Vaccination for asthma exacerbations

Most asthma exacerbations are caused by common cold virus infections, predominantly rhinovirus infections. Full protection against repeat infections with the same rhinovirus serotype is given by serum neutralizing antibody, but cross-reactive antibody developed against other serotypes could yield partial protection and result in attenuated cold and airway symptoms. It is proposed that vaccine-mediated induction of cross-reactive antibody might not prevent rhinovirus infections but might reduce severe asthma symptoms and exacerbations.     

Managing outpatient asthma exacerbations

Asthma is a chronic inflammatory disease that renders individuals prone to acute exacerbations. Several allergic and nonallergic triggers can incite an asthma exacerbation. The goals of managing an asthma exacerbation are prompt recognition, rapid reversal of airflow obstruction, prevention of relapses, and forestalling future episodes. A written asthma home-management plan is essential to minimize the severity of exacerbations. Short-acting β-agonists, oxygen, and corticosteroids are fundamental to early intervention in acute asthma exacerbation. Anticholinergics and magnesium sulfate can help nonresponders. Newer agents such as levalbuterol and long-acting β-agonists might be future additions to our armamentarium of drugs to treat acute exacerbations. Initiation or intensification of long-term controller therapy, treatment of co-morbid conditions, and avoidance of possible triggers along with prompt follow-up can help prevent relapses. Listening to patient preferences and concerns to enhance adherence and regular follow-up care can help prevent future episodes.     

Viruses in asthma exacerbations

PURPOSE OF REVIEW: Respiratory viruses are well recognized as major triggers of acute exacerbations of asthma in children and adults, resulting in frequent outpatients visits and hospitalizations. Clinical and epidemiologic evidence supports this association. The application of molecular diagnostic methods has improved understanding of viral epidemiology and the pathophysiological mechanisms involved in viral induced acute asthma. This article reviews publications since October 2002 for an update of the role of viruses in exacerbations of asthma. RECENT FINDINGS: Respiratory viruses are present in most patients hospitalized for life-threatening asthma and acute non life-threatening asthma. Rhinovirus is the most common, but coinfection with other viruses may be important. Patients with asthma are not more susceptible to upper respiratory tract rhinovirus infections than healthy people but suffer from more severe consequences of the lower respiratory tract infection. Recent epidemiologic studies suggest that viruses provoke asthma attacks by additive or synergistic interactions with allergen exposure or with air pollution. An impaired antiviral immunity to rhinovirus may lead to impaired viral clearance and hence prolonged symptoms. Respiratory viral infections cause asthmatic exacerbations by triggering recruitment of Th2-type cells into the lungs. There is no specific antiviral strategy for prevention of respiratory-triggered asthma exacerbations, although clinical trials of potential antiviral agents are ongoing. Indirect prevention strategies focus on the reduction of overall airway inflammation to reduce the severity of the host response to respiratory viral infections. SUMMARY: Respiratory viral infections are a major cause of morbidity and mortality in asthma. There is a lack of specific antiviral strategies in the prevention or reduction of viral-triggered asthma exacerbations. Recent advances in understanding of the epidemiology and immunopathogenesis of respiratory viral infection in asthma provide opportunities or identification of specific targets for antiviral agents and strategies for management and prevention.     

New treatment regimes for virus-induced exacerbations of asthma

This review will focus on the role of viruses as causes of asthma exacerbations. The article will briefly review the current literature supporting this view, with a special focus on human rhinovirus (RV), the main virus associated with exacerbations of asthma. The review will then refer to possible strategies for treatment, and will include discussion on treatment with specific anti-viral therapy and type I interferon as a treatment for RV. The review will also include a discussion on current therapies for asthma, such as glucocorticosteroid and beta(2) agonist therapy alone and in combination and why this may be relevant to virus-induced exacerbations of asthma. Finally, the potential for future anti-inflammatory/immunomodulatory therapies with a focus on NF-kappaB inhibition will be discussed.     

Risk factors of frequent exacerbations in difficult-to-treat asthma.

Recurrent exacerbations are a major cause of morbidity and medical expenditure in patients with asthma. Various exogenous and endogenous factors are thought to influence the level of asthma control, but systematical data on the involvement of these factors in the recurrence of asthma exacerbations are scarce. In this study, 13 clinical and environmental factors potentially associated with recurrent exacerbations were investigated in 136 patients with difficult-to-treat asthma. Patients with more than three severe exacerbations (n = 39) in the previous year were compared with those with only one exacerbation per year (n = 24). A systematic diagnostic protocol was used to assess 13 potential risk factors. Factors significantly associated with frequent exacerbations included: severe nasal sinus disease (adjusted odds ratio (OR) 3.7); gastro-oesophageal reflux (OR 4.9); recurrent respiratory infections (OR 6.9); psychological dysfunctioning (OR 10.8); and obstructive sleep apnoea (OR 3.4). Severe chronic sinus disease and psychological dysfunctioning were the only independently associated factors (adjusted OR 5.5 and 11.7, respectively). All patients with frequent exacerbations exhibited at least one of these five factors, whilst 52% showed three or more factors. In conclusion, the results show that recurrent exacerbations in asthma are associated with specific co-morbid factors that are easy to detect and that are treatable. Therapeutic interventions aimed at correcting these factors are likely to reduce morbidity and medical expenditure in these patients.     

Increased oxidative stress in acute exacerbations of asthma.

Oxidant-antioxidant imbalance may play an important role in the pathogenesis of asthma, especially during acute exacerbations. To compare the systemic oxidant-antioxidant status in patients with acute exacerbations and stable asthma, we measured a wide range of parameters of oxidant-antioxidant balance in leukocytes, plasma, and red cells of 32 patients with acute exacerbations and 97 patients with stable asthma. These included measurement of superoxide anion generation by leukocytes, lipid peroxidation (measured as TBARS), total nitrates and nitrites, protein carbonyls, and protein sulfhydryls in plasma. Antioxidant status was evaluated by measuring the red cell superoxide dismutase and catalase activity, total blood glutathione, glutathione peroxidase activity in red cell and plasma, and total antioxidant capacity (assessed as ferric reducing antioxidant power) in plasma. Plasma total antioxidant capacity and total protein sulfhydryls were found to be decreased (p < 0.01), whereas plasma lipid peroxides were found to be increased (p < 0.05), in acute exacerbations of asthma. No significant differences were found in plasma glutathione peroxidase, protein carbonyls, and total nitrates and nitrites, red cell antioxidative enzyme activities, superoxide anion release from leukocytes, and total blood glutathione between the two groups (p > 0.05). Our observations suggest that acute exacerbations of asthma are associated with increased oxidative stress that is evident from some of the parameters in the plasma. Failure to observe simultaneous changes in all parameters of oxidative stress may be due to the possibility of their responses being dissociated in time or compensatory changes occurring in some of these.     

Recent asthma exacerbations: a key predictor of future exacerbations

OBJECTIVE: The objective of this analysis was to investigate whether patients with severe or difficult-to-treat asthma who experienced recent severe asthma exacerbations are at increased risk of future asthma exacerbations. METHODS: We conducted a 1.5-year prospective analysis of 2780 patients 12 > or =years of age from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study. Severe exacerbations were defined as either an asthma-related emergency department visit or night of hospitalization in the 3 months prior to study visit; a secondary analysis assessed prior steroid bursts as an independent predictor and outcome. Potential confounding was assessed by statistical adjustment for demographic and clinical factors, as well as asthma severity and asthma control. RESULTS: Compared with patients without a recent severe exacerbation, patients with a recent exacerbation were at increased risk of future exacerbation (odds ratio=6.33; 95% CI 4.57, 8.76), even after adjustment for demographics and clinical factors (odds ratio=3.77; 95% CI 2.62, 5.43), asthma severity (physician-assessed: odds ratio=5.62; 95% CI 4.03, 7.83), National Asthma Education and Prevention Program (odds ratio=5.07; 95% CI 3.62, 7.11), Global Initiative for Asthma (odds ratio=5.32; 95% CI 3.80, 7.47), and asthma control (odds ratio=3.90; 95% CI 2.77, 5.50). CONCLUSION: This analysis suggests that recent severe asthma exacerbations are a strong independent factor predicting future exacerbations and, as such, should be considered as part of the clinical assessment of patients with severe or difficult-to-treat asthma.     

Adult asthma exacerbations in questions

In this article a French working party critically review the international literature to revise the definition, pathophysiology, treatment and cost of exacerbations of adult asthma. The various guidelines do not always provide a consistent definition of exacerbations of asthma. An exacerbation can be defined as deterioration of clinical and/or functional parameters lasting more than 24 hours, without return to baseline, requiring a change of treatment. No single clinical or functional criterion can be used as an early marker of an exacerbation. Innate and acquired immune mechanisms, modified by contact with infectious, irritant or allergenic agents, participate in the pathogenesis of exacerbations, which are accompanied by bronchial inflammation. In 2010, mortality is related to progression of exacerbations, often occurring before the patient seeks medical attention. The objective of treatment is to control asthma and prevent exacerbations. However, many factors can trigger exacerbations and often cannot be controlled. The efficacy of inhaled corticosteroids has been demonstrated on reduction of the number of exacerbations and the number of asthma-related deaths. This treatment is cost-effective, especially in terms of reduction of exacerbations.     

A self-management program for adult asthma. III. Maintenance and relapse of skills.

Patient self-management programs have become an integral part of asthma treatment. The goal of such programs is to strengthen the partnership between patients and health care providers in controlling the condition. The present study analyzed how well patients maintained or relapsed in performing asthma self-management skills over time and across settings. It was conducted by contacting patients who had been involved in a successful self-management program an average of 6 years after their participation or an average of 7 years after they completed training. Seventy percent of the patients agreed to participate and complete, either by themselves or over the telephone, a structured interview regarding their experiences in performing asthma self-management. On the basis of their responses, 53 participants were categorized into two groups: continuers or relapsers, according to previously developed and published criteria for relapse. Characteristics that distinguished the two groups were described. As anticipated, those classified as continuers reportedly exhibited broader repertoires of self-management skills across an array of settings. They credited their performance with maintaining control over their asthma. However, two unexpected findings emerged in the study: First, all patients continued to use self-management skills to one degree or another 7 years after they had acquired these skills. Even patients who were categorized as relapsers regularly performed some self-management skills, often involving self-monitoring of their breathing. Second, half of the patients in the relapse group reported that their asthma was in remission and that they were asymptomatic. The self-management skills they reportedly used were performed to monitor and prevent a return of asthma.     

Treatment strategies for asthma

Asthma is characterized by variable and reversible airflow limitation and bronchial hyperresponsiveness due to chronic airway inflammation. Asthma treatment is based on the patients' asthma control status. Central to treatment recommendations is anti-inflammatory therapy with inhaled corticosteroids plus a rapid-acting β(2)-agonist as required. If this is not sufficient to achieve at least partial asthma control, the dose of the inhaled corticosteroid should be increased and a long-acting β(2)-agonist should be added. Other controllers, such as leukotriene antagonists or slow-release theophylline are alternative or additive options. Systemic treatment with corticosteroids and/or the monoclonal anti-IgE antibody omalizumab are reserved for patients with severe asthma. Strategies aimed at preventing airway irritation, reducing exposure to exogenous allergens and inhaled irritants as well as asthma education are other key elements of asthma management.