Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease that affects primarily the sacroiliac joints, spine, peripheral joints, and entheses, and can progressively restrict spinal mobility.1 Loss of functional capacity due to the disease may lead to reduced quality of life.2
Previous studies in AS patients have found smoking to be associated with increased disease activity, poorer quality of life, and increased functional disability.3,4 One study demonstrated that smoking causes progression of structural damage in axial spondyloarthritis,5 another study established its association with not only progression but also pathogenesis. Smoking intensity can also be a major risk factor for AS.6
Ankylosing spondylitis limits the expansion of the chest by affecting costosternal and costovertebral joints, thereby leading to restrictive respiratory distress.7 Pleuropulmonary tissue was also found to be a possible primary target of AS, and fibrosis could develop because of inflammatory processes in the lung parenchyma in AS patients.8 Regardless of etiology, smoking has a negative effect on patients with restrictive respiratory distress.9
Although the influence of cigarette smoking on disease outcome is still unknown, an interaction between smoking and inflammation has been confirmed.10 In smokers, an increased proinflammatory cytokine production and a decreased anti-inflammatory cytokine level has been observed. This inhibitory effect is thought to be due to the direct toxic effect of nicotine. Smoking can also lead to an increase in pain level with the indirect toxic effects of nonspecific tissue damage due to vasoconstriction or hypoxia.11 Although these findings offer evidence on the importance of smoking cessation in improving long-term outcomes for AS patients, to our knowledge, there is a lack of study that focuses specifically on this subject. Therefore, we aimed to investigate how smoking cessation by AS patients affects disease activity and their psychological state, physical mobility, lung function, and quality of life.
MATERIALS AND METHODS
This was a longitudinal, single-blind, controlled, and observational study. An approval by a local ethics committee was obtained.
The participants were 118 patients, aged 18 to 65 years, who were diagnosed with AS in the physical medicine and rehabilitation clinic of the Health Sciences University Bursa Education Research Hospital, according to the 1984 Modified New York criteria. Of the 118 patients, 19 patients with infection, anemia (except for chronic disease anemia), metabolic and endocrine disorders (eg, diabetes and goiter), liver and renal insufficiency, and a cardiac, respiratory, neurological, or psychiatric disease were excluded. Two patients who quit smoking recently were also excluded, but those who had quit at least a year ago, at the beginning of the study, were included in the nonsmoker group. As a result, only 97 patients were divided into 2 groups of smokers (group 1 = 59) and nonsmokers (group 2 = 38). Of the 97 patients, 5 in group 1 were not assessed because they either did not attend the smoking cessation meetings or stopped smoking and then started again. At the end of the 6th month, the smokers were separated into subgroups of those who quit smoking (group 1a = 17) and those who did not (group 1b = 37) (Fig. 1).
All the patients were informed about the study, and a written informed consent was obtained. The first approach in the smoking cessation program was conducted with all the smokers (5A and 5R principles).12 The patients who agreed to quit smoking were treated with monotherapy (varenicline tartrate, nicotine replacement therapy, or bupropion hydrochloride) and cognitive behavioral therapy. Those who disagreed to participate in the smoking cessation program were invited to the meeting once a month, and the first approach in the program was repeated. Those who agreed to quit smoking were taken to the smoking cessation program. Those who refused to quit smoking were included in group 1b at the end of 6 months. The drug treatment in the monotherapy was selected by the physician who undertook the smoking cessation program, taking into consideration factors, such as the patient's psychological state, occupation, and treatment compliance. The drug treatment lasted for 3 months, and the cognitive behavioral therapy, for 6 months. A follow-up assessment after 6 months of smoking cessation was carried out; in this follow-up, the patients were asked to continue the treatment they had used for AS.
Necessary measurements and controls for AS were performed by an expert in physical medicine who did not know whether the patient was smoking. The pulmonary function test was evaluated by a chest physician who did not know whether the patient was smoking. Another physician, who specialized in chest diseases and was certified by the Ministry of Health, conducted a smoking cessation program and did not know the treatment the patient took for AS.
Pulmonary Function Test
Pulmonary function tests were performed spirometrically on all patients using the SpiroThor Wavefront; values for forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) of the forced breath were recorded.13
Fagerström Test for Nicotine Dependence
The Fagerström test for nicotine dependence was used to measure nicotine dependence using a 6-item questionnaire, scored 1 to 10.14
Cumulative Smoking Load
Pack-years measured cigarette smoking intensity, by multiplying the number of packs of cigarettes smoked per day by that of years the person had smoked.15
Carbon monoxide is measured in the expiratory air and reported to be significantly correlated with plasma nicotine level. Exhaled CO levels indicated that they had been smoking in the last 48 hours.16 Exhaled CO is recorded in parts per million (ppm). In this study, the ExhCO test was performed using the Bedfont piCO Smokerlyzer (piCO+ Smokerlyzer and Bedfont Micro + Breathalyzer, Kent, United Kingdom, 2016), with a cutoff level of 6 ppm CO.17
Bath Ankylosing Spondylitis Disease Activity Index
The index was obtained by averaging the qualitative and quantitative values of 10-cm visual analog scale, scored 0 to 10, that evaluated 5 items, namely, fatigue, spinal pain, peripheral joint pain, localized sensitivity, and morning stiffness. The validity and reliability of the Turkish version was established.18,19
Bath Ankylosing Spondylitis Functional Index
The index was obtained by averaging the 10-cm horizontal visual analog scale, scored 0 to 10, that evaluated 10 questions items, which determined the degree of functional restriction in AS patients.20
Bath Ankylosing Spondylitis Metrology Index
Cervical rotation, tragus-wall distance, lateral flexion, modified Schober test, and intermalleolar distance are the 5 best clinical measurements that best reflect the axial state. The sum of transformed points of each measurement, scored between 5 and 15, was calculated, with a lower score indicating a better level. This index described AS as a disease state, and was rapid at 7 minutes. It was reproducible and susceptible to change in the disease spectrum.21
The difference was measured by calculating the chest diameter during maximum inspiration and maximum expiration.22
The Short-Form 36 (SF-36), which comprised 36 items that assessed the condition of the illness and loss of power, was conducted. Specifically, 8 subparameters, namely, physical function, physical role strength, emotional role strength, power/live/vitality, emotional health, social functioning, pain, and general health perception, were calculated, with high scores indicating a better health level.23
Ankylosing Spondylitis Quality of Life
It consists of 18 questions answered with a yes or a no. The total number of yes answers gives the result score, with high scores indicating poor quality of life.24 The validity and reliability of the Turkish version was performed.
Psychological State Assessment
This was carried out using the Beck Depression Inventory (BDI) and Beck Anxiety Index (BAI).25,26
C-reactive protein (CRP) is an acute phase reactant produced in the liver and then secreted into the bloodstream within a few hours of infection or inflammation.27 To evaluate this, the nephelometric method was employed using Siemens BN II device, 2015 Germany.
Erythrocyte Sedimentation Rate
Erythrocyte sedimentation rate was performed to determine inflammation and monitor its activity. It measured the meniscus of the falling red blood cells in millimeter per hour. The Westergren method was used using ALSA device 100, 2016 Turkey.28
The evaluation parameters were initially applied to all patients by only 1 researcher who was blinded to the groups. Demographic and baseline data were compared between smokers (group 1) and nonsmokers (group 2). At the end of 6 months, the evaluation parameters were reapplied to patients in group 1. Group 1a and group 1b patients were compared in terms of their baseline data and data after 6 months of smoking cessation. In addition, group 1a’s baseline data and data after 6 months of smoking cessation were compared statistically.
The Statistical Package for Social Sciences (SPSS) software (IBM Corp, Released 2015, IBM SPSS Statistics for Windows, Version 23.0; IBM Corp, Armonk, NY) was used. Numerical values were expressed by the median (med) and minimum-maximum values (min-max); and their distribution was tested using the Kolmogorov-Smirnov test. Categorical values were evaluated in percentages. The independent t test was used to compare the mean values of smokers (group 1) and nonsmokers (group 2), and those who quit smoking and those who did not in group 1. The Mann-Whitney U test was used to compare the median values. The baseline data and data after 6 months of no smoking of patients who quit smoking and who did not were compared using the Wilcoxon test. The Pearson χ2 and Fisher tests were used to compare the ratios; p < 0.05 was considered statistically significant.
This study was conducted with 92 AS patients, with group 1 comprising 54 smokers and group 2, 38 nonsmokers. This study excluded 5 patients in group 1 (initially composed of 59 smokers) who either did not attend any smoking cessation meeting or stopped smoking and then started again. There were 68 male (74%) and 24 female (26%), with a mean age of 38.7 ± 9.3 years. Table 1 presents the patients' clinical and demographic characteristics. Extra-articular manifestations were absent in the patients. Three patients had hip joint involvement, and were smoking. The patients were treated with nonsteroid anti-inflammatory drug (NSAID; 38 [41.3%]), disease modifying antirheumatic drugs (DMARD; 37 [40.2%]), and tumor necrosis factor inhibitor drug (anti-TNFα; 17 [18.5%]).
In group 1, the mean age was 37.7 ± 8.4 years; the median body mass index (BMI) was 24.2 (18.5–40.4) kg/m2; and 83% of the patients (n = 45) were male and 17% (n = 9) were female. The median number of cigarettes smoked daily was 20 (2–60). The cumulative smoking load was 11.5 (1–60) packets. Fagerström Test for Nicotine Dependence (FTND) was 6 (1–10). The ExhCO test was 13.5 (2–27) ppm. As smoking cessation treatment, bupropion hydrochloride was given to 23 patients (42.6%); nicotine replacement therapy to 18 patients (33.3%); and varenicline tartrate to 13 patients (24.1%). In group 2, the mean age was 40.1 ± 10.4 years; the median BMI was 24.9 (17.3–32.9) kg/m2; and 60% of the patients (n = 23) were male and 40% (n = 15) were female. There was no statistically significant difference between the 2 groups in terms of BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), ankylosing spondylitis quality of life (ASQoL), subparameters of SF-36, FEV1, FVC, BDI, and BAI, as well as NSAID, DMARD, and anti-TNFα ratios (Table 2).
At the end of 6 months, of the 54 smokers, 17 quit smoking (group 1a, 32%) and 37 continued smoking (group 1b, 68%). There was no statistically significant difference between the 2 groups in terms of their demographic and baseline parameters (p > 0.05). The FTND values of group 1a were statistically lower than group 1b (p < 0.05), indicating that the nicotine dependence of the former was reduce than the latter. There was no statistically significant difference between groups 1a and 1b at the end of 6 months in terms of BASFI, BASMI, chest expansion, ASQoL, SF-36, FEV1, FVC, BDI, BAI, bupropion hydrochloride, nicotine replacement therapy, varenicline tartrate, NSAID, DMARD, and anti-TNF (p > 0.05). Bath Ankylosing Spondylitis Disease Activity Index was significantly lower in group 1a than group 1b (p < 0.05) (Table 3),
When the baseline and after-6-months data of group 1a were compared, a significant improvement was found in BASDAI, BASFI, chest expansion, ASQoL, and subparameters physical function, physical role strength, power/live/vitality, social functioning, pain, and general health perception of SF-36, as well as FEV1 and FVC at the end of 6 months (p < 0.05). There was no statistically significant difference in terms of BASMI, BDI, and BAI in this group (p > 0.05) (Table 4).
In group 1b, there was no statistically significant difference in disease activity, physical mobility, and quality of life parameters, except for the subparameter general health perception of SF-36, when the baseline and after-6-months data were compared. There was a statistically significant improvement in BDI and BAI at the end of 6 months (Table 5).
The most important findings of our study were that in the group of patients who quit smoking, significant improvements were found in BASDAI, BASFI, chest expansion, ASQoL, and subparameters physical function, physical role strength, power/live/vitality, social functioning, pain, and general health perception of SF-36 at the end of 6 months. Based on the literature review, we did not find any other study that evaluates disease activity, physical mobility, and quality of life after smoking cessation, by applying a smoking cessation program to AS patients who are smokers. Rodrigues et al29 reported a decrease in TNFα levels in blood serum of healthy subjects when not smoking for 30 days, and thus concluded that short-term smoking cessation reduced systemic inflammation. The results of our study were consistent with and supportive of these conclusions. Improvement in parameters of BASDAI, BASFI, chest expansion, and quality of life after smoking cessation can be considered as an expected result of decreased systemic inflammation.
Smoking affects humoral and cellular immune response. In smokers, numerous proinflammatory cytokines productions, such as TNFα, IL-1, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been shown to increase and reduce the level of anti-inflammatory cytokines, such as IL-10. This inhibitory effect of proinflammatory cytokines production is thought to be due to the direct toxic effect of nicotine. Chronic smoking also increases the level of acute phase proteins. Smoking may also cause an increase in pain level via the indirect toxic effect of vasoconstriction or hypoxia-induced nonspecific tissue damage.11 At the same time, smoking can reduce quality of life by increasing comorbidities.11,30,31 In certain studies, smoking was found to be associated with increased disease activity, worse functional status and physical mobility, and worse quality of life.3,32,33 However, other studies have also shown that there is no difference in disease activity, physical mobility, and quality of life between smoker and nonsmoker AS patients.4,34,35 We also found no significant difference between smoker and nonsmoker AS patients, but we observed a significant improvement in BASDAI 6 months after the patient quit smoking.
Willemse et al36 found that quitting smoking, with or without chronic obstructive pulmonary disease, prevented the decline in lung functions and improved respiratory symptoms in all smokers. In our study, comparing the baseline data and data after 6 months of no smoking in AS patients who quit smoking, we found a significant increase in FEV1 and FVC levels; this increase could be due to both the direct effect of smoking cessation on lung functions and an increase in chest expansion through anti-inflammatory effect.
Previous studies have indicated that those who were more addicted and mildly addicted are more successful at quitting smoking.37,38 In our study, patients who quit smoking were less addicted than those who did not quit smoking, which was consistent with the findings of Hymowitz et al.39
It has been reported that the prevalence of depression increases after smoking cessation.40 Another study reported that smoking was associated with depression and anxiety, which was shown to improve within a year after smoking cessation.41 In terms of the patients’ BDI and BAI scores in this study, we found no difference between smoking and nonsmoking AS patients, as well as in the depression and anxiety scores between baseline and 6 months after smoking cessation of patients who quit smoking. Meaning, quitting smoking does not create any additional depression and anxiety risk in our patients.
The most important limitation of our study is the relatively small sample size. We followed-up with the patients who quit smoking after 6 months. It is necessary to evaluate smoking cessation with longer-term follow-ups and observe the long-term outcomes in patients with AS. Our study did not use a double-blind experiment. Patients who quit smoking and continued smoking were not randomized. We recommended that smokers with AS quit smoking and then treated them based on their decisions.
In conclusion, we observed significant improvements in disease activity, physical mobility, and quality of life, as well as improvement in lung functions in AS patients who quit smoking. Based on the results of this study, smoking cessation in AS patients helps to improve treatment outcomes.
Smoking cessation in patients with AS helps to improve treatment outcomes.
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