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

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.

scholarly journals DNA Methylation at ATP11A cg11702988 Is a Biomarker of Lung Disease Severity in Cystic Fibrosis: A Longitudinal Study

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 441
Author(s):  
Fanny Pineau ◽  
Davide Caimmi ◽  
Sylvie Taviaux ◽  
Maurane Reveil ◽  
Laura Brosseau ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Dna Methylation ◽  
Clinical Trials ◽  
Lung Disease ◽  
Disease Severity ◽  
Genome Wide ◽  
A Genome ◽  
Lung Disease Severity ◽  
Epigenetic Biomarker

Cystic fibrosis (CF) is a chronic genetic disease that mainly affects the respiratory and gastrointestinal systems. No curative treatments are available, but the follow-up in specialized centers has greatly improved the patient life expectancy. Robust biomarkers are required to monitor the disease, guide treatments, stratify patients, and provide outcome measures in clinical trials. In the present study, we outline a strategy to select putative DNA methylation biomarkers of lung disease severity in cystic fibrosis patients. In the discovery step, we selected seven potential biomarkers using a genome-wide DNA methylation dataset that we generated in nasal epithelial samples from the MethylCF cohort. In the replication step, we assessed the same biomarkers using sputum cell samples from the MethylBiomark cohort. Of interest, DNA methylation at the cg11702988 site (ATP11A gene) positively correlated with lung function and BMI, and negatively correlated with lung disease severity, P. aeruginosa chronic infection, and the number of exacerbations. These results were replicated in prospective sputum samples collected at four time points within an 18-month period and longitudinally. To conclude, (i) we identified a DNA methylation biomarker that correlates with CF severity, (ii) we provided a method to easily assess this biomarker, and (iii) we carried out the first longitudinal analysis of DNA methylation in CF patients. This new epigenetic biomarker could be used to stratify CF patients in clinical trials.

scholarly journals Airway Inflammation and Host Responses in the Era of CFTR Modulators

2020 ◽  
Vol 21 (17) ◽  
pp. 6379
Author(s):  
Karen Keown ◽  
Ryan Brown ◽  
Declan F. Doherty ◽  
Claire Houston ◽  
Michael C. McKelvey ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Lung Disease ◽  
Airway Inflammation ◽  
Host Responses ◽  
Current Evidence ◽  
Future Research ◽  
Clinical Endpoints ◽  
New Class ◽  
Cftr Modulators

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.

scholarly journals Early follow-up of lung disease in infants with cystic fibrosis using the raised volume rapid thoracic compression technique and computed tomography during quiet breathing

2017 ◽  
Vol 52 (10) ◽  
pp. 1283-1290 ◽  
Author(s):  
Rémi Gauthier ◽  
Yann Cabon ◽  
Marie Agnes Giroux-Metges ◽  
Cecile Du Boisbaudry ◽  
Phillipe Reix ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Cystic Fibrosis ◽  
Lung Disease ◽  
Quiet Breathing ◽  
Compression Technique

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

2020 ◽  
Vol 29 (155) ◽  
pp. 190112 ◽  
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.

scholarly journals Early markers of cystic fibrosis structural lung disease: follow-up of the ACFBAL cohort

2020 ◽  
Vol 55 (4) ◽  
pp. 1901694 ◽  
Author(s):  
Naomi E. Wijker ◽  
Suzanna Vidmar ◽  
Keith Grimwood ◽  
Peter D. Sly ◽  
Catherine A. Byrnes ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bronchoalveolar Lavage ◽  
Lung Disease ◽  
Airway Disease ◽  
Ct Scans ◽  
Early Predictors ◽  
Early Markers ◽  
Lung Abnormalities ◽  
Poor Nutritional Status

Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study (CF-FAB).Eight Australian and New Zealand CF centres participated in CF-FAB and provided follow-up chest computed-tomography (CT) scans for children who had completed the ACFBAL study with baseline scans at age 5-years. CT scans were annotated using PRAGMA-CF scoring. Ordinal regression analysis and linear regression were used to investigate associations between PRAGMA-CF (Perth–Rotterdam Annotated Grid Morphometric Analysis for CF) outcomes at follow-up and variables measured during the ACFBAL study.99 out of 157 ACFBAL children (mean±sd age 13±1.5 years) participated in the CF-FAB study. The probability of bronchiectasis at follow-up increased with airway disease severity on the baseline CT scan. In multiple regression (retaining factors at p<0.05) the extent of bronchiectasis at follow-up was associated with baseline atelectasis (OR 7.2, 95% CI 2.4–22; p≤ 0.001), bronchoalveolar lavage (BAL) log2 interleukin (IL)-8 (OR 1.2, 95% CI 1.05–1.5; p=0.010) and body mass index z-score (OR 0.49, 95% CI 0.24–1.00; p=0.05) at age 5 years. Percentage trapped air at follow-up was associated with BAL log2 IL-8 (coefficient 1.3, 95% CI 0.57–2.1; p<0.001) at age 5 years.The extent of airway disease, atelectasis, airway inflammation and poor nutritional status in early childhood are risk factors for progressive structural lung disease in adolescence.

scholarly journals CF Fungal Disease in the Age of CFTR Modulators

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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