Clinimetric properties of bronchoalveolar lavage inflammatory markers in cystic fibrosis

Fayon, Michaël; Kent, Lisa; Bui, Stéphanie; Dupont, Lieven; Sermet, Isabelle

doi:10.1183/09031936.00017713

Cited by 27 publications

(23 citation statements)

References 72 publications

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“…Australian Respiratory Early Surveillance Team for CF) (78, 79), and in clinical trials of inhaled tobramycin (80) and recombinant human DNase (81). A recently published document from the European CF Society Clinical Trial Network concluded that the use of BAL in clinical research should be limited due to its invasive nature, but that it may be applicable to early-phase clinical trials conducted in specialized centers and in trials involving young children with early/mild lung disease (82). …”

Section: Biomarkers Of Inflammationmentioning

confidence: 99%

Biomarkers for cystic fibrosis drug development

Muhlebach

Clancy

Heltshe

et al. 2016

Journal of Cystic Fibrosis

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Purpose To provide a review of the status of biomarkers in cystic fibrosis drug development, including regulatory definitions and considerations, a summary of biomarkers in current use with supportive data, current gaps, and future needs. Methods Biomarkers are considered across several areas of CF drug development, including cystic fibrosis transmembrane conductance regulator modulation, infection, and inflammation. Results Sweat chloride, nasal potential difference, and intestinal current measurements have been standardized and examined in the context of multicenter trials to quantify CFTR function. Detection and quantification of pathogenic bacteria in CF respiratory cultures (e.g.: Pseudomonas aeruginosa) is commonly used in early phase antimicrobial clinical trials, and to monitor safety of therapeutic interventions. Sputum (e.g.: neutrophil elastase, myeloperoxidase, calprotectin) and blood biomarkers (e.g.: C reactive protein, calprotectin, serum amyloid A) have had variable success in detecting response to inflammatory treatments. Conclusions Biomarkers are used throughout the drug development process in CF, and many have been used in early phase clinical trials to provide proof of concept, detect drug bioactivity, and inform dosing for later-phase studies. Advances in the precision of current biomarkers, and the identification of new biomarkers with ‘omics-based technologies, are needed to accelerate CF drug development.

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Section: Biomarkers Of Inflammationmentioning

confidence: 99%

Biomarkers for cystic fibrosis drug development

Muhlebach

Clancy

Heltshe

et al. 2016

Journal of Cystic Fibrosis

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“…However, in a trial of BAL-directed therapy compared with standard treatment in children infected with P. aeruginosa (from diagnosis to 5 years of age), no difference in the rate of pseudomonas eradication or CT score between the two approaches was found [96]. BAL remains useful in the early stages of trials to describe pathophysiological processes in CF [87] and free neutrophil elastase activity detected in infants appears an important predictor for more severe lung disease.…”

Section: Previous Studies Of Bal In Children With Cfmentioning

confidence: 99%

“…It is recommended that lavage is performed in the most affected lobe if detected by prior imaging, or the right middle lobe in the presence of diffuse disease. However, as CF lung disease is ''patchy'', lavaging one lobe does have the potential to miss areas of disease [87]. There is no consensus on the number or volume of aliquots that should be taken at present.…”

Section: Balmentioning

confidence: 99%

“…There may be differences in volumes and dilution of fluid retrieved from each patient, and values of biomarkers vary in sequential aliquots. During analysis, individual or pooled aliquots can be studied, but are likely to yield different results [87]. There are many potential assays available which vary between laboratories, and data on reproducibility of markers are scarce.…”

Section: Balmentioning

confidence: 99%

“…There are many potential assays available which vary between laboratories, and data on reproducibility of markers are scarce. The European Cystic Fibrosis Society Clinical Trial Network Standardisation Committee have published a review on BAL markers and report neutrophil count or percentage, neutrophil elastase, interlukin-6 and interlukin-8 as the most useful currently in CF [87]. Limitations of this procedure in young children also include its invasive nature and need for general anaesthesia.…”

Section: Balmentioning

confidence: 99%

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Monitoring early lung disease in cystic fibrosis: where are we now?

Duncan

Aurora

2014

Breathe

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Educational aimsTo understand which techniques are available to monitor early lung disease in cystic fibrosis, recognise difficulties inherent to each measure, and describe the use of tests in clinical practice or interventional trials.SummaryIt is a particular challenge to detect and monitor lung disease in children younger than 6 years old. Various methods exist that can reveal abnormality in young children, but each technique presents difficulties on performing the test or interpreting results. Most children with cystic fibrosis are now diagnosed shortly after birth, but it is still unclear how to evaluate new therapies, or at what age to initiate them. This review summarises current options for monitoring early disease, limitations of individual techniques and how evidence to date influences their use in research and clinical practice.Key pointsLung disease remains the major cause of morbidity and mortality in cystic fibrosisDespite clear improvements in outcomes such as nutrition, the benefit of early diagnosis by newborn screening on pulmonary health in cystic fibrosis has yet to be proven.Early lung disease is challenging to detect and monitor in young children with cystic fibrosis, but there is an urgent requirement to define useful outcome measures in this population, particularly as new treatments emerge.Many techniques are available, but difficulties with measurement or interpretation must be recognised when appraising past studies, considering their use in practice or as endpoints in clinical trials.There is no superior monitoring test at present, but emerging evidence from longitudinal studies in children with cystic fibrosis will help define which are most useful.

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