Biomedical subjects
W E Pierson
Publications and source records attributed to W E Pierson.
Potential adverse health effects of wood smoke.
The use of wood stoves has increased greatly in the past decade, causing concern in many communities about the health effects of wood smoke. Wood smoke is known to contain such compounds as carbon monoxide, nitrogen oxides, sulfur oxides, aldehydes, polycyclic aromatic hydrocarbons, and fine respirable particulate matter. All of these have been shown to cause deleterious physiologic responses in laboratory studies in humans. Some compounds found in wood smoke--benzo[a]pyrene and formaldehyde--are possible human carcinogens. Fine particulate matter has been associated with decreased pulmonary function in children and with increased chronic lung disease in Nepal, where exposure to very high amounts of wood smoke occurs in residences. Wood smoke fumes, taken from both outdoor and indoor samples, have shown mutagenic activity in short-term bioassay tests. Because of the potential health effects of wood smoke, exposure to this source of air pollution should be minimal.
Studies of neutrophil chemotactic factor of anaphylaxis in metabisulfite sensitivity.
The mechanism(s) of adverse reactions to sulfites remains unclear. To determine whether mast cell degranulation is involved in sulfite sensitivity, we performed single-blind, placebo-controlled oral aqueous challenges with potassium metabisulfite in 13 patients with histories suggestive of sulfite sensitivity. Ten patients were also skin tested with potassium metabisulfite at 10 mg/mL and all had negative reactions. Serum samples were obtained from all the patients before the challenge and for 180 minutes after the challenge. The samples were tested for the presence of neutrophil chemotactic factor of anaphylaxis, using both a 51chromium microchamber chemotaxis assay and a leukocyte polarization technique. Six of 13 patients had positive challenges as defined by a fall equal to or greater than 20% in their forced expiratory volume in one second. No significant increase in neutrophil chemotactic factor activity was detected in the postchallenge serum samples from patients who experienced positive or negative challenges. We conclude that sensitivity to aqueous metabisulfite is not associated with mast cell degranulation in metabisulfite skin test-negative patients.
Is a uniform round-the-clock theophylline blood level necessary for optimal asthma therapy in the adolescent patient?
Twenty-one patients, 12 to 18 years of age, with nocturnal asthma controlled with sustained-release theophylline administered twice daily, were enrolled in a 10-week, double-blind, two-way crossover study that compared Theo-Dur tablets administered twice daily with an equivalent daily dose of Uniphyl tablets administered once daily at bedtime. Seventeen patients completed the study. The mean morning theophylline serum level obtained with Uniphyl tablets was significantly higher than that obtained with Theo-Dur tablets (13.1 versus 9.6 micrograms/ml, p = 0.02). The mean evening serum level was significantly lower with Uniphyl tablets (6.3 versus 10.1 micrograms/ml, p = 0.003). Despite these differences in serum concentrations, morning and evening pulmonary function test values (forced expiratory volume in one second and peak expiratory flow rate) and symptom scores were nearly identical for the two preparations, as was the supplemental use of aerosol bronchodilators. Once-daily dosing with Uniphyl tablets may benefit adolescent patients with nocturnal asthma by increasing compliance and providing better asthma control. In addition, the lower daytime theophylline levels produced by this preparation may also reduce long-term adverse effects on behavior and cognition.
Efficacy of azelastine in perennial allergic rhinitis: clinical and rhinomanometric evaluation.
Azelastine is a chemically novel medication that has been demonstrated to be clinically effective for asthma and seasonal allergic rhinitis. In a 10-week, multicenter, double-blind, placebo-controlled, crossover study, the efficacy and safety of azelastine, 1 mg and 2 mg twice daily, were evaluated in 192 patients with symptoms of perennial allergic rhinitis. Patients maintained daily symptom and adverse-experience diaries and were evaluated every 2 weeks by the investigators. Pseudoephedrine, 30 mg, was provided as backup medication. Amelioration of most individual symptoms and a decrease in the total symptom scores were observed with both dosages of azelastine; greater improvement with 2 mg twice daily than with 1 mg twice daily, was observed. Nasal congestion, as a symptom and as reflected by rhinomanometric assessment, was the least improved parameter. Backup decongestant medication decreased during treatment with azelastine and increased during the placebo regimen. There were no major adverse effects.
Objective measurements of nasal airway testing.
The objective measurement of nasal airway function has become increasingly important in the evaluation of both clinical responses and nasal challenge testing methodology when both the diagnosis and treatment of upper respiratory tract disease are assessed. Such measurements include the quantitation of nasal symptoms by use of symptom diaries, nasal physical examination, and scoring systems, and assessment of structural and functional changes of the nasal mucosa by light and electron microscopy and by other methods using radioisotopes. In addition, quantitation of nasal secretions along with qualitative analysis of various components of nasal secretions has recently shed new light on the pathologic picture of nasal disease. Various means of measuring changes in nasal blood flow and nasal airflow have enjoyed increasing use in both investigative and clinical application. Measurement of nasal cross-sectional area along with objective assessment of eustachian tube dysfunction and the use of various pharmacologic and immunologic probes have allowed varying approaches to the evaluation of nasal airway structure and function in both health and disease.
Diseases of the ear.
Otitis media with effusion is a major disorder in children and the most common cause for both major surgery (adenoidectomy with or without tonsillectomy) and minor surgery (middle ear ventilating tubes) in both the United States and Britain. It is frequently associated with respiratory allergy. Medical evaluation, diagnosis, and therapy are discussed. Environmental control measures and pharmacotherapy are reviewed, with a critical review of published appropriately designed studies for its treatment and prevention.
Cognitive and behavioral findings in children taking theophylline.
In a prior pilot study involving six children, we noted improved memory and concentration and improved behavior when these children were switched from theophylline to cromolyn sodium therapy. We now report the findings in 29 children (24 boys and five girls), aged 7 to 12 years. In this study, a double-blind, double-dummy randomized design was used so that half the subjects continued to receive theophylline and the other half was actually switched from theophylline to cromolyn sodium therapy. Assessment again consisted of the revised Wechsler Intelligence Scale for Children, the Selective Reminding test, the Benton Visual Retention test, Stroop tests I and II, and the Child Behavior Checklist. The group receiving placebo theophylline/active cromolyn sodium therapy demonstrated greater improvement on all tests of memory and concentration, with greatest significance for the Stroop test (p less than 0.03 by analysis of covariance). There were also significant correlations between length of time theophylline was taken and scores on the depression (p less than 0.03) and the obsessive-compulsive (p less than 0.04) subscales of the Child Behavior Checklist. These results support the findings of the previous pilot study but, in addition, raise concern about depression and anxiety as possible long-term side effects of long-term theophylline therapy.
Double-blind evaluation of nebulized cromolyn, terbutaline, and the combination for childhood asthma.
To evaluate whether the potency of a long-acting selective beta 2-agonist negates the need for cromolyn, 27 children, aged 6 to 12 years, with mild to moderate asthma requiring long-term medication, were assessed for the therapeutic effects of cromolyn and/or terbutaline by jet nebulizer. Patients received either cromolyn, 20 mg, terbutaline, 0.1 mg/kg up to 4 mg, or the combination, three times daily. The study design was double-blind, crossover with each patient receiving the three treatment regimens in randomized order for a period of 8 weeks each. Daily diary mean scores generally demonstrated best symptom control with cromolyn or the combination than with terbutaline alone. Cough was significantly less with cromolyn than with terbutaline (p less than 0.05). Morning peak flow measures were higher with combination therapy than with terbutaline (p less than 0.05). Evening peak flow measures were higher with the combination and cromolyn alone than with terbutaline alone (p less than 0.01). Methacholine challenge demonstrated less bronchial hyperreactivity with the combination or cromolyn alone than with terbutaline alone (p less than 0.02). The effectiveness of the nebulizer regimen for children with chronic asthma is better when cromolyn is used alone or in combination with terbutaline than when the beta-agonist is used alone.
Therapeutic range cromolyn dose-response inhibition and complete obliteration of SO2-induced bronchoconstriction in atopic adolescents.
Eight atopic adolescent subjects with exercise-induced bronchospasm were studied to determine whether cromolyn sodium could inhibit or block sulfur dioxide (SO2)-induced bronchoconstriction. Cromolyn or placebo were administered by turboinhaler 20 minutes before 10 minutes of SO2 exposure at 1.0 ppm during continuous moderate exercise on a treadmill. The exercise level that was chosen did not in itself produce bronchoconstriction. The cromolyn doses were 0 (placebo), 20, 40, and 60 mg. Pulmonary functions (FEV1, and total respiratory resistance) were measured before and after drug administration and after exposure. SO2 exposure after placebo produced significant bronchoconstriction. Pretreatment with 20 mg of cromolyn did not change the SO2 response, 40 mg significantly inhibited the response, and 60 mg completely abolished the pulmonary function changes. These results demonstrate for the first time a dose-response inhibition of SO2-induced bronchoconstriction in atopic subjects within a clinically acceptable dosage range and complete obliteration of SO2 sensitivity in this group with 60 mg of cromolyn pretreatment.
Measurement of circulating IgG and IgE food-immune complexes.
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Exercise-induced bronchospasm in children and adolescents.
The early recognition and appropriate management of EIB can allow children and adolescents to participate fully in physical activities and sport. The diagnosis by history of chest congestion, coughing, and decreasing performance with exercise is helpful but is aided by a more systematic questionnaire that can detect otherwise "normal" people with EIB. The diagnosis is documented by performance of an exercise challenge test such as a treadmill or cycloergometer to verify bronchospasm induced by exercise. The management can be accomplished by nonpharmacologic means such as an early vigorous warm-up, the use of a mask for rebreathing warmed air, and participation in a physical training program to increase anaerobic fitness. Pharmacologic management includes the appropriate use of cromolyn sodium, beta-adrenergic agonists, theophylline, ipratromium bromide, and calcium channel blocking agents. In addition, the antihistamine, terfenadine, can be used to block EIB effectively. These pharmacologic agents can be utilized in both national and international competition when approved by the appropriate national governing body or the U.S. Olympic Committee and the International Olympic Committee.
Pulmonary response to ozone exposures in healthy individuals aged 55 years or greater.
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The pulmonary effects of ozone and nitrogen dioxide alone and combined in healthy and asthmatic adolescent subjects.
Separate exposures to 0.12 ppm ozone (O3) or 0.18 ppm nitrogen dioxide (NO2) have not demonstrated consistent changes in pulmonary function in adolescent subjects. However, in polluted urban air, O3 and NO2 occur in combination. Therefore, this project was designed to investigate the pulmonary effects of combined O3 and NO2 exposures during intermittent exercise in adolescent subjects. Twelve healthy and twelve well-characterized asthmatic adolescent subjects were exposed randomly to clean air or 0.12 ppm O3 and 0.30 ppm NO2 alone or in combination during 60 minutes of intermittent moderate exercise (32.5 1/min). The inhalation exposures were carried out while the subjects breathed on a rubber mouthpiece with nose clips in place. The following pulmonary functional values were measured before and after exposure: peak flow, total respiratory resistance, maximal flow at 50 and 75 percent of expired vital capacity, forced expiratory volume in one second and forced vital capacity (FVC). Statistical significance of pulmonary function changes was tested by analysis of covariance for repeated measures. After exposure to 0.12 ppm O3 a significant decrease was seen in maximal flow at 50% of FVC in asthmatic subjects. After exposure to 0.30 ppm NO2 a significant decrease was seen in FVC also in the asthmatic subjects. One possible explanation for these changes is the multiple comparison effect. No significant changes in any parameters were seen in the asthmatic subjects after the combined O3-NO2 exposure or in the healthy subjects after any of the exposures.
Sugar "allergy" and children's behavior.
Sixteen children whose behavior was said to become aggressive, overly active, loud, and noncompliant when ingesting sugar were tested. Sugar-free home diet was maintained and an "open" challenge to a large dose (3 g/kg) of candy bar sucrose was given. Subsequent behavior was noted by actometer, quantitative playroom observation using several standard behavioral tests, and ability to do maze drawings. No significant changes were found on the open challenge test. A slight change from baseline was noted in seven cases on three or four behavioral parameters. Five of these children agreed to a double-blind challenge test utilizing lemon-flavored slushes of sucrose, honey, tapioca starch, or aspartame, administered after a standard lunch free of sucrose. One child reacted to both sucrose and honey and another child reacted only to sucrose. These two children were challenged a second time. The child who reacted to honey again did so according to actometer readings, but this time not by Stony Brook test. To sugar, he reacted only at the 70-minute Stony Brook. The other child reacted to placebo instead of sucrose when rechallenged. The results indicate that high doses of sugar are not related to abnormal behavior. "Open" challenge was sufficient to rule out such a relationship in most instances. A repeated double-blind challenge confirmed the absence of a sugar effect in cases showing initial possibility of response.
Exercise-induced bronchospasm in clinical practice.
The early recognition and appropriate management of EIB can allow children and adolescents to fully participate in physical activities and sports. The diagnosis by history of chest congestion, coughing, and decreasing performance with exercise is helpful but is aided by a more systematic questionnaire that can detect otherwise "normal" people with EIB. The diagnosis is documented by performance of an exercise challenge test such as a treadmill or cycloergometer to verify bronchospasm induced by exercise. The management can be accomplished by nonpharmacologic means such as an early vigorous warmup, the use of a mask for rebreathing warmed air, and participation in a physical training program to increase anaerobic fitness. Pharmacologic management includes the appropriate use of cromolyn sodium, beta adrenergic agonists, theophylline, ipratroprium bromide, and calcium channel blocking agents. In addition the antihistamine, terfenadine, can also be utilized to effectively block exercise-induced bronchospasm. These pharmacologic agents can be utilized in both national and international competition when approved by the appropriate national governing body and/or the US Olympic Committee and the International Olympic Committee.
The effects of ozone and nitrogen dioxide on lung function in healthy and asthmatic adolescents.
The aim of this project was to investigate whether or not well characterized groups of healthy adolescents and adolescents with asthma differed in their sensitivity to ozone and nitrogen dioxide at near ambient concentrations of these pollutants. The project was divided into three phases. In each phase, ten healthy and ten asthmatic adolescents were exposed via a mouthpiece to three different atmospheres (filtered air, ozone, and nitrogen dioxide, at either 0.12 or 0.18 ppm) on separate days at least one week apart. During Phase I, subjects at rest inhaled the test atmospheres at 0.12 ppm for two 30-minute periods. The following pulmonary functional values were measured before, during, and after exposure: peak flow, total respiratory resistance, thoracic gas volume at functional residual capacity, maximal flow at 50 and 75 percent of expired vital capacity (performed with both room air and a helium-oxygen mixture), and forced expiratory volume in one second. Pulmonary function was not consistently altered in either the asthmatic or the healthy nonasthmatic adolescents as a result of the exposures. As a result, the study was repeated with the addition of ten minutes of exercise to the 30-minute rest exposure period (Phase II). In Phase II, small but significant increases in total respiratory resistance to all test atmospheres were seen after exposure at 0.12 ppm during exercise in both healthy and asthmatic adolescents. However, the increase in resistance between the groups of subjects was not statistically different. On the basis of these results, Phase III was conducted at higher concentrations of the pollutants (0.18 ppm). In Phase III, statistically significant changes were seen in average total respiratory resistance values in both healthy and asthmatic adolescents exposed to 0.18 ppm ozone while exercising. Again, the difference between the groups was not significant. Small decreases in average forced expiratory volume were found in healthy subjects exposed to ozone and filtered air. After exposure to nitrogen dioxide there was a 3 percent decrease in the forced expiratory volume in one second in asthmatic subjects. This change was not significant. It is concluded that there were no differences in pulmonary function responses between asymptomatic, allergic asthmatic adolescents and healthy adolescents exposed to either ozone or nitrogen dioxide under the conditions of these studies. However, an increase in total respiratory resistance was observed in both asthmatic and healthy adolescent subjects after their exercise exposure to 0.18 ppm ozone.(ABSTRACT TRUNCATED AT 400 WORDS)
Double-blind, dose-response study of metaproterenol inhalant solution in children with acute asthma.
One hundred children, aged 6 to 12 years, with acute asthma received nebulized therapy with saline, 5, 10, or 15 mg of metaproterenol aerosol solution according to a prerandomized, double-blind protocol. Pulmonary function and cardiac function were assessed for 60 minutes. All patients then received 5 mg of metaproterenol aerosol solution, and observation continued for another 30 minutes. The best response to therapy in terms of rise in FEV1, forced expiratory flow rate between 25% and 75% of FVC, and area under the curve (change in lung function with time) occurred with 5 and 10 mg of metaproterenol. The highest dose, 15 mg, produced significantly less bronchodilation. Although there were no electrocardiographic abnormalities, pulse rate was significantly higher with 10 and 15 mg of metaproterenol than with 5 mg. Five milligrams of metaproterenol aerosol solution is the optimal bronchodilating dose for treating acute asthma in children. Repeating this dose provides some additional bronchodilation and is well tolerated.