Key findings and clinical implications from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study
2012; Elsevier BV; Volume: 130; Issue: 2 Linguagem: Inglês
10.1016/j.jaci.2012.04.014
ISSN1097-6825
AutoresBradley E. Chipps, Robert S. Zeiger, Larry Borish, Sally E. Wenzel, Ashley Yegin, Mary Lou Hayden, Dave P. Miller, Eugene R. Bleecker, F. Estelle R. Simons, Stanley J. Szefler, Scott T. Weiss, Tmirah Haselkorn,
Tópico(s)Allergic Rhinitis and Sensitization
ResumoPatients 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. 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. Patients with severe and difficult-to-treat asthma comprise a small portion ( 60% to 80%) received a course of OCS therapy in the 3 months before all follow-up visits. The frequency of OCS courses was significantly higher in those with abnormal than normal lung function in children at the 24-month time point and in adolescents/adults at all time points (Table III).15Zeiger R.S. Chipps B.E. Haselkorn T. Rasouliyan L. Simons F.E. Fish J.E. Comparison of asthma exacerbations in pediatric and adult patients with severe or difficult-to-treat asthma.J Allergy Clin Immunol. 2009; 124: 1106-1108Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar With the exception of month 12 for an FEV1 of 80% or less, the frequency of ED visits or overnight hospitalizations was significantly and clinically meaningfully higher (approximately 2- to 3-fold) in children than in adolescents/adults across both lung function strata. Medication adherence at baseline and at month 12 was not statistically significantly different across age or lung function strata; most patients (90% to 100%) self-reported regular adherence to their medication. These findings demonstrate that asthma exacerbations are frequent in patients with severe or difficult-to-treat asthma, notwithstanding treatment with multiple long-term asthma controllers, management by asthma specialists, and lung function of greater than 80% of predicted values. They also suggest that children with FEV1 values of 80% or less might have more severe disease than adults with similar lung function.Table IIFrequency of exacerbation outcomes in children aged 6 to 11 years and adolescents and adults aged 12 years and older stratified by lung function15Zeiger R.S. Chipps B.E. Haselkorn T. Rasouliyan L. Simons F.E. Fish J.E. Comparison of asthma exacerbations in pediatric and adult patients with severe or difficult-to-treat asthma.J Allergy Clin Immunol. 2009; 124: 1106-1108Abstract Full Text Full Text PDF PubMed Scopus (19) Google ScholarReprinted from Zeiger et al,15Zeiger R.S. Chipps B.E. Haselkorn T. Rasouliyan L. Simons F.E. Fish J.E. Comparison of asthma exacerbations in pediatric and adult patients with severe or difficult-to-treat asthma.J Allergy Clin Immunol. 2009; 124: 1106-1108Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar Copyright (2009), with permission from Elsevier.FEV1 (% predicted ≤80%)FEV1 (% predicted >80%)Age 6-11 y (n = 34)Age ≥12 y (n = 1081)P value∗P values compare differences between age groups.Age 6-11 y (n = 187)Age ≥12 y (n = 645)P value∗P values compare differences between age groups.ED visit or hospitalization (%) 12 mo14.79.9.38†Derived from the Fisher exact test; other P values were derived from the Pearson χ2 test.11.35.9.01 18 mo23.18.8.03†Derived from the Fisher exact test; other P values were derived from the Pearson χ2 test.11.95.4.004 24 mo22.28.7.03†Derived from the Fisher exact test; other P values were derived from the Pearson χ2 test.13.45.1.001OCS course (%) 12 mo41.236.4.5726.324.1.53 18 mo26.931.4.6222.821.8.80 24 mo51.930.7.0226.122.6.39∗ P values compare differences between age groups.† Derived from the Fisher exact test; other P values were derived from the Pearson χ2 test. Open table in a new tab Table IIIFrequency of exacerbation outcomes in lung function groups stratified by children aged 6 to 11 years and adolescents and adults aged 12 years and older15Zeiger R.S. Chipps B.E. Haselkorn T. Rasouliyan L. Simons F.E. Fish J.E. Comparison of asthma exacerbations in pediatric and adult patients with severe or difficult-to-treat asthma.J Allergy Clin Immunol. 2009; 124: 1106-1108Abstract Full Text Full Text PDF PubMed Scopus (19) Google ScholarAge 6-11 yAge ≥12 yFEV1 % predicted ≤80% (n = 34)FEV1 % predicted >80% (n = 187)P value∗P values compare differences between lung function groups.FEV1 % predicted ≤80% (n = 1081)FEV1 % predicted >80% (n = 645)P value∗P values compare differences between lung function groups.ED visit or hospitalization (%) 12 mo14.711.3.57†Derived from the Fisher exact test; other P values were derived from the Pearson χ2 test.9.95.9.004 18 mo23.111.9.13†Derived from the Fisher exact test; other P values were derived from the Pearson χ2 test.8.85.4.01 24 mo22.213.4.24†Derived from the Fisher exact test; other P values were derived from the Pearson χ2 test.8.75.1.02OCS course (%) 12 mo41.226.3.0836.424.1<.001 18 mo26.922.8.6431.421.8<.001 24 mo51.926.1.00730.722.6.001∗ P values compare differences between lung function groups.† Derived from the Fisher exact test; other P values were derived from the Pearson χ2 test. Open table in a new tab The less than optimal response to asthma medications in the TENOR cohort was further evidenced by assessing symptom control with the validated Asthma Therapy Assessment Questionnaire (ATAQ).16Asthma Therapy Assessment Questionnaire (ATAQ). Merck & Co Inc, West Point (PA)1997-1999Google Scholar Of 2942 adults examined at enrollment, 32.2% (n = 946) reported 3 or 4 asthma control problems17Sullivan S.D. Wenzel S.E. Bresnahan B.W. Zheng B. Lee J.H. Pritchard M. et al.Association of control and risk of severe asthma-related events in severe or difficult-to-treat asthma patients.Allergy. 2007; 62: 655-660Crossref PubMed Scopus (66) Google Scholar and, compared with those with no control problems (17.0%, n = 501), were at greater risk for unscheduled office visits (relative risk [RR], 2.8; 95% CI, 2.4-3.2), OCS bursts (RR, 2.9; 95% CI, 2.5-3.3), ED visits (RR, 4.1; 95% CI, 2.7-6.2), or hospitalization (RR, 13.6; 95% CI, 7.4-24.9). These findings showed that poorer levels of asthma control were associated with greater risk of severe asthma-related events. In a direct assessment of response to high-dose (500/50 μg) and low-dose (100/50 or 250/50 μg) fluticasone and salmeterol combination (FSC) compared with patients who never used FSC over a 2-year period, many of the adjusted asthma-related health outcomes were comparable between the high-dose FSC and the never-on-FSC group. The low-dose FSC group had significantly more favorable 24-month outcomes than the never-on-FSC group, including asthma-related QoL and asthma control (see Fig E2, Fig E3 in this article's Online Repository at www.jacionline.org).18Campbell J.D. Borish L. Haselkorn T. Rasouliyan L. Lee J.H. Wenzel S.E. et al.The response to combination therapy treatment regimens in severe/difficult-to-treat asthma.Eur Respir J. 2008; 32: 1237-1242Crossref PubMed Scopus (15) Google Scholar These data suggest limited clinical benefit with high-dose FSC. They also suggest that the benefits derived from FSC were optimally achieved by using low-dose FSC and that incremental doses of FSC did not provide added clinical benefit in the population with severe or difficult-to-treat asthma. This is consistent with other studies showing a lack of dose response with FSC19Aubier M. Pieters W.R. Schlosser N.J. Steinmetz K.O. Salmeterol/fluticasone propionate (50/500 microg) in combination in a Diskus inhaler (Seretide) is effective and safe in the treatment of steroid-dependent asthma.Respir Med. 1999; 93: 876-884Abstract Full Text PDF PubMed Scopus (148) Google Scholar, 20Bateman E.D. Homer A. Boushey J.B. Busse W.W. Clark T.J.H. Pauwels R.A. et al.Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL Study.Am J Respir Crit Care Med. 2004; 170: 836-844Crossref PubMed Scopus (1497) Google Scholar, 21Szefler S.J. Martin R.J. King T.S. Boushey H.A. Cherniack R.M. Chinchilli V.M. et al.Significant variability in response to inhaled corticosteroids for persistent asthma.J Allergy Clin Immunol. 2002; 109: 410-418Abstract Full Text Full Text PDF PubMed Scopus (540) Google Scholar and supports the role of persistent airflow limitation (PAFL), molecular mechanisms of corticosteroid resistance, a steroid-insensitive form of inflammation, or distal lung inflammation not accessible to inhaled medications in the population with difficult-to-treat asthma. Prospective studies evaluating the effect of asthma control on asthma-related QoL have been scarce, particularly those that assess QoL differences based on disease severity. One TENOR analysis used the Mini-Asthma Quality of Life Questionnaire22Juniper E.F. Guyatt G.H. Cox F.M. Ferrie P.J. King D.R. Development and validation of the Mini Asthma Quality of Life Questionnaire.Eur Respir J. 1999; 14: 32-38Crossref PubMed Scopus (600) Google Scholar and EuroQoL 5D23Mathews W.C. May S. EuroQol (EQ-5D) measure of quality of life predicts mortality, emergency department utilization, and hospital discharge rates in HIV-infected adults under care.Health Qual Life Outcomes. 2007; 5: 5Crossref PubMed Scopus (69) Google Scholar to assess QoL in 987 adults.24Chen H. Gould M.K. Blanc P.D. Miller D.P. Kamath T.V. Lee J.H. et al.Asthma control, severity, and quality of life: quantifying the effect of uncontrolled disease.J Allergy Clin Immunol. 2007; 120: 396-402Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar An inverse relationship was found between the number of asthma control problems and QoL: poorer control at enrollment predicted poorer QoL at follow-up. The number of asthma control problems was identified as a strong independent predictor of disease-specific QoL. General health status assessed by using the EuroQoL-5D was a better longitudinal predictor of health status than asthma severity (assessed by using the Global Initiative for Asthma guidelines10Global Initiative for Asthma (GINA), National Heart, Lung, and Blood Institute (NHLBI) Global Strategy for asthma management and preven
Referência(s)