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Background: As an opportunistic pathogenic fungus, Schizophyllum has been rarely reported to infect humans. By reporting a case of definite diagnosis of Schizophyllum infection, we aim to improve clinicians' understanding of this bacterium., Methods: By reporting a case with cough and sputum as the main manifestations, after empirical antiinfective chest CT suggesting a more progressive inflammatory lesion and a mass-like lesion in the paratracheal area of the main airways, a diagnosis of Schizophyllum infection was finally made by bronchoscopy with the delivery of metagenomic next-generation sequencing (mNGS)., Results: The patient was finally diagnosed with rare Schizophyllum infection. After antifungal treatment, the symptoms improved, and the patient was discharged., Conclusions: Although Schizophyllum is a rare fungal infection, it should be taken seriously in patients with diabetes or who are immunocompromised. At the same time, mNGS plays a key role in the detection of rare and emerging pathogens, which is worthy of clinical interest.

Rationale: Understanding the role of the airway microbiome in chronic obstructive pulmonary disease (COPD) inflammatory endotypes may help to develop microbiome-based diagnostic and therapeutic approaches. Objectives: To understand the association of the airway microbiome with neutrophilic and eosinophilic COPD at stability and during exacerbations. Methods: An integrative analysis was performed on 1,706 sputum samples collected longitudinally from 510 patients with COPD recruited at four UK sites of the BEAT-COPD (Biomarkers to Target Antibiotic and Systemic COPD), COPDMAP (Chronic Obstructive Pulmonary Disease Medical Research Council/Association of the British Pharmaceutical Industry), and AERIS (Acute Exacerbation and Respiratory Infections in COPD) cohorts. The microbiome was analyzed using COPDMAP and AERIS as a discovery data set and BEAT-COPD as a validation data set. Measurements and Main Results: The airway microbiome in neutrophilic COPD was heterogeneous, with two primary community types differentiated by the predominance of Haemophilus . The Haemophilus -predominant subgroup had elevated sputum IL-1β and TNFα (tumor necrosis factor α) and was relatively stable over time. The other neutrophilic subgroup with a balanced microbiome profile had elevated sputum and serum IL-17A and was temporally dynamic. Patients in this state at stability were susceptible to the greatest microbiome shifts during exacerbations. This subgroup can temporally switch to both neutrophilic Haemophilus-predominant and eosinophilic states that were otherwise mutually exclusive. Time-series analysis on the microbiome showed that the temporal trajectories of Campylobacter and Granulicatella were indicative of intrapatient switches from neutrophilic to eosinophilic inflammation, in track with patient sputum eosinophilia over time. Network analysis revealed distinct host-microbiome interaction patterns among neutrophilic Haemophilus -predominant, neutrophilic balanced microbiome, and eosinophilic subgroups. Conclusions: The airway microbiome can stratify neutrophilic COPD into subgroups that justify different therapies. Neutrophilic and eosinophilic COPD are interchangeable in some patients. Monitoring temporal variability of the airway microbiome may track patient inflammatory status over time.

Purpose of Review: To perform a nonsystematic review of the literature on the microbiota in the different types of non-IgE-mediated food allergy., Recent Findings: The commonest non-IgE-mediated disorders managed by allergists include: eosinophilic esophagitis, food protein-induced enteropathy, food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis. The review of the literature describes how at phylum level we observe an increase of Proteobacteria in eosinophilic esophagitis esophageal microbiota and in food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis gut microbiota, while we observe an increase of Bacteroidetes in healthy controls. Several studies endorse the concept that a bloom of Proteobacteria in the gut reflects dysbiosis or an unstable gut microbial community structure. In several studies, the type of diet, the use of probiotics and in a single experience the use of fecal microbiota transplantation has produced significant variations of the microbiota., Summary: Genetic factors alone cannot account for the rapid rise in food allergy prevalence and the microbiome might be contributing to allergy risk. Our review showed that common features of the pathological microbiota among different types of non-IgE-mediated food allergy can be identified. These evidences suggest a possible role of the microbiota in the pathogenesis and non-IgE-mediated food allergies and the need to understand the effects of its modulation on the disorders themselves.

Background: Children with severe asthma have frequent exacerbations despite guidelines-based treatment with high-dose corticosteroids. The importance of refractory lung inflammation and infectious species as factors contributing to poorly controlled asthma in children is poorly understood., Objective: To identify prevalent granulocyte patterns and potential pathogens as targets for revised treatment, 126 children with severe asthma underwent clinically indicated bronchoscopy., Methods: Diagnostic tests included bronchoalveolar lavage (BAL) for cell count and differential, bacterial and viral studies, spirometry, and measurements of blood eosinophils, total IgE, and allergen-specific IgE. Outcomes were compared among 4 BAL granulocyte patterns., Results: Pauci-granulocytic BAL was the most prevalent granulocyte category (52%), and children with pauci-granulocytic BAL had less postbronchodilator airflow limitation, less blood eosinophilia, and less detection of BAL enterovirus compared with children with mixed granulocytic BAL. Children with isolated neutrophilia BAL were differentiated by less blood eosinophilia than those with mixed granulocytic BAL, but greater prevalence of potential bacterial pathogens compared with those with pauci-granulocytic BAL. Children with isolated eosinophilia BAL had features similar to those with mixed granulocytic BAL. Children with mixed granulocytic BAL took more maintenance prednisone, and had greater blood eosinophilia and allergen sensitization compared with those with pauci-granulocytic BAL., Conclusions: In children with severe, therapy-resistant asthma, BAL granulocyte patterns and infectious species are associated with novel phenotypic features that can inform pathway-specific revisions in treatment. In 32% of children evaluated, BAL revealed corticosteroid-refractory eosinophilic infiltration amenable to anti-T H 2 biological therapies, and in 12%, a treatable bacterial pathogen., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by eosinophilic inflammation and polyposis at the nose and paranasal sinus and a high concentration of IgE in nasal polyps (NPs). The causative antigen and pathogenesis of CRSwNP remain unknown., Objective: We aimed to identify reactive allergens of IgE antibodies produced locally in NPs of patients with CRSwNP. We also attempted to unravel the differentiation pathway of IgE-producing B cells in NPs., Methods: IgE reactivity of patients with CRSwNP was investigated by characterizing single cell-derived mAbs. T-cell response against identified allergens was investigated in vitro. NP-infiltrating lymphocytes were characterized by using flow cytometry. Immunoglobulins expressed in NPs were analyzed by using high-throughput DNA sequencing for immunoglobulin., Results: About 20% of isolated IgE antibodies derived from NP-residing plasmablasts specifically recognized surface determinants of nasal bacteria, such as Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenzae. A T H 2 response against S pyogenes was observed in patients with CRSwNP. Flow cytometric analysis revealed sizable germinal center B-like cell and plasmablast subsets expressing IgE on the cell surface in NPs. High-throughput DNA sequencing immunoglobulin analysis highlighted the clonal connectivity of IgE with IgG and IgA 1 . The Iε-Cα 1 circle transcript was detected in NPs., Conclusions: In patients with CRSwNP, nasal bacteria-reactive B cells differentiate into IgE-producing B cells through IgG/IgA 1 -IgE class switching, suggesting that allergic conversion of the mucosal response against nasal bacteria underlies disease pathogenesis., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Eosinophilic meningitis caused by Angiostrongylus cantonensis is spreading worldwide, and it can manifest as a severe neurological disease. Angiostrongyliasis is a food- and water-borne parasitosis that usually exhibits a seasonal and circumscribed geographical distribution. To improve control and treatment of these infections, further studies of transmission dynamics under natural conditions and the development of better diagnostic tools and treatment options are needed.

Background: Asthmatic patients have higher microbiome diversity and an altered composition, with more Proteobacteria and less Bacteroidetes compared with healthy control subjects. Studies comparing airway inflammation and the airway microbiome are sparse, especially in subjects not receiving anti-inflammatory treatment., Objective: We sought to describe the relationship between the airway microbiome and patterns of airway inflammation in steroid-free patients with asthma and healthy control subjects., Methods: Bronchoalveolar lavage fluid was collected from 23 steroid-free nonsmoking patients with asthma and 10 healthy control subjects. Bacterial DNA was extracted from and subjected to Illumina MiSeq sequencing of the 16S rDNA V4 region. Eosinophils and neutrophils in the submucosa were quantified by means of immunohistochemical identification and computerized image analysis. Induced sputum was obtained, and airway hyperresponsiveness to mannitol and fraction of exhaled nitric oxide values were measured. Relationships between airway microbial diversity and composition and inflammatory profiles were analyzed., Results: In asthmatic patients airway microbial composition was associated with airway eosinophilia and AHR to mannitol but not airway neutrophilia. The overall composition of the airway microbiome of asthmatic patients with the lowest levels of eosinophils but not asthmatic patients with the highest levels of eosinophils deviated significantly from that of healthy subjects. Asthmatic patients with the lowest levels of eosinophils had an altered bacterial abundance profile, with more Neisseria, Bacteroides, and Rothia species and less Sphingomonas, Halomonas, and Aeribacillus species compared with asthmatic patients with more eosinophils and healthy control subjects., Conclusion: The level of eosinophilic airway inflammation correlates with variations in the microbiome across asthmatic patients, whereas neutrophilic airway inflammation does not. This warrants further investigation on molecular pathways involved in both patients with eosinophilic and those with noneosinophilic asthma., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

A young patient with relapsed diffuse large B-cell lymphoma presented with new onset respiratory symptoms and hypereosinophilia in the early stage post high-dose therapy/autologous stem cell rescue. Here, we present a step-wise practical approach to this unexpected laboratory finding for a not uncommon infective complication in the immunosuppressed patient., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: Patients presenting with refractory postinfectious cough may respond to glucocorticosteroids but it is unclear whether airway eosinophilic inflammation exists in those patients. We aimed to determine the airway inflammation and causes of subacute cough following acute upper respiratory tract infection (AURTI)., Methods: One hundred and sixteen patients with persistent cough lasting 3-8 weeks after upper respiratory tract infection were evaluated with differential cell count in induced sputum, spirometry and methacholine bronchial challenge testing., Results: In patients with subacute cough, sputum eosinophilia (median 8.5%,3.0-73.0%) was identified in 35 (33.6%) patients, 22 (18.5%) without bronchial hyperresponsiveness (BHR) were diagnosed as non-asthmatic eosinophilic bronchitis (NAEB), 13 (14.3%) of whom with BHR were diagnosed as cough variant asthma (CVA). Cough in patients with sputum eosinophilia improved after treatment with corticosteroids. Compared with postinfectious cough (PIC) and NAEB, CVA had significantly higher median eosinophil count in induced sputum (0.5% vs 7.5% vs 20.0%, P < 0.01). MMEF in CVA was significantly lower than PIC and NAEB (P < 0.05). The common causes of subacute cough following acute upper respiratory tract infection (AURTI) were PIC (37.8%), NAEB (18.5%), CVA (14.3%) and upper airway cough syndrome (UACS) (10.1%). Atopic cough (AC) (5.2%) and gastroesophageal reflux-related cough (GERC) (3.4%) were less common in subacute cough following AURTI, while 9 (7.8%) patients had unexplained cough., Conclusion: Subacute cough following AURTI can be attributed to different entities, eosinophilic airway inflammation is common. Induced sputum should be considered when evaluating patients with subacute cough following acute upper respiratory tract infection., (© 2016 Asian Pacific Society of Respirology.)

Background: The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on the microbial community composition and structure are not clear., Objectives: We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia., Methods: DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencing was used to compare the relative abundance of bacterial genera with clinical characteristics., Results: Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus, Pseudomonas, and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella, Streptococcus, and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV1 and the proportion of lavage eosinophils., Conclusion: The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

A higher than 350 eosinophils/mm(3) is strongly associated with Chlamydia trachomatis in term born babies coursing with respiratory distress. However, in preterm newborns infected with this pathogen, the levels of eosinophils are unknown. Forty newborn infants with clinical data of respiratory problems and/or sepsis were analyzed. DNA of leukocytes from peripheral blood was used to identify C. trachomatis. Detection of chlamydial infection was performed by amplifying the ompA gene by an in-house PCR, and eosinophil levels were evaluated in an XT-2000-hematology analyzer. Eighteen infants showed chlamydial infection and 14 of them showed pneumonia (RR = 2.6; CI95% 1.03-6.5; p =.027). Their eosinophil levels were 719 ± 614 cells/mm(3). A significant association between eosinophilia ≥1250 cells/mm(3) and gestational age of less than 29 weeks (RR = 5.8; 1.35; CI95% [1.4-24.5], p <.008) was observed. The preterm infants with chlamydial infection did not show higher eosinophil levels than uninfected infants.

A 51-year-old African-American man with underlying pulmonary, hepatic and splenic sarcoidosis, reported a 3-day history of headache, neck stiffness and photophobia. He was not using medication for chronic sarcoidosis. Physical examination was significant for nuchal rigidity. Lumbar puncture revealed marked eosinophilia in the cerebrospinal fluid, which, on further analysis, demonstrated a positive cryptococcal antigen. HIV antibody and PCR tests were negative. Bronchoscopy and fungal blood cultures were also negative. The patient was started on amphotericin B and flucytosine, with significant clinical improvement. He recovered well without any neurological sequelae and remained symptom-free at 2-week follow-up. Cryptococcal central nervous infections are uniformly fatal if left untreated. Prompt diagnosis and treatment is essential, to prevent the associated high morbidity and mortality., (2015 BMJ Publishing Group Ltd.)

The differential diagnosis for eosinophil-rich skin lesions often includes a drug reaction, allergic contact dermatitis and rarely, response to a helminth infection. However, many unrelated entities, such as infections, neoplasms and inflammatory dermatoses, can have a prominent eosinophilic infiltrate. Syphilis is classically associated with plasma cells, but other patterns of inflammation have been reported, including ulcerative, granulomatous and eosinophil-rich. Classic teaching might indicate that the presence of eosinophils argues against a diagnosis of syphilis. We present four cases of secondary syphilis with increased eosinophils, ranging from 8 to >200 eosinophils per 10 high-power fields (×400 magnification). Patient 1 had lesions on the penis and scrotum, with greater than 200 eosinophils per 10 high-power fields. Patient 2 had lesions on the back, with 150 eosinophils per 10 high-power fields. Patient 3 had lesions on the bilateral arms, with 8 eosinophils per 10 high-power fields. Patient 4 had lesions involving the anus, with 17 eosinophils per 10 high-power fields. These cases highlight that the presence of an eosinophil-rich infiltrate on skin biopsy should not exclude syphilis from the differential diagnosis., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We studied possible mechanisms of immunosuppression mediated by regulatory T cells that promotes suppression of antigen-specific immune response to Mycobacterium tuberculosis in patients with pulmonary tuberculosis and eosinophilia. It was shown that the number of CD4(+)CD25(+)Foxp3(+) regulatory T cells with immunosuppressive activity (Treg) increased in the peripheral blood of patients with disseminated destructive forms of pulmonary tuberculosis with multiple resistance of the causative agent to antituberculosis substances and eosinophilia. These changes were accompanied by imbalance in secretion of Treg-associated cytokines (in vitro) manifested in hyperproduction of TGFβ and IL-10 and decreased production of IL-2.

Objective: This study compared the results of nasal Staphylococcus aureus carriage and nasal cytology in men with and without a moustache., Methods: The study group comprised 118 adult men with a moustache, and the control group consisted of 123 adult men without a moustache. Samples were taken from the participants' right nasal cavity for cytology and from the left nasal cavity for microbiology., Results: The results for S aureus were positive in 19.5 per cent (n = 23) of participants with a moustache and in 20.3 per cent (n = 25) of men without a moustache. This difference was not significant (p > 0.05). However, nasal cytology revealed rich eosinophil clusters in participants with a moustache., Conclusion: The presence or absence of a moustache had no effect on nasal S aureus colonisation. However, further research is needed to understand whether the presence of a moustache increases the risk of allergic or non-allergic rhinitis.

Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by patchy or diffuse eosinophilic infiltration of the bowel wall to a variable depth and various gastrointestinal manifestations. We describe a case of severe eosinophilic gastroenteritis presenting as frequent bowel obstruction and diarrhea in a 35-year-old man. The patient was misdiagnosed and underwent surgery because of intestinal obstruction when he was first admitted to a local hospital. Then he was misdiagnosed as having Crohn's disease in another university teaching hospital. Finally, the patient asked for further treatment from our hospital because of the on-going clinical trial for treating refractory Crohn's disease by fecal microbiota transplantation. Physical examination revealed a slight distended abdomen with diffuse tenderness. Laboratory investigation showed the total number of normal leukocytes with neutrophilia as 90.5%, as well as eosinopenia, monocytopenia and lymphocytopenia. Barium radiography and sigmoidoscopy confirmed inflammatory stenosis of the sigmoid colon. We diagnosed the patient as having eosinophilic gastroenteritis by multi-examinations. The patient was treated by fecal microbiota transplantation combined with oral prednisone, and was free from gastrointestinal symptoms at the time when we reported his disease. This case highlights the importance of awareness of manifestations of a rare disease like eosinophilic gastroenteritis.

Objectives/hypothesis: The role of fungi in chronic rhinosinusitis (CRS) is still controversial. The present study was conducted to detect and identify fungal species from the nasal polyp tissues of eosinophilic and noneosinophilic CRS, and to determine the role of fungal antigens in cytokine production., Study Design: Prospective study., Methods: Thirty-five specimens of nasal polyps were collected from patients with CRS and examined for fungus using culture, histology, and polymerase chain reaction analysis. The secretion of 14 cytokines stimulated by fungal extracts using dispersed nasal polyp cells (DNPCs) was determined by multiplex immunoassay., Results: There was no microbiological growth (including fungus) in the cultures of homogenized nasal polyps. Furthermore, Grocott methanamine silver staining for all nasal polyps showed no fungal bodies. Sixteen of 35 samples of the nasal polyps showed amplification of fungal DNA. In none of the mucosa of the sphenoid sinus was fungal DNA detected. The number of eosinophils in the nasal polyps in which fungal DNA was detected was significantly higher than in the nasal polyps in which fungal DNA was not detected (P < .01). The extract of fungus enhanced the secretion of eosinophil-associated cytokines such as interleukine (IL)-5, IL-13, IL-17A, and RANTES (regulated on activation normal T-cell expressed and secreted), and proinflammatory cytokines such as IL-6, IL-8, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor from DNPCs., Conclusions: The present study offers direct evidence supporting that fungal elements modify the inflammatory response in the nasal polyps of eosinophilic CRS., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: The diagnosis of allergic bronchopulmonary mycosis (ABPM) has traditionally relied widely on Rosenberg's criteria, which emphasize immunologic responses while overlooking the investigation of mucous plugs as a primary criterion. Therefore, the characteristics of biopsy-proven ABPM require further elucidation. The aim of this study was to analyze the clinical characteristics of biopsy-proven ABPM and address whether full compliance with clinical criteria, such as the presence of asthma, and certain laboratory findings is necessary to establish a diagnosis of ABPM., Methods: We retrospectively analyzed 17 patients with biopsy-proven ABPM focusing on causative fungi and laboratory findings., Results: Causative fungi included Aspergillus sp. in seven patients, Schizophyllum commune in four patients, Penicillium sp. in two patients and unknown in five patients. Bronchial asthma was observed in 10 patients, eosinophilia was observed in 10 patients and an increased serum immunoglobulin (Ig) E level was observed in 14 of the 17 patients. IgG for Aspergillus sp. was positive in six of the seven patients with ABPM due to Aspergillus and turned positive in the remaining patient during follow-up. Technological limitations prevented the measurement of specific IgE for S. commune and IgG for S. commune and Penicillium sp. in most patients. Computed tomography revealed central bronchiectasis, pulmonary infiltration and mucous plugs in all patients., Conclusion: Causative fungi other than Aspergillus sp. are not uncommon, and immunological tests for other fungi should be popularized. Asthma and characteristic laboratory findings, such as peripheral blood eosinophilia, increased serum IgE and precipitating antibodies, may not always be required to diagnose ABPM. The importance of typical pathologic findings of mucous plugs for diagnosing ABPM requires reevaluation. Further studies are needed to establish more elaborate diagnostic criteria for ABPM.

Drug reaction with eosinophilia and systemic symptoms is a potentially life-threatening syndrome of medication hypersensitivity associated with a wide variety of triggers. Diagnosis can be challenging, as clinical features suggest other conditions. We describe a 12-year-old boy with typical drug reaction with eosinophilia and systemic symptoms syndrome after antituberculosis therapy.

Purpose: To quantify the number of defense cells and immunoglobulin E (IgE) levels in peripheral blood sampled from women with recurrent vulvovaginal candidiasis., Methods: A cross-sectional study was conducted on 60 women, 40 with vulvovaginal candidiasis and 20 controls. The defense cells were identified using an impedance system combined with flow cytometry and total and specific IgE was measured by chemiluminescence. The Mann-Whitney test was used for nominal variables and the Spearman test was used to determine the correlation of IgE concentration and eosinophils in peripheral blood., Results: The number of eosinophils in peripheral blood from patients with recurrent vulvovaginal candidiasis, 302.60 (± 253.07), was significantly higher compared to control, 175.75 (± 109.24) (p=0.037). Serum levels of total and specific IgE were similar in the groups of women with and without recurrent vulvovaginal candidiasis (p=0.361). However, there was a moderate positive correlation between eosinophils and total serum IgE in the candidiasis group (r=0.25)., Conclusion: Women with recurrent vulvovaginal candidiasis are more likely to have eosinophils in peripheral blood.

Chlamydia pneumoniae is associated with chronic inflammatory lung diseases like bronchial asthma and chronic obstructive pulmonary disease. The existence of a causal link between allergic airway disease and C. pneumoniae is controversial. A mouse model was used to address the question of whether preceding C. pneumoniae lung infection and recovery modifies the outcome of experimental allergic asthma after subsequent sensitization with house dust mite (HDM) allergen. After intranasal infection, BALB/c mice suffered from pneumonia characterized by an increased clinical score, reduction of body weight, histopathology, and a bacterial load in the lungs. After 4 weeks, when infection had almost resolved clinically, HDM allergen sensitization was performed for another 4 weeks. Subsequently, mice were subjected to a methacholine hyperresponsiveness test and sacrificed for further analyses. As expected, after 8 weeks, C. pneumoniae-specific antibodies were detectable only in infected mice and the titer was significantly higher in the C. pneumoniae/HDM allergen-treated group than in the C. pneumoniae/NaCl group. Intriguingly, airway hyperresponsiveness and eosinophilia in bronchoalveolar lavage fluid were significantly lower in the C. pneumoniae/HDM allergen-treated group than in the mock/HDM allergen-treated group. We did observe a relationship between experimental asthma and chlamydial infection. Our results demonstrate an influence of sensitization to HDM allergen on the development of a humoral antibacterial response. However, our model demonstrates no increase in the severity of experimental asthma to HDM allergen as a physiological allergen after clinically resolved severe chlamydial lung infection. Our results rather suggest that allergic airway disease and concomitant cellular changes in mice are decreased following C. pneumoniae lung infection in this setting.

Background: Chronic sinusitis is one of the most common otolaryngological diagnoses. Allergic fungal sinusitis and eosinophilic mucin rhinosinusitis can easily be misdiagnosed and treated as chronic sinusitis, causing continuing harm., Aim: To better identify and characterise these two subgroups of patients, who may suffer from a systemic disease requiring multidisciplinary treatment and prolonged follow up., Methods: A retrospective, longitudinal study of all patients diagnosed with allergic fungal sinusitis or eosinophilic mucin rhinosinusitis within one otolaryngology department over a 15-year period., Results: Thirty-four patients were identified, 26 with eosinophilic mucin rhinosinusitis and 8 with allergic fungal sinusitis. Orbital involvement at diagnosis was commoner in allergic fungal sinusitis patients (50 per cent) than eosinophilic mucin rhinosinusitis patients (7.7 per cent; p < 0.05). Asthma was diagnosed in 73 per cent of eosinophilic mucin rhinosinusitis patients and 37 per cent of allergic fungal sinusitis patients., Conclusion: Allergic fungal sinusitis and eosinophilic mucin rhinosinusitis have the same clinical presentation but different clinical courses. The role of fungus and the ability to confirm its presence are still problematic issues, and additional studies are required.

Introduction: Diagnosis of Angiostrongylus cantonensis meningitis is not always obvious, even in endemic areas., Case Report: We report a 51-year-old Polynesian man, farmer without past medical history, who was admitted for mild fever, headache, neurological subjective symptoms, and severe muscle pain impeding walking. The diagnosis of A. cantonensis meningitis, guided by hypereosinophilia was confirmed by lumbar puncture and positive specific serology. Lumbar puncture and administration of corticosteroids rapidly reduced headache whereas paraesthesias declined more progressively., Conclusion: Diagnosis of A. cantonensis meningitis should be considered in patients living or returning from endemic areas with headache associated with subjective neurological symptoms and hypereosinophilia., (Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

"Candidatus Mycoplasma turicensis" (CMt) is a hemoplasma species of felids. Recent evidence has shown that cats that overcome bacteremia may be protected from reinfection. The purposes of this study were to (1) re-inoculate ostensibly recovered cats, (2) evaluate the immune response and (3) assess CMt tissue loads. Fifteen specified pathogen-free cats were subcutaneously inoculated with CMt: 10 cats (group A) had previously undergone bacteremia and recovered, and 5 naïve cats (group B) served as controls. CMt infections were monitored by real-time PCR using blood and tissue, and the humoral immune response was assessed using DnaK ELISA. Cytokine mRNA expression levels were measured by real-time PCR, and lymphocyte subsets were detected by flow cytometry. The cats in group A were protected from reinfection (no detectable bacteremia) and showed a transient decrease in antibodies. Eosinophilia was noted in cats from group A. The cats from group B became PCR-positive and seroconverted. All of the tissues analyzed from the cats in group B but none of the tissues analyzed from the cats in group A were CMt PCR-positive. Significant changes were observed in the expression of tumor necrosis factor-α, interferon-γ, interleukin-4 and the Th2/Th1 ratio in both groups. The cats from group A occasionally showed higher numbers of CD4+, CD8+, CD4+CD25+ and CD5+MHCII+ T lymphocytes than the control cats. In conclusion, this study describes, for the first time, the occurrence of immunological protection within the same hemoplasma species. Furthermore, the immune response during CMt infections appeared to be skewed toward the Th2 type.

Objectives: Bacteria and viruses are rarely isolated from the middle ear fluid in cases of otitis media with effusion (OME). However, since endotoxins are often detected in such effusions, it is suspected that patients with OME have a previous history of gram-negative infection. Recently, fungi have drawn attention as microorganisms that cause chronic sinusitis. We investigated the involvement of fungi in the formation of middle ear effusions of patients with OME and eosinophilic otitis media, in which patients have viscous middle ear effusions and a history of adult bronchial asthma indicating definite involvement of eosinophils., Methods: Middle ear effusions and nasal secretions were collected from patients with eosinophilic otitis media (7 patients) or OME (12 patients), and smears were prepared for methenamine silver staining. The remaining specimens were embedded in Epon and stained with toluidine blue for observation under a light microscope, and ultrathin sections were prepared for examination under an electron microscope., Results: Fungal hyphae were detected in the middle ear fluid in all of the patients with eosinophilic otitis media or OME. Charcot-Leyden crystals (CLCs) were observed in 6 of the 7 patients with eosinophilic otitis media. In regard to the findings in the nasal secretions, fungal hyphae were also detected in the nasal secretions of all patients, whereas CLCs were detected in only 1 patient with eosinophilic otitis media., Conclusions: It was clarified by use of the methenamine silver staining method that fungi were present in the middle ear fluid in 100% of the studied cases of eosinophilic otitis media or OME. Whether fungi are also present in the middle ear cavity of normal persons is unknown, but the possibility that they may contribute as a cause of both diseases cannot be excluded. Particularly in eosinophilic otitis media, the observation of numerous CLCs in the middle ear fluid suggests that many eosinophils have degenerated. The eosinophil granule proteins released from the degenerated eosinophils can cause epithelial injury of the middle ear. The possibility that fungi induce the eosinophils in the middle ear also cannot be excluded.

Conclusion: We found no significant differences in the bacterial features of the maxillary sinuses between eosinophilic and neutrophilic chronic rhinosinusitis (CRS) with nasal polyps., Objectives: Since neutrophilic CRS is often influenced by a predisposition to bacterial infection, and eosinophilic CRS is likely to be developed by allergic antigens, differences in the microbiology between the two pathologies of CRS can be expected. The present study was designed to investigate the bacterial findings from the maxillary sinus in eosinophilic and neutrophilic CRS., Methods: Seventy patients with CRS with nasal polyps were divided into eosinophilic and neutrophilic types based on histopathological observations of the nasal polyps. The specimens for bacterial culture were obtained from the maxillary sinus during endoscopic sinus surgery., Results: In all, 29 and 41 patients were classified as having eosinophilic and neutrophilic CRS with nasal polyps, respectively. The isolation rate of bacteria showed no significant difference between eosinophilic (90%) and neutrophilic CRS (98%). Aerobic bacteria were found in 25 patients (86%) with eosinophilic CRS, which was not significantly different from that in neutrophilic CRS (40 patients, 98%). The isolation rate for aerobic and anaerobic bacteria showed no significant differences.

Acquired eosinophilia is currently classified into secondary (reactional to underlying diseases), clonal (presence of a bone marrow histological, cytogenetic or molecular marker of a myeloid malignancy) and idiopathic (neither secondary nor clonal) categories. We report the case of a 47-year-old male who was admitted to the hospital for Staphylococcus aureus recurring infections. An hypereosinophilia was discovered and led to molecular analysis. The identification of FIP1L1-PDGFRA fusion gene permitted the diagnostic of clonal eosinophilia. Treatment by imatinib mesylate induced an haematological remission, the control of the infection and thoracotomy cicatrization. This case is original because of its infectious presentation and the efficacy of imatinib mesylate to control the infectious process., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: Tuberculosis. toxocariasis and toxoplasmosis are among the common infectious causes of lymphadenitis in children. Cases of Toxoplasma gondii and Toxocara spp co-infection have been reported., Case Presentation: This case report describes a co-infection of Toxoplasma gondii, Toxocara spp and tuberculosis in a child with chronic lymphadenopathy and eosinophilia., Conclusion: The case report highlights two important points. First is the diagnostic challenges that are encountered by clinicians in tropical countries such as Sri Lanka, where lymphadenopathy and eosinophilia with a positive serology commonly point towards a parasitic infection. Secondly the importance of proper history taking and performing the Mantoux test as a first line investigation in a country where the incidence of tuberculosis is low, even in the absence of a positive contact history.

A marked peripheral blood eosinophilia is an uncommon finding in a complete blood count (CBC). According to Wardlaw and Kay (Eosinophils and Their Disorders. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, editors. Williams Hematology. 6(th) ed. New York: McGraw-Hill, 2001. p. 790-93), the most common causes are infection by helminthic parasites, atopic disease, and, less commonly, primary hypereosinophilic syndromes. Therefore, when eosinophilia is seen in a CBC, it can provide an important clue to the correct diagnosis. We present a case of a patient with a finding of pulmonary nodules in the setting of cancer and a CBC finding of profound peripheral blood eosinophilia. As a result of the high level of clinical suspicion for Coccidioides infection due in part to the eosinophilia, adequate steps were taken in the clinical laboratory not only to correctly diagnosis the patient, but also to protect the laboratory staff from work-related exposure to this easily aerosolizable infectious agent., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Allergic asthma is a dysregulation of the immune system which leads to the development of Th2 responses to innocuous antigens (allergens). Some infections and microbial components can re-direct the immune response toward the Th1 response, or induce regulatory T cells to suppress the Th2 response, thereby inhibiting the development of allergic asthma. Since Acinetobacter baumannii infection can modulate lung cellular and cytokine responses, we studied the effect of A. baumannii in modulating airway eosinophilia in a mouse model of allergic asthma. Ovalbumin (OVA)-sensitized mice were treated with live A. baumannii or phosphate buffered saline (PBS), then intranasally challenged with OVA. Compared to PBS, A. baumannii treatment significantly reduced pulmonary Th2 cytokine and chemokine responses to OVA challenge. More importantly, the airway inflammation in A. baumannii-treated mice was strongly suppressed, as seen by the significant reduction of the proportion and the total number of eosinophils in the bronchoalveolar lavage fluid. In addition, A. baumannii-treated mice diminished lung mucus overproduction and pathology. However, A. baumannii treatment did not significantly alter systemic immune responses to OVA. Serum OVA-specific IgE, IgG1 and IgG2a levels were comparable between A. baumannii- and PBS-treated mice, and tracheobronchial lymph node cells from both treatment groups produced similar levels of Th1 and Th2 cytokines in response to in vitro OVA stimulation. Moreover, it appears that TLR-4 and IFN-γ were not directly involved in the A. baumannii-induced suppression of airway eosinophilia. Our results suggest that A. baumannii inhibits allergic airway inflammation by direct suppression of local pulmonary Th2 cytokine responses to the allergen.

A 53-year-old healthy patient was admitted with unilateral nasal obstruction of one month duration which was suspected to be a malignancy because of mass-like finding on radiology and peripheral eosinophilia. The biopsy of the involved sinus showed tissue invasion by aseptate hyphae suggestive of a zygomycete and tissue infiltration of eosinophilia. He was diagnosed as invasive paranasal mucomycosis and treated with complete endoscopic sinus surgery and amphotericin B deoxycholate. Paranasal symptoms with peripheral eosinophilia might be a presentation of invasive fungal sinusitis.

Eosinophilic peritonitis is a response of the peritoneum to foreign substances. It presents as cloudy dialysate and may be missed because not all laboratories report the eosinophil count, giving only the total number of polymorphonuclear cells. Over a 2-year period, eight children developed 13 episodes of eosinophilic peritonitis. Three episodes were asymptomatic other than cloudy fluid, five followed surgery and two were associated with gastroenteritis. Despite recurrent episodes, there were no adverse outcomes, although a raised peritoneal eosinophil count persisted in most cases. Eosinophilic peritonitis is under-diagnosed and may lead to unnecessary antibiotic therapy.

Background: Over 40% of chronic stable asthma patients have evidence of respiratory Mycoplasma pneumoniae (Mp) infection as detected by PCR, but not by serology and culture, suggesting that a low-level Mp is involved in chronic asthma. However, the role of such a low-level Mp infection in the regulation of allergic inflammation remains unknown., Objective: To determine the impact of a low-level Mp infection in mice with established airway allergic inflammation on allergic responses such as eosinophilia and chemokine eotaxin-2, and the underlying mechanisms [i.e. the prostaglandin E(2) (PGE(2)) pathway] since PGE(2) inhalation before an allergen challenge suppressed the eosinophil infiltration in human airways., Methods: BALB/c mouse models of ovalbumin (OVA)-induced allergic asthma with an ensuing low- or high-dose Mp were used to assess IL-4 expression, bronchoalveolar lavage (BAL) eosinophil, eotaxin-2 and PGE(2) levels, and lung mRNA levels of microsomal prostaglandin E synthase-1 (mPGES-1). Primary alveolar macrophages (pAMs) from naïve BALB/c mice were cultured to determine whether Mp-induced PGE(2) or exogenous PGE(2) down-regulates IL-4/IL-13-induced eotaxin-2., Results: Low-dose Mp in allergic mice significantly enhanced IL-4 and eotaxin-2, and moderately promoted lung eosinophilia, whereas high-dose Mp significantly reduced lung eosinophilia and tended to decrease IL-4 and eotaxin-2. Moreover, in both OVA-naïve and allergic mice, lung mPGES-1 mRNA and BAL PGE(2) levels were elevated in mice infected with high-dose, but not low-dose Mp. In pAMs, IL-4/IL-13 significantly increased eotaxin-2, which was reduced by Mp infection accompanied by dose-dependent PGE(2) induction. Exogenous PGE(2) inhibited IL-4/IL-13-induced eotaxin-2 in a dose-dependent manner., Conclusions: This study highlights a novel concept on how different bacterial loads in the lung modify the established allergic airway inflammation and thus interact with an allergen to further induce Th2 responses. That is, unlike high-level Mp, low-level Mp fails to effectively induce PGE(2) to down-regulate allergic responses (e.g. eotaxin-2), thus maintaining or even worsening allergic inflammation in asthmatic airways.

We recently reported a critical role for T cells in the induction of eosinophilic esophagitis (EE) in mice; however, the role of specific T cell subsets in disease pathogenesis is not yet understood. In the current study, we tested the hypothesis that allergen-induced EE develops in response to the disproportion of functionally different effector and regulatory T cells in the esophagus. Fluorescence-activated cell sorter analysis was performed to examine activated T cell subsets using the cell surface activation markers CD25 and CD69. A significant increase in activated CD4(+) and CD4(-) T cells was observed in the total esophageal cells isolated from the mouse model of EE. Furthermore, an imbalance in the effector and regulatory T cells was observed in the esophagus. The esophageal CD4(+)CD45RB(high) effector T cells in allergen-challenged mice increased compared with saline-challenged mice (65.4 +/- 3.6 x 10(3) to 44.8 +/- 4.2 x 10(3)), whereas CD4(+)CD45RB(low) mostly regulatory T cells decreased in allergen-challenged mice compared with saline-challenged mice (5.8 +/- 0.9 x 10(3) from 10.2 +/- 1.7 x 10(3)). The functional characteristics were examined by analysis of the pro- and anti-inflammatory cytokine profile of purified low and high CD4(+)CD45RB subsets from the spleen. Additionally, a significantly reduced interleukin (IL)-2 production by CD4(+)CD45RB(low) cells in allergen-challenged mice compared with saline-challenged mice was observed. The reduced IL-2 in the CD4(+)CD45RB(low) subset may be associated with reduction of CD4(+)CD45RB(low) subset. In conclusion, our results suggest that local regulatory interaction of CD45RB(high) and CD45RB(low) CD4(+) T cells may be required for protective and pathogenic immunity in EE.

Hydatid cysts of the liver are known to occasionally rupture into the bile ducts and cause cholangitis. The histological features of this complication have not been adequately described in the literature. Herein is reported a case of severe eosinophilic cholangitis of the left hepatic lobe, occurring in a 24-year-old man with a large (16 cm) hydatid cyst, which obstructed and eroded the left hepatic duct. The patient presented with upper abdominal discomfort and low-grade fever of 3 weeks' duration. Sections of the left lobectomy specimen showed marked inflammatory infiltrates in the portal tracts, predominantly composed of eosinophils, extensively involving bile ducts of all sizes. Occasional small bile ducts were replaced by epithelioid cell granulomas surrounding eosinophilic microabscesses. The inflammatory infiltrates extended into the lobules, resulting in marked hepatocyte loss. This case demonstrates that echinococcosis may cause severe eosinophilic cholangitis with extensive parenchymal destruction, apparently resulting from a hypersensitivity reaction to parasitic antigens.

Nontuberculous mycobacteria (NTM) are human opportunistic pathogens with an environmental source of infection. The reports of cutaneous NTM infections has increased, and NTM have been regarded as important pathogens in recent years. This study aimed to identify characteristic clinical and histological features of cutaneous NTM infections. We evaluated the medical records and histopathologic slides of 7 cases of NTM infections that were confirmed by polymerase chain reaction between 2003 and 2007. The results showed that cutaneous NTM infections occurred in various aged people independent of their immune states and were associated with fish-related jobs or intramuscular medicinal injection. The main clinical feature was a painful erythematous nodule. Histopathologically, the most common findings were diffuse infiltration of mixed inflammatory cells and small vessel proliferation in the dermis (100%). Epidermal proliferation (71%) and dermal granuloma (71%) were also very common. Suppurative granuloma was found in 43% of the cases, and eosinophil infiltration was uncommon (14%). The lesions disappeared after a mean of 7 months (range, 1.5-12 months) with treatment by oral clarithromycin alone or in combination with other antimycobacterial agents. These clinical and histopathological data should assist clinicians in the diagnosis of NTM.

A 63-year-old woman living in a rural area presented in 2004 with a granulomatous necrotizing axillary lymphadenitis caused by Corynebacterium pseudotuberculosis, a Gram positive bacillus belonging to the group of Corynebacterium diphtheriae, which is found primarily in animal infections. In the human being, around 30 cases of infection due to C. pseudotuberculosis have been described, mainly among people working in contact with infected animals. For this reason, this infection, which induces exclusively lymphadenitis and abscesses with granulomatous necrotizing lesions, should be regarded as an occupational disease. In this patient, due to ignorance of the disease, this bacterium was considered to be merely saprophytic. The first treatment introduced was probabilistic antibiotherapy followed by a second course of antibiotics after aspiration. The trend confirmed that this was not the correct treatment and that surgery was the only way to achieve a cure.

Background: Recent clinical trials, epidemiological studies and animal experiments have suggested that probiotics may help suppress the development of allergic responses., Objective: To investigate whether the application of the probiotic Escherichia coli strain Nissle 1917 (EcN) protects mice from developing ovalbumin (OVA)-specific T helper-2 responses in the airways., Methods: OVA-specific Th2 responses were induced by 2 intraperitoneal (i.p.) injections with OVA/alum followed by 1 intranasal (i.n.) challenge with OVA. EcN was given orally during the entire sensitization and challenge period, together with OVA/alum during the i.p. sensitizations, or i.n. before or during the airway challenge with OVA., Results: We found that when the bacteria were given together with OVA/alum airway eosinophilia, airway hyper-reactivity, goblet cell metaplasia and IL-5 levels in the bronchoalveolar lavage and mediastinal lymph node cell cultures were reduced. This effect was associated with increased numbers of IFN-gamma producing T helper-1 cells and IFN-gamma levels in the airways and strongly increased OVA-specific IgG(2a) titers in the serum. The suppressive effect on airway eosinophilia was dependent on IFN-gamma but not TLR-4. Applying EcN i.n. or orally did not reduce the development of allergen-specific Th2 responses., Conclusions: Our results suggest that EcN can inhibit the development of allergic responses when the bacteria are present at the site of Th2 cell priming and that this immunomodulatory effect is due to a shift from Th2 to Th1 response. The data support the hypothesis that probiotics may help reduce allergic responses and that EcN may also be used as adjuvant therapy to induce allergen-specific Th1 responses.

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.

Background: Eosinophilic meningitis caused by Parastrongylus cantonensis, the rat lung worm is a major public health problem in Thailand. Humans acquire this parasite by eating raw food containing infective Parastrongyliasis is dificult to make because identification of parasite materials by biopsy or chance finding is rarely possible., Objective: Develop alternative approaches of Parastrongylus cantonensis infection employing crude antigen by dot-blot ELISA., Material and Method: The investigation was carried out between October 2003 and July 2004 in Khon Kaen, which is an endemic area. One hundred thirty two serum samples from several villagers of the present study area were divided into five groups. Group 1 consisted of 30 patients with Cryptococcal meningitis, group 2 were 22 cases of Bacterial meningitis, group 3 were 32 cases of eosinophilic meningitis, group 4 were other parasitic infections (4 from Cysticercosis, 2 from Fascioliasis, 12 from Malaria), and group 5 were 30 negative healthy control., Results: The result demonstrated that 26 cases of eosinophilic meningitis, were positive with Dot-blot ELISA (81.3%). None of the other groups of sample reacted with this antigen., Conclusion: The data obtained showed that Dot-blot ELISA has a potential for diagnosis of eosinophilic meningitis caused by Parastrongylus cantonensis.

Introduction: Coccidioidomycosis is a common fungal infection primarily affecting the lungs. The prevalence and the characteristics of pleural effusion in Coccidioidomycosis are not well described. Therefore, a retrospective analysis of data from patients admitted to a teaching hospital with a diagnosis of Coccidioidomycosis and pleural effusion was done., Methods: All patients admitted with a diagnosis of Coccidioidomycosis were identified using ICD 9 from 114 to 114.9 from computerized medical records. Epidemiological, clinical and laboratory data were transcribed from medical records of all inpatients. Pleural effusion was identified using reports of chest radiography, ultrasound and CT scan of chest., Results: Pleural effusion occurred in 22 of 146 (15%) patients hospitalized for Coccidioidomycosis. The proportion of patients with pleuritic chest pain, cough and dyspnea were significantly higher in patients with effusion than without effusion (p<0.01). There was a tendency for pleural effusions to occur more often on the left side (p=0.064). Empyema occurred in 22.7% of pleural effusions. Pleural fluid chemistry showed that all effusions were exudates with a mean (+/-S.E.M.) pleural fluid eosinophil count of 10.3+/-4.65., Conclusion: Pleural effusions are common in hospitalized patients with Coccidioidomycosis. Pleural fluid eosinophilia should alert clinician to Coccidioides immitis as a possible etiological agent especially in an endemic area. Empyema occurred in a quarter of pleural effusions and resolution required thoracotomy.