Ramsook, Andrew H

Three-dimensional reconstruction of airways has shown increased luminal area in patients with COVID-19 and post-acute sequelae of COVID-19 when compared with healthy controls. These findings suggest the role of large conducting airways in the pathogenesis of post-acute sequelae of COVID 19.

Background: Patients with respiratory manifestations of acute COVID-19 infection have enlarged luminal areas of central conducting airways demonstrated on computed tomography imaging and abnormal pulmonary function. In some cases, COVID-19 symptoms may persist for more than 4 weeks, referred to as long COVID, and the effect on airway luminal area remains unknown. Herein, we report airway luminal cross-sections areas among a long COVID group, compared to individuals with an acute COVID-19. We aim to investigate if large conducting airways sizes are different between acute COVID-19 and long COVID patients. Methods: A cohort of 181 people with long COVID were screened, of which 20 people (9 men, 11 women; 55.9 ± 14.1 years) were included in analyses. Twenty age, height, and sex matched patients with an acute (< 4 weeks of persistent symptoms from diagnosis) COVID-19 infection (55.7 ± 15.2 years) served as a comparison group. We used a three-dimensional reconstruction of computed tomography imaging to measure luminal areas of the trachea, right and left main bronchi, bronchus intermediate, right and left upper lobe, and left lower lobe bronchi at proximal, middle, and distal cross-sectional points in both groups. Airway luminal area was taken as the average of the three points. We compared average lumen area of long COVID patients with acute COVID-19 individuals, using an independent samples t-test. Results: We found no significant difference comparing measurements of the following airway luminal cross-sectional areas: trachea (277.7 ± 100.4 vs. 268.0 ± 70.5 mm2 p=0.73), right main bronchus (191.0 ± 66.1 vs. 190.1 ± 49.0 mm2, p=0.96), bronchus intermediate (112.3 ± 33.4 vs. 109.3 ± 27.9 mm2, p=0.76), right upper lobe bronchus (74.4 ± 21.0 vs. 73.7 ± 25.5 mm2, p=0.92), left main bronchus (129.1 ± 50.1 vs. 136.9 ± 38.0 mm2, p=0.58), left lower lobe bronchus (57.8 ± 18.2 vs. 59.0 ± 13.4 mm2, p=0.82), and left upper lobe bronchus (80.1 ± 19.5 vs. 77.9 ± 22.9 mm2, p=0.75) in the long COVID and acute COVID-19 groups respectively. Conclusion: In patients with long COVID, compared to those with an acute COVID-19 infection, we did not see differences in central airway luminal areas. Further analysis of a larger cohort is needed to determine whether enlarged airway luminal areas, associated with acute COVID-19, persist in long COVID. This research will expand knowledge on functional consequences for patients with long COVID. Funding: F32HL154320 to JWS; 5R35HL139854 to MJJ. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Background: Interstitial lung disease (ILD) encompasses several pulmonary disorders associated with scarring and fibrosis of pulmonary tissue. People with idiopathic pulmonary fibrosis, a subset of ILD, have greater central airway luminal area compared to age- and sex-matched healthy controls when evaluated using microcomputed tomography, a process examining the luminal area of ex-vivo lung tissue. In this study we aimed to confirm these findings using a different method of airway assessment, three-dimensional (3D) reconstruction of computed tomography (CT) scans. Moreover, in health, males have larger central airways than height-matched females, but it remains unknown if there are sex differences in airway area among people with ILD. We hypothesized that sex differences observed in healthy people would persist among people with ILD. Methods: A cohort of 399 patients with lung CT scans were screened, of which 19 people (7 females) with ILD were included in analyses after exclusions. People with ILD were matched based on sex, age, and height to 19 healthy controls. We assessed cross-sectional luminal area at the midpoint of seven conducting airways (trachea, left and right main bronchus, intermediate bronchus, left and right upper lobe, and left lower lobe). Results from pulmonary function tests were also abstracted, as available. To examine sex differences, we compared airway luminal area, normalized to participant height, between males and females with ILD. Sex differences were analyzed using a univariate ANOVA test. Results: People with ILD had a preserved ratio of forced expiratory volume in the first second to forced vital capacity (101 ±12%predicted) and decreased diffusing capacity for carbon monoxide (55 ±23%predicted). People with ILD had airways that were between 19.6%-45.0% larger than controls (p<0.05). Composite physiologic index, a marker of ILD severity, was not different between sexes (p=0.07). Males with ILD had significantly larger, luminal areas than females in two central airways - right main bronchus (1.46±0.41 vs. 1.07±0.22 mm2/cm, p=0.04) and left upper lobe (0.54±0.10 vs. 0.43±0.08 mm2/cm, p=0.02). However, luminal area of other central airways, including: trachea (2.15±0.57 vs. 1.65±0.32 mm2/cm, p=0.051), bronchus intermediate (0.77±0.23 vs. 0.61±0.13 mm2/cm, p=0.12), right upper lobe (0.47±0.15 vs. 0.40±0.06 mm2/cm, p=0.26), left main bronchus (0.93±0.33 vs. 0.69±0.16 mm2/cm, p=0.09), and left lower lobe (0.41±0.13 vs. 0.40±0.08 mm2 /cm, p=0.79) were not different between sexes in people with ILD. Conclusion: Sex differences observed in healthy people are potentially preserved in ILD, but a more robust sample is required to fully elucidate these findings. Illuminating any sex differences in ILD pathophysiology may provide knowledge to treat and improve clinical outcomes in ILD. Funding: National Heart, Lung, and Blood Institute (F32HL154320 to JWS; 5R35HL139854 to MJJ). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.