Asthma Symptom Utility Index Research Articles

Bronchodilator response does not associate with asthma control or symptom burden among patients with poorly controlled asthma

PurposeThe purpose of this study was to determine how four different definitions of bronchodilator response (BDR) relate to asthma control and asthma symptom burden in a large population of participants with poorly controlled asthma. ProceduresWe examined the baseline change in FEV1 and FVC in response to albuterol among 931 participants with poorly controlled asthma pooled from three clinical trials conducted by the American Lung Association - Airways Clinical Research Centers. We defined BDR based on four definitions and analyzed the association of each with asthma control as measured by the Asthma Control Test or Asthma Control Questionnaire, and asthma symptom burden as measured by the Asthma Symptom Utility Index. Main findingsA BDR was seen in 31–42% of all participants, depending on the definition used. There was good agreement among responses (kappa coefficient 0.73 to 0.87), but only 56% of participants met all four definitions for BDR. A BDR was more common in men than women, in Blacks compared to Whites, in non-smokers compared to smokers, and in non-obese compared to obese participants. Among those with poorly controlled asthma, 35% had a BDR compared to 25% of those with well controlled asthma, and among those with a high symptom burden, 34% had a BDR compared to 28% of those with a low symptom burden. After adjusting for age, sex, height, race, obesity and baseline lung function, none of the four definitions was associated with asthma control or symptom burden. ConclusionA BDR is not associated with asthma control or symptoms in people with poorly controlled asthma, regardless of the definition of BDR used. These findings question the clinical utility of a BDR in assessing asthma control and symptoms.

Preference for and impact of telehealth vs in-person asthma visits among Black and Latinx adults

BackgroundBlack and Latinx adults experience disproportionate asthma-related morbidity and limited specialty care access. The severe acute respiratory syndrome coronavirus 2 pandemic expanded telehealth use. ObjectiveTo evaluate visit type (telehealth [TH] vs in-person [IP]) preferences and the impact of visit type on asthma outcomes among Black and Latinx adults with moderate-to-severe asthma. MethodsFor this PREPARE trial ancillary study, visit type preference was surveyed by e-mail or telephone post-trial. Emergency medical record data on visit types and asthma outcomes were available for a subset (March 2020 to April 2021). Characteristics associated with visit type preferences, and relationships between visit type and asthma outcomes (control [Asthma Control Test] and asthma-related quality of life [Asthma Symptom Utility Index]), were tested using multivariable regression. ResultsA total of 866 participants consented to be surveyed, with 847 respondents. Among the participants with asthma care experience with both visit types, 42.0% preferred TH for regular checkups, which associated with employment (odds ratio [OR] = 1.61; 95% confidence interval [CI], 1.09-2.39; P = .02), lower asthma medication adherence (OR = 1.06; 95% CI, 1.01-1.11; P = .03), and having more historical emergency department and urgent care asthma visits (OR = 1.10 for each additional visit; 95% CI, 1.02-1.18; P = .02), after adjustment. Emergency medical record data were available for 98 participants (62 TH, 36 IP). Those with TH visits were more likely Latinx, from the Southwest, employed, using inhaled corticosteroid–only controller therapy, with lower body mass index, and lower self-reported asthma medication adherence vs those with IP visits only. Both groups had comparable Asthma Control Test (18.4 vs 18.9, P = .52) and Asthma Symptom Utility Index (0.79 vs 0.84, P = .16) scores after adjustment. ConclusionTH may be similarly efficacious as and often preferred over IP among Black and Latinx adults with moderate-to-severe asthma, especially for regular checkups. Trial RegistrationClinicalTrials.gov Identifier: NCT02995733.

Comparing asthma control assessment using the Asthma Control Test and the Asthma APGAR in African American/Black and Hispanic/Latinx populations

Introduction The objective of this analysis was to compare the Asthma Control Test (ACT) and the Asthma APGAR asthma control assessment tools in African-Ancestry/Black (AA/B) and Hispanic/Latinx (H/L) adults with moderate to severe asthma. Methods This pre-planned sub-study of the PREPARE clinical trial compares the baseline ACT and Asthma APGAR scores for the PREPARE populations using correlation coefficients, generalized linear modeling and receiver operating curve (ROC) analyses. Correlations were also assessed for both control tests and the Asthma Symptom Utility Index (ASUI). Results Among the 1201 adults (603 AA/B and 598 H/L) with moderate to severe asthma, most had uncontrolled asthma by both the ACT and the Asthma APGAR. Correlation coefficients between the ACT, Asthma APGAR and ASUI were strong and did not differ significantly by race/ethnicity. The ACT consistently assessed more patients as uncontrolled compared with the Asthma APGAR. The differences in ACT and Asthma APGAR scores did not differ by age, gender, race/ethnicity, self-reported health literacy or medication adherence but did differ by education level. Both the ACT and Asthma APGAR had similar ROCs for predicting an asthma exacerbation in the next 3 months. Conclusions Both the ACT and the Asthma APGAR can be used for asthma control assessment in AA/B and H/L populations with moderate to severe asthma, providing comparable rates of uncontrolled asthma and similar limited ability to predict exacerbations. Further work is required to better understand the basis and clinical implications of the higher rates of uncontrolled asthma identified using the ACT.

Intraclass Correlation and Variance in the Characteristics of Primary Care Patients Managing Chronic Medical and Behavioral Conditions.

Background To avoid statistical errors, researchers who recruit patients from selected medical practices and analyze them at the individual level need to account for the clustered nature of their sample. This is most often done using the intraclass correlation coefficients (ICCs), a measure of how strongly subjects recruited from the same cluster (in this case patients from a clinic) resemble each other. Aims The aim is to support the design of cluster-randomized studies by supplying estimates of variance and ICC of various measures using a population of patients from multiple primary care clinics. Materials and methods ICCs were extracted from a large cluster-randomized pragmatic clinical trial of adult primary care patients managing multiple chronic conditions, the Integrating Behavioral Health and Primary Care study (IBH-PC). IBH-PC collected demographics and patient-reported health outcomes on over 3,000 adults from 44 primary care practices in 13 states across the US. We present estimates of the standard deviation and ICC for gender, race, ethnicity, marital status, employment, income, education, social determinants of health, PROMIS-29 functional status, Duke Activity Status Index (DASI), nine-item Patient Health Questionnaire (PHQ-9) depression score, Generalized Anxiety Disorder (GAD-7) anxiety score, Asthma Symptom Utility Index, restricted activity days, medication adherence, health care visits in the past month, emergency room visits in the past year, hospital days in the past year, perception of quality and patient-centeredness of care, alcoholic drinks per month, and the GAIN substance use disorder screener. Results ICCs varied broadly with the highest values found for race and income and the lowest for short-term estimates of the GAIN. Conclusions These values can be used to inform the design, especially power estimates and sample size requirements, of future studies.

Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma

BackgroundBlack and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations.MethodsIn this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 μg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed.ResultsOf 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P=0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups.ConclusionsAmong Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.)

Psychometric Properties of the Asthma Symptom Index in Patients with Severe Asthma

Evaluation of symptoms is essential in asthma clinical research. Daily symptom diaries require once- or twice-daily recording, making them less suited to real-world use. A modified version of the established Asthma Symptom Utility Index (ASUI) that includes symptom attributes (Asthma Symptom Index [ASI]) was developed as a less-burdensome measure of asthma symptoms. To evaluate the ASI and replicate ASUI psychometric properties, including validity, reliability, responsiveness, and minimal clinically important difference (MCID) estimation in patients ≥12 years of age with severe asthma. Patients from a randomized trial (MUSCA [n=497]) and a cross-sectional study (IDEAL [n= 721]) were analyzed post hoc. Demographic information, spirometry, ASI and ASUI scores, and other patient-reported outcome measures such as Asthma Control Questionnaire (ACQ-5) and St George's Respiratory Questionnaire (SGRQ) at baseline and during follow-up (MUSCA only) were obtained. Internal consistency reliability and test-retest reliability were considered good (>0.70 [Cronbach's alpha] and 0.87-0.90 [intraclass correlation]). ASI/ASUI scores correlated strongly with ACQ-5 and SGRQ scores (spearman correlation [rs] magnitude: 0.67-0.85). ASI and ASUI scores differed for asthma control (defined by ACQ-5) and lung function (% predicted forced expiratory volume in 1 second). Changes in ASI and ASUI scores from baseline to week 4 and week 12 had high correlations with changes in ACQ-5 (rs magnitude: 0.57-0.69). MCIDs ranged from-0.42 to-0.26 (ASI) and 0.07 to 0.11 (ASUI). Findings show the good reliability, validity, and responsiveness of the ASI, indicating potential value for real-world symptom assessment in severe asthma.

Assessing the impact of a remote digital coaching engagement program on patient-reported outcomes in asthma

ABSTRACTBackground: Low adherence and poor outcomes provide opportunity for digital coaching to engage patients with uncontrolled asthma in their care to improve outcomes. Objective(s): To examine the impact of a remote digital coaching program on asthma control and patient experience. Methods: We recruited 51 adults with uncontrolled asthma, denoted by albuterol use of >2 times per week and/or exacerbations requiring corticosteroids, and applied a 12-week patient-centered remote digital coaching program using a combination of educational pamphlets, symptom trackers, best peak flow establishment, physical activity, and dietary counseling, as well as coaches who implemented emotional enforcement to motivate disease self-management through telephone, text, and email. Baseline and post-intervention measures were quality of life (QOL), spirometry, Asthma Control Test (ACT), Asthma Symptom Utility Index (ASUI), rescue albuterol use, and exacerbation history. Results: Among 51 patients recruited, 40 completed the study. Eight subjects required assistance reading medical materials. Significant improvements from baseline were observed for Patient-Reported Outcomes Measurement Information System mental status (p = 0.010), body weight, and outpatient exacerbation frequency (p = 0.028). The changes from baseline in ACT (p = 0.005) were statistically significant but did not achieve the pre-specified minimum clinically important difference (MCID), whereas for ASUI, the MCID and statistical significance were achieved. Spirometry and rescue albuterol use were no different. Conclusion: A patient-oriented, remote digital coaching program that utilized trained health coaches and digital materials led to statistically significant improvement in mental status, outpatient exacerbations, body weight, and ASUI. Digital coaching programs may improve some outcomes in adults with uncontrolled asthma.

A new measure to assess asthma's effect on quality of life from the patient's perspective

The Asthma Impact on Quality of Life Scale (A-IQOLS) assesses the negative effect of asthma on quality of life (QoL) from the patient's perspective by using dimensions of Flanagan's Quality of Life Scale (QOLS), a measure of current QoL. We sought to determine and compare the psychometric properties of the A-IQOLS and QOLS, including their sensitivities to differences and change in asthma status. In a test-retest design (3- to 5-week interval) adults with persistent asthma underwent spirometry and were administered the A-IQOLS, other asthma outcome measures (Asthma Control Test, Asthma Symptom Utility Index, and the Marks and Juniper Asthma Quality of Life Questionnaires), and the QOLS. Participants' (n=147) mean age was 49years, 76% were white, 12% were Hispanic, and 65% were female. A-IQOLS and QOLS scores were significantly correlated with other asthma outcomes scores, except FEV1, but shared relatively low common variance with these measures. A-IQOLS but not QOLS score changes were significantly correlated with changes in asthma outcomes. An A-IQOLS standard error of measurement of 0.27 implies that a within-person score change of ±0.73 or greater constitutes a true change. The QOLS standard error of measurement was 0.43. A-IQOLS provides a reliable, valid, and unique assessment of the patient-perceived negative effect of asthma on QoL that is suitable for use in asthma clinical research and potentially in clinical care. Further studies are needed in diverse patient populations. QOLS, a measure of current QoL, is less sensitive to disease status changes but might be useful in characterizing study populations, in treatment adherence research, and as a clinical and research tool in patients with multiple, severe, and/or life-limiting chronic conditions.

Reslizumab for Inadequately Controlled Asthma With Elevated Blood Eosinophil Levels: A Randomized Phase 3 Study

This phase 3 study further characterizes the efficacy and safety of reslizumab (a humanized anti-IL-5 monoclonal antibody) in patients aged 12 to 75 years with asthma inadequately controlled by at least a medium-dose inhaled corticosteroid and with a blood eosinophil count≥ 400 cells/μL. Patients were randomized to receive reslizumab 0.3 or 3.0mg/kg or placebo administered once every 4weeks for 16weeks (total four doses). The primary end point was change from baseline in pre-bronchodilator FEV1 over 16weeks. Secondary end points included FVC, forced expiratory flow at 25%to 75%of FVC (FEF25%-75%), patient-reported control of asthma symptoms, short-acting β-agonist (SABA) use, blood eosinophil levels, and safety. Reslizumab significantly improved FEV1 (difference vsplacebo [reslizumab 0.3 and 3.0mg/kg], 115mL [95%CI, 16-215; P= .0237] and 160mL [95%CI, 60-259; P= .0018]). Clinically meaningful increases in FVC (130mL) and FEF25%-75% (233mL/s) were observed with reslizumab 3.0mg/kg. Reslizumab improved scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) vsplacebo (greater effects seen with 3.0mg/kg; P<.05). The minimally important difference was reached for the AQLQ (reslizumab 3.0mg/kg) but not on the ACQ. Scores on the Asthma Symptom Utility Index and SABA use were improved with reslizumab. The most common adverse events were worsening of asthma, headache, and nasopharyngitis; most events were mild to moderate in severity. Reslizumab improved lung function, asthma control and symptoms, and quality of life. It was well tolerated in patients with inadequately controlled asthma (despite standard therapy) and elevated blood eosinophil levels. Overall, the 3.0-mg/kg dose of reslizumab provided greater improvements in asthma outcomes vsthe 0.3-mg/kg dose, with comparable safety. ClinicalTrials.gov; No.: NCT01270464; URL: www.clinicaltrials.gov.

Anticholinergic vs Long-Acting β-Agonist in Combination With Inhaled Corticosteroids in Black Adults With Asthma: The BELT Randomized Clinical Trial.

The efficacy and safety of long-acting β-agonists (LABAs) have been questioned. Black populations may be disproportionately affected by LABA risks. To compare the effectiveness and safety of tiotropium vs LABAs, when used with inhaled corticosteroids (ICS) in black adults with asthma and to determine whether allelic variation at the Arg16Gly locus of the β2-adrenergic receptor (ADRB2) geneis associated with treatment response. A multisite (n = 20), open-label, parallel-group, pragmatic randomized clinical trial conducted from March 2011 through July 2013, enrolling black adults with moderate to severe asthma in the United States. Patients eligible for, or receiving, step 3 or step 4 combination therapy per National Heart, Lung, and Blood Institute guidelines, received ICS plus either once-daily tiotropium (n = 532) or twice-daily LABAs (n = 538,) and were followed up for up to 18 months. Patients underwent genotyping, attended study visits at baseline, 1, 6, 12, and 18 months, and completed monthly questionnaires. The primary outcome was time to asthma exacerbation, defined as a worsening asthma event requiring oral or parenteral corticosteroids. Secondary outcomes included patient-reported outcomes (Asthma Quality of Life Questionnaire, Asthma Control Questionnaire [ACQ], Asthma Symptom Utility Index, and Asthma Symptom-Free Days questionnaire), spirometry (FEV1), rescue medication use, asthma deteriorations, and adverse events. There was no difference between LABA + ICS vs tiotropium + ICS in time to first exacerbation (mean No. of exacerbations/person-year, 0.42 vs 0.37 (rate ratio, 0.90 [95% CI, 0.73 to 1.11], log-rank P = .31). There was no difference in change in FEV1 at 12 months (0.003 L for LABA + ICS vs -0.018 L for tiotropium + ICS; between-group difference, 0.020 [95% CI, -0.021 to 0.061], P = .33) and at 18 months (-0.053 L vs -0.078 L; between-group difference, 0.025 [95% CI, -0.045 to 0.095], P = .49). There were no differences in ACQ score at 18 months (change in score from baseline, -0.68 for LABA + ICS vs -0.72 for tiotropium + ICS; between-group difference, 0.04 [95% CI, -0.18 to 0.27], P = .70). There were no differences in other patient-reported outcomes. Arg16Gly ADRB2 alleles were not associated with differences in the effects of tiotropium + ICS vs LABA + ICS (hazard ratio for time to first exacerbation, 0.84 [95% CI, 0.47 to 1.51] for Arg/Arg vs 0.85 [95% CI, 0.63 to 1.15] for Arg/Gly or Gly/Gly, P = .97). Among black adults with asthma treated with ICS, adding a LABA did not improve time to asthma exacerbation compared with adding tiotropium. These findings were not affected by polymorphisms at the Arg16Gly locus of ADRB2. These findings do not support the superiority of LABA + ICS compared with tiotropium + ICS for black patients with asthma. ClinicalTrials.gov identifier: NCT01290874.

Efficacy of nasal mometasone for the treatment of chronic sinonasal disease in patients with inadequately controlled asthma

Chronic sinonasal disease is common in asthmatic patients and associated with poor asthma control; however, there are no long-term trials addressing whether chronic treatment of sinonasal disease improves asthma control. We sought to determine whether treatment of chronic sinonasal disease with nasal corticosteroids improves asthma control, as measured by the Childhood Asthma Control Test and Asthma Control Test in children and adults, respectively. A 24-week multicenter, randomized, placebo-controlled, double-blind trial of placebo versus nasal mometasone in adults and children with inadequately controlled asthma was performed. Treatments were randomly assigned, with concealment of allocation. Two hundred thirty-seven adults and 151 children were randomized to nasal mometasone versus placebo, and 319 participants completed the study. There was no difference in the Childhood Asthma Control Test score (difference in change with mometasone - change with placebo [ΔM - ΔP], -0.38; 95% CI, -2.19 to 1.44; P = .68; age 6-11 years) or the Asthma Control Test score (ΔM - ΔP, 0.51; 95% CI, -0.46 to 1.48; P = .30; age ≥12 years) in those assigned to mometasone versus placebo. In children and adolescents (age 6-17 years) there was no difference in asthma or sinus symptoms but a decrease in episodes of poorly controlled asthma defined by a decrease in peak flow. In adults there was a small difference in asthma symptoms measured by using the Asthma Symptom Utility Index (ΔM - ΔP, 0.06; 95% CI, 0.01 to 0.11; P < .01) and in nasal symptoms (sinus symptom score ΔM - ΔP, -3.82; 95% CI, -7.19 to -0.45; P = .03) but no difference in asthma quality of life, lung function, or episodes of poorly controlled asthma in adults assigned to mometasone versus placebo. Treatment of chronic sinonasal disease with nasal corticosteroids for 24 weeks does not improve asthma control. Treatment of sinonasal disease in asthmatic patients should be determined by the need to treat sinonasal disease rather than to improve asthma control.

Sex differences in asthma symptom profiles and control in the American Lung Association Asthma Clinical Research Centers

Important differences between men and women with asthma have been demonstrated, with women describing more symptoms and worse asthma-related quality of life (QOL) despite having similar or better pulmonary function. While current guidelines focus heavily on assessing asthma control, they lack information about whether sex-specific approaches to asthma assessment should be considered. We sought to determine if sex differences in asthma control or symptom profiles exist in the well-characterized population of participants in the American Lung Association Asthma Clinical Research Centers (ALA-ACRC) trials. We reviewed baseline data from four trials published by the ALA-ACRC to evaluate individual item responses to three standardized asthma questionnaires: the Juniper Asthma Control Questionnaire (ACQ), the multi-attribute Asthma Symptom Utility Index (ASUI), and Juniper Mini Asthma Quality of Life Questionnaire (mini-AQLQ). In the poorly-controlled population, women reported similar overall asthma control (mean ACQ 1.9 vs. 1.8; p=0.54), but were more likely to report specific symptoms such as nocturnal awakenings, activity limitations, and shortness of breath on individual item responses. Women reported worse asthma-related QOL on the mini-AQLQ (mean 4.5 vs. 4.9; p<0.001) and more asthma-related symptoms with a lower mean score on the ASUI (0.73 vs. 0.77; p≤0.0001) and were more likely to report feeling bothered by particular symptoms such as coughing, or environmental triggers. In participants with poorly-controlled asthma, women had outwardly similar asthma control, but had unique symptom profiles on detailed item analyses which were evident on evaluation of three standardized asthma questionnaires.

Lansoprazole for Children With Poorly Controlled Asthma: A Randomized Controlled Trial

To study the efficacy of proton pump inhibitor (PPI) therapy over 24 weeks in reducing symptoms in asthmatic children without symptomatic gastroesophageal reflux (GER) who had poor asthma control.Subjects were between 6 and 17 years old with physician-diagnosed asthma and “labile airways function” defined as (1) 12% or greater increase in postbronchodilator forced expiratory volume in 1 second (FEV1), (2) methacholine PC20 less than 16 mg/mL, or (3) positive exercise challenge with a 20% or greater decrease in FEV1.This is a multicenter, randomized, double-masked, placebo-controlled parallel clinical trial in children with asthma. All subjects were on stable doses of inhaled corticosteroids and had poor asthma control defined by study specific criteria. Subjects were excluded if they self-reported any symptoms of GER requiring treatment with a PPI or other reflux medication. The primary outcome was change in asthma control questionnaire score at the 24-week visit. Secondary outcomes included rate of acute episodes of poor asthma control, change in Asthma Symptom Utility Index, change in Asthma Control Test, change in asthma-specific quality of life for children score, methacholine PC20, spirometry, FeNO, gastrointestinal symptoms, and nocturnal awakenings. Esophageal pH studies were performed before randomization in a subset. Participating children were randomly assigned to receive lansoprazole dosed by weight.One hundred forty-nine children were randomized to lansoprazole therapy and 157 were randomized to placebo. Mean age at randomization was 11 years in both groups. More than 88% of participants completed the study. Of 115, 49 (43%) 24-hour pH probe studies demonstrated abnormal esophageal acid exposure. Gastrointestinal symptom scores were not different between patients with normal versus abnormal pH studies. No differences were seen in initial prebronchodilator FEV1 or forced vital capacity in those with normal or abnormal pH studies. At week 24 of therapy, mean Asthma Control Questionnaire score had decreased by <0.5 (the predetermined clinically important difference) in both groups and was not statistically different between the 2 groups (P = .12). There were no statistically significant treatment effects for any of the secondary outcome measurements. In a subanalysis of the children with abnormal pH probe studies (n = 49), there was no significant effect of lansoprazole treatment for 24 weeks on any of the study outcomes. Adverse event monitoring showed treatment with lansoprazole was associated with statistically greater prevalence of upper respiratory tract infection, sore throat, and bronchitis. Activity-related bone fractures were seen in 6 of 149 lansoprazole-treated subjects and 1 of 157 placebo-treated children (P = .06).In children 6 to 17 years old with mild or moderate persistent asthma on inhaled corticosteroids, without GER symptoms, abnormal pH probe diagnostic of GER disease is present in 43%. Yet 24-week treatment with lansoprazole had no significant effect on measures of asthma control, quality of life, lung function, or bronchial responsiveness compared with placebo in the total group and in the subgroup of patients with abnormal pH probe studies. Increased adverse events, upper respiratory tract infection , sore throat, and bronchitis were seen in the lansoprazole-treated subjects. Activity-related bone fractures were slightly increased in the lansoprazole-treated subjects.The same investigators have shown similar results in adults. This study contributes to the questioning of the true association between asthma and GER disease in children and adults and potential overuse of PPI therapy in patients without symptomatic GER. These data were obtained in asthmatic children without symptomatic GER and may not be comparable in children with active GER symptoms. Impedance monitoring was not done and the results cannot be extrapolated to the possible effect of non–acid reflux on asthma control. Increased fracture risk has been reported in adults on long-term PPI therapy. This is the first large study to suggest possible association in children, although specific cause-and-effect was not investigated.

Asthma Symptom Utility Index: Reliability, validity, responsiveness, and the minimal important difference in adult asthmatic patients

The evaluation of asthma symptoms is a core outcome measure in asthma clinical research. The Asthma Symptom Utility Index (ASUI) was developed to assess the frequency and severity of asthma symptoms. The psychometric properties of the ASUI are not well characterized, and a minimal important difference (MID) is not established. We assessed the reliability, validity, and responsiveness to change of the ASUI in a population of adult asthmatic patients. We also sought to determine the MID for the ASUI. Adult asthmatic patients (n = 1648) from 2 previously completed multicenter randomized trials were included. Demographic information, spirometric results, ASUI scores, and other asthma questionnaire scores were obtained at baseline and during follow-up visits. Participants also kept a daily asthma diary. The internal consistency reliability of the ASUI was 0.74 (Cronbach α). Test-retest reliability was 0.76 (intraclass correlation). Construct validity was demonstrated by significant correlations between ASUI scores and Asthma Control Questionnaire scores (Spearman correlation r = -0.79; 95% CI, -0.85 to -0.75; P < .001) and Mini Asthma Quality of Life Questionnaire scores (r = 0.59; 95% CI, 0.51-0.61; P < .001). Responsiveness to change was demonstrated, with significant differences between mean changes in ASUI scores across groups of participants differing by 10% in percent predicted FEV(1) (P < .001) and by 0.5 points in Asthma Control Questionnaire scores (P < .001). Anchor-based and statistical methods support an MID for the ASUI of 0.09 points. The ASUI is reliable, valid, and responsive to changes in asthma control over time. The MID of the ASUI (range of scores, 0-1) is 0.09.

Effects of Obstructive Sleep Apnea and Gastroesophageal Reflux Disease on Asthma Control in Obesity

Background. Obesity is a risk factor for asthma. Obese asthmatics often have poor asthma control and respond poorly to therapy. It has been suggested that co-morbidities associated with obesity, such as reflux and obstructive sleep apnea, could be important factors contributing to poor asthma control in obese patients. Objectives. The purpose of this study was to determine if (1) reflux and/or (2) symptoms of sleep apnea contribute to poor asthma control in obesity. Methods. We studied asthmatic subjects participating in a trial of reflux treatment. Participants underwent baseline evaluation of asthma symptoms and lung function. Overall 304 participants underwent esophageal pH probe testing; 246 participants were evaluated for obstructive sleep apnea symptoms. Results. Of 402 participants in this trial, 51% were obese. Role of reflux in asthma control. Those with higher body mass index (BMI) reported a higher prevalence of reflux symptoms, but the prevalence of pH probe acid reflux was similar in all groups. Reflux was not associated with measures of asthma control in obese patients. Role of obstructive sleep apnea in asthma control. Symptoms and self-report of obstructive sleep apnea were more common with increasing BMI and associated with worse asthma control as measured by the Juniper Asthma Control questionnaire and Asthma Symptom Utility Index. Conclusions. Our data suggest that obstructive sleep apnea, but not gastroesophageal reflux disease, may contribute significantly to poor asthma control in obese patients.

Evaluating preference weights for the Asthma Symptom Utility Index (ASUI) across countries

BackgroundThe Asthma Symptom Utility Index (ASUI) is a preference-based outcome measure used in US clinical trials and cost-effectiveness studies for asthma. This study evaluated ASUI preference weights in Europe to determine whether the multi-attribute utility function, based on preferences from a US population, is generalizable across countries.MethodsData were collected from ninety asthma patients from Italy, France, and the United Kingdom using the Asthma Control Questionnaire, the Asthma Quality of Life Questionnaire, and the ASUI. Subjects rated their preferences for 10 asthma health states using a visual analogue scale (VAS) and a standard gamble (SG) interview.ResultsAll multi-symptom states showed statistically significant differences (p < 0.001) between countries in mean VAS scores. Mean SG utility scores between the US and France and the US and Italy demonstrated statistically significant differences (p < 0.001) for three states: severe wheeze; moderate cough and wheeze; and moderate cough and dyspnea. Because of these differences, the multi-attribute utility functions derived within countries were somewhat different. Despite these differences, country-specific algorithms captured a similar rank ordering of patients by disease severity, were strongly correlated (r = 0.971 to 0.995), and demonstrated similar relationships with symptom and AQLQ scores.ConclusionResults of this study suggest that the ASUI may be a complementary patient-reported outcome for clinical studies and may be useful for applications in cost-effectiveness studies comparing different asthma treatments.

Association between preference-based health-related quality of life and asthma severity

Preference-based measures of health-related quality of life (HRQL) focus on choice and strength of preference for health outcomes. If the value people attach to the health improvement they receive from medical treatments for asthma is known, preference-based measures can be used in cost-effectiveness analyses to aid resource allocation decisions. International guidelines have been developed to guide medical management according to asthma severity defined by lung function and symptom frequency. To test the hypothesis that preferences correlate with asthma severity and that the relationships vary among the preference instruments used and the components of asthma severity studied. Preferences for subjects' health states were measured using (1) a rating scale (RS), (2) standard gamble (SG), (3) time tradeoff (TTO), (4) Health Utilities Index 3 (HUI3), and (5) Asthma Symptom Utility Index (ASUI). We measured level of airways obstruction by forced expiratory volume in 1 second (FEV1) and symptom frequency of cough, wheeze, dyspnea, and nighttime awakening. Asthma severity was defined by either percentage of predicted FEV1 or symptom frequency. One hundred adults with asthma were studied. Preference scores were lowest for the HUI3 (mean, 0.57) and highest for the SG (mean, 0.91). Spearman correlations showed that the strength of the relationship between preference scores and percentage of predicted FEV1 was weak to moderate (r = 0.14-0.36). One-way analysis of variance showed that RS, TTO, and ASUI scores were significantly associated with the percentage of predicted FEV1 (P < or = .01). Both RS and HUI3 scores were significantly associated with frequency of all symptoms (P < .05). Preference-based measures of HRQL are correlated with asthma severity defined by lung function or symptoms. The RS was significantly associated with level of airways obstruction and all 4 symptoms evaluated, whereas the SG was not correlated with either marker of asthma severity.

Dietary Intake of Soy Genistein is Associated with Lung Function in Patients with Asthma

To determine if micronutrient intake is associated with asthma severity, we administered the Block food frequency questionnaire to participants in a randomized clinical trial of the safety of influenza vaccine for asthmatics. The nutrition substudy included 1033 participants, aged 12–75. Intake of antioxidant vitamins, soy isoflavones, total fruits and vegetables, fats, and fiber was compared with asthma severity at baseline [forced expiratory volume in 1 second (FEV1), peak expiratory flow rate (PEF), asthma symptoms] and the rate of asthma exacerbations during the 2 weeks following influenza vaccination. The only nutrient that had a consistent association with asthma severity was genistein, a soy isoflavone. None of the nutrients evaluated were related to asthma exacerbation rate when adjusted for known confounders. The FEV1 in genistein consumers of at least 250 µg/1000 Kcal/day was 82.1% predicted, 79.9% predicted for those who consumed between 1 and 249 µg/1000 kcal, and 76.2% predicted in genistein nonconsumers (p = 0.006); the PEF was 82.7% predicted, 80.8% predicted, and 78.3% predicted, respectively (p = 0.009). There were no differences in the Asthma Symptom Utility Index (ASUI). We could not account for these results based on differences in demographics, body mass index, or consumption of other nutrients. Thus, increasing consumption of genistein is associated with better lung function in patients with asthma. Further studies are needed to determine whether dietary supplementation with genistein can reduce asthma severity.

Allergy: a global problem. Quality of life.

Allergy: a global problem. Quality of life.

Integrating Patient Preferences Into Health Outcomes Assessment: The Multiattribute Asthma Symptom Utility Index

To develop and evaluate a brief, easy-to-administer symptom assessment scale for use as a preference-based outcome measure in clinical trials and cost-effectiveness studies in asthma. Cross-sectional survey with 2-week reproducibility assessment. Ambulatory care: university asthma and allergy center. One hundred sixty-one adults with asthma, 59% female, mean age 35+/-11 years. Mean FEV1 percent predicted was 86+/-17%. The 11-item Asthma Symptom Utility Index (ASUI). Mean ASUI score for this sample was 0.71+/-0.23, with a range from 0.02 to 1.0. The ASUI was reproducible (intraclass correlation coefficient = 0.74) and able to distinguish patients known to differ on disease severity according to clinician ratings (p < 0.001) and by an asthma disease severity scale score (p < 0.001). The instrument was also significantly correlated with FEV1 percent predicted (r = 0.27, p < 0.001), the Asthma Quality of Life Questionnaire (r = 0.77, p < 0.001), and the Health Utilities Index Mark 2 (r = 0.36, p < 0.001). The results of this study support the reliability and validity of the ASUI, suggesting it will be a useful, complementary patient outcome measure for clinical trials and cost-effectiveness studies comparing treatment alternatives for persons with asthma.