Diagnosis and Management of Cystic Fibrosis Exacerbations

Milinic, Tijana; McElvaney, Oliver J; Goss, Christopher H.

doi:10.1055/s-0042-1760250

Cited by 7 publications

(6 citation statements)

References 263 publications

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“…Individuals who suffer from CF have altered airway physiology and inherent susceptibility to pulmonary infections. 1,2 These infections often have a complex lung infection microbiomes complicating treatment strategies. 2,3 Nosocomial infections are also complicated and require innovative approaches to treat an array of different types of bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…Individuals who suffer from CF have altered airway physiology and inherent susceptibility to pulmonary infections 1,2 . These infections often have a complex lung infection microbiomes complicating treatment strategies 2,3 .…”

Section: Discussionmentioning

confidence: 99%

“…1 However, even with improved CFTR management, all patients with CFs continue to struggle with pulmonary infections, often with more than one type of bacteria. 1,2 The complexity of treating these infections has resulted in the development of resistant strains of bacteria and issues with patient therapeutic tolerability. 2,3 Carbapenems have been utilized to treat pulmonary infections in individuals with CF as well as individuals with nosocomial infections, however inefficient delivery to the lungs frequently results in resistant bacterial species.…”

Section: Introductionmentioning

confidence: 99%

“…Pharmacological drugs that can directly enhance the function of the protein cystic fibrosis transmembrane conductance regulator (CFTR), the causative defect in patients with cystic fibrosis (CF), have improved morbidity and decreased mortality 1 . However, even with improved CFTR management, all patients with CFs continue to struggle with pulmonary infections, often with more than one type of bacteria 1,2 . The complexity of treating these infections has resulted in the development of resistant strains of bacteria and issues with patient therapeutic tolerability 2,3 …”

Section: Introductionmentioning

confidence: 99%

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Polymerized cyclodextrin microparticles for sustained antibiotic delivery in lung infections

Bonfield,

Zuckerman,

Sutton

et al. 2024

J Biomedical Materials Res

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Pulmonary infections complicate chronic lung diseases requiring attention to both the pathophysiology and complexity associated with infection management. Patients with cystic fibrosis (CF) struggle with continuous bouts of pulmonary infections, contributing to lung destruction and eventual mortality. Additionally, CF patients struggle with airways that are highly viscous, with accumulated mucus creating optimal environments for bacteria colonization. The unique physiology and altered airway environment provide an ideal niche for bacteria to change their phenotype often becoming resistant to current treatments. Colonization with multiple pathogens at the same time further complicate treatment algorithms, requiring drug combinations that can challenge CF patient tolerance to treatment. The goal of this research initiative was to explore the utilization of a microparticle antibiotic delivery system, which could provide localized and sustained antibiotic dosing. The outcome of this work demonstrates the feasibility of providing efficient localized delivery of antibiotics to manage infection using both preclinical in vitro and in vivo CF infection models. The studies outlined in this manuscript demonstrate the proof‐of‐concept and unique capacity of polymerized cyclodextrin microparticles to provide site‐directed management of pulmonary infections.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Polymerized cyclodextrin microparticles for sustained antibiotic delivery in lung infections

Bonfield,

Zuckerman,

Sutton

et al. 2024

J Biomedical Materials Res

View full text Add to dashboard Cite

show abstract

“…More recent approaches have included the use of an alternative method to identify pulmonary exacerbations, known as the FEV1-indicated exacerbation signal (FIES) [ 12 ]. While pulmonary exacerbation has historically been defined heterogeneously through assessment primarily of lung function drops, there has been limited consensus on how to define such drops [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Predicting lung function decline in cystic fibrosis: the impact of initiating ivacaftor therapy

Zhou,

Wang,

Palipana

et al. 2024

Respir Res

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Background Modulator therapies that seek to correct the underlying defect in cystic fibrosis (CF) have revolutionized the clinical landscape. Given the heterogeneous nature of lung disease progression in the post-modulator era, there is a need to develop prediction models that are robust to modulator uptake. Methods We conducted a retrospective longitudinal cohort study of the CF Foundation Patient Registry (N = 867 patients carrying the G551D mutation who were treated with ivacaftor from 2003 to 2018). The primary outcome was lung function (percent predicted forced expiratory volume in 1 s or FEV1pp). To characterize the association between ivacaftor initiation and lung function, we developed a dynamic prediction model through covariate selection of demographic and clinical characteristics. The ability of the selected model to predict a decline in lung function, clinically known as an FEV1-indicated exacerbation signal (FIES), was evaluated both at the population level and individual level. Results Based on the final model, the estimated improvement in FEV1pp after ivacaftor initiation was 4.89% predicted (95% confidence interval [CI]: 3.90 to 5.89). The rate of decline was reduced with ivacaftor initiation by 0.14% predicted/year (95% CI: 0.01 to 0.27). More frequent outpatient visits prior to study entry and being male corresponded to a higher overall FEV1pp. Pancreatic insufficiency, older age at study entry, a history of more frequent pulmonary exacerbations, lung infections, CF-related diabetes, and use of Medicaid insurance corresponded to lower FEV1pp. The model had excellent predictive accuracy for FIES events with an area under the receiver operating characteristic curve of 0.83 (95% CI: 0.83 to 0.84) for the independent testing cohort and 0.90 (95% CI: 0.89 to 0.90) for 6-month forecasting with the masked cohort. The root-mean-square errors of the FEV1pp predictions for these cohorts were 7.31% and 6.78% predicted, respectively, with standard deviations of 0.29 and 0.20. The predictive accuracy was robust across different covariate specifications. Conclusions The methods and applications of dynamic prediction models developed using data prior to modulator uptake have the potential to inform post-modulator projections of lung function and enhance clinical surveillance in the new era of CF care.

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Detection of pathogenic bacteria and biomarkers in lung specimens from cystic fibrosis patients

Tolle,

Jadhao,

Patel

et al. 2024

J. Breath Res.

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Diagnosing lung infections is often challenging because of the lack of a high-quality specimen from the diseased lung. Since persons with cystic fibrosis are subject to chronic lung infection, there is frequently a need for a lung specimen. In this small, proof of principle study, we determined that PneumoniaCheckTM, a non-invasive device that captures coughed droplets from the lung on a filter, might help meet this need. We obtained 10 PneumoniaCheckTM coughed specimens and 2 sputum specimens from adult CF patients hospitalized with an exacerbation of their illness. We detected amylase (upper respiratory tract) with an enzymatic assay, surfactant A (lower respiratory tract) with an immunoassay, pathogenic bacteria by PCR, and markers of inflammation by a Luminex multiplex immunoassay. The amylase and surfactant A levels suggested that 9/10 coughed specimens were from lower respiratory tract with minimal upper respiratory contamination. The PCR assays detected pathogenic bacteria in 7 of 9 specimens and multiplex Luminex assay detected a variety of cytokines or chemokines. These data indicate that the PneumoniaCheckTM coughed specimens can capture good quality lower respiratory tract specimens that have the potential to help in diagnosis, management and understanding of CF exacerbations and other lung disease.

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Diagnosis and Management of Cystic Fibrosis Exacerbations

Cited by 7 publications

References 263 publications

Polymerized cyclodextrin microparticles for sustained antibiotic delivery in lung infections

Polymerized cyclodextrin microparticles for sustained antibiotic delivery in lung infections

Predicting lung function decline in cystic fibrosis: the impact of initiating ivacaftor therapy

Detection of pathogenic bacteria and biomarkers in lung specimens from cystic fibrosis patients

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