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).
Project description:The human respiratory tract is constantly exposed to a wide variety of viruses, microbes and inorganic particulates from environmental air, water and food. Physical characteristics of inhaled particles and airway mucosal immunity determine which viruses and microbes will persist in the airways. Here we present the first metagenomic study of DNA viral communities in the airways of diseased and non-diseased individuals. We obtained sequences from sputum DNA viral communities in 5 individuals with cystic fibrosis (CF) and 5 individuals without the disease. Overall, diversity of viruses in the airways was low, with an average richness of 175 distinct viral genotypes. The majority of viral diversity was uncharacterized. CF phage communities were highly similar to each other, whereas Non-CF individuals had more distinct phage communities, which may reflect organisms in inhaled air. CF eukaryotic viral communities were dominated by a few viruses, including human herpesviruses and retroviruses. Functional metagenomics showed that all Non-CF viromes were similar, and that CF viromes were enriched in aromatic amino acid metabolism. The CF metagenomes occupied two different metabolic states, probably reflecting different disease states. There was one outlying CF virome which was characterized by an over-representation of Guanosine-5'-triphosphate,3'-diphosphate pyrophosphatase, an enzyme involved in the bacterial stringent response. Unique environments like the CF airway can drive functional adaptations, leading to shifts in metabolic profiles. These results have important clinical implications for CF, indicating that therapeutic measures may be more effective if used to change the respiratory environment, as opposed to shifting the taxonomic composition of resident microbiota.
Project description:Cystic fibrosis (CF) is characterized by recurrent respiratory infections and progressive lung disease. Although environmental factors account for 50% of the variation in CF lung function, few specific exposures have been identified. Studies using small study samples focusing on environmental allergies in CF have had inconsistent results. Our objective was to examine the role of environmental allergies in upper and lower respiratory tract morbidities in CF.A total of 1,321 subjects with CF were recruited through the U.S. CF Twin-Sibling Study. Questionnaires were used to determine the presence/absence of environmental allergies. Questionnaires, chart review, and U.S. CF Foundation Patient Registry data were used to track outcomes.Within the study sample 14% reported environmental allergies. Environmental allergies were associated with a higher risk of sinus disease (adjusted OR: 2.68; P < 0.001) and nasal polyps (adjusted OR: 1.74; P?=?0.003). Environmental allergies were also associated with a more rapid decline in lung function (additional -1.1%/year; P?=?0.001). However, allergies were associated with a later median age of acquisition of Pseudomonas aeruginosa (6.6 years vs. 4.4 years; log rank P?=?0.027). The reported use of common allergy medications, anti-histamines and leukotriene inhibitors, did not alter the frequency of respiratory morbidities.Environmental allergies are associated with an increased risk of sinus disease and nasal polyps and a more rapid decline in CF lung function, but may have a protective effect against the acquisition of P. aeruginosa. Prospective studies are needed to confirm these associations which have implications for more aggressive management of allergies.
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.
Project description:Since the discovery of the gene associated with cystic fibrosis (CF), there has been tremendous progress in the care of patients with this disease. New therapies have entered the market and are part of the standard treatment of patients with CF, and have been associated with marked improvement in survival. Now there are even more promising therapies directed at different components of the pathophysiology of this disease. In this review, our current knowledge of the pathophysiology of lung disease in patients with CF is described, along with the current treatment of CF lung disease, and the therapies in development that offer great promise to our patients.
Project description:BACKGROUND:Aspergillus species are increasingly detected in the respiratory tracts of individuals with cystic fibrosis (CF), and chronic Aspergillus fumigatus is associated with more frequent hospitalizations for pulmonary exacerbations. However, patient and clinical factors that may contribute to the acquisition of persistent Aspergillus infection have yet to be identified. The objective of this study was to identify risk factors for development of Aspergillus respiratory isolation in CF. METHODS:A retrospective cohort study of participants in the CF Foundation Patient Registry between 2006 and 2012 was conducted. Generalized estimating equation models were used to evaluate the association between the development of persistent Aspergillus respiratory isolation and individual level demographic and clinical characteristics. RESULTS:Among 16,095 individuals with CF followed from 2006 to 2012, 1541 (9.6%) subjects developed persistent Aspergillus isolation. White race (Odds Ratio [OR] 1.74, 95% confidence interval 1.23, 2.48, p<0.001) and pancreatic insufficiency (OR 1.50, 95% CI 1.09, 2.06, p<0.001) were found to be risk factors for persistent Aspergillus isolation. Chronic therapies, including inhaled antibiotics (OR 1.33; 95% CI 1.21, 1.46), macrolides (OR 1.23, 95% CI 1.14, 1.32, p<0.001), and inhaled corticosteroids (OR 1.13, 95% CI 1.04, 1.20, p<0.001) were also independently associated with an increased risk for persistent Aspergillus isolation. CONCLUSIONS:We identified macrolides and inhaled antibiotics, which individually have been shown to improve CF outcomes, and inhaled corticosteroids as risk factors for developing persistent Aspergillus isolation. Further work is needed to determine whether these associations are causal or due to confounding by other factors.
Project description:To investigate a possible role for human rhinovirus C in respiratory exacerbations of children with cystic fibrosis, we conducted microbiologic testing on respiratory specimens from 103 such patients in São Paulo, Brazil, during 2006-2007. A significant association was found between the presence of human rhinovirus C and respiratory exacerbations.
Project description:BackgroundLittle is known about the response of the equine respiratory muscles to training.ObjectivesTo measure an index of inspiratory muscle strength (IMSi) before and after a period of conventional exercise training (phase 1) and inspiratory muscle training (IMT), comparing high-load (treatment) and low-load (control) groups (phase 2).Study designProspective randomised controlled trial.MethodsPhase 1: Twenty National Hunt Thoroughbred racehorses performed an inspiratory muscle strength test (IMST) twice on two occasions; when unfit at timepoint A (July), and when race fit at timepoint B (October). Phase 2: Thirty-five Thoroughbred racehorses at race fitness were randomly assigned into a high-load (treatment, n = 20) or low-load (control, n = 15) IMT group. The high-load group followed an IMT protocol that gradually increased the inspiratory pressure applied every 4 days. The low-load group underwent sham IMT with a low training load. The IMT was performed 5 days/week for 10 weeks. The IMST was performed twice on two occasions, timepoint B (October) and timepoint C (January). Conventional exercise training and racing continued during the study period. The peak IMSi values obtained from the different groups at timepoints A, B and C were compared using a Wilcoxon Signed Rank Test.ResultsPhase 1: There was a significant increase in IMSi from timepoint A: 22.5 cmH2 O (21-25) to timepoint B: 26 cmH2 O (24-30) (p = 0.015). Phase 2: From timepoint B to C there was a significant increase in IMSi for the high-load group 34 cmH2 O (28-36) (p = 0.001) but not the low-load group 26 cmH2 O (24-30) (p = 0.929). The peak IMSi at timepoint C was significantly higher for the high-load than low-load group (p = 0.019).Main limitationsSingle centre study with only National Hunt horses undergoing race-training included.ConclusionsIn horses undergoing race training there is a significant increase in IMSi in response to conventional exercise training and high-load IMT.