Original ArticleThe link between COPD and ankylosing spondylitis: A population based study
Introduction
Ankylosing spondylitis (AS) is a chronic inflammatory arthropathy and belongs to a group of diseases which share common features known as seronegative spondyloarthropathies (SpA) [1]. In general, the AS often presents with sacroiliitis and vertebral joint involvement, yet in some cases, peripheral joints or extra-articular involvement may precede the inflammation of the sacro-iliac joint [2]. Another hallmark manifestation of AS is chronic inflammation of the enthesis, which is defined as the point in which a ligament, tendon, or joint capsule integrates into the bone [2]. The onset of AS usually occurs during the 2nd to 3rd decade of life [3]. Men are twice to three times more likely to be affected than women [4]. In the general population, the prevalence of AS has been reported to be 0.9%, varying slightly according to geography [5].
The exact mechanism of the pathogenesis of AS is as yet unclear, however it is widely accepted that AS develops due to a complex interplay between genetic and environmental factors [6]. The close relationship of the HLA-B27 haplotype with the development of AS clearly supports the theory of genetic predisposition [7], while the contribution of environmental factors, including infections, to disease etiopathogenesis has been demonstrated as well [8,9]. The clinical diagnosis of AS is challenging and requires a high index of suspicion. The initial symptom is often a slow onset of insidious lower back pain, characterized by morning stiffness which improves with activity and worsens during rest [10]. Extra-articular involvement of the lungs has been documented in AS, the most frequent of which includes apical fibrosis, mycetoma formation, and pleural thickening [11].
Chronic obstructive pulmonary disease (COPD) is a chronic progressive lung disease in which air flow obstruction manifests clinically as exertional dyspnea and cough [12]. The prevalence of COPD in the general population is estimated to be close to 5% [13]. Far from a benign disease, COPD is considered to be the third highest cause of death in the United States [14]. The most important risk factor for COPD development is smoking [15]. Recently, theories of an autoimmune basis for the etiopathogenesis of COPD are emerging, which highlight the role of cytokine production and autoimmunity against self-antigens in the development of the disease [16].
To the best of our knowledge, reports on the association between AS and COPD in the literature are scarce. Therefore, the aim of this study was to determine whether a link exists between these two diseases, the former of which has a clear autoimmune basis and the latter which has been recently associated with immune dysregulation.
Section snippets
Material and methods
This study was designed as a cross-sectional study using data extracted from Clalit Heath Services (CHS) database. CHS is the largest integrated health service in Israel which provides healthcare to >4,400,000 insured enrollees (>50% of the Israeli population). CHS has a large central database which collects medical and administrative data from its' health facilities. The data in the digitized medical records undergoes multiple series of verification and the validity of the data was found to be
Results
The study included 4076 patients with AS and 20,290 age- and sex-frequency matched controls. Characteristics of the study population are presented in Table 1. The proportion of COPD was found to be significantly higher among AS patients in comparison with controls (46% vs. 18%, respectively, p < .001) (Table 1).
Table 2 presents the interactions between COPD, stratified study covariates and AS. Significant interaction was observed among subjects aged 18–44 years, despite the relatively small
Discussion
Our study supports the existence of an independent association between COPD and AS. To the best of our knowledge, there are very few studies in the English literature which describe such a link. However, in a population-based cohort study which was based on data collected from the national health insurance (NHI) system in Taiwan, a reported increase of asthma was documented among patients with AS [20]. In the same study, COPD was enlisted as part of the baseline descriptive characteristics of
Acknowledgements
None.
Conflict of interest
Prof. Arnon Cohen: Relationships relevant to this manuscript: Prof. Arnon Cohen received research grants from Novartis. Other relationships: In the last 3 years, Prof. Arnon Cohen served as a consultant, advisor or speaker to Abbvie, Dexcel pharma, Janssen, Novartis, Perrigo, Pfizer, and Rafa. All other authors have no conflict of interest to disclose.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
References (32)
- et al.
Pulmonary manifestations of ankylosing spondylitis
Clin Chest Med
(2010) - et al.
Investigating the link between ischemic heart disease and Behcet's disease: a cross-sectional analysis
Int J Cardiol
(Aug. 15 2017) - et al.
Hypothyroidism among SLE patients: case-control study
Autoimmun Rev
(2016) - et al.
Th17: an effector CD4 T cell lineage with regulatory T cell ties
Immunity
(2006) - et al.
Smoke and autoimmunity: the fire behind the disease
Autoimmun Rev
(2016) - et al.
Associations between ankylosing spondylitis, psoriatic arthritis, Reiter's disease, the intestinal arthropathies, and Behcet's syndrome
Medicine
(1974) - et al.
Ankylosing spondylitis: an overview
Ann Rheum Dis
(2002) - et al.
Inception cohorts for spondyloarthropathies
Z Rheumatol
(2000) - et al.
Disability and handicap in rheumatoid arthritis and ankylosing spondylitis—results from the German rheumatological database. German collaborative arthritis centers
J Rheumatol
(2000) - et al.
Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors
Arthritis Rheum
(1998)
The genetic basis of ankylosing spondylitis: new insights into disease pathogenesis
Appl Clin Genet
Similarities and differences between nonradiographic and radiographic axial spondyloarthritis: a clinical, epidemiological and therapeutic assessment
Curr Opin Rheumatol
Cytokine gene polymorphisms relevant for the spondyloarthropathies
Curr Opin Rheumatol
Intolerance of the dirty intestine
Gut
New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS)
Ann Rheum Dis
Ankylosing spondylitis and axial spondyloarthritis
N Engl J Med
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The two last authors share equal contribution.