Human toxocariasis is the most prevalent helminthiasis in Korea and other industrialized countries. The clinical features of toxocariasis are diverse, according to the involved organ. Typically, Toxocara spp. infection is easily treated with 400 mg albendazole twice a day for 5 days. However, we experienced a case of recurrent toxocariasis that was refractory to this standard therapy and presented with urticaria, an uncommon symptom in toxocariasis. A 35-year-old male visited our emergency room because of abdominal pain. He had recently consumed raw cow liver (3 weeks prior to presentation). Laboratory analyses revealed eosinophilia (1,612 cells/microliter) and increased total IgE (3,060 IU/mL). Chest X-ray showed multiple lung nodules in both lungs, and computed tomography revealed multiple ground-glass opacities in both lungs and multiple tiny liver abscesses. Liver biopsy revealed an eosinophilic abscess. Enzyme-linked immunosorbent assay findings for Toxocara antigens were positive (optical density, 2.140), leading to a diagnosis of toxocariasis. We initiated a 5-day treatment with albendazole and prednisolone; however, 6 days after completing the treatment, the patient again experienced urticaria and severe itching that could not be controlled by antihistamines or hydrocortisone cream. A second bout of eosinophilia suggested recurring toxocariasis, for which we prescribed a second round of albendazole. Despite an initial improvement in his symptoms, the patient returned after 6 weeks complaining of abdominal pain for 6 hours, which was reminiscent of his first attack; he also exhibited eosinophilia. Accordingly, albendazole was administered once more for an additional 3 weeks, and his symptoms resolved.
Abdominal Pain ; Abscess ; Adult ; Albendazole ; Biopsy ; Developed Countries ; Emergencies ; Enzyme-Linked Immunosorbent Assay ; Eosinophilia ; Eosinophils ; Helminthiasis ; Histamine Antagonists ; Humans ; Hydrocortisone ; Immunoglobulin E ; Korea ; Liver ; Liver Abscess ; Lung ; Male ; Pruritus ; Thorax ; Toxocara ; Toxocariasis ; Urticaria

PURPOSE: A genetic polymorphism of the beta 2-adrenergic receptor is a major factor associated with the asthmatic phenotype. The association of this polymorphism with toluene diisocyanate (TDI)-induced asthma has not been investigated. We examined 103 TDI-induced asthma patients (TDI-OA), 60 asymptomatic exposed controls (AEC), and 263 unexposed healthy controls (NC) in order to identify beta 2-adrenergic receptor gene (ADRB2) polymorphisms and the possible association with TDI-induced asthma. METHODS: Single nucleotide polymorphisms (SNPs) of ADRB2 were genotyped by direct sequencing. Serum-specific IgE and IgG levels were measured using an enzyme-linked immunosorbent assay. Phenotypes and clinical patient parameters were compared. RESULTS: SNPs were identified (-47 T>C, -20 T>C, Arg16Gly A>G, Gln27Glu C>G, Leu134Leu G>A, Arg175Arg C>A) during ADRB2 screening (from -231 to 793 bp). No significant differences in allelic and genotypic frequencies were noted for any of the six ADRB2 SNPs. The Arg16Gly A>G, Leu134Leu G>A, and Arg175Arg C>A SNPs and haplotype 1 [TTACGC] were significantly associated with specific IgE antibodies to the TDI-human serum albumin (HSA) conjugate in TDI-exposed subjects (P<0.05). Exposed workers with the ADRB2 ht1/ht1 homozygote had a significantly higher TDI-HSA conjugate-specific IgE sensitization rate than did those with the null ht1 haplotype (odds ratio, 15.40; 95% confidence interval, 1.81-131.06). CONCLUSIONS: ADRB2 polymorphisms may affect IgE-specific sensitization to TDI-HSA conjugate in TDI-exposed workers.
Antibodies ; Asthma ; Enzyme-Linked Immunosorbent Assay ; Genetic Predisposition to Disease ; Haplotypes ; Homozygote ; Humans ; Immunoglobulin E ; Immunoglobulin G ; Mass Screening ; Phenotype ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Serum Albumin ; Toluene ; Toluene 2,4-Diisocyanate

PURPOSE: Smoking elicits airway inflammation and airflow obstruction in patients with asthma, even after smoking cessation. The aim of this study was to examine the effects of smoking cessation on lung function and quality of life (QOL) in asthmatic patients. METHODS: Thirty-two patients with asthma who were active smokers were recruited. After education on the effects of smoking on asthma, 22 patients continued to smoke, and 10 quit smoking. All patients were treated with inhaled fluticasone propionate (1 mg/day) for 3 months. We compared forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow between 25 and 75% FVC (FEF(25-75%)), and scores on a QOL questionnaire at baseline, 1, 2, and 3 months. RESULTS: Quitters showed a greater percent change in FEV1 (19.1+/-6.3 vs. 7.9+/-2.4%, P=0.024) and FEV1/FVC (6.5+/-4.14 vs. 3.5+/-1.5%, P=0.05) than smokers. Both quitters and smokers showed improved QOL scores after 1, 2, and 3 months of fluticasone treatment. CONCLUSIONS: Patients with asthma who quit smoking showed less airway obstruction, suggesting that smoking cessation is crucial in the management of asthma.
Airway Obstruction ; Androstadienes ; Asthma ; Diethylpropion ; Forced Expiratory Volume ; Humans ; Inflammation ; Lung ; Quality of Life ; Smoke ; Smoking ; Smoking Cessation ; Vital Capacity ; Fluticasone ; Surveys and Questionnaires

PURPOSE: Patient care based on asthma guidelines is cost-effective and leads to improved treatment outcomes. However, ineffective implementation strategies interfere with the use of these recommendations in clinical practice. This study investigated physicians' preferences for asthma guidelines, including content, supporting evidence, learning strategies, format, and placement in the clinical workplace. METHODS: We obtained information through a questionnaire survey. The questionnaire was distributed to physicians attending continuing medical education courses and sent to other physicians by airmail, e-mail, and facsimile. RESULTS: A total of 183 physicians responded (male to female ratio, 2.3:1; mean age, 40.4+/-9.9 years); 89.9% of respondents were internists or pediatricians, and 51.7% were primary care physicians. Physicians preferred information that described asthma medications, classified the disease according to severity and level of control, and provided methods of evaluation/treatment/monitoring and management of acute exacerbation. The most effective strategies for encouraging the use of the guidelines were through continuing medical education and discussions with colleagues. Physicians required supporting evidence in the form of randomized controlled trials and expert consensus. They preferred that the guidelines be presented as algorithms or flow charts/flow diagrams on plastic sheets, pocket cards, or in electronic medical records. CONCLUSIONS: This study identified the items of the asthma guidelines preferred by physicians in Korea. Asthma guidelines with physicians' preferences would encourage their implementation in clinical practice.
Asthma ; Consensus ; Surveys and Questionnaires ; Education, Medical, Continuing ; Electronic Health Records ; Electronic Mail ; Female ; Humans ; Korea ; Learning ; Patient Care ; Physician's Practice Patterns ; Physicians, Primary Care ; Plastics ; Surveys and Questionnaires

Staphylococcus aureus (SA) is usually present not only in the skin lesions of atopic dermatitis (AD) but also in the atopic dry skin. SA discharges various toxins and enzymes that injure the skin, results in activation of epidermal keratinocytes, which produce and release IL-18. IL-18 that induces the super Th1 cells secreting IFN-gamma and IL-13 is supposed to be involved in development of AD and its pathogenesis. Indeed, the number of SA colonies on the skin surface and the serum IL-18 levels in patients with AD significantly correlated with the skin scores of AD lesions. Also, there is strong positive correlation between the skin scores and serum IL-18 levels in DS-Nh mice (P<0.0001, r=0.64), which develop considerable AD-like legions when they are housed under conventional conditions, but develop skin legions with less severity and less frequency under specific pathogens free (SPF) conditions. Therefore, they are well-known as model mice of AD, in which SA is presumed to be critical factor for the development of AD lesions. Also, theses DS-Nh mice pretreated with Cy developed more remarkable AD-like lesions in comparison with non-treated ones. The levels of INF-r and IL-13 in the supernatants of the lymph node cell cultures stimulated with staphylococcal enterotoxin B (SEB) or ConA were increased in the Cy-treated mice, although the serum levels of total IgE were not. In this experiment, we revealed that Cy-treated mice, to which CD25 +CD4 + reguratory T cells taken from non-treated ones had been transferred, developed the AD-like legions with less severity and less number of SA colonies on the skin surface. Therefore, it is presumed that CD25 +CD4 + reguratory T cells might be involved in the suppression of super Th1 cells which are induced by IL-18 and are involved in the development of AD-like lesions rather than IgE production. The efficient induction of CD25 +CD4 + reguratory T cells is expected for the new type of treatment of AD. We also found that farnesol (F) and xylitol (X) synergistically inhibited biofilm formation by SA, and indeed the ratio of SA in total bacteria at sites to which the FX cream containing F and X had been applied was significantly decreased 1 week later, accompanied with improvement of AD, when compared with that before application and at placebo sites. Therefore, the FX cream is a useful skin-care agent for atopic dry skin colonized by SA. The nerve growth factor (NGF) in the horny layer (the horn NGF) of skin lesions on the cubital fossa was collected by tape stripping and measured using ELISA in AD patients before and after 2 and 4 weeks treatments. Simultaneously, the itch and eruptions on the whole body and on the lesions, in which the horn NGF was measured, were recorded, and also the peripheral blood eosinophil count, serum LDH level and serum total IgE level were examined. The level of NGF was significantly higher in AD patients than in healthy controls, correlated with the severity of itch, erythema, scale/xerosis, the eosinophil count and LDH level, and also significantly decreased after treatments with olopatadine and/or steroid ointment for 2 and 4 weeks. Therefore, the measurement of the NGF by this harmless method seems to be useful to assess the severity of AD and the therapeutic effects on AD. In AD patients, C-fiber in the epidermis increase and sprout, inducing hypersensitivity, which is considered to aggravate the disease. Semaphorin 3A (Sema3A), an axon guidance molecule, is a potent inhibitor of neurite outgrowth of sensory neurons. We administered recombinant Sema3A intracutaneously into the skin lesions of NC/Nga mice, an animal model of AD, and investigated the effect of Sema3A on the skin lesions and their itch. Sema3A dose-dependently improved skin lesions and attenuated the scratching behavior in NC/Nga mice. Histological examinations revealed a decrease in the epidermal thickness, the density of invasive nerve fibers in the epidermis, inflammatory infiltrate including mast cells and CD4 +T cells, and the production of IL-4 in the Sema3A-treated lesions. Because the interruption of the itch-scratch cycle likely contributes to the improvement of the AD-like lesions, Sema3A is expected to become a promising treatment of patients with refractory AD.
Animals ; Axons ; Bacteria ; Biofilms ; Cell Culture Techniques ; Colon ; Dermatitis, Atopic ; Dibenzoxepins ; Enterotoxins ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; Epidermis ; Erythema ; Farnesol ; Horns ; Humans ; Hypersensitivity ; Immunoglobulin E ; Interleukin-13 ; Interleukin-18 ; Interleukin-4 ; Keratinocytes ; Lymph Nodes ; Mast Cells ; Mice ; Models, Animal ; Nerve Fibers ; Nerve Growth Factor ; Neurites ; Semaphorin-3A ; Semaphorins ; Sensory Receptor Cells ; Skin ; Staphylococcus aureus ; T-Lymphocytes ; Th1 Cells ; Xylitol ; Olopatadine Hydrochloride

New information regarding the molecular mechanisms of allergic disorders has led to a variety of novel therapeutic approaches. This article briefly reviews the pathogenesis of asthma and allergic diseases, discusses the rationale behind using immunomodulators in these diseases; and examines the therapeutic effects of immunomodulators on allergic diseases. There are a number of immunomodulators that have been developed for the treatment of allergic disorders. Some have looked very promising in pre-clinical trials, but have not shown significant benefits in human clinical trials thus indicating the disparity between mouse models and human asthma. This review focuses on immunomodulators that are in human clinical trials and not molecules in pre-clinical development.
Animals ; Asthma ; Cytokines ; Humans ; Immunologic Factors ; Mice

Asthma and allergic diseases are believed to be complex genetic diseases which may result from the interaction of multiple genetic factors and environmental stimuli. In past decades, great efforts have been exerted in unraveling their genetic basis. The strategies in discovering genes and genetic variants, confirming their importance in pathogenesis of asthma and allergic diseases, as well as their strengths and limitations are summarized comprehensively and concisely. The current consensus about the genetic basis of asthma and allergic diseases is briefly described as well.
Asthma ; Consensus

Asthma and chronic obstructive pulmonary disease (COPD) are traditionally recognized as distinct diseases, with some clearly separate characteristic. Asthma originates in childhood, is associated with allergies and eosinophils, and is best treated by targeting inflammation, whereas COPD occurs in adults who smoke, involves neutrophils, and is best treated with bronchodilators and the removal of risk factors. However, the distinction between the two is not always clear. Patients with severe asthma may present with fixed airway obstruction, and patients with COPD may have hyperresponsiveness and eosinophilia. Recognizing and understanding these overlapping features may offer new insight into the mechanisms and treatment of chronic airway inflammatory diseases.
Adult ; Airway Obstruction ; Asthma ; Bronchodilator Agents ; Eosinophilia ; Eosinophils ; Humans ; Hypersensitivity ; Inflammation ; Neutrophils ; Pulmonary Disease, Chronic Obstructive ; Risk Factors ; Smoke

PURPOSE: Live/killed mycobacteria and culture supernatants can suppress asthmatic reactions. This study investigated whether mycobacterial secretory proteins have therapeutic effects on asthma. METHODS: Mycobacterium bovis bacille Calmette-Guerin (BCG; 2x105 CFUs) and mycobacterial secretory proteins (Ag85 complex, 38-kDa protein or MPB70; 4 or 20 microg) were administered intraperitoneally to female BALB/c mice with established airway hyperresponsiveness. One week after treatment, the mice underwent a methacholine challenge test, and then inflammatory cell numbers in bronchoalveolar lavage fluid (BAL) and around bronchi (<500 microm), and cytokine levels in splenocyte supernatants, were assessed. RESULTS: BCG and all of the tested secretory proteins significantly improved airway sensitivity compared to baseline values (P<0.05). The secretory protein Ag85 complex significantly suppressed airway reactivity also (P<0.05), while 38-kDa protein significantly suppressed reactivity and maximal narrowing (P<0.05). The number of eosinophils in BAL and around bronchi, and the goblet cell proportion, were also significantly reduced in mice in both the BCG and secretory protein groups compared to the asthma control group. IFN-gamma/IL-5 ratios were significantly higher in mice treated with BCG, 4 microg MPB70 or 4 microg 38-kDa protein than in asthma control mice (P<0.05), and were negatively associated with airway hyperresponsiveness, peribronchial eosinophil numbers and goblet cell proportion (all P<0.05). IL-17A was positively correlated with IL-5 (r=0.379, P<0.001), maximal airway narrowing, peribronchial eosinophil numbers and goblet cell proportion (all P<0.05). CONCLUSIONS: Secretory proteins from BCG and M. tuberculosis and live BCG were effective against established asthma, their effects being accompanied by increased IFN-gamma/IL-5 ratios. Thus, allergic asthma could be effectively treated with mycobacterial secretory proteins.
Animals ; Asthma ; Bronchi ; Bronchoalveolar Lavage Fluid ; Cell Count ; Eosinophils ; Female ; Goblet Cells ; Humans ; Indoles ; Interleukin-17 ; Interleukin-5 ; Methacholine Chloride ; Mice ; Mycobacterium bovis ; Proteins ; Tuberculosis

PURPOSE: Recent studies have reported that Asian sand dust (ASD) has a potential risk of aggravating airway inflammation. The purpose of this study was to investigate the effect of ASD on inflammation and mucin production in the airways of allergic mice. METHODS: Forty BALB/c female mice were divided into four groups: saline (group 1); ASD (group 2); ovalbumin (OVA) alone (group 3); and OVA+ASD (group 4). OVA-specific immunoglobulin E (IgE) in serum and interleukin (IL)-4, IL-5, IL-13, and interferon-gamma (IFN-gamma) in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Hematoxylin & eosin (H&E) and Periodic acid-Schiff (PAS) staining was performed on lung tissues. In addition, immunohistochemical staining for IL-4, IL-5, MUC5AC, and transforming growth factor alpha (TGF-alpha) was conducted. RESULTS: Serum IgE levels were significantly higher in group 4 than in group 3 (P<0.05). IL-4 and IL-5 in BALF were significantly higher in group 4 than in group 3 (P<0.05, respectively). Based on H&E staining, inflammatory cell numbers were significantly greater in group 4 than in the other groups (P<0.05). The number of PAS-positive cells was also significantly greater in groups 3 and 4 than in groups 1 and 2 (P<0.05). The numbers of IL-4 and IL-5-positive cells were higher in group 4 than in group 3 (P<0.05). The number of MUC5AC and TGF-alpha-positive cells were also higher in group 4 than in group 3 (P<0.05). CONCLUSIONS: Our data suggest that ASD increases cytokine expression and mucin production in an allergic murine model. The increased inflammatory reactions were related to cytokine production.
Animals ; Asian Continental Ancestry Group ; Bronchoalveolar Lavage Fluid ; Cell Count ; Dust ; Enzyme-Linked Immunosorbent Assay ; Eosine Yellowish-(YS) ; Female ; Hematoxylin ; Humans ; Immunoglobulin E ; Immunoglobulins ; Inflammation ; Interferon-gamma ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Interleukins ; Lung ; Mice ; Mucins ; Ovalbumin ; Silicon Dioxide ; Transforming Growth Factor alpha