Changes in fractional exhaled nitric oxide, forced expiratory volume in one second, and forced oscillation technique parameters over three years in adults with bronchial asthma managed under Yokohama Seibu Hospital's coordinated care system.

BACKGROUND: In western Yokohama, our hospital and primary care clinics manage adults with asthma via a coordinated care system. We investigated the changes in the fractional expired nitric oxide (FeNO), forced expiratory volume in 1 second (FEV1), and forced oscillation technique (FOT) parameters over 3 years in a cohort of patients in our collaborative system. METHODS: From 288 adults with well controlled asthma managed under the Yokohama Seibu Hospital coordinated care system between January 2009 and May 2018, we selected 99 subjects to undergo spirometry, FeNO and FOT testing over 3 years and analyzed the changes in these parameters. RESULTS: Of the 99 patients enrolled, 17 (17.2%) experienced at least one exacerbation (insufficiently controlled (IC)), whereas, 82 (82.8%) remained in well controlled during the 3-year study period. Of well-controlled patients, 54 patients (54.5%) met the criteria for clinical remission under treatment (CR); the remaining 28 patients did not meet the CR criteria (WC). There were no differences in FeNO, FEV1, or FOT parameters at baseline among the IC, WC, and CR groups. The levels of FEV1 decreased gradually, whereas the levels of FeNO decreased significantly over 3 years. The levels of percent predicted FEV1 (%FEV1) significantly increased. We also observed significant improvement in FOT parameters; reactance at 5 Hz (R5), resonant frequency (Fres), and integral of reactance up to the resonant frequency (AX). The CR group demonstrated significant relationships between the change in FeNO and the change in FEV1 and between the change in FEV1 and the change in FOT parameters. No significant correlations emerged in the IC or WC group. CONCLUSION: The decrease in FeNO and increase in %FEV1, we observed in all study participants suggest that the coordinated care system model benefits patients with asthma. Although it is difficult to predict at baseline which patients will experience an exacerbation, monitoring changes in FeNO and FEV1 is useful in managing patients with asthma. Furthermore, monitoring changes in R5, Fres, and AX via forced oscillation technique testing is useful for detecting airflow limitation.

[THE RELATIONSHIP AMONG BRONCHIAL HYPERSENSITIVITY, BRONCHIAL HYPER REACTIVITY, AND BRONCHIAL HYPERRESPONSIVENESS IN ASTOGRAPH].

BACKGROUND: Bronchial hyperresponsiveness testing is useful for diagnosing and predicting the risk of bronchial asthma attacks. The Astograph is a tidal breathing method often used in as bronchial provocation testing in Japan. The minimum methachorine dose (Dmin) indicates bronchial sensitivity and is used mainly as an index of bronchial hyperresponsiveness. However, Dmin does not measured hyperresponsiveness, it cannot be compared directly with PC20 in standard methods using FEV1. METHODS: We investigated the relationship among sensitivity, reactivity, and hyperresponsiveness with the Astograph. We recruited 142 patients with confirmed or suspected bronchial asthma from outpatient clinic at St. Marianna University School of Medicine, Yokohama City Seibu Hospital. We calculated Dmin, SGrs/Grscont, PD35Grs, and PD15Grs compared them as bronchial hyperresponsiveness indices. RESULTS: Subjects had suspected asthma (n=103), or required assessment of asthma remission (n=39). There were significant relationships between logDmin and logPD35Grs (r=0.838, p<0.001), and between parameters and SGrs/Grscont (log PD35Grs r=-0.504, p<0.001, strong, logDmin: r=-0.191, p=0.023, weaker). Among subjects positive for hypersensitivity, (Dmin<10), 38 (36.5%) showed negative hyperresponsiveness (PD35Grs>25). PD15Grs was a strongly and significantly correlated with Dmin and PD35Grs. The ROC curve to detect PD35Grs<25, showed that the cutoff of PD15Grs was 10.7 (AUC 0.983, sensitivity 0.984, specificity 0.905). CONCLUSION: In Astograph, evaluation of bronchial hyperresponsiveness, we focused on relationship differences between sensitivity and reactivity, and hyperresponsiveness. We revealed the usefulness of the PD15Grs evaluation method.

[THE INFLUENCE OF SENSITIZATION TO ASPERGILLUS AND ALTERNARIA IN ADULT BRONCHIAL ASTHMATICS MANAGED VIA YOKOHAMA CITY SEIBU HOSPITAL'S COORDINATED-CARE SYSTEM].

BACKGROUND: The sensitizations to various fungal allergens influence to exacerbation of bronchial asthma. Aspergillus (Asp) and Alternaria (Alt) were one of important fungal allergens for asthma. AIM AND METHODS: To investigate the influence of sensitization to Asp or Alt in adult asthmatics managed via our asthma coordinated-care system, we recruited 119 patients (91 women) who were measured IgE for Asp (IgE-Asp) and IgE for Alt (IgE-Alt) at three times during two years,Results: In 119 patients, we detected positive IgE for Asp (IgE-Asp(+)) in 19 patients and positive IgE for Alt (IgE-Alt(+)) in 11 patients. 9 patients showed positive both of them. During two years, 7 patients became positive IgE-Asp and 3 cases became negative. And also, 3 cases became positive IgE-Alt and 3 cases became negative. At baseline, serum IgE, IgG4, and inhaled corticosteroid (ICS) dose of the group with IgE-Asp (+) or IgE-Alt (+), were significant higher than those of negative group. Among three groups, there was no significant change about other parameters at baseline, exacerbation frequency, or the change of parameters during two years. CONCLUSION: The sensitizations to Asp or Alt were present in 19 asthmatics (16%) managed via our coordinate-care system. During 2 years, there was not significant change at exacerbation frequency among three groups, but the levels of IgE, IgG4, or ICS dose were significantly higher at IgE-Asp (+) or IgE-Alt (+) group than negative group. In the asthma management, it was considered necessary to pay attention to the sensitization to Asp or Alt.

Omalizumab ameliorates extrarespiratory symptoms in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Omalizumab, an anti-IgE antibody, has clinical efficacy against respiratory symptoms of aspirin-exacerbated respiratory disease (AERD). However, some patients with AERD also present with extrarespiratory (chest, gastrointestinal, and/or cutaneous) symptoms, which are resistant to conventional treatment but can be alleviated by systemic corticosteroids. OBJECTIVE: We evaluated the efficacy of omalizumab on extrarespiratory symptoms related to AERD. METHODS: In study 1, a total of 27 consecutive patients with AERD initially prescribed omalizumab at Sagamihara National Hospital between July 2009 and March 2019 were retrospectively studied. Frequency of exacerbations of AERD-related extrarespiratory symptoms was compared before and after omalizumab treatment. In study 2, we reported 3 AERD cases with aspirin challenge-induced extrarespiratory symptoms among patients studied in our previous randomized trial (registration UMIN000018777), which evaluated the effects of omalizumab on hypersensitivity reactions during aspirin challenge to AERD patients. Extrarespiratory symptoms induced during the aspirin challenge were compared between placebo and omalizumab phases. RESULTS: In study 1, omalizumab treatment was associated with decrease in frequency of exacerbation of chest pain (no. [%] of patients with exacerbation frequency ≥1 time per year, 6 [22.2%] vs 0; P < .001), gastrointestinal symptoms (9 [33.3%] vs 2 [7.4%]; P = .016), and cutaneous symptoms (16 [59.3%] vs 2 [7.4%]; P < .001), even under conditions of treatment-related reduction in systemic corticosteroid dose. Omalizumab also attenuated all the extrarespiratory symptoms during aspirin challenge in study 2. CONCLUSION: Omalizumab ameliorated extrarespiratory symptoms at baseline (without aspirin exposure) and during aspirin challenge.

[A RESEARCH OF ADULT BRONCHIAL ASTHMATICS MANAGED UNDER YOKOHAMA CITY SEIBU HOSPITAL'S COORDINATED-CARE SYSTEM].

BACKGROUND: Our hospital in the western part of Yokohama City managed adult bronchial asthma patients via a coordinated care system with primary care clinics. The aim of the system is to provide effective daily and emergency medical care. METHODS: The study comprised 288 adult stable asthmatics (201 women) who were examined at Yokohama City Seibu Hospital between Jan 2009 and May 2018 and who were being managed under our coordinated care system at one of 80 primary clinics or hospitals. RESULTS: Of the 288 patients enrolled, 188 continued, 37 ended under management, and 63 dropped out from this system. The drop-out rate was highest at visit 1 (9%). The main reasons for end of cooperation under management were readjustment of asthma treatment and treatment for other diseases. The reasons for dropping out were low adherence, older age, and mild symptoms. There was a significant tendency in the frequency of patients who continued, ended under management, or dropped out (x2: 26.053, p=0.016), and the drop-out rate was significantly higher at visit 1. Comparing the characteristics of the patients who continued, ended under management, and dropped out within two visit, those who had dropped out were significantly younger (p=0.0067) and their duration of asthma was shorter (p=0.0009). The frequencies of emergency department visit and hospitalization were high until visit 2, but no significant trends were observed. CONCLUSION: Our coordinated care system managed 188 asthmatic patients (65.2%) properly. Patients with low adherence tended to drop out from the system at visit 1.

The relationship between peak inspiratory flow and hand grip strength measurement in men with mild chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) decreases quality of life and muscular strength. Inspiratory flow is important for inhalants in the bronchi but is complicated to measure in routine practice. We hypothesized that hand grip strength (HGS) would correlate with inhalation rate in patients with mild COPD. METHODS: The COPD patients were recruited at the St. Marianna University School of Medicine, Yokohama Seibu Hospital, from 2015 to 2018. We measured peak inspiratory flow (PIF) through an In-Check flow meter attached with Diskus [PIF(D)] and Turbuhaler [PIF(T)] inhalers. The 6-min walking test (6MWT), and the fraction of exhaled nitric oxide (FENO), spirometry, HGS, or forced oscillation technique (FOT) parameters were measured. RESULTS: Forty-four subjects were enrolled. All were men, with a mean age (± SD) of 77.8 ± 9.36 years. Thirty-nine patients had mild COPD. PIF(D) was 110 (80, 140) L/min (median, interquartile range), PIF(T) was 80 (70, 90) L/min, and HGS was 28.7 (13.8, 43.6) kgf. PIF(D) and PIF(T) were significantly correlated (r = 0.443, p = 0.003). PIF(D) was significantly correlated with age (r = - 0.327, p = 0.030) and HGS (r = 0.326, p = 0.031). PIF(T) was significantly correlated with age (r = - 0.328, p = 0.030), FVC (r = 0.351, p = 0.019), 6MWT distance (r = 0.392, p = 0.011), and HGS (r = 0.328, p = 0.030). CONCLUSION: HGS might be more useful for predicting PIF than other parameters. Also, elderly COPD patients need to be taught inhaled methods carefully.

An official JRS statement: The principles of fractional exhaled nitric oxide (FeNO) measurement and interpretation of the results in clinical practice.

Nitric oxide (NO) is produced in the body and has been shown to have diverse actions in the abundance of research that has been performed on it since the 1970s, leading to Furchgott, Murad, and Ignarro receiving the Nobel Prize in Physiology or Medicine in 1998. NO is produced by nitric oxide synthase (NOS). NOS is broadly distributed, being found in the nerves, blood vessels, airway epithelium, and inflammatory cells. In asthma, inflammatory cytokines induce NOS activity in the airway epithelium and inflammatory cells, producing large amounts of NO. Measurement of fractional exhaled nitric oxide (FeNO) is a simple, safe, and quantitative method of assessing airway inflammation. The FeNO measurement method has been standardized and, in recent years, this noninvasive test has been broadly used to support the diagnosis of asthma, monitor airway inflammation, and detect asthma overlap in chronic obstructive pulmonary disease (COPD) patients. Since the normal upper limit of FeNO for healthy Japanese adults is 37 ppb, values of 35 ppb or more are likely to be interpreted as a signature of inflammatory condition presenting features with asthma, and this value is used in clinical practice. Research is also underway for clinical application of these measurements in other respiratory diseases such as COPD and interstitial lung disease. Currently, there remains some confusion regarding the significance of these measurements and the interpretation of the results. This statement is designed to provide a simple explanation including the principles of FeNO measurements, the measurement methods, and the interpretation of the measurement results.

Omalizumab for Aspirin Hypersensitivity and Leukotriene Overproduction in Aspirin-exacerbated Respiratory Disease. A Randomized Controlled Trial.

Rationale: Aspirin-exacerbated respiratory disease is characterized by severe asthma, nonsteroidal antiinflammatory drug hypersensitivity, nasal polyposis, and leukotriene overproduction. Systemic corticosteroid therapy does not completely suppress lifelong aspirin hypersensitivity. Omalizumab efficacy against aspirin-exacerbated respiratory disease has not been investigated in a randomized manner.Objectives: To evaluate omalizumab efficacy against aspirin hypersensitivity, leukotriene E4 overproduction, and symptoms during an oral aspirin challenge in patients with aspirin-exacerbated respiratory disease using a randomized design.Methods: We performed a double-blind, randomized, crossover, placebo-controlled, single-center study at Sagamihara National Hospital between August 2015 and December 2016. Atopic patients (20-79 yr old) with aspirin-exacerbated respiratory disease diagnosed by systemic aspirin challenge were randomized (1:1) to a 3-month treatment with omalizumab or placebo, followed by a >18-week washout period (crossover design). The primary endpoint was the difference in area under logarithm level of urinary leukotriene E4 concentration versus time curve in the intent-to-treat population during an oral aspirin challenge.Measurements and Main Results: Sixteen patients completed the study and were included in the analysis. The area under the logarithm level of urinary leukotriene E4 concentration versus time curve during an oral aspirin challenge was significantly lower in the omalizumab phase (median [interquartile range], 51.1 [44.5-59.8]) than in the placebo phase (80.8 [interquartile range, 65.4-87.8]) (P < 0.001). Ten of 16 patients (62.5%) developed oral aspirin tolerance up to cumulative doses of 930 mg in the omalizumab phase (P < 0.001).Conclusions: Omalizumab treatment inhibited urinary leukotriene E4 overproduction and upper/lower respiratory tract symptoms during an oral aspirin challenge, resulting in aspirin tolerance in 62.5% of the patients with aspirin-exacerbated respiratory disease.

[CHARACTERISTICS OF ADULT ASTHMATICS COMPLICATED WITH PULMONARY THROMBOEMBOLISM IN YOKOHAMA CITY SEIBU HOSPITAL].

BACKGROUND: Evidences have shown that bronchial asthma (BA) enhances the risk of pulmonary thromboembolism (PTE). We previously reported the cases of adult BA patients complicated with PTE. (Aim) To clarify the risk factors of PTE in BA patients, we investigated about the characteristics and risk of contrast medium about patients coexisting asthma and PTE. METHODS: We investigated adult asthmatics who visited our hospital and examined chest contrasted CT from January 2011 to 2018.March, retrospectively. RESULTS: Fifty seven times examinations (33 asthmatics) were detected from 304 times of enhanced chest CT. We examined twenty times enhanced CT without premedication, but no subjects had side effect such as asthma attack. And also, we diagnosed 12 asthmatics as PTE from 33 patients. The subjects with PTE were high BMI (p=0.024) heavy weight (p=0.033), compared with asthmatics without PTE. There were no significant changes about lung function test, smoking history, sex and the levels of D-dimer among two groups. CONCLUSION: Adult asthmatics with PTE were high BMI and heavy compared with those without PTE.

Relationships among bronchodilator reversibility, the fraction of exhaled nitric oxide, and the parameters of the forced oscillation technique in adult asthma treated with inhaled corticosteroids and long-acting ß2 agonists combination.

In bronchial asthma, both airway inflammation and reversible airway narrowing require assessment and treatment. These two pathologies are treated primarily with inhaled corticosteroids (ICS) and long-acting ß2 agonists (LABA), respectively. Therefore, ICS-LABA combinations are widely used to treat asthma. Airway inflammation and reversible airway narrowing are assessed primarily with fraction of exhaled nitric oxide (FENO) and bronchodilator reversibility (BDR). The forced oscillation technique (FOT) has recently attracted attention as a method for assessing obstructive respiratory disturbance. However, little is known about the relationships among these assessments. Therefore, we investigated the relationships among BDR, FENO, and FOT during ICS-LABA combination therapy. The subjects comprised 87 patients (25 men and 62 women) with asthma undergoing ICS/LABA combination therapy from July to September 2017. We applied the FENO test, FOT, and BDR testing without the patients stopping their therapy. The rates of change in FEV1 (ΔFEV1%) was correlated with FENO (r = 0.278). Among the FOT parameters, X5 (r = -0.263), Fres (r = 0.292), and AX (r = 0.245) were significantly correlated with ΔFEV1%. FENO, Fres and %FEV1 at baseline in these stable asthmatics were significantly assosiated with ΔFEV1% independently of the effects of age, atopy and body mass index (BMI). These results suggest that FENO and the results of respiratory function testing and FOT reflect different aspects of asthma and should be combined and comprehensively evaluated.

Complicating effects of obstructive sleep apnea syndrome on the severity of adult asthma.

Introduction: Bronchial asthma (BA) and obstructive sleep apnea syndrome (OSAS) are common causes of respiratory disturbance. Many cases of patients with both conditions have been reported, and BA and OSAS may exacerbate each other, but information remains sparse.Methods:We retrospectively evaluated 60 patients under treatment for BA in our department between April 2016 and March 2018 who also underwent portable polysomnography (PSG) for suspected OSAS to assess potential association between PSG results and asthma treatment or respiratory function. BA was diagnosed and treated according to the Asthma Prevention and Management Guideline 2015.Results: We found that BA treatment intensity step was significantly higher for patients with BA who had concurrent moderate or severe OSAS (p = 0.0016). However, neither respiratory function, fraction of exhaled nitric oxide (FeNO), nor forced oscillation technique (FOT) differed significantly between patients with and without OSAS, and apnea hypopnea index was not significantly correlated with respiratory function, FeNO or FOT parameters.Conclusion:We conclude that even though BA patients with OSAS had good respiratory function, their BA was more severe than that of patients without OSAS, suggesting that OSAS may exacerbate BA. Background factors and asthma parameters were not predictive of PSG results, and patients with suspected OSAS should be evaluated proactively by using PSG.

[A CASE OF BRONCHIAL ASTHMA ASSOCIATED WITH BRONCHIOLAR EOSINOPHILIA AND TREATED WITH MEPOLIZUMAB].

A 68 year-old woman with dyspnea and cough had been treated with inhaled corticosteroids for X-15 years, but her symptoms worsened in X year. High-resolution chest CT revealed small centrilobular nodules in the right upper lobe in March X year. The patient was diagnosed with asthma and diffuse panbronchiolitis and treated with inhaled corticosteroids, a long-acting beta agonist, and clarithromycin, but her condition did not improve and her peripheral blood eosinophil count increased. In August X year, we performed a transbronchial biopsy of the right upper lung. Histopathological examination revealed eosinophilia in the bronchial secretions and mild nonspecific inflammatory changes. The diagnosis was bronchial asthma associated with bronchiolitis. The patient was treated successfully with mepolizumab.

Innate immune response reflects disease activity in eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease characterized by allergic granulomatosis, necrotizing vasculitis, and peripheral blood eosinophilia. Interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and type 2 innate lymphoid cells (ILC2) are involved in the innate and type 2 immune responses in EGPA. However, the relationships among these molecules and the mechanisms underlying the development of EGPA remain unknown. OBJECTIVE: We investigated the relationships among peripheral blood eosinophil count, serum IL-33 and TSLP concentration, and peripheral blood ILC2 count in patients with EGPA, chronic eosinophilic pneumonia (CEP), or bronchial asthma (BA). METHODS: We recruited 86 patients with EGPA in three groups (remission, relapse, and onset), 25 patients with CEP at active or inactive stages of disease, and 11 patients with BA. In patients with EGPA, CEP, or BA, serum IL-33, sST2, and TSLP concentrations were determined using ELISA and peripheral blood ILC2 counts (as Lin-1- CD127+ CRTH2+ cells) were determined using flow cytometry. RESULTS: Peripheral blood eosinophil count or ILC2 count, and serum sST2 or TSLP concentration were higher in patients with EGPA at onset than in those with EGPA at relapse or remission, or in those with BA or CEP. Serum IL-33 concentration was higher in patients with EGPA at relapse than in those with EGPA at onset or remission, or in those with BA or CEP. In a logistic regression model, EGPA disease activity was correlated with serum IL-33 concentration and peripheral blood ILC2 count, but not daily systemic and inhaled corticosteroid dose or immunosuppressant use. Eosinophil count was correlated with peripheral blood ILC2 count and serum TSLP concentration, but not serum IL-33 concentration. CONCLUSIONS: Increased peripheral blood ILC2 count and serum IL-33 concentration were associated with disease activity in EGPA. Increases in serum IL-33 concentration may indicate the presence of active vasculitis rather than peripheral or tissue eosinophilia.

Low Variability in Peak Expiratory Flow Predicts Successful Inhaled Corticosteroid Step-Down in Adults with Asthma.

BACKGROUND: The prognosis for patients beyond 1 year after reduction of their inhaled corticosteroid (ICS) dose remains unknown. Predictive factors that can be evaluated before the initiation of asthma treatment or at ICS dose reduction are unknown. METHODS: We prospectively studied 223 patients in 6 hospitals in the National Hospital Organization of Japan during the 36 months after 50% reduction of their daily ICS dose. All patients recorded their morning and evening peak expiratory flows (PEFs) in their diaries. Lung function, bronchial hyperresponsiveness, fractional nitric oxide levels, number of eosinophils in sputum, and serum IgE levels were measured in most patients. Serum levels of IL-10, IL-33, and thymic stromal lymphopoietin before ICS dose reduction were measured in all patients. RESULTS: During the 36-month study period, asthma control was retained in 127 (59.6%) of the 213 enrolled patients who underwent ICS dose reduction. Multivariate logistic regression analysis revealed that, at the initiation of dose reduction, the factors most predictive of maintenance of asthma control after ICS dose reduction were a low serum IL-33 level (P < .01), low PEF variability over 1 week (P = .014), childhood onset of asthma (at age <10 years) (P = .03), and high serum IL-10 level (P = .035). CONCLUSIONS: We demonstrated that low PEF variability over 1 week, high serum IL-10 level, and low serum IL-33 concentration were useful factors for predicting that an adult's asthma will remain in control for months to years after a 50% reduction in the daily ICS dose.

Smoking Cessation as a Possible Risk Factor for the Development of Aspirin-Exacerbated Respiratory Disease in Smokers.

BACKGROUND: The pathogenesis of aspirin-exacerbated respiratory disease (AERD) is characterized by the low expression of cyclooxygenase-2 (COX-2) in airway epithelia, which decreases the production of prostaglandin E2 (PGE2). Conversely, cigarette smoke stimulates COX-2 expression in airway epithelia. Therefore, it was hypothesized that the development of AERD would be suppressed by elevated PGE2 levels in smokers, and smoking cessation might increase susceptibility to AERD. OBJECTIVE: The objective of this study was to evaluate the relationship between smoking and the risk of AERD development. METHODS: The smoking status of patients with AERD (n = 114) was compared with 2 control groups with aspirin-tolerant asthma (ATA), patients diagnosed by a systemic aspirin provocation test (ATA-1, n = 83) and outpatients randomly selected from a large-scale dataset (ATA-2, n = 914), as well as a healthy control group (HC, n = 2313). RESULTS: At the age of asthma onset, there was a low frequency of current smokers (9.7%), but a high frequency of past smokers (20.2%) in the AERD group compared with the ATA-1 (20.5% and 12.0% for current and past smokers, respectively), ATA-2 (24.5% and 10.3%, respectively), and HC group (26.2% and 12.6%, respectively). After adjustment for confounding variables, AERD was positively associated with smoking cessation between 1 and 4 years before disease onset compared with the ATA-2 group (adjusted odds ratio [aOR] 4.63, 95% confidence interval [CI]: 2.16-9.93) and the HC group (aOR 4.09, 95% CI: 2.07-8.05), implying that smoking cessation was followed by the development of AERD. CONCLUSION: Smoking cessation may be a risk factor for the development of AERD.

[A CASE OF PERTUSSIS IN ADULT THAT COULD BE DIAGNOSED BY DETECTION OF BORDETELLA PERTUSSIS FROM SPUTUM].

Bordetella pertussis isolation by culture has low detection sensitivity for diagnosing pertussis; the diagnosis is confirmed by measuring serum anti-pertussis toxin (anti-PT) or anti-filamentous hemagglutinin antibody titers, and by genetic testing (polymerase chain reaction/loop-mediated isothermal amplification). Isolation of B. pertussis in adults is difficult, resulting in a delayed diagnosis, as a delayed cough may present ≥3 months after onset. Differentiation from bronchial asthma is also important. We encountered an adult patient in whom B. pertussis was isolated by culture who previously received rituximab for mucosa-associated lymphoid tissue (MALT) lymphoma and steroids for prolonged cough. No elevation of anti-PT antibody titers was observed in the patient.

Longterm Prognosis of 121 Patients with Eosinophilic Granulomatosis with Polyangiitis in Japan.

OBJECTIVE: We investigated the risk factors for relapse or prognosis of eosinophilic granulomatosis with polyangiitis (EGPA) in Japanese patients presenting to our hospital. METHODS: From June 1999 through March 2015, we retrospectively recruited 121 patients with EGPA according to the American College of Rheumatology criteria. Frequent relapse was defined as disease occurrence at least once every 2 years after a period of initial remission. The study endpoint was the last examination performed. We used multiple logistic regression to analyze risk factors for relapse or survival in EGPA. RESULTS: Gastrointestinal (GI) involvement with both abnormalities on endoscopy and biopsy (p < 0.01) and symptoms; myocardial involvement with both abnormalities on 1 or more cardiac investigations and symptoms (p < 0.01); and treatment at initial or maintenance with immunosuppressants (p < 0.01) or administration of intravenous immunoglobulin (IVIG; p < 0.01) were associated significantly more often with frequent relapse than with infrequent. Overall 5-, 10-, and 20-year survival rates were 91.1%, 83.7%, and 68.6%, respectively. Survival in EGPA was associated with age of onset < 65 years. Age at onset of EGPA was the only significant predictor of survival (p < 0.01). Myocardial or GI tract involvement did not affect mortality risk. CONCLUSION: Patients with myocardial or GI tract involvement had frequent relapses, but these conditions were not reflected in increased mortality. Treatment with immunosuppressants or IVIG in addition to corticosteroids might have improved the prognosis in Japanese patients with EGPA.