Dynamic laryngeal narrowing during exercise: a mechanism for generating intrinsic PEEP in COPD?

INTRODUCTION: Patients with COPD commonly exhibit pursed-lip breathing during exercise, a strategy that, by increasing intrinsic positive end-expiratory pressure, may optimise lung mechanics and exercise tolerance. A similar role for laryngeal narrowing in modulating exercise airways resistance and the respiratory cycle volume–time course is postulated, yet remains unstudied in COPD. The aim of this study was to assess the characteristics of laryngeal narrowing and its role in exercise intolerance and dynamic hyperinflation in COPD. METHODS: We studied 19 patients (n=8 mild–moderate; n=11 severe COPD) and healthy age and sex matched controls (n=11). Baseline physiological characteristics and clinical status were assessed prior to an incremental maximal cardiopulmonary exercise test with continuous laryngoscopy. Laryngeal narrowing measures were calculated at the glottic and supra-glottic aperture at rest and peak exercise. RESULTS: At rest, expiratory laryngeal narrowing was pronounced at the glottic level in patients and related to FEV(1) in the whole cohort (r=−0.71, p<0.001) and patients alone (r=−0.53, p=0.018). During exercise, glottic narrowing was inversely related to peak ventilation in all subjects (r=−0.55, p=0.0015) and patients (r=−0.71, p<0.001) and peak exercise tidal volume (r=−0.58, p=0.0062 and r=−0.55, p=0.0076, respectively). Exercise glottic narrowing was also inversely related to peak oxygen uptake (% predicted) in all subjects (r=−0.65, p<0.001) and patients considered alone (r=−0.58, p=0.014). Exercise inspiratory duty cycle was related to exercise glottic narrowing for all subjects (r=−0.69, p<0.001) and patients (r=−0.62, p<0.001). CONCLUSIONS: Dynamic laryngeal narrowing during expiration is prevalent in patients with COPD and is related to disease severity, respiratory duty cycle and exercise capacity

Exercise Ventilatory Irregularity can be quantified by Approximate Entropy to detect Breathing Pattern Disorder

Background Breathing pattern disorder (BPD) is a prevalent cause of exertional dyspnea and yet there is currently no reliable objective measure for its diagnosis. We propose that statistical analysis of ventilatory irregularity, quantified by approximate entropy (ApEn), could be used to detect BPD when applied to cardiopulmonary exercise test (CPET) data. We hypothesized that ApEn of ventilatory variables (tidal volume (VT), breathing frequency (Bf), minute ventilation (VE)) would be greater, i.e. more irregular, in patients with BPD than healthy controls. Methods We evaluated ventilatory ApEn in 20 adults (14 female) with exertional dyspnoea, undergoing CPET and independently diagnosed with BPD by a specialist respiratory physiotherapist. Data were compared with 15 age- gender- and BMI-matched controls. ApEn for VT, Bf and VE were calculated for an incremental cycle exercise test. Results Patients with BPD more frequently rated breathlessness as the reason for exercise limitation and had a lower mean (SD) peak oxygen uptake compared with controls: 80 (18) vs. 124 (27) % predicted (P  0.88, conferred a sensitivity and specificity of 70% and 87% respectively, for detection of BPD. Conclusions Non-linear statistical interrogation of CPET-acquired ventilatory data has utility in the detection of BPD. A simple calculation of approximate entropy of ventilation, during an incremental cardiopulmonary exercise test, provides a quantitative method to detect BPD

End-stage renal disease in young black males in a black-white population: longitudinal analysis of the Bogalusa Heart Study

<p>Abstract</p> <p>Background</p> <p>Risk factors in childhood create a life-long burden important in the development of cardiovascular (CV) disease in adulthood. Many risk factors for CV disease (e.g., hypertension) also increase the risk of renal disease. However, the importance of childhood risk factors on the development of chronic kidney disease and end-stage renal disease (ESRD) is not well characterized.</p> <p>Methods</p> <p>The current observations include data from Bogalusa Heart Study participants who were examined multiple times as children between 1973 and 1988.</p> <p>Results</p> <p>Through 2006, fifteen study participants subsequently developed ESRD in adulthood; seven with no known overt cause. Although the Bogalusa Heart Study population is 63% white and 37% black and 51% male and 49% female, all seven ESRD cases with no known overt cause were black males (p < 0.001). Mean age-adjusted systolic and diastolic blood pressure in childhood was higher among the ESRD cases (114.5 mmHg and 70.1 mmHg, respectively) compared to black (103.0 mmHg and 62.3 mmHg, respectively) and white (mean = 103.3 mmHg and 62.3 mmHg, respectively) boys who didn't develop ESRD. The mean age-adjusted body mass index in childhood was 23.5 kg/m²among ESRD cases and 18.6 kg/m²and 18.9 kg/m²among black and white boys who didn't develop ESRD, respectively. Plasma glucose in childhood was not significantly associated with ESRD.</p> <p>Conclusion</p> <p>These data suggest black males have an increased risk of ESRD in young adulthood. Elevated body mass index and blood pressure in childhood may increase the risk for developing ESRD as young adults.</p

Correction: Reusable snorkel masks adapted as particulate respirators

ntroduction During viral pandemics, filtering facepiece (FFP) masks together with eye protection form the essential components of personal protective equipment (PPE) for healthcare workers. There remain concerns regarding insufficient global supply and imperfect protection offered by currently available PPE strategies. A range of full-face snorkel masks were adapted to accept high grade medical respiratory filters using bespoke-designed 3D-printed connectors. We compared the protection offered by the snorkel to that of standard PPE using a placebo-controlled respirator filtering test as well as a fluorescent droplet deposition experiment. Out of the 56 subjects tested, 42 (75%) passed filtering testing with the snorkel mask compared to 31 (55%) with a FFP3 respirator mask (p = 0.003). Amongst the 43 subjects who were not excluded following a placebo control, 85% passed filtering testing with the snorkel versus to 68% with a FFP3 mask (p = 0.008). Following front and lateral spray of fluorescence liquid particles, the snorkel mask also provided superior protection against droplet deposition within the subject’s face, when compared to a standard PPE combination of FFP3 masks and eye protection (3.19x108 versus 6.81x108 fluorescence units, p<0.001). The 3D printable adaptors are available for free download online at https://www.ImperialHackspace.com/COVID-19-Snorkel-Respirator-Project/. Conclusion Full-face snorkel masks adapted as particulate respirators performed better than a standard PPE combination of FFP3 mask and eye protection against aerosol inhalation and droplet deposition. This adaptation is therefore a promising PPE solution for healthcare workers during highly contagious viral outbreaks

Siponimod (BAF312) prevents synaptic neurodegeneration in experimental multiple sclerosis

Data from multiple sclerosis (MS) and the MS rodent model, experimental autoimmune encephalomyelitis (EAE), highlighted an inflammation-dependent synaptopathy at the basis of the neurodegenerative damage causing irreversible disability in these disorders. This synaptopathy is characterized by an imbalance between glutamatergic and GABAergic transmission and has been proposed to be a potential therapeutic target. Siponimod (BAF312), a selective sphingosine 1-phosphate1,5 receptor modulator, is currently under investigation in a clinical trial in secondary progressive MS patients. We investigated whether siponimod, in addition to its peripheral immune modulation, may exert direct neuroprotective effects in the central nervous system (CNS) of mice with chronic progressive EAE

Angiotensin-converting enzyme inhibition as an adjunct to pulmonary rehabilitation in COPD

Rationale: Epidemiological studies in older individuals have found an association between use of ACE-inhibition (ACE-I) therapy and preserved locomotor muscle mass, strength and walking speed. ACE-I therapy might therefore have a role in the context of pulmonary rehabilitation. Objectives: We investigated the hypothesis that enalapril, an ACE-inhibitor, would augment the improvement in exercise capacity seen during pulmonary rehabilitation. Methods: We performed a double-blind, placebo-controlled, parallel-group randomised controlled trial. COPD patients, with at least moderate airflow obstruction and taking part in pulmonary rehabilitation, were randomised to either 10 weeks therapy with an ACE-inhibitor (10mg enalapril) or placebo. Measurements: The primary outcome measurement was the change in peak power (assessed using cycle ergometry) from baseline. Main Results: Eighty patients were enrolled, seventy-eight randomised (age 67±8years, FEV1 48±21% predicted), and sixty-five completed the trial (34 placebo, 31 ACE-inhibitor). The ACE-inhibitor treated group demonstrated a significant reduction in systolic blood pressure (Δ-16mmHg, 95% CI -22 to -11) and serum ACE activity (Δ-18IU/L, 95% CI -23 to -12) versus placebo (between group differences p<0.0001). Peak power increased significantly more in the placebo group (placebo Δ+9 Watts, 95% CI 5 to 13 vs. ACE-I Δ+1 Watt, 95% CI -2 to 4, between group difference 8 Watts, 95% CI 3 to 13, p=0.001). There was no significant between group difference in quadriceps strength or health-related quality of life. Conclusion: Use of the ACE-inhibitor enalapril alongside a programme of pulmonary rehabilitation, in patients without an established indication for ACE-inhibition, reduced the peak work rate response to exercise training in COPD patients. Clinical trial registration available at www.controlled-trials.com, ID ISRCTN79038750

Reusable snorkel masks adapted as particulate respirators

ntroduction During viral pandemics, filtering facepiece (FFP) masks together with eye protection form the essential components of personal protective equipment (PPE) for healthcare workers. There remain concerns regarding insufficient global supply and imperfect protection offered by currently available PPE strategies. A range of full-face snorkel masks were adapted to accept high grade medical respiratory filters using bespoke-designed 3D-printed connectors. We compared the protection offered by the snorkel to that of standard PPE using a placebo-controlled respirator filtering test as well as a fluorescent droplet deposition experiment. Out of the 56 subjects tested, 42 (75%) passed filtering testing with the snorkel mask compared to 31 (55%) with a FFP3 respirator mask (p = 0.003). Amongst the 43 subjects who were not excluded following a placebo control, 85% passed filtering testing with the snorkel versus to 68% with a FFP3 mask (p = 0.008). Following front and lateral spray of fluorescence liquid particles, the snorkel mask also provided superior protection against droplet deposition within the subject’s face, when compared to a standard PPE combination of FFP3 masks and eye protection (3.19x108 versus 6.81x108 fluorescence units, p<0.001). The 3D printable adaptors are available for free download online at https://www.ImperialHackspace.com/COVID-19-Snorkel-Respirator-Project/. Conclusion Full-face snorkel masks adapted as particulate respirators performed better than a standard PPE combination of FFP3 mask and eye protection against aerosol inhalation and droplet deposition. This adaptation is therefore a promising PPE solution for healthcare workers during highly contagious viral outbreaks