Variability of aerosol delivery via spacer devices in young asthmatic children in daily life

Pressurized metered dose inhalers (pMDI) are widely used together with spacers for the treatment of asthma in children. However, the variability of daily medication dose for pMDI/spacer combinations is not known. Electrostatic charge is a potential source of dose variability. Metal spacers have no static charge. This study assessed and compared within-subject variability of aerosol delivery of metal and plastic spacers. This was a randomized, crossover study in children with stable asthma aged 1-4 (group I, n=17) and 5-8 (group II, n=16) yrs. In both groups the amount of drug delivered to the mouth by a metal spacer (Nebuchamber) and one of two plastic (polycarbonate) spacers, i.e. Babyhaler in group I and Volumatic in group II was measured. The metal and plastic spacers were tested at home in a randomized order for 7 days each, using budesonide (200 microg b.i.d.). Aerosol was collected on a filter positioned between spacer and facemask or mouth. Budesonide on the filter was assessed by high performance liquid chromatography. The mean filter dose for each child (mean+/-SD) during the 7 days was expressed as a percentage of the nominal dose. Within-subject variability was expressed as coefficient of variation (CV). Mean filter dose in group I was 41.7+/-10.1% for Nebuchamber and 26.0+/-4.0% for Babyhaler (p<0.001). Mean filter dose in group II was 50.2+/-9.2% for Nebuchamber and 19.4+/-7.2% for Volumatic (p<0.001). Mean CV in group I was 34% for Nebuchamber and 37% for Babyhaler (p=0.44). Mean CV in group II was 23% for Nebuchamber and 34% for Volumatic (p=0.003). There was substantial within-subject dose variability in aerosol delivery in children using a pMDI/spacer at home. This variability was lower for the metal than for the plastic spacer in children 5-8 yrs of age. The dose delivered to the mouth was about two-fold higher fo

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

We have developed a new technique that allows assessment of infant lung function over an extended volume range. The lungs are rapidly inflated to a predetermined inflation pressure (PP) using a modified diaphragm pump. Forced expiratory flow-volume (FEFV) curves are then generated from raised lung volumes using an inflatable plastic jacket. We studied 26 normal infants with a median age of 14 mo (range, 3 to 23 mo). FEFV curves were obtained in each infant from end-tidal inspiration and from lung volumes set by a range of PP (15 to 20 cm H2O). Mean (SE) volume above FRC was 107 ml (9 ml), and mean forced expiratory time was 0.73 s (0.05 s) at end-tidal inspiration. Both measurements increased progressively with increases in PP to 251 ml (13 ml) and 1.04 s (0.06 s), respectively, at 20 cm H2O PP (p < 0.0001). Mean intrasubject coefficient of variation was 15.5% (95% confidence interval, 12 to 19%) for maximal flow at FRC, but it was less than 6% (95% CI, 4 to 8%) for forced expiratory volume-time (FEV(t)) measurements at all levels of PP. Twenty-seven recurrently wheezy infants with a median age of 13 mo (range, 6 to 18 mo) were subsequently studied using a PP of 17.5 cm H2O. Wheezy infants had a lower VmaxFRC [mean (1.39 ml/s/cm) and 95% CI (1.15 to 1.63 ml/s/cm)] than did normal infants (1.78, ml/s/cm; CI, 1.51 to 2.05) (p < 0.05). FEV(1) measurements were all lower in wheezy infants than in normals infants: mean FEV(0.5), 1.86 ml/cm (CI, 1.73 to 1.98) and 2.31 ml/cm (CI, 2.15 to 2.48), respectively (p < 0.0001); FEV(0.75), 2.20 ml/cm (CI, 2.07 to 2.32) and 2.72 ml/cm (CI, 2.52 to 2.91), respectively (p < 0.0001); FEV(1.0), 2.42 ml/cm (CI, 2.26 to 2.58) and 2.84 ml/cm (CI, 2.63 to 3.06), respectively (p < 0.005). The CI values of each FEV(t) measurement did not overlap between the wheezy and normal groups; however, the CI values of VmaxFRC overlapped markedly. in addition, FEV(1) parameters showed greater sensitivity in detecting reduced lung function (71 to 89%) than did VmaxFRC parameters (56%). We conclude that (1) FEV(t) measurements derived from a lung volume set by a standardized pressure are more reproducible than flow measurements in the tidal volume range; (2) FEV(t) measurements are significantly lower in wheezy infants than in normal infants, show less overlap than flow measurements in the tidal volume range, and therefore are better able to separate the two populations

Improved detection of abnormal respiratory function using forced expiration from raised lung volume in infants with cystic fibrosis

The raised volume rapid thoracic compression (RVRTC) technique is a recently developed method of measuring lung function in infants. The measurements of forced expiratory volume-time (FEV(0)) parameters from raised lung volumes have been shown to be less variable than maximal flow at functional residual dual capacity (VmaxFRC), obtained from the conventional rapid thoracic compression (RTC) technique, Measurements of VmaxFRC are highly variable, and may not be sensitive enough to detect a difference between normal infants and infants with cystic fibrosis (CF). The aim of this study was to determine whether the raised volume rapid thoracic compression technique could detect abnormal lune function in a group of CF infants with no current respiratory symptoms

Pressure transmission across the respiratory system at raised lung volumes in infants

Forced expiratory flow-volume (FEFV) curves can be generated from end-tidal inspiration in infants with use of an inflatable jacket. We have developed a technique to raise lung volume in the infant before generation of FEFV curves. Measurements of pressure transmission to the airway opening by use of static maneuvers have shown no change with increasing lung volume above end-tidal inspiration. The aim of this study was to determine, under dynamic conditions (i.e., during rapid thoracic compression), whether the efficiency of pressure transmission across the chest wall is altered by raising lung volume above the tidal range. Dynamic pressure transmission (Ptx,dyn) was measured in five infants (age 6-17 mo). Jacket pressure (Pj), esophageal pressure, and volume were measured throughout passive and FEFV curves at lung volumes set by 10, 15, and 20 cmH(2)O preset pressure. The group mean Ptx,dyn was 37 +/- 6% (SE) of Pj at end-tidal inspiration, and no change was seen with further increases in lung volume. However, a mean decrease in Ptx,dyn of 42% was evident throughout the tidal volume range (i.e., from end-tidal inspiration to end expiration). Isovolume static pressure transmission (Ptx,st) was measured in three of the five infants by inflation of the jacket in a stepwise manner with the airway closed. Measurements were made at end-tidal inspiration and lung volumes at 10, 15, and 20 cmH(2)O preset pressure. Resulting changes in Pj, esophageal pressure, and airway opening pressure were compared using linear regressions to determine Ptx,st. Mean Ptx,st to the airway opening was 56 +/- 4% (SE) at end-tidal inspiration and remained constant with increasing lung volume. We conclude that the transmission of Pj across the chest wall, during rapid thoracic compression, decreases throughout the tidal volume range but does not change with increased lung volume above end-tidal inspiration

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

Introduction Infants of mothers who smoke have reduced respiratory function and are more likely to develop wheezing, Little evidence is available on the effect of inutero cigarette-smoke exposure as opposed to postnatal exposure to environmental tobacco smoke, We used a previously validated non-invasive method to measure the time to peak tidal expiratory flow (tPTEF) as a proportion of expiratory time (tE) in newborn infants soon after birth to examine the effects of a family history of asthma and in-utero cigarette-smoke exposure on the infants' respiratory function

Methacholine responsiveness using the raised volume forced expiration technique in infants

Infant lung function can be assessed with the tidal volume ''squeeze'' technique or, over an extended volume range, with the newer raised volume forced expiration technique (RVFET). We assessed methacholine responsiveness in 11 infants, measuring both maximal expiratory flow at functional residual capacity (Vmax,FRC) with the tidal volume technique, and forced expiratory volume/time (FEVt) with RVFET. We used a standard methodology for the former. FEVt was measured by inflating the infant's lungs to 20 cm H2O and forcing expiration using a jacket setup to transmit a pressure of 20 cm H2O to the airway. Lung function was measured at baseline and after methacholine inhalations, increasing from 0.1 g/L to 10 g/L in half log dosage increments (DI). The provocative concentrations (PC) of methacholine leading to a 40% fall in Vmax,FRC and a 15 or 20% fall in FEVt were calculated. The mean provocative concentration of methacholine required to produce a 40% fall in Vmax,FRC was less than that required to produce a 20% fall in FEV0.5 by 0.39 DI (95% CII -0.60 to 1.38) and less than that required to produce a 20% fall in FEV0.75 by 0.42 DI (95%, CI, -0.54 to 1.39). Similarly, the provocative concentration of methacholine required to produce a 40% fall in Vmax,FRC was less than that required to produce a 15% fall in FEV0.5 by 0.14 DI (95% CI, -0.99 to 1.28) or a 15% fall in FEV0.75 by 0.13 DI (95% CI, -0.80 to 1.08), but the differences were small and not significant. Despite these differences the agreement between the two methods was good, and bronchoconstriction was not attenuated by the forced inspiration delivered by the raised volume maneuver. We conclude that the raised volume forced expiration technique is able to detect methacholine-induced bronchoconstriction

Parental factors affecting respiratory function during the first year of life

In a prospective, longitudinal, population-based cohort study of familial and environmental influences on the development of wheezing respiratory illness in early childhood, we identified infant length, weight, gender, and exposure to maternal cigarette smoking as significant determinants of lung function during the first year of life. A cohort of 237 infants (106 females: 131 males) was evaluated, and 496 lung function measurements were made between the ages of 1 1312 months. Respiratory function was assessed using the rapid thoracic compression technique to obtain maximum expiratory flow at functional residual capacity (V 32maxFRC). Parental history of asthma and smoking habits during pregnancy were obtained by questionnaire. Data were analyzed using a longitudinal random effects model. Infants with a parental history of asthma and/or in utero passive smoke exposure were compared to a reference group of infants who had no parental history of asthma and in whom neither parent smoked pre- or postnatally. Boys were found to have a consistently lower V 32maxFRC ("1221.05 mL.s"121) throughout the first year of life in comparison to girls (P < 0.05). Maternal smoking during pregnancy was associated with a lower V 32maxFRC in both genders in comparison to unexposed infants (P < 0.05). V 32maxFRC was unaffected by parental history of asthma. Gender-specific normative equations for V 32maxFRC throughout the first year of life were derived for the infant cohort as a whole and also for subgroups of infants, based on parental asthma and smoking history. We conclude that lung function during the first year of life differs between genders and is adversely affected by in utero passive tobacco smoke exposure. Gender-specific predictive equations for V 32maxFRC should be used during infancy

Distinctive immunoglobulin E anti-house dust allergen-binding specificities in a tropical Australian Aboriginal community

10.1111/j.1365-2222.2007.02786.xClinical and Experimental Allergy3791357-136

Evolved Th2 immune response bias in humans due to adaptation to climate

No abstract availabl