Novel end points for clinical trials in young children with cystic fibrosis

Early Lung Disease in Infants and Preschool Children with Cystic Fibrosis. What Have We Learned and What Should We Do about It?

“…Many studies now identify infancy and the early preschool years as a critical period when structural changes in the CF lung begin (8,9,18,45). Advances in CT technology, the advent of low-dose radiation acquisition protocols, and improved algorithms for acquisition of chest CT images have both reduced the radiation risk to the young child and markedly improved the sensitivity with which lung disease can be detected (46). Recent studies suggest that bronchiectasis, defined as a bronchus-to-arterial ratio of greater than 1.0, is present in many asymptomatic infants shortly after diagnosis (8).…”

Mapping targetable inflammation and outcomes with cystic fibrosis biomarkers

“…Testing of anti-inflammatory therapies and other treatments in CF has become increasingly challenging, as overall improvements in lung function and health make observing changes in traditional endpoints such as lung function or pulmonary exacerbations more difficult to assess without large and expensive trials. 38 However, accurately measuring airway inflammation directly as a marker of therapeutic activity can be difficult. Indeed, most of the major trials of anti-inflammatory therapies described above [24][25][26]36 did not include an airway inflammation biomarker, with the exception of the azithromycin trial that demonstrated statistically significant though modest changes in neutrophil elastase.…”

“…The dearth of effective anti‐inflammatory therapies represents an ongoing barrier to normalcy in CF and suggests a need to identify new therapeutic targets. Testing of anti‐inflammatory therapies and other treatments in CF has become increasingly challenging, as overall improvements in lung function and health make observing changes in traditional endpoints such as lung function or pulmonary exacerbations more difficult to assess without large and expensive trials . However, accurately measuring airway inflammation directly as a marker of therapeutic activity can be difficult.…”

Narrowing in on Early Cystic Fibrosis Lung Disease

“…Although the widespread implementation of newborn screening programs for CF enables diagnosis during the first weeks of life, detecting the onset of lung disease in infants and young children remains challenging (2). Overt respiratory symptoms among children with CF are minimal, and monitoring techniques used in older patients, such as spirometry and sputum cultures, are not directly translatable to younger patients.…”

“…Dysregulation of this pathway has been implicated in the induction and/or progression of many diseases, including several respiratory diseases such as asthma and chronic obstructive pulmonary disease (2). Furthermore, this pathway is aberrantly activated in human cancer and plays a critical role in both the initiation and progression of experimental non-small cell lung cancer (3,4).…”