Early Interleukin-22 and Neutrophil Proteins Are Correlated to Future Lung Damage in Children With Cystic Fibrosis (original) (raw)
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Journal of Cystic Fibrosis, 2020
and IBL were responsible for the conception and design of study; AC and ASB provided technical advice on imaging and undertook all scoring; JS and LPT were responsible for supervision of the study and research governance; AFH provided technical training, supervision and audit of lung function data collection and analyses. LPT supervised CT imaging and audited data collection and analyses. Infants with CF were recruited by the paediatric respiratory consultants participating in the LCFC, including IBL, AB, CW, SC, RS, CP and GR.TDN, LPT and AFH recruited the healthy infants, undertook all lung function measurements and, together with JS and GD calculated and interpreted lung function results. NK performed inflammatory analyses. GD and AW
Thorax, 2011
Introduction Improved nutrition is the major proven benefit of newborn screening programmes for cystic fibrosis (CF) and is associated with better clinical outcomes. It was hypothesised that early pulmonary inflammation and infection in infants with CF is associated with worse nutrition. Methods Weight, height and pulmonary inflammation and infection in bronchoalveolar lavage (BAL) were assessed shortly after diagnosis in infants with CF and again at 1, 2 and 3 years of age. Body mass index (BMI) was expressed as z-scores. Inflammatory cells and cytokines (interleukin 1b (IL-1b), IL-6, IL-8 and tumour necrosis factor a (TNFa)), free neutrophil elastase activity and myeloperoxidase were measured in BAL. Mixed effects modelling was used to assess longitudinal associations between pulmonary inflammation, pulmonary infection (Staphylococcus aureus and Pseudomonas aeruginosa) and BMI z-score after adjusting for potential confounding factors. Results Forty-two infants were studied (16 (38%) male; 39 (93%) pancreatic insufficient); 36 were diagnosed by newborn screening (at median age 4 weeks) and six by early clinical diagnosis (meconium ileus). Thirty-one (74%) received antistaphylococcal antibiotics. More than two-thirds were asymptomatic at each assessment. Mean BMI z-scores were À1.5 at diagnosis and 0.5, À0.2 and À0.1 at 1, 2 and 3 years, respectively. Neutrophil elastase and infection with S aureus were associated with lower BMI, whereas age (p¼0.01) and antistaphylococcal antibiotics (p¼0.013) were associated with increased BMI. On average, each log 10 increase in free neutrophil elastase activity was associated with a 0.43 (95% CI 0.06 to 0.79) reduction in BMI z-score. Discussion Early nutritional status is associated with the underlying pulmonary pathophysiology in CF, and better understanding of these relationships is required. Studies are required to assess whether interventions can decrease pulmonary inflammation and improve nutrition. Early surveillance will enable such targeted interventions with the aim of improving these important clinical outcomes.
PLOS ONE, 2016
Background Cystic Fibrosis (CF) is characterized by chronically inflamed airways, and inflammation even increases during pulmonary exacerbations. These adverse events have an important influence on the well-being, quality of life, and lung function of patients with CF. Prediction of exacerbations by inflammatory markers in exhaled breath condensate (EBC) combined with early treatment may prevent these pulmonary exacerbations and may improve the prognosis. Aim To investigate the diagnostic accuracy of a set of inflammatory markers in EBC to predict pulmonary exacerbations in children with CF. Methods In this one-year prospective observational study, 49 children with CF were included. During study visits with an interval of 2 months, a symptom questionnaire was completed, EBC was collected, and lung function measurements were performed. The acidity of EBC was measured directly after collection. Inflammatory markers interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), and macrophage migration inhibitory factor (MIF) were measured PLOS ONE |
Pediatric Pulmonology, 2011
To analyze cross-sectional and longitudinal associations between lung function measures and clinical features in a cohort of preschool children with cystic fibrosis (CF). Methods: Longitudinal eight-center observational study of children with CF aged 36-60 months at enrollment, who underwent semiannual pulmonary function tests (PFTs) for up to 2 years consisting of spirometry (all 8 sites), forced oscillometry (FO, 5 sites), and measures of thoracoabdominal asynchrony using respiratory inductive plethysmography (IP, 5 sites). Results: Ninety-three subjects were enrolled; 181 acceptable spirometry measurements from 71 subjects, 128 FO from 47 subjects, and 142 IP from 50 subjects were available for analysis. Cross sectional analyses did not detect an association between any PFT parameter at enrollment and Pseudomonas aeruginosa (Pa) status, CF gene mutation class, Wisconsin cough score, Shwachman score, environmental tobacco smoke exposure, family history of asthma, or nutritional indices. In longitudinal analyses, Pa infection within 6 months preceding enrollment was associated with a significantly greater rate of decline in z-scores for forced expiratory flow between 25 and 75% of forced vital capacity (FEF 25-75) (À1.3 vs. À0.4 Z scores/year, P ¼ 0.024) and greater thoracoabdominal asynchrony measured by IP (mean phase angle difference 4.68, P ¼ 0.004). No other significant longitudinal associations were observed. Conclusions: Prior Pa infection is associated with a greater rate of decline in FEF 25-75 z-score and mild thoracoabdominal asynchrony in preschool children with CF. In this multicenter US study, significant associations between other lung function measures and clinical features were not detected. Pediatr Pulmonol.
Lung function from infancy to preschool in a cohort of children with cystic fibrosis
European Respiratory Journal, 2012
This study aimed to describe lung function in a cohort of children with cystic fibrosis (CF) who underwent infant pulmonary function tests (IPFTs) and preschool spirometry. Children performed up to four IPFTs (raised volume rapid thoracic compression technique) over 1 yr and five preschool spirometry tests over up to 2 yrs during participation in prospective, multicentre studies of infant and preschool lung function. All lung function data were reviewed centrally for measurement acceptability. 45 children had 252 acceptable measurements (137 IPFTs and 115 preschool spirometries) at ages 0.3-6.5 yrs. The median number of measurements per participant was 6 (range 3-9). Recent Pseudomonas aeruginosa infection was associated with 5.1% (95% CI 0.01-9.9%) lower forced expiratory volume in 0.5 s (FEV0.5) and 16.4% (95% CI 7.0-24.9%) lower forced expiratory flow at 25-25% of forced vital capacity (FEF25-75%), after adjustment for length, test type and centre. Recent cough was associated with 5.7% (95% CI 1.1-10.1%) lower FEV0.5 and 10.1% (95% CI 0.6-18.7%) lower FEF25-75%. Even after accounting for infection status, cough, sex, length, test type and centre, there was significant inter-individual variability in lung function (p,0.01 for each of FEV0.5, FEF25-75% and forced vital capacity). Recent P. aeruginosa infection and cough are associated with lower lung function in children with CF. Significant inter-individual variability in lung function remains to be explained.
Distinct cytokine production by lung and blood neutrophils from children with cystic fibrosis
American Journal of Physiology-Lung Cellular and Molecular Physiology, 2003
Inflammation plays a critical role in lung disease progression in cystic fibrosis (CF). This inflammatory process is dominated by a neutrophil influx in the airways. To determine whether the accumulation of neutrophils in the airways of CF patients is associated with an altered function, we analyzed the capacity of neutrophils isolated from the lung compartment and the blood to release the major neutrophil pro- and anti-inflammatory cytokines IL-8 and IL-1-receptor antagonist (ra) spontaneously and in the presence of LPS. Comparison of cytokine production by blood neutrophils from CF patients and from control subjects showed significantly increased IL-8 and decreased IL-1ra release by CF neutrophils. Comparison of cytokine production by airway and blood neutrophils from CF patients also documented distinct profiles: the spontaneous release of IL-8 and IL-1ra by airway neutrophils was significantly higher than that from blood neutrophils. Culture in the presence of LPS failed to furt...
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 2018
Little is known about the role of interleukin (IL)-1 in the pathogenesis of cystic fibrosis (CF) lung disease. This study investigated the relationship between IL-1 signalling, neutrophilic inflammation and structural lung changes in children with CF. Bronchoalveolar lavage fluid (BALf) from 102 children with CF were used to determine IL-1α, IL-1β, IL-8 levels and neutrophil elastase (NE) activity, which were then correlated to structural lung changes observed on chest computed tomography (CT) scans. IL-1α and IL-1β were detectable in BAL in absence of infection, increased in the presence of bacterial infection and correlated with IL-8 (p < 0.0001), neutrophils (p < 0.0001) and NE activity (p < 0.01 and p < 0.001). IL-1α had the strongest association with structural lung disease (p < 0.01) in the absence of infection (uninfected: p < 0.01 vs. infected: p = 0.122). Our data associates IL-1α with early structural lung damage in CF and suggests this pathway as a novel...