Recovery of lung function following a pulmonary exacerbation in patients with cystic fibrosis and the G551D-CFTR mutation treated with ivacaftor

Flume, Patrick A.; Wainwright, Claire; Tullis, D. Elizabeth; Rodriguez, Sally; Niknian, Minoo; Higgins, Mark; Davies, Jane C.; Wagener, Jeffrey S.

doi:10.1016/j.jcf.2017.06.002

Cited by 37 publications

(20 citation statements)

References 28 publications

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“…Despite all demonstrated benefits, patients receiving ivacaftor may eventually experience pulmonary exacerbations, thus requiring hospitalizations and worsening quality of life (Solem et al, 2016). Furthermore, ivacaftor treatment does not improve the rate of complete lung function recovery after an exacerbation episode (Flume et al, 2018). Lung function also declines in the long term, albeit at a slower rate.…”

Section: Potentiators: Restoring the Channel Gating And Conductancementioning

confidence: 99%

CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine

2020

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Cystic fibrosis (CF) is a lethal inherited disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which result in impairment of CFTR mRNA and protein expression, function, stability or a combination of these. Although CF leads to multifaceted clinical manifestations, the respiratory disorder represents the major cause of morbidity and mortality of these patients. The life expectancy of CF patients has substantially lengthened due to early diagnosis and improvements in symptomatic therapeutic regimens. Quality of life remains nevertheless limited, as these individuals are subjected to considerable clinical, psychosocial and economic burdens. Since the discovery of the CFTR gene in 1989, tremendous efforts have been made to develop therapies acting more upstream on the pathogenesis cascade, thereby overcoming the underlying dysfunctions caused by CFTR mutations. In this line, the advances in cell-based high-throughput screenings have been facilitating the fast-tracking of CFTR modulators. These modulator drugs have the ability to enhance or even restore the functional expression of specific CF-causing mutations, and they have been classified into five main groups depending on their effects on CFTR mutations: potentiators, correctors, stabilizers, read-through agents, and amplifiers. To date, four CFTR modulators have reached the market, and these pharmaceutical therapies are transforming patients' lives with short-and long-term improvements in clinical outcomes. Such breakthroughs have paved the way for the development of novel CFTR modulators, which are currently under experimental and clinical investigations. Furthermore, recent insights into the CFTR structure will be useful for the rational design of next-generation modulator drugs. This review aims to provide a summary of recent developments in CFTR-directed therapeutics. Barriers and future directions are also discussed in order to optimize treatment adherence, identify feasible and sustainable solutions for equitable access to these therapies, and continue to expand the pipeline of novel modulators that may result in effective precision medicine for all individuals with CF.

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Section: Potentiators: Restoring the Channel Gating And Conductancementioning

confidence: 99%

CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine

2020

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“…The proportion of children with at least one pulmonary exacerbation treated with IV antibiotics per year is between 20% and 30% for ages 5‐13 years, and has not changed appreciably in at least 20 years . Although the use of CFTR modulators decreases the frequency of pulmonary exacerbations, patients continue to be at‐risk for loss of FEV 1 following these events . It is imperative that we identify patients at‐risk for pulmonary exacerbations to prevent the occurrence of these important patient‐centered outcomes.…”

Section: Discussionmentioning

confidence: 99%

Quantitative chest computerized tomography and FEV₁ equally identify pulmonary exacerbation risk in children with cystic fibrosis

Sanders

Parker-McGill

et al. 2018

Pediatric Pulmonology

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“…65,66 Studies that have focused on clinical outcomes after PEx have noted poorer short-term outcomes, including reduced recovery of lung function in a substantial fraction of events (up to 50%). 65,132 It is possible that some PEx treatment decisions may account for poorer outcomes. 55 For example, in the United States, treatment with IV antibiotics for less than 9 days and treatment entirely as an outpatient have both been associated with an increased risk of retreatment with IV antibiotics within 30 days of PEx treatment completion, despite similar patient characteristics at IV antibiotic initiation.…”

Section: Duration Of Treatment For a Pulmonary Exacerbationmentioning

confidence: 99%

Acute Pulmonary Exacerbations in Cystic Fibrosis

Goss

2019

Semin Respir Crit Care Med

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With the improving survival of cystic fibrosis (CF) patients and the advent of highly effective cystic fibrosis transmembrane conductance regulator therapy, the clinical spectrum of this complex multisystem disease continues to evolve. One of the most important clinical events for patients with CF in the course of this disease is an acute pulmonary exacerbation. Clinical and microbial epidemiology studies of CF pulmonary exacerbations continue to provide important insight into the disease course, prognosis, and complications. This work has now led to a number of large scale clinical trials with the goal of improving the treatment paradigm for CF pulmonary exacerbation. The primary goal of this review is to provide a summary of the pathophysiology, the clinical epidemiology, microbial epidemiology, outcome and the treatment of CF pulmonary exacerbation.

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Recovery of lung function following a pulmonary exacerbation in patients with cystic fibrosis and the G551D-CFTR mutation treated with ivacaftor

Abstract: Ivacaftor treatment reduces the frequency of PEx but does not improve on the rate of complete lung function recovery after PEx when compared with placebo.

Cited by 37 publications

References 28 publications

CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine

CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine

Quantitative chest computerized tomography and FEV₁ equally identify pulmonary exacerbation risk in children with cystic fibrosis

Acute Pulmonary Exacerbations in Cystic Fibrosis

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Recovery of lung function following a pulmonary exacerbation in patients with cystic fibrosis and the G551D-CFTR mutation treated with ivacaftor

Abstract: Ivacaftor treatment reduces the frequency of PEx but does not improve on the rate of complete lung function recovery after PEx when compared with placebo.

Cited by 37 publications

References 28 publications

CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine

CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine

Quantitative chest computerized tomography and FEV1 equally identify pulmonary exacerbation risk in children with cystic fibrosis

Acute Pulmonary Exacerbations in Cystic Fibrosis

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Product

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Quantitative chest computerized tomography and FEV₁ equally identify pulmonary exacerbation risk in children with cystic fibrosis