Background -A study was undertaken to determine the influences of electrostatic charge, flow, delay, and multiple actuations on the in vitro delivery of salbutamol generated by a pressurised metered dose inhaler (pMDI) from small volume spacers used in infants. Methods -Ten actuations from a salbutamol pMDI were drawn at different flow rates after either single or multiple actuations, with or without delay, through either static or reduced static spacers. An ionic detergent was used to reduce the charge of plastic spacers (Babyhaler, Babyspacer, Aerochamber, Nebuhaler). Electrostatic charge was measured using an electrometer. A multistage liquid impinger was used to determine the particle size distribution of the output of the pMDI through the spacers. Results -Electrostatic charge on the surface of plastic spacers had the greatest influence on delivery, causing a decrease in drug delivery. Reducing charge by coating the surface with ionic detergent resulted in an increase of 46.5-71.1% (p<0.001) in small (<6.8 pm) particle delivery from small volume plastic spacers. Lower flow, delay, and multiple actuations resulted in decreased delivery from static spacers. Lower flow resulted in a decrease of 15% in small (<9.6 gm) particle delivery. Delay and multiple actuations resulted in a decrease of 40.7% and 76.0%, respectively, in small (<6.8 tm) particle delivery. The influences of lower flow, delay, and multiple actuations were greatly reduced or even eliminated by reducing charge. However, multiple actuations still resulted in a significant decreased delivery (p<0.05). The reduced static Nebuhaler had a higher delivery than all small volume spacers. Conclusions -Electrostatic charge has a major influence on the delivery of salbutamol from small volume spacers. Using a metal spacer or ionic detergent coating ofplastic spacers resulted in no or reduced charge and hence in improved delivery. Lower flow, delay, and multiple actuations played a major part only in static spacers. (Thorax 1996;51:985-988)

Low-frequency respiratory impedance (Zrs) data permit the separate estimation of the mechanical properties of the airways and the tissues, but they are difficult to collect in humans because of the need for apneic conditions. We exploited the apneic phase produced by invoking the Hering-Breuer reflex with end-inspiratory airway occlusion in five sedated infants aged 9 to 16 mo. A computer-controlled pump and solenoid valves were used to inflate the supine infants through a face mask to a transrespiratory pressure of 20 cm H2O and to affect the airway occlusion. A loudspeaker-in-box system was connected to the mask through a side-arm, and small-amplitude pseudorandom oscillations containing 23 frequency components between 0.5 and 20.75 Hz were applied for 6 s. Four consecutive measurements were made in each infant, and the averaged Zrs spectra were evaluated on the basis of a model containing the frequency-independent resistance (Raw) and inertance (law) of the airways, and the viscous damping (G) and elastance (H) parameters of the constant-phase compartment of the chest wall and parenchymal tissues. The measured Zrs values were consistent with the model up to 15 Hz, and the average fitting error was 0.89 +/- 0.11 (SD) cm H2O.s/L. The following parameter values were obtained: Raw = 10.0 +/- 2.1 cm H2O.s/L, law = 0.061 +/- 0.014 cm H2O.s2/L, G = 28.6 +/- 4.9 cm H2O/L, H = 141 +/- 55 cm H2O/L. The tissue hysteresivity (G/H) values were 0.218 +/- 0.061. Our results indicate that, in short apneic periods evoked by the Hering-Breuer reflex, reliable low-frequency Zrs data can be collected to partition the tissue and airway impedances in sedated 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 (V.max,FRC)with the tidal volume technique, and forced expiratory volume/time (FEV(t)) with RVFET. We used a standard methodology for the former. FEV(t) 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 V.max,FRC and a 15 or 20% fall in FEV(t) were calculated. The mean provocative concentration of methacholine required to produce a 40% fall in V.max,FRC was less than that required to produce a 20% fall in FEV0.5 by 0.39 DI (95% CI, -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 V.max,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.

Inhalation therapy for wheezy infants with either a nebulizer or a pressurized metered‐dose inhaler (pMDI) through a spacer is common practice. The aim of our study was to compare aerosol delivery to wheezy infants from a nebulizer and from a pMDI via two small volume spacers. Twenty wheezy infants (aged 4–12 months) were recruited. They inhaled salbutamol from a Pari‐Baby® nebulizer, from a detergent‐coated Babyhaler®, and from a Nebuchamber® in random order. A filter was placed between the inhalation systems and the patients. The amount of salbutamol deposited on the filter was measured using an ultraviolet spectrophotometer and was expressed as a percentage of the total nebulized or actuated doses. The mean total nebulized dose for the Pari‐Baby® (1030 μg) was higher (P < 0.001) than the mean actuated dove from a pMDI for the Babyhaler® (374 μg) and for the Nebuchamber® (378 μg). Mean drug deposition on the filter was 40.2% (150 μg) of the total actuated dose for the detergent‐coated Babyhaler® and 40.7% (154 μg) of the total actuated dose for the Nebuchamber®. There was no significant difference in drug deposition on the filter between the two spacers. Mean drug deposition on the filter was 25.3% (260 μg) of the total nebulized dose for the Pari‐Baby® nebulizer. There was no weight dependence in drug deposition on the filter for the two spacers, but, drug deposition increased with the subject's weight for the nebulizer. We have shown that aerosol delivery to wheezy infants from a pMDI through small volume spacers is effective and that a higher percentage of the total amount of salbutamol is delivered than from a nebulizer. The weight dependence in drug deposition for the nebulizer can be of clinical relevance. Pediatr Pulmonol. 1997; 23:212–216 © 1997 Wiley‐Liss, Inc.

No abstract

We previously studied low-frequency respiratory impedance (Zrs) data at an elevated lung volume to separate airway and tissue mechanical properties in normal infants (Am. I. Respir. Crit. Care Med. 1996; 154:161-166). The aim of the present study was to determine the volume dependence of the airway and tissue mechanics by extending Zrs measurements to lower lung volumes. Zrs spectra between 0.5 and 21 Hz were measured in supine sleeping infants (n = 8; 7 to 26 mo of age) at mean transrespiratory pressures (Ptr[mean]) of 20, 10, and 0 cm H2O, during periods of apnea induced by inflating the infants' lungs to a pressure of 20 cm H2O through a face mask. At each inflation pressure, a model containing airway resistance (Raw) and inertance (law) and tissue damping (G) and elastance (H) was fitted to Zrs data. At FRC, the values of Raw, law, G, and H were 20.6+/-4.9 (SD) cm H2O x s/L, 0.037+/-0.014 cm H2O x s2/L, 39.6+/-10.3 cm H2O/L, and 147+/-35 cm H2O/L, respectively. Increase of Ptr(mean) caused a monotonous decrease in Raw (42+/-7% of the value at FRC), while law remained constant. The tissue parameters were minimal at a Ptr(mean) of 10 cm H2O (68+/-10% and 78+/-6% in G and H, respectively) and significantly higher at both 0 and 20 cm H2O. Although Zrs measurements can be made in most infants at lung volumes as low as FRC, an inflation pressure of 20 cm H2O provides a higher success rate and is therefore a more suitable condition for general use.

No abstract

The raised-volume forced-expiration technique measures infant lung function over an extended volume range. To improve comparisons between individuals and populations, we investigated the influence of jacket pressure on outcome variables in 21 infants. To quantify pressure transmitted from the jacket to the pleural space at a given lung volume, the jacket was inflated against an occluded airway, and the increase in pressure at the mouth was measured. Flow-volume curves were recorded at transmitted pressure (Ptrans) values ranging from 0 to 41.9 cm H20. The effect of Ptrans on the FEV measures of FEV0.5, FEV0.75, and FVC, and on the forced expiratory flow measures of FEF25%, FEF50% and FEF75% was assessed. At Ptrans values between 0 to 20 cm H20, a significant positive relationship existed between transmitted pressure (Ptrans) and all outcome variables except FVC. At higher Ptrans values, all outcome variables demonstrated pressure independence, with the exception of FEF25% (which remained positive) and FVC (which was negative in a subgroup of wheezy infants). FEF75% values tended to decrease at Ptrans values > 25 cm H20. At Ptrans values between 20 and 25 cm H20, most outcome variables are pressure independent. This range is therefore the most suitable for use with the raised-volume forced expiration technique.