Johannes H. Wildhaber

Measurement of lung volume and ventilation distribution with an ultrasonic flow meter in healthy infants

Small airway disease in infants is characterised by abnormal lung volume and uneven ventilation distribution. An inert tracer gas washin/washout technique using a pulsed ultrasonic flow meter is presented to measure functional residual capacity (FRC) and ventilation distribution in spontaneously breathing and unsedated infants. With a pulsed ultrasound sent through the main stream of the flow meter, flow, volume and MM of the breathing gas can be calculated. Sulphur hexafluoride was used as a tracer gas. In a mechanical lung model (volume range 53–188u2005mL) and in 12 healthy infants (aged 38.3±9.2 days; mean±sd) accuracy and reproducibility of the technique was assessed. Indices of ventilation distribution such as alveolar-based mean dilution number (AMDN) and pulmonary clearance delay (PCD) were calculated. Mean error of volume measurement in the lung model was 0.58% (coefficient of variance (CV) 1.3%). FRC was in the low predicted range for normal infants (18.0±2.0u2005mL·kg−1) and highly reproducible (5.5±1.7% intra-subject CV). AMDN was 1.63±0.15 and PCD was 52.9±11.1%. Measurement of functional residual capacity and ventilation distribution using a sulphur hexafluoride washin/washout and an ultrasonic flow meter proved to be highly accurate and reproducible in a lung model and in healthy, spontaneously breathing and unsedated infants.

Exhaled nitric oxide distinguishes between subgroups of preschool children with respiratory symptoms

BACKGROUNDnRespiratory symptoms are common in early childhood. The clinical characterization of disease presentation and hence its likely disease progression has so far been proven difficult.nnnOBJECTIVEnTo investigate whether exhaled nitric oxide (NO) could be helpful to distinguish between subgroups of nonwheezy and wheezy young children less than 4 years of age.nnnMETHODSnExhaled NO was measured in 391 children (age 3-47 months) with nonwheezy and wheezy respiratory symptoms. Children were divided into 3 groups: children with recurrent cough but no history of wheeze (group 1), with early recurrent wheeze and a loose index for the prediction of asthma at school age (group 2), and with frequent recurrent wheeze and a stringent index for the prediction of asthma at school age (group 3).nnnRESULTSnChildren from group 3 showed significantly higher median (interquartile range) fractional exhaled NO (FeNO) levels (11.7 [11.85]) than children from groups 1 (6.5 [5.5]; P < .001) and 2 (6.4 [6.5]; P < .001). No difference in FeNO levels was found between children from groups 1 and 2 (P = .91).nnnCONCLUSIONnWheezy young children less than 4 years of age with a stringent index for the prediction of asthma at school age have elevated levels of FeNO compared with children with recurrent wheeze and a loose index for the prediction of asthma at school age or children with recurrent cough.

Elevated nitrite in breath condensates of children with respiratory disease

The aim of the study was to determine the differences in nitrite, in the exhaled breath condensates of healthy children and those children with asthma, cystic fibrosis (CF) and nonasthmatic, episodic cough. Breath condensates were obtained from 66 children (43 males:23 females, 3.1–16u2005yrs) and included 29 asthmatics, 12 clinically stable CF patients, 12 children with cough but not asthma and 13 healthy volunteers. The collected condensate was assayed colourimetrically using the Griess reaction to determine nitrite concentrations. Patients with CF (median: 5–95% percentiles; 2.02: 0.43–6.37u2005µM) or asthma (2.10: 0.63–5.45u2005µM) had significantly higher levels of nitrite compared to healthy subjects (0.41: 0.13–1.83u2005µM; p<0.05) or subjects with cough (0.75: 0.03–1.75u2005µM; p<0.05). Airway inflammation, as assessed by the nitrite in breath condensates, is present in children with asthma and cystic fibrosis, but not those children with nonasthmatic, episodic cough. Nitrite can be conveniently, cheaply and rapidly measured in breath condensates of children as young as 3u2005yrs of age, and may prove useful for the assessment of airway inflammation in children with respiratory disease.

The effect of montelukast on lung function and exhaled nitric oxide in infants with early childhood asthma

Effective treatment of respiratory symptoms, airway inflammation and impairment of lung function is the goal of any asthma therapy. Although montelukast has been shown to be a possible add-on therapy for anti-inflammatory treatment in older children, its efficacy in infants and young children is not well known. The aim of this study was to investigate its effect in infants and young children with early childhood asthma. In a prospective randomised double-blind placebo-controlled study, 24 young children (10–26 months) with wheeze, allergy and a positive family history of asthma consistent with the diagnosis of early childhood asthma were randomised to receive montelukast 4u2005mg or placebo. The forced expiratory volume in 0.5 seconds (FEV0.5) was measured using the raised volume rapid thoracic compression technique, and fractional exhaled nitric oxide (FeNO) and symptom scores were determined. No change was noted in FEV0.5, FeNO or symptom score in the placebo group following the treatment period. In contrast, significant improvements in mean±sd FEV0.5 (189.0±37.8 and 214.4±44.9u2005mL before and after treatment, respectively), FeNO (29.8±10.0 and 19.0±8.5u2005ppb) and median symptom score (5.5 and 1.5) were noted following treatment with montelukast. In conclusion, montelukast has a positive effect on lung function, airway inflammation and symptom scores in very young children with early childhood asthma.

Respiratory Flow Phenomena and Gravitational Deposition in a Three-Dimensional Space-Filling Model of the Pulmonary Acinar Tree

The inhalation of micron-sized aerosols into the lungs acinar region may be recognized as a possible health risk or a therapeutic tool. In an effort to develop a deeper understanding of the mechanisms responsible for acinar deposition, we have numerically simulated the transport of nondiffusing fine inhaled particles (1 mum and 3 microm in diameter) in two acinar models of varying complexity: (i) a simple alveolated duct and (ii) a space-filling asymmetrical acinar branching tree following the description of lung structure by Fung (1988, A Model of the Lung Structure and Its Validation, J. Appl. Physiol., 64, pp. 2132-2141). Detailed particle trajectories and deposition efficiencies, as well as acinar flow structures, were investigated under different orientations of gravity, for tidal breathing motion in an average human adult. Trajectories and deposition efficiencies inside the alveolated duct are strongly related to gravity orientation. While the motion of larger particles (3 microm) is relatively insensitive to convective flows compared with the role of gravitational sedimentation, finer 1 microm aerosols may exhibit, in contrast, complex kinematics influenced by the coupling between (i) flow reversal due to oscillatory breathing, (ii) local alveolar flow structure, and (iii) streamline crossing due to gravity. These combined mechanisms may lead to twisting and undulating trajectories in the alveolus over multiple breathing cycles. The extension of our study to a space-filling acinar tree was well suited to investigate the influence of bulk kinematic interaction on aerosol transport between ductal and alveolar flows. We found the existence of intricate trajectories of fine 1 microm aerosols spanning over the entire acinar airway network, which cannot be captured by simple alveolar models. In contrast, heavier 3 microm aerosols yield trajectories characteristic of gravitational sedimentation, analogous to those observed in the simple alveolated duct. For both particle sizes, however, particle inhalation yields highly nonuniform deposition. While larger particles deposit within a single inhalation phase, finer 1 microm particles exhibit much longer residence times spanning multiple breathing cycles. With the ongoing development of more realistic models of the pulmonary acinus, we aim to capture some of the complex mechanisms leading to deposition of inhaled aerosols. Such models may lead to a better understanding toward the optimization of pulmonary drug delivery to target specific regions of the lung.

High-percentage lung delivery in children from detergent-treated spacers.

Pressurized metered‐dose inhalers attached to spacers are now the most common form of delivery of anti‐asthma medication in children. However, no reliable data are available of how much drug reaches the lungs in children of different ages. This information is crucial, as it determines the efficacy of therapy. In this study, we present information on the amount of drug reaching the lungs in children from a pressurized metered‐dose inhaler attached to a detergent‐coated spacer. We studied 18 asthmatic children inhaling radiolabeled salbutamol through detergent treated spacers to minimize electrostatic charge on the spacer wall.

Eicosanoids in exhaled breath condensates in the assessment of childhood asthma

The value of measurements of eicosanoids in exhaled breath condensate (EBC) for the evaluation of childhood asthma is still inconclusive most likely because of the limited value of the methods used. In this case–control study in 48 asthmatic and 20 healthy children, we aimed to characterize the baseline profile of the inflammatory mediators cysteinyl leukotrienes (cysLTs), 9α11βPGF2, PGE2, PGF2α, 8‐isoprostane (8‐iso‐PGF2α) within EBC in asthmatic compared with healthy children using new methods. In addition, we investigated their relation to other inflammatory markers. The assessment included collection of EBC, measurement of fractional exhaled nitric oxide (FENO) and evaluation of urinary excretion of leukotriene E4. cysLTs were measured directly in EBC by radioimmunoassay and prostanoids were measured using gas chromatography negative‐ion chemical ionization mass spectrometry. Only cysLT levels were significantly higher in asthmatic compared with healthy children (pu2003=u20030.002). No significant differences in cysLTs were found between steroid naïve and patients receiving inhaled corticosteroids. In contrast, FENO was significantly higher in steroid naïve compared with steroid‐treated asthmatic and healthy children (pu2003=u20030.04 and 0.024, respectively). The diagnostic accuracy of cysLTs in EBC for asthma was 73.6% for the whole group and 78.2% for steroid‐naïve asthmatic children. The accuracy to classify asthmatic for FENO was poor (62.9%) for the whole group, but improved to 79.9% when only steroid‐naïve asthmatic children were taken into consideration. cysLTs in EBC is an inflammatory marker which distinguishes asthmatics, as a whole group, from healthy children.

Asthma control in Switzerland: a general practitioner based survey

ABSTRACT Background: Achievement of optimal asthma control is the goal of the Global Initiative for Asthma (GINA) guidelines. Methods: In a survey involving 281 physicians, asthma control was assessed using the Juniper asthma control questionnaire (ACQ); physicians were also asked to judge patients’ asthma control subjectively. Results: In total, 2127 patients were included. Follow-up was available in 1893 (89%) patients (885 females). The mean time between visits was 62 ± 29.3 days; mean age was 45 years (± 19 years) and 30% were smokers. Well-controlled asthma was found in 298 patients (16%). Smokers were less likely to have well-controlled asthma (smokers 12% vs. non-smokers 18%). Physicians assessed asthma control to be good in 292 patients (15%), sufficient in 504 (27%), insufficient in 954 (50%) and poor in 137 (7%) patients. Of the 292 patients assessed by their physicians as ‘good asthma control’, only 142 (49%) were confirmed as ‘well-controlled’ by the ACQ. At the first visit, 1308 (69%) patients were pre-treated with any inhaled corticosteroids (ICS). Pre-treatment with leukotriene receptor antagonists (LTRAs) was reported in 127 patients (7%). Add-on therapy with the LTRA montelukast was the most frequent treatment adjustment at the first visit. Out of 1893 patients who had a follow-up visit, 298 (16%) were well controlled at the first visit and 1170 (62%) at the follow-up visit. Conclusion: Asthma control is insufficient in the majority of patients. Improvement of asthma control can be achieved by using objective measures such as the ACQ in regular clinical practice and adapting therapy.

Comparison of subjective and objective measures in recurrently wheezy infants.

Objectives: The aim of this study was to compare subjective measures (overall health assessment both by the study physician and the child’s mother) with objective measurements of forced expiratory volumes (FEVt) and maximal flow at functional residual capacity v̇maxFRC) in recurrently wheezy infants. Methods: Sixteen wheezy infants (12 boys) aged 8–26 months were studied. A clinical assessment at visit 1 was followed by the run-in period during which day- and nighttime asthma symptom scores were obtained. The actual study period consisted of 2 visits when patient’s lung function was assessed. The first of which was during an acute exacerbation (visit 2), while the second was when the infant was asymptomatic (visit 3). FEVt were obtained by the raised volume rapid thoracic compression technique (RVRTC) and v̇maxFRC by the tidal volume rapid thoracic compression technique (TVRTC). Results: Mean FEVt but not mean v̇maxFRC were significantly lower at visit 2 compared to visit 3 (FEV0.5: p = 0.005, and FEV0.75: p = 0.002; v̇maxFRC: p = 0.15) and correlated well with overall health assessment by the study physician (FEV0.5: r = 0.82, and FEV0.75: r = 0.84), but not with the overall health assessment by the mother. Conclusions: We have shown in the present study that objective measurements of FEVt from a raised lung volume correlate well with the overall health assessment by the study physician; this was in contrast to measurements of v̇maxFRC in the tidal volume range. We therefore conclude that the RVRTC technique is a feasible method to assess and monitor obstructive lung disease in infancy.

Evaluation of the interrupter technique in healthy, unsedated infants

The interrupter technique may be used to monitor respiratory resistance and does not require active patient cooperation, but has yet to be applied in unsedated, spontaneously breathing infants. The aim of this study was to determine if the interrupter technique is feasible in spontaneously breathing infants and to investigate the influence of facemask types and analysis techniques on the interrupter resistance (Rint). Rint was measured in 14 healthy, unsedated, sleeping infants (aged 38.4 (31–56) days (mean (range)). Paired measurements were made using large volume, compliant (Mcomp) and small volume, rigid (Mrigid) facemasks. Flow and pressure were measured at the airway opening prior to- and following a brief airway occlusion (500u2005ms). Rint was calculated using four previously reported analysis techniques. Rint could be measured in all infants. Mcomp, independent of the analysis method significantly underestimated Rint (p<0.001). The variability and magnitude of Rint were significantly influenced by the choice of analysis method. The conclusion is that the interrupter technique is feasible in spontaneously breathing, unsedated infants. Equipment design and analysis method significantly influences interrupter resistance. Studies standardizing equipment and identifying the most appropriate analysis technique in this age group are needed.