Introduction
Sjogren syndrome (SS) is one of the most common rheumatology diseases with limited information about it. It manifests as either primary or secondary (with another rheumatic condition). Although the most involved organs are salivary and lachrymal glands, but any organ can be involved such as respiratory system. The respiratory manifestations are asymptomatic in up to 65% of cases and reduce disease-related quality of life and prognosis. Timely diagnosis of lung involvement relies on availability of data regarding the frequency, type (e.g. bronchial involvement, interstitial lung disease), severity, and association with the other organ involvement. Based on our knowledge, no comparable, interpretable, actionable and timely data exists on lung involvement in Iranian people with primary Sjogren syndrome (pSS). Therefore, to address this gap, this study aims to explore the findings from cases registered by the Iran pSS (IRAPSS).

Methods
The pilot phase of IRAPSS was launched in January 2020 in Guilan province of Iran. Based on the clinical symptoms and lung specialists' opinions, the patients underwent lung imaging and lung function tests. In addition to demographic characteristics (Gender, age, familial history of malignancy, personal history, drug history, and comorbidities), pSS outcomes including its activity (using the Eular SS activity index), patients' related quality of life (using the Eular SS patient reported index), and damage (SS damage index) were recorded.

Results
Of 71 registered cases, 96% were female with a mean age at onset of lung involvement as 51.46±11.7 years. The mean disease duration was 4.5±3.07 years. Also, 95.8% were seropositive (anti-Ro Ab and/or anti-La antibody positive). In 70.4%, the pSS was in the early stage (had the disease for ≤3 years) and in 69.5%, the pSS was inactive. Moreover, 3% were smokers and 97.18% had Sicca symptoms. The most common involved organ in patients was lung (11.76 %). In 37.5% of pSS cases with lung involvements, there were other organ involvement including articular and or hematologic involvement. Other organ involvements were glandular involvement, renal involvement, cutaneous involvement, and lymph nodes. Types of lung involvement secondary to pSS were bronchial dilation (87.5 %) and interstitial lung disease (37.5%) that their functional class was normal, except one case (Type II based on the New York heart association functional classification) and all have normal force vital capacity (FVC). Other characteristics of patients have been demonstrated in Table 1.




Conclusion
The first actionable data about lung involvement in Iranians with pSS was provided in this study. Based on the results, most of patients had disease for ≤3 years (early pSS), and 11.76% had lung involvement with normal FVC. In other studies which had been used data bank of a pSS registry, the prevalence of pulmonary involvement was reported as 9.6–20.2%. The difference may be explained by pSS cases’ different characteristics, genetics, risk factors, health system structure, cultural issues, and different sample size of studies. The findings in this study indicate the importance of lung assessment at time of pSS diagnosis, although this should be confirmed in the future studies based on the IRAPSS data bank.

Ethical Considerations

Compliance with ethical guidelines
This study was approved by Ethics Committee of Guilan University of Medical Sciences (Code: IR.GUMS.REC.1401.175)

Funding
This study was supported from Guilan University of Medical Sciences.

Authors contributions
All authors contributed equally to the conception and design of the study, data collection and analysis, interpretation of the results, and drafting of the manuscript. Each author approved the final version of the manuscript for submission.

Conflicts of interest
The authors declare no conflict of interest.

 
 

1. Daniels TE, Shiboski C, Shiboski S, Lanfranchi H, Yi D, Schiødt M, et al. An early view of the international Sjögren’s syndrome registry. Arthritis and Rheumatism. 2009; 61(5):711-4. [PMID]
2. Thomas E, Hay EM, Hajeer A, Silman AJ. Sjögren's syndrome: A community-based study of prevalence and impact. British Journal of Rheumatology. 1998; 37(10):1069-76. [PMID]
3. Ng WF, Bowman SJ, Griffiths B; UKPSSR study group. United Kingdom Primary Sjogren's Syndrome Registry--a united effort to tackle an orphan rheumatic disease. Rheumatology (Oxford). 2011; 50(1):32-9. [DOI:10.1093/rheumatology/keq240] [PMID]
4. Haugen AJ, Peen E, Hulten B, Johannessen AC, Brun JG, Halse AK, et al. Estimation of the prevalence of primary Sjogren’s syndrome in two age-different community-based populations using two sets of classification criteria: The Hordaland Health Study. Scandinavian Journal of Rheumatology. 2008; 37(1):30-4. [DOI:10.1080/03009740701678712] [PMID]
5. Thurtle E, Grosjean A, Steenackers M, Strege K, Barcelos G, Goswami P. Epidemiology of Sjogren’s: A systematic literature review. Rheumatology and Therapy. 2024; 11(1):1-17. [DOI:10.1007/s40744-023-00611-8] [PMID] 
6. Beydon M, McCoy S, Nguyen Y, Sumida T, Mariette X, Seror R. Epidemiology of Sjogren syndrome. Nature reviews Rheumatology. 2024; 20(3):158-69. [DOI:10.1038/s41584-023-01057-6] [PMID]
7. William S, Clair DL. Sjogren Syndrome. In: Firestein GS, Budd RC, Gabriel SE, McInnes IB, O'Dell JR. Kelley and Firestein's textbook of rheumatology. Amsterdam: Elsevier Health Sciences: 2016. [Link]
8. Lee AS, Scofield RH, Hammitt KM, Gupta N, Thomas DE, Moua T, et al. Consensus guidelines for evaluation and management of pulmonary disease in Sjögren's. Chest. 2021; 159(2):683-98. [DOI:10.1016/j.chest.2020.10.011] [PMID] 
9. Lee J, Koh JH, Kwok SK, Park SH. The EULAR Sjögren's Syndrome Patient-Reported Index is an independent determinant of health-related utility values of Korean patients with primary Sjögren's syndrome. Clinical and Experimental Rheumatology. 2016; 34(4):663-7. [PMID]
10. Seror R, Bowman SJ, Brito-Zeron P, Theander E, Bootsma H, Tzioufas A, et al. EULAR Sjögren's syndrome disease activity index (ESSDAI): A user guide. RMD Open. 2015; 1(1):e000022. [PMID]
11. Zhang Y, Li M, Zhang L, Li Q, Yang P, Kong X, et al. Association between comorbidities and extraglandular manifestations in primary Sjögren's syndrome: A multicenter cross-sectional study. Clinical Rheumatology. 2020; 39(9):2677-88. [DOI:10.1007/s10067-020-04992-x] [PMID]
12. Park Y, Lee J, Koh JH, Sung YK, Lee SS, Choe JY, et al. Distinct clinical characteristics of anti-Ro/SSA-negative primary Sjögren's syndrome: Data from a nationwide cohort for Sjögren's syndrome in Korea. Clinical and Experimental Rheumatology. 2019; 37 Suppl 118(3):107-13. [PMID] 
13. Brito-Zerón P, Acar-Denizli N, Ng WF, Horváth IF, Rasmussen A, Seror R, et al. Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjogren’s syndrome. Rheumatology (Oxford, England). 2020; 59(9):2350-9. [DOI:10.1093/rheumatology/kez578] [PMID]
14. Seror R, Gottenberg JE, Devauchelle-Pensec V, Dubost JJ, Le Guern V, Hayem G, et al. European League Against Rheumatism Sjögren's Syndrome Disease Activity Index and European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index: A complete picture of primary Sjögren's syndrome patients. Arthritis Care & Research. 2013; 65(8):1358-64. [DOI:10.1002/acr.21991] [PMID]
15. Brito-Zerón P, Acar-Denizli N, Ng WF, Zeher M, Rasmussen A, Mandl T, et al. How immunological profile drives clinical phenotype of primary Sjögren's syndrome at diagnosis: Analysis of 10,500 patients (Sjögren Big Data Project). Clinical and Experimental Rheumatology. 2018; 36 Suppl 112(3):102-12. [PMID]
16. Retamozo S, Acar-Denizli N, Horváth IF, Ng WF, Rasmussen A, Dong X, et al. Influence of the age at diagnosis in the disease expression of primary Sjögren syndrome. Analysis of 12,753 patients from the Sjögren Big Data Consortium. Clinical and Experimental Rheumatology. 2021; 39 Suppl 133(6):166-74. [DOI:10.55563/clinexprheumatol/egnd1i] [PMID] 
17. Lyne SA, Downie-Doyle S, Lester SE, Quinlivan A, Toby Coates P, Gordon TP, et al. Primary Sjögren's syndrome in South Australia. Clinical and Experimental Rheumatology. 2020; 38 Suppl 126(4):57-63. [PMID]
18. Westerlund A, Kejs AMT, Beydogan H, Gairy K. Primary Sjögren's Syndrome: A retrospective cohort study of burden of illness in Sweden. Rheumatology and Therapy. 2021; 8(2):955-71. [DOI:10.1007/s40744-021-00314-y] [PMID] 
19. Gottenberg JE, Seror R, Miceli-Richard C, Benessiano J, Devauchelle-Pensec V, Dieude P, et al. Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sjögren's syndrome. Data at enrollment in the prospective ASSESS cohort. PLoS One. 2013; 8(5):e59868.  [DOI:10.1371/journal.pone.0059868] [PMID] 
20. Lin W, Xin Z, Zhang J, Liu N, Ren X, Liu M, et al. Interstitial lung disease in Primary Sjögren's syndrome. BMC Pulmonary Medicine. 2022; 22(1):73. [DOI:10.1186/s12890-022-01868-5] [PMID] 
21. Flament T, Bigot A, Chaigne B, Henique H, Diot E, Marchand-Adam S. Pulmonary manifestations of Sjögren's syndrome.  European Respiratory Review . 2016; 25(140):110-23.[DOI:10.1183/16000617.0011-2016] [PMID] 
22. Huang Y, Qiu Y, Xie Z, Zhang F, Zhang Y, Guan M, et al. Risk factors and prognosis of interstitial lung disease for primary Sjögren syndrome patients: A retrospective case-control study. Clinical Rheumatology. 2023; 42(11):3033-41. [DOI:10.1007/s10067-023-06596-7] [PMID]