Improving outcomes of infections in cystic fibrosis in the era of CFTR modulator therapy

Saiman, Lisa

doi:10.1002/ppul.24522

Cited by 26 publications

(28 citation statements)

References 46 publications

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“…However, it is claimed that at least 90 percent of Canadian CF patients could eventually benefit from such CFTR modulators as they improve and become the standard of care [ 8 ]. In addition to its expanding scope, the implementation of personalized medicines into healthcare systems has introduced complexities for policy and regulation.…”

Section: Introductionmentioning

confidence: 99%

The Equitable Implementation of Cystic Fibrosis Personalized Medicines in Canada

Shemie

Nguyen

Wallenburg

et al. 2021

JPM

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This article identifies the potential sources of inequity in three stages of integrating cystic fibrosis personalized medicines into the Canadian healthcare system and proposes mitigating strategies: (1) clinical research and diagnostic testing; (2) regulatory oversight and market authorization; and (3) implementation into the healthcare system. There is concern that differential access will cast a dark shadow over personalized medicine by stratifying the care that groups of patients will receive—not only based on their genetic profiles, but also on the basis of their socioeconomic status. Furthermore, there is a need to re-evaluate regulatory and market approval mechanisms to accommodate the unique nature of personalized medicines. Physical and financial accessibility ought to be remedied before personalized medicines can be equitably delivered to patients. This article identifies the socio–ethical and legal challenges at each stage and recommends mitigating policy solutions.

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Section: Introductionmentioning

confidence: 99%

The Equitable Implementation of Cystic Fibrosis Personalized Medicines in Canada

Shemie

Nguyen

Wallenburg

et al. 2021

JPM

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“…It has been shown that the decreased sputum loads of P. aeruginosa after ivacaftor therapy rebounded later in most samples ( Hisert et al., 2017 ). This phenomenon suggests other measures for controlling infection should be applied in parallel to reach the best treatment effect ( Saiman, 2019 ). Besides, although fungi and viruses exist in CF respiratory specimens, the effect of modulator therapy on them is unknown.…”

Section: How Cftr Modulator Therapies Affect the Airway Microbiomementioning

confidence: 99%

Changes in the Cystic Fibrosis Airway Microbiome in Response to CFTR Modulator Therapy

Dalpke

Boutin

2021

Front. Cell. Infect. Microbiol.

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The development of CFTR modulator therapies significantly changed the treatment scheme of people with cystic fibrosis. However, CFTR modulator therapy is still a life-long treatment, which is not able to correct the genetic defect and cure the disease. Therefore, it becomes crucial to understand the effects of such modulation of CFTR function on the airway physiology, especially on airway infections and inflammation that are currently the major life-limiting factors in people with cystic fibrosis. In this context, understanding the dynamics of airway microbiome changes in response to modulator therapy plays an essential role in developing strategies for managing airway infections. Whether and how the newly available therapies affect the airway microbiome is still at the beginning of being deciphered. We present here a brief review summarizing the latest information about microbiome alterations in light of modern cystic fibrosis modulator therapy.

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“…An ongoing clinical trial may untangle potential antagonism between inhaled tobramycin and chronic oral azithromycin in CF: Testing the Effect of Adding Chronic Azithromycin to Inhaled Tobramycin (TEACH; NCT02677701), randomizes participants to receive inhaled tobramycin with azithromycin vs. placebo [29].…”

Section: Azithromycinmentioning

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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Improving outcomes of infections in cystic fibrosis in the era of CFTR modulator therapy

Cited by 26 publications

References 46 publications

The Equitable Implementation of Cystic Fibrosis Personalized Medicines in Canada

The Equitable Implementation of Cystic Fibrosis Personalized Medicines in Canada

Changes in the Cystic Fibrosis Airway Microbiome in Response to CFTR Modulator Therapy

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

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