Impact of Clinical Characteristics and Biomarkers on Asthma Impairment and Risk Questionnaire Exacerbation Prediction Ability.

BACKGROUND: Complex models combining impairment-based control assessments with clinical characteristics and biomarkers have been developed to predict asthma exacerbations. The composite Asthma Impairment and Risk Questionnaire (AIRQ) with adjustments for demographics (age, sex, race, and body mass index) predicts 12-month exacerbation occurrence similarly to these more complex models. OBJECTIVE: To examine whether AIRQ exacerbation prediction is enhanced when models are adjusted for a wider range of clinical characteristics and biomarkers. METHODS: Patients aged 12 years and older completed monthly online surveys regarding exacerbation-related oral corticosteroid use, emergency department or urgent care visits, and hospitalizations. Univariate logistic regressions to predict exacerbations were performed with sociodemographics, comorbidities, exacerbation history, lung function, blood eosinophils, IgE, and FeNO. Significant (P ≤ .05) variables were included in multivariable logistic regressions with and without AIRQ control categories to predict 12-month exacerbations (log odds ratio [95% Wald confidence interval]). Model performances were compared. RESULTS: Over 12 months, 1,070 patients (70% female; mean [SD] age, 43.9 [19.4] years; 22% non-White; body mass index [SD], 30.6 [8.7]) completed one or more survey (mean [SD], 10.5 [2.8] surveys). In the multivariable analysis, AIRQ control category adjusted for significant clinical characteristics and biomarkers was predictive of one or more exacerbations: odds ratio (95% CI) not well-controlled versus well-controlled: 1.93 (1.41-2.62), very poorly controlled versus well-controlled: 3.81 (2.65-5.47). Receiver operating characteristic area under the curve (AUC) for this more complex model of exacerbation prediction (AUC = 0.72) did not differ from AIRQ (AUC = 0.70). Models with AIRQ performed better than those without AIRQ (AUC = 0.67; P < .05). CONCLUSION: Costly and time-consuming complex modeling with clinical characteristics and biomarkers does not enhance the strong exacerbation prediction ability of AIRQ.

Advancing assessment of asthma control with a composite tool: The Asthma Impairment and Risk Questionnaire.

BACKGROUND: National and international asthma guidelines and reports do not include control tools that combine impairment assessment with exacerbation history in one instrument. OBJECTIVE: To analyze the performance of the composite Asthma Impairment and Risk Questionnaire (AIRQ) in assessing both domains of control and predicting exacerbation risk compared with the Global Initiative for Asthma (GINA) 4-question symptom control tool (GINA SCT), Asthma Control Test (ACT), and physician expert opinion (EO) informed by GINA SCT responses and appraisal of GINA-identified risk factors for poor asthma outcomes. METHODS: Multivariable logistic regressions evaluated AIRQ and GINA SCT as predictors of ACT. McNemar's test compared the proportion of patients categorized at baseline as completely or well-controlled by each assessment but with current impairment or previous-year and subsequent-year exacerbations. RESULTS: The analysis included 1064 patients aged 12 years or older; mean (SD) age 43.8 years (19.3); 70% female; 79% White; and 6% Hispanic or Latino. AIRQ and GINA SCT were highly predictive of ACT well-controlled vs not well-controlled and very poorly controlled (receiver operator characteristic area under curve AIRQ = 0.90, GINA SCT = 0.86, P = .03 AIRQ vs GINA SCT) and ACT very poorly controlled vs well-controlled and not well-controlled asthma (receiver operator characteristic area under curve AIRQ = 0.91, GINA SCT = 0.87, P = .01 AIRQ vs GINA SCT). AIRQ rated fewer patients as having completely or well-controlled asthma who had current impairment (P < .01) or with previous-year and subsequent-year exacerbations (P < .001) than did GINA SCT, ACT, and EO. CONCLUSION: AIRQ performs better in assessing both domains of current control and predicting exacerbation risk than do control tools and EO informed by GINA SCT and risk factors for poor asthma outcomes.

Assessing meaningful change in the Asthma Impairment and Risk Questionnaire.

BACKGROUND: The Asthma Impairment and Risk Questionnaire (AIRQ) is a 10-item, yes/no, equally weighted control tool. Lower scores indicate better control. Moreover, 7 impairment items reflect previous 2-week symptoms, and 3 risk items assess previous 12-month exacerbations. The Follow-up AIRQ for use between annual assessments has a 3-month recall period for exacerbation items. OBJECTIVE: To evaluate the responsiveness of the AIRQ over time and identify a minimal important difference (MID). METHODS: The AIRQ longitudinal study data were analyzed from patients with asthma aged 12 years and older. Anchor-based methods assessed differences in AIRQ scores relative to Patient Global Impression of Change, the accepted MIDs for St. George's Respiratory Questionnaire and Asthma Control Test, and exacerbation occurrence over 12 months. Baseline and 12-month data reflected 12-month recall AIRQ scores; Follow-up AIRQ scores were used for 3-, 6-, and 9-month analyses. RESULTS: A total of 1070 patients were included. The Patient Global Impression of Change rating of "much improved" was associated with AIRQ mean score changes from baseline to months 3, 6, 9, and 12 of -2.0, -1.9, -1.9, and -1.8, respectively. The mean AIRQ score change among patients who met the St. George's Respiratory Questionnaire MID (≥4-point decrease) was -1.8 at 6 and 12 months. The AIRQ mean scores decreased from baseline by -2.2 to -2.5 points at months 3, 6, 9, and 12 for patients who met the Asthma Control Test MID (≥ 3-point increase). A 2-point higher baseline AIRQ score was associated with a 1.7 odds ratio of 12-month exacerbation occurrence (95% CI, 1.53-1.89). CONCLUSION: A change score of 2 is recommended as the AIRQ MID.

The Asthma Impairment and Risk Questionnaire enhances the assessment of asthma control.

BACKGROUND: Asthma control is often overestimated in routine practice, and despite advances in the understanding of immunopathology and the availability of new precision therapies, the burden of disease remains unacceptably high. OBJECTIVE: To compare the performance of the Asthma Impairment and Risk Questionnaire (AIRQ) with patient and physician assessments and the Asthma Control Test (ACT) in identifying asthma control. METHODS: Baseline data from a longitudinal study of the AIRQ were analyzed. Patients with asthma in the United States aged 12 years and older followed in 24 specialty practices and 1 specialty-affiliated primary care clinic were enrolled between May and November 2019. At entry, participants completed AIRQ and ACT, and participants and physicians completed 5-point Likert scale assessments of control. RESULTS: A total of 1112 participants were enrolled (mean [SD] age = 43.9 [19.3] years, 70% of the female sex, 78% White). Overall, 62% of participants rated themselves as well- or completely controlled, and 54% were rated comparably by physicians. The ACT classified 49% of participants as well-controlled, with 35% similarly categorized by AIRQ. Previous-year exacerbations were experienced by 32% of participants who self-rated as well- or completely controlled, 30% who were rated as well- or completely controlled by physicians, and 29% assessed as well-controlled by ACT, but only 15% of those classified as well-controlled by AIRQ. CONCLUSION: The burden of asthma is substantial in patients cared for by asthma specialists, and asthma control is overestimated by patients, physicians, and the symptom-based ACT. The AIRQ assesses risk in addition to symptom control and may serve to improve asthma control determination by assessing previous exacerbations.

Relationship Between Asthma Control as Measured by the Asthma Impairment and Risk Questionnaire (AIRQ) and Patient Perception of Disease Status, Health-Related Quality of Life, and Treatment Adherence.

Purpose: Critical asthma outcomes highlighted in clinical guidelines include asthma-related quality of life, asthma exacerbations, and asthma control. An easy-to-implement measure of asthma control that assesses both symptom impairment and exacerbation risk and reflects the impact of asthma on patients' lives is lacking. Hence, the objective of this study was to assess the Asthma Impairment and Risk Questionnaire (AIRQ®) construct validity relative to patient self-perception of asthma status and validated disease-specific patient-reported outcome (PRO) measures. Patients and methods: Baseline data were analyzed from patients (aged ≥ 12 years) with asthma participating in a 12-month observational study assessing the ability of AIRQ to predict exacerbations. At entry, patients completed a sociodemographic questionnaire, AIRQ, 3 questions addressing self-perceived asthma status, Saint George's Respiratory Questionnaire (SGRQ), mini-Asthma Quality of Life Questionnaire (AQLQ), and Adult Asthma Adherence Questionnaire (AAAQ). Descriptive statistics were calculated for demographic and clinical characteristics. AIRQ construct validity was evaluated by assessing correlations between total AIRQ score and patient self-assessments, SGRQ, mini-AQLQ, and AAAQ scores. Comparisons of SGRQ, mini-AQLQ, and AAAQ total and component/domain scores by AIRQ control category were performed using general linear models and Scheffe's post hoc adjustments for pairwise comparisons. Results: A total of 1112 patients were enrolled: 70% female, 78% White, mean (standard deviation) age 43.9 (19.5) years. There were highly significant correlations between AIRQ score and patient self-perception of overall control (r = 0.69; p < 0.001), total SGRQ (r = 0.74, p < 0.001), and mini-AQLQ (r = -0.78, p < 0.001) scores. As AIRQ control category worsened, so did total and domain SGRQ, mini-AQLQ, and AAAQ impediment-to-inhaled-corticosteroid-adherence scores (all pairwise comparisons p < 0.001). Conclusion: Findings demonstrate the construct validity of AIRQ relative to patient self-perception of asthma status, disease-specific PRO measures, and treatment adherence barriers. AIRQ can be a useful instrument to raise awareness of the unrecognized impacts of asthma on patients' lives.

The Asthma Impairment and Risk Questionnaire (AIRQ) Control Level Predicts Future Risk of Asthma Exacerbations.

BACKGROUND: The Asthma Impairment and Risk Questionnaire (AIRQ) is a 10-item, equally weighted, yes/no control tool validated in patients with asthma aged 12 years and older. OBJECTIVE: To evaluate AIRQ's ability to predict patient-reported exacerbations over 12 months. METHODS: Patients completed a baseline AIRQ during an in-person enrollment visit and reported exacerbations (ie, asthma-related courses of oral corticosteroids, emergency department/urgent care visits, and hospitalizations) via monthly online surveys. Logistic regressions were performed using AIRQ control level (well-controlled [WC], not well-controlled [NWC], very poorly controlled [VPC]), age, sex, race, and body mass index as covariates and 1 or more and 2 or more exacerbations as the dependent variables (adjusted odds ratios [OR] and 95% Wald CIs). Kaplan-Meier analyses of time to first exacerbation by AIRQ control level were performed. RESULTS: A total of 1,112 patients were enrolled; 1,070 completed 1 or more surveys over 12 months (mean ± SD 10.5 ± 2.8 months); 70.5% female; age 43.9 ± 19.3 years; 20.4% non-White; body mass index 30.6 ± 8.7 kg/m2; AIRQ: WC 35.2%, NWC 38.1%, VPC 26.6%. A total of 45.7% of patients reported 1 or more exacerbations and 26.7% 2 or more exacerbations (WC 28.4% ≥ 1, 11.1% ≥ 2; NWC 46.3% ≥ 1, 27.9% ≥ 2; VPC 67.7% ≥ 1, 45.6% ≥ 2). The ORs for 1 or more exacerbations NWC versus WC were 2.1 (CI 1.6-2.9), and VPC versus WC were 4.6 (CI 3.3-6.5). The ORs for 2 or more exacerbations NWC versus WC were 3.1 (CI 2.1-4.6), and VPC versus WC were 6.1 (CI 4.0-9.1). Kaplan-Meier curves demonstrated clear differentiation of time to first exacerbation by AIRQ control level (P < .001). CONCLUSIONS: The AIRQ control level predicts exacerbation risk over 12 months and probability of time to first exacerbation.

Evaluating construct validity of the Asthma Impairment and Risk Questionnaire using a 3-month exacerbation recall.

BACKGROUND: Recurrent assessment of asthma control is essential to evaluating disease stability and intervention impacts. An assessment that can be administered between annual clinic visits is needed. The Asthma Impairment and Risk Questionnaire (AIRQ) is a cross-sectionally validated, 10-item, yes or no, composite control tool evaluating previous 2-week symptoms and previous 12-month exacerbations. OBJECTIVE: To evaluate the construct validity of the AIRQ using a 3-month recall period for exacerbation-based risk questions and retaining the 2-week recall for symptom-based impairment items. METHODS: At baseline, patients completed the AIRQ with 12-month recall exacerbation items, Asthma Control Test (ACT), St. George's Respiratory Questionnaire (SGRQ), and global self-assessments of asthma risk, control, and symptom severity. Patient-reported exacerbations were captured monthly. The AIRQ with 3-month recall exacerbation items, ACT, and global self-assessments was administered at months 3, 6, and 9, and SGRQ at month 6. RESULTS: A total of 1112 patients aged 12 years or older were enrolled (mean [SD] age, 43.9 [19.5] years). The AIRQ and each administration of the AIRQ with 3-month recall exacerbation items classified asthma control similarly to an ACT plus exacerbation validation standard. For both AIRQ versions, SGRQ scores were higher with worsening asthma control (P < .001). At months 3, 6, and 9, worse AIRQ control levels were associated with higher proportions of patients with 1 or more and 2 or more exacerbations in the previous 3 months and patient global self-assessments indicating greater asthma morbidity (all P < .001). CONCLUSION: The AIRQ using exacerbation risk items with a 3-month recall period exhibits construct validity for classifying current asthma control and can be administered between annual AIRQ assessments.

Development of the Asthma Impairment and Risk Questionnaire (AIRQ): A Composite Control Measure.

BACKGROUND: Asthma exacerbation risk increases with worsening asthma control. Prevailing numerical control tools evaluate only current symptom impairment despite the importance of also assessing risk based on exacerbation history. An easy-to-use questionnaire addressing impairment and risk domains of control is needed. OBJECTIVE: To validate a composite asthma control tool that includes impairment and risk assessments (Asthma Impairment and Risk Questionnaire [AIRQ]). METHODS: Four-hundred forty-two patients aged ≥12 years with physician-diagnosed asthma who were followed in specialty practices completed 15 impairment and risk questions with dichotomized yes/no responses. Patients spanned all Global Initiative for Asthma severities and were classified as well-controlled, not well-controlled, or very poorly controlled according to a standard of Asthma Control Test (ACT) score plus prior-year exacerbations. Logistic regression analyses identified questions with the greatest predictive validity to discriminate among patients and determine cut points for these 3 classifications. RESULTS: The final AIRQ comprises 10 equally weighted yes/no impairment and risk questions. The final 10-item models yielded receiver operating characteristic curves of 0.94 to identify well-controlled versus not well-/very poorly controlled and 0.93 to identify well-/not well-controlled versus very poorly controlled asthma, as reflected by the ACT plus prior-year exacerbations standard. Cut points of 0-1, 2-4, and 5-10 best represented well-, not well-, and very poorly controlled asthma. CONCLUSIONS: AIRQ is a rigorously validated composite measure designed to identify adults and adolescents with varying degrees of asthma control. Ongoing investigations will determine test-retest reliability, responsiveness to change, and predictive ability for future exacerbations.

An official American Thoracic Society Workshop report: obesity and asthma.

RATIONALE: The developed world is currently facing an epidemic of obesity. With the increased prevalence of obesity has come the recognition that obesity is a risk factor for asthma. OBJECTIVES: The purpose of this workshop was to bring together experts in the field of asthma, with experts in the field of obesity to review the current state-of-the-art knowledge regarding obesity and asthma, with the goal of furthering our understanding of the link between these two disease entities to help define important future directions for research. METHODS: Speakers were invited to give presentations highlighting recent developments in their area of expertise that were related to obesity and lung disease. These presentations were followed by interactive discussion. A writing committee from among the participants produced a document summarizing the proceedings. MEASUREMENTS AND MAIN RESULTS: The participants found that obesity was a risk factor for asthma in all demographic groups studied. Asthma in the obese may represent a unique phenotype of asthma, with more severe disease that does not respond as well to conventional therapy. Factors that could contribute to the pathogenesis of asthma in the obese include both mechanical factors and altered inflammation and immune responses related to the obese state. CONCLUSIONS: There is an urgent need for research to better understand the mechanisms of asthma in the obese, and to develop new therapies specifically targeted to this unique patient population.

Update on infection and antibiotics in asthma.

Asthma pathogenesis seems to be a result of a complex mixture of genetic and environmental influences. There is evidence that Mycoplasma pneumoniae and Chlamydophila pneumoniae (formerly known as Chlamydia pneumoniae) play a role in promoting airway inflammation that could contribute to the onset and clinical course of asthma. Evidence also indicates that when antimicrobial therapy can eradicate or suppress these organisms, it may be possible to alter the course of the disease. Certain macrolide antibiotics have been shown to improve control of asthma symptoms and lung function in patients diagnosed with acute C. pneumoniae or M. pneumoniae infection. Positive polymerase chain reaction studies for C. pneumoniae or M. pneumoniae are needed to select asthma patients for chronic treatment. Macrolide antibiotics may also have independent anti-inflammatory activity that may be useful in the management of asthma and other inflammatory diseases.

Recent insight into obesity and asthma.

PURPOSE OF REVIEW: The worldwide pandemic of obesity is creating unique challenges for the diagnosis and treatment of asthma. A wealth of epidemiologic literature has established that whereas asthma can lead to obesity, obesity is a risk factor for asthma, but mechanisms are unclear. This review assesses the current understanding of the relationship between obesity and asthma. RECENT FINDINGS: Recent studies are developing a more sophisticated understanding of the possible inflammatory, immunologic, genetic, and mechanical mechanisms underlying the association between obesity and asthma. Obese asthma may be a unique phenotype of asthma, with a more difficult clinical course and altered response to asthma controller therapy. Adipokines such as leptin and adiponectin are thought to be important, but there is new interest in other inflammatory mechanisms related to visceral obesity, insulin resistance, and the metabolic syndrome. SUMMARY: There are still far more questions than answers as to how obesity might cause or worsen asthma. It is clear that weight gain and obesity are particularly troublesome in asthmatics, and clinicians should target these individuals for aggressive intervention. Randomized controlled trials are needed to determine the best treatment approaches for obese asthma, and prospective studies in which both obesity and asthma are well characterized are needed to better understand the underlying mechanisms.

Obesity and asthma.

Population-based studies have defined a significant, bidirectional, dose-dependent association between obesity and asthma. Obesity does not cause airflow obstruction, but can result in pulmonary restriction and a reduction in airway diameter, and that could contribute to airway hyper-responsiveness. Mouse models of asthma have demonstrated that obesity and adipokines can enhance airway hyper-responsiveness, airway inflammation, and allergic responses, but it is unclear whether obesity-associated inflammatory mechanisms are relevant in human asthma. Shared environmental and genetic factors are incompletely understood, but very likely to be relevant. Obese asthma appears to be a distinct and novel phenotype of asthma, associated with a reduction in lung volumes, lack of eosinophilic inflammation, altered response to asthma controller therapy, glucocorticoid resistance, and poor asthma control.

Hypoventilation in asthma and chronic obstructive pulmonary disease.

Chronic hypoventilation is a marker of disease severity in asthma and chronic obstructive pulmonary disease (COPD). The degree to which this predicts severity or objective measures of lung function is variable, and more reliable for COPD than for asthma. Patients with COPD are particularly susceptible to nocturnal hypoventilation, but at-risk patients can be identified by abnormalities in daytime gas exchange. Continuous positive airway pressure and noninvasive ventilation have no demonstrated efficacy in the treatment of chronic hypoventilation solely due to asthma or COPD. There is consensus that early treatment with noninvasive ventilation for acute hypoventilation due to a COPD exacerbation is not only highly effective, but it reduces mortality, the need for endotracheal intubation, and hospital length of stay. There is probable benefit to the use of noninvasive ventilation in acute asthma, but the evidence to support this is far less robust than for COPD.

Body mass and glucocorticoid response in asthma.

RATIONALE: Obesity may alter glucocorticoid response in asthma. OBJECTIVES: To evaluate the relationship between body mass index (BMI, kg/m(2)) and glucocorticoid response in subjects with and without asthma. METHODS: Nonsmoking adult subjects underwent characterization of lung function, BMI, and spirometric response to prednisone. Dexamethasone (DEX, 10(-6) M)-induced mitogen-activated protein kinase phosphatase-1 (MKP-1) and baseline tumor necrosis factor (TNF)-alpha expression were evaluated by polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage cells. The relationship between BMI and expression of MKP-1 and TNF-alpha was analyzed. MEASUREMENTS AND MAIN RESULTS: A total of 45 nonsmoking adults, 33 with asthma (mean [SD] FEV(1)% of 70.7 [9.8]%) and 12 without asthma were enrolled. DEX-induced PBMC MKP-1 expression was reduced in overweight/obese versus lean patients with asthma, with mean (+/- SEM) fold-induction of 3.11 (+/-0.46) versus 5.27 (+/-0.66), respectively (P = 0.01). In patients with asthma, regression analysis revealed a -0.16 (+/-0.08)-fold decrease in DEX-induced MKP-1 per unit BMI increase (P = 0.04). PBMC TNF-alpha expression increased as BMI increased in subjects with asthma, with a 0.27 unit increase in log (TNF-alpha [ng/ml]) per unit BMI increase (P = 0.01). The ratio of PBMC log (TNF-alpha):DEX-induced MKP-1 also increased as BMI increased in patients with asthma (+0.09 +/- 0.02; P = 0.004). In bronchoalveolar lavage cells, DEX-induced MKP-1 expression was also reduced in overweight/obese versus lean patients with asthma (1.36 +/- 0.09-fold vs. 1.76 +/- 0.15-fold induction; P = 0.05). Similar findings were not observed in control subjects without asthma. CONCLUSIONS: Elevated BMI is associated with blunted in vitro response to dexamethasone in overweight and obese patients with asthma.

Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies.

RATIONALE: Although obesity has been implicated as an asthma risk factor, there is heterogeneity in the published literature regarding its role in asthma incidence, particularly in men. OBJECTIVES: To quantify the relationship between categories of body mass index (BMI) and incident asthma in adults and to evaluate the impact of sex on this relationship. METHODS: Online bibliographic databases were searched for prospective studies evaluating BMI and incident asthma in adults. Independent observers extracted data regarding annualized asthma incidence from studies meeting predetermined criteria, within defined categories of normal weight (BMI < 25), overweight (BMI, 25-29.9), and obesity (BMI >or= 30). Data were analyzed by inverse-variance-weighted, random-effects meta-analysis. Stratified analysis between BMI categories and within sex was performed. RESULTS: Seven studies (n=333,102 subjects) met inclusion criteria. Compared with normal weight, overweight and obesity (BMI >or= 25) conferred increased odds of incident asthma, with an odds ratio (OR) of 1.51 (95% confidence interval [CI], 1.27-1.80). A dose-response effect of elevated BMI on asthma incidence was observed; the OR for incident asthma for normal-weight versus overweight subjects was 1.38 (95% CI, 1.17-1.62) and was further elevated for normal weight versus obesity (OR, 1.92; 95% CI, 1.43-2.59; p<0.0001 for the trend). A similar increase in the OR of incident asthma due to overweight and obesity was observed in men (OR, 1.46; 95% CI, 1.05-2.02) and women (OR, 1.68; 95% CI, 1.45-1.94; p=0.232 for the comparison). CONCLUSIONS: Overweight and obesity are associated with a dose-dependent increase in the odds of incident asthma in men and women, suggesting asthma incidence could be reduced by interventions targeting overweight and obesity.

Efficacy of a heat exchanger mask in cold exercise-induced asthma.

STUDY OBJECTIVES: To determine the efficacy of a novel mask device in limiting cold air exercise-induced decline in lung function in subjects with a history of exercise-induced asthma (EIA). SETTING: In spite of appropriate medical therapy, many asthma patients are limited in cold weather activities. DESIGN: In study 1, 13 asthmatic subjects performed two randomized, single-blind treadmill exercise tests while breathing cold air (- 25 to - 15 degrees C) through a placebo or active heat exchanger mask. In study 2, five subjects with EIA performed three treadmill exercise tests while breathing cold air: one test using the heat exchanger mask, one test without the mask but with albuterol pretreatment, and one test with neither the mask nor albuterol pretreatment (unprotected exercise). For all studies, spirometry was performed before and at 5, 15, and 30 min after exercise challenge. PATIENTS: For both studies, a total of 15 subjects with a history of asthma symptoms during cold air exercise were recruited. RESULTS: In study 1, the mean decrease (+/- SE) in FEV1 was 19 +/- 4.9% with placebo, and 4.3 +/- 1.6% with the active device (p = 0.0002). The mean decrease in maximum mid-expiratory flow (FEF(25-75)) was 31 +/- 5.7% with placebo and 4.7 +/- 1.7% with the active device (p = 0.0002). In study 2, the mean decrease in FEV1 was 6.3 +/- 3.9%, 11 +/- 3.7%, and 28 +/- 10% for the heat exchanger mask, albuterol pretreatment, and unprotected exercises, respectively (p = 0.4375 for mask vs albuterol, p = 0.0625 for mask vs unprotected exercise). The mean decrease in FEF(25-75) was 10 +/- 4.8%, 23 +/- 6.0%, and 36 +/- 11%, respectively (p = 0.0625 for mask vs albuterol, p = 0.0625 for mask vs unprotected exercise). CONCLUSIONS: This heat exchanger mask blocks cold exercise-induced decline in lung function at least as effectively as albuterol pretreatment.