Eosinophil cationic protein and interleukin-8 levels in bronchial lavage fluid from children with asthma and infantile wheeze

It has been shown previously that airway eosinophils characterize childhood asthma and neutrophils contribute to the pathophysiology of both infantile wheezing and asthma. Therefore, eosinophil cationic protein (ECP) and interleukin‐8 (IL‐8) levels in bronchoalveolar lavage fluid (BALF) from asthmatics (n = 16) and infantile wheezers (n = 30) were analyzed as markers of eosinophil‐ and neutrophil‐mediated inflammation. To aid the interpretation, a control group of children (n = 10) with no lower airway pathology were included. Disease severity was assessed by using a symptom score. Surprisingly, no significant difference was found in IL‐8 or ECP levels among asthma, infantile wheeze, and control groups. Asthma was characterized by: a correlation between ECP levels and eosinophil counts (r = 0.618, p = 0.014); a correlation between neutrophil number and IL‐8 levels (r = 0.747, p = 0.002); and increasing IL‐8 levels with symptom score (p = 0.03). In infantile wheezers, IL‐8 levels were poorly related to neutrophil number but were significantly increased when neutrophils were > 10%. Although detectable levels were found in all but one symptomatic infant, IL‐8 concentrations did not reflect the symptom score in infantile wheeze. ECP was unexpectedly correlated to neutrophil percentages (Rho = 0.832, p = 0.001), and a threshold of ECP > 20 ng/ml was associated with persistent symptoms in these infantile wheezers. Hence, in accordance with BALF cellularity, activation of eosinophils was suggested by raised levels of ECP in childhood asthma, but not in infantile wheeze. Neutrophil‐mediated inflammation appeared to better reflect the severity of asthma than that of infantile wheeze. Although its meaning remains to be elucidated, ECP was suggested to be a helpful indicator of persistent infantile wheeze. However, its utility as a marker predicting ongoing asthma remains to be established.     

Analysis of sputum taken from wheezy and asthmatic infants and children, with special reference to respiratory infections

Children who are destined to develop asthma are considered to be susceptible to a variety of respiratory pathogens. To elucidate respiratory inflammation among these children, we measured the levels of eosinophil cationic protein (ECP) and tryptase in sputum taken from three different groups of wheezy infants and young children: those with a first wheeze (n = 15); those with recurrent wheeze (n = 27); and those with recurrent wheeze with respiratory distress, namely asthma (n = 56). The numbers of eosinophils or metachromatic cells determined by microscopic analysis of sputum samples were also evaluated in combination with the ECP and tryptase levels. Although neither sputum ECP nor tryptase was a clear discriminative marker that differentiated the three different types of wheezy disease, ECP levels in sputum from the asthma group were significantly higher (2,269.2 ± 6,216.8 ng/g) than those in the recurrent wheezy group (440.3 ± 1,199.8 ng/g) or in the first‐wheeze group (209.0 ± 172.9 ng/g). A similar trend was observed with tryptase levels in sputum, but there were no significant differences among the three groups. Sputum taken from asthmatic children showed a marked accumulation of eosinophils. However, an accumulation of eosinophils in sputum (even in the presence of an elevated level of sputum ECP) was not identified in the asthmatic infants < 1 year of age. An accumlation of eosinophils in sputum was not evident until children became > 1 year old and thereafter the eosinophils rapidly increased in number until the children reached 5 years of age. It was noteworthy that sputa positive for pathogenic bacteria, taken from the 1‐ and 2‐year‐old asthmatic infants, had a tendency to show high levels of ECP but a reduced number of eosinophils. Along with the wheezy episodes induced by viral infection, primarily and occasionally in combination with secondary bacterial infection, eosinophil activation and infiltration may develop. These predestined immune reactions to various pathogens might be associated with triggering the onset of asthma.     

Screening for PTLD in lung and heart-lung transplant recipients by measuring EBV DNA load in bronchoalveolar lavage fluid using real time PCR

Abstract:  Pediatric L-HLTx recipients are at risk for developing PTLD with the lung being a primary site of disease. We hypothesized that BALF is a better sample than peripheral blood for measuring EBV DNA load in this high-risk population. Archived BALF specimens from pediatric L-HLTx recipients with and without PTLD were assayed for EBV DNA load using a quantitative real time TaqMan PCR assay. These values were compared with values determined in peripheral blood by a competitive PCR assay. Fifty-five BALF specimens from 16 L-HLTx patients were evaluated. Three patients with PTLD had mean BALF EBV DNA load values almost 50-fold higher than subjects without PTLD (4.6 × 10⁵ copies/mL vs. 1.0 × 10⁴ copies/mL). Patients who were EBV seronegative pretransplantation (i.e., high risk for PTLD) had elevated EBV DNA load values vs. patients who were EBV seropositive pretransplantation, regardless of the diagnosis of PTLD (mean values of 3.2 × 10⁵ copies/mL vs. 1.1 × 10⁴ copies/mL). Lastly, BALF analysis identified all subjects with PTLD, whereas peripheral blood analysis identified only one of these cases. Therefore, it can be concluded that monitoring EBV DNA load in BALF following L-HLTx facilitates detection of PTLD in high-risk patients and may be superior to peripheral blood assays.     

Increased bronchoalveolar lavage CD8 lymphocyte subset population in wheezy infants

Episodes of wheezing are very common in infancy but, despite their high prevalence, their mechanism is still poorly understood. To better understand the airway inflammation of wheezing infants, we examined cells of the bronchoalveolar lavage (BAL), focusing on the phenotype of lymphocytes and macrophages by using cytofluorimetry. Twenty-one wheezers (mean age 15.4 months) and seven non-wheezers (mean age 24.1 months) were studied. BAL was collected at fiberoptic bronchoscopy. Total and differential cell counts were similar in both populations. Eosinophils were not detected in the BAL fluid. The cell-surface markers CD2, CD3, CD4, CD7, CD8, CD19, and CD45 were studied for the lymphocyte sub-population analysis. The cell-surface markers CD14, CD54, CD62L, and human leucocyte antigen (HLA)-DR were studied for the macrophage sub-population analysis. A significant increase in the CD8⁺ lymphocyte population (p = 0.03) was observed in wheezers (median 43.1%, 25–75% percentile: 30.1–54.9%), as compared to non-wheezers (median 29.3%, 25–75% percentile: 13.5–34.7%). A significantly (p = 0.04) decreased expression of HLA-DR (mean fluorescence intensity [MFI]) was detected in the macrophage population of the wheezers (median MFI, 7,016; range 2135–7986), as compared to non-wheezers (median MFI, 8,369; range: 6478–8860). The results of the present study suggest that viral infection may have induced a CD8⁺ response in BAL cells.     

Neutrophil but not eosinophil inflammation is related to the severity of a first acute epidemic bronchiolitis in young infants

Acute bronchiolitis is the main cause of emergency visits and hospitalizations in infants. Recent data suggest that neutrophil- and eosinophil-mediated inflammations were part of bronchiolitis pathophysiology. Apart from the defined risk factors, few was known on the underlying pathophysiology, which might point out the differences observed in the severity of the disease. The aim of this study was to assess whether the clinical severity of acute epidemic bronchiolitis in young infants might be related to a specific underlying inflammatory process. Total and differential cell counts, IL-8, eotaxin, eosinophil cationic protein (ECP) and albumin levels were assessed at the time of admission in bronchial secretions from 37 infants (median age 17 wk) with acute bronchiolitis. Outcome severity variables were: hypoxemia, Silverman score, tachypnea, feeding alteration, and duration of hospitalization. Neutrophils predominated, and eosinophils were present in 54% of the infants. IL-8 levels strongly correlated with ECP and albumin levels. Albumin levels were correlated with ECP and eotaxin levels. IL-8 levels were higher in infants with hypoxemia and inversely related with SaO₂ levels. IL-8 and albumin levels significantly rose with respiratory rate, and Silverman score. IL-8, albumin and ECP levels were significantly higher in infants hospitalized ≥7 days. Furthermore, IL-8 levels were correlated with the duration of hospitalization. Neither cell counts nor eotaxin levels were related to the severity criteria studied. This study suggests that IL-8-associated airway inflammation significantly contributed to the severity of acute epidemic bronchiolitis.     

Unrelated cord blood transplantation in children with severe congenital neutropenia

Abstract:  SCN is an inherited hematological disorder with severe neutropenia and recurrent infections. Although there are some reports that recombinant rhG-CSF improves clinical outcome, allogeneic HSCT appears to be the only curative treatment for these patients. We report here two children with SCN successfully treated by CBT from unrelated donors. They were refractory to rhG-CSF treatment and have no identical family donor. Bu + CY were given as conditioning. Case 1 and Case 2 received 6/6 and 5/6 HLA-matched unrelated umbilical cord blood, respectively. The number of infused nucleated cells was 6, 18 × 10⁷/kg and CD34⁺  cell number was 3, 74 × 10⁵/kg in Case 1. Those cell numbers were 8, 8 × 10⁷/kg and 5, 34 × 10⁵/kg for Case 2, respectively. Neutrophil/platelet engraftments were 45/49 days in Case 1 and 24/36 days in Case 2. Grade II cutaneous acute GVHD was seen in Case 2 that was treated successfully with prednisolone. Both patients are well with normal hematological findings and full donor chimerism for post-transplant 20 and 24 months, respectively. We conclude that UCB can be considered as a safe source of stem cell in patients with SCN who need urgent HSCT.     

Eosinophilia in premature infants: correlation with chronic lung disease

We attempted to clarify the possible pathophysiological significance of eosinophilia in bronchopulmonary dysplasia (BPD). The subjects studied were 17 premature infants, i.e. seven with respiratory distress syndrome (RDS) followed by bronchopulmonary dysplasia (the BPD group: four with stage IV and three with stage III BPD) and 10 infants without BPD (the non-BPD group), who comprised seven with RDS, two with meconium aspiration syndrome and one with transient tachypnea of the newborn. Peripheral eosinophil counts, the number of nuclei of eosinophils and serum eosinophilic cationic protein (ECP) levels, and ECP and polymorphonuclear leukocyte (PMN) elastase levels of intratracheal aspirates (TA) were determined once a week during the first 4 weeks of life. Peripheral eosinophil counts were higher in infants with BPD than those in the non-BPD group. Hypersegmented nuclei of peripheral eosinophils with more than four nuclei were more frequently present in the infants with BPD. A good correlation was observed between peripheral eosinophil counts and serum ECP levels. ECP levels of the TA in the infants with BPD were significantly elevated. There was a good correlation between ECP and PMN elastase levels of the TA. Lung tissue specimens of two infants of the BPD group, both of whom had patent ductus arteriosus (PDA), were obtained from the lower portion of the left lung when they underwent an operative procedure for PDA at 24 and 25 days of life, respectively. Immunohistochemical staining of eosinophil-derived granular major basic protein (MBP) was performed on the lung tissue specimens. Infiltration of a few MBP-staining eosinophils was observed on the specimens from both infants. Our results suggest that peripheral eosinophils in sick premature infants may be activated and appear to be correlated with the severity of BPD. Further studies will be needed to more clarify the physiological role of eosinophils in premature infants.     

Expression of chemokine receptor CX3CR1 in infants with respiratory syncytial virus bronchiolitis

Respiratory syncytial virus (RSV) glycoprotein G mimics fractalkine, a CX₃C chemokine, which mediates chemotaxis of leukocytes expressing its receptor, CX₃CR1. The aim of this study was to examine the relationship between RSV infection and expression of perforin and IFN- γ in CX₃CR1-expressing peripheral blood CD8⁺ T cells. Samples were collected from infants with RSV bronchiolitis, both in the acute and convalescence phase (n = 12), and from their age- and sex-matched healthy controls (n = 15). Perforin expression and IFN- γ secretion in CX₃CR1⁺ CD8⁺ T cells were assessed by four-color flow cytometry. The NF- κ B p50 and p65 subunit levels were also determined as markers of RSV-induced inflammation. Study results showed perforin and CX₃CR1 expression to be significantly lower in the convalescent phase of infected infants than in healthy controls. There was no significant difference in IFN- γ secretion and NF- κ B binding activity between two time-points in RSV-infected infants, or when compared with healthy controls. Infants with prolonged wheezing had lower acute-phase CX₃CR1 levels in peripheral blood. These data indicate existence of an event persisting after acute RSV infection that is able to modulate effector functions of cytotoxic T cells, and also link disease severity with CX₃CR1 expression.     

Factors that influence vocabulary development in two-year-old children

Background:  This research explored the relative impact of demographic, cognitive, behavioural, and psycholinguistic factors on vocabulary development in two-year-old children.
Methods:  Two hundred and thirty-two children (24–30 months) were tested on expressive and receptive vocabulary, cognitive development, word learning and working memory skills. Parents completed a British adaptation ( Klee & Harrison, 2001 ) of the MacArthur–Bates Communicative Development Inventory (CDI; Fenson et al., 1993 ), a demographic questionnaire and a questionnaire regarding the child's social-emotional behaviour.
Results:  Several demographic, child and processing variables were significantly correlated with CDI (vocabulary) scores, but the only significant unique predictors of CDI scores were nonword repetition (NWR; R ² change = .36), sex ( R ² change = .05) and age ( R ² change = .04). Scores were only included when a child completed the entire NWR test (77% of toddlers).
Conclusions:  The NWR task used in this experiment maximised participation in this group of toddlers, and was a strong predictor of vocabulary ability. Longitudinal research is warranted to explore the independent and reciprocal growth in working memory and language skills in children.     

Peripheral blood eosinophil counts and eosinophil cationic protein content of respiratory secretions in bronchiolitis: relationship to severity of disease

Infants and young children with acute viral respiratory illness were studied to determine the association of peripheral blood eosinophil counts and concentrations of eosinophil cationic protein (ECP) in nasopharyngeal secretions with the development and severity of bronchiolitis. Subjects included those with upper respiratory illness (URI) alone, pneumonia or bronchiolitis. Controls consisted of healthy infants, and those hospitalized with non-respiratory illnesses. While peripheral blood eosinophil counts were suppressed in all infected infants greater than two months of age, eosinophil counts in patients with bronchiolitis were significantly greater than in those with URI alone. ECP concentrations were significantly greater among individuals with bronchiolitis than other infected infants. For bronchiolitis cases with detectable peripheral blood eosinophils, eosinophil counts correlated weakly and inversely with oxygen saturations. In contrast, ECP concentrations were strongly inversely correlated with initial oxygen saturation. ECP concentrations were also significantly correlated with peripheral blood eosinophil counts. Viral infections suppress peripheral blood eosinophil counts in infants greater than two months of age, although the effect is somewhat overcome in patients with bronchiolitis. The form and severity of bronchiolitis is much more strongly related to degranulation of eosinophils in the respiratory tract than to peripheral blood eosinophil counts.     

Early intervention with suplatast tosilate for prophylaxis of pediatric atopic asthma: A pilot study

The onset of asthma may be related to Th2 cytokine dominance at the time when food allergies occur several months after birth. This study investigated the effectiveness of early intervention with a Th2 cytokine inhibitor (suplatast tosilate) for prevention of asthma in infants with food allergies and atopic dermatitis. Suplatast tosilate dry syrup (6 mg/kg daily) or a histamine H₁-blocker (ketotifen fumarate dry syrup: 0.06 mg/kg daily) was administered randomly to 53 infants with atopic dermatitis caused by food allergies. The primary endpoints were the incidence of asthma and the time to the onset of wheezing. The peripheral blood Th1/Th2 ratio, total IgE level, and eosinophil count were measured before and after treatment. After 24 months of treatment, the prevalence of asthma was significantly lower in the suplatast group (20.8%) than in the ketotifen group (65.6%, p < 0.01). Additionally, the time from the start of treatment to the initial episode of wheezing for infants who developed asthma was significantly longer in the suplatast group than the ketotifen group (p < 0.01). Furthermore, the eosinophil count was significantly decreased by suplatast treatment (p < 0.05), and there was a significant difference between the suplatast and ketotifen groups with respect to both the eosinophil count (p < 0.01) and the Th1/Th2 ratio (p < 0.05). The results of the present pilot study suggest that suplatast tosilate is useful for the primary prevention of wheezing and asthma in children.     

Eosinophil activation in preterm infants with lung disease

AIM: We investigated the role of eosinophils in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Fifteen preterm infants with BPD were compared to 13 preterms with respiratory distress syndrome (RDS) and to 16 healthy preterms. We assessed total eosinophil and neutrophil counts in venous blood samples and the levels of the eosinophilic activity markers eosinophilic cationic protein (ECP) and the cellular surface antigen (CD9). RESULTS: The eosinophil count was greater in BPD compared with RDS and healthy infants (1414 vs. 797 and 471 cells per microlitre, respectively, p = 0.03). ECP levels were elevated (34 vs. 12.8 and 9.8 microg/L, respectively, p = 0.002) and CD9 levels reduced (75 vs. 94 and 86 mean fluorescence intensity units, respectively, p = 0.01) in BPD compared with RDS and healthy infants, suggesting eosinophilic activation in BPD. These findings were not solely explained by differences between gestational age or birth weight of the different groups. ECP levels were positively correlated with the duration of oxygen supplementation in the BPD group. The eosinophil count fell promptly after steroid treatment was commenced in the BPD group. CONCLUSION: The findings suggest that BPD is linked to eosinophil activation, which might contribute to the pathogenesis.     

Asthma severity and inflammation markers in children

The relationship of airway inflammation with asthma severity remains unclear. Our aim was to correlate the results of recommended methods of assessment of inflammation with measures of asthma control, in children with a wide range of asthma severity. The study was a cross-sectional investigation of 58 children receiving a wide range of treatment, including 10 treated without regular maintenance therapy and 29 treated with high-dose inhaled corticosteroids (CS). Exhaled nitric oxide (NO), serum eosinophil cationic protein (ECP), and induced sputum (processed for eosinophil count and ECP level) were related to recent symptoms, lung function, and bronchial responsiveness. There was no significant correlation between the results of any method. Neither did any marker of airway inflammation relate to recent symptoms, unlike PC₂₀, which did. There was a significant, inverse correlation between the forced expiratory volume in 1 s ( FEV ₁) and both NO and sputum ECP ( r =−0.46, p=<0.001; r =−0.48, p=0.004, respectively). Sputum eosinophils were inversely related to the dose of methacholine that corresponded to a 20% fall in FEV ₁ (PC₂₀) ( r =−0.57, p=0.02). Serum ECP did not relate to any measure of asthma control. There was no association of any recommended inflammation markers with current symptoms and only a weak relationship between them and physiological measures. The place of these markers remains unclear and their use in clinical practice needs further investigation by long-term longitudinal studies.     

喘息婴幼儿鼻咽分泌物嗜酸粒细胞与血清特异性IgE的关系分析

目的 探讨婴幼儿喘息时鼻咽分泌物涂片中嗜酸粒细胞计数及与血清特异性IgE的关系.方法 选择2002-2004年收治的1个月～3岁的喘息及支气管肺炎患儿223例,分为3组,其中反复喘息(包括婴幼儿哮喘和喘息发作≥2次)组76例,毛细支气管炎组65例,支气管肺炎(无喘息症状)组82例.吸取鼻咽分泌物1ml进行嗜酸粒细胞计数,并测定血清特异性IgE的水平.结果 反复喘息组鼻咽分泌物嗜酸粒细胞计数明显高于其他两组,差异有统计学意义(P=0.000);反复喘息组血清食物变应原(fx5E)的阳性检出率及吸入性变应原(Phadiatop)阳性检出率均明显高于其他两组,差异有统计学意义(P=0.000),毛支组和支气管肺炎组之间差异则无统计学意义;血清特异性IgE与鼻咽分泌物嗜酸粒细胞计数之间存在显著正相关;鼻咽分泌物嗜酸粒细胞水平在同时存在喘息和特应性的患儿最高,在既没有喘息也无个人特应性的患儿最低,有喘息或血清IgE一项者介于两组之间.结论 鼻咽分泌物嗜酸粒细胞计数方法操作简单、无创、快速,费用低,且能在一定程度上反映哮喘的病理特征,与血清特异性IgE之间呈正相关,可以在临床进一步推广应用.     

Neonatal Bacteriuria — The Value of Bladder Puncture in Resolving Problems of Interpretation Arising from Voided Urine Specimens

Neonatal Bacteriuria — The value of bladder puncture in resolving problems of interpretation arising from voided urine specimens. During a study of neonatal bacteriuria in 1460 infants born consecutively it was found that 76% had either sterile urine, or less than 10 × 10⁶organisms/1 (10,000 organisms/ml) in a single 'clean catch' specimen.
To establish the level of bacteriuria in voided specimens which correlates with bacteriuria obtained by aspirating urine suprapubically, check bladder punctures were carried out. This was done in infants with varying levels of colony counts obtained from voided specimens. No bladder puncture specimens showed evidence of infection when the colony count on the voided urine culture was less than 10 × 10⁶organisms/1. When the colony count on the voided urine culture was between 10 and 100 × 10⁶organisms/1, 2.2% of bladder puncture urines showed evidence of infection. When the voided urine colony count exceeded 100 × 10⁶organisms/1, 11.1% of bladder punctures showed evidence of infection. There was no significant correlation between baoteriuria and pyuria or proteinuria.
While repeated collection and culture of 'clean catch' urines may reduce the Ca fusion due to contaminated specimens, this approach can be time consuming. It is recommended that if the colony count on a carefully collected 'clean catch' specimen exceeds 10 × 10⁶organisms/1, or if the infant has symptoms suggestive of infection, bladder puncture should be performed.     

Transfusion-associated fall in platelet count in very low birthweight infants

Abstract Thirty-three infants with a birthweight of less than 1500 g were investigated retrospectively for the incidence and aetiology of thrombocytopenia occurring during the first week of life. The platelet count fell below 100 × 10⁹/l in 16 infants (48%). There was a moderately strong inverse correlation between the platelet count at its nadir during the first week or the first value below 100 × 10⁹/l and the percentage of blood volume transfused prior to this ( r =−0.61; P < 0.0001). When the platelet count was expressed as a percentage of the initial count the correlation was −0.74 ( P < 0.0001). The results were not affected by the elimination of the 10 infants with clinical conditions regarded as a probable cause of thrombocytopenia. The fitted least-squares regression line suggests that a transfusion equal to 10% of the blood volume on average reduced the platelet count by 19 × 10⁹/l or by 7% in these very low birthweight infants during the first week of life.     

Steroid-sensitive indices of airway inflammation in children with seasonal allergic rhinitis

Previous studies involving adults have demonstrated that airway glucocorticosteroids inhibit plasma exudation and eosinophil activity in allergic rhinitis. This study explores the possibility that plasma exudation, exudative responsiveness, and the occurrence of eosinophil activity-related proteins are glucocorticosteroid-sensitive nasal mucosal indices in allergic children. Using a placebo-controlled, parallel-group design effects of nasal budesonide (64 µg per nasal cavity b.i.d) were determined in children with seasonal allergic rhinitis. Nasal lavage fluid levels of eotaxin, eosinophil cationic protein (ECP), and α₂-macroglobulin, indicating plasma exudation, were determined, the latter with and without challenge with topical histamine. Nasal lavage fluid levels of α₂-macroglobulin and ECP increased significantly during the pollen season, and the acute plasma exudation response to histamine was significantly greater during than outside the season. There was a trend towards a seasonal increase in nasal lavage fluid levels of eotaxin. Budesonide significantly inhibited the seasonal increase in α₂-macroglobulin as well as the exudative hyperresponsiveness to histamine. Any tendency of increases in mucosal output of eotaxin and ECP was abolished by the glucocorticosteroid treatment. We conclude that mucosal exudation of plasma, as a global sign of active inflammatory processes, is a glucocorticosteroid-sensitive facet of allergic rhinitis in children. Exudative hyperresponsiveness, potentially caused by several weeks of mucosal inflammation, emerges as a significant feature of allergic rhinitis in children, and its development is prevented by local treatment with a glucocorticosteroid drug. The seasonal increase in ECP and the trend for an increase in eotaxin were absent in the glucocorticosteroid-treated subjects.     

Eosinophil counts and urinary eosinophil protein X in children hospitalized for wheezing during the first year of life: prediction of recurrent wheezing

Early identification of wheezing children with an increased risk of recurrent wheezing or subsequent asthma is important. The aim of the study was to determine the role of markers of eosinophil activation, along with other parameters, in the prediction of recurrent wheezing and allergic sensitization in children with early and severe wheezing. We examined 105 children without atopic dermatitis, hospitalized for wheezing during the first year of life. At a 20-mo follow-up, 101 of the children were assessed for the occurrence of recurrent wheezing (at least 3 episodes, including 1 in the previous 6 mo) and allergic sensitization (positive skin-prick test). By univariate analysis, levels of eosinophil counts at the time of hospitalization (p = 0.005, OR = 18.9), age in months (p < 0.0001, OR = 1.5), respiratory syncytial virus (RSV)-negative disease (p < 0.0001, OR = 8.8), parental atopy (p = 0.006, OR = 3.3) and male sex (0.02, OR = 2.7) were all predictive factors for recurrent wheezing at follow-up. With all parameters included in a multiple regression analysis, RSV-negative disease was not a predictive factor for recurrent wheezing. A simple model including eosinophil counts > or = 0.1 x 10(9)/L and age had a predictive accuracy of 79%, with only a 6% chance of a child being wrongly predicted as symptomatic. Urinary protein X (U-EPX) was not a predictive factor for recurrent wheezing. When included in a multiple logistic regression analysis, a level of U-EPX > or = 100 microg/mmol creatinine was the only parameter with a positive predictive value for allergic sensitization (p = 0.007, OR = 18.9), whereas age, parental allergy or parental asthma were not. CONCLUSION: Children with severe wheezing during the first year of life and subsequent recurrent wheezing are characterized by a normal or high eosinophil count in response to viral infections.     

Wheezing in early life and asthma at school age: Predictors of symptom persistence

Early childhood wheezing is associated with asthma later in life. However, the high spontaneous recovery rate and the lack of firm predictors for persistence of wheezing complicates the development of evidence-based guidelines for long-term management of wheezy infants and toddlers. Our aim was to define variables that could be used to identify wheezy individuals younger than 3 years of age who would continue to be symptomatic at school age. The method used was a questionnaire-based cross-sectional survey of 2027 randomly chosen, 6–13-year-old school children. Altogether 1829 (90%) questionnaires were returned. Emergency medical care had been sought for 186 (10.2%) children for wheezing during the first 3 years of life, and only 17.2% of these children had received similar emergency treatment during the 12 months preceding the survey. The total proportion of children with current asthma at school age was 11.4%. A logistic regression analysis indicated that for the early wheezers, a family history of asthma, an itchy rash or food allergy, and exposure to tobacco smoke at home before the age of 3 years, were all independently associated with symptom persistence until school age. Among all wheezy children younger than 3 years, those who have a history of food allergy, itchy rash, asthma occurrence in a sibling or parent, or are exposed to tobacco smoke during the first years of life are at highest risk for symptom persistence until school age.     

喘息婴幼儿外周血气道炎症相关介质水平的研究

目的 通过检测喘息婴幼儿外周血相关炎症介质水平,从辅助性T细胞（Th）1/Th2失衡及气道炎症两个方面探讨婴幼儿喘息发生的可能机制。方法 选取急性喘息发作婴幼儿50例为喘息组,25例健康婴幼儿为健康对照组。喘息组患儿依据喘息发生次数分为首次喘息组（首发组）25例和反复喘息组（反复组,发作次数≥ 2次）25例;根据是否存在哮喘发生的高危因素分为有高危因素组22例和无高危因素组28例;根据病原学检测结果分为病原学阳性组23例和病原学阴性组27例。检测各组外周血Th1细胞因子白介素（IL）-2,Th2细胞因子IL-4、IL-5、IL-13、转化生长因子-β1（TGF-β1）,以及总IgE （TIgE）水平。喘息组患儿同时送检外周血嗜酸性粒细胞（EOS）计数,并采集标本进行呼吸道病原学检测。结果 喘息组外周血IL-4、IL-5、IL-13、TGF-β1及TIgE水平较健康对照组均明显升高（P < 0.05）;外周血IL-2、IL-4、IL-5、IL-13、TGF-β1及TIgE水平在首发组与反复组,有哮喘高危因素组与无哮喘高危因素组,以及病原学阳性组与病原学阴性组之间比较,差异均无统计学意义（P > 0.05）。相关性分析表明喘息组外周血EOS计数与IL-4水平呈正相关（P < 0.01）;IL-4水平与IL-5、IL-13水平呈正相关（P < 0.01）;IL-5水平与IL-13水平呈正相关（P < 0.01）;IL-2水平与TGF-β1水平呈正相关（P < 0.05）。结论 喘息婴幼儿存在Th1/Th2失衡,表现为Th2优势表达;IL-4、IL-5、IL-13、TGF-β1及IgE共同参与了婴幼儿喘息性疾病的发病过程。喘息婴幼儿存在气道炎症,与喘息发作次数、是否存在哮喘高危因素及病原学检测是否阳性无关。