The allergic sensitization in infants with atopic eczema from different countries.

BACKGROUND: No study has compared allergic sensitization patterns in infants with atopic eczema from different countries. The aim of this study was to investigate the patterns of allergic sensitization in a cohort of infants with atopic eczema participating in a multicentre, international study. METHODS: Two thousand one hundred and eighty-four infants (mean age 17.6 months) with atopic eczema from allergic families were screened in 94 centres in 12 countries to participate in a randomized trial for the early prevention of asthma. Clinical history, Severity Scoring of Atopic Dermatitis Index, measurements for total serum IgE and specific IgE antibodies to eight food and inhalant allergens were entered into a database before randomization to treatment. A history of type of feeding in the first weeks of life and exposure to animals was recorded. RESULTS: A total of 52.9% of the infants had raised total IgE, and 55.5% were sensitized to at least one allergen. There was a wide difference in the total IgE values and in the sensitization rates to foods and aeroallergens among infants from different countries. The highest prevalence rates of allergen-sensitized infants were found in Australia (83%), the UK (79%) and Italy (76%). Infants from Belgium and Poland consistently had the lowest sensitization rates. In each country, a characteristic pattern of sensitization was found for aeroallergens (house dust mite > cat > grass pollen > Alternaria), but not for food allergens. CONCLUSIONS: In infants with atopic eczema, there is a wide variation in the pattern of allergic sensitization between countries, and data from one country are not necessarily generalizable to other countries.

Lack of control of severe asthma is associated with co-existence of moderate-to-severe rhinitis.

BACKGROUND: Retrospective studies provide evidence that rhinitis is associated with more severe asthma. The aim of this study was to evaluate prospectively whether rhinitis is a predictor of increased asthma severity. METHODS: Five hundred and fifty-seven patients with severe asthma were enrolled. During 1 year of follow-up, each patient was evaluated every 3 months with a record of emergency room visits and supply of topical corticosteroids for asthma and rhinitis. In the 1 year of follow-up visit, the patients were checked for rhinitis diagnosis, severity and answered questionnaires for asthma symptoms and quality of life. RESULTS: Eighty-two (15%) patients had no rhinitis, 299 (54%) had mild rhinitis and 176 (31%) moderate/severe rhinitis. In logistic regression models, moderate/severe rhinitis was a predictor for any emergency room visit in the follow-up period [3.83 (2.00-7.35)], for the presence of uncontrolled asthma after 1 year of follow-up [12.68 (1.73-92.85)], for <10% improvement of the airway obstruction [2.94 (1.48-5.85)] and <50% reduction in the number of emergency room visits [2.90 (1.02-8.26)] in the year of follow-up. It was also associated with a smaller chance of more than 90% reduction in the number of emergency room visits in the year of follow-up [0.27 (0.12-0.60)]. In a multivariate linear regression model, severity of rhinitis was positively correlated with a score of asthma severity and inversely correlated to an index of quality of life. CONCLUSIONS: In a population with severe asthma, moderate/severe rhinitis is a strong predictor for greater severity of asthma.

IgE antibody responses in young children with atopic dermatitis.

In 2184 young children aged 13-24 months with atopic dermatitis (SCORAD 5-59) serum IgE antibodies to a standard panel of food and inhalant allergens were assayed. The frequency of positive IgE responses (>0.35 kU/l) increased with greater severity of skin disease. A significant minority of infants had levels of IgE antibody to foods to suggest they were at risk of acute reaction to those foods (7% to hen's egg, 3% to cow's milk, 4% to peanut). Our findings indicate that the frequency of positive IgE responses is related to disease severity and suggest that differences in the time course of the development of IgE responses to food, which are at maximum prevalence within the first year of life, while inhalant allergies, are still developing between 1 and 2 yr and beyond.

Prevalence of symptoms of asthma, rhinitis, and atopic eczema in Brazilian adolescents related to exposure to gaseous air pollutants and socioeconomic status.

OBJECTIVES: To evaluate the relationship between exposure to gaseous air pollutants (ozone [O3], carbon monoxide [CO], nitrogen dioxide [NO2], and sulfur dioxide [SO2]) socioeconomic status and the prevalence of symptoms of asthma, rhinitis and atopic eczema in adolescents. SUBJECTS AND METHODS: A sample of 16 209 adolescents from São Paulo West (SPW), São Paulo South (SPS), Santo André (SA), Curitiba (CR), and Porto Alegre (PoA) were enrolled. Data on air pollutants and socioeconomic status were compared to prevalence of symptoms with the Spearman correlation coefficient. RESULTS: Socioeconomic status was quite similar in all cities. The levels of O3 in SPW, SPS, and SA, and of CO in SA were higher than the acceptable ones. In relation to O3 and CO exposures, adolescents from SPW and SA had a significant risk of current wheezing, whereas living in SPW was associated with a high risk of rhinoconjunctivitis, eczema, and flexural eczema and living in CR to rhinitis. Exposure to NO2 was associated with a high risk of current wheezing in SPW and SA, and of severe asthma in SPW and PoA. Exposure to SO2 was associated with a high risk of current wheezing in SPW and SA, severe asthma in SPW and PoA, and nighttime cough, eczema, flexural eczema and severe eczema in SPW. Living in SPW, CR, or PoA was associated with a high risk of rhinitis, rhinoconjunctivitis, and severe rhinitis. CONCLUSIONS: Although we did not detect a characteristic pattern for all symptoms evaluated or a specific air pollutant, our data suggest a relationship between higher exposure to photochemical pollutants and high prevalence or risk of symptoms of asthma, rhinitis, and atopic eczema.

Antibody response to pneumococcal capsular polysaccharide vaccine in Down syndrome patients.

The majority of children with Down syndrome (DS) tend to have frequent bacterial infections including recurrent respiratory infections. Our objective was to evaluate the production of antibodies to pneumococcal polysaccharide antigens after active immunization in DS subjects. IgG antibodies to pneumococcal serotypes (1, 3, 6B, 9V, and 14) were measured before and 6 weeks after immunization with a 23-valent pneumococcal vaccine (Pneumo23, Pasteur-Merrieux) in 6- to 13-year-old DS children (N = 17) and in aged-matched normal controls (N = 30). An adequate response was defined as a 4-fold increase over baseline or a post-immunization level of specific pneumococcal serotype antibody > or = 1.3 microg/mL. After immunization, all DS children had an increase in post-immunization levels against all serotypes analyzed. A 4-fold or more increase was observed in all DS children concerning serotypes 1 and 14, in 90% of subjects for serotypes 3 and 9V, and in 65% for serotype 6B. Regarding this increase, 8 of the 17 DS children had an adequate response to all serotypes analyzed, 8/17 patients to 4 serotypes and 1/17 to 3 serotypes. However, when we compared post-immunization levels between DS children and controls, we observed lower levels in the former group (P < 0.05) for all serotypes except serotype 3. We conclude that pneumococcal polysaccharide immunization could be beneficial for these DS children.

Abnormal maxillary sinus radiographs in children: do they represent bacterial infection?

Thirty-three children with chronic tonsillitis and/or adenoid enlargement and without previous diagnosis of sinusitis were studied regarding the bacterial flora of their maxillary sinuses. Puncture of maxillary sinus was performed at surgery (adenoidectomy and/or tonsillectomy) and aspirates were cultured. Streptococcus pneumoniae was isolated from 8 of 12 (66.7%) patients whose x-rays showed completely opacified maxillary sinus. Streptococcus viridans, Streptococcus faecalis, and Staphylococcus epidermidis were recovered from 6 (28.6%) of the 21 patients with normal maxillary sinus radiographs. Bacterial titers were greater than 10(4) colonies/mL in all but one of the positive cultures. No anaerobic bacteria were isolated. History of bronchial asthma, presence of nasal purulent secretion, elevated blood eosinophils, and elevated serum IgE were found more frequently in children with complete opacification of maxillary sinus. Serum levels of IgG2 were low in 29% of the children, but no correlation was found between low IgG2 levels and positive cultures from maxillary sinus aspirates. We concluded that children with complete radiologic opacification of maxillary sinus had bacterial infection in almost 70% of the cases with symptoms that did not prompt their physicians to consider the diagnosis of sinusitis.

Hereditary angioedema type II--a study of two families.

Hereditary angioedema (HA) is caused by a quantitative or qualitative deficiency of C1 esterase inhibitor (C1 INH). We present a study of nine patients with HA belonging to two different families. The symptoms started before 10 years of age in most cases (78%). Facial edema (lips, eyes) and of the extremities (feet, hands) were the most frequent complaints. Three patients presented edema of the glottis and one of them underwent a tracheostomy twice. Laboratory tests, outside the acute crisis, revealed low levels of C4 in all patients. The serum levels of C1 INH were normal in seven patients; however, functional activity was not observed in any of them. After the use of a modified androgen (danazol), control of symptoms was observed in all patients, although functional activity was re-established in only five patients.

Bronchoprovocation with methacholine in children under two years old: a follow-up study.

Fifty-one wheezing babies (WB) under two years of age and 20 controls (C) within the same age range were submitted to a bronchial provocation test (BPT) with methacholine. The appearance of wheezing on pulmonary auscultation was used to determine PCW (provocative concentration of methacholine causing wheezing). For all tests, methacholine diluted in saline at increasing concentrations (0.025, 0.125, 0.25, 0.5, 1.0, 2.5, 5.0 and 10.0 mg/ml) was delivered with O2 (5 ml/min) via a face mask. Solution was inhaled through the mouth and nose during two minutes of quiet tidal breathing via a nebulizer containing a 2 ml volume. No collateral effects were observed, except for tachypnea and tachycardia. There was a statistically significant difference between the PCW for WB (2.3 mg/ml) and the PCW for C (9.2 mg/ml). A 5 mg/ml concentration of methacholine provides the clearest distinction between the WB and C groups. Indeed, we observed that 96% of WB and 25% of C demonstrated PCW below this concentration. In the WB group, those with mild symptoms had higher PCW values. When the BPT was repeated in 27 WB at an 8-month interval, statistically significant differences between the two PCV values were observed. The highest PCW values were evidenced in the second BPT. The use of BPT with methacholine could establish PCW as a parameter of bronchial hyperreactivity in infants.

Comparative performance for immediate hypersensitivity skin testing using two skin prick test devices.

Fifty-five patients were skin-tested by Multi-Test (M) and needle prick test (NPT) to compare the reproducibility of the methods. We used 6 allergenic extracts: Dermatophagoides pteronyssinus, Dermatophagoides farinae, dog epithelium, cat pelt, American cockroach and mixed molds. A glycerosaline and a positive control (histamine 1 mg/ml) were performed in both methods. Statistically significant differences in histamine and Dermatophagoides farinae wheal reactions between the two methods (M > NPT) were found, with no differences with the other allergenic extracts. We concluded that the two methods are similar with respect to determining the immediate hypersensitivity, but the Multi-Test is better accepted by children.

Magnetic resonance imaging in a patient with X-linked agammaglobulinemia and chronic meningoencephalitis.

The case of a boy with congenital agammaglobulinemia is reported. In spite of regular immunoglobulin replacement therapy (fresh plasma transfusion from family donors--20 ml/kg/month), he developed chronic meningoencephalitis (ME). Besides characteristic clinical signs of ME, he also presented at cerebrospinal fluid analysis pleocytosis with lymphocyte predominance and class II cytomorphology, and delta and theta waves in the EEG. Computerized tomography showed dilatation of the ventricles and marked cortical fissures (sulci). Magnetic resonance imaging showed a disease affecting white and gray matter. After diagnosis of ME, replacement therapy with Sandoglobulin (700 mg/kg every 2 weeks) was started. His condition gradually worsened, and coma and death occurred after a follow-up of 18 months. The etiological agent could not be identified.

Specific sensitization to Dermatophagoides pteronyssinus and cutaneous reactivity to histamine in Brazilian children.

The immediate hypersensitivity cutaneous test is a recognized method for etiologic diagnosis of allergic diseases. It is easily conducted, painless and can be quickly interpreted, making it deal for use with children. However, its low positivity in infants limits its use this population. The purpose of our study was to evaluate the skin reactivity to atopic and non-atopic children of different ages to increasing concentrations of histamine and to an extract of Dermatophagoides pteronyssinus (Dpt). Atopic children (A, n = 217) and non-atopic children (C, n = 198), under 15 years of age were grouped by age and administered skin prick tests. Increasing concentrations of histamine (1, 9, 81 and 243 mg/ml) and Dpt (10,000 AU/ml) were applied to the forearm. Skin reactions were recorded after 15 minutes and expressed as the mean of the largest wheal and its midpoint perpendicular diameter. Cutaneous reactions were observed in the early phases of life with a progressive increase observed in both groups. Significant differences were noted between the two groups starting at 48 months of life. As the concentration of histamine was increased, we observed a higher level of cutaneous reactivity in younger children. Comparative analysis of cutaneous reactivity to the histamine solution (1 mg/ml) and the Dpt extract showed parallelism between them and wheals with diameters larger than 3 mm after 12 months of age. We concluded that the skin prick test with Dpt is reliable in atopic children after 1 year of age. Reactivity to higher concentrations of histamine was observed after 3 months of age for all children. However, considering all age groups, the skin reactivity in atopic children to histamine (1 mg/ml) was more precocious when compared to controls.

Diagnostic value of nasal provocation testing and rhinomanometry in allergic rhinitis.

We studied 32 patients, aged 7 to 17 years, with clinical symptoms of perennial allergic rhinitis, isolated (n = 21) or associated with asthma (n = 11), all of them with positive skin test and specific serum IgE for Dermatophagoides pteronyssinus (Dpt). The control group consisted of 10 children aged 7 to 16 years, with no personal or family history of allergy and with negative skin tests and negative specific serum IgE for mites. Total and specific IgE measurements in nasal secretion and nasal provocation testing (NPT) were also performed with increasing concentrations of Dermatophagoides pteronyssinus (Dpt) extracts. The nasal response was evaluated using a clinical score and active anterior rhinomanometry. The levels of total and specific IgE in nasal secretion were higher in patients with allergic rhinitis than in individuals from the control group. The NPT presented a significant correlation with clinical symptoms, skin tests and specific serum IgE. None of the individuals from the control group presented a positive NPT. No generalized reactions or bronchial response at the immediate phase of NPT were observed. The NPT constitutes a safe, dependable investigative procedure of nasal reactivity to a specific allergen, presenting a good sensitivity and specificity when compared to the other methods classically used in allergy studies.

IgE antibodies to aeroallergens in allergic children in São Paulo, Brazil.

The sensitization to inhaled allergens was studied in 80 Brazilian children and 12 controls, aged 6 to 16 years. We performed skin tests with Alternaria alternata, cat, dog, Lolium perenne, grasses and the following domestic mites: Blomia tropicalis, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Lepidoglyphus destructor, Chortoglyphus arcutus and Aleuroglyphus ovatus. The frequencies of positive skin tests (mean diameter > or = 23 mm) were respectively 15%, 11%, 11%, 6%, 7%, 95%, 92%, 88%, 76%, 75% and 71%. The mean diameter of the wheal to domestic mites was higher to D. pteronyssinus than to B. tropicalis, L. destructor, A. ovatus and C. arcuatus (p < 0.05). The skin test results to domestic mites by regression analysis revealed highly significant correlation (p < 0.0001), suggesting considerable cross-reactivity between them. Specific IgE to each mite was determined and the results expressed as the mean of the percentage of total counts bound (% TCB). We had the highest levels of % TCB to D. farinae, followed by D. pteronyssinus, E. maynei, B. tropicalis, C. arcuatus, L. destructor and A. ovatus. The Brazilian children with asthma had more positive skin tests to domestic mites than to other inhalant allergens, and based on previous studies performed in São Paulo that have shown D. pteronyssinus and B. tropicalis as the most prevalent mite species in house dust, we assumed that IgE Ab to D. farinae reflects cross-reactivity with D. pteronyssinus in most cases. The observed high levels of IgE Ab to domestic mites stress the importance of environmental avoidance measures, decreasing the rate of sensitization or perhaps the development of symptoms of asthma in genetically predisposed children.

Non-specific nasal provocation in children with chronic allergic rhinitis.

Twenty-three children with chronic allergic rhinitis (Group A) and eleven normal non-atopic subjects (group C) were submitted to non-specific nasal provocation tests with histamine (0.03; 0.06; 0.125; 0.25; 0.5; 1.0; 2.0 and 4.0 mg/ml), and one week later with methacholine (0.025; 0.1; 0.25, 0.5; 1.0; 2.5; 5.0 and 10.0 mg/ml). Measurements of total nasal resistance were performed by active anterior rhinomanometry (Berger, S.A.) and symptoms were recorded. Challenges were carried out in the morning with all children in an acclimatized room (25 degrees C/77 degrees F). Concentrations of the tested drugs were increasingly instilled, and after 5 min were followed by total nasal resistance, FEV, and FVC measurements. Considering as positive those tests in which total nasal resistance had a 100% increase, we observed that both histamine and methacholine caused an increase in total nasal resistance as instilled drug concentration rose; histamine provocations were significantly more positive among group A than group C patients (91% sensitivity, 80.8% positive predictive value). This was not observed with methacholine (55% sensitivity, 75% positive predictive value). In neither provocation was there correlation between the concentration that induced a positive response and symptoms. There were no changes in spirometric values during the tests. Nasal provocations with histamine and methacholine are safe and well tolerated. Histamine seems to be more adequate for differentiating children with allergic rhinitis from normal controls.

Lysine-vasopressin in the evaluation of the hypothalamic-pituitary-adrenal axis in children with allergic rhinitis treated with intranasal beclomethasone dipropionate or oral prednisone.

One of the complications of steroid therapy is the hypothalamic-pituitary-adrenal (HPA) axis' suppression, particularly in children where this can lead to growth suppression and other well known complications. Although there are a large number of studies on suppression of the HPA axis with the use of topical steroids, the subject is still controversial. We measured the HPA axis function in 3 groups of allergic children treated with: 1) intranasal beclomethasone dipropionate (BDP) 400 micrograms/day for 4 weeks or 2) BDP 800 micrograms/day for 4 weeks and 3) oral prednisone, 1 mg/kg/day for 2 weeks. The HPA response was obtained after lysine-vasopressin (LVP) stimulation. LVP acts on the pituitary or hypothalamus level, stimulating the whole axis. Peripheral blood samples through an intravenous line were obtained for serum cortisol measurement at zero, 30, 60, and 90 minutes after the intravenous injection of LVP, before and after the treatment period. Our results showed no suppression of the HPA axis in children medicated with BDP at either 400 micrograms/day or 800 micrograms/day. On the other hand, there was a suppression of the HPA axis after prednisone treatment (p < 0.05). During the LVP test some side effects, possibly due to systemic vasoconstriction, were noted such as abdominal pain, nausea and vomiting, and transient hypertension. In conclusion, intranasal BDP at the dose of 400 or 800 micrograms/day during 4 weeks did not induce HPA axis suppression. The LVP test is efficient to demonstrate HPA hypofunction or suppression and it produced only mild to moderate transient side effects. However, due to the side effects observed, a safer test such as urinary free cortisol (24 hours), should be used in the investigation of the HPA axis.

Serum penicillin concentrations after intramuscular administration of benzathine penicillin G in children with rheumatic fever and controls.

Serum and urine penicillin levels were determined in 11 children with rheumatic fever (RF) who were receiving benzathine penicillin G (BPG) prophylactically every 3 weeks and in 10 children without RF who received the drug for the treatment of other infections. The dose given was 600,000 units for children weighing less than 25 kg and 1,200,000 units for those with a weight above 25 kg. Blood and urine samples were collected from both groups before and on days 7, 14 and 21 after BPG administration. Our results showed that: minimum inhibitory concentrations (MICs) of BPG for group A beta-hemolytic streptococci were 0.02 IU/ml or 0.0125 microgram/ml; intramuscular BPG did not give adequate serum levels to block the growth of group A beta-hemolytic streptococci in approximately 24 and 62% of children included in the study on days 14 and 21 after its administration, respectively; BPG metabolism was similar in both groups and did not depend on the underlying disease; serum and urine levels did not vary according to sex and weight; and there was a small correlation between serum and urine levels.

Nasal provocation test (NPT) with isolated and associated dermatophagoides pteronyssinus (Dp) and endotoxin lipopolysaccharide (LPS) in children with allergic rhinitis (AR) and nonallergic controls.

BACKGROUND: Inhalation of endotoxin may enhance inflammatory airway response in sensitized asthmatics persons after allergen(s) inhalation. OBJECTIVE: To evaluate nasal response to intranasal instillation of Dermatophagoides pteronyssinus (Dp), endotoxin (LPS), and to Dp+LPS in children with perennial allergic rhinitis (PAR). METHODS: 10 PAR children (positive skin prick test to Dp) and 10 nonallergic controls (C) undergoing nasal provocation test (NPT), who were quantified by active anterior rhinomanometry and measurement of Total Nasal Resistance (TNR). The NPTs were initially performed with histamine (H; 0.03 to 16.0 mg/mL), and then, at least at weekly intervals, the NPTs were done with Dp (1/100,000 to 1/2.5), LPS (1 to 500 mg/mL) and to Dp+LPS. During NPT with Dp+LPS, Dp concentration was kept constant (1/100,000; 1/10,000; 1/1,000) and was combined with different concentrations of LPS (1, 5, 10, 20 mg/mL). The NPT was considered positive when TNR reached twice the basal TNR. RESULTS: H and Dp NPTs were positive in all AR children. In group C, H NPT was positive in 60% and Dp NPT was negative in all children. NPT with LPS was positive only in 30% of the AR children. NPT with Dp+LPS was positive in 90% of the AR patients in Dp concentration of 1/1,000 and in LPS concentrations of 5, 10, and 20 mcg/ mL. This positive association was observed with Dp concentrations lower than those obtained during NPT with Dp in 60% of AR patients. There were no changes in pulmonary function tests in all children after NPT. CONCLUSIONS: This study suggests that LPS enhances the effects of allergen challenges on nasal airflow. The daily inhalation of allergens plus endotoxin in AR patients does increase the nasal responsiveness.

International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire: validation of the asthma component among Brazilian children.

Written questionnaires have been widely used in epidemiological studies of asthma. However, when translated to another language, they must be validated. The International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire had been previously validated by a comprehensive study, but this had not been done in Brazil. Our objective was to validate the asthma component of the ISAAC self-applicable written questionnaire following its translation to Portuguese. A group of 10 pediatricians and 10 pediatric allergists graded the questions from 0 to 2, and established a maximum score for each question. The questionnaire was answered by parents or guardians of asthmatic children, aged 6 to 7 years old (n = 26) and of nonasthmatic control children of the same age (n = 26); and by asthmatic (n = 33) and nonasthmatic (n = 33) adolescents, aged 13 to 14 years. Half of these individuals responded to the same questionnaire after 2 to 4 weeks. This second response allowed the evaluation of the reproducibility of the ISAAC questionnaire. The maximum global score possible was 14, and cut-off levels of 5 and 6 were found for the groups of 6 to 7 and 13 to 14 year olds, respectively. There was significant agreement between the adolescents' responses to the questionnaire and those from their parents or guardians (74.3%); however, significant discordance was observed for individual questions including "wheezing with exercise." In both age periods the questionnaire was significantly reproducible (Kappa test) (6 to 7 year olds Kw = 1; 13 to 14 year olds Kw = 0.89). In conclusion, the asthma component of the ISAAC written questionnaire was proven to be reproducible, adequate and able to differentiate between asthmatics and controls. Adolescents answered the questionnaire appropriately, however the results suggest that adolescents' parents or guardians underestimate asthma symptoms which interfere little with the adolescent's daily activities.

Methotrexate in the treatment of corticodependent asthmatic children.

Methotrexate has been used as an anti-inflammatory agent in chronic asthma. We evaluated the action of methotrexate in eight corticodependent severely asthmatic children (more than 10 mg of prednisone per day for at least one year). The patients (3 males and 5 females; aged 8 to 14 years) received a single weekly dose of 0.6 mg/kg methotrexate (maximum 25 mg) and folic acid (15 mg/day for 5 days in the week). The children were examined and had their pulmonary function test evaluated weekly. As the study progressed, the dose of prednisone was reduced and maintained till the next evaluation if the patient's symptoms were under control. After the 3rd month of treatment, we observed a significant reduction in the dose of prednisone and maintenance of the spirometric parameters. At the end of the trial, in 4 patients it was possible to reduce the basal prednisone dose 56% or more. In the remaining 4, one did not show any benefit and in the other 3, it was possible to obtain an average reduction of 40% of the basal prednisone dose. The total mean reduction was 55.9%. This oral corticoid reduction was not associated with clinical or pulmonary function deterioration, except in one patient. The patients were submitted to white blood cell count, hepatic transaminases, urine tests and other determinations at least once a month. There were no changes in biochemical tests. The side-effects were nausea, vomiting and abdominal pain. In conclusion, methotrexate given to severely corticodependent asthmatic children permitted a reduction in the daily intake of prednisone, reducing the severe side-effects of chronic corticotherapy.