Anatomical variability in the upper tracheobronchial tree: sex-based differences and implications for personalized inhalation therapies

Abstract

The morphometry of the large conducting airways is presumed to have a strong effect on the regional deposition of inhaled aerosol particles. Nevertheless, sex-based differences have not been fully quantified and are still largely ignored in designing inhalation therapies. To this end, we retrospectively analyzed high-resolution computer-tomography scans for 185 individuals (90 women, 95 men) in the age range of 12−89 years to determine airway luminal areas, airway lengths and bifurcation angles. Only subjects free of chronic airway disease were considered. In men, luminal areas of the upper conducting airways were on the average ~ 30-50% larger when compared to those in women, with the largest differences found in the trachea (289.72±54.25mm2 vs. 193.50±42.37mm2 for men/women respectively). The ratio of the largest luminal area in men to the smallest luminal area in women (in any given segment) ranged between 4.5 and 8.6, the largest differences being found in the lobar bronchi. Sex-based differences were minor in the case of bifurcation angles (e.g. average main bifurcation angle: 93.04±9.58o vs. 91.03±9.81o for men/women respectively), but large inter-subject variability was found irrespective of sex (e.g. range of main bifurcation angle: 65.04−122.01o vs. 69.46−113.94o for men/women respectively). Bronchial segments were shorter by ~ 5-20% in women relative to men, the largest differences being located in the upper lobes. False discovery rate (FDR) analysis revealed statistically significant associations among morphometric measures of the right lung in women (but not in men) suggesting two phenotypes among women that we attribute to the smaller female thoracic volume.

Sex, gender and the pulmonary physiology of exercise

“…Studies involving x-ray and acoustic reflectance measures noted that tracheal area was smaller in females than in males [43,44]. Recently, studies involving computed tomography imaging demonstrated that females have smaller central conducting airways (i.e., trachea to third generation bronchi) and the difference persists when subjects are matched for lung size [18,19] or height [17]. Upstream of the ∼third generation, the magnitude of sex differences in airway size decreases; however, this may be due to the size of these airways approaching the resolution limits of computed tomography.…”

“…• Males above the age of ∼14 years have proportionally greater airway luminal area of the large conducting airway (i.e., trachea to the third generation) than females [15,[17][18][19][20] • Males have larger absolute lung volumes and more alveoli than females [9, 21] • Females have "prismatic" geometry of the ribcage and lung while males have "pyramidal" ribcage and lung geometry [22][23][24] Functional differences • Higher W b and V ̇O2 RM for a given absolute V ̇E during exercise in females compared to males [10,13,53-27] Due to a higher resistive component of W b [25,[28][29][30] • Females have greater activation of "extra-diaphragmatic" inspiratory muscles for a relative or absolute V ̇E during exercise Noted in the scalene and sternocleidomastoid muscles [31,32] • Highly trained males are less likely to develop expiratory flow limitation during exercise than highly trained females [13,25] • Females have a blunted respiratory muscle metaboreflex [33][34][35][36][37] • EIAH can occur in untrained females but does not appear to occur in untrained males [38][39][40] • Older females have a higher perception of dyspnoea at absolute and relative exercise intensities than older males [10,11,41] EIAH: exercise-induced arterial hypoxaemia; V ̇E: minute ventilation; V ̇O2 RM : oxygen uptake of the respiratory muscles; W b : work of breathing.…”

Gender Modifies the Effect of Body Mass Index on Lung Function Decline in Mild-to-Moderate COPD Patients: A Pooled Analysis

“…In addition, emphysema might have also played a role, because emphysema is signi cantly associated with reduced BMI (24), and is also more common in male patients (25). Furthermore, sex-modi ed effects of BMI on FEV 1 decline may be related to anatomical differences in the large airways that have been observed between men and women, such as smaller central airways and lower thoracic volume in females (26,27). Due to concerns regarding reverse causality, we were unable to study the effects of dynamic changes in BMI (i.e., increased lung burden caused weight loss).…”

Anatomical Engineering and 3D Printing for Surgery and Medical Devices: International Review and Future Exponential Innovations

“…3DP plays a crucial role in the management of complex respiratory diseases. The high variability in the anatomy of the tracheobronchial tree [ 109 ] makes standardized interventional treatments very challenging especially for stent placement.…”