Risk factors for recurrent asthma hospital visits and death among a population of indigent older adults with asthma.

BACKGROUND: Little is known about the morbidity and mortality among older adults with asthma requiring hospital care. OBJECTIVES: To determine whether an initial hospital visit for asthma was associated with an increase in use of inhaled corticosteroids (CCS) at discharge, and to identify risk factors for recurrent asthma hospital visits and death. METHODS: A retrospective cohort analysis identified 93,174 persons 65 years and older enrolled in the Tennessee Medicaid program for at least 1 year and free of asthma hospital visits during that year; 510 survived a single hospital visit for asthma in 1992 and comprised the study population. Main outcome measures included recurrent hospital visit for asthma and all-cause mortality during the year after an asthma hospital visit. RESULTS: Among the 510 study subjects, 10% were on inhaled CCS at admission compared with 11% at discharge. Twenty-three percent of the population had recurrent asthma hospital visits and 12% died during 1-year followup. Asthma severity was the strongest independent risk factor for both a recurrent hospital visit [relative risk for moderate to severe disease 1.92 (1.01 to 3.66), and for near-fatal disease 2.28 (1.01 to 5.13), respectively] and death [relative risk for moderate to severe disease 2.99 (1.07 to 8.32) and for near-fatal disease 4.44 (1.34 to 4.69), respectively]. CONCLUSIONS: In this population, older adults with an exacerbation of asthma requiring hospital care experienced significant morbidity and mortality. An acute hospital visit for an asthma exacerbation did not result in initiation of inhaled CCS therapy. Asthma severity predicted both recurrent hospital visits and all-cause mortality among older adults with asthma requiring hospital care.     

Role of rhinovirus infections in asthma

Human rhinoviruses are not only the main pathogens responsible for the common cold, but are now recognized to have a major impact on asthma pathogenesis. There is evidence that rhinovirus infections play a role in asthma development, asthma exacerbations and, potentially, airway remodeling. Children who experience repeated rhinovirus-induced wheezing episodes in infancy have a significantly increased risk of developing asthma, even when compared to children who experience wheezing induced by respiratory syncytial virus. Rhinovirus is also the dominant virus type associated with acute exacerbations of asthma. The epithelial cell is the principal site of rhinovirus infection in both the upper and lower airways and there is strong evidence that virus-induced alterations of epithelial cell biology play a critical role in regulating clinical outcomes. This includes rhinovirus-induced epithelial generation of a variety of chemokines, cytokines and growth factors that likely play a role in viral modulation of airway inflammation. It has also become clear, however, that epithelial cells play an important role in the innate antiviral response to rhinovirus infection, raising the possibility that the relative induction of epithelial host innate antiviral responses versus proinflammatory responses may be one factor regulating the susceptibility of asthmatic subjects to virus-induced disease exacerbations. Recent evidence has also highlighted that rhinovirus infection induces epithelial production of a number of growth factors and other mediators that could contribute to the development and progression of airway remodeling processes in asthma. The current article reviews our current state of knowledge in these areas.     

Short-term clinical outcomes of acute treatment of childhood asthma

PURPOSE OF REVIEW: Acute exacerbations of asthma are the leading cause of emergency department visits in the pediatric patient. The present review is focused on the identification of those factors that may contribute to improving the short-term outcome of children after discharge from an emergency department visit for acute asthma. RECENT FINDINGS: Several recent studies have documented that children treated at the emergency department because of an asthma-related event present a high morbidity at 7 and 15 days after discharge, mainly associated with symptom persistence, need for rescue bronchodilator medication, and absenteeism from school or day nursery. A better control of the disease, particularly adequate outpatient follow-up and maintenance treatment with inhaled steroids, could improve short-term clinical outcomes. SUMMARY: All efforts of emergency room management of children with asthma, identification of severity of the current exacerbation episode, and intensive treatment of the acute asthma attack have usually been directed at reducing the rates of hospitalization and the return for medical care. However, according to reported data on short-term morbidity, it is necessary to define therapeutic and follow-up strategies after treatment for acute asthma and emergency department discharge. Besides standard treatment for an acute asthma exacerbation in a pediatric emergency department, action plans should include a review of the maintenance treatment of asthma to improve underlying disease control and a strong recommendation for close follow-up by the primary care pediatrician.     

Asthma exacerbations: origin, effect, and prevention

Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children in the Western world. Despite advances in asthma management, acute exacerbations continue to occur and impose considerable morbidity on patients and constitute a major burden on health care resources. Respiratory tract viruses have emerged as the most frequent triggers for exacerbations in both children and adults; however, the mechanisms underlying these remain poorly understood. More recently, it has become increasingly clear that interactions might exist between viruses and other triggers, increasing the likelihood of an exacerbation. In this article we begin with an overview of the health, economic, and social burden that exacerbations of asthma carry with them. This is followed by a review of the pathogenesis of asthma exacerbations, highlighting the various triggers responsible and multiple interactions that exist between them. The final section first addresses what preventative measures are currently available for asthma exacerbations and subsequently examines which of the new treatments in development might lessen the burden of exacerbations in the future.     

A behavioral intervention can decrease asthma exacerbations in older adults

BackgroundOlder adults have higher rates of asthma morbidity and mortality compared with younger age groups. Few interventions are tailored to this population.ObjectiveTo evaluate a self-management asthma intervention in older adults.MethodsAdults age 55 and older with persistent asthma were enrolled into blinded, randomized controlled trial of a 6-session asthma self-management intervention. This educational intervention was conducted in group sessions and through individual telephone calls. Outcomes including asthma exacerbations (defined as unscheduled office visits, emergency department visits, or hospitalizations for asthma), spirometric values, FeNO, asthma control, asthma quality of life, and asthma self-management were assessed at 3, 6, and 12 months.ResultsOne hundred eighty-nine subjects were enrolled, 172 were randomized and received at least 1 treatment dose, and 145 (84%) were analyzed at 12 months. On a modified intent-to-treat analysis, those in the intervention group were less likely to have an asthma exacerbation (26.9% vs 47.1%, P = .01), had a lower asthma exacerbation rate (0.8 vs 1.9, P = .02), had better asthma control (19.9 vs 18.6, P = .08), and had a higher asthma self-management score (8.9 vs 8.4, P = .03). After a mixed-model analysis to control for confounding factors, a decrease in asthma exacerbations (P = .02), as well as a decreased asthma exacerbation rate (P = .04), remained statistically significant, whereas asthma control and self-management did not. No other significant outcome differences were found.ConclusionA 6-session asthma self-management intervention can successfully decrease asthma exacerbations among older adults.     

Role of viral infections in asthma and chronic obstructive pulmonary disease

Substantial evidence implicates common respiratory viral infections in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Children who experience recurrent virally induced wheezing episodes during infancy are at greater risk for developing asthma. In addition, respiratory viral infections are a major trigger for acute exacerbations of both asthma and COPD. Despite the importance of viral infections in asthma and COPD, the mechanisms by which viruses predispose to, or cause exacerbations of, these diseases remain poorly understood. It is clear that viral infections lead to enhanced airway inflammation and can cause airways hyperresponsiveness. The epithelial cell is the principal site of viral infection in the airways and plays a central role in viral modulation of airway inflammation via release of a variety of cytokines, chemokines, and growth factors. The mechanisms by which viral infections modulate epithelial function, therefore, is a topic of intense investigation. The epithelium also contributes to the host innate defense response to viral infection by releasing products that are antiviral and/or can lead to increased recruitment of dendritic cells and lymphocytes. Some evidence supports a role for the epithelial cell in specific immunity, although the response of more conventional cells of the immune system to viral infections is likely the dominant factor in this regard. Although current therapies may help combat virally induced disease exacerbations, they are less than ideal. A better understanding of the mechanisms underlying viral modulation of these diseases, therefore, may lead to new therapeutic approaches.     

Response to infections in patients with asthma and atopic disease: An epiphenomenon or reflection of host susceptibility?

Associations between respiratory tract infections and asthma inception and exacerbations are well established. Infant respiratory syncytial virus and rhinovirus infections are known to be associated with an increased risk of asthma development, and among children with prevalent asthma, 85% of asthma exacerbations are associated with viral infections. However, the exact nature of this relationship remains unclear. Is the increase in severity of infections an epiphenomenon, meaning respiratory tract infections just appear to be more severe in patients with underlying respiratory disease, or instead a reflection of altered host susceptibility among persons with asthma and atopic disease? The main focus of this review is to summarize the available levels of evidence supporting or refuting the notion that patients with asthma or atopic disease have an altered susceptibility to selected pathogens, as well as discussing the biological mechanism or mechanisms that might explain such associations. Finally, we will outline areas in need of further research because understanding the relationships between infections and asthma has important implications for asthma prevention and treatment, including potential new pathways that might target the host immune response to select pathogens.     

Current control and future risk in asthma management

Despite international and national guidelines, poor asthma control remains an issue. Asthma exacerbations are costly to both the individual, and the healthcare provider. Improvements in our understanding of the therapeutic benefit of asthma therapies suggest that, in general, while long-acting bronchodilator therapy improves asthma symptoms, the anti-inflammatory activity of inhaled corticosteroids reduces acute asthma exacerbations. Studies have explored factors which could be predictive of exacerbations. A history of previous exacerbations, poor asthma control, poor inhaler technique, a history of lower respiratory tract infections, poor adherence to medication, the presence of allergic rhinitis, gastro-oesophageal reflux disease, psychological dysfunction, smoking and obesity have all been implicated as having a predictive role in the future risk of asthma exacerbation. Here we review the current literature and discuss this in the context of primary care management of asthma.     

Thymic stromal lymphopoietin (TSLP) as a bridge between infection and atopy

The rising worldwide prevalence of asthma has intensified interest in the natural history of asthma. An improved understanding of the genetic, environmental, and developmental factors contributing to the inception and exacerbation of asthma will be crucial to efforts to devise effective preventive and therapeutic interventions. There is increasing evidence that the complex interplay of early life respiratory viral infections and allergic sensitization is important in the development of asthma. Major causes of asthma exacerbations are respiratory viral infections and aeroallergen exposure, which may have interactive co-morbid effects. This review describes the potential role of thymic stromal lymphopoietin (TSLP) as a connection between the innate immune response to respiratory viral infections and the type-2 adaptive immune response in the development and exacerbation of asthma.     

How rhinovirus infections cause exacerbations of asthma

Rhinovirus (RV) infections are closely linked to exacerbations of asthma, and yet most RV infections of patients with asthma cause only upper respiratory symptoms. These findings suggest that RV and other viral infections contribute to the causation of acute exacerbations of asthma, but that additional cofactors are generally required. In fact, factors related to the host, virus, and environment have been identified that affect the severity of RV infections, and propensity to develop lower respiratory tract symptoms. This review will discuss these factors and how their effects may act alone or in combination to increase the probability of RV‐induced exacerbations of asthma.     

Asthma control and future asthma-related morbidity in inner-city asthmatic children

BACKGROUND: Asthma guidelines recommend routine evaluation of asthma control, which includes measurements of impairment and risk. It is unclear whether rigorous asthma control changes risk of asthma morbidity. OBJECTIVE: To examine whether the degree of asthma control in inner-city asthmatic children results in differential risk reduction of future asthma-related morbidity. METHODS: This retrospective observational study examines 960 inner-city children with asthma who were highly engaged in an asthma-specific disease management program for a minimum of 2 years. Degree of asthma control was determined during the first year of enrollment and was categorized as well controlled (> or = 80% of visits in control), moderately controlled (50%-79% of visits in control), or difficult to control (< 50% of visits in control). Risk and probability of asthma-related morbidity at each visit were determined during the second year of enrollment and included self-reported asthma exacerbations requiring systemic corticosteroid rescue and emergency department visits or hospitalizations. RESULTS: Increasing the degree of asthma control measured during the first year of enrollment led to statistically significant incremental reductions in risk of acute asthma exacerbations and emergency department visits or hospitalizations during the second year of enrollment. CONCLUSIONS: Achieving and maintaining asthma control in inner-city children with asthma results in significant reductions in asthma-related morbidity. Systematic assessments of asthma control may be useful for predicting future risk in children with asthma.     

Macrolide antibiotics and asthma treatment

Treatment for acute asthma exacerbations is a major need not adequately met by current therapies. Although virus infections are the major cause of acute exacerbations, other factors can increase the risk/severity of exacerbations. Increasing evidence suggests atypical bacterial infections contribute to exacerbation severity, as well as stable asthma, particularly severe asthma. Macrolide antibiotics and the new ketolide antibiotic telithromycin are active against atypical bacteria and also have anti-inflammatory activity. A recent study has shown telithromycin to be effective in the treatment of acute exacerbations of asthma, although the mechanism or mechanisms of action were not determined. Controlled studies report small improvements in lung function with macrolide treatment of stable asthma. Further studies are urgently required to assess the role of such therapies in acute exacerbations and in severe stable asthma, in which the risk/benefit ratios are likely to be most in favor of therapy demonstrated to be effective.     

Expression of costimulatory molecules in peripheral blood mononuclear cells of atopic asthmatic children during virus-induced asthma exacerbations

BACKGROUND: Respiratory viruses are the most frequent triggers of acute asthma exacerbations. Herein we investigate costimulatory molecule expression on peripheral blood mononuclear cells (PBMC) during such exacerbations. METHODS: Eleven children with atopic asthma were followed prospectively and respiratory symptoms were recorded on diary cards. A blood sample and nasopharyngeal wash (NPW) were obtained at baseline and subsequently during an exacerbation. PBMC were immunophenotyped using flow cytometry. NPW samples were examined for the presence of respiratory viruses by RT-PCR. RESULTS: A virus was detected in 73% of exacerbations and none at baseline. A drop of NK cells and a marginal increase of monocytes were the only changes of cell count during the exacerbation. A significant downregulation of B7-2 on NK cells and of B7-1 on monocytes was also observed during exacerbations. CONCLUSIONS: The above observations are in contrast to in vitro findings showing an upregulation of costimulatory molecules after exposure of blood cells to viruses or allergens. It is possible that activated immune cells leave the blood stream to migrate to the inflammation site during acute asthma exacerbations.     

Diagnosis and management of early asthma in preschool-aged children

Asthma is a common disease in young children and is associated with significant morbidity and an increasing prevalence over time. Early childhood wheezing and asthma are heterogeneous disorders; thus identifying phenotypes of asthma remains a goal to identify high-risk children who might benefit from specific therapies or secondary prevention interventions. The typical pattern of illness in preschool-aged children consists of short but recurrent exacerbations of cough and wheeze usually triggered by viral respiratory tract infections. Documenting reversible airflow obstruction on lung function, allergen sensitization, increased IgE levels, or blood eosinophilia is helpful in establishing a diagnosis of asthma in preschool-aged children, if present; however, the diagnosis is most often based on symptom patterns, presence of risk factors, and therapeutic responses. The preschool-aged asthmatic population tends to be characterized as exacerbation prone with relatively limited impairment, unlike older children and adolescents who have more impairment-dominant disease. However, management of persistent disease is based largely on expert opinion and extrapolation from studies in older children given the relative lack of data in this age group. Strategies used to manage intermittent disease include daily and intermittent controller therapy. Management strategies for persistent asthma include daily inhaled corticosteroids, daily leukotriene receptor antagonists, and combination therapies. Finally, regular monitoring of symptom control and medication side effects is important along with titrating controllers to the minimally effective dose.     

Management of acute asthma exacerbations by general practitioners: a cross-sectional observational survey.

BACKGROUND: General practitioners (GPs) have a central place in the management of asthma, particularly in the context of acute exacerbations. AIM: To evaluate the management of asthma exacerbations by GPs, and to investigate the ability of risk factors for near fatal asthma to predict the severity of asthma attacks in the community. Design of study: A 1-month multicentre cross-sectional survey. SETTING: One thousand and ninety-four GPs of the French Sentinel Network were contacted; 365 responded. METHOD: Asthma exacerbations were classified according to severity at presentation. Univariate and multivariate analyses were performed by logistic regression to identify those factors associated with severe exacerbations. RESULTS: Exacerbations were described in 219 patients with asthma. Over half (54%) of exacerbations were severe. Peak expiratory flow was recorded during the consultation in 55% of patients who were more than 5 years old. beta(2) agonists were prescribed to 93% of patients, systemic corticosteroids to 71%, and antibiotics to 64%. Only 42% of patients had a written action plan for self-management of exacerbations. Risk factors for near fatal asthma, identified in 26% of patients, were not significantly associated with severe asthma exacerbations. Short duration of exacerbation before consultation (<3 hours) was associated with an increase in relative risk of severe exacerbation of 3.38, 95% confidence intervals (CIs) = 1.19 to 9.61, compared with duration of >3 hours. CONCLUSION: Risk factors for near fatal asthma identified in previous studies were not predictive of a severe exacerbation in general practice, with the exception of short duration of exacerbation before consultation. This suggests that new methods to predict risk in the outpatient settings should be developed.     

Toll-like receptor 4 signaling promotes epithelial-mesenchymal transition in human hepatocellular carcinoma induced by lipopolysaccharide

Chronic pulmonary diseases are a major cause of morbidity and mortality and their impact is expected to increase in the future. Respiratory viruses are the most common cause of acute respiratory infections and it is increasingly recognized that respiratory viruses are a major cause of acute exacerbations of chronic pulmonary diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. There is now increasing evidence that the host response to virus infection is dysregulated in these diseases and a better understanding of the mechanisms of abnormal immune responses has the potential to lead to the development of new therapies for virus-induced exacerbations. The aim of this article is to review the current knowledge regarding the role of viruses and immune modulation in chronic pulmonary diseases and discuss avenues for future research and therapeutic implications.     

Viral respiratory infections in association with asthma and sinusitis: a review.

OBJECTIVE: Viral respiratory infections (VRIs) commonly precede asthma exacerbations in both children and adults. Likewise, VRIs may affect the paranasal sinuses, predisposing infected individuals to the development of subsequent acute bacterial sinusitis. This article discusses the role that viruses play in both the development of asthma and in acute asthma exacerbations. Mechanisms by which viral infections provoke asthma exacerbations are reviewed, and treatment of such episodes is discussed. The pathogenesis of sinusitis and association with VRIs is reviewed along with treatment recommendations. DATA SOURCES: Relevant articles in the medical literature were reviewed with sources including randomized, controlled clinical trials, review articles, epidemiologic studies, and standard textbooks in allergy and immunology. CONCLUSIONS: This review highlights the prominent role that viral pathogens (especially rhinovirus) play in exacerbation of asthma and in the development of sinus disease. The specific mechanisms whereby viral infection leads to an acute asthma exacerbation or to subsequent bacterial sinusitis are described. Treatment options are outlined including the potential future application of antiviral compounds.     

Role of infections in the induction and development of asthma: genetic and inflammatory drivers

Genetic and environmental factors interact to initiate and even maintain the course of asthma. As one of the highly risky environmental factors, infections in predisposed individuals can promote asthma development and exacerbations and/or prolong symptoms. This review will describe our current understanding of the genetic markers of innate immunity in the induction and development of asthma, the diverse roles of infections in modulating allergic inflammation, host susceptibility to infections and subsequent acute exacerbations in an allergic setting, and the therapeutic or preventive implications of existing knowledge. Current challenges and future directions in basic and clinical research of asthma are also discussed.     

Long-Term Prognosis of Asthma-Bronchiectasis Overlapped Patients: A Nationwide Population-Based Cohort Study

PurposeAsthma and bronchiectasis are common chronic respiratory diseases, and their coexistence is frequently observed but not well investigated. Our aim was to study the effect of comorbid bronchiectasis on asthma.MethodsA propensity score-matched cohort study was conducted using the National Health Insurance Service-Health Screening Cohort database. From 2005 to 2008, 8,034 participants with asthma were weighted based on propensity scores in a 1:3 ratio with 24,099 participants without asthma. From the asthma group, 141 participants with overlapped bronchiectasis were identified, and 7,892 participants had only asthma. Clinical outcomes of acute asthma exacerbation(s) and mortality rates were compared among the study groups.ResultsThe prevalence of bronchiectasis (1.7%) was 3 times higher in asthmatics than in the general population of Korea. Patients who had asthma comorbid with bronchiectasis experienced acute exacerbation(s) more frequently than non-comorbid patients (11.3% vs. 5.8%, P = 0.007). Time to the first acute exacerbation was also shorter in the asthmatics with bronchiectasis group (1,970.9 days vs. 2,479.7 days, P = 0.005). Although bronchiectasis was identified as a risk factor for acute exacerbation (adjusted odds ratio, 1.73; 95% confidence interval [CI], 1.05–2.86), there was no significant relationship between bronchiectasis and all-cause or respiratory mortality (adjusted hazard ratio [aHR], 1.17; 95% CI, 0.67–2.04 and aHR, 0.81; 95% CI, 0.11–6.08).ConclusionsComorbid bronchiectasis increases asthma-related acute exacerbation, but it does not-raise the risk of all-cause or respiratory mortality. Close monitoring and accurate diagnosis of bronchiectasis are required for patients with frequent exacerbations of asthma.     

Oxidants and the pathogenesis of lung diseases

The increasing number of population-based and epidemiologic associations between oxidant pollutant exposures and cardiopulmonary disease exacerbation, decrements in pulmonary function, and mortality underscores the important detrimental effects of oxidants on public health. Because inhaled oxidants initiate a number of pathologic processes, including inflammation of the airways, which may contribute to the pathogenesis and/or exacerbation of airways disease, it is critical to understand the mechanisms through which exogenous and endogenous oxidants interact with molecules in the cells, tissues, and epithelial lining fluid of the lung. Furthermore, it is clear that interindividual variation in response to a given exposure also exists across an individual lifetime. Because of the potential impact that oxidant exposures may have on reproductive outcomes and infant, child, and adult health, identification of the intrinsic and extrinsic factors that may influence susceptibility to oxidants remains an important issue. In this review, we discuss mechanisms of oxidant stress in the lung, the role of oxidants in lung disease pathogenesis and exacerbation (eg, asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome), and the potential risk factors (eg, age, genetics) for enhanced susceptibility to oxidant-induced disease.