November 3, 2020/Pulmonary

Assessing the Relationship Between Systemic Lupus Erythematosus and Asthma

Study finds patients with asthma are at higher risk for developing SLE

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By Patompong Ungprasert, MD, MS

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Systemic lupus erythematosus (SLE) is one of the most common autoimmune connective tissue diseases among women of reproductive age. Despite decades of research, the exact etiology and pathogenesis of SLE remain unknown. It is clear that multiple factors, including genetic, hormonal, immunologic and environmental factors, play a role in the development of this autoimmune disease. Previous studies suggest an association between asthma, which affects approximately 4% of the population, and elevated risk of certain chronic diseases including diabetes mellitus,1 inflammatory bowel disease,2 coronary artery disease3 and SLE.4-13 However, the relationship between asthma and SLE remains unclear as some studies suggest a positive association,5,12,13 while others demonstrate a non-significant negative association.6,7

The study

Our recent epidemiologic work attempts to shed more light into the pathogenesis of SLE.14 Through systematic review and meta-analysis, we identified all existing cohort and case-control studies that investigate whether patients with asthma have an increased risk of SLE compared with individuals without asthma. Qualifying cohort studies included one cohort of patients with asthma and another cohort of comparators without asthma. Additionally, qualifying cohort studies compared the incidence of SLE between the groups. Qualifying case-control studies consisted of patients with SLE and controls without SLE. Further, the case-control studies must compare the prior history of asthma between the two groups in order to be included.

We screened more than 20,000 articles from Pubmed/Medline and EMBASE and identified 10 qualified studies. The pooled results from those 10 studies show that the odds of developing SLE later in life is 37% greater for individuals with asthma than for those without asthma (pooled odds ratio of 1.37 with 95% confidence interval of 1.14–1.65, moderate statistical heterogeneity with I2 of 67%). No evidence of publication bias was detected using visualization of funnel plot.

Overlapping immunogenic pathways

Our observation may help illuminate the pathogenesis of SLE by highlighting the role of the overlapping immunopathogenic pathways between asthma and SLE. Increased levels of TH2 class cytokines, including IL-4, IL-5 and IL-13, have been observed in both asthma and SLE patients.15,16 Therefore, it is possible that up-regulation of TH2 activity along with increased circulating inflammatory markers in asthma patients could trigger systemic inflammation and, subsequently, SLE in the same individuals later in their lives. This hypothesis would emphasize the role of TH2 class cytokines in the pathogenesis, which may warrant more attention from investigators.

Shared environmental risk factors

However, it is also possible that increased risk of SLE is a function of shared common environmental risk factors rather than shared immunopathogenic pathways. Cigarette smoking, for example, is a well-known risk factor for asthma.17 Smoking is also associated a significant increase in risk of SLE, which is probably mediated by oxidative stress causing DNA damage, epigenetic changes and the formation of anti-dsDNA and dysfunctional T and NK cells.18

Surveillance bias less likely

Lastly, it is also plausible that the observed increased risk of SLE in asthma patients was partly due to surveillance bias since patients with asthma are more likely to receive continuous medical care because of the chronicity of the disease. Nevertheless, it is unlikely that surveillance bias alone would entirely explain the increased risk, as patients are usually symptomatic from SLE and most patients would eventually seek for medical attention.

References

  1. Rayner L, McGovern A, Creagh-Brown B, Woodmansey C, de Lusignan S. Type 2 diabetes and asthma: systematic review of the bidirectional relationship. Curr Diabetes Rev. 2019;15(2):118–126.
  2. Kuenzig ME, Bishay K, Leigh R, Kaplan GG, Benchimol EI, Crowdscreen SR Review Team. Co-occurrence of asthma and the inflammatory bowel diseases: a systematic review and meta-analysis. Clin Transl Gastroenterol. 2018 Sep;9(9):188.
  3. Liu H, Fu Y, Wang K. Asthma and risk of coronary heart disease: a meta-analysis of cohort studies. Ann Allergy Asthma Immunol. 2017 Jun;118(6):689-695.
  4. Goldman JA, Klimek GA, Ali R. Allergy in systemic lupus erythematosus. IgE levels and reaginic phenomenon. Arthritis Rheum. 1976;19(4):669–676

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  1. Sequeira JF, Cesic D, Keser G, et al. Allergic disorders in systemic lupus erythematosus. Lupus. 1993 Jun;2(3):187-191.
  2. Morton S, Palmer B, Muir K, Powell RJ. IgE and non-IgE mediated allergic disorders in systemic lupus erythematosus. Ann Rheum Dis. 1998 Nov;57(11):660–663.
  3. Sekigawa I, Yoshiike T, Iida N, Hashimoto H, Ogawa H. Allergic disorders in systemic lupus erythematosus: prevalence and family history. Lupus. 2002 Jul;11(7):426-429.
  4. Parks CG, Biagini RE, Cooper GS, Gilkeson GS, Dooley MA. Total serum IgE levels in systemic lupus erythematosus and associations with childhood onset allergies. Lupus. 2010 Dec;19(14):1614-1622.
  5. Hsiao YP, Tsai JD, Muo CH, et al. Atopic diseases and systemic lupus erythematosus: an epidemiological study of the risks and correlations. Int J Environ Res Public Health. 2014 Aug;11(8):8112–8122.
  6. Lin CH, Hung PH, Hu HY, et al. Clinically diagnosed urticaria and risk of systemic lupus erythematosus in children: a nationwide population-based case-control study. Pediatr Allergy Immunol. 2018 Nov;29(7):732–739.
  7. Hemminki K, Li X, Sundquist J, Sundquist K. Subsequent autoimmune or related disease in asthma patients: clustering of diseases or medical care? Ann Epidemiol. 2010 Mar;20(3):217–222.
  8. Wei CC, Lin CL, Tsai JD, Shen TC, Sung FC. Increased incidence of juvenile onset systemic lupus erythematosus in children with atopic dermatitis. Lupus. 2014 Dec;23(14):1494-1499.
  9. Krishna MT, Subramanian A, Adderley NJ, Zemedikun DT, Gkoutos GV, Nirantharakumar K. Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis. Eur Respir J. 2019 Nov;54(5):1900476.
  10. Charoenngam N, Ponvilawan B, Wongtrakul W, Ungprasert P. Patients with asthma have a higher risk of systemic lupus erythematosus: a systematic review and meta-analysis. Clin Rheum. 2020 Jul. doi:10.1007/s10067-020-05279-x. [Epub ahead of print].

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  1. Romagnani S. Lymphokine production by human T cells in disease states. Ann Rev Immunol. 1994;12(1):227-257.
  2. Barnes PJ. TH2 cytokines and asthma: an introduction. Respir Res. 2001 Mar;2(2):64-65.
  3. Stapleton M, Howard-Thompson A, George C, Hoover RM, Self TH. Smoking and Asthma. J Am Board Fam Med. 2011 May-Jun;24(3):313.
  4. Speyer CB, Costenbader KH. Cigarette smoking and the pathogenesis of systemic lupus erythematosus. Expert Rev Clin Immunol. 2018 Jun;14(6):481-487.

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