Academic, Foundation, and Industry Collaboration in Finding New Therapies.

N Engl J Med. 2017 May 04;376(18):1762-1769

Authors: Ramsey BW, Nepom GT, Lonial S

PMID: 28467868 [PubMed - indexed for MEDLINE]

Allergic Bronchopulmonary Aspergillosis: AllA Radiologist Needs To Know.

Curr Pediatr Rev. 2016;12(3):179-189

Authors: Garg MK, Sharma M, Agarwal R, Aggarwal AN, Gupta P, Sodhi KS, Chakrabarty A, Khandelwal N

Abstract
BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an immunological lung disorder occurring due to hypersensitivity to fungus Aspergillus fumigatus. Early diagnosis of ABPA is desirable as the disease can cause irreversible damage and end stage lung disease. Diagnosis of ABPA is based upon a set of clinical, serological and radiological criteria. Radiology plays an important role in the diagnosis of ABPA. However a radiologist should also be familiar with various clinical and serological criteria, so as to have a complete understanding of the disease process and to give a confident diagnosis.
OBJECTIVE: To describe various clinical, laboratory and radiological findings in ABPA with a comprehensive review of various diagnostic criteria.
METHOD: We searched the literature for various criteria that have been used for diagnosis of ABPA. We also extensively reviewed the radiology literature to look for various imaging findings described in ABPA. We searched the role of various imaging modalities used in evaluation of ABPA starting with conventional radiography to computed tomography to magnetic resonance imaging.
RESULTS: In this article, we have reviewed clinical, serological and radiological aspects of ABPA, with emphasis on the radiological findings. We have also described the various diagnostic criteria of ABPA.
CONCLUSION: In recent years, role of radiology in ABPA has evolved. Radiology plays an important role not only in diagnosis but also classification and prognostication of the disease. A radiologist should also be familiar with the clinical spectrum and laboratory findings of the disease.

PMID: 27585455 [PubMed - indexed for MEDLINE]

Phosphoryl Group Flow within the Pseudomonas aeruginosa Pil-Chp Chemosensory System: DIFFERENTIAL FUNCTION OF THE EIGHT PHOSPHOTRANSFERASE AND THREE RECEIVER DOMAINS.

J Biol Chem. 2016 Aug 19;291(34):17677-91

Authors: Silversmith RE, Wang B, Fulcher NB, Wolfgang MC, Bourret RB

Abstract
Bacterial chemosensory signal transduction systems that regulate motility by type IV pili (T4P) can be markedly more complex than related flagellum-based chemotaxis systems. In T4P-based systems, the CheA kinase often contains numerous potential sites of phosphorylation, but the signaling mechanisms of these systems are unknown. In Pseudomonas aeruginosa, the Pil-Chp system regulates T4P-mediated twitching motility and cAMP levels, both of which play roles in pathogenesis. The Pil-Chp histidine kinase (ChpA) has eight "Xpt" domains; six are canonical histidine-containing phosphotransfer (Hpt) domains and two have a threonine (Tpt) or serine (Spt) in place of the histidine. Additionally, there are two stand-alone receiver domains (PilG and PilH) and a ChpA C-terminal receiver domain (ChpArec). Here, we demonstrate that the ChpA Xpts are functionally divided into three categories as follows: (i) those phosphorylated with ATP (Hpt4-6); (ii) those reversibly phosphorylated by ChpArec (Hpt2-6), and (iii) those with no detectable phosphorylation (Hpt1, Spt, and Tpt). There was rapid phosphotransfer from Hpt2-6 to ChpArec and from Hpt3 to PilH, whereas transfer to PilG was slower. ChpArec also had a rapid rate of autodephosphorylation. The biochemical results together with in vivo cAMP and twitching phenotypes of key ChpA phosphorylation site point mutants supported a scheme whereby ChpArec functions both as a phosphate sink and a phosphotransfer element linking Hpt4-6 to Hpt2-3. Hpt2 and Hpt3 are likely the dominant sources of phosphoryl groups for PilG and PilH, respectively. The data are synthesized in a signaling circuit that contains fundamental features of two-component phosphorelays.

PMID: 27354279 [PubMed - indexed for MEDLINE]

Bacteria isolated from the airways of paediatric patients with bronchiectasis according to HIV status.

S Afr Med J. 2017 Apr 25;107(5):435-439

Authors: Verwey C, Velaphi S, Khan R

Abstract
BACKGROUND: Knowledge of which bacteria are found in the airways of paediatric patients with bronchiectasis unrelated to cystic fibrosis (CF) is important in defining empirical antibiotic guidelines for the treatment of acute infective exacerbations.
OBJECTIVE: To describe the bacteria isolated from the airways of children with non-CF bronchiectasis according to their HIV status.
METHODS: Records of children with non-CF bronchiectasis who attended the paediatric pulmonology clinic at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, from April 2011 to March 2013, or were admitted to the hospital during that period, were reviewed. Data collected included patient demographics, HIV status, and characteristics of the airway samples and types of bacteria isolated.
RESULTS: There were 66 patients with non-CF bronchiectasis over the 2-year study period. The median age was 9.1 years (interquartile range 7.2 - 12.1). The majority of patients (78.8%) were HIV-infected. A total of 134 samples was collected (median 1.5 per patient, range 1 - 7), of which 81.3% were expectorated or induced sputum samples. Most bacteria were Gram negatives (72.1%). Haemophilus influenzae was the most common bacterium identified (36.0%), followed by Streptococcus pneumoniae (12.6%), Moraxella catarrhalis (11.1%) and Staphylococcus aureus (10.6%). There were no differences between HIV-infected and uninfected patients in prevalence or type of pathogens isolated.
CONCLUSION: Bacterial isolates from the airways of children with non-CF bronchiectasis were similar to those in other paediatric populations and were not affected by HIV status.

PMID: 28492126 [PubMed - in process]

Burkholderia cepacia complex and limited cutaneous vasculitis in patients with cystic fibrosis: a case series.

JRSM Open. 2017 Apr;8(4):2054270417692732

Authors: Kayria M, Chris O, Dhasmana DJ, Nilesh M, Hodson ME, Khin G, Diana B, Simmonds NJ

Abstract
There is a high association of reactive skin presentations, mainly limited cutaneous vasculitis in patients with cystic fibrosis and Burkholderia cepcia complex chronic infection. This may be due to raised levels of circulating inflammatory mediators.

PMID: 28491333 [PubMed - in process]

What's new in the management of adult bronchiectasis?

F1000Res. 2017;6:527

Authors: Koser U, Hill A

Abstract
Bronchiectasis is a heterogeneous, chronic condition with many aetiologies. It poses a significant burden on patients and healthcare practitioners and services. Clinical exacerbations often result in reduced quality of life, increased rate of lung function decline, increased hospitalisation, and mortality. Recent focus in respiratory research, guidelines, and future management options has improved this clinical field in evidence-based practice, but further work and phase III clinical trials are required. This article aims to summarise and explore advances in management strategies in recent years and highlight areas of research and future focus.

PMID: 28491293 [PubMed - in process]

Adherence to tobramycin inhaled powder vs inhaled solution in patients with cystic fibrosis: analysis of US insurance claims data.

Patient Prefer Adherence. 2017;11:831-838

Authors: Hamed K, Conti V, Tian H, Loefroth E

Abstract
PURPOSE: Tobramycin inhalation powder (TIP), the first dry-powder inhaled antibiotic for pulmonary Pseudomonas aeruginosa infection, is associated with reduced treatment burden, increased patient satisfaction, and higher self-reported adherence for cystic fibrosis (CF) patients. We compared adherence in CF patients newly treated with TIP with those newly treated with the traditional tobramycin inhalation solution (TIS), using US insurance claims data.
PATIENTS AND METHODS: From the Truven MarketScan(®) database, we identified CF patients chronically infected with P. aeruginosa who had been prescribed TIP between May 1, 2013 to December 31, 2014, or TIS between September 1, 2010 to April 30, 2012 with at least 12 months of continuous medical and pharmacy benefits prior to and following prescription. TIP and TIS adherence levels were assessed.
RESULTS: A total of 145 eligible patients were identified for the TIP cohort and 306 for the TIS cohort. Significant differences in age distribution (25.0 vs 21.9 years for TIP vs TIS, respectively, P=0.017), type of health plan (P=0.014), employment status (72.4% vs 63.4% of TIP vs TIS patients in full-time employment, P=0.008), and some comorbidities were observed between the two cohorts. Although a univariate analysis found no significant differences between TIP and TIS (odds ratio [OR] 1.411, 95% confidence interval [CI] 0.949-2.098), TIP was moderately associated with higher adherence levels compared with TIS in a multivariable analysis, once various demographic and clinical characteristics were adjusted for. These included geographic location (OR: 1.566, CI: 1.016-2.413) and certain comorbidities.
CONCLUSION: This study of US patient data supports previous findings that TIP is associated with better adherence compared with TIS; however, further studies will be required to fully elucidate differences in adherence between TIP and TIS.

PMID: 28490864 [PubMed - in process]

Human Bocavirus Type-1 Capsid Facilitates the Transduction of Ferret Airways by Adeno-Associated Virus Genomes.

Hum Gene Ther. 2017 May 10;:

Authors: Yan Z, Feng Z, Sun X, Zhang Y, Zou W, Wang Z, Jensen-Cody C, Liang B, Park SY, Qiu J, Engelhardt JF

Abstract
Human bocavirus type-1 (HBoV1) has a high tropism for the apical membrane of human airway epithelia. The packaging of a recombinant adeno-associated virus 2 (rAAV2) genome into HBoV1 capsid produces a chimeric vector (rAAV2/HBoV1) that also efficiently transduces human airway epithelia. As such, this vector is attractive for use in gene therapies to treat lung diseases such as cystic fibrosis. However, preclinical development of rAAV2/HBoV1 vectors has been hindered by the fact that humans are the only known host for HBoV1 infection. Here, we report that rAAV2/HBoV1 vector is capable of efficiently transducing the lungs of both newborn (3-7 day-old) and juvenile (29 day-old) ferrets, predominantly in the distal airways. Analyses of in vivo, ex vivo, and in vitro models of the ferret proximal airway demonstrate that infection of this particular region is less effective than human. Studies of vector binding and endocytosis in polarized ferret proximal airway epithelial cultures revealed that a lack of effective vector endocytosis is the main cause of inefficient transduction in vitro. While transgene expression declined proportionally with growth of the ferrets following infection at 7 days of age, reinfection of ferrets with rAAV2/HBoV1 at 29 days gave rise to ~5-fold higher levels of transduction than observed in naive infected 29-day old animals. The findings presented here lay a foundation for clinical development of HBoV1 capsid-based vectors for lung gene therapy in cystic fibrosis using ferret models.

PMID: 28490200 [PubMed - as supplied by publisher]

Scaling the Oxygen Uptake Efficiency Slope for Body Size in Cystic Fibrosis.

Med Sci Sports Exerc. 2017 May 09;:

Authors: Tomlinson OW, Barker AR, Oades PJ, Williams CA

Abstract
PURPOSE: The aim of this study was to describe the relationship between body size and the oxygen uptake efficiency slope (OUES) in paediatric patients with cystic fibrosis (CF) and healthy controls (CON), in order to identify appropriate scaling procedures to adjust the influence of body size upon OUES.
METHODS: The OUES was derived using maximal and submaximal points from cardiopulmonary exercise testing in 72 children (36 CF and 36 CON). OUES was subsequently scaled for stature, body mass (BM) and body surface area (BSA) using ratio-standard (Y/X) and allometric (Y/X) methods. Pearson's correlation coefficients were utilised to determine the relationship between body size and the OUES.
RESULTS: When scaled using the ratio-standard method, OUES had a significant positive relationship with stature (r = 0.54, P < 0.001) and BSA (r = 0.25, P = 0.031) and significant negative relationship with BM (r = -0.38, P = 0.016) in the CF group. Combined allometric exponents (b) for CF and CON were: stature 3.00, BM 0.86, BSA 1.40. A significant negative correlation was found between OUES and stature in the CF group when scaled allometrically (r = -0.37, P = 0.027). Non-significant (P > 0.05) correlations for the whole group were found between OUES and allometrically scaled BM (CF: r = -0.25, CON: r = 0.15) and BSA (CF r = -0.27, CON r = 0.13).
CONCLUSIONS: Only allometric scaling of either BM or BSA, and not ratio-standard scaling, successfully eliminates the influence of body size upon OUES. Therefore this enables a more direct comparison of the oxygen uptake slope between patients with CF and healthy controls.

PMID: 28489686 [PubMed - as supplied by publisher]

Current Concepts of Transition of Care in Cystic Fibrosis.

Pediatr Ann. 2017 May 01;46(5):e188-e192

Authors: Patel A, Dowell M, Giles BL

Abstract
Over the past 6 decades, advances in cystic fibrosis (CF) diagnosis and management have extended the life expectancy of patients far beyond childhood; therefore, all pediatric CF patients must prepare for transition to adult care. Readiness assessment, knowledge and skill education, and support structures are all elements of ideal transition. Transition should begin early in life with teaching skills and knowledge for disease care, and in adolescence the readiness to transition should be addressed. Transition is a gradual process of increasing responsibilities in self-care and disease management, an improvement in the understanding of CF, and an iterative process of self-assessment with knowledge acquisition. Communication and collaboration between pediatric and adult providers is necessary to ensure a smooth and successful transition with minimum effect on outcomes. Although there is increased knowledge of successful transition practices, this area presents many opportunities for advancement of care for the patient with CF. [Pediatr Ann. 2017;46(5):e188-e192.].

PMID: 28489224 [PubMed - in process]

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Systematic Computational Identification of Variants That Activate Exonic and Intronic Cryptic Splice Sites.

Am J Hum Genet. 2017 May 04;100(5):751-765

Authors: Lee M, Roos P, Sharma N, Atalar M, Evans TA, Pellicore MJ, Davis E, Lam AN, Stanley SE, Khalil SE, Solomon GM, Walker D, Raraigh KS, Vecchio-Pagan B, Armanios M, Cutting GR

Abstract
We developed a variant-annotation method that combines sequence-based machine-learning classification with a context-dependent algorithm for selecting splice variants. Our approach is distinctive in that it compares the splice potential of a sequence bearing a variant with the splice potential of the reference sequence. After training, classification accurately identified 168 of 180 (93.3%) canonical splice sites of five genes. The combined method, CryptSplice, identified and correctly predicted the effect of 18 of 21 (86%) known splice-altering variants in CFTR, a well-studied gene whose loss-of-function variants cause cystic fibrosis (CF). Among 1,423 unannotated CFTR disease-associated variants, the method identified 32 potential exonic cryptic splice variants, two of which were experimentally evaluated and confirmed. After complete CFTR sequencing, the method found three cryptic intronic splice variants (one known and two experimentally verified) that completed the molecular diagnosis of CF in 6 of 14 individuals. CryptSplice interrogation of sequence data from six individuals with X-linked dyskeratosis congenita caused by an unknown disease-causing variant in DKC1 identified two splice-altering variants that were experimentally verified. To assess the extent to which disease-associated variants might activate cryptic splicing, we selected 458 pathogenic variants and 348 variants of uncertain significance (VUSs) classified as high confidence from ClinVar. Splice-site activation was predicted for 129 (28%) of the pathogenic variants and 75 (22%) of the VUSs. Our findings suggest that cryptic splice-site activation is more common than previously thought and should be routinely considered for all variants within the transcribed regions of genes.

PMID: 28475858 [PubMed - in process]

Thymosin α1: a single drug with multiple targets in cystic fibrosis.

Nat Med. 2017 May 05;23(5):536-538

Authors: Cantin AM, Hanrahan JW

PMID: 28475572 [PubMed - in process]

Malnutrition among Hospitalized Children in the United States: Changing Prevalence, Clinical Correlates, and Practice Patterns between 2002 and 2011.

J Acad Nutr Diet. 2017 Apr 28;:

Authors: Carvalho-Salemi J, Salemi JL, Wong-Vega MR, Spooner KK, Juarez MD, Beer SS, Canada NL

Abstract
BACKGROUND: Pediatric malnutrition has been associated with adverse clinical outcomes, longer lengths of stay, and higher health care costs.
OBJECTIVE: To characterize prevalence, temporal trends, and short-term clinical outcomes of coded diagnoses of pediatric malnutrition (CDM) across sociodemographic, clinical, and hospital characteristics from 2002 to 2011.
DESIGN: This study is a retrospective cross-sectional analysis of nationally representative data from the Nationwide Inpatient Sample and the Kids' Inpatient Database.
PARTICIPANTS/SETTING: The study sample included pediatric inpatient hospitalizations in the United States.
MAIN OUTCOME MEASURES: International Classification of Diseases-9th Revision-Clinical Modification diagnosis codes were used to identify CDM and coded malnutrition subtypes based on an etiology-related definition of pediatric malnutrition.
STATISTICAL ANALYSES: The national frequency and prevalence of CDM overall and across patient- and hospital-level characteristics were estimated for children aged 1 month to 17 years. Logistic regression was used to assess the association between CDM and each characteristic. Analyses evaluated conditions associated with the highest burden and risk of CDM, and compared clinical outcomes across malnutrition subtypes. Joinpoint regression was used to describe temporal trends in CDM.
RESULTS: Of the 2.1 million pediatric patients hospitalized annually, more than 54,600 had CDM, a national prevalence of 2.6%. Considerable variation was observed based on primary diagnosis, with fluid and electrolyte disorders contributing the most malnutrition cases. Highest CDM rates were among patients with stomach cancer, cystic fibrosis, and human immunodeficiency virus. Patients with CDM experienced worse clinical outcomes, longer lengths of stay, and increased costs of inpatient care. The overall prevalence of CDM increased from 1.9% in 2002 to 3.7% in 2011, an 8% annual increase, and temporal increases were observed in nearly all population subgroups.
CONCLUSIONS: Despite improvements, pediatric malnutrition remains underdiagnosed in inpatient settings when relying exclusively on International Classification of Diseases-based codes, which underscores the need for a national benchmarking program to estimate the true prevalence, clinical significance, and cost of pediatric malnutrition.

PMID: 28473256 [PubMed - as supplied by publisher]

Abdominal symptoms in cystic fibrosis and their relation to genotype, history, clinical and laboratory findings.

PLoS One. 2017;12(5):e0174463

Authors: Tabori H, Arnold C, Jaudszus A, Mentzel HJ, Renz DM, Reinsch S, Lorenz M, Michl R, Gerber A, Lehmann T, Mainz JG

Abstract
BACKGROUND & AIMS: Abdominal symptoms (AS) are a hallmark of the multiorgan-disease cystic fibrosis (CF). However, the abdominal involvement in CF is insufficiently understood and, compared to the pulmonary manifestation, still receives little scientific attention. Aims were to assess and quantify AS and to relate them to laboratory parameters, clinical findings, and medical history.
METHODS: A total of 131 patients with CF of all ages were assessed with a new CF-specific questionnaire (JenAbdomen-CF score 1.0) on abdominal pain and non-pain symptoms, disorders of appetite, eating, and bowel movements as well as symptom-related quality of life. Results were metrically dimensioned and related to abdominal manifestations, history of surgery, P. aeruginosa and S. aureus colonization, genotype, liver enzymes, antibiotic therapy, lung function, and nutritional status.
RESULTS: AS during the preceding 3 months were reported by all of our patients. Most common were lack of appetite (130/131) and loss of taste (119/131) followed by abdominal pain (104/131), flatulence (102/131), and distention (83/131). Significantly increased AS were found in patients with history of rectal prolapse (p = 0.013), distal intestinal obstruction syndrome (p = 0.013), laparotomy (p = 0.022), meconium ileus (p = 0.037), pancreas insufficiency (p = 0.042), or small bowel resection (p = 0.048) as well as in patients who have been intermittently colonized with P. aeruginosa (p = 0.006) compared to patients without history of these events. In contrast, no statistically significant associations were found to CF-associated liver disease, chronic pathogen colonization, lung function, CF-related diabetes, and nutritional status.
CONCLUSION: As the complex abdominal involvement in CF is still not fully understood, the assessment of the common AS is of major interest. In this regard, symptom questionnaires like the herein presented are meaningful and practical tools facilitating a wider understanding of the abdominal symptoms in CF. Furthermore, they render to evaluate possible abdominal effects of novel modulators of the underlying cystic fibrosis transmembrane (conductance) regulator (CFTR) defect.

PMID: 28472055 [PubMed - in process]

Increased Fat Absorption from Enteral Formula Through an In-Line Digestive Cartridge in Patients with Cystic Fibrosis.

J Pediatr Gastroenterol Nutr. 2017 May 03;:

Authors: Freedman S, Orenstein D, Black P, Brown P, McCoy K, Stevens J, Grujic D, Clayton R

Abstract
OBJECTIVES: Supplemental enteral nutrition (EN) is used by approximately 12% of people with cystic fibrosis (CF). The objective of this study was to evaluate the safety, tolerability, and fat absorption of a new in-line digestive cartridge (Relizorb) that hydrolyzes fat in enteral formula provided to patients with CF.
METHODS: Patients with CF receiving EN participated in a multicenter, randomized, double-blind, crossover trial with an open-label safety evaluation period. Plasma omega-3 fatty acid (FA) concentrations were measured and used as markers of fat absorption. Gastrointestinal (GI) symptoms were recorded to evaluate safety and tolerability. Information regarding the effect of EN on appetite and breakfast consumption was also collected.
RESULTS: Prior to study entry, participants had received EN for a mean of 6.6 years at a mean volume of approximately 800 mL, yet had a mean body mass index of only 17.5 kg/m and omega-3 FA plasma concentrations were only 60% of levels found in normal healthy subjects. Compared with placebo, cartridge use resulted in a statistically significant 2.8-fold increase in plasma omega-3 FA concentrations. There were no adverse experiences associated with cartridge use, and a decrease in the frequency and severity of most symptoms of malabsorption was observed with cartridge use. Participants reported increased preservation of appetite and breakfast consumption with cartridge use compared with their pre-study regimen.
CONCLUSIONS: Use of this in-line digestive cartridge was safe and well tolerated, and resulted in significantly increased levels of plasma omega-3 FA used with enteral formula, suggesting an overall increased fat absorption.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

PMID: 28471913 [PubMed - as supplied by publisher]

Comprehensive Review on Colorectal Cancer and Transplant.

Am J Transplant. 2017 May 04;:

Authors: Prenner S, Levitsky J

Abstract
Colon cancer (CRC) is a common malignancy worldwide. Some studies suggest that organ recipients are at a higher risk for CRC than the general population. The underlying transplant indications and their inherent risk factors for CRC may drive the variation in incidence rates that are seen in patients receiving different allografts. Recipients with cystic fibrosis are now recognized as a population at high risk for CRC at a young age. Transplant recipients have high mortality following a CRC diagnosis, even if it is detected at an early stage. Certain types of immunosuppression have been shown to accelerate cancer transformation and may contribute to the more aggressive phenotype seen in organ recipients. Given the high incidence and progressive nature of post-transplant CRC, shorter screening intervals with a modality that can detect early stage polyps may be essential to prevent mortality. Future research is needed to better elucidate the role of immunosuppression in carcinogenesis. This comprehensive review examines CRC risk, screening, and management specific to organ transplant candidates and recipients. This article is protected by copyright. All rights reserved.

PMID: 28471512 [PubMed - as supplied by publisher]

Oscillating devices for airway clearance in people with cystic fibrosis.

Cochrane Database Syst Rev. 2017 May 04;5:CD006842

Authors: Morrison L, Innes S

Abstract
BACKGROUND: Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis. Oscillating devices generate intra- or extra-thoracic oscillations orally or external to the chest wall. Internally they create variable resistances within the airways, generating controlled oscillating positive pressure which mobilises mucus. Extra-thoracic oscillations are generated by forces outside the respiratory system, e.g. high frequency chest wall oscillation. This is an update of a previously published review.
OBJECTIVES: To identify whether oscillatory devices, oral or chest wall, are effective for mucociliary clearance and whether they are equivalent or superior to other forms of airway clearance in the successful management of secretions in people with cystic fibrosis.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conference proceedings. Latest search of the Cystic Fibrosis Trials Register: 27 April 2017.In addition we searched the trials databases ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Latest search of trials databases: 26 April 2017.
SELECTION CRITERIA: Randomised controlled studies and controlled clinical studies of oscillating devices compared with any other form of physiotherapy in people with cystic fibrosis. Single-treatment interventions (therapy technique used only once in the comparison) were excluded.
DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria to publications and assessed the quality of the included studies.
MAIN RESULTS: The searches identified 76 studies (302 references); 35 studies (total of 1138 participants) met the inclusion criteria. Studies varied in duration from up to one week to one year; 20 of the studies were cross-over in design. The studies also varied in type of intervention and the outcomes measured, data were not published in sufficient detail in most of these studies, so meta-analysis was limited. Few studies were considered to have a low risk of bias in any domain. It is not possible to blind participants and clinicians to physiotherapy interventions, but 11 studies did blind the outcome assessors.Forced expiratory volume in one second was the most frequently measured outcome. One long-term study (seven months) compared oscillatory devices with either conventional physiotherapy or breathing techniques and found statistically significant differences in some lung function parameters in favour of oscillating devices. One study identified an increase in frequency of exacerbations requiring antibiotics whilst using high frequency chest wall oscillation when compared to positive expiratory pressure. There were some small but significant changes in secondary outcome variables such as sputum volume or weight, but not wholly in favour of oscillating devices. Participant satisfaction was reported in 15 studies but this was not specifically in favour of an oscillating device, as some participants preferred breathing techniques or techniques used prior to the study interventions. The results for the remaining outcome measures were not examined or reported in sufficient detail to provide any high level evidence.
AUTHORS' CONCLUSIONS: There was no clear evidence that oscillation was a more or less effective intervention overall than other forms of physiotherapy; furthermore there was no evidence that one device is superior to another. The findings from one study showing an increase in frequency of exacerbations requiring antibiotics whilst using an oscillating device compared to positive expiratory pressure may have significant resource implications. More adequately-powered long-term randomised controlled trials are necessary and outcomes measured should include frequency of exacerbations, individual preference, adherence to therapy and general satisfaction with treatment. Increased adherence to therapy may then lead to improvements in other parameters, such as exercise tolerance and respiratory function. Additional evidence is needed to evaluate whether oscillating devices combined with other forms of airway clearance is efficacious in people with cystic fibrosis.There may also be a requirement to consider the cost implication of devices over other forms of equally advantageous airway clearance techniques. Using the GRADE method to assess the quality of the evidence, we judged this to be low or very low quality, which suggests that further research is very likely to have an impact on confidence in any estimate of effect generated by future interventions.

PMID: 28471492 [PubMed - as supplied by publisher]

Genomic sequencing in cystic fibrosis newborn screening: what works best, two-tier predefined CFTR mutation panels or second-tier CFTR panel followed by third-tier sequencing?

Genet Med. 2017 May 04;:

Authors: Currier RJ, Sciortino S, Liu R, Bishop T, Alikhani Koupaei R, Feuchtbaum L

Abstract
PurposeThe purpose of this study was to model the performance of several known two-tier, predefined mutation panels and three-tier algorithms for cystic fibrosis (CF) screening utilizing the ethnically diverse California population.MethodsThe cystic fibrosis transmembrane conductance regulator (CFTR) mutations identified among the 317 CF cases in California screened between 12 August 2008 and 18 December 2012 were used to compare the expected CF detection rates for several two- and three-tier screening approaches, including the current California approach, which consists of a population-specific 40-mutation panel followed by third-tier sequencing when indicated.ResultsThe data show that the strategy of using third-tier sequencing improves CF detection following an initial elevated immunoreactive trypsinogen and detection of only one mutation on a second-tier panel.ConclusionIn a diverse population, the use of a second-tier panel followed by third-tier CFTR gene sequencing provides a better detection rate for CF, compared with the use of a second-tier approach alone, and is an effective way to minimize the referrals of CF carriers for sweat testing. Restricting screening to a second-tier testing to predefined mutation panels, even broad ones, results in some missed CF cases and demonstrates the limited utility of this approach in states that have diverse multiethnic populations.GENETICS in MEDICINE advance online publication, 4 May 2017; doi:10.1038/gim.2017.32.

PMID: 28471435 [PubMed - as supplied by publisher]

Pediatric Cystic Fibrosis (CF) lung disease: a review.

Minerva Pediatr. 2017 May 03;:

Authors: Liu G, Li Z, Wu H

PMID: 28471146 [PubMed - as supplied by publisher]