Sex-related differences in pulmonary vascular volume distribution

Abstract

Pulmonary arterial hypertension affects females more frequently than males, and there are known sex-related differences in the lungs. However, normal sex-related differences in pulmonary vascular structure remain incompletely described. We aimed to contrast computed tomography-derived pulmonary vascular volume and its distribution within the lungs of healthy adult females and males. From the CanCOLD Study, we retrospectively identified healthy never-smokers. We analyzed full-inspiration computed tomography images, using vessel and airway segmentation to generate pulmonary vessel volume, vessel counts, and airway counts. Vessels were classified by cross-sectional area >10, 5-10, and <5 mm² into bins, with volume summed within each area bin and in total. We included 46 females and 36 males (62 ± 9 years old). Females had lower total lung volume, total airway counts, total vessel counts, and total vessel volume (117 ± 31 vs. 164 ± 28 mL) versus males (all p < 0.001). Females also had lower vessel volume >10 mm² (14 ± 8 vs. 27 ± 9 mL), vessel volume 5-10 mm² (35 ± 11 vs. 55 ± 10 mL), and vessel volume <5 mm² (68 ± 18 vs. 82 ± 19 mL) (all p < 0.001). Normalized to total vessel volume, vessel volume >10 mm² (11 ± 4 vs. 16 ± 4%, p < 0.001) and 5-10 mm² (30 ± 6 vs. 34 ± 5%, p = 0.001) remained lower in females but vessel volume <5 mm² relative to total volume was 18% higher (59 ± 8 vs. 50 ± 7%, p < 0.001). Among healthy older adults, pulmonary vessel volume is distributed into smaller vessels in females versus males.

Keywords: aging; multislice computed tomography; pulmonary arterial hypertension; pulmonary circulation; sex characteristics.

Figure 1

Consolidated Standards of Reporting Trials diagram of case selection. Of 1521 participants with spirometry at Visit 1, 1419 were removed for an exclusion criterion, and 20 were removed for incomplete CT data, leaving 82 healthy participants including 36 males and 46 females. From each group, 16 were matched based on total lung volume within 5%. We were able to match 16 of each group by age ±5 years, CT total lung volume ±5%, and height as closely as possible in a subsample.

Figure 2

(a) Total lung volume (TLV) and total vascular volume (TVV) in males (M) and females (F). TVV is presented in absolute terms (b) and indexed to height (c) and TLV (d). TVV was lesser in females compared to males, even when controlling for their smaller statures and lung sizes. Mean and SD laid over individual data. N = 82.

Figure 3

Relative frequency histograms of pulmonary vascular volume (VV). Females more frequently had lower absolute VV contained within vessels with cross‐sectional areas (a) >10 mm² (VV > 10), (b) 5–10 mm² (VV5–10), and (c) <5 mm² (VV < 5). When VV in each cross‐sectional area was expressed as a proportion of total vascular volume (%TVV), females more frequently had lower (d) >10 mm² and (e) 5–10 mm², but higher (f) <5 mm². N = 82.

Figure 4

Pulmonary blood volume distribution across large, medium, and small vessels in females (♀) and males (♂) in the entire sample of N = 82 (upper), and in the matched subsample of n = 32 (lower). In females, the percentage of total vascular volume contained in small vessels was ~10% greater compared to males.

Figure 5

Relationships between (a) total vessel count and total lung volume (r = 0.753, p < 0.001), (b) total airway count and total lung volume (r = 0.382, p < 0.001), and (c) total vessel count and total airway count (r = 0.521, p < 0.001). N = 82.