidelines, so that their asthma control level (well controlled, partly controlled, uncontrolled) according to GINA could be determined. According to GINA guidelines, 66 (34.7%) patients had their asthma well controlled, 81 (42.6%) had their asthma partly controlled, and 43 (22.6%) were uncontrolled. Current smokers had more often uncontrolled asthma than ex-smokers OR 2.54 (95%CI 1.25-5.14, p=0.01). Patients with asthma exacerbation during the previous year had uncontrolled asthma more often than the patients without exacerbation OR 2.17 (95%CI 1.06-4.47, p=0.04), and patients with FEV1 < 80% of predicted had their asthma more often uncontrolled than patients with FEV1 > 80% of predicted OR 2.04 (95%CI 1.02-4.08, p=0.04).

Primary care asthmatic patients who are either current or ex-smokers, are often not well controlled. The asthma control level was associated with current smoking status. Therefore, every attempt should be made to get smoking asthmatics to quit smoking.

Background
Asthmatic patients smoke roughly as much as population in general. Around 20% of asthmatics are smokers. 1,2,3 Among asthmatic patients smoking is associated with increased morbidity and mortality, higher frequency of asthma exacerbations, accelerated 3 decline of lung function, reduced response to inhaled corticosteroids, and increased asthma severity, when compared to asthmatics who do not smoke. 4,5 It has been shown that especially current, but also previous, smoking is associated with poorer asthma control level, when compared to non-smoking asthmatics. 6,7,8,9 However, surprisingly little is known about asthma control level among smoking asthmatics.
The aim of this study was to investigate asthma control level according to GINA guidelines 10 among primary care asthmatic patients who are either current or ex-smokers and to find the patient characteristics that may associate with asthma control level.

Methods
This was a cross-sectional study. The study was approved by the Ethics Committee of Pirkanmaa Health Care District, and every patient gave written informed consent before any study-related procedures were performed.
We have earlier investigated the prevalence of asthma-COPD overlap syndrome among primary care asthmatic patients who were either current or ex-smokers. 14 In addition to pulmonary function tests (Medikro, Kuopio, Finland) and demographic questionnaires, the patients completed also a questionnaire, with questions set according to the GINA guidelines, so that their asthma control level (well controlled, partly controlled, uncontrolled) according to GINA could be determined. 10 The inclusion criteria were as follows: age 18-70 years, current or ex-smoker with 10 or more pack-years and doctor-diagnosed asthma. The exclusion criteria were as follows: any severe illness, any known pulmonary disease other than asthma, use of inhaled anticholinergic or indacaterol or oral roflumilast.
Patients were considered to have had an exacerbation during the previous year if they had been hospitalized, or had used a course of oral corticosteroids, for their asthma during the 4 previous year.

Statistical analysis
The primary variable was asthma control level according to GINA guidelines (well controlled, partly controlled or uncontrolled). Baseline characteristics of patients with well controlled, partly controlled and uncontrolled asthma were compared using the Kruskal-Wallis test for continuous variables and Chi-squared test for categorical variables.
Jonckheere-Terpstra test for trend was applied if Kruskal-Wallis test yielded a significant association, and Mantel-Haenzel test for trend was applied if Chi-squared test yielded a significant association. Univariate logistic regression analyses were performed to assess the association of asthma control with patient characteristics. Before analysis, the 3 asthma control categories were dichotomized in separate analyses as: well controlled versus partly controlled and uncontrolled; uncontrolled versus well and partly controlled.
In other words, the opposite categories, well controlled asthma and uncontrolled asthma were set as separate dependent variables. Independent variables that were significant or almost significant (p < 0.10) factors in univariate models were introduced into the multivariate models. Multivariate logistic regression analyses were then performed using the forward and backward stepping covariate selection procedures. At each step, the criterion for entry was p < 0.05 and for remove p > 0.05. First-order interactions between the covariates were tested. The results are given as odds ratios (OR) with 95% confidence intervals (95% CI).
P-values less than 0.05 were considered statistically significant. The analyses were
Exacerbation during the previous year associated significantly (p = 0.001) and current smoking nearly significantly (p = 0.08) with well controlled asthma ( Table 2).

Discussion 8
One third of asthmatics with smoking history had their asthma well controlled. The number is relatively low and suggests that good asthma control among current or exsmokers in primary care is not often achieved, even in a country like Finland where asthmatics in general do quite well. 1 In a recent survey of 8000 European asthmatics, with only 22.8% of the patients being current smokers, Price at al. 2 found that only 20.1% of asthmatics had their asthma well controlled according to GINA guidelines. Compared to that, our finding that 34.7% of current or ex-smoking asthmatics had their asthma well controlled was surprisingly high.
Most probably this is due to fact that in our study practically all patients were using inhaled corticosteroids regularly, which was not the case in the study by Price et al. 2 In the study by Braido et al. 9 43,5% of the patients had controlled asthma. In that study 35% of patients were either current or ex-smokers. However, they did not use GINA criteria to define asthma control level, and therefore their result cannot be directly compared with our result.
From the GOAL-study we have learned that it is possible to achieve good asthma control in at least 70% of the cases by stepping up with asthma medication. 11 More than 94% percent of our patients were using inhaled corticosteroids (ICS) regularly, and 64.2% of the patients used ICS in combination with long-acting B2-adrenergic (LABA). Still, only one third of our patients had their asthma well controlled. This is most probably due to fact that our patients had smoked more than 10 pack-years, and 44,1% of our patients were current smokers which is known to reduce response to ICS. 12,13 However, also in the current study using ICS + LABA increased the likelihood of asthma being well controlled among the subgroup of current smokers OR 3.  14 it is probable that more patients would have had their asthma better controlled if they had used also LAMA.
We found that uncontrolled patients were current smokers more often than well/partly controlled patients (61.9% vs 39.0%; p = 0.009). The finding that current smoking is associated with worse asthma control is also found by the others, 6,8 and may reflect the fact that cigarette smoke is known to reduce the response of ICS in asthmatic patients. 12,13 Furthermore, there is good evidence that asthma outcome improves in several ways after smoking cessation, 3,5 which also is in line with our observation that exsmokers had their asthma better controlled than current smokers.

Conclusions
Primary care asthmatic patients who are either current or ex-smokers, are often not well controlled. The asthma control level was associated with current smoking status, so that current smokers' asthma was more often uncontrolled. Therefore, every attempt should be made to get smoking asthmatics to quit smoking.

Ethics
The study was approved by the Ethics Committee of Pirkanmaa Health Care District, and every patient gave written informed consent before any study-related procedures were performed.
All the authors have given a consent of publication Due to local legislation on data protection we are not allowed to provide original data on individual level, but on a reasonable request, aggregated data is available from the authors.

Funding
The study was funded by Boehringer-Ingelheim, Finland

Contributions
TK and TP were responsible for writing the manuscript, and TK is the guarantor. All the authors were involved in planning of the study and writing the manuscript.