Background: Dyspnea is a major contributor to emotional distress in patients with amyotrophic lateral sclerosis (ALS). Sex differences in the reporting of dyspnea have been reported in adults affected by ALS as well as unaffected adults. Acute intermittent hypoxia (AIH), a passive experimental therapeutic intervention used to induce respiratory motor plasticity in ALS and other clinical populations, may elevate perceived dyspnea. However, it is unknown whether dyspnea during AIH differs by sex.
Objectives: To evaluate sex differences in dyspnea intensity associated with AIH in ALS.
Methods: Twenty-four adults (13 ALS and 11 controls) from an ongoing randomized controlled trial completed 4 laboratory visits: 2, 45-minute AIH sessions (15 hypoxic episodes – FiO2 0.10, for 1 minute alternating with 2 minutes of normoxia – FiO2 0.21) while 2 sham sessions delivered normoxic-inspired gas throughout. Dyspnea intensity was the primary outcome, reported by participants during gas interventions based on a 0-10 dyspnea scale. A linear mixed-effects model was used to assess the effects of sex, gas condition, and group on dyspnea responses.
Results: During hypoxic episodes, control females reported significantly higher dyspnea scores than control males (p=.017) with a strong effect size. Females with ALS also reported higher dyspnea scores than males with ALS during hypoxia, with a strong effect size, but did not achieve statistical significance (p=.066). During sham sessions, dyspnea ratings did not differ significantly between sexes.
Conclusions: Previous studies suggest females report higher levels of dyspnea during exertion than males, but almost none have examined dyspnea reporting during a passive therapeutic intervention, such as AIH. In patients with ALS, increased reports of dyspnea can be a precursor to impending ventilatory failure and may be a more sensitive indicator of the need for enhanced respiratory support. Future research is needed to evaluate the causes of increased dyspnea reporting in females.