Data-driven questionnaire-based cluster analysis of asthma in Swedish adults.

The aim of this study was to identify asthma phenotypes through cluster analysis. Cluster analysis was performed using self-reported characteristics from a cohort of 1291 Swedish asthma patients. Disease burden was measured using the Asthma Control Test (ACT), the mini Asthma Quality of Life Questionnaire (mini-AQLQ), exacerbation frequency and asthma severity. Validation was performed in 748 individuals from the same geographical region. Three clusters; early onset predominantly female, adult onset predominantly female and adult onset predominantly male, were identified. Early onset predominantly female asthma had a higher burden of disease, the highest exacerbation frequency and use of inhaled corticosteroids. Adult onset predominantly male asthma had the highest mean score of ACT and mini-AQLQ, the lowest exacerbation frequency and higher proportion of subjects with mild asthma. These clusters, based on information from clinical questionnaire data, might be useful in primary care settings where the access to spirometry and biomarkers is limited.

Persistent asthma phenotype related with late-onset, high atopy, and low socioeconomic status in school-aged Korean children.

BACKGROUND: Treatment guidelines for asthma have been established based on asthma severity; there are limitations in the identification of underlying pathophysiology and prediction of prognosis in heterogeneous phenotypes of asthma. Although the complex interactions between environmental and genetic factors affect the development and progression of asthma, studies on asthma phenotypes considering environmental factors are limited. This study aimed to identify asthma phenotypes using latent class analysis including environmental factors in school-age children. METHODS: We included 235 children (6-8 years) with parent-reported, physician-diagnosed asthma from the Children's HEalth and Environmental Research (CHEER) study, which is a 4-year prospective follow-up study with 2-year intervals. At every survey, pulmonary function tests, methacholine challenge tests and blood tests with questionnaire were conducted. RESULTS: Four asthma phenotypes were identified. Cluster 1 (22% of children) was characterized by high prevalence of atopy and mild symptoms; subjects in cluster 2 (17%) consisted of less atopy and normal lung function, but intermittent troublesome; cluster 3 (29%) experienced late-onset atopic troublesome asthma with decreased lung function in combination with low socioeconomic status; and cluster 4 was associated with early-onset and less-atopic infrequent asthma. CONCLUSIONS: Late-onset, high atopy, and low socioeconomic status are associated with troublesome persistent asthma phenotype in school-age children. Environmental factors might be implicated in the clinical heterogeneity of asthma. Asthma phenotypes considering diverse factors might be more helpful in the identification of asthma pathogenesis and its prevention.

Burden of asthma with elevated blood eosinophil levels.

BACKGROUND: Asthma is a common chronic condition with an economic burden of almost $56 billion annually in the US. Biologic markers like blood eosinophils, that help predict the risk of exacerbation could help guide more optimal treatment plans and reduce cost. The purpose of this study was to determine whether healthcare resource use and expenditures vary by eosinophil level among patients with asthma. METHODS: Patients with a diagnosis of asthma defined by ICD-9-CM code 493.xx between January 2004 and July 2011 were extracted from EMRClaims + database (eMAX Health, White Plains NY). Patients were classified as mild, moderate, or severe by medication use following diagnosis, based on recommendations of National Institutes of Health Expert Panel Report 3. Patients were classified as those with elevated eosinophils (≥400 cells/µL) and normal eosinophil level (<400 cells/µL). Patients were followed for resource use, defined as hospitalizations, ER visits and outpatient visit and associated costs were calculated to assess whether an economic difference exists between eosinophil groups. Non-parametric tests were used to compare resource use and associated cost between elevated and normal eosinophil groups. Multivariate modeling was performed to assess the contribution of eosinophil level on the likelihood of study outcomes among patients with severe asthma. RESULTS: Among the 2,164 patients meeting eligibility criteria, 1,144 had severity designations. Of these, 179(16 %) of patients had severe asthma of which 20 % (n = 35) had elevated eosinophils. Seventeen percent of patients with elevated eosinophils were admitted to the hospital during the follow-up period, significantly greater than patients with normal eosinophil levels (12 %; p = 0.011). Overall, compared to patients with normal eosinophil levels (n = 1734), patients with elevated eosinophil levels (n = 430) had significantly greater mean annual hospital admissions (0.51 vs. 0.21/year, p = 0.006) and hospital costs (2,536 vs. $1,091, p = 0.011). Logistic regressions showed that elevated eosinophil level was associated with 5.14 times increased odds of all cause admissions (95 % CI:1.76-14.99, p = 0.003) and 4.07 times increased odds of asthma related admissions (95 % CI: 1.26-13.12, p = 0.019). CONCLUSION: Eosinophil elevation was associated with greater healthcare resource use in patients with asthma.

Heterogeneity in asthma care in a statewide collaborative: the Ohio Pediatric Asthma Repository.

BACKGROUND AND OBJECTIVE: Asthma heterogeneity causes difficulty in studying and treating the disease. We built a comprehensive statewide repository linking questionnaire and medical record data with health outcomes to characterize the variability of clinical practices at Ohio children's hospitals for the treatment of hospitalized asthma. METHODS: Children hospitalized at 6 participating Ohio children's hospitals for asthma exacerbation or reactive airway disease aged 2 to 17 were eligible. Medical, social, and environmental histories and past asthma admissions were collected from questionnaires and the medical record. RESULTS: From December 2012 to September 2013, 1012 children were enrolled. There were significant differences in the population served, emergency department and inpatient practices, intensive care unit usage, discharge criteria, and length of stay across the sites (all P < .0001, total n = 1012). Public insurance was highest in Cleveland and Cincinnati (72 and 65%). In the emergency department, Cincinnati and Akron had the highest intravenous magnesium sulfate use (37% and 33%); Columbus administered the most intramuscular epinephrine (15%). Cleveland and Columbus had the highest intensive care unit admittance (44% and 41%) and proportion of long-stay patients (95% and 85%). Moderate/severe asthma severity classification was associated with discharge prescription for inhaled corticosteroids (odds ratio = 2.7; 95% confidence interval: 1.6-4.5; P = .004) but not stay length. CONCLUSIONS: These data highlight the need for standardization of treatment practices for inpatient asthma care. There is considerable opportunity for personalized care plans that incorporate a patient's asthma impairment, risk, and treatment response history into hospital practices for asthma exacerbation treatment. The Ohio Pediatric Asthma Repository is a unique statewide resource in which to conduct observational, comparative effectiveness, and ultimately intervention studies for pediatric asthma.

The additional values of microarray allergen assay in the management of polysensitized patients with respiratory allergy.

BACKGROUND: The IgE response is directed against specific components from an allergenic source. The traditional diagnostic methods use whole extracts, containing allergenic, nonallergenic and cross-reactive molecules. This may pose diagnostic challenges in polysensitized patients. Microarray techniques detect specific IgE against multiple molecules, but their value in term of additional information and economic saving has not been yet defined. OBJECTIVE: We assessed the additional diagnostic information provided by an allergen microarray in a large population of polysensitized subjects. METHODS: In this multicentre study, allergists were required to carefully record diagnosis and treatment of consecutive patients referred for asthma/rhinitis, using the standard methodology (history, skin prick test, IgE assay). Then, a microarray allergen assay was carried out. Clinicians were required to review their diagnosis/treatment according to microarray results. RESULTS: 318 allergic patients (30% reporting also nonrespiratory symptoms) and 91 controls were enrolled. The clinicians reported at least one additional information from the microarray in about 60% of patients, this resulting in therapeutic adjustments. In 66% of patients IgE to pan-allergens were detectable, being this clinically relevant in 38% of patients with polysensitization to pollens. CONCLUSION: Microarray IgE assay represents an advancement in allergy diagnosis, as a third-level approach in polysensitized subjects, when the traditional diagnosis may be problematic.

[ARIA (Allergic Rhinitis and its Impact on Asthma). Achievements in 10 years and future needs in Latin America]. / ARIA (Rinitis Alérgica y su Impacto en Asma). Logros en 10 años y necesidades futuras en América Latina.

Allergic rhinitis and asthma represent global problems of public health affecting all age groups; asthma and allergic rhinitis frequently coexist in the same patients. In Latin American prevalence of allergic rhinitis, although variable, is very high. Allergic rhinitis and its Impact on Asthma (ARIA) started during a workshop of the World Health Organization performed in 1999 and was published in 2001. ARIA proposed a new classification of allergic rhinitis in intermittent or persistent and mild or moderate-severe. This approach of classification reflects more nearly the impact of allergic rhinitis in patients. In its review of 2010 ARIA developed guidelines for diagnosis and treatment of allergic rhinitis and of clinical practices for management of comorbidities of allergic rhinitis and asthma based on GRADE (Grading of Recommendations, Development and Evaluation). ARIA has been spread and implemented in more than 50 countries. In Latin American an intense activity has been developed to spread these recommendations in almost all the countries of the region and it is important to record the obtained goals in the diffusion and implementation of ARIA, as well as to identify the unsatisfied needs from the clinical, research and implementation points of view. Final objective is to reinforce the priority that allergy and asthma should have, especially in children, in the programs of public health, as they have been prioritized in European Union in 2011.

La rinitis alérgica y el asma representan problemas globales de salud pública que afectan a todos los grupos etarios; el asma y la rinitis alérgica frecuentemente coexisten en los mismos pacientes. En América Latina la prevalencia de rinitis alérgica, aunque variable, es muy elevada. La iniciativa Rinitis Alérgica y su Impacto en Asma (globalmente conocida como ARIA, de su nombre en inglés Allergic Rhinitis and its Impact on Asthma) comenzó durante un taller de la Organización Mundial de la Salud (OMS) realizado en 1999 que se publicó en el año 2001. ARIA propuso una nueva clasificación de rinitis alérgica en intermitente o persistente y leve o moderada-severa. Este esquema de clasificación refleja más estrechamente el impacto de la rinitis alérgica en los pacientes. En su revisión de 2010, la guía ARIA desarrolló pautas para el diagnóstico y tratamiento de la rinitis alérgica y de prácticas clínicas para el manejo de las comorbilidades de la rinitis alérgica y el asma basadas en GRADE (Gradación de Recomendaciones, Desarrollo y Evaluación). ARIA se ha diseminado e implantado en más de 50 países. En América Latina se ha desarrollado una intensa actividad para diseminar estas recomendaciones en casi todos los países de la región y es importante llevar un registro de los logros obtenidos en la difusión e implantación de ARIA, además de identificar las necesidades insatisfechas desde el punto de vista clínico, de la investigación y de la implantación. El objetivo final es reforzar la prioridad que deben tener la alergia y el asma ­especialmente en niños­ en los programas de Salud Pública, tal como los priorizó la Unión Europea en 2011.

Current topics in occupational asthma.

The study of occupational asthma (OA) provides insights into asthma in general, as the cause is known. The relationships between the cause and response can be measured and modifying factors can be identified and their influence quantified. Developing OA has much more serious consequences for the patient than new onset asthma unrelated to work exposures, as the patient's livelihood is nearly always affected. Many healthcare professionals are more ready to accept and act on asthmatic symptoms when they are unrelated to work than when work may be the cause; antagonism can also occur in the workplace. This article reviews some of the areas where development and controversy enrich the study of OA. It makes no attempt to be comprehensive.

Fuzzy rule-based expert system for assessment severity of asthma.

Prescription medicine for asthma at primary stages is based on asthma severity level. Despite major progress in discovering various variables affecting asthma severity levels, disregarding some of these variables by physicians, variables' inherent uncertainty, and assigning patients to limited categories of decision making are the major causes of underestimating asthma severity, and as a result low quality of life in asthmatic patients. In this paper, we provide a solution of intelligence fuzzy system for this problem. Inputs of this system are organized in five modules of respiratory symptoms, bronchial obstruction, asthma instability, quality of life, and asthma severity. Output of this system is degree of asthma severity in score (0-10). Evaluating performance of this system by 28 asthmatic patients reinforces that the system's results not only correspond with evaluations of physicians, but represent the slight differences of asthmatic patients placed in specific category introduced by guidelines.

Checking coding completeness by mining discharge summaries.

Incomplete coding is a known problem in hospital information systems. In order to detect non-coded secondary diseases we developed a text classification system which scans discharge summaries for drug names. Using a drug knowledge base in which drug names are linked to sets of ICD-10 codes, the system selects those documents in which a drug name occurs that is not justified by any ICD-10 code within the corresponding record in the patient database. Treatment episodes with missing codes for diabetes mellitus, Parkinson's disease, and asthma/COPD were subject to investigation in a large German university hospital. The precision of the method was 79%, 14%, and 45% respectively, roughly estimated recall values amounted to 43%, 70%, and 36%. Based on these data we predict roughly 716 non-coded diabetes cases, 13 non-coded Parkinson cases, and 420 non-coded asthma/COPD cases among 34,865 treatment episodes.

The investigation of asthma phenotypes.

PURPOSE OF REVIEW: Asthma is a heterogeneous disease constituted by overlapping separate syndromes. This review discusses recent published data relevant to asthma and severe asthma classification, resting either on the 'candidate' approach based on criteria chosen by experts or on the 'exploratory' approach based on unsupervised statistical methods. RECENT FINDINGS: Following the 'candidate' approach, groups of experts recently reviewed the classification of severe asthma to be applicable in low-income, milddle-income, and high-income countries and provided a systematic algorithm to diagnose severe refractory asthma. The concept of asthma endotypes involving different biological mechanisms has recently being proposed. Results from the 'exploratory' approach support the clinical heterogeneity in severe asthma and the need for new approaches for the classification of asthma severity. The novel childhood and adult asthma phenotypes recently identified using the exploratory approach were supported by first evidence of validity (replication in independent studies, assessment of their discriminative properties, and effect on clinical prognosis). SUMMARY: Research on asthma phenotypes has increased exponentially in the last year. The main focus has been on severe asthma, likely due to its clinical and socioeconomic burden. Interestingly, many of the phenotypes identified are stable across populations and methodological approaches. Further analyses on the asthma phenotypes are needed to address their stability over time and their relevance from clinical and etiological perspectives.

Development and evaluation of a tool for retrospective exposure assessment of selected endocrine disrupting chemicals and EMF in the car manufacturing industry.

OBJECTIVES: A system for retrospective occupational exposure assessment combining the efficiency of a job exposure matrix (JEM) and the precision of a subsequent individual expert exposure assessment (IEEA) was developed. All steps of the exposure assessment were performed by an interdisciplinary expert panel in the context of a case-control study on male germ cell cancer nested in the car manufacturing industries. METHODS: An industry-specific JEM was developed and automatic exposure estimation was performed based on this JEM. A subsample of exposure ratings was done by IEEA to identify determinants of disagreement between the JEM and the individual review. Possible determinants were analyzed by calculating odds ratios (ORs) of disagreement between ratings with regard to different dimensions (e.g. high versus low intensity of exposure). Disagreement in ≥20% of the sampled exposure ratings with a statistically significant OR was chosen as a threshold for inclusion of the exposure ratings into a final IEEA. RESULTS: The most important determinants of disagreement between JEM and individual review were working outside of the production line (disagreement 80%), low probability of exposure (disagreement 25%), and exposure depending on specific activities like usage of specific lacquers (disagreement 32%) for jobs within the production line. These determinants were the selection criteria of exposure ratings for the subsequent final IEEA. CONCLUSIONS: Combining a JEM and a subsequent final IEEA for a selected subset of exposure ratings is a feasible and labor-saving approach for exposure assessment in large occupational epidemiological studies.

Vital signs: asthma prevalence, disease characteristics, and self-management education: United States, 2001--2009.

BACKGROUND: Most persons with asthma can be symptom-free if they receive appropriate medical care, use inhaled corticosteroids when prescribed, and modify their environment to reduce or eliminate exposure to allergens and irritants. This report reviews recent progress in managing asthma and reducing its prevalence in the United States. METHODS: CDC analyzed asthma data from the 2001--2009 National Health Interview Survey concerning children and adults, and from the 2001, 2005, and 2009 state-based Behavioral Risk Factor Surveillance System concerning adults. RESULTS: Among persons of all ages, the prevalence of asthma increased from 7.3% (20.3 million persons) in 2001 to 8.2% (24.6 million persons) in 2009, a 12.3% increase. Prevalence among children (persons aged <18 years) was 9.6%, and was highest among poor children (13.5%) and among non-Hispanic black children (17.0%). Prevalence among adults was 7.7%, and was greatest in women (9.7%) and in adults who were poor (10.6%). More uninsured persons with asthma than insured could not afford to buy prescription medications (40.3% versus 11.5%), and fewer uninsured persons reported seeing or talking with a primary-care physician (58.8% versus 85.6%) or specialist (19.5% versus 36.9%). Among persons with asthma, 34.2% reported being given a written asthma action plan, and 68.1% had been taught the appropriate response to symptoms of an asthma attack. Only about one third of children or adults were using long-term control medicine such as inhaled corticosteroids at the time of the survey. CONCLUSIONS AND COMMENT: Persons with asthma need to have access to health care and appropriate medications and use them. They also need to learn self-management skills and practice evidence-based interventions that reduce environmental risk factors.

Oxygen-enhanced MRI vs. quantitatively assessed thin-section CT: pulmonary functional loss assessment and clinical stage classification of asthmatics.

PURPOSE: The purpose of this study was to prospectively compare the efficacy of oxygen-enhanced MR imaging (O(2)-enhanced MRI) and CT for pulmonary functional loss assessment and clinical stage classification of asthmatics. MATERIALS AND METHODS: O(2)-enhanced MRI, CT and %FEV(1) measurement were used 34 consecutive asthmatics classified into four stages ('Mild Intermittent [n=7]', 'Mild Persistent [n=8], 'Moderate Persistent [n=14]' and 'Severe Persistent [n=5]'). Relative enhancement ratio maps for every subject were generated, and determine mean relative enhancement ratios (MRERs). Mean lung density (MLD) and the airway wall area (WA) corrected by body surface area (WA/BSA) were also measured on CT. To compare the efficacy of the two methods for pulmonary functional loss assessment, all indexes were correlated with %FEV(1). To determine the efficacy of the two methods for clinical stage classification, all parameters for the four clinical stages were statistically compared. RESULTS: %FEV(1) showed fair or moderate correlation with all parameters (0.15≤r(2)≤0.30, p<0.05). WA, WA/BSA and MRER of the 'Severe Persistent' group were significantly larger than those of 'Mild Intermittent' and 'Mild Persistent' groups (p<0.05), and MRER of the 'Moderate Persistent' group significantly lower than that of the 'Mild Intermittent' group (p<0.05). CONCLUSION: O(2)-enhanced MRI is as effective as CT for pulmonary functional loss assessment and clinical stage classification of asthmatics.

Asthma severity in primary care asthma patients: a comparative study of four different approaches to severity classification.

AIMS: To explore the factor structure of asthma severity and asthma control and to compare the results of different approaches to asthma severity classification on the distribution of costs of asthma medication. METHODS: Comparison of four different approaches to asthma severity classification and factor analysis of asthma control descriptors. A correlation analysis between costs and the different approaches to severity classification was performed. RESULTS: The factor analysis suggests that asthma control consists of at least two factors. Four approaches to severity classification were explored and all except the 'GINA EXPANDED' classification tended to place patients in the most severe category. The pharmaceutical costs varied between 0 and 75 SEK per day (0 and 5.31 GBP; 0 and 7.68 EURO). CONCLUSIONS: There is a considerable overlap between asthma control and asthma severity. None of the approaches used in this study present a superior satisfactory solution to the classification problem.

Distinct clinical phenotypes of airways disease defined by cluster analysis.

Airways disease is currently classified using diagnostic labels such as asthma, chronic bronchitis and emphysema. The current definitions of these classifications may not reflect the phenotypes of airways disease in the community, which may have differing disease processes, clinical features or responses to treatment. The aim of the present study was to use cluster analysis to explore clinical phenotypes in a community population with airways disease. A random population sample of 25-75-yr-old adults underwent detailed investigation, including a clinical questionnaire, pulmonary function tests, nitric oxide measurements, blood tests and chest computed tomography. Cluster analysis was performed on the subgroup with current respiratory symptoms or obstructive spirometric results. Subjects with a complete dataset (n = 175) were included in the cluster analysis. Five clusters were identified with the following characteristics: cluster 1: severe and markedly variable airflow obstruction with features of atopic asthma, chronic bronchitis and emphysema; cluster 2: features of emphysema alone; cluster 3: atopic asthma with eosinophilic airways inflammation; cluster 4: mild airflow obstruction without other dominant phenotypic features; and cluster 5: chronic bronchitis in nonsmokers. Five distinct clinical phenotypes of airflow obstruction were identified. If confirmed in other populations, these findings may form the basis of a modified taxonomy for the disorders of airways obstruction.

Complexity of chronic asthma and chronic obstructive pulmonary disease: implications for risk assessment, and disease progression and control.

Although assessment of asthma control is important to guide treatment, it is difficult since the temporal pattern and risk of exacerbations are often unpredictable. In this Review, we summarise the classic methods to assess control with unidimensional and multidimensional approaches. Next, we show how ideas from the science of complexity can explain the seemingly unpredictable nature of bronchial asthma and emphysema, with implications for chronic obstructive pulmonary disease. We show that fluctuation analysis, a method used in statistical physics, can be used to gain insight into asthma as a dynamic disease of the respiratory system, viewed as a set of interacting subsystems (eg, inflammatory, immunological, and mechanical). The basis of the fluctuation analysis methods is the quantification of the long-term temporal history of lung function parameters. We summarise how this analysis can be used to assess the risk of future asthma episodes, with implications for asthma severity and control both in children and adults.

Identifying high-risk asthma with utilization data: a revised HEDIS definition.

OBJECTIVE: To develop a definition of high-risk asthma that more precisely identifies patients needing case management than the 2006 Healthcare Effectiveness Data and Information Set (HEDIS) definition. STUDY DESIGN: Two-year claims-based study, with cross-sectional phone survey data, for a sample of 769 youths (age 11-17 years) with asthma. METHODS: The 2006 HEDIS measure defines high-risk asthma as meeting any of the following criteria: >1 emergency department (ED) visits, > or =1 hospitalizations for asthma, > or =4 asthma medication prescriptions, or > or =4 ambulatory visits for asthma with > or =2 prescriptions for asthma medication in 1 year. We created a revised definition (> or =1 ED visits or > or =1 hospitalizations for asthma or > or =1 oral steroid prescriptions for asthma) and identified patients with high-risk asthma in year 1 according to each definition. We compared the 2 groups on demographic and clinical characteristics, and healthcare utilization and costs in years 1 and 2. RESULTS: The revised definition identified 29% of the sample as having high-risk asthma, whereas the 2006 definition identified 67%. Compared with the 2006 definition, the revised definition identified patients with significantly greater asthma-related physical health problems and higher medical costs in year 1. In year 2, youths classified as high risk by the revised definition made more ED visits and were more likely to use oral steroids than those classified as high risk by the 2006 definition. CONCLUSION: The revised high-risk asthma definition identifies half as many individuals and is better able to identify patients with poorly controlled asthma in the subsequent year.

Emergency department utilization by patients not meeting Health Plan and Employer Data and Information Set (HEDIS) criteria for persistent asthma.

Emergency hospital utilization rates for asthma remain high despite advances in asthma controller medications and the presence of widely accepted asthma treatment guidelines. To explore this phenomenon, we analyzed administrative data to determine characteristics of patients seen in the emergency department (ED) for asthma. Complete pharmacy and diagnostic coding records were obtained from consecutive adults (aged 19-56 years) treated for asthma in the ED of a closed-network health maintenance organization between April and July of 2002. Subjects were stratified into asthma severity categories (persistent or non-persistent) based on the National Committee for Quality Assurance 2006 Health Plan and Employer Data and Information Set (HEDIS) criteria for persistent asthma. Eighty-one unique patients made a total of 89 ED visits for asthma during the study period. Of the 89 total ED visits for asthma, 44 (49%) occurred in patients that did not meet HEDIS criteria for persistent asthma. Of the 81 unique patients making asthma-related ED visits, 41 (51%) did not meet HEDIS criteria for persistent asthma. Over one-half (51%) of this nonpersistent population were not given either asthma reliever or asthma controller medications during the 12-month period before their index ED visit. Over the 24-month period before their index ED visit, 37% of nonpersistent patients were dispensed neither asthma reliever nor controller medications. Patients that do not meet HEDIS criteria for persistent asthma account for a substantial percentage of asthma-related ED visits. These patients have a history of low use of asthma medications before their ED visit.

The Pediatric Respiratory Assessment Measure: a valid clinical score for assessing acute asthma severity from toddlers to teenagers.

OBJECTIVE: To determine the performance characteristics of the Preschool Respiratory Assessment Measure (PRAM) in preschool and school-aged children with acute asthma. STUDY DESIGN: In a prospective cohort study, we examined the validity, responsiveness, and reliability of the PRAM in children aged 2 to 17 years with acute asthma. The study involved more than 100 nurses and physicians who recorded the PRAM on triage, after initial bronchodilation, and at disposition. Predictive validity and responsiveness were examined using disposition as outcome. RESULTS: The PRAM was recorded in 81% (n = 782) of patients at triage. The PRAM at triage and after initial bronchodilation showed a strong association with admission (r = 0.4 and 0.5, respectively; P < .0001), thus supporting its ability to distinguish across severity levels. The responsiveness coefficient of 0.7 indicated good ability to identify change after bronchodilation. The PRAM showed good internal consistency (Cronbach alpha = 0.71) and inter-rater reliability (r = 0.78) for all patients and across all age groups. CONCLUSIONS: Good performance characteristics were observed in all age groups, making the PRAM an attractive score for assessing asthma severity and response to treatment.

Canadian economic evaluation of budesonide-formoterol as maintenance and reliever treatment in patients with moderate to severe asthma.

OBJECTIVES: To compare the cost-effectiveness of budesonide-formoterol in a single inhaler used as both maintenance and reliever medication versus clinician-directed titration of salmeterol-fluticasone as maintenance medication, plus salbutamol taken as needed, in controlling asthma in adults and adolescents. METHODS: A Canadian economic evaluation was conducted based on the results of a large (n=2143), open-label, randomized, controlled effectiveness trial in which health resource use was prospectively collected. The primary outcome measurement was the time to the first severe exacerbation. Costs included direct medical costs (physician and emergency room visits, hospitalizations, asthma drug costs, etc) and productivity (absenteeism). The time horizon was one year, which corresponded to the duration of the clinical trial. Prices were obtained from 2005 Canadian sources. Both health care and societal perspectives were considered, and deterministic univariate sensitivity analyses were conducted. RESULTS: In the clinical trial, budesonide-formoterol as maintenance and reliever treatment was superior to salmeterol-fluticasone with respect to the time to the first severe exacerbation, overall rate of exacerbations and use of as-needed reliever medication. The annualized rate of severe exacerbations was 0.24 events/patient in the budesonide-formoterol arm and 0.31 events/patient in the salmeterol-fluticasone arm (P=0.0025). From a health care perspective, the mean cost per patient-year was $1,315 in the budesonide-formoterol arm versus $1,541 in the salmeterol-fluticasone arm. From a societal perspective, the mean cost per patient-year was $1,538 in the budesonide-formoterol arm and $1,854 in the salmeterol-fluticasone arm. Budesonide-formoterol was dominant (more effective and less expensive) in the base case analysis from both perspectives. The results were robust under sensitivity testing. CONCLUSIONS: The strategy that allows budesonide-formoterol to be used in a single inhaler as both maintenance and reliever medication proved to be more effective and less expensive than a strategy of clinician-directed titration of salmeterol-fluticasone with salbutamol as reliever therapy.