Drug-resistant temporal lobe epilepsy due to middle fossa meningoencephalocele in a child: A surgical case report.

BACKGROUND: Meningoencephalocele (ME) of the temporal lobe through a bone defect in the middle cranial fossa is a rare known cause of refractory temporal lobe epilepsy (TLE). ME-induced drug-resistant TLE has been described in adults; however, its incidence in children is very rare. CASE REPORT: A 7-year-old girl presented at our hospital with brief episodes of impaired consciousness and enuresis. Initial brain MRI results were interpreted as normal. Her seizures could not be controlled even with multiple anti-seizure medications. She was diagnosed with drug-resistant TLE, which presented with prolonged impaired awareness seizures for 30-60 s and secondary bilateral tonic seizures. At 9 years of age, brain MRI revealed a left temporal anteroinferior ME with a congenital bone defect in the left middle cranial fossa. She was referred for presurgical epilepsy evaluation. Long-term video electroencephalography (EEG) failed to reveal regional abnormality in the left temporal lobe; invasive evaluation using stereoelectroencephalography (SEEG) was thus indicated. Ictal onset SEEG was identified in the temporal pole near the ME which was rapidly propagated to the mesial temporal structures and other cortical regions. The left temporal pole including the ME was micro-surgically disconnected while preserving the hippocampus and amygdala. The patient's seizures have been completely controlled for 1 year and 6 months post-operatively. CONCLUSION: SEEG revealed rapid propagation of ictal activity in this patient's case, confirming that the ME was epileptogenic. Since the majority of patients with refractory epilepsy caused by ME have favorable postoperative seizure outcomes, it is important to carefully check for ME in drug-resistant TLE patients with apparently normal MRI.

Novel mutations of MVK gene in Japanese family members affected with hyperimmunoglobulinemia D and periodic fever syndrome.

Hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) is a recessively inherited recurrent fever syndrome. We describe a family of eldest son and monozygotic twin younger sisters with characteristic syndrome of HIDS, but normal level of IgD. Mevalonate kinase (MK) activity was deficient in all of them, and analysis of the MVK gene revealed compound heterozygosity for 2 new mutations, one of which was the disease-causing splicing mutation and the other was a novel missense mutation. All the patients had the same compound heterozygous mutations c.227-1 G > A and c.833 T > C, which resulted in exon 4 skipping and p.Val278Ala. This is the first case in which exon skipping mutation of the MVK gene has been certainly identified at the genomic DNA level. In each case, in which HIDS is clinically suspected, despite normal IgD level, analysis of MK activity and the MVK gene should be performed.

Glucocorticoids inhibit MUC5AC production induced by transforming growth factor-α in human respiratory cells.

BACKGROUND: Mucus hypersecretion from airway epithelium is a characteristic feature of severe asthma. Glucocorticoids (GCs) may suppress mucus production and diminish the harmful airway obstruction. We investigated the ability of GCs to suppress mRNA expression and protein synthesis of a gene encoding mucin, MUC5AC, induced by transforming growth factor (TGF)-α in human mucoepidermoid carcinoma (NCI-H292) cells and the molecular mechanisms underlying the suppression. METHODS: We determined if GCs such as dexamethasone (DEX), budesonide (BUD), and fluticasone (FP) could suppress MUC5AC production induced by a combination of TGF-α and double-strand RNA, polyinosinic-polycytidylic acid (polyI:C). MUC5AC mRNA expression and MUC5AC protein production were evaluated. The signaling pathways activated by TGF-α and their inhibition by GCs were tested using a phosphoprotein assay and MUC5AC promoter assay. RESULTS: DEX significantly suppressed the expression of MUC5AC mRNA and MUC5AC protein induced by TGF-α. The activation of the MUC5AC promoter by TGF-α was significantly inhibited by DEX. DEX did not affect activation of downstream pathways of the EGF receptor or mRNA stability of MUC5AC transcripts. DEX, BUD, and FP suppressed MUC5AC protein expression induced by a combination of TGF-α and polyI:C in a dose-dependent manner. CONCLUSIONS: GCs inhibited MUC5AC production induced by TGF-α alone or a combination of TGF-α and polyI:C; the repression may be mediated at the transcriptional but not post-transcriptional level.

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).

Relationship between exhaled nitric oxide and small airway lung function in normal and asthmatic children.

BACKGROUND: In children, exhaled nitric oxide (eNO) is usually confounded by factors such as age and height. We evaluated the relationship between eNO and lung function by minimizing the effects of aging and height. METHODS: In Study 1, the subjects comprised 738 elementary school children and junior high school children (aged 6 to 15 years, 366 males and 372 females). They were divided into two groups according to age (6-10 years and 11-15 years). A height range was determined by a histogram of height in each group. In Study 2, lung function, respiratory resistance and eNO level were measured in age- and height-limited groups. RESULTS: In Study 1, total of 148 younger children ranging in height from 120 to 130 cm and 180 older children ranging in height from 148 to 158 cm participated in Study 2. The level of eNO among asthmatic children was higher than that of normal children in both the younger and the older groups. The decrease in forced expiratory volume in 1 second (FEV(1)) and other parameters of central airway resistance did not correlate with the eNO level. However, the small airway parameters of MMEF and V(25)/HT in older asthmatic children, and V(25)/HT and R(5)-R(20) in younger asthmatic children inversely correlated with eNO. CONCLUSIONS: Our data suggest that eNO level inversely correlates with small airway narrowing, and airway inflammation has a significant effect on small airway lung function in asthmatic school children.

Changes in the highest frequency of breath sounds without wheezing during methacholine inhalation challenge in children.

BACKGROUND AND OBJECTIVE: It is difficult for clinicians to identify changes in breath sounds caused by bronchoconstriction when wheezing is not audible. A breath sound analyser can identify changes in the frequency of breath sounds caused by bronchoconstriction. The present study aimed to identify the changes in the frequency of breath sounds during bronchoconstriction and bronchodilatation using a breath sound analyser. METHODS: Thirty-six children (8.2 +/- 3.7 years; males : females, 22 : 14) underwent spirometry, methacholine inhalation challenge and breath sound analysis. Methacholine inhalation challenge was performed and baseline respiratory resistance, minimum dose of methacholine (bronchial sensitivity) and speed of bronchoconstriction in response to methacholine (Sm: bronchial reactivity) were calculated. The highest frequency of inspiratory breath sounds (HFI), the highest frequency of expiratory breath sounds (HFE) and the percentage change in HFI and HFE were determined. The HFI and HFE were compared before methacholine inhalation (pre-HFI and pre-HFE), when respiratory resistance reached double the baseline value (max HFI and max HFE), and after bronchodilator inhalation (post-HFI and post-HFE). RESULTS: Breath sounds increased during methacholine-induced bronchoconstriction. Max HFI was significantly greater than pre-HFI (P < 0.001), and decreased to the basal level after bronchodilator inhalation. Post-HFI was significantly lower than max HFI (P < 0.001). HFI and HFE were also significantly changed (P < 0.001). The percentage change in HFI showed a significant correlation with the speed of bronchoconstriction in response to methacholine (P = 0.007). CONCLUSIONS: Methacholine-induced bronchoconstriction significantly increased HFI, and the increase in HFI was correlated with bronchial reactivity.

Fatal interstitial pneumonia in juvenile dermatomyositis.

A 5-year-old girl presented with a two-month-history of skin rash and general fatigue. She had a slight fever, progressive muscle weakness and liver dysfunction. Gottron's papules on her fingers and purple-reddish papules on her elbows were noted. Serum aldolase levels were highly elevated, however, creatine phosphokinase levels were normal. An MRI revealed abnormal high signal changes in her gluteus minimus muscles. Interstitial pneumonia suddenly developed and she died despite aggressive treatment with methylprednisolone pulse therapy followed by intravenous administration of cyclophosphamide, immunoglobulin and cyclosporine A. Interstitial pneumonia is rare in juvenile dermatomyositis; however, as in adult cases, it can be fatal. In order to prevent severe complications and functional disabilities, early aggressive treatments should be considered when muscle inflammation is refractory to ordinary treatment.

Variant in the neuronal vesicular SNARE VAMP2 (synaptobrevin-2): First report in Japan.

BACKGROUND: A report presenting five heterozygous de novo variants in VAMP2 in unrelated individuals with a neurodevelopmental disorder characterized by axial hypotonia, intellectual disability, and autistic features was first published in April 4, 2019. CASE REPORT: We report the case of a male child with VAMP2 variant who was delivered at 38 weeks and 4 days without neonatal asphyxia. At 4 months of age he showed hypotonia and no visual pursuit and fixation. He presented with infantile spasms at 6 months, and electroencephalography (EEG) showed hypsarrhythmia. His infantile spasms completely disappeared by adrenocorticotropic hormone therapy, but his EEG findings continued to show high voltage slow-waves with multi-focal spikes. At 2 years of age he was non-verbal, had an absence of purposeful hand movements, and no visual fixation. He had somnolence tendency in the daytime. Biochemical and extensive genetic examinations were unrevealed. Magnetic resonance imaging showed slight brain atrophy. At 2 years and 7 months of age, he suffered from myoclonic seizures of the eyelid and tongue, which propagated to unilateral fingers, and sometimes to the bilateral legs. At 8 years of age hyperkinetic movement occurred. At age 13, whole-exome sequence identified a heterozygous missense variant, NM_014232.2:c.199G>C,[p.(Ala67Pro)] in exon 3 of VAMP2 which was a de novo non-synonymous variant. CONCLUSION: This is the first case report of VAMP2 variant in Japan. Hypotonia at early infancy, poor visual fixation, and absence of purposeful hand movements may be indicative of the diagnosis for VAMP2 variant.

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.

Effects of skin care with shower therapy on children with atopic dermatitis in elementary schools.

For elementary school children with atopic dermatitis, a skin care program using shower therapy was performed during the school lunch break for 6 weeks from June to July in 2004 and 2005. All 53 participants showed an improvement in their atopic dermatitis during the 6-week periods studied. Skin care with daily showering at an elementary school was thus found to be effective for the treatment of atopic dermatitis.

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.

Brainstem infarction associated with HHV-6 infection in an infant.

INTRODUCTION: The relevant literature includes several case reports on cerebral infarction in children with HHV-6 infection; however, there is no report of brain stem infarction. CASE: An 11-month-old girl was hospitalized because of fever. She was unable to stand up and meet her mother's gaze. Magnetic resonance imaging (MRI) indicated a right pons and mid-brain lesion; a diagnosis of brainstem infarction was made. After her fever subsided, a rash developed on her trunk and limbs; blood examination results indicated a primary HHV-6 infection. She was treated with aspirin, edaravone, and mannitol to prevent further complications. At the age of 18months, the auditory brainstem response (ABR) was unremarkable and she is developing well. DISCUSSION AND CONCLUSION: A limited number of studies have reported HHV-6 infection-associated infarction, and no cases of brainstem infarction have been reported. One possible cause of cerebral infarction is antiphospholipid antibody syndrome (APS) triggered by the infection. HHV-6 may also directly infect vascular endothelial cells and cause angiopathy. However, the real mechanism of infarction remains unclear. Our patient had a favorable prognosis despite brainstem infarction.

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.

Enteral Nutrition Related Complications Relevant to Alteration of Formulas in Two Critically Ill Pediatric Patients.

The early institution of enteral nutrition is associated with beneficial outcomes and intestinal growth in pediatric patients. However, the number, frequency, and types of unfavorable events occurring with particular formulas are undefined. We experienced unexpected complications in two cases following a change in formula. One case diagnosed with myotubular myopathy experienced highly-increased gastric residuals and watery diarrhea leading to decreased calorie intake and weight loss. The second case with campomelic dysplasia suffered liver dysfunction and fever. In both cases, symptoms developed soon after of the change in formula and improved after resumption of the previous formula. Both cases had undergone tracheostomy and artificial ventilation, and had a history of feeding the same formula for an extended period of time. In chronic care patients such as ours, a change in formula may cause unexpected adverse events; therefore, caution is warranted.

Relationship between bronchial hyperreactivity and asthma remission during adolescence.

BACKGROUND: Many children with asthma outgrow this disease after the onset of puberty. However, the precise mechanism of outgrowing asthma in children is still unclear. OBJECTIVE: To evaluate the characteristics of respiratory physiology during adolescence. METHODS: The results of the lung function test and methacholine inhalation challenge were prospectively evaluated in adolescent patients with asthma with and without symptoms. One hundred sixty children with asthma participated. Twenty-eight children had symptom-free adolescent asthma (i.e., remission asthma) (boy to girl ratio, 16:12; mean age, 14.6 years), 25 had intermittent adolescent asthma (boy to girl ratio, 16:9; mean age, 14.9 years), and 47 had symptomatic adolescent asthma (boy to girl ratio, 27:20; mean age, 12.7 years). For comparison purposes, 60 younger children with symptomatic asthma participated. The parameters of bronchial hyperresponsiveness, baseline respiratory resistance, threshold of methacholine (Dmin) (bronchial sensitivity), and speed of bronchial constriction (Sm) (bronchial reactivity) were measured by methacholine inhalation challenge using the continuous oscillation method. RESULTS: There was no significant difference in lung function results, such as forced vital capacity and forced expiratory volume in 1 second, between the intermittent asthma and the remission asthma groups. Also, there was no significant difference in baseline respiratory resistance and Dmin between the 2 groups. However, the value of Sm of the remission asthma group was significantly lower than that of the intermittent asthma group (P = .02) and the symptomatic asthma group (P = .02). CONCLUSIONS: These data show that the adolescents with asthma remission showed a significant decrease of Sm, whereas Dmin was not changed. These results suggest one of the mechanisms by which asthma is outgrown in children and explain the common clinical aspects of adolescent asthma, such as symptom-free but bronchial hyperresponsive asthma.

Effect of bronchoconstriction on exhaled nitric oxide levels in healthy and asthmatic children.

BACKGROUND: Exhaled nitric oxide (eNO) has recently been proposed to be a noninvasive marker of airway inflammation in asthma. OBJECTIVE: To evaluate the effect of bronchoconstriction by means of methacholine inhalation challenge on levels of eNO in children. METHODS: Spirometry, impulse oscillometry, and eNO measurements were performed before and after methacholine inhalation challenge (bronchoconstriction phase) and after beta2-agonist inhalation (bronchodilation phase) in 92 children (62 children with asthma, 13 wheezy children, and 17 healthy children). RESULTS: A significant decrease occurred in the eNO level after methacholine inhalation challenge (P < .01). This decrease did not correlate with the percentage decrease in forced expiratory volume in 1 second or with the change in large airway resistance (R20), but it did correlate with the percentage decline in maximal expiratory flow at 50% vital capacity and with the change in small airway resistance (R5-R20). The eNO decrease lasted for 15 minutes after beta2-agonist inhalation in the group with a high percentage decrease in R5-R20 (>200%). On the other hand, in the group with a low percentage decrease in R5-R20 (< or =200%), eNO recovered to the previous level immediately after beta2-agonist inhalation. CONCLUSIONS: The eNO level significantly decreases after methacholine inhalation challenge. This decrease primarily depends on bronchoconstriction of the small airways.

A flow- and pressure-controlled offline method of exhaled nitric oxide measurement in children.

BACKGROUND: Exhaled nitric oxide (eNO) is a noninvasive marker of airway inflammation. However, previous studies show that the offline value is lower than the online value. OBJECTIVE: To compare a standard offline eNO measurement apparatus with a modified apparatus that can monitor flow volume and respiratory pressure. METHODS: We studied 73 cooperative individuals aged 5 to 28 years (32 children: mean age, 8.3 years; 41 adults: mean age, 21.5 years). We modified the standard device by including a flow meter with a manometer and attaching a plastic tube connected to a 3-way valve to control the resistance. The online and offline (measured using the modified device and the standard device) eNO determinations were compared in a single session and were analyzed using a nitric oxide analyzer. RESULTS: There was a good relationship between the online and modified offline eNO measurements in children. The modified offline method showed a stronger correlation with the online method (r = .97 vs. r = .92), and the modified offline eNO value was more similar to the online eNO value than to the standard offline value. The mean difference between the online and standard offline eNO values was 52%, whereas the mean difference between the online and modified offline eNO values was only 10%. CONCLUSIONS: Using the offline method, we can easily control the resistance and flow volume to reach the same value measured by the online method in childhood respiratory diseases.

Early-life risk factors for occurrence of atopic dermatitis during the first year.

OBJECTIVE: In a prospective birth cohort study, we sought to identify perinatal predictors of the occurrence of atopic dermatitis in the first year of life. METHODS: Associations of family history, infection during pregnancy, cord blood cytokine concentrations, and skin function parameters with atopic dermatitis were analyzed. Stratum corneum hydration was measured with an impedance meter until 5 days after delivery and again at 1 month. RESULTS: Complete data were obtained for 213 infants, including 27 diagnosed by a physician as having atopic dermatitis during their first year and 26 diagnosed as having infantile eczema during their first month. The risk of atopic dermatitis during the first year of life was related to maternal atopic dermatitis, lower concentrations of macrophage inflammatory protein-1beta in cord blood, and greater skin moisture in the surface and stratum corneum of the forehead and cheek at 1 month of age but not to viral or bacterial infection during pregnancy or breastfeeding. Paternal hay fever was associated negatively with the development of atopic dermatitis. High concentrations of interleukin-5, interleukin-17, and macrophage chemotactic protein-1 and only surface moisture in the cheek were associated with greater risk of infantile eczema in the first month. CONCLUSIONS: The association of atopic dermatitis in infancy with reduced neonatal macrophage inflammatory protein-1beta levels suggests a link with immature immune responses at birth. Stratum corneum barrier disruption in atopic dermatitis may involve impairment of cutaneous adaptation to extrauterine life. The majority of risk factors had different effects on infant eczema and atopic dermatitis, indicating different causes.

Effect of aging on the relationship between asthma severity and bronchial hyperresponsiveness in children with asthma.

An association between asthma and bronchial hyperresponsiveness (BHR) has been demonstrated. It is possible that the relationship between asthma severity and BHR in children with asthma is different in infants and in adolescents. The aim of this study is therefore to evaluate the effect of aging on the relationship between the severity of asthma and BHR in children with asthma. We measured BHR in 386 subjects ranging from 2 to 20 years of age. The subjects consisted of 323 children with asthma (boys:girls = 193:130, mean age 9.7 years) and 63 age-matched controls (boys:girls = 25:38, mean age 8.2 years). BHR was measured using the methacholine inhalation challenge by measuring the transcutaneous oxygen pressure (tcPO2) in children less than 6 years of age (Dmin-PO2) and by measuring the respiratory resistance (Rrs) in children 6 years of age and older (Dmin-Rrs). Throughout the whole age range, both the Dmin-PO2 and Dmin-Rrs in each asthma severity group were higher than those in the controls. In the asthmatics aged 2-5 years, the Dmin-PO2 levels in the mild asthma group were higher than those in the moderate and severe asthma groups (p < 0.001, p < 0.001, respectively), and the Dmin-PO2 levels in the moderate asthma group were also higher than those in the severe asthma group. This tendency was also found in the age ranges of 6-9 years and 10-13 years. In the asthmatics aged 14-20 years, the Dmin-Rrs levels were not significantly different among the three groups. Taken together, these data show that aging has an effect on the relationship between the severity of asthma and BHR during childhood and that BHR may not be the sole determinant for the severity of asthma in adolescence.

Effect of disodium cromoglycate on airway mucus secretion during antigen-induced late asthmatic responses in a murine model of asthma.

BACKGROUND: Disodium cromoglycate (DSCG) is known to inhibit both immediate and late asthmatic responses (IAR and LAR). However, its effect on mucus hypersecretion is unknown. Using a murine model of asthma, we aimed to determine whether mucus secretion increased during IAR and LAR. We also studied the potency of DSCG in inhibiting mucus secretion and on airway eosinophilia. METHODS: Mice were subjected to initial intraperitoneal sensitization and airway challenge to ovalbumin (OVA) and then provoked by additional exposure to OVA. Some mice were pretreated with aerosolized DSCG (20 mg/ml) 1 h before the provocation with OVA. After serial measurements of enhanced pause (Penh), an indicator of airflow obstruction, serum samples and bronchoalveolar lavage fluids (BALF) were collected. Then, the lungs were excised and a morphometric analysis for mucus hypersecretion was performed. RESULTS: A biphasic increase in Penh (IAR and LAR) was observed in sensitized animals after provocation with OVA. Airway eosinophilia was observed during both responses. Intraluminal mucus significantly increased during LAR, but not during IAR. DSCG significantly attenuated both IAR and LAR, and significantly inhibited the increase in intraluminal mucus during LAR, but had no effect on eosinophilia in BALF. CONCLUSION: Our results suggest that airway hypersecretion may be involved as a component of airflow obstruction during LAR, and that this is unlikely during IAR. DSCG may be effective in reducing excessive airway mucus caused by exposure to allergens.