Kelly Shepherd

Collapsibility of the Upper Airway at Different Concentrations of Propofol Anesthesia

Background:This study investigated the effect of varying concentrations of propofol on upper airway collapsibility and the mechanisms responsible for it. Methods:Upper airway collapsibility was determined from pressure–flow relations at three concentrations of propofol anesthesia (effect site concentration = 2.5, 4.0, and 6.0 &mgr;g/ml) in 12 subjects spontaneously breathing on continuous positive airway pressure. At each level of anesthesia, mask pressure was transiently reduced from a pressure sufficient to abolish inspiratory flow limitation (maintenance pressure = 12 ± 1 cm H2O) to pressures resulting in variable degrees of flow limitation. The relation between mask pressure and maximal inspiratory flow was determined, and the critical pressure at which the airway occluded was recorded. Electromyographic activity of the genioglossus muscle (EMGgg) was obtained via intramuscular electrodes in 8 subjects. Results:With increasing depth of anesthesia, (1) critical closing pressure progressively increased (−0.3 ± 3.5, 0.5 ± 3.7, and 1.4 ± 3.5 cm H2O at propofol concentrations of 2.5, 4.0, and 6.0 &mgr;g/ml respectively; P < 0.05 between each level), indicating a more collapsible upper airway; (2) inspiratory flow at the maintenance pressure significantly decreased; and (3) respiration-related phasic changes in EMGgg at the maintenance pressure decreased from 7.3 ± 9.9% of maximum at 2.5 &mgr;g/ml to 0.8 ± 0.5% of maximum at 6.0 &mgr;g/ml, whereas tonic EMGgg was unchanged. Relative to the levels of phasic and tonic EMGgg at the maintenance pressure immediately before a decrease in mask pressure, tonic activity tended to increase over the course of five flow-limited breaths at a propofol concentration of 2.5 &mgr;g/ml but not at propofol concentrations of 4.0 and 6.0 &mgr;g/ml, whereas phasic EMGgg was unchanged. Conclusions:Increasing depth of propofol anesthesia is associated with increased collapsibility of the upper airway. This was associated with profound inhibition of genioglossus muscle activity. This dose-related inhibition seems to be the combined result of depression of central respiratory output to upper airway dilator muscles and of upper airway reflexes.

High-intensity inspiratory muscle training in COPD

The aim of the present study was to investigate the effects of an interval-based high-intensity inspiratory muscle training (H-IMT) programme on inspiratory muscle function, exercise capacity, dyspnoea and health-related quality of life (QoL) in subjects with chronic obstructive pulmonary disease. A double-blind randomised controlled trial was performed. Sixteen subjects (11 males, mean forced expiratory volume in one second (FEV1) 37.4±12.5%) underwent H-IMT performed at the highest tolerable inspiratory threshold load (increasing to 101% of baseline maximum inspiratory pressure). Seventeen subjects (11 males, mean FEV1 36.5±11.5%) underwent sham inspiratory muscle training (S-IMT) at 10% of maximum inspiratory pressure. Training took place three times a week for 8 weeks and was fully supervised. Pre- and post-training measurements of lung function, maximum inspiratory pressure, maximum threshold pressure, exercise capacity, dyspnoea and QoL (Chronic Respiratory Disease Questionnaire; CRDQ) were obtained. H-IMT increased maximum inspiratory pressure by 29%, maximum threshold pressure by 56%, 6-min walk distance by 27 m, and improved dyspnoea and fatigue (CRDQ) by 1.4 and 0.9 points per item, respectively. These changes were significantly greater than any seen following S-IMT. In conclusion, high-intensity inspiratory muscle training improves inspiratory muscle function in subjects with moderate-to-severe chronic obstructive pulmonary disease, yielding meaningful reductions in dyspnoea and fatigue.

Elastic properties of the central airways in obstructive lung diseases measured using anatomical optical coherence tomography

RATIONALE Our understanding of how airway remodeling affects regional airway elastic properties is limited due to technical difficulties in quantitatively measuring dynamic, in vivo airway dimensions. Such knowledge could help elucidate mechanisms of excessive airway narrowing. OBJECTIVES To use anatomical optical coherence tomography (aOCT) to compare central airway elastic properties in control subjects and those with obstructive lung diseases. METHODS After bronchodilation, airway lumen area (Ai) was measured using aOCT during bronchoscopy in control subjects (n = 10) and those with asthma (n = 16), chronic obstructive pulmonary disease (COPD) (n = 9), and bronchiectasis (n = 8). Ai was measured in each of generations 0 to 5 while airway pressure was increased from -10 to 20 cm H(2)O. Airway compliance (Caw) and specific compliance (sCaw) were derived from the transpulmonary pressure (Pl) versus Ai curves. MEASUREMENTS AND MAIN RESULTS Caw decreased progressively as airway generation increased, but sCaw did not differ appreciably across the generations. In subjects with asthma and bronchiectasis, Caw and sCaw were similar to control subjects and the Pl-Ai curves were left-shifted. No significant differences were observed between control and COPD groups. CONCLUSIONS Proximal airway elastic properties are altered in obstructive lung diseases. Although central airway compliance does not differ from control subjects in asthma, bronchiectasis, or COPD, Ai is lower in asthma and the Pl-Ai relationship is left-shifted in both asthma and bronchiectasis, suggesting that airways are maximally distended at lower inflating pressures. Such changes reflect alteration in the balance between airway wall distensibility and radial traction exerted on airways by surrounding lung parenchyma favoring airway narrowing. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN12607000624482).

Gastro‐oesophageal reflux symptoms are related to the presence and severity of obstructive sleep apnoea

Repetitive airway occlusion during sleep in patients with obstructive sleep apnoea (OSA) results in the generation of negative intrathoracic pressures and ends in arousal, both of which may predispose to reflux during sleep (nocturnal reflux). We aimed to determine and compare the prevalence of nocturnal reflux symptoms and their sleep‐associated risk factors in untreated OSA patients, OSA patients using continuous positive airway pressure (CPAP) therapy, and the general population. Gastro‐oesophageal reflux and sleep questionnaires were completed by 1116 patients with polysomnography diagnosed OSA and by 1999 participants of the 2007 Busselton population health survey. Of the OSA patients, 137 completed the reflux questionnaire before and after treatment. Risk of OSA in the general population was assessed using the Berlin score. The prevalence of frequent (>weekly) nocturnal reflux symptoms was increased (P < 0.001) in OSA patients (10.2%) versus the general population (5.5%), in individuals from the general population at high (8.7%) versus low risk (4.3%) of OSA and in patients with severe (13.9%) versus mild OSA (5.1%). Frequent nocturnal reflux symptoms were associated with high risk (general population) (OR 1.9, P < 0.01) and severity of OSA (OSA population) OR 3.0, severe versus mild OSA, P < 0.001) after correcting for age, gender and body mass index. Treatment with CPAP decreased the prevalence of reflux symptoms significantly. In conclusion, the prevalence of nocturnal reflux symptoms is increased in those with or suspected of having OSA. This association is independent of other risk factors including age, gender and body mass index, suggesting a causal relationship between OSA and nocturnal reflux.

Radiation of the Australian Salicornioideae (Chenopodiaceae)—based on evidence from nuclear and chloroplast DNA sequences

In phylogenetic analyses of nuclear ITS and chloroplast trnL DNA sequences, the mostly endemic Australian genera; Halosarcia, Pachycornia, Sclerostegia, Tecticornia, and Tegicornia of the subfamily Salicornioideae (Chenopodiaceae) together form a monophyletic group, congruent with the hypothesis that they evolved from a common ancestor. However, limited genetic differentiation evident in both nrDNA and cpDNA sequences among these taxa suggests a possible rapid radiation. Based on fossil pollen records and climatic models of other authors, it is hypothesized that the expansion of the Australian endemic Salicornioideae most likely occurred during the Late Miocene to Pliocene, when increasing aridity caused the formation of extensive salt lakes along endorheic paleodrainage channels. Moreover, Australian Sarcocornia representatives were supported as monophyletic, nested within a paraphyletic Sarcocornia clade that also comprised European Salicornia in the ITS analysis. This suggests that Sarcocornia arrived in Australia subsequent to the ancestor of the Australian endemic genera most likely via long-distance dispersal.

Pharyngeal Dysphagia in Inflammatory Muscle Diseases Resulting from Impaired Suprahyoid Musculature

Dysphagia has previously been reported in the inflammatory myopathies (IMs): inclusion body myositis (IBM), dermatomyositis (DM), and polymyositis (PM). Patients report coughing, choking, and bolus sticking in the pharynx. Myotomy has been the treatment of choice, with variable success reported. We sought to determine underlying causes of dysphagia in IM patients using instrumental evaluation. Eighteen subjects participated in the study: four with DM, six with PM, and eight with IBM. They underwent simultaneous videofluoroscopy and manometry, yielding 214 swallows for analysis regarding function of the upper esophageal sphincter (UES), swallow initiation, hyolaryngeal excursion, and pharyngeal residue. Penetration and aspiration were also recorded. UES failed to relax in two participants. High incidence of pharyngeal dysphagia was noted; 72% of participants demonstrated abnormalities, including delayed swallow initiation (24%), decreased hyolaryngeal excursion (22%), pyriform residue (17%), and penetration (22%). Dysphagia in IM patients appears to be more due to impaired muscle contraction and reduced hyolaryngeal excursion than the often held belief of failed UES relaxation. The distinction between mechanisms causing patients’ dysphagia should be examined, particularly if CP myotomy is being considered as it may be contraindicated for patients with normal UES relaxation. More studies investigating IM patients pre- and post-myotomy are needed.

Comparison of incremental and constant load tests of inspiratory muscle endurance in COPD

The aim of the present study was to determine the relative value of incremental and constant load tests in detecting changes in inspiratory muscle endurance following high-intensity inspiratory muscle training (H-IMT) in chronic obstructive pulmonary disease. In total, 16 subjects (11 males; forced expiratory volume in one second (FEV1) 37.4±12.5%) underwent H-IMT. In addition, 17 subjects (11 males; FEV1 36.5±11.5%) underwent sham inspiratory muscle training (S-IMT). Training took place three times a week for 8 weeks. Baseline and post-training measurements were obtained of maximum threshold pressure sustained during an incremental load test (Pth,max) and time breathing against a constant load (tlim). Breathing pattern was unconstrained. H-IMT increased Pth,max and tlim relative to baseline and to any change seen following S-IMT. The effect size for Pth,max was greater than for tlim. Post-training tests were accompanied by changes in breathing pattern, including decreased duty cycle, which may have served to decrease inspiratory work and thereby contribute to the increase in Pth,max and tlim in both groups. When assessing inspiratory muscle function in chronic obstructive pulmonary disease via tests in which the pattern of breathing is unconstrained, the current authors recommend incremental load tests be used in preference to constant load tests. However, to attribute changes in these tests to improvements in inspiratory muscle endurance, breathing pattern should be controlled.

The effect of partial acclimatization to high altitude on loop gain and central sleep apnoea severity.

Background and objective:  Loop gain is an engineering term that predicts the stability of a feedback control system, such as the control of breathing. Based on earlier studies at lower altitudes, it was hypothesized that acclimatization to high altitude would lead to a reduction in loop gain and thus central sleep apnoea (CSA) severity.

Phylogenetic analysis of the Australian Salicornioideae (Chenopodiaceae) based on morphology and nuclear DNA

The Salicornioideae Kostel. are distinctive among the Chenopodiaceae Venet.. However, their phylogenetic relationships are poorly understood. Analyses of morphological and molecular characters were undertaken to evaluate relationships within the subfamily and to test the monophyly of the endemic Australian genera Halosarcia Paul G. Wilson, Pachycornia Hook.f., Sclerostegia Paul G. Wilson, Tecticornia Hook.f. and Tegicornia Paul G. Wilson. Kalidium Moq. and Halopeplis Bunge ex Ung.-Sternb. of the tribe Halopeplideae were used as outgroup representatives in the morphological analysis and resolved sister to the tribe Salicornieae. Allenrolfea Kuntze; Halocnemum Bieb. and Heterostachys Meyer formed an early branching group sister to a moderately supported clade comprised of the remaining Salicornieae. Only terminal groups of closely related species received significant bootstrap support in this analysis. In contrast, the current tribal classification of the Salicornioideae was not supported in the molecular analysis as Allenrolfea occidentalis Kuntz (tribe Salicornieae) positioned sister to Kalidium foliatum Moq. (tribe Halopeplideae) and the remaining Salicornieae. Three major clades received strong bootstrap support: Microcnemum+Arthrocnemum, Sarcocornia+Salicornia, and the endemic Australian genera. None of the endemic Australian genera was individually supported as monophyletic in either the morphological or the molecular analyses. Subspecies complexes, polyploids and hybrids may contribute to the lack of resolution and apparently high levels of homoplasy in the morphological analysis. A greater understanding of population level processes is required to begin to resolve the phylogeny of this complex group.

Worsening of central sleep apnea at high altitude--a role for cerebrovascular function.

Although periodic breathing during sleep at high altitude occurs almost universally, the likely mechanisms and independent effects of altitude and acclimatization have not been clearly reported. Data from 2005 demonstrated a significant relationship between decline in cerebral blood flow (CBF) at sleep onset and subsequent severity of central sleep apnea that night. We suspected that CBF would decline during partial acclimatization. We hypothesized therefore that reductions in CBF and its reactivity would worsen periodic breathing during sleep following partial acclimatization. Repeated measures of awake ventilatory and CBF responsiveness, arterial blood gases during wakefulness. and overnight polysomnography at sea level, upon arrival (days 2-4), and following partial acclimatization (days 12-15) to 5,050 m were made on 12 subjects. The apnea-hypopnea index (AHI) increased from to 77 ± 49 on days 2-4 to 116 ± 21 on days 12-15 (P = 0.01). The AHI upon initial arrival was associated with marked elevations in CBF (+28%, 68 ± 11 to 87 ± 17 cm/s; P < 0.05) and its reactivity to changes in PaCO2 [>90%, 2.0 ± 0.6 to 3.8 ± 1.5 cm·s(-1)·mmHg(-1) hypercapnia and 1.9 ± 0.4 to 4.1 ± 0.9 cm·s(-1)·mmHg(-1) for hypocapnia (P < 0.05)]. Over 10 days, the increases resolved and AHI worsened. During sleep at high altitude large oscillations in mean CBF velocity (CBFv) occurred, which were 35% higher initially (peak CBFv = 96 cm/s vs. peak CBFv = 71 cm/s) than at days 12-15. Our novel findings suggest that elevations in CBF and its reactivity to CO(2) upon initial ascent to high altitude may provide a protective effect on the development of periodic breathing during sleep (likely via moderating changes in central Pco2).