Merkus, P.J.F.M.

Improved treatment response to dornase alfa in cystic fibrosis patients using controlled inhalation (Article)

2011-12-01T00:00:00Z

Better treatment of obstructed small airways is needed in cystic fibrosis. This study investigated whether efficient deposition of dornase alfa in the small airways improves small airway obstruction. In a multicentre, double-blind, randomised controlled clinical trial, cystic fibrosis patients on maintenance treatment with 2.5 mL dornase alfa once daily were switched to a smart nebuliser and randomised to small airway deposition (n=24) or large airway deposition (n=25) for 4 weeks. The primary outcome parameter was forced expiratory flow at 75% of forced vital capacity (FEF75%). FEF75% increased significantly by 0.7 SD (5.2% predicted) in the large airways group and 1.2 SD (8.8%pred) in the small airways group. Intention-to-treat analysis did not showa significant difference in treatment effect between groups. Per-protocol analysis, excluding patients not completing the trial or with adherence <70%, showed a trend (p=0.06) in FEF75% Z-score and a significant difference (p=0.04) between groups in absolute FEF75% (L·s-1) favouring small airway deposition. Improved delivery of dornase alfa using a smart nebuliser that aids patients in correct inhalation technique resulted in significant improvement of FEF75% in children with stable cystic fibrosis. Adherent children showed a larger treatment response for small airway deposition. Copyright

Validation of a web-based version of the asthma control test and childhood asthma control test (Article)

2011-10-01T00:00:00Z

Rationale Recent guidelines focus on adjusting asthma treatment to the level of asthma control. The availability of a web-based asthma control questionnaire offers the possibility to assess asthma control without the need of outpatient clinic visits. The aim of this study was to evaluate the agreement between web-based and paper-based versions of the Asthma Control Test (ACT) and Childhood Asthma Control Test (C-ACT), short-term reproducibility and satisfaction with both versions. Methods One hundred seventy-three children with stable asthma and a normal lung function were randomized to fill in a web-based or paper-based version of the C-ACT (4-11 years) or ACT (12-18 years). According to a cross-over design, they completed the opposite version after 1 week. Reproducibility was evaluated by repeating the 2nd version (web- or paper-based) 7 days later. Results Eighty-eight children filled in the C-ACT, 68 children filled in the ACT. Intraclass Correlation Coefficient (ICC) for web-based versus paper-based C-ACT was 0.81 (95% confidence interval [95% CI] 0.72-0.87). For ACT this was 0.84 (95% CI 0.76-0.90). For web-based and paper-based C-ACT the reproducibility ICC was 0.82 (95% CI 0.67-0.90) and 0.75 (95% CI 0.59-0.85), respectively. The reproducibility ICC of the ACT for web- and paper-based versions was 0.93 (95% CI 0.87-0.97) and 0.77 (95% CI 0.59-0.88), respectively. Eighty-six percent of patients preferred the web-based version. Conclusion The web-based version of the C-ACT and ACT is reproducible and comparable with the paper-based version in assessing asthma control. Most children and their parents prefer the web-based version. Copyright

Comparing Global Initiative for Asthma (GINA) criteria with the Childhood Asthma Control Test (C-ACT) and Asthma Control Test (ACT) (Article)

2011-09-01T00:00:00Z

Several tools are useful in detecting uncontrolled asthma in children. The aim of this study was to compare Global Initiative for Asthma (GINA) guidelines with the Childhood Asthma Control Test (C-ACT) and the Asthma Control Test (ACT) in detecting uncontrolled asthma in children. 145 children with asthma filled in a web-based daily diary card for 4 weeks on symptoms, use of rescue medication and limitations of activities, followed by either the C-ACT or ACT. For predicting uncontrolled asthma, score cut-off points of 19 were used for C-ACT and ACT. According to GINA guidelines, asthma was uncontrolled in 71 (51%) children and completely controlled in 19 (14%) children. The area under the curve in the receiver operating characteristic curves for C-ACT and ACT versus GINA guidelines were 0.89 and 0.92, respectively. Cut-off points of 19 for C-ACT and ACT resulted in a sensitivity of 33% and 66% in predicting uncontrolled asthma, respectively. C-ACT and ACT correlate well with GINA criteria in predicting uncontrolled asthma, but commonly used cut-off points for C-ACT and ACT seem to underestimate the proportion of children with uncontrolled asthma as defined by GINA. Copyright

Prospective longitudinal evaluation of lung function during the first year of life after extracorporeal membrane oxygenation (Article)

2011-03-01T00:00:00Z

Objective: To collect longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation and to evaluate relationships between lung function and perinatal factors. Longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation are lacking. Design: Prospective longitudinal cohort study. Setting: Outpatient clinic of a tertiary level pediatric hospital. Patients: The cohort consisted of 64 infants; 33 received extracorporeal membrane oxygenation for meconium aspiration syndrome, 14 for congenital diaphragmatic hernia, four for sepsis, six for persistent pulmonary hypertension of the neonate, and seven for respiratory distress syndrome of infancy. Evaluation was at 6 mos and 12 mos; 39 infants were evaluated at both time points. Interventions: None. Measurements And Main Results: Functional residual capacity and forced expiratory flow at functional residual capacity were measured and expressed as z score. Mean (sem) functional residual capacities in z score were 0.0 (0.2) and 0.2 (0.2) at 6 mos and 12 mos, respectively. Mean (sem) forced expiratory flow was significantly below average (z score = 0) (p <.001) at 6 mos and 12 mos:-1.1 (0.1) and-1.2 (0.1), respectively. At 12 mos, infants with diaphragmatic hernia had a functional residual capacity significantly above normal: mean (sem) z score = 1.2 (0.5). Conclusions: Infants treated with extracorporeal membrane oxygenation have normal lung volumes and stable forced expiratory flows within normal range, although below average, within the first year of life. There is reason to believe, therefore, that extracorporeal membrane oxygenation either ameliorates the harmful effects of mechanical ventilation or somehow preserves lung function in the very ill neonate. Copyright

Effect of enzyme therapy in juvenile patients with Pompe disease: A three-year open-label study (Article)

2010-12-01T00:00:00Z

Pompe disease is a rare neuromuscular disorder caused by deficiency of acid α-glucosidase. Treatment with recombinant human α-glucosidase recently received marketing approval based on prolonged survival of affected infants. The current open-label study was performed to evaluate the response in older children (age 5.9-15.2 years). The five patients that we studied had limb-girdle muscle weakness and three of them also had decreased pulmonary function in upright and supine position. They received 20-mg/kg recombinant human α-glucosidase every two weeks over a 3-year period. No infusion-associated reactions were observed. Pulmonary function remained stable (n= 4) or improved slightly (n= 1). Muscle strength increased. Only one patient approached the normal range. Patients obtained higher scores on the Quick Motor Function Test. None of the patients deteriorated. Follow-up data of two unmatched historical cohorts of adults and children with Pompe disease were used for comparison. They showed an average decline in pulmonary function of 1.6% and 5% per year. Data on muscle strength and function of untreated children were not available. Further studies are required.

Dutch Cochlear Implant Group (CI-ON) consensus protocol on postmeningitis hearing evaluation and treatment (Article)

2010-10-01T00:00:00Z

Objective: One of the most devastating sequelae of bacterial meningitis is profound hearing loss or even deafness. Although cochlear implantation is able to restore (some) hearing abilities, obliteration due to fibrosis and especially calcification of the cochlea in the postmeningitis period is limiting the success rate of an implantation. A national consensus assembled in a postmeningitis follow-up protocol has to increase awareness and thus the chances of an early detection and possible intervention when profound hearing loss occurs. Setting: All cochlear implant (CI) centers of The Netherlands located in the 8 academic otorhinolaryngology and audiology departments of The Netherlands, gathered in the Dutch Cochlear Implant Group (CI-ON, Cochlear Implant Overleg Nederland). Intervention: A protocol proposed by 3 centers was sent to all other CI centers in The Netherlands to review and agree on. Main Outcome Measures: The CI centers agreed on the need for, and use of, the proposed protocol. Keystones of the protocol are treatment with dexamethasone before start of antibiotics, early magnetic resonance imaging and repeated audiological follow-up, and urgent referral to a CI center in all cases with greater than 30 dB SNHL. Conclusion: The Cochlear Implant Centers in The Netherlands (CI-ON) have agreed on a protocolized follow-up after bacterial meningitis to increase the chances of an early detection and possible intervention should profound hearing loss occur.

Reference ranges for interrupter resistance technique: The Asthma UK Initiative (Article)

2010-07-01T00:00:00Z

Measuring interrupter resistance (Rint) is an increasingly popular lung function technique and especially suitable for preschool children because it is simple, quick and requires only passive cooperation. A European Respiratory Society (ERS)/American Thoracic Society (ATS) Task Force recently published empirical recommendations related to procedures, limitations and interpretation of the technique. However, for valid interpretation, high-quality reference equations are required and these have been lacking. The aim of the present study was to collate Rint data from healthy children in order to produce more robust reference equations. A further aim was to examine the influence of methodological differences on predicted Rint values. Rint data from healthy children were collected from published and unpublished sources. Reference equations for expiratory and inspiratory Rint were developed using the LMS (lambda, mu, sigma) method. Data from 1,090 children (51% males) aged 3-13 yrs were collated to construct sex-specific reference equations for expiratory Rint and data from 629 children (51% males) were collated for inspiratory Rint. Height was the best independent predictor of both expiratory and inspiratory Rint. Differences between centres were clinically irrelevant, and differences between ethnic groups could not be examined. The availability of a large and generalisable sample and the use of modern statistical techniques enabled the development of more appropriate reference equations for Rint in young children.

Respiratory medicines for children: Current evidence, unlicensed use and research priorities (Article)

2010-02-01T00:00:00Z

This European Respiratory Society task force has reviewed the evidence for paediatric medicines in respiratory disease occurring in adults and children. We describe off-licence use, research priorities and ongoing studies. Off-licence and off-label prescribing in children is widespread and potentially harmful. Research areas in asthma include novel formulations and regimens, and individualised prescribing. In cystic fibrosis, future studies will focus on screened infants and robust outcome measures are needed. Other areas include new enzyme and antibiotic formulations and the basic defect. Research into pneumonia should include evaluation of new antibacterials and regimens, rapid diagnostic tests and, in pleural infection, antibiotic penetration, fibrinolytics and surveillance. In uncommon conditions, such as primary ciliary dyskinesia, congenital pulmonary abnormalities or neuromuscular disorders, drugs indicated for other conditions (e.g. dornase alfa) are commonly used and trials are needed. In neuromuscular disorders, the β-agonists may enhance muscle strength and are in need of evaluation. Studies of antibiotic prophylaxis, immunoglobulin and antifungal drugs are needed in immune deficiency. We hope that this summary of the evidence for respiratory medicines in children, highlighting gaps and research priorities, will be useful for the pharmaceutical industry, the paediatric committee of the European Medicines Agency, academic investigators and the lay public. Copyright

Recombinant human DNase in children with airway malacia and lower respiratory tract infection (Article)

2009-10-01T00:00:00Z

Background: Children with airway malacia often have protracted courses of airway infections, because dynamic airway collapse during coughing results in impaired mucociliary clearance. The aim of this study was to determine the effect of the mucolytic drug recombinant human deoxyribonuclease (rhDNase) on the recovery of respiratory symptoms in children with airway malacia and lower respiratory tract infection (LRTI). Methods: In a randomized double-blind controlled clinical trial, 40 children with airway malacia andLRTIwere randomlyassigned to receive either 2.5mg nebulized rhDNase or placebo twice daily for 2 weeks. The primary endpoint was the change in the cough diary score (CDS) (scale 0-5) from baseline to the second week of treatment. Secondary endpoints were VAS symptom scores for cough, dyspnea, and difficulty in expectorating sputum, need for an antibiotic course, and lung function data (FVC, FEV1, FEF75, Rinte ). Results: There was no significant difference in the mean change in CDSs from baseline between the rhDNase group and the placebo group (mean difference for daytime 0.19 (95% CI -0.53 to 0.90); for nighttime 0.38 (95% CI -0.30 to 1.05). Proportions of patients requiring antibiotics, and the mean changes in symptom scores and lung function from baseline did not significantly differ between both groups. Conclusion:Treatment with 2weeks of nebulized rhDNase does not enhance recovery or reduce the need for antibiotics in children with airway malacia and LRTI. (Controlled-trials.com number, ISRCTN85366144).

Pathophysiology, diagnosis and treatment of chronic cough (Article)

2009-10-01T00:00:00Z

Cough is a frequent symptom in childhood. For daily practice, it is important to distinguish between non-specific cough (dry cough without other symptoms and without abnormal investigations) and specific cough (resulting from underlying illness). Non-specific cough requires a different approach than specific cough. We propose a systematic approach for the investigation and treatment of cough to prevent missing important diagnoses.

Cross-sectional and longitudinal spirometry in children and adolescents interpretative strategies (Article)

2008-12-15T00:00:00Z

Rationale: Single and serial spirometric data are commonly compared with predicted values to assess pulmonary function and normal lung growth. Objectives: Do reference equations adequately describe pulmonary function in a population and in growing individuals? Methods: We applied five sets of reference equations with appropriate age ranges to cross-sectional data of FEV1, FVC, and FEV1/FVC from the United States, Estonia, and The Netherlands (1,487 boys and 1,340 girls, 6 to 18 years of age), and to serial measurements in Dutch (430 girls and 769 boys, 6 to 19 years of age) and in German and Austrian children (1,305 girls and 1,303 boys, 6 to 13 years of age). Measurements and Main Results: Compared with reference equations from Polgar and Zapletal, cross-sectional FEV1and FVC declined between the ages of 6 and 12 and then increased, leading to a spurious change of up to 25% predicted; this pattern was most pronounced in boys. In cross-sectional data this trend was much weaker when using reference equations from Hankinson, Quanjer, and Stanojevic, and these equations provided a good fit from the age of 12 upward. In longitudinal data (i.e., within individuals), the trend was more pronounced for FEV1in boys than in girls. No set of equations provideda satisfactoryfit in the lower limits of normal, but Hankinson and Stanojevic equations performed best. Conclusions: Spirometric reference equations that use only height for predicting pulmonary function are unsuitable for describing the progression of pulmonary function. Those that incorporate height and age demonstrate some discrepancy with longitudinal data. Failure to take these spurious trends into account leads to significant errors in estimating the natural course of respiratory disease, in allocating patients to treatment groups, or in assessing long-term effects of drug intervention in school children and adolescents.

Definition, assessment and treatment of wheezing disorders in preschool children: An evidence-based approach (Article)

2008-10-01T00:00:00Z

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting β2-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes. Copyright

Yield from Flexible Bronchoscopy in Pediatric Cystic Fibrosis Patients (Article)

2008-10-01T00:00:00Z

BACKGROUND : Recent data on the yield of bronchoscopy in pediatric cystic fibrosis (CF) patients are lacking. Therapeutic bronchoscopic lavage with the mucolytic recombinant human deoxyribonuclease (rhDNase) has been used during CF bronchoscopies, but efficacy data are scarce. METHODS: A retrospective review of all bronchoscopies performed in pediatric CF patients in our hospital in the past 15 years. AIMS OF THE STUDY: To evaluate indications for and safety of bronchoscopy in pediatric CF patients, to describe the findings of bronchoscopy and the contribution of these findings to clinical management, and to evaluate the application of bronchoscopic lavage with rhDNase. RESULTS: Between 1992 and 2007, 66 bronchoscopies were performed in 48 CF patients (25 males) at a median (range) age of 8.3 (0.1 to 20.4) years. Indications for bronchoscopy were persistent atelectasis (42%), refractory symptoms (29%), need for microbiologic culture (11%), suspected anatomic abnormality (11%), and bronchial toilet (7%). Relevant new information with therapeutic consequences was obtained in 28 (42%) bronchoscopies, including a first Pseudomonas aeruginosa infection (n≤3), infection with atypical mycobacteria (n≤3), or Aspergillus fumigatus (n≤5), and severe tracheo(broncho)malacia (n≤4). In patients with atelectasis, rhDNase lavage was associated with improved chest radiograph scores and a transient decline in forced vital capacity. In 7 of 11 patients with refractory symptoms, lung function tended to improve after rhDNase lavage. No serious complications were observed after bronchoscopy and rhDNase lavage. CONCLUSIONS: Bronchoscopy provides clinically relevant information in about 40% of these pediatric CF patients. Lavage with rhDNase seemed safe, and was associated with improved chest radiographs in patients with therapy resistant atelectasis. Copyright

Pulmonary complaints and lung function after pediatric kidney transplantation (Article)

2008-03-01T00:00:00Z

Recently four of 38 children with a kidney transplant were diagnosed with bronchiectasis. The aim of the current study was to identify patients with increased risk for pulmonary damage. In this cross-sectional observational study, children with a functioning kidney graft in the Netherlands and Antwerp, Belgium, were screened with the use of a symptom checklist and spirometry. Maximum score for upper airway complaints was 21 (normal: <8), for lower airway complaints 28 (<10). Results of FVC, FEV1and MEF25were expressed as percentage predicted for height and sex. One hundred and thirty-five patients completed the interview (122) and/or spirometry (103); 91 did both. Lower airways symptoms were above acceptable levels in 18 (14%) patients. Forty-nine patients (48%) had an abnormal lung function test: in 12 concerning FVC%, in 11 FEV1%, in 24 MEF25% and in 36 FEV1/FVC. Of correlations between symptomatology or spirometry data, and clinical parameters, only that between GFR and MEF25% was statistically significant. Children with a kidney transplant are at increased risk for obstructive lung disease. We recommend to monitor lung function during the follow-up after renal transplantation.

Pharmacotherapy of impaired mucociliary clearance in non-CF pediatric lung disease. A review of the literature (Article)

2007-11-01T00:00:00Z

Mucoactive agents are used to treat a variety of lung diseases involving impaired mucociliary clearance or mucus hypersecretion. The mucoactive agents studied most frequently are N-acetylcysteine (NAC), recombinant human DNase (rhDNase), and hypertonic saline. Studies on the efficacy of these have been mainly conducted in adults, and in patients with cystic fibrosis (CF). The exact role of mucoactive agents in children with non-CF lung disease is not well established. We present an overview of the current literature reporting clinical outcome measures of treatment with NAC, rhDNase, and hypertonic saline in children.

Recombinant human deoxyribonuclease in infants with respiratory syncytial virus bronchiolitis (Article)

2007-03-01T00:00:00Z

Background: Treatment of hospitalized infants with respiratory syncytial virus (RSV) bronchiolitis is mainly supportive. Bronchodilators and systemic steroids are often used but do not reduce the length of hospital stay. Because hypoxia and airways obstruction develop secondary to viscous mucus in infants with RSV bronchiolitis, and because free DNA is present in RSV mucus, we tested the efficacy of the mucolytic drug recombinant human deoxyribonuclease (rhDNase). Methods: In a multicenter, randomized, double-blind, controlled clinical trial, 225 oxygen-dependent infants admitted to the hospital for RSV bronchiolitis were randomly assigned to receive 2.5 mg bid of nebulized rhDNase or placebo until discharge. The primary end point was length of hospital stay. Secondary end points were duration of supplemental oxygen, improvement in symptom score, and number of intensive care admissions. Results: There were no significant differences between the groups with regard to the length of hospital stay (p = 0.19) or the duration of supplemental oxygen (p = 0.07). The ratio (rhDNase/placebo) of geometric means of length of stay was 1.12 (95% confidence interval, 0.96 to 1.33); for the duration of supplemental oxygen, the ratio was 1.28 (95% confidence interval, 0.97 to 1.68). There were no significant differences in the rate of improvement of the symptom score or in the number of intensive care admissions. Conclusions: Administration of rhDNase did not reduce the length of hospital stay or the duration of supplemental oxygen in oxygen-dependent infants with RSV bronchiolitis.

Methodological aspects of exhaled nitric oxide measurements in infants (Article)

2007-02-01T00:00:00Z

Guidelines for the measurement of fractional exhaled nitric oxide (FENO) recommend refraining from lung function tests (LFT) and certain foods and beverages before performing FENOmeasurements, as they may lead to transiently altered FENOlevels. Little is known of such factors in infants. The aim of the present study was to evaluate whether forced expiratory maneuvers, sedation, nasal contamination, and breastfeeding affect FENOvalues in infants. FENOwas measured off-line during tidal breathing by means of a facemask covering nose and mouth. FENOmeasurements were performed in 45 sedated infants (mean age 12.1 months) who underwent LFT because of airway diseases and in 83 unsedated healthy infants (mean age 4.3 months). In infants with airway diseases, no difference was found in FENOvalues before and 5 min after LFT (n = 19 infants, p = 0.7) and FENOvalues before sedation did not differ from FENOvalues during sedation (n = 10 infants, p = 0.2).Oral FENOvalues were significantly lower than mixed (nasal + oral) FENO(n = 42 infants, p < 0.001). FENOvalues before and 5 min after breastfeeding were not different (n = 11 healthy infants, p = 0.57). The short-term reproducibility in healthy infants (n = 54) was satisfactory (intraclass correlation coefficient = 0.94). We conclude that, in infants with airway diseases, LFT prior to FENOmeasurement did not influence FENOvalues and FENOvalues did not change after sedation. Oral FENOvalues were significantly lower than mixed (oral + nasal) FENO, and breastfeeding did not influence FENO. Short-term reproducibility in awake healthy infants was good.

A population-based nested case control study on recurrent pneumonias in children with severe generalized cerebral palsy: ethical considerations of the design and representativeness of the study sample. (Article)

2005-07-19T00:00:00Z

BACKGROUND: In children with severe generalized cerebral palsy, pneumonias are a major health issue. Malnutrition, dysphagia, gastro-oesophageal reflux, impaired respiratory function and constipation are hypothesized risk factors. Still, no data are available on the relative contribution of these possible risk factors in the described population. This paper describes the initiation of a study in 194 children with severe generalized cerebral palsy, on the prevalence and on the impact of these hypothesized risk factors of recurrent pneumonias. METHODS/DESIGN: A nested case-control design with 18 months follow-up was chosen. Dysphagia, respiratory function and constipation will be assessed at baseline, malnutrition and gastro-oesophageal reflux at the end of the follow-up. The study population consists of a representative population sample of children with severe generalized cerebral palsy. Inclusion was done through care-centres in a predefined geographical area and not through hospitals. All measurements will be done on-site which sets high demands on all measurements. If these demands were not met in "gold standard" methods, other methods were chosen. Although the inclusion period was prolonged, the desired sample size of 300 children was not met. With a consent rate of 33%, nearly 10% of all eligible children in The Netherlands are included (n = 194). The study population is subtly different from the non-participants with regard to severity of dysphagia and prevalence rates of pneumonias and gastro-oesophageal reflux. DISCUSSION: Ethical issues complicated the study design. Assessment of malnutrition and gastro-oesophageal reflux at baseline was considered unethical, since these conditions can be easily treated. Therefore, we postponed these diagnostics until the end of the follow-up. In order to include a representative sample, all eligible children in a predefined geographical area had to be contacted. To increase the consent rate, on-site measurements are of first choice, but timely inclusion is jeopardized. The initiation of this first study among children with severe neurological impairment led to specific, unexpected problems. Despite small differences between participants and non-participating children, our sample is as representative as can be expected from any population-based study and will provide important, new information to bring us further towards effective interventions to prevent pneumonias in this population.

Efficacy of fluticasone propionate on lung function and symptoms in wheezy infants. (Article)

2005-02-15T00:00:00Z

The role of inhaled corticosteroids in the treatment of recurrent or persistent wheeze in infancy remains unclear. We evaluated the effect of 3 months of treatment with inhaled fluticasone propionate, 200 microg daily (FP200), on lung function and symptom scores in wheezy infants. Moreover, we evaluated whether infants with atopy and/or eczema respond better to FP200 as compared with non-atopic infants. Forced expiratory flow (Vmax(FRC)) was measured at baseline and after treatment. Sixty-five infants were randomized to receive FP200 or placebo, and 62 infants (mean age, 11.3 months) completed the study. Mean Vmax(FRC), expressed as a Z score, was significantly below normal at baseline and after treatment in both groups. The change from baseline of Vmax(FRC) was not different between the two treatment arms. After 6 weeks of treatment, and not after 13 weeks, the FP200 group had a significantly higher percentage of symptom-free days and a significant reduction in mean daily cough score compared with placebo. Separate analysis of treatment effect in infants with atopy or eczema showed no effect modification. We conclude that in wheezy infants, after 3 months of treatment with fluticasone, there was no improvement in lung function and no reduction in respiratory symptoms compared with placebo.

Inhaled corticosteroids and growth of airway function in asthmatic children (Article)

2004-01-01T00:00:00Z

Airway inflammation and remodelling play an important role in the pathophysiology of asthma. Remodelling may affect childhood lung function, and this process may be reversed by anti-inflammatory treatment. The current study assessed longitudinally whether asthma affects growth of airway function relative to airspaces, and if so whether this is redressed by inhaled corticosteroids (ICS). Every 4 months for up to 3 yrs, lung function was assessed in 54 asthmatic children (initial age 7-16 yrs), who inhaled 0.2 mg salbutamol t.i.d. and 0.2 mg budesonide t.i.d. (beta2-agonist (BA)+ICS), or placebo (PL) t.i.d. (BA+PL) in a randomised, double-blind design. Measurements were carried out before and after maximal bronchodilation. Airway growth was assessed from the change of forced expiratory volume in one second and of maximal expiratory flows (at 60% and 40% of total lung capacity (TLC) remaining in the lung) relative to TLC, as measures of more central, intermediate and more peripheral airways. Growth patterns were compared with the longitudinal findings in 376 healthy children. Airway patency after maximal bronchodilation in patients on BA+PL remained reduced compared to healthy subjects, whereas in patients on BA+ICS a marked improvement was observed to subnormal. No differences between patients and controls could be demonstrated for growth patterns of central and intermediate airway function. Compliance with BA+ICS was 75% of the prescribed dose, resulting in significant, sustained improvement of symptoms and postbronchodilator calibre of central and intermediate airways to subnormal within 2 months, but postbronchodilator small airway patency remained reduced, though improved compared to patients on BA+PL. Anti-inflammatory treatment of asthmatic children is associated with normal functional development of central and intermediate airways. The persistently reduced postbronchodilator patency of peripheral airways may reflect remodelling, or insufficient anti-inflammatory treatment.

Estimation of lung growth using computed tomography (Article)

2003-01-01T00:00:00Z

Anatomical studies suggest that normal lungs grow by rapid alveolar addition until about 2 yrs of age followed by a gradual increase in alveolar dimensions. The aim of this study was to examine the hypothesis that normal lung growth can be monitored by computed tomography (CT). Therefore, the gas volume per gram of lung tissue was estimated from measurements of lung density obtained from CT scans performed on children throughout the growth period. CT scans were performed on 17 males and 18 females, ranging in age from 15 days-17.6 yrs. CT-measured lung weight was correlated with predicted post mortem values and CT measured gas volume with predicted values of functional residual capacity. The median value for lung expansion was 1.86 mL x g(-1) at 15 days, decreased to 0.79 mL x g(-1) by 2 yrs and then increased steadily to 5.07 mL x g(-1) at 17 yrs. Computed tomography scans can be used to estimate lung weight, gas volume and expansion of normal lungs during the growth period. The increase in the lung expansion after the age of 2 yrs suggests progressive alveolar expansion with increasing lung volume.

Bronchodilation in infants with malacia or recurrent wheeze (Article)

2003-01-01T00:00:00Z

BACKGROUND: Controversy remains regarding the effectiveness of bronchodilators in wheezy infants. AIMS: To assess the effect of inhaled beta(2) agonists on lung function in infants with malacia or recurrent wheeze, and to determine whether a negative effect of beta(2) agonists on forced expiratory flow (V'(maxFRC)) is more pronounced in infants with airway malacia, compared to infants with wheeze. METHODS: We retrospectively analysed lung function data of 27 infants: eight with malacia, 19 with recurrent wheeze. Mean (SD) age was 51 (18) weeks. Mean V'(maxFRC) (in Z score) was assessed before and after inhalation of beta(2) agonists. RESULTS: Baseline V'(maxFRC) was below reference values for both groups. Following inhalation of beta(2) agonists the mean (95% CI) change in mean V'(maxFRC) in Z scores was -0.10 (-0.26 to 0.05) and -0.33 (-0.55 to -0.11) for the malacia and wheeze group, respectively. CONCLUSIONS: In infants with wheeze, inhaled beta(2) agonists caused a significant reduction in mean V'(maxFRC). Infants with malacia were not more likely to worsen after beta(2) agonists than were infants with recurrent wheeze.

Adverse health effects of prenatal and postnatal tobacco smoke exposure on children (Article)

2003-01-01T00:00:00Z

Parents who choose to smoke are possibly not aware of, or deny, the negative effects of passive smoking on their offspring. This review summarises a wide range of effects of passive smoking on mortality and morbidity in children. It offers paediatricians, obstetricians, specialists in preventive child health care, general practitioners, and midwives an approach to promote smoking cessation in smoking parents before, during, and after pregnancy.

Worsening of V'maxFRC in infants with chronic lung disease in the first year of life: a more favorable outcome after high-frequency oscillation ventilation. (Article)

2002-12-15T00:00:00Z

Little is known about the development of maximal flow at functional residual capacity, a measure of airway patency, in infants with chronic lung disease (CLD). In a follow-up study, we evaluated V'maxFRC in very low birth weight infants with CLD, treated with high-frequency oscillation ventilation (HFOV) or conventional mechanical ventilation. In 36 infants with CLD, V'maxFRC was evaluated at 6 and/or 12 months corrected age, and the relationship between perinatal factors and lung function was studied. Mean (SD) birth weight and gestational age were 837 (152) g and 26.8 (1.7) weeks, respectively. At 6 and 12 months, mean V'maxFRC was significantly below normal. Between 6 and 12 months, there was a mean (95% confidence interval) reduction in V'maxFRC (Z score) of 0.5 (0.2-0.7) (p < 0.001). At 12 months, the mean V'maxFRC (Z score) was higher for children initially treated with HFOV (n = 15), as compared with children treated with conventional mechanical ventilation (n = 16): mean (95% confidence interval) difference was 0.6 (0.2-1.0) (p = 0.008). We conclude that very low birth weight infants with CLD have decreased V'maxFRC that worsen during the first year of life. Initial treatment with HFOV was associated with a more favorable outcome of V'maxFRC at 12 months corrected age.

Measurements of interrupter resistance: reference values for children 3-13 yrs of age (Article)

2002-01-01T00:00:00Z

The interrupter technique is a convenient and sensitive technique for studying airway function in subjects who cannot actively participate in (forced) ventilatory function tests. Reference values for preschool children exist but are lacking for children >7 yrs. Reference values were obtained for expiratory interrupter resistance (R(int,e)) in 208 healthy Dutch Caucasian children 3-13 yrs of age. A curvilinear relationship between R(int,e) and height was observed, similar to published airways resistance data measured by plethysmography. No significant differences in cross-sectional trend or level of R(int,e) were observed according to sex. It was found that Z-scores could be used to express individual R(int,e) values and to describe intra- and interindividual differences based on the reference equation: 10logR(int,e)=0.645-0.00668x standing height (cm) kPa x L(-1) x s(-1) and residual SD (0.093 kPa x L(-1) x s(-1)). Expiratory interrupter resistance provides a tool for clinical and epidemiological assessment of airway function in a large age range.

Annual lung function changes in young patients with chronic lung disease (Article)

2002-01-01T00:00:00Z

Reference equations for ventilatory function that use different statistical models may introduce artifacts that affect the estimated change of lung function during growth in young subjects. The effect of differently modelled reference equations on the estimated annual change of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in young patients with chronic lung disease was assessed. Four frequently used reference equations were used to describe the longitudinal changes of FEV1 and FVC in 52 patients (23 females) with cystic fibrosis (CF) during a mean follow-up of 3.9 yrs. Choice of reference equations directly affected value and, most importantly, estimated annual change of FVC and FEV1. Mean+/-SD annual change of FEV1 varied from 2.2+/-6.2 to -2.2+/-3.6% of predicted. For two reference equations the estimated individual changes of FEV1 and FVC in CF were positively correlated with mean individual age. This probably reflects underestimation of deteriorating lung function. Variability of annual change was independent of age only when reference equations that were designed to accurately predict lung function during the pubertal growth spurt were used. These findings have implications for patient care and clinical research.

Interrupter resistance in preschool children: measurement characteristics and reference values (Article)

2001-01-01T00:00:00Z

There is a need for quick, reliable, and noninvasive lung function tests to assess airway obstruction in preschool children both for pediatric pulmonary care as well as for research purposes. We studied feasibility, reproducibility, and validity of measurements of the respiratory system using the interrupter technique (interrupter resistance [Rint]) and obtained reference values in children from a general population, 2 to 7 yr of age. Accuracy was studied by comparisons of Rint with plethysmographic airway resistance (Raw) in 20 patients (7 to 14 yr) with mild to severe chronic airways obstruction and was satisfactory in patients with FEV(1) > 60% predicted. The technique proved sensitive enough to detect changes in airway caliber within a small group of 12 children who developed mild respiratory tract infections. Among children from a general population, subgroups with mild respiratory symptoms or mild respiratory disease had higher mean Rint values. Airway obstruction was better detected using expiratory rather than inspiratory interruptions, both programmed at peak tidal ventilatory flow. Reproducibility within subjects was satisfactory (intraclass correlation 0.82 and 0.79). The same applied to interobserver agreement (intraclass correlation 0.98). The interrupter technique proves to be a reliable and practical test of airway function, suitable for clinical and epidemiologic studies in preschool children.

DNase treatment for atelectasis in infants with severe respiratory syncytial virus bronchiolitis (Article)

2001-01-01T00:00:00Z

Respiratory insufficiency due to respiratory syncytial virus (RSV) bronchiolitis is partly due to the abundance of thickened mucus and the inability to clear it from the airways. Mucus in RSV bronchiolitis contains necrotic inflammatory and epithelial cells. The viscoelastic properties of purulent airway secretions are largely due to the presence of highly polymerized deoxyribonucleic acid (DNA). Recombinant human deoxyribonuclease (rhDNase) is known to liquefy such mucus in patients with cystic fibrosis, whereas case reports described a beneficial effect in other respiratory disorders. The authors hypothesized that rhDNase would diminish atelectasis and mucus plugging in infants with severe RSV bronchiolitis. Two infants with RSV bronchiolitis with massive unilateral atelectasis in whom mechanical ventilation was imminent due to exhaustion, and three mechanically ventilated infants (two neonates, one with bronchopulmonary dysplasia) with RSV bronchiolitis with pneumonia received treatment with 2.5 mg nebulized rhDNase twice daily. Following administration of nebulized recombinant human deoxyribonuclease, clinical and radiological parameters improved quickly. Mechanical ventilation could be avoided in two infants while in three infants on artificial ventilation, clinical recovery started following the first dose of the drug. A therapeutic trial of recombinant human deoxyribonuclease may be an option in the treatment for atelectasis in severe or complicated respiratory syncytial virus bronchiolitis in infancy.

A family with extrinsic allergic alveolitis caused by wild city pigeons: A case report (Article)

2000-01-01T00:00:00Z

We describe a family in which the mother died of unresolved lung disease and whose 5 children, some of whom had previous signs of asthma, were subsequently affected by extrinsic allergic alveolitis caused by contact with wild city pigeon antigens. The children received systemic corticosteroids for 1 month and inhaled steroids for 24 months, while antigen exposure was reduced as much as feasible. This was followed by a quick clinical recovery and a slow normalization of chest radiographs and pulmonary function indices, especially of diffusion capacity, during a follow-up of 24 months. Because pigeon-breeder's lung caused by free-roaming city pigeons has not been previously described, it remains unclear whether this family developed the disease because of high antigen exposure or because of increased susceptibility. None of the supposedly high-risk human leukocyte antigen types were found in the children. Whether human leukocyte antigen B7 in 1 child played a role in the course of the illness remains speculative. It is unknown to what extent pigeon-breeder's lung caused by nondomestic birds remains undetected and misdiagnosed as difficult or steroid-resistant asthma. The question remains whether free-roaming city pigeons are indeed a public health risk. We suggest that atypical outdoor antigens be considered in all patients with nonresolving chest disease or therapy-resistant asthma.