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Cystic fibrosis [keywords]
- Pulmonary Hypertension in Cystic Fibrosis with Advanced Lung Disease. [JOURNAL ARTICLE]
- Am J Respir Crit Care Med 2014 Sep 15.
Rationale: Impact of pulmonary hypertension (PH) on survival in cystic fibrosis (CF) remains unclear. Objectives: To determine influence of PH on survival in the CF population. Methods: The UNOS database was queried from 1987 to 2013 to identify first-time lung transplant candidates who were tracked from wait list entry date until death or censoring to determine influence of PH. Using right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure (PAP) ≥ 25 mmHg and severe ≥ 35 mmHg. Measurements and Main Results: Of 2781 CF patients, 2100 were used for univariate analysis, 764 for Kaplan-Meier (KM) survival function, 687 for multivariate Cox models, and 576 (mild PH) and 132 (severe PH) for propensity score matching, respectively. Univariate analysis with KM functions found significant differences in survival for mild PH (HR = 1.747, 95% CI: 1.387, 2.201, p < 0.001) and severe PH (HR = 2.299, 95% CI: 1.639, 3.225, p < 0.001). Further assessment by multivariate Cox models identified significant risk for death for mild PH (HR = 1.757, 95% CI: 1.367, 2.258, p < 0.001) and severe PH (HR = 2.284, 95% CI: 1.596, 3.268, p < 0.001). Propensity score matching confirmed the risk for death for mild PH (HR = 1.919, 95% CI: 1.290, 2.85, p = 0.001) and severe PH (HR = 4.167, 95% CI: 1.709, 10.157, p = 0.002). Conclusions: The manifestation of PH is associated with significantly increased risk for death in CF patients with advanced lung disease.
- Effect of Different Breathing Aids on Ventilation Distribution in Adults with Cystic Fibrosis. [JOURNAL ARTICLE]
- PLoS One 2014; 9(9):e106591.
We investigated the effect of different breathing aids on ventilation distribution in healthy adults and subjects with cystic fibrosis (CF).In 11 healthy adults and 9 adults with CF electrical impedance tomography measurements were performed during spontaneous breathing, continuous positive airway pressure (CPAP) and positive expiratory pressure (PEP) therapy randomly applied in upright and lateral position. Spatial and temporal ventilation distribution was assessed.The proportion of ventilation directed to the dependent lung significantly increased in lateral position compared to upright in healthy and CF. This effect was enhanced with CPAP but neutralised with PEP, whereas the effect of PEP was larger in the healthy group. Temporal ventilation distribution showed exactly the opposite with homogenisation during CPAP and increased inhomogeneity with PEP.PEP shows distinct differences to CPAP with respect to its impact on ventilation distribution in healthy adults and CF subjects EIT might be used to individualise respiratory physiotherapy.
- The expanding armamentarium of drugs to aid sputum clearance: how should they be used to optimize care? [JOURNAL ARTICLE]
- Curr Opin Pulm Med 2014 Sep 12.
This review examines the evidence for use of agents that improve sputum clearance in cystic fibrosis.The basic defect in cystic fibrosis causes abnormal airway surface liquid leading to mucus plugging and subsequent infection and inflammation in the airways. Agents that improve clearance of secretions should improve lung function, reduce infective exacerbations and may enhance survival. There are two main varieties of mucoactive therapy, namely mucolytic therapy, which reduces viscosity in order to improve clearance, and hyperosmolar therapy, which increases the airway surface liquid volume and increases mucociliary clearance. The development of mannitol as a hyperosmolar agent in dry powder form has heightened the debate regarding the optimal approach to sputum clearance. The evidence for use of individual agents is discussed, as well as a practical approach to combining therapies.Dornase alfa, a mucolytic agent, and hypertonic saline and mannitol, both hyperosmolar agents, have all been shown to benefit patients with cystic fibrosis. The optimal combination of therapies has not been identified, but a combination of a hyperosmolar agent combined with a mucolytic provides the most logical approach to improving lung function and reducing exacerbations.
- Dry powder inhalers in cystic fibrosis: same old drugs but different benefits? [JOURNAL ARTICLE]
- Curr Opin Pulm Med 2014 Sep 12.
Newer 'innovative' formulations of antibiotics for Pseudomonas aeruginosa lung infection in patients with cystic fibrosis include colistimethate sodium and tobramycin in the form of dry powders for inhalation (DPIs). Whilst these DPIs are anticipated to improve patient adherence because of increased convenience and ease of administration, questions remain concerning whether they are as clinically effective, safe and cost-effective as nebulized antibiotics.This review describes the recent findings of a health technology assessment of the clinical effectiveness and cost-effectiveness of colistimethate sodium and tobramycin DPIs with regard to how innovative treatments may be judged to be incrementally better than existing treatments. The original assessment was undertaken to inform the National Institute for Health and Care Excellence's Technology Appraisal Programme to inform national clinical guidance on the use of these new treatments in the National Health Service.Three trials were included in the systematic review. Issues surrounding the clinical effectiveness and cost-effectiveness of colistimethate sodium DPI and tobramycin DPI are discussed in light of the considerable uncertainties associated with the available evidence.
- Non-invasive detection of Helicobacter pylori in cystic fibrosis - The fecal test vs. the urea breath test. [Journal Article]
- Eur Rev Med Pharmacol Sci 2014 Aug; 18(16):2343-8.
Only recently it has been proven that cystic fibrosis (CF) patients have the same prevalence of Helicobacter pylori (HP infection) as the general population, as well as the same spectrum of changes caused by this pathogen. The aim of this study was to assess the reliability of the two most popular noninvasive tests - the urea breath test (UBT) and the fecal test (FT) in diagnosing HP infection in CF patients.The study was conducted on 79 CF patients and 49 healthy subjects (HS). The presence of HP infection was evaluated using the 13C isotope-labeled urea breath test and the fecal test (ELISA).Fifteen (19.0%) CF patients and eight (16.3%) HS were found to be HP positive using the UBT. The HP stool antigen was detected in twelve (15.2%) CF patients and seven (14.3%) HS. Discordant results for the two tests were obtained in 9 out of 18 (50.0%) CF patients and 3 out of 9 (33.3%) HS. Although the differences were not statistically significant, the risk of potentially false negative and false positive results in CF subjects seems to be high. Similarly, no statistical differences in the basic clinical parameters were documented between the CF subgroups with concordant and divergent HP results.Since there is convincing evidence of divergent UBT and FT results in the CF patients, we suggest that UBT is kept as the standard method for HP detection in this population, at least until obtaining reliable and valid results allows for a change in such an approach.
- Putting lung function and physiology into perspective: cystic fibrosis in adults. [JOURNAL ARTICLE]
- Respirology 2014 Sep 15.
Adult cystic fibrosis (CF) is notable for the wide heterogeneity in severity of disease expression, both between patients and within the lungs of individuals. Although CF airways disease appears to start in the small airways, in adults there is typically widespread bronchiectasis, increased airway secretions, and extensive obstruction and inflammation of the small airways. The complexity and heterogeneity of airways disease in CF means that although there are many different methods of assessing and describing lung 'function', none of these single-dimensional tests is able to provide a comprehensive assessment of lung physiology across the spectrum seen in adult CF. The most widely described measure, the forced expiratory volume in 1 s, remains a useful and simple clinical tool, but is insensitive to early changes and may be dissociated from other more detailed assessments of disease severity such as computed tomography. In this review, we also discuss the use of more sensitive novel assessments such as multiple breath washout tests and impulse oscillometry, as well as the role of cardiopulmonary exercise testing. In the future, hyperpolarized gas magnetic resonance imaging techniques that combine regional structural and functional information may help us to better understand these measures, their applications and limitations.
- Applications. [Journal Article]
- Clin Lab Sci 2014; 27(3):179-84.
Next generation sequencing platforms and the applications that are offered have revolutionized the way a physician will treat and monitor a patient based on the individual's own genetic make-up. Whether whole genome sequencing, exome sequencing, or targeted sequencing is performed, the information generated must be analyzed, interpreted, and reported correctly. Since the various platforms and application panels are not FDA cleared (with the exception of the Illumina MiSeqDx Cystic Fibrosis Clinical Sequencing Assay and the Illumina MiSeqDx Cystic Fibrosis 139-Variant Assay) clinical laboratorians are faced with the challenge of standardizing and validating the various panels and platforms for appropriate quality management. Therefore, the American College of Medical Genetics and Genomics published guidelines for ordering, test development, validation and reporting of genetic information. These guidelines should be followed by all laboratorians performing NGS to ensure quality results and to provide proper interpretation of all genomic variants identified.
- PNA-Based Fluorescence In Situ Hybridization for Identification of Bacteria in Clinical Samples. [JOURNAL ARTICLE]
- Methods Mol Biol 2014.:261-271.
Fluorescence in situ hybridization with PNA probes (PNA-FISH) that target specific bacterial ribosomal RNA sequences is a powerful and rapid tool for identification of bacteria in clinical samples. PNA can diffuse readily through the bacterial cell wall due to its uncharged backbone, and PNA-FISH can be performed with high specificity due to the extraordinary thermal stability of RNA-PNA hybrid complexes. We describe a PNA-FISH procedure and provide examples of the application of PNA-FISH for the identification of bacteria in chronic wounds, cystic fibrosis lungs, and soft tissue fillers. In all these cases, bacteria can be identified in biofilm aggregates, which may explain their recalcitrance to antibiotic treatment.
- Female cystic fibrosis mutation carriers and assisted reproductive technology: does carrier status affect reproductive outcomes? [JOURNAL ARTICLE]
- Fertil Steril 2014 Sep 10.
To evaluate the association between female cystic fibrosis (CF) carrier status and in vitro fertilization (IVF) response and outcomes. The presence of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in male carriers has been associated with infertility, yet possible adverse effects on the ovarian function and reproductive outcomes of female carriers have not been studied to date.Retrospective cohort study.Private academic, clinical reproductive center.Females <40 years of age who were screened for CFTR mutations and received IVF treatment between July 2002 and March 2013.Patients initiated controlled ovarian hyperstimulation with frequent monitoring, vaginal oocyte retrieval, fertilization, embryo transfer, and a pregnancy test. Various measures of IVF stimulation response and cycle outcome were evaluated for both carriers and noncarriers.Analysis was performed by logistic regression and Poisson regression.IVF cycles (n = 199) from CFTR mutation carrier patients (n = 112) were analyzed. No significant differences in outcome were noted when carriers of different mutation loci were compared in aggregate with the noncarrier group (n = 6,420 cycles from 3,555 patients). Significant differences were noted for some metrics when the carriers were grouped by mutation loci.Overall, no significant differences in stimulation response and cycle outcome were noted between female CFTR mutation carriers and noncarriers. Further research is needed to investigate whether the differences noted between specific CFTR mutation loci are clinically relevant and whether CFTR mutations may impact reproductive outcomes outside the context of assisted reproductive technologies.
- Hypermutation in Burkholderia cepacia complex is mediated by DNA mismatch repair inactivation and is highly prevalent in cystic fibrosis chronic respiratory infection. [JOURNAL ARTICLE]
- Int J Med Microbiol 2014 Aug 28.
The Burkholderia cepacia complex (Bcc) represents an important group of pathogens involved in long-term lung infection in cystic fibrosis (CF) patients. A positive selection of hypermutators, linked to antimicrobial resistance development, has been previously reported for Pseudomonas aeruginosa in this chronic infection setting. Hypermutability, however, has not yet been systematically evaluated in Bcc species. A total of 125 well characterized Bcc isolates recovered from 48 CF patients, 10 non-CF patients and 15 environmental samples were analyzed. In order to determine the prevalence of mutators their spontaneous mutation rates to rifampicin resistance were determined. In addition, the genetic basis of the mutator phenotypes was investigated by sequencing the mutS and mutL genes, the main components of the mismatch repair system (MRS). The overall prevalence of hypermutators in the collection analyzed was 13.6%, with highest occurrence (40.7%) among the chronically infected CF patients, belonging mainly to B. cenocepacia, B. multivorans, B. cepacia, and B. contaminans -the most frequently recovered Bcc species from CF patients worldwide. Thirteen (76.5%) of the hypermutators were defective in mutS and/or mutL. Finally, searching for a possible association between antimicrobial resistance and hypermutability, the resistance-profiles to 17 antimicrobial agents was evaluated. High antimicrobial resistance rates were documented for all the Bcc species recovered from CF patients, but, except for ciprofloxacin, a significant association with hypermutation was not detected. In conclusion, in the present study we demonstrate for the first time that, MRS-deficient Bcc species mutators are highly prevalent and positively selected in CF chronic lung infections. Hypermutation therefore, might be playing a key role in increasing bacterial adaptability to the CF-airway environment, facilitating the persistence of chronic lung infections.