Maternal history, sensitization to allergens, and current wheezing, rhinitis, and eczema among children in Costa Rica

Little is known about the factors associated with asthma, allergic rhinitis, and eczema in Latin American countries. We investigated the relation between potential risk factors and current wheezing, allergic rhinitis, and eczema among 208 Costa Rican children aged 10-13 years participating in phase II of the International Study of Asthma and Allergies in Childhood (ISAAC). The geometric mean ( +/- SD) serum total IgE level of children with current wheezing was significantly higher than that of children without current wheezing (533.8 +/- 5.2 vs. 144.7 +/- 6.0 IU/mL, P < 0.01). In a multivariate analysis, a maternal history of asthma, skin test reactivity (STR) to house dust mites, and STR to Alternaria were significantly associated with current wheezing. Children who had a maternal history of asthma had 2.4 times higher odds of current wheezing than those without maternal history of asthma (95% CI for OR = 1.1-5.3). Sensitization to either house dust mite or Alternaria was associated with 3.3 times increased odds of current wheezing (95% CI for OR for STR to dust mite = 1.6-6.7; 95% CI for OR for STR to Alternaria = 1.1-11.0). In a multivariate analysis, STR to house dust mite and STR to cat dander were significantly associated with allergic rhinitis, and a maternal history of eczema and STR to dog dander were associated with eczema in the child. The interaction between familial factors and lifestyle changes resulting from social reforms implemented 60 years ago may explain the high prevalence of atopic diseases in Costa Rica.     

Airway responses to salbutamol after exposure to chemical warfare

Background and objectives:   Increased airway responsiveness to β-agonists is noted in asthmatics and smokers. The lung may be exposed to chemical warfare agents such as mustard gas and pulmonary complications of exposure range from no effect to severe bronchial stenosis. There is little understanding of airway hyperresponsiveness to β-agonist drugs in chemical war victims and this study examined airway responsiveness to salbutamol in victims of chemical warfare.
Methods:   The threshold concentrations of inhaled salbutamol required for a 20% change in FEV₁ as PC₂₀, or a 35% change in specific airway conductance (sGaw) as PC₃₅ were measured in 22 persons exposed to chemical warfare and 15 normal control subjects.
Results:   In 11 of the 22 subjects PC₂₀ salbutamol could be measured and in 15 of the 22 subjects PC₃₅ salbutamol could be measured. This group of patients was the responder group (PC₂₀ = 10.79 and PC₃₅ = 8.55 mg/L) and in them the concentration of salbutamol needed for a response was significantly lower than that required in normal controls (PC₂₀ = 237.68 and PC₃₅ = 88.72 mg/L, P  < 0.001). There was a significant correlation between FEV₁ and PC₂₀ salbutamol ( r  = 0.815, P  < 0.001).
Conclusions:   These results showed increased airway responsiveness to salbutamol in most subjects exposed to chemical warfare; this was correlated with airway calibre.     

磷酸二酯酶抑制剂与呼吸道疾病

磷酸二酯酶(PDE)存在于许多炎症细胞及结构细胞中,目前已发现11种.PDE抑制剂主要抑制体内环磷酸腺苷(cAMP)及环磷酸鸟苷(cGMP)水解,使细胞内cAMP及cGMP浓度增加,引起一系列生理功能,如平滑肌舒张、减轻细胞炎症及免疫反应等.PDE4特异性水解cAMP,选择性PDE4抑制剂具有广泛抗炎作用,如抑制细胞趋化,抑制中性粒细胞、嗜酸粒细胞、巨噬细胞及T细胞细胞因子及化学趋化物质释放.第二代PDE4抑制剂Cilomilast和Roflumilast已进入临床实验阶段,并已证实对支气管哮喘(简称哮喘)及慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)有效.由于胃肠道副作用,这类药物临床应用受到一定限制.PDE5可特异性水解cGMP,对缺氧性肺动脉高压和血管重塑有效.PDE3和PDE7特异性水解cAMP,PDE7参与T细胞激活.目前其他PDE抑制剂与PDE4抑制剂混合制剂正在研发中.PDE4-PDE7双重抑制剂可能对哮喘及COPD更有效.PDE3-PDE4双重抑制剂具有更强的支气管舒张作用及气道保护作用.     

Respiratory impedance response to a deep inhalation in children with history of cough or asthma

The aim of this study was to describe the change in respiratory impedance induced by a deep inhalation (DI) in children who developed a positive response to inhalation of methacholine (Mch). Eighteen children aged 4.5-12.5 years, presenting with chronic cough or doctor-diagnosed asthma, were studied at baseline after inhalation of Mch and after inhalation of a bronchodilator. Respiratory resistance (Rrs) and reactance (Xrs) were measured by the forced oscillation technique, varying transrespiratory pressure at 12 Hz around the head. The tidal flow (V') and volume (V) dependence of Rrs before and after the DI was characterized according to the equation Rrs = K1 + K2 x /V'/ + K3 x V. DI induced no significant change at baseline or after inhalation of a bonchodilator. During Mch challenge, Rrs and K1 were significantly lower, and K3 and Xrs significantly less negative after DI than before, during both inspiration and expiration; there was no change in K2.We conclude that DI results in a decrease in Rrs in children with induced bronchoconstriction. The associated changes in Xrs, K1, and K3, and lack of decrease in K2, suggest that dilatation of airways occurs at the bronchial level, with little contribution of the upper airways or of a change in breathing patterns.     

不同雾化吸入方法在激素依赖性哮喘中的效果研究

目的　探讨压缩雾化吸入给药在激素依赖性哮喘中的作用。方法随机将32例激素依赖性哮喘病人分为研究组和对照组各16例。研究组利用布地奈德混悬液和沙丁胺醇雾化溶液混合压缩雾化吸入治疗。对照组采用以上二种气雾剂喷射雾化吸入,比较两种给药的疗效。结果压缩雾化吸入给药疗效明显高于气雾剂喷射雾化给药(P<0.01)。肺功能监测结果有显著性差异(P<0.01)。结论联合用药压缩雾化吸入是治疗激素依赖性哮喘的有效方法。     

MMP-9及TIMP-1在支气管哮喘发病中作用及雷公藤多甙干预研究

目的观察支气管哮喘（简称哮喘）大鼠肺组织中细胞外基质（ECM）代谢相关因子基质金属蛋白酶9（MMP-9）及其抑制剂组织金属蛋白酶抑制剂1（TIMP-1）的表达，研究雷公藤多甙在哮喘肺组织ECM重塑中可能的作用及其机制。方法建立大鼠哮喘模型，采用逆转录-聚合酶链反应技术（RT-PCR）测定肺组织中MMP-9、TIMP-1mRNA的表达。结果哮喘组MMP-9、TIMP-1在肺组织中的蛋白表达明显高于对照组（P〈0．01），应用药物雷公藤多甙干预后，MMP-9、TIMP-1蛋白表达明显低于哮喘组（P〈0．05）。哮喘组MMP-9、TIMP-1在肺组织的mRNA表达也高于对照组（P〈0．01），应用雷公藤多甙药物干预后，MMP-9、TIMP．1在肺组织的mRNA表达明显低于哮喘组（P〈0．01）。哮喘组肺组织中MMP-9／TIMP-1〉1，明显高于对照组（P〈0．05），应用药物雷公藤多甙干预后，MMP-9／TIMP．1〈1，明显低于对照组（P〈0．05）和哮喘组（P〈0．01）。结论雷公藤多甙可能下调MMP-9的表达，调节MMP-9／TIMP-1的平衡，干预细胞外基质重塑。     

The role of air nicotine in explaining racial differences in cotinine among tobacco-exposed children

OBJECTIVE: African-American children have higher rates of tobacco-associated morbidity. Few studies have objectively measured racial differences in the exposure of children to tobacco smoke. The objective of this study was to test whether African-American children have higher levels of cotinine compared to white children while accounting for ambient measures of tobacco smoke. SETTING: Community-based sample of asthmatic children (n = 220) enrolled in an environmental tobacco smoke (ETS) reduction trial. PARTICIPANTS: A biracial sample (55% African American) of children with asthma aged 5 to 12 years who were routinely exposed to ETS. MEASUREMENTS: We measured cotinine levels in serum and hair samples at baseline, 6 months, and 12 months. We measured the level of ETS exposure over a 6-month period by placing air nicotine dosimeters in the homes of the children at baseline and at 6-month study visits. RESULTS: African-American children had significantly higher levels of cotinine at all time points in the study. At the 12-month visit, African-American children had higher levels of serum cotinine (1.39 mug/dL vs 0.80 mug/dL, p = 0.001) and hair cotinine (0.28 ng/mg vs 0.08 ng/mg, p < 0.0001) when compared with white children. In a repeated-measures analysis, African-American children had significantly higher levels of serum cotinine (beta = 0.28, p = 0.04) and hair cotinine (beta = 1.40, p < 0.0001) compared with white children. Air nicotine levels and housing volume were independently associated with higher levels of cotinine. CONCLUSIONS: Among children with asthma, African-American children have higher levels of serum and hair cotinine compared with white children.     

Predictors for failed dose reduction of inhaled corticosteroids in childhood asthma

Background and objective:   Studies of Western populations have shown that increased exhaled nitric oxide (FeNO) and/or sputum eosinophils (sp-Eos) are predictive of asthma exacerbations. However, the utility of these measurements in different populations and settings is unknown. This study aimed to determine the predictors for failure of reduction of inhaled corticosteroid (ICS) doses in children with stable asthma.
Methods:   Fifty children (median age 11.8 years, interquartile range (IQR) 5.9 years) had their dose of ICS halved every 8 weeks until they reached the study end-point (exacerbation or weaned off ICS). Spirometry, FeNO and induced sputum cells were measured at baseline and at each stage of ICS reduction.
Results:   Eleven subjects suffered an asthma exacerbation and the remainder was successfully weaned off ICS. Subjects with an exacerbation were older (15.4 years (IQR 5.4) vs 11.4 years (IQR 3.9), P  = 0.019) and more likely to be boys ( P  = 0.035). FeNO (median 156 p.p.b. (IQR 131) vs 76.1 p.p.b. (IQR 79.5), P  = 0.013) and sp-Eos (17.3% (IQR 33.8%) vs 7.1% (IQR 9.9%), P  = 0.019) were significantly greater in those who had an exacerbation. The areas under the receiver operating characteristic curves for FeNO (0.78, 95% CI: 0.59–0.97, P  = 0.013) and sp-Eos (0.76, 95% CI: 0.56–0.96, P  = 0.016) were similar ( P  = 0.88) and both were significantly greater than that for FEV₁% predicted (0.12, 95% CI: 0.08–0.56, P  = 0.0013).
Conclusions:   Older boys with raised FeNO and sp-Eos are at higher risk of failure of reduction in their ICS dose. Monitoring airway inflammation in children with asthma using FeNO or sp-Eos is clinically useful in guiding ICS dose reduction in a non-Western outpatient setting.     

吸烟对致敏大鼠肺组织基质金属蛋白酶9及其抑制剂1表达的影响

目的 通过观察吸烟对致敏大鼠肺组织基质相关因子基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)及金属蛋白酶组织抑制因子1(tissue inhibitor of metallopmteinase-1,TIMP-1)表达的影响,探讨吸烟在支气管哮喘(简称哮喘)气道重塑中的作用.方法 24只雄性Wistar大鼠随机分为对照组、致敏组和吸烟致敏组,每组8只.后两组用卵白蛋白(OVA)致敏并长期(8周)吸人激发,制备哮喘模型,在激发第3周开始,吸烟致敏组大鼠置于自制熏箱内进行被动吸烟.采用免疫组织化学法检测大鼠气道上皮细胞MMP-9、TIMP-1的蛋白表达,同时测量支气管壁的厚度,并用逆转录-聚合酶链反应法检测各组肺组织的MMP-9 mRNA、TIMP-1 mRNA含量.结果 ①吸烟致敏组气道壁厚度[(23.28±2.38)μm2/μm]明显高于致敏组[(20.06±2.94)/μm2/μm]和对照组[(11.64±2.42)μm2/μm](P值均＜0.05),致敏组高于对照组(P＜0.05),②吸烟致敏组肺组织中MMP-9 mRNA表达(0.49±0.02)和气道上皮细胞MMP-9蛋白含量(32.78±2.60)均明显高于致敏组(0.41±0.04,23.05±2.11)和对照组(0.23±0.03,15.88±1.69)(P值均＜0.01),致敏组高于对照组(P值均＜0.01),③吸烟致敏组肺组织中TIMP-1mRNA表达(0.53±0.02)和气道上皮细胞TIMP-1蛋白含量(34.54±2.90)均高于致敏组(0.37±0.05,21.25±2.28)和对照组(0.235=0.04,15.78±1.97)(P值均＜0.01),致敏组高于对照组(P值均＜0.01);④肺组织MMP-9/TIMP-1 mRNA比值:吸烟致敏组(0.91±0.05)低于致敏组(1.12±0.06)和对照组(1.03±0.09)(P值均＜0.01).致敏组高于对照组(P＜0.01),⑤气道上皮细胞MMP-9/TIMP-1蛋白含量比值:吸烟致敏组(0.94±0.03)低于致敏组(1.09±0.07)和对照组(1.01±0.06)(P＜0.05,P＜0.01),致敏组高于对照组(P＜0.01).结论 吸烟可使致敏大鼠肺组织MMP-9和TIMP-1过度表达,比例失调,加重气道重塑.     

Airway cough sensitivity to inhaled capsaicin and bronchial responsiveness to methacholine in asthmatic and bronchitic subjects

The objective of this study was to evaluate the effect of chronic airway inflammation on airway cough sensitivity and non-specific bronchial responsiveness, and the relationship between them. The capsaicin cough threshold, defined as the lowest concentration of capsaicin causing five or more coughs, and non-specific bronchial responsiveness, defined as the methacholine concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1) (PC20-FEV1), were measured in 18 asthmatic, 13 bronchitic (sinobronchial syndrome) and 28 healthy non-atopic subjects. All subjects were non-smoking men. The geometric mean values (mumol) of the cough threshold were 18.9 (GSEM 1.29), 8.69 (GSEM 1.29) and 27.6 (GSEM 1.31) in asthmatic, bronchitic and normal subjects, respectively. The value in bronchitic subjects was significantly lower (P < 0.02) than that in normal subjects. The geometric mean value of PC20-FEV1 in asthmatic subjects (0.48 mg/ml (GSEM 1.38)) was significantly lower than that in bronchitic subjects (18.5 mg/ml (GSEM 1.75)) (P < 0.001). There was no correlation between cough threshold and PC20-FEV1 values (correlation coefficient (r) = 0.155). These results indicate that cough sensitivity is potentiated by chronic airway inflammation in bronchitis but not in asthma, and suggest that cough sensitivity and bronchial responsiveness may be independently potentiated by different mechanisms resulting from chronic airway inflammation.