Papers by Anne Fuhlbrigge
New England Journal of Medicine, 2022
BACKGROUND Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce ... more BACKGROUND Black 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. METHODS In 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. RESULTS Of 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. CONCLUSIONS Among 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.).
Council on Clinical Information Technology Program, 2021
Respiratory Medicine, 2020
BACKGROUND Frequency of moderate and severe chronic obstructive pulmonary disease exacerbations i... more BACKGROUND Frequency of moderate and severe chronic obstructive pulmonary disease exacerbations is an important endpoint in clinical trials, but makes them large and lengthy when powered to evaluate it. We aimed to develop a composite endpoint (COPDCompEx) that could predict treatment effect on exacerbations, enabling the design of shorter early phase clinical trials requiring fewer patients. METHODS In this post hoc analysis, data from 20 randomized controlled trials were used to develop and test COPDCompEx. Diary events were tested against predefined threshold values for peak expiratory flow, reliever medication use, and symptoms. A COPDCompEx event was defined as first occurrence of a diary event, a moderate or severe exacerbation, or a study dropout. Ratios of event frequency, treatment effect and future trial sample size were compared between COPDCompEx and moderate and severe exacerbations. FINDINGS At 3 months, the proportion of patients experiencing COPDCompEx events increased over 3-fold versus exacerbations alone. All components contributed to COPDCompEx event rate. Treatment effects at 3 months were closely matched between COPDCompEx and exacerbations, and the large net gain in power substantially reduced the required sample size. INTERPRETATION COPDCompEx may be used to predict treatment effect on moderate and severe exacerbations of chronic obstructive pulmonary disease. This may enable the design of shorter Phase 2 clinical trials requiring fewer patients when compared with current exacerbation studies, with exacerbations as a key Phase 3 endpoint. This would, therefore, allow more efficient decision-making with reduced burden and risk to study participants.
A31. ASTHMA: CLINICAL STUDIES I, 2019
D101. CLINICAL AND TRANSLATIONAL STUDIES IN ASTHMA AND COPD, 2019
The Journal of Allergy and Clinical Immunology: In Practice, 2019
BACKGROUND FEV1 as a percentage of predicted (FEV1%pred) is commonly measured in asthma clinical ... more BACKGROUND FEV1 as a percentage of predicted (FEV1%pred) is commonly measured in asthma clinical studies; however, reports vary on its association with asthma control instruments evaluating symptoms. OBJECTIVE Assess the association between FEV1%pred and Asthma Control Questionnaire (ACQ) scores in a managed-care population with persistent asthma. METHODS Retrospective analysis of survey responses and spirometry results of patients (aged ≥12 years) with persistent asthma from the Observational Study of Asthma Control and Outcomes was done. Eligible patients received 4 identical surveys including the 5-item ACQ (ACQ-5)/6-item ACQ (ACQ-6) and completed spirometry in parallel. Longitudinal analyses, comparisons of change over time, and fixed- and random-effects regression analyses were conducted, with/without adjustment for covariates. RESULTS There were 1748 survey responses with valid spirometry results. In unadjusted models, coefficients for ACQ-5/ACQ-6 scores were not statistically significant and coefficient of determination (R2) was low (0.03). When adjusted for covariates, ACQ-5 and ACQ-6 scores were significantly associated with FEV1%pred (P < .001) and R2 increased to 0.11 and 0.12, respectively. In adjusted models, every 1-point increase in ACQ-5 and ACQ-6 scores was associated with a 1.7% and 1.9% decrease, respectively, in FEV1%pred. Change in FEV1%pred and change in ACQ-5/ACQ-6 scores were not significantly associated in regressions with/without covariates. CONCLUSIONS The weak and statistically insignificant association between FEV1%pred and ACQ-5/ACQ-6 scores in unadjusted models suggests a high degree of unexplained variation between these measures. Results support the use of both symptoms and pulmonary function, rather than relying on one measure alone, to assess asthma control in clinical care and outcomes studies.
Journal of Molecular Medicine, 2018
The Lancet. Respiratory medicine, Jul 2, 2017
Occurrence of severe asthma exacerbations are the cornerstone of the evaluation of asthma managem... more Occurrence of severe asthma exacerbations are the cornerstone of the evaluation of asthma management, but severe asthma exacerbations are rare events. Therefore, trials that assess drug efficacy on exacerbations are done late in clinical development programmes. We aimed to establish an endpoint capturing clinically relevant deteriorations (diary events) that, when combined with severe exacerbations, create a composite outcome (CompEx). CompEx needs to strongly mirror results seen with the severe exacerbation-validated outcome, to allow the design of clinical trials of shorter duration and that include fewer patients than trials assessing severe exacerbations. Data from 12 asthma trials of 6 months or 12 months duration and, with standardised collection of exacerbations and diary card variables, were used to construct and test CompEx. The study populations had a mean age of 35-53 years, 59-69% were female, and had a mean FEV1 percentage of predicted normal of 63-84%. With data from f...
Medical Care, 2008
The use of physician profiles in &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more The use of physician profiles in &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;pay for performance&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; initiatives depend on their reliability and accuracy. To evaluate whether health care delivery units (practices) can be reliably differentiated using the Health Employers Data Information System (HEDIS) performance measure. Simulation was used to describe the relationship between practice size (number of children with persistent asthma) and precision of practice measures to estimate performance. Children enrolled in 1 of the 39 practice groups from 1 of 3 managed care organizations participating in the Pediatric Asthma Care Patient Outcomes Research Team (PAC PORT). The main outcome was reproducibility of 4 performance measures, the HEDIS measure and 3 additional measures available from automated claims data: the proportion of children with asthma related-hospitalization, emergency department visits and oral steroid dispensings for asthma. The ability to reproducibly rank a practice is dependent on the performance measure, practice size, and the reproducibility threshold chosen. Of measures evaluated, none achieved a reproducibility &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;85% for practice size of 50 or less. At a practice size of 100 subjects, the HEDIS measure reproducibly ranked practices 89% of the time, compared with 85% for emergency department visits and 83% for hospitalizations. Only at a practice size of 100 children with persistent asthma, was reproducibility of ranking greater than 85% with all performance measures evaluated. The reliability of ranking medical practices depends on practice size. Only at the level of the health care organization can asthma measures, available within claims data, be used to rank performance reliably.
Journal of Clinical Epidemiology, 2002
Journal of Asthma, 2011
Asthma treatment guidelines recommend medications based on the level of asthma control. To evalua... more Asthma treatment guidelines recommend medications based on the level of asthma control. To evaluate differences in asthma control between patients who initiated asthma controller monotherapy versus combination therapy. Children (5-16 years; n = 488) and adults (17-80 years; n = 530) with asthma and no controller therapy in the prior 6 months were included. Telephone surveys were conducted within 5 days of filling a new asthma controller prescription with either the caregiver of children or the adult patient. Demographics, asthma control before therapy, and asthma-related resource use were assessed for patients initiating monotherapy (filling one asthma controller prescription) and combination therapy (filling more than one controller medication or a fixed-dose combination). Mean pediatric age was 10 years; 53% were male. Mean adult age was 47 years; 25% were male. There were no significant differences in asthma control score between patients receiving monotherapy and combination therapy. Children on combination therapy did not have more nighttime awakening or short-acting β-agonist use but were more likely to have been hospitalized due to asthma attack (p = .05) and have more unscheduled (p = .0374) and scheduled (p = .009) physician visits. Adults on combination therapy were more likely to have been hospitalized due to asthma attack (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) and have regular doctor visits for asthma (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01). Assessment of asthma control scores in the 4 weeks before index medication suggests that asthma severity during a treatment-free period did not differ significantly for patients initiating controller monotherapy versus combination therapy. From these findings, it appears that although physicians may not focus on asthma control when choosing the intensity of initial controller therapy, the intensity of health-care encounters may be an influence.
Journal of Asthma, 2007
... 393413. Tormo MJ, Navarro C, Chirlaque MD, Barber X. Validation of self diagnosis of high bl... more ... 393413. Tormo MJ, Navarro C, Chirlaque MD, Barber X. Validation of self diagnosis of high blood pressure in a sample of the Spanish EPIC cohort: overall agreement and predictive values. EPIC Group of Spain. J Epidemiol Community Health 2000; 54: 221226. Klungel OH ...
Journal of Allergy and Clinical Immunology, 2005
The goal of asthma therapy is to maintain consistent control. We sought to examine the patterns o... more The goal of asthma therapy is to maintain consistent control. We sought to examine the patterns of asthma control recorded over 3 years using administrative claims and resource utilization definition. We performed a retrospective observational study with a nationally representative patient-level database containing pharmacy and medical claims. Patients with asthma (International Classification of Diseases, Ninth Revision-Clinical Modification code 493.xx), patients undergoing treatment with at least 1 asthma medication, and patients with 36 months of continuous claims coverage during the calendar years 1996 through 2002 were identified. A total of 63,324 patients were included in the study. Patients were classified as having controlled asthma in year 1 if they had less than 4 claims for a short-acting beta 2 -agonist, no claims for an OCS, and no asthma-related emergency department visits or hospitalizations. Patients were then followed over the next 8 quarters (2 years) to observe whether control was maintained. Control during a quarter was defined with the same criteria, except the reliever threshold was adjusted to 2 or more claims per quarter. Thirty-nine thousand ninety-five (57%) patients were defined as having controlled asthma during year 1. During the 2-year follow-up period, a range of 10% to 14% of these patients with controlled asthma met the criteria of uncontrolled asthma during any given quarter. Overall, 46,227 (73%) patients identified met the criteria for uncontrolled asthma at least once during the 3-year period. This study demonstrates that almost 75% of asthmatic patients experience an uncontrolled asthma episode 1 or more times over a 3-year period. Furthermore, we found that significant fluctuations in asthma control exist, even in patients with prior controlled asthma.
Journal of Allergy and Clinical Immunology, 2004
RationaleA decision to implement innovative disease management interventions in health plans ofte... more RationaleA decision to implement innovative disease management interventions in health plans often requires evidence of clinical benefit and financial impact. The Pediatric Asthma Care PORT II trial evaluated the outcomes of two asthma care strategies in children (ages 3 – 17) – a peer leader based physician behavior change intervention (PLE) and a practice-based redesign (Planned Asthma Care Intervention (PACI)).
Journal of Allergy and Clinical Immunology, 2004
ABSTRACT
Journal of Allergy and Clinical Immunology, 2007
Although inhaled corticosteroids (ICSs) generally protect against severe exacerbations in asthma,... more Although inhaled corticosteroids (ICSs) generally protect against severe exacerbations in asthma, they may result in elevated IgE levels, which are associated with exacerbations. To determine whether variation in the low-affinity IgE receptor gene, FCER2, is associated with severe exacerbations defined as emergency department visits and/or hospitalizations in patients with asthma on ICSs. We resequenced, then genotyped 10 FCER2 single nucleotide polymorphisms (SNPs) in 311 children randomized to inhaled budesonide as part of the Childhood Asthma Management Program. We evaluated the association of FCER2 variants with IgE levels and presence or absence of severe exacerbations over the 4-year clinical trial. We also evaluated differences in cellular expression of the novel FCER2 SNP, T2206C. In white subjects, 3 FCER2 SNPs were significantly associated (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) with elevated 4-year IgE level; each was also associated with increased severe exacerbations. Final multivariable models demonstrated associations between T2206C and severe exacerbations in both white and African American children (hazard ratio, 3.95; 95% CI, 1.64-9.51; and hazard ratio, 3.08; 95% CI, 1.00-9.47), despite ICS use. Interaction models supported a true gene-environment effect in white subjects (interaction P = .004). T2206C was also associated with decreased FCER2 expression (P = .02). FCER2 predicts the likelihood of treatment protocol success in asthma. The associations of T2206C with IgE level, severe exacerbations, and FCER2 expression may provide a mechanistic basis for the observed findings. Genetic variation in FCER2 may help form a prognostic model for ICS response in asthma.
Journal of Allergy and Clinical Immunology, 2002
Uploads
Papers by Anne Fuhlbrigge