Ramsook, Andrew H.

Abstract On average, females have smaller airways than males. The largest discrepancy in airway size occurs during puberty, when endogenous sex hormone concentrations diverge between males and females. Transgender individuals often use gender‐affirming hormone therapy (GAHT) to align physical characteristics with gender identity. It is unknown whether GAHT influences airway size (luminal area and length). We evaluated the large conducting airways before starting GAHT and while undergoing years of GAHT. This retrospective within‐subject study included 12 adult transgender individuals who underwent CT scanning before starting GAHT and again after ≥1 year of GAHT. For each transgender individual, we identified two matched cisgender controls (one male and one female) who also underwent two CT scans over a comparable time interval for longitudinal comparison. We used a three‐dimensional reconstruction of CT imaging to measure luminal areas. Within‐subject changes in airway size between scans were assessed using Student's paired t ‐tests in transgender individuals undergoing feminizing hormone therapy. Variance between scans was assessed using Levene's test. Pre‐scans occurred an average of 2.0 ± 3.1 years before beginning GAHT. Transgender persons were on GAHT for an average of 3.3 ± 1.7 years (range, 1.0 – 6.7 years) at their second scan. We found no significant differences in airway luminal cross‐sectional areas for transgender persons on feminizing hormone therapy. The variance in airway size change between scans was not statistically different between transgender individuals and control subjects. Our findings suggest that the size of large conducting airways might remain unchanged after a period (>1 year) on GAHT.

AbstractInterstitial lung disease (ILD) encompasses pulmonary disorders characterized by chronic inflammation and fibrosis that disrupt pulmonary gas exchange. While ILD‐related changes in the lung parenchyma are well‐documented, less is known about how ILD affects luminal area within the large conducting airways. This retrospective, case–control study tested the hypothesis that patients with ILD would have greater large conducting airway luminal areas than healthy matched controls. Three‐dimensional reconstructions of computed tomography images were used to quantify airway luminal areas in patients with ILD (n = 82; 54% female) and healthy controls matched for age, sex, and height. Patients with ILD had 16%–22% greater airway luminal areas across all seven measured large conducting airways compared to controls (all p < 0.001). Among patients with ILD, males had 17%–34% greater height‐normalized airway luminal areas than females (all p < 0.05). These data provide evidence that ILD is associated with greater large conducting airway luminal area, even when matched for key demographic factors. Consistent with observations in health, males with ILD exhibited greater height‐normalized airway size than females. These findings offer new insight into airway remodeling in ILD and highlight potential sex differences in airway luminal area.

AbstractFatiguing inspiratory work has been shown to evoke a sympathetically mediated reflex that has systemic cardiovascular consequences, including increases in heart rate and blood pressure and a decrease in resting limb vascular conductance. Moreover, the response to this reflex appears to be attenuated in females compared with males. It remains to be seen whether this respiratory muscle metaboreflex also exerts an effect on cerebral blood flow. Cerebral blood flow is tightly regulated to maintain homeostasis and critical function. Therefore, it stands to reason that cerebrovascular haemodynamics would not be compromised through this respiratory muscle metaboreflex. We hypothesized that fatiguing inspiratory work would reduce resting limb conductance, but cerebral blood flow would be minimally impaired. Females (34 ± 10 years old, n = 12) and males (31 ± 8 years old, n = 12) performed a 5 min, high‐intensity bout of inspiratory pressure threshold loading (IPTL) designed to evoke the respiratory muscle metaboreflex. In response to IPTL, mean arterial pressure increased in both males and females (p < 0.001), and limb vascular conductance decreased to a greater degree in males than in females (p = 0.005). The cerebrovascular conductance index was higher in females (p = 0.007) but not affected by IPTL (p = 0.417). Our findings suggest that cerebral blood flow is spared from the redistribution of blood flow in response to fatiguing inspiratory work and that this protection is true in both males and females.

Key points The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex‐differences in respiratory system morphology. During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea. Using a single‐blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate‐intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults. When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. AbstractWe aimed to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. Eighteen healthy subjects (aged 60–80 years; nine men and nine women) completed two days of testing. On day 1, subjects were assessed for pulmonary function and performed a maximal incremental cycle exercise test. On day 2, subjects performed three 6‐min bouts of cycling at ventilatory threshold, in a single‐blind randomized manner, while breathing: (i) normoxic helium‐oxygen (HEL) to reduce the work of breathing (Wb) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH2O L−1 s−1 to increase Wb; and (iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (category‐ratio 10 Borg scale) were monitored throughout exercise. During the HEL condition, there was a significant decrease in Wb (men: –21 ± 6%, women: –17 ± 10%) relative to CON (both P < 0.01). Moreover, if EFL was present during CON (four men and five women), it was alleviated during HEL. Conversely, during the RES condition, Wb (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on Wb (P = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, P < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, the intensity of dyspnoea was unaffected, independent of sex (P = 0.46). When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea.