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Background: It is known that eosinophilic chronic rhinosinusitis is often associated with adult-onset bronchial asthma, and undiagnosed bronchial asthma is also known to be included. The purpose of this study is to screen patients with eosinophilic chronic rhinosinusitis using fractional exhaled nitric oxide, and to examine its usefulness in detecting undiagnosed bronchial asthma., Methods: We retrospectively examined the data of patients with eosinophilic chrnoic rhinosinusitis who underwent surgical treatment at Kagawa University from April 2015 to July 2022. Patients were included if they received examinations of fractional exhaled nitric oxide and spirometry before surgical treatment., Results: Of the 127 subjects, 52 had no history of treatment or diagnosis of bronchial asthma at the initial consultation. Among them, 15 patients who had high fractional exhaled nitric oxide value were diagnosed with bronchial asthma by the respiratory medicine department. Comorbid of bronchial asthma was eventually increased to 70.9% even though it was 59.1% at initial consultation., Conclusion: A certain number of patients with eosinophilic chronic rhinosinusitis have undiagnosed bronchial asthma, which can be difficult to detect with basic examination alone therefore fractional exhaled nitric oxide is useful as an additional screening examination.

A 74-year-old man presented to our hospital because of anorexia. Upper gastrointestinal endoscopy revealed type 3 gastric cancer. Further examination disclosed metastasis to the perigastric lymph nodes and to the liver, and a diagnosis of non- resectable advanced gastric cancer(cT4N2H1P0M0)in cStage Ⅳ was made. A total of 4 courses of S-1 plus oxaliplatin therapy(80 mg/body/day and 100 mg/m2/cycle, respectively, for 2 weeks followed by a 1-week rest)were administered as the primary chemotherapy. Then, another metastasis to the abdominal lymph nodes and increased liver metastasis were found; thus, the patient's condition was rated as progressive disease(PD). Secondary chemotherapy comprising 10 courses of weekly nab-paclitaxel(nab-PTX)plus ramucirumab(RAM)therapy(100 mg/m2 on days 1, 8, and 15 and 8 mg/kg on days 1 and 15, respectively, every 4 weeks)were administered. Although temporary reductions in the perigastric lymph node metastasis and liver metastasis as compared with the baseline were observed, another metastasis to the abdominal lymph nodes occurred subsequently, resulting in PD. As tertiary chemotherapy, nivolumab therapy(240 mg/body, every 3 weeks) was repeated up to a total of 30 courses over 13 months. This therapy was markedly effective, achieving a near complete response. The patient is currently being followed up as an outpatient.

ALLESAGA ® TAPE is the first transdermal drug delivery system of emedastine difumarate, as a second-generation antihistamine, for allergic rhinitis. It has been suggested that the efficacy of emedastine difumarate in allergic rhinitis is mediated through a combination of chemical mediator release inhibitory effects and eosinophil chemotaxis inhibitory effects, in addition to a strong anti-histaminic effect. In the pharmacological evaluation on histamine-induced vascular hyperpermeability in rats, ALLESAGA ® TAPE showed an anti-histaminic effect in a dose-dependent manner and exhibited a long-lasting anti-histaminic effect until 24 hours after administration. In the patients having allergic nasal symptoms, the plasma concentration of emedastine reached at steady-state within 7 days after multiple administration of ALLESAGA ® TAPE. ALLESAGA ® TAPE was effective for treating seasonal allergic rhinitis with sustained action throughout the day. Long-term application of ALLESAGA ® TAPE raised no safety concerns in patients with perennial allergic rhinitis. Plasma drug concentrations showed little change over a long period and there was no decrease of efficacy. Based on the above results, ALLESAGA ® TAPE is possible to provide a new option for the treatment of allergic rhinitis.

A 9-year-old girl was referred to our hospital because of facial palsy. Both physical and blood examination revealed hepatosplenomegaly and leukocytosis, respectively. A bone marrow examination demonstrated marked hypercellularity involving myeloblasts and lymphoblasts. Based on these results, we suspected mixed phenotype acute leukemia. However, her leukemic blasts expressed B-cell antigens, and a chromosomal analysis of her bone marrow cells revealed the following karyotype: 46, XX, t (9;22) (q34;q11.2). All her neutrophils were positive for the breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 fusion protein. Based on these findings, she was diagnosed with a lymphoblastic crisis of chronic myelogenous leukemia (CML). Combined chemotherapy, involving imatinib, resulted in complete molecular remission. She received cord blood transplant (CBT) during the first complete remission; she is alive and has not suffered a relapse since two years after the CBT. The sudden onset of a blastic crisis in pediatric CML is rare, and it may be difficult to distinguish such cases from de novo Ph-positive leukemia. For diagnostic purposes, it is essential to consider a patient's clinical course and blood test results.

According to the current status of chronic dialysis therapy in Japan 2016, the average age at the time of dialysis initiation is 68.57 years for males and 71.19 years for females, which has been rising continuously. Frailty is a geriatric syndrome that is frequently seen in the elderly. It is known that frailty among dialysis patients are more common than the general population of the same age, and that frailty is associated with life prognosis. As eGFR decreases, BMD decreases and fracture risk increase, and dialysis patients are at the highest risk of fracture in CKD patients. Various factors such as frailty, sarcopenia, PEW(protein-energy wasting), dynapenia, uremic osteoporosis, diabetes, AGEs(advanced glycation end products), oxidative stress, falls are involved in the increased risk of fracture in dialysis patients, and consequently, fragile fractures occur frequently in dialysis patients. Fragile fracture is a common complication in dialysis patients, and it is reported that the hospitalization for fracture, and the subsequent course is associated with poor prognosis. In diabetes, bone quality declines without loss of BMD, so the conventional DXA method may be insufficient in predicting fracture risk among dialysis patients, and the evaluation method using HR-pQCT or FRAXR may be useful. It has been reported that bisphosphonate is an established therapy in patients with primary osteoporosis, but many bisphosphonates cannot be used at eGFR of less than 30 mL/min per 1.73 m2. Bisphosphonate-related adverse effects such as accumulation, ossification, osteomalacia, ADB(adynamic bone), and jaw bone necrosis were reported, there are few reports of usefulness in CKD patients. Denosumab administration trial results for women with osteoporosis in dialysis patients have been waited(NCT 01464931). In this article, we outline the relation, diagnosis, and treatment of fragile fractures and frailty in dialysis patients.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis in patients with bronchial asthma and eosinophilic rhinosinusitis. Serum IgG4 levels are markedly elevated in patients with active EGPA, a disease which has been closely associated with IgG4-related disease (IgG4RD). A 68-year-old male with a history of asthma and eosinophilic rhinosinusitis developed vasculitis and orbital symptoms. The results of a laboratory examination showed eosinophilia (4,067/μl; 39%), while image evaluations revealed hypertrophy of the rectus muscles, trigeminal nerve, lachrymal gland, and bilateral submandibular glands. Biopsy of the paranasal sinus showed the prominent infiltration of eosinophils and IgG4-positive plasma cells. The patient was diagnosed with EGPA concomitant with IgG4RD and treated with systemic steroids. Although concomitant cases of EGPA with IgG4RD are extremely rare, clinical manifestations associated with both diseases are sometimes mixed. Therefore, systemic scrutiny may be required for cases of EGPA with high serum IgG4 levels and pathognomonic symptoms or findings of IgG4RD

We report a patient treated with rituximab for interstitial pneumonia (IP) associated with microscopic polyangiitis (MPA) and who was undergoing hemodialysis. A 59-year-old woman who had been treated with tacrolimus for 1 year for rheumatic arthritis was referred to the Department of Nephrology for fatigue, fever, weight loss, and rapidly developing renal dysfunction. On the first admission, severe renal dysfunction, proteinuria, hematuria, and an elevated titer of MPO-ANCA were observed, and the woman was diagnosed with rapidly progressive glomerulonephritis because of MPA. At that point, IP was found to be present but not active. Although steroid semipulse therapy following an initial prednisolone (PSL) administration of 40 mg/day, IVCY, and plasma exchange were administered, renal dysfunction did not recover, and the patient required maintenance hemodialysis. Upon discharge, a high titer of MPO-ANCA was continuously observed. Nine months after the initiation of hemodialysis, respiratory discomfort and desaturation developed. Interstitial shadow and ground glass opacity were seen on a CT scan, and the patient was diagnosed with exacerbation of interstitial pneumonia caused by MPA recurrence. At the second admission, acute findings identified by imaging techniques had improved. However, the high titer of MPO-ANCA continued in spite of the steroid semi-pulse therapy following PSL administration, and rituximab corresponding to 200 mg/weekly for 1 month was also administered. The dose of rituximab was decreased subsequently because the patient was judged to be compromised by the hemodialysis. At the same time, internal administration of sulfamethoxazole/trimethoprim was initiated. After the rituximab treatment, MPO-ANCA antibodies gradually decreased, and the respiratory condition improved. Five months after the rituximab treatment, respiratory dysfunction recurred. Based on the CT findings and a high level of β-D-glycan, the patient was diagnosed with ARDS due to pneumocystis pneumonia. In this case, rituximab was effective for IP due to MPA, but pneumocystis pneumonia could not be prevented in spite of prophylactic antibiotics. This case suggests that deliberative dose adjustments, careful patient observation, and prophylactic measures for infection are critical in rituximab treatment.

Background and Aims: Asthma is a chronic disease characterized by airway inflammation; it is sometimes difficult to diagnose. For clinical diagnosis, forced oscillation technique (FOT) measures airway reactance and resistance. By FOT, we investigated respiratory resistance and ventilation perfusion ratio inequality in adults with mild asthma., Methods: We examined 58 adult patients with mild asthma having no inhaled corticosteroid treatment, and 10 adult patients with post-infectious prolonged cough. Using a MostGraph-01 FOT instrument, we evaluated these patients before and after bronchial hyperresponsiveness to acetylcholine (ACh) or histamine (Hist). We measured the following conditions: change of resistance at 5Hz (R5) and 20Hz (R20), R5-R20, reactance at 5Hz, frequency of resonance (Fres), low-frequency reactance area (ALX), and forced expiratory volume in 1 second (FEV1)., Results: There were significant changes of R5, R20, R5-R20, X5, Fres, ALX after provocations for ACh or Hist in all patients with asthma, but not in patients with post-infectious prolonged cough. We calculated the percent decrease in FEV1 after provocation with ACh or Hist. For Ach, this decrease in FEV1 correlated with changes in R20 and Fres for all patients. For Hist, the percent decrease in FEV1 correlated with changes in R5, R20, Fres, and ALX for all patients. Furthermore, we investigated these correlations in patients with normalized bronchial hyperresponsiveness to ACh or Hist. For Ach, the percent decrease in FEV1 correlated with changes in Fres or R5-R20. For Hist, this decrease in FEV1 correlated with changes in R5, R20, and Fres. ROC analysis was used to evaluate the diagnostic value of the ratio of change of Fres in BHR to Hist. The area under the curve was 0.7808 (95% CI=0.657-0.904). A reasonably high specificity (100.0%) and a high sensitivity (53.8%) with a cut-off point of 1.5 in the ratio before and after of Fres were obtained., Conclusion: The changes in FOT parameters (before and after bronchial airway responses) may detect airway resistance and ventilation perfusion ratio inequality even in adult patients with asthma having normalized bronchial hyperresponsiveness to ACh or Hist. That results may be useful for an early diagnosis of asthma.

Background: The fraction of exhaled nitric oxide (FeNO) is a useful marker of eosinophilic airway inflammation in asthmatics. Clinical application of FeNO measurement in Japan is expected increase because the procedure is now covered through health insurance. However, the measurement system used is known to affect FeNO results, and it remains unknown whether results from offline methods correlate with those from traditional online methods, such as NO breath®., Methods: The study population comprised 48 patients at our hospital. FeNO levels were measured by using two offline methods (Sievers and CEIS) and a standard online method, NO breath®, Results: FeNONO breath levels were significantly correlated with FeNOSievers(r=0.875) and FeNOCEIS(r=0.888) levels. FeNONO breath levels were nearly equal to FeNOSievers results (FeNONO breath=1.05×FeNOSievers), but both of these levels were lower (p=0.02) than FeNOCEIS data (FeNONO breath=0.74×FeNOCEIS). A Bland-Altman plot of values obtained by the NO breath® and Sievers methods revealed that the NO breath® result was lower than the Sievers level when FeNO was low but was higher than the Sievers level when FeNO was high., Conclusion: Differences exist in the levels of FeNO measurement by three methods (two offline methods and NO breath®): conversion equations are needed to compare the FeNO levels obtained by using these three methods. In addition, NO breath® may be more useful to distinguish asthmatic patients from non-asthmatics, compared with Sievers method.

Asparaginase (ASNase) is one of the most important key drugs in the treatment of acute lymphoblastic leukemia (ALL). However, clinical hypersensitivity reactions often occur and lead to the discontinuation of ASNase treatment. Here, we report a retrospective study of 68 Erwinia ASNase (Erw-ASNase) administrations in 11 patients with childhood ALL who developed allergic reactions to E.coli-ASNase in our hospital between 2006 and 2012. The median age of the patients was 6 (range, 0 to 14). Erw-ASNase purchased overseas by the patients' guardians had already been administered when we obtained informed consent from the guardians. In all patients, fibrinogen and/or anti-thrombin III levels were decreased, but thrombosis did not develop. There was only one mild adverse event (grade 2 urticaria) in one patient, in whom Erw-ASNase could be continued after increasing the doses of premedication with antihistamine and prednisolone. Erw-ASNase could be safely administered to all patients.

Recently, bone marrow transplantation from an unrelated donor has been recommended as an option for the treatment of very severe aplastic anemia (vSAA) refractory to immunosuppressive therapy (IST) in the absence of a human leukocyte antigen-matched related donor (MRD). For SAA patients with complications such as bacterial infections, prompt transplantation using either a mismatched related donor or cord blood (CB) becomes necessary. However, the former option is associated with graft-versus-host disease, whereas the latter option is associated with a more significant risk of graft failure. We report a patient with vSAA refractory to IST that was repeatedly complicated by bacterial infection. An MRD was unavailable for this patient, so we decided on emergent transplantation and successfully performed CB transplantation (CBT) using a low-dose TBI conditioning regimen. Although it may be necessary to examine more clinical cases in the future, a conditioning regimen such as that involving low-dose TBI may decrease the risk of graft failure, and CBT may become a treatment option for vSAA in the absence of a suitable donor.

We report a case of a 15-year-old girl with severe aplastic anemia who underwent orthotopic liver transplantation 5 years ago for fulminant hepatic failure during the course of immunodeficiency of unknown etiology. She previously exhibited similar immunodeficiency and experienced recurrent viral infections. She developed jaundice at 9 years of age and was diagnosed with fulminant hepatitis. One month later, she underwent living donor liver transplantation, with the donor being her father. Five years after the liver transplant, pancytopenia was noted; she did not respond to treatment with increasing doses of tacrolimus/prednisone and administration of granulocyte-colony stimulating factor. Bone marrow biopsy was performed, and severe aplastic anemia was diagnosed. Six years after the liver transplant, she underwent bone marrow transplantation (BMT), with the donor being her HLA-matched sibling. However, she developed liver dysfunction with recovery of white blood cells. She developed sepsis, which eventually led to her death on day 30 after BMT.

Background: Several allergen sampling methods are available for the assessment of personal or indirect exposure to indoor allergens. As an index of exposure to inhalant allergens, assays of the amount of airborne allergens directly reflect personal exposure., Objective: We evaluated the Petri dish sampling method of assessing the level of airborne Dermatophagoides dust mite group 1 (Der 1) allergens., Methods: We collected settling dust samples from one person's bedroom over a period of 2 years by using a Petri dish, adhesive tape, and a vacuumed reservoir. We also collected settling dust samples from the bedrooms of 42 asthma patients by using a Petri dish and adhesive tape. The amounts of Der 1 collected on the Petri dishes and adhesive tapes were measured by sensitive fluorometric ELISA., Results: Der 1 was detected in all samples by using a Petri dish. The mean coefficient of variation was approximately 15%. We found that Petri dishes set at lower sampling heights contained more Der 1 than those higher up. There were also seasonal changes in the amounts of Der 1 collected, with the highest amounts collected from summer to autumn, and the lowest amounts collected in winter., Conclusion: The Petri dish sampling method for collecting settling Der 1 is very simple and can be used as an alternative to personal air sampling, especially in large-scale studies.

Pheochromocytoma occurs in 0.1-5.7% of patients with neurofibromatosis type 1 (NF1), while dopamine-secreting pheochromocytoma is rare. We report here a rare case of dopamine-secreting pheochromocytoma in a patient with NF1. A 46-year-old woman with NF1 was referred to our hospital with epigastralgia. The patient had no history of hypertension. Abdominal sonography incidentally revealed a left adrenal tumor, while abdominal computed tomography and magnetic resonance imaging findings showed a left adrenal tumor, sized 63×58 mm. Laboratory evaluations revealed exclusively elevated urine dopamine levels in addition to elevated serum adrenaline and noradrenaline levels. Laparoscopic left adrenalectomy was performed and the dopamine levels and other cathecolamine levels returned to normal postoperatively.

Background: The forced oscillation technique (FOT) is a noninvasive method that is used to measure respiratory mechanics, including respiratory resistance and reactance at multiple frequencies. The advantage of FOT over spirometry is that FOT does not require forced expiratory maneuvers. Moreover, a new FOT machine called MostGraph (Chest Co. Ltd., Tokyo, Japan), has been developed in Japan, and can be used clinically to diagnose and monitor asthma. The purpose of this study is to show the standard of FOT measured with MostGraph in adult Japanese asthmatics., Methods: From our outpatient clinic, we recruited 151 stable asthmatics who were being treated with inhaled corticosteroids at the time of the study. For each subject, we measured the fraction of exhaled nitric oxide (FeNO) by using a chemiluminescent nitric oxide analyzer (Sievers280, GE, Boulder, Co); we determined the levels of forced expiratory volume in 1s (%FEV1) and maximum mid-expiratory flow rate (%MMF) by using spirometory; and we measured resistance at 5 Hz(R5), resistance at 20 Hz(R20), R5-R20, reactance at 5 Hz(X5), frequency of resonance (Fres), and low-frequency reactance area (ALX), by using a MostGraph FOT machine., Results: Each of the FOT parameters measured by using the MostGraph machine was significantly correlated with %FEV1 and %MMF (p<0.001), with Fres showing the strongest association. Three of the FOT parameters, X5, Fres, and ALX, were significantly associated with the subject's age (p=0.01, p<0.001, p<0.001, respectively), and all FOT parameters were significantly associated with the subject's body mass index (BMI) (p<0.001 to p=0.018). The results of multiple regression analyses between FOT parameters and FEV1, age, BMI, and FeNO, showed that Fres was significantly associated with FEV1(p<0.001) and BMI (p<0.001). From the results of the simple linear regression between Fres and FEV1, we estimated that Fres values of 17.5 Hz corresponded to %FEV1 values of 60%; Fres values of 11.3 Hz corresponded to %FEV1 values of 80%; and Fres values of 4.94 Hz corresponded to %FEV1 values of 100%., Conclusion: FOT parameters measured by using a MostGraph machine can be used successfully to assess the level of airflow limitation in adult stable asthmatics.

A 53-year-old man who had been suffering from asthma presented to our hospital because of abnormal shadows detected on a chest X-ray film during a routine medical examination. A biopsy specimen of a mucus plug obtained by bronchoscopy showed fungal hyphae, eosinophils, and Charcot-Leyden crystals, with evidence of lung tissue eosinophilia. Schizophyllum commune and Aspergillus fumigatus were isolated from his sputum, bronchial washing specimens and the mucus plug. We detected specific immunoglobulin E anti-Aspergillus fumigatus responses and precipitating antibodies against Schizophyllum commune and Aspergillus fumigatus, which led to the diagnosis of allergic bronchopulmonary mycosis caused by both fungi. We gave him fluticasone/salmeterol and itraconazole; thereafter, his symptoms of cough and sputum production and his radiological findings all improved.

We report a case of nephrotic syndrome associated with MALT lymphoma. The patient was a 66-year-old woman who had a 21-year history of MALT lymphoma. She was admitted to our hospital for the evaluation of systemic edema and purpura during two months. Urinary protein excretion was quantified at 3.3 g/24h. Serum creatinine was elevated to 1.63 mg/dL. An immunoserological investigation showed the presence of IgM-kappa type monoclonal cryoglobulin accompanied by a decreased serum complement level. HCV infection was negative. A renal biopsy specimen revealed membranoproliferative glomerulonephritis (MPGN) with cryoglobulin deposition and focal atypical lymphoid cells infiltration in the renal interstitium. Immunoperoxidase staining of the atypical lymphoid cell population was positive for CD20 and CD79. Combined therapy with prednisolone, plasma exchange and rituximab was commenced. Her proteinuria disappeared and renal function improved after rituximab therapy. In our case, nephrotic syndrome due to cryoglobulinemic glomerulonephritis was successfully treated mainly by rituximab.

Individual assistance plan in the event of disaster has been formulated for neurodegenerative disease patients who wear a ventilator. This study was conducted for evacuation drills by simulating an actual disaster. Disaster assistance drills were conducted with the participation of relevant parties like home care service providers and local community association; the drills were sought to make sure that patients could be transported safely. Problems and issues encountered in the drills were resolved by assistance plans for individuals who need assistance. Under the direction of visiting nurses, the drills were involved in removing the patient from the ventilator, transferring the patient from his or her bed to a reclining wheelchair, and transporting the patient to a nearby evacuation area. Two individuals were needed to move the wheelchair safely, one was needed to observe the patient's status and provide respiratory care, and the other one was to carry a portable aspirator, so a minimum of four individuals was needed. These drills revealed four things: (1) the patient should be registered with the local municipality as an individual who needs assistance in the event of a disaster, (2) patients should routinely interact with neighbors, (3) home care service providers should periodically assist patients in leaving the home, and (4) visiting nurses' stations should play a leading role in disaster assistance for patients on medical equipment.

A 91-year-old man underwent aortic valve replacement using a pulmonary artery catheter (PAC). Intraoperative hemodynamic monitoring with the PAC showed no abnormality except for bleeding from optical module connection port. In the intensive care unit, difficulty in withdrawing the PAC was noted. Surgical removal of the PAC was performed, revealing the PAC sutured to the right atrium. When bleeding from the PAC connection ports is noted, it is advisable to suspect that the PAC might have been sutured.

Background: The fraction of exhaled nitric oxide (FeNO) is a useful marker of asthma control. The FeNO measurement with two offline methods and NIOXmino may be more affordable, no studies have examined the differences in FeNO values measured with various methods in adult asthmatics., Methods: The study population comprised 39 stable asthmatics treated with inhaled steroids at our outpatient clinic. FeNO values were measured by two offline methods (Sievers and CEIS), NIOXmino., Results: FeNO(NIOXmino) values were significantly correlated with those of FeNO(Sievers) (r=0.935, P< 0.001) and FeNOCEIS (r=0.908, P< 0.001). However, FeNO(NIOXmino) values were low compared with FeNO(Sievers) (FeNO(NIOXmino)=0.848 x FeNO(Sievers)) and FeNO(CEIS) (FeNO(NIOXmino)=0.672 x FeNO(CEIS))., Conclusion: Differences exist in the values of FeNO measured by various methods: conversion equations are needed to compare the FeNO values among these three methods.

Background: The purpose of this study was to clarify disease control and medication use among Japanese adult asthmatic patients., Method: We studied the reality of adult outpatients and inpatients with asthma at 26 national hospitals across Japan who visited the clinic between September and October 2006. Anti-asthma medication use and asthma control were assessed. Disease severity was determined according to the 2006 Japanese Guideline. The results of this study were compared with those obtained in 1995 after standardization by age and gender., Results: Of 2524 patients, the prevalence of inhaled corticosteroid use in 2006 was 89%, which was higher than that in 1995 (62%). Although the prevalence of patients who experienced asthma hospitalization once or more in their lifetime in 1995 was 73%, that in 2006 decreased to 49%. The prevalences of hospitalization and unscheduled doctor visit in the last 12 months in 2006 were 8% and 25% respectively. The percentage of patients in 2006 who did not reach an acceptable level of control despite treatment at step 4 of the 2006 Japanese guideline was 15%., Conclusions: A favorable change in asthma medication use and asthma control was observed from 1995 to 2006; that is, increased prevalence of inhaled corticosteroid use and decreased prevalence of patients who experienced hospitalization for asthma once or more in their lifetime. However, some patients remained symptomatic despite high-dose inhaled corticosteroid treatment.

An improvement of support system for patients who need assistance in the event of a disaster is crucial. Evacuation support plan (individual plan) has recently begun to include patients with intractable disease, and specific guidelines are being drafted to establish a support plan for patients with intractable disease in the event of disaster. Here, we report our attempt to a disaster response for patients receiving home ventilator care. To examine in the event of disaster, specific methods of verifying safety of patients with severe intractable disease and transporting them safely to a shelter, a Discussion Group and the Committee on Intractable Disease examined two cases with amyotrophic lateral sclerosis (those who are ventilator-bound, and those who have a gastrostomy tube). While some providers of visiting care were found to be actively involved in steps to verify patient's safety, problems such as a concentration of information at the municipal level were present. The current reality is that an ambulance, in principle, cannot be readily dispatched to provide transportation in the event of disaster. So patients must depend on neighbors and volunteer disaster response groups. In the future, evacuation drills must be conducted along with a verification of patient safety, and steps must be taken in cooperation with the local municipality to aid patients who need assistance during the disaster.

A 57-year-old woman was referred because of exertional dyspnea, fever, and cough in June 2006. She had been employed to culture roses in greenhouses since 1991 and had developed a cough during the summer from 2003. Chest CT scan revealed diffuse centrilobular micronodules. Transbronchial lung biopsy specimens demonstrated alveolitis with lymphocytes and non-necrotizing epithelioid cell granulomas. After admission, both the patient's symptoms and laboratory data improved without medication. However, upon her return to work in the greenhouse, cough and exertional dyspnea reappeared. Aspergillus niger was detected in the greenhouse. Her serum was assayed for precipitating antibodies against various antigens, and precipitating antibodies against Aspergillus fumigatus, Aspergillus flavus, Aspergillus glaucus, and Aspergillus niger were demonstrated. In a double immunodiffusion test, cross-reactivity between Aspergillus niger and other Aspergillus species was indicated. Consequently, she was diagnosed as having hypersensitivity pneumonitis resulting from the inhalation of Aspergillus niger.

Objective: There are no specific signs or symptoms in Multiple Chemical Sensitivity (MCS), so diagnosis of MCS depends on a history, QEESI symptom scores and exclusion of other diseases. A gold standard of diagnosis of MCS is a chemical compound exposure test in which changes of symptoms are used to decide the results positive or negative. We have done chemical compound exposure tests to diagnose MCS in 51 patients., Methods: Chemical compound exposure tests were done in a special facility (the exposure chamber) in our hospital. Used VOC were formaldehyde or toluene. Maximum exposure concentrations were 0.08 ppm and 0.07 ppm for formaldehyde and toluene, respectively. Forty patients had the tests by a open test manner and 11 patients by a single blinded manner., Results: In the open tests, 18 patients had positive results and 22 patients negative. In 22 patients who had negative results, eleven showed no symptoms by chemical exposures, and other 11 claimed symptoms before VOC went into the chamber. In the single blinded tests, 4 patients had positive results and 7 patients negative., Conclusion: The chemical exposure test is the most reliable test to diagnose MCS, so standardization of the methods of the test is necessary.

Background: The fraction of exhaled nitric oxide (FeNO) is a useful marker of asthma control. The FeNO measurement with our offline method using SIEVERS bag collection kit may be more affordable, but there have been no studies to show the effect of anti-asthmatic therapy on FeNO with our offline method., Methods: The study population comprised 36 steroid-naïve asthmatics at our outpatient clinic. We treated them according to asthma prevention and management guideline 2006, Japan. We also measured eNO levels by our offline method and spirometory on baseline, 4weeks, and 12 weeks of treatment., Results: All asthmatics were symptom-free on 12 weeks of treatment. The levels of FeNO FEV1/FVC were significantly decreased on 4 weeks and 12 weeks of treatment, compared with that on first visit. We classified the subjects into two groups; (A) FEV1/FVC <70% (n=11) or (B) FEV1/FVC > or =70% (n=25) on baseline. In (A) group, the level of FeNO and FEV1/FVC were significantly improved on 4 and 12 weeks of treatment. In (B) group, on 4 weeks of treatment, the level of FEV1/FVC was significantly increased but the level of FeNO was not significantly changed. On 12 weeks of treatment, the levels of FeNO was significantly decreased, but the level of FEV1/FVC was not significantly changed., Conclusion: The levels of FeNO were decreased by antiasthmatic therapy, so that offline monitoring of eNO will facilitate the management of bronchial asthma in patients treated with these drugs.

Background: In asthmatic patients, first asthmatic symptoms are not often typical. In those cases, it takes long time before asthma diagnosis, and the severities are progressed in some patients. For early intervention, we tried to make the diagnostic criteria for asthma, which are useful to diagnose as early stage of asthma., Methods: Three hundred and eighty eight of asthmatic patients, who were recorded first their symptoms in asthma, were enrolled. Their first symptoms and examinations were analyzed., Results: In first asthmatic symptoms, 79% of patients had cough, 68% patients had wheezing, 49% patients had dyspnoea, and 15% of patients did not have typical asthmatic symptoms in the early stage. The percentages of abnormal in first examinations were 99% in airway hypersensitivity, 92% of low %V25, 82% of eosinophila in sputum and 77% of low %V50. Low FEV1% and reversible airway obstruction were not seen in a lot of patients., Conclusion: We advocate that the diagnostic criteria for early stage of asthma are the following three elements. First criterion is spasmodic cough, wheezing and dyspnoea. Second criterion is airway hypersensitivity, or over 3% of eosinophils in sputum, or under 70% of %V50, or under 50% of %V25, or effect of bronchodilator. Effect of bronchodilator will be required, when the symptom is cough only. Third criterion is the exclusion of other lung and heart diseases.

Background: Because both allergic rhinitis and asthma are caused by eosinophilic airway inflammation, using the same method to measure the eosinophilic inflammation of both the upper and lower airway would be advantageous. The levels of nitric oxide in exhaled air (FeNO) and nasal air (nNO) are useful as noninvasive markers of eosinophilic airway inflammation. Although the off-line method of measuring these parameters is easier and more useful than the on-line method, studies using the off-line method are rare in Japan., Methods: In Study 1, we measured the levels of nNO and FeNO in 9 healthy controls and 9 subjects with allergic rhinitis, to validate the methodology for using the off-line method to measure nNO. In Study 2, we measured the nNO and FeNO levels of and performed spirometry on 69 stable asthmatics treated with inhaled corticosteroid., Results: In Study 1, nNO levels were significantly increased in patients with allergic rhinitis compared with healthy subjects (31.0 [20.8 to 41.2] versus 7.4 [0.0 to 14.8] ppb {median [95% confidence interval]}, p=0.018). The 69 patients with asthma that comprised the study population in Study 2 were classified as asthmatics with rhinitis (treatment-naïve, n=14; treated with antiallergic drugs, n=11; treated with intranasal corticosteroid, n=19) and asthmatics without rhinitis (n=15). Although FeNO did not differ among groups, nNO was significantly increased in treatment-naïve asthmatics with rhinitis compared with patients with asthma only (26.5 [17.1 to 35.9] versus 8.0 [-1.1 to 17.1] ppb, p=0.033)., Conclusion: nNO levels measured by the off-line method are useful markers of allergic rhinitis.

Purpose: To investigate the prevalence of adult asthma and allergic rhinitis, and to analyze associations between smoking habit, obesity and disease in Kamishihoro town, Hokkaido., Methods: The Japanese edition of the European Community Respiratory Health Survey (ECRHS) Questionnaire was completed by 3096 residents (men: 1520, women: 1576) who ranged in age from 18 to 81., Results: Among the respondents, 12.9% of the males and 9.8% of the females responded "Yes" to the questionnaire item, "Wheezing at any time in the last 12 months" (defined as having asthma) and 17.6% of the males and 23.0% of the females responded "Yes" to the question, "Do you have any nasal allergies including hay fever?" (defined as having allergic rhinitis). This prevalence tended to be higher among younger respondents. Smoking habit and obesity were significantly associated with wheezing over the last 12 months, but not with allergic rhinitis., Conclusion: Smoking habit and obesity are significantly associated with asthma in Kamishihoro town, located in a rural area of Hokkaido, Japan.

Evidences have shown that the fraction of exhaled nitric oxide (FeNO) is a useful marker of eosinophilic airway inflammation in asthmatics. There is no study to show the FeNO cutoff point for detecting asthma and the influence of smoking, measured by the Sievers Bag collection kit. The study population comprised 60 steroid-naive asthmatic patients (BA) (32 non-smokers, 28 smokers) and 59 patients with chronic cough (CC) without asthma (42 non-smokers, 17 smokers) in our outpatient clinic. We measured FeNO levels, spirometory, bronchial hyperresponsiveness against acetylcholine, and other parameters. The levels of FeNO were significantly increased in asthmatics compared with subjects with chronic cough. According to the ROC curve, the cutoff point of FeNO was 30 ppb (AUC = 0.83, sensitivity 78.1%, specificity 73.5%, p < 0.001) in non-smokers. The levels of FeNO in smokers were not significantly different from those in non-smokers, both bronchial asthma and chronic cough subjects. But the cutoff point of FeNO was 40 ppb (AUC = 0.65, sensitivity 67.8%, specificity 70.6%, p = 0.012). In conclusion, the cutoff point of FeNO was 30 ppb in non-smokers and 40 ppb in smokers. In smokers, FeNO measurement was less useful.

Background: The measurement of several mediators in exhaled breath condensate (EBC) can be useful as the biomarker for asthma. But there are a few reports about EBC of asthmatics in Japan., Aim: We examined the safety of the collection of EBC and the utility of cysteinyl leukotriene (cysLTs) in EBC as the biomarker of asthma., Methods: Fifty-three asthmatics and eleven subjects without asthma were recruited. After the measuring of exhaled nitric oxide (eNO) and spirometory, EBC were collected. The levels of cysLTs in EBC were measurement by ELISA within 2 months., Results: The collection of EBC did not induce any other symptoms in all subjects. In 48 subjects, the collection significantly increased their FEV1 and MMF level (DeltaFEV1: 2.27+/-0.77%, DeltaMMF 14.6+/-3.92% (mean+/-SEM). The level of cysLTs in EBC on asthmatics treated with high-dose ICS was significantly high compared with control group (p=0.0034), steroid-naïve asthmatics or asthmatics treated with low-dose ICS (steroid naive vs. high dose ICS, p=0.041, low dose ICS vs. high dose ICS, p=0.021). The relationship between cysLTs in EBC and the levels of LTE4 in urine was significantly correlated (n=34, r=0.32, p=0.0435). The relationship between cysLTs in EBC and the levels of eNO was significantly correlated only in steroid-naïve asthmatics (r=-0.57, p=0.0369). There was no relationship between cysLTs in EBC and FEV1, or log PC20Ach., Conclusion: The collection of EBC was perfectly non-invasive. The level of cysLTs can be useful as a biomarker of asthma.

We examined immunological differences by non-specific and specific stimuli, using Trichosporon asahii (Ta), in 5 subjects in one family. The mother and her eldest daughter, among the 5 subjects in the family, were given diagnoses of summer-type hypersensitivity pneumonitis (HP) as a result of imaging, serological and histological examinations. The symptoms in both cases improved immediately after systemic corticosteroid therapy. Their home environment was cleaned up, and there has been no recurrence. All family subjects showed a positive reaction for the precipitin of Ta crude antigen, in addition four subjects, but not the father, revealed positive reactions for Type II Ta antigen in agglutination tests. In patients with HP, the concentrations of IFN-gamma by anti-CD3 + and anti-CD28 antibody stimulation were lower than those of healthy subjects. The concentrations of IFN-gamma and TNF-alpha for Ta antigen stimulation revealed no differences between the patients and healthy subjects in the family. In conclusion, we could not find any differences between the patients and non-patients in the family from the results of the serological and cytokine production measurement.

Background: Recently, it is recognized that the patients of oral allergy syndrome (OAS) to fruits are increasing. However, there are little knowledges of the background, character, and seriousness about these patients in Kanto regions., Objective: We aimed to investigate the clinical features of OAS patients to plant origin foods in Kanto regions., Methods: The patient, who visited Sagamihara National Hospital from 2000 to 2005 and developed some allergic symptoms to plant origin foods, were studied by a questionary survey., Results: As for the 42 subjects, average age are 36 years old, male:female=8:34, merger of other allergic disease is 35 allergic rhinitis of 42 subjects (83%), 34 of asthma (81%), 14 of atopic dermatitis (33%). The causes of OAS symptoms are 32 rose-family fruits, 34 non-rose family fruits, 14 vegetables, 11 nuts, 2 grains subjects. As for the symptom, only in the oral and pharynx symptoms are found in 12, the systemic symptoms is 29, anaphylaxis is 11 subjects. Allergic rhinitis preceded on the 90% subjects with pollinosis, very high rate. On the other hand, the 20% of all subjects have no symptoms of allergic rhinitis., Conclusion: A nasal catarrh symptoms went ahead in most of the OAS subjects in Kanto regions. In addition, considering from some patients have no black alder pollinosis and/or are allergic to many non-rose-family fruits at high frequency, there might be a broad cross-reactivity between many pollens other than alder and plant origin foods.

Background: Inhaled antigen increases exhaled nitric oxide (eNO) in atopic asthmatics. Recent study showed that the increase of eNO levels was observed in late response (8-10 hours after inhaled antigen) but not in early response (1.5 hour after inhaled antigen). But we recognized that in some asthmatics eNO levels were increased during early response induced by antigen., Methods: Atopic stable subjects with asthma induced by specific antigen (mite 11, housedust 3) were recruited in this study. Through bronchial provocation test with Mite or Housedust antigen, eNO levels were examined. As the control group, 7 atopic asthmatics who were not induced by specific antigen were recruited., Results: In 7 subjects, the levels of eNO were increased during early response after inhaled antigen, and in other 7 subjects the levels of eNO were decreased. There were significant difference in the falling of FEV1 at threshold between the two groups (eNO increased group vs eNO decreased group, 22.1+/-0.87 (%) vs. 44.2+/-6.57 (%), p=0.016). In 6 subjects in control group, the levels of eNO were decreased., Conclusion: Inhaled antigen increased the levels of eNO in some asthmatics during early response in bronchial provocation test. The level of eNO has possibility of predicting the sudden decrease of FEV1 in bronchial provocation test.

The measurement of exhaled nitric oxide (eNO) is a non-invasive biomarker of bronchial inflammation. Despite the usefulness of eNO measurement, NO analyzers are too expensive for widespread use by general practitioners. In comparison, the off-line (bag collection) method of eNO measurement may be more useful. In Japan, however, there have been few studies about eNO in asthmatics using the off-line method. This study shows methodological aspects of the off-line method. Briefly, with a SIEVERS bag collection kit, we recommend that the flow rate and pressure level of exhaled air should be 70 ml/sec and 10 cm H2O, respectively and that the sampled air should be measured within 12 hours.

Purpose: This study was designed to clarify the definition of sick house syndrome (SHS)., Methods: SHS was defined based on the disease related to habitation as follows. 1. The cause of the onset of a disease relates to house. 2. Symptoms appear within house. 3. Symptoms will be less serious or disappear if patient away from house. 4. If patient goes into house, symptoms will appear repeatedly. When it corresponded to all above, it was defined to SHS, and it classified as MCS (multiple chemical sensitivities) without above conditions. Even if SHS is isolated from similar disease completely, characteristic symptoms of MCS are hard to be detected because MCS are combination of two or more diseases. Based on this working hypothesis, the logistic regression by setting MCS as reference was performed so that characteristic symptoms of SHS show odds ratios with exceeding one., Results: The odds ratios with more than two of characteristic symptoms in SHS were "nausea or vomiting" "Troublesome in everything" and the causative substances to which symptoms get worse was "The smell of a perfume and cosmetics". Characteristic symptoms of an allergy disease were detected by comparison with the allergic conjunctivitis, allergic rhinitis, and bronchial asthma, respectively., Conclusion: These results showed that the classification method was appropriate. This definition is not fundamentally differed from the definition of the sick-building syndrome of WHO.

Purpose: To enable international comparison of prevalence in asthma, we translated and evaluated ECRHS Questionnaire, which is introduced in GINA. Considering COPD prevalence in elder people, we added two questions to the ECRHS Questionnaire., Method: The Japanese edition of ECRHS Questionnaire was responded by 366 patients who were diagnosed asthma without COPD, 61 patients who were diagnosed COPD without asthma, and 137 healthy persons who were not diagnosed asthma or COPD. We analyzed the answers of the each group and evaluated the validity of the questionnaire to use for the nation-wide prevalence study of adult asthma in future., Results: The question of 'Wheezing at any time in the last 12 months' had the highest Youden's index and validity to pick up asthma patients. The questions of 'Waking up with a feeling of tightness in chest at any time in the last 12 months' and 'Waking up by an attack of shortness of breath at any time in the last 12 month' had the highest specificity to pick up asthma patients. Most of the questions which were related asthma were able to be answered by asthma patients properly, but some questions were improperly answered by patients and healthy persons in elderly. The results in this study showed the less recognition of their diseases in elderly patients than younger patients and the limitation of the study with written questionnaire for elderly people. Not a few COPD patients complained wheezing or whistling in the chests as same as asthma patients in this study., Conclusion: We concluded that we had almost enough reliability in the Japanese edition of the ECRHS questionnaire for screening survey of asthma prevalence in Japan.

A 50-year-old asthmatic woman showed peripheral blood eosinophilia, significantly increased level of CEA in serum (102.5ng/ml), and atelectasis of the right middle lobe on chest radiograph and CT. The level of CEA subsequently increased further, and then decreased with systemic corticosteroid therapy. Pathological findings of surgically biopsied lung showed eosinophilic broncho-bronchiolitis, without malignant cells. Two years later, chest CT demonstrated various findings such as mucoid impaction, peripheral bronchiectasis and centrilobular nodules, but allergic bronchopulmonary mycosis was not proved. These findings suggest that the eosinophilic bronchiolar inflammation in bronchial asthma caused an increase in serum CEA levels and various findings on chest CT.

We reported a 46-year-old woman with Marfan's syndrome exhibiting an incomplete Currarino triad and recurrent bacterial meningitis which recurred three times in about six months. An anterior sacral meningocele (ASM) was noted in a lumbar MRI, and multiple bone defects in the sacrum were noted in 3D-CT. Surgical approach to prevent the recurrence of infection was limited to plasty for the meningocele, but no meningitis has been observed for two years. Radical surgery should be considered in cases with ASM who recurred bacterial meningitis.