PubMed Health⌕ Search

Biomedical subjects

S M Stick

Publications and source records attributed to S M Stick.

At least 19 recordsLinked to original sources
PubMed2006

Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis.

BACKGROUND: This is the first study to measure inducible nitric oxide synthase (iNOS) gene and protein expression quantitatively in primary epithelial cells from very young children with cystic fibrosis (CF). Low levels of exhaled nitric oxide (NO) in CF suggest dysregulation of NO production in the airway. Due to the importance of NO in cell homeostasis and innate immunity, any defect in the pathway associated with CF would be a potential target for treatment. METHODS: Cells were obtained by tracheobronchial brushing from 40 children with CF of mean (SD) age 2.1 (1.5) years and from 12 healthy non-atopic children aged 3.4 (1.2) years. Expression of iNOS mRNA was measured using quantitative PCR and iNOS protein by immunofluorescence and Western blot analysis. RESULTS: Inducible NOS mRNA expression was significantly lower in CF patients with and without bacterial infection than in healthy children (0.22 and 0.23 v 0.76; p=0.002 and p=0.01, respectively). Low levels of iNOS gene expression were accompanied by low levels of iNOS protein expression as detected by Western blot analysis. CONCLUSIONS: These results support the findings of previous studies in adult patients with advanced disease, cell lines, and animal models. Our findings reflect the situation in children with mild lung disease. They indicate that low iNOS expression may be an innate defect in CF with potential consequences for local antimicrobial defence and epithelial cell function and provide evidence for an approach to treatment based on increasing epithelial NO production or the sensitivity of NO dependent cellular processes.

Analysis of Variance↗
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

Parental smoking increases exhaled nitric oxide in young children.

The present study investigated the association between reported parental smoking and exhaled nitric oxide fraction (F(eNO)) in young children. In total, 78 children (24 females, mean age 51.3 weeks) were recruited. Fourteen lived with one smoking parent and eight with two smoking parents. F(eNO) was measured using the modified single-breath technique. Mean+/-sd F(eNO) levels were 33.0+/-18.9, 38.3+/-15.0 and 48.3+/-14.7 ppb for children with no, one and two smoking parents, respectively. There was a significant linear trend across the groups and, after controlling for other relevant factors, a significant difference between the groups. In the present study, exposure to environmental tobacco smoke was associated with increased exhaled nitric oxide fraction in young children. Furthermore, there was evidence of a dose-response relationship between childhood exhaled nitric oxide fraction and the number of smoking parents.

Breath Tests↗
PubMed2006

Exhaled nitric oxide is not reduced in infants with cystic fibrosis.

Fractional exhaled nitric oxide (F(eNO)) has been reported to be reduced in cystic fibrosis (CF) patients. However, data from young children are conflicting and it is not clear whether this is a primary feature of the disease or a secondary response. The present study compared F(eNO) between CF and healthy infants using a validated single-breath technique. A total of 23 healthy infants (11 females; mean age 40.1 weeks) and 18 infants with CF (nine females; 64.9 weeks) underwent tests of lung function and F(eNO). Bronchoalveolar lavage (BAL) was collected from all CF infants 2-5 days after lung function testing. There was no significant difference in F(eNO) between the CF and healthy infants (geometric mean: 23.1 parts per billion (ppb) and 17.0 ppb, respectively). There was an inverse relationship between age and F(eNO) in the CF patients, but not in the healthy group. Within the CF group, there was no association between F(eNO) and any marker of airway inflammation measured in the BAL. Exhaled nitric oxide is not reduced in cystic fibrosis infants, but does decrease with age. The current data indicate that F(eNO) is not a good marker of airway inflammation in cystic fibrosis.

Age Factors↗
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

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

Comparison of single-breath and tidal breathing exhaled nitric oxide levels in infants.

The aim of this study was to compare two different methods, tidal breathing (TB) and single-breath (SB), for measuring fractional exhaled nitric oxide (FENO) in infants. FENO was measured in 71 infants with either recurrent wheeze (n=32), recurrent cough (n=16) or no symptoms (healthy, n=23) using both methods. For TB measurements five breaths were collected into a gas sampling bag (off-line reservoir sampling). The SB method was modified from the raised volume rapid thoraco-abdominal technique. Agreement between the two methods was investigated and both methods were used to compare FENO in infants with and without symptoms. Flow dependence of SB FENO was demonstrated using two expiratory flows (11 and 40 mL x s(-1)). There was a moderate correlation (r=0.60) but poor agreement between levels using the TB and SB methods. A significant difference in FENO between healthy children and children with wheeze was found using the SB but not the TB method. Due to lower expiratory flow and reduced nasal nitric oxide contamination the single-breath technique may be more sensitive than the tidal breathing method for detecting differences in exhaled nitric oxide between infants with and without respiratory symptoms.

Breath Tests↗
PubMed2003

Exhaled nitric oxide and asthma: complex interactions between atopy, airway responsiveness, and symptoms in a community population of children.

BACKGROUND: Exhaled nitric oxide (FE(NO)) is raised in asthmatic children, but there are inconsistencies in the relationship between FE(NO) and characteristics of asthma, including atopy, increased airway responsiveness (AR), and airway inflammation. The aim of this study was to investigate the relationship between FE(NO) and asthma, atopy, and increased AR in children. METHODS: One hundred and fifty five children (79 boys) of mean age 11.5 years underwent an assessment that included FE(NO) measurements, spirometric tests, inhaled histamine challenge, and a skin prick test. Blood was collected for eosinophil count. Current and past asthma like symptoms were determined by questionnaire. RESULTS: In multiple linear regression analyses FE(NO) was associated with atopy (p<0.001), level of AR (p = 0.005), blood eosinophil count (p = 0.007), and height (p = 0.002) but not with physician diagnosed asthma (p = 0.1) or reported wheeze in the last 12 months (p = 0.5). Separate regression models were conducted for atopic and non-atopic children and associations between FE(NO) and AR, blood eosinophils and height were only evident in atopic children. Exhaled NO was raised in children with a combination of atopy and increased AR independent of symptoms. CONCLUSION: Raised FE(NO) seems to be associated with an underlying mechanism linking atopy and AR but not necessarily respiratory symptoms.

Adolescent↗
PubMed2002

Domestic exposure to formaldehyde significantly increases the risk of asthma in young children.

Concern has arisen in recent years about indoor air pollution as a risk factor for asthma. Formaldehyde exposure was examined in relation to asthma among young children (between 6 months and 3 yrs old) in a population-based control study carried out in Perth, Western Australia, between 1997-1999. An association between exposure to formaldehyde and asthma in young children has been suggested. Cases (n=88), whose parents were recruited at Princess Margaret Hospital Accident and Emergency Dept (Perth, Western Australia), were children discharged with asthma as the primary diagnosis. Controls (n=104), who were children in the same age group without asthma diagnosed by a doctor, were identified from birth records through the Health Dept of Western Australia (Perth, Western Australia). Health outcomes for the children were studied using a respiratory questionnaire and skin-prick tests. Formaldehyde, average temperature and relative humidity were measured on two occasions, winter (July-September 1998) and summer (December 1998-March 1999) in the child's bedroom and in the living room. The study found seasonal differences in formaldehyde levels in the children's bedrooms and living rooms with significantly greater formaldehyde exposure during the summer period for case and control subjects. The generalised estimating equation model showed that children exposed to formaldehyde levels of > or = 60 microg x m(-3) are at increased risk of having asthma. The results suggest that domestic exposure to formaldehyde increases the risk of childhood asthma.

Age Factors↗
PubMed1999

Control of breathing in infants born to smoking mothers.

OBJECTIVE: To determine whether infants born to smoking mothers have an abnormal respiratory drive and a blunted ventilatory response to hypoxia. STUDY DESIGN: Sixty-four healthy infants, aged 2 to 24 months, were classified into smoking (n = 19) or non-smoking (n = 45) groups based on maternal smoking habits. Resting ventilation, lung function, and mouth pressure 100 milliseconds after an airway occlusion at the onset of inspiration (P(0.1 )) were measured. The ventilatory response to hypoxia was assessed in 15 infants (6 in the smoking group and 9 in the non-smoking group) while breathing 14% oxygen. RESULTS: Respiratory drive (P(0.1 ) = 4.9 +/- 1.3 cm H(2 )O) was lower in infants in the smoking group compared with those in the non-smoking group (P(0.1 ) = 5.9 +/- 1.2 cm H(2 )O) (P <.05). The time to peak tidal expiratory flow (tPTEF) was also shorter (0.25 +/- 0.04 seconds vs 0.32 +/- 0.09 seconds, P <.05). Infants born to non-smoking mothers showed a significant ventilatory response to hypoxia and a 24.6% increase in P(0.1 ). Infants in the smoking group showed a blunted ventilatory response to hypoxia and no increase in P(0.1 ). A dose-response relationship existed between the number of cigarettes smoked by the mother (0, 1 to 10, >10 per day) and the results for P(0.1 ) and tPTEF. Paternal smoking had no influence on the infant's resting ventilation, respiratory drive, or ventilatory response to hypoxia. CONCLUSIONS: Infants born to smoking mothers have a reduced drive to breathe and a blunted ventilatory response to hypoxia. These findings may contribute to the increased risk of sudden infant death syndrome in these infants.

Analysis of Variance↗
PubMed1999

A community study of exhaled nitric oxide in healthy children.

Exhaled nitric oxide (eNO) is elevated in patients with inflammatory pulmonary diseases and it has attracted increasing interest as a simple, noninvasive marker of airway inflammation. Little is known, however, about factors that might affect eNO in healthy subjects. We measured eNO in 157 healthy 7- to 13-yr-old children (mean 9.7 yr, 77 girls), with no history of respiratory tract disease, using a recently validated, single-breath technique. Measurements of eNO were obtained at driving (mouth) pressures of 10, 15, and 20 cm H2O and 3 eNO plateaux were achieved for each child at each pressure. Exhaled NO decreased with increasing pressure (increasing expiratory flow) (p < 0.001) and increased with age (p < 0.001). Concentrations were greater in children with a positive skin prick test (p < 0.0001). Geometric mean eNO levels were 7.2 ppb in children with no positive skin prick tests (n = 116), 10.9 ppb in children with one positive reaction (n = 24), and 20.1 ppb in children with two or more skin reactions (n = 17). Age and immunological reactions to common allergens are associated with increased eNO in children and should be controlled for in studies of eNO. The mechanisms responsible for these associations require further study.

Adolescent↗
PubMed1999

Measurements of exhaled nitric oxide with the single-breath technique and positive expiratory pressure in infants.

The aim of this study was to adapt the single-breath technique with positive expiratory pressure to measure exhaled nitric oxide (eNO) in infants. We hypothesized that exhaled eNO was greater in wheezy than in healthy infants. We studied 30 infants (16 wheezy and 14 healthy). The forced expiratory volume in 0.5 s (FEV0.5) was determined with the raised volume rapid thoracic compression technique, and eNO was measured during constant expiratory flow with a rapid-response chemiluminescence analyzer. After passive inflation to a preset pressure of 20 cm H2O, thoracic compression with an inflatable jacket caused forced expiration to occur through a face-mask with an expiratory flow resistor attached. During the forced expiration, the jacket pressure was increased to maintain a constant driving mouth pressure and hence a constant expiratory flow (50 ml/s). The mean level of eNO in the wheezy infants (31.8 ppb) was significantly higher than the level in healthy infants (18.8 ppb) (p = 0.03). A family history of atopy in parents was associated with increased eNO levels (p < 0.001) independent of age, sex, weight, length, wheezing, and FEV0.5. We conclude that the single-breath technique with positive expiratory pressure is a feasible method for measuring eNO in infants. Levels of eNO were significantly higher in wheezy infants and in those with a family history of atopy.

Feasibility Studies↗
PubMed1997

Childhood antecedents of adult respiratory disease.

This review examines the relations between early childhood lower respiratory symptoms and adult respiratory disease. The problems associated with investigating potential associations between respiratory disease in children and adults are discussed. Some studies have limitations because they are retrospective and early childhood respiratory symptoms have not been accurately diagnosed. Therefore, in this review, particular attention is paid to longitudinal studies (some from birth) that have used strict diagnostic criteria for respiratory episodes. These studies provide unique insights into the risk factors for the development of childhood respiratory problems and for persistence of symptoms into adulthood. Although cross-sectional studies have indicated that early childhood respiratory disease is more frequent in adults with respiratory disease, evidence from longitudinal studies suggests that respiratory symptoms such as wheezing, are transient in the majority of infants and result from developmentally small airways. These longitudinal investigations have also indicated that persistence of symptoms into later childhood is associated with atopy. The important role of cigarette-smoke exposure as a risk factor for abnormal pulmonary development, persistence of respiratory disease and reduction in lung function is discussed. The discovery of genetic markers associated with respiratory syndromes such as asthma, should facilitate studies that investigate the childhood antecedents of adult respiratory disease. Future longitudinal studies using genetic markers, will allow relations between specific genotypes and phenotypic outcomes to be examined.

Adult↗
PubMed1996

Effects of maternal smoking during pregnancy and a family history of asthma on respiratory function in newborn infants.

INTRODUCTION: Infants of mothers who smoke have reduced respiratory function and are more likely to develop wheezing. Little evidence is available on the effect of in-utero cigarette-smoke exposure as opposed to postnatal exposure to environmental tobacco smoke. We used a previously validated non-invasive method to measure the time to peak tidal expiratory flow (tPTEF) as a proportion of expiratory time (tE) in newborn infants soon after birth to examine the effects of a family history of asthma and in-utero cigarette-smoke exposure on the infants' respiratory function. METHODS: We collected respiratory-function data from 500 healthy infants of mothers taking part in the Western Australia Pregnancy Cohort Study. During behaviourally defined quiet sleep, measurements were obtained a median of 58 h (range 26-159) after the infants were born. We used uncalibrated inductance plethysmography. The uncalibrated volume signal was differentiated to flow and used to calculate respiratory rate, total inspiratory time, tE, and tPTEF. Mothers answered questionnaires on demographic, medical, and pregnancy characteristics, including smoking history. Serum cotinine measurements were available to validate self-reported smoking history in a subset of mothers (238). RESULTS: Data suitable for analysis were obtained from 461 infants. In multivariate regression analysis, lower values of tPTEF/tE were independently associated with respiratory rate (beta coefficient per 10 breaths/min 0.018 [SE 0.005], p < 0.01), age (beta coefficient per 10 h -0.008 [0.003], p < 0.01), maternal smoking during pregnancy (> 10 cigarettes daily; beta coefficient -0.049 [0.022], p < 0.05), maternal hypertension during pregnancy (-0.037 [0.015], p < 0.02), and a family history of asthma (-0.028[0.014], p < 0.05). CONCLUSIONS: In-utero smoke exposure, a family history of asthma, and maternal hypertension during pregnancy are associated with reduced respiratory function after birth. We speculate that these factors adversely affect lung development in utero.

Asthma↗
PubMed1995

The effects of inhaled beclomethasone dipropionate on lung function and histamine responsiveness in recurrently wheezy infants.

Inhaled steroids improve pulmonary function and bronchial responsiveness in older asthmatics. Data from studies using subjective outcome measures to determine the effectiveness of inhaled steroids in infants with recurrent wheezing are equivocal. Therefore, this study tested the hypothesis that beclomethasone dipropionate improves pulmonary function, including bronchial responsiveness to histamine, in recurrently wheezy infants. The study was double blind, placebo controlled lasting nine weeks. After the first baseline week, pulmonary function was measured using the rapid thoracoabdominal compression technique and bronchial responsiveness assessed with a histamine challenge test. Infants were then randomly allocated to receive doses of placebo or beclomethasone dipropionate (100 micrograms/puff) from metered aerosols. Two puffs of test aerosol were administered twice daily for eight weeks via a large volume spacer fitted with a facemask. Symptoms were recorded daily and pulmonary function and bronchial responsiveness assessed at the end of the treatment period; 50 infants, median age 12 months (range 5 to 18 months), were recruited. Twenty three in the beclomethasone dipropionate group and 15 in the placebo group completed the study and had pairs of pulmonary function measurements. Three were probable treatment failures (one beclomethasone dipropionate, two placebo), three were possible treatment failures (placebo), and others were non-compliant with study protocol. Baseline variables were not significantly different between those infants who completed the study and those who did not. Beclomethasone dipropionate and placebo groups were similar in all respects at baseline. Lung function and symptoms improved for both groups of infants during the study. Bronchial responsiveness increased significantly in the placebo group but there were not statistically significant differences between groups for any of the other outcome measures. It is concluded that beclomethasone dipropionate (400 microgram daily) via a large volume spacer does not significantly improve lung function or symptoms in recurrently wheezy infants but might hav a beneficial effect on bronchial responsiveness.

Administration, Inhalation↗
PubMed1995

A new technique to generate and assess forced expiration from raised lung volume in infants.

We have developed a new technique that allows assessment of infant lung function over an extended volume range. The lungs are rapidly inflated to a predetermined inflation pressure (PP) using a modified diaphragm pump. Forced expiratory flow-volume (FEFV) curves are then generated from raised lung volumes using an inflatable plastic jacket. We studied 26 normal infants with a median age of 14 mo (range, 3 to 23 mo). FEFV curves were obtained in each infant from end-tidal inspiration and from lung volumes set by a range of PP (15 to 20 cm H2O). Mean (SE) volume above FRC was 107 ml (9 ml), and mean forced expiratory time was 0.73 s (0.05 s) at end-tidal inspiration. Both measurements increased progressively with increases in PP to 251 ml (13 ml) and 1.04 s (0.06 s), respectively, at 20 cm H2O PP (p < 0.0001). Mean intrasubject coefficient of variation was 15.5% (95% confidence interval, 12 to 19%) for maximal flow at FRC, but it was less than 6% (95% CI, 4 to 8%) for forced expiratory volume-time (FEVt) measurements at all levels of PP. Twenty-seven recurrently wheezy infants with a median age of 13 mo (range, 6 to 18 mo) were subsequently studied using a PP of 17.5 cm H2O. Wheezy infants had a lower VmaxFRC [mean (1.39 ml/s/cm) and 95% CI (1.15 to 1.63 ml/s/cm)] than did normal infants (1.78 ml/s/cm; CI, 1.51 to 2.05) (p < 0.05). FEV1 measurements were all lower in wheezy infants than in normals infants: mean FEV0.5, 1.86 ml/cm (CI, 1.73 to 1.98) and 2.31 ml/cm (CI, 2.15 to 2.48), respectively (p < 0.0001); FEV0.75, 2.20 ml/cm (CI, 2.07 to 2.32) and 2.72 ml/cm (CI, 2.52 to 2.91), respectively (p < 0.0001); FEV1.0, 2.42 ml/cm (CI, 2.26 to 2.58) and 2.84 ml/cm (CI, 2.63 to 3.06), respectively (p < 0.005). The Ci values of each FEVt measurement did not overlap between the wheezy and normal groups; however, the CI values of VmaxFRC overlapped markedly. In addition, FEVt parameters showed greater sensitivity in detecting reduced lung function (71 to 89%) than did VmaxFRC parameters (56%). We conclude that (1) FEVt measurements derived from a lung volume set by a standardized pressure are more reproducible than flow measurements in the tidal volume range; (2) FEVt measurements are significantly lower in wheezy infants than in normal infants, show less overlap than flow measurements in the tidal volume range, and therefore are better able to separate the two populations.

Forced Expiratory Flow Rates↗
PubMed1993

The effect of age on oxygen desaturation during histamine inhalation challenge in normal infants.

Arterial oxygen saturation (SaO2) is usually measured during inhalation challenges in infants as desaturation has been demonstrated with provoked bronchoconstriction. We wished to examine whether measurement of SaO2 would provide a simple noninvasive indicator of respiratory function (RF) changes occurring during inhalation challenge in infants. Histamine inhalation challenges were performed longitudinally in 22 normal healthy infants at 4 and 26 weeks of age. RF was measured by calculating maximum forced expiratory flow at functional residual capacity (VmaxFRC) using the rapid thoracic compression technique. Airway responsiveness was assessed using histamine; the provoking concentration (PC) was that which caused a fall in VmaxFRC of at least 40% from baseline. The provocative concentration for an exact fall of 40% in VmaxFRC (PC40) from baseline was derived by linear interpolation. SaO2 was continuously monitored by pulse oximetry. One month old infants had higher SaO2 levels throughout the inhalation challenge in comparison to their SaO2 levels at 6 months of age. Significant falls in SaO2 were observed at the PC at both ages. However, at the age of 26 weeks the infants had greater median falls in SaO2 [PC, 4.5% (95%CI: 3.0, 7.0)] compared to the response at age 4 weeks [3.0% (95%CI: 1.0, 4.0) (P < 0.01)]. Median falls in VmaxFRC at the PC were not different between the ages. These results indicate an age-dependent discordance between airway and SaO2 response in healthy infants during histamine-induced bronchoconstriction.

Age Factors↗