Publications by authors named "Yuko Komase"

35 Publications

Back to normal; serological testing for COVID-19 diagnosis unveils missed infections.

J Med Virol 2021 Mar 19. Epub 2021 Mar 19.

Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.

Background: The gold standard for coronavirus disease (COVID-19) diagnosis has been the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by nucleic acid amplification testing (NAAT). On the other hand, serological testing for COVID-19 may offer advantages in detecting possibly overlooked infections by NAAT.

Methods: To evaluate seroconversion of NAAT-negative pneumonia patients, immunoglobulin M (IgM) and IgG targeting the spike protein of SARS-CoV-2 were semiquantified by an immunofluorescence assay. Seroconversion was confirmed by another serological method, targeting the nucleocapsid protein.

Results: Eight suspected but unconfirmed COVID-19 pneumonia patients (median age, 39 years; range, 21-55) were included. The median period between symptom onset and NAAT sample collection was 6 days (2-27 days). None of them had tested positive for SARS-CoV-2 by NAAT. In contrast, all eight patients revealed seropositivity with the two serological methods, indicating actual seroconversion against SARS-CoV-2. The median period between onset and blood sampling was 26.5 days (7-51 days).

Conclusion: Eight patients with COVID-19 pneumonia, initially tested negative for SARS-CoV-2 by NAAT, were finally confirmed of the diagnosis by serological testing. To cover the whole spectrum of this heterogenous infectious disease, serology testing should be implemented to the multitiered diagnostic algorithm for COVID-19.
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http://dx.doi.org/10.1002/jmv.26949DOI Listing
March 2021

Gastroesophageal reflux-like symptoms are associated with hyposalivation and oropharyngeal problems in patients with asthma.

Respir Investig 2021 Jan 19;59(1):114-119. Epub 2020 Jul 19.

Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan; NPO Association of Inhalation Therapist, 1197-1 Yasashi-cho, Asahi-Ku, Yokohama, Kanagawa, 241-0811, Japan. Electronic address:

Background: Previous studies have suggested a significant relationship between hyposalivation and inhalation therapy-induced oropharyngeal problems. However, salivary secretion tests are not widely performed in daily clinical practice. In fact, xerostomia, the complaint of dry mouth, may not indicate hyposalivation. Therefore, we determined the clinical factors associated with hyposalivation in patients with asthma.

Methods: This study is a post-hoc analysis of our previous studies. Adult patients with asthma on maintenance inhalation therapy were enrolled. The participants completed questionnaires on oropharyngeal symptoms and underwent a salivary secretion test. Symptom severity was evaluated using a numerical rating scale (NRS), and salivary secretion was measured using the modified cotton roll method. Using logistic regression analysis, we identified the clinical factors associated with hyposalivation.

Results: In total, 531 patients completed the questionnaire (43.8 ± 16.9 years and male/female = 171/360), and 234 patients successfully performed a salivary secretion test, of which 126 (53.8%) were diagnosed with hyposalivation (<0.25 g/min). The patients with hyposalivation were significantly older (p < 0.0001) and had severe xerostomia and/or gastroesophageal reflux-like symptoms (GERLS) (p < 0.0001). Many of these patients had also used inhaled long-acting beta agonists (p = 0.012) and high-dose inhaled corticosteroids (p = 0.024). Multivariate analysis revealed that advanced age (odds ratio [OR] 1.05, p < 0.0001), severe xerostomia (OR 1.02, p = 0.0006) and severe GERLS (OR 1.02, p = 0.001) were independently and significantly associated with hyposalivation.

Conclusions: Age, xerostomia, and GERLS were significantly related to hyposalivation in patients with asthma. To identify oropharyngeal problems in these patients, a careful assessment of the suspected symptoms of gastroesophageal reflux may be useful.
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http://dx.doi.org/10.1016/j.resinv.2020.06.004DOI Listing
January 2021

The Impact of EGFR Mutation Status and Brain Metastasis for Non-Small Cell Lung Cancer Treated with Ramucirumab plus Docetaxel.

Oncology 2020 28;98(9):661-668. Epub 2020 May 28.

Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.

Objectives: Currently, combination therapy of ramucirumab (RAM) + docetaxel (DOC) must play a more important role as a second-line treatment. Epithelial growth factor receptor (EGFR) mutation accounts for around 50% of oncogenic driver mutations in patients with advanced non-small cell lung cancer (NSCLC) in Asian subsets. The number of brain metastases (BM) is relatively higher in EGFR mutation-positive patients compared to EGFR wild-type patients. The objective of this study is to evaluate the efficacy of RAM + DOC focusing on EGFR mutation and BM.

Methods: We retrospectively reviewed consecutive advanced NSCLC patients who received combination therapy of RAM + DOC at three institutions. A total of 112 patients with NSCLC were enrolled for efficacy analyses. We evaluated the efficacy of RAM + DOC for EGFR-mutated NSCLC with endpoints including progression-free survival (PFS), time to treatment failure (TTF) and overall survival.

Results: Median PFS was 5.7 months for the EGFR mutant group compared with 3.6 months for the EGFR wild-type group (HR 0.53, 95% CI 0.32-0.87; p = 0.01). Median TTF was 5.1 months for the EGFR mutant group compared with 2.8 months for the EGFR wild-type group (HR 0.53, 95% CI 0.33-0.85; p = 0.007). Median PFS and TTF of the EGFR mutant group was significantly longer than median PFS and TTF of the EGFR wild-type group. The multivariate analysis identified EGFR mutation status as an independent favorable factor of PFS. In subset analyses of BM, median PFS of the EGFR mutant group (2.8 months) was significantly shorter than that of the EGFR wild-type group (5.1 months) (HR 7.27, 95% CI 1.78-29.68; p = 0.002).

Conclusion: This study revealed that EGFR mutation status and BM might be predictive or prognostic factors for PFS.
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http://dx.doi.org/10.1159/000507050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592951PMC
September 2020

Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship.

J Infect Chemother 2020 Aug 13;26(8):865-869. Epub 2020 May 13.

Department of Respiratory Internal Medicine, St. Marianna University School of Medicine, Yokohama City Seibu Hospital, Japan.

We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.
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http://dx.doi.org/10.1016/j.jiac.2020.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218347PMC
August 2020

Effectiveness and Safety of Omalizumab in Patients with Allergic Bronchopulmonary Aspergillosis Complicated by Chronic Bacterial Infection in the Airways.

Int Arch Allergy Immunol 2020 8;181(7):499-506. Epub 2020 May 8.

Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan,

Background: Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence of predisposing conditions such as asthma and cystic fibrosis. Even ABPA accompanied by asthma is often complicated by chronic Pseudomonas aeruginosa or nontuberculous mycobacterial infection of the lower respiratory tract, rendering treatment with corticosteroids difficult. There have been several reports on the effectiveness of omalizumab, an anti-IgE antibody, in patients with ABPA. We analyzed the effectiveness and adverse effects of omalizumab in ABPA patients with chronic respiratory infections.

Methods: Using our nationwide survey database and published case reports, we identified patients with severe asthma and ABPA who fulfilled the International Society for Human and Animal Mycology criteria and who had been treated with omalizumab. Exacerbation rates, control of symptoms, doses of oral corticosteroids, and pulmonary function were evaluated.

Results: Among 25 patients with ABPA treated with omalizumab (median age 62 years, range 33-83 years), 12 patients had a chronic bacterial infection of the lower airways attributable to P. aeruginosa (n = 6) or nontuberculous mycobacteria (n = 6) at the initiation of omaliz-umab. Treatment with omalizumab reduced the frequency of exacerbations and systemic corticosteroid doses and improved pulmonary function. There were no significant adverse events or worsening of infection during treatment with omalizumab, except for injection-site reactions.

Conclusions: Treatment with omalizumab was effective and safe in patients with ABPA, regardless of comorbid chronic respiratory tract infections.
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http://dx.doi.org/10.1159/000507216DOI Listing
November 2020

The efficacy and safety of ramucirumab plus docetaxel in older patients with advanced non-small cell lung cancer.

Thorac Cancer 2020 06 14;11(6):1559-1565. Epub 2020 Apr 14.

Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.

Background: Ramucirumab plus docetaxel (RAM+DOC) is expected to prolong survival in patients with advanced non-small cell lung cancer (NSCLC); however, the efficacy and safety for older patients remains unknown. The objective of this study was to evaluate the efficacy and safety of RAM+DOC in patients 75 years and older.

Methods: We retrospectively reviewed consecutive patients with advanced NSCLC who had received RAM+DOC treatment at three institutions. We compared the efficacy and safety in patients 75 years and older to those under 75 years of age.

Results: A total of 114 patients were identified. The median progression-free survival, time to treatment failure and overall survival was 3.6 (95% CI: 0.4-6.7), 3.1 (95% CI: 2.4-3.9) and 11.2 months (95% CI: 5.6-16.8) in the older group (N = 23), and 4.2 (95% CI: 3.3-5.0), 3.4 (95% CI: 3.3-5.0) and 12.2 months (95% CI: 9.1-15.4) in the younger group (N = 91), respectively. Survival curves were similar for each group, while the objective response rate was 30.4% (95% CI: 13.2-52.9%) in older patients and 35.2% (95% CI, 25.4-45.9%) for the younger group. A total of 22 older patients (95.7%) and 73 (80.2%) younger patients received primary prophylactic pegylated-granulocyte-colony stimulating factor (PEG-G-CSF). Four older patients (17.3%) and 14 younger patients (15.3%) discontinued RAM+DOC due to adverse events.

Conclusions: RAM+DOC is expected to be efficacious and tolerable in older patients when supported with prophylactic PEG-G-CSF therapy.

Key Points: Significant findings of the study ・PFS, OS, and ORR in older patients were similar to those under 75 years of age. ・Safety of RAM+DOC was well tolerated in older patients with prophylactic PEG-G-CSF. ・Prophylactic PEG-G-CSF with RAM+DOC may contribute to better efficacy. What this study adds ・This study suggests that RAM+DOC with prophylactic PEG-G-CSF is expected to be a useful option in older patients with advanced NSCLC.
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http://dx.doi.org/10.1111/1759-7714.13429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262941PMC
June 2020

The Incidence of Hemorrhagic Complications Was Lower With the Guide Sheath Than With the Conventional Forceps Biopsy Method: Results of Bronchoscopy in the 2016 Nationwide Survey by the Japan Society for Respiratory Endoscopy.

J Bronchology Interv Pulmonol 2020 Oct;27(4):253-258

Kagawa Kenritsu Chuo Hospital, Kagawa, Japan.

Background: The Japan Society for Respiratory Endoscopy performed a nationwide survey to evaluate the current status and complications of bronchoscopy. Data on deaths due to bronchoscopy, complications after bronchoscopy, and particularly, complications of forceps biopsy were surveyed.

Methods: The survey form was mailed to 532 facilities accredited by the society. The numbers of procedures, complications, and deaths were investigated.

Results: The response rate was 79.1% (421 facilities). Deaths attributable to diagnostic bronchoscopy occurred in 11 (0.011%) of 98,497 cases.In regards to forceps biopsy, the guide sheath method was applied in 23,916 cases and the conventional method in 31,419 cases was done with conventional method. Complications of forceps biopsy developed in 1019 cases in total, with an incidence rate of 1.84%. The most frequent complication was pneumothorax (0.70%), followed by pneumonia/pleurisy (0.46%) and hemorrhage (0.45%). The incidence of hemorrhagic complication was significantly lower in the guide sheath group than in the non-guide sheath group (0.29% vs. 0.58%; P<0.001). The overall incidence of complications (1.63% vs. 2.00%; P=0.002) and the mortality rate (0% vs. 0.02%; P=0.04) were significantly lower in the guide sheath group.

Conclusion: The incidence of hemorrhagic complications in forceps biopsy of peripheral pulmonary lesions was lower when the guide sheath method was applied. It is necessary to increase the awareness for safety control in diagnostic bronchoscopy for new procedures.
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http://dx.doi.org/10.1097/LBR.0000000000000669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523573PMC
October 2020

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

Arerugi 2020 ;69(2):119-122

Department of Respiratory Medicine, St. Marianna University School of Medicine.

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.
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http://dx.doi.org/10.15036/arerugi.69.119DOI Listing
April 2020

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 β2 agonists combination.

J Breath Res 2020 03 31;14(2):026013. Epub 2020 Mar 31.

Department of Respiratory Medicine, St. Marianna University school of Medicine, Yokohama City Seibu Hospital, Yasashi-chou 1197-1, Asahi, Yokohama, Kanagawa 241-0811, Japan. Department of Respiratory Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.

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 β2 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 FEV (ΔFEV%) 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 ΔFEV%. FENO, Fres and %FEV at baseline in these stable asthmatics were significantly assosiated with ΔFEV% 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.
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http://dx.doi.org/10.1088/1752-7163/ab7b8cDOI Listing
March 2020

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

J Asthma 2020 11 26;57(11):1173-1178. Epub 2019 Aug 26.

Division of Respiratory Diseases, Saint Marianna University School of Medicine, Kawasaki, Japan.

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.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. We found that BA treatment intensity step was significantly higher for patients with BA who had concurrent moderate or severe OSAS ( = 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.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.
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http://dx.doi.org/10.1080/02770903.2019.1652643DOI Listing
November 2020

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

Arerugi 2019;68(2):101-106

Department of Respiratory Medicine, St. Marianna University.

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.
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http://dx.doi.org/10.15036/arerugi.68.101DOI Listing
May 2019

Current status of diagnostic and therapeutic bronchoscopy in Japan: 2016 national survey of bronchoscopy.

Respir Investig 2019 May 6;57(3):238-244. Epub 2019 Feb 6.

Kagawa Kenritsu Chuo Hospital, Kagawa 760-8557, Japan. Electronic address:

Background: The safety management committee of the Japan Society for Respiratory Endoscopy (JSRE) conducted national surveys to clarify the state of diagnostic and therapeutic bronchoscopy in 2016.

Methods: Questionnaire forms were mailed to 532 JSRE-accredited facilities throughout Japan. We surveyed the actual condition of clinical practice and cases of bronchoscopy during 2016.

Results: Four hundred and thirty-three facilities responded giving a response rate of 81.4%; 67.6% held more than 400 beds. The average number of board accredited senior Fellows and Fellows per facility was 1.9 and 3.2, respectively. Diagnostic bronchoscopy was performed in a hospitalized setting in 74.6% of all facilities. The radial type ultrasound probe was operated in 51.7% of all facilities. The number of facilities has markedly increased compared with that reported in the 2010 survey (19.6%). The bronchoscopic navigation system had been in operation in 41.7% of all facilities. Antithrombotic drugs were adjusted before biopsy in 96.8% of all facilities. For intravenous sedation, midazolam was the first choice in 76.9% of all facilities. Endobronchial ultrasound guided transbronchial lymph node needle aspiration (EBUS-TBNA) has become popular over the decade (19.6% in 2010 to 68.1% in 2016). The mean number of the board accredited senior Fellows and board accredited Fellows increased in comparison with that in 2010. As a new technique, radial type ultrasound-guided peripheral approach has become popular.

Conclusions: Through this survey, the advanced safety of bronchoscopic examination has been secured in many facilities. A continuous monitoring of bronchoscopic practices with respect to safety management is recommended.
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http://dx.doi.org/10.1016/j.resinv.2018.12.007DOI Listing
May 2019

Assessment of inhalation flow patterns of soft mist inhaler co-prescribed with dry powder inhaler using inspiratory flow meter for multi inhalation devices.

PLoS One 2018 20;13(2):e0193082. Epub 2018 Feb 20.

Department of Pharmacy, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan.

The patients' inhalation flow pattern is one of the significant determinants for clinical performance of inhalation therapy. However, the development of inhalation flow meters for various inhalation devices has been unable to keep up with the increasing number of newly launched inhalation devices. In the present study, we developed simple attachment orifices for the inhalation flow pattern monitoring system, which are suitable for all commercial inhalers, and investigated the efficacy of the system on the clinical inhalation instruction for patients co-prescribed dry powder inhaler (DPI) and soft mist inhaler (SMI). First, we constructed simple attachment orifices that were adjusted for 13 commercial inhalers, and examined the correlation between orifice and inhalation device. Second, the inhalation flow patterns (peak inspiratory flow rate, PIFR; inhalation duration time, DT) of patients prescribed a combination of DPI and SMI were monitored before and after inhalation instruction. The inhalation resistance of commercial inhalers are listed in the following order; Twincaps® > Handihaler® > Swinghaler® = Clickhaler® > Twisthaler® > Turbuhaler® > Jenuair® > Diskus® = Ellipta® > Diskhaler® > Breezhaler® > Respimat® = pMDI. The pressure drop via orifice was significantly correlated with that via the commercial inhaler. For the confirmation, all participants achieved the DPI criterion of PIFR. On the other hand, 4 participants (6 clinical visits) of 10 experimented participants could not achieve the essential criterion of DT (> 1.5 sec) for SMI, but all participants improved their duration time after inhalation instruction by pharmacists (P<0.05). In the present study, we successfully developed simple attachment orifice suitable for 13 commercial inhalation devices. These data suggested that our simple attachment orifices for the inhalation flow pattern monitoring system can detect patients with inadequate inhalation patterns via SMI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193082PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819805PMC
May 2018

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

Arerugi 2017;66(10):1230-1235

Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine Yokohama City Seibu Hospital.

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.
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http://dx.doi.org/10.15036/arerugi.66.1230DOI Listing
June 2018

Comparison of clinical and pathological features of lung lesions of systemic IgG4-related disease and idiopathic multicentric Castleman's disease.

Histopathology 2017 Jun 3;70(7):1114-1124. Epub 2017 Apr 3.

Division of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

Aims: The lung lesion [immunoglobulin (Ig)G4-L] of IgG4-related disease (IgG4-RD) is a condition that occurs together with IgG4-RD and often mimics the lung lesion [idiopathic multicentric Castleman's disease (iMCD-L)] of idiopathic multicentric Castleman's disease (iMCD). Because no clinical and pathological studies had previously compared features of these diseases, we undertook this comparison with clinical and histological data.

Methods And Results: Nine patients had IgG4-L (high levels of serum IgG4 and of IgG4 cells in lung specimens; typical extrapulmonary manifestations). Fifteen patients had iMCD-L (polyclonal hyperimmunoglobulinaemia, elevated serum interleukin-6 levels and polylymphadenopathy with typical lymphadenopathic lesions). Mean values for age, serum haemoglobin levels and IgG4/IgG ratios were higher in the IgG4-L group and C-reactive protein levels were higher in the iMCD-L group. All IgG4-RD lung lesions showed myxomatous granulation-like fibrosis (active fibrosis), with infiltration of lymphoplasmacytes and scattered eosinophils within the perilymphatic stromal area, such as interlobular septa and pleura with obstructive vasculitis. All 15 lung lesions of iMCD, however, had marked accumulation of polyclonal lymphoplasmacytes in lesions with lymphoid follicles and dense fibrosis, mainly in the alveolar area adjacent to interlobular septa and pleura without obstructive vasculitis.

Conclusions: Although both lesions had lymphoplasmacytic infiltration, lung lesions of IgG4-RD were characterized by active fibrosis with eosinophilic infiltration within the perilymphatic stromal area with obstructive vasculitis, whereas lung lesions of iMCD had lymphoplasmacyte proliferating lesions mainly in the alveolar area adjacent to the perilymphatic stromal area. These clinicopathological features may help to differentiate the two diseases.
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http://dx.doi.org/10.1111/his.13186DOI Listing
June 2017

Interviewing of patients, physical findings, laboratory findings.

Authors:
Yuko Komase

Nihon Rinsho 2016 10;74(10):1628-1633

When diagnosing bronchial asthma, it is necessary to make a comprehensive assessment of the information obtained by interviewing the patient, physical findings, and laboratory findings, while taking into consideration the course of the condition. This is not an easy task unless it is a classic case. On the other hand, based on the information obtained from the patient interview, it is possible to make predictions to some extent and conduct laboratory tests accordingly. During the patient interview, considerations should be given to other possible diseases, concomitant diseases, degree of severity with/without attacks.
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October 2016

Problems of elderly patients on inhalation therapy: Difference in problem recognition between patients and medical professionals.

Allergol Int 2016 Oct 5;65(4):444-449. Epub 2016 May 5.

Department of Pharmacy, Shiga University of Medical Science Hospital, Shiga, Japan.

Background: There is no systematic analysis to identify problems involved with instruction on inhalation therapy for elderly patients. We conducted a nationwide questionnaire survey for patients and medical professionals.

Methods: A questionnaire survey was conducted of adult patients on inhaled drugs (ages 18-92 years, 820 individuals) and medical professionals (pharmacists or nurses) who provided instruction on inhalation therapy to these patients in 23 institutions in Japan to investigate the technique and the level of understanding (knowledge) of the inhalation therapy. Changes in the recognition of performance of inhalation technique and inhalation knowledge with increasing age were analyzed.

Results: According to patients' subjective assessment, there was no deterioration in the performance of the inhalation technique or loss of the knowledge with increasing age. On the other hand, medical professionals' objective assessment revealed a significant loss of both inhalation technique and knowledge with increasing age. Not many elderly patients noticed their own problems themselves, revealing a great perception gap between elderly patients and medical professionals. Thus, there was concern that patients would unconsciously practice the inhalation procedure improperly. On the other hand, in comparison with non-elderly patients, elderly patients were less resistant to continuation of therapy, suggesting that they would be more likely to accept instruction on inhalation therapy.

Conclusions: Elderly patients are apt to assume that they "understand well", therefore, in order to recognize and close the perception gap between elderly patients and medical professionals, it is necessary to provide them with more aggressive (frequent) instructions on inhalation therapy.
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http://dx.doi.org/10.1016/j.alit.2016.04.002DOI Listing
October 2016

A prospective, multicentre phase II trial of low-dose erlotinib in non-small cell lung cancer patients with EGFR mutations pretreated with chemotherapy: Thoracic Oncology Research Group 0911.

Eur J Cancer 2015 Sep 11;51(14):1904-10. Epub 2015 Jul 11.

Thoracic Oncology Research Group, Kanagawa, Japan.

Background: Low-dose erlotinib may be as effective as gefitinib or erlotinib at full dose in non-small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor (EGFR) gene.

Methods: Patients with chemotherapy pretreated NSCLC harbouring EGFR mutations received erlotinib at 50 mg/d until disease progression or unacceptable toxicities. The dose was escalated to 150 mg/d in patients showing no response (i.e. without major tumour shrinkage according to Response Evaluation Criteria in Solid Tumours (RECIST)) to the initial dose during the first 4 weeks. The primary end-point was the objective response rate at the dose of 50 mg/d.

Results: Thirty-four patients from seven institutes were enrolled. The study was closed early when no response was confirmed in 15 patients, excluding the possibility that the primary end-point would be met. The objective response and disease control rates at the dose of 50 mg/d as determined by an independent review committee were 54.5% and 84.8%, respectively. Four additional patients achieved partial response with increased 150 mg/d dose. Progression-free survival and median survival times during the entire period of the study were 9.5 and 28.5 months, respectively. Treatment-related toxicities were generally mild, the most common being skin disorders and diarrhoea. Only one case experienced grade 3 toxicity, which was transient increase of hepatic enzymes.

Conclusion: The primary end-point was not met; low-dose erlotinib is not recommended for fit patients with NSCLC harbouring EGFR mutations. However, it may merit further evaluation for elderly or frail patients.
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http://dx.doi.org/10.1016/j.ejca.2015.06.120DOI Listing
September 2015

Ease-of-use preference for the ELLIPTA® dry powder inhaler over a commonly used single-dose capsule dry powder inhaler by inhalation device-naïve Japanese volunteers aged 40 years or older.

Int J Chron Obstruct Pulmon Dis 2014 11;9:1365-75. Epub 2014 Dec 11.

Global Respiratory Franchise Medical Department, GSK, Stockley Park, UK.

Background: In patients receiving inhaled medication, dissatisfaction with and difficulty in using the inhaler can affect treatment adherence. The incidence of handling errors is typically higher in the elderly than in younger people. The aim of the study was to assess inhaler preference for and handling errors with the ELLIPTA® dry powder inhaler (DPI), (GSK), compared with the established BREEZHALER™, a single-dose capsule DPI (Novartis), in inhalation device-naïve Japanese volunteers aged ≥40 years.

Methods: In this open-label, nondrug interventional, crossover DPI preference study comparing the ELLIPTA DPI and BREEZHALER, 150 subjects were randomized to handle the ELLIPTA or BREEZHALER DPIs until the point of inhalation, without receiving verbal or demonstrative instruction (first attempt). Subjects then crossed over to the other inhaler. Preference was assessed using a self-completed questionnaire. Inhaler handling was assessed by a trained assessor using a checklist. Subjects did not inhale any medication in the study, so efficacy and safety were not measured.

Results: The ELLIPTA DPI was preferred to the BREEZHALER by 89% of subjects (odds ratio [OR] 70.14, 95% confidence interval [CI] 33.69-146.01; P-value not applicable for this inhaler) for ease of use, by 63% of subjects (OR 2.98, CI 1.87-4.77; P<0.0001) for ease of determining the number of doses remaining in the inhaler, by 91% for number of steps required, and by 93% for time needed for handling the inhaler. The BREEZHALER was preferred to the ELLIPTA DPI for comfort of the mouthpiece by 64% of subjects (OR 3.16, CI 1.97-5.06; P<0.0001). The incidence of handling errors (first attempt) was 11% with ELLIPTA and 68% with BREEZHALER; differences in incidence were generally similar when analyzed by age (< or ≥65 years) or sex.

Conclusion: These data, obtained in an inhalation device-naïve population, suggest that the ELLIPTA DPI is preferred to an established alternative based on its ease-of-use features and is associated with fewer handling errors.
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http://dx.doi.org/10.2147/COPD.S72762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267517PMC
August 2015

Dry mouth as a novel indicator of hoarseness caused by inhalation therapy.

J Asthma 2015 Apr 22;52(3):296-300. Epub 2014 Oct 22.

Department of Pharmacy, Shiga University of Medical Science Hospital , Seta Tsukinowa-cho, Otsu, Shiga , Japan .

Objective: To investigate the influence of dry mouth on the incidence and severity of inhalation therapy-induced hoarseness.

Methods: The volume of saliva secreted without stimulation was measured in patients with asthma or chronic obstructive pulmonary disease (COPD) who also answered a questionnaire on subjective ratings for hoarseness. The relationship between salivary secretion and hoarseness was analyzed by the Pearson correlation and multiple linear regression. The prediction accuracy of salivary secretion for the grade of hoarseness was evaluated using a receiver-operating characteristic (ROC) analysis.

Results: A total of 232 patients participated in this study. The subjective rating score of hoarseness was negatively correlated with the volume of saliva secreted (r = -0.273, p < 0.001). A stepwise multiple linear regression analysis revealed that salivary secretion (p < 0.001) and the dose of fluticasone administered (p < 0.05) were significant variables for predicting hoarseness. The ROC analysis for predicting severe hoarseness by salivary secretion showed significant prediction accuracy (AUC = 0.690, 95% CI: 0.614-0.766, p < 0.001) and was higher in patients administered fluticasone (AUC = 0.732, 95% CI: 0.644-0.821, p < 0.001).

Conclusions: Hyposalivation is a significant prediction factor of hoarseness induced by inhaled corticosteroids (ICS). The prediction accuracy was higher in patients administered fluticasone than in those administered another inhalation drug. Although the pharmaceutical efficacy of fluticasone is high, patients with hyposalivation should be prescribed other inhalation drugs.
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http://dx.doi.org/10.3109/02770903.2014.971965DOI Listing
April 2015

[Current status of "hospital-clinic" and "hospital-pharmacy" cooperation for inhalation therapy -based on hospital surveys throughout Japan].

Arerugi 2014 Feb;63(2):178-86

International University of Health and Welfare, Clinical Medicine Study Center Department of Allergy, Sanno Hospital.

Background: The "zero death from asthma strategy" in the medical treatment for bronchial asthma has been promoted by the Ministry of Health, Labour, and Welfare from 2006, and it indicates that medical and non-medical specialists, as well as pharmacists, should cooperate, and strives to build cooperation which is suited the actual conditions of an area. It is also important for COPD. Although hospitals in some areas cooperate with clinics and pharmacies, the overall concept of cooperation appears to be absent in most Japanese hospitals.

Method: A questionnaire was administered in early March, 2012 to 477 allergology institutions, and was authorized by an educational establishment.

Result: Among 246 replies from the institutions, cooperation between hospitals and clinics was carried out by 98 institutions (39.8%) specializing in bronchial asthma, and in 64 institutions (37.2%) specializing in COPD. However, cooperation tools were used in only 37 of these institutions (15.0%). The ability to fill prescriptions outside the hospital was available in 209 institutions (85.0%). One-hundred and seventeen institutions (47.6%) replied that they have no tools for hospital-pharmacy cooperation. Direct indications were written in prescriptions by 82 institutions (33.3).

Conclusion: In order to build inter-regional association and to equalize medical treatment, we suggest that developing tools and organization for cooperation between health professionals who treat patients with bronchial asthma and COPD is necessary.
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February 2014

Successful treatment with noninvasive positive-pressure ventilation based on the prediction of disease onset using CT and respiratory function tests in an elderly patient with relapsing polychondritis.

Intern Med 2013 15;52(10):1085-9. Epub 2013 May 15.

Department of Respiratory Medicine, Yokohama-City Seibu Hospital of St. Marianna University School of Medicine, Japan.

An 83-year-old man who had been receiving treatment for bronchial asthma since 62 years of age experienced difficulty breathing on exertion and was admitted to the hospital. On admission, computed tomography revealed tracheal wall thickening, while test results for antinuclear antibodies and anti-type II collagen antibodies were positive. Since a saddle nose deformity, malacia of the auricles and sensorineural deafness were also observed, relapsing polychondritis was diagnosed. Measuring the peak expiratory flow rate was useful in the early airway assessment. During the follow-up period, the patient's dyspnea worsened and noninvasive positive-pressure ventilation was introduced. As a result, the subjective symptoms improved.
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http://dx.doi.org/10.2169/internalmedicine.52.9035DOI Listing
January 2014

[A case of severe influenza (H1N1) 2009 virus pneumonia identified by virus culture instead of PCR].

Kansenshogaku Zasshi 2011 Nov;85(6):670-3

Department of Respiratory Internal Medicine, St. Marianna University, School of Medicine, Yokohama-City Seibu Hospital.

A 70-year-old man was being treated for asthma and chronic obstructive pulmonary disease, which had been well controlled. He was seen at our emergency outpatient department on October 24, 2009, for respiratory distress and mild fever. Point-of-care testing for influenza, general bacteria, and acid-fast bacilli in the sputum, were negative. With antibiotics ineffective, his respiratory status worsened, requiring him to be intubated and ventilated mechanically. Steroid pulse therapy temporarily improved his condition, as confirmed by imaging studies, but he died on hospital day 38. Polymerase chain reaction (PCR) analysis of tracheal secretion and bronchial washings collected on hospital day 14 and 21 were negative for influenza (H1N1) 2009 virus, which was identified in a subsequent culture. Negative results for reverse transcriptase-PCR analysis leave (H1N1) 2009 virus unable to be diagnosed clinically. Culture tests and repeated PCR analysis have been done in cases of strongly suspected clinical infection to confirm results. Our case, in which the virus was identified by culture, suggests that the viral load may have been too low or the time of culture inappropriate.
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http://dx.doi.org/10.11150/kansenshogakuzasshi.85.670DOI Listing
November 2011

Time trend in the prevalence of adult asthma in Japan: findings from population-based surveys in Fujieda City in 1985, 1999, and 2006.

Allergol Int 2011 Dec 25;60(4):443-8. Epub 2011 May 25.

Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Kanagawa, Japan.

Background: The burden of asthma is recognized as an important public health problem worldwide. In most countries, the prevalence of asthma has been reported to increase in the last few decades. However, more recent epidemiological studies have shown that the prevalence of asthma has been flat or even decreasing after the 1990 s in some developed countries. The recent time trend in the prevalence of adult asthma in Japan is unknown.

Methods: Population-based surveys were conducted three times in the same region, in 1985, 1999, and 2006, at Fujieda City, Shizuoka, Japan, and the results were reported previously. We compared the results of these surveys to reveal the time trend in the prevalence of adult asthma. Although the questionnaires used in these surveys were not exactly the same, the time trend was assessed by comparing the responses to relevant questions between questionnaires.

Results: The prevalences of wheeze following a common cold and dyspneal feeling at night increased significantly from 1985 to 1999 (4.2% to 7.6%, and 3.2% to 5.3%, respectively). The prevalences of lifetime asthma and current asthma also significantly increased from 1999 to 2006 (5.1% to 6.7%, and 1.5% to 3.4%, respectively).

Conclusions: The prevalences of asthma among adults in Fujieda City consistently increased from 1985 to 2006. There was no evidence that the prevalences were in plateau or decreasing. These findings suggest that more efforts are required to stop the increase in the burden of this disease in Japan.
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http://dx.doi.org/10.2332/allergolint.10-OA-0282DOI Listing
December 2011

Organizing pneumonia in a patient with rheumatoid arthritis treated with etanercept.

Mod Rheumatol 2010 Dec 24;20(6):611-6. Epub 2010 Jun 24.

Odoriba Sakaida Clinic, 8-2-1 Gumisawa-cho, Totsuka-ku, Yokohama, 245-0061, Japan.

Etanercept-induced organizing pneumonia (OP) has not been reported in Japan. We describe the case of a rheumatoid arthritis patient who developed OP during etanercept treatment and discuss the possible mechanisms underlying the development of etanercept-induced OP and the existence of factors that predispose Japanese patients to drug-induced OP.
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http://dx.doi.org/10.1007/s10165-010-0327-1DOI Listing
December 2010

Nationwide cross-sectional population-based study on the prevalences of asthma and asthma symptoms among Japanese adults.

Int Arch Allergy Immunol 2010 20;153(3):280-7. Epub 2010 May 20.

Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Japan.

Background: Asthma is a common respiratory disease worldwide. However, few reports are available on the prevalences of asthma and asthma symptoms among Asian subjects.

Methods: To determine the prevalences of asthma and asthma symptoms among Japanese subjects, we performed a nationwide cross-sectional, population-based study on Japanese adults aged 20-79 years. Ten areas spread throughout the country were randomly selected. Door-to-door or postal surveys were performed using a translated version of the European Community Respiratory Health Survey questionnaire.

Results: The survey was completed by 23,483 participants. The overall response rate was 70.6%. The prevalences of wheeze and current asthma among all participants aged 20-79 years were 10.1% (95% CI: 9.7-10.5%) and 4.2% (95% CI: 4.0-4.5%), respectively. The prevalences among young adults aged 20-44 years were 9.3% (95% CI: 8.7-9.9%) and 5.3% (95% CI: 4.8-5.8%), respectively. The prevalence of current asthma was highest in females aged 30-39 years in comparison with the other gender and age groups.

Conclusions: This nationwide study determined the prevalences of asthma and asthma symptoms among Japanese adults. The results provide fundamental information on the respiratory health of Japanese adults.
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http://dx.doi.org/10.1159/000314369DOI Listing
November 2010

Paragonimiasis in a person whose symptoms were shown 22 years after emigrating to Japan from Laos.

J Infect Chemother 2010 Feb;16(1):49-52

Department of Respiratory Medicine, Yokohama-City Seibu Hospital, St. Marianna University School of Medicine, Asahi-ku, Yokohama, Japan.

We report a patient, a 52-year-old man from Laos, who had come to Japan at 30 years of age, but had maintained a habit of eating raw freshwater crabs. The patient visited a physician for left chest pain in January 2007. Infiltration and mass-like shadows were noted in the left superior and inferior lobes on chest X-ray. Diagnosis could not be made by bronchial brushing, but eggs were present in sputum cytology 3 days after bronchoscopy. Therefore, paragonimiasis was diagnosed. The peripheral eosinophil count had increased to 2550/μl and the serum IgE level was elevated, at 71000 IU/ml. Multiple-dot enzyme-linked immunosorbent assay (ELISA) for specific IgG antibodies in serum was positive for Paragonimus westermani and P. miyazakii. Paragonimiasis may have been caused by the style of Laotian cooking without heating. Because the habit of eating raw freshwater crabs is common in Laos, Laos is one of the countries where paragonimiasis is prevalent. For patients from Laos with lung diseases, differentiation including paragonimiasis is required.
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http://dx.doi.org/10.1007/s10156-009-0005-4DOI Listing
February 2010

Survey on the handling of chronic obstructive pulmonary disease by annual health check in Japan.

Intern Med 2008 15;47(20):1791-6. Epub 2008 Oct 15.

St. Marianna University School of Medicine, Yokohama-City Seibu Hospital, Yokohama.

Objective: Since mild COPD can be detected in the annual health check by lung function tests, we conducted a questionnaire survey on how such examinations are used to assess chronic obstructive pulmonary disease (COPD).

Methods: We mailed questionnaires to 633 facilities performing comprehensive medical check-up from June to July 2005 and obtained responses from 254 (40.1%).

Results: At participating facilities, the proportion of full or part-time physicians specializing in respiratory diseases was low [40 of 366 full timers (10.9%) and 114 of 2,044 part-timers (5.6%)], with very few physicians certified by the Japanese Respiratory Society (6.8%). Non respiratory physicians were involved in evaluating the results of thoracic diagnostic imaging at 32 facilities. Lung function tests were carried out at 98.2% of facilities though relatively few facilities evaluated test results with COPD in mind. All stages (mild, moderate, severe) of COPD were diagnosed in patients at 85 facilities (39.2%), while only severe COPD was targeted by chest imaging at 97 facilities (44.7%), disregarding mild and moderate cases. Counseling for smoking cessation was provided at 113 facilities (20.6%), while 30 facilities (14.4%) provided no form of smoking cessation.

Conclusion: At most facilities performing a comprehensive medical check-up, there was not a sufficient number of respirologists to ensure early diagnosis of COPD and this may have compromised COPD diagnosis. The newly proposed Japan Society of Comprehensive Medical Check-up (Ningen-dock) Standards based on the Japanese Respiratory Society may be useful to reveal early stages of COPD.
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http://dx.doi.org/10.2169/internalmedicine.47.1006DOI Listing
January 2009

Disseminated cryptococcal infection with eosinophilia in a healthy person.

J Infect Chemother 2008 Aug 17;14(4):319-24. Epub 2008 Aug 17.

Department of Respiratory Internal Medicine, St. Marianna University School of Medicine, Yokohama-city Seibu Hospital, 1197-1 Yasashi-cho, Asahi-ku, Yokohama 241-0811, Japan.

A 23-year-old man with no recent medical history was hospitalized complaining of high fever and cough. In addition to very marked eosinophilia, chest X-ray revealed extensive bronchovascular bundle thickening. Transbronchial lung biopsy (TBLB) showed moderate eosinophil infiltration. Cryptococcus neoformans infection was diagnosed, based on blood culture, cerebrospinal fluid culture, urine culture, and lung biopsy specimens. The eosinophilia was successfully alleviated by treatment for cryptococcal meningitis. Furthermore, cryptococcal sepsis resolved with amphotericin B and 5-flucytosine treatment. Eosinophilia commonly occurs following chronic Aspergillus infection, but the present case suggests the involvement of Cryptococcus in another mechanism for eosinophilia.
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http://dx.doi.org/10.1007/s10156-008-0618-zDOI Listing
August 2008