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

Abstract

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.

Longitudinal course of clinical lung clearance index in children with cystic fibrosis

“…Lung disease in cystic fibrosis (CF) starts early in life with bacterial infection and pulmonary inflammation leading to structural abnormalities [1,2]. Damage to the lung during sensitive periods of lung growth and development can influence the trajectory of lung disease [1][2][3]. Therefore, early and sensitive monitoring of lung disease progression is essential.…”

Novel Anti-Inflammatory Approaches for Cystic Fibrosis Lung Disease: Identification of Molecular Targets and Design of Innovative Therapies

“…Different authors have also highlighted the central role of neutrophil in CF airway inflammation, and many believed that bronchiectasis results from the proteolytic and oxidative damage induced by these cells. Longitudinal data from the Australian Respiratory Early Surveillance Team for Cystic Fibrosis demonstrated that neutrophil elastase activity at 3 months of age was a predictor of bronchiectasis at 12 months and 3 years ( Wijker et al, 2020 ). The central role of neutrophils and its genesis has been extensively review by Nichols et al.…”

Leveraging early markers of cystic fibrosis structural lung disease to improve outcomes

“…Prescription of inhaled antipseudomonal antibiotics upon the identification of bacteria, notably Pseudomonas, has become standard of care [6], but what of the chronic therapies such as hypertonic saline, dornase alfa and macrolides? The data presented by WIJKER et al [4] suggest that earlier interventions guided by CT and inflammatory marker findings may be warranted.…”

“…This is the next hurdle for CT imaging as an outcome measure: to demonstrate resolution or attenuation of abnormalities following effective interventions. WIJKER et al [4] have left little doubt that addressing early inflammation in the CF lung will be integral to slowing or stopping CF lung disease progression [4]. Further, their results suggest that studies of intervention-associated change in atelectasis, airway thickening and/or IL-8 concentrations may be justified in infants with CF.…”

“…Although the global CF community likely concurs that there is potential for early modulator access to retard lung disease progression by improving CFTR activity in the airway, the reality is that the cost of these drugs to payers (whether public or private) has produced regional disparities in modulator access to very young children with CF. It may be that a decade from now, it will be possible to use the CT methodologies described by WIJKER et al [4] to discriminate between those children with CF who enjoyed access to CFTR modulators early in life and those who did not.…”