Ward Hofhuis

Exhaled nitric oxide predicts asthma relapse in children with clinical asthma remission

Background: Nitric oxide in exhaled air (FENO) is a marker of eosinophilic airway inflammation. A study was undertaken to determine whether FENO predicts asthma relapse in asymptomatic asthmatic children in whom inhaled corticosteroids are discontinued. Methods: Forty children (21 boys) of mean age 12.2 years on a median dose of 400 μg budesonide or equivalent (range 100–400) were included. FENO was measured before and 2, 4, 12, and 24 weeks after withdrawal of steroids. A relapse was defined as more than one exacerbation per month, or need for β agonist treatment on 4 days per week for at least 2 weeks, or diurnal peak flow variability of >20%. FENO measurements were performed online with an expiratory flow of 50 ml/s. Results: Nine patients relapsed. Two and 4 weeks after withdrawal of steroids geometric mean FENO in children who were about to relapse was higher than in those who did not relapse: 35.3 ppb v 15.7 ppb at 2 weeks (ratio 2.3; 95% CI 1.2 to 4.1; p = 0.01) and 40.8 ppb v 15.9 ppb at 4 weeks (ratio 2.6; 95% CI 1.3 to 5.1). An FENO value of 49 ppb at 4 weeks after discontinuation of steroids had the best combination of sensitivity (71%) and specificity (93%) for asthma relapse. Conclusion: FENO 2 and 4 weeks after discontinuation of steroids in asymptomatic asthmatic children may be an objective predictor of asthma relapse.

Exhaled Nitric Oxide Differentiates Airway Diseases in the First Two Years of Life

Fractional exhaled nitric oxide (FENO) levels are increased in children and adults with asthma, whereas low levels have been found in cystic fibrosis and primary ciliary dyskinesia. The aim of this study was to investigate whether FENO measurements could distinguish between children below the age of 2 with different airway diseases. FENO measurements were performed in 118 infants aged between 4.6 and 25.2 mo: 74 infants with recurrent wheezing (RW), 24 with bronchopulmonary dysplasia (BPD), and 20 with cystic fibrosis (CF). FENO was measured also in 100 healthy controls aged between 1.1 and 7.7 mo. Geometric mean (95% confidence interval) FENO values were 10.4 (9.1–12.0) parts per billion (ppb) in healthy infants, 18.6 (15.6–22.2) ppb in wheezy infants, 11.7 (8.2–16.8) ppb in BPD infants and 5.9 (3.4–10.1) ppb in CF infants. FENO in wheezers was higher than in controls, BPD, and CF (p = 0.009, p = 0.038, and p < 0.001, respectively). Atopic wheezers showed higher FENO than nonatopic wheezers (p = 0.04). CF infants had lower FENO than healthy controls and BPD infants (p = 0.003 and p = 0.043, respectively). FENO values in BPD and control infants were not different. We conclude that FENO is helpful to differentiate various airway diseases already in the first 2 y of life.

Exhaled nitric oxide measurements with dynamic flow restriction in children aged 4-8 yrs

Fractional exhaled nitric oxide concentration (FEno) depends on exhalation flow; however, children often are unable to perform controlled flow procedures. Therefore, a device was developed for off-line FEno sampling, with dynamic flow restriction (DFR). The authors compared off-line with on-line FEno, assessed feasibility, and obtained normal values for FEno in children aged 4–8 yrs. Subjects inhaled nitric oxide (NO)-free air and exhaled into the device, where DFR kept exhalation flow constant at 50 mL·s−1. Dead space air was discarded. Exhaled air was collected in a 150 mL mylar balloon. On-line measurements were performed and values compared with off-line FEno in 19 adult volunteers. Seventy-nine children performed off-line sampling. All samples were analysed with a chemiluminescence NO-analyser. Normal values were obtained in 34 healthy children. There was an excellent correlation between on- and off-line values. Bland and Altman plots showed good agreement between on- and off-line FEno. Seventy-four out of 79 children were able to perform a correct off-line procedure. Geometric mean±sem FEno in healthy children was 4.9±1.2 parts per billion (ppb) for male children and 7.6±1.1 ppb for female children. It can be concluded that off-line fraction of exhaled nitric oxide measurements with dynamic flow restriction are feasible in young children and correspond to on-line values.

Bronchodilation in infants with malacia or recurrent wheeze

Background: Controversy remains regarding the effectiveness of bronchodilators in wheezy infants. Aims: To assess the effect of inhaled β2 agonists on lung function in infants with malacia or recurrent wheeze, and to determine whether a negative effect of β2 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 β2 agonists. Results: Baseline V′maxFRC was below reference values for both groups. Following inhalation of β2 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 β2 agonists caused a significant reduction in mean V′maxFRC. Infants with malacia were not more likely to worsen after β2 agonists than were infants with recurrent wheeze.

Airway dimensions in bronchopulmonary dysplasia: Implications for airflow obstruction

The cause of lung function abnormalities in bronchopulmonary dysplasia (BPD) is incompletely understood, even in the “new era” of this disease. Altered airway wall dimensions are important in the pathogenesis of airflow obstruction in diseases such as asthma and chronic obstructive pulmonary disease. Whether airway wall dimensions contribute to lung function abnormalities in BPD is unknown. The purpose of this study was to investigate airway wall dimensions in relation to airway size in BPD. Lung tissue of patients with BPD was obtained at autopsy, and lung tissue from children who died from sudden infant death syndrome (SIDS) served as control. Airway wall dimensions and epithelial loss were measured in 75 airways from 5 BPD patients and 176 airways from 11 SIDS patients. Repeated measures analysis of variance was used to assess the relationships between airway wall dimensions and airway size for BPD and SIDS patients. Little epithelial loss was present in the BPD patients while extensive loss was observed in some of the SIDS patients. The inner wall area, outer wall area, epithelium area and smooth muscle area were all substantially larger (all P < 0.001) in BPD than in SIDS patients. It is likely that the increased thickness of the airway wall components contributes to airflow obstruction in BPD patients. Pediatr. Pulmonol. 2008; 43:1206–1213.

Blue rubber-bleb naevus syndrome: report of a case with consumption coagulopathy complicated by manifest thrombosis

Blue rubber-bleb naevus (BRBN) syndrome is a rare disorder characterized by subcutaneous and gastrointestinal haemangiomas. The latter may lead to bleeding complications. A case is reported in which a process of chronic intravascular coagulation resulted in serious thrombotic complications. In the presence of a chronic consumption coagulopathy, it remains uncertain whether antiplatelet drugs are of prophylactic antithrombotic value.

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

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.