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Biomedical subjects

P D Sly

Publications and source records attributed to P D Sly.

At least 19 recordsLinked to original sources
PubMed2006

Pre-flight testing of preterm infants with neonatal lung disease: a retrospective review.

BACKGROUND: The low oxygen environment during air travel may result in hypoxia in patients with respiratory disease. However, little information exists on the oxygen requirements of infants with respiratory disease planning to fly. A study was undertaken to identify the clinical factors predictive of an in-flight oxygen requirement from a retrospective review of hypoxia challenge tests (inhalation of 14-15% oxygen for 20 minutes) in infants referred for fitness to fly assessment. METHODS: Data from 47 infants (median corrected age 1.4 months) with a history of neonatal lung disease but not receiving supplemental oxygen at the time of hypoxia testing are reported. The neonatal and current clinical information of the infants were analysed in terms of their ability to predict the hypoxia test results. RESULTS: Thirty eight infants (81%) desaturated below 85% and warranted prescription of supplemental in-flight oxygen. Baseline oxygen saturation was >95% in all infants. Age at the time of the hypoxia test, either postmenstrual or corrected, significantly predicted the outcome of the hypoxia test (odds ratio 0.82; 95% confidence intervals 0.62 to 0.95; p = 0.005). Children passing the hypoxia test were significantly older than those requiring in-flight oxygen (median corrected age (10-90th centiles) 12.7 (3.0-43.4) v 0 (-0.9-10.9) months; p < 0.0001). CONCLUSIONS: A high proportion of ex-preterm infants not currently requiring supplemental oxygen referred for fitness-to-fly assessment and less than 12 months corrected age are at a high risk of requiring in-flight oxygen. Referral of this patient group for fitness to fly assessment including a hypoxia test may be indicated.

Aerospace Medicine↗
PubMed2006

Value of eosinophil cationic protein and tryptase levels in bronchoalveolar lavage fluid for predicting lung function impairment in anaesthetised, asthmatic children.

Bronchial hyperactivity, a key feature of active asthma in children, is a risk factor for respiratory adverse events in the peri-operative period. The presence of activated eosinophils in the lungs and mast cell degranulation can contribute to bronchial hyperreactivity. Eosinophil cationic protein is released by activated eosinophils and tryptase reflects mast cell degranulation. This study focused on the relationship of respiratory mechanics, eosinophil cationic protein and tryptase levels in bronchoalveolar lavage fluid in asthmatic and healthy children under general anaesthesia. We measured eosinophil cationic protein and tryptase levels in bronchoalveolar lavage fluid from 21 asthmatic and 21 healthy children following induction of general anaesthesia. Respiratory system resistance and dynamic compliance were measured during mechanical ventilation. Eosinophil cationic protein was more common in bronchoalveolar lavage fluid from asthmatics (12/21) than from controls (4/21, p = 0.01) and was present at higher levels (p = 0.002). Tryptase was also more common in the asthmatics (8/21 vs 1/21, p = 0.01). Respiratory resistance was significantly higher in asthmatic children with detectable eosinophil cationic protein levels than in those with undetectable eosinophil cationic protein levels (p = 0.019). Furthermore, 50% of the asthmatics with detectable eosinophil cationic protein exhibited bronchospasm after sampling their bronchoalveolar lavage fluid. These findings suggested that high levels of eosinophil cationic protein in the bronchoalveolar lavage fluid are associated with irritable airways, presumably secondary to airway inflammation, and this might be a useful marker for respiratory adverse events in the peri-operative period.

Airway Resistance↗
PubMed2005

CD14 C-159T and early infection with Pseudomonas aeruginosa in children with cystic fibrosis.

Early acquisition of Pseudomonas aeruginosa is associated with a poorer prognosis in patients with cystic fibrosis. We investigated whether polymorphisms in CD14, the lipopolysaccharide receptor, increase the risk of early infection. Forty-five children with cystic fibrosis were investigated with annual bronchoalveolar lavage (BAL) and plasma sCD14 levels. Plasma sCD14 levels were significantly lower in children from whom P.aeruginosa was subsequently isolated (492.75 microg/ml vs. 1339.43 microg/ml, p = 0.018). Those with the CD14 -159CC genotype had a significantly increased risk of early infection with P.aeruginosa suggesting that CD14 C-159T plays a role in determining the risk of early infection with P.aeruginosa.

Australia↗
PubMed2005

Nasal wash as an alternative to bronchoalveolar lavage in detecting early pulmonary inflammation in children with cystic fibrosis.

OBJECTIVE: The aim of this study was to determine whether nasal inflammation reflects pulmonary inflammation in young children with cystic fibrosis (CF), as assessed by inflammatory markers in nasal wash (NW) and bronchoalveolar lavage (BAL), respectively. METHODS: CF patients younger than 6 years of age who were to undergo bronchoscopy for routine BAL from May 2000 to October 2001 were recruited for this study. NW was collected immediately after the patient was sedated for bronchoscopy. Total cell counts (TCC), differential cell counts and interleukin (IL)-8 levels (enzyme-linked immunosorbent assay) were assessed in NW and BAL. RESULTS: In total, 19 children with CF (mean age, 1.9 years; SD, 1.7 years) were included in the study. There was a significant relationship between IL-8 and the percentages of neutrophils in NW (r (2) = 0.76; P < 0.001) and in BAL fluid (r 2 = 0.62; P = 0.006). Similarly, IL-8 concentrations in the NW correlated with those in the BAL (r 2 = 0.48; P = 0.036) and neutrophil percentages in NW correlated significantly with those in BAL (r 2 = 0.7; P = 0.004). CONCLUSION: When measured under 'ideal' conditions, nasal IL-8 reflects lower airway levels and may reflect the inflammatory stimulus that results in neutrophilic inflammation. These data encourage further assessment of nasal wash under clinically appropriate conditions to determine its utility for assessing inflammation in young children with CF.

Biomarkers↗
PubMed2005

Correlation of forced oscillation technique in preschool children with cystic fibrosis with pulmonary inflammation.

BACKGROUND: Lung disease in cystic fibrosis (CF) is established in early childhood with recurrent bacterial infections and inflammation. Using spirometry, the effect of this early lung damage cannot be measured until a child is 6 years of age when some irreversible lung damage may already have occurred. Techniques for measurement of lung function in infants and young children include raised volume rapid thoracic compression (RVRTC) and low frequency forced oscillation (LFFOT). The aim of this study was to investigate the role of inflammation and infection on a population of infants and young children with CF and to determine whether lung function in this population (measured by LFFOT) is affected by early lung disease. METHODS: Lung function was measured by LFFOT in 24 children undergoing bronchoalveolar lavage (BAL) on 27 occasions as part of an annual programme while still under general anaesthesia. Following lung function testing, three aliquots of saline were instilled into the right middle or lower lobe. The first aliquot retrieved was processed for the detection of microbes, and the remaining aliquots were pooled to assess inflammatory markers (cytology, IL-8, NE, LTB(4)). RESULTS: Inflammation (percentage and number of neutrophils) was significantly higher in children with infections (p<0.001, p = 0.04, respectively), but not in those with symptoms. Several markers of inflammation significantly correlated with LFFOT parameters (R, G, and eta). CONCLUSION: Infections and inflammation are established before symptoms are apparent. Inflammation is correlated with measures of parenchymal changes in lung function measured by LFFOT.

Airway Resistance↗
PubMed2004

Enhancement of vaccine-specific cellular immunity in infants by passively acquired maternal antibody.

The known protective effects of passively acquired maternal antibody on the resistance of newborns to infections have prompted widespread interest in maternal vaccination. However, a range of animal model and human studies indicate potential inhibitory effects of maternal antibody on vaccine-specific humoral responses in infants. In the present study we have examined the relationship between maternally acquired TT-specific IgG present before DTaP vaccination and subsequent TT-specific T-cell memory responses at 12 and 18 months, in a cohort of 118 infants. We demonstrate a strong positive association between TT-specific cellular immunity as evidenced by increased IL-4, IL-5 and IL-13 responses, and maternal TT-specific IgG.

Antibodies, Bacterial↗
PubMed2004

Preoperative pulmonary hemodynamics determines changes in airway and tissue mechanics following surgical repair of congenital heart diseases.

To characterize the effect of changes in pulmonary hemodynamics on airway and tissue mechanics, forced oscillatory input impedance of the respiratory system (Zrs) was measured between 0.4-12 Hz in two groups of children undergoing surgical repair of congenital heart disease (CHD) immediately before sternotomy and after chest closure during short apneic intervals. Children with lesions associated with high pulmonary blood flow and/or pressure (septal defects; HP group, n = 12) and children with hypoperfused lungs (tetralogy of Fallot; LP group, n = 12) were included in the study. Airway resistance (Raw), and coefficients of respiratory tissue damping (G) and elastance (H), were estimated from Zrs by model-fitting. A postoperative reduction in pulmonary blood flow and/or pressure in the HP group resulted in an immediate decrease in Raw of 29 +/- 9 (SE)% (P < 0.05), whereas children in the LP group had increases in Raw (24 +/- 17%, no significance) after surgery. No significant change was observed in G in either the HP (6.4 +/- 13%) or LP (27 +/- 23%) group, while H increased in children of both the HP (23 +/- 8%, P < 0.05) and LP (36 +/- 7%, P < 0.01) groups. These results suggest that the preoperative pulmonary hemodynamic condition determines changes in airway mechanics: surgical repair of CHD leads to an improvement in airway function only in children with congested lungs. The adverse effects of surgery, mechanical ventilation, and/or cardiopulmonary bypass may be responsible for the increased stiffness of the respiratory system observed in both groups of children.

Airway Resistance↗
PubMed2003

Association between antenatal cytokine production and the development of atopy and asthma at age 6 years.

BACKGROUND: Various lines of evidence suggest that antenatal factors are important in determining susceptibility to atopy and asthma. One possible mechanism is cytokines, production of which in the placenta is high throughout gestation and which protect placental integrity via control of local immunological homoeostasis. We investigated antenatal cytokine concentrations in a prospective birth cohort, intensively monitored for atopy and asthma outcomes at age 6 years. METHODS: Cryopreserved cord-blood serum samples from 407 children were assayed for interleukins 4, 5, 6, 10, 12, and 13, interferon gamma, and tumour necrosis factor alpha (TNFalpha). Associations between family, antenatal, and perinatal factors, cord-blood cytokine concentrations, and atopy or asthma outcomes were analysed by logistic regression. Causal effects of cytokines on outcomes were estimated by propensity scores based on family, antenatal, and perinatal factors. FINDINGS: Detectable cord-blood concentrations of interleukin 4 and interferon gamma were each associated with lower risk of physician-diagnosed asthma (adjusted odds ratios 0.60 [95% CI 0.37-0.99] and 0.60 [0.37-0.97] respectively), current asthma (0.59 [0.33-1.00] and 0.39 [0.22-0.71]), and current wheeze (0.55 [0.32-0.93] and 0.52 [0.31-0.90]) and atopy (sensitisation to some inhalant allergens) outcomes at 6 years. High concentrations of TNFalpha were associated with lower risk of atopy but not with asthma risk. These associations were broadly unaltered by propensity-score adjustment. Maternal smoking was associated with higher risk of both wheeze at 6 years and lower concentrations of interleukin 4 and interferon gamma in cord blood. INTERPRETATION: The mechanism underlying attenuated T-helper-1/T-helper-2 cytokine production in high-risk children also apparently operates in control of cytokine production in the fetoplacental unit. The finding that this mechanism is dysregulated by maternal smoking suggests it is a target for antenatal environmental factors relevant to asthma aetiology.

Asthma↗
PubMed2003

Developmental factors associated with risk for atopic disease: implications for vaccine strategies in early childhood.

There is growing interest in the potential interactions between infant vaccination and risk for development of atopic disease. The aspect of this issue which has dominated this debate concerns suggestions that infant vaccination may stimulate allergic sensitisation. These suggestions derive from retrospective epidemiological analyses and will remain speculative unless they can be confirmed in prospective studies, particularly as conflicting findings have been reported. However, there is a potentially more important issue surfacing in this debate, which entails the converse situation, i.e. that genetic risk for atopy influences capacity to respond to vaccination during infancy. Support for the latter possibility comes from recent studies on the role of developmental factors which determine immune competence during infancy, and attendant risk for inflammatory and infectious diseases. The relevant findings are reviewed briefly below.

Environment↗
PubMed2003

Specific patterns of responsiveness to microbial antigens staphylococcal enterotoxin B and purified protein derivative by cord blood mononuclear cells are predictive of risk for development of atopic dermatitis.

BACKGROUND: Mononuclear cells from children with active atopic dermatitis (AD) have been reported to be hyper-responsive to certain microbial stimuli, in particular staphylococcal enterotoxin B (SEB). However, it is not known whether this responsiveness is acquired during disease development, or is inherent. We investigated this question in a cohort of children at high risk of atopy followed prospectively from birth to age 3 years. We asked whether their cord blood mononuclear cell (CBMC) cytokine responses to SEB, to an unrelated microbial stimulus purified protein derivative (PPD), or to common allergens, were predictive of risk for subsequent AD development during infancy. METHODS: Children at high risk of developing atopy were randomly selected from an ongoing prospective cohort. Cord blood was collected at birth. The children were seen at 6 months, 1, 2 and 3 years and examined for the development of AD. IFN-gamma, IL-5, IL-10 and IL-13 production by CBMC cultured in the presence of SEB, PPD, PHA, house dust mite (HDM) allergen, ovalbumin (OVA) and cat allergen was determined. RESULTS: SEB-induced IL-5 production by CBMC was elevated in children who developed AD at 6 months (P = 0.01) and 2 years (P = 0.009). PPD-induced IL-5 responses were also elevated in CBMC from children who developed AD at 6 months, 2 years and 3 years (P = 0.05, P = 0.06 and P = 0.06, respectively), as were PPD-induced IL-10 responses (P = 0.05 at 1 years, P = 0.007 at 2 years, P = 0.003 at 3 years) and corresponding IFN-gamma responses (P = 0.05 at 6 months, P = 0.003 at 2 years, P = 0.0004 at 3 years). Increased IL-10 responses to HDM allergen were also observed throughout the observation period in CBMC from children who developed AD. CONCLUSION: Children who develop infantile AD appear to have a predisposition to respond to SEB in a Th2-dominant manner involving selective stimulation of IL-5 production. The increased IL-10 and IFN-gamma induced in response to PPD by children with AD may point to additional intrinsic differences in responses to microbial stimuli between those at high vs. those at low risk for AD, which merit more detailed investigations.

Cells, Cultured↗
PubMed2003

Breast feeding and respiratory morbidity in infancy: a birth cohort study.

AIM: To examine the relation between the duration of breast feeding and morbidity as a result of respiratory illness and infection in the first year of life. METHODS: Prospective birth cohort study of 2602 live born children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth, Western Australia. Main outcome measures were hospital, doctor, or clinic visits, and hospital admissions for respiratory illness and infection in the first year of life. Main exposure measures were the duration of predominant breast feeding (defined as the age other milk was introduced) and partial (any) breast feeding (defined as the age breast feeding was stopped). Main confounders were gender, gestational age less than 37 weeks, smoking in pregnancy, older siblings, maternal education, and maternal age. RESULTS: Hospital, doctor, or clinic visits for four or more upper respiratory tract infections were significantly greater if predominant breast feeding was stopped before 2 months or partial breast feeding was stopped before 6 months. Predominant breast feeding for less than six months was associated with an increased risk for two or more hospital, doctor, or clinic visits and hospital admission for wheezing lower respiratory illness. Breast feeding for less than eight months was associated with a significantly increased risk for two or more hospital, doctor, or clinic visits or hospital admissions because of wheezing lower respiratory illnesses. CONCLUSIONS: Predominant breast feeding for at least six months and partial breast feeding for up to one year may reduce the prevalence and subsequent morbidity of respiratory illness and infection in infancy.

Bottle Feeding↗
PubMed2002

Reciprocal patterns of allergen-induced GATA-3 expression in peripheral blood mononuclear cells from atopics vs. non-atopics.

BACKGROUND: T helper (Th)2 cytokines are considered to play a central role in the induction and expression of allergic disease. However, the relative importance of individual cytokines is unclear, and overall disease pathogenesis appears to involve the coordinate activities of a range of Th2 cytokines acting in sequence or in parallel. The present study examines an alternative approach to the study of cytokine gene function in atopy, focusing instead upon T cell transcription factors (TFs) which play a role in the regulation of multiple cytokine genes. OBJECTIVE: To investigate the allergen-induced expression of the TF GATA-3 and c-Maf in peripheral blood mononuclear cells (PBMCs) and in cytokine-driven Th polarization. METHODS: PBMC from house dust mite (HDM)-atopic and non-atopics were stimulated in vitro with allergen or anti-CD3/IL-2. TF expression was analysed by semiquantitative RT-PCR and major findings were validated by real-time PCR. Cell separations were performed to analyse the contribution of CD45RO+ cells. CD4+ cord blood cells were Th1 or Th2 polarized in vitro by exogenous cytokines and TF expression analysed by Northern blot and real-time PCR. Results We demonstrate for the first time that during differentiation of CD4+ CD45RA+ naïve human T cells towards Th2 commitment, and during allergen-specific reactivation of peripheral CD4+ CD45RO+ Th2 memory cells in established atopics, expression of the Th2-associated TF GATA-3 is rapidly up-regulated, whereas T cells from non-atopics display equally rapid GATA-3 down-regulation under identical conditions of allergen stimulation. CONCLUSION: These findings identify Th2-associated TFs as key determinants of the atopic phenotype, suggesting their unique potential as therapeutic targets for disease control.

Adult↗
PubMed2002

Contribution of nasal pathways to low frequency respiratory impedance in infants.

BACKGROUND: In infants the impedance of the nasal pathways (Zn) is a significant proportion of the total respiratory impedance (Zrs). METHODS: In 11 infants Zrs was partitioned into Zn and lower respiratory system impedance (Zlrs) using a nasal catheter. A low frequency oscillatory signal (0.5-20 Hz) was applied during a pause in breathing to obtain the impedance spectra. A model of the respiratory system containing an airway and tissue compartment was then fitted to Zrs and Zlrs. The airway compartment consisted of a frequency independent resistance (R) and inertance (I), while the tissue compartment was described by coefficients of tissue damping (G) and elastance (H). RESULTS: Zrs could be reliably partitioned into Zn and Zlrs. The nasal pathway acted as a purely resistive-inertive impedance and contributed approximately half of the airway resistance (mean (SE) 44.6 (4.9)%) and most of the respiratory system inertance (71.7 (3.5)%). CONCLUSIONS: In studies investigating changes in airway resistance in nasally breathing infants, the separation of nasal and lower respiratory system mechanics will increase the sensitivity of the tests.

Airway Resistance↗
PubMed2002

The effects of respiratory infections, atopy, and breastfeeding on childhood asthma.

The objectives of the present study were to quantify the association of atopy and respiratory infections with asthma, and exclusive breastfeeding with respiratory illness, atopy and asthma in children. A cohort study of 2,602 children enrolled prior to birth and followed prospectively, provided data on respiratory illness, the method of feeding in the first year of life, as reported on a prospective diary card, and current asthma at the age of 6 yrs (defined as doctor-diagnosed asthma with wheeze in the last year or cough without a cold, and currently taking either preventer or reliever asthma medication), as reported by parental questionnaire. Atopy was defined by a positive skin-prick test assessed at the age of 6 yrs. Wheezing lower respiratory illness (LRI) in the first year of life, particularly multiple episodes of wheezing LRI, increased the risk for current asthma in both nonatopic (odds ratio (OR) 4.10, p< or =0.0005) and atopic children (OR 9.00, p< or =0.0005), but did not increase the risk for atopy. In contrast, up to three upper respiratory tract infections demonstrated a negative association and four or more a positive risk for current asthma in unadjusted (p=0.006) and adjusted (p=0.057) analysis. Following adjustment, exclusive breastfeeding for <4 months was associated with an increased risk for current asthma (OR 1.36, 95% confidence interval 1.00-1.85, p=0.047). Wheezing lower respiratory illness in the first year of life and atopy are independently associated with increased risk for current asthma at the age of 6 yrs, suggesting that their effects are mediated via different causal pathways and that these risk factors are multiplicative when they operate concomitantly within individual children. Exclusive breastfeeding protects against asthma via effects on both these pathways, as well as through other as yet undefined mechanisms.

Asthma↗
PubMed2002

Interactions between respiratory tract infections and atopy in the aetiology of asthma.

The prevalence of asthma, in particular atopic asthma, has markedly increased in recent years. Accumulating evidence suggests that environmental factors associated with allergic sensitization and exposure to microbial stimuli during infancy and early childhood, are associated with these changes in prevalence. However, considerable controversy surrounds the role of microbial agents, as evidence has been presented for both positive and negative effects in this context. The review below focuses upon interactions between immune competence during infancy, the development of T-helper (Th)1-polarized versus Th2-polarized memory against inhalant allergens, and susceptibility to virus infection. In particular, recent finding are highlighted which suggest that delayed postnatal maturation of Th1 function is associated with increased risk for early postnatal sensitization to inhalant allergens, and also with risk for viral bronchiolitis during infancy. Variations in the kinetics of postnatal maturation of T-helper 1 function may in part be attributable to polymorphisms in the CD14 gene, which influence host responsiveness both to bacterial as well as viral stimuli.

Adult↗