Growth of Nasal and Laryngeal Airways in Children: Implications in Breathing and Inhaled Aerosol Dynamics

Abstract

BACKGROUND:The human respiratory airway undergoes dramatic growth during infancy and childhood, which induces substantial variability in air flow pattern and particle deposition. However, deposition studies have typically focused on adult subjects, the results of which cannot be readily extrapolated to children. We developed models to quantify the growth of human nasallaryngeal airways at early ages, and to evaluate the impact of that growth on breathing resistance and aerosol deposition. METHODS: Four image-based nasal-laryngeal models were developed from 4 children, ages 10 days, 7 months, 3 years, and 5 years, and were compared to a nasallaryngeal model of a 53-year-old adult. The airway dimensions were quantified in terms of different parameters (volume, cross-section area, and hydraulic diameter) and of different anatomies (nose, pharynx, and larynx). Breathing resistance and aerosol deposition were computed using a highfidelity fluid-particle transport model, and were validated against the measurements made with the 3-dimensional models fabricated from the same airway computed tomography images. RESULTS: Significant differences in nasal morphology were observed among the 5 subjects, in both morphology and dimension. The turbinate region appeared to experience the most noticeable growth during the first 5 years of life. The nasal airway volume ratios of the 10-day, 7-month, 3-year, and 5-year-old subjects were 6.4%, 18.8%, 24.2%, and 40.3% that of the adult, respectively. Remarkable inter-group variability was observed in air flow, pressure drop, deposition fraction, and particle accumulation. The computational fluid dynamics predicted pressure drops and deposition fractions were in close agreement with in vitro measurements. CONCLUSIONS: Age effects are significant in both breathing resistance and micrometer particle deposition. The image/computational-fluid-dynamics coupled method provides an efficient and effective approach in understanding patient-specific air flows and particle deposition, which have important implications in pediatric inhalation drug delivery and respiratory disorder diagnosis.

Clinical Controversies in Aerosol Therapy for Infants and Children

“…1 In vivo comparative studies evaluating aerosol deposition within different regions of the human respiratory tract in infants, young children, and adults are lacking. A recent study 2 evaluating drug deposition using a 3-dimensional model rendering from computed tomography scans of healthy infants, children, and adults showed that substantial variability exists in airway morphology, air-flow dynamics, and regional aerosol deposition among subjects of different ages.…”

“…Younger patients have smaller nostrils, a shorter turbinate region, a narrower nasopharynx, a narrower pharynx-larynx, and a relatively larger anatomic dead space than do adults, making drug delivery a challenge. 2 Nasal airway resistance accounts for nearly half of the respiratory resistance in healthy infants, 3 and turbulent flow in this region likely accounts for a large amount of impactive drug loss in the upper airways. Interestingly, nasal breathing for aerosol delivery to the distal airways is similar to, or more efficient than, mouth breathing in infant and toddler models, 4 contrary to what is observed in older children and adults, who have more well-developed nasal turbinates and less complex airway structures.…”

“…The majority of aerosolized drugs that are provided to pediatric patients are used off-label, meaning that: (1) the drug either has not been cleared for aerosolization, (2) it has been cleared in a different patient population (adults), or (3) it is being used with a different delivery device than that cleared by the United States FDA. Drug manufacturers very seldom perform dose range and efficacy studies in infants and children, and doses may or may not be adjusted based on weight.…”

Upper airway resistance during growth: A longitudinal study of children from 8 to 17 years of age

“…Inconsistent changes in nasal patency occur at the same time as the most significant somatic growth, changes in nasal and orofacial morphology, and development of the permanent dentition. 17,[28][29][30] Among changes in size and shape of the respiratory and vocal tracts, laryngeal descent, associated with hyoideal descent, is greater in males, resulting in relatively longer airways. 31,32 No gender differences in nasal resistance have been found for children, 13,14,16 while Kim et al 23 reported lower resistance for females and also a decrease in resistance with age among adults.…”

Assessing New Technologies in Aerosol Medicine: Strengths and Limitations

“…Over the past several years, anatomically correct airway models have been used in an attempt to provide a more realistic evaluation of the drug output of a device under specific breathing conditions. [104][105][106] One area of significant concern is the fact that each laboratory, either academic or industry-affiliated, has developed its own model, making data comparison across laboratories very difficult.…”