Bisgaard Hans, Hermansen Mette Northman, Buchvald Frederik, Loland Lotte, Halkjaer Liselotte Brydensholt, Bønnelykke Klaus, Brasholt Martin, Heltberg Andreas, Vissing Nadja Hawwa, Thorsen Sannie Vester, Stage Malene, Pipper Christian Bressen
Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Copenhagen.
N Engl J Med. 2007 Oct 11;357(15):1487-95. doi: 10.1056/NEJMoa052632.
Pathological features of the airway in young children with severe recurrent wheeze suggest an association between bacterial colonization and the initiating events of early asthma. We conducted a study to investigate a possible association between bacterial colonization of the hypopharynx in asymptomatic neonates and later development of recurrent wheeze, asthma, and allergy during the first 5 years of life.
The subjects were children from the Copenhagen Prospective Study on Asthma in Childhood birth cohort who were born to mothers with asthma. Aspirates from the hypopharyngeal region of asymptomatic 1-month-old infants were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Wheeze was monitored prospectively on diary cards during the first 5 years of life. Blood eosinophil count and total IgE and specific IgE were measured at 4 years of age. Lung function was measured and asthma was diagnosed at 5 years of age.
Hypopharyngeal samples were cultured from 321 neonates at 1 month of age. Twenty-one percent of the infants were colonized with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms; colonization with one or more of these organisms, but not colonization with S. aureus, was significantly associated with persistent wheeze (hazard ratio, 2.40; 95% confidence interval [CI], 1.45 to 3.99), acute severe exacerbation of wheeze (hazard ratio, 2.99; 95% CI, 1.66 to 5.39), and hospitalization for wheeze (hazard ratio, 3.85; 95% CI, 1.90 to 7.79). Blood eosinophil counts and total IgE at 4 years of age were significantly increased in children colonized neonatally with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms, but specific IgE was not significantly affected. The prevalence of asthma and the reversibility of airway resistance after beta2-agonist administration at 5 years of age were significantly increased in the children colonized neonatally with these organisms as compared with the children without such colonization (33% vs. 10% and 23% vs. 18%, respectively).
Neonates colonized in the hypopharyngeal region with S. pneumoniae, H. influenzae, or M. catarrhalis, or with a combination of these organisms, are at increased risk for recurrent wheeze and asthma early in life.
重度复发性喘息幼儿气道的病理特征提示细菌定植与早期哮喘的起始事件之间存在关联。我们开展了一项研究,以调查无症状新生儿下咽细菌定植与生命最初5年内复发性喘息、哮喘及过敏症后期发生之间可能存在的关联。
研究对象为来自哥本哈根儿童哮喘前瞻性研究出生队列中母亲患有哮喘的儿童。对无症状1月龄婴儿的下咽吸出物进行肺炎链球菌、流感嗜血杆菌、卡他莫拉菌和金黄色葡萄球菌培养。在生命的最初5年通过日记卡对喘息进行前瞻性监测。在4岁时测量血嗜酸性粒细胞计数、总IgE和特异性IgE。在5岁时测量肺功能并诊断哮喘。
从321名1月龄新生儿获取下咽样本进行培养。21%的婴儿被肺炎链球菌、卡他莫拉菌、流感嗜血杆菌或这些细菌的组合定植;被这些细菌中的一种或多种定植,但不包括被金黄色葡萄球菌定植,与持续性喘息(风险比,2.40;95%置信区间[CI],1.45至3.99)、喘息急性重度加重(风险比,2.99;95%CI,1.66至5.39)及因喘息住院(风险比,3.85;95%CI,1.90至7.79)显著相关。4岁时,新生儿期被肺炎链球菌、卡他莫拉菌、流感嗜血杆菌或这些细菌的组合定植的儿童血嗜酸性粒细胞计数和总IgE显著升高,但特异性IgE未受到显著影响。与未发生此类定植的儿童相比,5岁时,新生儿期被这些细菌定植的儿童哮喘患病率及β2受体激动剂给药后气道阻力的可逆性显著升高(分别为33%对10%和23%对十八%)。
下咽被肺炎链球菌、流感嗜血杆菌或卡他莫拉菌或这些细菌的组合定植的新生儿在生命早期发生复发性喘息和哮喘的风险增加。