Key findings and clinical implications from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study

Abstract

Patients with severe or difficult-to-treat asthma are an understudied population but account for considerable asthma morbidity, mortality, and costs. The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study was a large, 3-year, multicenter, observational cohort study of 4756 patients (n=3489 adults ≥ 18 years of age, n=497 adolescents 13-17 years of age, and n=770 children 6-12 years of age) with severe or difficult-to-treat asthma. TENOR's primary objective was to characterize the natural history of disease in this cohort. Data assessed semiannually and annually included demographics, medical history, comorbidities, asthma control, asthma-related health care use, medication use, lung function, IgE levels, self-reported asthma triggers, and asthma-related quality of life. We highlight the key findings and clinical implications from more than 25 peer-reviewed TENOR publications. Regardless of age, patients with severe or difficult-to-treat asthma demonstrated high rates of health care use and substantial asthma burden despite receiving multiple long-term controller medications. Recent exacerbation history was the strongest predictor of future asthma exacerbations. Uncontrolled asthma, as defined by the 2007 National Heart, Lung, and Blood Institute guidelines' impairment domain, was highly prevalent and predictive of future asthma exacerbations; this assessment can be used to identify high-risk patients. IgE and allergen sensitization played a role in the majority of severe or difficult-to-treat asthmatic patients.

FIG 1

TENOR study design. *Daily high doses of inhaled steroids were defined by the American Thoracic Society refractory asthma guidelines for adults and by the NHLBI guidelines for children.AEs, Adverseevents.

FIG 2

Rates of HCU by number of long-term controller medications in patients aged 6 to 11 years (left panel), 12-17 years (center panel), and 18 or more years (right panel). Long-term controllers included ICSs, long-acting β-agonists, leukotriene modifiers, methylxanthines, and cromolyn sodium or nedocromil. No statistically significant differences were found in rates of HCU by number of long-term controllers in children and adolescents; *P < .01 for all HCU measures in adults except history of intubation, which was not significant. Adapted from Chipps et al, Copyright (2007), with permission from Elsevier.

FIG 3

Risk of asthma exacerbations at the month 30 visit associated with consistently VPC asthma, as defined by the impairment domain of the NHLBI guidelines. Final adjusted models for hospitalizations and ED visits include prior hospitalizations or ED visits, number of long-term controllers, BMI, allergic triggers, nonallergic triggers, percent predicted FVC, race/ethnicity, and age. Final adjusted models for corticosteroid bursts include prior corticosteroid burst, chronic obstructive pulmonary disease, nonallergic triggers, percent predicted FEV₁/FVC ratio, race/ethnicity, and age. Reprinted from Haselkorn et al, Copyright (2009), with permission from Elsevier.

FIG E1

Physician assessment of treatment difficulty.

FIG E2

Least mean square difference and 95% confidence intervals (low-dose salmeterol/fluticasone combination [SFC] minus never-on-SFC: high-dose SFC minus never-on-SFC) in mean Mini Asthma Quality of Life Questionnaire (miniAQLQ) overall scores at 24 months. ^#Baseline differences between treatment groups, including severity differences, were adjusted with propensity scores; ¶quality of life (QoL) 0.40, P = .0015; ⁺QoL 0.20, P = .0456; §QoL 0.23, P = .0672; ^fQoL 0.01, P = .8915.

FIG E3

Least mean square difference and 95% confidence intervals (low-dose salmeterol/fluticasone combination [SFC] minus never-on-SFC; high-dose SFC minus never-on-SFC) in mean Asthma Therapy Assessment Questionnaire (ATAQ) scores at 24 months. ^#Baseline differences between treatment groups, including severity differences, were adjusted with propensity scores; ¶asthma control –0.46, P < .0001; ⁺asthma control –0.33, P = .0018; §asthma control 0.18, P = .1328; ^fasthma control –0.04, P = .7428.