Combination treatment with inhaled corticosteroid/long-acting beta 2-adrenergic bronchodilator in the treatment of asthma]

Several classes of medications are used in the treatment of bronchial asthma. Inhaled corticosteroids are the most potent and effective anti-inflammatory agents. The addition of a long-acting beta 2-adrenergic bronchodilator to inhaled corticosteroids for the treatment of asthma has been shown to improve pulmonary function. Combining an inhaled corticosteroid, fluticasone propionate with a long-acting beta 2-adrenergic bronchodilator, salmeterol in a single inhaler permits treatment of both the inflammatory and bronchoconstrictive components of asthma. Combination treatment with fluticasone and salmeterol improves symptoms and lung function, reduces supplemental use of short-acting beta 2-adrenergic bronchodilator. The combination therapy provides better asthma control and may simplify the management of asthma.     

Inhaled corticosteroids in obstructive airway disease

Inhaled corticosteroids play an important role in the management of obstructive airway disease, by suppressing airway inflammation that is central to the pathophysiology of these conditions. In asthma there is strong clinical evidence supporting the use of inhaled corticosteroids in mild, moderate, and severe persistent asthma to improve lung function, reduce exacerbations, and prevent death. In chronic obstructive pulmonary disease, inhaled corticosteroids improve symptoms, reduce frequency of exacerbations and hospitalizations, and should be considered in patients with moderate-to-severe airflow limitation who have persistent symptoms despite optimal bronchodilator therapy. Though the adverse effects of corticosteroids are less when given via inhalation than when given systemically, nevertheless, the adverse effects are important and need to be considered. Newer inhaled corticosteroids with better pharmacologic properties are being developed and will probably be available in the near future.     

Therapeutic modulation of allergic airways disease with leukotriene receptor antagonists

Although asthma is one of the most common chronic respiratory conditions, it often remains unrecognized and undertreated, while patients are often reluctant to comply with regular inhaled anti-inflammatory and bronchodilator therapy. Allergic rhinitis co-exists with asthma in as many as 40% of patients, and can be regarded as a continuum of the same inflammatory disease process. Corticosteroids are the 'gold standard' first-line treatment for both conditions, and have a significant impact upon underlying inflammation, symptoms and long-term outcome. Cysteinyl leukotrienes are potent airway inflammatory mediators, suggesting that treatment antagonizing their effects could play a role in disease management. In recent years, leukotriene receptor antagonists have provided a further therapeutic option in the management of allergic airways disease. These drugs are orally active, can be administered once daily, and provide a systemic approach to the management of patients with asthma and allergic rhinitis. We review the pharmacology of leukotriene receptor antagonists, their potential role in clinical practice in patients with allergic airways disease, and likely areas for further research.     

Asthma in infants and children

Asthma is the most common chronic illness in childhood and represents a significant burden to health care and educational systems. Between one quarter and two thirds of childhood asthma cases persist into adulthood. Childhood asthma may be particularly difficult to diagnose because of the high prevalence of episodic wheezing and cough in childhood illnesses such as upper respiratory tract infections. National and worldwide guidelines for the management of asthma in children are continually being updated. These guidelines recommend first establishing a diagnosis and assessing the severity of disease, initiating pharmacologic therapy based on symptoms and lung function, and adjusting doses and agents as required based on the level of asthma control. Inhaled corticosteroids are the cornerstone of long-term asthma management in children of all ages. Recent research efforts have focused on ways to improve inhalant drug delivery to the lungs and minimize oral and systemic bioavailability so as to improve the therapeutic benefit:risk ratio.     

Advances in therapy for adult asthma

There are >22 million Americans with asthma. Chronic asthma is a worldwide problem with an increasing socioeconomic burden on individuals and on society. Recent advances have been made in diagnostic lung imaging, defining control of asthma, as well as in the education of patients with asthma. Accurate diagnosis of the cause of chronic cough in adults and of asthma in elderly individuals will help affected individuals receive appropriate treatment. Inhaled corticosteroids are the recommended first-line therapy for persistent asthma and can help prevent exacerbations in patients with asthma that are not well controlled. Early intervention and improved management can significantly reduce the socioeconomic burden of asthma. Patient education is an essential part of asthma management.     

National guidelines for the management of asthma in adults.

Asthma is now considered primarily an inflammatory disease in which bronchospasm occurs secondary to airway inflammation. Management strategies include the use of inhaled anti-inflammatory agents, notably inhaled corticosteroids and cromolyn. Mild intermittent asthma may be treated with inhaled bronchodilators. Moderate asthma should be treated with an inhaled anti-inflammatory agent in addition to an inhaled beta agonist. If symptoms persist, an oral bronchodilator (either a beta-adrenergic agonist or theophylline) should be added. Therapy for severe asthma includes combinations of the foregoing medications, with the possible addition of oral corticosteroids. Other aspects of management include the use of a spacer device with inhaler therapy, control of concomitant allergies and triggering factors such as chronic sinusitis, tobacco smoke and gastroesophageal reflux, and home use of a portable peak flow meter to monitor the disease.     

Asthma: 2015 and beyond

Asthma is a multifactorial, chronic inflammatory disease of the airways. The knowledge that asthma is an inflammatory disorder has become a core fundamental in the definition of asthma. Asthma's chief features include a variable degree of air-flow obstruction and bronchial hyper-responsiveness, in addition to the underlying chronic airways inflammation. This underlying chronic airway inflammation substantially contributes to airway hyper-responsiveness, air-flow limitation, respiratory symptoms, and disease chronicity. However, this underlying chronic airway inflammation has implications for the diagnosis, management, and potential prevention of the disease. This review for the respiratory therapy community summarizes these developments as well as providing an update on asthma epidemiology, natural history, cause, and pathogenesis. This paper also provides an overview on appropriate diagnostic and monitoring strategies for asthma, pharmacology, and newer therapies for the future as well as relevant management of acute and ambulatory asthma, and a brief review of educational approaches.     

Medical Therapy for Asthma: Updates from the NAEPP Guidelines

Proper care of patients with asthma involves the triad of systematic chronic care plans, self-management support, and appropriate medical therapy. Controller medications (inhaled corticosteroids, long-acting beta2 agonists, and leukotriene receptor antagonists) are the foundation of care for persistent asthma and should be taken daily on a long-term basis to achieve and maintain control of symptoms. Inhaled corticosteroids are the preferred controller medication; studies have demonstrated that when inhaled corticosteroids are used consistently, they improve asthma control more effectively than any other single long-term control medication. Combining long-acting beta2 agonists and inhaled corticosteroids is effective and safe when inhaled corticosteroids alone are insufficient, and such combinations are an alternative to increasing the dosage of inhaled corticosteroids. For patients with mild persistent asthma, leukotriene receptor antagonists are an alternative, second-line treatment option. They are easy to use, have high rates of compliance, and can provide good symptom control in many patients. Leukotriene receptor antagonists can also be used as an adjunctive therapy with inhaled corticosteroids, but for persons 12 years and older the addition of long-acting beta2 agonists is preferred. Inhaled short-acting beta2 agonists are the most effective therapy for rapid reversal of airflow obstruction and prompt relief of asthmatic symptoms. Increasing the use of short-acting beta2 agonists or using them more than two days per week or more than two nights per month generally indicates inadequate control of asthma and the need to initiate or intensify anti-inflammatory therapy. Oral systemic corticosteroids should be used to treat moderate to severe asthma exacerbations.     

Understanding airway wall remodeling in asthma: a basis for improvements in therapy?

Current strategies for the management of asthma focus on suppressing airway inflammation. Other characteristic features of human asthma, such as airway hyperreactivity and the structural changes collectively referred to as airway remodeling, are largely ignored in existing guidelines for monitoring the effectiveness of treatment. Evidence is accumulating that pharmacologic therapy targeting airway wall remodeling may be valuable in treating asthma. However, development of appropriate therapeutic agents will require a better understanding of the pathogenesis of remodeling, which appears to be regulated by a variety of cytokines and growth factors produced by inflammatory, epithelial, and stromal cells. Furthermore, testing the effectiveness of novel agents that specifically target the process of remodeling will require appropriate experimental models, but most currently available animal models of asthma have major limitations. A recently described murine model of chronic human asthma offers considerable potential for dissection of the mechanisms of airway wall remodeling, as well as for investigation of the therapeutic potential of drugs that can modulate chronic inflammation and remodeling.     

Current approaches in adult asthma: assessment, education and emergency management.

Asthma is a chronic respiratory disease characterized by smooth-muscle constriction of the airway, bronchial hyperresponsiveness, and an ongoing inflammatory process. Although more common in children, asthma in adults also requires careful management to decrease morbidity and mortality. The majority of chronic asthma cases have an allergic component; therefore, efforts to identify and eliminate environmental triggers may decrease the symptoms of most asthmatics. Asthma-education programs based on patient self-management have been shown to decrease asthma morbidity. Mastery of the following topics is necessary for patient self-management: identifying and avoiding exposure to symptom precipitators, using prescribed medications correctly, managing medication side effects, and recognizing and responding to exacerbations. Advances in diagnostic and treatment modalities include the home use of peak-flow meters to monitor respiratory function, and the use of metered-dose inhalers and spacers for the delivery of inhaled medication. Inhaled beta-adrenergic agonists, administered in higher than usual doses, have become the bronchodilators of choice in the treatment of acute asthma. Studies have demonstrated that metered-dose inhalers can be used for this purpose, even with severe asthma attacks that require hospitalization. Systemic corticosteroids are also important in the management of acute attacks. Care providers who teach patients about common symptom triggers and encourage avoidance techniques, who employ current strategies to enhance patients' medication use and patients' recognition of exacerbations, and who incorporate up-to-date treatment plans for acute asthma attacks may help reverse distressing trends in asthma morbidity and mortality.     

Patient-Centered Care for Childhood Asthma

Asthma, the most common chronic disease in children, is characterized by chronic inflammation of the respiratory system. If left uncontrolled, persistent asthma can have serious negative clinical outcomes. Thus, the earliest possible diagnosis based on the recognition of specific clinical indicators, treatment with anti-inflammatory controller medications such as an inhaled corticosteroid (ICS) or a leukotriene receptor antagonist (LTRA), and patient-centered strategies for monitoring disease and improving patient adherence are essential to successful asthma care. Recent clinical studies support the efficacy of ICSs over LTRAs as daily treatment for pediatric asthma. Routine follow-up and patient education can facilitate adherence to daily controller therapy and successful asthma control in children.     

Outpatient management of bronchial asthma

The current approach to asthma treatment centers around the recognition that asthma is primarily an inflammatory condition; airway hyperresponsiveness and bronchospasm are secondary phenomena. Anti-inflammatory treatments that produce sustained improvement in airway hyperresponsiveness (environmental control, cromolyn, inhaled and ingested corticosteroids) are the mainstay of treatment to keep symptoms and bronchodilator use to a minimum. Adequate control of chronic asthma with clearly defined treatment goals, accompanied by early recognition and patient-initiated treatment of worsened asthma, generally with inhaled/ingested corticosteroid, can successfully reduce the high morbidity and the low, but significant, mortality from this common condition.     

Use of magnesium sulfate for pediatric patients with acute asthma exacerbations.

The number of children with a diagnosis of asthma has increased significantly over the years, and asthma currently is the most common pediatric chronic disease. Asthma continues to take the lives of children at an alarming rate. Proper diagnosis, education, and appropriate management are essential for decreasing morbidity and mortality. Asthma can be diagnosed with a thorough medical history, family history, and physical examination. Diagnostic and assessment tools such as pulmonary function tests and pediatric asthma scores are valuable for determining the severity of asthma. Immediate assessment and initiation of appropriate medications and management are essential for a positive outcome. The use of bronchodilator therapy with corticosteroids is the gold standard for acute asthma exacerbation, but it may not be effective for certain moderate to severe exacerbations. This article discusses the prevalence, pathophysiology, and diagnosis and treatment of asthma, including the role of magnesium sulfate for acute asthma exacerbations.     

Drug development for severe asthma: what are the metrics?

Although reversible airway obstruction in part defines asthma, lung function as measured by spirometry alone inadequately predicts the value of new therapeutic agents in the treatment of severe asthma. Our objectives are 1) to review whether pulmonary function and bronchodilator reversibility are endpoints for drug discovery and 2) to identify parameters that predict efficacy in drug development in severe asthma. An English language literature search using MedLine and PubMed was conducted from 1997 to present concerning pathophysiology, diagnosis and therapy of severe asthma using the terms "severe asthma," "irreversible asthma," "difficult asthma," "airway remodeling," "fixed airway obstruction," "reversibility" and "bronchodilator reversibility" as index terms. Eight studies were characterized that encompass 1424 subjects with asthma. Our review identified the limitations of using bronchodilator reversibility as a predictor in drug development for severe asthma. Neither improvement in lung function nor bronchodilator reversibility characterized the benefit of new drugs in the treatment of severe asthma. Newly approved drugs in the treatment of severe asthma show decreased asthma exacerbations and improved quality of life associated with steroid-sparing benefits without altering bronchodilator responsiveness or improving lung function. Although changes in lung function predict asthma control in mild/moderate asthma, lung function alone is inadequate to assess improvement in asthma control in severe asthma manifested by fixed airway obstruction. Endpoints that focus on asthma control, as defined by the Expert Panel Report 3 and GINA guidelines, may predict the value of new therapeutics in the management of severe asthma.     

Pathophysiology and management of pulmonary emphysema]

The predominant physiological abnormalities of pulmonary emphysema are chronic airway obstruction, hyperinflation of the lung, decrease of lung elastic recoil, and impaired gas exchange. Patient who still smokes must be advised and supported in an effort to stop smoking before medical treatment. The treatment goals are to induced bronchodilation, decreased the inflammatory change and promote expectoration to prevent the progressive deterioration in lung function and improves quality of life. Inhaled beta 2-agonists, anticholinergics, and oral theophylines, as bronchodilators improved exertional dyspnea and exercise tolerance. Inhaled and oral corticosteroids have an anti inflammatory effect for chronic airway inflammation. Comprehensive respiratory treatments including home oxygen therapy and rehabilitation are also successfully applied for these patients.     

Early discharge of people with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is an umbrella term used to describe any respiratory condition that causes long-standing airflow obstruction, which is non or only partially reversible with bronchodilator therapy. These diseases include emphysema, chronic bronchitis, chronic airflow limitation and some cases of chronic asthma. The World Health Organization global initiative for chronic obstructive lung disease (GOLD) recommendations proposed a new definition of COPD as 'a disease state characterised by a progressive airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases' (Pauwels et al, 2001).     

Issues and advances in the pharmacotherapy of asthma.

Evidence is accumulating that inflammation of the airways is directly responsible for the increased bronchial hyperresponsiveness (BHR) and lung function obstruction in asthma. Bronchoprovocation with non-specific, direct bronchoconstrictors (methacholine and/or histamine) can be used as an indirect measurement of inflammation. Thus bronchoprovocation is a useful method for evaluating the long-term benefits of various therapies in asthma. The focus of asthma therapy research is now on the development of anti-inflammatory agents. Inhaled corticosteroids are currently the most potent anti-inflammatory agents in the treatment of asthma and so are generally the most effective in reducing BHR with long-term use. Non-corticosteroid anti-inflammatory agents that are currently available are reviewed. Recent studies have suggested that regular use of inhaled bronchodilators may actually be detrimental in asthma. At this time the data is still inconclusive but certainly warrants the attention of practitioners and requires further research, particularly in relation to the long-acting beta 2-agonists, formoterol and salmeterol.     

Cough-variant asthma in children and adults: case reports and review

Two cases of cough-variant asthma are presented, one in an adult and one in a child. We discuss the diagnosis, treatment, and course of this common, yet often unrecognized entity. The keys to diagnosis are a typical history, clinical suspicion, and subsequent response to bronchodilator therapy. Treatment of cough-variant asthma is no different from that of classic asthma.     

Categorizing asthma severity: an overview of national guidelines

Asthma is an inflammatory disease of the airways associated with intermittent episodes of bronchospasm. Corticosteroids are the most effective anti-inflammatory class of medication currently available for the treatment of asthma. However, as higher doses of inhaled corticosteroids are used the risks of systemic exposure and side effects will correspondingly increase. Justification of the benefits from higher doses of inhaled corticosteroids can only be made if patients with more severe asthma can be identified. Methods to categorize asthma severity have been introduced in various national asthma management guidelines. Unfortunately, there are substantial conceptual and practical differences among these recommended approaches to asthma severity categorization. Furthermore, these recommended approaches suffer from a focus on features of asthma control, such as symptoms, short-acting beta-agonist use, and lung function rather than actual measures of asthma severity that would encompass markers of airway inflammation. Without the endpoints necessary to assess airway inflammation, current recommendations for asthma severity categorization may lead to systematic under dosing of appropriate anti-inflammatory therapy with subsequent perpetuation of the asthma exacerbation cycle.