Early treatment of asthma

The early treatment of asthma was not greatly studied before the 1990s. Subjects included in intervention trials have usually had persistent asthma with a long duration of symptoms. Only a few studies have been done on early intervention. It has also become obvious that eosinophilic airway inflammation is common and does not always significantly affect lung function. If patients do not fulfill the functional criteria for asthma, they may not receive specific diagnosis and effective treatment. I have suggested the term "asthma-like inflammation" to describe the disorder of such patients. Bronchial obstruction and increased bronchial responsiveness are outcomes of the inflammatory process, and it may be argued that detection of eosinophilic inflammation is always late at the time asthma is diagnosed. The diagnosis of asthma is often severely delayed, a fact which influences the prognosis and efficacy of therapeutic interventions. The benefits of early treatment of symptomatic asthma have been shown, and several international guidelines recommend anti-inflammatory medication, preferably with inhaled steroids as first-line treatment to gain control of the disease as fast as possible. Very few studies, however, have addressed the long-term influence of various therapeutic approaches. Usually, the beneficial effects gradually disappear when treatment is withdrawn. There is no convincing evidence that any of the current pharmacologic therapies can change the natural course of asthma. Nevertheless, inhaled steroids seem to have a disease-modifying effect if started early enough, and there is a consensus that steroids abolish symptoms, improve lung function, and decrease the need for hospitalization and probably the mortality rate. In future, various combinations of immunologic and pharmacologic treatments may offer more permanent results in asthma therapy.     

Heterogeneity in response to asthma medications

PURPOSE OF REVIEW: Evidence for the heterogeneity of response to asthma medications including inhaled corticosteroids and leukotriene receptor antagonists is mounting. beta2-Adrenoceptor gene polymorphisms may contribute to asthma responsiveness to short- and long-acting beta2-agonists. This review examines recent articles describing variability in response to inhaled corticosteroids, leukotriene receptor antagonists and short-acting beta2-agonists specifically in pediatric persistent asthmatics. RECENT FINDINGS: In the late 1990's, differences in the response to a leukotriene receptor antagonist and an inhaled corticosteroid in adults with moderate persistent asthma were first described. Subsequently, similar findings have recently been elucidated in children with mild to moderate persistent asthma. The variability in response to these two classes of control medicines now appears to encompass all ages with persistent asthma. In general, despite the variability in response to these medications, both resulted in improved clinical and physiologic control measures. SUMMARY: Childhood asthma is a complex disease with numerous clinical phenotypes that contribute to response variability to asthma medications.     

Long-term effects of asthma medications in children

PURPOSE OF REVIEW: This review describes recent studies in children that evaluated long-term outcomes of controller asthma medications. RECENT FINDINGS: The literature is replete with studies demonstrating the immediate profound effects of inhaled corticosteroids on symptom control, reduction in morbidity and mortality rates, improvement in lung function, bronchial hyperresponsiveness, and inflammatory markers. Recent evidence supports that even this most effective class of medication does not alter the progression of recurrent wheeze to asthma, and that its effects on decline in lung function are limited. The lack of evidence supporting the superiority of lower dose inhaled corticosteroids combined with a long-acting beta-agonist over a full dose inhaled corticosteroid with respect to long-term efficacy measures and growth effects suggests that monotherapy with acceptable inhaled corticosteroid dose is the preferred treatment in children with mild to moderate persistent asthma. Montelukast has been shown to significantly reduce asthma exacerbations and lower use of supplemental inhaled corticosteroids compared with placebo. SUMMARY: There is mounting evidence that the currently available medications for childhood asthma have a substantial impact on multiple dimensions of asthma control. No drug in our current armamentarium, however, has been found to alter the natural progression of childhood asthma nor halt progressive airway damage in the more susceptible children.     

Exercise-induced asthma: diagnosis and management.

OBJECTIVE: To review the diagnosis and management of exercise-induced asthma (EIA). DATA SOURCES: Computer-assisted literature searches on MEDLINE for articles, abstracts, and other relevant data on exercise-induced asthma STUDY SELECTION: Published articles, abstracts, and conference proceedings were selected. RESULTS: EIA is seen in 40 to 90% of asthmatic patients. Exercise can be the sole trigger or be one of multiple triggers of asthma exacerbations. A good history and physical examination can diagnose most cases of EIA. Spirometry can confirm the diagnosis. Exercise testing may be necessary in certain cases. Prevention through both pharmacologic and nonpharmacologic measures is the key to EIA management. Inhaled beta-agonists remain the medications of choice for EIA prophylaxis. Inhaled cromolyn and antileukotrienes are alternatives. Good long-term control of asthma with anti-inflammatory medications such as inhaled steroids will also decrease the incidence of EIA. CONCLUSIONS: Early diagnosis and proper preventive and maintenance therapy can reduce episodes of EIA and enable patients to continue to engage in sports and lead an active life.     

Clinical implications of airway inflammation in mild intermittent asthma.

OBJECTIVE: To determine whether inhaled corticosteroids should be prescribed to patients with milder forms of asthma and whether markers of airway inflammation should be considered when making therapy decisions. DATA SOURCES: A PubMed search was performed of the English-language literature published in the preceding 10 years (January 1, 1993, through December 31, 2003) concerning epidemiology, pathophysiology, therapy, and prognosis of mild intermittent asthma, with asthma, mild, and intermittent as indexing terms. STUDY SELECTION: All relevant studies including author's expert opinions were selected. RESULTS: Several studies have addressed the question of a possible benefit of maintenance therapy (ie, inhaled steroids) in patients with mild intermittent asthma. Although a diminishing effect on airway inflammation has been widely demonstrated, even in patients with mild disease, the impact of inhaled steroids on the long-term prognosis is much less clear. For patients with mild disease who are long-term inhaled steroid users, alternative therapy strategies, including low-dose inhaled steroids and leukotriene receptor antagonists, have been advocated. CONCLUSIONS: Mild intermittent asthma is a disease characterized not only by infrequent symptoms and normal lung function but also by chronic airway inflammation, possibly resulting in irreversible airflow limitation if left unattended. Therefore, maintenance therapy, such as (low-dose) inhaled steroids or leukotriene receptor antagonists, should be considered in patients with mild disease. Future studies should give more insight into the impact of prolonged anti-inflammatory therapy on the long-term prognosis of mild intermittent asthma patients. Whether results from these studies will justify a more aggressive treatment for these patients remains to be answered.     

Childhood Asthma Management Program: lessons learned

The National Heart, Lung, and Blood Institute Childhood Asthma Management Program was initiated in 1991 and is now the largest and most comprehensive study of long-term intervention with anti-inflammatory therapy in children with mild to moderate asthma. The purpose of this perspective is to review key findings of the study and lessons learned in conducting research in more than 1000 children with persistent asthma for more than 10 years. A key lesson was absence of a continued effect of inhaled corticosteroid on lung growth during long-term follow-up even as symptoms and airway responsiveness remained improved.     

Safety of inhaled corticosteroids in the treatment of persistent asthma

OBJECTIVE: Inhaled corticosteroids (ICSs) are the most effective medications available for patients with persistent asthma of all severities and currently are recommended as the preferred asthma controller therapy by the National Heart, Lung and Blood Institute. Nevertheless, lingering concerns about potential adverse systemic effects of ICSs contribute to their underuse. This review discusses the safety of ICSs with respect to potential systemic effects of most concern to physicians and patients. METHODS: Articles reporting on the safety of ICSs in children and adults with persistent asthma were identified from the Medline database from January 1966 through December 2003, reference lists of review articles and international respiratory meetings. RESULTS: Ocular effects of ICSs and ICS effects on bone mineral density and adrenal function are minimal in patients maintained on recommended ICS doses. One-year growth studies in children have shown decreased growth velocity with ICSs, but long-term studies with inhaled budesonide and beclomethasone show no effect on final adult height, suggesting that these effects are transient. In addition, extensive data from the Swedish Medical Birth Registry show no increased risk of adverse perinatal outcomes when inhaled budesonide is administered to pregnant women with asthma. CONCLUSIONS: ICSs have minimal systemic effects in most patients when taken at recommended doses. The benefits of ICS therapy clearly outweigh the risks of uncontrolled asthma, and ICSs should be prescribed routinely as first-line therapy for children and adults with persistent disease.     

Benefits and risks of inhaled glucocorticoids in children with persistent asthma

In children, an inhaled glucocorticoid is currently the medication of choice for the long-term control of persistent asthma. Inhaled glucocorticoids are significantly more effective than nonsteroidal medications on all outcome measures of asthma treatment. They reduce the frequency of symptoms and of acute asthma exacerbations, decrease the need for “rescue” medications, improve airway patency, and reduce airway hyperresponsiveness. These considerable long-term benefits are worth the minimal risks of clinically significant local or systemic adverse effects. An inhaled glucocorticoid should be used in the lowest dose that prevents symptoms and eliminates the need for supplemental courses of ingested glucocorticoids. Pulmonary function and height velocity of children receiving an inhaled glucocorticoid should be monitored at regular intervals. (J Allergy Clin Immunol 1998;102:S77-84.)     

The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial

BACKGROUND: Although guidelines recommend anti-inflammatory therapy for persistent asthma, recent studies suggest that 25% to 35% of patients with asthma may not improve lung function with inhaled corticosteroids. OBJECTIVE: To evaluate potential biomarkers of predicting short-term (6-week) response to inhaled corticosteroid with subsequent evaluation of responders and nonresponders to asthma control over a longer interval (16 additional weeks). METHODS: Eighty-three subjects with asthma off steroid were enrolled in this multicenter study. Biomarkers and asthma characteristics were evaluated as predictors of inhaled corticosteroid response over a 6-week trial for changes in FEV(1) and methacholine PC(20). After this, an additional 4-month trial evaluated asthma control. RESULTS: Although multiple baseline predictors had significant correlations with improvements for short-term inhaled steroid success, the only strong correlations (r >or= +/- 0.6) were albuterol reversibility (r = 0.83; P < .001), FEV(1)/forced vital capacity (r = -0.75; P < .001), and FEV(1) % predicted (r = -0.71; P < .001). Dividing the subjects in the short-term inhaled steroid trial into responders (>5% FEV(1) improvement) and nonresponders (相似文献   

As-needed anti-inflammatory reliever therapy for asthma management: evidence and practical considerations

Asthma is a chronic respiratory disease in which airway inflammation is a key feature, even in the milder expressions of the disease. The conventional pharmacological approach to mild asthma has long relied on reliever therapy with as-needed short-acting beta-agonists (SABAs), while anti-inflammatory maintenance with inhaled corticosteroids (ICSs) has been reserved for patients with more persistent asthma. Poor adherence to maintenance treatment is an important issue in asthma management, and can partly explain suboptimal symptom control. Over-reliance on SABA bronchodilators for rapid symptom relief is common in real life and potentially leads to an increased risk of asthma morbidity and mortality. Combined anti-inflammatory and reliever medications in a single inhaler have the potential to overcome these limitations. Recent studies in patients with mild asthma have shown that anti-inflammatory reliever therapy with budesonide-formoterol, given on an as-needed basis, is superior to SABA in ensuring asthma control and non-inferior to budesonide maintenance therapy in preventing exacerbations. To address the implications of these important findings for the management of patients with asthma, Italian specialists convened at a series of meetings held during the second half of 2018 across Italy. This article presents their position on these topics and includes a review of the evidence supporting the use of anti-inflammatory reliever therapy in mild asthma and the implementation of this novel approach in clinical practice.     

Use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth

BACKGROUND: Inhaled steroids are recommended for the treatment of persistent asthma during pregnancy, but their potential effects on intrauterine growth have been inadequately evaluated. OBJECTIVE: The purpose of this study was to evaluate the association between maternal use of specific inhaled steroids and inhaled steroid dose during pregnancy and the incidence of infants who are small for gestational age (SGA) and mean birth weight. METHODS: Pregnant asthmatic women being treated with inhaled steroids were enrolled in the study before delivery by their managing allergists. Information regarding the specific inhaled steroid and daily dose used, requirement for oral steroids, occurrence of acute asthmatic episodes, maternal race, birth weight, gestational age, and congenital malformations was obtained for each patient. SGA was defined through use of a published normative sample of American births. RESULTS: A total of 474 women were enrolled in the study; of the 451 enrolled participants whose pregnancy ended in a singleton live birth, 396 (88%) completed the study. The incidence of infants with low birth weight, preterm births, and congenital malformations in this cohort was not greater than expected in the general population. The incidence of SGA was 7.1% (95% CI, 5.0% to 10.1%). No significant relationships between specific inhaled steroid or dose of inhaled steroid used and either SGA or mean birth weight were observed. CONCLUSION: These data suggest that the use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth and supports the recommendation that inhaled steroids should be used in the management of persistent asthma during pregnancy.     

Intermittent steroid inhalation for the treatment of childhood asthma

Inhaled corticosteroids have long been considered a mainstay of therapy for asthma in children. However, concerns over long-term side effects of chronic steroid administration have led providers to turn to intermittent dosing of these medications in an attempt to treat exacerbations while limiting total corticosteroid received. The data have been somewhat mixed in this area, likely at least partially due to the difficulty providers have in classifying asthma phenotypes in young children. This review will analyze the evidence for chronic daily inhaled corticosteroid use, intermittent inhaled corticosteroid use, and dynamic dosing approaches utilizing inhaled corticosteroid/long-acting beta agonist combination therapy.     

Impact of intranasal corticosteroids on asthma outcomes in allergic rhinitis: a meta‐analysis

Given the relationship between allergic rhinitis (AR) and asthma, it can be hypothesized that reducing inflammation in the upper airway with intranasal corticosteroid (INCS) medications may improve asthma outcomes. The goal of this study was to perform a systematic review with meta‐analysis of the efficacy of INCS medications on asthma outcomes in patients with AR and asthma. Asthma‐specific outcomes from randomized, controlled studies evaluating INCS medications in patients with AR were evaluated, including studies that compared INCS sprays to placebo, INCS sprays plus orally inhaled corticosteroids to orally inhaled corticosteroids alone, and nasally inhaled corticosteroids to placebo. Sufficient data for meta‐analysis were retrieved for 18 trials with a total of 2162 patients. Asthma outcomes included pulmonary function, bronchial reactivity, asthma symptom scores, asthma‐specific quality of life, and rescue medication use. The subgroup of studies comparing INCS spray to placebo had significant improvements in FEV1 (SMD = 0.31; 95% CI, 0.04–0.58), bronchial challenge (SMD = 0.46; 95% CI, 0.12–0.79), asthma symptom scores (SMD = −0.42; 95% CI, −0.53 to −0.30), and rescue medication use (SMD = −0.29; 95% CI, −0.58 to −0.01). Nasal inhalation of corticosteroids significantly improved morning and evening peak expiratory flow. There were no significant changes in asthma outcomes with the addition of INCS spray to orally inhaled corticosteroids. Thus, the results of this meta‐analysis demonstrated that intranasal corticosteroid medications significantly improve some asthma‐specific outcome measures in patients suffering from both AR and asthma. This effect was most pronounced with INCS sprays when patients were not on orally inhaled corticosteroids, or when corticosteroid medications were inhaled through the nose into the lungs. Overall, intranasal corticosteroid medications improve some asthma‐specific outcome measures in patients with both AR and asthma. Further research is needed to clarify the role of INCS sprays as asthma‐specific therapy, as well as the role of the nasal inhalation technique as a monotherapy in patients suffering from both asthma and AR.

     

Advances in adult and pediatric asthma

This review summarizes the highlights in the study of adult and pediatric asthma from October 2002 through October 2003. It is easiest to categorize this year's advances into physiologic, epidemiologic, therapeutic, and primarily pediatric developments. In physiology the identification of the ADAM33 gene as an asthma susceptibility gene has led to a new hypothesis concerning the pathogenesis of asthma. Understanding the integration of the upper and lower airways is likely to have important implications for patient management. Epidemiologic studies continue to show that asthma is a significant and costly disease, with medications comprising the most significant direct costs. Early intervention and improved management can significantly reduce the burden of illness. Research presented indicates there is an opportunity for allergist-immunologists to improve diagnostic and therapeutic approaches to asthma management. Our community has a strong commitment to health care quality, education, and delivery. The Journal will reflect this commitment with a new section devoted to these issues.     

Management of asthma in preschool children with inhaled corticosteroids and leukotriene receptor antagonists

PURPOSE OF REVIEW: The aim of this article is to review the recently published studies addressing various treatment approaches for asthma in preschool children. RECENT FINDINGS: The heterogeneity of wheezing in the preschool years complicates the study of asthma in this age group. Once children at highest risk for persistence of wheezing are identified, various management strategies may be thoroughly studied. Several recent studies have confirmed the efficacy and safety of both inhaled corticosteroids and leukotriene receptor antagonists in the management of early childhood asthma. In addition to examining clinical efficacy, studies investigating the effects of these treatment modalities on the underlying airway inflammation have recently increased in number and quality and confirm the anti-inflammatory actions of these therapeutic strategies in the preschool child with asthma. SUMMARY: Evidence for the preferred treatment strategies for persistent asthma in young children remains incomplete. Based on the current body of evidence, there is rationale for further investigation of these management strategies, including direct comparisons between inhaled corticosteroids and leukotriene receptor antagonists, as well as the role of long-acting beta-agonists, potentially targeting the subpopulations of early childhood with wheezing who are at highest risk for persistence of asthma symptoms.     

Multicolored simplified asthma guideline reminder (MSAGR) for better adherence to national/global asthma guidelines.

BACKGROUND: Clinicians in general have not widely and consistently used asthma guidelines in their practices around the world. This study identifies reasons for the poor adherence to asthma guidelines by primary care physicians (PCPs), and simultaneously introduces multicolored simplified asthma guideline reminder (MSAGR) as a practical tool to enhance adherence to asthma guidelines. METHODS: Sixty-nine PCPs were given a simple, one-page, fill-in-the-blank questionnaire on the classification of asthma severity as defined in National Asthma Education and Prevention Program guidelines, using patients' symptoms, peak expiratory flow rate (PEFR)/forced expiratory volume in 1 second (FEV1) value, PEFR variability, and step therapy based on asthma severity. Also, they were given a questionnaire on barriers to using asthma guidelines and MSAGR for evaluation. In one targeted community, free copies of MSAGR were made available to PCPs, and data on emergency room visits and hospitalization of asthmatic patients were analyzed. RESULTS: Of the PCPs, 16% correctly classified mild, intermittent asthma, 13% mild, persistent asthma, 8% moderate, persistent asthma, and 8% severe, persistent asthma based on the combined patient's symptoms, PEFR or FEV1 value and PEFR variability as defined in National Asthma Education and Prevention Program guidelines. One hundred percent of the PCPs chose inhaled beta2-agonists as quick relief medication. Fifty percent of the PCPs chose inhaled steroids, leukotriene antagonists, oral theophylline, and long acting beta-agonists in various combinations for different severity of asthma. Eighty percent of the physicians failed to select the appropriate dosages of inhaled steroids for different severities of asthma. Ninety-five percent of PCPs reported that MSAGR made using the guidelines easier for them. In the targeted community, asthma-related emergency room visits decreased 22.5% and hospitalizations by 26.9%. CONCLUSIONS: This is the first study that identified the reasons for poor adherence to asthma guidelines by PCPs, and introduced MSAGR as a practical "low-tech" tool to promote better adherence to asthma guidelines. MSAGR presents patient-specific recommendations, based on asthma guidelines in a user-friendly format that can save the physician time in real-world primary care settings, where such information is often needed instantly. The overwhelming majority of PCPs strongly agreed that MSAGR helped them recall the classification of asthma severity in a timely manner, to inquire about various triggers, and to use step therapy accurately and confidently. In one targeted community, MSAGR helped clinicians in primary care settings to achieve better asthma outcomes and to reduce both emergency room visits and hospitalizations.     

How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma?

PURPOSE OF REVIEW: The purpose of this review is to describe the scientific evidence that specific immunotherapy can prevent the development of asthma in patients suffering from rhinoconjunctivitis as well as reduce the number of new allergies developing. RECENT FINDINGS: Proposed strategies for the prevention of the development of allergic rhinoconjunctivitis and asthma include allergen avoidance, pharmacological treatment (antihistamines and steroids) and specific immunotherapy. Long-term follow-up on immunotherapy studies demonstrates that specific immunotherapy for 3 years shows persistent long-term effects on clinical symptoms after termination of treatment and long-term, preventive effects on later development of asthma in children with seasonal rhinoconjunctivitis. It is so far the only treatment for allergic diseases that has been shown to be able to prevent worsening of disease and development of asthma. Also, specific immunotherapy seems to reduce the development of new allergic sensitivities as measured by the skin prick test as well as specific IgE measurements. SUMMARY: Specific immunotherapy is the only treatment that interferes with the basic pathophysiological mechanisms of the allergic disease and thereby carries the potential for changes in the long-term prognosis of respiratory allergy. Specific immunotherapy should be recognized not only as first-line therapeutic treatment for allergic rhinoconjunctivitis, but also as secondary preventive treatment for respiratory allergic diseases.     

Advair: combination treatment with fluticasone propionate/salmeterol in the treatment of asthma

Several classes of medications are available for the treatment of asthma, and often they must be taken concurrently to achieve asthma control. Based on the understanding of asthma as an inflammatory disease, the National Heart Lung and Blood Institute guidelines provide a stepwise approach to pharmacologic therapy. Corticosteroid therapy, principally inhaled corticosteroid (ICS) therapy, is considered the most effective anti-inflammatory treatment. In cases of moderate-to-severe persistent asthma, the addition of a second long-term control medication to ICS therapy is one recommended treatment option. A combination-product inhaler (Advair, Seretide) was developed to treat both the inflammatory and bronchoconstrictive components of asthma by delivering a dose of the ICS, fluticasone propionate, and a dose of the long-acting beta2-adrenergic (LABA) bronchodilator, salmeterol. The Advair Diskus is available in 3 strengths of fluticasone propionate (100, 250, and 500 microg) and a fixed dose (50 microg) of salmeterol. Combination treatment with both ICS and LABA provides greater asthma control than increasing the ICS dose alone, while at the same time reducing the frequency and perhaps the severity of exacerbations. Furthermore, salmeterol added to ICS therapy provides superior asthma control compared with the addition of leukotriene modifiers or theophylline. The superior control is likely a consequence of the complementary actions of the drugs when taken together, including the activation of the glucocorticoid receptor by salmeterol. By combining anti-inflammatory treatment with a long-acting beta2-agonist in a single inhaler (1 inhalation twice daily), physicians can provide coverage for both the inflammatory and bronchoconstrictive aspects of asthma without introducing any new or unexpected adverse consequences. The most common drug-related adverse events were those known to be attributable to the constituent medications (ICS therapy and/or LABA therapy). Although the benefits of combined ICS plus LABA therapy can be achieved with separate inhalers, the convenience of the combination product may improve patient adherence and may therefore reduce the morbidity of asthma.     

An update on the health economics of asthma and allergy

Health economics is receiving more attention as decision-makers--whether purchaser, physician, or patient--are looking for a more comprehensive understanding of the impact of adopting new healthcare strategies. In this article we review the recent advances in the health economics of asthma and allergy. In burden of illness studies, estimates of the economic burden of asthma and allergy were reported from countries and regions not previously detailing these costs. There were economic evaluations comparing medications and those that evaluated disease management programs. The recent studies of pharmaceuticals have focused on evaluating the cost-effectiveness of various controller medications for the treatment of asthma. Although mostly observational, such studies increase the evidence that these medications are relatively cost-effective. A few recent economic evaluations have been published examining disease management and education programs. These studies are generally long-term evaluations and have not shown consistent health economic impact. The field of health economics in asthma and allergy continues to evolve and aims to provide information to aid in decision making.