Arturo Berber

Primary Prevention of Acute Respiratory Tract Infections in Children Using a Bacterial Immunostimulant: A Double-Masked, Placebo-Controlled Clinical Trial

BACKGROUND Acute respiratory tract infections (ARTIs) are among the main causes of morbidity and mortality in children. The bacterial extract OM-85 BV has shown some protective effect for ARTIs in preschool children and a reduction in exacerbations of chronic bronchitis in adults. OBJECTIVES This trial reports results of a double-masked, placebo-controlled, parallel-group clinical study that assessed the efficacy and tolerability of OM-85 BV in the prevention of ARTIs in school girls living in an orphanage. METHODS Two hundred girls (age range, 6 to 13 years) living in an orphanage entered the trial. Participants were randomly allocated to receive either OM-85 BV or placebo for 10 consecutive days a month for 3 consecutive months. Patients were followed up for 6 months, including the administration period. The trial began in September 1996 and finished in March 1997. Primary end points were the type and number of infections. Secondary end points included when an infection occurred, time to clinical cure, severity of infection, absenteeism from school due to an ARTI, number of antibiotics or other drugs prescribed, and duration of concomitant drug treatment. RESULTS During the trial, patients in the OM-85 BV group experienced 143 ARTIs (135 upper ARTIs and 8 otitis episodes) and patients in the placebo group experienced 299 ARTIs (273 upper ARTIs, 1 lower ARTI, and 25 otitis episodes). The median number of ARTIs was 1.0 (0.0, 3.0; 5th percentile, 95th percentile) in the OM-85 BV group compared with 3.0 (2.0, 4.0; 5th percentile, 95th percentile) in the placebo group. This difference was statistically significant (P < 0.001). Participants who received OM-85 BV also showed significantly better results (P < 0.001) than participants who received placebo in terms of median duration of illness, median number of missed school days due to an ARTI, median number of antibiotic and drug courses, and median duration of concomitant treatment. There were significant differences (P < 0.05) in severity of ARTIs during month 4 of the trial, with patients receiving OM-85 BV showing less severe ARTIs than patients receiving placebo and shorter mean time to clinical cure from the second month to the fourth month. No adverse events related to the trial medications were reported. CONCLUSIONS OM-85 BV had a preventive effect on ARTIs in the school girls, with a reduction in the antibiotic requirements and the duration of ARTIs. Future studies are needed to further explore the role of OM-85 BV in the prevention of ARTIs.

Obesity and Metabolic Risks in Children

BACKGROUND We undertook this study to establish the prevalence of overweight, obesity, abdominal obesity, high blood pressure, and high glucose and triglyceride levels in school-age children from Mexico City, as well as to determine how overweight and obesity are related to the other risk factors. METHODS The study was a cross-sectional survey comprised of 1819 children (6-13 years of age) attending six elementary schools. Gender, age, weight, height, waist circumference, blood pressure, and levels of triglycerides and glucose were registered. Percentiles were calculated according to American standards for BMI, height, waist circumference, and blood pressure. RESULTS Compared to American references, mean percentiles for waist circumference and BMI were >50, and mean height percentiles were <50. Prevalence of overweight was 22.3 and 23.6% for boys and girls, respectively; obesity, 28 and 21.2%; abdominal obesity, 22.1 and 11.7%; high triglyceride levels, 11.3 and 15.4%; high blood pressure, 4.8 and 5.8%, respectively. Overweight, obesity, and abdominal obesity are associated with higher blood pressure and triglyceride levels (odds ratio>1.0, p<0.05). Percentiles for BMI, waist circumference, systolic blood pressure, and diastolic blood pressure also had significant correlations (r>0.2, p<0.001). CONCLUSIONS This population of Mexican school-age children was shorter and heavier than their American standards. The prevalence of metabolic risks was similar to those reported in American adolescents in NHANES surveys.

Obesity risk factors in the ISAAC (International Study of Asthma and Allergies in Childhood) in Mexico City

BACKGROUND The International Study of Asthma and Allergies in Childhood (ISAAC) has promoted surveys in asthma and allergic diseases using standardized methodologies including validated questionnaires. Many items in the questionnaires have also been implied in the overweight and obesity etiology. OBJECTIVE To describe the factors associated with obesity in subjects of 6-7 years and 13-14 years in the ISAAC survey in Mexico City. MATERIAL AND METHODS Data were obtained from questionnaires of children participating in a phase 3b ISAAC survey. Logistic regression was used to determine the obesity risks factors. RESULTS The factors related to obesity were weekly consumption of meat (+, positive relationship), vegetables, pasta, rice (+) and quartiles of birth weight (+) in boys of 6-7 years. Having suffered eczema at any time, weekly consumption of fruit, pasta, butter, nuts, potato (+), fast food (+), daily TV viewing (+) in girls of 6-7years. Having suffered eczema at any time, weekly consumption of pasta (+), butter, potato, weekly physical exercise in boys of 13-14 years; weekly consumption of pasta, margarine, milk, fast food (+), currently smoking in girls of 13-14 years. CONCLUSIONS There were not common factor patterns for the different groups, birth weight, fast food, TV viewing and lack of exercise have been previously related to pediatric obesity. Asthma was not associated with a higher risk of obesity but medical history of eczema was associated with lower risk of obesity in the 6-7 years girls, and 13-14 years boys. The present study provides the bases for future epidemiological studies and gives some clues on possible public health actions.

Higher metabolic syndrome in obese asthmatic compared to obese nonasthmatic adolescent males.

The relationship between asthma and obesity has been documented in children and adolescents; however, few studies on metabolic syndrome and asthma have been performed. Objective. To determine the prevalence of metabolic syndrome in adolescents among the following groups: obese with asthma (OA), obese without asthma (ONA), nonobese with asthma (NOA), and nonobese without asthma (NONA). Patients and Methods. The authors measured anthropometric (height, weight, waist circumference, body mass index, and waist-hip ratio), clinical (Tanner stage, blood pressure, fat and muscle reserve, and exercise), and biochemical parameters (basal and load glucose, cholesterol, triglycerides, high-density lipoproteins, uric acid, and insulin) in 500 Mexican adolescents. Results. A total of 111 OA, 198 ONA, 63 NOA, and 71 NONA adolescents completed the study. There were no differences in age, height, Tanner stage, high-density lipoproteins, or basal glucose among groups. Cholesterol, triglycerides, uric acid, basal insulin, and homeostasis model assessment (HOMA)-IR were significantly higher among the obese than nonobese groups but were similar between the OA and ONA groups. The prevalence of impaired fasting glucose was significantly higher among ONA versus OA males. The prevalence of metabolic syndrome (define as ≥3 abnormal cardiometabolic risk factors by de Ferranti, Cook, and International Diabetes Federation [IDF] criteria) was higher among OA teens than in the ONA group; however, this association was significant only among males. Adolescents from the ONA group were able to perform significantly more vigorous exercise than the other groups. Conclusion. Adolescent males who were obese and also had mild persistent asthma had a significantly higher prevalence of metabolic syndrome than obese males without asthma. However, overall, asthma seems to confer a protective effect against the prediabetes condition in males.

Use of OM-85 BV in children suffering from recurrent respiratory tract infections and subnormal IgG subclass levels

BACKGROUND Recurrent acute respiratory tract infections (RARTIs) in children are related to IgG subclass deficiencies. The aim of the trial was to evaluate the effect of OM-85 BV in the number of RARTIs as well as in the IgG subclass levels. METHODS This was a randomized, double-blind, placebo-controlled clinical trial. Patients of ages three to six years, having three or more documented ARTIs during the last six months with subnormal IgG subclass levels were included. Patients took either one capsule of OM-85 BV (3.5 mg) or placebo orally every day for ten consecutive days per month during three consecutive months. Patients were followed three further months without drug intake. IgG subclass levels were determined before and after treatment. RESULTS IgG4 levels diminished after the OM-85 BV treatment (-3 [-8.0, -1.0] median difference [95 % CI] p < 0.05 by Wilcoxon test). No other significant changes in IgG subclasses were observed. After six months the patients in the OM-85 BV group (n = 20) experienced 2.8 1.4 (mean SD) ARTIs, while the patients in the placebo group (n = 20) suffered 5.2 1.5 ARTIs (-2.4 [3.3, -1.5] mean difference [95 % CI] p < 0.001 by Students t test). Three patients with OM-85 BV had gastrointestinal events related to drug administration, as well as three placebo patients. CONCLUSION This study demonstrated the clinical benefit of OM-85 BV in patients suffering from RARTIs and subnormal levels of IgG subclasses. This trial opens new perspectives in the research of the mechanism of action of OM-85 BV.

Use of sibutramine in obese hispanic adolescents

A study on the treatment of obese adolescents with the use of sibutramine in private practice is presented. Patients consisted of 24 boys and 43 girls with obesity (body mass index [BMI] < 85th percentile sex-specific BMI for age and sex) ranging from 12 to 18 years of age. Patients were given sibutramine 10 mg per day for 6 months. With the last observation carried forward adjustment, after 6 months of treatment, patients’ average weight changed from 91.6±19.7 kg to 81.9±19.0 kg (P > .001), that is, 89.5±7.3% of initial weight. The most frequently reported adverse events included increased blood pressure and pulse rate (n=7), constipation (n=8), dry mouth (n=4), and constipation and dry mouth (n=3). Sibutramine may be considered effective for the treatment of obese adolescents, with a level of safety similar to that observed in adult patients.

Safety and efficacy of sibutramine in overweight Hispanic patients with hypertension

This 6-month randomized study evaluated the safety and efficacy of sibutramine in 57 overweight Hispanic patients with hypertension. Following a 2-week washout to confirm the diagnosis of hypertension, antihypertensive medication was adjusted to achieve a blood pressure less than 140/90 mm Hg before institution of either sibutramine 10 mg or placebo once a day. A body mass index in excess of 27 kg/m2 was required for entry. At study end, weight had changed from 75.4±9.6 to 70.0±9.5 kg in the sibutramine group and from 77.9±9.0 to 74.5±9.4 kg in the placebo group. In the sibutramine group, systolic blood pressure was 127.8±5.8 mm Hg after stabilization and 125.2±8.5 mm Hg after completion of the trial; respective values for diastolic blood pressure were 82.4±3.7 and 81.5±4.6 mm Hg. With placebo, blood pressure dropped from 129.0±7.1/80.9±4.9 mm Hg to 122.8±9.7/80.3±5.4 mm Hg at the same timepoints. In the sibutramine group, 14 patients reported 21 adverse events, most frequently headache (n=5), constipation (n=4), and dry mouth (n=4). In the placebo group, 13 patients had 20 adverse events. Sibutramine is safe and effective in overweight Hispanic patients with hypertension, but monitoring of blood pressure and titration of antihypertensive medication are necessary.

Effect of salmeterol and salmeterol plus beclomethasone on saliva flow and IgA in patients with moderate-persistent chronic asthma

BACKGROUND The use of short-acting beta2-agonists is associated with oral mucosa injuries that are probably provoked by decreased saliva flow and decreased concentrations of immunoglobulin (Ig)A in saliva. OBJECTIVES To explore the effect of salmeterol, alone or combined with beclomethasone, on the health of oral mucosa, as well as its effect on saliva flow and IgA concentration in saliva. METHODS Patients ranging in age from 6 to 15 years with moderate-persistent chronic asthma were enrolled. Patients received two 6-week treatments, one with salmeterol plus beclomethasone and the other with only salmeterol, with a 1-week washout period between treatments. Patients had oral cavity examinations and assessments of saliva flow, IgA in saliva, and total protein in saliva before the beginning and at the end of each treatment RESULTS The results of the baseline oral examinations were normal in all patients. The postsalmetrol (PS) examinations detected 13 patients with gingivitis and the postbeclomethasone-salmeterol (PBS) examinations disclosed 10 patients with gingivitis and 1 with lower-lip ulceration. Baseline saliva flow was 16.25 +/- 7.04 mm/minute (confidence interval [CI] 95% 13.67; 18.89), PS was 13.53 +/- 5.93 mm/minute (CI 95% 11.33; 15.73), and PBS was 16.57 +/- 5.54 mm/minute (CI 95% 14.51; 18.62). No statistical differences between the different assessments were found. Mean saliva IgA at baseline was 4.99 +/- 1.96 mg/dL (CI 95% 4.26; 5.71), PS IgA was 6.53 +/- 3.02 mg/dL (CI 95% 5.41; 7.65), and PBS IgA was 4.82 +/- 1.98 mg/dL (CI 95% 4.08; 5.56). PS IgA was significantly higher than the other two determinations (P < 0.05 by Bonferroni and Tukey tests). Baseline saliva IgA-to-protein ratio was 0.72 +/- 0.24 (95% CI 0.64; 0.80), PS IgA:protein ratio was 1.02 +/- 0.38 (95% CI 0.88; 1.16), and PBS IgA:protein ratio was 0.72 +/- 0.25 (95% CI 0.62; 0.82). PS IgA:protein ratio was significantly higher than the other two determinations (P < 0.05 by Bonferroni and Tukey tests). CONCLUSIONS In the present study it was demonstrated that salmeterol alone or in combination with beclomethasone induced injuries in the oral mucosa, but only salmeterol alone induced increases in the total and protein-adjusted IgA in saliva.

Use of Broncho-Vaxom® in private practice: Phase IV trial in 587 children

We conducted a Phase IV, open-label clinical trial to test the efficacy and safety of the immunomodulating agent Broncho-Vaxom in private practice. The trial comprised 587 children younger than 12 years of age who had an acute respiratory tract infection at entry and a history of recurrent respiratory tract infections. The patients were given one capsule daily, 10 days per month, for 3 consecutive months. During the acute phase of the disease the patients also received antibiotic therapy. Comparing the infection present at entry with previous infections, the time to improvement (mean +/- SD) decreased from 6.77 +/- 4.42 days to 3.76 +/- 2.18 days, while the time to cure decreased from 11.86 +/- 8.41 days to 7.36 +/- 4.93 days. During the 3 months of therapy, the number of infections decreased from 1.79 +/- 0.96 1 month before treatment to 0.24 +/- 0.46 in the third month of treatment; absenteeism decreased from 3.17 +/- 3.07 days to 0.16 +/- 0.63 days; and the number of antibiotic treatments decreased from 1.71 +/- 1.06 to 0.16 +/- 0.51. In the patients who experienced a recurrent respiratory tract infection during the study, the time to improvement decreased from 5.46 +/- 3.28 days before treatment to 2.79 +/- 1.36 days after treatment, and the time to cure decreased from 8.71 +/- 3.96 days to 4.54 +/- 2.26 days. Adverse events included asthenia and adynamia in 3 patients, diarrhea in 3, rash in 2, fever in 2, exacerbation of symptoms in 2, adenitis in 1, and flulike syndrome in 1. We conclude that Broncho-Vaxom is effective and safe for the treatment of acute episodes of respiratory tract infections and for preventing recurrences.

Use of OM-85 BV in primary prevention of acute respiratory tract infections in children in orphanages

A multicenter, open-label clinical trial was conducted to assess the safety and efficacy of OM-85 BV in the primary prevention of acute respiratory tract infections (ARTIs) in children residing in orphanages. Seventy-four children (42 boys and 32 girls; median age, 9 years [2 to 12 years]) received one capsule (3.5 mg) of OM-85 BV once daily for 10 days a month during 3 consecutive months. The incidence of ARTIs was reduced significantly from the month before treatment to the final month of treatment, as were the number of days absent from school and the number of antibiotic treatments. In patients experiencing an ARTI, the time to clinical improvement and the convalescent time decreased from the month before treatment to the final month of treatment; both changes were statistically significant. Serum immunoglobulin G levels increased significantly from before treatment to after the end of treatment; serum immunoglobulin M levels increased significantly during the same period. No significant changes were detected in serum immunoglobulin A levels. No adverse events related to the administration of OM-85 BV were reported. This study shows that OM-85 BV may induce significant primary prevention of ARTI in children living in close contact.