Relationship Between Annual Airbornepollen Levels (1974–2014) and the Occurrence of Idiopathic Dilated Cardiomyopathy, Myasthenia Gravis, Polymyositis/ Dermatomyositis, and Vasculitis Syndrome Based on the National Registry Database of Specific Intractable Disease in Japan: A Retrospective Study

Research Article

Austin J Clin Immunol. 2022; 8(1):1048.

Relationship Between Annual Airbornepollen Levels (1974–2014) and the Occurrence of Idiopathic Dilated Cardiomyopathy, Myasthenia Gravis, Polymyositis/ Dermatomyositis, and Vasculitis Syndrome Based on the National Registry Database of Specific Intractable Disease in Japan: A Retrospective Study

Akira Awaya1,2*, Yoshiyuki Kuroiwa3,4,5

1Dermatology & Epidemiology Research Institute (DERI), 4978 Totsuka-cho, Totsuka-ku, Yokohama, Kanagawa, Japan

2Department of Genome System Science, Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama, Kanagawa, Japan

3Department of Neurology, University Hospital Mizonokuchi, Teikyo University School of Medicine, 5-1-1, Futago, Takatsu-ku, Kawasaki, Kanagawa, Japan

4Department of Medical Office, Ministry of Finance, 3-1-1, Kasumigaseki, Chiyoda-ku, Tokyo, Japan

5Yokohama City University Graduate School of Medicine, 3-9, Fukuura, Kanazawa-ku, Yokohama, Japan

*Corresponding author: Akira Awaya, Dermatology & Epidemiology Research Institute (DERI), Totsuka-cho, Totsuka-ku, Yokohama 244-0003, Japan

Received: June 23, 2022; Accepted: June 28, 2022; Published: June 30, 2022

Abstract

Background: In Japan, pollen counts increased between 1977 and 1987, including three peaks (1978-1980, 1982, 1984-1986) coinciding with Kawasaki disease (KD) outbreaks. KD and related diseases may be related to pollen exposure (PE).

Methods and Results: To elucidate the effects of PE on outbreaks of intractable muscular diseases and vasculitis syndromes, we evaluated the annual occurrence of disorders in relation to pollen counts using data from a national database. Specifically, we evaluated the occurrence of idiopathic dilated cardiomyopathy (IDCM), myasthenia gravis (MG), polymyositis/dermatomyositis (PM/DM), Takayasu arteritis (TAK), granulomatosis with polyangiitis (GPA), and periarteritis nodosa (PAN). While we did not observe increased disease rates during the first pollen count peak (1978-1980), increased rates of all evaluated diseases were observed during the 1982 and 1984-86 peaks. Furthermore, simultaneous outbreaks coincided with 10pollen count peaks between 1988 and 2013. We observed significant correlations between the annual number of newly registered patients (nRPs) with IDCM, MG, PM/DM, and PAN and annual pollen levels (PL). Significant correlations were also observed between nRPs and the annual PL measured with a lag of 2 years for IDCM and GPA, 1–4 years for PAN, and 6 years for MG, PM/DM, TAK, GPA, and PAN.

Conclusion: Data suggest that the cumulative effects of PE within 6 years prior to diagnosis might possibly trigger onset of muscular specific intractable diseases.

Keywords: Idiopathic Dilated Cardiomyopathy (IDCM); Myasthenia Gravis (MG); Polymyositis/Dermatomyositis (PM/DM); Muscular Specific Intractable Diseases; Takayasu Arteritis (TAK); Granulomatosis with Polyangiitis (GPA), and Periarteritis Nodosa (PAN); Kawasaki Disease (KD); Pollen Levels (PL); Pollen Exposure (PE); Tokyo Metropolitan; Sagamihara City of Kanagawa Prefecture

Abbreviations

IDM: Idiopathic Dilated Cardiomyopathy; MG: Myasthenia Gravis; PM/DM: Polymyositis/Dermatomyositis; TAK: Takayasu Arteritis; GPA: Granulomatosis with Polyangiitis; PAN: Periarteritis Nodosa; SIDs: Specific Intractable Diseases; KD: Kawasaki Disease; PIDs: Pollen-Induced Diseases; Present RPs: Presently Registered Patients; Newly RPs: Newly Registered Patients; AP: Airborne Pollen; PL: Pollen Levels; PE: Pollen Exposure.

Introduction

Idiopathic dilated cardiomyopathy (IDCM) is one of the most common cardiovascular diseases [1,2]. Both IDCM and two other types of cardiomyopathy (hypertrophic cardiomyopathy and restrictive cardiomyopathy) have been registered as specific intractable diseases (SIDs) in Japan [3]. IDCM can be diagnosed only after differential diagnosis regarding cardiac failures such as various types of cardiomyopathy and myocarditis [4]. There is evidence that infants with an allergic constitution may be more susceptible to Kawasaki disease (KD), a systemic vasculitis related to IDCM [5-10].

Previous studies on KD have evaluated the relationship between development of this disease and weekly, monthly, and annual airborne pollen (AP) exposure [6-10]. During 1977–1987, KD patients in all of Japan, specifically in Tokyo and Kanagawa, showed triphasic outbreaks of KD (1978-79, 1982, 1984-86), with the highest peak in 1982. These outbreaks coincided exactly with triphasic peaks of AP release [6,9,10]. KD may be a pollen-induced delayed-type hypersensitivity disease, and suppressed onset may be observed during influenzaepidemics [6-10].

Successive epidemiological studies have evaluated the occurrence of another vasculitis, Takayasu arteritis (TAK) [11]. Research has shown an increase in TAK occurrence starting in 1984,based on data from national databases for presently registered patients (present RPs), defined as the total patient-registry number in each fiscal year, and newly registered patients (newly RPs), defined as the difference between the total patient-registry number in each fiscal year as compared to the previous year. This research helped distinguish sudden TAK outbreaks, involving 590 newly RPs in 2,985 present RPs in just1 year (1984).

Continued epidemiological research has been conducted regarding approximately40 SIDs to clarify the relationship between the annual occurrence of SIDs and annual AP exposure during 1974-2014. This research specifically evaluated vasculitis syndromes such as TAK, Behçet’s disease, Buerger’s disease or thromboangiitis obliterans, granulomatosis with polyangiitis (GPA), and periarteritis nodosa (PAN), as well as connective tissue diseases accompanying autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid vasculitis, scleroderma, sarcoidosis, and pemphigus, and a plastic anemia [11]. A 2019 study further evaluated the occurrence of digestive disorders including inflammatory bowel disease, ulcerative colitis (UC), Crohn’s disease (CD), primary biliary cirrhosis (PBC), fulminant hepatitis, and severe acute pancreatitis, as well as interstitial pneumonia, idiopathic thrombocytopenic purpura, amyloidosis and a plastic anemia [12].

We now further report this research with a manuscript concerning muscular intractable diseases such as IDCM, myasthenia gravis, and polymyositis/dermatomyositis (PM/DM) and the disorders TAK, Behçet’s disease, Buerger’s disease, GPA, and PAN, and a plastic anemia, too, which are reported to be associated with these muscular diseases, as cited below. Previous studies have reported on the relation between IDCM and TAK [13], inflammatory dilated cardiomyopathy (DCM) andeosinophilic GPA [14], and autoimmune or autoinflammatory diseases and myocarditis, such as sarcoidosis, Behçet’s disease, eosinophilic GPA, myositis, and SLE [15].

In this research, we examined the relationship between upward peaks of AP released in the Bunkyo-City area of Tokyo, in the whole area of Tokyo Metropolitan, and in Sagamihara City of Kanagawa Prefecture in relation to the increase in the annual number of newly RPs during 1974-2014. The aim of our study was to evaluate the associations between AP exposure peaks and the occurrence of immune-related, principal 40 SIDs including IDCM, MG, PM/DM, vasculitis syndrome, connective tissue diseases, gastroenterological diseases, neuro intractable diseases and so on in Japan. We hypothesized that these immune-related diseases might belong to the class of pollen-induced diseases (PIDs), or “pollen diseases,” because so far accumulated data have suggested that these conditions may be triggered when susceptible patients receive AP exposure that exceed the pollen-responsive threshold of the individuals, and reach a starting line to development of diseases.

Materials and Methods

Since 1974, the Japanese governmental authority (JIDRF) has assigned certificates to SID patients to support their treatment financially following registration in a national database [3]. The homepage of the JIDRF reports the “numbers of recipient certificates issued for specific disease treatment” based on registration beginning in 1974 or 1975, 1983 or 1984, and so on until 2014. The data show the number of presently RPs in the current fiscal year as well as the number of newly RPs relative to the previous fiscal year for all the major SIDs. These increments could be negative if the number of presently RPs in the present fiscal year was smaller than that in the previous fiscal year, which occurs occasionally. Since KD is not included in the list of SIDs, the number of KD patients in every calendar year was downloaded from the homepage of the Department of Public Health at Jichi Medical University [16]. This study was performed in accordance with the ethical principles for medical research outlined in the Declaration of Helsinki 1964 and subsequent revisions (https:// www.wms.net/).

Data on AP release were provided by Dr. Yozo Saito, Dr. Hiroshi Yasueda, and Professor Norio Sahashi. Dr. Saito gathered the AP data from data at the research unit in the Tokyo Medical Dental University Graduate School of Medicine, Bunkyo-City, Tokyo, and Dr. Yasueda surveyed AP data based on the research at the National Hospital Organization Sagamihara National Hospital, Sagamihara, Kanagawa. The AP data in Tokyo Metropolis were collected from 12 sites in Tokyo and were donated by Mr. Hiroshi Kaneko. The AP data were downloaded after administrative information disclosures from the website of the Tokyo Metropolitan Institute of Public Health [17].

In the present study, data of numbers of SID patients in all the Japan were imported into tables in Microsoft Excel. This data was used to create figures of line graphs for each SID. These figures represent annual numbers of presently RPs as well as newly RPs, and the scattered pollen counts in three areas in Japan (the Bunkyo-City area of Tokyo, the whole area of Tokyo Metropolitan, and Sagamihara City in Kanagawa).

A correlation analysis was performed for each SIDs, to evaluate the association between the annual number of newly RPs in each patient-registry year “x” during 1974–2014, and the annual amount of AP levels in Tokyo and Sagamihara, measured in the same year as the patient-registry data. A correlation shift analysis was also performed between the annual number of newly RPs in each patientregistry year “x” between 1975 and 2014 and the annual AP levels in both cities measured “α” years prior to the patient-registry year “x”(“α”=1~20). Correlation coefficients and p values were calculated using the Excel function PEARSON via the method described in the brochure http://imnstir.blogspot.com/2014/04/p.htm. A statistically significant positive correlation was defined as p<0.05. Marginally significant associations that indicated a possible positive tendency (0.05≤p≤0.10) were also reported for reference.

Results

Occurrence of Upward Peaks in the Line Graphs of the Annual Number of Newly RPs for Ten SIDs in Relation to the Annual Levels of AP Scatter

The five line graphs in our figures for muscular SIDs, IDCM (Figure 1), MG (Figure 2), PM/DM (Figure 3), and the disorders TAK, Behçet’s disease, Buerger’s diseas and a plastic anemia (Figure 4), GPA (Figure 5), and PAN (Figure 6) consist of two line graphs visualizing the annual patient-registry data for presently RPs and newly RPs, and three line graphs visualizing the annual amount of AP scatter measured in three geographical areas. Our earlier research report regarding 11 SIDs showed only two line graph indicating change in the numbers of presently RPs and newly RPs for vasculitis syndrome and connective tissue disorders (including TAK, Behçet’s disease, Buerger’s disease, GPA, PAN, SLE, rheumatoid vasculitis, scleroderma, sarcoidosis, pemphigus) and a plastic anemia, occurring between 1974 and 2014 [11].