Phenotypes of severe asthma among children and adolescents in Brazil: a prospective study.
BACKGROUND
The 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.


METHODS
This 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.


RESULTS
We 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).


CONCLUSIONS
Although 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.
Graduate Program in Health Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. wendersonclay@hotmail.com.
Wenderson Clay Correia
WC
de Andrade
Pediatric Pulmonology Unit, University Hospital, Federal University of Minas Gerais, Avenida Alfredo Balena, 190, sala 267, Belo Horizonte, MG, Brazil. laurabl@medicina.ufmg.br.
Laura Maria de Lima Belizário Facury
LM
Lasmar
Pediatric Pulmonology Unit, University Hospital, Federal University of Minas Gerais, Avenida Alfredo Balena, 190, sala 267, Belo Horizonte, MG, Brazil. cristonelliricci@bol.com.br.
Cristiane de Abreu Tonelli
Cde A
Ricci
Pediatric Pulmonology Unit, University Hospital, Federal University of Minas Gerais, Avenida Alfredo Balena, 190, sala 267, Belo Horizonte, MG, Brazil. pauloamcamargos@gmail.com.
Paulo Augusto Moreira
PA
Camargos
ProAR-Center of Excellence in Asthma, Federal University of Bahia School of Medicine, Salvador, Brazil. cruz.proar@gmail.com.
Álvaro A
ÁA
Cruz
D000293:Adolescent; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D001938:Brazil; D001944:Breath Tests; D002648:Child; D015331:Cohort Studies; D003951:Diagnostic Errors; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009569:Nitric Oxide / Q000032:analysis*; D010641:Phenotype; D011446:Prospective Studies; D012720:Severity of Illness Index
D018927:Anti-Asthmatic Agents; D009569:Nitric Oxide