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Biomedical subjects

Andrew Bush

Publications and source records attributed to Andrew Bush.

At least 55 records · Page 3Linked to original sources
PubMed2005

Sputum induction in children with difficult asthma: safety, feasibility, and inflammatory cell pattern.

Difficult childhood asthma is defined by persistent symptoms despite maximal conventional therapy. We aimed to establish a safe method of sputum induction for these children and to study cytology and the relationship to exhaled nitric oxide (eNO). Sputum induction was performed in 38/40 children (aged 6-16 years) with difficult asthma, using 3.5% saline for four 5-min periods after bronchodilator pretreatment. Two children were excluded from sputum induction because postbronchodilator forced expired volume in 1 sec (FEV(1)) was <65% predicted. Seven of 38 children had symptoms (dyspnea and wheezing) during induction; of these, 3 experienced a fall in FEV(1) of >20% from postbronchodilator FEV(1), readily reversed with salbutamol. Sputum induction was successful in 28/38 children, with a higher success rate in children >/= 12 years than in younger children (87% vs. 50%, P = 0.02). Only 9/28 had abnormal sputum cytology; of these, 6 had predominant sputum eosinophilia (>2.5% eosinophils, </=54% neutrophils), while 3 had sputum neutrophilia (</=2.5% eosinophils, >54% neutrophils). Of 23 children with elevated eNO values, only 6 had sputum eosinophilia. In conclusion, sputum induction can be used to assess airway inflammation in children with difficult asthma, but abnormal sputum cytology is only present in a minority. Raised nitric oxide is only poorly predictive of sputum eosinophilia in these children.

Adolescent↗
PubMed2005

Is a two-week trial of oral prednisolone predictive of target lung function in pediatric asthma?

We used a 2-week trial of prednisolone to determine "target" lung function for subsequent asthma therapy. The aim of this study was to evaluate whether some children exceed their "target" forced expired volume in 1 sec (FEV1) on subsequent visits in the following year, and whether this is associated with particular clinical or pathological features. Children (aged 6-16 years) with difficult asthma underwent spirometry and exhaled nitric oxide (FE(NO)) measurements before and after 2 weeks of prednisolone 40 mg/day. At the end of the course, subepithelial eosinophils and reticular basement membrane thickness were assessed. The highest FEV1 obtained in a 1-year follow-up was compared with the poststeroid postbronchodilator ("target") FEV1. Four of 22 children (18%) demonstrated an increase of > 9% above their "target" FEV1 during follow-up. None of these children had been prescribed additional asthma medications. Three of 7 children with persistent airflow limitation (PAL; poststeroid postbronchodilator FEV1 < 80% predicted) recorded an FEV1 > 80% predicted during follow-up. The median (interquartile range) number of subepithelial eosinophils was significantly higher in children who exceeded their target FEV1 than in children who did not (12.4 (8.5-39.9) vs. 1.4 (0.0-4.8) cells/mm2, P = 0.018). In conclusion, a 2-week course of prednisolone is not necessarily predictive of "target" lung function. Definitions such as PAL should be regularly reviewed on individual basis.

Adolescent↗
PubMed2005

Correlation between cough frequency and airway inflammation in children with primary ciliary dyskinesia.

Cough is common in airway disease. We measured cough frequency in children with primary ciliary dyskinesia (PCD), to determine how accurately families assess this symptom; and to assess the relationship between cough frequency and airway inflammation, measured using induced sputum and exhaled nitric oxide (eNO). Twenty stable PCD children (7 boys), median age 10.8 years (interquartile range (IQR), 9-14), and 10 healthy control children, median age 12 years (IQR, 10.5-12.7), were recruited. ENO was measured using a chemiluminescence analyzer, with sputum induction with 3.5% saline. PCD children underwent ambulatory cough monitoring. Sputum neutrophils were higher in PCD (median, 70.3%; IQR, 55.3-78%) compared to controls (median, 27%; IQR, 24.5-33%; P = 0.004); cough frequency was higher (median episodes, 19; IQR, 11-22.5) compared to healthy children (median episodes, 6.7; IQR, 4.1-10.5; P < 0.001). Forced expiratory volume in 1 sec (FEV(1) percent predicted) and eNO were lower in PCD (median, 63%; IQR, 57-85%; P < 0.0001); eNO (median, 7.1 ppb (IQR, 4.8-19.1 ppb) vs. 12.4 ppb (IQR, 10.3-17.3 ppb), P = 0.043). Parental scoring of day and night cough correlated with recorded cough (r = 0.930, P < 0.0001, daytime; r = 0.711 for nighttime, P = 0.002). Visual analogue score and cough episodes also correlated positively (r = 0.906; P < 0.0001). There was a positive correlation between cough frequency and sputum neutrophil count in PCD (Spearman's r = 0.693, P < 0.002), but not percent FEV(1) or eNO. Stable PCD children have increased cough frequency and neutrophilic airway inflammation. In conclusion, cough frequency correlated with sputum neutrophils but not with FEV1 or eNO.

Adolescent↗
PubMed2005

Immunisation in the current management of cystic fibrosis patients.

Although no special recommendations exist, clearly patients with cystic fibrosis (CF) can benefit from immunisation. We reviewed the literature regarding vaccination in CF and other chronic diseases. CF subjects should follow national immunisation programmes without delay to obtain optimal vaccination coverage. Indeed they may escape normal programmes due to frequent hospital admissions and school absenteeism and may be more at risk to get "vaccine-controlled" diseases at any age. There is no uniform European immunisation schedule for basic infant and childhood vaccines or for vaccines against hepatitis A (HAV) and B (HBV), varicella (VZ) and booster vaccinations. HAV and HBV vaccination is appropriate in CF as recommended in general for patients with chronic liver disease (CLD). Varicella (VZ) vaccination is not recommended in all European countries. There are no recent data about possible worsening of pulmonary status following VZ in CF, but it is known to cause pulmonary damage in non-CF adults and to be potentially fatal post transplantation and during steroid treatment. Therefore it is recommended at least for seronegative adolescents and transplant candidates. Influenza vaccine is recommended annually for CF patients aged > or =6 months. Pneumococcal vaccine is generally indicated for CF patients. RSV infection might play a role in the initial Pseudomonas colonization and the decline in pulmonary function. However no RSV vaccine is available at present. There are no recommendations for palivizumab in CF as an alternative but expensive prophylaxis. Anti-bacterial vaccinations protecting directly against Pseudomonas aeruginosa colonisation are promising for the future, potential candidates are currently being assessed in phase III clinical trials. More studies are needed to complete recommendations especially for CF adults and transplant candidates.

Adolescent↗
PubMed2005

Asthma research: the real action is in children.

Many adult diseases have their roots in infancy or even prenatally. If events that initiate these diseases, as opposed to those that propagate the disease state, are to be understood, then the difficult area of how ethically to research problems in infancy must be tackled. Furthermore, the predisposition to archetypally 'pure' adult problems such as chronic obstructive pulmonary disease, may lie antenatally, the effects being masked until the lung starts to age. An additional factor is that the success of paediatricians, for example in ensuring the survival of extremely premature, low birth weight infants leads to adult survivors with potentially a whole new morbidity. The first prerequisite to making progress is a sound understanding of the development of the normal lung and how adverse environmental and genetic influences, such as exposure to environmental tobacco smoke and maternal atopy, respectively, may affect growth. This paper focuses on three key areas: the implications of different pre-school wheezing phenotypes for adult disease; the importance of very early life events in cystic fibrosis; and the long term consequences of chronic lung disease of prematurity. Finally, the ethical principles that must underpin future research in pre-school children is discussed, as well as the means we might use to further our understanding of the relevant early disease processes.

Adult↗
PubMed2005

Early detection of lung disease in preschool children with cystic fibrosis.

PURPOSE OF REVIEW: Babies with cystic fibrosis are born with essentially normal lungs but rapidly develop inflammation and infection. Evaluation is generally based on history and physical examination until school age, when children become able to perform spirometry. In these 'silent years', however, unrecognized lung damage can occur. Recently, techniques to improve the evaluation of preschool children have been developed, and an assessment of where they fit into clinical and research practice is now needed. This is particularly urgent to select groups of children for new, phenotype-specific therapies, and monitor their effects. RECENT FINDINGS: The techniques in which there have been major recent advances include physiologic methods, particularly indices of gas mixing; imaging techniques, especially high-resolution computed tomographic scanning; and bronchoscopic studies. The clinical roles of these techniques need to be explored, as do comparisons between techniques. SUMMARY: The preschool years need no longer be silent. Some simple techniques such as spirometry can be performed in much younger children than conventionally believed to be practical. Others currently require sophisticated apparatus (lung clearance index) or carry potential risks (radiation, high-resolution computed tomographic scanning). We need good long-term, prospective comparisons of these techniques, with measurement of inflammatory markers. We also need to know which are sufficiently reproducible, and indicative of prognosis, for use as endpoints in clinical trials.

Bronchoscopy↗
PubMed2005

Is there still a gender gap in cystic fibrosis?

OBJECTIVES: Previous studies have shown that female patients with cystic fibrosis (CF) have a significantly poorer prognosis than male patients. Such studies investigating gender-related differences have generally combined data from several centers. The aim of this study was to determine whether with modern aggressive treatment of CF this is still true when care is standardized within a single center. DESIGN: Retrospective analysis of annual assessment data constructing two cross-sectional studies for the year 1993 (56 female patients, 49 male patients) and 2002 (115 female patients, 94 male patients) and two longitudinal studies, each lasting 5 years, starting in 1993 (21 female patients, 19 male patients) and 1998 (40 female patients, 41 male patients). Outcome measures included mortality, height, and weight SD scores (z scores), and percent predicted for lung function. RESULTS: In neither cross-sectional study were there significant differences between the sexes for median FEV(1) percent predicted (1993: female patients, 86%; male patients, 84%; 2002: female patients, 93%; male patients, 92%). Female height and weight z scores were at least as good as those of male scores. In the longitudinal studies, there were no clear trends toward declining lung function or growth, but the overall FEV1 percent predicted appeared to be better in female patients than male patients for both cohorts. This was statistically significant for the 1998 cohort (female median FEV1, 91.5% [range, 28 to 134%]; male median FEV1, 84.8% [range, 32 to 145%]; p < 0.05). Female nutritional status was at least as good as male nutritional status, other than the 1998 weight z scores (-0.54 vs -0.21, respectively; p < 0.02). Since 1993, there have been 13 deaths altogether (7 female patients). CONCLUSION: During childhood and adolescence, the lung function and nutrition of CF patients should be at least as good in female patients as in male patients. Individual clinic practice should be reviewed if a gender gap persists.

Child↗
PubMed2005

Does lidocaine gel alleviate the pain of bladder catheterization in young children? A randomized, controlled trial.

OBJECTIVE: Bladder catheterization (BC) is a commonly performed, painful procedure in the pediatric emergency department (ED). A survey demonstrated that analgesia is infrequently used for several brief painful procedures, including BC, in pediatric patients. In this study, we evaluated the use of 2% lidocaine gel to alleviate the pain associated with BC in young children (<2 years) in the ED. METHODS: We conducted a randomized, double-blind, placebo-controlled trial comparing pain scores during bladder catheterization with 2% lidocaine gel versus nonanesthetic lubricant. We used a previously validated scale for measuring brief procedure-related pain in preverbal children (Face Legs Arms Cry Consolability Pain Scale [FLACC]). A total of 115 patients were recruited; 56 patients were randomized to the control group, and 59 were randomized to the lidocaine group. Lubricant was applied to both the genital mucosa and the catheter. Pain measurements were recorded at 3 time intervals: before insertion of the catheter, during catheterization, and after catheterization. Interobserver reliability had been previously established in an observational pilot study. RESULTS: The difference in mean FLACC scores between the control (7.55 +/- 2.56) and study groups (7.37 +/- 2.87) during catheterization was not statistically significant. The change in FLACC from time 1 (preprocedure) to time 2 (during procedure) was statistically significant in both groups, suggesting that bladder catheterization is a painful procedure. CONCLUSIONS: Altering the standard practice of use of nonanesthetic lubricant with 2% lidocaine gel as lubricant during bladder catheterization in young children may not be helpful in alleviating the pain associated with the procedure.

Anesthetics, Local↗
PubMed2004

Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis.

Sensitive measures of lung function applicable to young subjects are needed to detect early cystic fibrosis (CF) lung disease. Forty children with CF aged 2 to 5 years and 37 age-matched healthy control subjects performed multiple-breath inert gas washout, plethysmography, and spirometry. Thirty children in each group successfully completed all measures, with success on first visit being between 68 and 86% for all three measures. Children with CF had significantly higher lung clearance index (mean [95% CI] difference for CF control 2.7 [1.9, 3.6], p < 0.001) and specific airway resistance (1.65 z-scores [0.96, 2.33], p < 0.001), and significantly lower forced expired volume in 0.5 seconds (-0.49 z-scores [-0.95, -0.03], p < 0.05). Abnormal lung function results were identified in 22 (73%) of 30 children with CF by multiple-breath washout, compared with 14 (47%) of 30 by plethysmography, and 4 (13%) of 30 by spirometry. Children with CF who were infected with Pseudomonas aeruginosa had significantly higher lung clearance index, but no significant difference in other lung function measures, when compared with noninfected children. Most preschool children can perform multiple-breath washout, plethysmography, and spirometry at first attempt. Multiple-breath washout detects abnormal lung function in children with CF more readily than plethysmography or spirometry.

Age Factors↗
PubMed2004

Quality control for spirometry in preschool children with and without lung disease.

The reliability of spirometry is dependent on strict quality control. We examined whether quality control criteria recommended for adults could be applied to children aged 2-5 years. Forty-two children with cystic fibrosis and 37 healthy children attempted spirometry during their first visit to our laboratory. Whereas 59 children (75%) were able to produce a technically satisfactory forced expiration lasting 0.5 second, only 46 (58%) could produce an expiration lasting 1 second, with the youngest children having the most difficulty. Start of test criteria for adults were inappropriate for this age group, with only 16 of 59 children producing a volume of back extrapolation as a proportion of forced vital capacity of less than 5%, whereas all but 4 could produce a volume of back extrapolation of 80 ml or less. More than 90% of children were able to produce a second forced vital capacity and a second forced expired volume in 0.75 second within 10% of their highest. Errors in the spirometry software resulted in inaccurate reporting of expiratory duration and inappropriate timed expired volumes in some children. We describe recommendations for modified start of test and repeatability criteria for this age group, and for improvements in software to facilitate better quality control.

Case-Control Studies↗
PubMed2004

The evolution of airway function in early childhood following clinical diagnosis of cystic fibrosis.

This study aimed to investigate the evolution of airway function in infants newly diagnosed with cystic fibrosis (CF). FEV(0.5) was measured soon after diagnosis (median age of 28 weeks) and 6 months later in subjects with CF and on two occasions 6 months apart (median ages of 7.4 and 33.7 weeks) in healthy infants, using the raised-volume technique. Repeated measurements were successful in 34 CF and 32 healthy subjects. After adjustment for age, length, sex, and exposure to maternal smoking, mean FEV(0.5) was significantly lower in infants with CF both shortly after diagnosis and at the second test, with no significant difference in rate of increase in FEV(0.5) with growth between the two groups. When compared with published reference data, FEV(0.5) was reduced by an average of two z scores on both test occasions in those with CF, with 72% of individuals having an FEV(0.5) of less than 1.64 z-scores (i.e., less than the fifth percentile) on one or both test occasions. On longitudinal analysis, subjects with CF experienced a mean (95% confidence interval) reduction in FEV(0.5) of 20% (11, 28). Airway function is diminished soon after diagnosis in infants with CF and does not catch up during infancy and early childhood. These findings have important implications for early interventions in CF.

Body Height↗
PubMed2004

Comparison of active cycle of breathing and high-frequency oscillation jacket in children with cystic fibrosis.

High-frequency chest compressions (HFCC) have been suggested as an alternative to conventional chest physiotherapy to aid sputum clearance in patients with cystic fibrosis (CF). We aimed to compare the active cycle of breathing techniques (ACBT) with the Hayek Oscillator Cuirass, performing HFCC on secretion clearance in children with CF during an exacerbation. Ten children (7 males; median age, 14 years; range, 9-16) received either two supervised sessions using HFCC or two self-treatment ACBT sessions in random order on successive days. Baseline pulmonary function was similar prior to treatments. Sputum weight increased significantly with ACBT compared with HFCC during treatment (5.2 g vs. 1.1 g, P < 0.005, morning; 4.1 g vs. 0.7 g, P < 0.01, afternoon). Pulmonary function improved significantly after morning ACBT (forced vital capacity (FVC): 2.67 l to 2.76 l, P < 0.03; forced expiratory volume in 1 sec (FEV1): 1.59 l to 1.62 l, P < 0.03). Following afternoon ACBT, there was a significant increase in FVC (2.64 to 2.79, P < 0.02), but no significant change in FEV1. Pulmonary function did not change at any time following HFCC. Compared with ACBT, HFCC by Hayek Cuirass is not an effective airway clearance treatment modality for children with CF during an infective exacerbation.

Adolescent↗
PubMed2004

Repeatability of sodium and chloride in exhaled breath condensates.

Exhaled breath condensate (EBC) has been proposed as a noninvasive tool to study airway inflammation. The reproducibility of breath condensates was recently questioned. We therefore measured sodium and chloride concentrations in EBC and assessed the repeatability of these measurements in healthy adults and children with airway disease. We investigated technical repeatability and within-day repeatability in five healthy adults, and compared these results with those of 10 asthmatic children and 9 children with cystic fibrosis (CF). We also assessed within-period repeatability in the healthy controls. We report that the variability of measurements was similar for within sample, within day, and between visits, for both normals and children with asthma and CF, and that the major source of variability of sodium and chloride measurements is restricted by the reproducibility of the measurement assay method used. The wide use of EBC is more likely to depend on the development of highly sensitive and reproducible assays, rather than further refinements of the collection technique.

Adult↗
PubMed2004

Predicting response to rhDNase and hypertonic saline in children with cystic fibrosis.

Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis (CF). Alternate-day rhDNase and hypertonic saline (HS) represent potential cheaper alternative therapies. However, not all patients improve on treatment. To assess response, many CF centers have developed formal n-of-1 trials of treatment to find out who benefits. Response to daily rhDNase at 3 months has been shown to be a good predictor of response at 1 year. There are no data correlating individual response at a shorter time period with 3-month response. We assessed whether individual responses to daily rhDNase, alternate-day rhDNase, and HS could be predicted from lung function response at 6 weeks, thus shortening the n-of-1 trial, or from baseline patient characteristics, therefore avoiding the need for an n-of-1 trial. In a randomized crossover trial, 48 CF children were allocated consecutively to 12 weeks of once-daily 2.5-mg rhDNase, alternate-day 2.5-mg rhDNase, and twice-daily 5 ml of 7% HS. Forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) were measured at baseline and then at 6 and 12 weeks into each treatment period. Lung function response to the drugs at 6 weeks was highly predictive of response at 3 months. There was some evidence that response to HS was worse in patients with lower baseline lung function. However, there was no association between response to alternate-day or daily rhDNase and baseline characteristics. In conclusion, response to rhDNase and HS at 6 weeks was highly predictive of response at 3 months. For daily and alternate-day rhDNase, at least, the drug needs to be administered for at most 6 weeks initially to assess long-term response to treatment. Response to treatment could not be reliably predicted from baseline characteristics.

Adolescent↗
PubMed2004

Symptoms, lung function, and beta2-adrenoceptor polymorphisms in a birth cohort followed for 10 years.

As little is known about the natural history of bronchial responsiveness and the development of wheezing symptoms in early childhood, a cohort of children at risk of allergy, whose lung function and bronchial responsiveness had been measured in the neonatal period, was followed prospectively for 10 (SD, 0.8) years in order to determine the role of neonatal measurements on wheezing history and later lung function. A potential role for beta-2 adrenoceptor (beta2AR) polymorphisms in these relationships was also sought as a secondary objective. Of the original 73 children, wheezing history was available in 65 (89%), and 49 (67%) attended the laboratory for physiological measurements and genotyping of beta2AR. Wheezing was categorized as occurring 1) only before the fourth birthday, 2) after the fourth birthday, or 3) never. No relation was seen between neonatal and later lung function. However, neonatal bronchial responsiveness predicted subsequent FEV1 (P = 0.03). Increased neonatal bronchial responsiveness was associated with transient wheeze <4 years but not with later wheeze. Neonatal V'maxFRC was reduced in those possessing Gln27 or Arg16 alleles, but there was no effect of beta2AR polymorphisms on FEV1 at 10 years. Wheeze after 4 years of age was typical of classical asthma, as it was strongly related to atopy and bronchial responsiveness at age 10. In conclusion, we confirmed the association of neonatal bronchial responsiveness with both early wheezing and later lung function. We also showed an influence of polymorphisms at both aa16 and aa27 on neonatal lung function. Wheezing beyond 4 years, typical of classical asthma, was unrelated to early measurements of lung function or bronchial responsiveness.

Analysis of Variance↗
PubMed2004

Usefulness of a program of hospital-supervised physical training in patients with cystic fibrosis.

Exercise is an important part of normal childhood, but the ability to exercise may be impaired in chronic lung diseases such as cystic fibrosis (CF). Improving exercise performance by training is very attractive. The aim of the present study was the evaluation of the effects of a physical aerobic training program, performed in the Children's Hospital and Research Institute "Bambino Gesù" (Rome, Italy) in outpatient CF children, supervised by a physician. Twelve patients (mean forced expiratory flow in 1 sec (FEV1), 71%), age range 12-24 years (16.7 +/- 4.4 years), were enrolled. They performed a maximal exercise stress test on the treadmill (modified Bruce protocol) with breath-by-breath determination of oxygen consumption (VO2) to maximum at end-exercise; we measured time of exercise (TE), maximal heart rate (Hrmax) in beats per minute (bpm), and maximal systolic blood pressure (SBPm) in mmHg. The program consisted of 12 weeks of training twice a week. Each training session consisted of walking or running on the treadmill for 30 min at the speed that allowed the child to attain 60% of the maximal heart rate obtained during a baseline stress test for 4 weeks, 70% in the following 4 weeks, and 80% in the last 4 weeks, under strict medical supervision. HR was continously monitored. There was no change in FEV1 and forced vital capacity after the treatment period. Hrmax and SBPm also remained the same (P = 0.37 and P = 0.25, respectively). There was a significant increase in TE (P < 0.002), VO2, VO2/kg, and pulmonary ventilation (VE) (P < 0.0001, P < 0.001, and P < 0.001, respectively). This pilot study showed that a simple training program improves short-term cardiopulmonary fitness in children with CF. Further studies with a larger sample and for a more prolonged time are necessary to assess if sport can have a long-term effect on lung function or survival in CF patients.

Adolescent↗
PubMed2004

Effect of inhalation times on exhaled NO.

Recent work suggests that exhaled nitric oxide (eNO) can be divided into airway and alveolar components, using varying expiratory flow rates. It is known that higher values of eNO are found with lower expiratory flow rates, thought to be due to prolonged contact of the expirate with the bronchial epithelium. However, whether a prolonged inspiratory time could contaminate the alveolar signal with bronchial derived NO, by the same mechanism, is unknown. We aimed to study the effect, including repeatability, of inhalation time on eNO measurements performed at three different flow rates. We measured eNO in 21 children with asthma of different severity (no steroids, n = 2; inhaled corticosteroid (IC) dose up to 200 mcg/day, n = 3; IC up to 500 mcg/day, n = 3; IC >500 mcg/day, n = 6; IC >500 mcg/day and oral steroid, n = 7) and 24 normal adult controls at 50, 100, and 200 ml/s expiratory flow rate. The effect of either a rapid or a slow inhalation on measured eNO was studied at each flow rate. Furthermore, 12 asthmatic children and 12 adults had repeated measurements 1 hr apart. Repeatability within 1 day was assessed by calculating the single-determination standard deviation (SD) and 95% range. Our results showed that repeatability was equally good for the three expiratory flow rates, and inhalation time had no influence on the results. The inhalation maneuver does not influence eNO measurements using the variable expiratory flow technique.

Administration, Inhalation↗