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BACKGROUND: Several genetic variants have been associated with the susceptibility to allergic disease in adults, but it remains unclear whether these genetic variants are also associated with the onset of allergic disease early in life. The aim of this study was to develop a genetic risk score (GRS) for allergy based on findings in adults and study its predictive capacity for allergy in children. METHODS: A GRS was constructed based on 10 SNPs previously associated with allergies in adults. The GRS was tested in children who participated in a population-based newborn cohort (WHISTLER) and were followed from birth to school age. Logistic regression analysis was used to study the association between the GRS and the parental-reported allergies at age 5 (based on a reported allergy to ≥1 of the following allergens: pollen, house dust mites, or pets). A Cox regression model was used to study the association between GRS and a physician-diagnosed allergy during follow-up (allergic conjunctivitis, allergic rhinitis, and eczema/dermatitis). Cohen's kappa coefficient was calculated to study the agreement between physician-diagnosed allergy and parental-reported allergy at age 5. RESULTS: The GRS was significantly associated with parental-reported allergy (odds ratio: 15.9, 95% confidence interval (CI): 1.07-233.73) at age 5, as well as with a physician-diagnosed allergy during follow-up (hazard ratio: 1.89, 95% CI: 1.05-3.41). The overall agreement between physician-diagnosed and parental-reported allergies was 70.5% (kappa: 0.10, 95% CI: 0.03-0.18). CONCLUSIONS: An adult-derived GRS for allergy predicts the risk of developing allergies in childhood.
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Hipersensibilidad/genética , Adulto , Niño , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Hipersensibilidad/epidemiología , Lactante , Recién Nacido , Masculino , Países Bajos/epidemiología , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Análisis de Regresión , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
BACKGROUND: Breastfeeding has been suggested to influence the risk of asthma and asthma severity in children. However, the conclusions from epidemiologic studies are inconsistent. METHODS: We used data from 960 children (aged 4-12 years) using regular asthma medication who participated in the PACMAN study. Breastfeeding exposure was based on questionnaire data and stratified into (i) ever vs never, and (ii) ≥6 vs <6 months duration of breastfeeding. Asthma severity was based on the occurrence of asthma exacerbations in the preceding year and/or poorly controlled asthma symptoms during the last week of study visit. Odds ratios (ORs) were derived from univariate and multivariable logistic regression analyses. RESULTS: Breastfeeding was associated with a decreased risk of asthma exacerbations; adjusted (adj.) OR: 0.55 (95% confidence interval [CI]: 0.35-0.87). After stratification for duration of breastfeeding, the adj. ORs were 0.48 (95% CI: 0.27-0.84) for duration <6 months and 0.71 (95% CI: 0.43-1.20) for duration ≥6 months breastfeeding. When we stratified the analysis by family history of asthma, the association between breastfeeding and asthma exacerbations was strong and statistically significant only in children with a positive family history of asthma; adj. OR: 0.34 (95% CI: 0.18-0.66). There was no association between breastfeeding and risk of poor asthma control; adj. OR: 1.04 (95% CI: 0.76-1.41). CONCLUSION: In a pediatric population with asthma, children who had been breastfed had a statistically significantly lower risk of asthma exacerbations later in life compared to asthmatic children who had not been breastfed.
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Asma/epidemiología , Lactancia Materna/estadística & datos numéricos , Niño , Preescolar , Femenino , Humanos , Masculino , Conducta de Reducción del Riesgo , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
BACKGROUND: The use of antibiotic therapy early in life might influence the risk of developing asthma. Studies assessing the influence of early life antibiotic use on the risk of asthma exacerbations are limited, and the results are inconsistent. Therefore, the aim of this study was to assess the association between use of antibiotic during the first 3 years of life and the risk of developing childhood asthma and the occurrence of asthma exacerbations. METHODS: Data from four large childhood cohorts were used; two population-based cohorts to study the risk of developing asthma: Generation R (n=7393, The Netherlands) and SEATON (n=891, Scotland, UK), and two asthma cohorts to assess the risk of asthma exacerbations: PACMAN (n=668, The Netherlands) and BREATHE (n=806, Scotland, UK). Odds ratios (ORs) were derived from logistic regression analysis within each database followed by pooling the results using a fixed- or random-effect model. RESULTS: Antibiotic use in early life was associated with an increased risk of asthma in a meta-analysis of the Generation R and SEATON data (OR: 2.18, 95% CI: 1.04-4.60; I2 : 76.3%). There was no association between antibiotic use in early life and risk of asthma exacerbations later in life in a meta-analysis of the PACMAN and BREATHE data (OR: 0.93, 95% CI: 0.65-1.32; I2 : 0.0%). CONCLUSION: Children treated with antibiotic in the first 3 years of life are more likely to develop asthma, but there is no evidence that the exposure to antibiotic is associated with increased risk of asthma exacerbations.
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Antibacterianos/efectos adversos , Asma/inducido químicamente , Adolescente , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Oportunidad Relativa , Factores de Riesgo , Adulto JovenRESUMEN
To estimate the association between obesity and poor asthma control or risk of exacerbations in asthmatic children and adolescents, and to assess whether these associations are different by sex.A meta-analysis was performed on unpublished data from three North-European paediatric asthma cohorts (BREATHE, PACMAN (Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects) and PAGES (Pediatric Asthma Gene Environment Study)) and 11 previously published studies (cross-sectional and longitudinal studies). Outcomes were poor asthma control (based on asthma symptoms) and exacerbations rates (asthma-related visits to the emergency department, asthma-related hospitalisations or use of oral corticosteroids). Overall pooled estimates of the odds ratios were obtained using fixed- or random-effects models.In a meta-analysis of 46â070 asthmatic children and adolescents, obese children (body mass index ≥95th percentile) compared with non-obese peers had a small but significant increased risk of asthma exacerbations (OR 1.17, 95% CI 1.03-1.34; I2: 54.7%). However, there was no statistically significant association between obesity and poor asthma control (n=4973, OR 1.23, 95% CI 0.99-1.53; I2: 0.0%). After stratification for sex, the differences in odds ratios for girls and boys were similar, yet no longer statistically significant.In asthmatic children, obesity is associated with a minor increased risk of asthma exacerbations but not with poor asthma control. Sex does not appear to modify this risk.
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Asma/fisiopatología , Asma/terapia , Obesidad Infantil/fisiopatología , Administración por Inhalación , Adolescente , Corticoesteroides/administración & dosificación , Antiasmáticos/uso terapéutico , Asma/complicaciones , Índice de Masa Corporal , Niño , Preescolar , Estudios Transversales , Femenino , Hospitalización , Humanos , Estudios Longitudinales , Masculino , Obesidad Infantil/complicaciones , Obesidad Infantil/terapia , Riesgo , Adulto JovenRESUMEN
Pancreatic insufficiency cystic fibrosis (CF) patients receive vitamin E supplementation according to CF-specific recommendations in order to prevent deficiencies. It has been suggested that higher serum α-tocopherol levels could have protective effects on pulmonary function (PF) in patients with CF. Whether current recommendations are indeed optimal for preventing deficiency and whether vitamin E has therapeutic benefits are subjects of debate. Therefore, we studied vitamin E intake as well as the long-term effects of vitamin E intake, the coefficient of fat absorption (CFA) and IgG on α-tocopherol levels. We also examined the long-term effects of serum α-tocopherol and serum IgG on forced expiratory volume in 1 s expressed as percentage of predicted (FEV1% pred.) in paediatric CF patients during a 7-year follow-up period. We found that CF patients failed to meet the CF-specific vitamin E recommendations, but serum α-tocopherol below the 2·5th percentile was found in only twenty-three of the 1022 measurements (2 %). Furthermore, no clear effect of vitamin E intake or the CFA on serum α-tocopherol was found (both P≥ 0·103). FEV1% pred. was longitudinally inversely associated with age (P< 0·001) and serum IgG (P= 0·003), but it was not related to serum α-tocopherol levels. We concluded that in the present large sample of children and adolescents with CF, vitamin E intake was lower than recommended, but serum α-tocopherol deficiency was rare. We found no evidence that higher serum α-tocopherol levels had protective effects on PF. Adjustment of the recommendations to the real-life intake of these patients may be considered.
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Fibrosis Quística/dietoterapia , Suplementos Dietéticos , Cooperación del Paciente , Sistema Respiratorio/fisiopatología , Deficiencia de Vitamina E/prevención & control , Vitamina E/uso terapéutico , alfa-Tocoferol/sangre , Adolescente , Desarrollo del Adolescente , Niño , Desarrollo Infantil , Fenómenos Fisiológicos Nutricionales Infantiles , Preescolar , Estudios de Cohortes , Fibrosis Quística/sangre , Fibrosis Quística/fisiopatología , Dieta/efectos adversos , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Absorción Intestinal , Estudios Longitudinales , Masculino , Países Bajos/epidemiología , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Vitamina E/administración & dosificación , Vitamina E/metabolismo , Deficiencia de Vitamina E/epidemiología , Deficiencia de Vitamina E/etiología , alfa-Tocoferol/metabolismoRESUMEN
This statement summarizes the information available on specific exercise test protocols and outcome parameters used in patients with cystic fibrosis (CF) and provides expert consensus recommendations for protocol and performance of exercise tests and basic interpretation of results for clinicians. The conclusions were reached employing consensus meetings and a wide-band Delphi process. Although data on utility are currently limited, standardized exercise testing provides detailed information on physiological health, allows screening for exercise-related adverse reactions and enables exercise counselling. The Godfrey Cycle Ergometer Protocol with monitoring of oxygen saturation and ventilatory gas exchange is recommended for exercise testing in people 10 years and older. Cycle ergometry only with pulse oximetry using the Godfrey protocol or treadmill exercise with pulse oximetry - preferably with measurement of gas exchange - are second best options. Peak oxygen uptake, if assessed, and maximal work rate should be reported as the primary measure of exercise capacity. The final statement was reviewed by the European Cystic Fibrosis society and revised based on the comments received. The document was endorsed by the European Respiratory Society.
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Fibrosis Quística , Prueba de Esfuerzo , HumanosRESUMEN
Cystic fibrosis (CF) is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and is characterized by chronic pulmonary infections. The mechanisms underlying chronic infection and inflammation remain incompletely understood. Mutant CFTR in nonepithelial tissues such as immune cells has been suggested to contribute to infection, inflammation, and the resultant lung disease. However, much controversy still exists regarding the intrinsic role of CFTR in immune cells, especially phagocytes. Therefore, we investigated CFTR expression and function in neutrophils and monocytes isolated from human peripheral blood. CFTR function was assessed by comparing non-CF and CF cells, before and after the chemical inhibition of CFTR. We found CFTR protein expression in monocytes, but this expression was limited or undetectable in neutrophils. Furthermore, the phagocytosis and intracellular killing of Pseudomonas aeruginosa was reduced in CF monocytes, and impaired phagocyte effector mechanisms were phenocopied in non-CF monocytes upon the pharmacological inhibition of CFTR. Reduced phagocytosis in CF monocytes relied on the complement-dependent opsonization of Pseudomonas aeruginosa, and was also observed in the context of latex particles labeled with purified C3b. In mechanistic terms, we observed that CFTR function in monocytes is required for the optimal expression of CD11b. We observed no role for CFTR in neutrophil-mediated phagocytosis. These data support an intrinsic role for CFTR in monocytes, and suggest that CFTR-dependent alterations in complement-mediated interactions between Pseudomonas aeruginosa and monocytes may contribute to enhanced susceptibility to infection in patients with CF.
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Proteínas del Sistema Complemento/inmunología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/inmunología , Fibrosis Quística/inmunología , Monocitos/inmunología , Fagocitosis/inmunología , Antígeno CD11b/genética , Antígeno CD11b/inmunología , Estudios de Casos y Controles , Células Cultivadas , Fibrosis Quística/microbiología , Fibrosis Quística/patología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Expresión Génica , Interacciones Huésped-Patógeno , Humanos , Monocitos/microbiología , Monocitos/patología , Mutación , Neutrófilos/inmunología , Neutrófilos/patología , Pseudomonas aeruginosa/inmunologíaRESUMEN
Inert gas washout tests, performed using the single- or multiple-breath washout technique, were first described over 60 years ago. As measures of ventilation distribution inhomogeneity, they offer complementary information to standard lung function tests, such as spirometry, as well as improved feasibility across wider age ranges and improved sensitivity in the detection of early lung damage. These benefits have led to a resurgence of interest in these techniques from manufacturers, clinicians and researchers, yet detailed guidelines for washout equipment specifications, test performance and analysis are lacking. This manuscript provides recommendations about these aspects, applicable to both the paediatric and adult testing environment, whilst outlining the important principles that are essential for the reader to understand. These recommendations are evidence based, where possible, but in many places represent expert opinion from a working group with a large collective experience in the techniques discussed. Finally, the important issues that remain unanswered are highlighted. By addressing these important issues and directing future research, the hope is to facilitate the incorporation of these promising tests into routine clinical practice.
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Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/fisiopatología , Neumología/normas , Ventilación Pulmonar , Pruebas de Función Respiratoria/normas , Adulto , Europa (Continente) , Humanos , Lactante , Gases Nobles , Neumología/métodos , Respiración , Pruebas de Función Respiratoria/métodos , EspirometríaRESUMEN
BACKGROUND: Esophageal atresia (EA) is most often accompanied by some degree of tracheomalacia (TM), which negatively influences the airway by ineffective clearance of secretions. This can lead to lower airway bacterial colonization (LABC), which may cause recurrent respiratory tract infections (RTIs). This study aims to evaluate the prevalence and specific pathogens of LABC in EA patients. METHODS: A 5-year retrospective single-site cohort study was conducted including all EA patients that had undergone an intraoperative bronchoalveolar lavage (BAL) during various routine surgical interventions. Concentrations of greater than 10 cfu were considered evidence of LABC. RESULTS: We recruited 68 EA patients, of which 12 were excluded based on the exclusion criteria. In the remaining 56 patients, a total of 90 BAL samples were obtained. In 57% of the patients, at least 1 BAL sample was positive for LABC. Respiratory symptoms were reported in 21 patients at the time of the BAL, of which 10 (48%) had LABC. Haemophilus influenzae (14%) and Staphylococcus aureus (16%) were most frequently found in the BAL samples. The number of respiratory tract infections and the existence of a recurrent fistula were significantly associated with LABC ( P = 0.008 and P = 0.04, respectively). CONCLUSIONS: This is the first study showing that patients with EA have a high prevalence of bacterial colonization of the lower airways which may be a leading mechanism of severe and recurrent respiratory complications.
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Atresia Esofágica , Infecciones del Sistema Respiratorio , Humanos , Niño , Atresia Esofágica/complicaciones , Atresia Esofágica/cirugía , Líquido del Lavado Bronquioalveolar/microbiología , Estudios Retrospectivos , Estudios de Cohortes , Infecciones del Sistema Respiratorio/diagnósticoRESUMEN
Esophageal atresia (EA) is a rare birth defect in which respiratory tract disorders are a major cause of morbidity. It remains unclear whether respiratory tract disorders are in part caused by alterations in airway epithelial cell functions such as the activity of motile cilia. This can be studied using airway epithelial cell culture models of patients with EA. Therefore, the aim of this study was to evaluate the feasibility to culture and functionally characterize motile cilia function in the differentiated air-liquid interface cultured airway epithelial cells and 3D organoids derived from nasal brushings and bronchoalveolar lavage (BAL) fluid from children with EA. We demonstrate the feasibility of culturing differentiated airway epithelia and organoids of nasal brushings and BAL fluid of children with EA, which display normal motile cilia function. EA patient-derived airway epithelial cultures can be further used to examine whether alterations in epithelial functions contribute to respiratory disorders in EA.
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BACKGROUND: A high fraction of nitric oxide in exhaled breath (FeNO) has been suggested to be a marker of ongoing airway inflammation and poorly controlled disease in asthma. The usefulness of FeNO to monitor asthma control is still debated today. AIM: To assess the validity of FeNO as a marker of asthma control in children with reported use of asthma medication. METHODS: Fraction of nitric oxide in exhaled breath was measured in 601 children (aged 4-12 yr) with reported use of asthma medication in the past 6 months and in 63 healthy non-asthmatic children (aged 5-12). Asthma control was assessed by the Asthma Control Questionnaire (ACQ). A receiver-operator characteristics (ROC) curve was generated to assess the accuracy of FeNO as a marker for asthma control. Logistic regression analysis was used to study whether clinical, healthcare, medication, and environmental factors are associated with high FeNO levels (>25 ppb). RESULTS: Fraction of nitric oxide in exhaled breath had a poor accuracy to discriminate well-controlled from not well-controlled asthma [area under the ROC curve: 0.56 (95% CI: 0.52-0.61, p = 0.008)]. In addition, high FeNO (>25 ppb) was associated with lower medication adherence rates (OR: 0.4; 95% CI 0.3-0.6), fewer antibiotic courses in the past year (OR: 0.6; 95% CI: 0.4-0.9), fewer leukotriene antagonists use in the past year (OR: 0.4; 95% CI: 0.2-0.9), and fewer visits to a (pulmonary) pediatrician (OR: 0.6; 95% CI: 0.4-0.9). Children living in a non-urban environment had more often high FeNO levels (OR: 1.7; 95% CI: 1.1-2.6). CONCLUSION: High FeNO is a poor marker of asthma control in children with reported use of asthma medication. Various other factors, including medication adherence and medication use, are associated with increased FeNO levels.
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Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Óxido Nítrico/análisis , Biomarcadores/análisis , Pruebas Respiratorias , Niño , Preescolar , Femenino , Estado de Salud , Humanos , Masculino , Cooperación del Paciente , Farmacias/estadística & datos numéricos , Curva ROC , Encuestas y CuestionariosRESUMEN
PURPOSE: To study whether peak oxygen uptake ((Equation is included in full-text article VO2 peak), attained in traditional cardiopulmonary exercise testing (CPET) in adolescents with cystic fibrosis (CF), could be verified by a supramaximal exercise test. METHODS: Sixteen adolescents with CF (forced expiratory volume in 1 second as % of predicted [range, 45%-117%]) volunteered and successively performed CPET and a supramaximal test (Steep Ramp Test [SRT] protocol). RESULTS: Cardiopulmonary exercise testing and the SRT resulted in comparable cardiorespiratory peak values. We found no significant difference in oxygen uptake ((Equation is included in full-text article VO2 peak/kg) between CPET and the SRT (38.9 ± 7.4 and 38.8 ± 8.5 mL min kg, respectively; P = .81). We found no systemic bias for CPET and SRT measurements of (Equation is included in full-text article VO2 peak/kg and no differences between CPET and SRT (Equation is included in full-text article VO2 peak values within and between the maximal and non-maximal effort groups (P > .4). CONCLUSION: The (Equation is included in full-text article VO2 peak measured in CPET seems to reflect the true (Equation is included in full-text article.)O2 peak in adolescents with CF.
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Fibrosis Quística/rehabilitación , Prueba de Esfuerzo , Volumen Espiratorio Forzado , Consumo de Oxígeno , Capacidad Vital , Adolescente , Factores de Edad , Análisis de Varianza , Ergometría , Femenino , Humanos , Masculino , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
Background: Esophageal atresia (EA) is often accompanied by tracheomalacia (TM). TM can lead to severe respiratory complaints requiring invasive treatment. This study aims to evaluate if thoracoscopic primary posterior tracheopexy (PPT) can prevent the potential sequelae of TM in patients with EA. Methods: A cohort study including all consecutive EA patients treated between 2014 and July 2019 at the Wilhelmina Children's Hospital was conducted. Two groups were distinguished: (group 1) all EA patients born between January 2014 and December 2016 and (group 2) all EA patients born between January 2017 and July 2019, after introduction of PPT. In the latter group, PPT was performed in EA patients with moderate (33-66%) or severe (67-100%) tracheomalacia, seen during preoperative bronchoscopy. Group differences were assessed using the Fisher's exact test for bivariate variables and the Mann-Whitney U-test for continuous variables. Results: A total of 64 patients were included in this study (28 patients in group 1; 36 patients in group 2). In group 2, PPT was performed in 14 patients. Respiratory tract infections (RTIs) requiring antibiotics within the first year of life occurred significantly less in group 2 (61 vs. 25%, p = 0.004). Brief resolved unexplained events (BRUEs) seemed to diminish in group 2 compared to group 1 (39 vs. 19%, p = 0.09). Conclusion: Thoracoscopic primary posterior tracheopexy decreases the number of respiratory tract infections in EA patients. The clinical impact of reducing RTIs combined with the minimal additional operating time and safety of PPT outweighs the risk of overtreatment.
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Ivacaftor has been shown to restore the functionality of the S1251N (also known as c.3752G>A) mutated CFTR, which may cause alterations in both airway and gut physiology and micro-environment, resulting in a change of microbiota in these organs. The aim of the present study was to analyze the effects of ivacaftor on the microbial community composition of both airway and gut in subjects with CF carrying one S1251N mutation, using a 16S rRNA gene-based sequencing approach. In 16 subjects with CF, repetitive samples from airways and gut were collected just before, and 2 months after, and, for 8 patients, also 9 and 12 months after, start of ivacaftor. 16S rRNA based sequencing identified 344 operational taxonomical units (OTUs) in a total of 139 samples (35 nasopharyngeal, 39 oropharyngeal, 29 sputum, and 36 fecal samples). Ivacaftor significantly enhanced bacterial diversity and overall microbiota composition in the gut (p < 0.01). There were no significant changes in the overall microbial composition and alpha diversity in upper and lower airways of these patients after ivacaftor treatment. Treatment with ivacaftor induces changes in gut microbiota whereas airway microbiota do not change significantly over time.
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BACKGROUND: Antimicrobial peptides are considered potential alternatives to antibiotics. Here we describe the antibacterial properties of a family of novel cathelicidin-related (CR-) peptides, which we named PepBiotics, against bacteria typically present in cystic fibrosis (CF) patients. METHODS: Broth dilution assays were used to determine antibacterial activity of PepBiotics under physiological conditions, as well as development of bacterial resistance against these peptides. Toxicity was tested in mice and cell cultures while molecular interactions of PepBiotics with bacterial membrane components was determined using CD, ITC and LPS/LTA induced macrophage studies. RESULTS: A relatively small number of PepBiotics remained highly antibacterial against CF-related respiratory pathogens Pseudomonas aeruginosa and Staphylococcus aureus, at high ionic strength and low pH. Interestingly, these PepBiotics also prevented LPS/LTA induced activation of macrophages and was shown to be non-toxic to primary human nasal epithelial cells. Furthermore, both P. aeruginosa and S. aureus were unable to induce resistance against CR-163 and CR-172, two PepBiotics selected for their excellent antimicrobial and immunomodulatory properties. Toxicity studies in mice indicated that intratracheal administration of CR-163 was well tolerated in vivo. Finally, interaction of CR-163 with bacterial-type anionic membranes but not with mammalian-type (zwitterionic lipid) membranes was confirmed using ITC and 31P solid state NMR. CONCLUSIONS: PepBiotics are a promising novel class of highly active antimicrobial peptides, of which CR-163 showed the most potential for treatment of clinically relevant (CF-) pathogens in physiological conditions. GENERAL SIGNIFICANCE: These observations emphasize the therapeutic potential of PepBiotics against CF-related bacterial respiratory infections.
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Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Animales , Antibacterianos/administración & dosificación , Antibacterianos/química , Péptidos Catiónicos Antimicrobianos/administración & dosificación , Péptidos Catiónicos Antimicrobianos/química , Células Cultivadas , Relación Dosis-Respuesta a Droga , Humanos , Inyecciones Espinales , Masculino , Ratones , Ratones Endogámicos C57BL , Pruebas de Sensibilidad Microbiana , CatelicidinasRESUMEN
Screening for cystic fibrosis (CF) was recently added to the neonatal screening programme in the Netherlands. Four patients with renal failure whose heel prick tests were positive for CF as defined by raised levels of immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) are described. Both cystic fibrosis transmembrane conductance regulator (CFTR) DNA analysis and sweat tests were negative. Limited renal function can be a cause of false positive neonatal screening for CF using IRT and PAP.
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Fibrosis Quística/diagnóstico , Tamizaje Neonatal/métodos , Insuficiencia Renal/sangre , Antígenos de Neoplasias/sangre , Biomarcadores/sangre , Biomarcadores de Tumor/sangre , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Reacciones Falso Positivas , Humanos , Recién Nacido , Lectinas Tipo C/sangre , Masculino , Proteínas Asociadas a Pancreatitis , Tripsinógeno/sangreRESUMEN
OBJECTIVES: To investigate bacterial colonization and pulmonary function longitudinally in patients with cystic fibrosis (CF) receiving drugs for gastric acid (GA) inhibition for fat malabsorption or for gastroesophageal reflux disease (GERD). STUDY DESIGN: A retrospective cohort study of 218 pediatric patients with CF was performed. Multilevel modeling was used to perform longitudinal analysis of forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), maximum expiratory flow at 50% of FVC (MEF(50)), and maximal mid-expiratory flow between 25% and 75% of FVC (MMEF(25-75)). Cox regression was used to calculate Pseudomonas aeruginosa- and Staphylococcus aureus-free survival. RESULTS: Patients with CF and GA inhibition had a significantly smaller yearly decline of MEF(50) and MMEF(25-75) compared with control subjects. Other pulmonary function parameters and P aeruginosa or S aureus acquisition or colonization were not different from that of control subjects. GERD was associated with a significantly reduced pulmonary function (FEV(1) and FVC) and an earlier acquisition of P aeruginosa and S aureus. CONCLUSIONS: GA inhibition did not affect pulmonary function or bacterial acquisition and therefore is not contraindicated in patients with CF. GA inhibition might improve pulmonary function with time, because the decline of MEF(50) and MMEF(25-75) was less pronounced. GERD was associated with a reduced pulmonary function and an earlier acquisition of P aeruginosa and S aureus. Therefore the diagnosis and treatment of GERD should be aggressively pursued in patients with CF.
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Fibrosis Quística/microbiología , Reflujo Gastroesofágico/tratamiento farmacológico , Síndromes de Malabsorción/tratamiento farmacológico , Inhibidores de la Bomba de Protones/uso terapéutico , Pseudomonas aeruginosa/aislamiento & purificación , Staphylococcus aureus/aislamiento & purificación , Adolescente , Niño , Estudios de Cohortes , Recuento de Colonia Microbiana , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado/efectos de los fármacos , Volumen Espiratorio Forzado/fisiología , Ácido Gástrico/metabolismo , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/diagnóstico , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Síndromes de Malabsorción/complicaciones , Síndromes de Malabsorción/diagnóstico , Masculino , Análisis Multivariante , Oportunidad Relativa , Probabilidad , Modelos de Riesgos Proporcionales , Pseudomonas aeruginosa/efectos de los fármacos , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Staphylococcus aureus/efectos de los fármacos , Resultado del Tratamiento , Capacidad Vital/efectos de los fármacosRESUMEN
PURPOSE: Diagnosing asthma in children with asthmatic symptoms remains a challenge, particularly in preschool children. This challenge creates an opportunity for variability in prescribing. The aim of our study was to investigate how and to what degree patient, family, and physician characteristics influence prescribing of asthma medication in children. METHODS: We undertook a multilevel population-based study using the second Dutch national survey of general practice (DNSGP-2), 2001. Participants were 46,371 children aged 1 to 17 years belonging to 25,537 families registered with 109 general practitioners. Using a multilevel multivariate logistic regression analysis with 3 levels, our main outcome measure was the prescribing of asthma medication, defined as at least 1 prescription for beta(2)-adrenergic agonists, inhaled corticosteroids, cromones, or montelukast during the 1-year study period. RESULTS: We identified characteristics significantly associated with prescribing asthma medication on all 3 levels (child, family, and physician). The variance in prescribing among physicians was significantly higher with children who were younger than 6 years than with children aged 6 years and older (95% CI, 3.5%-25.2% vs 2.4%-13.4%). Several diagnoses other than asthma and asthmatic complaints were strongly associated with prescribing asthma medication, including bronchitis/bronchiolitis (OR = 9.04; 95% CI, 7.57-10.8) and cough (OR = 6.51; 95% CI, 5.68-7.47). CONCLUSIONS: Our study shows a much higher variance in prescribing patterns among general practitioners for children younger than 6 years compared with older children, which could be a direct result of the diagnostic complexities found in young children with asthmatic symptoms. Thus diagnostic gaps may lead to more physician-driven prescribing irrespective of the clinical context.
Asunto(s)
Antiasmáticos/administración & dosificación , Asma/diagnóstico , Asma/tratamiento farmacológico , Medicina Familiar y Comunitaria , Pautas de la Práctica en Medicina , Adolescente , Factores de Edad , Análisis de Varianza , Asma/epidemiología , Asma/fisiopatología , Niño , Preescolar , Diagnóstico Diferencial , Revisión de la Utilización de Medicamentos , Composición Familiar , Femenino , Humanos , Lactante , Modelos Logísticos , Masculino , Países Bajos/epidemiología , Ruidos Respiratorios/diagnóstico , Ruidos Respiratorios/etiologíaRESUMEN
BACKGROUND: We aimed to assess whether final height in children with cystic fibrosis (CF) is affected by body mass index (BMI), BMI increase, pulmonary function, and cystic fibrosis-related diabetes (CFRD). STUDY DESIGN: A longitudinal, retrospective study was performed in a cohort of 57 patients with CF (30 boys, 27 girls) born between 1997 and 2001. Height and weight were recorded annually from ages 0.5 to 10 years and biannually up to the age of 18. Measurements were converted to height-for-age-adjusted-for-target-height (HFA-TH) and BMI-for-age z-scores. Analyses were performed using the independent t tests and the Pearson's correlation. RESULTS: For both boys and girls, HFA-TH and BMI-for-age z-scores were significantly lower in the first year of life, these scores increased rapidly until the age of 11 and 8 years, respectively. In boys, HFA-TH z-scores declined during puberty, with subsequently significantly impaired final height (z-score, -0.56, n = 30, standard deviation [SD] = 0.81, P = 0.001). In girls, HFA-TH z-scores briefly declined after the age of 8 years, but then increased to a z-score of -0.21 (n = 27, SD = 0.87) at age 18, which is not significantly lower than the national average (P = 0.22). Pulmonary function and the presence of CFRD were not associated with final height. However, rapid BMI increase between ages 1 and 6 was negatively associated with final height in boys (n = 29, r =-0.420; P = 0.023) and girls (n = 25, r =-0.466; P = 0.019). CONCLUSIONS: In boys and girls, early BMI increase was associated with impaired final height. We suggest that early childhood serves as a "window" in which nutritional variations may program subsequent growth. Further refinement of nutritional strategies could be needed.