Clinicopathological and Radiological Features of Chronic Rhinosinusitis with Eosinophilic Mucin in Chungcheong Province of Korea

Background

Chronic rhinosinusitis (CRS) with eosinophilic mucin is considered rare in Korea. The object of this study was to categorize CRS patients with eosinophilic mucin into several groups and compared the groups based on their clinicopathological and radiological features.

Methods

In total, 105 CRS patients with eosinophilic mucin from four tertiary medical centers which are located at Chungcheong province of Korea were included for this study. The patients were divided into four groups for analysis, based on the presence or absence of an allergy (A) to a fungus or fungal element (F) in the mucin. The following were the four groups: allergic fungal rhinosinusitis (AFRS, A+F+), AFRS-like sinusitis (A+F?), eosinophilic fungal rhinosinusitis (EFRS, A?F+), and eosinophilic mucin rhinosinusitis (EMRS, A?F?). Their clinical manifestation, the presence of associated disease, radiological finding, treatment, and treatment outcome were reviewed and compared.

Results

There were no patients in the AFRS-like sinusitis group, 47 patients were assigned to the AFRS group, 27 to the EFRS group, and 41 to the EMRS group. Patients of AFRS group showed a significantly higher association with allergic rhinitis than did the other groups. The mean total serum IgE level in the AFRS patients was significantly higher than in the EFRS and EMRS patients. In the AFRS group and EFRS group, 67.6% and 74.1% had unilateral disease, respectively, in contrast to the EMRS group (4.9%). The mean Hounsfield unit values of the area of high attenuation in the AFRS patients were significantly higher than those in the other groups.

Conclusions

Significant clinicopathological differences existed among the subgroups of CRS with eosinophilic mucin. AFRS tends to be an allergic response to colonizing fungi in atopic individuals. In EFRS, local allergies to fungi might play a role in the disease. EMRS is thought to be unconnected with fungal allergies, and it showed different form compared with the AFRS and EFRS groups.

     

Animal models of allergic bronchopulmonary aspergillosis

Among the allergic fungi, Aspergillus fumigatus, a saprophytic mold, distributed widely in the environment is a frequently recognized etiologic agent in a number of allergic conditions. Among the different allergic diseases caused by this fungus, allergic bronchopulmonary aspergillosis (ABPA) is by far the most significant one. The immunopathogenesis of this disease is not fully understood. Although several immunomodulatory treatments are available for allergic disease, none of them are applicable or relevant or useful in fungal induced allergy. It is essential to understand the pathogenesis of the disease including the antigen induced immunoregulation and the resulting factors, such as cytokine, chemokines, pathways activating factors, inflammatory and airway remodeling factors need to be understood for intervening with appropriate treatment. Animal models are essential in understanding these features of the disease. Several models of allergic aspergillosis have been developed in recent years in various animals. However, murine models have been studied more carefully and extensively. The exposure to antigen in mice leads to allergy very similar to ABPA with high IgE, elevated peripheral blood and lung eosinophils, pulmonary inflammation, and airway hyperreactivity. The role of various cytokines and chemokines and their receptors were also studied. In addition, immunotherapy and vaccination have been attempted in recent years using the murine model of ABPA. This review covers the murine model of Aspergillus induced allergy and asthma and presented critically our current understanding of the subject and the potential application of such a model in future for developing treatment modalities. This revised version was published online in June 2006 with corrections to the Cover Date.     

Choosing wisely: practical considerations on treatment efficacy and safety of asthma in the elderly

The prevalence of asthma in the most advanced ages is similar to that of younger ages. However, the concept that older individuals may suffer from allergic asthma has been largely denied in the past, and a common belief attributes to asthma the definition of “rare” disease. Indeed, asthma in the elderly is often underdiagnosed or diagnosed as COPD, thus leading to undertreatment of improper treatment. This is also due to the heterogeneity of clinical and functional presentations of geriatric asthma, including the partial loss of reversibility and the lower occurrence of the allergic component in this age range. The older asthmatic patients are also characterized the coexistence of comorbid conditions that, in conjunction with age-associated structural and functional changes of the lung, may contribute to complicate the management of asthma. The current review addresses the main issues related to the management of allergic asthma in the geriatric age. In particular, the paper aims at revising current pharmacological and non pharmacological treatments for allergic asthmatics of advanced ages, primarily focusing on their safety and efficacy, although most behaviors are an arbitrary extrapolation of what has been tested in young ages. In fact, age has always represented an exclusion criterion for eligibility to clinical trials. Experimental studies and real life observations specifically testing the efficacy and safety of therapeutic approaches in allergic asthma in the elderly are urgently needed.     

Fenofibrate: a novel formulation (Triglide) in the treatment of lipid disorders: a review

Cardiovascular disease is the major cause of mortality worldwide and accounts for approximately 40% of all deaths. Dyslipidemia is one of the primary causes of atherosclerosis and effective interventions to correct dyslipidemia should form an integral component of any strategy aimed at preventing cardiovascular disease. Fibrates have played a major role in the treatment of hyperlipidemia for more than two decades. Fenofibrate is one of the most commonly used fibrates worldwide. Since fenofibrate was first introduced in clinical practice, a major drawback has been its low bioavailability when taken under fasting conditions. Insoluble Drug Delivery-Microparticle fenofibrate is a new formulation that has an equivalent extent of absorption under fed or fasting conditions. In this review, we will discuss the clinical pharmacology of fenofibrate, with particular emphasis on this novel formulation, as well as its lipid-modulating and pleiotropic actions. We will also analyze the major trial that evaluated fibrates for primary and secondary prevention of cardiovascular disease, the safety and efficacy profile of fibrate-statin combination treatment, and the current recommendations regarding the use of fibrates in clinical practice.     

Novel antimicrobial strategies to treat multi-drug resistant Staphylococcus aureus infections

Antimicrobial resistance is a major obstacle for the treatment of infectious diseases and currently represents one of the most significant threats to global health. Staphylococcus aureus remains a formidable human pathogen with high mortality rates associated with severe systemic infections. S. aureus has become notorious as a multidrug resistant bacterium, which when combined with its extensive arsenal of virulence factors that exacerbate disease, culminates in an incredibly challenging pathogen to treat clinically. Compounding this major health issue is the lack of antibiotic discovery and development, with only two new classes of antibiotics approved for clinical use in the last 20 years. Combined efforts from the scientific community have reacted to the threat of dwindling treatment options to combat S. aureus disease in several innovative and exciting developments. This review describes current and future antimicrobial strategies aimed at treating staphylococcal colonization and/or disease, examining therapies that show significant promise at the preclinical development stage to approaches that are currently being investigated in clinical trials.     

Genetic variation in BDNF is associated with allergic asthma and allergic rhinitis in an ethnic Chinese population in Singapore

Allergic diseases affect more than 25% of the world population and result from a complex interplay between genetic and environmental factors. Recent evidence has shown that BDNF (Brain Derived Neurotrophic Factor) could serve as an important marker of allergic disease. Increased levels of BDNF in blood, bronchoalveolar lavage fluid and nasal lavage fluid positively correlate with disease activity and severity in patients with allergic rhinitis (AR), asthma and atopic eczema. However, reports on the association between genetic variation in BDNF and allergic disease have been controversial. This study therefore aims to clarify the relationship between single nucleotide polymorphisms (SNPs) in BDNF and a genetic predisposition to AR and asthma in an ethnic Chinese population of Singapore. Volunteers with a self-reported history of asthma (718 subjects) or a history of AR as determined by a researcher-administered questionnaire (795 subjects) were used in this study, alongside controls with no personal or family history of allergy (717 subjects). The association results identified a significant association for the tagSNP rs10767664 with a significant P_Dominant = 0.0007 and OR = 1.3 for AR and P_Dominant = 0.0005 and OR = 1.3 for asthma (using a dominant model of association). The haplotype based analysis also identified a significant association further confirming the single SNP association. The SNP rs10767664 is strongly linked (r² = 0.95) to the functional polymorphism rs6265 (Val66Met), which has previously been reported to be associated to allergic phenotypes and also shown to affect BDNF expression. BDNF is a therefore a key molecular player in allergy. Further studies on polymorphisms within BDNF may shed light on its role in the pathogenesis of allergic diseases and potentially serve as biomarkers for allergic disease.     

肠道微生物与过敏性疾病关系研究进展

目前,过敏性疾病的防治主要依赖于使用抗生素,然而抗生素的滥用已造成了严重的危害。近年来随着肠道微生物相关研究的不断深入以及人们对过敏性疾病的日益关注与重视,肠道微生物与过敏性疾病间的关系逐渐受到科学家们的关注。调整肠道菌群结构可能为过敏性疾病的防治提供新的思路。目前对肠道微生物与过敏性疾病间的相关性报道相对较少且未有深层次的剖析。本文总结了关于肠道微生物与过敏性疾病关系的研究起源、发展与现状,旨在为过敏性疾病的防治提供新策略。     

Proteomic analysis of <Emphasis Type="Italic">Parietaria judaica</Emphasis> pollen and allergen profiling by an immunoproteomic approach

Parietaria judaica pollen is a common cause of airway allergic disease in the Mediterranean area. Proteome analysis of mature Parietaria judaica pollen by two-dimensional gel electrophoresis (2-DE) and mass spectrometry has established the first reference proteome map of this weed. Proteins involved in a variety of cellular functions as well as the occurrence of allergens were detected. By using 2-DE and immunoblotting with sera from Parietaria judaica allergic patients we obtained a more detailed characterization of Parietaria judaica allergen profile so to improve our comprehension of the pathogenesis of pollen-induced allergic reaction.     

ASTHMA IN CHILDREN—PROBLEMS IN DIAGNOSIS

Bronchial asthma in children may be difficult to diagnose. Education of the parents regarding allergic conditions, specifically bronchial asthma, is exceedingly important in order to assure satisfactory treatment and clinical results.Chest symptoms of unexplained origin in early life should immediately arouse suspicion of allergic disease. Other causes of asthmatic symptoms must be borne in mind and excluded before a positive diagnosis of bronchial asthma is established.Of the many factors to be considered in investigating a child with asthma, a comprehensive history is most essential. The climate to which the patient is exposed and the psychic influences must be taken into account. Physical examination, x-ray films and laboratory procedures should be carefully executed. Skin testing, especially with food allergens, should not be relied upon to give all the information in allergic disease. Some form of diet trial, such as elimination diets, should be used if sensitivity to food is suspected.     

Asthma in children--problems in diagnosis

Bronchial asthma in children may be difficult to diagnose. Education of the parents regarding allergic conditions, specifically bronchial asthma, is exceedingly important in order to assure satisfactory treatment and clinical results. Chest symptoms of unexplained origin in early life should immediately arouse suspicion of allergic disease. Other causes of asthmatic symptoms must be borne in mind and excluded before a positive diagnosis of bronchial asthma is established. Of the many factors to be considered in investigating a child with asthma, a comprehensive history is most essential. The climate to which the patient is exposed and the psychic influences must be taken into account. Physical examination, x-ray films and laboratory procedures should be carefully executed. Skin testing, especially with food allergens, should not be relied upon to give all the information in allergic disease. Some form of diet trial, such as elimination diets, should be used if sensitivity to food is suspected.     

Mesenchymal stem cells and immunomodulation: current status and future prospects

The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them an invaluable cell type for the repair of tissue/ organ damage caused by chronic inflammation or autoimmune disorders. Although they hold great promise in the treatment of immune disorders such as graft versus host disease (GvHD) and allergic disorders, there remain many challenges to overcome before their widespread clinical application. An understanding of the biological properties of MSCs will clarify the mechanisms of MSC-based transplantation for immunomodulation. In this review, we summarize the preclinical and clinical studies of MSCs from different adult tissues, discuss the current hurdles to their use and propose the future development of pluripotent stem cell-derived MSCs as an approach to immunomodulation therapy.     

Management of Mild-to-Moderate Hypertriglyceridemia

ObjectiveHypertriglyceridemia (HTG) is highly prevalent globally, and its prevalence is rising, with a worldwide increase in the incidence of obesity and diabetes. This review examines its current management and future therapies.MethodsFor this review, HTG is defined as mild-to-moderate elevation in the levels of triglyceride (TG): a fasting or nonfasting TG level of ≥150 mg/dL and <500 mg/dL. We reviewed scientific studies published over the last 30 years and current professional society recommendations regarding the evaluation and treatment of HTG.ResultsGenetics, lifestyle, and other environmental factors impact TG levels. In adults with mild-to-moderate HTG, clinicians should routinely assess and treat secondary treatable causes (diet, physical activity, obesity, metabolic syndrome, and reduction or cessation of medications that elevate TG levels). Because atherosclerotic cardiovascular disease risk is the primary clinical concern, statins are usually the first-line treatment. Patients with TG levels between ≥150 mg/dL and <500 mg/dL whose low-density lipoprotein cholesterol is treated adequately with statins (at “maximally tolerated“ doses, per some statements) and have either prior cardiovascular disease or diabetes mellitus along with at least 2 additional cardiovascular disease risk factors should be considered for added icosapent ethyl treatment to further reduce their cardiovascular disease risk. Fibrates, niacin, and other approved agents or agents under development are also reviewed in detail.ConclusionThe treatment paradigm for mild-to-moderate HTG is changing on the basis of data from recent clinical trials. Recent trials suggest that the addition of icosapent ethyl to background statin therapy may further reduce atherosclerotic cardiovascular disease risk in patients with moderate HTG, although a particular TG goal has not been identified.     

Lipedema: A Call to Action!

Lipedema is a chronic progressive disease characterized by abnormal fat distribution resulting in disproportionate, painful limbs. It almost exclusively affects women, leading to considerable disability, daily functioning impairment, and psychosocial distress. Literature shows both scarce and conflicting data regarding its prevalence. Lipedema has been considered a rare entity by several authors, though it may be a far more frequent condition than thought. Despite the clinical impact on women's health, lipedema is in fact mostly unknown, underdiagnosed, and too often misdiagnosed with other similarly presenting diseases. Polygenic susceptibility combined with hormonal, microvascular, and lymphatic disorders may be partly responsible for its development. Furthermore, consistent information on lipedema pathophysiology is still lacking, and an etiological treatment is not yet available. Weight loss measures exhibit minimal effect on the abnormal body fat distribution, resulting in eating disorders, increased obesity risk, depression, and other psychological complaints. Surgical techniques, such as liposuction and excisional lipectomy, represent therapeutic options in selected cases. This review aims to outline current evidence regarding lipedema epidemiology, pathophysiology, clinical presentation, differential diagnosis, and management. Increased awareness and a better understanding of its clinical presentation and pathophysiology are warranted to enable clinicians to diagnose and treat affected patients at an earlier stage.     

Myelin basic protein-reactive T cells in multiple sclerosis: Pathologic relevance and therapeutic targeting

Autoreactive T cells specific for myelin proteins, such as myelin basic protein (MBP), are thought to play an important role in the pathogenesis of multiple sclerosis (MS). In MS, these MBP-reactive T cells are activated and clonally expandedin vivo and found to accumulate in the brain compartment, suggesting their pathologic role in the disease. There is experimental evidence supporting the beliefs that MBP-reactive T cells are regulatedin vivo by the clonotypic regulatory network. This concept has led to the paradigm of T cell vaccination where attenuated MBP-reactive T cells are used as vaccines to effectively prevent and treat experimental autoimmune encephalomyelitis, an animal model for MS. In this paper, the recent evidence regarding the pathologic relevance encephalomyelitis, an animal model for MS. In this paper, the recent evidence regarding the pathologic relevance of MBP-reactive T cell in MS is reviewed. In particular, we discuss our recent clinical trial in which patients with MS were vaccinated with inactivated autologous MBP-reactive T cell clones to investigate the nature of clonotypic responsesin vivo, and whether the responses are effective in depleting circulating MBP-reactive T cells in patients with MS. Our study presented in this paper demonstrated the successful depletion of MBP-reactive T cells by T cell vaccination and touched upon important issues related to the clinical application of T cell vaccination in humans. This review provides new insights into the current development in designing effective therapeutic strategies, such as T cell vaccination, to treat patients with MS and other autoimmune diseases.     

T rypanosoma cruzi trans-sialidase as a multifunctional enzyme in Chagas' disease

Trypanosoma cruzi trans‐sialidase (TS) was identified three decades ago. TS catalyses a trans‐glycosylation reaction, transferring SA from sialylated donors to the terminal galactose mucin‐glycoconjugates, or non‐mucin galactyosyl‐glycoconjugates. It is an external surface protein that is also released from the parasite, displaying several binding properties in addition to its enzymatic function. TS structure has been solved and its catalytic properties are well known, providing tools for development of new inhibitors, as potential chemotherapeutic agents against Chagas’ disease. However, there are still several unsolved questions regarding TS role in the biology of T. cruzi and in the pathology of Chagas’ disease. In this review, we will describe the multifunctional roles of TS regarding the development of Chagas’ disease and propose that these multiple functions have to be considered in future investigations aiming to use TS as a drug target.     

The immunomodulatory role of probiotics in allergy therapy

The increased incidence of allergic disorders may be the result of a relative fall in microbial induction in the intestinal immune system during infancy and early childhood. Probiotics have recently been proposed as viable microorganisms for the prevention and treatment of specific allergic diseases. Different mechanisms have been considered for this probiotic property, such as generation of cytokines from activated pro-T-helper type 1 after bacterial contact. However, the effects of its immunomodulatory potential require validation for clinical applications. This review will focus on the currently available data on the benefits of probiotics in allergy disease.     

The Effects of Air Pollution on Structures, Proteins and Allergenicity of Pollen Grains

The prevalence of allergic disease has increased world wide during the last decades. Pollen allergy is the most typical form of allergic disease. The increase in its frequency during recent years is the most evident. Environmental factors play an important role in the problem of pollen allergy in large cities. The aim of this research is determination of allergenicity of Canna pollen in polluted and non-polluted conditions, detection of their allergenic proteins and also elucidation of some microscopic effects of air pollutants on pollen structure and proteins. Mature and immature pollen grains of Canna indica were collected from polluted and non-polluted areas. Pollen grains were studied by scanning electron microscopy. Mice were sensitized by injection of pollen extract and an adjuvant for five times. Allergy potency of different pollen extracts were compared by means of skin test, blood eosinophills number and IgE levels in sensitized and treated animals. Pollen proteins were studied by SDS-PGE and allergenic proteins were detected by immunoblotting techniques. Scanning electron microscope study of the pollen grains showed that in polluted areas, air born particles accumulated on the surface of pollen and changed both pollen's shape and pollen's tectum. Also many vesicles were released out of polluted pollen and the pollen material agglomerated on the surface of pollen. SDS-PAGE showed that different proteins exist in mature and immature pollen. In pollen collected from polluted area, some of protein bands between 22 and 45 kDa were disappeared . Also in all polluted pollen grains, protein content of pollen decreased in response to air pollution causing the release of pollen proteins. According to our experiments and regarding induction of allergic symptoms, the polluted pollen is more effective than non-polluted one, and mature pollen has more allergy potency than immature one.     

Clinical and Treatment Aspects of Brown–Black Fungi

Brown–black (or dematiaceous) fungi are responsible for a wide variety of infectious syndromes in both immunocompetent and immunocompromised patients, including local infections, allergic disease, pneumonia, brain abscess, and disseminated infection. They are distinct from the more common hyaline molds, Aspergillus and Fusarium, that cause human disease. They are often found in soil and generally distributed worldwide. In recent years, these fungi have been increasingly recognized as important pathogens. Dematiaceous fungi may have unique pathogenic mechanisms owing to the presence of melanin in their cell walls, which imparts the characteristic dark color to their spores and hyphae. Diagnosis rests on careful microscopic and pathologic examination, as there are no specific laboratory tests to reliably identify these fungi. Therapy depends upon the clinical syndrome, although disseminated infection often has high mortality. Triazoles such as voriconazole, posaconazole, and itraconazole are the most active antifungal agents available. Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections.     

Current utilization of interferon alpha for the treatment of coronavirus disease 2019: A comprehensive review

Recent studies have identified an association between perturbed type I interferon (IFN) responses and the severity of coronavirus disease 2019 (COVID-19). IFNα intervention may normalize the dysregulated innate immunity of COVID-19. However, details regarding its utilization and therapeutic evidence have yet to be systematically evaluated. The aim of this comprehensive review was to summarize the current utilization of IFNα for COVID-19 treatment and to explore the evidence on safety and efficacy. A comprehensive review of clinical studies in the literature prior to December 1st_, 2021, was performed to identify the current utilization of IFNα, which included details on the route of administration, the number of patients who received the treatment, the severity at the initiation of treatment, age range, the time from the onset of symptoms to treatment, dose, frequency, and duration as well as safety and efficacy. Encouragingly, no evidence was found against the safety of IFNα treatment for COVID-19. Early intervention, either within five days from the onset of symptoms or at hospital admission, confers better clinical outcomes, whereas late intervention may result in prolonged hospitalization.     

Pathophysiological mechanisms for the respiratory syncytial virus-reactive airway disease link

Pulmonary surfactant is a unique mixture of lipids and surfactant-specific proteins that covers the entire alveolar surface of the lungs. Surfactant is not restricted to the alveolar compartment; it also reaches terminal conducting airways and is present in upper airway secretions. While the role of surfactant in the alveolar compartment has been intensively elucidated both in health and disease states, the possible role of surfactant in the airways requires further research. This review summarizes the current knowledge on surfactant functions regarding the airway compartment and highlights the impact of various surfactant components on allergic inflammation in asthma.