# Bibliometric Analysis of the Scientific Literature on Rheumatoid Arthritis-Associated Interstitial Lung Disease

Authors: Yuan Zhang; Tingxiao Zhao; Tianjin Wu; Wei Huang; Teng Wu; Yunjuan Shi; Zhenhua Ying
Journal: BioMed Research International
 (2021)

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## Abstract

Background. In recent years, the number of studies on rheumatoid arthritis-related interstitial lung disease (RA-ILD) has been increasing, which has led to many publications on this topic. Our purpose is to identify research trends in RA-ILD and analyze the most-cited RA-ILD-related high-quality scientific publications. Methods. All publications on RA-ILD in the Core Collection database of Web of Science were searched. The publication year, country, institution, total citations, and journal were extracted and analyzed. We used VOSviewer software or an online bibliometric analysis platform for cooccurrence analysis of the keywords, institutions, and countries involved. The 100 most frequently cited RA-ILD publications were analyzed. Results. In total, 596 publications related to RA-ILD were obtained. Over time, the frequency of RA-ILD publications has increased. Globally, the United States provides the most publications on RA-ILD (n=195). The institution with the highest publication output was the Mayo Clinic (n=43). The journal “Annals of the Rheumatic Diseases” published most with 93 articles and received 338 citations. A clinical description was the most common research topic in RA-ILD-related publications. Conclusions. In recent years, there has been an increasing number of studies on RA-ILD, and related publications have increased rapidly. This study is the first bibliometric study of RA-ILD-related publications. It can be used as a guide for clinicians and can help researchers choose research directions of interest in this field.


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## Body

## 1. Introduction

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by articular and extra-articular manifestations affecting approximately 1-2% of the general population [1]. Interstitial lung disease (ILD) is an extra-articular manifestation of RA, which occurs frequently in up to 80% of patients with RA. This may be the result of chronic immune activation and inflammation in RA, or the pulmonary toxicity caused by immunomodulatory drugs used to treat RA [2–6]. The prevalence of RA-ILD ranges from 1% to 58%, depending on the diagnostic means used and the severity in the RA population studied [6, 7]. Currently, ILD is the second leading cause of death in patients with RA after cardiovascular disease [8]. Research on RA-ILD has increased to include its natural history, pathogenesis, radiological evaluation, clinical manifestations, and treatment [9–12]. However, the trend of RA-ILD research is unclear, and the most influential research in this field has not been systematically determined. Therefore, our purpose was to provide a bibliometric study of publications on RA-ILD.Bibliometric analysis is a convenient and reliable statistical method that can quantitatively and qualitatively evaluate research trends in the research field. This analysis has long been used in the field of medical research and has been widely accepted by scientific researchers [13–15]. To the best of our knowledge, no bibliometric studies on RA-ILD have been published to date. Therefore, in this study, we use bibliometric statistical methods to identify the most influential publications and analyze the research status and trends in the RA-ILD research field.


## 2. Materials and Methods

### 2.1. Datasource

All the data of this study were obtained from articles retrieved from the core collection database of Web of Science on July 1, 2021.


### 2.2. Search Strategy

The retrieval steps and strategies were as follows: Title = rheumatoid arthritis AND Title = (interstitial lung disease OR interstitial pneumonia) AND Language = English AND Document type = (review OR article) AND Time span =1980 to 2021.


### 2.3. Statistical Tools

VOSviewer, an online bibliometric analysis platform (https://bibliometric.com), and Excel software were used to extract and analyze all data. VOSviewer is a software that is usually used to visually analyze the collaborative network between countries, institutions, and authors and cocitation of keyword clusters to analyze research trends and hotspots. The role of the online bibliometric analysis platform is similar to that of VOSviewer. Excel software was used to extract and analyze various details of the publication, including author, title, journal, year of publication, institution, country, journal impact factors, and number of total citations.


### 2.4. Data Extraction

According to the retrieval steps and strategies, the two authors independently fetched the article information and discussed the differences until they reached a consensus. Data were obtained from the core collection database of Web of Science, and the publication information was extracted and analyzed using Excel, online bibliometric analysis, and VOSviewer software.


## 2.1. Datasource

All the data of this study were obtained from articles retrieved from the core collection database of Web of Science on July 1, 2021.


## 2.2. Search Strategy

The retrieval steps and strategies were as follows: Title = rheumatoid arthritis AND Title = (interstitial lung disease OR interstitial pneumonia) AND Language = English AND Document type = (review OR article) AND Time span =1980 to 2021.


## 2.3. Statistical Tools

VOSviewer, an online bibliometric analysis platform (https://bibliometric.com), and Excel software were used to extract and analyze all data. VOSviewer is a software that is usually used to visually analyze the collaborative network between countries, institutions, and authors and cocitation of keyword clusters to analyze research trends and hotspots. The role of the online bibliometric analysis platform is similar to that of VOSviewer. Excel software was used to extract and analyze various details of the publication, including author, title, journal, year of publication, institution, country, journal impact factors, and number of total citations.


## 2.4. Data Extraction

According to the retrieval steps and strategies, the two authors independently fetched the article information and discussed the differences until they reached a consensus. Data were obtained from the core collection database of Web of Science, and the publication information was extracted and analyzed using Excel, online bibliometric analysis, and VOSviewer software.


## 3. Results

### 3.1. Publication Analysis

A total of 596 RA-ILD research articles were found in the core collection database of the Web of Science. The number of articles increased from 1981 to 2021 (Figure1(a)). Quantitative analysis shows that in the past 10 years, global research on RA-ILD has increased rapidly, from four articles from 1981 to 1985 to 326 articles from 2016 to 2020. This result shows that RA-ILD has attracted increasing attention, and the research process of RA-ILD continues to accelerate.Figure 1
Overview of publications. (a) Number of publications and citations from 1981 to 2021. (b) Sources of publications. (c) Top 10 countries. (d) International collaborations.
(a)(b)(c)(d)


### 3.2. Countries Analysis

These articles cover 46 countries and regions. Globally, the United States (US) published the most studies (n=195), followed by Japan (n=105), the United Kingdom (n=66), Spain (n=58), China (n=49), Italy (n=40), South Korea (n=32), France (n=23), Mexico (n=22), and Canada (n=14) (Figures 1(b) and 1(c)).The online bibliometric analysis platform was used to analyze cooperative relations between countries. The visual analysis shows that the USA has always been the center of RA-ILD research in the world, and Japan, France, China, and South Korea have been found to be potential research powers. (Figure1(d)).


### 3.3. Institutions Analysis

All the publications involve 1000 institutions. The results show that many institutions in the United States actively participate in RA-ILD research. The 10 most productive institutions internationally were Mayo Clinic (n=43), National Jewish Health (n=41), Brigham and Women’s Hospital (n=31), Colorado State University (n=31), University of California, San Francisco (n=19), University of Ulsan (n=19), University of Modena and Reggio Emilia (n=17), Harvard Medical School (n=15), Queen Elizabeth’s Hospital (n=15), and University of Miami (n=15), respectively (Figure 2(a)). According to the citation report, Mayo Clinic’s articles were cited the most, namely, 1408 times, followed by the National Jewish Health, which was cited 858 times, and the University of California, San Francisco, 851 (Figure 2(b)).Figure 2
Highest impact institutions. (a) The top 10 institutions (publications). (b) The top 10 institutions (citations). (c) Institutional collaborations.
(a)(b)(c)VOSviewer software was used to analyze the extent of cooperative relations between institutions. The institution with the most links, i.e., the highest link strength was recorded by the National Jewish Health Organization (n=131), followed by the University of Colorado (n=123), Mayo Clinic (n=119), and Brigham and Women’s Hospital (n=117). In the VOSviewer software, the width of the line reflects the close relationship of interinstitution cooperation. The National Jewish Health had close collaborations with the University of Colorado and Mayo Clinic. Mayo Clinic had large collaborations with National Jewish Health, University of Colorado, Brigham and Women’s Hospital, and Harvard Medical School (Figure 2(c)).


### 3.4. Journals Analysis

All 596 articles in this study were published in 123 journals. Among these, the journals which had published at least 20 articles on the topic accounted for 73.8% of the total (Table1). The five journals with the most articles on the topic were Annals of the Rheumatic Diseases, Arthritis & Rheumatology, American Journal of Respiratory and Critical Care Medicine, Rheumatology, and Arthritis and Rheumatism. Moreover, articles in the Annals of the Rheumatic Diseases have been cited the most. More than 20 journals published on RA-ILD, and the average impact factor was 11.8, indicating a high level of reliability of the included studies.Table 1
Active journals on rheumatoid arthritis-associated interstitial lung disease.
JournalArticleTotal citationMean citationImpact factorAnnals of the Rheumatic Diseases933383.6319.103Arthritis & Rheumatology752192.9210.995American Journal of Respiratory and Critical Care Medicine535149.7021.405Rheumatology3871018.6820.543Arthritis and Rheumatism3655215.335.532European Respiratory Journal3053717.9016.671Clinical Rheumatology1824813.784.098Chest1248540.422.878Internal Medicine1115614.182.048Clinical and Experimental Rheumatology10989.804.473Respiratory Medicine825832.253.772Modern Rheumatology810813.503.023Seminars in Arthritis and Rheumatism620834.675.532Rheumatology International615425.672.631Journal of Rheumatology614724.504.666New England Journal of Medicine613322.1791.245PLos one612721.173.24Scandinavian Journal of Rheumatology610417.333.641Respirology69215.336.424JCR-Journal of Clinical Rheumatology6264.333.517


### 3.5. Research Status and Analysis

VOSviewer software was used to analyze the cooccurrence analysis of keywords in the RA-ILD research articles. When the minimum number of keywords appearing in the publication was set to five, 72 keywords were selected and divided into four clusters:“Clinical-Features,” “Pathological-Features,” “Treatment,” and “Prevalence and mortality.” In the “Clinical-Features” cluster, the most common keywords were “pneumonia,” “idiopathic pulmonary-fibrosis,” and “prognosis.” In the “Pathological-Features” cluster, the most frequent keywords were “rheumatoid arthritis,” “interstitial lung disease,” and “fibrosis.” In the “treatment” cluster, the most frequent keywords were “classification,” “criteria,” and “safety.” In the “prevalence and mortality” cluster, the most frequent keywords were “prevalence,” “mortality,” and “risk” (Figure3(a)).Figure 3
Keyword analysis. (a) Cluster analysis of keywords. (b) Evolution of keyword frequency.
(a)(b)To better understand the dynamic process of the RA-ILD research trends, we evaluated the evolution of the keywords (Figure3(b)). We assigned colors based on the year the keyword appears in the article. For example, the yellow keyword appears later than the purple keyword. In the early stages, “idiopathic pulmonary fibrosis,” “alveolitis,” and “systemic sclerosis” were the main topics. Trends in recent years show that the terms “management,” “predictors,” “inflammation,” and “progress” are becoming more and more popular.


### 3.6. The 100 Most-Cited Publications

The 100 most-cited publications on RA-ILD were published between 1984 and 2020 (Table2). The analysis indicated that 2001-2005 was the period when most of these studies were published, with 41 publications, followed by 2016-2020, with 29 publications (Figure 4(a)).Table 2
The top 100 cited publications on rheumatoid arthritis-associated interstitial lung disease.
RankTitleAuthorJournalYearTotal citationCitation/year1Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based studyBongartz, T.Arthritis and Rheumatism2010324272Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung diseaseKim, E. J.European Respiratory Journal201028323.583Histopathologic pattern and clinical features of rheumatoid arthritis associated interstitial lung diseaseLee, H. KChest200524514.414Rheumatoid arthritis-interstitial lung disease-associated mortalityOlson, A. L.American Journal of Respiratory and Critical Care Medicine201122220.185Interstitial lung disease in recent onset rheumatoid arthritisGabbay, E.American Journal of Respiratory and Critical Care Medicine19972208.86Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics-a large multicentre UK studyKelly, C. A.Rheumatology201420525.637Progressive preclinical interstitial lung disease in rheumatoid arthritisGochuico, B. R.Archives of Internal Medicine200819814.148Rheumatoid arthritis-associated interstitial lung disease the relevance of histopathologic and radiographic patternKim, E. J.Chest200918914.549Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohortKoduri, G.Rheumatology201014912.4210Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumatoid arthritis: A systematic literature reviewRoubille, C.Seminars in Arthritis and Rheumatism201412615.7511Predictors of mortality in rheumatoid arthritis-associated interstitial lung diseaseSolomon, J. J.European Respiratory Journal201612420.6712MUC5B promoter variant and rheumatoid arthritis with interstitial lung diseaseJuge, P. A.New England Journal of Medicine20181082713Influence of anti-TNF therapy on mortality in patients with rheumatoid arthritis-associated interstitial lung disease: results from the British Society for Rheumatology Biologics RegisterDixon, W. G.Annals of the Rheumatic Diseases2010108914High-resolution computed-tomography of the lungs in patients with rheumatoid-arthritis and interstitial lung-diseaseMcdonagh, JBritish Journal of Rheumatology19941023.6415Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritisSuissa, S.Arthritis and Rheumatism2006955.9416Different risk factors between interstitial lung disease and airway disease in rheumatoid arthritisMori, S.Respiratory Medicine2012898.917A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortalityHyldgaard, C.Annals of the Rheumatic Diseases20178316.618Predictors of mortality in rheumatoid arthritis-related interstitial lung diseaseAssayag, D.Respirology20148310.3819Rheumatoid arthritis-associated interstitial lung disease: radiologic identification of usual interstitial pneumonia patternAssayag, D.Radiology2014779.6320Correlation between HRCT findings, pulmonary function tests and bronchoalveolar lavage cytology in interstitial lung disease associated with rheumatoid arthritisBiederer, J.European Radiology2004744.1121Association of fine specificity and repertoire expansion of anticitrullinated peptide antibodies with rheumatoid arthritis associated interstitial lung diseaseGiles, J. T.Annals of the Rheumatic Diseases2014718.8822Fibrosing interstitial pneumonia predicts survival in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD)Solomon, J. J.Respiratory Medicine2013717.8923Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years’ experience at a single centreYusof, M. M.Rheumatology20176913.824Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosisJuge, P. A.European Respiratory Journal20176913.825Rheumatoid arthritis (RA)-specific autoantibodies in patients with interstitial lung disease and absence of clinically apparent articular RAGizinski, A. M.Clinical Rheumatology2009685.2326Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkersDoyle, T. J.American Journal of Respiratory and Critical Care Medicine2015679.5727Leflunomide-induced interstitial lung disease: prevalence and risk factors in Japanese patients with rheumatoid arthritisSawada, T.Rheumatology2009665.0828Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control studyHozumi, H.BMJ open201363729The lung in rheumatoid arthritis focus on interstitial lung diseaseSpagnolo, P.Arthritis & Rheumatology20186215.530Abatacept in patients with rheumatoid arthritis and interstitial lung disease: a national multicenter study of 63 patientsFernandez-Diaz, C.Seminars in Arthritis and Rheumatism20186215.531Rheumatoid arthritis (RA) associated interstitial lung disease (ILD)O’Dwyer, D. N.European Journal of Internal Medicine2013626.8932Rheumatoid arthritis treatment and the risk of severe interstitial lung diseaseWolfe, F.Scandinavian Journal of Rheumatology200760433Rheumatoid arthritis complicated with acute interstitial pneumonia induced by leflunomide as an adverse reactionKamata, YInternal Medicine2004563.1134Morphologic and quantitative assessment of CD20+ B cell infiltrates in rheumatoid arthritis-associated nonspecific interstitial pneumonia and usual interstitial pneumoniaAtkins, S. R.Arthritis and Rheumatism2006553.4435Biomarkers of rheumatoid arthritis-associated interstitial lung diseaseChen, J.Arthritis & Rheumatology2015547.7136Acute exacerbation of preexisting interstitial lung disease after administration of etanercept for rheumatoid arthritisHagiwara, K.Journal of Rheumatology2007523.4737Nonspecific interstitial pneumonia pattern as pulmonary involvement of rheumatoid arthritisYoshinouchi, TRheumatology International2005492.8838Progressive decline of lung function in rheumatoid arthritis-associated interstitial lung diseaseZamora-Legoff, J. A.Arthritis & Rheumatology2017489.639Retrospective study of the clinical characteristics and risk factors of rheumatoid arthritis-associated interstitial lung diseaseZhang, Y. F.Clinical Rheumatology2017469.240Rheumatoid arthritis-interstitial lung disease in the United States: prevalence, incidence, and healthcare costs and mortalityRaimundo, K.Journal of Rheumatology2019451541The multifaceted aspects of interstitial lung disease in rheumatoid arthritisCavagna, L.Biomed Research International201345542Association of human leukocyte antigen with interstitial lung disease in rheumatoid arthritis: a protective role for shared epitopeFurukawa, H.PLos one2012454.543Clinical and radiological features of acute-onset diffuse interstitial lung diseases in patients with rheumatoid arthritis receiving treatment with biological agents: importance of PneuKameda, H.Internal Medicine2011454.0944Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohortsKiely, P.BMJ open20194414.6745High resolution computed tomography pattern of usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease: relationship to survivalYunt, Z. X.Respiratory Medicine2017448.846Interstitial lung disease in rheumatoid arthritis: recent advancesKim, D. S.Current Opinion in Pulmonary Medicine2006442.7547Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective reviewIqbal, K.Therapeutic Advances in Musculoskeletal Disease2015436.1448Clinical course and outcome of rheumatoid arthritis-related usual interstitial pneumoniaSong, J. W.Sarcoidosis Vasculitis and Diffuse Lung Diseases2013424.6749Increased levels of interleukin-33 associated with bone erosion and interstitial lung diseases in patients with rheumatoid arthritisZhu X. YCytokine2012424.250Incidence of and risk factors for interstitial pneumonia in patients with rheumatoid arthritis in a large Japanese observational cohort, IORRAShidara, K.Modern Rheumatology2010423.551Interstitial lung-disease in rheumatoid-arthritis - assessment with high-resolution computed-tomographyFujii, MJournal of Thoracic Imaging1993421.4552Patterns of interstitial lung disease and mortality in rheumatoid arthritisZamora-Legoff, J. A.Rheumatology2017418.253Standard and pocket-size lung ultrasound devices can detect interstitial lung disease in rheumatoid arthritis patientsCogliati, C.Rheumatology2014415.1354Potential risk of TNF inhibitors on the progression of interstitial lung disease in patients with rheumatoid arthritisNakashita, T.BMJ open2014415.1355A fatal case of acute exacerbation of interstitial lung disease in a patient with rheumatoid arthritis during treatment with tocilizumabKawashiri, S.Rheumatology International2012414.156Interstitial lung disease in patients with rheumatoid arthritis: comparison with cryptogenic fibrosing alveolitis over 5 yearsRajasekaran, A.Journal of Rheumatology2006412.5657Interstitial lung disease in patients with rheumatoid arthritis: a comparison with cryptogenic fibrosing alveolitisRajasekaran, B. A.Rheumatology2001401.958A roadmap to promote clinical and translational research in rheumatoid arthritis-associated interstitial lung disease a dance promote clinical and translational researchDoyle, T. J.Chest2014394.8859Rheumatoid arthritis-related interstitial lung disease (RA-ILD): methotrexate and the severity of lung disease are associated to prognosisRojas-serrano, J.Clinical Rheumatology2017387.660Rheumatoid arthritis associated interstitial lung disease: a reviewAssayag, D.Medicina-Buenos Aires2014384.7561Sonographic assessment of interstitial lung disease in patients with rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosusMoazedi-Fuerst, F.Clinical and Experimental Rheumatology2015375.2962Association of cross-reactive antibodies targeting peptidyl-arginine deiminase 3 and 4 with rheumatoid arthritis-associated interstitial lung diseaseGiles, J. T.PLos one2014374.6363Clinical and laboratory factors associated with interstitial lung disease in rheumatoid arthritisRestrepo, J. F.Clinical Rheumatology201535564Rheumatoid arthritis interstitial lung disease: mycophenolate mofetil as an antifibrotic and disease-modifying antirheumatic drugSaketkoo, L. A.Archives of Internal Medicine2008342.4365Survival and quality of life in rheumatoid arthritis-associated interstitial lung disease after lung transplantationYazdani, A.Journal of Heart and Lung Transplantation2014334.1366Rheumatoid arthritis-associated autoantibodies and subclinical interstitial lung disease: the multi-ethnic study of atherosclerosisBernstein, E. J.Thorax2016325.3367Nintedanib reduces pulmonary fibrosis in a model of rheumatoid arthritis-associated interstitial lung diseaseRedente, E. F.American Journal of Physiology-Lung Cellular and Molecular phy2018317.7568Profibrotic effect of IL-17A and elevated IL-17RA in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated lung disease support a direct role for IL-17A/IL-17RA in human fibZhang, J.American Journal of Physiology-Lung Cellular and Molecular phy2019301069Variable course of disease of rheumatoid arthritis-associated usual interstitial pneumonia compared to other subtypesNurmi, H. M.BMC Pulmonary Medicine201630570Risk of interstitial lung disease associated with leflunomide treatment in Korean patients with rheumatoid arthritisJu, J. H.Arthritis and Rheumatism200730271Anti-cyclic citrullinated peptide antibody is associated with interstitial lung disease in patients with rheumatoid arthritisYin, Y. F.PLos one2014293.6372A novel model of rheumatoid arthritis-associated interstitial lung disease in SKG miceKeith, R. C.Experimental Lung Research2012292.973Treatment strategies for a rheumatoid arthritis patient with interstitial lung diseaseKelly, C.Expert Opinion on Pharmacotherapy200828274Rheumatoid arthritis disease activity predicting incident clinically apparent rheumatoid arthritis-associated interstitial lung disease: a prospective cohort studySparks, J. A.Arthritis & Rheumatology201927975Changes in peripheral CD19(+) Foxp3(+) and CD19(+) TGF beta(+) regulatory B cell populations in rheumatoid arthritis patients with interstitial lung diseaseGuo, Y. Y.Journal of Thoracic Disease2015273.8676Interstitial lung disease in patients with rheumatoid arthritis: spontaneous and drug inducedHallowell, R. W.Drugs2014273.3877HLA-A∗31:01 and methotrexate-induced interstitial lung disease in Japanese rheumatoid arthritis patients: a multidrug hypersensitivity marker?Furukawa, H.Annals of the Rheumatic Diseases201327378Asymptomatic preclinical rheumatoid arthritis-associated interstitial lung diseaseChen, J.Clinical & Developmental Immunology201327379Rheumatoid arthritis-associated interstitial lung disease and idiopathic pulmonary fibrosis: shared mechanistic and phenotypic traits suggest overlapping disease mechanismsPaulin, F.Revista de Investigacion Clinica-Clinical and Translational Investig2015263.7180Lymphoid interstitial pneumonia in juvenile rheumatoid-arthritisLovell, D.Journal of Pediatrics1984260.6881Ultrasound screening for interstitial lung disease in rheumatoid arthritisMoazedi-Fuerst, F. C.Clinical and Experimental Rheumatology2014253.1382Interstitial pneumonia due to cytomegalovirus following low-dose methotrexate treatment for rheumatoid-arthritisAglas, F.Arthritis and Rheumatism1995250.9383Therapeutic management of patients with rheumatoid arthritis and associated interstitial lung disease: case report and literature reviewDiamanti, A. P.Therapeutic Advances in Respiratory Disease2017244.884Interstitial lung disease in rheumatoid arthritis: response to IL-6R blockadeMohr, M.Scandinavian Journal of Rheumatology2011242.1885Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: a multicentre retrospective studyManfredi, A.Internal Medicine Journal20202311.586Recent advances in the pathogenesis, prediction, and management of rheumatoid arthritis-associated interstitial lung diseaseJohnson, C.Current Opinion in Rheumatology2017234.687Abatacept therapy in rheumatoid arthritis with interstitial lung diseaseMera-Varela, A.Journal of Clinical Rheumatology2014232.8888The clinical significance of HRCT in evaluation of patients with rheumatoid arthritis-associated interstitial lung disease: a report from ChinaZou, Y. Q.Rheumatology International2012232.389A case of adalimumab-associated interstitial pneumonia with rheumatoid arthritisYamazaki, H.Modern Rheumatology2010231.9290Prevalence and effects of emphysema in never-smokers with rheumatoid arthritis interstitial lung diseaseJacob, J.Ebiomedicine2018225.591Association of disease activity with acute exacerbation of interstitial lung disease during tocilizumab treatment in patients with rheumatoid arthritis: a retrospective, case-control studyAkiyama, M.Rheumatology International2016223.6792Predicting outcomes in rheumatoid arthritis related interstitial lung diseaseJacobt, J.European Respiratory Journal201921793Plasma miRNA expression profiles in rheumatoid arthritis associated interstitial lung diseaseOka, S.BMC Musculoskeletal Disorders2017214.294Patients with limited rheumatoid arthritis-related interstitial lung disease have a better prognosis than those with extensive diseaseSathi, N.Rheumatology2011211.9195Risk of serious infection in patients with rheumatoid arthritis-associated interstitial lung diseaseZamora-Legoff, J. A.Clinical Rheumatology2016203.3396Possible effect of abatacept on the progression of interstitial lung disease in rheumatoid arthritis patientsNakashita, T.Respiratory Investigation2016203.3397Up-to-date information on rheumatoid arthritis-associated interstitial lung diseaseSuda, T.Clinical Medicine Insights-Circulatory Respiratory and Pulmonary2015202.8698Eternacept for the treatment of patients with rheumatoid arthritis and concurrent interstitial lung diseaseHorai, Y.Journal of Clinical Pharmacy and Therapeutics201220299Myofibroblasts and S-100 protein positive cells in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial pneumoniaYoshinouchi, T.European Respiratory Journal1999200.87100The performance of the GAP model in patients with rheumatoid arthritis associated interstitial lung diseaseMorisset, J.Respiratory Medicine2017193.8Figure 4
Top 100 most-cited publications on RA-ILD. (a) Year of publication. (b) Distribution of country. (c) Institution analysis. (e) Publication topics.
(a)(b)(c)(d)The 100 most-cited articles were from 18 countries and regions. Thirty-four articles were published by authors from the USA, followed by Japan (n=20), the United Kingdom (n=11), China (n=7), Italy (n=5), Canada (n=3), Austria (n=3), Spain, France, and Germany (n=2), and Mexico, Argentina, Australia, Bangladesh, Denmark, Finland, and Ireland (n=1) (Figure 4(b)).Of these 100 articles, the Mayo Clinic Medicine and National Jewish Health each generated seven publications, resulting in their being the most represented institutions on this topic, followed by the University of California in San Francisco (n=5) and Queen Elizabeth Hospital (n=4) (Figure 4(c)).Overall, there were 52 different journals which published the 100 articles. “Rheumatology” was the most productive journal, with 8 articles and 632 citations, followed by “Arthritis and Rheumatism,” with five articles and 529 citations (Table3).Table 3
Journal with more than three of the 100 most-cited publications on rheumatoid arthritis-associated interstitial lung disease.
JournalArticleTotal citationMean citationImpact factorRheumatology8632793.494Arthritis and Rheumatism5529105.85.532Clinical Rheumatology520741.44.098European Respiratory Journal5517103.416.671Annals of the Rheumatic Diseases428972.2519.103Arthritis & Rheumatology419147.7510.995Respiratory Medicine422355.753.772Rheumatology International413533.752.631When considering the individual authors’ academic contributions, Jay H Ryu, provided 11 publications, followed by Joyce C Lee and Eric L Matteson, each with 8 publications (Table4).Table 4
Most frequent authors of the 100 most-cited publications on rheumatoid arthritis-associated interstitial lung disease.
AuthorArticleFirst authorLast authorCo-authorRyu, Jay H.11000Lee, Joyce S.8026Matteson, Eric L.8242Brown, Kevin K.6024Collard, Harold R.6015Kelly, Clive A.6240Kim, Dong Soon.6114Rosas, Ivan O.6033Solomon, Joshua J.6213Doyle, Tracy J.5211Ascherman, Dana P.5023Fischer, Aryeh.5000Swigris, Jeffrey J.5023The most common research topic on RA-ILD addressed the clinical description (n=44), followed by clinical research (n=13), diagnosis (n=8), mortality (n=7), and risk factors (n=6) (Figure 4(d)).


## 3.1. Publication Analysis

A total of 596 RA-ILD research articles were found in the core collection database of the Web of Science. The number of articles increased from 1981 to 2021 (Figure1(a)). Quantitative analysis shows that in the past 10 years, global research on RA-ILD has increased rapidly, from four articles from 1981 to 1985 to 326 articles from 2016 to 2020. This result shows that RA-ILD has attracted increasing attention, and the research process of RA-ILD continues to accelerate.Figure 1
Overview of publications. (a) Number of publications and citations from 1981 to 2021. (b) Sources of publications. (c) Top 10 countries. (d) International collaborations.
(a)(b)(c)(d)


## 3.2. Countries Analysis

These articles cover 46 countries and regions. Globally, the United States (US) published the most studies (n=195), followed by Japan (n=105), the United Kingdom (n=66), Spain (n=58), China (n=49), Italy (n=40), South Korea (n=32), France (n=23), Mexico (n=22), and Canada (n=14) (Figures 1(b) and 1(c)).The online bibliometric analysis platform was used to analyze cooperative relations between countries. The visual analysis shows that the USA has always been the center of RA-ILD research in the world, and Japan, France, China, and South Korea have been found to be potential research powers. (Figure1(d)).


## 3.3. Institutions Analysis

All the publications involve 1000 institutions. The results show that many institutions in the United States actively participate in RA-ILD research. The 10 most productive institutions internationally were Mayo Clinic (n=43), National Jewish Health (n=41), Brigham and Women’s Hospital (n=31), Colorado State University (n=31), University of California, San Francisco (n=19), University of Ulsan (n=19), University of Modena and Reggio Emilia (n=17), Harvard Medical School (n=15), Queen Elizabeth’s Hospital (n=15), and University of Miami (n=15), respectively (Figure 2(a)). According to the citation report, Mayo Clinic’s articles were cited the most, namely, 1408 times, followed by the National Jewish Health, which was cited 858 times, and the University of California, San Francisco, 851 (Figure 2(b)).Figure 2
Highest impact institutions. (a) The top 10 institutions (publications). (b) The top 10 institutions (citations). (c) Institutional collaborations.
(a)(b)(c)VOSviewer software was used to analyze the extent of cooperative relations between institutions. The institution with the most links, i.e., the highest link strength was recorded by the National Jewish Health Organization (n=131), followed by the University of Colorado (n=123), Mayo Clinic (n=119), and Brigham and Women’s Hospital (n=117). In the VOSviewer software, the width of the line reflects the close relationship of interinstitution cooperation. The National Jewish Health had close collaborations with the University of Colorado and Mayo Clinic. Mayo Clinic had large collaborations with National Jewish Health, University of Colorado, Brigham and Women’s Hospital, and Harvard Medical School (Figure 2(c)).


## 3.4. Journals Analysis

All 596 articles in this study were published in 123 journals. Among these, the journals which had published at least 20 articles on the topic accounted for 73.8% of the total (Table1). The five journals with the most articles on the topic were Annals of the Rheumatic Diseases, Arthritis & Rheumatology, American Journal of Respiratory and Critical Care Medicine, Rheumatology, and Arthritis and Rheumatism. Moreover, articles in the Annals of the Rheumatic Diseases have been cited the most. More than 20 journals published on RA-ILD, and the average impact factor was 11.8, indicating a high level of reliability of the included studies.Table 1
Active journals on rheumatoid arthritis-associated interstitial lung disease.
JournalArticleTotal citationMean citationImpact factorAnnals of the Rheumatic Diseases933383.6319.103Arthritis & Rheumatology752192.9210.995American Journal of Respiratory and Critical Care Medicine535149.7021.405Rheumatology3871018.6820.543Arthritis and Rheumatism3655215.335.532European Respiratory Journal3053717.9016.671Clinical Rheumatology1824813.784.098Chest1248540.422.878Internal Medicine1115614.182.048Clinical and Experimental Rheumatology10989.804.473Respiratory Medicine825832.253.772Modern Rheumatology810813.503.023Seminars in Arthritis and Rheumatism620834.675.532Rheumatology International615425.672.631Journal of Rheumatology614724.504.666New England Journal of Medicine613322.1791.245PLos one612721.173.24Scandinavian Journal of Rheumatology610417.333.641Respirology69215.336.424JCR-Journal of Clinical Rheumatology6264.333.517


## 3.5. Research Status and Analysis

VOSviewer software was used to analyze the cooccurrence analysis of keywords in the RA-ILD research articles. When the minimum number of keywords appearing in the publication was set to five, 72 keywords were selected and divided into four clusters:“Clinical-Features,” “Pathological-Features,” “Treatment,” and “Prevalence and mortality.” In the “Clinical-Features” cluster, the most common keywords were “pneumonia,” “idiopathic pulmonary-fibrosis,” and “prognosis.” In the “Pathological-Features” cluster, the most frequent keywords were “rheumatoid arthritis,” “interstitial lung disease,” and “fibrosis.” In the “treatment” cluster, the most frequent keywords were “classification,” “criteria,” and “safety.” In the “prevalence and mortality” cluster, the most frequent keywords were “prevalence,” “mortality,” and “risk” (Figure3(a)).Figure 3
Keyword analysis. (a) Cluster analysis of keywords. (b) Evolution of keyword frequency.
(a)(b)To better understand the dynamic process of the RA-ILD research trends, we evaluated the evolution of the keywords (Figure3(b)). We assigned colors based on the year the keyword appears in the article. For example, the yellow keyword appears later than the purple keyword. In the early stages, “idiopathic pulmonary fibrosis,” “alveolitis,” and “systemic sclerosis” were the main topics. Trends in recent years show that the terms “management,” “predictors,” “inflammation,” and “progress” are becoming more and more popular.


## 3.6. The 100 Most-Cited Publications

The 100 most-cited publications on RA-ILD were published between 1984 and 2020 (Table2). The analysis indicated that 2001-2005 was the period when most of these studies were published, with 41 publications, followed by 2016-2020, with 29 publications (Figure 4(a)).Table 2
The top 100 cited publications on rheumatoid arthritis-associated interstitial lung disease.
RankTitleAuthorJournalYearTotal citationCitation/year1Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based studyBongartz, T.Arthritis and Rheumatism2010324272Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung diseaseKim, E. J.European Respiratory Journal201028323.583Histopathologic pattern and clinical features of rheumatoid arthritis associated interstitial lung diseaseLee, H. KChest200524514.414Rheumatoid arthritis-interstitial lung disease-associated mortalityOlson, A. L.American Journal of Respiratory and Critical Care Medicine201122220.185Interstitial lung disease in recent onset rheumatoid arthritisGabbay, E.American Journal of Respiratory and Critical Care Medicine19972208.86Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics-a large multicentre UK studyKelly, C. A.Rheumatology201420525.637Progressive preclinical interstitial lung disease in rheumatoid arthritisGochuico, B. R.Archives of Internal Medicine200819814.148Rheumatoid arthritis-associated interstitial lung disease the relevance of histopathologic and radiographic patternKim, E. J.Chest200918914.549Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohortKoduri, G.Rheumatology201014912.4210Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumatoid arthritis: A systematic literature reviewRoubille, C.Seminars in Arthritis and Rheumatism201412615.7511Predictors of mortality in rheumatoid arthritis-associated interstitial lung diseaseSolomon, J. J.European Respiratory Journal201612420.6712MUC5B promoter variant and rheumatoid arthritis with interstitial lung diseaseJuge, P. A.New England Journal of Medicine20181082713Influence of anti-TNF therapy on mortality in patients with rheumatoid arthritis-associated interstitial lung disease: results from the British Society for Rheumatology Biologics RegisterDixon, W. G.Annals of the Rheumatic Diseases2010108914High-resolution computed-tomography of the lungs in patients with rheumatoid-arthritis and interstitial lung-diseaseMcdonagh, JBritish Journal of Rheumatology19941023.6415Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritisSuissa, S.Arthritis and Rheumatism2006955.9416Different risk factors between interstitial lung disease and airway disease in rheumatoid arthritisMori, S.Respiratory Medicine2012898.917A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortalityHyldgaard, C.Annals of the Rheumatic Diseases20178316.618Predictors of mortality in rheumatoid arthritis-related interstitial lung diseaseAssayag, D.Respirology20148310.3819Rheumatoid arthritis-associated interstitial lung disease: radiologic identification of usual interstitial pneumonia patternAssayag, D.Radiology2014779.6320Correlation between HRCT findings, pulmonary function tests and bronchoalveolar lavage cytology in interstitial lung disease associated with rheumatoid arthritisBiederer, J.European Radiology2004744.1121Association of fine specificity and repertoire expansion of anticitrullinated peptide antibodies with rheumatoid arthritis associated interstitial lung diseaseGiles, J. T.Annals of the Rheumatic Diseases2014718.8822Fibrosing interstitial pneumonia predicts survival in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD)Solomon, J. J.Respiratory Medicine2013717.8923Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years’ experience at a single centreYusof, M. M.Rheumatology20176913.824Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosisJuge, P. A.European Respiratory Journal20176913.825Rheumatoid arthritis (RA)-specific autoantibodies in patients with interstitial lung disease and absence of clinically apparent articular RAGizinski, A. M.Clinical Rheumatology2009685.2326Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkersDoyle, T. J.American Journal of Respiratory and Critical Care Medicine2015679.5727Leflunomide-induced interstitial lung disease: prevalence and risk factors in Japanese patients with rheumatoid arthritisSawada, T.Rheumatology2009665.0828Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control studyHozumi, H.BMJ open201363729The lung in rheumatoid arthritis focus on interstitial lung diseaseSpagnolo, P.Arthritis & Rheumatology20186215.530Abatacept in patients with rheumatoid arthritis and interstitial lung disease: a national multicenter study of 63 patientsFernandez-Diaz, C.Seminars in Arthritis and Rheumatism20186215.531Rheumatoid arthritis (RA) associated interstitial lung disease (ILD)O’Dwyer, D. N.European Journal of Internal Medicine2013626.8932Rheumatoid arthritis treatment and the risk of severe interstitial lung diseaseWolfe, F.Scandinavian Journal of Rheumatology200760433Rheumatoid arthritis complicated with acute interstitial pneumonia induced by leflunomide as an adverse reactionKamata, YInternal Medicine2004563.1134Morphologic and quantitative assessment of CD20+ B cell infiltrates in rheumatoid arthritis-associated nonspecific interstitial pneumonia and usual interstitial pneumoniaAtkins, S. R.Arthritis and Rheumatism2006553.4435Biomarkers of rheumatoid arthritis-associated interstitial lung diseaseChen, J.Arthritis & Rheumatology2015547.7136Acute exacerbation of preexisting interstitial lung disease after administration of etanercept for rheumatoid arthritisHagiwara, K.Journal of Rheumatology2007523.4737Nonspecific interstitial pneumonia pattern as pulmonary involvement of rheumatoid arthritisYoshinouchi, TRheumatology International2005492.8838Progressive decline of lung function in rheumatoid arthritis-associated interstitial lung diseaseZamora-Legoff, J. A.Arthritis & Rheumatology2017489.639Retrospective study of the clinical characteristics and risk factors of rheumatoid arthritis-associated interstitial lung diseaseZhang, Y. F.Clinical Rheumatology2017469.240Rheumatoid arthritis-interstitial lung disease in the United States: prevalence, incidence, and healthcare costs and mortalityRaimundo, K.Journal of Rheumatology2019451541The multifaceted aspects of interstitial lung disease in rheumatoid arthritisCavagna, L.Biomed Research International201345542Association of human leukocyte antigen with interstitial lung disease in rheumatoid arthritis: a protective role for shared epitopeFurukawa, H.PLos one2012454.543Clinical and radiological features of acute-onset diffuse interstitial lung diseases in patients with rheumatoid arthritis receiving treatment with biological agents: importance of PneuKameda, H.Internal Medicine2011454.0944Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohortsKiely, P.BMJ open20194414.6745High resolution computed tomography pattern of usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease: relationship to survivalYunt, Z. X.Respiratory Medicine2017448.846Interstitial lung disease in rheumatoid arthritis: recent advancesKim, D. S.Current Opinion in Pulmonary Medicine2006442.7547Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective reviewIqbal, K.Therapeutic Advances in Musculoskeletal Disease2015436.1448Clinical course and outcome of rheumatoid arthritis-related usual interstitial pneumoniaSong, J. W.Sarcoidosis Vasculitis and Diffuse Lung Diseases2013424.6749Increased levels of interleukin-33 associated with bone erosion and interstitial lung diseases in patients with rheumatoid arthritisZhu X. YCytokine2012424.250Incidence of and risk factors for interstitial pneumonia in patients with rheumatoid arthritis in a large Japanese observational cohort, IORRAShidara, K.Modern Rheumatology2010423.551Interstitial lung-disease in rheumatoid-arthritis - assessment with high-resolution computed-tomographyFujii, MJournal of Thoracic Imaging1993421.4552Patterns of interstitial lung disease and mortality in rheumatoid arthritisZamora-Legoff, J. A.Rheumatology2017418.253Standard and pocket-size lung ultrasound devices can detect interstitial lung disease in rheumatoid arthritis patientsCogliati, C.Rheumatology2014415.1354Potential risk of TNF inhibitors on the progression of interstitial lung disease in patients with rheumatoid arthritisNakashita, T.BMJ open2014415.1355A fatal case of acute exacerbation of interstitial lung disease in a patient with rheumatoid arthritis during treatment with tocilizumabKawashiri, S.Rheumatology International2012414.156Interstitial lung disease in patients with rheumatoid arthritis: comparison with cryptogenic fibrosing alveolitis over 5 yearsRajasekaran, A.Journal of Rheumatology2006412.5657Interstitial lung disease in patients with rheumatoid arthritis: a comparison with cryptogenic fibrosing alveolitisRajasekaran, B. A.Rheumatology2001401.958A roadmap to promote clinical and translational research in rheumatoid arthritis-associated interstitial lung disease a dance promote clinical and translational researchDoyle, T. J.Chest2014394.8859Rheumatoid arthritis-related interstitial lung disease (RA-ILD): methotrexate and the severity of lung disease are associated to prognosisRojas-serrano, J.Clinical Rheumatology2017387.660Rheumatoid arthritis associated interstitial lung disease: a reviewAssayag, D.Medicina-Buenos Aires2014384.7561Sonographic assessment of interstitial lung disease in patients with rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosusMoazedi-Fuerst, F.Clinical and Experimental Rheumatology2015375.2962Association of cross-reactive antibodies targeting peptidyl-arginine deiminase 3 and 4 with rheumatoid arthritis-associated interstitial lung diseaseGiles, J. T.PLos one2014374.6363Clinical and laboratory factors associated with interstitial lung disease in rheumatoid arthritisRestrepo, J. F.Clinical Rheumatology201535564Rheumatoid arthritis interstitial lung disease: mycophenolate mofetil as an antifibrotic and disease-modifying antirheumatic drugSaketkoo, L. A.Archives of Internal Medicine2008342.4365Survival and quality of life in rheumatoid arthritis-associated interstitial lung disease after lung transplantationYazdani, A.Journal of Heart and Lung Transplantation2014334.1366Rheumatoid arthritis-associated autoantibodies and subclinical interstitial lung disease: the multi-ethnic study of atherosclerosisBernstein, E. J.Thorax2016325.3367Nintedanib reduces pulmonary fibrosis in a model of rheumatoid arthritis-associated interstitial lung diseaseRedente, E. F.American Journal of Physiology-Lung Cellular and Molecular phy2018317.7568Profibrotic effect of IL-17A and elevated IL-17RA in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated lung disease support a direct role for IL-17A/IL-17RA in human fibZhang, J.American Journal of Physiology-Lung Cellular and Molecular phy2019301069Variable course of disease of rheumatoid arthritis-associated usual interstitial pneumonia compared to other subtypesNurmi, H. M.BMC Pulmonary Medicine201630570Risk of interstitial lung disease associated with leflunomide treatment in Korean patients with rheumatoid arthritisJu, J. H.Arthritis and Rheumatism200730271Anti-cyclic citrullinated peptide antibody is associated with interstitial lung disease in patients with rheumatoid arthritisYin, Y. F.PLos one2014293.6372A novel model of rheumatoid arthritis-associated interstitial lung disease in SKG miceKeith, R. C.Experimental Lung Research2012292.973Treatment strategies for a rheumatoid arthritis patient with interstitial lung diseaseKelly, C.Expert Opinion on Pharmacotherapy200828274Rheumatoid arthritis disease activity predicting incident clinically apparent rheumatoid arthritis-associated interstitial lung disease: a prospective cohort studySparks, J. A.Arthritis & Rheumatology201927975Changes in peripheral CD19(+) Foxp3(+) and CD19(+) TGF beta(+) regulatory B cell populations in rheumatoid arthritis patients with interstitial lung diseaseGuo, Y. Y.Journal of Thoracic Disease2015273.8676Interstitial lung disease in patients with rheumatoid arthritis: spontaneous and drug inducedHallowell, R. W.Drugs2014273.3877HLA-A∗31:01 and methotrexate-induced interstitial lung disease in Japanese rheumatoid arthritis patients: a multidrug hypersensitivity marker?Furukawa, H.Annals of the Rheumatic Diseases201327378Asymptomatic preclinical rheumatoid arthritis-associated interstitial lung diseaseChen, J.Clinical & Developmental Immunology201327379Rheumatoid arthritis-associated interstitial lung disease and idiopathic pulmonary fibrosis: shared mechanistic and phenotypic traits suggest overlapping disease mechanismsPaulin, F.Revista de Investigacion Clinica-Clinical and Translational Investig2015263.7180Lymphoid interstitial pneumonia in juvenile rheumatoid-arthritisLovell, D.Journal of Pediatrics1984260.6881Ultrasound screening for interstitial lung disease in rheumatoid arthritisMoazedi-Fuerst, F. C.Clinical and Experimental Rheumatology2014253.1382Interstitial pneumonia due to cytomegalovirus following low-dose methotrexate treatment for rheumatoid-arthritisAglas, F.Arthritis and Rheumatism1995250.9383Therapeutic management of patients with rheumatoid arthritis and associated interstitial lung disease: case report and literature reviewDiamanti, A. P.Therapeutic Advances in Respiratory Disease2017244.884Interstitial lung disease in rheumatoid arthritis: response to IL-6R blockadeMohr, M.Scandinavian Journal of Rheumatology2011242.1885Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: a multicentre retrospective studyManfredi, A.Internal Medicine Journal20202311.586Recent advances in the pathogenesis, prediction, and management of rheumatoid arthritis-associated interstitial lung diseaseJohnson, C.Current Opinion in Rheumatology2017234.687Abatacept therapy in rheumatoid arthritis with interstitial lung diseaseMera-Varela, A.Journal of Clinical Rheumatology2014232.8888The clinical significance of HRCT in evaluation of patients with rheumatoid arthritis-associated interstitial lung disease: a report from ChinaZou, Y. Q.Rheumatology International2012232.389A case of adalimumab-associated interstitial pneumonia with rheumatoid arthritisYamazaki, H.Modern Rheumatology2010231.9290Prevalence and effects of emphysema in never-smokers with rheumatoid arthritis interstitial lung diseaseJacob, J.Ebiomedicine2018225.591Association of disease activity with acute exacerbation of interstitial lung disease during tocilizumab treatment in patients with rheumatoid arthritis: a retrospective, case-control studyAkiyama, M.Rheumatology International2016223.6792Predicting outcomes in rheumatoid arthritis related interstitial lung diseaseJacobt, J.European Respiratory Journal201921793Plasma miRNA expression profiles in rheumatoid arthritis associated interstitial lung diseaseOka, S.BMC Musculoskeletal Disorders2017214.294Patients with limited rheumatoid arthritis-related interstitial lung disease have a better prognosis than those with extensive diseaseSathi, N.Rheumatology2011211.9195Risk of serious infection in patients with rheumatoid arthritis-associated interstitial lung diseaseZamora-Legoff, J. A.Clinical Rheumatology2016203.3396Possible effect of abatacept on the progression of interstitial lung disease in rheumatoid arthritis patientsNakashita, T.Respiratory Investigation2016203.3397Up-to-date information on rheumatoid arthritis-associated interstitial lung diseaseSuda, T.Clinical Medicine Insights-Circulatory Respiratory and Pulmonary2015202.8698Eternacept for the treatment of patients with rheumatoid arthritis and concurrent interstitial lung diseaseHorai, Y.Journal of Clinical Pharmacy and Therapeutics201220299Myofibroblasts and S-100 protein positive cells in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial pneumoniaYoshinouchi, T.European Respiratory Journal1999200.87100The performance of the GAP model in patients with rheumatoid arthritis associated interstitial lung diseaseMorisset, J.Respiratory Medicine2017193.8Figure 4
Top 100 most-cited publications on RA-ILD. (a) Year of publication. (b) Distribution of country. (c) Institution analysis. (e) Publication topics.
(a)(b)(c)(d)The 100 most-cited articles were from 18 countries and regions. Thirty-four articles were published by authors from the USA, followed by Japan (n=20), the United Kingdom (n=11), China (n=7), Italy (n=5), Canada (n=3), Austria (n=3), Spain, France, and Germany (n=2), and Mexico, Argentina, Australia, Bangladesh, Denmark, Finland, and Ireland (n=1) (Figure 4(b)).Of these 100 articles, the Mayo Clinic Medicine and National Jewish Health each generated seven publications, resulting in their being the most represented institutions on this topic, followed by the University of California in San Francisco (n=5) and Queen Elizabeth Hospital (n=4) (Figure 4(c)).Overall, there were 52 different journals which published the 100 articles. “Rheumatology” was the most productive journal, with 8 articles and 632 citations, followed by “Arthritis and Rheumatism,” with five articles and 529 citations (Table3).Table 3
Journal with more than three of the 100 most-cited publications on rheumatoid arthritis-associated interstitial lung disease.
JournalArticleTotal citationMean citationImpact factorRheumatology8632793.494Arthritis and Rheumatism5529105.85.532Clinical Rheumatology520741.44.098European Respiratory Journal5517103.416.671Annals of the Rheumatic Diseases428972.2519.103Arthritis & Rheumatology419147.7510.995Respiratory Medicine422355.753.772Rheumatology International413533.752.631When considering the individual authors’ academic contributions, Jay H Ryu, provided 11 publications, followed by Joyce C Lee and Eric L Matteson, each with 8 publications (Table4).Table 4
Most frequent authors of the 100 most-cited publications on rheumatoid arthritis-associated interstitial lung disease.
AuthorArticleFirst authorLast authorCo-authorRyu, Jay H.11000Lee, Joyce S.8026Matteson, Eric L.8242Brown, Kevin K.6024Collard, Harold R.6015Kelly, Clive A.6240Kim, Dong Soon.6114Rosas, Ivan O.6033Solomon, Joshua J.6213Doyle, Tracy J.5211Ascherman, Dana P.5023Fischer, Aryeh.5000Swigris, Jeffrey J.5023The most common research topic on RA-ILD addressed the clinical description (n=44), followed by clinical research (n=13), diagnosis (n=8), mortality (n=7), and risk factors (n=6) (Figure 4(d)).


## 4. Discussion

ILD is one of the most common complications of RA and poses a great challenge to clinicians and researchers [16]. The prevalence of RA-ILD ranged from 1% to 58% in the different studies, which was related to the diagnostic techniques used and the study population that was included [17–19]. According to the literature, there are many risk factors for RA-ILD, including male sex, smoking, older age, high disease activity of RA, characteristics of extra-articular diseases (subcutaneous nodules), and seropositive RA autoantibodies (rheumatoid factor and anticitrulline protein antibody) [2, 20–23]. The most common presenting symptoms include exertional dyspnea, tachypnea, and bibasilar inspiratory crackles. In the advanced stages of the disease, symptoms of cyanosis, edema, and pulmonary hypertension may occur, leading to a reduced quality of life [24].In addition to its impact on the quality of life, RA-ILD places a huge burden on the medical system, with an average total medical cost of more than $170,000 per patient over five years [8]. Our statistical and quantitative analysis shows a gradual increase in RA-ILD research results from 2011 to 2020, with more researchers and physicians focusing on this area of research. Despite the wide range of RA-ILD research, an analysis of the current status and trends in RA-ILD research is not clear. In this study, we analyzed, discussed, and described the current status, priorities, and trends of RA-ILD research. At the same time, our study will help RA-ILD researchers gain a more comprehensive understanding of the current state of RA-ILD research and thus guide the direction of future research.


### 4.1. Publication Trends in RA-ILD Research

The number of articles related to RA-ILD has increased rapidly over the last 10 years. Globally, the USA ranks first in terms of the number of publications and citations, indicating that the USA has led to research on RA-ILD in the past few years. In terms of institutional contributions, the institution with the highest publication output is the Mayo Clinic (USA) and ranked first in the total citations. This reflects the institution’s leadership in the field of RA-ILD research. Analysis of cooperation between countries and institutions shows that regional clusters are usually geographically specific. As a leader in the world economy and science, the USA has the most frequent cooperation with Japan, France, China, and South Korea. Researchers working on RA-ILD should pay close attention to them and collaborate with these institutions and countries. Annals of the Rheumatic Diseases, Arthritis & Rheumatology, American Journal of Respiratory and Critical Care Medicine, Rheumatology, and Arthritis and Rheumatism are the five most prolific journals in RA-ILD.


### 4.2. Research Foci

Keyword analysis results showed that RA-ILD, rheumatoid arthritis, interstitial lung disease, and pneumonia were keyword cluster centers. In the early stages, “idiopathic pulmonary fibrosis,” “alveolitis,” and “systemic sclerosis” were the main topics. In recent years, more common keywords have included “management,” “predictors,” “inflammation,” and “progression.”


### 4.3. The Most-Cited Articles

The most-cited publication in RA-ILD was the 2010 article in Arthritis and Rheumatism by Bongartz et al. with 324 citations: “Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study,” which introduced incidence, risk factors, and mortality of RA-ILD [2]. The mean follow-up time of 582 RA patients and 603 non-RA patients was 16.4 years and 19.3 years, respectively. The lifetime risk of ILD was 7.7% in patients with rheumatoid arthritis and 0.9% in those without rheumatoid arthritis. Studies have shown that the prevalence of ILD is higher in older male patients and in individuals with more severe RA parameters. RA patients diagnosed with ILD have poorer survival than RA patients without ILD, and ILD accounts for approximately 13% of the excess mortality in RA patients compared to the general population.“Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease” by Kim et al. in 2010 was the second most-cited article with 283 citations [16]. The authors determined that the pattern of common interstitial pneumonia (IP) found on high-resolution computed tomography (HRCT) is important for the prognosis of RA-ILD. Eighty-two patients with RA-ILD were identified retrospectively. “We determined the relationship between survival and the pattern of IP common on HRCT and compared it with patients diagnosed radiologically with idiopathic pulmonary fibrosis. Twenty (24%) of the 82 patients with RA-ILD had definite common IP. Survival in patients with RA-ILD was lower than that in patients without this pattern, similar to the survival of patients with idiopathic pulmonary fibrosis. In addition, a clear pattern of common IP on HRCT was associated with poor survival. Analysis of feature-specific HRCTs showed that traction bronchiectasis and cellular fibrosis were associated with poor survival. Women and a higher baseline carbon monoxide lung diffusing capacity were associated with better survival.”“Histopathological and clinical features of interstitial lung disease associated with rheumatoid arthritis” by Lee et al. was the third most-cited article with 245 citations [25]. The authors studied the histopathological patterns and clinical characteristics of patients with RA-ILD according to the American Thoracic Society/European Respiratory Society consensus classification of idiopathic IP. “Eighteen patients with RA who underwent surgical lung biopsy for suspected ILD were included in this study. This study revealed diverse histopathological findings. Ten patients had a common interstitial pneumonia (UIP) pattern, six patients had a nonspecific interstitial pneumonia (NSIP) pattern, and two patients had inflammatory airway disease with tissue-type pneumonia. Thus, the UIP pattern appears to be more common than the NSIP pattern in our study population.”


### 4.4. Limitations

Our study had several limitations. First, we extracted information related to RA-ILD from the Core Collection database of the Web of Science. It is possible that some influential publications were not included in this database and were therefore excluded from our study. Second, the date of our retrieval and extraction of data was July 1, 2021. Part of the data correspond to dynamic changes, but the trend of changes will not be extensive. Third, we retained only English articles in our search strategy.


## 4.1. Publication Trends in RA-ILD Research

The number of articles related to RA-ILD has increased rapidly over the last 10 years. Globally, the USA ranks first in terms of the number of publications and citations, indicating that the USA has led to research on RA-ILD in the past few years. In terms of institutional contributions, the institution with the highest publication output is the Mayo Clinic (USA) and ranked first in the total citations. This reflects the institution’s leadership in the field of RA-ILD research. Analysis of cooperation between countries and institutions shows that regional clusters are usually geographically specific. As a leader in the world economy and science, the USA has the most frequent cooperation with Japan, France, China, and South Korea. Researchers working on RA-ILD should pay close attention to them and collaborate with these institutions and countries. Annals of the Rheumatic Diseases, Arthritis & Rheumatology, American Journal of Respiratory and Critical Care Medicine, Rheumatology, and Arthritis and Rheumatism are the five most prolific journals in RA-ILD.


## 4.2. Research Foci

Keyword analysis results showed that RA-ILD, rheumatoid arthritis, interstitial lung disease, and pneumonia were keyword cluster centers. In the early stages, “idiopathic pulmonary fibrosis,” “alveolitis,” and “systemic sclerosis” were the main topics. In recent years, more common keywords have included “management,” “predictors,” “inflammation,” and “progression.”


## 4.3. The Most-Cited Articles

The most-cited publication in RA-ILD was the 2010 article in Arthritis and Rheumatism by Bongartz et al. with 324 citations: “Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study,” which introduced incidence, risk factors, and mortality of RA-ILD [2]. The mean follow-up time of 582 RA patients and 603 non-RA patients was 16.4 years and 19.3 years, respectively. The lifetime risk of ILD was 7.7% in patients with rheumatoid arthritis and 0.9% in those without rheumatoid arthritis. Studies have shown that the prevalence of ILD is higher in older male patients and in individuals with more severe RA parameters. RA patients diagnosed with ILD have poorer survival than RA patients without ILD, and ILD accounts for approximately 13% of the excess mortality in RA patients compared to the general population.“Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease” by Kim et al. in 2010 was the second most-cited article with 283 citations [16]. The authors determined that the pattern of common interstitial pneumonia (IP) found on high-resolution computed tomography (HRCT) is important for the prognosis of RA-ILD. Eighty-two patients with RA-ILD were identified retrospectively. “We determined the relationship between survival and the pattern of IP common on HRCT and compared it with patients diagnosed radiologically with idiopathic pulmonary fibrosis. Twenty (24%) of the 82 patients with RA-ILD had definite common IP. Survival in patients with RA-ILD was lower than that in patients without this pattern, similar to the survival of patients with idiopathic pulmonary fibrosis. In addition, a clear pattern of common IP on HRCT was associated with poor survival. Analysis of feature-specific HRCTs showed that traction bronchiectasis and cellular fibrosis were associated with poor survival. Women and a higher baseline carbon monoxide lung diffusing capacity were associated with better survival.”“Histopathological and clinical features of interstitial lung disease associated with rheumatoid arthritis” by Lee et al. was the third most-cited article with 245 citations [25]. The authors studied the histopathological patterns and clinical characteristics of patients with RA-ILD according to the American Thoracic Society/European Respiratory Society consensus classification of idiopathic IP. “Eighteen patients with RA who underwent surgical lung biopsy for suspected ILD were included in this study. This study revealed diverse histopathological findings. Ten patients had a common interstitial pneumonia (UIP) pattern, six patients had a nonspecific interstitial pneumonia (NSIP) pattern, and two patients had inflammatory airway disease with tissue-type pneumonia. Thus, the UIP pattern appears to be more common than the NSIP pattern in our study population.”


## 4.4. Limitations

Our study had several limitations. First, we extracted information related to RA-ILD from the Core Collection database of the Web of Science. It is possible that some influential publications were not included in this database and were therefore excluded from our study. Second, the date of our retrieval and extraction of data was July 1, 2021. Part of the data correspond to dynamic changes, but the trend of changes will not be extensive. Third, we retained only English articles in our search strategy.


## 5. Conclusions

Quantitative analysis showed that in the past 10 years, global research on RA-ILD has increased rapidly. Of all the countries, the USA publishes most articles on RA-ILD.The USA has contributed the most to the RA-ILD literature. Mayo Clinic, National Jewish Health, Brigham and Women’s Hospital, Colorado State University, and University of California, San Francisco are the most prolific institutions associated with RA-ILD research. Annals of the Rheumatic Diseases, Arthritis & Rheumatology, American Journal of Respiratory and Critical Care Medicine, Rheumatology, and Arthritis and Rheumatism are the top five most popular journals on RA-ILD publications.



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