WAO News and Notes - Medical Reviews
Volume 5, Issue 10 Reviews - October 2008
Medical Journal Reviews

Reviewed by Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief, and Guest Editor Mark Glaum, MD PhD

1. INHALED CORTICOSTEROID USE IS ASSOCIATED WITH DECREASED CARDIOVASCULAR AND ALL-CAUSE MORTALITY IN ASTHMATIC WOMEN
Inhaled corticosteroid (ICS) use decreases the risk of asthma exacerbations and may decrease all-cause mortality. In the 1970's the Nurses' Health Study (NHS) enrolled 121,700 registered nurses aged 33-55 years. In 1998, asthmatic participants from NHS were sent supplementary questionnaires on asthma diagnosis and ICS use. Mortality was assessed through 2003 and odds ratios (ORs) for death were adjusted for age, asthma severity, smoking, heart disease, cancer, stroke, aspirin and statin use. Of 2671 eligible women who responded to the 1998 survey, 2270 (85%) met criteria for persistent asthma and 1442 (54%) reported ICS use. Compared to asthmatic women who did not use ICS, those receiving ICS therapy had lower risk for all-cause mortality (OR, 0.58; 95% confidence interval [CI], 0.36-0.92) and cardiovascular death (OR, 0.35; 95% CI, 0.13-0.93) but not death from cancer (OR, 0.66; 95% CI, 0.32-1.38) or other causes (OR, 0.62; 95% CI, 0.30-1.27). Editor's comment: ICS may exert anti-inflammatory benefits beyond the airway. Camargo CA, Barr RG, Chen R, Speizer FE. Chest 2008; 134: 546-51.

吸入性糖皮质激素可以降低女性哮喘患者心血管病死亡率及全因死亡率

吸入性糖皮质激素(ICS)减少哮喘恶化,降低全因死亡率。20世纪70年代,护士健康调查(NHS)纳入了121,700名年龄33-55岁的注册护士。1998年,NHS哮喘患者回答了哮喘诊断及ICS使用的补充问卷。评估了直至2003年的死亡率,以及根据年龄,哮喘严重度,吸烟情况,心脏疾病,肿瘤,卒中,阿司匹林使用及他汀使用进行调整后的死亡危险比。回答了1998年问卷的2671位合格女性患者中,2270 (85%)名患者符合持续性哮喘的标准,1442 (54%)使用过ICS。与没有使用ICS的女性哮喘患者相比,用ICS治疗的患者全因死亡低(OR, 0.58; 95% 置信区间 [CI], 0.36-0.92),心血管疾病致死率也更低(OR, 0.35; 95% CI, 0.13-0.93),但因癌症所致的死亡或其它原因致死的危险不低。编者点评:ICS对气道外的器官也有抗炎作用。Camargo CA, Barr RG, Chen R, Speizer FE. Chest 2008; 134: 546-51.

2. SERIAL RHINOVIRUS INFECTIONS IN INFANTS WITH RECURRENT RESPIRATORY ILLNESSES
Acute viral infections are a major cause of respiratory morbidity and asthma exacerbations in infants and young children. This study examines the viral etiology of respiratory illnesses in a subgroup of infants from the Childhood Origins of ASThma (COAST) study, a prospective birth cohort of 300 newborns at increased risk of developing asthma based on family history. Attention was focused on infants who were frequently ill (27 infants out of 285), with five or more moderate-to-severe respiratory illnesses (MSIs) during the first year of life. In frequently ill infants, rhinoviruses were most commonly detected in nasal washes (detected in 61% of cases of moderate-to-severe respiratory illnesses and in 43% of mild illnesses). Rhinovirus infections occurred early in life, with the mean age of four months at first infection. Extended viral syndromes were usually caused by sequential infections with distinct rhinovirus strains, as opposed to a protracted infection with a single strain. Editor's comment: Human rhinovirus infection occurs early, pervasively and repetitively in infants with increased risk for asthma. Jartti J, Lee W-M, Pappas T, et al. Eur Respir J 2008; 32: 314-20.

反复发生呼吸道疾病的婴儿患者有鼻病毒的序贯感染

急性病毒感染是婴儿及幼儿呼吸道疾病发作及哮喘恶化的主要原因。Coast研究是针对基于家族史而哮喘发病危险高的300名新生儿的前瞻性出生队列研究。本研究选取COAST研究中的部份患儿,分析病毒在呼吸道疾病的致病作用。重点关注经常生病的小儿(285名中的27名),这些小儿在出生后第一年有5次或更多的中至重度呼吸道疾病。经常患病的小儿,鼻冲洗物中最常见的是鼻病毒(存在于 61%中至重度呼吸道疾病患儿中,以及43%轻度疾病患儿中)。鼻病毒感染发生在早期,首次感染平均发生在4个月时。持续病毒症状通常是由于不同鼻病毒株导致的序贯感染,而单一病毒株导致感染时间延长。编者点评:鼻病毒感染在婴儿早期就有发生,主要发生在哮喘危险增高的患者中。Jartti J, Lee W-M, Pappas T, et al. Eur Respir J 2008; 32: 314-20.

3. BACTERIAL INFECTIONS IN HUMANS WITH MyD88 DEFECTS
MyD88 is an essential adapter molecule for many Toll-like receptors (TLR) that provides pivotal protection in innate immune defense. This report describes a series of nine children with autorecessive MyD88 deficiency who suffered from life-threatening recurrent pyogenic bacterial infections. While subjects were susceptible to infection with organisms such as Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa, they were otherwise healthy with normal resistance to most common bacteria, viruses, fungi and parasites. Susceptibility to bacterial infections tended to improve with age. Editor's comment: MyD88-dependent TLRs provide important but redundant protection against certain pyogenic bacteria. Von Bernuth H, Picard C, Jin Z, et al. Science 2008; 321: 691-6.

MyD88缺陷者细菌感染的情况

MyD88是很多Toll样受体(TLR)的重要辅助分子,对内源性免疫应答起到关键保护作用。本文报道了9名常染色体隐性MyD88缺陷患儿,他们反复出现致命性脓毒菌感染。患者对诸如肺炎链球菌,金黄色葡萄球菌,以及铜绿假单孢菌等病原体易感,但对于多数细菌,病毒,真菌及寄生虫有正常的抵抗力。他们对细菌的易感性随着年龄增加而降低。编者点评:MyD88依赖的TLR对某些脓毒性细菌感染有重要保护作用。Von Bernuth H, Picard C, Jin Z, et al. Science 2008; 321: 691-6.

4. NONATOPIC CHILDREN WITH MULTITRIGGER WHEEZING HAVE AIRWAY PATHOLOGY COMPARABLE TO ATOPIC ASTHMA
Epidemiologic studies suggest that wheezing in children with infections is transient, while wheezing in atopic children persists into adolescence. This study examined differences in histopathology of airway biopsies from children with atopic and non-atopic asthma. Bronchial biopsies were obtained from 18 non-atopic asthmatic children, 20 atopic asthmatics and 17 non-asthmatic controls. There were no differences in biopsy specimens between atopic and non-atopic asthmatics in regard to epithelial cell loss, basement membrane thickening, angiogenesis, or number of IL-4 and IL-5 positive cells in the subepithelium. Editor's comment: When subjective symptoms of asthma occur in non-atopic children, the airway pathology is still typical of allergic asthma. Turato G, Barbato A, Barlado S, et al. Am J Respir Crit Care Med 2008; 178:476-82. Please see related editorial: Am J Respir Crit Care Med 2008; 178:437.

对多种触发物敏感的非特应性喘息患儿的气道病理与特应性哮喘的患儿相似

流行病学研究显示感染后的儿童喘息是暂时性的,但特应性患儿的喘息可以持续到成人阶段。本研究观察了特应性哮喘患儿及非特应性哮喘患儿气道活检的病理。获得18名非特应性哮喘患儿,20名特应性哮喘患儿及17名非哮喘的对照儿童的的支气管活检标本。特应性及非特应性哮喘患儿的活检标本在上皮细胞缺失,基底膜增厚,血管化生,以及上皮下层Il-4及Il-5阳性细胞的数量上均无差异。编者点评:非特应性儿童发生主观的哮喘症状时,气道病理仍然是典型的过敏性哮喘的表型。Turato G, Barbato A, Barlado S, et al. Am J Respir Crit Care Med 2008; 178:476-82. Please see related editorial: Am J Respir Crit Care Med 2008; 178:437.

5. AVIAN IGY BINDS TO A MONOCYTE RECEPTOR WITH IGG-LIKE KINETICS DESPITE AN IGE-LIKE STRUCTURE
IgY is an immunoglobulin produced by birds, reptiles and amphibians that is structurally similar to IgE and is thought to protect against parasitic infections. This study finds that binding characteristics of IgY to its receptor are much weaker those of human IgE despite highly homologous structural motifs. Determining reasons for this discrepancy may provide new therapeutic strategies for blocking IgE binding. Editor's comment: Binding affinity of IgE to its receptor may be an attractive therapeutic target for allergic diseases. Taylor AI, Gould HJ, Calvert RA. J Biol Chem 2008; 24: 16384-90. Please see related editorial: Nature Medicine 2008; 14: 797.

禽类IgY与单核细胞受体的结合虽然是IgE样的结构,但具有IgG样的结合力

IgY是禽类、爬行动物以及两栖类产生的免疫球蛋白,与IgE结构相似,可以防御寄生虫感染。本研究发现尽管IgY和人IgE在结构基序上高度同源,但IgY与其受体的结合特点不同于IgE,明确这种差异的原因可以为阻断IgE结合提供新的治疗方案。编者点评:IgE与其受体的亲和力为过敏性疾病的治疗带来了前景。Taylor AI, Gould HJ, Calvert RA. J Biol Chem 2008; 24: 16384-90. Please see related editorial: Nature Medicine 2008; 14: 797.

6. DIFFERENTIATION OF HUMAN TH17 CELLS FROM NAÏVE T CELLS
TH17 cells are a subset of interleukin (IL)-17-producing T helper cells thought to contribute to the pathogenesis of a number of human autoimmune diseases. This study examines cytokines required for the production of IL-17A by memory and naive human CD4 T cells. The data demonstrate that transforming growth factor-beta (TGF-β) and IL-21, through the induction of the transcription factor RORC2, are critical for the differentiation of TH17 cells from highly purified naive (but not memory) CD4+ T cells. Editor's comment: This study helps further delineate human TH17 inflammatory responses associated with infection and autoimmune diseases. Yang L, Anderson D, Baecher-Allan C, et al. Nature 2008;454: 350-2.

人纯真T细胞分化为TH17细胞

TH17细胞是分泌Il-17的T辅助细胞的亚群之一,对许多人自身免疫性疾病的发生有致病作用。本研究观察了记忆及纯真CD4T细胞产生Il-17A所需要的细胞因子。资料显示转换生长因子(TGF-β)及Il-21,通过诱导转录因子RORC2,对纯化的幼稚CD4+T细胞分化为TH17细胞很关键。编者点评:本研究有助于进一步明确与感染及自身免疫疾病相关的人Th17炎症应答。Yang L, Anderson D, Baecher-Allan C, et al. Nature 2008;454: 350-2.

7. HEREDITARY ANGIOEDEMA
Hereditary angioedema (HA) is an autosomal dominant condition caused by deficiency of functional C1 inhibitor. HA is characterized by recurrent episodes of nonpruritic, nonpitting, subcutaneous or submucosal edema involving the face, tongue, larynx, extremities, trunk, or viscera. This report is an excellent case presentation and review of clinical features, laboratory evaluation and treatment of this unusual but clinically challenging condition. Editor's comment: Outstanding updated review of hereditary angioedema. Zuraw BL. N Engl J Med 2008; 359: 1027-36.

遗传性血管水肿

遗传性血管水肿(HA)是由于功能性C1抑制物缺乏导致的常染色体显性遗传。HA的特征表现为反复发生的非瘙痒性,非可凹性,皮下或粘膜下水肿,累及面部,舌,咽,肢端,或内脏。本文是一篇优秀的病例展示,同时对这一不同寻常但很有临床挑战性的疾病的临床特点,实验室诊断,以及治疗方法的回顾。编者点评:这是对遗传性血管水肿的优秀的最新回顾。Zuraw BL. N Engl J Med 2008; 359: 1027-36.

8. ROLE OF BISPHOSPHONATES IN CLINICAL PRACTICE
This excellent review outlines the mechanism of action and appropriate clinical use of bisphosphonates in osteoporosis. Potential complications of bisphosphonate use and the roles of calcium and vitamin D supplementation are discussed. Editor's comment: Persistent asthmatics are at increased risk for side effects from high-dose inhalational and systemic corticosteroids. Asthma specialists should be familiar with appropriate use of bisphosphonates. Drake MT, Clark BL, Khosla S. Mayo Clin Proc 2008: 83:1032-45.

双磷酸盐在临床工作中的应用

本综述阐述了双磷酸盐在骨质疏松中的作用机制。讨论了双磷酸盐的潜在并发症以及元素钙和维生素C替代治疗的作用。编者点评:持续哮喘的患者更容易出现高剂量吸入及系统糖皮质激素相关的副作用。哮喘专科医生应该熟悉双磷酸盐的使用。Drake MT, Clark BL, Khosla S. Mayo Clin Proc 2008: 83:1032-45.

9. PRACTICE PARAMETER: DIAGNOSIS AND MANAGEMENT OF RHINITIS
This supplement to the Journal of Allergy and Clinical Immunology provides graded quality of evidence recommendations for the diagnosis and management of rhinitis. Editor's comment: A must-read for anyone who treats patients with chronic nasal symptoms. Wallace DV, Dykewicz MS, et al. J Allergy Clin Immunol 2008: 122 (suppl 1):1-84

 临床指南:鼻炎的诊断治疗

本文是JACI的补充期刊,对哮喘的诊断治疗提出了建议。编者点评:本文是治疗慢性鼻病患者之必读。Wallace DV, Dykewicz MS, et al. J Allergy Clin Immunol 2008: 122 (suppl 1):1-84

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