Original Article
The link between COPD and ankylosing spondylitis: A population based study

https://doi.org/10.1016/j.ejim.2018.04.002Get rights and content

Highlights

  • In this population-based cross sectional study AS has been shown to be associated with increased risk of COPD.

  • Smoking or the underlying pro-inflammatory milieu in AS could plausibly account for this association.

  • Smoking cessation should be encouraged in AS patients, and COPD screening may be warranted.

Abstract

Background

Ankylosing spondylitis (AS) is one of the most common and severe subtypes of the spondyloarthropathies. Extra-articular involvement among AS patients, including lung disease, has been described widely. Chronic obstructive pulmonary disease (COPD) has been linked to several autoimmune diseases, however, very few studies have investigated the association between AS and COPD.

Objective

To assess whether an association exists between AS and COPD.

Material and methods

A population-based cross-sectional study was conducted using data retrieved from the largest electronic medical records database in Israel, the Clalit Health Services (CHS). Patients were defined as having AS or COPD when there was at least one such documented diagnosis in their medical records. The proportion of COPD was compared between AS patients and controls. A logistic regression model was used to estimate the association between AS and COPD in a multivariate analysis adjusted for age, gender and smoking status.

Results

The study included 4076 patients with AS and 20,290 age- and sex-frequency matched controls. The proportion of COPD in AS patients was higher than in controls (46% vs. 18%, respectively, p < .001). Multivariate logistic regression demonstrated a robust independent association between AS and COPD (OR 1.225, p = .031).

Conclusion

Our study supports an association between AS and COPD, further extending the link between COPD and autoimmune diseases. This finding highlights the importance of smoking cessation in AS patients and raises the question of whether COPD screening may be warranted.

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.

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