Effects of Age on Deposition of Inhaled Aerosols in the Human Lung

Xu, Gu; Yu, C.P.

doi:10.1080/02786828608959099

Cited by 73 publications

(50 citation statements)

References 14 publications

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“…The lack of correlation between the P:C ratio and age noted in this study is likely to reflect two opposing effects. Previous deposition studies [25] and theoretical models of deposition [27] suggest that there is a trend for increased deposition in larger central airways as age decreases. However the pattern of deposition of aerosols is very sensitive to airways obstruction and, indeed, can detect progressive obstructive airways disease long before changes in lung function become apparent [28,29].…”

Section: Resultsmentioning

confidence: 99%

Lung deposition from the Turbuhaler in children with cystic fibrosis

Devadason¹,

Everard²,

MacEarlan³

et al. 1997

Eur Respir J

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Drug delivery to patients using dry powder inhalers, such as the Turbuhaler®, is believed to be influenced by the inspiratory flow used. Clinical studies have indicated that this delivery system can be used effectively by children. However, it is not known how the total and weight-corrected dose delivered to the airways varies with age. A deposition study using technetium-99m ( 99m Tc)-labelled budesonide was performed in order to determine the effect of age on delivery.Twenty one children with cystic fibrosis, aged 4-16 yrs, were recruited. They were clinically stable with normal lung function. Initially, a gamma camera scan was taken in front of a flood source containing 37 MBq of 99m Tc. Subsequently, subjects inhaled through a low resistance inspiratory filter connected to a commercially available Turbuhaler®. Immediately afterwards they inhaled from a noncommercial Turbuhaler® containing budesonide labelled with 99m Tc, and then underwent anterior and posterior gamma camera scans. Both Turbuhaler® inhalers were attached to a portable spirometer and the peak inspiratory flow through the Turbuhaler® was recorded for each inhalation. The total body dose was calculated from the dose deposited on the inspiratory filter connected to the commercial Turbuhaler®. Analysis of the gamma camera images provided information on the proportion of the radiolabel delivered to the lungs compared to that deposited in the upper airway and stomach.As expected, a highly significant positive correlation was noted between the peak inspiratory flow generated by the patient through the Turbuhaler® and the dose delivered to the lung. Similarly, there was a highly significant positive correlation between age and "total lung dose". However, when total lung dose was corrected for body weight, there was a nonsignificant negative correlation with age. This study suggests that the "weight-corrected lung dose" achieved when children aged >6 yrs use the Turbuhaler®, is largely independent of age. It would appear that the flow-dependent properties of this device are such that the reduced peak inspiratory flow generated by younger children results in a lower dose to the lungs, but that this is off-set by their lower body weight. This is unlikely to be a property of other devices with different flow/drug delivery characteristics. Eur Respir J 1997; 10: 2023-2028 The convenience and ease of use of Turbuhaler®, a multidose dry powder inhaler (DPI), has resulted in its widespread use for the treatment of children with respiratory disease. Scintigraphic and pharmacokinetic deposition studies have indicated that this device is capable of delivering a mean of 20-30% of the nominal dose to the lungs of adults [1,2]. Although it is difficult to compare results from studies utilizing different methods [3], these results suggest that the device delivers a greater proportion of the nominal dose to the lungs of adult patients than do other DPIs [4,5], metereddose inhalers (MDIs) [4,6,7], and jet nebulizers [8,9], and these results are similar to o...

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Section: Resultsmentioning

confidence: 99%

Lung deposition from the Turbuhaler in children with cystic fibrosis

Devadason¹,

Everard²,

MacEarlan³

et al. 1997

Eur Respir J

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“…As the respiratory system develops, the differences in both airway geometry and respiratory condition are likely to affect its dosimetry and responsiveness (32). Development of the human respiratory system involves the differentiation and proliferation of over 40 different cell types as well as the formation of a highly ordered airway branching system with 25,000 distinct terminations giving rise to > 300 million alveoli.…”

Section: The Respiratory Systemmentioning

confidence: 99%

Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.

Dietert

Etzel

Chen

et al. 2000

Environ Health Perspect

226

122

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Fetuses, infants, and juveniles (preadults) should not be considered simply "small adults" when it comes to toxicological risk. We present specific examples of developmental toxicants that are more toxic to children than to adults, focusing on effects on the immune and respiratory systems. We describe differences in both the pharmacokinetics of the developing immune and respiratory systems as well as changes in target organ sensitivities to toxicants. Differential windows of vulnerability during development are identified in the context of available animal models. We provide specific approaches to directly investigate differential windows of vulnerability. These approaches are based on fundamental developmental biology and the existence of discrete developmental processes within the immune and respiratory systems. The processes are likely to influence differential developmental susceptibility to toxicants, resulting in lifelong toxicological changes. We also provide a template for comparative research. Finally, we discuss the application of these data to risk assessment.

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“…Pioneering work on adopting these computational methods to children was motivated by radiation protection considerations -from nuclear weapon or accident fallout, natural radon in homes, and other natural and anthropogenic sources (Hofmann et al, 1979;Crawford, 1982;Hofmann, 1982;Crawford and Eckerman, 1983). More recent modeling efforts were stimulated by an interest in other environmental contaminants including combustion products as well as inhaled medications (Phalen et al, 1985;Xu and Yu, 1986;Yu and Xu, 1987;Ferron et al, 1989;Martonen and Zhang, 1993).…”

Section: Models Proposedmentioning

confidence: 99%

“…Healy, unpublished;Crawford, 1982;Crawford and Eckerman, 1983;ICRP, 1994;NCRP, 1997). Recently, interest in medicinal aerosols and particulate urban air pollutants have stimulated model developments (Xu and Yu, 1986;Yu and Xu, 1987;Ferron et al, 1989;Hofmann et al, 1989;Kim and Hu, 1998;Martonen and Zhang, 1993). Modern aerosol deposition models are elegant with respect to the aerosol physics involved, the quantitative specification of respiratory tract anatomy, and the application of modern computers.…”

Section: Introductionmentioning

confidence: 99%

Methods for modeling particle deposition as a function of age

Phalen

Oldham

2001

Respiration Physiology

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The purpose of this paper is to review the application of mathematical models of inhaled particle deposition to people of various ages. The basic considerations of aerosol physics, biological characteristics and model structure are presented along with limitations inherent in modern modeling techniques. Application of the models to children and senescent adults has been largely based on extrapolating anatomical and physiological data from young adults to match the changes observed during growth and aging. Sample results are included for total particle deposition and deposition in the bronchial and pulmonary regions. The models proposed provide particle deposition predictions that are consistent with the scant measurements available. The models discussed appear to be on firm theoretical grounds, but they are largely limited in application to simple aerosols and average individuals. Also, additional validation of the computational predictions is needed.

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Effects of Age on Deposition of Inhaled Aerosols in the Human Lung

Cited by 73 publications

References 14 publications

Lung deposition from the Turbuhaler in children with cystic fibrosis

Lung deposition from the Turbuhaler in children with cystic fibrosis

Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.

Methods for modeling particle deposition as a function of age

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