Racial Disparities in Asthma-Related Health Outcomes in Children with Severe/Difficult-to-Treat Asthma.

BACKGROUND: There are limited data that examine differences in asthma etiology between black and white children with severe or difficult-to-treat asthma. OBJECTIVE: To describe demographic, clinical, and asthma-related outcomes in black and white children and examine whether differences in outcomes are explained by confounding factors in sequential multivariable models. METHODS: Black (n = 86) and white (n = 262) children aged 6-11 years from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens 3-year observational study were analyzed. Baseline demographics and clinical characteristics were described for both cohorts, and outcomes at month 12 were analyzed using statistical models, sequentially adjusting for potential confounders. RESULTS: Black children were more likely to be male (79.1% vs 66.4%; P < .05), obese (12.8% vs 1.5%; P < .001), and from a lower income stratum (USD43,400 vs 55,770; P < .001) than white children. Black children had higher geometric mean IgE levels (434.8 vs 136.8 IU/mL; P < .001), were more likely to have very poorly controlled asthma (72.1% vs 53.4%), use long-term systemic corticosteroids (30.2% vs 9.2%; P < .001), have poorer quality of life (5.5 vs 6.1; P < .001), and have an emergency department visit (27.4% vs 7.7%, P < .001) in the 3 months before month 12. Differences in asthma control and the severity of exacerbations persisted even after accounting for all confounding factors. CONCLUSIONS: Among children with severe or difficult-to-treat asthma, asthma burden is greater in black than white children particularly related to several clinical and patient-reported outcome measures that are not explained by differences in background or clinical characteristics.

Baseline and Serial Brain Natriuretic Peptide Level Predicts 5-Year Overall Survival in Patients With Pulmonary Arterial Hypertension: Data From the REVEAL Registry.

BACKGROUND: Plasma brain natriuretic peptide (BNP) level is a prognostic biomarker in pulmonary arterial hypertension (PAH). Its impact on long-term overall survival (OS) was investigated in the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL), a 5-year observational, multicenter, US registry of patients with PAH. METHODS: Patients were ≥ 18 years of age, met right heart catheterization criteria at rest, had World Health Organization group I PAH, and had BNP measurement at enrollment. Optimal BNP threshold was obtained via receiver operating characteristic curve analysis. OS was compared in patients with low (≤ 340 pg/mL) vs high (> 340 pg/mL) BNP at baseline; changes between baseline and last assessment were also examined. Patients were categorized based on baseline (low or high) and follow-up (low or high) BNP values; hazard ratios (HRs) for OS were estimated and compared using Cox regression. RESULTS: Overall, 1,426 patients were analyzed. Mortality risk was significantly higher in patients with baseline high vs low BNP (HR, 3.6; 95% CI, 3.0-4.2). BNP change analysis at ≤ 1 year postenrollment demonstrated that the low-low group had the lowest and the high-high group had the highest 5-year mortality risk (HR, 0.23; 95% CI, 0.19-0.27). Changes in BNP score also correlated with change of risk of death. CONCLUSIONS: Baseline BNP threshold of 340 pg/mL strongly predicted survival up to 5 years in patients with PAH. A BNP reduction at 1 year since enrollment was associated with decreased mortality risk, whereas an increase in BNP at 1 year was associated with an increased mortality risk, supporting BNP as a surrogate marker of PAH survival.

Asthma Exacerbations and Triggers in Children in TENOR: Impact on Quality of Life.

BACKGROUND: Data examining associations between asthma exacerbations, triggers, and asthma-related quality of life (QOL) in children with severe/difficult-to-treat asthma are unavailable. OBJECTIVE: To evaluate real-world data on relationships between asthma exacerbations, triggers, and QOL in children using data from TENOR (The Epidemiology and Natural History of Asthma Outcomes and Treatment Regimens), a 3-year observational study of patients with severe/difficult-to-treat asthma, including those aged 6 to 12 years. METHODS: QOL was examined using the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and defined exacerbations hierarchically (descending order of severity): hospitalization, emergency department visit, steroid burst, no exacerbation, using the highest value from months 6 and 12. One-way ANOVA was used to test for differences in PAQLQ domain scores at month 12 across exacerbation severity, total number of asthma exacerbations, and number of baseline asthma triggers. Mantel-Haenszel chi-square test was used to test the association between the number of triggers and exacerbation hierarchy. RESULTS: Greater severity of asthma exacerbations was associated with significantly (P < .001) lower mean PAQLQ domain scores, indicating poorer QOL. A higher number of asthma exacerbations was associated with significantly (P < .001) lower mean PAQLQ domain scores. PAQLQ scores were significantly lower with higher numbers of baseline triggers. Higher baseline number of asthma triggers was associated with greater severity (P = .05) and number of asthma exacerbations (P < .001). CONCLUSIONS: A higher number of asthma triggers at baseline was associated with greater asthma severity and number of asthma exacerbations and lower QOL in children with severe/difficult-to-treat asthma.

Impact of declining renal function on outcomes in pulmonary arterial hypertension: A REVEAL registry analysis.

BACKGROUND: Renal dysfunction is associated with abnormal cardiopulmonary hemodynamics, in-hospital death and poor survival in patients with pulmonary arterial hypertension (PAH), and thus it may be a prognostic biomarker. In our analysis we assess the relationship between change in estimated glomerular filtration rate (eGFR) and outcomes in PAH patients in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL). METHODS: Overall 2,368 patients were classified into chronic kidney disease (CKD) stages based on baseline eGFR: normal or Stages 1 or 2 (n = 1,699); Stage 3a (n = 399); Stage 3b (n = 196); and Stages 4 or 5 (n = 74). We evaluated the relationship between baseline CKD stage and survival, as well as the composite end-point of survival and freedom from all-cause hospitalization. The relationships between change in eGFR at ≥1 year and these clinical end-points were also evaluated. RESULTS: Patients with a ≥10% decline in eGFR from baseline over ≥1 year had a significantly increased risk of death (hazard ratio 1.66; p < 0.0001) and the composite of all-cause hospitalization and death (hazard ratio 1.33; p = 0.002). This decline predicted survival independently of changes in 6-minute walk distance and functional class. However, a ≥10% increase in eGFR was not significantly associated with either end-point. CONCLUSION: In REVEAL, a ≥10% decline in eGFR over ≥1 year independently predicted poorer survival. Thus, eGFR may be a simple and economical biomarker in PAH.

Clinical burden and predictors of asthma exacerbations in patients on guideline-based steps 4-6 asthma therapy in the TENOR cohort.

BACKGROUND: Patients with severe or difficult-to-treat asthma on guideline-recommended Steps 4/5/6 therapy have not previously been described. OBJECTIVE: To characterize patients with severe or difficult-to-treat asthma on Steps 4/5/6 therapy and assess predictors of future asthma exacerbations. METHODS: Patients ages ≥12 years with baseline and month 12 medication data were assigned to Steps 4/5/6 care levels from the 2007 National Heart, Lung, and Blood Institute guidelines. Demographic, atopic, and clinical characteristics at baseline and month 12 were assessed by using descriptive statistics. Asthma-related quality of life was assessed by using the Mini Asthma Quality of Life Questionnaire, and work and activity impairment was assessed by the Work Productivity and Activity Impairment Questionnaire-Asthma. Odds ratios (OR) and 95% CI for asthma exacerbation risk at month 12 were generated by using multivariable logistic regression. RESULTS: A total of 1186 patients were included. More than two-thirds of the patients (67.4%) were on ≥3 long-term controllers, and 55.1% were considered difficult to treat due to frequent exacerbations. Patients reported low asthma-related quality of life scores and considerable impairment in overall work and daily activity (21.4% and 32.1%, respectively). After adjustment for covariates, exacerbation history (hospitalization, OR 6.27 [95% CI, 3.61-10.88]; emergency department visit, OR 3.84 [95% CI, 2.50-5.91]; corticosteroid burst, OR 2.89 [95% CI, 2.18-3.82]) and very poorly controlled asthma (OR 1.95 [95% CI, 1.41-2.71] vs not well controlled) were independently associated with risk of a future exacerbation (all P < .001). CONCLUSION: Despite multiple long-term controller medications, patients with severe or difficult-to-treat asthma on Steps 4/5/6 therapy present with significant clinical burden and risk of future asthma exacerbations.

Economic burden of impairment in children with severe or difficult-to-treat asthma.

BACKGROUND: The cost associated with asthma impairment in children with severe asthma has not been determined. OBJECTIVE: To assess the asthma cost burden in children with severe or difficult-to-treat asthma based on asthma impairment. METHODS: Children aged 6 to 12 years in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study with available data at baseline (n = 628), month 12 (n = 385), and month 24 (n = 280) corresponding to the National Heart, Lung, and Blood Institute asthma guidelines' impairment domain were included. Children were categorized as either very poorly controlled (VPC), not well controlled (NWC), or well controlled (WC) and assessed cross-sectionally and longitudinally. Mean total asthma costs based on direct (medication usage, unscheduled office visits, emergency department visits, hospitalizations) and indirect (school/work days lost) asthma costs were assessed. RESULTS: Mean annual total asthma costs were more than twice as high in the VPC group compared with NWC and WC groups (baseline: $7,846, $3,526, $3,766.44, respectively; month 12: $7,326, $2,959, $2,043, respectively; month 24: $8,879, $3,308, $1,861, respectively (all P < .001). Indirect costs accounted for approximately half the total asthma costs for VPC asthma patients at each time point. Significantly lower costs were observed for patients whose impairment status improved or temporarily improved from VPC after baseline. CONCLUSION: The economic burden of severe or difficult-to-treat asthma in children is associated with VPC asthma and improvement in asthma control and is associated with reducing cost. Further attention to patients with poorly controlled asthma, through better management strategies or more effective medications, may significantly reduce this burden of illness.

Allergy, total serum immunoglobulin E, and airflow in children and adolescents in TENOR.

In children and adolescents with difficult-to-treat asthma, few data exist characterizing the relationships between basic patient characteristics (e.g., age, sex) and atopic indicators in asthma. These associations were examined in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR), an observational study of a large cohort of patients with severe or difficult-to-treat asthma. To characterize allergy patterns and the relationship between total serum immunoglobulin E (IgE) and airflow in young patients with severe or difficult-to-treat asthma. A total of 1261 patients from the TENOR study were stratified into four age groups at baseline (6-8, 9-11, 12-14, and 15-17 yr). The objective was to characterize allergy patterns and the relationship between total serum immunoglobulin E (IgE) and ratio of pre-bronchodilator forced expiratory volume in 1 second to forced vital capacity (FEV(1) /FVC) in young patients with severe or difficult-to-treat asthma. The chi-square test for categorical variables and analysis of variance for continuous variables were used to identify significant differences among age groups. Multivariable linear regression was used to evaluate the association between IgE and FEV(1) /FVC. Allergic rhinitis was reported in approximately two-thirds of patients. Up to 25% of patients had atopic dermatitis, which differed across age groups in boys (p < 0.05). Positive allergen skin test rate differed across age groups in boys (p < 0.05). Rates of asthma triggers were higher and differed across age groups in girls (p < 0.05), particularly around menarche (12-14 yr). IgE levels were higher in boys and differed across age groups in boys (p < 0.01) and girls (p < 0.05). IgE was associated with a lower FEV(1) /FVC after adjusting for age and sex (p < 0.01). Severe or difficult-to-treat asthma in children and adolescents is characterized by high frequencies of comorbid allergic diseases, allergen sensitization, and high IgE levels. This burden is amplified by the association of more airflow limitation with higher IgE levels, suggesting the need for allergy evaluations.

Minimal clinically important difference for the ocular surface disease index.

OBJECTIVE: To assess the minimal clinically important difference (MCID) for the Ocular Surface Disease Index (OSDI; Allergan Inc, Irvine, California, holds the copyright), a 12-item patient-reported outcome questionnaire designed to quantify ocular disability due to dry eye disease. METHODS: Study data were collected within the Restasis Review of Efficacy and Safety vs Tears in the Relief of Dry Eye (RESTORE), an observational registry. A clinician global impression (CGI) and a subject global assessment (SGA) served as anchors to estimate the MCID for the overall OSDI score (range, 0-100). The overall OSDI score defined the ocular surface as normal (0-12 points) or as having mild (13-22 points), moderate (23-32 points), or severe (33-100 points) disease. RESTORE patients were included if they completed the OSDI at the baseline visit and at a follow-up visit and had a global change rating (SGA or CGI). RESULTS: Three hundred ten patients were included (82.3% white and 81.6% female [mean age, 57.8 years]). The CGI and SGA correlated with the OSDI score change for all OSDI categories except the normal category. The MCID ranged from 7.0 to 9.9 for all OSDI categories. The MCID ranged from 4.5 to 7.3 for mild or moderate disease and from 7.3 to 13.4 for severe disease. CONCLUSIONS: Using observational data, we estimated the MCIDs for different baseline OSDI categories of dry eye disease. These results will assist clinicians and researchers when interpreting OSDI score changes.

Recent asthma exacerbations predict future exacerbations in children with severe or difficult-to-treat asthma.

BACKGROUND: Children with severe/difficult-to-treat asthma experience high morbidity including frequent severe exacerbations. More knowledge is required to identify predictors of these exacerbations to reduce their occurrence. OBJECTIVE: To investigate the risk of future severe exacerbations (FSEs) in children with severe/difficult-to-treat asthma and recent severe exacerbations (RSEs). METHODS: We analyzed the occurrence and association of RSE (defined as 1 or more corticosteroid bursts during the 3 months before each of 3 annual visits) and FSE (defined as 1 or more corticosteroid bursts 6 or 12 months later) in children age 6 to 11 years in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens 3-year observational study. Repeated measures logistic regression analysis assessed the risk of FSE adjusted for demographics and clinical variables. RESULTS: In a multivariable model, FSE at 6 months was most strongly predicted by RSE (odds ratio [OR], 3.08; 95% CI, 2.21-4.28) and having 3 to 4 allergic triggers (OR, 2.05; 95% CI, 1.31-3.20). Race (OR, 1.77; 95% CI, 1.25-2.51) and being very poorly controlled according to the impairment component of the National Heart, Lung, and Blood Institute guidelines (OR, 1.59; 95% CI, 1.14-2.23) also significantly predicted FSE. CONCLUSION: Recent severe asthma exacerbations are an important independent predictor of FSE in children with severe/difficult-to-treat asthma and should be considered when establishing asthma management plans.

Predicting asthma control using patient attitudes toward medical care: the REACT score.

BACKGROUND: The association between patients' degree of asthma control and their attitudes toward medical professionals and asthma therapy is unknown. OBJECTIVE: To develop a tool, the REACT Score, that can be used by physicians to compute the risk of having uncontrolled asthma based on patient attitudes toward medical professionals and asthma treatment. METHODS: A nationally representative sample of adult patients (> or = 18 years old) with moderate to severe asthma completed the Asthma Control Test and were surveyed regarding their attitudes about relationships with medical professionals and asthma treatments. Competing predictive models were developed to determine the association between attitude questions and asthma control. Using the model with the highest c-index, a REACT Score was computed. RESULTS: The proportion of uncontrolled patients (Asthma Control Test score < 20) in the high-, medium-, and low-risk REACT Score categories was 75%, 50%, and 24%, respectively. Patients who believed that their physician recognized lifestyle compromises due to asthma, who were not satisfied with their treatment regimen, and who took asthma medication more frequently than prescribed had a higher risk of poor asthma control. CONCLUSION: The REACT Score is a novel way to predict asthma control and to identify key attitudes and behaviors that need to be addressed to engage a patient in ongoing, effective care. This tool may also improve communication between asthmatic patients and their physicians by identifying patient concerns regarding their treatment and quality of life.

Racial disparities in asthma-related health outcomes in severe or difficult-to-treat asthma.

BACKGROUND: The underlying reasons for racial disparities in asthma morbidity are not well understood. Multivariate epidemiologic studies evaluating the presence and extent of racial differences in a large cohort of adults with severe or difficult-to-treat asthma are lacking. OBJECTIVE: To analyze an extensive array of clinical and patient-reported outcomes, using multivariate analysis with a sequential approach, to explain racial differences in asthma-related outcomes in one of the largest cohorts of difficult-to-treat asthmatic patients. METHODS: Black and white patients (> or = 18-years-old at baseline) were included (n = 2,128). Differences between the 2 racial groups were assessed using several outcome measures at month 12. Assessments were adjusted for confounding variables using a sequence of statistical models. RESULTS: Most patients were white (88.6%). Blacks were slightly younger, less educated, and more likely to live in urban areas than whites. Blacks were more likely to have severe asthma and to be treated with 3 or more long-term controllers. Poorer quality of life, more asthma control problems, and higher risk of emergency department visits were observed in blacks compared with whites; differences were not explained by adjustment for broad sets of confounding variables. Differences in asthma-related health outcomes remained statistically significant after adjusting for asthma severity. CONCLUSIONS: Asthma is a serious health problem in blacks and is not explained by differences in demographics, severity, or other health conditions.

Shifting patterns of inhaled antibiotic use in cystic fibrosis.

RATIONALE: Antibiotic inhalation has become widely accepted as a standard treatment for cystic fibrosis (CF) airway infection. We assessed the prevalence and context of inhaled antibiotic use in the North American CF population. Our working hypothesis was that a shift from acute to chronic use of inhaled antibiotics has coincided with increased prevalence of use among CF patients. METHODS: Descriptive statistics were collected for 30,833 patients enrolled in the Epidemiologic Study of CF (ESCF) during 1996 through 2005. A multivariate analysis was performed on data from a subgroup of 18,021 patients enrolled in ESCF during 2003 through 2005. RESULTS: The prevalence of inhaled antibiotic use in the North American CF population increased during 1996 through 2005 due to increased chronic use, while acute use to treat pulmonary exacerbations decreased. In 2005, 50% of CF patients used inhaled tobramycin and 9% used inhaled colistin chronically; most of the latter used both agents concurrently. Airway obstruction severity and airway infection status were predictors of inhaled antibiotic use. CONCLUSIONS: Increased chronic use and decreased acute use of inhaled antibiotics presumably reflect a shift toward more proactive management of airway infections in the North American CF population. The effects of these usage patterns on long-term clinical outcomes and emergence of antibiotic-resistant Pseudomonas aeruginosa strains warrant further study.

Real-world Evaluation of Asthma Control and Treatment (REACT): findings from a national Web-based survey.

BACKGROUND: Despite health initiatives for advancing the management of asthma, evidence suggests that many asthmatic subjects have uncontrolled disease. However, the prevalence of uncontrolled asthma in the United States is not known and has not been fully characterized. OBJECTIVE: We sought to assess the prevalence, morbidity, and factors associated with uncontrolled asthma in a nationally representative sample of patients with moderate-to-severe asthma using standard asthma medications. METHODS: A Web-based survey was administered to patients with diagnoses of asthma for at least 1 year who were receiving multiple controller medications. The Asthma Control Test score was used to stratify respondents into controlled and uncontrolled cohorts. RESULTS: A total of 1812 patients were assessed; 809 (45%) had controlled asthma, and 1003 (55%) had uncontrolled asthma. Most patients had health care coverage and received care from a general practitioner; a large proportion of patients with controlled asthma (74%) and patients with uncontrolled asthma (65%) reported never receiving an asthma action plan. Inhaled corticosteroid plus long-acting beta-agonist was the most common medication regimen in patients with controlled asthma (60%) and patients with uncontrolled asthma (48%) patients. Patients with uncontrolled asthma reported significantly higher rates of health care use. Several comorbidities were predictive of uncontrolled asthma. CONCLUSION: Uncontrolled asthma is highly prevalent (55%) in patients using standard asthma medications. There is need for improved asthma care in patients with moderate-to-severe asthma, including a global evaluation of asthma control, implementation of treatment plans and asthma control tests, and addressing comorbid conditions. CLINICAL IMPLICATIONS: Improved asthma care requires broader assessments of asthma control, including asthma-related health care and medication use, comorbidities, and the implementation of treatment plans and formal asthma control tests.

Demographic and clinical characteristics of children and adolescents with severe or difficult-to-treat asthma.

BACKGROUND: Young patients with severe or difficult-to-treat asthma are an understudied population. OBJECTIVE: To assess age-associated and gender-associated differences in children and adolescents in the observational study, The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens. METHODS: Cross-sectional baseline data for patients greater than or equal to 6 years and less than or equal to 17 years (n = 1261) were stratified by age group (6-8, 9-11, 12-14, and 15-17 years). The chi(2) test for categorical variables and analysis of variance for continuous variables were used to identify differences among age groups, stratified by gender. RESULTS: Most patients had moderate (55%) or severe (41%) asthma by physician assessment. Of those using greater than or equal to 3 long-term controllers (62%), 53% of children (6-11 years) and 44% of adolescents (12-17 years) reported an oral corticosteroid burst and 25% and 19%, respectively, had an emergency department visit in the previous 3 months; 10% and 15%, respectively, reported past intubation. In females, weight for age ranged between the 67th and 70th percentiles; height for age was between the 42nd and 54th percentiles (P < .01 among age groups). Lung function was lower in adolescents than children: prebronchodilator percent predicted forced expiratory volume in 1 second (FEV(1))/forced vital capacity was 0.92 (6-8 years) and 0.83 (15-17 years), P less than .05, in males; and 0.94 (6-8 years) and 0.87 (15-17 years), P less than .05, in females. CONCLUSIONS: Children and adolescents demonstrated high rates of health care use and loss of lung function, despite using multiple long-term controllers. CLINICAL IMPLICATIONS: Asthma treatments that prevent loss of lung function and reduce health care resource use are needed in young patients with severe or difficult-to-treat asthma.