Single photon emission computerized tomography in childhood hydrocephalus

Single photon emission computerized tomography (SPECT) is now widely used as one of the tools in evaluating cerebral blood flow (CBF). The authors report the CBF changes in childhood hydrocephalus. Five pediatric cases studied by ¹²³I-IM SPECT in children are presented. The authors counted radioactivities both in early and delayed images in each patient, and calculated the reabsorption ratio (RR). Two negative-RR cases and three positive-RR cases were found. All of the negative-RR patients had a poor prognosis, while all of the positive-RR patients had a favorable outcome.     

Methotrexate therapy of oral corticosteroid-dependent asthmatics reduces serum immunoglobulins: correlation with clinical response to therapy

BACKGROUND: Concomitant methotrexate (MTX) therapy of oral corticosteroid (CS)-dependent asthmatics has been shown to spare CS therapy, but the mechanism is unknown. In a previous report, we showed that MTX increases T cell inhibition by CS. In this report we focus on effects of MTX on immunoglobulin concentrations and their possible clinical relevance. OBJECTIVE: To monitor changes in circulating leucocytes and Ig in a group of these patients during MTX therapy, and to relate these changes to clinical 'response' as defined by oral CS reduction. METHODS: Sixteen severe asthmatics dependent on oral prednisolone 15 (7.5-25) mg/day in addition to high dose inhaled CS were treated with MTX 15 mg intramuscularly, weekly for 28 weeks. Prednisolone dosages were maintained constant for 12 weeks then reduced systematically over the next 16 weeks provided that asthma control did not deteriorate. Patients were classified a priori as 'responders' or 'non-responders' to MTX (reduction of initial oral prednisolone requirement by >or=50% or <50%, respectively). Patients were followed-up for a further 12 weeks after MTX withdrawal. Serum Ig and differential blood leucocyte counts were measured at baseline, 12, 28 and 40 weeks. RESULTS: MTX therapy allowed significant, but individually variable, reductions in oral prednisolone dosages (P<0.00001) without alteration of lung function or symptoms. This was associated with significant reductions in mean serum concentrations of Ig of all classes, which reversed following MTX withdrawal. Reductions in IgE and IgG were significantly greater in the MTX 'responders' as compared with 'non-responders', and changes in IgE, IgG and IgM correlated with changes in prednisolone requirements. Differential blood leucocyte counts showed no significant variation. CONCLUSION: MTX therapy reduced oral CS requirements in these severe asthmatics to a degree which correlated with reduced circulating Ig but not lymphopaenia, suggesting a possible cause and effect relationship. These reductions might also contribute to the documented incidence of opportunistic infection in these circumstances.     

Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study

Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6-12 yr) with mild-to-moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild-to-moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies.     

Polymorphisms in manganese superoxide dismutase and catalase genes: functional study in Hong Kong Chinese asthma patients

BACKGROUND: Reactive oxygen species may contribute to the pathogenesis of asthma. Functional genetic polymorphisms of antioxidant enzymes, superoxide dismutase (SOD) and catalase are good candidates for asthma susceptibility. OBJECTIVE: To investigate the association of the manganese-containing form of SOD (MnSOD) gene at amino acid position 16 (Val16Ala) and catalase gene in the promoter at A-21T and C-262T polymorphisms and asthma in a Hong Kong Chinese population. METHODS: The association study was conducted in a case-control design in asthma patients (n=251) and healthy controls (n=316) by genotyping. The functional significance was assessed by determining erythrocyte SOD and catalase activity. RESULTS: The Val allele of MnSOD at Val16Ala and the A allele of catalase gene at A-21T were not different between patients and controls, while the C allele of catalase gene at C-262T was found to be significantly different between patients and controls (P=0.033). The less frequent variant of catalase gene (-262T) was found to be protective from the development of asthma in a Hong Kong Chinese non-smoking population (adjusted odds ratio=0.35, 0.15-0.85; P=0.017). Asthma patients had elevated erythrocyte SOD and catalase activities in comparison with healthy controls (P<0.01). However, their activities were not associated with different genotypes within healthy controls or asthma patients. CONCLUSION: This is the first report showing that SOD and catalase functional activities are not associated with their respective genetic polymorphisms but related to the presence of asthma in a Hong Kong Chinese population.     

TLR4 Asp299Gly、Thr399Ile基因多态性对变应性哮喘的发病及IgE水平的影响

目的　探讨TLR4 (toll likereceptor 4 )Asp2 99Gly、Thr399Ile基因多态性对变应性哮喘的发病和血浆IgE水平的影响。方法　利用聚合酶链反应 限制性片段长度多态性分析技术 (PCR RFLP) ,对 1 97例变应性哮喘患者和 1 5 6例健康人进行TLR4的Asp2 99Gly、Thr399Ile两位点的基因型检测。同时利用免疫发光法检测血浆IgE的水平。结果　 1 97例变应性哮喘患者TLR4基因Asp2 99Gly位点Asp Asp、Asp Gly和Gly Gly的基因型频率为 0 .81 7、0 .1 4 7和 0 .0 36 ,与正常对照组相比差异无统计学意义 (χ2 =0 .0 32 ,P =0 .984 ) ;但变应性哮喘患者Gly Gly、Asp Gly基因型血浆总IgE对数值 ( x±s:2 .6 1 5± 0 .6 0 0 1 ,n =36 )与Asp Asp基因型血浆总IgE对数值 ( x±s:2 .2 4 0± 0 .6 894 ,n =1 6 1 )相比较高 ,差异有统计学意义 (P =0 .0 0 2 )。TLR4基因Thr399Ile位点Thr Thr、Thr Ile和Ile Ile的基因型频率为 0 .970、0 .0 2 0和 0 .0 1 0 ,与正常对照组相比差异无统计学意义 (χ2 =0 .6 2 0 ,P =0 .733) ;变应性哮喘患者Ile Ile、Thr Ile基因型血浆总IgE对数值 ( x±s:2 .4 1 7± 0 .4 4 2 3,n =6 )与Thr Thr基因型血浆总IgE对数值 ( x±s:2 .30 5± 0 .6 94 9,n =1 91 )相比差异无统计学意义 (P =0 .5 71 )。     

Occupational asthma in bakeries caused by sensitivity to α-amylase

We report on a patient with asthma induced by occupational exposure to alpha-amylase derived from Aspergillus oryzae, which is a component of bread additives. A type I hypersensitivity to this enzyme was demonstrated by means of skin test, immunoassay for specific IgE, and immediate bronchial provocation test response to an alpha-amylase extract.     

A 500‐ml plastic bottle: An effective spacer for children with asthma

Inhaled therapy using a metered‐dose inhaler (MDI) with attached spacer has been increasingly recognized as the optimal method for delivering asthma medication for acute attacks and chronic prophylaxis. However, in developing countries the cost and availability of commercially produced spacers limit the use of MDI‐spacer delivery systems. A 500‐ml plastic bottle has been recently adapted to function as a spacer. This article reviews the current data on the efficacy of this bottle‐spacer and discusses its advantages and limitations. It is concluded that a modified 500‐ml plastic bottle is an effective spacer; modification and use of this device should be incorporated into international guidelines for the management of children with asthma.     

变应性鼻炎、哮喘患者血白细胞介素的循证医学研究

目的 评价变应性鼻炎、哮喘患者血清中白细胞介素IL-4、IL-6、IL-8检测指标的意义。方法 检索策略:通过中国生物医学文献数据库(CBMdisc)、中文全文数据库全面检索国内已发表的相关文献。选择标准:中国成人变应性鼻炎、哮喘患者与对照组血清白细胞介素IL-4、IL-6、IL-8水平检测。资料收集和分析:由2位评价者按照上述检索策略收集文献。排除那些不符合选择标准要求的试验。结果 经Meta分析,发作期、缓解期变应性鼻炎患者血清中IL-4水平分别较对照组上升129.45 ng/mL(95％CI 124.95～133.96)、35.00 ng/mL(95％CI 32.01～39.78),有显著统计学意义(P<0.000 01):缓解期IL-6水平较对照组上升21.87 ng/mL(95％CI 19.83～23.91),有显著统计学意义(P<0.000 01);发作期、缓解期IL-8水平分别较对照组上升41.75 ng/mL(95％CI 29.14-54.36)、98.94 ng/mL(95％CI 96.48-101.41),有显著统计学意义(P<0.000 01);发作期IL-4水平较缓解期上升129.99 ng/mL(95％CI 125.00～134.99),有显著统计学意义(P<0.000 01)。结论 IL-4、IL-6和IL-8参与了变应性鼻炎、哮喘的发生和促进了变态反应性疾病的发展,有必要开展更广泛研究和更深层的原因探索。     

High serum levels of tumour necrosis factor‐α and interleukin‐8 in severe asthma: markers of systemic inflammation?

BACKGROUND: Severe asthma is characterized by elevated levels of pro-inflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, markers of 'systemic' inflammation, may be a feature of amplified inflammation in severe asthma. OBJECTIVE: To detect differences in IL-8, TNF-alpha, IL-16 and IL-13 levels in the serum(s) of stable severe and mild-moderate asthmatics related to blood leucocytes proportion, airway calibre and exhaled nitric oxide (NO) levels. METHODS: We assessed cytokine serum levels by ELISA and blood leucocyte counts by an alkaline peroxidase method in 20 healthy controls, 22 mild-moderate [forced expiratory volume in 1 s (FEV1)(%pred): 89+/-3] and 14 severe asthmatics [FEV1(%pred): 49+/-2]. RESULTS: IL-8 and TNF-alpha levels were higher in severe asthmatics than in mild-moderate asthmatics or in controls (P<0.05). No differences in IL-16 and IL-13 levels were detected. Severe asthmatics showed higher circulating neutrophil and eosinophil number than controls (P<0.05). In severe asthmatics, exhaled NO levels were superior than in controls (P<0.05), but inferior than in mild-moderate asthmatics (P<0.05). We found positive correlation between TNF-alpha levels and exhaled NO (r=0.67; P=0.01) or circulating neutrophil counts (r=0.57; P=0.03) in severe asthmatics. CONCLUSION: sTNF-alpha and sIL-8 are markers of 'systemic' inflammation in severe asthmatics, in conjunction with augmented circulating neutrophils, suggesting the involvement of neutrophil-derived cytokine pattern in severe asthma.     

Role of interleukin-17F in chronic inflammatory and allergic lung disease

IL-17 family members belong to a distinct category of cytokines that coordinate local tissue inflammation by inducing the release of pro-inflammatory and neutrophil-mobilizing cytokines. The importance of the IL-17 family in inflammatory and autoimmune disease is becoming increasingly apparent. IL-17F is a recently discovered member of the IL-17 family that has a number of biological activities through induction of various cytokines, chemokines, and mediators. IL-17A, the founding member of the IL-17 family, and IL-17F are produced by several inflammatory cells, including activated T cells, in response to infectious and antigenic stimuli. Overexpression of IL-17A or IL-17F in the lungs results in induction of CXC chemokines and neutrophil recruitment. In a case-control study of 1125 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL17F gene was shown to be associated with asthma and chronic obstructive pulmonary disease (COPD). Functionally, this variant failed to induce cytokines and chemokines, and interestingly, was able to antagonize the activity of wild-type IL-17F. These results provide an experimental basis for the observed genetic association with chronic inflammatory lung diseases, and also suggest the potential therapeutic utility of this antagonistic variant of IL-17F. Given that asthma and COPD are complex diseases involving a number of genetic and environmental factors, the genetic impact of IL-17F H161R with regard to the development of chronic airway inflammation likely varies among individuals with different genetic backgrounds and environmental exposures.