Long acting inhaled beta 2 agonists and inhaled anticholinergic drugs: benefits and side effects in childhood asthma.
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Publications and source records attributed to C K Naspitz.
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BACKGROUND: Inhaled furosemide has been shown, in patients with asthma, to have prophylactic properties similar to those of disodium cromoglycate. OBJECTIVE: The aim of this study was to evaluate the protective effect of these drugs in the treatment of exercise-induced asthma. METHODS: Fifteen children with exercise-induced asthma (mean age, 10.8 years) underwent exercise challenge after a single dose of nebulized placebo, furosemide (20 mg/m7 body area), or disodium cromoglycate (20 mg), 2 days apart, in a single-blind crossover trial. RESULTS: Both furosemide and disodium cromoglycate exerted significant protection against the bronchial response to exercise challenge, with a mean maximum percentage falls in FEV1 of 4.66% and 7.22%, respectively (p < 0.05). On the placebo day, the mean maximum percentage fall in FEV1 was 34.50% (p < 0.05). CONCLUSION: The results of this study suggest that furosemide and disodium cromoglycate provide comparable efficacy in preventing exercise-induced asthma in children, with no side effects.
BACKGROUND: There appears to be an association between sinusitis and asthma. The effect on bronchial hyperresponsiveness of clinical therapy for sinusitis in children may help to decipher whether sinusitis and asthma are independent manifestations of the same disease. OBJECTIVE: To evaluate the effect of clinical treatment for sinusitis in patients with rhinitis and/or asthma on symptoms and on bronchial hyperresponsiveness to methacholine. METHODS: Open label, randomized, non-treatment control in a teaching hospital in São Paulo, Brazil. Forty-six atopic and 20 normal children were studied. The atopic children consisted of 18 with allergic rhinitis (12 without sinusitis and 6 with sinusitis), and 28 children with rhinitis with asthma (13 with normal sinus radiographs and 15 with complete opacification of the maxillary sinuses). Methacholine PC20 was determined before and 30 days after treatment with nasal saline, sulfamethoxazole-trimethoprim, antihistamine/decongestant, and five days of prednisone. Sinus radiographs were also repeated. RESULTS: The only patients with increase in methacholine PC20 were patients with rhinitis and asthma with opacified maxillary sinuses at entry and who at 30 days had normal sinus radiographs (P < .05). CONCLUSION: In this study, children with allergic rhinitis and sinusitis with asthma improved their bronchial hyperresponsiveness to methacholine and decreased their symptoms with appropriate response of their sinuses to clinical therapy.
Endotoxins (ET) are pro-inflammatory substances present in house dust which may increase non-specific bronchial reactivity in asthmatic patients. Endotoxins (EU/g) and Der p 1 levels were compared in the homes of ten asthmatic and ten control children, aged 6-16 years, living in São Paulo, Brazil. The houses were visited once a month from February 1993 to February 1994 and dust samples were collected from the bedding and floor of each subject's house. No significant differences were observed in ET and Der p 1 levels in the homes of asthmatics and controls. The highest ET levels were detected in January and November, whereas the lowest levels were detected in April and August (p < 0.05), demonstrating a distinct seasonal distribution. The highest Der p 1 levels in bedding were observed in July and the lowest in February (p < 0.05), while Der p 1 levels in floor did not show significant differences throughout the year. Symptom and medication scores were evaluated monthly in the group of asthmatic children. There was a significant correlation (p < 0.05, r = 0.63) between clinical symptom scores and ET exposure, however no significant correlation was found for mite exposure (p > 0.05, r = 0.19). The results suggest that ET exposure exacerbates asthmatic symptoms in mite allergic, asthmatic children.
The purpose of the present study was to analyze the frequency of HLA-DR and DQ antigens in Brazilian asthmatic children with skin-test and RAST positivity to Dermatophagoides pteronyssinus. The comparison of HLA-DR and DQ antigenic frequencies between patients (n = 30) and controls disclosed a significantly higher HLA-DQ2 frequency in the patients (60% versus 34%, p = 0.013; R. R. = 2.8).
In tropical and subtropical regions of the world, allergens produced by Blomia tropicalis are an important cause of IgE-mediated sensitization among patients with asthma. We compared the relative importance of sensitization to the two mite species among asthma patients from Florida, Puerto Rico, and Brazil (n = 83), who were concurrently exposed to B. tropicalis and D. pteronyssinus, with patients from the United States and from the United Kingdom (n = 56) exposed to D. pteronyssinus. In addition, molecular cloning techniques were used to clone and express a major B. tropicalis allergen. There were significant differences between IgE antibody responses to B. tropicalis and D. pteronyssinus that were related to exposure: only 22% of patients exposed to both species had a high ratio (> 10) of IgE D. pteronyssinus:B. tropicalis, whereas 68% of patients exposed only to D. pteronyssinus had a ratio of > 10 (p < 0.001). A major 14-kD allergen (Blo t 5), cloned from a B. tropicalis cDNA library, showed 43% sequence homology to D. pteronyssinus Der p 5. Recombinant Blo t 5 produced in E. coli reacted with 45 to 69% of sera from B. tropicalis-allergic asthmatics and induced positive immediate skin tests at 10(-3) to 1 microg/ml. In vivo and in vitro comparisons of IgE responses to B. tropicalis, D. pteronyssinus, rBlo t 5, and rDer p 5, showed that B. tropicalis has unique allergens that cause specific IgE responses. The results suggest that B. tropicalis is an independent cause of sensitization and that use of recombinant Blo t 5 should lead to a better understanding of the role of B. tropicalis in causing asthma in tropical environments.
With the purpose of analyzing the neurological involvement due to systemic lupus erythematosus (SLE), we evaluated 17 female patients who were seen regularly at the hospital and had been diagnosed as having SLE according to classification criteria proposed by the American College of Rheumatology revised in 1982, before the age of 16. Neurological involvement was detected in 12 patients (71%): headache (35%), extrapyramidal syndrome (35%), epileptic syndrome (24%) pyramidal syndrome (24%), peripheral neuropathy (12%) and optic neuritis (6%). The findings of CT scan (58%) and cerebrospinal fluid (50%) were most closely correlated to clinical neurological involvement.
BACKGROUND: Although it is commonly accepted that the immune response is affected by malnutrition there are very few data about its effect in allergic diseases. OBJECTIVE: The aim of the present study was to investigate the effect of malnutrition in allergic lung inflammation. METHODS: An anaphylactic reaction was induced in rat lungs and the increased vascular permeability was measured in the trachea, internal and external bronchi and parenchyma by the Evans blue extravasation method. These studies were conducted in two dietary groups: one fed a normoproteic diet (18%) and the other a hypoproteic diet (4.5%). When the animals were 60 days old the group fed the hypoproteic diet presented a reduction of 77.86% in bodyweight, 63.3% in food intake and 36% in plasma protein concentration characterizing a severe protein-calorie malnutrition. RESULTS: The anaphylactic reaction in the lungs induced a significant increase in vascular permeability in the trachea and bronchi of both dietary groups. However, the intensity of this effect was significantly lower in the malnourished group. Analysis of immunoglobulin isotypes in the serum by ELISA showed that whereas IgG1 and IgG2a levels were similar in both groups, the levels of IgE were significantly lower in the malnourished animals. Moreover, the levels of antigen-specific IgG1, IgG2a and IgE were all significantly inhibited by the protein-calorie malnutrition. When antibodies were passively transfered to the malnourished rats, they developed a reaction as intense as the normoproteic group. CONCLUSION: These results suggest that the capacity to release inflammatory mediators and the vascular response to these mediators is not affected by this type of malnutrition and, therefore, the diminished response of the airways reported here is probably due to the lower levels of anaphylactic antibodies produced by the malnourished rats.
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We evaluated the prevalence of short stature (SS) among children with respiratory allergic disease followed up in a specialised centre. These patients (N = 617; 8 months to 16 years) with respiratory allergy (asthma and/or rhinitis) were evaluated for SS (stature shorter than the 3rd percentile, NCHS pattern). The possible links between SS and gender; current age; type, severity, and duration of the allergic disease, treatment with corticosteroid and birth weight were also studied. To assess the influence of the socioeconomic level on SS frequency among atopics, 120 of these patients were compared to their non-atopics siblings. The overall prevalence of SS was 7.9%. Relationship between SS and gender type and severity of the allergic disease and treatment with corticosteroids were not observed. A significant higher frequency of SS occurred among patients with longer period of disease and birth weight less than 2,500 gr. Analysis of the pairs of brothers showed significant higher frequency of SS between allergics (12.5% x 4.2%) showing influence of allergic disease per se. Longitudinal studies for long periods of time are required to properly establish the relation between atopic disease and SS.
Thirty-seven separate episodes of acute bronchial asthma were studied in 21 asthmatic children. The bronchodilator, cardiovascular, and tremorigenic responses following administration of salbutamol (SAL), terbutaline (TER) and fenoterol (FEN) by closed-port intermittent nebulization were compared for a period of 8 hr. SAL was used at the maximum dose recommended by the manufacturer and TER and FEN at the average doses commonly used in children. Eleven acute attacks were treated with SAL, 12 with TER, and 14 with FEN. Pulmonary function was evaluated by clinical assessment and by the spirometric indices FEV1 and FEF25-75. Tremor was objectively measured, as well as heart rate (HR), respiratory rate, and blood pressure. The onset of bronchodilating effect occurred at 5 min for all three drugs and there were no differences in intensity and duration of bronchodilation between drugs. All three drugs caused rapid onset of tremor (5 min) and this tended to be more intense with SAL. There was a slight decrease in HR in the TER group, whereas SAL and FEN caused increase in HR, with mean values significantly greater than in the TER group from 5 to 30 min after drug administration. Our results indicate that the three short-acting beta 2-agonists studied are equally effective in treatment of acute bronchospasm by the inhaled route in children, in the doses used. Our findings imply that a dose of SAL twice as great as that commonly used by nebulization in children is equipotent to those usually employed for TER and FEN, as far as therapeutic effect is concerned, but it could generate more intense tremorigenic and tachycardic side effects.
In order to study placental transfer of IgG subclasses, paired blood samples were collected from mothers and umbilical cord of preterm (N = 69) and full-term (N = 68) newborns. The full-term group was further divided into 3 subgroups: appropriate for gestational age (AGA, N = 43), large for gestational age (LGA, N = 13) and small for gestational age (SGA, N = 12), according to birth weight. IgG subclasses (IgG1, IgG2, IgG3 and IgG4) were measured by the single radial immunodiffusion technique using monoclonal antibodies. IgG1 and IgG3 newborn subclass concentrations (10.17 and 0.57 g/l, respectively) increased with increasing gestational age and reached maternal levels (IgG1 = 8.86; IgG3 = 0.67 g/l) during the 37th week of pregnancy. Low levels of these subclasses were found in premature newborns. IgG2 from newborns were always lower than maternal levels (P < 0.05). LGA and SGA newborns had equivalent levels of IgG1 and IgG2 compared with AGA. SGA newborns had higher levels of IgG3 and lower levels of IgG4 than LGA and AGA newborns.
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OBJECTIVE: To determine the frequency and type of lesions of the temporomandibular joints (TMJ) as well as orthodontic alterations present in patients with juvenile rheumatoid arthritis (JRA). METHODS: Twenty-six patients had their TMJ evaluated clinically and by high resolution computer tomography. The patients were also submitted to orthodontic evaluation. Children with isolated malocclusion were used as a control group. RESULTS: Computer tomography detected TMJ alterations in 13 (50%) patients with JRA. Bilateral mild lesions were the most frequent. TMJ alterations were especially observed in young patients with JRA with the systemic and polyarticular type of onset. Worse functional class and corticosteroid therapy were also related to TMJ involvement. We observed orthodontic alterations in 18 patients with JRA (69%): midline deviation, convex facial profile. Class II molar relation, crowded lower anterior teeth, anterior open bite, and reduction in the maximum opening of the mouth. Severe TMJ lesions were correlated to cephalometric alterations, suggesting decreased mandibular growth.
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Thirty-five separate episodes of acute bronchial asthma were studied in 21 asthmatic children. The bronchodilator, cardiovascular, and tremorogenic responses following three modes of administration of salbutamol were compared: open continuous nebulization (ON), closed-port intermittent nebulization (CN), and oral route (OR), for a period of 8 hours. Eleven acute attacks were treated by ON, 11 by CN, and 13 by OR. Pulmonary function was evaluated by clinical assessment and by the spirometric indices FEV1 and FEF25-75. Tremor was objectively measured, as well as heart rate (HR), respiratory rate (RR), and blood pressure (BP). Fastest onset of bronchodilator action, maximal response, and longest duration were seen when the drug was administered by the CN. Onset of tremorogenic effect was registered at 5 minutes when salbutamol was used by CN and ON and at 30 minutes when used by OR. During the first 30 minutes, tremor was significantly greater when salbutamol was used by CN than by OR. There were minor cardiovascular effects, except regarding HR after CN, which was significantly greater than after OR, at 5 and 30 minutes. Our findings indicate the inhaled route as the most effective route for administration of salbutamol to treat acute bronchospasm in children. The use of CN is a good alternative to jet nebulizers, but the greater dose of drug effectively administered by this system can briefly cause more tremor and heart acceleration.
We compared exposure and levels of IgE and IgG antibodies to inhalant allergens in 20 children with asthma and positive skin tests to Dermatophagoides pteronyssinus, living in São Paulo, to 20 control children without history of asthma or allergy and negative skin tests to D. pteronyssinus, D. farinae, and Blomia tropicalis. In 16/20 and 17/20 houses of asthmatic and control children, respectively, at least one sample was obtained which contained > 10 micrograms Der p I/g of dust. Serum IgE antibodies to D. pteronyssinus and Blomia tropicalis were > 200 RAST U/mL in 19/20 and in 16/20 asthmatic children, respectively. In the control group, IgE antibodies to either mite species were < 40 RAST U/mL in most cases. IgG anti-Der p I and anti-Der f I antibodies were detected in 17/20 asthmatics, as opposed to 3/20 controls. Neither cat nor cockroach allergens caused significant sensitization among asthmatic or control children. Although exposure to high levels of mite allergens was common in São Paulo, significant IgE and IgG antibody responses were detected only in children with asthma.