Giulio S. Dominelli

Exercise‐induced arterial hypoxaemia and the mechanics of breathing in healthy young women

•  By virtue of their smaller lung volumes and airway diameters, women develop more mechanical ventilatory constraints during exercise, which may result in increased vulnerability to hypoxaemia during exercise. •  Hypoxaemia developed at all exercise intensities with varying patterns and was more common in aerobically trained subjects; however, some untrained women also developed hypoxaemia. •  Mechanical respiratory constraints directly lead to hypoxaemia in some women and prevent adequate reversal of hypoxaemia in most women. •  Experimentally reversing mechanical constraints with heliox gas partially reversed the hypoxaemia in subjects who developed expiratory flow limitation. •  Due in part to increased mechanical ventilatory constraints, the respiratory systems response to exercise is less than ideal in most women.

Systematic review of non-invasive positive pressure ventilation for chronic respiratory failure

BACKGROUND This systematic review examined the effect of non-invasive positive pressure ventilation (NIPPV) on patient reported outcomes (PROs) and survival for individuals with or at risk of chronic respiratory failure (CRF). METHODS Randomised controlled trials (RCTs) and prospective non-randomised studies in those treated with NIPPV for CRF were identified from electronic databases, reference lists and grey literature. Diagnostic groups included in the review were amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), Duchenne muscular dystrophy (DMD), restrictive thoracic disease (RTD) and obesity hypoventilation syndrome (OHS). RESULTS Eighteen studies were included and overall study quality was weak. Those with ALS/MND had improved somnolence and fatigue as well as prolonged survival with NIPPV. For OHS, improvements in somnolence and fatigue, dyspnoea and sleep quality were demonstrated, while for RTD, measures of dyspnoea, sleep quality, physical function and health, mental and emotional health and social function improved. There was insufficient evidence to form conclusions regarding the effect of NIPPV for those with DMD. CONCLUSIONS This review has demonstrated that NIPPV influences PROs differently depending on the underlying cause of CRF. These findings may provide assistance to patients and clinicians to determine the relative costs and benefits of NIPPV therapy and also highlight areas in need of further research.

Hypoxia, not pulmonary vascular pressure, induces blood flow through intrapulmonary arteriovenous anastomoses

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased by acute hypoxia during rest by unknown mechanisms. Oral administration of acetazolamide blunts the pulmonary vascular pressure response to acute hypoxia, thus permitting the observation of IPAVA blood flow with minimal pulmonary pressure change. Hypoxic pulmonary vasoconstriction was attenuated in humans following acetazolamide administration and partially restored with bicarbonate infusion, indicating that the effects of acetazolamide on hypoxic pulmonary vasoconstriction may involve an interaction between arterial pH and PCO2 . We observed that IPAVA blood flow during hypoxia was similar before and after acetazolamide administration, even after acid–base status correction, indicating that pulmonary pressure, pH and PCO2 are unlikely regulators of IPAVA blood flow.

Exercise‐induced quadriceps muscle fatigue in men and women: effects of arterial oxygen content and respiratory muscle work

High work of breathing and exercise‐induced arterial hypoxaemia (EIAH) can decrease O2 delivery and exacerbate exercise‐induced quadriceps fatigue in healthy men. Women have a higher work of breathing during exercise, dedicate a greater fraction of whole‐body V̇O2 towards their respiratory muscles and develop EIAH. Despite a greater reduction in mens work of breathing, the attenuation of quadriceps fatigue was similar between the sexes. The degree of EIAH was similar between sexes, and regardless of sex, those who developed the greatest hypoxaemia during exercise demonstrated the most attenuation of quadriceps fatigue. Based on our previous finding that women have a greater relative oxygen cost of breathing, women appear to be especially susceptible to work of breathing‐related changes in quadriceps muscle fatigue.

Effect of Different Single-Session Educational Modalities on Improving Medical Students' Ability to Demonstrate Proper Pressurized Metered Dose Inhaler Technique

Objective. Pressurized metered dose inhalers (pMDIs) remain important therapeutic options for obstructive lung diseases. The ability to instruct and evaluate inhaler technique is a crucial skill that all medical professionals should possess; unfortunately, many professionals lack proficiency with pMDIs. We aimed to determine if brief education interventions of differing modalities can positively affect medical students’ skills over the long term. Methods. The baseline ability of medical students and first year residents to use pMDIs was scored via a 10-point scoring system. Students were randomized to receive no education, one-on-one instruction, or video instruction. Students were then retested immediately after the education and at the 3-month mark for retention of acquired skills. Results. Video, one-on-one and the placebo groups modalities statistically improved the average medical student’s score in the immediate retesting (7.5 and 7.4 vs. 4.7, p < .01, respectively). Moreover, the proportion of passing grades at the immediate recall significantly improved for both modalities. During retention testing, only video education had a statistically significant improvement in pass rate over the control group, as defined by an average score of 7 or better (8 vs. 1, p < .05). Conclusions. One-on-one teaching and video education were able to improve medical students’ ability to use pMDIs in short-term testing. However, only video education retained significant improvement compared with control after 3 months. This suggests that compared with traditional one-on-one teaching, video education is an effective means of teaching medical students how to improve their pMDI technique.

Quantifying the shape of the maximal expiratory flow–volume curve in mild COPD

Maximal expiratory flow-volume (MEFV) curve evaluation using absolute and percent predicted values of flow and volume are used to diagnose respiratory disease, but the shape of the curve is rarely used. Three mathematical methods were used to quantify shape of MEFV curves in subjects with mild COPD (n=19) and matched healthy controls (n=15). Those with mild COPD had a significantly greater slope-ratio (SR) (1.90 ± 0.24 vs. 1.28 ± 0.32) and Beta-angle (160 ± 6.7 vs. 186 ± 15.0) compared to healthy individuals (p<0.05). The flow-ratio method showed no difference between groups. A significant positive SR-volume relationship during expiration was observed in a greater number of mild COPD subjects (94%) compared to controls (20%) (p<0.001). With its increased spatial resolution and the potential to discern etiology behind specific curvature, we suggest using the SR method when available. The change in SR throughout expiration could help identify those who fall within the lower limit of normal lung function and those who may have pathological obstruction.

Repeated exercise-induced arterial hypoxemia in a healthy untrained woman

A healthy 36-year-old untrained (maximal oxygen consumption (V(O2max)): 39 mL/kg/min) woman completed multiple graded exercise tests on a treadmill. Temperature-corrected arterial blood samples were obtained in addition to esophageal pressure. Significant hypoxemia (-13 mm Hg arterial oxygen tension decrease) and arterial oxyhemoglobin desaturation (-6% decrease) was observed relative to rest and occurred during submaximal exercise and worsened at maximal intensities. Expiratory flow limitation (28-40% intersection of tidal volume) was present at near-maximal intensities. Relieving mechanical ventilatory constraints with a helium inspirate (79% He:21% O(2)) partially reversed the hypoxemia. Conversely, increasing chemical ventilatory stimuli, with hypercapnia (3.5% CO(2)), failed to increase ventilation. Maintaining oxyhemoglobin saturation, via a mildly hyperoxic (26% O(2)) inspirate, increased exercise duration (+45 s) and V(O2max) (+5 mL/kg/min). We attribute the hypoxemia to an excessive A-a(O2) resulting from ventilation-perfusion mismatch and secondarily to mechanical ventilatory constraints. We conclude that a healthy untrained woman can develop EIAH and this remains stable over a period of 6 months.

Effect of acetazolamide and methazolamide on diaphragm and dorsiflexor fatigue: a randomized controlled trial

Acetazolamide, a carbonic anhydrase (CA) inhibitor used clinically and to prevent acute mountain sickness, worsens skeletal muscle fatigue in animals and humans. In animals, methazolamide, a methylated analog of acetazolamide and an equally potent CA inhibitor, reportedly exacerbates fatigue less than acetazolamide. Accordingly, we sought to determine, in humans, if methazolamide would attenuate diaphragm and dorsiflexor fatigue compared with acetazolamide. Healthy men (dorsiflexor: n = 12; diaphragm: n = 7) performed fatiguing exercise on three occasions, after ingesting acetazolamide (250 mg three times a day) and then in random order, methazolamide (100 mg twice a day) or placebo for 48 h. For both muscles, subjects exercised at a fixed intensity until exhaustion on acetazolamide, with subsequent iso-time and -workload trials. Diaphragm exercise was performed using a threshold-loading device, while dorsiflexor exercise was isometric. Neuromuscular function was determined pre- and postexercise by potentiated transdiaphragmatic twitch pressure and dorsiflexor torque in response to stimulation of the phrenic and fibular nerve, respectively. Diaphragm contractility 3-10 min postexercise was impaired more for acetazolamide than methazolamide or placebo (82 ± 10, 87 ± 9, and 91 ± 8% of pre-exercise value; P < 0.05). Similarly, dorsiflexor fatigue was greater for acetazolamide than methazolamide (mean twitch torque of 61 ± 11 vs. 57 ± 13% of baseline, P < 0.05). In normoxia, methazolamide leads to less neuromuscular fatigue than acetazolamide, indicating a possible benefit for clinical use or in the prophylaxis of acute mountain sickness. NEW & NOTEWORTHY Acetazolamide, a carbonic anhydrase inhibitor, may worsen diaphragm and locomotor muscle fatigue after exercise; whereas, in animals, methazolamide does not impair diaphragm function. Compared with both methazolamide and the placebo, acetazolamide significantly compromised dorsiflexor function at rest and after exhaustive exercise. Similarly, diaphragm function was most compromised on acetazolamide followed by methazolamide and placebo. Methazolamide may be preferable over acetazolamide for clinical use and altitude illness prophylaxis to avoid skeletal muscle dysfunction.

Quantifying the shape of maximal expiratory flow-volume curves in healthy humans and asthmatic patients

Differences in the absolute flow and volume of maximal expiratory flow-volume (MEFV) curves have been studied extensively in health and disease. However, the shapes of MEFV curves have received less attention. We questioned if the MEFV curve shape was associated with (i) expiratory flow limitation (EFL) in health and (ii) changes in bronchial caliber in asthmatics. Using the slope-ratio (SR) index, we quantified MEFV curve shape in 84 healthy subjects and 8 matched asthmatics. Healthy subjects performed a maximal exercise test to assess EFL. Those with EFL during had a greater SR (1.15 ± 0.20 vs. 0.85 ± 0.20, p<0.05) yet, there was no association between maximal oxygen consumption and SR (r=0.14, p>0.05). Asthmatics average SR was greater than the healthy subjects (1.35 ± 0.03 vs. 0.90 ± 0.11, p<0.05), but there were no differences when bronchial caliber was manipulated. In conclusion, a greater SR is related to EFL and this metric could aid in discriminating between groups known to differ in the absolute size of MEFV curves.

Tracheal Epstein-Barr virus-associated smooth muscle tumour in an HIV-positive patient.

Epstein-Barr virus-related smooth muscle tumours (EBV-SMTs) are a rare but well recognized non-AIDS-defining malignancy that can also be found in several other immunosuppressed states. Pulmonary involvement of EBV-SMTs is not uncommon, but it can present with multifocal lesions in any anatomical site. The present article describes an HIV-positive woman with dyspnea who was found to have a large tracheal EBV-SMT. The authors discuss their approach to diagnosis and management, and present unique follow-up bronchoscopic imaging.