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1.
Transpl Int ; 37: 12355, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38433973

RESUMO

This study aimed to preliminary test the effectiveness of 12-week virtual physical prehabilitation program followed by a maintenance phase. The main objective was to estimate the extent to which it affects exercise capacity, frailty, lower limb strength and health-related quality of life (HRQOL) in lung transplant candidates. The program offered supervised strengthening exercises, independent aerobic exercises and weekly phone calls (maintenance phase). Primary outcome was the six-minute walk distance (6MWD). Secondary outcomes: the Short Physical Performance Battery (SPPB), five-times sit-to-stand test (5STS), the St George's Respiratory Questionnaire (SGRQ) for HRQOL. Twenty patients were included (mean age 57.9; 6 women/14 men); fourteen completed the prehabilitation program and 5 completed the maintenance phase. There was no statistically significant improvement in 6MWD, SPPB or SGRQ after the 12-week program. Most patients either maintained or improved the 6MWT and SPPB scores. There was a significant improvement in the 5STS. After the maintenance phase, most patients either improved or maintained their scores in all outcomes except for the sub-score of symptoms in the SGRQ. A 12-week virtual physical prehabilitation program with a 12-week maintenance phase can help lung transplant candidates improve or maintain their physical function while waiting for transplantation.


Assuntos
Fragilidade , Transplante de Pulmão , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Exercício Pré-Operatório , Qualidade de Vida
2.
Paediatr Respir Rev ; 49: 24-27, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37704463

RESUMO

Respiratory Syncytial Virus (RSV) is a leading cause of hospitalization in young children and represents a substantial health-care burden around the world. Advances in research have helped identify the prefusion F protein as the key target component in RSV immunization. In this article, we review the previous, current, and ongoing research efforts for immunization against RSV in children. We present the different types of immunization which include monoclonal antibodies, maternal immunization and vaccines while addressing the challenges of preventing RSV infections in the pediatric population.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Criança , Humanos , Pré-Escolar , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra Vírus Sincicial Respiratório/uso terapêutico , Infecções por Vírus Respiratório Sincicial/prevenção & controle
3.
Am J Respir Crit Care Med ; 205(3): 330-339, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34735776

RESUMO

Rationale: The long-term effects of vigorous physical activity (PA) on lung function in cystic fibrosis are unclear. Objectives: To evaluate effects of a 12-month partially supervised PA intervention using motivational feedback. Methods: In a parallel-arm multicenter randomized controlled trial (ACTIVATE-CF), relatively inactive patients aged at least 12 years were randomly assigned (1:1 ratio) to an intervention group or control group. The intervention group consented to add 3 hours of vigorous PA per week, whereas the control group was asked not to change their PA behavior. Primary endpoint was change in percent predicted FEV1 (ΔFEV1) at 6 months. Secondary endpoints included PA, exercise capacity, exercise motives, time to first exacerbation and exacerbation rates, quality of life, anxiety, depression, stress, and blood glucose control. Data were analyzed using mixed linear models. Measurements and Main Results: A total of 117 patients (40% of target sample size) were randomized to an intervention (n = 60) or control group (n = 57). After 6 months, ΔFEV1 was significantly higher in the control group compared with the intervention group (2.70% predicted [95% confidence interval, 0.13-5.26]; P = 0.04). The intervention group reported increased vigorous PA compared with the control group at each study visit, had higher exercise capacity at 6 and 12 months, and higher PA at 12 months. No effects were seen in other secondary outcomes. Conclusions: ACTIVATE-CF increased vigorous PA and exercise capacity, with effects carried over for the subsequent 6 months, but resulted in better FEV1 in the control group.


Assuntos
Fibrose Cística/reabilitação , Terapia por Exercício/métodos , Condicionamento Físico Humano/métodos , Adolescente , Adulto , Criança , Fibrose Cística/fisiopatologia , Fibrose Cística/psicologia , Retroalimentação Psicológica , Feminino , Seguimentos , Humanos , Pulmão/fisiopatologia , Masculino , Motivação , Aptidão Física , Testes de Função Respiratória , Resultado do Tratamento , Adulto Jovem
4.
N Engl J Med ; 381(19): 1809-1819, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31697873

RESUMO

BACKGROUND: Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, and nearly 90% of patients have at least one copy of the Phe508del CFTR mutation. In a phase 2 trial involving patients who were heterozygous for the Phe508del CFTR mutation and a minimal-function mutation (Phe508del-minimal function genotype), the next-generation CFTR corrector elexacaftor, in combination with tezacaftor and ivacaftor, improved Phe508del CFTR function and clinical outcomes. METHODS: We conducted a phase 3, randomized, double-blind, placebo-controlled trial to confirm the efficacy and safety of elexacaftor-tezacaftor-ivacaftor in patients 12 years of age or older with cystic fibrosis with Phe508del-minimal function genotypes. Patients were randomly assigned to receive elexacaftor-tezacaftor-ivacaftor or placebo for 24 weeks. The primary end point was absolute change from baseline in percentage of predicted forced expiratory volume in 1 second (FEV1) at week 4. RESULTS: A total of 403 patients underwent randomization and received at least one dose of active treatment or placebo. Elexacaftor-tezacaftor-ivacaftor, relative to placebo, resulted in a percentage of predicted FEV1 that was 13.8 points higher at 4 weeks and 14.3 points higher through 24 weeks, a rate of pulmonary exacerbations that was 63% lower, a respiratory domain score on the Cystic Fibrosis Questionnaire-Revised (range, 0 to 100, with higher scores indicating a higher patient-reported quality of life with regard to respiratory symptoms; minimum clinically important difference, 4 points) that was 20.2 points higher, and a sweat chloride concentration that was 41.8 mmol per liter lower (P<0.001 for all comparisons). Elexacaftor-tezacaftor-ivacaftor was generally safe and had an acceptable side-effect profile. Most patients had adverse events that were mild or moderate. Adverse events leading to discontinuation of the trial regimen occurred in 1% of the patients in the elexacaftor-tezacaftor-ivacaftor group. CONCLUSIONS: Elexacaftor-tezacaftor-ivacaftor was efficacious in patients with cystic fibrosis with Phe508del-minimal function genotypes, in whom previous CFTR modulator regimens were ineffective. (Funded by Vertex Pharmaceuticals; VX17-445-102 ClinicalTrials.gov number, NCT03525444.).


Assuntos
Aminofenóis/administração & dosagem , Benzodioxóis/administração & dosagem , Agonistas dos Canais de Cloreto/administração & dosagem , Fibrose Cística/tratamento farmacológico , Indóis/administração & dosagem , Mutação , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Pirrolidinas/administração & dosagem , Quinolonas/administração & dosagem , Adolescente , Adulto , Aminofenóis/efeitos adversos , Benzodioxóis/efeitos adversos , Criança , Agonistas dos Canais de Cloreto/efeitos adversos , Cloretos/análise , Fibrose Cística/genética , Fibrose Cística/fisiopatologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Volume Expiratório Forçado , Genótipo , Humanos , Indóis/efeitos adversos , Masculino , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Pirrolidinas/efeitos adversos , Quinolonas/efeitos adversos , Suor/química , Adulto Jovem
5.
Paediatr Respir Rev ; 42: 49-52, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35428587

RESUMO

The COVID-19 pandemic continues with new waves of intensification. This review provides an update based on international recommendations concerning the conduct of pulmonary function testing in a manner to limit risk to both patient and tester.


Assuntos
COVID-19 , Criança , Humanos , Pandemias , Equipamento de Proteção Individual , SARS-CoV-2
6.
Paediatr Respir Rev ; 43: 67-77, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35131174

RESUMO

Mobile (m) Health technology is well-suited for Remote Patient Monitoring (RPM) in a patient's habitual environment. In recent years there have been fast-paced developments in mHealth-enabled pediatric RPM, especially during the COVID-19 pandemic, necessitating evidence synthesis. To this end, we conducted a scoping review of clinical trials that had utilized mHealth-enabled RPM of pediatric asthma. MEDLINE, Embase and Web of Science were searched from September 1, 2016 through August 31, 2021. Our scoping review identified 25 publications that utilized synchronous and asynchronous mHealth-enabled RPM in pediatric asthma, either involving mobile applications or via individual devices. The last three years has seen the development of evidence-based, multidisciplinary, and participatory mHealth interventions. The quality of the studies has been improving, such that 40% of included study reports were randomized controlled trials. In conclusion, there exists high-quality evidence on mHealth-enabled RPM in pediatric asthma, warranting future systematic reviews and/or meta-analyses of the benefits of such RPM.


Assuntos
Asma , COVID-19 , Aplicativos Móveis , Telemedicina , Criança , Humanos , Pandemias , Asma/terapia
7.
J Pharmacol Exp Ther ; 375(3): 414-429, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33012706

RESUMO

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel that impair airway salt and fluid secretion. Excessive release of proinflammatory cytokines and chemokines by CF bronchial epithelium during airway infection leads to chronic inflammation and a slow decline in lung function; thus, there is much interest in finding safe and effective treatments that reduce inflammation in CF. We showed previously that the cyclic nucleotide phosphodiesterase (PDE) inhibitor ensifentrine (RPL554; Verona Pharma) stimulates the channel function of CFTR mutants with abnormal gating and also those with defective trafficking that are partially rescued using a clinically approved corrector drug. PDE inhibitors also have known anti-inflammatory effects; therefore, we examined whether ensifentrine alters the production of proinflammatory cytokines in CF bronchial epithelial cells. Ensifentrine reduced the production of monocyte chemoattractant protein-1 and granulocyte monocyte colony-stimulating factor (GM-CSF) during challenge with interleukin-1ß Comparing the effect of ensifentrine with milrinone and roflumilast, selective PDE3 and PDE4 inhibitors, respectively, demonstrated that the anti-inflammatory effect of ensifentrine was mainly due to inhibition of PDE4. Beneficial modulation of GM-CSF was further enhanced when ensifentrine was combined with low concentrations of the ß 2-adrenergic agonist isoproterenol or the corticosteroid dexamethasone. The results indicate that ensifentrine may have beneficial anti-inflammatory effects in CF airways particularly when used in combination with ß 2-adrenergic agonists or corticosteroids. SIGNIFICANCE STATEMENT: Airway inflammation that is disproportionate to the burden of chronic airway infection causes much of the pathology in the cystic fibrosis (CF) lung. We show here that ensifentrine beneficially modulates the release of proinflammatory factors in well differentiated CF bronchial epithelial cells that is further enhanced when combined with ß2-adrenergic agonists or low-concentration corticosteroids. The results encourage further clinical testing of ensifentrine, alone and in combination with ß2-adrenergic agonists or low-concentration corticosteroids, as a novel anti-inflammatory therapy for CF.


Assuntos
Brônquios/citologia , Diferenciação Celular/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Isoquinolinas/farmacologia , Inibidores da Fosfodiesterase 4/farmacologia , Pirimidinonas/farmacologia , Linhagem Celular , Quimiocina CCL2/biossíntese , AMP Cíclico/metabolismo , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Células Epiteliais/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Humanos , Interleucina-8/biossíntese , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Regulação para Cima/efeitos dos fármacos
8.
Clin Transplant ; 34(10): e14045, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32686160

RESUMO

Home-based exercise programs may offer a less costly alternative to providing exercise pre-transplant to a large number of patients. We describe the changes in 6-minute walk distance (6MWD) in lung transplant candidates who participated in a home-based exercise program and their relationship to post-transplant outcomes. Retrospectively, we investigated 159 individuals while awaiting transplantation who performed the surgery between 2011 and 2015. Primary outcome was 6MWD at time of assessment for transplant, last test prior to transplant and one-month post-transplant. 6MWD decreased by 28 ± 93.9 m between the time of assessment and the last 6MWD prior to transplantation (P < .001). Forty-one patients (25.8%) increased their 6MWD (mean + 85.8 ± 42.8 m); 72 patients (45.3%) decreased their 6MWD (mean -109.8 ± 71.2 m); and 46 patients (28.9%) had no change in 6MWD (-1.5 ± 15.7 m). There was a moderate correlation (r = .528; P < .001) between the last 6MWD prior to transplant and 6MWD post-transplant. Change in 6MWD prior to transplant weakly correlated with length of time on mechanical ventilation (r = -.185; P = .034). When adjusted for covariates, change in 6MWD prior to transplant was not associated with length of time on mechanical ventilation, total hospital LOS, or intensive care unit LOS. The majority of the patients were able to either increase or maintain their 6MWD while participating in a home-based pre-habilitation program during the waiting list period. Prospective research is needed to evaluate the effects of home-based pre-habilitation program for lung candidates.


Assuntos
Transplante de Pulmão , Caminhada , Teste de Esforço , Tolerância ao Exercício , Humanos , Estudos Prospectivos , Estudos Retrospectivos
9.
Am J Respir Crit Care Med ; 199(8): 987-995, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30321487

RESUMO

RATIONALE: The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors, is unclear. OBJECTIVES: To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake ( V. o2peak) following rigorous adjustment for other predictors. METHODS: Data from 10 CF centers in Australia, Europe, and North America were collected retrospectively. A total of 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death/lung transplantation was analyzed using Cox proportional hazards regression. In addition, phenotyping using hierarchical Ward clustering was performed to characterize high-risk subgroups. MEASUREMENTS AND MAIN RESULTS: Cox regression showed, even after adjustment for sex, FEV1% predicted, body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model, that V. o2peak in % predicted (hazard ratio [HR], 0.964; 95% confidence interval [CI], 0.944-0.986), peak work rate (% predicted; HR, 0.969; 95% CI, 0.951-0.988), ventilatory equivalent for oxygen (HR, 1.085; 95% CI, 1.041-1.132), and carbon dioxide (HR, 1.060; 95% CI, 1.007-1.115) (all P < 0.05) were significant predictors of death or lung transplantation at 10-year follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high-risk cluster characterized by poor lung function, nutritional status, and exercise capacity. CONCLUSIONS: CPET provides additional prognostic information to established predictors of death/lung transplantation in CF. High-risk patients may especially benefit from regular monitoring of exercise capacity and exercise counseling.


Assuntos
Fibrose Cística/diagnóstico , Teste de Esforço , Adolescente , Adulto , Criança , Fibrose Cística/mortalidade , Fibrose Cística/fisiopatologia , Fibrose Cística/cirurgia , Feminino , Humanos , Transplante de Pulmão/estatística & dados numéricos , Masculino , Consumo de Oxigênio , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem
10.
Cochrane Database Syst Rev ; 9: CD001505, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31499593

RESUMO

BACKGROUND: Progressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration and morbidity in cystic fibrosis. This is an update of a previously published review. OBJECTIVES: To assess the effectiveness of treatment with oral non-steroidal anti-inflammatory drugs in cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings. We contacted manufacturers of non-steroidal anti-inflammatory drugs and searched online trials registries.Latest search of the Group's Trials Register: 21 November 2018. SELECTION CRITERIA: Randomized controlled trials comparing oral non-steroidal anti-inflammatory drugs, at any dose for at least two months, to placebo in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for inclusion the review and their potential risk of bias. Two authors independently rated the quality of the evidence for each outcome using the GRADE guidelines. MAIN RESULTS: The searches identified 17 trials; four are included (287 participants aged five to 39 years; maximum follow-up of four years) and one is currently awaiting classification pending publication of the full trial report and two are ongoing. Three trials compared ibuprofen to placebo (two from the same center with some of the same participants); one trial assessed piroxicam versus placebo.The three ibuprofen trials were deemed to have good or adequate methodological quality, but used various outcomes and summary measures. Reviewers considered measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival and adverse effects. Combined data from the two largest ibuprofen trials showed a lower annual rate of decline for lung function, % predicted forced expiratory volume in one second (FEV1), mean difference (MD) 1.32 (95% confidence interval (CI) 0.21 to 2.42) (moderate-quality evidence); forced vital capacity (FVC), MD 1.27 (95% CI 0.26 to 2.28) (moderate-quality evidence); forced expiratory flow (FEF25%-75%), MD 1.80 (95% CI 0.15 to 3.45). The post hoc analysis of data from two trials split by age showed a slower rate of annual decline of FEV1 % predicted and FVC in the ibuprofen group in younger children, MD 1.41% (95% CI 0.03 to 2.80) (moderate-quality evidence) and MD 1.32% (95% CI 0.04 to 2.60) (moderate-quality evidence) respectively. Data from four trials demonstrated the proportion of participants with at least one hospitalization may be slightly lower in the ibuprofen group compared to placebo, Peto odds ratio 0.61 (95% CI 0.37 to 1.01) (moderate-quality evidence). In one trial, long-term use of high-dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported, but the power of the trials to identify clinically important differences in the incidence of adverse effects was low.We did not have any concerns with regards to risk of bias for the trial comparing piroxicam to placebo. However, the trial did not report many data in a form that we could analyze in this review. No data were available for the review's primary outcome of lung function; available data for hospital admissions showed no difference between the groups. No analyzable data were available for any other review outcome. AUTHORS' CONCLUSIONS: High-dose ibuprofen can slow the progression of lung disease in people with cystic fibrosis, especially in children, which suggests that strategies to modulate lung inflammation can be beneficial for people with cystic fibrosis.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Fibrose Cística/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Criança , Feminino , Humanos , Ibuprofeno/administração & dosagem , Ibuprofeno/uso terapêutico , Masculino , Piroxicam/administração & dosagem , Piroxicam/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
11.
BMC Pulm Med ; 18(1): 31, 2018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29422091

RESUMO

BACKGROUND: Physical activity (PA) and exercise have become an accepted and valued component of cystic fibrosis (CF) care. Regular PA and exercise can positively impact pulmonary function, improve physical fitness, and enhance health-related quality of life (HRQoL). However, motivating people to be more active is challenging. Supervised exercise programs are expensive and labour intensive, and adherence falls off significantly once supervision ends. Unsupervised or partially supervised programs are less costly and more flexible, but compliance can be more problematic. The primary objective of this study is to evaluate the effects of a partially supervised exercise intervention along with regular motivation on forced expiratory volume in 1 s (FEV1) at 6 months in a large international group of CF patients. Secondary endpoints include patient reported HRQoL, as well as levels of anxiety and depression, and control of blood sugar. METHODS/DESIGN: It is planned that a total of 292 patients with CF 12 years and older with a FEV1 ≥ 35% predicted shall be randomised. Following baseline assessments (2 visits) patients are randomised into an intervention and a control group. Thereafter, they will be seen every 3 months for assessments in their centre for one year (4 follow-up visits). Along with individual counselling to increase vigorous PA by at least 3 h per week on each clinic visit, the intervention group documents daily PA and inactivity time and receives a step counter to record their progress within a web-based diary. They also receive monthly phone calls from the study staff during the first 6 months of the study. After 6 months, they continue with the step counter and web-based programme for a further 6 months. The control group receives standard care and keeps their PA level constant during the study period. Thereafter, they receive the intervention as well. DISCUSSION: This is the first large, international multi-centre study to investigate the effects of a PA intervention in CF with motivational feedback on several health outcomes using modern technology. Should this relatively simple programme prove successful, it will be made available on a wider scale internationally. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01744561 ; Registration date: December 6, 2012.


Assuntos
Fibrose Cística/reabilitação , Terapia por Exercício/métodos , Condicionamento Físico Humano/métodos , Adolescente , Ansiedade/psicologia , Glicemia/metabolismo , Criança , Fibrose Cística/metabolismo , Fibrose Cística/fisiopatologia , Fibrose Cística/psicologia , Depressão/psicologia , Retroalimentação , Volume Expiratório Forçado , Humanos , Motivação , Qualidade de Vida
12.
Pediatr Blood Cancer ; 64(10)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28417544

RESUMO

BACKGROUND: Cisplatin (Cis), carboplatin (Carb), and ifosfamide (Ifos) are common nephrotoxic chemotherapies. Biomarkers of tubular injury may allow for early acute kidney injury (AKI) diagnosis. PROCEDURE: We performed a two-center (Canada, United States) pilot study to prospectively measure serum creatinine (SCr), urine neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18) in children receiving Cis/Carb (27 episodes), Ifos (30 episodes), and in 15 hospitalized, nonchemotherapy patients. We defined AKI using the Kidney Disease Improving Global Outcomes (KDIGO) definition. We compared postchemotherapy infusion NGAL and IL-18 concentrations (immediate postdose to 3 days later) to pre-infusion concentrations. We calculated area under the receiver operating characteristic curve (AUC) for postinfusion biomarkers to discriminate for AKI. RESULTS: Prechemotherapy infusion NGAL and IL-18 concentrations were not higher than nonchemotherapy control concentrations. Increasing chemotherapy dose was associated with increasing postinfusion (0-4 hr after infusion) NGAL (P < 0.05). Post-Ifos, immediate postdose, and daily postdose NGAL and IL-18 were significantly higher than pre-infusion biomarker concentrations (P < 0.05), during AKI episodes. NGAL and IL-18 did not rise significantly after Cis-Carb infusion, relative to predose concentrations (P > 0.05). NGAL and IL-18 measured immediately after Ifos infusion discriminated for AKI with AUCs is 0.80 (standard error = 0.13) and 0.73 (standard error = 0.16), respectively. NGAL and IL-18 were not diagnostic of Cis-Carb-associated AKI. When AUCs were adjusted for age, all biomarker AUCs (Cis-Carb and Ifos) improved. CONCLUSION: Urine NGAL and IL-18 show promise as early AKI diagnostic tests in children treated with ifosfamide and may have a potential role in drug toxicity monitoring.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/urina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Injúria Renal Aguda/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores/urina , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Interleucina-18/sangue , Lipocalina-2/sangue , Masculino , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Neoplasias/urina , Projetos Piloto , Estudos Prospectivos
13.
J Immunol ; 195(6): 2829-41, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26283481

RESUMO

Pharmacological stimulation of the antiviral cytokine IFN-ß in the airways may help to counter deleterious virus-induced exacerbations in chronic inflammatory lung diseases (asthma, chronic obstructive pulmonary disease, or cystic fibrosis). Polyinosinic-polycytidylic acid [poly(I:C)] is a known inducer of IFN-ß but also costimulates an inflammatory response. The latter response is undesirable given the pre-existing airway inflammation in these diseases. The objective of our study was to identify conditions for poly(I:C) to selectively upregulate IFN-ß in airway epithelial cells without a concomitant inflammatory response. The inflammatory response was gauged by production of the chemokine IL-8. Using cell lines and primary airway epithelial cells (both submerged and well-differentiated), we observed that pure poly(I:C) stimulated IFN-ß mainly through the TLR3/TRIF pathway and IL-8 through an unidentified pathway. The magnitude of the IL-8 response stimulated by pure poly(I:C) matched or even exceeded that of IFN-ß. Furthermore, this IL-8 response could not be pharmacologically downregulated without affecting IFN-ß. In contrast, we show that stimulation of the RIG-I/MAVS pathway, such as when poly(I:C) is delivered intracellularly in a complex with liposomes or via nucleofection, selectively stimulates IFN-ß with low IL-8 costimulation. The magnitude of IFN-ß stimulation by liposome-encapsulated poly(I:C) is markedly diminished in well-differentiated cells. In conclusion, it is feasible to augment IFN-ß production in airway epithelial cells without excessive costimulation of IL-8 if the RIG-I/MAVS pathway is stimulated, such as via liposomal delivery of poly(I:C). Better cytoplasmic delivery vehicles are needed to efficiently stimulate this pathway in well-differentiated cells.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , RNA Helicases DEAD-box/metabolismo , Interferon beta/biossíntese , Interleucina-8/biossíntese , Poli I-C/farmacologia , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Linhagem Celular , Proteína DEAD-box 58 , Células Epiteliais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Inflamação/imunologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Receptores Imunológicos , Mucosa Respiratória/citologia , Mucosa Respiratória/metabolismo , Transdução de Sinais/genética , Receptor 3 Toll-Like/metabolismo , Ativação Transcricional , Regulação para Cima/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Paediatr Respir Rev ; 24: 29-31, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28433261

RESUMO

Dyspnea in children has important physical and psychosocial impact. It is useful to define the quality of the dyspnea and quantify its magnitude in a child-friendly manner. Through careful history taking and physical examination, a targeted investigation can lead to identification of the cause and potential treatment. This article provides a framework for the clinical approach to dyspnea in children, including important information to gather during the history, physical assessment, how to quantify dyspnea, and choice and use of laboratory measurements.


Assuntos
Dispneia/diagnóstico , Teste de Esforço , Anamnese , Oximetria , Exame Físico , Radiografia Torácica , Testes de Função Respiratória , Acidose/complicações , Acidose/diagnóstico , Anemia/complicações , Anemia/diagnóstico , Asma/complicações , Asma/diagnóstico , Asma Induzida por Exercício/complicações , Asma Induzida por Exercício/diagnóstico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Criança , Dispneia/etiologia , Humanos , Laringismo/complicações , Laringismo/diagnóstico , Doenças Musculoesqueléticas/complicações , Doenças Musculoesqueléticas/diagnóstico , Esforço Físico
15.
Paediatr Respir Rev ; 23: 16-26, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27986502

RESUMO

Bronchopulmonary dysplasia (BPD) is a common complication of extreme prematurity, which has increased over the last 20 years. BPD is associated with increased morbidities and mortality. It has been increasingly recognized that BPD affects overall lung development including the pulmonary vasculature. More recent studies have demonstrated an increased awareness of pulmonary arterial hypertension (PH) in BPD patients and recent international guidelines have advocated for better screening. This review will describe the current understanding of the pathophysiology of PH in infants with BPD, the in-depth assessment of the available literature linking PH and BPD, and propose an approach of screening and diagnosis of PH in infants with BPD.


Assuntos
Displasia Broncopulmonar , Hipertensão Pulmonar , Pulmão , Programas de Rastreamento/métodos , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/fisiopatologia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Lactente Extremamente Prematuro/fisiologia , Recém-Nascido , Pulmão/irrigação sanguínea , Pulmão/crescimento & desenvolvimento , Pulmão/fisiopatologia
16.
Pediatr Nephrol ; 32(1): 163-171, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27743042

RESUMO

BACKGROUND: Serum cystatin C (CysC) is a more accurate glomerular filtration rate marker than serum creatinine (SCr) and may rise more quickly with acute kidney injury (AKI). METHODS: We performed a prospective cohort study of 81 non-critically ill children during 110 aminoglycoside (AG) treatments. We calculated area under the curve (AUC) for CysC to diagnose SCr-defined AKI and predict persistent AKI. SCr-AKI definition was based on the Kidney Disease: Improving Global Outcomes (≥stage 1: ≥50 % or 26.5 µmol/l SCr rise from baseline; stage 2: SCr doubling); CysC-AKI was based on a modified version using CysC rise. RESULTS: SCr-AKI and CysC-AKI developed in 45 and 48 % treatments, respectively. CysC rise predicted stage 1 (AUC = 0.75, 95 % CI 0.60-0.90) and 2 (AUC = 0.85, 95 % CI 0.75-0.95) SCr-AKI 2 days before SCr-AKI attainment. The best combined sensitivity/specificity for percent CysC rise to predict stage 1 SCr-AKI was with a 44 % CysC rise (sensitivity = 65 %, specificity = 83 %). CysC rise on day of SCr-AKI development was associated with SCr-AKI ≥48 h (AUC = 0.73, 95 % CI 0.56-0.90) and ≥50 % persistent SCr rise at treatment end (AUC = 0.76, 95 % CI 0.61-0.90). CONCLUSIONS: CysC is as an early AKI biomarker and predictive of persistent AKI on aminoglycoside treatment.


Assuntos
Injúria Renal Aguda/sangue , Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Cistatina C/sangue , Injúria Renal Aguda/complicações , Injúria Renal Aguda/epidemiologia , Adolescente , Área Sob a Curva , Infecções Bacterianas/complicações , Infecções Bacterianas/tratamento farmacológico , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos de Coortes , Creatinina/sangue , Feminino , Humanos , Incidência , Masculino , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Resultado do Tratamento
17.
Paediatr Respir Rev ; 39: 40, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34301494
18.
Paediatr Respir Rev ; 19: 39-41, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26796416

RESUMO

Pediatric pulmonary plethysmography is an important tool used in the diagnosis of lung diseases. Understanding the physiology underlying the functioning of the test can aid the health care provider in its interpretation. The following article reviews the basic science behind whole body plethysmography, and provides an overview of the types of plethysmographs available. Finally, the limitations of the available normative values are discussed.


Assuntos
Pletismografia Total , Criança , Humanos , Pletismografia Total/instrumentação
19.
Cochrane Database Syst Rev ; 4: CD001505, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27055154

RESUMO

BACKGROUND: Progressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration and morbidity in cystic fibrosis. OBJECTIVES: To assess the effectiveness of treatment with non-steroidal anti-inflammatory drugs in cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings. We contacted manufacturers of non-steroidal anti-inflammatory drugs.Latest search of the Group's Trials Register: 04 February 2016. SELECTION CRITERIA: Randomized controlled trials comparing oral non-steroidal anti-inflammatory drugs, at any dose for at least two months, to placebo in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for inclusion the review and their potential risk of bias. MAIN RESULTS: The searches identified 10 trials; four are included (287 participants aged five to 39 years; maximum follow up of four years) and one is currently awaiting classification pending publication of the full trial report. Three trials compared ibuprofen to placebo (two from the same centre with some of the same participants); one trial assessed piroxicam versus placebo.The three ibuprofen trials were deemed to have good or adequate methodological quality, but used various outcomes and summary measures. Reviewers considered measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival and adverse effects. Combined data from the two largest ibuprofen trials showed a significantly lower annual rate of decline for lung function, percent predicted forced expiratory volume in one second mean difference 1.32 (95% confidence interval 0.21 to 2.42); forced vital capacity mean difference 1.27 (95% confidence interval 0.26 to 2.28); forced expiratory flow (25-75%) mean difference 1.80 (95% confidence interval 0.15 to 3.45). The post-hoc analysis of data from two trials split by age showed a statistically significant slower rate of annual decline of percent predicted forced expiratory volume in one second and forced vital capacity in the ibuprofen group in younger children, mean difference 1.41% (95% confidence interval 0.03 to 2.80) and mean difference 1.32% (95% confidence interval 0.04 to 2.60) respectively. In one trial, long-term use of high-dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported, but the power of the trials to identify clinically important differences in the incidence of adverse effects was low.We did not have any concerns with regards to risk of bias for the trial comparing piroxicam to placebo. However, the trial did not report many data in a form that we could analyse in this review. No data were available for the review's primary outcome of lung function; available data for hospital admissions showed no difference between the groups. No analysable data were available for any other review outcome. AUTHORS' CONCLUSIONS: High-dose ibuprofen can slow the progression of lung disease in people with cystic fibrosis, especially in children, which suggests that strategies to modulate lung inflammation can be beneficial for people with cystic fibrosis.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Fibrose Cística/tratamento farmacológico , Ibuprofeno/administração & dosagem , Piroxicam/administração & dosagem , Administração Oral , Adolescente , Adulto , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Humanos , Pulmão/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto
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