BMC Pulmonary Medicine | |
Phenotypes of severe asthma among children and adolescents in Brazil: a prospective study | |
Álvaro A Cruz3  Paulo Augusto Moreira Camargos2  Cristiane de Abreu Tonelli Ricci2  Laura Maria de Lima Belizário Facury Lasmar2  Wenderson Clay Correia de Andrade1  | |
[1] Graduate Program in Health Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil;Pediatric Pulmonology Unit, University Hospital, Federal University of Minas Gerais, Avenida Alfredo Balena, 190, sala 267, Belo Horizonte, MG, Brazil;ProAR-Center of Excellence in Asthma, Federal University of Bahia School of Medicine, Salvador, Brazil | |
关键词: Sputum; Fractional exhaled nitric oxide; Inflammatory biomarkers; Difficult-to-treat asthma; Refractory severe asthma; | |
Others : 1177625 DOI : 10.1186/s12890-015-0029-8 |
|
received in 2014-11-03, accepted in 2015-03-31, 发布年份 2015 | |
【 摘 要 】
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.
【 授权许可】
2015 Andrade et al.; licensee BioMed Central.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150503020427284.pdf | 433KB | download |
【 参考文献 】
- [1]Bousquet J, Mantzouranis E, Cruz AA, Ait-Khaled N, Baena-Cagnani CE, Bleecker ER, et al.: Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organization Consultation on Severe Asthma. J Allergy Clin Immunol 2010, 126:926-38.
- [2]Bush A, Zar HJ: WHO universal definition of severe asthma. Curr Opin Allergy Clin Immunol 2011, 11:115-21.
- [3]Lodrup Carlsen KC, Hedlin G, Bush A, Wennergren G, de Benedictis FM, De Jongste JC, et al.: Assessment of problematic severe asthma in children. Eur Respir J 2011, 37:432-40.
- [4]Sharples J, Gupta A, Fleming L, Bossley CJ, Bracken-King M, Hall P, et al.: Long-term effectiveness of a staged assessment for paediatric problematic severe asthma. Eur Respir J 2012, 40:264-7.
- [5]Konradsen JR, Nordlund B, Lidegran M, Pedroletti C, Grönlund H, van Hage M, et al.: Problematic severe asthma: a proposed approach to identifying children who are severely resistant to therapy. Pediatr Allergy Immunol 2011, 22:9-18.
- [6]Cruz AA, Bousquet PJ: The unbearable cost of severe asthma in underprivileged populations. Allergy 2009, 64:319-21.
- [7]Mallol J, Solé D, Asher I, Clayton T, Stein R, Soto-Quiroz M: On behalf of the Latin American ISAAC Collaborators Group. Prevalence of Asthma Symptoms in Latin America: The International Study of Asthma and Allergies in Childhood (ISAAC) phase three: a global synthesis. Pediatr Pulmonol 2000, 30:439-44.
- [8]Lasmar L, Camargos P, Champs NS, Fonseca MT, Fontes MJ, Ibiapina C, et al.: Adherence rate to inhaled corticosteroids and their impact on asthma control. Allergy 2009, 64(5):784-9.
- [9]Global Strategy for Asthma Management and Prevention. Global initiative for asthma (GINA); 2012. Available from www.ginasthma.org. Date last updated.
- [10]Nathan RA, Sorkness CA, Kosinski M, Schatz M, Li JT, Marcus P, et al.: Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol 2004, 113:59-65.
- [11]Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al.: Standardisation of spirometry. Eur Respir J 2005, 26(2):319-38.
- [12]Polgar G, Promdhat V: Pulmonary function testing in children: techniques and standards. W. B, Sauncers Co, Philadelphia; 1971.
- [13]Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B: Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis 1983, 127(6):725-34.
- [14]Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al.: Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008, 63(Suppl 86):8-160.
- [15]Wilson AM, Dempsey OJ, Sims EJ, Lipworth BJ: A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma. Clin Exp Allergy 2001, 31(4):616-24.
- [16]Camargos P, Ibiapina C, Lasmar L, Cruz AA: Obtaining concomitant control of allergic rhinitis and asthma with a nasally inhaled corticosteroid. Allergy 2007, 62(3):310-6.
- [17]Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, et al.: Practical guide to skin prick tests in allergy to aeroallergens. Allergy 2012, 67:18-24.
- [18]Hamilton RG: Clinical laboratory assessment of immediate-type hypersensitivity. J Allergy Clin Immunol 2010, 125(2 Suppl 2):S284-96.
- [19]Laube BL, Janssens HM, de Jongh FH, Devadason SG, Dhand R, Diot P, et al.: What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011, 37(6):1308-31.
- [20]Bourdin A, Halimi L, Vachier I, Paganin F, Lamouroux A, Gouitaa M, et al.: Adherence in severe asthma. Clin Exp Allergy 2012, 42(11):1566-74.
- [21]Bracken M, Fleming L, Hall P, Stiphout NV, Bossley C, Biggart E, et al.: The importance of nurse-led home visits in the assessment of children with problematic asthma. Arch Dis Child 2009, 94:780-4.
- [22]Efthimiadis A, Spanevello A, Hamid Q, Kelly MM, Linden M, Louis R, et al.: Methods of sputum processing for cell counts, immunocytochemistry and in situ hybridisation. Eur Respir J Suppl 2002, 37:19s-23.
- [23]Lex C, Payne DN, Zacharasiewicz A, Li AM, Wilson NM, Hansel TT, et al.: Sputum induction in children with difficult asthma: safety, feasibility, and inflammatory cell pattern. Pediatr Pulmonol 2005, 39(4):318-24.
- [24]American Thoracic Society Documents. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005;171(8):912–30.
- [25]Hashimoto S, Bel EH: Current treatment of severe asthma. Clin Exp Allergy 2012, 42(5):693-705.
- [26]Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al.: International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014, 43:343-73.
- [27]Franco R, Nascimento HF, Cruz AA, Santos AC, Souza-Machado C, Ponte EV, et al.: The economic impact of severe asthma to low-income families. Allergy 2009, 64(3):478-83.
- [28]Lasmar LM, Camargos PA, Costa LF, Fonseca MT, Fontes MJ, Ibiapina CC, et al.: Compliance with inhaled corticosteroid treatment: rates reported by guardians and measured by the pharmacy. J Pediatr 2007, 83(5):471-6.
- [29]Bush A, Pedersen S, Hedlin G, Baraldi E, Barbato A, de Benedictis F, et al.: Pharmacological treatment of severe, therapy-resistant asthma in children: what can we learn from where? Eur Respir J 2011, 38(4):947-58.
- [30]Bossley CJ, Fleming L, Gupta A, Regamey N, Frith J, Oates T, et al.: Pediatric severe asthma is characterized by eosinophilia and remodeling without T (H)2 cytokines. J Allergy Clin Immunol 2012, 129(4):974-82.
- [31]Palomino AL, Bussamra MH, Saraiva-Romanholo BM, Martins MA, Nunes Mdo P, Rodrigues JC: Induced sputum in children and adolescents with asthma: safety, clinical applicability and inflammatory cells aspects in stable patients and during exacerbation. J Pediatr 2005, 81(3):216-24.
- [32]Cox G: Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes. J Immunol 1995, 154(9):4719-25.
- [33]Tai A, Tran H, Roberts M, Clark N, Wilson J, Robertson CF: The association between childhood asthma and adult chronic obstructive pulmonary disease. Thorax 2014, 0:1-6.
- [34]Bossley CJ, Saglani S, Kavanagh C, Payne DNR, Wilson N, Tsartsali L, et al.: Corticosteroid responsiveness and clinical characteristics in childhood difficult asthma. Eur Respir J 2009, 34:1052-9.
- [35]Vicencio AG, Santiago MT, Tsirilakis K, Stone A, Worgall S, Foley EA, et al.: Fungal sensitization in childhood persistent asthma is associated with disease severity. Pediatr Pulmonol 2014, 49(1):8-14.