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ABSTRACT: 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.
Journal of Asthma 10/2001; 38(6):461-7. · 1.52 Impact Factor
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ABSTRACT: 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.
Pediatric Pulmonology 08/2001; 32(1):49-55. · 2.53 Impact Factor
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ABSTRACT: To evaluate the parameters which could predict the persistence of respiratory symptoms in asthmatic children who have been treated with a considerably uniform therapy.
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.
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).
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.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 05/2001; 86(4):449-55. · 2.83 Impact Factor
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ABSTRACT: 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.
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.
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.
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).
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.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 04/2001; 86(3):318-22. · 2.83 Impact Factor
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ABSTRACT: 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.
Journal of Asthma 07/2000; 37(4):329-34. · 1.52 Impact Factor
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ABSTRACT: 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.
This study was undertaken to assess whether inhaled corticosteroid (CS) therapy reactivates latent TB infection in PPD-positive asthmatic children.
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.
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.
Long term inhaled budesonide therapy appears to be safe in PPD-positive asthmatic children.
The Pediatric Infectious Disease Journal 03/2000; 19(3):215-8. · 3.58 Impact Factor
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ABSTRACT: A recently advanced hypothesis suggests that decreased exposure to T-helper (Th) 1-inducing agents causes Th2-biased differentiation in response to concomitant allergens. We therefore examined the effect of pre-immunization with killed Mycobacterium bovis and killed M. vaccae which are known to be very potent inducers of Thl immune response, on serum IgE response in ovalbumin (OVA)-sensitized newborn mice. Eighty-four newborn Balb/c mice were divided into four groups and were immunized intraperitoneally 24 h after birth with 50 microl of 5 x 10(4) colony-forming units (c.f.u.) of killed M. bovis in group I (M. bovis group, n = 19), with 25 microl of 2.5 x 10(8) c.f.u. of killed M. vaccae plus 25 microl of 5 x 10(4) c.f.u. of killed M. bovis in group II (M. vaccae + M. bovis group, n = 28) and with 50 microl of only phosphate-buffered saline (PBS) in group III (no mycobacterial immunization, n = 18). No injection was applied to mice in group IV (control group, n = 19). Starting from 8 weeks of age, all mice except the control group were sensitized with 0.5 ml of 20 mg/ml OVA administered intraperitoneally 7 times every other day. Thirty days after the final injection, all animals except those in the control group were challenged with an aerosol of 2 mg/ml OVA. Forty-eight hours later, blood was collected from all mice for determination of serum IgE levels. A statistically significant difference was observed in the serum total IgE levels between groups III and IV (p = 0.0099), indicating that the mice were successfully sensitized with OVA. Serum total IgE values of the female mice in M. bovis group were found to be significantly lower than group III (p = 0.009), while no difference was observed in males. Serum total IgE levels of the M. vaccae + M. bovis group were found to be significantly lower than group III both in male and female mice (p < 0.0001 and p = 0.0001, respectively). Female values were even lower than controls (p = 0.0092). Pre-immunization in the newborn period with killed M. bovis alone or in addition to M. vaccae may potentially be helpful in down-regulating an IgE response.
Pediatric Allergy and Immunology 05/1999; 10(2):107-11. · 2.46 Impact Factor
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ABSTRACT: To determine whether parental reports of smoking habits and modifications in smoking behavior are associated with urinary cotinine levels (UCLs), UCLs were measured in 77 asthmatic children. Parental reports and UCLs agreed for 58 of the 77 children (75%). Although UCLs of children whose parents smoked indoors and outdoors were significantly higher than UCLs of children whose parents did not smoke (p<0.0001, p<0.002, respectively), there was no statistically significant difference between the UCLs of children whose parents smoked indoors and outdoors (p = 0.286). We concluded that encouraging smoking parents of asthmatic children to smoke outdoors may not be an effective way to lessen exposure.
Journal of Asthma 01/1999; 36(2):171-5. · 1.52 Impact Factor
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ABSTRACT: 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.
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.
A statistically significant association is found between high anti-streptolysin-O titers and decreased number of exacerbations in those children.
Our data suggests that streptococcal infections might be a factor attenuating asthma in childhood.
Allergologia et Immunopathologia 28(6):307-9. · 1.04 Impact Factor
