epiglucan and Pneumonia

We report an invasive pulmonary aspergillosis (IPA) with negative (1,3)-β-D-glucan and dynamically elevated white blood cells combined with procalcitonin proven by bronchoalveolar lavage fluid (BALF) culture.. Appropriate laboratory tests are carried out. Chest CTs were performed to assess the lungs. The cause of infection was determined using BALF culture.. Serum (1,3)-β-D-glucan was negative, white blood cells and procalcitonin were significantly higher than normal. The bronchoscopy revealed obvious necrotic detritus and pseudo membrane in the trachea, left and right main bronchi, and branches. BALF culture revealed the presence of Aspergillus.. Negative (1,3)-β-D-glucan is not safe to rule out invasive pulmonary aspergillosis. BALF culture is critical for IPA diagnosis.

Topics: Aspergillus; beta-Glucans; Bronchoalveolar Lavage Fluid; Diabetes Complications; Diagnosis, Differential; Humans; Invasive Pulmonary Aspergillosis; Leukocyte Count; Male; Middle Aged; Pneumonia; Procalcitonin; Proteoglycans

We review the role of bioaerosols in the pathogenesis of inflammatory airway disease. The focus is on recent discoveries in innate immune responses induced by common components of bioaerosols.. Common components of bioaerosols include endotoxin, peptidoglycan and beta-glucan; all of which have been associated with inflammatory airway disease. Endotoxin signaling through toll-like receptor 4 is well characterized and updated. Peptidoglycan is now known to signal through three types of molecules: toll-like receptor 2; peptidoglycan recognition proteins; and nucleotide-binding oligomerization domain molecules. Beta-glucan, a common fungal cell wall component, signals through the newly discovered receptor, dectin-1. Emerging data indicate that genetic polymorphisms influence the response to bioaerosols.. Activation of the innate immune system by bioaerosols is becoming better understood. This knowledge provides an opportunity to better prevent and treat airway diseases that result from environmental exposure.

Topics: Aerosols; Air Pollutants; beta-Glucans; Endotoxins; Humans; Immunity, Innate; Peptidoglycan; Pneumonia

In a effect to prevent nosocomial pneumonia and sepsis, we treated patients with severe multiple trauma with an immunomodulator--beta 1-3 polyglucose (glucan). Forty-one patients with no infection at admission were stratified using Trauma Score and included in a randomized double-blind controlled trial. They were divided into a control group (n = 20) and a glucan group (n = 21). Pneumonia occurred in 11 of 20 patients in the control group and in two of 21 recipients of glucan (p < 0.01). Sepsis occurred in seven of 20 patients in the control group and in two of 21 patients treated with glucan (p < 0.05). Considering patients with pneumonia and sepsis, a decrease was observed in nosocomial infection from 65.0 to 14.4 percent (p < 0.001). The mortality rate related to infection was 30.0 percent in patients in the control group and 4.8 percent in the group treated with glucan (p < 0.05). The general mortality rate, cerebral deaths excluded, was 42.1 percent in the control group and 23.5 percent in the glucan group.

Topics: Adjuvants, Immunologic; Adult; Bacterial Infections; beta-Glucans; Craniocerebral Trauma; Cross Infection; Double-Blind Method; Female; Glucans; Humans; Incidence; Male; Multiple Trauma; Pneumonia

Fungal contamination is omnipresent, and inhalation of fungi-contaminated organic dust leads to hypersensitivity pneumonitis (HP), in which neutrophils played a pivotal role. Existing studies have suggested that cell homeostasis is crucial for the pathogenesis of the inflammatory disease. Although HMGB1 has been shown to contribute to suppressing HP, there is a lack of studies on its mechanisms, especially the regulation of neutrophil homeostasis. This study aims to investigate how HMGB1 regulates neutrophil function by affecting neutrophil homeostasis, and then affects lung inflammation induced by β-glucan, the exposure marker of fungi. Our results showed that deficient HMGB1 led to neutrophil death by disrupting the balance between autophagy and pyroptosis after β-glucan treatment. And HMGB1 deficiency exacerbated the β-glucan-induced lung inflammation and neutrophil dysfunction both in vivo and in vitro. Furthermore, HMGB1 contributed to remodeling neutrophil function by restricting autophagy and aggravating pyroptosis β-glucan exposure. Our funding suggested that HMGB1 deficiency could break the balance between autophagy and pyroptosis towards pyroptosis to cause neutrophil dysfunction during the exacerbated inflammatory response, which provides insights into the pathogenesis of HP and the potential biological targets for its treatment. DATA AVAILABILITY: The datasets used during the current study are available from the corresponding author on reasonable request.

Topics: Animals; Autophagy; beta-Glucans; HMGB1 Protein; Mice; Neutrophils; Pneumonia; Pyroptosis

During. We have mimicked the lung inflammation by administering intranasal β-glucan in mice model. YVAD was used for caspase-1 inhibition.. We have shown that caspase-1 inhibition by YVAD did not alter inflammasome independent inflammatory cytokines, while it significantly reduced inflammasome activation and IL-1β secretion. Caspase-1 inhibited bone marrow derived dendritic cells (BMDCs), co-cultured with T cells showed decreased T-cell proliferation and direct them to secrete high TGF-β and IL-10 compared to the T cells co-cultured with β-glucan primed dendritic cells. Caspase-1 inhibition in BMDCs also induced IL-22 secretion from CD4. Caspase-1 inhibition can thus be an attractive target to prevent inflammation mediated tissue damage during

Topics: Animals; beta-Glucans; Caspase 1; Inflammasomes; Inflammation; Interleukin-10; Interleukin-17; Interleukin-1beta; Interleukin-22; Interleukins; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Pneumonia

Due to limited data on the link between gut barrier defects (leaky gut) and neutrophil extracellular traps (NETs) in coronavirus disease 2019 (COVID-19), blood samples of COVID-19 cases-mild (upper respiratory tract symptoms without pneumonia;

Topics: beta-Glucans; COVID-19; Cytokines; Extracellular Traps; Humans; Hypoxia; Lipopolysaccharides; Pneumonia; SARS-CoV-2

Allergen-specific immunotherapy via the skin targets a tissue rich in antigen-presenting cells, but can be associated with local and systemic side effects. Allergen-polysaccharide neoglycogonjugates increase immunization efficacy by targeting and activating dendritic cells via C-type lectin receptors and reduce side effects.. We investigated the immunogenicity, allergenicity, and therapeutic efficacy of laminarin-ovalbumin neoglycoconjugates (LamOVA).. The biological activity of LamOVA was characterized in vitro using bone marrow-derived dendritic cells. Immunogenicity and therapeutic efficacy were analyzed in BALB/c mice. Epicutaneous immunotherapy (EPIT) was performed using fractional infrared laser ablation to generate micropores in the skin, and the effects of LamOVA on blocking IgG, IgE, cellular composition of BAL, lung, and spleen, lung function, and T-cell polarization were assessed.. Conjugation of laminarin to ovalbumin reduced its IgE binding capacity fivefold and increased its immunogenicity threefold in terms of IgG generation. EPIT with LamOVA induced significantly higher IgG levels than OVA, matching the levels induced by s.c. injection of OVA/alum (SCIT). EPIT was equally effective as SCIT in terms of blocking IgG induction and suppression of lung inflammation and airway hyperresponsiveness, but SCIT was associated with higher levels of therapy-induced IgE and TH2 cytokines. EPIT with LamOVA induced significantly lower local skin reactions during therapy compared to unconjugated OVA.. Conjugation of ovalbumin to laminarin increased its immunogenicity while at the same time reducing local side effects. LamOVA EPIT via laser-generated micropores is safe and equally effective compared to SCIT with alum, without the need for adjuvant.

Topics: Allergens; Animals; Asthma; beta-Glucans; Lasers; Mice; Mice, Inbred BALB C; Ovalbumin; Pneumonia

Infections caused by the Scedosporium genus have become recognized as a fatal complication after lung transplantation in Europe and Australia, but the reports have been rare from Asian countries including Japan. We present a case of pneumonia caused by a mixed infection of Scedosporium apiospermum (SA) and Lomentospora prolificans (LP) that developed after augmentation of immunosuppression for chronic lung allograft dysfunction (CLAD) after lung transplantation. A 13-year-old man underwent bilateral lung transplantation for pulmonary hypertension. One year after surgery, he was treated with a series of augmented immunosuppressive therapy for severe acute rejection and subsequent CLAD. Three months following the first steroid pulse therapy, his serum β-D-glucan elevated without any sign of fungal infection by other tests. The serum β-D-glucan once returned to a normal level by empirical administration of micafungin; however, the patient's condition worsened again by discontinuation of it. He did not recover by restarting micafungin, and computed tomography (CT) scans eventually demonstrated new infiltrates in his lung field 6 weeks after the elevation of serum β-D-glucan. Microscopic findings of transbronchial lung biopsy specimens showed filamentous fungi, and the culture of bronchoalveolar lavage fluid revealed the growth of SA and LP. Despite subsequent voriconazole administration, he died 14 days after the start of voriconazole. Early and aggressive inspection including bronchoscopy should be performed for the diagnosis of Scedosporium infection in immunocompromised patients, even if CT scans and sputum culture show no evidence of infection.

Topics: Adolescent; beta-Glucans; Bronchoalveolar Lavage Fluid; Forced Expiratory Volume; Humans; Hypertension, Pulmonary; Immunocompromised Host; Invasive Fungal Infections; Lung Transplantation; Male; Pneumonia; Scedosporium; Thorax; Tomography, X-Ray Computed

Detection of (1,3)-beta-D-glucan (BDG), a component of the cell wall of many fungi, was studied in bronchoalveolar lavage fluid (BALF) as a possible aid for the diagnosis of proven/probable invasive pulmonary aspergillosis (IPA). BDG was measured on stored BALF from 13 patients with EORTC/MSGERC defined proven/probable IPA and 26 matched control patients without IPA. The median BALF BDG was 80 pg/mL (range < 45-8240 pg/mL) in the IPA cohort and 148 pg/mL (range < 45-5460 pg/mL) in the non-IPA cohort. Using a positive cutoff of ≥ 80 pg/mL, sensitivity was 54% and specificity was 38%. Higher cutoff values led to improvement in specificity but a dramatic decrease in sensitivity. ROC/AUC analysis was unable to identify an optimal cutoff value at which test performance was enhanced: AUC 0.43, 95% CI 0.24-0.63. When the BDG assay was performed on BALF, neither sensitivity nor specificity was sufficient for use in the diagnosis of IPA.

Topics: Adult; Aged; beta-Glucans; Bronchoalveolar Lavage Fluid; Cohort Studies; Diagnostic Tests, Routine; Female; Humans; Invasive Pulmonary Aspergillosis; Male; Middle Aged; Pneumonia; Proteoglycans; Sensitivity and Specificity

Chronic obstructive pulmonary disease (COPD), a lung disease caused by chronic exposure to cigarette smoke, increases the number of inflammatory cells such as macrophages and neutrophils and emphysema. Isoflavone is a polyphenolic compound that exists in soybeans. Daidzein and genistein, two types of isoflavones, have been reported to have anti-inflammatory effects in various organs. We hypothesized that the daidzein-rich soy isoflavone aglycones (DRIAs) attenuate cigarette smoke-induced emphysema in mice. Mice were divided into four groups: the (i) control group, (ii) isoflavone group, (iii) smoking group, and (iv) isoflavone + smoking group. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and the airspace enlargement using the mean linear intercept (MLI) were determined 12 weeks after smoking exposure. Expressions of neutrophilic inflammatory cytokines and chemokines were also examined. In the isoflavone + smoking group, the number of neutrophils in BALF and MLI was significantly less than that in the smoking group. Furthermore, the gene-expressions of TNF-α and CXCL2 (MIP-2) in the isoflavone + smoking group were significantly less than those in the smoking group. Supplementation of the COPD murine model with DRIAs significantly attenuates pathological changes of COPD via suppression of neutrophilic inflammation.

Topics: Animals; Anti-Inflammatory Agents; beta-Glucans; Cytokines; Disease Models, Animal; Inflammation Mediators; Isoflavones; Lung; Male; Mice, Inbred C57BL; Neutrophil Infiltration; Neutrophils; Pneumonia; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Signal Transduction; Smoke; Tobacco Products

While Candida pneumonia is life-threatening, biomarker measurements to early detect suspected Candida pneumonia are lacking. This study compared the diagnostic values of measuring levels of (1, 3)-β-D-glucan in endotracheal aspirate, bronchoalveolar lavage fluid, and serum to detect suspected Candida pneumonia in immunocompromised and critically ill patients.. This prospective, observational study enrolled immunocompromised, critically ill, and ventilated patients with suspected fungal pneumonia in mixed intensive care units from November 2010 to October 2011. Patients with D-glucan confounding factors or other fungal infection were excluded. Endotracheal aspirate, bronchoalveolar lavage fluid and serum were collected from each patient to perform a fungal smear, culture, and D-glucan assay.. After screening 166 patients, 31 patients completed the study and were categorized into non-Candida pneumonia/non-candidemia (n = 18), suspected Candida pneumonia (n = 9), and non-Candida pneumonia/candidemia groups (n = 4). D-glucan levels in endotracheal aspirate or bronchoalveolar lavage were highest in suspected Candida pneumonia, while the serum D-glucan level was highest in non-Candida pneumonia/candidemia. In all patients, the D-glucan value in endotracheal aspirate was positively correlated with that in bronchoalveolar lavage fluid. For the detection of suspected Candida pneumonia, the predictive performance (sensitivity/specificity/D-glucan cutoff [pg/ml]) of D-glucan in endotracheal aspirate and bronchoalveolar lavage fluid was 67%/82%/120 and 89%/86%/130, respectively, accounting for areas under the receiver operating characteristic curve of 0.833 and 0.939 (both P < 0.05), respectively. Measuring serum D-glucan was of no diagnostic value (area under curve =0.510, P = 0.931) for the detection of suspected Candida pneumonia in the absence of concurrent candidemia.. D-glucan levels in both endotracheal aspirate and bronchoalveolar lavage, but not in serum, provide good diagnostic values to detect suspected Candida pneumonia and to serve as potential biomarkers for early detection in this patient population.

Topics: Adult; Aged; beta-Glucans; Biomarkers; Bronchoalveolar Lavage Fluid; Candidemia; Candidiasis; Critical Illness; Early Diagnosis; Female; Humans; Immunocompromised Host; Intensive Care Units; Male; Middle Aged; Pneumonia; Prospective Studies; Proteoglycans; Sensitivity and Specificity

The aim of this study was to compare the clinical characteristics of pneumocystis pneumonia (PCP) between patients with rheumatoid arthritis (RA) being treated with biologics and those being treated without biologics.. From 8,630 patients with RA in our institution, we enrolled 24 patients who had developed PCP during the course of their treatment. They were divided into two groups according to the treatment they were receiving for RA: the biologics group (. At PCP diagnosis, the biologics group showed significantly lower serum levels of. The finding that RA patients being treated with biologics developed PCP with relatively normal lymphocyte counts and lower

Topics: Aged; Arthritis, Rheumatoid; beta-Glucans; Biological Products; Demography; Female; Humans; Lymphocyte Count; Male; Pneumocystis; Pneumonia; Severity of Illness Index

Pseudallescheria boydii is a fungal organism known to affect immunocompromised patients. This organism is known to cause, in severe cases, invasive infection of various organs such as the central nervous, cardiovascular, and respiratory systems. We report an unusual case of pulmonary P. boydii pneumonia in an immunocompromised critically ill patient with a co-infection of Aspergillus fumigatus and Aspergillus terreus with ARDS. This case highlights the importance of a high index of suspicion for superimposed fungal infections in patients who are critically ill and immunocompromised. Uncommon fungal pathogens should be considered in the differential diagnosis of respiratory failure, especially if diagnostic markers such as galactomannan (from BAL and serum) or 1,3-beta-D-glucan are elevated. Further diagnostic interventions are warranted when insufficient clinical improvement is observed to prevent treatment failure and adverse outcomes.

Topics: Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; beta-Glucans; Clarithromycin; Coinfection; Critical Illness; Extracorporeal Membrane Oxygenation; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Linezolid; Male; Mannans; Meropenem; Pneumonia; Pseudallescheria; Severe Acute Respiratory Syndrome; Thienamycins; Transplant Recipients; Voriconazole

β-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis In the current study, we examined whether β-1,3-glucans are masked by surface proteins in Pneumocystis and what role β-glucans play in Pneumocystis-associated inflammation. For 3 species, including Pneumocystis jirovecii, which causes Pneumocystis pneumonia in humans, Pneumocystis carinii, and Pneumocystis murina, β-1,3-glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using quantitative polymerase chain reaction and microarray techniques, we demonstrated in a mouse model of Pneumocystis pneumonia that treatment with caspofungin, an inhibitor of β-1,3-glucan synthesis, for 21 days decreased expression of a broad panel of inflammatory markers, including interferon γ, tumor necrosis factor α, interleukin 1β, interleukin 6, and multiple chemokines/chemokine ligands. Thus, β-glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses.

Topics: Animals; Antifungal Agents; beta-Glucans; Caspofungin; Cytokines; Disease Models, Animal; Echinocandins; Lipopeptides; Mice, Knockout; Microarray Analysis; Pneumocystis; Pneumonia; Pneumonia, Pneumocystis; Real-Time Polymerase Chain Reaction

Recently, a cluster of patients with an intractable allergic fungal cough who were characterized by sensitization to Bjerkandera adusta was reported. In the present study, the role of Toll-like receptors and myeloid differentiation factor 88 (MyD88) in B. adusta-induced lung inflammation was investigated.. Wild-type (WT), TLR2-/-,TLR4-/-, and MyD88-/- BALB/c mice were intratracheally challenged with B. adusta 4 times at 2-week intervals. Lung pathology, bronchoalveolar lavage fluid (BALF) cytological profiles, and inflammatory mediators in BALF were investigated. Bone marrow-derived macrophages (BMDM) from TLR2-/-,TLR4-/-, TLR2/4-/-, TLR7/9-/-,MyD88-/-, and WT C57BL/6J mice were stimulated with B. adusta for 12 h, and inflammatory mediators in the culture medium were measured.. B. adusta caused lung inflammation along with Th2 cytokine [interleukin (IL)-5 and IL-13] and eosinophil-related chemokine [eotaxin and monocyte chemotactic protein (MCP-3)] production, an increase in eosinophils in BALF, and eosinophil infiltration in the airways in WT and TLR4-/- mice. However, Th2 and eosinophil-related responses in TLR2-/- and MyD88-/- mice were low or undetectable. The induction of neutrophils and IL-6, IL-12, IL-17A, and MCP-1 in the BALF of MyD88-/- mice was attenuated compared to that in WT mice. The induction of IL-6, TNF-α, MCP-1, and macrophage inflammatory protein-1α was reduced or undetectable in B. adusta-stimulated BMDM from TLR7/9-/- and MyD88-/- mice compared to WT mice.. These results suggest that TLR2 and the adapter protein MyD88 may play an important role in the induction of eosinophils by B. adusta. However, TLR7/9-MyD88 might be important in the induction of neutrophils and the relevant inflammatory mediators, especially IL-17A.

Topics: Animals; beta-Glucans; Bone Marrow Cells; Bronchoalveolar Lavage Fluid; Cell Count; Cells, Cultured; Coriolaceae; Cytokines; Lipopolysaccharides; Lung; Macrophages; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mycoses; Myeloid Differentiation Factor 88; Pneumonia; Toll-Like Receptors

The ubiquitous fungal pathogen Aspergillus fumigatus is a mediator of allergic sensitization and invasive disease in susceptible individuals. The significant genetic and phenotypic variability between and among clinical and environmental isolates are important considerations in host-pathogen studies of A. fumigatus-mediated disease. We observed decreased radial growth, rate of germination, and ability to establish colony growth in a single environmental isolate of A. fumigatus, Af5517, when compared to other clinical and environmental isolates. Af5517 also exhibited increased hyphal diameter and cell wall β-glucan and chitin content, with chitin most significantly increased. Morbidity, mortality, lung fungal burden, and tissue pathology were decreased in neutropenic Af5517-infected mice when compared to the clinical isolate Af293. Our results support previous findings that suggest a correlation between in vitro growth rates and in vivo virulence, and we propose that changes in cell wall composition may contribute to this phenotype.

Topics: Animals; Aspergillosis; Aspergillus fumigatus; beta-Glucans; Cell Wall; Chitin; Colony Count, Microbial; Disease Models, Animal; Humans; Mice, Inbred BALB C; Neutropenia; Pneumonia; Virulence

Deep mycosis (aspergillus pneumonia (AsP)) and carinii pneumonitis (PCP) are complications of immunosuppressive treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The objective was to clarify the clinical significance of plasma titer of antibody against beta-glucans (anti-BG antibody) as a predictor of complications such as AsP or PCP and the prognosis of patients. Enzyme-linked immunosorbent assay was used to measure the plasma titer of antibodies against beta-glucans (BG) from Candida albicans in 22 healthy subjects and 52 patients with various stages of AAV. The mean plasma titer of the anti-BG antibody was 2,677 +/- 1,686 U in healthy subjects, 691 +/- 522 U in patients with untreated active vasculitis (n = 14), and 547 +/- 416 U in patients soon after immunosuppressive treatment (n = 24). Healthy subjects had significantly higher antibody titers than the other two groups (P < 0.05). Repeated measurements over the clinical course of AAV revealed an increase during remission to 1,180 +/- 130 U (n = 11), while there was a significant rapid decrease to 369 +/- 441 U (P < 0.01) concomitantly with elevation in plasma C-reactive protein and BG levels in patients with AAV that had AsP or PCP infection. Antifungal therapy resulted in a rapid rise of anti-BG antibody titer. Experiments in mice suggested that the anti-BG antibody neutralizes BG. Rapid decrease of the anti-BG antibody titer may be a useful indicator for diagnosis of the presence of AsP or PCP and for estimating the prognosis of patients with these opportunistic infections during immunosuppressive treatment of AAV.

Topics: Aged, 80 and over; Antibodies, Antineutrophil Cytoplasmic; Antifungal Agents; Aspergillus; beta-Glucans; Candida albicans; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycoses; Pneumonia; Remission Induction; Reproducibility of Results; Vasculitis

To elucidate the clinical and radiological features of Pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA), compared with methotrexate (MTX) pneumonitis in RA and Pneumocystis pneumonia in acquired immunodeficiency syndrome (AIDS).. Retrospective analysis of 14 PCP cases in RA (RA-PCP), 10 MTX pneumonitis cases in RA (MTX-P) and 11 PCP cases in AIDS (AIDS-PCP) from 9 centers in the Kanto area in the last 6 years.. Compared with AIDS-PCP, both RA-PCP and MTX-P developed more rapidly, showing higher serum CRP and lower plasma beta-D-glucan levels, and more severe oxygenation impairment. In most of the RA-PCP cases, a high dose of corticosteroid was administered as adjunctive therapy, resulting in a favorable outcome. The mortality was 14% in RA-PCP, 0% in AIDS-PCP and 0% in MTX-P cases. In RA-PCP patients the CD4 cell count showed only mild suppression, not reaching the predisposing level for PCP in HIV infection, suggesting that there are risk factors for RA-PCP other than immunosuppression. Radiologic analysis revealed some characteristic patterns of each disease. In MTX-P, diffuse homogeneous ground glass opacity (GGO) with sharp demarcation by interlobular septa (type A GGO) was found in 70%, while in AIDS-PCP diffuse, homogeneous or nonhomogeneous GGO without interlobular septal boundaries (type B GGO) was predominant (91%). In RA-PCP, type A GGO was found in 6 cases and type B GGO in 5 cases, showing the complex nature of this disease.. RA-PCP differed considerably from AIDS-PCP clinically and radiologically. Clinically it occurred without severe immunosuppression, and showed characteristic aspects, with more intense inflammation and less parasite burden. Radiologically it mimicked MTX-P in some cases sharing the conspicuous CT features of MTX-P, rendering the distinction of these two disorders difficult.

Topics: Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Arthritis, Rheumatoid; beta-Glucans; C-Reactive Protein; Diagnosis, Differential; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Pneumocystis carinii; Pneumonia; Pneumonia, Pneumocystis; Retrospective Studies; Tomography, X-Ray Computed

Inhalation of fungal spores (conidia) occurs commonly and, in specific circumstances, can result in invasive disease. We investigated the murine inflammatory response to conidia of Aspergillus fumigatus, the most common invasive mold in immunocompromised hosts. In contrast to dormant spores, germinating conidia induce neutrophil recruitment to the airways and TNF-alpha/MIP-2 secretion by alveolar macrophages. Fungal beta-glucans act as a trigger for the induction of these inflammatory responses through their time-dependent exposure on the surface of germinating conidia. Dectin-1, an innate immune receptor that recognizes fungal beta-glucans, is recruited in vivo to alveolar macrophage phagosomes that have internalized conidia with exposed beta-glucans. Antibody-mediated blockade of Dectin-1 partially inhibits TNF-alpha/MIP-2 induction by metabolically active conidia. TLR-2- and MyD88-mediated signals provide an additive contribution to macrophage activation by germinating conidia. Selective responsiveness to germinating conidia provides the innate immune system with a mechanism to restrict inflammatory responses to metabolically active, potentially invasive fungal spores.

Topics: Animals; Aspergillosis; Aspergillus fumigatus; beta-Glucans; Cytokines; Dendritic Cells; Inhalation Exposure; Intubation, Intratracheal; Lectins, C-Type; Lung; Macrophages, Alveolar; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Knockout; Nerve Tissue Proteins; Pneumonia; Specific Pathogen-Free Organisms; Spores, Fungal

Glucan, a folded high-molecular-weight polysaccharide, has multiple effects in animals when administered intravenously or intraperitoneally, but not when administered by inhalation. The hypotheses tested were whether intratracheal administration of glucan can cause lung damage and whether some of the resulting lung injury is immunologically mediated. There was a dose-response relationship between the amount of intratracheally injected glucan and the extent of pulmonary histologic abnormalities, which consisted of peribronchiolar and intraalveolar infiltration with chronic inflammatory cells. An attempt to adoptively transfer increased susceptibility to glucan induced lung injury was made. Cells cultured with glucan were transferred into naive recipients before intratracheal glucan exposure. The extent of pulmonary inflammation that occurred as a result of intratracheal injection of glucan was not affected by transfer of cultured cells from glucan-treated animals. However, high concentrations of glucan in culture did produce cells with the appearance of lymphoblasts. These data indicate that glucan induces lung injury, but that there is no evidence of cell mediation of pulmonary injury induced by intratracheal exposure to glucan.

Topics: Animals; beta-Glucans; Cells, Cultured; Dose-Response Relationship, Drug; Glucans; Lung; Male; Mice; Mice, Inbred C3H; Pneumonia; Polysaccharides, Bacterial

Pulmonary diseases are important cause of morbidity and mortality in patients with PM/DM. Thirteen (27%) out of 49 PM/DM patients in the study had developed respiratory failure. Respiratory failure resulted form interstitial pneumonitis (i.p.) in 6, pulmonary infection in 2 and both in 5 patients with PM/DM. Respiratory failure was fatal in PM/DM patients with pulmonary diseases and eleven of the 13 patients expired. More importantly, 2 PM/DM patients with respiratory failure had responded to chemotherapy, if it was due to pulmonary infection. Accordingly, it is almost important to distinguish i.p. and infection for the cause of respiratory failure. However, plain chest X-ray as well as standard laboratory tests failed to differentiate i.p. and pulmonary infection. On the other hand, high resolution CT of the lungs, serum endotoxin and serum beta-D-glucan were found to be useful for the differentiation of these conditions associated with respiratory failure in PM/DM patients. And additionally low serum level of IgG and lymphopenia at the onset of respiratory failure may suggest that the patients may have pulmonary infection rather than i.p.

Topics: Adult; beta-Glucans; Biomarkers; Dermatomyositis; Diagnosis, Differential; Endotoxins; Female; Glucans; Humans; Immunoglobulin G; Lung Diseases, Interstitial; Lymphocyte Count; Male; Middle Aged; Pneumonia; Polymyositis; Prognosis; Respiratory Insufficiency; Tomography, X-Ray Computed