Lavage Fluid Of Children Research Articles

IL-27 Levels in Bronchoalveolar Lavage Fluid in Children with Post-infectious Bronchiolitis Obliterans.

Pulmonary neutrophils may play a crucial role in the development of bronchiolitis obliterans (BO) following measles virus infection. IL-27 could potentially have a negative regulatory effect on the release of reactive oxygen species and cytotoxic granules in neutrophils. To investigate the levels of IL-27 in the bronchoalveolar lavage fluid (BALF) of children with post-infectious bronchiolitis obliterans (PIBO) and analyze the relationship between IL-27 levels and neutrophil proportions. A total of 24 children with PIBO were recruited for the experimental group, while 23 children with bronchial foreign bodies were included in the control group. Bronchoscopic alveolar lavage was performed in both groups. The levels of IL-27 in BALF were measured using enzyme-linked immunosorbent assay (ELISA). The proportions of neutrophils in BALF were determined by smear staining. The relationship between the levels of IL-27 in BALF and the neutrophil proportions was analyzed by the Pearson test. The levels of IL-27 in BALF were significantly lower in children with PIBO compared to children with bronchial foreign bodies (p<0.05). Additionally, the proportions of neutrophils in BALF were significantly higher in children with PIBO compared to children with bronchial foreign bodies (p<0.05). The levels of IL-27 were negatively correlated with the neutrophil proportions in BALF in children with PIBO (p<0.05), but not in children with bronchial foreign bodies (p>0.05). The present study suggests that a decrease in IL-27 may be associated with an increase in neutrophils in BALF and may contribute to the pathogenesis of PIBO.

Diagnostic Value of IP-10 Level in Plasma and Bronchoalveolar Lavage Fluid in Children with Tuberculosis and Other Lung Diseases.

Objectives: IP-10 has been proposed as a new diagnostic biomarker for Mycobacterium tuberculosis infection (MTBI). However, data on IP-10 concentration in bronchoalveolar lavage fluid (BALF) for pediatric tuberculosis are lacking. Aim: To determine IP-10 levels in unstimulated BALF and plasma in children with and without MTBI. Methods: IP-10 concentrations in BALF and plasma were measured in children hospitalized with suspected tuberculosis or other respiratory disease and scheduled for bronchoscopy. Thirty-five children were enrolled: 13 with suspected tuberculosis and 22 controls. The association between IP-10 and age was examined. Results: The IP-10 expression was increased in BALF compared to plasma (p = 0.008). We noticed higher BALF IP-10 levels in children with asthma, interstitial lung disease, and lung anomaly than in children with MTBI and other respiratory tract infections, but the differences were statistically insignificant. There was a moderate correlation between plasma and BALF IP-10 concentrations (rs = 0.46, p = 0.018). No correlation between IP-10 level and age was detected. Conclusions: IP-10 is detectable in unstimulated BALF in children with respiratory diseases, reaches higher concentrations in unstimulated BALF vs plasma, and does not correlate with age. However, it could not discriminate MTBI from other respiratory diseases.

Attenuated lncRNA NKILA Enhances the Secretory Function of Airway Epithelial Cells Stimulated by Mycoplasma pneumoniae via NF-κB.

The secretory function of airway epithelial cells is important in the pathogenesis of Mycoplasma pneumoniae pneumonia (MPP). To investigate the regulatory function of NKILA (nuclear factor-κB (NF-κB) interacting long noncoding RNA (lncRNA)) in MPP, we first detected NKILA as well as the concentration of interleukin 8 (IL-8) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid of children with MPP. Then, NKILA was knocked down in epithelial cells to investigate its effect on their secretory function. The results suggested that NKILA was downregulated in children with MPP, while IL-8 and TNF-α levels increased. Knockdown of NKILA in vitro promoted the inflammatory effects of Mycoplasma pneumoniae (MP) in epithelial A549 and BEAS-2B cells. Knockdown of NKILA promoted inhibitor of κBα (IκBα) phosphorylation and degradation, and NF-κB p65 nuclear translocation. Furthermore, RNA immunoprecipitation showed that NKILA could physically bind to IκBα in MP-treated A549 cells. Collectively, our data demonstrated that attenuation of NKILA enhances the effects of MP-stimulated secretory functions of epithelial cells via regulation of NF-κB signaling.

Broad range detection of viral and bacterial pathogens in bronchoalveolar lavage fluid of children to identify the cause of lower respiratory tract infections

BackgroundKnowledge on the etiology of LRTIs is essential for improvement of the clinical diagnosis and accurate treatment. Molecular detection methods were applied to identify a broad range of bacterial and viral pathogens in a large set of bronchial alveolar lavage (BAL) fluid samples. The patterns of detected pathogens were correlated to the clinical symptoms.MethodsBAL fluid samples and clinical data were collected from 573 hospitalized children between 1 month and 14 years of age with LRTIs, enrolled from January to December 2018. Pathogens were detected using standardized clinical diagnostics, with a sensitive, high-throughput GeXP-based multiplex PCR and with multiplex qPCR. Data were analyzed to describe the correlation between the severity of respiratory tract disease and the pathogens identified.ResultsThe pathogen detection rate with GeXP-based PCR and multiplex qPCR was significantly higher than by clinical routine diagnostics (76.09% VS 36.13%,χ2 = 8.191, P = 0.004). The most frequently detected pathogens in the BAL fluid were human adenovirus (HADV)(21.82%), Mycoplasma pneumoniae (20.24%), human rhinovirus (13.96%), Streptococcus pneumoniae (8.90%) and Haemophilus influenzae (8.90%). In 16.4% of the cases co-detection with two or three different pathogens was found. Viral detection rates declined with age, while atypical pathogen detection rates increased with age. Oxygen supply in the HADV and Influenza H1N1 infected patients was more frequent (49.43%) than in patients infected with other pathogens.ConclusionBroad range detection of viral and bacterial pathogens using molecular methods is a promising and implementable approach to improve clinical diagnosis and accurate treatment of LRTI in children.

Intraoperative Peritoneal Interleukin-6 Concentration Changes in Relation to the High-Mobility Group Protein B1 and Heat Shock Protein 70 Levels in Children Undergoing Cholecystectomy.

The aim was the evaluation of IL-6 concentration in peritoneal lavage fluid of children which underwent cholecystectomy to ascertain if there is a difference in early inflammatory response depending on the type of surgical approach (open vs. laparoscopy). The analysis of high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70) was performed to find out if the source of IL-6 was related to tissue damage. IL-6 concentration in peritoneal lavage fluid samples, obtained at the beginning and at the end of the laparoscopic (N = 23) and open cholecystectomy (N = 14), was tested with a routinely used electrochemiluminescence assay. The concentrations of HMGB1 and HSP70 were analyzed with the use of an ELISA method. Statistical analysis was performed using the STATISTICA PL release 12.5 Program. The differences were assessed using the Mann-Whitney U test and Wilcoxon matched pairs test. Correlations were studied by using the Spearman correlation test. Our results demonstrated significant peritoneal lavage fluid IL-6 concentration growth measured at the end of the cholecystectomy as compared to the beginning, regardless of the type of the procedure. IL-6 growth during open cholecystectomy was greater compared to laparoscopic cholecystectomy (62.51-fold vs. 3.19-fold). IL-6 concentration did not correlate with HMGB1 and HSP70, which indicate that the significant growth of this cytokine was not related to mechanical tissue damage due to surgical procedure. A clinical significance of the study could be related to the fact that the evaluation of IL-6 concentration in peritoneal lavage fluid may be useful to assess an early local inflammatory response.

Study on the significance of cytokine in bronchoalveolar lavage fluid in children with refractory mycoplasma pneumoniae pneumonia and the correlation with serum C reactive protein

Objective To explore the levels and clinical significance of MCP-4, IL-25, TNF-α and CysLTR-1 in bronchoalveolar lavage fluid(BALF)of children with refractory mycoplasma pneumoniae pneumonia(RMPP)and their correlation with serum C-reactive protein(CRP). Methods One hundred and nine children diagnosed as RMPP who underwent fiberoptic bronchoscopy in acute stage(course of disease within 2 weeks)were selected as the experimental group.According to the manifestations of mucosa, secretions and lumen under bronchoscope, the patients were divided into RMPP1 group(68 cases of severe pathological injury under bronchoscope)and RMPP2 group(41 cases of mild pathological injury under bronchoscope). They were divided into RMPP1 wheezing group(20 cases), RMPP1 non- wheezing group(48 cases), RMPP2 wheezing group(15 cases)and RMPP2 non-wheezing group(26 cases).15 children with non-mycoplasma pneumoniae pneumonia(NMPP)and non-wheezing lobar pneumonia in the same period were selected as control group 1.At the same time, 15 children without pneumonia underwent bronchial foreign body(FB)removal as control group 2.The levels of MCP-4, IL-25, TNF-α and CysLTR-1 in BALF of children in experimental group were determined by double antibody sandwich ELISA.Serum CRP, D dimer(DD), ALT and peripheral blood neutrophil percentage(N%)were also detected. Results (1)The levels of CRP, DD, ALT and N% in RMPP1 group with severe bronchoscopic manifestations were higher than those in RMPP2 group with relatively mild bronchoscopic manifestations(all P 0.05). (3)CRP was positively correlated with IL-25, MCP-4 and TNF-a(all P<0.05), but not with CysLTR-1. Conclusion (1)Clinical laboratory indicators such as CRP, DD, ALT and N% can assist in early identification of RMPP.The higher the above indicators, the more serious performance of RMPP under microscope.(2)Cytokines MCP-4, IL-25, CysLTR-1 and TNF-α all participate in the pathogenesis of RMPP, and may play an important role in the occurrence of wheezing and development of asthma in children induced by MP infection.(3)Serum CRP levels were positively correlated with the levels of IL-25, MCP-4 and TNF-α in BALF of RMPP wheezing children.Both MCP-4 and IL-25 selectively affected Th2-induced Th2 cells.CRP is associated with IL-25 and MCP-4 who mediated immune inflammation injury.It is speculated that CRP may also cause Th2-mediated immune inflammation injury by affecting Th2 cells. Key words: Refractory mycoplasma pneumoniae pneumonia; Electronic fiberoptic bronchoscope; Cell factor; C-reactive protein; Children

Multiplex PCR of bronchoalveolar lavage fluid in children enhances the rate of pathogen detection

BackgroundCulturing of bronchoalveolar lavage (BAL) fluid is a commonly used method for pathogen detection in pneumonia. However, the sensitivity is low, especially in patients pre-treated with anti-infective agents. The early detection of a pathogen is crucial for the outcome of respiratory tract infections. For bloodstream infections, a multiplex polymerase chain reaction (PCR) assay (SeptiFast®, SF) is available for improved pathogen detection from blood.ObjectiveThe aim of the present study was to determine whether the SF assay is applicable to the BAL of children with pulmonary infections and whether the frequency of pathogen detection is enhanced by the use of this multiplex PCR method.MethodsWe investigated 70 BAL samples of 70 children simultaneously by culture and multiplex PCR. The frequency of pathogen detection was compared.ResultsPathogens were detected more frequently by SF than by culture (83% vs. 31%; p < 0.001). This advantage was shown for immunocompetent patients (p = 0.001) as well as for immunocompromised patients (p = 0.003). The majority (38/44; 86%) of the Gram positive cocci were only detected by SF. Fungal organisms were detected in 7/70 patients (10%) by SF and in 2/70 (3%) by culture (p = 0.125).ConclusionCompared to conventional culture, the use of the SF assay on the BAL of children with pneumonia increases pathogen detection rates and therefore adds important information to guide anti-infective therapy.

Diagnostic Yield of Xpert MTB/RIF in Bronchoalveolar Lavage in Children with Probable Pulmonary Tuberculosis

To evaluate utility of Xpert MTB/RIF in bronchoalveolar lavage fluid in children with probable pulmonary tuberculosis. Children with probable pulmonary tuberculosis with negative smear and Xpert on induced sputum/gastric aspirate were subjected to bronchoalveolar lavage (BAL) for Xpert assay and mycobacterial liquid culture. Data of children <14 y undergoing bronchoscopy for suspected MDR-TB (n=12) were also analyzed. The sensitivity of Xpert in BAL fluid for diagnosis of probable and confirmed pulmonary tuberculosis was calculated with clinico-radiological diagnosis and culture as gold standards, respectively. Of 41 enrolled children, 24 (58.5%) had Xpert positive in BAL fluid and 11 (26.8%) had culture confirmed tuberculosis (BAL fluid;10; sputum,1). The sensitivity of Xpert in BAL fluid among probable and culture confirmed tuberculosis cases was 58.5% (24/41) and 81.8% (9/11), respectively. Xpert in bronchoalveolar lavage fluid has good sensitivity in both probable and confirmed pulmonary tuberculosis in children.

Associations between patient clinical characteristics and the presence of cytomegalovirus DNA in the bronchoalveolar lavage fluid of children with recurrent wheezing

BackgroundThis study aimed to investigate the occurrence of Cytomegalovirus (CMV) DNA in the Bronchoalveolar lavage fluid (BALF) of children with recurrent wheezing and to identify associations with certain patient clinical characteristics.MethodsIn this cross-sectional study, pediatric patients (age < 36 months) admitted to Soochow University Hospital with recurrent wheezing (≥ 4 episodes of wheezing per year) were enrolled in the study. Cytomegalovirus DNA from their BALF was detected by real-time PCR. Subpopulations of blood immunoglobulins and T lymphocytes were quantified. The clinical characteristics of patients with and without BALF CMV DNA were compared. Comparisons of non-normally distributed continuous variables between groups were made using the Mann-Whitney U-test. Comparisons of frequency distributions were made using the Chi-squared test. Spearman’s rank correlation coefficient was used to evaluate correlations between the number of CMV DNA copies and continuous variables.ResultsA total of 111 patients aged 4 to 36 months (median 14.0 (IQR 8.0–22.0) months) were enrolled on to the study. Cytomegalovirus DNA was detected in 51.4% of patients (n = 111) with recurrent wheeze and was more prevalent among those aged 12 to 36 months with a positive modified asthma predictive index (mAPI) (n = 38, median 23.5 (IQR 19.7–31.2) months) than in those of the same age group with a negative mAPI (n = 25, median 15.0 (IQR 13.0–19.0) months) (57.9% vs. 20.0%, p = 0.003). Bronchoalveolar lavage fluid CMV DNA copy number [median 7560 (IQR 1200–71,150) copies/mL] was positively correlated with the duration of hospitalization (r = 0.33, p = 0.013), and negatively correlated with patient age (r = − 0.41, p = 0.002) and the percentage of BALF eosinophils (r = − 0.38, p = 0.004).ConclusionsCMV infection or reactivation in children with recurrent wheeze is associated with certain clinical characteristics, including younger age and lower levels of BALF eosinophils. Higher CMV DNA copy numbers were associated with a longer duration of hospitalization. Further studies are needed to address whether specific antiviral treatment could be beneficial for BALF CMV positive patients.

The clinical significance of T-cell subset, cytokine levels in bronchoalveolar lavage fluid of children with mycoplasma pneumoniae pneumonia

Objective To explore the levels and clinical significances of T-cell subset, interleukin(IL)-6, interferon(IFN)-γ, and monocyte chemotactic protein(MCP)-1 in bronchoalveolar lavage fluid(BALF) of children with mycoplasma pneumoniae pneumonia(MPP). Methods Thirty-six children with pneumonia were admitted in our hospital from October 2014 to March 2016.They were divided into refractory mycoplasma pneumoniae pneumonia (RMPP) group (n=18) and MPP group(n=18). Sixteen cases with bronchial foreign body were selected as the control group.The levels of IL-6, MCP-1, IFN-γ and T-cell subset in BALF were detected by ELISA and alkaline phosphatase-anti-alkaline phosphatase(APAAP) bridging enzyme linked immunosorbent assay. Results (1)The levels of CD3+ and CD8+ T cells in BALF of MPP group and RMPP group were higher than those in the control group (P 0.05). (2) The level of IL-6 in acute phase of RMPP group was higher than that in the control group (P<0.05). The levels of IL-6 in acute phase of RMPP group and MPP group were both higher than that in recovery period (P<0.05, respectively). (3)The levels of IFN-γ in the acute phase of RMPP group and MPP group were higher than that in the control group, and the differences were statistically significant (P<0.05). The IFN-γ levels in acute and recovery phases of RMPP group were both significantly higher than those in MPP group respectively(P< 0.05). (4)The level of MCP-1 in BALF in control group was lower than those in the acute phase of RMPP group and MPP group(P<0.05). The level of MCP-1 in RMPP acute group was significantly higher than that in MPP acute group, and higher in acute phase than those in recovery phase both in two groups(P<0.05). Conclusion There are cell immune regulation and function disorders when children are infected mycoplasma pneumoniae.IL-6, IFN-γ and MCP-1 may participate in the pathogenesis of MPP, and more importantly, IFN-γ and MCP-1 may be the important indicator to forecast the severity of MPP. Key words: Mycoplasma pnuemoniae; Bronchoalveolar lavage fluid; T-cell subset; Cytokine,

Expressions of granulocyte-macrophage colony-stimulating factor and myeloperoxidase in bronchoalveolar lavage fluid in children with Mycoplasma pneumoniae pneumonia and its clinical significance

目的 检测肺炎支原体肺炎(MPP)患儿支气管肺泡灌洗液(BALF)中粒细胞巨噬细胞集落刺激因子(GM－CSF)表达水平，探讨其在MPP中的临床意义。 方法 收集2013年1月至2014年12月在苏州大学附属儿童医院呼吸科住院的40例MPP患儿BALF标本，30例患儿因病情治疗需要行第2次支气管肺泡灌洗，收集治疗后(恢复期)BALF标本，并采用酶联免疫吸附法检测GM－CSF和髓过氧化物酶(MPO)水平。同时收集患儿临床和实验室检查资料。以15例急性气管支气管异物患儿的BALF作为对照。 结果 MPP患儿BALF中性粒细胞分类高于对照组[(62.1±23.5)%比(4.5±3.3)%，t＝2.73，P<0.01]。肺炎支原体DNA高值组(≥ 1010 copies/L)白细胞总数[(9.7±4.2)×109/L比(6.4±2.2)×109/L，t＝2.131，P＝0.04]和中性粒细胞数[(6.9±3.4)×109/L比(3.6±1.2)×109/L，t＝2.599，P＝0.01]均高于肺炎支原体DNA低值组(<1010 copies/L)。MPP患儿BALF中GM－CSF[(153.8±36.4) ng/L比(23.0±25.7) ng/L, P<0.05]和MPO[(21.4±7.0) ng/L比(13.8±3.5)ng/L，P<0.05]水平均明显高于对照组。MPP患儿BALF中GM－CSF水平与热程(r＝0.42，P<0.05)及MPO水平均呈正相关(r＝0.75, P<0.05)。恢复期GM－CSF和MPO水平均明显降低(均P<0.05)。 结论 GM－CSF可能在儿童MPP发生发展中起重要作用，可作为疾病转归的有效预测指标之一。

Mycoplasma pneumoniae pneumonia coinfected with hypermastigote in 18 children

Objective To explore the clinical manifestations of hypermastigote detected from bronchoalveolar lavage fluid in children with mycoplasma pneumoniae pneumonia(MPP). Methods The clinical data from 18 cases(7 male cases, 11 female cases; the age raged from 5 months to 13 years; 13 case lived in rural cottage, 5 cases lived in town building; the course ranged from 2 to 60 days)of MPP coinfected with hypermastigote were retrospectively analyzed, including the symptomatic and physical examination data, laboratory test, chest imaging features, bronchoscopic manifestation imaging, treatment and prognosis.The clinical characteristics and treatment of MPP coinfected with hypermastigote were analyzed. Results Clinical symptoms showed that 18 cases had cough, 14 cases had fever and 4 cases had asthma; laboratory blood routine test detected that 13 cases had increased leukocytes, 5 cases with increased eosinophils; 11 cases with increased C reactive protein and 8 cases with increased erythrocyte sedimentation rate.Eleven of 18 cases received immunological examination, which showed that 3 cases had increased IgG, 2 cases with increased IgM, 5 cases with increased IgA, and 11 cases with decreased ratio of CD4 and CD8; bronchoalveolar lavage fluid test showed that 1 case had increased eosinophils and hypermastigote were detected in 18 cases.High density spotty shadow were seen in chest imaging.Mucosal congestion, attached with white sputamentum, longitudinal folds, floc floating and sputum bolt obstructing within the lumen were seen under the bronchoscopy.The macrolides antibiotics combined with metro-nidazole(5 cases received metronidazole lung lavage) were effective. Conclusions Hypermastigote is a new type pathogen isolated from the lower respiratory tract in Liaocheng.For patients with MPP who have unsatisfactory response, hypermastigote should be taken into account and combined with metronidazole in therapy for better effect. Key words: Hypermastigote; Mycoplasma pneumoniae pneumonia; Bronchoalveolar lavage fluid; Bronchoscope; Child

Levels of interleukin-6, interleukin-10 and T cell subsets in bronchoalveolar lavage fluid of children with refractory mycoplasma pneumonia

Objective To explore the interleukin (IL)-6, IL-10 and T cell subsets levels in bronchoalveolar lavage fluid (BALF) of children with refractory mycoplasma pneumonia. Methods A total of 53 children with refractory mycoplasma pneumonia were selected as the observation group, 30 children with bronchial foreign body in our hospital were chosen as controls during the same period. ABC-double antibody sandwich ELISA method was used to detect IL-6, IL-10 levels and the CD3+ , CD4+ and CD8+ T levels were measured by means of flow cytometry in BALF. Results The IL-6 and IL-10 levels in BALF of children in the observation group were (63.25±18.61) ng/ml, (31.83±8.33) ng/ml respectively, and they were significantly higher than those of the controls [(30.51±1.34) ng/ml, (11.01±2.91) ng/ml] (P<0.05, respectively). The percentage of CD3+ , CD4+ , CD8+ T cells and the ratio of CD4+ /CD8+ T cells in BALF of the observation group were (48.47±2.88)%, (21.16±6.29)%, (23.04±4.63)%, 0.94±0.33, respectively, and they were significantly lower than those of the controls [(64.24±3.06)%, (34.34±7.59)%, (26.71±5.29)%, 1.56±0.67] (P<0.05, respectively). Conclusion The IL-6, IL-10 levels in BALF of children with refractory mycoplasma pneumonia significantly increased, suggesting that cell-mediated immunity play an important role in the pathogenesis of refractory mycoplasma pneumonia. Key words: Refractory mycoplasma pneumonia; Mycoplasma; Lavage fluid; interleukin-6; interleukin-10; T cell subsets

The Role ofMycoplasma pneumoniaeInfection in Asthma

The Role of<i>Mycoplasma pneumoniae</i>Infection in Asthma

Lymphocyte Subsets in Bronchoalveolar Lavage Fluid of Children with Lung Infiltrates

Lymphocyte Subsets in Bronchoalveolar Lavage Fluid of Children with Lung Infiltrates

Microbiology of Bronchoalveolar Lavage Fluid in Children With Acute Nonresponding or Recurrent Community-Acquired Pneumonia: Identification of Nontypeable Haemophilus influenzae as a Major Pathogen

Precise etiologic diagnosis in pediatric community-acquired pneumonia (CAP) remains challenging. We conducted a retrospective study of CAP etiology in 2 groups of pediatric patients who underwent flexible bronchoscopy (FOB) with bronchoalveolar lavage (BAL); children with acute nonresponsive CAP (NR-CAP; n = 127) or recurrent CAP (Rec-CAP; n = 123). Procedural measures were taken to limit contamination risk and quantitative bacterial culture of BAL fluid (significance cutoff point, ≥ 10⁴ colony-forming units/mL) was used. Blood culture results, serological test results, nasopharyngeal secretion findings, and pleural fluid culture results were also assessed, where available. An infectious agent was detected in 76.0% of cases. In 51.2% of infections, aerobic bacteria were isolated, of which 75.0%, 28.9%, and 13.3% were Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, respectively. Most (97.9%) of the H. influenzae strains were nontypeable (NTHi). H. influenzae was detected in 26.0% of NR-CAP cases and 51.2% of Rec-CAP cases, whereas Mycoplasma pneumoniae was the predominant pathogen in the NR-CAP group (accounting for 34.9% of cases) but not in the Rec-CAP group (19.3%). Viruses were found in 30.4% of cases, with respiratory syncytial virus, parainfluenzaviruses, and influenzaviruses detected most frequently. Mixed infections were found in 18.9% of NR-CAP cases and 30.1% of Rec-CAP cases. A variety of microorganisms were isolated with frequent mixed infection. NTHi was one of the major pathogens found, especially in association with recurrent CAP, possibly because of improved detection with the FOB with BAL procedure. This suggests that the burden of pediatric CAP could be reduced by addressing NTHi as a major causative pathogen.

Airway molecular phenotypes in pediatric asthma

The review discusses what is known regarding airway molecular phenotypes in pediatric asthma, specifically biomarkers that have been studied and their relation to the various clinical phenotypes of asthma. Pediatric asthma is a complex and heterogeneous disease that consists of several clinical phenotypes. There have been numerous studies investigating inflammatory markers that would increase our understanding of the underlying pathogenesis of asthma as well as facilitate the discovery of therapies for these patients. Some of these biomarkers, such as exhaled nitric oxide, exhaled breath condensate, urine leukotriene E4 and induced sputum are less invasive measures of inflammation than obtaining bronchoalveolar lavage fluid in children. Although recent data reveal that some of these measures may be helpful in classifying and managing pediatric asthma, further studies are critically needed before any of these biomarkers are able to be routinely used in clinical asthma care. The search for noninvasive biomarkers to help elucidate specific underlying molecular phenotypes in pediatric asthma should be a continued priority as we work towards improved care and management of these children.

Cysteinyl‐leukotrienes in nasal lavage fluid in children with asthma

The aim of this study was to investigate repeatability of cysteinyl-leukotrienes (cys-LT) measurements in nasal lavage fluid (NLF) and to determine if cys-LT levels in NLF are related to asthma severity in children. As a second outcome, we investigated if cys-LT in NLF reflect lower airway inflammation as assessed by exhaled NO measurement. To assess the repeatability of cys-LT measurements, two NLF samples were obtained from eight healthy controls 24 h apart. Sixty-nine asthmatic children (mean age; range: 12.8; 7.3-17.7 yr), which were grouped according to asthma severity were studied cross-sectionally on one occasion. Cys-LT in NLF were analyzed using a specific enzyme immunoassay, exhaled NO, and pulmonary function parameters were measured. The coefficient of repeatability for the repeated cys-LT measurements was 1.45 pg/ml. Cys-LT levels in NLF differed significantly between asthma severity groups (p < 0.001): mild intermittent: [median (IQR)] 6.88 pg/ml (2.00-27.87); mild persistent: 21.09 pg/ml (4.50-84.67); and moderate persistent asthmatics: 36.41 pg/ml (11.03-118.40). Concentration of cys-LT in NLF and exhaled NO was positively correlated (r = 0.85; p < 0.001). In conclusion, concentration of cys-LT in NLF correlates with asthma severity in children and is related to lower airway inflammation.

Immunoglobulin levels in bronchoalveolar lavage fluid of children with chronic chest disease

Immunoglobulin levels in bronchoalveolar lavage fluid of children with chronic chest disease

The immunopharmacology of mild asthma

If cell numbers, activation state, or mediators, for example, can be correlated with some clinical measure of disease severity, a major effector role in the disease may be postulated. Mast cells, along with eosinophils and lymphocytes, are present in increased numbers in the airways of patients with asthma. Mast cell mediators are also increased in persons with allergies, with the concentrations of histamine, tryptase, and prostaglandin D 2 being proportional to the degree of airway obstruction and bronchial hyperresponsiveness. Increased numbers of activated mast cells and eosinophils (but not T cells or macrophages) were also found in bronchoalveolar lavage fluid in children. The mast cell is also known to release a range of cytokines (e.g., tumor necrosis factor–α and IL-4) that have various important functions, including upregulation of the endothelial adhesion molecules that are responsible for eosinophil recruitment from the microvascular circulation into the airways and subsequent activation. Mast cell staining for secreted IL-4 was found to be proportional to the infiltration of eosinophils and lower airway symptoms in patients with seasonal asthma, which is compatible with the concept that mast cells alone can sustain a continuing allergic inflammatory response. The mast cell proteases chymase and tryptase are also important for eosinophil recruitment and activation and for increasing mucus secretion and microvascular permeability. The evidence that the human mast cell is capable of releasing proteases and cytokines that have the capacity to initiate and maintain a chronic inflammatory response provides a mechanism whereby the clinical efficacy of nedocromil sodium in patients with chronic mild to moderate asthma can be explained. (J A LLERGY C LIN I MMUNOL 1996;98:S7-16.)