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.

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.

[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.

[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 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.

[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.

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.

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.

[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.

[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.

Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by respiratory reactions on ingestion of COX-1 inhibitors and cysteinyl leukotriene overproduction. The hypersensitivity reaction is induced by low doses of aspirin that inhibit COX-1 in platelets. OBJECTIVE: We sought to explore the role of platelets in the pathogenesis of AERD in patients under stable conditions and during an aspirin challenge test. METHODS: Stable patients with AERD (n = 30), aspirin-tolerant asthma (ATA; n = 21), or idiopathic chronic eosinophilic pneumonia (n = 10) were enrolled. Platelet activation was estimated based on expression levels of P-selectin (CD62P), CD63, CD69, and GPIIb/IIIa (PAC-1) in peripheral platelets; percentages of circulating platelet-adherent leukocytes; and plasma levels of soluble P-selectin (sP-selectin) and soluble CD40 ligand (sCD40L). RESULTS: In the stable condition, expression of all surface markers on platelets, the percentage of platelet-adherent eosinophils, and the plasma levels of sP-selectin and sCD40L were significantly higher in patients with AERD compared with those in patients with ATA. P-selectin and CD63 expression on platelets and plasma sP-selectin and sCD40L levels were positively correlated with the percentage of platelet-adherent eosinophils. Among these markers, P-selectin expression and plasma sP-selectin levels positively correlated with urinary concentrations of leukotriene E4. Additionally, plasma sP-selectin and sCD40L levels were negatively correlated with lung function. In contrast, platelet activation markers in patients with AERD did not change during the aspirin challenge test. CONCLUSION: Peripheral platelets were activated more in patients with stable AERD compared with those in patients with stable ATA, patients with idiopathic chronic eosinophilic pneumonia, and control subjects. Platelet activation was involved in cysteinyl leukotriene overproduction and persistent airflow limitations in patients with 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.

THE FRACTION OF EXHALED NITRIC OXIDE (FENO) AND FORCED OSCILLATION TECHNIQUE (FOT) CAN PREDICT BRONCHIAL HYPERRESPONSIVENESS AGAINST ACETYLCHOLINE IN TREATED ASTHMATICS.

BACKGROUND: The bronchial hyperresponsiveness (BHR) test is useful to diagnose or evaluate effect of therapy in asthmatics, but invasive. On the other hands, the fraction of exhaled nitric oxide (FENO) is a useful noninvasive marker of eosinophilic airway inflammation in asthmatics. And also, the forced oscillation technique (FOT) is a noninvasive method that is used to measure respiratory mechanics, including respiratory resistance and reactance at multiple frequencies. AIM: To evaluate the complementary roles of FENO and FOT to predict bronchial hyperresponsiveness in adult stable asthmatic patients taking inhaled corticosteroids. METHODS: From our outpatient clinic, we recruited 115 stable asthmatics that were being treated with inhaled corticosteroids at the time of the study. For each subject, we measured FENO by using an offline methods (CEIS' method); and we measured resistance at 5Hz (R5), resistance at 20Hz (R20), R5-R20, reactance at 5Hz (X5), frequency of resonance (Fres), and low-frequency reactance area (ALX), by using a MostGraph FOT machine. We also used spirometry to test BHR to acetylcholine (PC20Ach). RESULTS: LogPC20Ach was significantly correlated with FENO, R5, R20, R5-R20 and %FEV1. The ROC curve decided that the cutoff point of FENO was 37.8ppb (AUC=0.647, sensitivity 83.3%, specificity 55.6%, p=0.007) and that of R5 was 3.03cmH2O/L/S (AUC=0.684, sensitivity 72.2%, specificity 52.8%, p=0.001) and that of R20 was 2.77cmH2O/L/S (AUC=0.684, sensitivity 74.5%, specificity 59.4%, p=0.001). When R5 was >3.03 and FENO was >37.8ppb, 25 of 38 subjects (65.7%) had bronchial hyperresponsiveness. If R5 was <3.03 and FENO was <37.8 ppb, only 5 of 29 (17.2%) subjects had. When R20 was >2.77 and FENO was >37.8ppb, 29 of 43 subjects (67.4%) had bronchial hyperresponsiveness. If R20 was <3.03 and FENO was <37.8ppb, only 2 of 18 (11.1%) subjects had. CONCLUSION: Combining R5 or R20 and FENO can predict the level of bronchial hyperresponsiveness in adult stable asthmatics.

DIFFERENCES IN FRACTION OF EXHALED NITRIC OXIDE VALUES MEASURED BY TWO HAND-HELDED ANALYZERS (NObreath® AND NIOX Vero®).

BACKGROUND: The fraction of exhaled nitric oxide (FENO) is a useful marker of asthma control. The FENO measurement with two hand-helded analyzers (NObreath® and NIOX Vero®) may be more affordable, no studies have examined the differences in FENO values measured with those methods in adult. METHODS: The study population comprised 44 subjects at our outpatient clinic. FeNO values (FENOb and FENOv) were measured by two methods (NObreath® and NIOX Vero®). RESULTS: FENOb values were significantly correlated with FENOv (r = 0.911, p < 0.001). However, FENOv values were high compared with FENOb (FENOv = 1.40 × FENOb). CONCLUSION: Differences exist in the values of FENO measured by two hand-helded analyzers: conversion equations are needed to compare the FENO values between these methods.

A CASE OF BRONCHIAL ASTHMA WITH HYPEREOSINOPHILIA WITH EFFECTIVE SAIBOKUTOU THERAPY.

A 42 year old woman visited on our hospital because of cough, sputum, pruritus and erythema. She showed peripheral blood eosinophilia, high level of FENO, bronchial hyperresponsiveness. Diagnosis of bronchial asthma and atopic dermatitis was made, but she rejected therapy except for Saibokutou, a Kampo herbal medicine. After 1 year, her symptoms and her laboratory data were improved.

Th17 cells reflect colon submucosal pathologic changes in active eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Chronic eosinophilic pneumonia (CEP) or eosinophilic gastroenteritis (EG), or both, with asthma precede the onset of eosinophilic granulomatosis with polyangiitis (EGPA) in half of all EGPA patients. It is not known what determines whether patients with CEP or with EG following asthma will develop EGPA. METHODS: We studied 17 EGPA patients and 12 patients with CEP but without EGPA. We assayed serum ICAM-1, VCAM-1, and VEGF, and the percentage of peripheral blood CD4(+) T cells producing IL-17 (Th17 cells), at both onset and remission. We also examined the numbers of submucosal eosinophils and the basement membrane-to-crypt and crypt-to-crypt distance to evaluate edema in the colon submucosa at onset and remission in EGPA and at onset in CEP. RESULTS: Nine of 12 (75.0%) CEP patients had symptoms or endoscopic findings. Colonic submucosal eosinophil counts and edema in EGPA at onset were greater than at remission or in CEP at onset. Th17 cells (%) and serum ICAM-1 levels at onset were greater in EGPA than in CEP. In EGPA, peripheral blood Th17 cells (%) were significantly correlated with serum ICAM-1 level, colonic submucosal eosinophil count, and degree of edematous change; inversely correlated with serum VEGF level; but not correlated with VCAM-1 level. CONCLUSIONS: Eosinophilia and colonic submucosal edematous change were greater in EGPA than in CEP. The mechanism of vasculitis in EGPA appears related to increases in serum Th17 cell numbers and ICAM-1 levels and decreases in VEGF levels.

IgE Abs to Der p 1 and Der p 2 as diagnostic markers of house dust mite allergy as defined by a bronchoprovocation test.

BACKGROUND: Limited information is available regarding the clinical usefulness of measuring the levels of IgE to allergen components from house dust mites (HDMs) in the diagnosis of genuine HDM allergy. METHODS: To evaluate the diagnostic usefulness of measuring levels of serum IgE antibodies (Abs) to allergen components from Dermatophagoides pteronyssinus (DP) as a predictor of immediate asthmatic response (IAR) to bronchoprovocation, we studied 55 DP-sensitized asthmatic patients who underwent a bronchoprovocation test using crude DP extract. The levels of IgE Abs to crude DP, nDer p 1, rDer p 2, and rDer p 10 in patients who showed IAR (n = 41) were compared with those in patients who showed no IAR (n = 14). RESULTS: While the frequencies of positivity for IgE Abs to nDer p 1 and rDer p 2 among the entire study population were 89 and 86%, respectively, all patients with IAR tested positive for both of them with high IgE concentrations. The areas under the receiver operating characteristic curves for IgE to nDer p 1 and rDer p 2 as predictors of IAR were 0.913 and 0.906, respectively. The specificity of IgE to nDer p 1 and rDer p 2 was higher than IgE to crude DP even at low cut-off points. CONCLUSIONS: IgE to nDer p 1 and/or rDer p 2 was highly predictive of allergen-induced IAR. These findings validate the clinical usefulness of measuring the levels of IgE to nDer p 1 and rDer p 2 as a diagnostic tool for genuine HDM allergy.