Evaluation of the National Heart, Lung, and Blood Institute guidelines impairment domain for classifying asthma control and predicting asthma exacerbations

BackgroundAccurate assessment of asthma control may help predict future asthma exacerbations.ObjectiveTo evaluate asthma guidelines impairment domain components as predictors of exacerbations in severe/difficult-to-treat asthma.MethodsChildren (aged 6–11 years; n = 289) and adolescents/adults (aged ≥12 years; n = 2,094) with complete baseline and 12-month data from The Epidemiology and Natural History of Asthma Outcomes and Treatment Regimens study were included. Asthma was categorized as very poorly controlled, not well-controlled, and well-controlled using impairment domain components. Effects of omitting each component on very poorly controlled and not well controlled groups were examined. Multivariable logistic regression determined the relationship of components in predicting asthma exacerbations.ResultsOmission of individual impairment domain components led to misclassification of asthma control in 11% to 39% of patients. A baseline exacerbation was the strongest independent predictor of exacerbation at month 12 in children (odds ratio = 2.94; P < .001) and adolescents/adults (odds ratio = 2.93; P < .001). In children, very poorly controlled asthma-based short-acting β2-agonist use was associated with a 2-fold higher exacerbation risk (odds ratio = 2.03; P = .011). In adolescents/adults, not well controlled or very poorly controlled asthma based on short-acting β2-agonist use (odds ratio = 1.49), lung function (odds ratio = 1.66), and the Asthma Therapy Assessment Questionnaire (odds ratio = 1.94) were also independent predictors of exacerbations (P < .001).ConclusionsAlthough the combined use of individual components of the impairment domain increases the sensitivity of identifying patients at high risk for future asthma exacerbations, specific components may be more important than others in severe/difficult-to-treat asthma. Prior exacerbations, short-acting β2-agonist use, lung function, and (in adolescents/adults) the Asthma Therapy Assessment Questionnaire were independent predictors of exacerbations.     

Familial resemblance for hostility: the National Heart, Lung, and Blood Institute Family Heart Study

OBJECTIVE: The purpose of this study was to examine whether several aspects of hostility as measured by the Cook-Medley Hostility Scale (ie, aggressive responding, hostile affect, cynicism, and overall hostility score) were determined in part by family factors (ie, genes and/or familial environments). METHODS: Analyses were based on 680 European-American families (2525 individuals) from the NHLBI Family Heart Study (FHS), a population-based study of genetic and nongenetic determinants of CHD, atherosclerosis, and cardiovascular risk factors. The influence of family relationships, age, and education on the variation in each of the four hostility scores were estimated. RESULTS: Significant familial resemblance in all hostility scores was found, accounting for 42% of the variance in total hostility, 30% in cynicism, 38% in aggressive responding, and 18% in hostile affect. Very little of this resemblance could be explained by similarities in education. Familial resemblance for cynicism was solely due to significant parent-offspring and sibling correlations (ie, no spouse resemblance), suggesting the possibility of genetic influences. Gender and generation differences were also evident in the familial correlations. CONCLUSIONS: Hostility aggregates in families. Both family environmental and genetic sources of resemblance are suggested for hostility.     

Racial disparities in asthma-related health care use in the National Heart,Lung, and Blood Institute's Severe Asthma Research Program

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Enrollment of women in cardiovascular clinical trials funded by the National Heart, Lung, and Blood Institute

BACKGROUND: With the recognition that certain aspects of cardiovascular disease are specific to sex, the government has sought to ensure that federally funded clinical research yields adequate high-quality information about heart disease in women. METHODS: We tabulated the numbers of men and women in cardiovascular clinical trials funded by the National Heart, Lung, and Blood Institute (NHLBI) between 1965 and 1998, recording both total numbers and the numbers for each type of cardiovascular disease. We analyzed the data according to the sex-specific prevalence of disease and assessed changes in enrollment over time. We performed a similar analysis after excluding all single-sex trials. RESULTS: A total of 398,801 subjects (215,796 women and 183,005 men) were enrolled in NHLBI-funded studies of cardiovascular disease. The overall enrollment rate for women (54 percent) exceeded the prevalence of cardiovascular disease in women in the general population (49 percent) and increased over time (P=0.002). With single-sex trials excluded, the enrollment rate for women was 38 percent, which did not change significantly over time. In studies of coronary artery disease and hypertension the rates of enrollment of women were similar to or exceeded the prevalence of these disorders in women. The enrollment rate increased significantly over time in studies of coronary artery disease (P<0.001) but not in studies of hypertension or arrhythmia. Women were under-enrolled in studies of heart failure, and the rate of enrollment did not change significantly over time. When single-sex trials were excluded from the analysis of enrollment rates according to the prevalence of disease, the results were similar. There was no change in enrollment rates overtime for any category of disease. CONCLUSIONS: Federal efforts to increase the representation of women in clinical trials have been moderately successful primarily because of the institution of a small number of large, single-sex trials involving coronary artery disease. There has been no change in the sex composition of cohorts in the majority of studies of cardiovascular disease.     

Increasing the number of competing awards at the National Heart, Lung, and Blood Institute: projections of a model

In the mid 1980s, the National Heart, Lung, and Blood Institute (NHLBI) sought to extend the benefits of longer award terms to the research community by supporting requests for longer award terms that were scientifically justified. Although investigators welcomed the resultant increase in support stability, concerns were raised about the institute's ability to fund competing awards. A model was developed to assess alternative policies that might result in increased numbers of competing awards. Assuming that the NHLBI receives budget increases sufficient only to keep pace with inflation, the transitory effects of moving to the current policy of longer award terms should largely have passed by 1993. In the long term, the annual number of competing awards will exceed the average number funded between 1980 and 1983. To increase the annual number of competing awards over the long term would require either a reduction in the current percentage of five-year awards or an increase in the total number of active grants. A reduction in the current percentage of five-year awards would subject productive scientists to greater instability in their research support (that is, they would have to apply more frequently for grants) and would introduce greater variability in the number of competing awards available each year. A substantial increase in the total number of active NHLBI awards would be necessary to return the institute's competing awards to the levels of 1984 to 1988.     

Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group.

BACKGROUND. Acute non-A, non-B hepatitis after blood transfusion often progresses to chronic hepatitis and sometimes culminates in cirrhosis or even hepatocellular carcinoma. However, the frequency of these sequelae and their effects on mortality are not known. METHODS. We traced patients with transfusion-related non-A, non-B hepatitis who had been identified in five major prospective studies conducted in the United States between 1967 and 1980. We matched each patient with two control subjects (identified as the first and second controls) who received transfusions but who did not have hepatitis. The mortality rates in the three groups were determined with use of data from the National Death Index and Social Security Death Tapes. Cause-specific mortality was determined by reviewing death certificates. RESULTS. Vital status was established for over 94 percent of the 568 patients who had had non-A, non-B hepatitis and the two control groups (526 first controls and 458 second controls). After an average follow-up of 18 years, the estimate by life-table analysis of mortality from all causes was 51 percent for those with transfusion-associated non-A, non-B hepatitis, as compared with 52 percent for the first controls and 50 percent for the second controls. The survival curves for the three groups were virtually the same. Mortality related to liver disease was 3.3, 1.1, and 2.0 percent, respectively, among the three groups (P = 0.033 for the comparison of the group with non-A, non-B hepatitis with the combined control group). Seventy-one percent of the deaths related to liver disease occurred among patients with chronic alcoholism. CONCLUSIONS. In this long-term follow-up study, there was no increase in mortality from all causes after transfusion-associated non-A, non-B hepatitis, although there was a small but statistically significant increase in the number of deaths related to liver disease.     

Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program

BACKGROUND: Severe asthma causes the majority of asthma morbidity. Understanding mechanisms that contribute to the development of severe disease is important. OBJECTIVE: The goal of the Severe Asthma Research Program is to identify and characterize subjects with severe asthma to understand pathophysiologic mechanisms in severe asthma. METHODS: We performed a comprehensive phenotypic characterization (questionnaires, atopy and pulmonary function testing, phlebotomy, exhaled nitric oxide) in subjects with severe and not severe asthma. RESULTS: A total of 438 subjects with asthma were studied (204 severe, 70 moderate, 164 mild). Severe subjects with asthma were older with longer disease duration (P < .0001), more daily symptoms, intense urgent health care utilization, sinusitis, and pneumonia (P < or = .0001). Lung function was lower in severe asthma with marked bronchodilator reversibility (P < .001). The severe group had less atopy by skin tests (P = .0007), but blood eosinophils, IgE, and exhaled nitric oxide levels did not differentiate disease severity. A reduced FEV(1), history of pneumonia, and fewer positive skin tests were risk factors for severe disease. Early disease onset (age < 12 years) in severe asthma was associated with longer disease duration (P < .0001) and more urgent health care, especially intensive care (P = .002). Later disease onset (age > or = 12 years) was associated with lower lung function and sinopulmonary infections (P < or = .02). CONCLUSION: Severe asthma is characterized by abnormal lung function that is responsive to bronchodilators, a history of sinopulmonary infections, persistent symptoms, and increased health care utilization. CLINICAL IMPLICATIONS: Lung function abnormalities in severe asthma are reversible in most patients, and pneumonia is a risk factor for the development of severe disease.     

Percutaneous transluminal coronary angioplasty in 1985-1986 and 1977-1981. The National Heart, Lung, and Blood Institute Registry

In August 1985, the Percutaneous Transluminal Coronary Angioplasty Registry of the National Heart, Lung, and Blood Institute reopened at its previous sites to document changes in angioplasty strategy and outcome. The new registry entered 1802 consecutive patients who had not had a myocardial infarction in the 10 days before angioplasty. Patient selection, technical outcome, and short-term major complications were compared with those of the 1977 to 1981 registry cohort. The new-registry patients were older and had a significantly higher proportion of multivessel disease (53 vs. 25 percent, P less than 0.001), poor left ventricular function (19 vs. 8 percent, P less than 0.001), previous myocardial infarction (37 vs. 21 percent, P less than 0.001), and previous coronary bypass surgery (13 vs. 9 percent, P less than 0.01). The new-registry cohort also had more complex coronary lesions, and angioplasty attempts in these patients involved more multivessel procedures. Despite these differences, the in-hospital outcome in the new cohort was better. Angiographic success rates according to lesion increased from 67 to 88 percent (P less than 0.001), and overall success rates (measured as a reduction of at least 20 percent in all lesions attempted, without death, myocardial infarction, or coronary bypass surgery) increased from 61 to 78 percent (P less than 0.001). In-hospital mortality for the new cohort was 1 percent, and the nonfatal myocardial infarction rate was 4.3 percent. Both rates are similar to those for the old registry. The long-term efficacy of current angioplasty remains to be determined.     

National Cancer Institute, National Heart, Lung and Blood Institute/Pediatric Blood and Marrow Transplantation Consortium First International Consensus Conference on late effects after pediatric hematopoietic cell transplantation: the need for pediatric-specific long-term follow-up guidelines

Existing standards for screening and management of late effects occurring in children who have undergone hematopoietic cell transplantation (HCT) include recommendations from pediatric cancer networks and consensus guidelines from adult-oriented transplantation societies applicable to all HCT recipients. Although these approaches have significant merit, they are not pediatric HCT-focused, and they do not address post-HCT challenges faced by children with complex nonmalignant disorders. In this article we discuss the strengths and weaknesses of current published recommendations and conclude that pediatric-specific guidelines for post-HCT screening and management would be beneficial to the long-term health of these patients and would promote late effects research in this field. Our panel of late effects experts also provides recommendations for follow-up and therapy of selected post-HCT organ and endocrine complications in pediatric patients.     

The relationship of asthma therapy and Churg-Strauss syndrome: NIH workshop summary report

The Churg-Strauss syndrome (CSS) is a distinct form of vasculitis that is notable for its eosinophilia and frequent associations with asthma and sinusitis. Because there has been an increasing recognition that CSS can develop in patients with asthma and that CSS might be associated with specific asthma treatments, the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Office of Rare Diseases, National Institutes of Health, and the US Food and Drug Administration jointly sponsored a workshop to consider interrelationships among CSS, asthma, and asthma therapeutics and to assess what is known about underlying mechanisms of CSS. Issues related to the criteria for defining and diagnosing CSS were reviewed, including the contemporary understanding that diagnostic biopsies need only reveal eosinophilic perivascular infiltrates and that asthma need not be present when CSS develops. From published reports and reports to the US Food and Drug Administration, treatment of patients with asthma with any of 3 cysteinyl leukotriene receptor antagonists, a 5-lipoxygenase inhibitor, and inhaled corticosteroids has been associated with CSS development. It is unknown whether these agents were eliciting CSS. A variety of physiologic and study design issues might lead to the reported associations of these drugs with CSS. Because many asthma patients receiving these therapies were able to diminish their systemic corticosteroid therapy, it is possible that incipient CSS was unmasked by lessened steroid use. The underlying pathophysiologic mechanisms of CSS, however, are unknown, and there is no means of identifying which patients with asthma might be at risk for CSS. Accordingly, investigations with the goals of defining the underlying pathophysiologic processes of CSS and establishing the relationships of asthma and its therapies to CSS are needed.