ABSTRACT
BACKGROUND: The detrimental role of viruses has been well described in CF, although the pattern of virus infections has not been investigated in a longitudinal study. The primary aim was to determine the feasibility of fortnightly parent collected swabs in young children with CF. METHODS: Children under three years with CF were recruited. Nasal swabs were collected by parents every fortnight and during periods of symptoms over 12 months. Nasal swabs were posted and virus detected using real-time PCR. RESULTS: Only 27% of the patients completed the study to 10 months, although 98% of the swabs returned were adequate for analysis. Mould was observed growing on 23% of the returned swabs. There was no evidence to demonstrate relationships with symptoms and viruses, prolonged symptoms, prolonged shedding or patterns of virus infections. CONCLUSIONS: This study highlights the need to further investigate the role of viruses in children with CF using a robust method of frequent collection in children for a longitudinal study, with appropriate storage and shipping techniques to avoid mould growth or other potential contaminants.
Subject(s)
Cystic Fibrosis/virology , Nasal Cavity/virology , Parents , Respiratory Tract Infections/virology , Specimen Handling/methods , Virus Diseases/diagnosis , Child, Preschool , Cross-Sectional Studies , Cystic Fibrosis/complications , Feasibility Studies , Female , Humans , Infant , Longitudinal Studies , Male , Pilot Projects , Real-Time Polymerase Chain Reaction , Respiratory Tract Infections/diagnosis , Virus Diseases/virologyABSTRACT
Early detection of the cyanobacterium Pseudomonas aeruginosa in the lungs of young children with cystic fibrosis (CF) is considered the key to delaying chronic pulmonary disease. We investigated whether cyanide in bronchoalveolar lavage (BAL) fluid could be used as an early diagnostic biomarker of infection. Cyanide was measured in 226 BAL samples (36 P. aeruginosa infected) obtained from 96 infants and young children with CF participating in an early surveillance programme involving annual BAL. Cyanide was detected in 97.2% of P. aeruginosa infected and 60.5% of uninfected samples. Cyanide concentrations were significantly higher in BALs infected with P. aeruginosa (median (25th-75th percentile) 27.3 (22.1-33.3) µM) than those which were not (17.2 (7.85-23.0) µM, p<0.001). The best sensitivity, specificity, positive and negative predictive values were obtained with a cut-off concentration of 20.6 µM, and were 83%, 66%, 32% and 96%, respectively. Neutrophil number in BAL was a significant predictor of cyanide concentration (p<0.001). Cyanide concentration can distinguish between P. aeruginosa infected and uninfected BALs as a group, but not individually; therefore, cyanide is a poor diagnostic biomarker of P. aeruginosa infection. Cyanide levels in BAL are related to the level of neutrophilic inflammation.
Subject(s)
Bronchoalveolar Lavage , Cyanides/metabolism , Cystic Fibrosis/complications , Pseudomonas Infections/diagnosis , Pseudomonas aeruginosa/metabolism , Biomarkers/metabolism , Calibration , Child , Child, Preschool , Cystic Fibrosis/diagnosis , Cystic Fibrosis/microbiology , Female , Humans , Infant , Longitudinal Studies , Lung Diseases/microbiology , Male , Microscopy, Fluorescence/methods , Neutrophils/pathology , Predictive Value of Tests , Pseudomonas Infections/metabolismABSTRACT
Airway inflammation is an important component of cystic fibrosis (CF) lung disease. We sought to determine whether alveolar macrophages were involved in early CF lung disease. Children with CF (median age 3.1 yrs) participated in a surveillance programme that included annual bronchoalveolar lavage (BAL). Control samples were obtained from non-CF children (median age 3.1 yrs; n = 24) investigated for persistent respiratory symptoms. Pulmonary infection was detected in 31% (16 out of 51) and 38% (nine out of 24) of children from the CF and non-CF groups, respectively. Alveolar macrophages in BAL were increased in CF compared with non-CF in the absence of infection (223x10(3) versus 85x10(3) cells.mL(-1); p = 0.001) and were associated with elevations in the CC chemokines (macrophage inflammatory protein (MIP)-3alpha (chemokine (C-C motif) ligand (CCL)20; 355.8 versus 46.0 pg.mL(-1); p<0.001), monocyte chemotactic protein-1 (CCL2; 263.5 versus 25.3 pg.mL(-1); p<0.001), MIP-1alpha (CCL3; 38.2 versus 4.9 pg.mL(-1); p<0.001) and MIP-1beta (CCL4; 326.6 versus 27.5 pg.mL(-1); p<0.001)). Total cell counts and neutrophil numbers increased in the presence of infection; however, there was no additional effect of CF. Alveolar macrophages and CC chemokines are elevated in the lungs in young children with CF even in the absence of pulmonary infection. Longitudinal studies are required to determine the clinical relevance of these findings.
Subject(s)
Chemokine CCL2/metabolism , Chemokine CCL5/metabolism , Cystic Fibrosis/metabolism , Cystic Fibrosis/pathology , Macrophage Inflammatory Proteins/metabolism , Macrophages, Alveolar/physiology , Bronchoalveolar Lavage , Case-Control Studies , Cell Count , Child, Preschool , Cystic Fibrosis/microbiology , Female , Humans , Infant , Lung/metabolism , Lung/pathology , Male , Respiratory Tract Infections/complications , Respiratory Tract Infections/metabolism , Respiratory Tract Infections/pathologyABSTRACT
The extent of respiratory dysfunction is not well characterised in children with neonatal chronic lung disease (nCLD) too young to perform spirometry. Forced oscillations are easily performed by healthy young children; however, they may be more difficult for those with nCLD. The present study aimed to describe the feasibility of using the forced oscillation technique in children with nCLD in a routine clinical setting and to investigate the influence of neonatal factors on subsequent lung function. Respiratory function tests were attempted in 64 patients with nCLD aged 3.2-6.6 yrs. Respiratory resistance and reactance at 6, 8 and 10 Hz were expressed as z-scores derived from a healthy reference population. The within-test variation and between-test repeatability were also assessed. Technically, satisfactory data were obtained from 77% of children. On grouped data, z-scores for all oscillatory indices were different from zero and related to hospital oxygen administration in the neonatal period. In conclusion, the forced oscillation technique was feasible in preschool children with neonatal chronic lung disease in the clinical outpatient setting. These children had lung function significantly worse than that predicted from healthy children. Respiratory function assessed using forced oscillations appeared to reflect the severity of lung disease during the neonatal period.
Subject(s)
Airway Resistance , Infant, Newborn, Diseases/physiopathology , Lung Diseases/physiopathology , Oscillometry/methods , Case-Control Studies , Child , Child, Preschool , Chronic Disease , Feasibility Studies , Female , Humans , Infant, Newborn , Male , Reference Values , Reproducibility of Results , Severity of Illness IndexABSTRACT
Measurement of lung function is an important component of clinical management in cystic fibrosis (CF), but has been difficult in young children. The present study aimed to characterise the utility of the forced oscillation technique for measurement of lung function in preschool-aged children with CF in a routine clinical setting. Lung function was assessed in 56 young children (aged 2-7 yrs) with CF. Respiratory system resistance (R(rs)) and reactance (X(rs)) at 6, 8 and 10 Hz were measured and expressed as Z-scores. Children were classified as asymptomatic or symptomatic based on an administered respiratory questionnaire and physical examination at the time of testing. Between-test repeatability was assessed in 25 children. Measurement of lung function using the forced oscillation technique was feasible in the CF clinic. The children with CF, as a group, had Z-scores for R(rs) at 6 Hz (R(rs,6)) R(rs,8), R(rs,10), X(rs) at 6 Hz (X(rs,6)) and X(rs,8) that were significantly different from zero. Children with current symptoms showed significantly decreased X(rs) and increased R(rs,6) compared with asymptomatic children. Measurement of lung function using the forced oscillation technique is feasible in young children with cystic fibrosis in a clinical setting. The technique has the potential to improve knowledge concerning early cystic fibrosis lung disease.
