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1.
Eur Respir J ; 55(1)2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31558662

RESUMEN

This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force's questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using a blood eosinophil cut-point ≥150 µL-1 to guide anti-IL-5 initiation in adult patients with severe asthma; 3) suggest considering specific eosinophil (≥260 µL-1) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy; 4) suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4-5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies; 5) suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.


Asunto(s)
Asma , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Asma/tratamiento farmacológico , Eosinófilos , Espiración , Humanos , Óxido Nítrico/análisis , Estados Unidos
2.
Thorax ; 73(9): 813-824, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29871982

RESUMEN

INTRODUCTION: Asthma attacks are responsible for considerable morbidity and may be fatal. We aimed to identify and weight risk factors for asthma attacks in children (5-12 years) in order to inform and prioritise care. METHODS: We systematically searched six databases (May 2016; updated with forward citations January 2017) with no language/date restrictions. Two reviewers independently selected studies for inclusion, assessed study quality and extracted data. Heterogeneity precluded meta-analysis. Weighting was undertaken by an Expert Panel who independently assessed each variable for degree of risk and confidence in the assessment (based on study quality and size, effect sizes, biological plausibility and consistency of results) and then achieved consensus by discussion. Assessments were finally presented, discussed and agreed at a multidisciplinary workshop. RESULTS: From 16 109 records, we included 68 papers (28 cohort; 4 case-control; 36 cross-sectional studies). Previous asthma attacks were associated with greatly increased risk of attack (ORs between 2.0 and 4.1). Persistent symptoms (ORs between 1.4 and 7.8) and poor access to care (ORs between 1.2 and 2.3) were associated with moderately/greatly increased risk. A moderately increased risk was associated with suboptimal drug regimen, comorbid atopic/allergic disease, African-American ethnicity (USA), poverty and vitamin D deficiency. Environmental tobacco smoke exposure, younger age, obesity and low parental education were associated with slightly increased risk. DISCUSSION: Assessment of the clinical and demographic features identified in this review may help clinicians to focus risk reduction management on the high-risk child. Population level factors may be used by health service planners and policymakers to target healthcare initiatives. TRIAL REGISTRATION NUMBER: CRD42016037464.


Asunto(s)
Asma/etiología , Asma/terapia , Asma/diagnóstico , Niño , Humanos , Factores de Riesgo
3.
Thorax ; 73(3): 231-239, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29056600

RESUMEN

BACKGROUND: Children's interstitial lung diseases (chILD) cover many rare entities, frequently not diagnosed or studied in detail. There is a great need for specialised advice and for internationally agreed subclassification of entities collected in a register.Our objective was to implement an international management platform with independent multidisciplinary review of cases at presentation for long-term follow-up and to test if this would allow for more accurate diagnosis. Also, quality and reproducibility of a diagnostic subclassification system were assessed using a collection of 25 complex chILD cases. METHODS: A web-based chILD management platform with a registry and biobank was successfully designed and implemented. RESULTS: Over a 3-year period, 575 patients were included for observation spanning a wide spectrum of chILD. In 346 patients, multidisciplinary reviews were completed by teams at five international sites (Munich 51%, London 12%, Hannover 31%, Ankara 1% and Paris 5%). In 13%, the diagnosis reached by the referring team was not confirmed by peer review. Among these, the diagnosis initially given was wrong (27%), imprecise (50%) or significant information was added (23%).The ability of nine expert clinicians to subcategorise the final diagnosis into the chILD-EU register classification had an overall exact inter-rater agreement of 59% on first assessment and after training, 64%. Only 10% of the 'wrong' answers resulted in allocation to an incorrect category. Subcategorisation proved useful but training is needed for optimal implementation. CONCLUSIONS: We have shown that chILD-EU has generated a platform to help the clinical assessment of chILD. TRIAL REGISTRATION NUMBER: Results, NCT02852928.


Asunto(s)
Enfermedades Pulmonares Intersticiales/diagnóstico , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Sistema de Registros , Reproducibilidad de los Resultados , Adulto Joven
4.
Rev Med Virol ; 27(1)2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27714929

RESUMEN

Vitamin D, in addition to its classical functions in bone homeostasis, has a modulatory and regulatory role in multiple processes, including host defense, inflammation, immunity, and epithelial repair. Patients with respiratory disease are frequently deficient in vitamin D, implying that supplementation might provide significant benefit to these patients. Respiratory viral infections are common and are the main trigger of acute exacerbations and hospitalization in children and adults with asthma and other airways diseases. Respiratory monocytes/macrophages and epithelial cells constitutively express the vitamin D receptor. Vitamin D, acting through this receptor, may be important in protection against respiratory infections. Whether the in vitro findings can be translated into a substantial in vivo benefit still remains uncertain. Here we review the in vitro data on the role of vitamin D in antiviral innate immunity, the data concerning the deficient levels of vitamin D in lung diseases, and the in vivo role of supplementation as protection against respiratory viral infections in healthy individuals and in patients with chronic respiratory diseases. Finally, we suggest ways of improving the effectiveness of vitamin D as an adjuvant in the prevention and treatment of acute respiratory infections.


Asunto(s)
Inmunidad Innata , Infecciones del Sistema Respiratorio/inmunología , Virosis/inmunología , Vitamina D/metabolismo , Humanos , Factores Inmunológicos/metabolismo
10.
J Infect Dis ; 204(7): 996-1002, 2011 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-21881113

RESUMEN

BACKGROUND: Respiratory syncytial virus (RSV) disease severity was thought to be a result of host immunopathology but alternatively may be driven by high-level viral replication. The relationships between RSV load, viral clearance dynamics, and disease severity have not been carefully evaluated. METHODS: Previously healthy RSV-infected children <2 years old were recruited. RSV load was measured in respiratory secretions by fresh quantitative culture over 3 hospital days. Measures of disease severity were hospital admission, duration of hospitalization, requirement for intensive care, and respiratory failure. RESULTS: Multivariate logistic regression models revealed independent predictors of increased duration of hospitalization: male sex, lower weight, and higher viral load on any day. Viral loads at day 3 were more significantly associated with requirement for intensive care and respiratory failure than were viral loads at earlier time points. Faster RSV clearance was independently associated with shorter hospitalization. DISCUSSION: These observations challenge the immunopathology-based pathogenesis paradigm. They also have major therapeutic implications, suggesting that application of antiviral agents early in the disease course, even at a time when viral replication is at its highest, might improve subsequent morbidity by significantly lowering viral load and direct viral cytopathic effects, and aborting the potential downstream immunopathology.


Asunto(s)
Infecciones por Virus Sincitial Respiratorio/fisiopatología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitiales Respiratorios , Carga Viral , Cuidados Críticos , Femenino , Hospitalización , Humanos , Lactante , Tiempo de Internación , Modelos Logísticos , Masculino , Líquido del Lavado Nasal/virología , Estudios Prospectivos , Insuficiencia Respiratoria/etiología , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios/inmunología , Índice de Severidad de la Enfermedad , Factores de Tiempo
11.
J Allergy Clin Immunol Pract ; 10(2): 359-375, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34838706

RESUMEN

The World Health Organization divides severe asthma into three categories: untreated severe asthma; difficult-to-treat severe asthma; and severe, therapy-resistant asthma. The apparent frequency of severe asthma in the general population of asthmatic children is probably around 5%. Upon referral of these children, it is important to evaluate the diagnosis of asthma carefully before modifying management and applying a long-term monitoring plan. Identification of pathophysiologic phenotypes using objective biomarkers is essential in our routine assessments of severe asthma. Although conventional pharmacologic approaches should be attempted first, there is growing recognition that children with difficult-to-treat asthma may have unique clinical phenotypes that may necessitate alternative treatment approaches including asthma biologics. These new medications, especially those with effects on multiple pathologic features of asthma, raise the hope that new treatment strategies could induce remission. Besides introducing new medications, the opportunity for closer monitoring is feasible with advances in digital health. Therefore, we have the opportunity to improve response to medications, individualize treatment, and monitor response along with potential steps to prevent severe asthma.


Asunto(s)
Antiasmáticos , Asma , Antiasmáticos/uso terapéutico , Asma/diagnóstico , Asma/tratamiento farmacológico , Asma/epidemiología , Biomarcadores , Humanos , Fenotipo , Instituciones Académicas
12.
Pediatr Pulmonol ; 57(4): 822-847, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35064651

RESUMEN

INTRODUCTION: Nonadherence to inhaled corticosteroids (ICSs) in children with asthma leads to significant morbidity and mortality. Few adherence interventions have been effective and little is known about what contributes to intervention effectiveness. This systematic review summarizes the efficacy and the characteristics of effective interventions. METHODS: Six databases were systematically searched on October 3, 2020 for randomized control trials measuring adherence to ICS in children with asthma. A narrative synthesis was conducted focusing on intervention efficacy and study reliability. Intervention content was coded based on the National Institute for Health and Care Excellence guidelines for medicines adherence (the Perceptions and Practicalities Approach, PAPA) and behavior change techniques (BCTs), to determine the effective aspects of the intervention. RESULTS: Of 240 studies identified, 25 were eligible for inclusion. Thirteen of the 25 studies were categorized as being highly reliable. Nine of the 13 interventions were effective at increasing adherence and 6 of those met the criteria for a PAPA intervention. Techniques targeting perceptions and practicalities in successful interventions included rewards, reminders, feedback and monitoring of adherence, pharmacological support, instruction on how to take their ICS/adhere, and information about triggers for symptoms and nonadherence. CONCLUSION: Adherence interventions in children with asthma have mixed effectiveness. Effective intervention studies were more frequently of higher quality, were tailored to individuals' perceptual and practical adherence barriers, and used multiple BCTs. However, due to the small number of included studies and varying study design quality, conclusions drawn here are preliminary. Future research is needed to test a PAPA-based intervention with a rigorous study design.


Asunto(s)
Asma , Corticoesteroides/uso terapéutico , Asma/tratamiento farmacológico , Niño , Humanos , Reproducibilidad de los Resultados
13.
Thorax ; 66(2): 157-62, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21199817

RESUMEN

BACKGROUND: Relationships between early deficits of lung function, infant airway pathology and outcome in symptomatic infants are unclear. A study was undertaken to determine the associations between early lung function, airway histology and inflammation in symptomatic infants with the continuance of respiratory symptoms, lung function and subsequent use of inhaled asthma medication at the age of 3 years. METHODS: 53 children who underwent lung function measurements and bronchoscopy following referral to a specialist children's hospital for recurrent lower respiratory symptoms at a mean age of 1 year were followed up at 3 years of age. Assessments were made of respiratory symptoms during the previous year, lung function by oscillometry and atopy by skin prick testing. Individual data on the purchase of asthma medications were obtained from the Social Insurance Institution for the 12 months preceding the follow-up visit. RESULTS: 50 children (94%) were re-evaluated, of whom 40 had ongoing airway symptoms. 11/39 (28%) who underwent successful oscillometry had reduced lung function, 31/50 (62%) used inhaled corticosteroids (ICS) regularly and 12/50 (24%) used ICS intermittently. Abnormal lung function at infancy was associated with ongoing airway symptoms (p<0.001) and with the purchase of ICS (p=0.009) and ß agonists (p=0.002). Reticular basement membrane thickness in infancy and the numbers of mucosal mast cells, but not eosinophils, correlated significantly with the amount of ICS purchased at 3 years (p=0.003 and p=0.018, respectively). CONCLUSIONS: Reduced lung function, thickening of the reticular basement membrane and increased density of mucosal mast cells in infancy are associated with respiratory morbidity and treatment needs at age 3 years in this highly selected group of children.


Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/fisiología , Asma/fisiopatología , Pulmón/fisiopatología , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Asma/patología , Membrana Basal/patología , Biopsia , Bronquios/patología , Broncodilatadores/uso terapéutico , Broncoscopía , Budesonida/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Hipersensibilidad Inmediata/fisiopatología , Lactante , Masculino , Pronóstico , Mucosa Respiratoria/patología , Ruidos Respiratorios/fisiopatología , Pruebas Cutáneas
15.
Eur Respir Rev ; 29(157)2020 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-32699025

RESUMEN

The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease. A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, whole-body plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome.PFTs may be useful in different stages of management of children with suspected or confirmed chILD, but the chILD spectrum is diverse and includes a heterogeneous patient group in all ages. Research studies in well-defined patient cohorts are needed to establish which PFT and outcomes are most relevant for diagnosis, evaluation of disease severity and course, and monitoring individual conditions both for improvement in clinical care and as end-points in future randomised controlled trials.


Asunto(s)
Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/fisiopatología , Pruebas de Función Respiratoria , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino
16.
Pediatr Pulmonol ; 55(5): 1282-1292, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32142219

RESUMEN

Childhood asthma is a huge global health burden. The spectrum of disease, diagnosis, and management vary depending on where children live in the world and how their community can care for them. Global improvement in diagnosis and management has been unsatisfactory, despite ever more evidence-based guidelines. Guidelines alone are insufficient and need supplementing by government support, changes in policy, access to diagnosis and effective therapy for all children, with research to improve implementation. We propose a worldwide charter for all children with asthma, a roadmap to better education and training which can be adapted for local use. It includes access to effective basic asthma medications. It is not about new expensive medications and biologics as much can be achieved without these. If implemented carefully, the overall cost of care is likely to fall and the global future health and life chance of children with asthma will greatly improve. The key to success will be community involvement together with the local and national development of asthma champions. We call on governments, institutions, and healthcare services to support its implementation.


Asunto(s)
Asma , Salud Infantil , Salud Global , Antiasmáticos/uso terapéutico , Asma/diagnóstico , Asma/tratamiento farmacológico , Niño , Participación de la Comunidad , Humanos , Guías de Práctica Clínica como Asunto , Atención Primaria de Salud
17.
Lancet ; 372(9643): 1100-6, 2008 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-18805338

RESUMEN

The long-term solution to the asthma epidemic is thought to be prevention, and not treatment of established disease. Atopic asthma arises from gene-environment interactions, which mainly take place during a short period in prenatal and postnatal development. These interactions are not completely understood, and hence primary prevention remains an elusive goal. We argue that primary-care physicians, paediatricians, and specialists lack knowledge of the role of atopy in early life in the development of persistent asthma in children. In this review, we discuss how early identification of children at high risk is feasible on the basis of available technology and important for potential benefits to the children. Identification of an asthmatic child's atopic status in early life has practical clinical and prognostic implications, and sets the basis for future preventative strategies.


Asunto(s)
Alérgenos/efectos adversos , Asma/etiología , Exposición a Riesgos Ambientales/efectos adversos , Ruidos Respiratorios/etiología , Infecciones del Sistema Respiratorio/complicaciones , Alérgenos/clasificación , Asma/genética , Asma/prevención & control , Niño , Preescolar , Humanos , Hipersensibilidad/complicaciones , Hipersensibilidad/diagnóstico , Fenotipo , Infecciones del Sistema Respiratorio/virología
19.
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