Stanley P. Galant

Association of lipid-laden alveolar macrophages and gastroesophageal reflux in children

The association of lipid-laden alveolar macrophages (LLAM) and gastroesophageal reflux (GER) was investigated prospectively in 115 patients in two groups. Group 1 included 74 children with chronic respiratory tract disorders and documented GER by prolonged esophageal pH monitoring, barium esophagram, and esophagoscopy; group 2 included 41 children with chronic respiratory tract disorders without GER. LLAM were present in 63 (85%) and eight (19%) children from groups 1 and 2, respectively (P less than 0.0001). Thus a strong association between the presence of LLAM and GER in children with chronic respiratory tract disorders was established. We suggest that LLAM from bronchial lavage may be a useful marker for tracheal aspiration in children with GER in whom chronic lung disease may subsequently develop.

A dose-ranging study of mometasone furoate aqueous nasal spray in children with seasonal allergic rhinitis

BACKGROUND The efficacy and safety of mometasone furoate aqueous nasal spray (MFNS; Nasonex) 200 microg once daily for the treatment and prophylaxis of seasonal allergic rhinitis (SAR) and treatment of perennial rhinitis have been demonstrated in adults. However, the dose response of MFNS in pediatric patients has not yet been characterized. OBJECTIVE This study was conducted to determine the dose-response relationship of 3 different doses of MFNS in a pediatric population. METHODS This was a multicenter, double-blind, active- and placebo-controlled study of 679 children 6 to 11 years of age with histories of SAR and documented positive skin test responses. Patients were randomized to one of the following treatment groups for 4 weeks: MFNS 25 microgram once daily, MFNS 100 microgram once daily, MFNS 200 microgram once daily, beclomethasone dipropionate 84 microgram twice daily (168 microgram/day), or placebo. Physician evaluations were performed at days 4, 8, 15, and 29, and patient evaluations were analyzed for days 1 to 15 and 16 to 29. RESULTS The mean reduction from baseline in physician-evaluated total nasal symptom scores at day 8 (the primary efficacy variable) was significantly greater in the MFNS and beclomethasone dipropionate groups than in the placebo group (P </=.02). No significant differences were observed among the 3 MFNS groups. However, as treatment continued, symptoms in patients treated with MFNS 100 or 200 microgram once daily continued to improve, whereas those treated with MFNS 25 microgram once daily demonstrated little further improvement. By day 29, MFNS 100 and 200 microgram once daily both were significantly more effective than MFNS 25 microgram once daily in relieving symptoms of SAR, but MFNS 200 microgram provided no additional benefit over MFNS 100 microgram. All doses of MFNS were well tolerated, and cosyntropin stimulation tests performed before and after treatment found no evidence of hypothalamic-pituitary-adrenal axis suppression. CONCLUSION These results indicate that the most appropriate therapeutic dosage of MFNS in the treatment of SAR in children 6 to 11 years of age is 100 microgram once daily. In addition, MFNS at doses up to 200 microgram once daily for 4 weeks was well tolerated and had no detectable effects on hypothalamic-pituitary-adrenal axis function.

Intracranial pressure monitoring as a guide to prognosis in the nearly drowned, severely comatose child

During a 34-month-period, 55 nearly drowned, comatose children who were admitted to our pediatric intensive care unit were divided into C1 (decorticate), C2 (decerebrate), and C3 (flaccid) subgroups. Patients in subgroup C3 were selected for intracranial pressure (ICP) measurements by the subarachnoid bolt, and were reclassified according to clinical outcome into recovered (group A), fatality (group B), and brain damaged (group C) categories. Six children (29%) had complete recovery, 10 died (48%), and five (23%) demonstrated residual brain damage. There was a highly significant difference between the ICP in group A and group B (P less than 0.001), and between group B and group C (P less than 0.001). Both group A and group C had highly significant differences in mean cerebral perfusion pressure (CPP) values compared with group B (P less than 0.001). There were no significant differences in ICP or CPP between groups A and C. Finally, using a combination of ICP and CPP, we found that ICP less than or equal to 20 mm Hg and CPP greater than or equal to 50 mm Hg were associated with survival in 11 of 12 patients (92%), whereas ICP greater than 20 mm Hg and CPP less than 50 mm Hg were associated with death in seven patients cases (100%). The two other patients who died had either CPP less than 50 mm Hg or ICP greater than 20 mm Hg, but not both. We find that intracranial pressure monitoring is a safe, useful tool in predicting death or survival, but not residual brain damage, in the nearly drowned, severely comatose child.

Fluticasone Propionate Compared with Theophylline for Mild-to-Moderate Asthma

BACKGROUND The inhaled corticosteroid, fluticasone propionate, was compared with the oral bronchodilator theophylline in the maintenance treatment of asthma. OBJECTIVE The objective of the present study was to compare the efficacy and safety of twice-daily inhaled fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, with that of theophylline in the maintenance treatment of mild-to-moderate asthma. METHODS In this randomized, double-blind, placebo-controlled, parallel-group study, 353 adult and adolescent patients with asthma inadequately controlled with inhaled beta-agonist therapy alone received fluticasone propionate, 50 micrograms, or fluticasone propionate, 100 micrograms, by metered-dose inhaler; theophylline capsules; or placebo twice daily for 12 weeks. Only inhaled albuterol was permitted as needed for acute symptoms. RESULTS Both fluticasone propionate groups had a significantly greater probability of remaining in the study (ie, meeting asthma stability criteria) than did either the theophylline or placebo group (P < or = .008); 39% and 51% in the theophylline and placebo groups, respectively, were withdrawn due to lack of treatment efficacy compared with 14% and 21% in the fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, groups. Both fluticasone propionate groups experienced significantly greater improvement in FEV1 and PEF compared with patients in the theophylline or placebo group (P < or = .004). The incidence of potentially drug-related adverse events was significantly greater in the theophylline group (25%) than in the placebo group (11%) (P = .031), while there were no differences between placebo and fluticasone propionate, 50 micrograms, (18%) or fluticasone propionate 100 micrograms, (22%). CONCLUSION Twice daily treatment with inhaled fluticasone propionate 50 micrograms or 100 micrograms was significantly more effective than theophylline in the treatment of mild-to-moderate asthma.

Predictive Value of a Cross-Cultural Asthma Case-Detection Tool in an Elementary School Population

Objective. Bronchial asthma, which affects ∼5 million US children, is vastly underdiagnosed and treated, particularly among minorities and those of low socioeconomic status. Because current methods of detecting those at greatest risk of asthma in a multicultural setting appear inadequate, we assessed the validity and reliability of a new asthma questionnaire across 3 dominant cultures in Orange County, California (white, Hispanic, and Vietnamese). Methods. Children in grades 1, 3, and 5 and their families, in 3 different schools representative of these major ethnic groups, were randomly selected to participate in the validation process. Two schools with low socioeconomic status and dominant Hispanic or Vietnamese minorities were designated inner-city schools, whereas the third school was a suburban school with predominately white students. Participants completed a 7-question, 11-element questionnaire in their primary language, followed by an asthma evaluation (history, physical examination, and spirometry) by an asthma specialist (who was blinded with respect to the results of the questionnaire), at their respective schools. The physician then made a determination regarding the presence and severity (according to National Institutes of Health guidelines) of asthma. Several weeks later, the entire student body was asked to complete the questionnaire at home and return it to school for analysis. Validation of each item was evaluated for sensitivity, specificity, and positive and negative predictive values, and application of univariate analyses provided an estimated probability of an asthma diagnosis by the asthma specialist. A “best-fit” algorithm was determined with all 11 elements, if possible, and an abbreviated algorithm that selected the fewest-question combination that yielded the best asthma predictability was established. Reliability was established with the percent agreement between the 2 questionnaires and the κ statistic. Results. Of the 401 children/families who participated in the validation analysis, 45% were Hispanic, 22% white, 19% Vietnamese, and 15% other. The overall prevalence of asthma specialist-diagnosed asthma was 28%, with 65% of cases being graded as intermittent and 35% as persistent. Sixty-two percent of the children had not been previously diagnosed with asthma. There were no significant differences among cultures in sensitivity or specificity for any of the individual questions or the complete or abbreviated algorithms. The abbreviated algorithm with 3 questions, ie, question 1 (asthma in the past 2 years), question 4 (cough, chest tightness, trouble breathing, or wheezing with exercise), and question 6 (same symptoms in the morning or day in the past 4 weeks) yielded comparable sensitivity and specificity for the complete algorithm in all groups. The abbreviated algorithm had >86% predictability in detecting children with persistent asthma and 56% predictability in detecting children with intermittent asthma. Reliability was also excellent, with percent agreement usually > 80% and κ values of >.70. Conclusions. This asthma detection tool has been shown to be suitable for detecting persistent asthma in a multicultural inner-city population, as well as in a suburban setting. An abbreviated algorithm with 3 questions and >80% predictability in detecting persistent asthma seems ideal for evaluating large numbers of school-aged children. The school setting is an excellent site for identifying children with asthma. Although there is concern that subjects detected in the school setting might not have access to ongoing medical care, case detection is an important first step that could lead to earlier diagnosis and treatment. Reducing the barriers to good care in inner-city environments is the next step.

Current Asthma Guidelines May Not Identify Young Children Who Have Experienced Significant Morbidity

BACKGROUND. The current guideline for classifying asthma severity, the National Asthma Education Prevention Program (NAEPP) 2002, is not evidence-based. We had the opportunity to validate this guideline in an untreated inner-city population, both in those ≤5 and those >5 years of age. The basis for this retrospective validation model was to determine how well the NAEPP severity classification based on symptom-frequency criteria alone identified patients in those age groups demonstrating significant morbidity the previous year and thus the potential need for controller therapy. METHODS. Using a mobile asthma van (Breathmobile) at the school site, children not receiving controller medication were evaluated by an asthma specialist for severity according to NAEPP guideline clinical criteria. Validation was determined by the relationship of guideline severity to ≥2 emergency department (ED) visits, any hospitalization, health care utilization (any ED visit, hospitalization), number of exacerbations, and school absenteeism resulting from asthma the prior year. RESULTS. Eight hundred twenty-six asthmatic children were evaluated; 89 (10.8%) were ≤2 years, 222 (26.9%) were 3 to 5 years, and 515 (62.3%) were >5 years of age; 60.5% were male, and 80.9% were Hispanic. Classification of asthma severity included 34.4% with mild intermittent, 10.2% with mild persistent, 31.5% with moderate persistent, and 24.0% with severe persistent asthma categories. There were significantly more Hispanic children and children ≤5 years classified as having mild intermittant asthma. Morbidity was clearly related to severity in the overall population. However, although the health care utilization was significantly related to severity, it was borderline in those 3 to 5 years and nonsignificant in children ≤2 years. CONCLUSIONS. The NAEPP guidelines 2002, based on symptom-frequency criteria as assessed in this study, seem to offer a valid basis for classifying asthma severity in those >5 years of age but may underclassify younger children. Our data suggest that morbidity experienced in the prior year may provide a useful additional criterion for classifying asthma severity, particularly in those children ≤5 years of age.

Bronchocentric granulomatosis: A complication of allergic bronchopulmonary aspergillosis☆

Hypersensitivity to the fungal antigens of Aspergillus fumigatus may result in a spectrum of immune injury collectively known as allergic bronchopulmonary aspergillosis (ABPA). This report describes a 14-yr-old boy who presented clinical findings consistent with ABPA,including a history of asthma, blood eosinophilia, serum precipitins, and IgE antibodies to Aspergillus fumigatus. Sputum Aspergillus, pulmonary infiltrates, and dual types I and III skin reactions to Aspergillus fumigatus were observed also. Pathology of the resected right upper lobe revealed severe bronchial destruction with the findings of bronchocentric granulomatosis. Noninvasive septate fungal hyphae compatible with Aspergillus were identified. Cultures from sputum and surgical specimens grew Aspergillus and Mycobacterium intracellulare avium. The PPD-B (purified protein derivative-Batty) intradermal skin test produced a 6 mm induration (PPD-S was negative). The patients condition has been well controlled with prednisone and several antituberculous drugs. In addition, inflammatory and immunologic parameters have begun to return to normal. The relationship between ABa and the atypical mycobacterial infection is not clear. The association of ABPA with the severe bronchial destruction seen in bronchocentric granulomatosis is emphasized to alert physicans to this serious sequelae of ABa seen in the asthmatic.

In vivo and in vitro cell-mediated immunity to tetanus toxoid in adults

The purpose of this study was to evaluate tetanus toxoid (TT) as an indicator of cutaneous delayed hypersensitivity (CDH) in adults. Fifty-two normal subjects, aged 25 to 64 yr, were skin tested with TT and streptokinase-streptodornase (SK/SD). Lymphocyte transformation was studied in seven normal TT reactors, four normal TT nonreactors, and seven hospitalized anergic patients. CDH was common with both TT and SK/SD; 90% of the adults, aged 25 to 39 yr, had CDH reactions to TT and 79% had CDH reactions to SK/SD. In adults aged 40 to 64 yr, 75% had DCH reactions to TT and 59% had CDH reactions to SK/SD. Lymphocyte transformation to TT correlated well with TT skin-test results. Punch biopsy specimens of TT reactions 48 hr after skin testing demonstrated DCH. We conclude that TT is an excellent antigen for assessing the presence or absence of CDH in adults aged 25 to 64 yr.

Heterogeneity of human lymphocyte subpopulations to pharmacologic stimulation: I. Lymphocyte responsiveness to beta adrenergic agents

Abstract Measurement of lymphocyte cyclic 3′5′-adenosine monophosphate (cyclic AMP) has been used in man to study the potential beta adrenergic defect in asthma. In this study, we evaluated the possibility of heterogeneity of beta adrenergic response with the use of the E rosette technique for thymic-derived (T) lymphocytes to compare a rosette-forming cell (RFC)-rich T cell population with a RFC-depleted (predominately bursal derived B lymphocyte) population. Lymphocytes were isolated and categorized into 4 populations: whole (unseparated) lymphocytes, RFC-rich, and RFC-depleted populations and a recombination population consisting of E-rosetting cells (T lymphocytes) + immunofluorescent-staining cells (primarily B lymphocytes) recombined in their initial proportion in the whole population. Kinetics and dose responses of isoproterenol-induced cyclic AMP were evaluated for each population. Maximal responses for all populations except the RFC-depleted population occurred at 5 and 12 min; the RFC-depleted population showed equal response at all incubation periods. Significant differences (p −5 M (377% compared with 74% above baseline), 10 −4 M (347% compared with 56%), and 10 −3 M (400% compared with 80%) isoproterenol. No consistent differences were found between the whole and recombination populations at any dose of isoproterenol, suggesting no marked effect of the separation procedure itself. Propranolol at 1 × 10 −4 M inhibited the isoproterenol stimulation of each population. The use of a phosphodiesterase inhibitor did not change the differences observed between RFC-rich and -depleted populations. These data suggest that striking heterogeneity of beta adrenergic responses exist between T lymphocytes and a B cell-enriched lymphocyte population. Studies evaluating beta adrenergic function in man must consider the suitability of this cell type because of the heterogeneity of peripheral blood lymphocyte subpopulations.

The effect of metaproterenol in chronic asthmatic children receiving therapeutic doses of theophylline

Abstract The effect of metaproterenol added to therapeutic doses of theophylline was compared with a combination of placebo and theophylline by measurement of the forced expiratory volume in 1 sec (FEV 1 ), forced vital capacity (FVC), and maximum midexpiratory flow rate (MMEFR) in 17 asthmatic children in a double-blind crossover study. Plasma theophylline levels were measured at 1.5 hr (peak) and 6 hr (trough) after drug administration on all test days. Children weighing less than 60 pounds received 10 mg of metaproterenol (1 tsp), while those weighing more than 60 pounds received 20 mg every 6 hr. The mean peak theophylline level for both metaproterenol and placebo treatment days was approximately 10 μg/ml, while the trough was 6 μg/ml. Metaproterenol caused a significantly greater increase in FEVI (p