Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
Mais filtros












Base de dados
Intervalo de ano de publicação
1.
Contemp Clin Trials Commun ; 39: 101301, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38711836

RESUMO

Cystic fibrosis (CF) is a multisystem, genetic disease with a significantly reduced life expectancy. Despite substantial progress in therapies in the last 10-15 years, there is still no cure. There are dozens of drugs in the development pipeline and multiple clinical trials are being conducted across the globe. The UK Cystic Fibrosis Trust's (CFT) Clinical Trials Accelerator Platform (CTAP) is a national initiative bringing together 25 UK based CF centres to support the CF community in accessing and participating in CF clinical trials. CTAP enables more CF centres to run a broader portfolio of trials and increases the range of CF studies available for UK patients. There are four large specialist CF centres based in London, all within a small geographical region as well as two smaller centres which deliver CF care. At the launch of CTAP, these centres formed a sub-network in a consortium-style collaboration. The purpose of the network was to ensure equity of access to trials for patients across the UK's capital, and to share experience and knowledge. Four years into the programme we have reviewed our practices through working group meetings and an online survey. We sought to identify strengths and areas for improvement. We share our findings here, as we believe they are relevant to others delivering research in regions outside of London and in other chronic diseases.

2.
J Cyst Fibros ; 23(3): 554-560, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38614868

RESUMO

BACKGROUND & AIMS: Cystic Fibrosis (CF) liver disease progresses to liver failure requiring transplantation in about 3 % of patients, 0.7 % of CF patients are post liver transplant. The prognosis of CF has improved with the introduction of elexacaftor/tezacaftor/ivacaftor (ETI). Due to the paucity of data and concerns regarding interactions with immunosuppressive drug regimens, there is no general consensus on use of ETI post liver transplantation. The aim of this review is to report the safety and efficacy of ETI in CF patients who underwent liver transplantation. METHODS: A systematic review was conducted through MEDLINE/Pubmed and EMBASE databases. English-written articles reporting clinical data on liver transplanted CF patients treated with ETI were included. Article quality was evaluated using the Critical Appraisal Checklist for Case Reports. RESULTS: Twenty cases were retrieved from 6 reports. Temporary discontinuation and/or dose reduction due to elevated transaminases was required in 5 cases. ETI restarted on a reduced dose was tolerated in 3 out of 5 patients, 1 patient tolerated full dose. Tacrolimus dose change was required in 14 cases, in 1 case ETI was discontinued due to tacrolimus toxicity. Improvement in percentage predicted FEV1 was noted in 15/19 patients (median +17 %, range 8 %-38 %). CONCLUSIONS: In the majority of liver transplanted patients ETI is well tolerated, although adverse events and liver function abnormalities may occur. Close monitoring of liver function and tacrolimus level is warranted. Significant improvement in lung function after ETI initiation is confirmed, highlighting the importance of accessing this medication for this group of patients.


Assuntos
Aminofenóis , Benzodioxóis , Fibrose Cística , Indóis , Transplante de Fígado , Quinolonas , Humanos , Aminofenóis/uso terapêutico , Aminofenóis/efeitos adversos , Benzodioxóis/uso terapêutico , Benzodioxóis/efeitos adversos , Agonistas dos Canais de Cloreto/uso terapêutico , Agonistas dos Canais de Cloreto/efeitos adversos , Fibrose Cística/cirurgia , Fibrose Cística/tratamento farmacológico , Combinação de Medicamentos , Indóis/efeitos adversos , Indóis/uso terapêutico , Transplante de Fígado/métodos , Transplante de Fígado/efeitos adversos , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Pirróis/uso terapêutico , Pirrolidinas , Quinolonas/uso terapêutico , Quinolonas/efeitos adversos
3.
Clin Immunol ; 259: 109901, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38218209

RESUMO

Chronic human norovirus (HuNoV) infections in immunocompromised patients result in severe disease, yet approved antivirals are lacking. RNA-dependent RNA polymerase (RdRp) inhibitors inducing viral mutagenesis display broad-spectrum in vitro antiviral activity, but clinical efficacy in HuNoV infections is anecdotal and the potential emergence of drug-resistant variants is concerning. Upon favipiravir (and nitazoxanide) treatment of four immunocompromised patients with life-threatening HuNoV infections, viral whole-genome sequencing showed accumulation of favipiravir-induced mutations which coincided with clinical improvement although treatment failed to clear HuNoV. Infection of zebrafish larvae demonstrated drug-associated loss of viral infectivity and favipiravir treatment showed efficacy despite occurrence of RdRp variants potentially causing favipiravir resistance. This indicates that within-host resistance evolution did not reverse loss of viral fitness caused by genome-wide accumulation of sequence changes. This off-label approach supports the use of mutagenic antivirals for treating prolonged RNA viral infections and further informs the debate surrounding their impact on virus evolution.


Assuntos
Amidas , Norovirus , Pirazinas , Vírus , Animais , Humanos , Norovirus/genética , Antivirais/farmacologia , Antivirais/uso terapêutico , Peixe-Zebra , Mutagênese , RNA Polimerase Dependente de RNA/genética , Hospedeiro Imunocomprometido
4.
Pediatr Pulmonol ; 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38131456

RESUMO

Lung transplantation is a recognized therapy for end-stage respiratory failure in children and young people. It is only available in selected countries and is limited by access to suitable organs. Data on disparities in access and outcomes for children undergoing lung transplantation are limited. It is clear from data from studies in adults, and from studies in other solid organ transplants in children, that systemic inequities exist in this field. While data relating specifically to pediatric lung transplantation are relatively sparse, professionals should be aware of the risk that healthcare systems may result in disparities in access and outcomes following lung transplantation in children.

5.
Am J Respir Crit Care Med ; 206(11): 1361-1369, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35816621

RESUMO

Rationale: The triple-combination regimen elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in children aged 6 through 11 years with cystic fibrosis and at least one F508del-CFTR allele in a phase 3, open-label, single-arm study. Objectives: To further evaluate the efficacy and safety of ELX/TEZ/IVA in children 6 through 11 years of age with cystic fibrosis heterozygous for F508del and a minimal function CFTR mutation (F/MF genotypes) in a randomized, double-blind, placebo-controlled phase 3b trial. Methods: Children were randomized to receive either ELX/TEZ/IVA (n = 60) or placebo (n = 61) during a 24-week treatment period. The dose of ELX/TEZ/IVA administered was based on weight at screening, with children <30 kg receiving ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 hours, and children ⩾30 kg receiving ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 hours (adult dose). Measurements and Main Results: The primary endpoint was absolute change in lung clearance index2.5 from baseline through Week 24. Children given ELX/TEZ/IVA had a mean decrease in lung clearance index2.5 of 2.29 units (95% confidence interval [CI], 1.97-2.60) compared with 0.02 units (95% CI, -0.29 to 0.34) in children given placebo (between-group treatment difference, -2.26 units; 95% CI, -2.71 to -1.81; P < 0.0001). ELX/TEZ/IVA treatment also led to improvements in the secondary endpoint of sweat chloride concentration (between-group treatment difference, -51.2 mmol/L; 95% CI, -55.3 to -47.1) and in the other endpoints of percent predicted FEV1 (between-group treatment difference, 11.0 percentage points; 95% CI, 6.9-15.1) and Cystic Fibrosis Questionnaire-Revised Respiratory domain score (between-group treatment difference, 5.5 points; 95% CI, 1.0-10.0) compared with placebo from baseline through Week 24. The most common adverse events in children receiving ELX/TEZ/IVA were headache and cough (30.0% and 23.3%, respectively); most adverse events were mild or moderate in severity. Conclusions: In this first randomized, controlled study of a cystic fibrosis transmembrane conductance regulator modulator conducted in children 6 through 11 years of age with F/MF genotypes, ELX/TEZ/IVA treatment led to significant improvements in lung function, as well as robust improvements in respiratory symptoms and cystic fibrosis transmembrane conductance regulator function. ELX/TEZ/IVA was generally safe and well tolerated in this pediatric population with no new safety findings.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Criança , Humanos , Aminofenóis/efeitos adversos , Benzodioxóis/efeitos adversos , Agonistas dos Canais de Cloreto/efeitos adversos , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/uso terapêutico , Volume Expiratório Forçado , Mutação
6.
Breathe (Sheff) ; 18(4): 220209, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36865938

RESUMO

Pulmonary hypertension (PH) can develop in babies with bronchopulmonary dysplasia (BPD). PH is common in those with severe BPD and is associated with a high mortality rate. However, in babies surviving beyond 6 months, resolution of PH is likely. There is currently no standardised screening protocol for PH in BPD patients. Diagnosis in this group relies heavily on transthoracic echocardiography. Management of BPD-PH should be led by a multidisciplinary team and focus on optimal medical management of the BPD and associated conditions that may contribute to PH. PH-targeted pharmacotherapies have been used in BPD-PH. To date, these have not been investigated in clinical trials and evidence of their efficacy and safety is absent. Educational aims: To identify those BPD patients most at risk of developing PH.To be aware of detection, multidisciplinary management, pharmacological treatment and monitoring strategies for BPD-PH patients.To understand the potential clinical course for patients with BPD-PH and that evidence on efficacy and safety of PH-targeted pharmacotherapy in BPD-PH is limited.

8.
BMJ Case Rep ; 14(3)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731398
9.
PLoS One ; 15(5): e0232040, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369498

RESUMO

Urban particulate matter (PM) enhances airway dendritic cell (DC) maturation in vitro. However, to date, there are no data on the association between exposure to urban PM and DC maturation in vivo. We sought to determine whether exposure of school-age children (8 to 14 y) to PM was associated with expression of CD86, a marker of maturation of airway conventional DCs (cDC). Healthy London school children underwent spirometry and sputum induction. Flow cytometry was used to identify CD86 and CCR7 expression on cDC subsets (CD1c+ cDC2 and CD141+ cDC1). Tertiles of mean annual exposure to PM ≤ 10 microns (PM10) at the school address were determined using the London Air Quality Toolkit model. Tertiles of exposure from the 409 children from 19 schools recruited were; lower (23.1 to 25.6 µg/m3, n = 138), middle (25.6 to 26.8 µg/m3, n = 126), and upper (26.8 to 31.0 µg/m3, n = 145). DC expression was assessed in 164/370 (44%) children who completed sputum induction. The proportion (%) of cDC expressing CD86 in the lower exposure tertile (n = 47) was lower compared with the upper exposure tertile (n = 49); (52% (44 to 70%) vs 66% (51 to 82%), p<0.05). There was a higher percentage of cDC1 cells in the lower tertile of exposure (6.63% (2.48 to 11.64) vs. 2.63% (0.72 to 7.18), p<0.05). Additionally; children in the lower exposure tertile had increased FEV1 compared with children in the upper tertile; (median z-score 0.15 (-0.59 to 0.75) vs. -0.21 (-0.86 to 0.48), p<0.05. Our data reveal that children attending schools in the highest areas of PM exposure in London exhibit increased numbers of "mature" airway cDCs, as evidenced by their expression of the surface marker CD86. This data is supportive of previous in vitro data demonstrating an alteration in the maturation of airway cDCs in response to exposure to pollutants.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Antígeno B7-2/metabolismo , Células Dendríticas/efeitos dos fármacos , Material Particulado/efeitos adversos , Adolescente , Criança , Células Dendríticas/imunologia , Exposição Ambiental , Feminino , Humanos , Londres , Masculino , Escarro/citologia , Saúde da População Urbana
10.
Paediatr Respir Rev ; 28: 80-86, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29793860

RESUMO

Outdoor air pollution is increasingly identified as a contributor to respiratory and cardiovascular disease. Pro-inflammatory particles and gases are inhaled deep into the lungs, and are associated with impaired lung growth and exacerbations of chronic respiratory diseases. The magnitude of these effects are of interest to patients and families, and have been assessed in studies specific to CF. Using systematic review methodology, we sought to collate these studies in order to summarise the known effects of air pollution in cystic fibrosis, and to present information on decreasing personal air pollution exposures.


Assuntos
Poluição do Ar , Fibrose Cística , Progressão da Doença , Humanos , Inflamação , Material Particulado , Infecções por Pseudomonas
11.
J Cyst Fibros ; 17(6): 791-797, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29329721

RESUMO

BACKGROUND: Cystic fibrosis related diabetes (CFRD) is associated with increased morbidity in CF. Variability in physiological systems is associated with dysfunctional homeostasis. We examined whether fluctuation in glucose is a marker of CFRD or "pre-diabetes". METHODS: Using a machine learning approach, we compared glucose IQR to current diagnostic criteria in a review of continuous glucose monitoring data. RESULTS: Analysis was performed on 248 studies from 142 children. Calculated IQR (cIQR) was increased between children with CFRD, normal glucose homeostasis and indeterminate status (p<0.0001) and impaired glucose tolerance (p<0.05, Kruskal-Wallis test). In subjects who developed CFRD (n=20), cIQR increased between baseline and diagnosis (1.4mmol/L versus 2.4mmol/L, p<0.0001, Wilcoxon test). Area under the curve for CFRD on the basis of cIQR was 0.865 (p<0.0001). Neither episodes of hypoglycaemia nor cIQR at baseline predicted CFRD. CONCLUSIONS: Glucose fluctuation on CGMS can be quantified by calculating the IQR. This information may improve early recognition of abnormal glucose homeostasis.


Assuntos
Glicemia , Fibrose Cística , Diabetes Mellitus , Estado Pré-Diabético , Adolescente , Glicemia/análise , Glicemia/metabolismo , Criança , Fibrose Cística/sangue , Fibrose Cística/complicações , Fibrose Cística/epidemiologia , Diabetes Mellitus/sangue , Diabetes Mellitus/etiologia , Diabetes Mellitus/prevenção & controle , Diagnóstico Precoce , Feminino , Humanos , Masculino , Monitorização Fisiológica/métodos , Pediatria/métodos , Estado Pré-Diabético/sangue , Estado Pré-Diabético/etiologia , Estado Pré-Diabético/terapia , Reino Unido/epidemiologia
13.
Acta Paediatr ; 106(12): 2011-2016, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28833606

RESUMO

AIM: Epidemiological studies of deoxyribonucleic acid (DNA) methylation in airway disease have largely been conducted using blood or buccal samples. However, given tissue specificity of DNA methylation, these surrogate tissues may not allow reliable inferences about methylation in the lung. We sought to compare the pattern of DNA methylation in blood, buccal and nasal epithelial cells to that in airway epithelial cells from children. METHODS: Samples of blood, and buccal, nasal and airway epithelium were obtained from six children undergoing elective anaesthesia for adenotonsillectomy. DNA methylation was assessed at 450 000 5'-C-phosphate-G-3' (CpG) sites using the Illumina HumanMethylation450 array. RESULTS: Eighteen samples from all sites were suitable for analysis. Hierarchical clustering demonstrated that the methylation profile in nasal epithelium was most representative of that in airway epithelium; the profile in buccal cells was moderately similar and that in blood was least similar. CONCLUSION: DNA methylation in blood poorly reflects methylation in airway epithelium. Future epidemiological studies of DNA methylation and airway diseases should consider measurement of methylation either in buccal cells or, preferably, in nasal epithelial cells.


Assuntos
Células Sanguíneas , Metilação de DNA , Células Epiteliais , Mucosa Bucal/citologia , Mucosa Nasal/citologia , Mucosa Respiratória/citologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino
14.
Int J Health Care Qual Assur ; 30(4): 319-326, 2017 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-28470130

RESUMO

Purpose The purpose of this paper is to establish the effect of incorporating Centor scoring into antibiotic prescribing in primary care in London, UK, before and after the introduction of an educational package and prescribing software tool. Design/methodology/approach A quality improvement project with analysis of all sore throat presentations in patients aged 3-14 years, in two phases. Phase 1 (retrospective): 1 January-31 December 2013, followed by an intervention (software tool/education package) and Phase 2 (prospective): 1 March 2014-28 February 2015. Findings In the initial analysis, 162 out of 202 (80.2 per cent) patients were prescribed antibiotics. Following the educational/software intervention, 191 out of 231 (82.7 per cent) patients were prescribed antibiotics ( p=0.56, χ2 test). The mean Centor score decreased significantly following the education/software intervention (3.1 vs 2.7, p<0.001, χ2 test). In all, 100 per cent of patients with tonsillar exudate were prescribed antibiotics in both phases. The apparent order of importance for predictive signs/symptoms given by the prescribers in both phases of the study was tonsillar exudate>lymphadenopathy>fever>absence of cough. Originality/value This is the first time a differential importance given by practitioners on individual Centor criteria has been described. With a low probability of bacterial infection, children with exudate or anterior lymphadenopathy almost always received antibiotics. This is interesting, since studies have previously found that the presence of tonsillar exudate had no significant association with culture-confirmed streptococcal tonsillitis.


Assuntos
Antibacterianos/administração & dosagem , Faringite/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Melhoria de Qualidade/organização & administração , Adolescente , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Educação Médica Continuada/organização & administração , Feminino , Humanos , Prescrição Inadequada/prevenção & controle , Londres , Masculino , Guias de Prática Clínica como Assunto , Estudos Retrospectivos
17.
Environ Int ; 74: 32-41, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25318022

RESUMO

Exposure to particulate matter (PM) is associated with adverse health effects, including chronic lung diseases, lung cancer and cardiovascular disease. Personal exposure varies depending on the generation of particles locally, background levels, activity patterns and meteorology. Carbon loading in airway macrophages (AM) is a novel marker to assess personal exposure to combustion-derived particles. This review summarizes the published evidence and describes the validity and reliability of this marker with a focus on the technical aspects. Carbon loading in AM is reported in nine published studies assessing personal exposure to particulate air pollution. The carbon content is quantified by image analysis and is suggested to be suited to assess cumulative exposures. While there is some variation in study technique, these studies each indicate that internal AM carbon reflects either external exposure or important health effects. However, some uncertainty remains regarding potentially confounding materials within particles, the time frame of exposures that this technique reflects, and the optimal strategy to accurately quantify AM carbon. These aspects need to be clarified or optimized before applying this technique in larger populations.


Assuntos
Poluentes Atmosféricos , Exposição por Inalação , Macrófagos Alveolares/química , Material Particulado , Fuligem/análise , Poluição do Ar , Biomarcadores/análise
18.
Lancet Respir Med ; 2(10): 796-803, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25212745

RESUMO

BACKGROUND: The effectiveness of intermittent montelukast for wheeze in young children is unclear. We aimed to assess whether intermittent montelukast is better than placebo for treatment of wheeze in this age group. Because copy numbers of the Sp1-binding motif in the arachidonate 5-lipoxygenase (ALOX5) gene promoter (either 5/5, 5/x, or x/x, where x does not equal 5) modifies response to montelukast in adults, we stratified by this genotype. METHODS: We did this multicentre, parallel-group, randomised, placebo-controlled trial between Oct 1, 2010, and Dec 20, 2013, at 21 primary care sites and 41 secondary care sites in England and Scotland. Children aged 10 months to 5 years with two or more wheeze episodes were allocated to either a 5/5 or 5/x+x/x ALOX5 promoter genotype stratum, then randomly assigned (1:1) via a permuted block schedule (size ten), to receive intermittent montelukast or placebo given by parents at each wheeze episode over a 12 month period. Clinical investigators and parents were masked to treatment group and genotype strata. The primary outcome was number of unscheduled medical attendances for wheezing episodes. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01142505. FINDINGS: We randomly assigned 1358 children to receive montelukast (n=669) or placebo (n=677). Consent was withdrawn for 12 (1%) children. Primary outcome data were available for 1308 (96%) children. There was no difference in unscheduled medical attendances for wheezing episodes between children in the montelukast and placebo groups (mean 2·0 [SD 2·6] vs 2·3 [2·7]; incidence rate ratio [IRR] 0·88, 95% CI: 0·77-1·01; p=0·06). Compared with placebo, unscheduled medical attendances for wheezing episodes were reduced in children given montelukast in the 5/5 stratum (2·0 [2·7] vs 2·4 [3·0]; IRR 0·80, 95% CI 0·68-0·95; p=0·01), but not in those in the 5/x+x/x stratum (2·0 [2·5] vs 2·0 [2·3]; 1·03, 0·83-1·29; p=0·79, pinteraction=0·08). We recorded one serious adverse event, which was a skin reaction in a child allocated to placebo. INTERPRETATION: Our findings show no clear benefit of intermittent montelukast in young children with wheeze. However, the 5/5 ALOX5 promoter genotype might identify a montelukast-responsive subgroup. FUNDING: Medical Research Council (UK) and National Institute for Health Research.


Assuntos
Acetatos/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Quinolinas/uso terapêutico , Sons Respiratórios/efeitos dos fármacos , Acetatos/administração & dosagem , Agendamento de Consultas , Araquidonato 5-Lipoxigenase/efeitos dos fármacos , Pré-Escolar , Ciclopropanos , Cisteína/urina , Esquema de Medicação , Feminino , Genótipo , Humanos , Lactente , Leucotrienos/urina , Masculino , Quinolinas/administração & dosagem , Sulfetos , Resultado do Tratamento
19.
Paediatr Respir Rev ; 15(2): 194-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24704510

RESUMO

Public awareness of the impact of air quality on health is increasing worldwide. Indoor and outdoor air pollutants impair children's growing lungs, and increase the risk of respiratory infections. In many cities, children face indoor air pollution from fuels used for cooking and heating, as well as outdoor pollution from vehicle exhausts. Research identifies at-risk groups and seeks to establish biological plausibility for the associations already observed; and looks towards identifying the harmful pollutants that are responsible for respiratory morbidity and mortality. These findings may then serve to influence public debate and future policy at national and international level to improve air quality in cities, and improve children's health.


Assuntos
Poluição do Ar/efeitos adversos , Infecções Respiratórias/etiologia , Saúde da População Urbana , Poluição do Ar/análise , Criança , Humanos
20.
Thorax ; 69(7): 654-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24567296

RESUMO

BACKGROUND: Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E2 and D2 are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls. METHODS: AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (µm(2)) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE2 and PGD2 metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocyte-derived macrophages and rat AM was assessed in vitro by image analysis. RESULTS: AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p<0.01) and healthy controls (n=47, p<0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE2 and D2 (n=33, rs=-0.40, p<0.05, and rs=-0.44, p<0.01). PGE2 10(-6) M, but not PGD2 10(-6) M, suppressed phagocytosis of PM10 by human macrophages in vitro (p<0.05 vs control). PGE2 10(-6) M also suppressed phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control). CONCLUSIONS: Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE2 may contribute to impaired AM phagocytic function in severe asthma.


Assuntos
Asma/fisiopatologia , Carbono/análise , Exposição Ambiental/análise , Macrófagos/química , Fagocitose/fisiologia , Escarro/química , Asma/imunologia , Asma/metabolismo , Carbono/imunologia , Estudos de Casos e Controles , Criança , Cromatografia Líquida de Alta Pressão , Dinoprostona/imunologia , Dinoprostona/fisiologia , Dinoprostona/urina , Feminino , Humanos , Londres , Macrófagos/imunologia , Masculino , Tamanho da Partícula , Fagocitose/imunologia , Prostaglandina D2/imunologia , Prostaglandina D2/fisiologia , Prostaglandina D2/urina , Espirometria , Escarro/imunologia , População Urbana
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...