Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction

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.     

New strategies in the medical management of asthma

Asthma, a common chronic inflammatory disease of the airways, may be classified as mild intermittent or mild, moderate, or severe persistent. Patients with persistent asthma require medications that provide long-term control of their disease and medications that provide quick relief of symptoms. Medications for long-term control of asthma include inhaled corticosteroids, cromolyn, nedocromil, leukotriene modifiers and long-acting bronchodilators. Inhaled corticosteroids remain the most effective anti-inflammatory medications in the treatment of asthma. Quick-relief medications include short-acting beta2 agonists, anticholinergics and systemic corticosteroids. The frequent use of quick-relief medications indicates poor asthma control and the need for larger doses of medications that provide long-term control of asthma. New guidelines from the National Asthma Education and Prevention Program Expert Panel II recommend an aggressive "step-care" approach. In this approach, therapy is instituted at a step higher than the patient's current level of asthma severity, with a gradual "step down" in therapy once control is achieved.     

Pharmacologic therapy of asthma during pregnancy

Asthma is a common, potentially serious medical complication during pregnancy. Optimal clinical and pharmacologic management is necessary to mitigate maternal and fetal complications. Mild asthma may be managed in most cases with inhaled beta 2-mimetics. Anti-inflammatory therapy is recommended for the treatment of moderate and severe asthma. Based on limited human experience, beclomethasone is currently the recommended inhaled corticosteroid during pregnancy. However, other inhaled corticosteroids may have advantages compared to beclomethasone because of reduced systemic absorption, which may adversely affect intrauterine growth. Based upon theoretic considerations, theophylline is now considered a secondary therapy, but data demonstrating the superiority of inhaled corticosteroids versus theophylline during pregnancy are lacking.     

Hospital treatment of asthma: lack of benefit from theophylline given in addition to nebulized albuterol and intravenously administered corticosteroid

STUDY OBJECTIVE: To determine the efficacy of theophylline when given in addition to nebulized albuterol and intravenously administered corticosteroid to children hospitalized with mild to moderate asthma. DESIGN: Randomized, prospective, placebo-controlled, double-blind trial. SETTING: Tertiary-care children's hospital. PATIENTS: Twenty-nine patients with asthma between the ages of 2 and 16 years completed the study. The treatment and placebo groups were similar in age, gender, race, illness severity, and emergency department treatment. INTERVENTIONS: All patients received intravenously administered methylprednisolone and nebulized albuterol. The treatment group received intravenous theophylline therapy and the placebo group dextrose in water. When intravenously administered medications were discontinued, therapy continued with oral administration of theophylline (or placebo) and of prednisone. MEASUREMENTS AND MAIN RESULTS: Twice-daily assessments of clinical asthma symptoms were made by using a scoring system consisting of respiratory rate, inspiratory/expiratory ratio, wheeze, and accessory muscle use. Time required to reach study discharge criteria (asthma score < or = 2) (30.4 +/- 16.8 vs 27.0 +/- 10.3 hours; p = 0.51) and the rate of improvement of the clinical asthma score (-0.10 +/- 0.05 unit/hr vs -0.11 +/- 0.09 unit/hr; p = 0.88) were not significantly different between the theophylline and placebo groups. The number of albuterol aerosol treatments required and the adverse effects experienced were not significantly different between groups. CONCLUSION: When the combination of systemically administered corticosteroid and inhaled albuterol is used in the treatment of children hospitalized with mild to moderate asthma, addition of theophylline may not be justified.     

Asthma treatment during pregnancy. What can be safely taken?

'Safe' pharmacological therapy for gestational asthma is defined as therapy during which the apparent risks of the drug appear to be lower than the maternal and potential fetal risks of uncontrolled asthma that could result if the drug were not used. Major malformations occur in 2 to 4% of all newborns, 1% of which can be attributed to medication in general. Information regarding the effects of drugs administered during pregnancy may come from animal studies, human case reports, and prospective cohort studies. Based on a review of the available information, it is recommended that mild asthma during pregnancy be managed with inhaled beta 2-agonists, as required; step therapy for moderate asthma would include inhaled sodium cromoglycate (cromolyn sodium), inhaled beclomethasone dipropionate and oral theophylline. Severe gestational asthma should be treated with oral corticosteroids at the lowest effective dosage. The pharmacological management of acute asthma during pregnancy should include nebulised beta 2-agonists and ipratropium bromide, and intravenous methylprednisolone. Intravenous aminophylline would not generally be recommended, unless the patient requires hospitalisation. Optimal medical practice medico-legal considerations demand that the patient's informed consent be obtained for that recommended gestational management programme.     

Nedocromil sodium (Tilade)

Nedocromil sodium is a well-tolerated antiasthmatic agent for initial therapy in patients with mild or moderate asthma not well controlled with inhaled beta-2 agonists and/or where methylxanthines are indicated. Like cromolyn sodium, nedocromil sodium offers a potential alternative to inhaled corticosteroids as maintenance therapy in patients with mild or moderate asthma not adequately controlled by bronchodilators. Furthermore, cromolyn sodium and nedocromil sodium may also reduce the usage of corticosteroids and provide some additional symptom control in patients whose asthma is not suitably controlled by optimal doses of inhaled corticosteroids. Both nedocromil sodium and cromolyn sodium are more efficacious than placebo for controlling of asthma, however, few studies have compared the effectiveness of cromolyn versus nedocromil at this time. Further experience and comparison studies of nedocromil sodium with cromolyn sodium in children are required before the role of nedocromil sodium as maintenance treatment in young asthmatic patients can be defined.     

Treatment of nocturnal asthma with nedocromil sodium

BACKGROUND: The association of nocturnal asthma symptoms with a diurnal increase in inflammatory activity suggests a role for anti-inflammatory therapy in nocturnal asthma. METHODS: Fifty patients with asthma with nocturnal symptoms entered a randomised, double blind, placebo controlled, crossover study. After a two week baseline period patients received nedocromil sodium (4 mg) or placebo four times daily. After eight weeks of treatment patients crossed to the alternative treatment for a further eight weeks. Symptom severity was recorded on a scale of 0-4 and inhaled bronchodilator use and peak flow (PEFR) were also recorded daily by the patients. Asthma severity, pulmonary function (FEV1, PEFR, FVC), and adverse events were recorded at clinic visits (baseline and after four and eight weeks of treatment). Global effectiveness was rated by clinician and patient, and treatment preference was recorded. RESULTS: Efficacy was assessed from data from 28 patients. Night-time asthma (mean (SE) difference between nedocromil sodium and placebo: -0.52 (0.13)), total nocturnal symptom severity defined as night-time asthma plus morning tightness (-0.72 (0.20)), and night-time bronchodilator use (-0.62 (0.23)) were reduced with nedocromil sodium compared with placebo treatment during the primary efficacy period (weeks 5-8) and during weeks 1-4 (-0.36 (0.12), -0.63 (0.20), and -0.55 (0.28), respectively). Morning and evening PEFR values improved slightly--but not significantly--compared with placebo. Patient and clinician opinions favoured nedocromil sodium treatment. Daytime asthma, daytime cough, and clinic assessment of asthma severity (secondary efficacy variables) were improved with nedocromil sodium treatment; day-time bronchodilator use and clinic pulmonary function were not. CONCLUSIONS: Nedocromil sodium was more effective than placebo in reducing nocturnal symptoms of asthma and bronchodilator use in this group of patients.     

Intravascular ultrasound elastography

Asthma, a chronic disease of the respiratory tract, affects approximately five percent of the U.S. population, including almost five million children. Childhood asthma has been identified as the leading cause of school absences. This study was to examined efficacy of a school-based program to prevent exacerbation of asthma symptoms and manage asthma in school children using measured doses of an inhaled anti-inflammatory medication. The sample consisted of 22 African-American children in one inner-city elementary school in Dallas, Texas, ages 5-12 years with confirmed diagnoses of asthma. For three months, each child came to the school clinic two times per day for medication administration and measurement of respiratory peak flow rates. Data were collected for a number of variables including bronchodilator use, school absences, self-report of asthma symptoms, and number of visits to the physician. During the study, mean peak flow rates improved approximately 15%, and bronchodilator use decreased 66%. Improvement also was evident in several other areas.     

Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. 1. General principles

The safety of long-term inhaled corticosteroid therapy at commonly prescribed doses is an issue of growing concern to physicians and international regulatory bodies. This is so because long-term use of these drugs has become the mainstay of chronic asthma management and their introduction now is widely recommended in official treatment guidelines at the 'mild persistent' stage of asthma, where regular daily therapy is first begun. In addition to more frequent use of inhaled corticosteroids, there is a further trend to use higher doses of existing inhaler therapies and to use the newer and more potent compounds that have recently become available. At the same time as these developments have been taking place, there has not been a concurrent move to a more rigorous examination of the safety profile of these inhaled corticosteroid treatments - especially to assess their effects on the hypothalamic-pituitary-adrenal (HPA) axis. Most safety data with respect to HPA axis effects have been derived from testing methods that are limited in their ability to detect HPA system impairment and, more seriously, that can give the impression of functional integrity in the HPA axis when there may be moderate (or even greater) impairment. In this first part of a two-part review of the HPA axis effects of inhaled corticosteroids and of how these effects should be assessed, we examine the currently used and the currently available testing methodologies and also review the present state of knowledge concerning the structure and function of the HPA axis and the effects of its suppression. It is clear that there are state-of-the-art tests to assess in a discriminating manner the safety profile of inhaled corticosteroids. These tests have been insufficiently employed, including during the drug development process, yet they are readily available, relatively inexpensive and can detect adrenal suppression before the appearance of clinical effects. In part 2 of this review we examine what can be learned about the effects of inhaled corticosteroid therapy on the HPA axis from the limited amount of reliable published information from clinical and pharmacological studies describing their use and safety.     

Persistence of sputum eosinophilia in children with controlled asthma when compared with healthy children

We aimed to describe induced sputum cell counts in healthy nonasthmatic children, and to compare these to children with controlled and uncontrolled asthma. Following clinical assessment and spirometry, ultrasonically nebulized hypertonic saline was used to induce sputum from children with asthma (n=50) and without asthma (n=72). Sputum was dispersed and cell counts performed to yield total and differential cell counts. Specific stains were used for eosinophil and mast cell counts. All of the children with asthma were receiving inhaled and/or oral corticosteroids. Current asthma control was assessed in terms of symptoms and lung function. Children were classified as controlled on inhaled corticosteroids (no current symptoms, normal lung function n=15), current symptomatic asthma (n=16) and asthma exacerbation (n=11). It was found that eosinophils comprised a median 0.3% (interquartile range (IQR): 0, 1.05) of cells in sputum from healthy children. Sputum eosinophils (4.3% (IQR: 15, 14.1) p=0.0005) and epithelial cells (14% (IQR: 6, 19.4) p=0.0005) were significantly higher in children with asthma than in nonasthmatic children. Children whose asthma was controlled, as well as those with symptoms, had more sputum eosinophils and epithelial cells than the nonasthmatics. Mast cells were found in the sputum of only four of the 42 children with asthma. This study demonstrates that eosinophilic airway inflammation and epithelial damage can occur in children with asthma. Airway inflammation persists even in those children who are receiving inhaled corticosteroids, have normal lung function and good symptomatic control of their disease.     

Effect of long-term treatment with salmeterol on asthma control: a double blind, randomised crossover study

OBJECTIVES: To determine the effect of adding salmeterol 50 micrograms twice daily for six months to current treatment in subjects with asthma who control their inhaled corticosteroid dose according to a management plan. DESIGN: A double blind, randomised crossover study. SETTING: Nottingham. SUBJECTS: 101 subjects with mild or moderate asthma taking at least 200 micrograms twice daily of beclomethasone dipropionate or budesonide. INTERVENTIONS: Salmeterol 50 micrograms twice daily and placebo for six months each, with a one month washout. Subjects adjusted inhaled steroid dose according to guidelines. MAIN OUTCOME MEASURE: Reduction in inhaled steroid use, exacerbations of asthma, and use of oral steroids. RESULTS: Data were available for 87 subjects. When compared with placebo salmeterol treatment was associated with a 17% reduction in inhaled steroid use (95% confidence interval 12% to 22%) with no significant difference in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%) or use of oral steroids. For secondary end points salmeterol treatment was associated with higher morning and evening peak expiratory flow and forced expiratory volume in one second; a reduction in symptoms, bronchodilator use and airway responsiveness to methacholine; and no effect on serum potassium concentration, 24 hour heart rate, or the final forced expiratory volume in one second achieved during a salbutamol dose-response study. CONCLUSIONS: In subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmeterol 50 micrograms twice daily was associated with a reduction in inhaled steroid use and improved lung function and symptom control.     

Studies on the stereoselective internal acyl migration of ketoprofen glucuronides using 13C labeling and nuclear magnetic resonance spectroscopy

BACKGROUND: To improve asthma disease management, the National Asthma Education Program (NAEP) Expert Panel published Guidelines for the Diagnosis and Management of Asthma in 1991. OBJECTIVES: To compare the current status of asthma disease management among patients in a large health maintenance organization with the NAEP guidelines and to identify the factors that may be associated with medical care (eg, emergency department visits and hospital admissions) and adherence to the guidelines. METHODS: Analyses of 1996 survey data from 5580 members with asthma (age range, 14 to 65 years) covered by a major health maintenance organization in California (Health Net). RESULTS: In general, adherence to NAEP guidelines was poor. Seventy-two percent of respondents with severe asthma reported having a steroid inhaler, and of those, only 54% used it daily. Only 26% of respondents reported having a peak flowmeter, and of those, only 16% used it daily. Age (older), duration of asthma (longer), increasing current severity of disease, and treatment by an asthma specialist correlated with daily use of inhaled steroids. Ethnicity (African American and Hispanic) correlated negatively with inhaled steroid use but positively with emergency department visits and hospital admissions for asthma. Increasing age and treatment by an asthma specialist were also identified as common factors significantly related to the daily use of a peak flowmeter and, interestingly, to overuse of beta2-agonist metered-dose inhalers. CONCLUSIONS: Although the NAEP guidelines were published 7 years ago, compliance with the guidelines was low. It was especially poor for use of preventive medication and routine peak-flow measurement. Furthermore, the results showed that asthma specialists provided more thorough care than did primary care physicians in treating patients with asthma. Combining the results of the regression analyses revealed that some of the variation in rates of emergency department visits and hospitalizations among some subpopulations can be explained by the underuse of preventive medication. This study serves the goal of documenting the quality of care and services currently provided to patients with asthma through a large health maintenance organization and provides baseline information that can be used to design and assess effective population-based asthma disease management intervention programs.     

Difficult asthma

Asthma is usually easy to manage, but approximately 5% of patients are not controlled even on high doses of inhaled corticosteroids. It is important to assess these patients carefully in order to identify whether there are any correctable factors that may contribute to their poor control. It is critical to make a diagnosis of asthma and to exclude other airway diseases, particularly chronic obstructive pulmonary disease (COPD), and vocal cord dysfunction ("pseudo-asthma"). Poor adherence to therapy, particularly inhaled corticosteroids, is a common reason for a poor response. There may be unidentified exacerbating factors, including unrecognized allergens, occupational sensitizers, dietary additives, drugs, gastro-oesophageal reflux, upper airway disease, or other systemic diseases, that need to be identified and avoided or treated. Psychological factors may be important in some patients, but it is difficult to know whether these are causal or secondary to troublesome disease. Some patients have instability of their asthma, with resistant nocturnal asthma, premenstrual exacerbations or chaotic and unpredictable instability (brittle asthma). A few patients are completely resistant to corticosteroids, but more patients are relatively resistant and require relatively high doses of corticosteroids to control their symptoms (steroid-dependent). Some patients develop progressive loss of lung function, as in patients with COPD. Management of patients with difficult asthma should be supervised by a respiratory specialist and should involve careful assessment to confirm a diagnosis of asthma, identification and treatment of exacerbating factors, particularly allergens, and recording of peak expiratory flow patterns. A period of hospital admission may be the best way to assess and manage these patients. Treatment involves optimizing corticosteroids therapy, assessing additional controllers such as long-acting inhaled or subcutaneous beta2-agonists or subcutaneous, theophylline and antileukotrienes. In some patients, the use of immunosuppressive treatments may reduce steroid requirements, although these treatments are rarely effective and have side-effects. In the future, the nonsteroid anti-inflammatory treatments now in development may be useful in these patients.     

Six-week trial of nebulized flunisolide nasal spray: efficacy in young children with moderately severe asthma

This study evaluated the clinical efficacy of nebulized flunisolide nasal solution (Nasalide) in young children with moderately severe asthma. Twenty-two asthmatic children, ages 12-72 months, completed this double-blind placebo-controlled study. After a 6-week observation period, 18 patients were paired according to asthma severity. One child from each pair was randomized to flunisolide, the other to placebo; 4 patients were independently randomized. Placebo or drug was then administered for 6 weeks. Throughout the study, symptoms, drug usage, and analog scales reflecting asthma severity and family disruption were recorded in a diary. Multiple regression analysis was used to compare the flunisolide and placebo groups in regard to the amount of improvement demonstrated from the observation to the active periods of the study. Analog scores of asthma severity and family disruption, albuterol aerosol use, and systemic corticosteroid use fell roughly 40% from baseline in the flunisolide group. This improvement was significant compared to the placebo group. We conclude that 1 ml (250 microg) of nebulized flunisolide nasal spray solution, administered three times daily, reduced the severity of asthma symptoms, and the need for both albuterol aerosol and systemic corticosteroid therapy in young children with moderately severe asthma during a 6-week trial. Longer term studies are warranted.