Developmental Milestones in Pediatric Research: A Case for Including Efficacy as Part of Interventional Trials in Infants with Cystic Fibrosis.
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ABSTRACT:
SUBMITTER: Sanders DB
PROVIDER: S-EPMC6519866 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Newborn screening for cystic fibrosis (CF) offers the opportunity for early medical and nutritional intervention that can lead to improved outcomes. Management of the asymptomatic infant diagnosed with CF through newborn screening, prenatal diagnosis, or sibling screening is different from treatment of the symptomatically diagnosed individual. The focus of management is on maintaining health by preventing nutritional and respiratory complications. The CF Foundation convened a committee to develop recommendations based on a systematic review of the evidence and expert opinion. These guidelines encompass monitoring and treatment recommendations for infants diagnosed with CF and are intended to help guide families, primary care providers, and specialty care centers in the care of infants with CF.
| S-EPMC6324931 | biostudies-other
Project description:BACKGROUND:There are urgent needs for clinically relevant biomarkers to identify children with cystic fibrosis (CF) at risk for more progressive lung disease and to serve as outcome measures for clinical trials. Our objective was to investigate three targeted biomarkers in a population of asymptomatic CF infants. METHODS:Urine, blood and lung function data were collected for 2 years from clinically stable infants diagnosed with CF by newborn screening. A subset of CF infants had bronchoscopy with lavage performed at 6 months and 1 year. Urine was collected quarterly from healthy control infants. Expectorated sputum and urine were collected quarterly for 2 years from clinically stable CF adults. Desmosine, club cell secretory protein (CCSP) and cathepsin B concentrations were measured and compared. Mixed effects models were used to identify associations between biomarker concentrations and clinical characteristics. Receiver operator characteristic curves were generated to investigate the sensitivity and specificity of the biomarkers. RESULTS:Urinary cathepsin B was significantly higher in CF infants compared to healthy infants (p?=?0.005). CF infant airway and urinary cathepsin B concentrations were significantly lower compared to adult CF subjects (p?=?0.002 & p?=?0.022, respectively). CF infant airway CCSP was significantly higher than adult CF subjects (p?<?0.001). There was a significant correlation between CF infant plasma CCSP and BALF CCSP (p?=?0.046). BALF CCSP was negatively associated with IL-8 (p?=?0.017). There was no correlation between biomarker concentration and FEV0.5. CONCLUSIONS:Cathepsin B and CCSP show promise as biomarkers of inflammation in CF infants. Further study is needed.
| S-EPMC5759377 | biostudies-literature
Project description:This multi-center study will compare multi-target DNA and quantitative FIT stool-based testing to colonoscopy in individuals with Cystic Fibrosis (CF) undergoing colon cancer screening with colonoscopy. The primary endpoint is detection of any adenomas, including advanced adenomas and colorectal cancer (CRC).
| 2726863 | ecrin-mdr-crc
Project description:BACKGROUND:Viral infections contribute to morbidity in cystic fibrosis (CF), but the impact of respiratory viruses on the development of airway disease is poorly understood. METHODS:Infants with CF identified by newborn screening were enrolled prior to 4 months of age to participate in a prospective observational study at 4 centers. Clinical data were collected at clinic visits and weekly phone calls. Multiplex PCR assays were performed on nasopharyngeal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and a subset underwent pulmonary function testing. We present findings through 8.5 months of life. RESULTS:Seventy infants were enrolled, mean age 3.1 ± 0.8 months. Rhinovirus was the most prevalent virus (66%), followed by parainfluenza (19%), and coronavirus (16%). Participants had a median of 1.5 viral positive swabs (range 0-10). Past viral infection was associated with elevated neutrophil concentrations and bacterial isolates in BAL fluid, including recovery of classic CF bacterial pathogens. When antibiotics were prescribed for respiratory-related indications, viruses were identified in 52% of those instances. CONCLUSIONS:Early viral infections were associated with greater neutrophilic inflammation and bacterial pathogens. Early viral infections appear to contribute to initiation of lower airway inflammation in infants with CF. Antibiotics were commonly prescribed in the setting of a viral infection. Future investigations examining longitudinal relationships between viral infections, airway microbiome, and antibiotic use will allow us to elucidate the interplay between these factors in young children with CF.
| S-EPMC6711838 | biostudies-literature
Project description:Infant HIV-1 infection is associated with impaired neurologic and motor development. Antiretroviral therapy (ART) has the potential to improve developmental outcomes but the relative contributions of pre-ART disease status, growth, treatment regimen and ART response during infancy are unknown.Kenyan ART-naive infants <5-months old initiated ART and had monthly assessment of age of full neck control, unsupported walking and monosyllabic speech during 24 months of follow-up. Pre-ART and post-ART correlates of age at milestone attainment were evaluated using t tests or multivariate linear regression.Among 99 infants, pre-ART correlates of later milestone attainment included: underweight and stunted (neck control, walking and speech, all P values <0.05), missed prevention of mother-to-child transmission (P = 0.04) (neck control), previous hospitalization, World Health Organization (WHO) Stage III/IV, low CD4 count, and wasting (speech and walking, all P values <0.05), and low maternal CD4 (speech, P = 0.04). Infants initiated ART at a median of 14 days following enrollment. Infants receiving nevirapinevs lopinavir/ritonavir-based ART attained later speech (18.1 vs. 15.5 months, P = 0.003) [corrected]. Adjusting for pre-ART level, lower 6-month gain in CD4% was associated with later walking (0.18 months earlier per unit increase in CD4%; P = 0.004) and speech (0.12 months earlier per unit increase in CD4%; P = 0.05), and lower 6-month gains in weight-for-age (P = 0.009), height-for-age (P = 0.03) and weight-for-height (P = 0.02) were associated with later walking.In HIV-infected infants, compromised pre-ART immune and growth status, poor post-ART immune and growth responses, and use of nevirapine- vs. lopinavir/ritonavir-based ART were each associated with later milestone attainment [corrected]. The long-term consequences of these delays are unknown.
| S-EPMC4336221 | biostudies-literature
Project description:The link between human gut microbiota (a complex group of microorganisms including not only bacteria but also fungi, viruses, etc.,) and the physiological state is nowadays unquestionable. Metaproteomic has emerged as a useful technique to characterize this microbial community, not just taxonomically, but also focusing on specific biological processes carried out by gut microbiota that may have an effect in the host health or pathological state. Cystic fibrosis is a genetic disease in which the microbiota of the respiratory tract determines the patient's survival and differences in composition of gut microbiota of cystic fibrosis patients respect to healthy infants have been reported. In order to characterize this host-microbiota inter-relation, we carried out the metaproteomic study of 30 stool samples from infants with cystic fibrosis.
2022-10-11 | PXD029284 | Pride
Project description:The pathogenesis of airway infection in cystic fibrosis (CF) is poorly understood. We performed a longitudinal study coupling clinical information with frequent sampling of the microbiota to identify changes in the airway microbiota in infancy that could underpin deterioration and potentially be targeted therapeutically. Thirty infants with CF diagnosed on newborn screening (NBS) were followed for up to two years. Two hundred and forty one throat swabs were collected as a surrogate for lower airway microbiota (median 35 days between study visits) in the largest longitudinal study of the CF oropharyngeal microbiota. Quantitative PCR and Illumina sequencing of the 16S rRNA bacterial gene were performed. Data analyses were conducted in QIIME and Phyloseq in R. Streptococcus spp. and Haemophilus spp. were the most common genera (55% and 12.5% of reads respectively) and were inversely related. Only beta (between sample) diversity changed with age (Bray Curtis r2?=?0.15, P?=?0.03). Staphylococcus and Pseudomonas were rarely detected. These results suggest that Streptococcus spp. and Haemophilus spp., may play an important role in early CF. Whether they are protective against infection with more typical CF micro-organisms, or pathogenic and thus meriting treatment needs to be determined.
| S-EPMC6435666 | biostudies-literature
Project description:BACKGROUND:Biologic pathways and metabolic mechanisms underpinning early systemic disease in cystic fibrosis (CF) are poorly understood. The Baby Observational and Nutrition Study (BONUS) was a prospective multi-center study of infants with CF with a primary aim to examine the current state of nutrition in the first year of life. Its secondary aim was to prospectively explore concurrent nutritional, metabolic, respiratory, infectious, and inflammatory characteristics associated with early CF anthropometric measurements. We report here metabolomics differences within the urine of these infants as compared to infants without CF. METHODS:Urine metabolomics was performed for 85 infants with predefined clinical phenotypes at approximately one year of age enrolled in BONUS via Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Samples were stratified by disease status (non-CF controls (n?=?22); CF (n?=?63, All-CF)) and CF clinical phenotype: respiratory hospitalization (CF Resp, n?=?22), low length (CF LL, n?=?23), and low weight (CF LW, n?=?15). RESULTS:Global urine metabolomics profiles in CF were heterogeneous, however there were distinct metabolic differences between the CF and non-CF groups. Top pathways altered in CF included tRNA charging and methionine degradation. ADCYAP1 and huntingtin were identified as predicted unique regulators of altered metabolic pathways in CF compared to non-CF. Infants with CF displayed alterations in metabolites associated with bile acid homeostasis, pentose sugars, and vitamins. CONCLUSIONS:Predicted metabolic pathways and regulators were identified in CF infants compared to non-CF, but metabolic profiles were unable to discriminate between CF phenotypes. Targeted metabolomics provides an opportunity for further understanding of early CF disease. TRIAL REGISTRATION:United States ClinicalTrials.Gov registry NCT01424696 (clinicaltrials.gov).
| S-EPMC6533170 | biostudies-literature
Project description:RationaleIn cystic fibrosis, abnormal glucose tolerance is associated with decreased lung function and worsened outcomes. Translational evidence indicates that abnormal glucose tolerance may begin in early life.ObjectivesTo determine whether very young children with cystic fibrosis have increased abnormal glucose tolerance prevalence compared with control subjects. The secondary objective was to compare area under the curve for glucose and insulin in children with cystic fibrosis with control subjects.MethodsThis is a prospective multicenter study in children ages 3 months to 5 years with and without cystic fibrosis.Measurements and main resultsOral glucose tolerance testing with glucose, insulin, and C-peptide was sampled at 0, 10, 30, 60, 90, and 120 minutes. Twenty-three children with cystic fibrosis and nine control subjects had complete data. All control subjects had normal glucose tolerance. Nine of 23 subjects with cystic fibrosis had abnormal glucose tolerance (39%; P = 0.03). Of those, two met criteria for cystic fibrosis-related diabetes, two indeterminate glycemia, and six impaired glucose tolerance. Children with cystic fibrosis failed to exhibit the normal increase in area under the curve insulin with age observed in control subjects (P < 0.01), despite increased area under the curve glucose (P = 0.02).ConclusionsAbnormal glucose tolerance is notably prevalent among young children with cystic fibrosis. Children with cystic fibrosis lack the normal increase in insulin secretion that occurs in early childhood despite increased glucose. These findings demonstrate that glycemic abnormalities begin very early in cystic fibrosis, possibly because of insufficient insulin secretion.
| S-EPMC5067820 | biostudies-literature
Project description:BackgroundSince public awareness of cystic fibrosis (CF) has increased, more children have been diagnosed with CF in China. This study aimed to investigate medical and other challenges faced by pediatric CF patients in China.MethodTreatments and treatment outcomes were retrospectively analyzed for 46 pediatric CF patients diagnosed from August 2009 to June 2019. Pre- and post-treatment results were compared using independent samples t-test.ResultsOf 46 pediatric CF study patients, four died and five were lost to follow-up. Thirty-seven patients were monitored for 0.03 to 9.21 years; patients exhibited fewer attacks of respiratory tract infections after diagnosis (4.49 ± 2.13 episodes/year before diagnosis vs 1.97 ± 1.87 times/year after 1-year treatment, p < 0.05), significantly reduced sputum production and experienced 1.62 ± 1.71 exacerbations/year. Patient mean body mass index was 16.87 ± 3.53 and pancreatic malfunction persisted in 15 patients. For 17 children, no significant differences in lung function were found at follow-up as compared to lung function at diagnosis (FEV1: 82.45% ± 16.56% vs 75.26% ± 22.34%, FVC: 87.18% ± 13.64% vs 86.99% ± 19.95%, FEF75%: 46.51% ± 28.78% vs 36.63% ± 24.30%, P = 0.27, 0.97, 0.20, respectively). Pseudomonas aeruginosa (17/27) and bronchiectasis (22/22) were found during follow-up evaluation. Twenty-four patients (64.8%) maintained good adherence to therapies. Overall, azithromycin and tobramycin treatments were administered for 0.5-62 months and 0.5-48 months, respectively, and triggered no obvious adverse reactions.ConclusionNo obvious declines in clinical presentation or lung function were found in Chinese pediatric CF patients after receiving standard therapeutic and active treatments, although malnutrition and low compliance were persistent challenges.
| S-EPMC8317407 | biostudies-literature