Chlamydia pneumoniae-immunoglobulin E antibody responses in serum from children with asthma.

Chlamydia pneumoniae is an obligate intracellular bacterium that causes respiratory infections in humans. An association between persistent C. pneumoniae infection and asthma pathogenesis has been described. It is unknown whether specific immunoglobulin E (IgE) is a marker of persistent immune activation responses. Therefore, the association between C. pneumoniae-specific-IgE antibodies (Abs) and interferon (IFN)-gamma produced by C. pneumoniae-stimulated peripheral blood mononuclear cells (PBMC) was examined. Blood was collected and serum separated. PBMC from 63 children with or without stable asthma (N = 45 and 18, respectively) were infected or not infected with C. pneumoniae AR-39 and cultured for up to 7 days. Supernatants were collected, and IFN-gamma levels measured (ELISA). Serum C. pneumoniae-IgE Abs were detected by immunoblotting. C. pneumoniae-IgE Abs were detected in asthmatics (27%), compared with non-asthmatics (11%) (P = NS). IFN-gamma responses were more prevalent among asthmatics who had positive C. pneumoniae-IgE Abs (60%) compared with asthmatics without C. pneumoniae-IgE Abs (20%) (P = 0.1432). IFN-gamma responses in C. pneumoniae-stimulated PBMC from children with asthma were more frequent in children who had specific anti-C. pneumoniae-IgE Abs compared to those who did not. This immune response may reflect persistent infection, which may contribute to ongoing asthma symptoms.

Intravenous methylprednisolone versus intravenous methylprednisolone combined with inhaled budesonide in acute severe pediatric asthma.

INTRODUCTION: Corticosteroids are important part of acute severe asthma (ASA) management in pediatric intensive care units. Few studies look at the efficacy of inhaled corticosteroids (ICS) in critical care settings. We aimed to investigate the potential beneficial effects of ICS when added to intravenous corticosteroids in pediatric patients with ASA admitted to the pediatric intensive care unit (PICU). METHODS: This was a randomized controlled trial involving pediatric patients aged 1-21 years admitted to PICU with ASA. Patients were randomized into 2 groups using block randomization. Patients in Group A received intravenous methylprednisolone (2 mg/kg/day) alone and patients in Group B received intravenous methylprednisolone (2 mg/kg/day) plus budesonide nebulization (0.5 mg every 12 h). Main outcomes were duration of continuous albuterol treatment, PICU and hospital length of stay (LOS), and need and duration of respiratory support. Kruskal-Wallis and Chi-square tests were used for statistical analysis, in which a p-value < 0.05 was considered statistically significant. RESULTS: Duration of continuous albuterol treatment was not different between the 2 groups median/(QR), 30/(18-51) vs. 25/(14-49). (p = 0.38) PICU and hospital LOS between the 2 groups was similar, median/(QR), 44/(30-64) vs. 46/(30-62), (p = 0.75) and 78/(65-95) vs.72/(58-92), (p = 0.19). Number of patients requiring respiratory support was 22(58%) in Group A and 25(64%) in Group B (p = 0.19). CONCLUSIONS: In critically ill children with ASA, intravenous methylprednisolone combined with inhaled budesonide did not shorten the duration of continuous albuterol inhalation treatment, the PICU and hospital LOS, and the need for respiratory support.

The impact of adenotonsillectomy on pediatric asthma.

OBJECTIVE: To determine asthma outcomes in children undergoing adenotonsillectomy (T&A) for treatment of sleep-disordered breathing (SDB). HYPOTHESIS: Asthmatic children will demonstrate improvement in asthma control after T&A compared to asthmatic children not undergoing surgical treatment. STUDY DESIGN: Prospective cohort. PATIENT-SUBJECT SELECTION: 80 children with diagnosed asthma, aged 4-11, undergoing T&A and 62 controls matched to the T&A subjects by age, sex, and asthma severity classification. METHODOLOGY: Parents and children completed the Childhood Asthma Control Test (C-ACT) and the Pediatric Sleep Questionnaire (PSQ). Parents were queried regarding the number of asthma exacerbations, the frequency of the use of systemic steroids, the number of emergency room visits and the number of hospitalizations in the prior 6 months. The identical questionnaires and interviews were completed 6 months after entry. RESULTS: The adjusted mean (95% CI) C-ACT score was 21.86 (20.94-22.68) at entry and 25.15 (24.55-25.71) at follow-up for the T&A group compared with 22.42 (21.46-23.28) and 23.59 (22.77-24.33) for the control group. There was a significant group by time interaction (P < 0.001). Simple effects analysis showed that group means did not differ at entry (P = 1.00) but did differ at follow-up (P = 0.006). Baseline PSQ was a significant predictor of improvement in C-ACT scores. Statistical modeling did not demonstrate significant group by time interactions for any of the asthma clinical outcomes, although these outcomes were very infrequent in both groups. CONCLUSION: Treatment of SDB improves asthma outcomes as measured by the C-ACT.

Chlamydia pneumoniae-induced tumour necrosis factor alpha responses are lower in children with asthma compared with non-asthma.

INTRODUCTION: Chlamydia pneumoniae respiratory tract infection has been implicated in the pathogenesis of reactive airway disease and asthma. Innate cytokine responses that are protective of infection with intracellular pathogens may be impaired in patients with asthma. Tumour necrosis factor alpha (TNF-α) is a cytokine related to functions of monocytes and may inhibit C. pneumoniae infection. We investigated TNF-α responses in C. pneumoniae-infected peripheral blood mononuclear cells (PBMCs) in patients with asthma and non-asthma, and whether ciprofloxacin, azithromycin or doxycycline affects TNF-α responses. METHODS: PBMC (1.5×106) from paediatric patients with asthma (n=19) and non-asthmatic controls (n=6) were infected or mock infected for 1 hour with or without C. pneumoniae AR-39 at a multiplicity of infection=0.1, and cultured+ciprofloxacin, azithromycin or doxycycline (0.1 ug/mL) for 48 hours. TNF-α levels were measured in supernatants by ELISA. RESULTS: When PBMC from patients with asthma were infected with C. pneumoniae, levels of TNF-α were significantly lower than in subjects without asthma (48 hours) (5.5±5.6, 38.4±53.7; p=0.0113). However, baseline responses (no infection with C. pneumoniae) were similar in asthma and non-asthma (1.0±1.7, 1.1±1.2; p=0.89). When PBMC frompatiens with asthma were infected with C. pneumoniae+ciprofloxacin, azithromycin or doxycycline, TNF-α levels increased (25%-45%); this affect was not observed in PBMC from patients without asthma. CONCLUSIONS: We identified differences in the quantity of TNF-α produced by C. pneumoniae-infected PBMC in asthma compared with non-asthma.

Doxycycline suppresses Chlamydia pneumoniae induced interferon-gamma responses in peripheral blood mononuclear cells in children with allergic asthma.

Persistent respiratory infections caused by Chlamydia pneumoniae have been implicated in the pathogenesis of chronic diseases (e.g. asthma). Antibiotics are used to treat C. pneumoniae respiratory infections; however, the use of antibiotics as anti-inflammatory agents in treatment of asthma remains controversial. The current study investigated whether ciprofloxacin, azithromycin, or doxycycline can suppress C. pneumoniae-induced production of immunoglobulin (Ig) E or cytokines in peripheral blood mononuclear cells (PBMC) obtained from asthmatic children. Apart from blood, nasopharyngeal swab specimens were also collected to test for the presence of C. pneumoniae and/or M. pneumoniae (qPCR). PBMC (1.5 x 106) from asthmatic pediatric patients (N = 18) were infected or mock infected for 1 h ± C. pneumoniae AR-39 at a multiplicity of infection (MOI) = 0.1, and cultured ± ciprofloxacin, azithromycin, or doxycycline (0.1 or 1.0 µg/mLmL) for either 48 h (cytokines) or 10 days (IgE). Interleukin (IL)-4, interferon (IFN)-γ and IgE levels in supernatants were measured (ELISA). When PBMC were infected with C. pneumoniae, IL-4 and IFNγ production increased (p = 0.06 and 0.03, respectively); IgE levels were low. The now-elevated levels of IL-4 didn't decrease significantly after addition of ciprofloxacin, azithromycin, or doxycycline. However, infected PBMC IFNγ formation decreased significantly when 0.1 µg/mL doxycycline was employed (p = 0.04); no dose of ciprofloxacin or azithromycin had any impact. This inhibitory outcome with doxycycline lends support to the use of tetracyclines as immune modulators and anti-inflammatory medications in treatment of C. pneumoniae-infected asthma patients.

IgE anti-respiratory syncytial virus antibodies detected in serum of pediatric patients with asthma.

Respiratory syncytial virus (RSV) causes lower respiratory tract disease in infants and young children, and is a public health concern, as is the increase in pediatric asthma. Respiratory viral infections may trigger asthma exacerbations. However, it remains unknown whether RSV infection may have a specific association with asthma. Total serum IgE, and IgE- and IgG-anti-RSV Ab responses were studied in older asthmatic compared with non-asthmatic children (M/F, mean age: 14) (N=30, N=43, respectively). We found: (1) total serum IgE was higher in asthmatic compared with non-asthmatics (P<0.001); (2) total serum IgE did correlate with IgE anti-RSV Abs (P<0.001), and with IgG anti-RSV Abs (P=0.008) in all subjects; (3) total serum IgE levels did correlate with IgE anti-RSV in asthmatics (P=0.047), but not in non-asthmatics (P=0.13); (4) IgE anti-RSV Abs did correlate with IgG anti-RSV Abs in all subjects (P=0.001); (5) IgE- and IgG-anti RSV Abs were higher in asthma compared with no asthma (P=0.003; <0.001, respectively); (6) there was a significant association between age and IgE anti-RSV in non-asthma (P=0.008), but not in asthma (P=0.64). Our findings indicate that IgE-anti-RSV Ab responses may play important roles in RSV infection and asthma.

The prevalence of sleep-disordered breathing in children with asthma and its behavioral effects.

OBJECTIVES: To determine the prevalence of sleep-disordered breathing (SDB) in children with asthma compared to non-asthmatic children and to determine if behavior problems are associated with asthma and SDB. STUDY DESIGN: Cross-Sectional. METHODS: Parents of 263 children with asthma and 266 controls ages 2 to 15 years attending routine pediatric office visits completed the Pediatric Sleep Questionnaire (PSQ) and the Child Behavior Checklist. Asthma severity was classified based on NIH guidelines. RESULTS: The prevalence of snoring was significantly higher in asthmatic children (35.5%) than controls (15.7%) and the prevalence of a positive PSQ was significantly higher in asthmatic children (25.9%) than controls (10.6%) (P < 0.001 for both). The effect of asthma was "dose-dependent" as children with more severe asthma had increased odds ratios for snoring and a positive PSQ. On multivariate analysis, there were significant interactions of gender with asthma and age with gender. A positive modified PSQ along with measures of socioeconomic status and age were the only independent predictors of abnormal Child Behavior Checklist scores and score classifications. CONCLUSIONS: There was a higher prevalence of SDB in asthmatic children compared to non-asthmatic children and the prevalence of SDB increased with increasing asthma severity. In multivariate analysis the role of asthma was much less clear as it predicted a positive PSQ in girls but not boys. SDB, but not asthma, was an independent predictor of behavioral problems.

IgE anti Hepatitis B virus surface antigen antibodies detected in serum from inner city asthmatic and non asthmatic children.

Viral Hepatitis type B (HBV) is a public health concern, but has not been linked to asthma. Immunoglobulin (Ig) G is involved in HBV immune responses; less is known about IgE antibodies (Abs) against HBV in asthma. Given the importance of HBV, we sought to determine whether HBV vaccine contributes to asthma in children, by stimulating specific IgE production. Total IgE, IgE- or IgG-anti-HBVs Abs were studied in vaccinated pediatric asthmatics and non asthmatics. We found: (1) total IgE was higher in asthmatics; (2) total IgE did not correlate with IgE anti-HBVs; (3) IgE anti-HBVs did correlate with IgG-anti-HBVs in all subjects; (4)IgE- and IgG-HBVs Abs were similar in both groups; (5) IgE- or IgG anti-HBVs Abs did not correlate with age. Our findings indicate that HBV vaccination induces IgE responses in asthmatics and non asthmatics.

Asthmatic children have increased specific anti-Mycoplasma pneumoniae IgM but not IgG or IgE-values independent of history of respiratory tract infection.

BACKGROUND: Bronchial asthma is exacerbated by Mycoplasma pneumoniae-induced upper respiratory tract infections (URTIs) in children. Specific IgM and IgG isotypes are involved in the immune response to M. pneumoniae, but little is known about the role of specific IgE antibodies against M. pneumoniae in asthma. OBJECTIVE: To investigate the role of IgM-, IgG- and IgE-specific antibody responses to M. pneumoniae in children with persistent asthma in relationship to history of URTI within the past 6 months. METHODS: Total or specific anti-M. pneumoniae IgM, IgG and IgE antibody responses were studied in stable asthmatic pediatric patients (M. pneumoniae positive and negative) without current exacerbation and nonasthmatic controls (N = 23 and 13, respectively) (UniCAP total IgE Fluoroenzymeimmunoassay, enzyme-linked immunosorbent assay). RESULTS: Values of specific IgM correlated with specific IgG (Spearman correlation, rho = 0.61, P < 0.0001) but not with specific IgE anti-M. pneumoniae antibodies (AMA) in asthmatic subjects compared with nonasthmatic controls. However, concentrations of specific IgG correlated with specific IgE AMA (rho = 0.49, P = 0.0017). Asthmatic subjects had higher levels of specific IgM AMA levels compared with nonasthmatics (median [interquartile range]: 0.57 [1.00] versus 0.21 [0.19]; Kruskal-Wallis test, P = 0.0008). In addition, IgM positivity was significantly higher in asthmatic compared with nonasthmatic subjects (39.1% versus 0.0%; Fisher's exact test, P = 0.01). These results were independent of URTI history in the past 6 months, which was not associated with higher IgM, IgG or IgE AMA levels compared with no URTI history (P = 0.25-0.64). CONCLUSIONS: Increased specific IgM anti-M. pneumoniae responses may indicate an important role for M. pneumoniae infection in asthma.

The business case as a strategic tool for change.

The authors discuss the clinically focused business case, when it is and is not needed, and the knowledge and skills the nurse executive must master to use the business case effectively as a strategic tool. Necessary skills include translating nursing practice proposals into cost-effective change initiatives and marketing those changes to colleagues.