Asthma Clinical Research Articles

Small airway dysfunction measured by impulse oscillometry is associated with exacerbations and poor symptom control in patients with asthma treated in a tertiary hospital subspecialist airways disease clinic.

Small airways dysfunction contributes to asthma pathophysiology and clinical outcomes including exacerbations and asthma control. Respiratory oscillometry is a simple, non-invasive and effort independent lung function test that provides vital information about small airway function. However, interpretation and clinical utility of respiratory oscillometry has been in part limited by lack of agreed parameters and the respective cutoffs. The aim of this study was to determine the prevalence of small airways dysfunction based on published impulse oscillometry (IOS) definition in patients with asthma referred to a tertiary asthma clinic and the extent to which it correlates with asthma clinical outcomes. We retrospectively reviewed the medical records of all patients with asthma managed in the severe asthma clinic between January 2019 and December 2022 who underwent routine lung function tests with oscillometry and spirometry. Small airways dysfunction was determined from various published IOS parameter cutoffs, and the data were analysed to determine correlations between IOS parameters and asthma outcomes. Amongst the 148 patients, the prevalence of small airways dysfunction ranged from 53% to 78% depending on the defining oscillometry parameter. All oscillometry parameters correlated with the severity of airflow obstruction (FEV1% predicted, p < 0.001). Several oscillometry parameters correlated with asthma symptom burden, the strongest correlation was seen for frequency dependent resistance (R5-R20) with scores of Asthma Control Questionnaire (ACQ6) (Spearman's rank coefficient 0.213, p = 0.028) and Asthma Control Test (ACT) (Spearman's rank coefficient -0.248, p = 0.012). R5-R20 was predictive of poor asthma control defined by ACQ6 >1.5 (OR 2.97, p = 0.022) or ACT <20 (OR 2.44, p = 0.055). Small airways dysfunction defined by R5-R20 and area under the reactance curve (AX) also significantly increases asthma exacerbation risk (OR 2.60, p = 0.02 and OR 2.31, p = 0.03 respectively). Respiratory oscillometry is a sensitive measure of small airways dysfunction that should complement spirometry in the routine assessment of asthma. Small airways dysfunction is highly prevalent in patients with asthma referred to a tertiary asthma clinic. R5-R20 was the metric most predictive in identifying patients at risk of asthma exacerbations and poor asthma control.

The Korean Academy of Asthma Allergy and Clinical Immunology guidelines for allergen immunotherapy

The Korean Academy of Asthma Allergy and Clinical Immunology guidelines for allergen immunotherapy

The Korean Academy of Asthma Allergy and Clinical Immunology guidelines for sublingual immunotherapy

The Korean Academy of Asthma Allergy and Clinical Immunology guidelines for sublingual immunotherapy

Dyslipidemia Is Associated With Worse Asthma Clinical Outcomes: A Prospective Cohort Study

Dyslipidemia has been widely documented to be associated with cardiovascular disease, and recent studies have found an association with asthma prevalence. However, longitudinal studies investigating the relationships between dyslipidemia, asthma phenotypes, and future asthma exacerbations (AEs) are lacking. To investigate the relationships between dyslipidemia, asthma phenotypes, and AEs. This study used an observational cohort study design with a 12-month follow-up. All subjects underwent serum lipid measurement, and they were then classified into 2 groups: the normal-lipidemia group and the dyslipidemia group. Demographic and clinical information and details regarding pulmonary function and asthma phenotypes at baseline were collected. All patients were followed up regularly to assess AEs. Associations of dyslipidemia with airway obstruction and asthma phenotypes were assessed at baseline, whereas dyslipidemia and AEs were assessed longitudinally. A total of 477 patients with asthma were consecutively enrolled in this study. At baseline, the dyslipidemia group (n= 218) had a higher proportion of uncontrolled asthma, defined by the 6-item Asthma Control Questionnaire score (≥1.5). Furthermore, dyslipidemia was associated with severe asthma, nonallergic asthma, asthma with fixed airflow limitation, and older adult asthma phenotypes at baseline. In addition, dyslipidemia was associated with increased frequencies of severe AEs and moderate to severe AEs during the 12-month follow-up. In sensitivity analyses, after excluding the patients who were receiving statins, results did not differ significantly from those of the main analysis. We identified the clinical relevance of dyslipidemia, which is associated with specific asthma phenotypes and increased AEs, independent of other components of metabolic syndrome. These findings highlight the importance of considering dyslipidemia as an "extrapulmonary trait" in asthma management.

Sub-stratification of type-2 high airway disease for therapeutic decision-making: A 'bomb' (blood eosinophils) meets 'magnet' (FeNO) framework.

Sub-stratification of type-2 high airway disease for therapeutic decision-making: A 'bomb' (blood eosinophils) meets 'magnet' (FeNO) framework.

The Racial and Ethnic Makeup of the Asthma Clinical Trials informing the 2020 NHLBI asthma guidelines update

Black/African American and Hispanic people in the United States are disproportionately impacted by asthma with increased prevalence, morbidity, and mortality. However, these groups are often under-represented in asthma clinical and translational research studies which is a barrier to achieving health equity. We describe the racial/ethnic makeup of participants in clinical trials which informed the recent 2020 National Heart, Lung, and Blood Institute (NHLBI) asthma management guidelines focused update.

Screening Social Determinants of Health in a Multidisciplinary Severe Asthma Clinical Program.

Patients with 2 or more ED visits in the past 6 months or 2 or more hospitalizations in the previous year were recruited to Rady Children's Hospital Severe Asthma Clinic. A multidisciplinary team evaluated each patient systematically. A subset of patients on capitated Medicaid insurance plans also had a comprehensive asthma home visit with community health workers as part of the Community Approach to Severe Asthma (CASA) program. A significant reduction in ED visits (75%, P < 0.001) and hospitalization days (73%, P < 0.001) was demonstrated in 74 Severe Asthma Clinic participants with 1 year of pre-/postdata to analyze. In a subset of 12 patients in the CASA program, further reductions in ED visits (90%, P = 0.002) were also demonstrated. Basic needs, including shelter, food, and assistance with utilities, were the most common domain of SDH identified and addressed in CASA participants. We demonstrate that a novel pediatric severe asthma clinic with a multidisciplinary approach, including actively addressing SDH, is associated with decreasing health care utilization.

Variation in Asthma Clinical Trial Results by Environmental and Socioeconomic Exposures

PDS 64: Health impact assessment and environmental justice, Johan Friso Foyer, Floor 1, August 26, 2019, 1:30 PM - 3:00 PM Randomized clinical trials (RCTs) are generally considered the gold standard in medical research; by randomizing participants to treatment and control arms, they maximize internal validity and reduce between-group biases. RCTs, however, do not routinely examine variation by environmental and social exposures, which may impact clinical outcomes, treatment response, and generalizability. To assess whether variation in socioeconomic positon (SEP) and environmental exposures modify treatment response, we have developed and applied Geographic Information Systems (GIS)-based methods to three RCTs performed by the NIH AsthmaNet network, which is recruiting and implementing RCTs using the same protocols across 17 U.S. cities. In preliminary analyses, we have found that: (1) compared to race-specific U.S. averages, blacks recruited into AsthmaNet disproportionately live in impoverished census tracts; recruited whites disproportionately live in wealthier tracts. (2) At baseline, traffic density and SEP predicted variation in lung function, in the hypothesized directions. (3) In one trial, we found that near-residence roadway density explained greater variation in asthma symptoms than did corticosteroid use, and that children in higher-poverty areas had significantly shorter times to first corticosteroid use. We are now refining analyses of effect modification by near-residence roadway traffic and noise exposures, neighborhood violent crime, and health care access. Using spatial analysis and GIS to understand the lived context of RCT participants – better accounting for socioeconomic and environmental factors – may improve the interpretability and applicability of RCT results, by more clearly identifying subpopulations for whom a given intervention may be most effective.

Exacerbation-prone asthma in the context of race and ancestry in Asthma Clinical Research Network trials

Minority groups of African descent experience disproportionately greater asthma morbidity compared with other racial groups, suggesting that genetic variation from a common ancestry could influence exacerbation risk. We evaluated clinical trial measures in the context of self-reported race and genetic ancestry to identify risk factors for asthma exacerbations. One thousand eight hundred forty multiethnic subjects from 12 Asthma Clinical Research Network and AsthmaNet trials were analyzed for incident asthma exacerbations with Poisson regression models that included clinical measures, self-reported race (black, non-Hispanic white, and other), and estimates of global genetic African ancestry in a subgroup (n=760). Twenty-four percent of 1840 subjects self-identified as black. Black and white subjects had common risk factors for exacerbations, including a history of 2 or more exacerbations in the previous year and FEV1 percent predicted values, whereas chronic sinusitis, allergic rhinitis, and gastroesophageal reflux disease were only associated with increased exacerbation risk in black subjects. In the combined multiethnic cohort, neither race (P=.30) nor percentage of genetic African ancestry as a continuous variable associated with exacerbation risk (adjusted rate ratio [RR], 1.26 [95% CI, 0.94-1.70; P=.13]; RR per 1-SD change [32% ancestry], 0.97 [95% CI, 0.78-1.19; P=.74]). However, in 161 black subjects with genetic data, those with African ancestry greater than the median (≥82%) had a significantly greater risk of exacerbation (RR, 3.06 [95% CI, 1.09-8.6; P=.03]). Black subjects have unique risk factors for asthma exacerbations, of which global African genetic ancestry had the strongest effect.

Identifying an at-risk population for poor asthma outcomes: Data from the American Lung Association Asthma Clinical Trials Registry

Identifying an at-risk population for poor asthma outcomes: Data from the American Lung Association Asthma Clinical Trials Registry

Editorial introductions

Editorial introductions

Discovering Pediatric Asthma Phenotypes on the Basis of Response to Controller Medication Using Machine Learning

Pediatric asthma has variable underlying inflammation and symptom control. Approaches to addressing this heterogeneity, such as clustering methods to find phenotypes and predict outcomes, have been investigated. However, clustering based on the relationship between treatment and clinical outcome has not been performed, and machine learning approaches for long-term outcome prediction in pediatric asthma have not been studied in depth. Our objectives were to use our novel machine learning algorithm, predictor pursuit (PP), to discover pediatric asthma phenotypes on the basis of asthma control in response to controller medications, to predict longitudinal asthma control among children with asthma, and to identify features associated with asthma control within each discovered pediatric phenotype. We applied PP to the Childhood Asthma Management Program study data (n = 1,019) to discover phenotypes on the basis of asthma control between assigned controller therapy groups (budesonide vs. nedocromil). We confirmed PP's ability to discover phenotypes using the Asthma Clinical Research Network/Childhood Asthma Research and Education network data. We next predicted children's asthma control over time and compared PP's performance with that of traditional prediction methods. Last, we identified clinical features most correlated with asthma control in the discovered phenotypes. Four phenotypes were discovered in both datasets: allergic not obese (A+/O-), obese not allergic (A-/O+), allergic and obese (A+/O+), and not allergic not obese (A-/O-). Of the children with well-controlled asthma in the Childhood Asthma Management Program dataset, we found more nonobese children treated with budesonide than with nedocromil (P = 0.015) and more obese children treated with nedocromil than with budesonide (P = 0.008). Within the obese group, more A+/O+ children's asthma was well controlled with nedocromil than with budesonide (P = 0.022) or with placebo (P = 0.011). The PP algorithm performed significantly better (P < 0.001) than traditional machine learning algorithms for both short- and long-term asthma control prediction. Asthma control and bronchodilator response were the features most predictive of short-term asthma control, regardless of type of controller medication or phenotype. Bronchodilator response and serum eosinophils were the most predictive features of asthma control, regardless of type of controller medication or phenotype. Advanced statistical machine learning approaches can be powerful tools for discovery of phenotypes based on treatment response and can aid in asthma control prediction in complex medical conditions such as asthma.

RAD: Reactive Airways Disease or Really Asthma Disease?

* Abbreviation: RAD — : reactive airways disease A resident presenting on rounds introduces her patient as “a 15-month-old with RAD. He’s had 2 days of wheezing, and we started albuterol and steroids.” A presentation like this is frequently heard on pediatric units despite the vagueness of the term “reactive airways disease,” commonly referred to as “RAD.” The term is often used as a substitute for asthma in young children on asthma medications when pediatricians are reticent to use the “A word.” Yet RAD has no accepted definition and does not add any specificity to the medical vocabulary. The reluctance to use the term “asthma” in a patient in whom asthma medications are being administered, no matter the age, is perplexing. In a field whose terminology is extensive enough to constitute its own language, it is surprising that we have allowed such a term to slip into the medical lexicon. Recently, members of the Canadian Thoracic Society Asthma Clinical Assembly partnered with the Canadian Pediatric Society to reevaluate clinical practice surrounding the diagnosis and management of asthma in preschoolers.1 Their position paper asserts that RAD, and other vague and nondiagnostic terms, be abandoned. Accordingly, we call on the analogous pediatric and respiratory societies in the United States and around the world to discourage the continued use of “RAD” across medical settings and … Address correspondence to Lindsey C. Douglas, MD, MS, Department of Pediatrics, The Children’s Hospital at Montefiore, 3415 Bainbridge Ave, Bronx, NY 10467. E-mail: douglas{at}montefiore.org

Patients With Moderate And Severe Asthma Are Physically Actives, But Present Poor Aerobic Fitness

BACKGROUND: The levels of physical activity are extensively studied in COPD than in asthmatic patients. PURPOSE: To quantify the level physical activity in patients with moderate and severe asthma. METHODS: In this study were randomly chosen 45 asthmatic patients clinically treated at least 5 years in a Department of Pneumology (School of Medicine, University of Sao Paulo) and without using oral corticosterone and at least one month. Outcomes: lung function (Spirometer KoKo), clinical control (by Asthma Control Test (ACT), Asthma Clinical Questionnaire-(ACQ)6 and 7), quality life by Asthma Quality of Life Questionnaire (AQLQ), VO2peak (cardiopulmonary exercise test (CPET), Carefusion System), and levels of physical activity measured by accelerometer PW610 (Yamax) during 7 consecutive days. RESULTS: The Table 1 showed that the patients present a poor asthma clinical control (disease controlled=4%; partially controlled= 22%; Uncontrolled= 73% by ACQ-7) and lung function reduced. Curiously, the asthmatics seems to present a life style active when observed the total steps per day (12,500 (26.6%), and the moderate steps per day (< 4000 (24%), 4000 to 7499 (69%), and 7500 to 10,000 (7%)) too (Graphic 1). However, the patients had a poor physical conditioning (classification: Very Poor =71,1%; Poor= 20.6%; Fair= 6.66%; Good=1%) (Graphic 2). CONCLUSION: Asthmatic are physically active, however, these patients have low aerobic fitness, which is likely to affect the clinical management of the disease. The recommendation is to include patients in the fitness program which could induces improvements in the physical capacity and in the clinical control too.

Effect of a Soy Isoflavone Supplement on Lung Function and Clinical Outcomes in Patients With Poorly Controlled Asthma: A Randomized Clinical Trial

A number of studies have suggested a potential role for dietary factors as modifiers of asthma severity. This study assessed whether a soy isoflavone supplement improves asthma control in patients with poorly controlled asthma.Three hundred eighty-six subjects ≥12 years old with symptomatic, poorly controlled asthma were enrolled from 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network.In this multicenter, randomized, double-blind, placebo-controlled trial, subjects were randomized (1:1) to receive either a soy isoflavone supplement or placebo twice daily for 6 months. The primary outcome measure was forced expiratory volume in 1 second (FEV1). Secondary outcomes included the Asthma Control Test score, the Asthma Symptoms Utility Index, and the Marx Asthma Quality of Life Questionnaire or Children’s Health Survey for Asthma for participants aged 12 to 16 years. Other outcomes included peak expiratory flow, symptom-free days, and rates of episodes of poor asthma control. Exhaled nitric oxide, peripheral blood eosinophil count, serum interleukin-6, serum C-reactive protein, urinary leukotriene E4, and quantification of total blood genistein level were also assessed.Mean changes in prebronchodilator FEV1 over 6 months were not significantly different between the placebo group (0.03 L, 95% confidence interval: –0.01 to 0.08 L) and the soy isoflavone group (0.01 L; 95% confidence interval: –0.07 to 0.07 L). No differences were observed for the other parameters measures when the placebo group was compared with the soy isoflavone group. Mean plasma genistein level increased from 4.87 to 37.67 ng/mL (P < .001) in participants receiving the supplement.In this study of adolescent and adult patients with poorly controlled asthma, use of a soy isoflavone supplement did not result in improved lung function or clinical outcomes compared with placebo.The authors had previously shown a relationship between dietary intake of the soy isoflavone genistein and improvement in FEV1 in a cross-sectional analysis of participants with varying asthma severity enrolled in a multicenter clinical trial. However, the results of this study do not support the use of soy isoflavone supplementation for patients with poorly controlled asthma. This highlights the limitations of cross-sectional, population-based studies of dietary nutrient intake and the use of surrogate markers of disease to predict clinically relevant outcomes in interventional studies for asthma.

Diagnosis and management of asthma in preschoolers: A Canadian Thoracic Society and Canadian Paediatric Society position paper.

Asthma often starts before six years of age. However, there remains uncertainty as to when and how a preschool-age child with symptoms suggestive of asthma can be diagnosed with this condition. This delays treatment and contributes to both short- and long-term morbidity. Members of the Canadian Thoracic Society Asthma Clinical Assembly partnered with the Canadian Paediatric Society to develop a joint working group with the mandate to develop a position paper on the diagnosis and management of asthma in preschoolers. In the absence of lung function tests, the diagnosis of asthma should be considered in children one to five years of age with frequent (≥8 days/month) asthma-like symptoms or recurrent (≥2) exacerbations (episodes with asthma-like signs). The diagnosis requires the objective document of signs or convincing parent-reported symptoms of airflow obstruction (improvement in these signs or symptoms with asthma therapy), and no clinical suspicion of an alternative diagnosis. The characteristic feature of airflow obstruction is wheezing, commonly accompanied by difficulty breathing and cough. Reversibility with asthma medications is defined as direct observation of improvement with short-acting ß2-agonists (SABA) (with or without oral corticosteroids) by a trained health care practitioner during an acute exacerbation (preferred method). However, in children with no wheezing (or other signs of airflow obstruction) on presentation, reversibility may be determined by convincing parental report of a symptomatic response to a three-month therapeutic trial of a medium dose of inhaled corticosteroids with as-needed SABA (alternative method), or as-needed SABA alone (weaker alternative method). The authors provide key messages regarding in whom to consider the diagnosis, terms to be abandoned, when to refer to an asthma specialist and the initial management strategy. Finally, dissemination plans and priority areas for research are identified.

Impact of Age and Sex on Response to Asthma Therapy.

Age and sex are associated with differences in asthma prevalence and morbidity. To determine if age and sex associate with distinct phenotypes and a variable response to therapy in subjects with mild to moderate asthma. We used Asthma Clinical Research Network data to determine the impact of age and sex on phenotypes and treatment failures among subjects participating in 10 trials from 1993 to 2003. A total of 1,200 subjects were identified (median age, 30.4 yr; male, 520 [43.3%]; female, 680 [56.7%]) and analyzed. A higher proportion of subjects greater than or equal to 30 years old experienced treatment failures (17.3% vs. 10.3%; odds ratio [OR], 1.82; confidence interval [CI], 1.30-2.54; P < 0.001), and rates increased proportionally with increasing age older than 30 across the cohort (OR per yr, 1.02 [CI, 1.01-1.04]; OR per 5 yr, 1.13 [CI, 1.04-1.22]; P < 0.001). Lower lung function and longer duration of asthma were associated with a higher risk of treatment failures. A higher proportion of subjects greater than or equal to 30 years old receiving controller therapy experienced treatment failures. When stratified by specific therapy, treatment failures increased consistently for every year older than age 30 in subjects on inhaled corticosteroids (OR per year, 1.03; CI, 1.01-1.07). Females had a slightly higher FEV1 % predicted (84.5% vs. 81.1%; P < 0.001) but similar asthma control measures. There was not a statistically significant difference in treatment failures between females and males (15.2% vs. 11.7%; P = 0.088). Older age is associated with an increased risk of treatment failure, particularly in subjects taking inhaled corticosteroids. There was no significant difference in treatment failures between sexes.

Genome-Wide Association Study Identifies Novel Pharmacogenomic Loci For Therapeutic Response to Montelukast in Asthma.

BackgroundGenome-wide association study (GWAS) is a powerful tool to identify novel pharmacogenetic single nucleotide polymorphisms (SNPs). Leukotriene receptor antagonists (LTRAs) are a major class of asthma medications, and genetic factors contribute to variable responses to these drugs. We used GWAS to identify novel SNPs associated with the response to the LTRA, montelukast, in asthmatics.MethodsUsing genome-wide genotype and phenotypic data available from American Lung Association - Asthma Clinical Research Center (ALA-ACRC) cohorts, we evaluated 8-week change in FEV1 related to montelukast administration in a discovery population of 133 asthmatics. The top 200 SNPs from the discovery GWAS were then tested in 184 additional samples from two independent cohorts.ResultsTwenty-eight SNP associations from the discovery GWAS were replicated. Of these, rs6475448 achieved genome-wide significance (combined P = 1.97 x 10-09), and subjects from all four studies who were homozygous for rs6475448 showed increased ΔFEV1 from baseline in response to montelukast.ConclusionsThrough GWAS, we identified a novel pharmacogenomic locus related to improved montelukast response in asthmatics.

Effect of a Soy Isoflavone Supplement on Lung Function and Clinical Outcomes in Patients With Poorly Controlled Asthma

Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control. To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult patients with poorly controlled disease. Multicenter, randomized, double-blind, placebo-controlled trial conducted between May 2010 and August 2012 at 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network. Three hundred eighty-six adults and children aged 12 years or older with symptomatic asthma while taking a controller medicine and low dietary soy intake were randomized, and 345 (89%) completed spirometry at week 24. Participants were randomly assigned to receive soy isoflavone supplement containing 100 mg of total isoflavones (n=193) or matching placebo (n=193) in 2 divided doses administered daily for 24 weeks. The primary outcome measure was change in forced expiratory volume in the first second (FEV1) at 24 weeks. Secondary outcome measures were symptoms, episodes of poor asthma control, Asthma Control Test score (range, 5-25; higher scores indicate better control), and systemic and airway biomarkers of inflammation. Mean changes in prebronchodilator FEV1 over 24 weeks were 0.03 L (95% CI, -0.01 to 0.08 L) in the placebo group and 0.01 L (95% CI, -0.07 to 0.07 L) in the soy isoflavone group, which were not significantly different (P = .36). Mean changes in symptom scores on the Asthma Control Test (placebo, 1.98 [95% CI, 1.42-2.54] vs soy isoflavones, 2.20 [95% CI, 1.53-2.87]; positive values indicate a reduction in symptoms), number of episodes of poor asthma control (placebo, 3.3 [95% CI, 2.7-4.1] vs soy isoflavones, 3.0 [95% CI, 2.4-3.7]), and changes in exhaled nitric oxide (placebo, -3.48 ppb [95% CI, -5.99 to -0.97 ppb] vs soy isoflavones, 1.39 ppb [95% CI, -1.73 to 4.51 ppb]) did not significantly improve more with the soy isoflavone supplement than with placebo. Mean plasma genistein level increased from 4.87 ng/mL to 37.67 ng/mL (P < .001) in participants receiving the supplement. Among adults and children aged 12 years or older with poorly controlled asthma while taking a controller medication, use of a soy isoflavone supplement, compared with placebo, did not result in improved lung function or clinical outcomes. These findings suggest that this supplement should not be used for patients with poorly controlled asthma. clinicaltrials.gov Identifier: NCT01052116.

Diagnostic accuracy of FEV1/forced vital capacity ratio z scores in asthmatic patients

The FEV1/forced vital capacity (FVC) ratio is used as a criterion for airflow obstruction; however, the test characteristics of spirometry in the diagnosis of asthma are not well established. The accuracy of a test depends on the pretest probability of disease. We wanted to estimate the FEV1/FVC ratio z score threshold with optimal accuracy for the diagnosis of asthma for different pretest probabilities. Asthmatic patients enrolled in 4 trials from the Asthma Clinical Research Centers were included in this analysis. Measured and predicted FEV1/FVC ratios were obtained, with calculation of z scores for each participant. Across a range of asthma prevalences and z score thresholds, the overall diagnostic accuracy was calculated. One thousand six hundred eight participants were included (mean age, 39 years; 71% female; 61% white). The mean FEV1 percent predicted value was 83% (SD, 15%). In a symptomatic population with 50% pretest probability of asthma, optimal accuracy (68%) is achieved with a z score threshold of -1.0 (16th percentile), corresponding to a 6 percentage point reduction from the predicted ratio. However, in a screening population with a 5% pretest probability of asthma, the optimum z score is -2.0 (second percentile), corresponding to a 12 percentage point reduction from the predicted ratio. These findings were not altered by markers of disease control. Reduction of the FEV1/FVC ratio can support the diagnosis of asthma; however, the ratio is neither sensitive nor specific enough for diagnostic accuracy. When interpreting spirometric results, consideration of the pretest probability is an important consideration in the diagnosis of asthma based on airflow limitation.