[A CASE OF VOCAL CORD DYSFUNCTION, WHO USED ADRENALIN AUTOINJECTOR (EPIPEN®) FREQUENTLY AFTER BEING DIAGNOSED AS ANAPHYLAXIS].

We experienced a case of vocal cord dysfunction (VCD) in a child to whom an adrenaline autoinjector (Epipen®) had been prescribed and frequently used following a diagnosis of exercise-induced anaphylaxis. An exercise test was performed to investigate her frequent episodes of anaphylaxis-like symptoms. A few minutes after starting the test, signs of dyspnea, such as throat tightness and stridor, appeared, although hypoxia was not present and her respiratory sounds were normal. Medications were not effective for treating her respiratory symptoms. Laryngoscopy performed at the test revealed bizarre vocal cord movement, which was diagnosed as VCD. The symptoms gradually diminished after the initiation of biofeedback therapy, including pursed lips breathing and abdominal breathing. Thereafter, she did not use an adrenaline autoinjector when symptoms appeared; instead, she would perform biofeedback therapy before using the adrenaline autoinjector. Thus, VCD should be included in the differential diagnosis of patients who show anaphylactic symptoms that are resistant to preventive therapy.

[A PEDIATRIC CASE OF DIFFUSE PANBRONCHIOLITIS WHO PREDOMINANTLY SHOWED RESTRICTIVE PULMONARY DYSFUNCTION AND DRAMATICALLY RESPONDED TO MACROLIDE LOW-DOSE LONG-TERM THERAPY.]

A 12-year-old boy visited our hospital with complaints of chronic cough and dyspnea. Chest X-ray and CT revealed diffuse granular shadow in the bilateral lung fields and "Tree-in-bud appearance" in the peripheral airways, respectively. Sinusitis was present, and restrictive disorder was predominantly found in pulmonary function. The patient was diagnosed with DPB, and long-term therapy was started with low-dose clarithromycin (CAM), The patient showed a dramatic response to CAM, with improvements of both the clinical symptoms and pulmonary function within 1-2 months. According to the relevant literature, in adult patients with this disease, pulmonary dysfunction starts from an obstructive pattern; however, this is not the case in pediatric patients. It was therefore suggested that the mechanisms underlying the development of pulmonary dysfunction in cases of childhood onset differs from those with an adult onset.

Airway reversibility and inflammation in stable pre- to late-adolescent asthmatics without long-term control medications.

Objective: Pulmonary function and airway inflammation were investigated in stable pre- to late-adolescent asthmatics without long-term control medications and compared with those in currently medicated asthmatics.Methods: Subjects comprised 34 well-controlled asthmatic children (aged 8.1-18.0 years; group without medication). Flow volume curves before and after inhaling a ß2 agonist, a bronchodilator (BD), were compared and fractional exhaled nitric oxide (FENO) concentrations were measured. All patients were attack-free for at least 12 months prior to testing without the use of asthma medications for at least three months. Fifty-one age-matched stable asthmatics with medications at the time of the present study (group with current medication) underwent the same examinations.Results: The rate of children whose respiratory function after BD improved by 20% or more in both the central and peripheral airways (High responder at total airways subtype: HTA) was significantly higher in the group without medication than in that with current medication (17.6 and 2.0%, respectively; p < 0.01). Furthermore, FEV1.0% pred after BD was significantly lower for HTA than for the low responder subtype in the same group (94.8 ± 3.5 and 104.1 ± 1.5% respectively, p < 0.05). FENO concentrations in the group without medication were high, but not significantly different from those in the group with current medication.Conclusions: Stable asthmatic children without medication include a certain percentage of those with irreversible airflow limitation possibly due to airway remodeling. The control of daily asthma symptoms with long-term control medications may effectively prevent airway remodeling.

Dermatophagoides farinae Upregulates the Effector Functions of Eosinophils through αMß2-Integrin and Protease-Activated Receptor-2.

BACKGROUND: Even in subjects who are not sensitized to house dust mite (HDM), allergic symptoms can be aggravated by exposure to dust, suggesting that innate immune responses may be involved in these processes. Since eosinophils express pattern recognition receptors, HDM may directly upregulate eosinophil functions through these re ceptors. The objective of this study was to examine whether Dermatophagoides farinae (Df), a representative HDM, or Der f 1, a major allergen of Df, modifies the effector functions of eosinophils. METHODS: Eosinophils isolated from the blood of healthy donors or allergic patients were stimulated with Df extract or Der f 1, and their adhesion to recombinant human intercellular adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. Generation of the eosinophil superoxide anion (O2-) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) concentrations in cell media were measured by ELISA as a marker of degranulation. RESULTS: Df extract or Der f 1 directly induced eosinophil adhesion to ICAM-1, O2- generation, and EDN release. Anti-αM- or anti-ß2-integrin antibodies or protease-activated receptor (PAR)-2 antagonists suppressed the eosinophil adhesion, O2- generation, and EDN release induced by Df extract or Der f 1. Eosinophils from allergic patients showed higher adhesion to ICAM-1 than those from healthy donors. CONCLUSIONS: These findings suggested that Df extract and Der f 1 directly activate eosinophil functions through αMß2-integrin and PAR-2. Eosinophil activation by HDM may play roles in the aggravation of allergic symptoms, not only in HDM-sensitized patients, but also in nonsensitized patients.

Definition, classification and differential diagnosis of childhood asthma.

The pathophysiology of childhood asthma has not been clarified compared to that of adults. Airway remodeling has been demonstrated even in younger children. On the other hand, high incidence of remission compared to that in adults has been shown, suggesting a het- erogeneity of childhood asthma. The diagnosis of childhood asthma is difficult because air- ways of younger children is easy to close, causing wheezing. Thus, differential diagnosis is important. The phenotypes of asthma in younger children is mainly classified into mild episodic viral wheeze and multiple-trigger atopic wheeze.

Usefulness of modified Pulmonary Index Score (mPIS) as a quantitative tool for the evaluation of severe acute exacerbation in asthmatic children.

BACKGROUND: Acute exacerbation of asthma is divided qualitatively into mild, moderate, and severe attacks and respiratory failure. This system is, however, not suitable for estimating small changes in respiratory condition with time and for determining the efficacy of treatments, because it has a qualitative, but not quantitative nature. METHODS: To evaluate the usefulness of quantitative estimation of asthma exacerbation, modified Pulmonary Index Score (mPIS) values were measured in 87 asthmatic children (mean age, 5.0 ± 0.4 years) during hospitalization. mPIS was calculated by adding the sum of scores for 6 items (scores of 0-3 were given for each item). These consisted of heart rate, respiratory rate, accessory muscle use, inspiratory-to-expiratory flow ratio, degree of wheezing, and oxygen saturation in room air. Measurements were made at visits and at hospitalization and were then made twice a day until discharge. RESULTS: mPIS values were highly correlated among raters. mPIS values at visits were 9.1 ± 0.1 and 12.6 ± 0.4 in subjects with moderate and severe attacks, respectively (p < 0.001). mPIS values of subjects requiring continuous inhalation therapy (CIT) with isoproterenol in addition to systemic steroids were significantly higher than the values of those without CIT (12.0 ± 0.5 and 9.3 ± 0.2, respectively, p < 0.001). A score of 10 was suggested to be the optimal cutoff for distinguishing between subjects requiring and not requiring CIT, from the perspectives of both sensitivity and specificity. mPIS at hospitalization correlated well with the period until discharge, suggesting that this score was a useful predictor for the clinical course after hospitalization. CONCLUSIONS: mPIS could be a useful tool for several aspects during acute asthma attacks, including the determination of a treatment plan, and prediction of the period of hospitalization in admitted patients, although prospective studies would be required to establish our hypothesis.

Japanese pediatric guideline for the treatment and management of bronchial asthma 2012.

A new version of the Japanese pediatric guideline for the treatment and management of bronchial asthma was published in Japanese at the end of 2011. The guideline sets the pragmatic goal for clinicians treating childhood asthma as maintaining a "well-controlled level" for an extended period in which the child patient can lead a trouble-free daily life, not forgetting the ultimate goal of obtaining remission and/or cure. Important factors in the attainment of the pragmatic goal are: (i) appropriate use of anti-inflammatory drugs; (ii) elimination of environmental risk factors; and (iii) educational and enlightening activities for the patient and caregivers regarding adequate asthma management in daily life. The well-controlled level refers to a symptom-free state in which no transient coughs, wheezing, dyspnea or other symptoms associated with bronchial asthma are present, even for a short period of time. As was the case in the previous versions of the guideline, asthmatic children younger than 2 years of age are defined as infantile asthma patients. Special attention is paid to these patients in the new guideline: they often have rapid exacerbation and easily present chronic asthmatic conditions after the disease is established.

Ablation of Mina53 in mice reduces allergic response in the airways.

The mina53 (myc-induced nuclear antigen with a 53 kDa molecular mass; also known as mina) was identified as a direct transcriptional target of the oncoprotein Myc and encodes a conserved protein in vertebrates. While Mina53 is known to be associated with tumorigenesis, it is not clear what role Mina53 plays in non-neoplastic tissues. To directly address the roles of Mina53 in non-neoplastic tissues, we created mina53-deficient mice. Both male and female mina53-deficient mice reached adulthood and were fertile, suggesting that Mina53 is dispensable for the basic developmental processes. Since we found that Mina53 was expressed in cells responsible for immune responses, we investigated whether Mina53 was involved in immune responses. When mice were exposed intranasally to house dust mites as an allergen, the airway tract showed hyperresponsiveness to methacholine in wild-type mice but not in mina53-deficient mice. The mina53-deficient mice also showed a significantly reduced migration of immune cells, including eosinophils, into bronchoalveolar lavage fluid compared with wild-type mice. The levels of Th2 cytokines, IL-4 and IL-5, produced in response to house dust mites were lower in the mina53-deficient mice than in wild-type mice. The level of IFN-γ in bronchoalveolar lavage fluid was significantly decreased by exposure to house dust mites in wild-type mice but not in the mina53-deficient mice. These results suggest that Mina53 plays a role in the allergic response to inhaled allergens, possibly through controlling IL-4 production.

[Prevalence of allergic rhinitis among asthmatic patients in two different seasons].

INTRODUCTION: Allergic rhinitis and asthma are often comorbid, and allergic rhinitis has been shown to be a risk factor for asthma in adults and children. Recently, the prevalence of allergic rhinitis among bronchial asthma (BA) patients was reported to be 67.3% in Japan. However, seasonal variation in the prevalence of rhinitis in Japan remains unclear. OBJECTIVES AND METHODS: To investigate the seasonal differences in comorbid allergic rhinitis among asthmatic patients, a survey of BA outpatients aged six years and older was conducted at the Allergy Center, Saitama Medical University. In total, 150 patients (mean age, 43.8±21.8 years old) in summer 2012 and 181 patients (mean age, 48.7±18.3 years old) in spring 2013 completed the Self Assessment of Allergic Rhinitis and Asthma (SACRA) questionnaire. RESULTS: The prevalence of allergic rhinitis in BA patients was 50% in the summer of 2012 and 85.6% in the spring of 2013, indicating a significant seasonal variation. Control of asthma was significantly poorer in both seasons in patients with rhinitis compared to those without rhinitis. Furthermore, in patients with moderate/severe-persistent rhinitis, control of asthma was significantly worse than in patients with mild-intermittent rhinitis in spring 2013, but not in summer 2012. CONCLUSION: Although the comorbidity rate of rhinitis among BA patients was greater in the spring than in the summer, rhinitis is thought to be closely related with asthma control regardless of the season.

Surveillance of pollen-food allergy syndrome in elementary and junior high school children in Saitama, Japan.

BACKGROUND: Because few studies have epidemiologically evaluated pollen-food allergy syndrome (PFAS), relevant information about this disease is limited in children. OBJECTIVE: We wanted to clarify the epidemiological details of PFAS by creating a questionnaire which enables to distinguish class 2 food allergy from that of class 1. METHODS: We conducted a questionnaire survey for schoolchildren attending to public elementary and junior high schools. In this questionnaire, we asked about both the allergy to fruits and/or vegetables and allergic rhinitis (AR). PFAS was, then, defined as allergy for fruits and/or vegetable which occurred after the symptoms of AR appeared. RESULTS: A total of 2,346 children (median age, 10.6±2.5 years; 1,157 boys) were evaluated. The prevalence of PFAS was 6.9% among subjects. The mean ages in the onset of AR and PFAS were 4.59±2.76 and 7.38±3.17 years old, respectively. Various kinds of foods were shown to be causative, among which kiwifruits were the commonest. As high as approximately 30% of children with PFAS experienced systemic symptoms including cutaneous (21.8%) and respiratory symptoms (9.6%). Anaphylaxis was diagnosed in 5.8% children. CONCLUSION: Our results indicated that the prevalence of PFAS was getting higher and the mean age of onset was getting lower. These may be attributed to the increasing number of patients with AR and also to the lower age of onset of AR. We have to be careful to not only local but also systemic symptoms when examining children with PFAS.

Lack of transient receptor potential vanilloid-1 enhances Th2-biased immune response of the airways in mice receiving intranasal, but not intraperitoneal, sensitization.

BACKGROUND: Transient receptor potential vanilloid-1 (TRPV1) may modulate allergic airway inflammation because it is expressed not only on the nerve endings but also on several cells of the immune system. We wanted to know the characteristics of airway and systemic responses against sensitization and challenge with allergens in TRPV1 receptor gene knockout mice (TRPV1(-/-)). METHODS: TRPV1(-/-) and their wild-type counterparts (TRPV1(+/+)) were sensitized with either house dust mite (HDM) or ovalbumin (OVA) via intranasal (i.n.) or intraperitoneal (i.p.) route before the final i.n. challenge with the corresponding allergen. One day after the final challenge, serum IgE levels, cytokine levels in the bronchoalveolar lavage fluid (BALF), and the number of BALF cells were examined after measuring bronchial hyperresponsiveness against methacholine. RESULTS: Compared to TRPV1(+/+), TRPV1(-/-) showed enhanced Th2-biased response after i.n. HDM or OVA sensitization, including increased levels of serum IgE, interleukin 4 (IL-4) and eosinophils in the BALF. By contrast, when sensitized via i.p. route, the response against OVA or HDM was almost similar between TRPV1(+/+) and TRPV1(-/-). CONCLUSION: TRPV1 receptor may downregulate Th2-biased immune response when sensitized via airways, although this was not the case when sensitized systemically.

Double-stranded RNA and TGF-alpha promote MUC5AC induction in respiratory cells.

Viral infection is a major trigger for exacerbation of asthma and induces overproduction of mucins. We investigated whether dsRNA could amplify the induction of mucin by TGF-alpha in human bronchial epithelial cells, as well as the molecular mechanisms regulating MUC5AC expression. Human pulmonary mucoepidermoid carcinoma (NCI-H292) cells and normal human bronchial epithelial cells were exposed to polyinosinic-cytidyric acid (poly(I:C)) and TGF-alpha. Then, MUC5AC protein production, mRNA expression, and promoter activity were evaluated. Cells were pretreated with a selective inhibitor of ERK, and phosphorylation of ERK was examined by Western blotting. Furthermore, the expression of MAPK phosphatase 3 (MKP3) mRNA was evaluated and the effect of MKP3 overexpression was assessed. Poly(I:C) synergistically increased MUC5AC induction by TGF-alpha in both NCI-H292 and normal human bronchial epithelial cells. This increase was dependent on MUC5AC gene transcription. A MEK1/2 inhibitor (U0126) significantly inhibited MUC5AC production. Phosphorylation of ERK was enhanced by poly(I:C). TGF-alpha stimulation up-regulated MKP3 mRNA expression, while costimulation with poly(I:C) inhibited this up-regulation dose-dependently. Enhanced expression of MUC5AC mRNA by poly(I:C) in wild-type cells was completely suppressed in cells transfected with the MKP3 expression vector. dsRNA can synergistically amplify the induction of MUC5AC mucin by TGF-alpha. This synergistic effect on MUC5AC production may be due to enhanced activation of ERK through inhibition of MKP3 by poly(I:C).

Japanese pediatric guidelines for the treatment and management of bronchial asthma 2008.

Abstract The fourth version of the Japanese Pediatric Guidelines for the Treatment and Management of Bronchial Asthma 2008 (JPGL 2008) was published by the Japanese Society of Pediatric Allergy and Clinical Immunology in December 2008. In JPGL 2008, the recommendations were revised on the basis of the JPGL 2005. The JPGL 2008 is different to the Global Initiative for Asthma guideline in that it contains the following items: a classification system of asthma severity; recommendations for long-term management organized by age; a special mention of infantile asthma; and an emphasis on prevention and early intervention. Here we show a summary of the JPGL 2008 revising our previous report concerning JPGL 2005.

Effects of ß2-adrenergic agonists on house dust mite-induced adhesion, superoxide anion generation, and degranulation of human eosinophils.

BACKGROUND: Even in subjects who are not sensitized to house dust mite (HDM), allergic symptoms can be clinically aggravated by exposure to dust. We previously reported that Dermatophagoides farinae (Df), an important HDM, or Der f 1, a major allergen of Df, induced the effector functions of eosinophils, which may be an important mechanism for HDM-induced symptoms in nonsensitized patients. In a clinical setting, ß2-adrenergic agonists, such as salbutamol and formoterol, are used for the treatment of asthma attacks or exacerbation to release the airway obstruction. Several reports have suggested that some ß2-adrenergic agonists have an anti-inflammatory capacity. OBJECTIVE: In this study, we investigated whether ß2-adrenergic agonist could modify the Df- or Der f 1-induced activation of eosinophils. METHODS: Blood eosinophils obtained from healthy donors were preincubated with either formoterol (1 µM), salbutamol (1 µM), or buffer control and then stimulated with Df extract (1 µg/mL) or Der f 1 (100 pg/mL). Eosinophil adhesion to intercellular adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. Generation of superoxide anion (O2 -) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) concentrations in cell media were measured by enzyme-linked immunosorbent assay. RESULTS: Formoterol, but not salbutamol, suppressed the Df- or Der f 1-induced eosinophil adhesion to ICAM-1. Furthermore, formoterol, but not salbutamol, suppressed Df-induced O2 - generation or EDN release. Neither formoterol nor salbutamol suppressed spontaneous eosinophil adhesion, O2 - generation, or EDN release. CONCLUSION: These findings suggested that formoterol, but not salbutamol, suppressed Df- or Der f 1-induced eosinophil activation when used at the same concentration. Therefore, formoterol could potentially be used for the treatment of bronchial asthma via both bronchodilation and anti-inflammatory effect.

Association of cord blood cytokine levels with wheezy infants in the first year of life.

As antenatal environment may influence the development of atopy-predisposing immune response, cord blood cytokine productions may be an important predictor for wheezing. We investigated cord blood cytokines in a prospective birth cohort, intensively monitored for wheezy infant outcome at 1 yr. Cord blood serum samples from 269 children were assayed for interleukin (IL)-1beta, -2, -4 to -8, -10, -12 (p70), -13, and -17, interferon-gamma, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein-1, and macrophage inflammatory protein-1beta. Associations between family histories, antenatal and perinatal factors, cord blood cytokine concentrations, and wheezy infant outcomes (wheezing more than two times) were analyzed. In cord blood sera from 269 children, there were associations between high levels of IL-6, -8 and G-CSF concentrations, and cesarean section. Data at 1 yr were obtained from 213 infants, including 33 wheezy infants. Risk of wheezing was related to gestational age, birth weight, cesarean section, and maternal eczema, but not to bacterial/viral infection during pregnancy, maternal asthma, maternal smoking, or paternal history. High level of cord blood IL-8 concentration had a significant association with wheezy infant outcomes at 1 yr (p = 0.025). By using multivariate logistic regression analysis, birth weight [odds ratio(OR) = 0.998, 95% confidence interval (CI) = 0.997-1.000] and maternal eczema (OR = 5.356, 95% CI = 1.340-21.41), but no other factors, were significant predictors of wheezy infants. Birth weight, gestational age, and maternal history were important risk factors for wheezing in the first year of life. Several cord blood cytokine productions were influenced by cesarean section, and IL-8 may be a predictor for recurrent wheezing at 1 yr.

Differential regulation of eotaxin expression by dexamethasone in normal human lung fibroblasts.

Lung fibroblasts are a major source of several cytokines including CC chemokine eotaxin. We aimed to study the regulation of eotaxin-1/CCL11 production by dexamethasone and analyze its molecular mechanisms in human lung fibroblasts. Normal human lung fibroblast cells were exposed to IL-4 (40 ng/ml) and/or dexamethasone (10(-6)-10(-9) M), and eotaxin mRNA expression and production was evaluated. Mechanisms of transcriptional regulation were assessed by Western blotting and dual luciferase assay for eotaxin promoter. The effects of dexamethasone on suppressor of cytokine signaling (SOCS)-1 and eotaxin mRNA expression in the cells transfected with expression vector (pAcGFP1-C1) or short interfering RNA (siRNA) for SOCS-1 were also investigated. Within 24 hours, dexamethasone inhibited IL-4-induced eotaxin mRNA expression and protein production, while eotaxin production was markedly increased at 48 and 72 hours after coincubation with IL-4 and dexamethasone. IL-4-induced eotaxin promoter activity was inhibited by dexamethasone at 8 hours, but enhanced at 48 hours after coincubation. Dexamethasone suppressed SOCS-1 mRNA expression but enhanced IL-4-induced STAT6 phosphorylation at 36 to 48 hours after coincubation. Enhanced expression of eotaxin mRNA by dexamethasone 48 hours after coincubation was completely diminished in the cells transfected with either expression vector or siRNA for SOCS-1. These results indicated that dexamethasone, depending on the exposure duration, can either inhibit or enhance IL-4-induced expression and production of eotaxin in the lung fibroblasts. The mechanisms of later enhanced production may depend on the prolonged transcriptional activity of the eotaxin gene, in part due to inhibition of SOCS-1 expression.

Age-related difference in the persistency of allergic airway inflammation and bronchial hyperresponsiveness in a murine model of asthma.

AIM: Asthmatic children are more likely to outgrow their symptoms than adult patients. Thus, we wanted to know whether there were any age-related differences in the time course of the allergic airway inflammation. METHODS: BALB/C mice at different ages (young: 3 days after birth, and mature: 8 weeks of age) were sensitized with ovalbumin (OVA). Subsequently, animals were challenged with aerosolized OVA during 1, 2, 4 or 8 consecutive weeks. Bronchial hyperresponsiveness (BHR), serum IgE levels, the degrees of inflammatory cell infiltration (ICI) and goblet cell metaplasia (GCM) in the airways, and the number of eosinophils and cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. RESULTS: At 1 week, airway inflammation and BHR occurred similarly between young and mature mice. However, BHR disappeared at 4 weeks in young, whereas it persisted even at 8 weeks in mature mice. GCM, ICI and eosinophilia in BALF attenuated with time, with more remarkable reduction in young mice. The BALF IL-4 level was high during the first 2 weeks in both groups, while the IL-2 level was significantly increased at 2 weeks solely in young mice. CONCLUSION: Different time courses in airway inflammation and in BHR may relate to the different prognoses between childhood and adult asthma. The understanding of the mechanisms underlying this age-related differences may be helpful to induce remission in asthmatic patients.

Bronchial sensitivity and bronchial reactivity in children with cough variant asthma.

BACKGROUND: Cough variant asthma (CVA) is diagnosed in some children with chronic cough who do not have wheezing. However, the precise mechanism of CVA in children is unclear. OBJECTIVE: To evaluate the physiologic differences in the airways of children with classic asthma and CVA, the methacholine dose-response curves of respiratory resistance (Rrs) were studied. PATIENTS AND METHODS: CVA was diagnosed in 31 children with chronic cough (age range, 5 to 14 years; 19 boys and 12 girls; mean age, 8.5 years) on the basis of methacholine inhalation challenge using an oscillation method. For comparison, the study included 86 age-matched children with classic asthma (age range, 5 to 15 years; 42 boys and 44 girls; mean age, 9.5 years), 25 age-matched children with cough (age range, 5 to 15 years; 17 boys and 8 girls; mean age, 8.8 years), and 23 age-matched control subjects (8 boys and 15 girls; mean age, 9.2 years). Consecutive doses of methacholine were doubled until a 200% increase in Rrs from baseline was reached. The cumulative dose of methacholine at the inflection point of Rrs was considered to represent the bronchial sensitivity to inhaled methacholine (minimum dose of methacholine [Dmin]). The slope of the methacholine dose-response curve (SRrs), which was considered to represent bronchial reactivity, was measured from the increasing Rrs curve. RESULTS: The values of Dmin in classic asthma patients and in CVA patients were significantly lower than those for cough patients and control subjects. There was no significant difference in the values of Dmin between the classic asthma and CVA patients. The value of SRrs in CVA patients was significantly lower than that in classic asthma patients, cough patients, and control subjects (p < 0.05, p < 0.01, and p < 0.01, respectively). There was no significant difference in the value of SRrs between classic asthma patients, cough patients, and control subjects. CONCLUSIONS: These data show that bronchial reactivity in the children with CVA was significantly lower than that in the children with classic asthma, and this specificity has an effect on prolonged cough without wheezing in children with CVA.

Immunoadsorption therapy for a child with Guillain-Barre syndrome subsequent to Mycoplasma infection: a case study.

We report an 11-year-old boy with apparently the motor axonal form of Guillain-Barre syndrome (GBS) who presented with severe paralysis and respiratory insufficiency by the 3rd day from onsets of symptoms. His serum anti-Mycoplasma pneumoniae and anti-Galactocerebroside (Gal-C) IgM antibody were significantly elevated. Magnetic resonance imaging, following contrast injection, showed enhancement of the cauda equina. The patient responded quickly and dramatically to immunoadsorption therapy using a tryptophan-immobilized column, with recovery of respiratory failure and muscle strength, dominantly in the left extremities. Immunoadsorption therapy should be considered for patients with anti Gal-C antibody-associated GBS.