Exhaled nitric oxide in childhood asthma

Endogenous synthesis of nitric oxide (NO) and its presence in exhaled air was observed in various species including humans. Particularly high levels were found in adults with bronchial asthma, possibly because of the underlying pulmonary inflammatory activity. We studied oral and nasal exhaled NO by chemiluminescence in 47 children aged between 6 and 10 years. Thirty children had bronchial asthma, 17 were healthy controls. In asthmatic children oral exhaled NO was 13.4±1.4 parts per billion (ppb) (mean±SEM), nasal exhaled NO was 21.7±1.5 ppb. In healthy controls oral exhaled NO was 7.2±1.0 ppb, nasal exhaled NO was 18.2±2.2 ppb. Oral exhaled NO was significantly higher in asthmatic children compared to healthy controls (P=0.0017). Nasal exhaled NO did not differ significantly in the two groups. There was a significant negative correlation between oral exhaled NO and forced expiratory volume in 1 s (FeV₁). No significant correlation between oral or nasal exhaled NO and other markers of obstructive lung function impairment, oral minute ventilation, the body mass index and the presence of upper respiratory tract infection could be found.     

Exhaled nitric oxide in paediatric asthma and cystic fibrosis

Nitric oxide (NO) is present in exhaled air of humans. This NO is mostly produced in the upper airways, whereas basal NO excretion in the lower airways is low. Children with Kartagener's syndrome have an almost total lack of NO in nasally derived air, whereas adult asthmatics have increased NO in orally exhaled air. NO excretion was measured in the nasal cavity and in orally exhaled air in 19 healthy children, in 36 age matched subjects with asthma, and in eight children with cystic fibrosis. NO levels in orally exhaled air were similar in controls and in children with cystic fibrosis, at 4.8 (SD 1.2) v 5.8 (0.8) parts per billion (ppb), but were increased in asthmatic children who were untreated or were being treated only with low doses of inhaled steroids (13.8 (2.5) ppb). Nasal NO levels were reduced by about 70% in children with cystic fibrosis compared to controls and asthmatics. Measurements of airway NO release in different parts of the airways may be useful in non-invasive diagnosis and monitoring of inflammatory airway diseases.     

Decreased levels of nitrosothiols in the lower airways of patients with cystic fibrosis and normal pulmonary function

Airway S-nitrosothiols (SNOs) are naturally occurring bronchodilators. SNOs, nitrate, and nitrite were measured in bronchoalveolar lavage fluid of 23 patients with cystic fibrosis (CF) and mild pulmonary disease (aged 6-16 years) and 13 healthy children (aged 8-15 years). Concentrations of SNOs were decreased in the lower airways of patients with CF and mild pulmonary disease (median, range: 0, 0-320 nmol/L vs 80, 0-970 nmol/L) despite normal levels of the inert nitric oxide metabolites nitrate and nitrite (mean +/- SEM: 3.7 +/- 0.5 micromol/L vs 4.8 +/- 0.9 micromol/L). S-nitrosolation- mediated bioreactivities may be impaired by depletion of the CF airway SNO reservoir.     

Tryptase and IgE concentrations in the respiratory tract of infants with acute bronchiolitis.

It has been proposed that a specific IgE response contributes to the immunopathology of acute respiratory syncytial virus (RSV) bronchiolitis but previous work has been difficult to replicate. Indirect evidence that might support this contention was sought by measuring total IgE concentrations in bronchoalveolar lavage (BAL) samples obtained from intubated infants and by attempting to detect mRNA for IgE in cells obtained from both the upper and lower respiratory tract. Evidence of significant mast cell activation was sought by measuring tryptase concentrations in BAL fluid and serum. Detectable concentrations of IgE were found in two of seven BAL samples obtained more than five days after intubation and mRNA for IgE was demonstrated in three of six BAL samples and three of six samples obtained from the upper respiratory tract. Tryptase was detectable in 11 of 12 BAL samples with the two highest values detected on day 1. These values were raised compared with control samples but were not such to suggest that mast cell degranulation is the major contributor to the inflammatory process. These results suggest that IgE may be produced in the airways of infants in response to RSV infection. The relationships between IgE production, RSV infection, and symptoms of acute bronchiolitis remain obscure.     

Exhaled carbon monoxide in childhood asthma.

OBJECTIVES: Oxidative stress and inflammation induce the expression of heme oxygenase-1, which produces carbon monoxide (CO), and nitric oxide synthase, which produces nitric oxide (NO). Exhaled CO and NO levels are elevated in asthmatic patients and are decreased after corticosteroid treatment, suggesting that they may be useful as noninvasive markers of airway inflammation. STUDY DESIGN: We measured forced expiratory volume in the first second, PC(20), and exhaled CO and NO levels in 29 children (18 boys, mean age 11.5 +/- 0.53 years) with asthma of different severity and 40 nonsmoking children without asthma (21 boys, mean age 8.1 +/- 0.35 years). We also studied whether upper respiratory tract infections were associated with elevated exhaled CO. RESULTS: Exhaled CO levels (ppm) were significantly higher (2.17 +/- 0.21) in children with persistent asthma compared with those in children with infrequent episodic asthma (1.39 +/- 0.18, P <.05) and healthy children (1.01 +/- 0.12, P <.001). The CO levels in children with infrequent episodic asthma and the normal control group, however, were not different. In contrast, exhaled NO levels (ppb) were higher in children with persistent asthma (24.2 +/- 5.9, P <.001) and infrequent episodic asthma (14.5 +/- 3.73, P <.05) than in normal subjects (5.1 +/- 0.24), but no significant difference was seen between the 2 asthmatic groups. In healthy children with upper respiratory tract infections (n = 12), exhaled CO concentrations were significantly elevated (2.16 +/- 0.33) during the acute symptomatic phase. No correlation was found between exhaled CO and forced expiratory volume in the first second or PC(20). CONCLUSIONS: Noninvasive measurement of exhaled CO may provide complementary data for assessment of asthma control in children. However, elevated CO levels are nonspecific and may be found in association with an acute viral illness.     

先天性心脏病并肺动脉高压患儿痰液及血液亚硝酸盐/硝酸盐的变化

目的探讨围手术期先天性心脏病(CHD)患儿痰液及血清亚硝酸盐/硝酸盐(NO2-/NO3-)变化及体外循环转流(CPB)和术后、外源性吸入一氧化氮(NO)对肺血管的影响。方法选择CHD并肺动脉高压(PH)患儿36例(A组),CHD未并PH患儿30例(B组),无CHD患者32例(C组)。3组术前及A、B组术后分别测定痰液及血清NO2-/NO3-,A组术后分别经NO吸入及静脉予硝普钠30 min,26、h测定痰液及血液NO2-/NO3-。结果术前痰液及血液NO2-/NO3-A组明显低于B、C组,术后A、B组痰液及血清NO2-/NO3-均减低,吸入NO后痰液NO2-/NO3-增加明显。相关分析示吸入NO后痰液和血液NO2-/NO3-呈明显正相关。结论吸入NO治疗对CHD并PH患儿效果更明显,反映在痰液和血液变化基本一致,对局部肺组织中NO2-/NO3-变化研究,痰液较血清标本更具针对性。     

Factors predisposing to abnormal pulmonary function after adenovirus type 7 pneumonia.

Adenoviruses are well known causes of respiratory illness in children. Long term sequelae reported with types 3, 7, and 21 include bronchiolitis obliterans, bronchiectasis, and the hyperlucent lung or McLeod syndrome. Twenty children admitted to hospital with adenovirus type 7 pneumonia between 1960 and 1978 were studied and compared with 20 controls admitted during the same period with adenovirus type 7 upper respiratory tract infections. Sixty five per cent of the pneumonia group had developed evidence of airways obstruction compared with 10% of controls. Young age at the time of pneumonia and a ''measles-like'' illness before its onset increase the chance of developing long term pulmonary function abnormalities. Sex and family history of smoking or atopy do not influence outcome.     

Bacterial reservoirs in cystic fibrosis.

To establish whether colonisation of the upper respiratory tract or bacterial contamination of inhaler devices or solutions predisposes to colonisation of the lower respiratory tract in patients with cystic fibrosis, bacterial isolates from groups of children who were positive (n = 13) or negative (n = 18) for Pseudomonas aeruginosa were studied. Cultures of swabs from inhaler devices, toothbrushes, and upper airways were compared with cough swabs or sputum cultures. No pathogens were obtained from inhaler equipment administering unit dose medications. Upper airway carriage of Staphylococcus aureus and Haemophilus influenzae was identified in both groups but correlated poorly with sputum isolates. P. aeruginosa was found only in the upper respiratory tract of children with established colonisation of the lower airways. No P aeruginosa isolates were obtained from the upper airways of the group with negative sputum, including one patient who became colonised by P aeruginosa during the study. Our results did not support the suggestion that colonisation of the upper respiratory tract by P aeruginosa predisposes to colonisation of the lower airways. Failure to isolate pathogenic organisms consistently from the upper airways in patients with positive sputum argues against a local epithelial factor predisposing to bacterial colonisation.     

Role of Moraxella (Branhamella) catarrhalis as a respiratory pathogen in children

During a 12-month surveillance period in 1981-1982, Moraxella catarrhalis was detected in cultures from nasopharyngeal aspirates from 76 (17%) of 449 children hospitalized with middle or lower respiratory tract infection. Seroconversion to M. catarrhalis was positive in 4(5%) of the 76 patients with M. catarrhalis present in nasopharyngeal aspirates and in 4(1%) of 373 patients with a negative finding. Although children with respiratory tract infections were often colonized by the organism, this was rarely the infective agent of the middle or lower airways. Four of 8 patients with seroconversion to M. catarrhalis exhibited a concomitant RSV infection. The carriage of this species was more closely associated with parainfluenza virus infections. Serological responses to M. catarrhalis were not associated with acute otitis media, and were also rare in children with pneumonia. It is concluded that bronchopulmonary infections caused by M. catarrhalis are rare in children, and that M. catarrhalis aetiology need not be considered in the selection of antibiotics in cases of community-acquired pneumonia or other infections of the middle or lower respiratory tract affecting primarily healthy children.     

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??Bacterial pneumonia is the main cause of severe pneumonia in children. It is difficult to collect the samples of children’s respiratory tract infection??especially the acquisition of lower respiratory tract specimens is a challenge for the primary pediatricians??and it also affects the etiological diagnosis of children’s respiratory tract infection. Among children under 5??bacterial pathogens include Streptococcus pneumoniae??Staphylococcus aureus and Streptococcus pyogenes. Streptococcus pneumoniae infection is more common in healthy children aged 5 and above. The etiology of bacterial pneumonia in children was reviewed in this paper.     

Differential cytology of bronchoalveolar lavage fluid in immunosuppressed children with pulmonary infiltrates.

OBJECTIVE: Bronchoalveolar lavage (BAL) is a well established technique for the detection of pathogens in immunosuppressed children, but its diagnostic yield is variable. The aim of this study was to investigate whether BAL differential cell counts are helpful in the evaluation of pulmonary infiltrates in immunocompromised children. STUDY DESIGN: BAL was performed 28 times in 27 febrile immunocompromised children with pulmonary infiltrates. All patients were pretreated with broad spectrum antibiotics; 11 children also received amphotericin B. BAL was conducted with a flexible bronchoscope wedged in the area of maximal pathology as suggested by the chest radiograph or in the middle lobe in patients with diffuse interstitial radiographic changes. Differential cell counts were performed from cell smears obtained after centrifugation of BAL fluid. RESULTS: Bacterial or fungal organisms were detected in BAL fluid of 12 patients. Patients with bacterial or fungal infections (group 1) had a significantly higher percentage of granulocytes in BAL fluid both compared with patients with sterile BAL cultures (group 2) and with a control group of children without pulmonary disease (p < 0.001, Wilcoxon test). The proportion of lymphocytes was not different from the control group in group 1 but significantly increased in group 2 (p < 0.001, Wilcoxon test). Blood differential cell counts were not different in the two patient groups. Lymphocyte subsets of BAL fluid obtained in a subgroup of patients were not significantly different from controls. CONCLUSION: These data suggest that BAL differential cell counts may be a useful adjunct in the differential diagnosis of pulmonary infection in immunocompromised children.     

癫痫和热性惊厥病儿一氧化氮一氧化氮合酶的研究

目的　探讨癫痫 (EP)和热性惊厥 (FC)病儿血清和脑脊液 (CSF)一氧化氮 (NO)和一氧化氮合酶(NOS)的含量及其与EP和FC的发病机制的关系。方法　分别采用硝酸还原酶法、酶测定法测定EP和FC病儿惊厥发作后 2 4h内血清和CSFNO和NOS的含量。结果　EP组和FC组CSFNO水平均明显低于对照组 ,差异有显著性 (P <0 .0 5 ) ;而EP组和FC组血清NO水平均明显高于对照组 ,差异有显著性 (P <0 .0 5 )。FC组CSFNOS活性也明显低于对照组 (P <0 .0 5 )。结论　EP和FC病儿CSFNO水平明显低于对照组 ,提示NO可能与阻止惊厥发作有关 ,并可能有抗惊厥作用。FC病儿CSFNOS活性明显低于对照组 ,与FC病儿CSFNO水平下降一致 ,进一步支持NO在FC中可能有抗惊厥作用 ,这一结果可为EP的临床药物治疗和研制开发提供新的思路。     

The use of acoustic reflectometry in the study of middle ear effusion in children suffering from acute otits media,upper respiratory tract infection and in healthy children

This report focuses on the occurrence of middle ear effusion in children with acute otitis media (n = 62), upper respiratory tract infection (n = 81) as well as in healthy control children (n = 152). Data are reported in age categories 0–4 and 5–13 years. Middle ear effusion was found in 86% of children with acute otitis media, 49% of children with upper respiratory infection and 13% of healthy children. The younger the child, the more likely the presence of middle ear effusion in all groups. Acute otitis media and upper respiratory tract infection were clinically indistinguishable in infants. Conclusion Middle ear effusion is not generally a particularly significant clinical problem in children. Received: 31 January 1996 Accepted: 12 April 1996     

儿童细菌性肺炎的病原学

细菌性肺炎是儿童重症肺炎的主要原因,但儿童呼吸道感染的病原因年龄和感染场所的不同而不同。儿童呼吸道感染标本采集较为困难,尤其是下呼吸道标本的获取更是基层儿科医师面临的挑战,也影响儿童呼吸道感染病原学诊断。在5岁以下的儿童中,细菌病原体包括肺炎链球菌、金黄色葡萄球菌和化脓性链球菌较为重要。在5岁及以上健康儿童中,肺炎链球菌感染较为常见。该文对儿童细菌性肺炎的病原学进行了简述。     

Circulating adhesion molecules ICAM-1, E-selectin, and von Willebrand factor in Henoch-Sch?nlein purpura

OBJECTIVE: Bronchoalveolar lavage (BAL) is a well established technique for the detection of pathogens in immunosuppressed children, but its diagnostic yield is variable. The aim of this study was to investigate whether BAL differential cell counts are helpful in the evaluation of pulmonary infiltrates in immunocompromised children. STUDY DESIGN: BAL was performed 28 times in 27 febrile immunocompromised children with pulmonary infiltrates. All patients were pretreated with broad spectrum antibiotics; 11 children also received amphotericin B. BAL was conducted with a flexible bronchoscope wedged in the area of maximal pathology as suggested by the chest radiograph or in the middle lobe in patients with diffuse interstitial radiographic changes. Differential cell counts were performed from cell smears obtained after centrifugation of BAL fluid. RESULTS: Bacterial or fungal organisms were detected in BAL fluid of 12 patients. Patients with bacterial or fungal infections (group 1) had a significantly higher percentage of granulocytes in BAL fluid both compared with patients with sterile BAL cultures (group 2) and with a control group of children without pulmonary disease (p < 0.001, Wilcoxon test). The proportion of lymphocytes was not different from the control group in group 1 but significantly increased in group 2 (p < 0.001, Wilcoxon test). Blood differential cell counts were not different in the two patient groups. Lymphocyte subsets of BAL fluid obtained in a subgroup of patients were not significantly different from controls. CONCLUSION: These data suggest that BAL differential cell counts may be a useful adjunct in the differential diagnosis of pulmonary infection in immunocompromised children.     

Perfluorochemical liquids do not stimulate endothelin-1 or nitric oxide production in human blood leukocytes

The purpose of these studies was to examine if perfluorochemical (PFC) liquids stimulate blood leukocytes to secrete nitric oxide (NO) and/or endothelin-1 (ET-1). As such, NO and ET-1 may modulate broncho- and vascular dilatation and constriction, respectively, and thereby influence the clinical condition of a patient in respiratory distress with persistent pulmonary hypertension. Blood leukocytes in their natural habitat (whole blood) were incubated in the presence of two different perfluorochemicals (perflubron and perfluorodecalin). The overall response in ET-1 or NO (indirectly measured as nitrite/nitrate) production was examined at increasing PFC percentages (wt/vol) of PFC/whole blood. The lowest proportion used, 0.001% (wt/vol), was relevant to serum concentrations of PFC observed in liquid-ventilated individuals, whereas the highest proportion PFC, 50% (wt/vol), would mimic a situation where leukocytes are presented to PFC-filled airways. Plasma levels of freshly drawn blood, similar to levels of incubated (6 h) non-PFC-supplemented cultures, were ET-1 0.59 +/- 0.07 pg/ml (6 h, mean +/- SEM) and NO(-2)/NO(-3) 50 +/- 9 microM (6 h). Perflubron or perfluorodecalin did not induce significant differences in ET-1 or NO(-2)/NO(-3) levels as function of PFC type or dose. In conclusion, PFC liquids do not stimulate production in leukocytes in vitro of substances that may modulate constriction or dilatation in the vascular and respiratory tract systems.     

Latex and coagglutination test of serum and urine in childhood pneumonia

41 children with pneumonia (proven by X-ray) and 271 children with upper respiratory tract infections were examined for bacterial antigens (Haemophilus influenzae type b and pneumococci) in serum and urine. In patients with pneumonia blood cultures, deep nasal swabs and antibody assay in serum (against Mycoplasma pneumoniae and Chlamydia) were made. In 271 patients with an upper respiratory tract infection also a deep nasal swab for bacterial cultures was performed. In 29 of 41 patients with pneumonia latex agglutination test was positive (in 15 patients for Haemophilus antigen, in 14 patients for pneumococcal antigen). Coagglutination test was positive in 6 patients (in 1 patient for Haemophilus antigen, in 5 patients for pneumococcal antigen). In 12 patients latex agglutination was negative; there were other causes of pneumonia (partially viral infections). In 5 of 271 patients with an upper respiratory tract infection (purulent otitis media) latex agglutination was positive (4 times for Haemophilus, once for pneumococcal antigen). Bacteriological investigations confirmed the results of latex agglutination test in serum and urine. To avoid false positive reactions we recommend heating of serum to 65 degrees C, of urine to 100 degrees C for 5 min. Urine should be concentrated 25 times (there were 3 times more positive results than with unconcentrated urine).     

Exhaled and nasal nitric oxide in mechanically ventilated preterm and term newborns

AIM: Nitric oxide (NO) is an important mediator required for neonatal pulmonary circulatory adaptation and for pulmonary defence. Both deficient and excessive NO production have been proposed to play a role in neonatal lung disease. This study aimed to establish a method that allows direct measurement of exhaled and nasal NO concentrations in newborn infants who require intubation and ventilation. METHODS: A rapid-response chemiluminescence NO analyser was used. Gas was sampled from the endotracheal intubation tube, and tidal volumes and flow rates were measured. The nasal NO was sampled from the non-intubated nostril. The accuracy of the method was validated using a lung model. NO levels from six preterm and six term/near-term newborns were studied. Measurements were performed on a daily basis during the first week. RESULTS: An expiration >0.2 s in duration with a flow rate >1.7 ml s(-1) could be accurately analysed for the presence of >1 parts per billion of NO. The very preterm infants with neonatal lung disease had a different postnatal NO output pattern from the lower and upper airways compared with the ventilated term/near-term infants. CONCLUSION: A novel method for measurement of exhaled NO of an intubated newborn is presented. The possible association of exhaled NO concentration with the development of chronic lung disease remains to be studied.     

Coronavirus-associated pneumonia in previously healthy children

The extent to which coronaviruses are associated with lower respiratory tract disease in previously healthy children without underlying medical conditions is unknown. We investigated instances of radiographically confirmed lower respiratory tract disease among symptomatic children with coronavirus infection. Here, we document the clinical courses of 2 previously healthy children with coronavirus-associated pneumonia.     

Use of polymerase chain reaction for detection of adenovirus in children with or without wheezing

Eighty percent of asthma attacks in children are accompanied by an upper respiratory tract viral infection. Adenovirus is one of the major viral causes of childhood bronchiolitis. As the polymerase chain reaction (PCR) is the most sensitive technique for documenting viral respiratory infections, the PCR method was performed on the throat swab samples of asthmatic children with and without wheezing to investigate the presence of the adenovirus genome in the upper respiratory tract. The frequencies of adenovirus in asymptomatic and symptomatic asthmatic patients, healthy controls and wheezy children were as follows: 33.3%, 71.4%, 37% and 62.96%, respectively. The adenovirus was detected in a significantly higher percentage in the upper airways of patients with asthma exacerbation and in children with wheezing than in patients without asthma exacerbation and in the healthy controls (p < 0.05). The frequency of adenovirus was not different between asthmatic patients receiving or not receiving inhaled corticosteroid. Adenovirus has the potential to precipitate asthma exacerbations in asthmatic patients; its frequency was not affected by the treatment of inhaled corticosteroid.