Meaghan J. MacNutt

Resting and exercise ventilatory chemosensitivity across the menstrual cycle

We hypothesized that resting and exercise ventilatory chemosensitivity would be augmented in women when estrogen and progesterone levels are highest during the luteal phase of the menstrual cycle. Healthy, young females (n = 10; age = 23 ± 5 yrs) were assessed across one complete cycle: during early follicular (EF), late follicular (LF), early luteal, and mid-luteal (ML) phases. We measured urinary conjugates of estrogen and progesterone daily. To compare values of ventilatory chemosensitivity and day-to-day variability of measures between sexes, males (n = 10; age = 26 ± 7 yrs) were assessed on 5 nonconsecutive days during a 1-mo period. Resting ventilation was measured and hypoxic chemosensitivity assessed using an isocapnic hypoxic ventilatory response (iHVR) test. The hypercapnic ventilatory response was assessed using the Read rebreathing protocol and modified rebreathing tests. Participants completed submaximal cycle exercise in normoxia and hypoxia. We observed a significant effect of menstrual-cycle phase on resting minute ventilation, which was elevated in the ML phase relative to the EF and LF phases. Compared with males, resting end-tidal CO(2) was reduced in females during the EF and ML phases but not in the LF phase. We found that iHVR was unaffected by menstrual-cycle phase and was not different between males and females. The sensitivity to chemical stimuli was unaffected by menstrual-cycle phase, meaning that any hormone-mediated effect is of insufficient magnitude to exceed the inherent variation in these chemosensitivity measures. The ventilatory recruitment threshold for CO(2) was generally lower in women, which is suggestive of a hormonally related lowering of the ventilatory recruitment threshold. We detected no effect of menstrual-cycle phase on submaximal exercise ventilation and found that the ventilatory response to normoxic and hypoxic exercise was quantitatively similar between males and females. This suggests that feed-forward and feed-back influences during exercise over-ride the effects of naturally occurring changes in sex hormones.

Anti-Oxidant N-Acetylcysteine Diminishes Diesel Exhaust-Induced Increased Airway Responsiveness in Person with Airway Hyper-Reactivity

BACKGROUND Inhalation of diesel exhaust (DE) at moderate concentrations causes increased airway responsiveness in asthmatics and increased airway resistance in both healthy and asthmatic subjects, but the effect of baseline airway responsiveness and anti-oxidant supplementation on this dynamic is unknown. OBJECTIVES We aimed to determine if changes in airway responsiveness due to DE are attenuated by thiol anti-oxidant supplementation, particularly in those with underlying airway hyper-responsiveness. METHODS Participants took N-acetylcysteine (600 mg) or placebo capsules three times daily for 6 days. On the last of these 6 days, participants were exposed for 2 h to either filtered air (FA) or DE (300 μg/m(3) of particulate matter smaller than 2.5 microns). Twenty-six non-smokers were studied under each of three experimental conditions (filtered air with placebo, diesel exhaust with placebo, and diesel exhaust with N-acetylcysteine) using a randomized, double-blind, crossover design, with a 2-week washout between conditions. Methacholine challenge was performed pre-exposure (baseline airway responsiveness) and post-exposure (effect of exposure). RESULTS Anti-oxidant supplementation reduced baseline airway responsiveness in hyper-responsive individuals by 20% (p = 0.001). In hyper-responsive individuals, airway responsiveness increased 42% following DE compared with FA (p = 0.03) and this increase was abrogated with anti-oxidant supplementation (diesel exhaust with N-acetylcysteine vs. filtered air with placebo, p = 0.85). CONCLUSIONS Anti-oxidant (N-acetylcysteine) supplementation protects against increased airway responsiveness associated with DE inhalation and reduces need for supplement bronchodilators in those with baseline airway hyper-responsiveness. Individuals with variants in genes of oxidative stress metabolism when exposed to DE are protected from increases in airway responsiveness if taking anti-oxidant supplementation.

Control of ventilation in humans following intermittent hypoxia

Exposure to chronic or intermittent hypoxia produces alterations in the ventilatory response to hypoxia. These adaptations can differ depending on the severity of the hypoxic stimulus, its duration, its pattern, and the presence or absence of other chemical stimuli. As such, there are significant differences between the responses to intermittent versus continuous hypoxia. Intermittent hypoxia (IH) has been shown to elicit significant changes in the peripheral chemoresponse, but the functional implications of these changes for resting and exercise ventilation are not clear. We summarize the impact of IH on resting chemosensitivity and discuss the use of IH to better understand ventilatory control during exercise. We also suggest future directions for this relatively young field, including potential clinical applications of IH research.

The pulmonary system during exercise in hypoxia and the cold

The demands for pulmonary O2 and CO2 transport in the exercising human are substantial. Fortunately, the regulatory and architectural limits of the pulmonary system meet the requirements of heavy exercise in most individuals. However, in some highly trained athletes the high metabolic demand of intense exercise is in excess of the capacity of the pulmonary system. Environmental considerations, in addition to those imposed by the demands of exercise, provide further physiological challenges that must be met. Winter athletes often encounter high‐altitude hypoxia and cold, either transiently during competition or repeatedly during training. In this brief review, we examine the pulmonary system during acute and chronic exercise in hypoxic and cold environmental conditions. Observations from studies conducted in humans are emphasized in order to ask questions about regulation, plasticity and the limits of human physiology. We also highlight new findings and controversial questions that would benefit from additional study.

Performance of Evacuated Blood Collection Tubes at High Altitude

Researchers and clinicians may not be aware that the performance of evacuated blood collection systems is impaired at high altitude. We tested four sizes of Vacutainer tubes at altitudes ranging from sea level to 5341 m to and determined that draw volumes are reduced by approximately 0.5 mL for every 1000 m gain in terrestrial elevation. Insufficient blood volume can limit possibilities for testing, inappropriate blood to additive ratios can skew test results and with smaller tubes at higher altitudes there is a possibility of air embolism. With foresight and proper planning, these problems can be avoided, and evacuated blood collection tubes can still be used safely and effectively at high altitude.

Glutathione-S-transferase P1, early exposure to mould in relation to respiratory and allergic health outcomes in children from six birth cohorts. A meta-analysis

There are conflicting study results regarding the association of exposure to visible mould and fungal components in house dust with respiratory and allergic diseases in children. It has been suggested that functional polymorphisms of the GSTP1 gene may influence the risk for allergic disorders through an impaired defence against oxidant injury.

Haematological acclimation and re-acclimation to hypoxia in the mouse

Haematological responses throughout 4 w of initial acclimation (IA) and three paradigms of re-acclimation (RA) to hypoxia (FI(O₂)) were examined in female mice. We hypothesised that (i) haematological responses would be increased during re-exposure, resulting in greater O₂-carrying capacity in RA compared to IA; and (ii) further improvements would occur when abbreviating the de-acclimation period to 1 w (RA↓DA) or extending the IA period to 8 w (RA↑IA). The serum [EPO] response was blunted in all RA groups compared to IA but the resulting reticulocyte response was similar in all experimental groups. The [Hb] response was the same in RA and RA↓DA as in IA but was blunted in RA↑IA due to a reduction in mean corpuscular Hb. The sensitivity of EPO-producing cells appears blunted but the sensitivity of erythroid precursors to EPO is enhanced by recent hypoxic exposure. Erythropoietic regulation is altered during RA in a manner that is dependent on the paradigm of initial exposure.