Normal lymphocyte function in the presence of delta-9-tetrahydrocannabinol.

Delta-9-tetrahydrocannabinol (delta-9-THC), the psychoactive component of marijuana, in concentrations of 0.6 X 10(-4) M to 10.6 X 10(-4) M, has no effect on the deoxyribonucleic acid (DNA) synthesis of resting normal human lymphocytes or on their responses to phytohemagglutinin or to allogeneic lymphocytes.

The wheezing child.

Asthma self-management is a new concept. Asthma Care Training for Kids (A.C.T.) was developed at the University of California at Los Angeles (UCLA); its concepts have been incorporated into the daily management of the asthmatic child. The child is allowed to be in the driver's seat, to have some control of his or her disease. Using the colors of the traffic signals--red, yellow, and green--pediatricians teach children about their symptoms, aggravators, and medications. The children keep daily diaries, which result in better control of disease, along with increased compliance. Causes of asthma are presented; pediatricians are advised to explain to their patients and the parents the concept of hyperreactive ("twitchy") airways; that is, asthma can be caused or aggravated by many things, including allergens, infection, and exercise. Proper home management is detailed, including environmental control. The use of antiasthmatic medications is stressed, especially the side effects.

Chronic sinus disease with associated reactive airway disease in children.

Sinus disease has been described as one of several aggravating factors for chronic adult-onset asthma. Forty-eight children whose reactive airway disease (asthma) was significantly improved with treatment of their sinusitis have been observed. All of the subjects were seen in the office with chronic (more than 3 months) respiratory symptoms; all had daytime and nighttime cough and/or wheeze. The 48 children (32 male and 16 female) had a mean age of 8.2 +/- 1.2 (SD) years (range 4 to 13 years). Fourteen (35%) were nonatopic as determined by family history, personal history, and skin test reactivity to inhalant and pollen antigens. Eighteen of the patients were receiving or had recently received oral corticosteroids. All had been taking bronchodilators daily for at least 3 months without adequate control of the asthma. Sinus radiographs (Waters view) revealed the following abnormalities of the maxillary sinuses: greater than 6 mm of mucosal thickening (ten children [21%]), one opacified (12 children [25%]), bilateral opacification (18 children [38%]) and air fluid level(s) (eight children [17%]). All children were treated with antimicrobial agents for 2 to 5 weeks. Thirty-nine responded both clinically and radiologically. Antral lavage was performed in nine children. Of the 48 subjects, 38 (79%) were able to discontinue taking the bronchodilators with resolution of their sinusitis. It is concluded that sinus disease in children may be an aggravating factor for chronic reactive airway disease and that proper, aggressive treatment of the former will notably improve the latter.

Blood gas in exercise-induced bronchospasm: a review.

Exercise-induced bronchospasm (EIB) in some cases of asthma is related to hypocapnia, hypoxemia, and acidosis, but studies have shown that children do not develop as abnormal PCO2, PO2, or pH levels with the induction of EIB. Gradient changes of alveolar-arterial oxygen differences reveal ventilation perfusion abnormalities existing at the onset of exercise in those patients who do develop EIB.

Aspirin intolerance in chronic childhood asthma: Detected by oral challenge.

Most previously reported individuals with acetylsalicylic acid (aspirin, ASA)-induced asthma have been adults. This study was undertaken to define the prevalence of ASA intolerance among children with intractable asthma. Fifty children (34 boys and 16 girls) ranging in age from 6 to 18 years with extrinsic (atopic) asthma were studied. None had a history of ASA sensitivity or nasal polyps; all required continuous medication including cromolyn sodium and daily or intermittent steroids. Anti-asthmatic medications were stopped 12 hours prior to testing. At the same time of day, each subject, in a doubleblind manner, on two separate days, ingested either 300 mg of ASA or 100 mg of lactose (placebo). Measurements of FVC, FEV1, and FEF25-75 were obtained prior to challenge and one half, one, two, three, and four hours after. ASA intolerance required a decrease of 30% in lung function with ASA as compared to placebo. Fourteen of 50 (28%) were ASA-intolerant; a greater number were girls, and they had more sinusitis and an onset of disease prior to 2 years of age. Steroid dependency, frequency of eczema, nasal eosinophilia, serum IgE levels, and peripheral eosinophil counts did not differ between the two groups. The use of aspirin in childhood asthma should be limited.

Oral albuterol in the treatment of childhood asthma.

The efficacy, safety, tolerance, and bio-equivalence of albuterol (a relatively selective beta 2-adrenergic drug) was evaluated in 20 asthmatic children (6 to 14 years of age). The study was divided into two phases: a single-blind multiple-dose treatment with placebo and three separate weekly treatments with 2, 4, and 6 mg of albuterol (tablets or syrup) administered four times a day; and a double-blind crossover period comparing 4-mg albuterol tablets to syrup and placebo. Patients recorded daily diaries and were seen weekly. Theophylline, isoproterenol, and/or epinephrine was administered as needed. In phase 1, the 4- and 6-mg albuterol doses were superior with the latter causing more side effects. In phase 2, a 4-mg dose of albuterol was superior to placebo. The syrup formulation was superior to tablets when extra medications (P less than .01) and six-hour change in pulmonary function were evaluated; the maximum effect of the 4-mg syrup dose was reached at four hours and lasted for six hours whereas the effect of the tablet peaked at two hours and was minimal after five hours. Heart rate changes from base line were greater with syrup. Four milligrams of albuterol syrup (2 mg/5 ml) four times a day is the preferred dose for the asthmatic child 6 to 14 years of age.

Serum enzyme abnormalities in juvenile rheumatoid arthritis.

Elevated serum transaminases, particularly SGOT, as a result of acetylsalicylic acid (ASA) therapy have been reported in patients with juvenile rheumatoid arthritis (JRA). In order to evaluate the possibilities that these elevated transaminases may result from JRA itself or from concomitant muscle injury, we correlated liver function tests and a specific test for muscle damage, creatine phosphokinase (CPK), with ASA therapy in 37 patients. These JRA patients were evaluated serially; 20 took ASA continuously, 6 took it intermittently, and 11 were on no therapy. Thirty-five healthy children were also studied to establish normal control values for the serum enzyme tests. Mean SGOT and SGPT in the 11 untreated subjects were significantly (P less than.001) higher than normal controls while CPK and alkaline phosphatase (AP) were not elevated. Mean SGOT and SGPT were also significantly (P less than .001) elevated in 20 children receiving ASA continuously; CPK was normal and AP less (P less than .05) than normal. CPK was elevated in 13 patients. Elevation of enzymes was sporadic and there was no correlation with serum salicylate, sex, age, disease duration, type, or activity. We conclude that mild abnormalities of SGOT and SGPT in JRA patients are common, but that they occur sporadically and elevated values appear to be unrelated to ASA therapy.

T-cell reconstitution by thymus transplantation and transfer factor in severe combined immunodeficiency.

Reconstitution of cell-mediated immunity was achieved in a 5-month old female infant with severe combined immunodeficiency by fetal thymus transplant given simultaneously with two units of transfer factor. Thymus was obtained from a 15-week gestational age male fetus, and the two units of transfer factor from the lymphocytes of 500 ml of peripheral blood. Three weeks after transplantation, two nel HL-A antigens were detected on the infant's lymphocytes, one of which was present in the mother of the thymus donor; at the same time, some of the infant's own HL-A antigens disappeared. Thereafter, the percent of rosette-forming cells (T-cells) increased and the in vitro response to phytohemagglutinin and allogeneic lymphocytes became normal, and delayed skin tests became positive. Karyotyping of peripheral blood lymphocytes posttransplantation reveals an XY (male) pattern. These results suggest lymphocyte re-population as a result of the thymus-transfer factor therapy. Five months after transplantation, the patient has normal cellular immunity but persistent hypogammaglobulinemia. She is free of infection and growing normally on gammaglobulin injections.

Gastroesophageal reflux-associated recurrent pneumonia and chronic asthma in children.

Forty of 82 patients with recurrent pneumonias and/or clinical asthma were found to have gastroesophageal reflux (GER) by the criteria of two or more of five tests positive for GER. Of 36 patients with GER followed for response to therapy, 32 patients attempted medical therapy and four had fundoplications. Ten of 32 (31%) patients on medical therapy had improvement in symptoms but none became asymptomatic. Twenty patients who failed a trial of medical therapy also had fundoplications for a total of 24 patients surgically treated. Of these, 22 (92%) had improvement or became asymptomatic. All seven patients with diagnosed GER and recurrent pneumonias responded to medical antireflux management or fundoplication. GER is an important treatable cause of recurrent pneumonias and/or chronic asthma in children.

Recurrent pulmonary disease in children: a complication of gastroesophageal reflux.

To evaluate the role of gastroesophageal reflux (GER) as a possible cause of recurrent pulmonary disease, 30 children, aged 1 to 18 years, were studied prospectively with esophageal function tests. These included esophagram (30 patients), esophageal manometry (29 patients), pH probe (Tuttle) test (29 patients), and esophagoscopy with esophageal biopsy (23 patients). The patients studied had either chronic asthma or two or more documented pneumonias within a one-year period. Nineteen (63%) had GER based on two or more positive tests. Eighteen had positive Tuttle tests; 13 had abnormal manometry studies; nine had esophagitis on biopsy; six had esophagitis on esophagoscopy; and five had reflux on esophagram. Of those with GER, 17 had a history of nocturnal cough and eight vomited during infancy. Children with recurrent pulmonary disease should have esophageal function testing to exclude GER as the cause.

Behavior abnormalities and poor school performance due to oral theophylline use.

Studies evaluating adverse effects of oral theophylline on learning and behavior have been performed on children with asthma receiving long-term theophylline therapy. To further differentiate the effects of asthma itself from the drugs used, we evaluated 20 asthmatic children (6 to 12 years of age) who had not received oral bronchodilators for at least 6 months. A double blind, placebo-controlled, parallel format was used with a 4-week theophylline or placebo period preceded by a 2-week baseline. Theophylline serum levels were maintained between 10 to 20 micrograms/mL. During baseline and treatment periods, the child's home and school behavior/performance were monitored independently by their parents and teachers using standardized report forms. A battery of psychologic tests was administered at the end of baseline and treatment periods. Seven children receiving theophylline were noted to have a change in school behavior and/or performance during their 4 weeks on drug compared to baseline, whereas none of the children receiving placebo were noted to be different (P = .004). Thus, the short-term administration of theophylline to asymptomatic asthmatic children not receiving oral bronchodilators can adversely affect school performance and behavior. Because this population represents the majority of asthmatic children, one needs to use theophylline cautiously in this age group, monitor school performance closely, or seek other treatment modalities.

Gastroesophageal fundoplication for the management of reflux in infants and children.

Gastroesophageal reflux (GER) has been recognized with increasing frequency as the source of a wide variety of symptoms in infants and children. During the past 8 years at the UCLA Hospital, 74 patients under 18 years of age have been identified as having sufficiently severe symptomatic reflux to warrant gastroesophageal fundoplication. Although repeated emesis was the most common primary symptom, failure to thrive was a major symptom in 20 patients, repeated pneumonia in 18, asthma in five, and dysphagia owing to stricture in 12. Nine patients with previously repaired esophageal atresia had severe reflux. Serious neurologic disorders were present in 14 children. The diagnosis of reflux in the majority of symptomatic children was established by combining the findings of an abnormal esophagogram, Tuttle test, esophageal manometry, and esophagoscopy with biopsy. Six infants experienced repeated symptomatic GER although results of all diagnostic studies were normal. Each of the patients had undergone an unsuccessful trial of medical management before the decision to operate was made. Transabdominal Nissen fundoplication with gastrostomy was performed on each of the 74 children (28 under 1 year of age). Each of the strictures was successfully managed by postoperative dilatations. No death and no major complications occurred, but six patients experienced transient dysphagia and four had delayed gastric emptying. Every patient has been relieved of clinical reflux, and the pulmonary status in each, including the asthmatic children, has been markedly improved. On the basis of this favorable experience with 74 patients, we believe that an aggressive surgical approach should be taken in the management of symptomatic GER in infants and children who fail to respond to an adequate trial of medical management.

Efficacy of parenteral albuterol in the treatment of asthma. Comparison of its metabolic side effects with subcutaneous epinephrine.

Three parenteral routes of albuterol sulfate were compared with placebo in their effects on serum potassium and glucose levels, heart rate, and pulmonary function in adult asthmatic subjects. In addition, the metabolic effects of subcutaneous epinephrine were compared directly with subcutaneous albuterol. Intravenous (IV) albuterol (250 micrograms) caused similar decreases in serum potassium (mean 0.6 +/- 0.3 mEq/L) as 500 micrograms albuterol by intramuscular (IM) or subcutaneous routes. With the combined data from all three albuterol routes, glucose increases (mean 25 +/- 15 mg/dl) and heart rate increases (mean 11 +/- 6 beats/min) were clinically less important than potassium decreases. Subcutaneous epinephrine (0.3 ml, 1:1,000) gave changes in serum potassium, serum glucose, and heart rate statistically similar to those of subcutaneous albuterol (500 micrograms). Peak FEV1 improvement (mean 61 percent) was similar with IV albuterol (250 micrograms), IM albuterol (500 micrograms) or subcutaneous albuterol (500 micrograms). Although the efficacy of albuterol in the doses studied was similar, the decrement in serum K+ produced was also similar and comparable to that produced by a standard dose of epinephrine. The potassium decrease may have important clinical implications.

Gastroesophageal fundoplication for the management of chronic pulmonary disease in children.

Gastroesophageal reflux is a common cause of chronic pulmonary disease in children. Forty-two children with recurrent pneumonia or severe asthma were evaluated and shown to have signicant reflux. Esophagography and esophageal pH testing proved the best diagnostic tests for determining reflux. Although the pulmonary symptoms were often due to repeated aspiration, they appeared in several cases to be related to bronchospasm caused by acid in the upper esophagus. All of the children underwent Nissen fundoplication and gastrostomy an average of 30 months after the onset of pulmonary symptoms. Of the children who had preoperative pneumonia, 87 percent had no recurrence after operation. In 13 of the 14 asthmatic children who underwent operation, symptoms improved and less bronchodilator medication was required. Morbidity and mortality were closely related to the duration and severity of pulmonary disease.

Chronic sinusitis in the allergic child.

Chronic inflammation of the paranasal sinuses, especially the maxillary sinuses, is common in children with respiratory allergy. The presence of sinusitis should be suspected in such children when they have chronic night and early morning cough or poorly controlled asthma. Treatment should be aggressive because morbidity can be high.

B-lymphocyte haplotypes in asthma families.

Thirty families in whom at least one member had asthma were typed for five new B-lymphocyte specificities, as well as the antigens of the A and B loci of HLA. The B-cell reactions were consistent with the concept that they were determined by genes linked to the HLA-A and HLA-B loci. Between 22 HLA-identical siblings and 16 two-haplotype different siblings, a significant difference in concordance of reactions for the B-cell groups was noted. The data obtained were most compatible with B-groups 1 and 2 being determined by one locus and B-groups 3, 4, and 5 by another locus. The superhaplotypes of HLA-A, HL-B, and B-cell loci 1 and 2 were then determined. The most striking linkages noted were for the second B-cell locus and the HLA-B locus: B-cell group 3 with HLA-B12, B-cell group 4 with HLA-B7, and B-cell group 5 with HLA-B8, B17, and Bw35.

Asthma update: new approaches and partnerships.

This article provides pediatric nurse practitioners with an update on new guidelines for the diagnosis and management of asthma. These guidelines, published in 1991 and 1992, are changing the way asthma is managed in the United States. The article highlights portions of the guidelines, with special emphasis on pediatric implications.