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1.
J Allergy Clin Immunol ; 145(1): 140-146.e9, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622688

RESUMO

BACKGROUND: Morbidity and mortality associated with childhood asthma are driven disproportionately by children with severe asthma. However, it is not known from longitudinal studies whether children outgrow severe asthma. OBJECTIVE: We sought to study prospectively whether well-characterized children with severe asthma outgrow their asthma during adolescence. METHODS: Children with asthma were assessed at baseline with detailed questionnaires, allergy tests, and lung function tests and were reassessed annually for 3 years. The population was enriched for children with severe asthma, as assessed by the American Thoracic Society/European Respiratory Society guidelines, and subject classification was reassessed annually. RESULTS: At baseline, 111 (59%) children had severe asthma. Year to year, there was a decrease in the proportion meeting the criteria for severe asthma. After 3 years, only 30% of subjects met the criteria for severe asthma (P < .001 compared with enrollment). Subjects experienced improvements in most indices of severity, including symptom scores, exacerbations, and controller medication requirements, but not lung function. Surprisingly, boys and girls were equally likely to has resolved asthma (33% vs 29%). The odds ratio in favor of resolution of severe asthma was 2.75 (95% CI, 1.02-7.43) for those with a peripheral eosinophil count of greater than 436 cells/µL. CONCLUSIONS: In longitudinal analysis of this well-characterized cohort, half of the children with severe asthma no longer had severe asthma after 3 years; there was a stepwise decrease in the proportion meeting severe asthma criteria. Surprisingly, asthma severity decreased equally in male and female subjects. Peripheral eosinophilia predicted resolution. These data will be important for planning clinical trials in this population.


Assuntos
Asma , Índice de Gravidade de Doença , Adolescente , Asma/sangue , Asma/tratamento farmacológico , Asma/patologia , Criança , Eosinófilos , Feminino , Humanos , Contagem de Leucócitos , Estudos Longitudinais , Masculino , Estudos Prospectivos
2.
J Allergy Clin Immunol ; 143(6): 2052-2061, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30635198

RESUMO

BACKGROUND: Despite advances in asthma care, disparities persist. Black patients are disproportionally affected by asthma and also have poorer outcomes compared with white patients. OBJECTIVE: We sought to determine associations between black and white patients and asthma-related health care use, accounting for complex relationships. METHODS: This study was completed as part of the National Heart, Lung, and Blood Institute's Severe Asthma Research Program, a prospective observational cohort. Between November 2012 and February 2015, it enrolled 579 participants 6 years and older with 1 year of observation time and complete data. Inverse probability of treatment weighting was used to balance racial groups with respect to community and family socioeconomic variables and environmental exposure variables. The primary outcome was emergency department (ED) use for asthma. Secondary outcomes included inhaled corticosteroid use, outpatient physician's office visits for asthma, and asthma-related hospitalization. RESULTS: Black patients had greater odds of ED use over 1 year (odds ratio, 2.19; 95% CI, 1.43-3.35) but also differed in the majority (>50%) of baseline variables measured. After statistical balancing of the racial groups, the difference between black and white patients with respect to ED use no longer reached the level of significance. Instead, in secondary analyses black patients were less likely to see an outpatient physician for asthma management (adjusted odds ratio, 0.57; 95% CI, 0.38-0.85). CONCLUSIONS: The disparity in ED use was eliminated after consideration of multiple variables. Social and environmental policies and interventions tailored to black populations with a high burden of asthma are critical to reduction (or elimination) of these disparities.


Assuntos
Asma/etnologia , Asma/terapia , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Adolescente , Adulto , Negro ou Afro-Americano , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , National Heart, Lung, and Blood Institute (U.S.) , Estados Unidos , População Branca , Adulto Jovem
3.
Am J Respir Crit Care Med ; 186(6): 501-7, 2012 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-22773731

RESUMO

RATIONALE: Severe asthma represents 5-10% of all asthma, yet remains problematic and poorly understood. Although it is increasingly recognized as consisting of numerous heterogenous phenotypes, their immunopathology, particularly in the distal airways and interstitium, remains poorly described. OBJECTIVES: To identify the pathobiology of atypical difficult asthma. METHODS: We report 10 from a total of 19 patients (17 women and 2 men) meeting asthma and severe asthma definitions, requiring daily systemic corticosteroid (CS) use, with inconsistent abnormalities on chest computed tomography scans, who underwent video-assisted thoracoscopic biopsies for further diagnosis and management. MEASUREMENTS AND MAIN RESULTS: The pathology of 10 of the 19 cases revealed small airway changes consistent with asthma (eosinophilia, goblet cell hyperplasia), but with the unexpected finding of interstitial nonnecrotizing granulomas. These patients had no evidence for hypersensitivity pneumonitis, but 70% of cases had a personal or family history of autoimmune-like disease. The 10 cases were treated with azathioprine, mycophenolic acid, methotrexate, or infliximab. Nine of 10 showed decreased CS requirements and improved or maintained FEV(1) despite lower CS doses. Of the remaining nine patients, six manifested asthmatic small airway disease, alone or in combination with alveolar septal mononuclear cells, but no granulomas, whereas three manifested other pathologic findings (aspiration, pneumonia, or thromboemboli). CONCLUSIONS: These data suggest that a subset of severe "asthma" manifests a granulomatous pathology, which we term "asthmatic granulomatosis." Although identification of this disease currently requires a thorascopic biopsy, alternative approaches to therapy lead to improvement in outcomes.


Assuntos
Asma/complicações , Asma/patologia , Granuloma do Sistema Respiratório/complicações , Granuloma do Sistema Respiratório/patologia , Corticosteroides/uso terapêutico , Adulto , Idoso , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/patologia , Asma/tratamento farmacológico , Biópsia por Agulha/métodos , Broncodilatadores/uso terapêutico , Estudos de Casos e Controles , Progressão da Doença , Feminino , Seguimentos , Granuloma do Sistema Respiratório/tratamento farmacológico , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Cirurgia Torácica Vídeoassistida/métodos , Toracoscopia , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
4.
Cell Rep Med ; 3(3): 100570, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35492881

RESUMO

A study by Bacharier et al. demonstrated that children with uncontrolled moderate-to-severe asthma with elevated type 2 biomarkers who received dupilumab had fewer exacerbations and better lung function.1 These results highlight precision medicine approaches in pediatric asthma.


Assuntos
Antiasmáticos , Asma , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Biomarcadores , Criança , Humanos , Inflamação/tratamento farmacológico , Medicina de Precisão/métodos
5.
Pediatr Pulmonol ; 57(6): 1447-1455, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35261210

RESUMO

BACKGROUND: Children with severe asthma have substantial morbidity and healthcare utilization. Pediatric severe asthma is a heterogeneous disease, and a multidisciplinary approach can improve the diagnosis and management of these children. METHODS: We reviewed the electronic health records for patients seen in the Severe Asthma Clinic (SAC) at UPMC Children's Hospital of Pittsburgh between August 2012 and October 2019. RESULTS: Of the 110 patients in whom we extracted data, 46% were female, 48% were Black/African American, and 41% had ≥1 admission to the pediatric intensive care unit (PICU) for asthma. Compared to patients without a PICU admission, those with ≥1 PICU admission were more likely to be non-White (64.4% vs. 41.5%, p = 0.031) and more atopic (eosinophil count geometric mean = 673 vs. 319 cells/mm3 , p = 0.002; total IgE geometric mean = 754 vs. 303 KU/L, p = 0.003), and to have lower pre-bronchodilator FEV1 (58.6% [±18.1%] vs. 69.9% [±18.7%], p = 0.002) and elevated FeNO (60% vs. 22%, p = 0.02). In this cohort, 84% of patients were prescribed high-dose ICS/LABA and 36% were on biologics. Following enrollment in the SAC, severe exacerbations decreased from 3.2/year to 2.2/year (p < 0.0001); compared to the year before joining the SAC, in the following year the group had 106 fewer severe exacerbations. CONCLUSIONS: This large cohort of children with severe asthma had a high level of morbidity and healthcare utilization. Patients with a history of PICU admissions for asthma were more likely to be nonwhite and highly atopic, and to have lower lung function. Our data support a positive impact of a multidisciplinary clinic on patients with severe childhood asthma.


Assuntos
Antiasmáticos , Asma , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/terapia , Criança , Estudos de Coortes , Eosinófilos , Feminino , Humanos , Unidades de Terapia Intensiva Pediátrica , Masculino
7.
Pediatrics ; 141(6)2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29773665

RESUMO

Electronic cigarette (e-cigarette) use, or "vaping," is gaining widespread popularity as an alternative to conventional cigarettes among adolescents. Little is known of the health risks of e-cigarette use, especially in children and adolescents. We present a Case Report of a previously healthy 18-year-old woman who presented with dyspnea, cough, and pleuritic chest pain after e-cigarette use. She developed respiratory failure with hypoxia and was intubated, and ultimately met diagnostic criteria for acute respiratory distress syndrome. Chest tubes were placed to drain worsening pleural effusions. Computed tomography of the chest revealed dependent opacities in both lung bases, superimposed smooth interlobular septal thickening, and pleural effusions. Bronchoalveolar lavage revealed cellular debris and reactive mononuclear cells, and cell counts were remarkable for elevated mononuclear cells and eosinophilia. After the results of a workup for an infectious etiology came back negative, the patient was diagnosed with hypersensitivity pneumonitis and intravenous methylprednisolone therapy was initiated. After this the patient rapidly improved, was weaned off vasopressor support, and was extubated. This is the first reported case of hypersensitivity pneumonitis and acute respiratory distress syndrome as a risk of e-cigarette use in an adolescent, and it should prompt pediatricians to discuss the potential harms of vaping with their patients. Hypersensitivity pneumonitis, lipid pneumonia, and eosinophilic pneumonia should be included in the differential diagnosis of patients who exhibit respiratory symptoms after the use of an e-cigarette.


Assuntos
Alveolite Alérgica Extrínseca/etiologia , Sistemas Eletrônicos de Liberação de Nicotina , Síndrome do Desconforto Respiratório/etiologia , Vaping/efeitos adversos , Adolescente , Alveolite Alérgica Extrínseca/terapia , Lavagem Broncoalveolar , Tubos Torácicos , Drenagem , Feminino , Glucocorticoides/uso terapêutico , Humanos , Metilprednisolona/uso terapêutico , Derrame Pleural/etiologia , Derrame Pleural/terapia , Respiração Artificial , Síndrome do Desconforto Respiratório/terapia
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