Cystic fibrosis year in review 2018, part 1

Savant, Adrienne P.; McColley, Susanna A.

doi:10.1002/ppul.24361

Cited by 12 publications

(13 citation statements)

References 99 publications

(205 reference statements)

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“…Analyses of long-term outcomes from registries around the globe offer insight into the non-pulmonary effects of IVA. Reductions in CF-related diabetes [CFRD] and improved measures of bone health were noted in the US CF Foundation registry and the UK CF Registry, but not in the French CF Registry [68]. Kelly and colleagues studied 12 subjects, all with at least one gating mutation, all but one under 18 years of age.…”

Section: Non-pulmonary Effectsmentioning

confidence: 99%

Cystic Fibrosis Therapy: From Chest Physiotherapy to Agents Targeting Specific Mutations

2020

Eur J Respir Med

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Cystic Fibrosis (CF) is an autosomal recessive genetic disorder that was a terminal illness in young children. Standardized care in accredited CF Centers and medical advances in maintenance medications targeting nutritional health, CF bacterial pathogens, inflammation, mucociliary clearance, and the underlying defect in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, improved life expectancy and quality of life for people with CF [1,2]. Today, half of the United States CF population is of adult age. According to the 2018 Cystic Fibrosis Foundation (CFF) Patient Registry, 54.6% were 18 years and older [3]. The life expectancy of people with CF born between 2014 and 2018 is predicted to be 44.4 years (95 percent confidence interval: 43.4-45.9 years) [3,4].The discovery of the CFTR gene 1989 triggered a a surge in basic research [5]. While this enhanced knowledge of the pathophysiology of CF and clarified genotype-phenotype relationships, it was not until 2012 that an agent targeted towards correcting the defective protein became a reality [6]. Until then, the available therapies could only improve symptoms and slow down the progression of the disease. Nevertheless, such therapies transformed CF from a fatal disease of children to a more treatable, albeit still fatal, chronic disease of adults [7].The most recent and swiftly evolving therapies in CF therapeutic pipeline are the CFTR modulator targeting the abnormal protein. The CFTR protein is a cAMP protein kinase chloride ion channel that regulates chloride and bicarbonate transport across the epithelial cell surface and, in turn, inhibits the absorption of sodium absorption. CFTR protein is encoded by the CF gene located on chromosome 7 (7q31.2) and is found in epithelial cells of the airway, intestine, pancreas, and sweat gland. In CF, the CFTR protein defect is dependent on the Class of CFTR mutations, and total CFTR activity is determined by the CFTR quantity and function [8]. There are six classes of CFTR mutations (Table 1)The full explanation of CF airway pathology is beyond this review. Briefly, normal cilia require a hydrated airway surface liquid layer to function appropriately in mucociliary clearance.When chloride ion transport is impaired or absent based on the type of CFTR mutation, sodium is hyper-absorbed along with water, resulting in a poorly hydrated airway surface liquid layer. This leads to a continual cycle of thick mucus, airway obstruction and inflammation, tissue injury and resultant bronchiectasis.Once bronchiectatic airways develop, airway clearance is not optimal. This environment promotes the acquisition of bacteria that become pathogenic in CF lungs [9,10]. This article summarizes the available treatments for CF categorized by the mechanism of action.We begin by explaining traditional CF therapies and go on to describe CFTR modulator therapy in more detail. Airway Clearance TherapiesAirway clearance remains a mainstay of CF therapy and is encouraged from birth to adulthood [10]. However, since many clinical tri...

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Section: Non-pulmonary Effectsmentioning

confidence: 99%

Cystic Fibrosis Therapy: From Chest Physiotherapy to Agents Targeting Specific Mutations

2020

Eur J Respir Med

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“…The associated symptoms mainly affect the respiratory and digestive systems, and are complex, progressive, and require lifelong multifactorial care [2]. Significant improvements in early detection via newborn screening tests and targeted modulator therapies have had a positive impact on life expectancy, but frequent, personalized, and aggressive interventions are still needed [2,3].…”

Section: Introductionmentioning

confidence: 99%

Piloting the Clinical Value of Wearable Cardiorespiratory Monitoring for People with Cystic Fibrosis

Vandendriessche

Bergh²,

Storms

et al. 2020

Preprint

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Introduction. Cystic Fibrosis (CF) is a disease without a primary cure that requires lifelong care and is characterized by pulmonary exacerbations (PEx). Wearable devices could provide a way for long-term monitoring of disease progression and early signs of PEx to intervene as early as possible, thereby improving long-term outcomes. Methods. In-hospital feasibility study (n = 26) to 1) assess the ability of Byteflies Sensor Dot to collect relevant cardiorespiratory data in people with CF and its compatibility with clinical workflows, 2) identify candidate digital biomarkers, and 3) collect user feedback from patients and healthcare providers. Results. Collected sample-level biopotential, bioimpedance and actigraphy data were of high quality. Sensor Dot heart rate (HR) correlated with hospital HR, whereas respiratory rate (RR) did not. HR and RR were associated with CF severity, and HR and coughing with PEx. Willingness to use the device was very high with CF patients and study coordinators considered the device easy-to-use. Conclusion. Determining if a wearable is fit-for-purpose is a long and multidisciplinary process that requires involvement from all stakeholders as early as possible in the development process. Our pilot identified interesting correlations between cardiorespiratory parameters as measured by the wearable, and CF severity and PEx. Together with the usability data, this will inform the next steps in the clinical development process.

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“…Consequently, there is no need of a dedicated electrical connection for the gate bias, and an OECT architecture with only two electrical terminals can be proposed (Figure 1H), realizing a simpler set up compared to other transistor configurations. When Ag/AgCl is used, the proposed sensor can determine the Cl − concentration that is relevant in sweat analysis, for instance in the diagnosis and monitoring of cystic fibrosis (Savant and McColley, 2019) and for the non-invasive evaluation of the body hydration level (Gao et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Organic Electrochemical Transistors as Versatile Analytical Potentiometric Sensors

Gualandi

Tessarolo

Mariani

et al. 2019

Front. Bioeng. Biotechnol.

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Potentiometric transduction is an important tool of analytical chemistry to record chemical signals, but some constraints in the miniaturization and low-cost fabrication of the reference electrode are a bottleneck in the realization of more-advanced devices such as wearable and lab-on-a-chip sensors. Here, an organic electrochemical transistor (OECT) has been designed with an alternative architecture that allows to record the potentiometric signals of gate electrodes, which have been chemically modified to obtain Ag/AgnX interfaces (X = Cl−, Br−, I−, and S2−), without the use of a reference electrode. When the OECT is immersed in a sample solution, it reaches an equilibrium state, because PEDOT:PSS exchanges charges with the electrolyte until its Fermi level is aligned to the one of Ag/AgnX. The latter is controlled by Xn− concentration in the solution. As a consequence, in this spontaneous process, the conductivity of PEDOT:PSS changes with the electrochemical potential of the modified gate electrode without any external bias. The sensor works by applying only a fixed drain current or drain voltage and thus the OECT sensor operates with just two terminals. It is also demonstrated that, in this configuration, gate potential values extracted from the drain current are in good agreement with the ones measured with respect to a reference electrode being perfectly correlated (linear slope equal to 1.00 ± 0.03). In the case of the sulfide anion, the OECT performance overcomes the limit represented by the Nernst equation, with a sensitivity of 0.52 V decade−1. The presented results suggest that OECTs could be a viable option to fabricate advanced sensors based on potentiometric transduction.

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Cystic fibrosis year in review 2018, part 1

Cited by 12 publications

References 99 publications

Cystic Fibrosis Therapy: From Chest Physiotherapy to Agents Targeting Specific Mutations

Cystic Fibrosis Therapy: From Chest Physiotherapy to Agents Targeting Specific Mutations

Piloting the Clinical Value of Wearable Cardiorespiratory Monitoring for People with Cystic Fibrosis

Organic Electrochemical Transistors as Versatile Analytical Potentiometric Sensors

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