CFTR Modulators to the Rescue of Individuals with Cystic Fibrosis and Advanced Lung Disease

The arrival of cystic fibrosis transmembrane conductance regulator (CFTR) modulators as a new class of treatment for cystic fibrosis (CF) in 2012 represented a pivotal advance in disease management, as these small molecules directly target the upstream underlying protein defect. Further advancements in the development and scope of these genotype-specific therapies have been transformative for an increasing number of people with CF (PWCF). Despite clear improvements in CFTR function and clinical endpoints such as lung function, body mass index (BMI), and frequency of pulmonary exacerbations, current evidence suggests that CFTR modulators do not prevent continued decline in lung function, halt disease progression, or ameliorate pathogenic organisms in those with established lung disease. Furthermore, it remains unknown whether their restorative effects extend to dysfunctional CFTR expressed in phagocytes and other immune cells, which could modulate airway inflammation. In this review, we explore the effects of CFTR modulators on airway inflammation, infection, and their influence on the impaired pulmonary host defences associated with CF lung disease. We also consider the role of inflammation-directed therapies in light of the widespread clinical use of CFTR modulators and identify key areas for future research.

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S58 Triple CFTR modulators improve sino-nasal and laryngopharyngeal reflux symptoms in people with advanced cystic fibrosis lung disease

10.1136/thorax-2021-btsabstracts.64 ◽

2021 ◽

Author(s):

S Shakir ◽

C Echevarria ◽

S Doe ◽

M Brodlie ◽

C Ward ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Disease ◽

Laryngopharyngeal Reflux ◽

Cystic Fibrosis Lung ◽

Reflux Symptoms ◽

Cystic Fibrosis Lung Disease ◽

Cftr Modulators

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Impact of CFTR modulator use on outcomes in people with severe cystic fibrosis lung disease

European Respiratory Review ◽

10.1183/16000617.0112-2019 ◽

2020 ◽

Vol 29 (155) ◽

pp. 190112 ◽

Cited By ~ 12

Author(s):

Michal Shteinberg ◽

Jennifer L. Taylor-Cousar

Keyword(s):

Cystic Fibrosis ◽

Lung Disease ◽

Case Series ◽

Lung Damage ◽

Cystic Fibrosis Lung Disease ◽

Drug Compounds ◽

The Impact ◽

Cftr Modulators ◽

Severe Lung Disease

Drug compounds that augment the production and activity of the cystic fibrosis (CF) transmembrane regulator (CFTR) have revolutionised CF care. Many adults and some children with CF suffer advanced and severe lung disease or await lung transplantation. While the hope is that these drug compounds will prevent lung damage when started early in life, there is an ongoing need to care for people with advanced lung disease. The focus of this review is the accumulating data from clinical trials and case series regarding the benefits of CFTR modulator therapy in people with advanced pulmonary disease. We address the impact of treatment with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor on lung function, pulmonary exacerbations, nutrition and quality of life. Adverse events of the different CFTR modulators, as well as the potential for drug–drug interactions, are discussed.

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CF Fungal Disease in the Age of CFTR Modulators

Mycopathologia ◽

10.1007/s11046-021-00541-5 ◽

2021 ◽

Author(s):

Amelia Bercusson ◽

George Jarvis ◽

Anand Shah

Keyword(s):

Cystic Fibrosis ◽

Innate Immunity ◽

Drug Interactions ◽

Aspergillus Fumigatus ◽

Lung Disease ◽

Disease Progression ◽

Fungal Disease ◽

Concurrent Use ◽

The Impact ◽

Cftr Modulators

AbstractFungi are increasingly recognised to have a significant role in the progression of lung disease in Cystic fibrosis with Aspergillus fumigatus the most common fungus isolated during respiratory sampling. The emergence of novel CFTR modulators has, however, significantly changed the outlook of disease progression in CF. In this review we discuss what impact novel CFTR modulators will have on fungal lung disease and its management in CF. We discuss how CFTR modulators affect antifungal innate immunity and consider the impact of Ivacaftor on fungal disease in individuals with gating mutations. We further review the increasing complication of drug–drug interactions with concurrent use of azole antifungal medication and highlight key unknowns that require addressing to fully understand the impact of CFTR modulators on fungal disease.

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Improvement in Non-Pulmonary CFTR-Related Symptoms in a Patient With p.Phe508del/p.Arg117His (7T) Cystic Fibrosis Treated with Ivacaftor

10.22541/au.163811198.89091254/v1 ◽

2021 ◽

Author(s):

Stephanie Kuek ◽

John Massie

Keyword(s):

Cystic Fibrosis ◽

Lung Disease ◽

Chronic Sinusitis ◽

Recurrent Pancreatitis ◽

Patient Centred Care ◽

Diagnosis And Management ◽

Pulmonary Manifestations ◽

Open Dialogue ◽

Cftr Modulators

Introduction: Diagnosis and management of CRMS/CFSPID and cystic fibrosis (CF) with mild phenotypes remains challenging, and this extends to expanding practice with the use of CFTR modulators. Case: We describe a case of an 18-year-old man with p.F508del/p.Arg117His(7T) initially presenting with CRMS/CFSPID. He went on to be diagnosed with pancreatic sufficient CF with minimal lung disease and no bronchiectasis. However, he has had significant CFTR-related symptoms with recurrent pancreatitis and chronic sinusitis. These non-pulmonary symptoms resolved following introduction of the CFTR modulator ivacaftor. Discussion/ Conclusion: Diagnosis and follow up of CRMS/CFSPID infants remains challenging, with most guidelines based on consensus opinion. Care for those with mild CF phenotypes, CRMS/CFSPID and those with CFTR-RD must be individualised, and open dialogue, education and patient centred care is necessary to ascertaining which patients might benefit from management in a multidisciplinary CF clinic and treatment. There may be a role for expanding the use of CFTR modulators to include non-pulmonary manifestations of CFTR dysfunction in some cases.

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