Long-Term Effect of Sublingual and Subcutaneous Immunotherapy in Dust Mite-Allergic Children With Asthma/Rhinitis: A 3-Year Prospective Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Specific allergen immunotherapy is the only treatment modality that might change the natural course of allergic diseases in childhood. We sought to prospectively compare the long-term clinical and immunological effects of sublingual (SLIT) and subcutaneous (SCIT) immunotherapy compared with pharmacotherapy alone. METHODS: In this single-center, prospective randomized controlled trial, 48 children with mild persistent asthma with/without rhinitis, monosensitized to house dust mites (HDMs) were followed for 3 years. At baseline and years 1 and 3 of follow-up, patients were evaluated and compared for total rhinitis (TRSS) and asthma (TASS) symptom scores, total symptom scores (TSS), total medication scores (TMS), safety profiles, skin-nasal-bronchial reactivity, and immunological parameters. RESULTS: A significant reduction was observed in TASS for both HDM-SCIT and HDM-SLIT at year 3 of treatment compared with baseline and controls (P<.05 for both), with significant improvement in rhinitis symptoms for both groups compared with controls (P=.01 for both). TSS decreased significantly in both HDM-SCIT and HDM-SLIT at year 3 compared with baseline (P=.007 and P=.04, respectively) and controls (P<.01 for both). A significant reduction in TMS was observed in HDM-SCIT and HDM-SLIT compared with baseline and controls (P=.01 in all cases), with a reduction in skin reactivity to HDM (P<.05). Finally, a significant increase in allergen specific IgG4 was observed in the SCIT group at year 3 compared with baseline, the SLIT group, and controls (P<.001 in all cases). CONCLUSIONS: HDM-sensitized asthmatic children treated for at least 3 years with either SCIT or SLIT showed sustained clinical improvement.

Efficacy of intravenous immunoglobulin treatment in children with common variable immunodeficiency.

BACKGROUND: Children with common variable immunodeficiency (CVID) have increased susceptibility to infections. OBJECTIVE: We evaluated the role of intravenous immunoglobulin (IVIG) replacement therapy on the clinical outcome of patients with CVID. METHODS: We studied children diagnosed with CVID and treated with IVIG (500 mg/kg every 3 weeks). RESULTS: The study population comprised 29 children with CVID (mean [SD] age, 11.8 [6.1] years) with at least 1 year of follow-up before IVIG replacement therapy. Mean follow-up duration was 5.6 (3.5) years (range, 15 months-14 years). During therapy, median serum IgG levels increased from 410 to 900 mg/dL. The mean number of respiratory infections per patient per year decreased significantly from 10.2 to 2.5. The annual number and length of hospital stays decreased significantly from 1.36 to 0.21 and 16.35 to 6.33 days per patient, respectively. The mean annual number of antibiotics used decreased significantly from 8.27 to 2.50 per patient. Twelve patients had developed bronchiectasis before initiation of IVIG; 3 patients were cured of this condition. Age at diagnosis, diagnostic delay, number of respiratory tract infections, and number of antibiotics were found to be significantly higher in patients with bronchiectasis, as was lower B-cell percentage. However, gastrointestinal involvement due to noninfectious causes did not improve significantly after IVIG replacement therapy. CONCLUSION: CVID patients treated with IVIG (500 mg/kg every 3 weeks) had satisfactory serum IgG levels, fewer respiratory tract infections, fewer and shorter hospital stays, and reduced antibiotic usage. However, no effect on gastrointestinal involvement was observed. Early IVIG replacement therapy is important in preventing bronchiectasis.

Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial.

BACKGROUND: In children, the clinical efficacy and immunological mechanisms of sublingual immunotherapy (SLIT) compared with subcutaneous immunotherapy (SCIT) is still to be elucidated. OBJECTIVES: To compare SLIT, SCIT and pharmacotherapy in relation to clinical efficacy and immunological mechanisms that govern its effect in asthmatic/rhinitis children who were sensitized to house dust mite (HDM). METHODS: In this single centre, prospective, randomized, controlled, open labelled, three parallel group trial, 48 patients mono-sensitized to HDM were randomized to receive either SLIT (n=16), SCIT (n=16) or pharmacotherapy alone (n=16). Symptom, medication and visual analogue score (VAS) were collected and bronchial-nasal hyper-reactivity, skin prick tests, total-specific IgE were performed at baseline and 12 months after treatment. In addition, peripheral blood mononuclear cells were cultured with recombinant Der p 1 and Bet v 1 extracts and allergen-specific IL-4, IL-5, IL-13, IFN-gamma, IL-10, and TGF-beta secretions were measured. RESULTS: SLIT and SCIT demonstrated a significant reduction of total rhinitis and asthma symptom score, total medication score, VAS and skin reactivity to HDM (P<0.05) when compared with pharmacotherapy. A significant reduction of serum-specific HDM-IgE in SCIT and SLIT were observed. Moreover, titrated nasal provocative dose significantly increased in both immunotherapy groups when compared with the pharmacotherapy group. No adverse effects were reported in SLIT, while two patients demonstrated serious adverse events in SCIT. After 1 year of treatment, Der p 1-driven IL-10 significantly increased in SLIT compared with pharmacotherapy, whereas Bet v 1-driven TGF-beta (negative control) increased significantly in SLIT only. No changes were observed for Th1-Th2 cytokines. CONCLUSION: Both SLIT and SCIT demonstrated clinical improvement compared with pharmacotherapy in asthma/rhinitis children sensitized to HDM.

Prevalence of immediate hypersensitivity reactions to cow's milk in infants based on skin prick test and questionnaire.

OBJECTIVE: Cow's milk (CM) hypersensitivity is one of the most frequent hypersensitivities in infants. The objective of our study was to investigate the prevalence of immediate hypersensitivity to CM based on skin prick test results and to evaluate associated allergic conditions ascertained by questionnaire in infants living in Istanbul. METHODS: All infants born between June 2001 and May 2002 were recalled to the hospital according to their dates of birth, and 1015 infants aged between 8-18 months were included in the study. An interview was conducted with each mother and a questionnaire requesting data on cow's milk hypersensitivity and other allergic diseases was completed during this interview. A cow's milk skin prick test (SPT) was applied to all infants. An open CM challenge test was then carried out on infants with a positive SPT to CM. RESULTS: Among the 1015 infants who underwent SPT, six (0.59 %) demonstrated immediate hyper-sensitivity to the CM allergen and three (0.29 %) developed a positive response to the CM challenge test. The results of the questionnaire revealed that 112 (11.0 %) of the infants had family history of allergic diseases, 96 infants (9.5 %) had a positive history of recurrent wheezing, and 166 (16.4 %) had a history of skin rash resembling atopic dermatitis. CONCLUSIONS: Our results suggest that CM hyper-sensitivity, with its low prevalence, might not be a serious health concern in Turkish infants.

Clinical and immunologic features of pediatric patients with common variable immunodeficiency and respiratory complications.

BACKGROUND: Common variable immunodeficiency (CVID) is the term used to describe a heterogeneous group of B-cell deficiency syndromes characterized by hypogammaglobulinemia, impaired antibody production, and recurrent bacterial infections. OBJECTIVES: To determine the clinical manifestations and perform an immunological analysis of pediatric CVID patients suffering from respiratory complications. METHODS: The records of 10 patients with CVID who were followed up from 1992 to 2005 (6 males and 4 females) with a median (interquartile range) age of 13.9 (10.4-19.4) years were reviewed. All patients met the standard criteria set for CVID. RESULTS: Median total serum levels of immunoglobulin (Ig) G, IgM, and IgA in mg/dL were 383.5 (239.2-574.5), 32.5 (17.0-117.0), and 12.5 (5.0-30.7), respectively. Median age at the onset of symptoms, at CVID diagnosis, and on starting intravenous Ig therapy was 4.0 (0.8-6.2), 9.4 (6.7-11.3), and 9.1 (7.0-11.6) years, respectively. Associated disorders were recurrent infections (100%), bronchiectasis (90%), and growth failure (80%), whereas malabsorption, malignant neoplasm, inflammatory bowel disease, and autoimmune disorders were less common. All bronchiectatic patients had a low percentage of B cells, with an average of 4% (range, 1%-7%). The characteristic computed tomography finding in patients with CVID was a multilobar pattern. Malignant neoplasm developed an average of 11.5 (range, 6.5-20.2) years after the diagnosis of CVID was made. CONCLUSION: Recurrent respiratory infection should be evaluated to rule out CVID. Early diagnosis and intravenous Ig replacement therapy may reduce the frequency of respiratory infection. Low levels of serum Ig and percentage of B lymphocytes at diagnosis are important parameters for identifying patients at risk of structural lung damage.

Prevalence of egg sensitization in Turkish infants based on skin prick test.

AIM: Egg allergy is one of the most frequent allergies in infants. The aim of this study was to determine the frequency of sensitization to egg in infants based on skin prick test results and to evaluate associated allergic conditions by questionnaire. METHODS: All infants born between June 2001 and May 2002 were recalled to the hospital according to their dates of birth, and 1015 infants aged between 8-18 months were included in the study. An interview was conducted with each mother and a questionnaire requesting data on food allergy and other allergic diseases was completed during this interview. An egg skin prick test (whole egg) was applied to all infants. RESULTS: Positive skin prick test results were recorded in 19 infants (1.87 %). There was no difference between the prick test-positive and -negative groups with respect to any of the demographic characteristics investigated (gender, age, birth weight, egg consumption, age of introduction of egg and other solids, breastfeeding). No significant association was demonstrated between sensitization to egg and family history of allergy. Moreover, there was no association between sensitization to egg and occurrence of atopic dermatitis, recurrent wheezing, gastrointestinal symptoms and doctor diagnosis of asthma. CONCLUSION: The prevalence of egg sensitization based on skin prick test results has been found as 1.87 % among Turkish infants in Istanbul. However, no significant relationship was found between allergic sensitization to egg and occurrence of allergic diseases in this study population.

Treatment with chitin microparticles is protective against lung histopathology in a murine asthma model.

BACKGROUND: Chitin, a natural polysaccharide extracted from shrimp, is a potent T and B cell adjuvant when delivered in the form of chitin microparticles and can shift a polarized T-helper type 2 (Th2) immune response towards a Th1 response. OBJECTIVE: We investigated the beneficial effects of the intranasal application of chitin microparticles in newborn mice before and after the establishment of a model of allergic asthma. METHODS: Mice were grouped as asthma (A), primary prevention (PP), treatment (T), primary prevention+treatment (PPT) and control (C) groups. All mice except controls were sensitized with ovalbumin intraperitoneally and challenged intratracheally to establish the asthma model. Mice in the PP and PPT groups received chitin microparticles intranasally during the newborn period before sensitization. Mice in the PPT and T groups received intranasal chitin microparticles after challenge. Airway histopathology was evaluated in all groups. RESULTS: All of the airway histopathologic parameters of small and medium-sized airways of the T and PPT groups were significantly ameliorated when compared with the asthma model group. In the large airways, thicknesses of basement membrane, epithelium and subepithelial smooth muscle layers of the PPT group and basement membrane thicknesses of the T group were also significantly lower compared with the asthma model group. Comparison of the PP group with the asthma model group revealed significantly reduced goblet cell numbers and significantly reduced epithelial and basement membrane thicknesses in small and medium airways, in addition to significantly reduced basement membrane thicknesses in the medium-sized airways. CONCLUSION: Intranasal application of microgram quantities of chitin microparticles had a beneficial effect in preventing and treating histopathologic changes in the airways of asthmatic mice.

Bacillus Calmette-Guérin-induced interleukin-12 did not additionally improve clinical and immunologic parameters in asthmatic children treated with sublingual immunotherapy.

OBJECTIVE: To evaluate the effect of bacillus Calmette-Guérin (BCG) as an adjuvant to specific sublingual immunotherapy (SLIT) on the cytokine profile of peripheral blood mononuclear cells (PBMCs) and clinical outcome. METHODS: Thirty-two children with asthma and rhinitis allergic to house dust mite (HDM) with negative purified protein derivative (PPD) skin test response were enrolled. After a run-in period of 8 weeks, patients were randomized to receive either SLIT only (n=16) or one dose of BCG immunization before initiation of SLIT (n=16) with a standardized Dermatophagoides pteronyssinus (D. pteronyssinus)+D. farinea 50/50 extract. PPD-negative asthmatics (n=5) allergic to HDM receiving inhaled therapy only were included for comparison of cytokine levels in PBMC cultures. Efficacy was assessed both at the end of run-in and 6 months of treatment periods with criteria including symptom, medication and quality-of-life (QoL) scores, IgE levels, lung function, provocation concentration (PC20), eosinophil count and skin prick tests. IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-gamma levels were determined in antigen specifically and polyclonally stimulated PBMC cultures. RESULTS: Both treatment groups showed significant improvement at the end of 6 months for asthma and rhinitis scores and QoL, number of asthma attacks, amount of beta2-agonists, inhaled and intranasal steroids, blood eosinophil counts and PC20. Interestingly, phytohaemagglutinin (PHA)-stimulated IL-12 and D. pteronyssinus-stimulated IFN-gamma in PBMC were significantly higher in the treatment groups than controls. In addition, IL-12 levels in response to D. pteronyssinus and PHA stimulation were significantly higher in the SLIT+BCG group than the SLIT alone group and controls. CONCLUSION: The present study demonstrates that successful SLIT is parallel to increased IFN-gamma production by PBMC. Although simultaneous BCG vaccination enhanced IL-12 production, it did not additionally improve the clinical outcome.

The effect of BCG vaccine at birth on the development of atopy or allergic disease in young children.

BACKGROUND: Exposure to infectious diseases may reduce the development of asthma or allergy. In particular, the role of the BCG vaccine in modulating asthma or allergy has been a source of speculation. OBJECTIVE: To study newborns from 3 international sites to evaluate the prospective effect of BCG vaccine on allergic diseases or atopic development. METHODS: Infants were enrolled from newborn and well-infant clinics in Thailand, Argentina, and Turkey. The standard BCG vaccine for each country was given at birth. Parents who consented to have their infant included in the protocol completed an allergy family questionnaire. Infants underwent a standard purified protein derivative (PPD) test at 9 to 12 months of age, and the reaction size was measured. At the age of 2 years, the children returned to be studied. Allergy skin tests to common allergens appropriate to location and age were performed, and the parents completed the International Study of Allergy and Asthma in Childhood questionnaire. The PPD reaction size was compared with the presence of atopy and allergy questionnaire responses. RESULTS: A total of 1,704 infants were studied. Statistical significance was found between a negative PPD response vs any positive PPD response and the risk of having an allergic history at the age of 2 years in Turkey (relative risk, 2.11; 95% confidence interval, 1.25-3.55; P = .005) and Thailand (relative risk, 2.16; 95% confidence interval, 1.18-3.94; P = .02) but not Argentina (relative risk, 1.09; 95% confidence interval, 0.70-1.68; P = .70). CONCLUSIONS: This study further supports the role of infectious agents in modulating asthma and allergy development.

Impact of Mycobacterium vaccae immunization on lung histopathology in a murine model of chronic asthma.

BACKGROUND: Therapeutic modalities of asthma have not been proved to be successful in reversing the already established chronic changes of airways. OBJECTIVE: We aimed to determine the impact of heat-killed Mycobacterium vaccae immunization, a potent Th1 stimulant, on chronic changes of asthma. METHODS: Newborn BALB/c mice were divided into three groups; mice in M. vaccae group received 107 colony-forming units (CFU)/50 micro L of heat-killed M. vaccae subcutaneously on days 3, 14 and 42 before the development of chronic asthma model, whereas mice in control and chronic asthma groups received saline. Subsequently, mice in M. vaccae and chronic asthma groups were administered 10 micro g/100 micro L of ovalbumin (OVA) on days 43, 45, 47, 49, 51, 53 and 55 intraperitoneally, and 20 micro g/10 micro L of OVA on days 83, 86 and 89 intratracheally. Mice in control group received saline on the same days. RESULTS: Comparison of M. vaccae and chronic asthma groups showed statistically significant differences in goblet cell numbers, thickness of basement membrane and subepithelial smooth muscle of small, medium and large airways and epithelial thickness of medium airways. There was no significant difference between the control and M. vaccae groups except for goblet cell numbers of medium and large airways, and epithelial thickness of medium airways. CONCLUSION: Results of our study suggested that immunization by M. vaccae of newborn mice would prevent some of the chronic changes of airways due to asthma.

Acute effect of inhaled budesonide on bronchial inflammation in asthmatic rats.

Although anti-inflammatory potency of inhaled corticosteroids is well established, little is known about their role in the acute phase. The aim of this study was to compare the acute anti-inflammatory effect of inhaled budesonide with systemic dexamethasone on allergen-induced inflammatory changes in asthmatic rats. Eighty-four Sprague Dawley rats were divided into four groups; group I (control, n = 24), group II (ovalbumin sensitized, n = 24), group III (systemic dexamethasone, n = 24), and group IV (budesonide, n = 12). All groups except group I were given ovalbumin aerosol challenges 14 days after sensitization with ovalbumin. The same procedure was applied to the control group using 0.9% saline. Group III received dexamethasone 0.3 mg/kg intraperitoneally and group IV received inhaled budesonide 10mL (0.5mg/mL) twice before the challenge. Eight hours after the challenge, bronchi of all the rats were evaluated for the degree of peribronchial inflammation. The most severe inflammation was seen in 8 of 24 rats (33%) in the second group, in 1 of 24 rats (4%) in the third group, and in 1 of 24 rats (4%) in the control group. None of the rats in group IV showed severe inflammation. No statistically significant difference was detected with respect to the presence of 3+ inflammation between the control vs. dexamethasone-, control vs. budesonide-, and dexamethasone vs. budesonide-receiving groups. Budesonide administration via nebulizer prior to exposure to an allergen may attenuate bronchial inflammation as effectively as systemic dexamethasone in rats.

Predictors for the severity of bronchial hyperreactivity in childhood asthma.

Bronchial hyperreactivity (BHR) is a common characteristic of asthma and is shown to be a risk factor in the development and outcome of asthma. In this study, we aimed to assess the risk factors at referral for the severity of BHR, which was determined at the end of a mean of 3 yr of follow-up in 98 children with asthma [mean (+/- SD) age, 11.0 (+/- 3.4) yr, male/female = 50/48]. We also evaluated the cross-sectional risk factors for the severity of BHR in the observed children. Information on risk factors at referral was collected from the computer records of the patients followed by an end-of-study visit. Lung function, skin-prick, and bronchial provocation tests were done and total serum IgE level was measured on this visit. The relationship between BHR and risk factors was investigated by multiple linear regression analysis. A lower level of FEV1 % at referral was found to be an important predictor of more severe BHR at the end of the follow-up. None of the other risk factors evaluated predicted the severity of current BHR. We concluded that decreased lung function at referral is associated with a more severe BHR determined at the end of a 3-yr follow-up in children with asthma.

Efficacy of sublingual immunotherapy in children with asthma and rhinitis: a double-blind, placebo-controlled study.

To evaluate the efficacy of specific sublingual immunotherapy (SLIT), we enrolled 15 children with asthma and rhinitis (7 girls, 8 boys, mean +/- SD age of 11.7 +/- 3.3) allergic to house dust mite (HDM) into a double-blind, placebo-controlled study. After a run-in period, patients were randomized to receive either placebo (n = 7) or SLIT (n = 8) with a standardized Dermatophagoides pteronyssinus (D. pteronyssinus) + Dermatophagoides farinea (D. farinea) 50/50 extract. They received increasing doses up to 100 index units of reactivity (IR) every day for 4 weeks, then 100 IR/day for another 4 weeks, followed by maintenance therapy consisting of 20 drops 2 times a week for 4 months. Efficacy was assessed at the end of 6 months of therapy according to symptom and medication scores, serum total IgE levels, results of lung function tests, methacholine provocation tests, and skin prick tests. Daily means for the asthma score and use of inhaled beta-2-mimetics decreased significantly in the SLIT group (P = 0.05, P = 0.028, respectively), whereas no such difference was observed in the placebo group. At the end of follow-up, mean daily doses of intranasal steroids needed for control of rhinitis symptoms decreased significantly in the SLIT group (P = 0.04). Baseline skin sensitivity to D. pteronyssinus and D. farinea was not significantly different between in the two groups, whereas end-point wheal diameter obtained with D. pteronyssinus extract was significantly less in the SLIT vs. the placebo group (P = 0.026). At the end of 6 months, peak expiratory flow (PEF) values in the placebo group was significantly lower than in the SLIT group (P = 0.049). Throughout the treatment period, the SLIT group was found to have less asthma exacerbations than the placebo group (P = 0.007). The provocation concentration causing a 20% drop in forced expired volume in 1 sec did not change throughout the treatment period in either groups. None of the patients reported local or systemic side effects from SLIT. Results of this study suggests that SLIT may be a useful alternative or additional therapy in the treatment of children with asthma/rhinitis due to HDM.

Risk factors for the persistence of respiratory symptoms in childhood asthma.

OBJECTIVE: To evaluate the parameters which could predict the persistence of respiratory symptoms in asthmatic children who have been treated with a considerably uniform therapy. METHODS: A retrospective review was performed on the records of 279 children with asthma. An end of study visit, results of spirometry and prick tests completed the data. The mean age at referral and at final visit was 6.2 +/- 3.7 years and 8.9 +/- 4.1 years, respectively; and the children were followed up for a mean of 3 +/- 1.2 years. RESULTS: Eighty-five of the 279 patients (30%) experienced no respiratory symptoms in the previous 12 months. There was no significant difference between those with and without current respiratory symptoms with respect to age, sex, age at onset of symptoms, duration of followup, age at referral, therapeutic choice, severity of asthma and duration of symptoms at referral. For subjects with current respiratory symptoms the initial serum total IgE level, and the percentage of RAST/prick test positivity was significantly higher than those without current respiratory symptoms (P = 0.0027, P = 0.011, respectively). Although the initial FEF 25%-75%, FEV1, and FEV1/FVC was significantly lower in those with current respiratory symptoms (P = 0.003; P = 0.005; and P = 0.04, respectively), there was no statistically significant difference between lung functions of the two groups at the end of followup. The persistence of respiratory symptoms was significantly predicted by initial FEF25%-75% and sensitivity to allergens (P = 0.03 and P = 0.04, respectively). CONCLUSIONS: We concluded that the risk factors for the persistence of respiratory symptoms in our patient population have been low FEF25%-75% value and sensitivity to allergens at referral.

The effectiveness of high-dose inhaled budesonide therapy in the treatment of acute asthma exacerbations in children.

BACKGROUND: International guidelines recommend the use of systemic steroids for the treatment of acute asthma attack if it has not been resolved within 24 to 36 hours of home management with regular beta2 mimetic inhalation. Such therapy for infrequent exacerbations is unlikely to have serious systemic effects. Unfortunately, many patients receiving frequent courses are potentially at risk for corticosteroid-induced side effects such as adrenal suppression, depression of linear growth, and osteoporosis. OBJECTIVE: To decrease the use of frequent oral corticosteroid courses in children, this study was designed to evaluate the efficacy of high-dose inhaled steroids in comparison with oral steroids, in the therapy of acute asthma exacerbations in children. METHODS: Sixty children who have experienced an acute exacerbation of asthma unresponsive to home management with regular use of inhaled beta2 mimetics, yet not severe enough to hospitalize, were randomized to be treated with either high-dose inhaled budesonide (1,600 microg daily) or oral methylprednisolone (1 mg/kg daily) plus medium-dose inhaled budesonide (800 microg daily, both in addition to inhaled terbutaline, 2,000 microg daily). Pre- and posttreatment pulmonary index scores, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow 25% to 75% (FEF25%-75%) were evaluated. RESULTS: The mean number of decrease in pulmonary index score was 2.61 +/- 1.12 in the high-dose budesonide-receiving group (group I) and 1.90 +/- 1.08 in the oral steroid-receiving group (group II). There was a statistically significant difference between the two groups, in favor of group I (P = .038). No statistically significant difference was detected between the two groups with respect to the increase in lung function test measurements (FEV1, FEV1/FVC, FEF25%-75%; P = .790, .959, .819, respectively). CONCLUSIONS: Short-term high-dose budesonide therapy can be considered an alternative for children who are experiencing an acute asthma attack that is unresponsive to home management with regular use of an inhaled beta2 mimetic, yet who are not severe enough to hospitalize.

Is serum ECP level helpful in determining discontinuation of inhaled corticosteroid therapy in asthmatic children?

BACKGROUND: Serum eosinophil cationic protein (ECP) has been promoted as a direct marker of eosinophilic inflammation of the airways in patients with asthma. However, its role in monitoring disease activity and management of inhaled corticosteroid (ICS) therapy is not well defined. METHODS: We determined serum ECP (s-ECP) levels in 95 children (mean +/- SD age, 6.2 +/- 3.9 years) with asthma. At the time of measurements, 34 out of 95 children were symptomatic whereas 61 were in stable condition; and 56 of 95 patients were on maintenance ICS therapy. ICS prophylaxis was withdrawn in 16 of those 56 patients who remained asymptomatic with a dose of 100 micrograms/day of budesonide for 8 weeks. Eight out of these 16 children had to restart ICS therapy within the following 12 weeks, while the remaining 8 children continued to be asymptomatic within the same period. RESULTS: ECP values and number of patients with a high ECP level (> or = 15 micrograms/L) were significantly higher in the symptomatic group (p = 0.01 and p = 0.006, respectively). Also, ECP levels were significantly lower in the group who achieved clinical remission (n = 16) in which ICS therapy was withdrawn when compared with those who needed to continue ICS prophylaxis. On the other hand, no difference was observed in the comparison of the ECP levels of children who had to restart ICS therapy and those who did not. CONCLUSION: Our results suggest that, although the determination of s-ECP levels are in accordance with clinical evaluation of disease activity, it is not useful in determining discontinuation of ICS therapy (AU)

Antecedentes: la proteína catiónica eosinófila (PCE) en suero ha sido propuesta como un marcador directo de la inflamación por eosinófilos de las vías aéreas en los pacientes que padecen asma.Sin embargo, su utilidad en la monitorización de la actividad de la enfermedad y el tratamiento de corticoides inhalados (CI) no ha sido bien definida.Métodos: determinamos la concentración sérica de PCE (PCE-s) en 95 niños asmáticos (edad media ñ DE 6.2 ñ 3.9 años). En el momento de realizar las mediciones, 34 de los 95 niños estuvieron sintomáticos y 61 estables; 56 de los 95 pacientes estaban recibiendo tratamiento de mantenimiento con CI. Se retiró la profilaxis de CI en 16 de los 56 pacientes que permanecieron asintomáticos con una dosis de 100 mg/día de budenosida durante ocho semanas. Ocho de estos 16 niños tuvieron que reanudar el tratamiento con CI en las 12 semanas siguientes, mientras que los ocho restantes permanecieron asintomáticos en el mismo período.Resultados: los valores de la PCE y el número de pacientes que tuvieron un nivel elevado de PCE ( 15 mg/L) fueron significativamente mayores en el grupo de pacientes sintomáticos (p = 0,01 y p = 0,006, respectivamente). Los niveles de PCE fueron significativamente más bajos en el grupo que lograron la remisión clínica (n = 16) y pudieron interrumpir el tratamiento de CI, comparado con los pacientes que precisaron el tratamiento profiláctico de CI. Por otro lado, no se observaron diferencias en los niveles de PCE de los niños que tuvieron que reanudar el tratamiento con CI y los niños que no tuvieron que hacerlo.Conclusión: nuestros resultados sugieren que, aunque los niveles de PCE-s corresponden a la evaluación clínica de la actividad de la enfermedad, éste no es un marcador útil para determinar cuando puede interrumpirse el tratamiento con CI. (AU)

Heat-killed Mycobacterium bovis-bacillus Calmette Guerin-suppressed total serum IgE response in ovalbumin-sensitized newborn mice.

To determine the impact of bacillus Calmette Guerin (BCG) vaccination on IgE production in ovalbumin (OVA)-sensitized newborn mice, four groups (I, II, III, IV) of BALB/c mice were immunized on the first day of life with live BCG, killed BCG, BCG diluent, and saline, respectively. No injection was applied to mice in group V (control). All mice except group V were sensitized and challenged with OVA in the fourth and sixth weeks, respectively, and serum total IgE levels were determined at 8 weeks, 2 weeks after the second OVA challenge. IgE levels of all groups were significantly higher than the control group except for group II (p = 0.95). Mice in group II showed significantly lower IgE values than group IV and I (p = 0.007 and p = 0.003, respectively). We concluded that heat-killed BCG may downregulate IgE response to OVA in newborn mice.

Inhaled corticosteroid therapy is safe in tuberculin-positive asthmatic children.

BACKGROUND: Although treatment with oral corticosteroids can cause reactivation of latent Mycobacterium tuberculosis (TB) infection in purified protein derivative (PPD)-positive individuals with no evidence of clinical disease, little is known about the effects of inhaled corticosteroids in this respect. OBJECTIVE: This study was undertaken to assess whether inhaled corticosteroid (CS) therapy reactivates latent TB infection in PPD-positive asthmatic children. METHOD: We studied 32 PPD skin test-positive (> or =10 mm) children [age (mean +/- SD), 7.9 +/- 4.1 years] with no family history and no evidence of TB infection on chest radiograms who were receiving inhaled budesonide for the treatment of asthma. They were further evaluated with thorax computed tomography (CT) and erythrocyte sedimentation rate and closely observed for an additional 9 months. RESULTS: At enrollment the mean diameter of PPD reaction was 12.8 +/- 2.7 mm. The mean duration of inhaled CS treatment and the mean cumulative CS dose were 9.8 +/- 7.6 months and 275 +/-199 mg, respectively. Thorax CT studies revealed mediastinal lymph nodes in 7 of the 32 patients. There was no significant difference between children with and without mediastinal lymph nodes according to age, gender, size of PPD skin testing, erythrocyte sedimentation rate and duration and cumulative CS dose of inhaled budesonide therapy before study. A second thorax CT was obtained 9 months later in those 7 patients with lymphadenopathy (additional mean cumulative CS dose, 222.57 mg). There was no change in the size of their lymph nodes. CONCLUSION: Long term inhaled budesonide therapy appears to be safe in PPD-positive asthmatic children.

The inverse association between serum anti-streptolysin-O titers and the frequency of exacerbations of asthma in childhood.

BACKGROUND: The decline in infections in childhood may contribute to the rising severity and prevalence of atopic disorders in developed countries. Support for this hypothesis has been obtained from findings of an inverse association between tuberculin responses and atopy and from findings of high prevalence of asthma in certain islands with low prevalence of respiratory infections. With this regard, we investigated the association between serum anti-streptolysin-O (ASO) titers and the frequency of exacerbations of asthma in childhood. METHODS: Thirty atopic asthmatic children who has no sign of upper respiratory tract infection at the time of presentation or during the previous two months were included in the study. Serum ASO titer was measured as an indicator of past streptococcal upper respiratory tract infections. ASO titer > or = 200 Todd units was accepted as positive. RESULTS: A statistically significant association is found between high anti-streptolysin-O titers and decreased number of exacerbations in those children. CONCLUSIONS: Our data suggests that streptococcal infections might be a factor attenuating asthma in childhood.