Abstract
BackgroundThe morbidity associated with severe uncontrolled asthma is disproportionately higher in low- and middle-income countries than in high-income countries. The aim of this study was to describe the phenotypic characteristics of difficult-to-treat severe asthma and treatment-resistant severe asthma in a sample of children and adolescents in Brazil.MethodsThis was a prospective study, conducted between 2010 and 2014, following 61 patients (6–18 years of age) who had been diagnosed with severe uncontrolled asthma. The patients were classified and managed in accordance with the World Health Organization asthma follow-up protocol, which calls for re-evaluations of the diagnosis, level of control (functional and clinical), comorbidities, inhaler technique, and environmental factors, together with adjustment of the treatment to achieve a target level of control. We assessed pulmonary function, measured fractional exhaled nitric oxide, and performed sputum cytology. After the target rate of ≥ 80% adherence to inhaled corticosteroid treatment had been reached and all of the re-evaluations had been performed, the patients incorrectly diagnosed with severe uncontrolled asthma were excluded and the remaining patients were classified as having treatment-resistant or difficult-to-treat severe asthma.ResultsWe found that, of the 61 patients evaluated, 10 had been misdiagnosed (i.e., they did not have asthma), 15 had moderate asthma, and 36 had severe uncontrolled asthma. Among those 36 patients, the asthma was classified as treatment-resistant in 20 (55.6%) and as difficult-to-treat in 16 (44.4%). In comparison with the patients with difficult-to-treat severe asthma, those with treatment-resistant severe asthma showed a higher median level of fractional exhaled nitric oxide (40 ppb vs. 12 ppb; P < 0.037) and a lower median forced expiratory volume in one second (61% vs. 87%; P < 0.001).ConclusionsAlthough patients with treatment-resistant severe asthma cannot always be distinguished from those with difficult-to-treat severe asthma on the basis of baseline clinical characteristics, reduced airflow and elevated fractional exhaled nitric oxide are factors that could distinguish the two groups. Patients diagnosed with severe uncontrolled asthma should be re-evaluated on a regular basis, in order to exclude other diagnoses, to reduce exacerbations, and to identify patients with persistent airflow limitation.
Highlights
The morbidity associated with severe uncontrolled asthma is disproportionately higher in low- and middle-income countries than in high-income countries
All of the patients had uncontrolled asthma and were taking high doses of inhaled corticosteroid (ICS), which is characteristic of severe uncontrolled asthma
Conclusions patients seen at a referral center for severe asthma constitute a relatively homogeneous group, higher fractional exhaled nitric oxide (FeNO) levels and greater impairment of pulmonary function at baseline are suggestive of treatmentresistant severe asthma
Summary
The morbidity associated with severe uncontrolled asthma is disproportionately higher in low- and middle-income countries than in high-income countries. Severe uncontrolled asthma comprises three categories [1]: untreated severe asthma; difficult-to-treat severe asthma; and treatment-resistant severe asthma Those categories differ in terms of their connotation in the context of public health, as well as in terms of the challenges they pose. Attempts should be made to determine whether the use of maintenance medications is optimal [1,2,3] The objective of such evaluations is to distinguish patients with treatment-resistant severe asthma, in whom the symptoms remain uncontrolled despite the highest level of recommended treatment or control can be maintained only with the highest level of recommended treatment, from those with difficult-totreat severe asthma, in whom control can be achieved after the removal of reversible risk factors [1]. It is important to make the distinction between treatment-resistant severe asthma and difficult-to-treat severe asthma, in order to avoid unnecessary invasive procedures, minimize adverse effects of asthma medications, and hold down health care costs, given that asthma control is possible in patients with difficult-to-treat severe asthma, whereas those with treatment-resistant severe asthma are candidates for clinical trials of other treatment strategies [1,3]
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