Obstructive sleep apnoea (OSA) and type 2 DM mellitus (T2DM) share obesity as a major risk factor. Furthermore, these conditions share overlapping mechanisms including inflammation, activation of the ...autonomic nervous system, and hypoxia-linked endocrinopathy. Hence, the pathogenesis of the two conditions may be more closely related than previously recognised. This raises the question of whether treatment of OSA might assist resolution of obesity and/or T2DM. Here, we present a narrative review of the literature to identify clinical and scientific data on the relationship between obstructive sleep apnoea and T2DM control. We found there is a paucity of adequately powered well-controlled clinical trials to directly test for a causal association. While routine screening of all T2DM patients with polysomnography cannot currently be justified, given the high prevalence of sleep disordered breathing in the overweight/obese population, all T2DM patients should at a minimum have a clinical assessment of potential obstructive sleep apnoea risk as part of their routine clinical care. In particular, screening questionnaires can be used to identify T2DM subjects at higher risk of OSA for consideration of formal polysomnography studies. Due to morbid obesity being a common feature in both T2DM and OSA, polysomnography should be considered as a screening tool in such high-risk individuals.
We compared the validity of a new portable polysomnographic recorder against a laboratory-based polysomnographic system from the same manufacturer.
Simultaneous, full polysomnographic recordings from ...the portable device (PSGP) and the laboratory-based system (PSGL) were obtained using separate sets of sensors on 20 patients referred for investigation of sleep apnea.
After initial optimization of signals, the portable device was left unattended in 10 of the patients (to simulate home studies), while in the other 10 the signals were reviewed on a laptop computer screen and adjustments to electrode or sensor placement made as needed during the studies. Recordings were manually scored by a technologist blinded to the origin of the data.
The quality of signals was comparable between the PSGP and PSGL studies, apart from a slight decrease in respiratory signal quality during PSGP studies that led to reduced confidence in respiratory event scoring. Sao2 signal loss was also greater in unattended PSGP. There was good agreement between PSGP and PSGL for sleep variables and the apnea-hypopnea index (r = 0.99). The periodic limb movement index was slightly lower during unattended PSGP. Blinded physician assessment of the records led to a recommendation for repeat studies due to poor signal quality in one (10%) attended and one (10%) unattended portable recording. There was no significant discordance between PSGP and PSGL in the final diagnostic formulations.
Portable polysomnography is a viable alternative to laboratory-based polysomnography and may be improved further by better sensor attachment.
Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in ...misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference.
After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores.
Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points.
A total of 18,577 patients with COPD 72.0% male; mean age: 66.3 years (standard deviation 9.6) were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points.
The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed.
Daytime pulmonary hypertension (PH) is relatively common in obstructive sleep apnea (OSA) and is thought to be associated with pulmonary vascular remodeling (PRm). The extent to which PH is ...reversible with treatment is uncertain. To study this, we measured pulmonary hemodynamics (Doppler echocardiography) in 20 patients with OSA (apnea-hypopnea index AHI 48.6 +/- 5.2/h, mean +/- SEM) before and after 1 and 4 mo of CPAP treatment (compliance 4.7 +/- 0.5 h/night). Patients had normal lung function, and no cardiac disease or systemic hypertension. Doppler studies were performed at three levels of inspired oxygen concentration (11%, 21%, and 50%) and during incremental increases in pulmonary blood flow (10, 20, and 30 microg/kg/min dobutamine infusions). Treatment resulted in a decrease in pulmonary artery pressure (Ppa, 16.8 +/- 1.2 mm Hg before CPAP versus 13.9 +/- 0.6 mm Hg after 4 mo CPAP, p < 0.05) and total pulmonary vascular resistance (231.1 +/- 19.6 versus 186.4 +/- 12.3 dyn. s. cm(-)(5), p < 0.05). The greatest treatment effects occurred in the five patients who were pulmonary hypertensive at baseline. The pulmonary vascular response to hypoxia decreased after CPAP (DeltaPpa/DeltaSa(O(2)) 10.0 +/- 1.6 mm Hg before versus 6.3 +/- 0.8 mm Hg after 4 mo CPAP, p < 0.05). The curve of Ppa versus cardiac output (Q), derived from the incremental dobutamine infusion, shifted downward in a parallel fashion during treatment. Systemic diastolic blood pressure also fell significantly. Improvements in pulmonary hemodynamics were not attributable to changes in left ventricular diastolic function or Pa (O(2)). We conclude that CPAP treatment reduces Ppa and hypoxic pulmonary vascular reactivity in OSA and speculate that this may be due to improved pulmonary endothelial function.
PURPOSE OF REVIEWPulmonary hypertension leads to progressive increase in pulmonary vascular resistance, heart failure, and death. Pulmonary arterial hypertension (PAH) is a subset of pulmonary ...hypertension affecting small pulmonary arteries and not associated with underlying heart or lung disease. Dyspnea and exercise intolerance are hallmarks of PAH and are used to monitor disease progression. This review focuses on recent advances in the pathophysiology and treatment of dyspnea in PAH.
RECENT FINDINGSThe etiological classification of pulmonary hypertension and World Health Organization functional class clinical classification, as used to guide management, have recently been revised. Dyspnea and PAH disease progression are best assessed by cardiopulmonary exercise testing and the six-minute walk test. Understanding of the molecular pathogenesis of PAH has led to new classes of treatments, including prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. Prostanoids have the longest track record in treatment of PAH but a short half-life and cumbersome delivery systems limit their utility. More convenient endothelin receptor antagonists are becoming mainstream in PAH management. Phosphodiesterase-5 inhibitors improve exercise capacity and quality of life, although long-term outcome data are pending. Combination therapy with different medication classes appears promising for progressive disease.
SUMMARYEstablishing the cause and clinical severity of pulmonary hypertension is critical for management. The pathophysiology of dyspnea in PAH is complex and related to pulmonary vascular resistance. Although disease-specific treatments are now available, a cure for PAH remains elusive and trials of combination treatments to improve symptoms and outcomes are ongoing.
Background: Timely vaccine supply is critical during influenza pandemics. A recombinant hemagglutinin (rHA)-based vaccine could overcome production hurdles of egg-based vaccines but has never ...previously been tested in a real-life pandemic setting. The primary aim was to determine the efficacy of a recombinant pandemic vaccine and whether its immunogenicity could be enhanced by a novel polysaccharide adjuvant (Advaxac). Methods: 281 adults aged 18a70 years were recruited in a randomized, subject and observer blinded, parallel-group study of rHA H1N1/2009 vaccine with or without adjuvant. Immunizations were at 0 and 3 weeks with rHA 3, 11 or 45 mu g. Serology and safety was followed for 6 months. Results: At baseline, only 9.1% of subjects (95% CI: 6.0a13.2) had seroprotective H1N1/2009 titers. Seroconversion rates varied by rHA dose, presence of adjuvant, subject age and number of immunizations. Eighty percent (95% CI: 52a96) of 18a49 year olds who received rHA 45 mu g with adjuvant were seroprotected at week 3, representing a 11.1-fold increase in antibody titers from baseline. Advaxac adjuvant increased seroprotection rates by 1.9 times after the first, and 2.5 times after the second, immunization when compared to rHA alone. Seroprotection was sustained at 26 weeks and the vaccine was well tolerated with no safety issues. Conclusions: The study confirmed the ability to design, manufacture, and release a recombinant vaccine within a short time from the start of an actual influenza pandemic. Advaxac adjuvant significantly enhanced rHA immunogenicity.
IntroductionBreathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are ...limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness. This paper presents the protocol for a large, adequately powered randomised study evaluating the use of sertraline for chronic breathlessness in people with progressive life-limiting illnesses.Methods and analysisA total of 240 participants with modified Medical Research Council Dyspnoea Scale breathlessness of level 2 or higher will be randomised to receive either sertraline or placebo for 28 days in this multisite, double-blind study. The dose will be titrated up every 3 days to a maximum of 100 mg daily. The primary outcome will be to compare the efficacy of sertraline with placebo in relieving the intensity of worst breathlessness as assessed by a 0–100 mm Visual Analogue Scale. A number of other outcome measures and descriptors of breathlessness as well as caregiver assessments will also be recorded to ensure adequate analysis of participant breathlessness and to allow an economic analysis to be performed. Participants will also be given the option of continuing blinded treatment until either study data collection is complete or net benefit ceases. Appropriate statistical analysis of primary and secondary outcomes will be used to describe the wealth of data obtained.Ethics and disseminationEthics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences.Trial registration numberACTRN12610000464066.
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