Impact of lung disease on respiratory impedance in young children with cystic fibrosis.

This study aimed to evaluate the ability of the forced oscillation technique (FOT) to detect underlying lung disease in preschool children with cystic fibrosis (CF) diagnosed following newborn screening.184 children (aged 3-6 years) with CF underwent lung function testing on 422 occasions using the FOT to assess respiratory resistance and reactance at the time of their annual bronchoalveolar lavage collection and chest computed tomography scan. We examined associations between FOT outcomes and the presence and progression of respiratory inflammation, infection and structural lung disease.

Brief exposure to cigarette smoke impairs airway epithelial cell innate anti-viral defence.

Background: Human rhinovirus (hRV) infections commonly cause acute upper respiratory infections and asthma exacerbations. Environmental cigarette smoke exposure is associated with a significant increase in the risk for these infections in children.

Objective: To determine the impact of short-term exposure to cigarette smoke on innate immune responses of airway epithelial cells infected with hRV.

Oxidation contributes to low glutathione in the airways of children with cystic fibrosis.

Glutathione is an important antioxidant in the lungs but its concentration is low in the airways of patients with cystic fibrosis. Whether this deficit occurs from an early age or how oxidative stress contributes to lowering glutathione is unknown. We measured glutathione, its oxidation products, myeloperoxidase, and biomarkers of hypochlorous acid in bronchoalveolar lavage from children with cystic fibrosis and disease controls using mass spectrometry and immunological techniques.

Airway, but not serum or urinary, levels of YKL-40 reflect inflammation in early cystic fibrosis lung disease.

Background: Cystic fibrosis (CF) lung disease begins in early life and is progressive with the major risk factor being an exaggerated inflammatory response. Currently, assessment of neutrophilic inflammation in early cystic fibrosis (CF) lung disease relies on bronchoalveolar lavage (BAL). The chitinase-like protein YKL-40 is raised in sputum and serum of adults with CF.

Risk factors for bronchiectasis in children with cystic fibrosis.

Background: Bronchiectasis develops early in the course of cystic fibrosis, being detectable in infants as young as 10 weeks of age, and is persistent and progressive. We sought to determine risk factors for the onset of bronchiectasis, using data collected by the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) intensive surveillance program.

Methods: We examined data from 127 consecutive infants who received a diagnosis of cystic fibrosis after newborn screening.

Reference ranges for Mexican preschool-aged children using the forced oscillation technique.

Introduction: Recently, multi-ethnic reference ranges for spirometry have been created for use worldwide. In comparison, forced oscillation technique (FOT) reference values are limited to specific equipment and study populations, with current FOT reference ranges created in a Caucasian population. We aimed to develop FOT reference ranges for preschool-aged Mexican children and to compare these with current FOT reference ranges.

Distribution of early structural lung changes due to cystic fibrosis detected with chest computed tomography.

Objective: To examine the distribution of early structural lung changes in clinically stable infants and young children with cystic fibrosis using chest computed tomography (CT).

Study Design: This cross-sectional study included 62 children aged 1-6 years with volume-controlled volumetric chest CT scans performed under general anesthesia as part of an early surveillance program. Each lobe was scored for presence and extent of bronchiectasis, mucus plugging, and air trapping using a semiquantitative score.

Progression of early structural lung disease in young children with cystic fibrosis assessed using CT.

Background: Cross-sectional studies implicate neutrophilic inflammation and pulmonary infection as risk factors for early structural lung disease in infants and young children with cystic fibrosis (CF). However, the longitudinal progression in a newborn screened population has not been investigated.

Aim: To determine whether early CF structural lung disease persists and progresses over 1 year and to identify factors associated with radiological persistence and progression.

Inflammatory responses to individual microorganisms in the lungs of children with cystic fibrosis.

Background: We hypothesized that the inflammatory response in the lungs of children with cystic fibrosis (CF) would vary with the type of infecting organism, being greatest with Pseudomonas aeruginosa and Staphylococcus aureus.

Methods: A microbiological surveillance program based on annual bronchoalveolar lavage (BAL) collected fluid for culture and assessment of inflammation was conducted. Primary analyses compared inflammation in samples that grew a single organism with uninfected samples in cross-sectional and longitudinal analyses.

Evolution of pulmonary inflammation and nutritional status in infants and young children with cystic fibrosis.

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.

Identifying peroxidases and their oxidants in the early pathology of cystic fibrosis.

We aimed to determine whether myeloperoxidase (MPO) is the main peroxidase present in the airways of children with cystic fibrosis (CF) and to assess which oxidants it produces and whether they are associated with clinical features of CF. Children with CF (n=54) and without CF (n=16) underwent bronchoscopy and bronchoalveolar lavage (BAL) for assessment of pulmonary infection and inflammation. BAL fluid was analyzed for MPO, halogenated tyrosines as markers of hypohalous acids, thiocyanate, and protein carbonyls.

Lung function testing in preschool-aged children with cystic fibrosis in the clinical setting.

In cystic fibrosis (CF) lung function testing is a means of monitoring progression of lung disease. The preschool years have often been referred to as the "silent years" due to the previous lack suitable measures of lung function testing in this age group. This review outlines the various techniques of lung function testing in preschool children with CF in the clinical setting.

Bronchiectasis in infants and preschool children diagnosed with cystic fibrosis after newborn screening.

Objectives: To determine the prevalence of bronchiectasis in young children with cystic fibrosis (CF) diagnosed after newborn screening (NBS) and the relationship of bronchiectasis to pulmonary inflammation and infection.

Study Design: Children were diagnosed with CF after NBS. Computed tomography and bronchoalveolar lavage were performed with anesthesia (n = 96).

Bronchiectasis in an asymptomatic infant with cystic fibrosis diagnosed following newborn screening.

Many countries have introduced newborn screening for cystic fibrosis to facilitate diagnosis prior to the development of lung disease. Although most infants with cystic fibrosis are asymptomatic from a respiratory point of view at diagnosis, structural lung disease has been detected by computed tomography. We present a case of an asymptomatic infant with cystic fibrosis diagnosed following newborn screening who had endobronchial infection with Pseudomonas aeruginosa and radiological evidence of bronchiectasis at 3 months of age.

Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening.

Rationale: The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis.

Objectives: To determine the extent of lung disease in a geographically defined population of infants with CF diagnosed after detection by NBS.

Application of a shortened inhaled adenosine-5'-monophosphate challenge in young children using the forced oscillation technique.

Background: Adenosine-5'-monophosphate (AMP) is an indirect challenge agent thought to reflect allergic airway inflammation. The forced oscillation technique (FOT) is ideal for use in young children and is suitable for inhaled challenge studies in patients who are in this age group. We assessed the agreement between a shortened and a standard AMP challenge and the repeatability of the shortened AMP challenge using FOT as a primary outcome variable.

Early detection of lung disease in children with cystic fibrosis using lung function.

Measurement of lung function is routine in older children and adults with cystic fibrosis (CF) but not in infants and preschool children. Pulmonary infection, neutrophil-dominated inflammation and clinical exacerbations in young children similar to those seen in older subjects have been identified and highlight the urgent need to evaluate lung function in early life. Mounting evidence suggests lung function techniques sensitive to changes in peripheral lung function may be required to detect the early functional abnormalities in infants and preschool children with CF.

Disease surveillance using bronchoalveolar lavage.

The role of pulmonary infection and inflammation in the pathogenesis of destructive lung disease in cystic fibrosis (CF) is undisputed. The use of bronchoscopy and bronchoalveolar lavage (BAL) has demonstrated that these processes may begin early in life and be present in the absence of overt clinical symptoms. Some children diagnosed following newborn screening can be infected with Pseudomonas aeruginosa in infancy.

Assessment of bronchodilator responsiveness in preschool children using forced oscillations.

Background: The forced oscillation technique (FOT) requires minimal patient cooperation and is feasible in preschool children. Few data exist on respiratory function changes measured using FOT following inhaled bronchodilators (BD) in healthy young children, limiting the clinical applications of BD testing in this age group. A study was undertaken to determine the most appropriate method of quantifying BD responses using FOT in healthy young children and those with common respiratory conditions including cystic fibrosis, neonatal chronic lung disease and asthma and/or current wheeze.

Respiratory function in healthy young children using forced oscillations.

Background: Monitoring of respiratory function is important in the diagnosis and management of respiratory disease. The forced oscillation technique requires minimal patient cooperation and is ideal for the determination of respiratory function in young children. This study aimed to develop reference ranges and to document the repeatability in healthy young children using commercially available forced oscillation equipment.