Adding omalizumab to the therapy of adolescents with persistent uncontrolled moderate--severe allergic asthma.

OBJECTIVE: This study aimed to evaluate the effectiveness of omalizumab among adolescents with moderate-severe allergic asthma inadequately controlled with inhaled corticosteroids. PATIENTS AND METHODS: Data from patients 12 to 17 years of age were pooled from 5 placebo-controlled registration trials of omalizumab. Impact on asthma control was assessed by need for rescue bursts of oral corticosteroids, lung function, symptom scores, and unscheduled office visits. RESULTS: In adolescents (n = 146), addition of omalizumab decreased mean number of rescue bursts (0.3 vs 0.9) versus placebo; relative risk 0.47 (95% confidence interval [CI], 0.22-0.99; P = .047). At study conclusion, mean forced expiratory volume in 1 second increased 268 mL (13.8%) in omalizumab-treated subjects versus 98 mL (5.5%) for placebo (least squares mean treatment difference 146 mL [95% CI, 19.4-272.6; P = .024]). Omalizumab significantly improved asthma symptom scores and reduced unscheduled office visits. CONCLUSION: Omalizumab added to baseline therapy improves measures of asthma control in adolescents with persistent moderate-severe allergic asthma.

Anti-IgE therapy in children with asthma.

The prevalence of asthma continues to grow rapidly among children in areas undergoing urbanization. Current pharmacotherapy for asthma reduces inflammation and provides symptomatic relief, but it does not work for all patients and it does not entirely suppress the underlying disease. For these reasons new therapeutic approaches are still needed. Anti-IgE, the newest therapeutic modality for asthma, a biologic agent to control allergic disorders, represents a fundamentally new concept in treatment.

Is there a role for treatment of asthma with omalizumab?

The allergic response is distinct from other immune reactions in its reliance on IgE, its high affinity receptor, Fc epsilon RI, and the primary effector cell--the tissue mast cell. Positive skin tests or raised concentrations of specific immunoglobulin E (IgE) in the serum define IgE sensitisation or "atopy". IgE participates both in immediate hypersensitivity response and in the induction of chronic allergic inflammation. It enhances allergen capture and Th2 cell activation, and may trigger other immunoregulatory pathways. Considerable effort in therapeutic research has focused on interference with IgE function because of its position high in the allergic cascade. Therapy with anti-IgE is one such approach that shows much promise.

Low-dose levalbuterol in children with asthma: safety and efficacy in comparison with placebo and racemic albuterol.

BACKGROUND: Racemic albuterol (RAC) is an equal mixture of (R)-albuterol and (S)-albuterol. Only the (R)-isomer, levalbuterol (LEV), is therapeutically active. Lower doses of LEV, devoid of (S)-albuterol, have demonstrated efficacy comparable to that of higher doses of the (R)-isomer administered as a component of RAC. OBJECTIVE: The purpose of this study was to determine whether LEV results in improved safety and efficacy in children. METHODS: Asthmatic children aged 4 to 11 years (n = 338; FEV(1), 40% to 85% of predicted) participated in this multicenter, randomized, double-blinded study and received 21 days of 3-times-a-day treatment with nebulized LEV (0.31 or 0.63 mg), RAC (1.25 or 2.5 mg), or placebo. The primary endpoint was FEV(1) (peak percent change). Adverse events, clinical laboratory test results, vital signs, and electrocardiograms were evaluated for safety. RESULTS: All active treatments significantly improved the primary endpoint in comparison with placebo (P < .001). Significant differences in FEV(1) were noted immediately after nebulization (median change, 2.0%, 19.0%, 18.1%, 12.4%, and 15.6% for placebo, LEV 0.31 and 0.63, RAC 1.25 and 2.5 mg, respectively; P < .05 vs placebo; P < .05 for LEV 0.31 and 0.63 vs RAC 1.25 mg). LEV 0.31 mg was the only treatment not different from placebo for changes in ventricular heart rate, QT(c) interval, and glucose (P > .05). All active treatments decreased serum potassium (range, -0.3 to -0.6; P < .002 vs placebo), and RAC 2.5 mg caused the greatest change (P < .005 vs other actives). In a patient subset with severe asthma, a dose-response relationship was observed for levalbuterol, indicating that higher doses were more effective. CONCLUSION: LEV was clinically comparable to 4- to 8-fold higher doses of RAC, and it demonstrated a more favorable safety profile. LEV 0.31 mg should be used as the starting dose in 4-11 year old children with mild to moderate persistent asthma. Patients with severe disease might benefit from higher doses.

Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab).

BACKGROUND AND OBJECTIVE: There seems to be a strong causal relationship between allergy and the origins of asthma. Susceptibility to both is determined by a combination of genetics and environment acting through a complex network of cytokines. Nearly 90% of affected children have positive skin tests indicating the presence of specific immunoglobulin E (IgE), with sensitivity to house dust mite, Alternaria, cockroach, cat, and dog most closely linked to the disease. Greater exposure to house dust mite during infancy leads to earlier onset of wheezing, and elevated serum IgE levels correlate with the appearance of asthma symptoms. Specific IgE binds to high-affinity (FcepsilonRI) receptors on mast cells and basophils. The IgE-mediated reactions that follow exposure of sensitized mast cells to an allergen are designated early- and late-phase asthmatic responses (EAR and LAR). EAR is characterized by release of histamine and other preformed mediators within 1 hour of allergen exposure. It is often followed by LAR, an infiltration of the airways by inflammatory cells associated with an episode of more prolonged, and usually more severe airflow obstruction, 4 to 8 hours after antigen exposure. Chronic airway symptoms result from persistent LAR caused by continuous allergen exposure. IgE antibodies are capable of passive transfer of both EAR and LAR sensitivity. IgE-mediated mast cell activation contributes to chronic tissue eosinophilia and airway remodeling, with permanent loss in pulmonary function. Omalizumab (rhuMAb-E25) is a recombinant, humanized, monoclonal anti-IgE antibody of mouse origin developed for the treatment of IgE-mediated diseases. Omalizumab binds to free IgE at the same site as the high-affinity receptor. Although it attaches to free IgE, it does not bind to IgA, IgG, or cell-bound IgE. It therefore does not induce cross-linking of cell-bound IgE, which would lead to the release of allergic mediators. It has been reported to decrease serum IgE levels in a dose-dependent manner, inhibit EAR and LAR, and cause a down-regulation of FcepsilonRI receptors on basophils. Omalizumab has been reported to be safe and effective in improving asthma control and reducing the requirement for oral and inhaled corticosteroids. This double-blind, randomized, placebo-controlled study evaluated the safety, steroid-sparing effects, and impact on disease exacerbations of omalizumab in the treatment of childhood asthma. Methods. Participants were 334 males and premenarchal females aged 6 to 12 years, with moderate to severe allergic asthma requiring treatment with inhaled corticosteroids. During a run-in phase, all children were switched to equivalent doses of beclomethasone dipropionate (BDP), and the dose was adjusted to assure maintenance of asthma control achieved with previous corticosteroid treatment. Children were randomized to subcutaneously administered placebo (N = 109) or omalizumab (N = 225) at a dose based on body weight and initial serum IgE (0.016 mg/kg/IgE [IU/mL] per 4 weeks). BDP dose (initial range 168-420 microg/d) was kept stable for 16 weeks (stable-steroid phase), reduced over 8 weeks to the minimum effective dose (steroid-reduction phase), and maintained constant for the final 4 weeks. RESULTS: More participants in the omalizumab group decreased their BDP dose, and their reduction was greater than that of the placebo group (median reduction 100% vs 66.7%). BDP was withdrawn completely in 55% of the omalizumab group versus 39% of the placebo group. The incidence and the frequency of asthma exacerbations requiring treatment with doubling of BDP dose or systemic corticosteroids were lower in the omalizumab group. The treatment differences were statistically significant during the steroid-reduction phase, during which fewer participants in the omalizumab group had asthma exacerbation episodes (18.2% vs 38.5%), and the mean number of episodes per patient was smaller than with placebo (0.42 vs 2.72). Five asthma exacerbations requiring hospitalization all occurred in the placebo group. Participants' and investigators' global evaluations of treatment effectiveness were more favorable for omalizumab than placebo. Investigators rated effectiveness excellent for 31.5% of the omalizumab group versus 16.3% of the placebo group and good for 44.7% of the omalizumab group versus 32.7% of the placebo group. There was little change in asthma symptom scores or spirometry measurements during either the stable-steroid or steroid dose-reduction phase, with minimal differences between the treatment groups. The requirement for rescue medication in the omalizumab group during both the stable-steroid and steroid dose-reduction phases was consistently lower than at baseline. At week 28, the median number of puffs of rescue medication taken daily was 0 in the omalizumab group and 0.46 in the placebo group. The change from baseline was significant in favor of omalizumab. (ABSTRACT TRUNCATED)

Children's school performance is not impaired by short-term administration of diphenhydramine or loratadine.

OBJECTIVE: The purpose of this study was to determine whether a second-generation H1 antihistamine produces less sedation in children and permits greater learning in a school setting than a classic antihistamine. STUDY DESIGN: Sixty-three 8- to 10-year-old children who had histories of seasonal allergic rhinitis but had no symptoms at the time of the study were randomly assigned to 1 of 3 treatment groups: placebo, diphenhydramine, or loratadine. Medications were administered on 3 of 4 study days, twice 6 hours apart, while participants attended a laboratory school. Classroom testing at the end of each school day evaluated the children's retention of curriculum material. Potential sedative effects were additionally evaluated by self-report of somnolence and computerized reaction-time testing. RESULTS: No treatment-related differences emerged on the verbal instruction score, reading test score, reaction time, or somnolence scale. CONCLUSIONS: Learning and response time in children attending a laboratory school were not significantly affected by either antihistamine.

Measurement of children's asthma medication adherence by self report, mother report, canister weight, and Doser CT.

BACKGROUND: Accurate assessment of medication adherence has been difficult to achieve but is essential to drug evaluation in clinical trials and improved outcomes in clinical care. OBJECTIVE: This study was conducted to compare four adherence assessment methods: child report, mother report, canister weight, and electronic measurements of metered dose inhaler (MDI) actuation. METHODS: Participants included 27 children with mild-to-moderate asthma who were followed prospectively for 6 months. All patients used an MDI equipped with an electronic Doser attached to their inhaled steroid. At each 2-month follow-up visit, Doser and canister weight data were recorded, while child and mother were interviewed separately regarding medication use. RESULTS: Children and mothers reported, on average, over 80% adherence with the prescribed inhaled steroid. Canister weight revealed, on average, adherence of 69%, significantly lower than self-report. When adherence recorded by the electronic Doser was truncated to no more than 100% of prescribed daily use, average adherence was 50%. Older children and adolescents, nonwhite children, and those from poorer functioning families were least adherent. CONCLUSIONS: Electronic adherence monitoring was significantly more accurate than self-report or canister weight measures. Such accuracy is an essential prerequisite to increasing understanding of the treatment, setting, and patient factors that influence adherence, and to the consequent design of effective intervention strategies.

Treatment of allergic asthma with monoclonal anti-IgE antibody. rhuMAb-E25 Study Group.

BACKGROUND: Immune responses mediated by IgE are important in the pathogenesis of allergic asthma. A recombinant humanized monoclonal antibody (rhuMAb-E25) forms complexes with free IgE and blocks its interaction with mast cells and basophils. We studied the efficacy of rhuMab-E25 as a treatment for moderate-to-severe allergic asthma. METHODS: After a 4-week run-in period, we randomly assigned 317 subjects (age range, 11 to 50 years) who required inhaled or oral corticosteroids (or both) to receive either placebo or one of two regimens of rhuMAB-E25: high-dose rhuMAb-E25 (5.8 microg per kilogram of body weight per nanogram of IgE per milliliter or low-dose rhuMAb-E25 (2.5 microg per kilogram per nanogram of IgE per milliliter) intravenously on days 0 (half a dose), 4 (half a dose), and 7 (full dose) and then once every 2 weeks thereafter for 20 weeks. For the first 12 weeks of the study, the subjects continued the regimen of corticosteroids they had received before enrollment. During the following eight weeks, the doses of corticosteroids were tapered in an effort to discontinue this therapy. The primary outcome measure was an improvement in the asthma symptom score at 12 weeks, according to a 7-point scale, in which a score of 1 indicated no symptoms and a score of 7 the most severe symptoms. RESULTS: A total of 106 subjects were assigned to receive a high dose of rhuMAb-E25, 106 were assigned to receive a low dose, and 105 were assigned to receive placebo. At base line, the mean asthma symptom score was 4.0. After 12 weeks of therapy, the mean (+/-SE) scores were 2.8+/-0.1 in the high-dose group (P=0.008) and 2.8+/-0.1 in the low-dose group (P=0.005), as compared with 3.8+/-0.1 in the placebo group. At 20 weeks, the mean scores were 2.7+/-0.1 in both the high-dose group (P=0.048) and the low-dose group (P=0.14), as compared with 2.9+/-0.1 in the placebo group. More subjects in the two rhuMAb-E25 groups were able to decrease or discontinue their use of corticosteroids than in the placebo group, but only some of the differences were significant. After 20 weeks, serum free IgE concentrations decreased by a mean of more than 95 percent in both rhuMAb-E25 groups. The therapy was well tolerated. After 20 weeks, none of the subjects had antibodies against rhuMAb-E25. CONCLUSIONS: A recombinant humanized monoclonal antibody directed against IgE has potential as a treatment for subjects with moderate or severe allergic asthma.

Fatal and near-fatal asthma questionnaire: prelude to a national registry.

BACKGROUND: Asthma mortality rates continue to be unacceptably high in the United States. As a follow-up to the initiatives proposed by the Asthma Mortality Task Force in 1987, the Committee on Asthma Mortality of the American Academy of Allergy, Asthma, and Immunology developed a questionnaire on fatal and near-fatal asthma. OBJECTIVE: This study assessed completeness of answers from participating physicians and described characteristics of patients with fatal and near-fatal asthma. METHODS: There were 111 survey items intended to characterize patients with fatal or near-fatal exacerbations of asthma. The questionnaire was sent to the members of the American Academy of Allergy, Asthma, and Immunology (approximately 3900), and a total of 143 usable questionnaires were received. RESULTS: Responding physicians had information on most items in the questionnaire; the mean number of responses was 120 of 143 possible, with a median of 128 and a range of 40 to 143. Patient demographics, description of the event, identification of overall risk for the event, use of medications, and characteristics of asthma management had the most complete responses (median response rates were 126-143). Presence of factors contributing to the event had fewer responses (range, 44-125). The physicians frequently had information on some psychologic characteristics (eg, 108 responses for depression and/or hopelessness and 127 responses for social support) but less information on several others (eg, 62 responses for family dysfunction). Statistical analysis of the completed surveys indicated that only 2 characteristics distinguished fatal from near-fatal asthma: progression in minutes (adjusted odds ratio, 4. 89; 95% confidence interval, 2.05-12.90) and absence of a past history of intubation (adjusted odds ratio, 3.55; 95% confidence interval, 1.55-8.97). CONCLUSIONS: There is a need to gather further data on patients with fatal and near-fatal events to design appropriate prospective studies on asthma morbidity and mortality rates. Physicians can contribute important information about these patients. Gathering such data would be enhanced by establishing a national registry on fatal and near-fatal asthma.

Keeping children with exercise-induced asthma active.

Exercise-induced bronchospasm, exercise-induced bronchoconstriction, and exercise-induced asthma (EIA) are all terms used to describe the phenomenon of transient airflow obstruction associated with physical exertion. It is a prominent finding in children and young adults because of their greater participation in vigorous activities. The symptoms shortness of breath, cough, chest tightness, and wheezing normally follow the brief period of bronchodilation present early in the course of exercise. Bronchospasm typically arises within 10 to 15 minutes of beginning exercise, peaks 8 to 15 minutes after the exertion is concluded, and resolves about 60 minutes later, but it also may appear during sustained exertion. EIA occurs in up to 90% of asthmatics and 40% of patients with allergic rhinitis; among athletes and in the general population its prevalence is between 6% and 13%. EIA frequently goes undiagnosed. Approximately 9% of individuals with EIA have no history of asthma or allergy. Fifty percent of children with asthma who gave a negative history for EIA had a positive response to exercise challenge.6 Among high school athletes, 12% of subjects not considered to be at risk by history or baseline spirometry tested positive. Before the 1984 Olympic games, of 597 members of the US team, 67 (11%) were found to have EIA. Remarkably, only 26 had been previously identified, emphasizing the importance of screening for EIA even in well-conditioned individuals who appear to be in excellent health. The severity of bronchospasm in EIA is related to the level of ventilation, to heat and water loss from the respiratory tree, and also to the rate of airway rewarming and rehydration after the challenge. Postexercise decrease in the peak expiratory flow rate of normal children may be as much as 15%; therefore, only a decrease in excess of 15% should be viewed as diagnostic. EIA is usually provoked by a workload sufficient to produce 80% of maximum oxygen consumption; however, in severe asthmatics even minimal exertion may be enough to produce symptoms. Patients with normal lung function at rest may have severe air flow limitation induced by exercise,10 and as many as 50% of patients who are well-controlled with inhaled corticosteroids still exhibit EIA. A challenge of sufficient magnitude will provoke EIA in all patients with asthma. PHARMACOLOGIC THERAPY: Exercise, unlike exposure to allergens, does not produce a long-term increase in airway reactivity. Accordingly, patients whose symptoms manifest only after strenuous activity may be treated prophylactically and do not require continuous therapy. Most asthma medications, even some unconventional ones such as heparin, furosemide, calcium channel blockers, and terfenadine, given before exercise, suppress EIA. McFadden accounts for the efficacy of these disparate classes of drugs by their potential effect on the bronchial vasculature that modulates the cooling and/or rewarming phases of the reaction. Short-acting -agonists provide protection in 80% to 95% of affected individuals with insignificant side effects and have been regarded for many years as first-line therapy. Two long-acting bronchodilators, salmeterol and formoterol, have been found effective in the prevention of EIA.18-21 A single 50-microg dose of salmeterol protects against EIA for 9 hours; its duration appears to wane in the course of daily therapy. Cromolyn sodium is highly effective in 70% to 87% of those diagnosed with EIA and has minimal side effects. Nedocromil sodium provides protection equal to that of cromolyn in children. Children commonly engage in unplanned physical activity and sometimes are not allowed to carry their own medication. Thus, a simple long-acting regimen given at home is likely to be more effective than short-acting drugs that must be administered in a timely manner. Although the 12-hour protection by salmeterol reported by Bronsky et al may not persist with continued use, the 9-hour duration of action is

Comparison of ipratropium bromide 0.03% with beclomethasone dipropionate in the treatment of perennial rhinitis in children.

OBJECTIVE: To compare the safety and efficacy of ipratropium bromide 0.03% (IB) with beclomethasone dipropionate 0.042% (BDP) in the treatment of perennial rhinitis in children. METHODS: Thirty-three children with nonallergic perennial rhinitis (NAPR) and 113 with allergic perennial rhinitis (APR) were randomly assigned to either IB or BDP for 6 months in a single-blind, multicenter protocol in which the physician was blinded to treatment. At each visit, patients and physicians rated symptom control of rhinorrhea, nasal congestion, and sneezing. Patients also completed quality of life questionnaires at baseline and after 6 months of therapy. RESULTS: Both treatments showed a significant improvement in control of rhinorrhea, congestion, and sneezing compared with baseline over the 6 months of treatment (P < .05). Only for the control of sneezing was BDP consistently better than IB (P < .05). Among the patients given IB, 61% to 73% assessed the control of rhinorrhea as good or excellent on different study visit days, 43% to 60% similarly rated the control of nasal congestion, and 39% to 43% the control of sneezing. The results for BDP were 68% to 78% for the control of rhinorrhea, 55% to 72% for the control of nasal congestion, and 54% to 68% for the control of sneezing. Quality of life assessment documented that both drugs significantly reduced interference with daily activities and disturbance of mood due to rhinorrhea compared with baseline (P < .05). Both treatments were well tolerated with IB causing less nasal bleeding and irritation than BDP. CONCLUSIONS: Ipratropium bromide was safe and effective in controlling rhinorrhea and diminishing the interference by rhinorrhea in school attendance, concentration on school work, and sleep. Ipratropium bromide was as effective as BDP in the control of rhinorrhea and showed a relatively good effect on congestion. Patient and physician assessment favored BDP in the control of sneezing.

Reliability of the model MC-311 MDI chronolog.

BACKGROUND: The Model MC-311 MDI Chronolog (Medtrac Technologies, Lakewood, Colo) is an electronic device for monitoring adherence to metered-dose inhalers (MDIs). It is a thermistor-actuated, microprocessor-equipped device that dispenses inhaled medication while recording the date and time of each canister activation. OBJECTIVE: We evaluated the reliability of the MC-311 MDI Chronolog to determine whether the model could accurately record and report the date, time, and number of MDI actuations. METHODS: Twenty-four of the MC-311 Chronologs were discharged at 8 hourly intervals across 8 days. Battery voltage was assessed before and after the experiment. The mouthpieces of 12 Chronologs were washed daily. RESULTS: By using generous criteria for acceptable reliability, only 10 of 24 (42%) were rated as acceptable. None of these 10 Chronologs recorded 320 or greater actuations (mean +/- SD, 293.9 +/- 13.3; range, 266 to 308); all reliable Chronologs underestimated MDI activation. An additional 6 devices had an initial signature of erroneous recordings dating from device initialization. After removing this signature, the remaining data showed acceptable reliability. All the remaining Chronologs judged to be unacceptable showed time series patterns of seizures (ie, bursts of clustered, erroneous records). Seizures were distributed across trial days, were associated with washing, and preceded all 4 cases of battery failure. Damage to the thermistor is the likely cause of seizure-pattern failures. CONCLUSIONS: In summary, because of a combination of a clear underreporting bias with frequent initialization and seizure-pattern failures, the Model MC-311 MDI Chronolog is not recommended for use in clinical care or research

Validation of the Doser, a new device for monitoring metered-dose inhaler use.

BACKGROUND: Electronic monitoring of medication use has proved valuable in both clinical and research settings. The Doser, a new and inexpensive commercially available device for monitoring metered-dose inhaler (MDI) use, displays 3 measures of daily use of an attached MDI: (1) the daily total of actuations, (2) the number of doses remaining in the MDI, and (3) the number of actuations on each of the preceding 30 days for later recall. OBJECTIVE: We sought to validate the accuracy of the Doser with several commonly prescribed MDIs. METHODS: In the laboratory, clinic personnel actuated an MDI with an attached Doser several times in succession on 3 consecutive days and recorded each of the 3 measures of MDI use (study 1). In study 2 clinic personnel carried an MDI and attached Doser with them for 4 weeks, actuating the MDI according to a prescribed protocol each morning and evening and again recording each of the 3 measures of daily use. In addition, during 2 weeks of study 2, a thermistor-based Nebulizer Chronolog was attached to the MDI to electronically record the date and time of each actuation. In study 3 clinic patients had both a Doser and Nebulizer Chronolog attached to their routinely used inhalers for 2 weeks and a Doser alone during a separate 2-week period. RESULTS: In study 1 agreement was 99% to 100% among the 3 Doser measures, and each measure agreed with actual use by self-report 97% of the time. In study 2 agreement among the 3 Doser measures of use ranged from 98% to 99%. Agreement between each of the 3 Doser measures and the Nebulizer Chronolog ranged from 90% to 93%. Agreement between each of the 3 Doser measures and actual use ranged from 96% to 97%, and the Nebulizer Chronolog agreed with actual use 93% of the time. In study 3 Doser and Nebulizer Chronolog agreement with patient self-report were 85% and 80%, respectively. Agreement between the Doser and Nebulizer Chronolog was 76%. Several failures of the thermistor-based Nebulizer Chronolog occurred, and occasional mechanical problems occurred with the Doser, primarily on particular types of MDI canisters. CONCLUSION: The Doser provides an accurate measure of MDI use with most commonly prescribed medications and may be useful for monitoring MDI use by investigators, clinicians, and patients.

Psychological factors associated with medication nonadherence in asthmatic children.

Adherence with inhaled beta-agonists and corticosteroids in 24 asthmatic children was tracked over 3 months utilizing the metered-dose inhaler chronolog (MDIC). Patients seldom took all of their medications as prescribed, and failed to take any inhaled corticosteroid doses on a median of 41.8% of days or inhaled beta-agonists on 28.1% of days despite prescribed daily use. Medication nonadherence was correlated with lower levels of asthma knowledge (Asthma Knowledge Questionnaire) and family dysfunction (Family Assessment Device), but not child behavior disorder (Child Behavior Checklist). Patients tended to dramatically over-report medication use. Improved identification of the markers of nonadherence can directly facilitate more efficient targeting of behavioral interventions, resulting in improved adherence, better illness control, and less requirement of urgent medication intervention.

Laparoscopic fundoplication to enhance pulmonary function in children with severe reactive airway disease and gastroesophageal reflux disease.

BACKGROUND: The relationship between severe reactive airway disease (RAD) and gastroesophageal reflux disease (GERD) has been noted but the relationship is poorly understood. This study reports our experience with laparoscopic fundoplication and its effect on the pulmonary status of children with severe steroid-dependent reactive airway disease. METHODS: Fifty-six patients with severe steroid-dependent RAD and medically refractory GERD underwent laparoscopic Nissen fundoplications. Mean age was 7 years and mean weight was 20 kg. All patients had the procedure completed successfully laparoscopically with an average operative time of 62 min. Average hospital stay was 1.6 days. RESULTS: Forty-eight of 56 patients noted significant improvement in their respiratory symptoms in the first week. Fifty of 56 patients have been weaned off their oral steroids and four others have had a greater than 50% decrease in their dose. Sixteen patients had a documented increase in their FEV1 in the initial postoperative period (avg. 26%). CONCLUSION: Patients with steroid-dependent RAD and GERD refractory to medical management show improvement in their respiratory status following fundoplication and the majority can be weaned off of their oral steroids. Laparoscopic techniques allow this procedure to be performed safely even in this high-risk group of patients.

Nonadherence in asthmatic patients: is there a solution to the problem?

LEARNING OBJECTIVES: Reading this article will reinforce the reader's awareness of the relationship between adherence and treatment outcome, of the causes of nonadherence, of methods of measurement, and of steps toward successful intervention. DATA SOURCES: Articles on adherence to asthma therapy were reviewed. A MEDLINE database using subject keywords was searched from 1990 through 1997. STUDY SELECTION: Pertinent articles were chosen, with preferential presentation of results from controlled studies. RESULTS: There is no evidence of recent improvement in the rates of nonadherence, and patients continue on average to take about 50% of prescribed medication. Nonadherence assessment is most accurate when it can be measured objectively, and relies neither on patient report nor physician estimate. The consequences of nonadherence are measured in patient suffering, financial cost, and serious compromise of clinical trial outcomes. Underlying causes of nonadherence are traced to characteristics of the disease, treatment, patient, and caregiver system. CONCLUSION: Improved adherence will lead to improved disease control, but only if medical care systems encourage and support the allocation of sufficient resources to allow barriers to self-management to be discussed and solutions negotiated. Attempts to improve adherence outside of the caregiver-patient relationship are less likely to succeed. Special programs for difficult-to-manage patients are necessary to change behavior, although significant illness improvement and cost savings are likely to result.

Adverse effects of medications for rhinitis.

LEARNING OBJECTIVES: Reading this article will reinforce the reader's awareness of the adverse effects of medications used for the treatment of rhinitis. DATA SOURCES: Articles on therapy of rhinitis and reports of associated side effects were reviewed. A MEDLINE database using subject keywords was searched from 1992 through 1997. STUDY SELECTION: Pertinent articles were chosen. A distinction was made in the text between controlled studies and case reports. RESULTS: Antihistamines, decongestants, anticholinergic agents, and corticosteroids, alone or in combination are used in the treatment of rhinitis. Reported side effects include sedation, psychosis, impaired learning and memory, and cardiac arrhythmias. CONCLUSION: Rhinitis and its complications are important medical conditions. Adverse reactions are often difficult to diagnose and assess. Side effects may arise from the use of individual drugs or from drug combinations. There is insufficient cause to abandon these medications, but physicians must be mindful of the inherent risks of the drugs that they prescribe and of others that their patients may be taking without the physicians' knowledge or approval.

Ipratropium nasal spray in children with perennial rhinitis.

OBJECTIVE: To compare the efficacy and safety of ipratropium nasal spray and placebo administered twice each day for 4 weeks in pediatric patients with perennial rhinitis who had rhinorrhea as a major complaint. METHODS: This was a multicenter, double-blind, parallel group study. Patients aged 6 to 18 years with symptoms of perennial nonallergic (PNAR) or perennial allergic rhinitis (PAR) were randomized to receive ipratropium (42 micrograms per nostril) or placebo nasal spray, double-blind, twice each day for 4 weeks. Efficacy was evaluated by nasal symptoms, especially anterior rhinorrhea, and quality of life. Previous caregivers for rhinitis and medications used in the past were also evaluated. RESULTS: A total of 202 patients were empanelled, 162 with PAR, 40 with PNAR; of these 151 with mild-severe rhinorrhea were evaluated for efficacy. Treatment with ipratropium reduced symptoms of rhinorrhea primarily in patients with PNAR. In patients with PAR this response was less pronounced, and was seen as a modest decrease in the severity of rhinorrhea noted in the first 2 weeks of treatment. Quality of life assessments confirmed that rhinorrhea was bothersome to these pediatric patients, and suggested that treatment with ipratropium nasal spray was associated with an improvement, especially in the patients with PNAR. There were few adverse events; these were similar in the two treatment groups. CONCLUSIONS: Ipratropium nasal spray 0.03% administered at a dose of 42 micrograms/nostril bid is a safe and effective new therapy for control of anterior rhinorrhea in pediatric patients with PNAR. Twice daily administration is adequate for patients with PNAR, but patients with PAR might benefit from more frequent administration (e.g., tid).