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Allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are important fungal infections caused by Aspergillus species. An overlap of ABPA and CPA has been reported; therefore, it is critical to determine whether the main pathology is ABPA or CPA and whether antifungals are required. In this study, we investigated whether the serum cytokine profile is useful for understanding the pathology and for differentiating between these diseases. We compared the various serum cytokine levels among healthy subjects and patients diagnosed with asthma, ABPA, or CPA at Nagasaki University Hospital between January 2003 and December 2018. In total, 14 healthy subjects, 19 patients with asthma, 11 with ABPA, and 10 with CPA were enrolled. Interleukin (IL) -5 levels were significantly higher in patients with ABPA than in those with CPA, and IL-33 and tumor necrosis factor (TNF) levels were significantly higher in patients with CPA than in those with asthma (p < 0.05, Dunn’s multiple comparison test). The sensitivity and specificity of the IL-10/IL-5 ratio (cutoff index 2.47) for diagnosing CPA were 70% and 100%, respectively. The serum cytokine profile is useful in understanding the pathology of ABPA and CPA, and the IL-10/IL-5 ratio may be a novel supplemental biomarker for indicating the pathology of CPA., Journal of Fungi, 8(5), art. no. 436; 2022

Managing mild illness in COVID-19 and predicting progression to severe disease are concerning issues. Here, we investigated the outcomes of Japanese patients with mild COVID-19, and identified triage risk factors for further hospitalization and emergency department (ED) visits at a single tertiary hospital. A triage checklist with 30 factors was used. Patients recommended for isolation were followed up for 10 days for subsequent ED visits or hospital admission. Overall, 338 patients (median age, 44.0; 45% women) visited the clinic 5.0 days (median) after symptom onset. Thirty-six patients were immediately hospitalized following triage; others were isolated. In total, 72 non-hospitalized patients visited the ED during their isolation, and 30 were hospitalized after evaluation for oxygen desaturation. The median ED visit and hospitalization durations after symptom onset were 5.0 and 8.0 days, respectively. The checklist factors associated with hospitalization during isolation were age > 50 years, body mass index > 25 kg/m2, hypertension, tachycardia with pulse rate > 100/min or blood pressure > 135 mmHg at triage, and >3-day delay in hospital visit after symptom onset. No patients died. Altogether, 80% of patients with mild COVID-19 could be safely isolated at home. Age, BMI, underlying hypertension, date after symptom onset, tachycardia, and systolic blood pressure at triage might be related to later hospitalization., Journal of Clinical Medicine, 11(18), art. no. 5444; 2022

BACKGROUND: Primary and secondary respiratory syncytial virus (RSV) infection differentially regulates preexisting allergic airway inflammation. OBJECTIVES: The present study was designed to determine the effects of primary and secondary low-grade RSV infections on pulmonary dendritic cell (DC) functions. METHODS: Eight groups of BALB/c mice were used: one group each for control primary and secondary sensitization, primary and secondary sensitization to Dermatophagoides farinae (Derf) allergen, primary and secondary infection with RSV, and primary and secondary sensitization to Derf plus infection with RSV. CD11c+ pulmonary DCs were isolated from these mice and then transferred to naive mice followed by intranasal Derf challenge. Furthermore, either anti-IL-12 monoclonal antibody (alphaIL-12 mAb) or anti-IL-10 (alphaIL-10) mAb were injected into donor mice after Derf challenge and during RSV infection to determine the involvement of IL-12 and IL-10. RESULTS: Primary RSV infection failed to induce polarization in DCs since it failed to induce IL-10 and IL-12 production in Derf-sensitized donor lung. In contrast, secondary RSV infection significantly enhanced IL-12 production from Derf-sensitized donor lung, thereby enhancing both Th1 and Th2 responses. During RSV infection, alphaIL-12 but not alphaIL-10 mAb treatment blocked these immunological effects. CONCLUSION: Via IL-12, DCs may play a critical role in shifting the immune response in this experimental model of repeated respiratory viral infection in allergic asthma., identifier:International Archives of Allergy and Immunology, 147(3), pp.197-205; 2008

BACKGROUND Focal nodular hyperplasia (FNH) of the liver is a rare benign nodular lesion that arises in women of reproductive age. Although a role of female hormones has been suggested, their influence on the course of FNH has remained controversial. CASE REPORT A 44-year-old woman with a 12-year history of oral contraceptive use was referred to our hospital for examination of an asymptomatic liver mass (3 cm in diameter) identified by computed tomography. We diagnosed FNH using imaging methods and fine-needle biopsy. Oral contraceptives were discontinued because the mass increased over a period of 21 months. Four months later, the mass had decreased in size, indicating that FNH can spontaneously regress when oral contraceptives are discontinued. CONCLUSIONS Discontinuation of oral contraceptives use can reduce the size of FNH, as in this case., The American journal of case reports, 20, pp.1124-1127; 2019

Background: Cysteinyl leukotrienes (cys-LTs) are very important factors in the pathophysiology of bronchial asthma. Cys-LT receptor antagonists (LTRAs) decrease allergic airway inflammation. The aim of the present study was to determine the differential effects of LTRAs and corticosteroids on allergic airway inflammation and allergen-specific cytokine production from lymphoid tissues using a murine model of asthma. Material/Methods: Four groups of female BALB/c mice [control (Cont); Dermatophagoides farinae allergen-sensitized (AS); pranlukast (Prl), an LTRA-treated AS; and dexamethasone (Dex)-treated AS] were examined. Lung pathology and cytokine production by prepared mononuclear cells isolated from mediastinal lymph nodes (MLNs) and spleen were compared among these groups. Results: AS mice exhibited allergic airway inflammation and significant increases in allergen-specific Th1 and Th2 cytokines in MLNs and spleen. Prl-treated mice showed significant attenuation of allergic airway inflammation concomitant with reduction of Th2 cytokines and IFN-g in MLNs but not in spleen. In contrast, Dex significantly decreased Th1 and Th2 cytokines in MLNs and also decreased them (except IL-13 and IL-2) in spleen. Conclusions: The inflammatory effects of cys-LTs could differ in lymphoid organs. LTRAs potentially regulate allergic airway inflammation in an organ- and cytokine-specific manner, while systemic corticosteroid shows nonspecific effects., Medical Science Monitor, 20, pp.297-302; 2014

Background: Fungal exposure is associated with particularly severe asthma. Nevertheless, the effects of anti-fungal treatments on fungus-exacerbated asthma need to be determined. Objectives: The present study aimed to compare the effects of itraconazole (ITCZ) and dexamethasone (Dex) on Aspergillus fumigatus (Af)-exacerbated preexisting Dermatophagoides farinae (Df) allergen-sensitized allergic airway inflammation. Methods: Four groups of BALB/c mice were prepared: control, Df-sensitized plus Af-infected mice (Df-Af), and Df-Af mice treated with Dex (Df-Af-Dex) or with ITCZ (Df-Af-ITCZ). Pulmonary pathology and cytokine profiles in the airway were evaluated. In a different set of experiments, the effects of Dex on alveolar macrophage (AM) phagocytosis of Af conidia were determined in Df-sensitized mice. Results:Af infection significantly increased the level of eosinophils and neutrophils in the airway of Df-sensitized mice. While Dex significantly decreased eosinophils, ITCZ significantly decreased both eosinophils and neutrophils in Df-Af mice. Dex significantly decreased IL-5, whereas ITCZ significantly reduced MIP-2 in the airway. Compared to controls, AM isolated from Df-sensitized mice had significantly reduced phagocytotic activity of Af conidia. However, Dex significantly improved phagocytotic activity of AM in Df-sensitized mice. Conclusions: The present study showed that Dex and ITCZ differently regulated Af-exacerbated allergic airway inflammation; the former inhibits eosinophilic inflammation and the latter inhibits neutrophilic as well as eosinophilic inflammation by regulating different cytokines. Additionally, Dex enhanced the phagocytotic activity of AM in allergic asthma. Thus, a combination of Dex and ITCZ might be effective for the management of fungus-exacerbated asthma., Respiration, 85(5), pp.429-435; 2013

Background. Upper respiratory tract infections (URIs) represent the most frequent cause of acute asthma exacerbation. Systemic corticosteroid (CS) is presently recommended for URI-induced asthma exacerbation, although it might inhibit cellular immunity against respiratory virus infection. Objectives. To determine the effects of adding a short course (2 weeks) of a leukotriene receptor antagonist (LTRA) to systemic CS on URI-induced acute asthma exacerbation. Methods. Twenty-three adult asthmatics (mean age, 42.8 ± 9.8 y; Male:Female, 10:13) with URI-induced acute asthma exacerbation confirmed by a questionnaire and physical findings were randomly assigned to receive either oral prednisolone (PSL) alone or oral PSL plus the LTRA pranlukast (PRL) for 2 weeks (PSL + PRL). The cumulative doses of PSL and the amount of time required to clear asthma-related symptoms were determined. Levels of respiratory syncytial virus (RSV) RNA and influenza viral (IV) antigen in nasopharyngeal swabs were also determined. Results. Adding PRL significantly reduced the cumulative dose of PSL and tended to reduce the time required to clear asthma-related symptoms. Either RSV or IV was detected in about one-third of the patients. Conclusion. The combination of an LTRA and CS might be more useful than CS alone for treating URI-induced acute exacerbation of asthma and reducing the cumulative CS dose., Journal of Asthma, 49(6), pp.637-641; 2012

Background: Respiratory syncytial virus (RSV) can infect myeloid dendritic cells (mDCs) and regulate their function in the development of allergy. It has been widely reported that plasmacytoid DCs (pDCs) play a critical role in antiviral innate immunity. In contrast, not much is known about the role of pDCs in the interaction between allergy and viral infection. The purpose of the present study was to investigate the effect of RSV infection on pDC function in the regulation of allergic airway inflammation in a murine model of Dermatophagoides farinae-sensitized allergic asthma. Methods: Splenic pDCs isolated from D. farinae-sensitized donor mice were infected with live RSV ex vivo. Subsequently, these pDCs were inoculated into the airways of D. farinae-sensitized recipient mice. Lung pathology, lung tissue cytokine profiles, the number of regulatory T cells (T(reg)) and mDCs as well as the effects of IL-10 neutralization in the lung tissue of recipient mice were determined. Results: Intranasal inoculation of D. farinae-sensitized pDCs significantly inhibited the development of allergic airway inflammation and both Th1 and Th2 immunity. Live RSV infection of these pDCs prior to inoculation interfered with their inhibitory effects through decreasing T(reg) and IL-10 and increasing mDCs. Conclusions: In asthmatic airways, pDCs mediate tolerance to inhaled allergens through the regulation of T(reg), IL-10 and mDCs. RSV infection of pDCs potentially inhibits their immunotolerogenic effects and thus exacerbates allergic airway inflammation., International Archives of Allergy and Immunology, 157(1), pp.21-30; 2011