Lumacaftor-ivacaftor-associated health stabilisation in adults with severe cystic fibrosis

IntroductionLumacaftor-ivacaftor (LUM-IVA) has been shown to improve clinical outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with ppFEV1>40%. We assessed the clinical utility of LUM-IVA in all eligible adult CF patients with ppFEV1<40% treated for at least 1 year under a single centre managed access program.MethodsFollowing clinical optimisation eligible patients (n=40) with ppFEV1<40% were commenced on LUM-IVA and monitored for tolerance and clinical outcomes including health service utilisation, pulmonary function, weight and body composition. Twenty-four patients reached 1 year of treatment by the time of evaluation. Six discontinued due to adverse events (five for increased airways reactivity) and 3 underwent lung transplantation.ResultsIn comparison to the year prior to LUM-IVA commencement, significant reductions (median/year) were observed in the treatment year in the number of pulmonary exacerbations requiring hospitalisation (3 to 1.5, p=0.002); hospitalisation days (27 to 17, p=0.0002) and intravenous antibiotic days (45 to 27, p=0.0007). Mean change in ppFEV1 was −2.10(se 1.18)% per year in the year prior, with the decline reversed in the year following (+1.45(se 1.13)% per year, p=0.035) although there was significant heterogeneity in individual responses. Mean weight gain at 1 year was 2.5±4.1 kg; p=0.0007), comprising mainly fat mass (mean 2.2 kg). The proportion of patients with severe underweight (BMI<18.5 kg·m−2) decreased from 33% at baseline to 13% at 1 year (p=0.003).ConclusionThis real-world evaluation study demonstrated benefits over several clinical domains (infective exacerbations requiring hospitalisation, intravenous antibiotics, pulmonary function decline and nutritional parameters) in CF patients with severe lung disease.

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Endoscopic sinus surgery in patients with cystic fibrosis: a systematic review and meta-analysis of pulmonary function

Rhinology Journal ◽

10.4193/rhino11.271 ◽

2012 ◽

Vol 50 (4) ◽

pp. 360-369

Author(s):

K.I. Macdonald ◽

A. Gipsman ◽

A. Magit ◽

M. Fandino ◽

E. Massoud ◽

...

Keyword(s):

Systematic Review ◽

Cystic Fibrosis ◽

Pulmonary Function ◽

Endoscopic Sinus Surgery ◽

Meta Analysis ◽

Pulmonary Function Tests ◽

Sinus Surgery ◽

Intravenous Antibiotics

Introduction: The role of endoscopic sinus surgery (ESS) in patients with cystic fibrosis (CF) is not clearly defined. Objective: TO perform a systematic review of subjective and objective outcomes of ESS in CF. Methods: A systematic review was performed using the keywords 'sinusitis,' 'sinus surgery,' 'nasal polyps' and 'cystic fibrosis.' The quality of papers was assessed using the NICE scoring scale. Outcomes included safety, subjective symptoms, objective endoscopy scores, days spent in hospital, courses of antibiotics, and pulmonary function tests (PFTs). Results: Nineteen studies involving 586 patients were included in the review. There were four prospective cohort trials, and three were rated as good quality. There were no major complications attributable to ESS. There was consistent evidence in four cohort studies of improved sinonasal symptoms, including nasal obstruction, facial pain, headaches, rhinorrhea and olfaction. Three studies reported conflicting results in post-operative endoscopy scores. Three studies showed a decrease in days spent in hospital, and two showed a significant decrease in courses of intravenous antibiotics. A recent study, however, did not show a difference in either days spent in hospital or courses of antibiotics. Pulmonary function tests were not improved by ESS in six cohort trials, and one small study found significant improvement. A meta-analysis of FEV1 scores confirmed no significant difference. Conclusion: THE most consistent findings of this review were that ESS in patients with CF is safe, produces symptomatic benefit, and does not consistently improve PFTs. There were more conflicting results with regards to endoscopy scores, days spent in hospital, and courses of intravenous antibiotics. Future prospective studies, utilizing validated quality of life, symptom and endoscopy scales, are needed to further elucidate the role of ESS in the management of chronic rhinosinusitis in CF patients.

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Improved Lung Function after Sinus Surgery in Cystic Fibrosis Patients with Moderate Obstruction

Otolaryngology ◽

10.1177/0194599817739284 ◽

2017 ◽

Vol 158 (2) ◽

pp. 381-385 ◽

Cited By ~ 14

Author(s):

Sabrina Khalfoun ◽

Dmitry Tumin ◽

Maroun Ghossein ◽

Meredith Lind ◽

Don Hayes ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Pulmonary Function ◽

Lung Disease ◽

Pulmonary Function Testing ◽

Sinus Surgery ◽

Before And After ◽

Function Testing ◽

Severe Lung Disease ◽

Severe Lung

Objectives Cystic fibrosis (CF) is characterized by infection and inflammation of the sinorespiratory tract. Functional endoscopic sinus surgery (FESS) is an option for patients with severe sinusitis. We sought to evaluate pulmonary function testing after FESS in pediatric and adult patients with CF. Study Design Retrospective chart review using data from all patients with CF who underwent FESS from January 2009 to July 2014. Setting Patients were from a single institution. Subjects and Methods Data were extracted for 181 patients and 320 surgeries. Lung function data, including the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC, were retrieved within 1 year before and after surgery. Mixed-effects regression was used to compare FEV1 trajectories before and after surgery. The effect of surgery was stratified by presurgery FEV1 to compare patients with mild/no lung disease (FEV1 >80%) and moderate/severe lung disease (FEV1 <80%). Results Of the 181 patients reviewed, 131 with primary FESS had FEV1 data. Presurgery average age was 16 years (95% confidence interval [CI], 14.27-17.73), and FEV1 mean was 85% (95% CI, 81.02-88.98). There were 88 patients with FEV1 >80% and 43 patients with FEV1 <80%. For the entire cohort, lung function did not change related to FESS. Among patients with FEV1 <80%, FEV1 declined presurgery by 3.5% per year (95% CI, −6.1% to −0.8%; P = .010), which halted after surgery with these patients, then showing no subsequent change in FEV1 (95% CI, 0.9%-3.7%; P = .240). No benefit was identified for patients with FEV1 >80%. Conclusion Pulmonary function testing improved in patients with moderate/severe lung disease 1 year following FESS. This suggests FESS may benefit pulmonary outcomes.

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Relationship of Pulmonary Outcomes, Microbiology, and Serum Antibiotic Concentrations in Cystic Fibrosis Patients

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-23.5.379 ◽

2018 ◽

Vol 23 (5) ◽

pp. 379-389

Author(s):

Andrea Hahn ◽

Caroline Jensen ◽

Hani Fanous ◽

Hollis Chaney ◽

Iman Sami ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pulmonary Function ◽

Clinical Outcomes ◽

Pulmonary Function Tests ◽

National Health System ◽

Antibiotic Exposure ◽

Pulmonary Exacerbation ◽

Prospective Longitudinal Study ◽

Lactam Antibiotic ◽

Prospective Longitudinal

OBJECTIVES To determine the frequency of subtherapeutic exposure to intravenously administered β-lactam antibiotics in a cohort of cystic fibrosis (CF) patients who were treated for a pulmonary exacerbation, and its impact on pulmonary function. METHODS Nineteen CF patients between the ages of 5 and 21 years treated at Children's National Health System for a pulmonary exacerbation were followed between March 2015 and August 2016 in a prospective, longitudinal study. Pharmacokinetic modeling and minimum inhibitory concentrations (MICs) of the involved pathogens were used to determine therapeutic or subtherapeutic β-lactam antibiotic exposure based on the time the antibiotic concentration was above the MIC. Clinical outcomes were measured by spirometry values. RESULTS The 19 participants were treated with a total of 29 courses of antibiotics. The most common β-lactam antibiotics used in a treatment course were ceftazidime (62%) and meropenem (45%). There was no difference in age, CF genotype, or creatinine clearance between the 9 participants (47%) who reached therapeutic concentrations versus the 10 (53%) who did not. Those who achieved sufficiently high antibiotic exposure had more significant improvement of their pulmonary function tests. CONCLUSIONS We found that sufficient antibiotic exposure during treatment of CF pulmonary exacerbations was associated with improved pulmonary function. Moreover, it was impossible to predict, solely from the dosing regimen used, which patients were going to reach therapeutic β-lactam antibiotic serum concentrations. This suggests that CF patients may benefit from closer monitoring of their β-lactam exposure and bacterial MIC for optimal clinical outcomes.

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