RESUMO
The present study aimed to evaluate whether titration of fixed continuous positive airway pressure at home using telemonitoring produces patient outcomes equal to auto-adjusting positive airway pressure titration at home for patients with moderate obstructive sleep apnea. Patients were randomized with a 1:1 allocation ratio to receive either auto-adjusting positive airway pressure titration based on the median of the 95th percentile pressure across seven nights or fixed continuous positive airway pressure titration based on a fixed calculated pressure and specific adaptations after telemonitoring of device data after 3 and 7 nights. The results of the ambulatory titration were evaluated with in-laboratory polysomnography after 2 weeks. We hypothesized that fixed continuous positive airway pressure titration would be non-inferior to auto-adjusting positive airway pressure titration in respect to continuous positive airway pressure adherence at a 3-month follow-up. A non-inferiority margin of -0.75 hr was prespecified. One-hundred and four patients were randomly allocated to fixed continuous positive airway pressure (n = 52) and auto-adjusting positive airway pressure (n = 52) titration. The mean difference and the 95% confidence intervals in continuous positive airway pressure adherence after 3 months between the two arms were 0.80 (-0.08, 1.69) hr. The non-inferiority hypothesis was confirmed as the lower one-sided 97.5% confidence interval for the mean difference was above the prespecified margin. Patients in the fixed continuous positive airway pressure titration arm were titrated at significantly lower pressure level and had a significantly lower amount of average leaks compared with auto-adjusting positive airway pressure-titrated patients, while there was no difference in residual obstructive apnea-hypopnea index on polysomnography. Telemonitoring enables ambulatory continuous positive airway pressure titration with fixed pressure that is non-inferior to ambulatory titration with auto-adjusting pressure in patients with moderate obstructive sleep apnea.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono , Humanos , Pressão Positiva Contínua nas Vias Aéreas/métodos , Apneia Obstrutiva do Sono/terapia , PolissonografiaRESUMO
PURPOSE: Obstructive sleep apnea (OSA) is a prevalent and multifaceted disease. To date, the presence and severity of objectively identified comorbidities and their association with specific OSA phenotypes, CPAP adherence, and survival remain to be elucidated. The aim of this study is to cluster patients with OSA based on 10 clinically important objectively identified comorbidities, and to characterize the comorbidity clusters in terms of clinical and polysomnographic characteristics, CPAP adherence, and survival. STUDY DESIGN AND METHODS: Seven hundred ten consecutive patients starting CPAP for moderate-to-severe OSA were included. Comorbidities were based on generally accepted cutoffs identified in the peer-reviewed literature. Self-organizing maps were used to order patients based on presence and severity of their comorbidities and to generate clusters. RESULTS: The majority of patients were men (80%). They were generally middle-aged (52 years) and obese (BMI: 31.5 kg/m2). Mean apnea-hypopnea index (AHI) was 41 ± 20 per h of sleep. More than 94% of the patients had one or more comorbidities with arterial hypertension, dyslipidemia, and obesity being the most prevalent. Nine comorbidity clusters were identified. The clinical relevance of these comorbidity clusters was highlighted by the difference in symptoms, PSG parameters, and cardiovascular risk. Also, differences in CPAP adherence, improvements in ESS, and long-term survival were present between the clusters. CONCLUSION: Comorbidity prevalence in patients with OSA is high, and different comorbidity clusters, demonstrating differences in cardiovascular risk, CPAP adherence, and survival, can be identified. These results further substantiate the need for a comprehensive assessment of patients with OSA beyond the AHI.
Assuntos
Apneia Obstrutiva do Sono/complicações , Pressão Positiva Contínua nas Vias Aéreas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/mortalidade , Apneia Obstrutiva do Sono/terapia , Taxa de SobrevidaRESUMO
Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered.
Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Humanos , Aconselhamento Genético/métodos , Hipertensão Arterial Pulmonar/genética , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/terapia , Mutação , Hipertensão Pulmonar Primária Familiar/diagnóstico , Hipertensão Pulmonar Primária Familiar/genética , Testes Genéticos/métodos , Predisposição Genética para DoençaRESUMO
OBJECTIVE: To analyze the implication of the beta3-adrenoceptor (beta3-AR) pathway in human septic myocardium and a murine model of sepsis, a condition associated with myocardial depression. METHODS AND RESULTS: beta3-AR and eNOS protein abundance were increased (332+/-66.4% and 218+/-39.3; P<0.05) in hearts from septic patients. The effect of BRL37344, a beta3-AR-preferential agonist, was analyzed by videomicroscopy on the contractility of neonatal mouse ventricular myocytes (NMVM) incubated with conditioned medium from LPS-stimulated cultured macrophages (Mc-LPS+ medium). Stimulation of untreated NMVM with BRL37344 dose-dependently decreased the amplitude of contractile shortening (P<0.05). This response was abolished by L-NAME (NOS inhibitor). Incubation in Mc-LPS+ medium potentiated the depressing effect of BRL37344 (P<0.05) as well as of SR58611A (P<0.05) in wild-type myocytes. Importantly, the contractile depression was abrogated in cardiomyocytes from beta3-AR KO mice. CONCLUSIONS: beta3-AR are upregulated during sepsis in the human myocardium and by cytokines in murine cardiomyocytes, where they mediate an increased negative inotropic response to beta3 agonists. Activation of the beta3-AR pathway by catecholamines may contribute to the myocardial dysfunction in sepsis.
Assuntos
Miócitos Cardíacos/metabolismo , RNA/genética , Receptores Adrenérgicos beta 3/genética , Sepse/metabolismo , Regulação para Cima , Agonistas de Receptores Adrenérgicos beta 3 , Agonistas Adrenérgicos beta/farmacologia , Adulto , Animais , Animais Recém-Nascidos , Western Blotting , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Modelos Animais de Doenças , Etanolaminas/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , RNA/biossíntese , Ratos , Ratos Wistar , Receptores Adrenérgicos beta 3/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sepse/patologia , Sepse/fisiopatologia , EstereoisomerismoRESUMO
The role of nitric oxide (NO) as a regulator of cardiac contraction was suggested in the early nineties, but a consensual view of its main functions in cardiac physiology has only recently emerged with the help of experiments using genetic deletion or overexpression of the three nitric oxide synthase (NOS) isoforms in cardiomyocytes. Contrary to the effects of exogenous, pharmacologic NO donors, signaling by endogenous NO is restricted to intracellular effectors co-localized with NOS in specific subcellular compartments. This both ensures coordinate signaling by the three NOS isoforms on different aspects of the cardiomyocyte function and helps to reconcile previous apparently contradictory observations based on the use of non-isoform-specific NOS inhibitors. This review will emphasize the role of NOS on excitation-contraction coupling in the normal and diseased heart. Endothelial NOS and neuronal NOS contribute to maintain an adequate balance between adrenergic and vagal input to the myocardium and participate in the early and late phases of the Frank-Starling adaptation of the heart. At the early phases of cardiac diseases, inducible NOS reinforces these effects, which may become maladaptive as disease progresses.
Assuntos
Miocárdio/química , Óxido Nítrico Sintase/análise , Óxido Nítrico/fisiologia , Eletrofisiologia , Cardiopatias/enzimologia , Cardiopatias/etiologia , Humanos , Modelos Biológicos , Miocárdio/enzimologia , Óxido Nítrico Sintase/metabolismoRESUMO
Unilateral diaphragm paralysis is an often not recognised cause of dyspnoea. We present a patient with a unilateral phrenic nerve paralysis treated with diaphragmatic plication. Patient presented with life-style limiting dyspnoea and pulmonary function showed a decrease in FVC when lying down. Since there was no improvement after respiratory muscle training, plication of the hemidiaphragm was performed by a small thoracotomy. The patient improved with regard to respiratory complaints and lung function. Furthermore, we also demonstrate for the first time a significant improvement in exercise capacity with accompanying striking amelioration of quality of life. The patient is now in follow up up for more than 2 years and the impressive improvement in exercise capacity remains present. Surgical treatment of unilateral diaphragm paralysis has been described in case reports and in small series since 1985. Although comparison of the available data is difficult a diaphragm plication seems an effective and safe procedure for patients with symptomatic, acquired unilateral diaphragm paralysis. Improvement of dyspnoea is present in the majority of patients and we even observed an impressive amelioration in exercise capacity. Consequently, it seems appropriate to propose plication to patients with clear symptoms from the moment spontaneous recovery seems unlikely; yet, prospective randomised controlled studies are needed to prove this.
Assuntos
Diafragma/cirurgia , Dispneia/cirurgia , Doenças do Sistema Nervoso Periférico/cirurgia , Nervo Frênico , Paralisia Respiratória/cirurgia , Dispneia/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/complicações , Paralisia Respiratória/complicações , Resultado do TratamentoRESUMO
Pulmonary artery intima sarcoma is an uncommon but fatal tumor, which often masquerades chronic thromboembolic pulmonary hypertension (CTEPH) and in the present case Takayasu arteritis. Pulmonary arterial pressure is mildly elevated in the presence of extensive proximal lesions. A parenchyma thin-walled cavitary lesion may be a sign of pulmonary extravasation of the tumor.
RESUMO
Induced nasal obstruction can cause obstructive apnoeas in healthy subjects during sleep, but the relationship between nasal resistance measured during wakefulness and obstructive sleep apnoea syndrome (OSAS) is weak. It was postulated that if the subjects could not breathe through the nose, the oral airway must be used, but if this airway is narrowed as well, then it could precipitate sleep-disordered breathing (SDB). Nasal patency, Mallampati score (MS), neck circumference and body mass index were measured in 202 subjects referred to the authors' hospital to undergo a full-night polysomnography for suspicion of SDB. A significant correlation was found between the MS and apnoea/hypopnoea index measured during sleep. However, the relationship between these parameters was only significant in patients with nasal obstruction. The relative risk of having OSAS with a MS of III or IV was 1.95 for the whole group and 2.45 in patients with nasal obstruction. In conclusion, a high Mallampati score represents a predisposing factor for obstructive sleep apnoea syndrome, especially if it is associated with nasal obstruction. These patients merit special attention from both the sleep physician and the anaesthetist.