Real-World Switching to Riociguat: Management and Practicalities in Patients with PAH and CTEPH.

PURPOSE: A proportion of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) do not achieve treatment goals or experience side effects on their current therapy. In such cases, switching patients to a new drug while discontinuing the first may be a viable and appropriate treatment option. CAPTURE was designed to investigate how physicians manage the switching of patients to riociguat in real-world clinical practice. Observations from the study were used to assess whether recommendations in the riociguat prescribing information are reflected in clinical practice. METHODS: CAPTURE was an international, multicenter, uncontrolled, retrospective chart review that collected data from patients with PAH or inoperable or persistent/recurrent CTEPH who switched to riociguat from another pulmonary hypertension (PH)-targeted medical therapy. The primary objective of the study was to understand the procedure undertaken in real-world clinical practice for patients switching to riociguat. RESULTS: Of 127 patients screened, 125 were enrolled in CAPTURE. The majority of patients switched from a phosphodiesterase type 5 inhibitor (PDE5i) to riociguat and the most common reason for switching was lack of efficacy. Physicians were already using the recommended treatment-free period when switching patients to riociguat from sildenafil, but a slightly longer period than recommended for tadalafil. In line with the contraindication, the majority of patients did not receive riociguat and PDE5i therapy concomitantly. Physicians also followed the recommended dose-adjustment procedure for riociguat. CONCLUSION: Switching to riociguat from another PH-targeted therapy may be feasible in real-world clinical practice in the context of the current recommendations.

Correction to: Real-World Switching to Riociguat: Management and Practicalities in Patients with PAH and CTEPH.

The original version of this article unfortunately contained a mistake. In the "Results" section, the percentage of patients with inoperable or persistent/recurrent CTEPH included in the study was reported as 85%. This has been corrected to 68% with this erratum.

Non-anaemic iron deficiency impairs response to pulmonary rehabilitation in COPD.

BACKGROUND AND OBJECTIVE: Non-anaemic iron deficiency (NAID) might alter the oxygen pathway in health and disease. The current study aims at assessing the impact of NAID on aerobic capacity in patients with chronic obstructive pulmonary disease (COPD). METHODS: A prospective sample of 70 non-anaemic COPD patients candidate to participate in an 8-week pulmonary rehabilitation (PR) programme was studied. Incremental cycling exercise to peak oxygen uptake (V'O2peak ) and constant work-rate exercise at 80% V'O2peak to exhaustion were assessed pre- and post-PR. Training-induced increase of endurance time (ET) ≥33%, which represented the minimal clinically important difference, classified patients as responders to exercise training. RESULTS: The prevalence of NAID was 48% (n = 34) showing no relationship with the Global Initiative for Chronic Obstructive Lung Disease stages (P = 0.209). Patients with NAID showed lower pre-training ET (P = 0.033) and V'O2peak (P = 0.007) than normal iron status (NIS) patients after adjustment for potential covariates. Significant training-induced physiological changes were seen in the NIS group (ΔV'O2peak 68(132) mL/min; P = 0.009), but not in the NAID group (ΔV'O2peak 26 (126) mL/min; P = 0.269). The NAID group showed lower percentage of responders to training (56%) than the NIS group (78%) (P = 0.041). CONCLUSIONS: COPD patients with NAID showed lower pre-training aerobic capacity and reduced training-induced response than NIS patients after adjusting for potential confounding variables.

NKG2D mediates NK cell hyperresponsiveness and influenza-induced pathologies in a mouse model of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial and perivascular inflammation and largely irreversible airflow obstruction. Acute disease exacerbations, due frequently to viral infections, lead to enhanced disease symptoms and contribute to long-term progression of COPD pathology. Previously, we demonstrated that NK cells from cigarette smoke (CS)-exposed mice exhibit enhanced effector functions in response to stimulating cytokines or TLR ligands. In this article, we show that the activating receptor NKG2D is a key mediator for CS-stimulated NK cell hyperresponsiveness, because CS-exposed NKG2D-deficient mice (Klrk1(-/-)) did not exhibit enhanced effector functions as assessed by cytokine responsiveness. NK cell cytotoxicity against MHC class I-deficient targets was not affected in a COPD model. However, NK cells from CS-exposed mice exhibit greater cytotoxic activity toward cells that express the NKG2D ligand RAET1ε. We also demonstrate that NKG2D-deficient mice exhibit diminished airway damage and reduced inflammation in a model of viral COPD exacerbation, which do not affect viral clearance. Furthermore, adoptive transfer of NKG2D(+) NK cells into CS-exposed, influenza-infected NKG2D-deficient mice recapitulated the phenotypes observed in CS-exposed, influenza-infected wild-type mice. Our findings indicate that NKG2D stimulation during long-term CS exposure is a central pathway in the development of NK cell hyperresponsiveness and influenza-mediated exacerbations of COPD.

Cured meat consumption increases risk of readmission in COPD patients.

Recent studies have shown that a high dietary intake of cured meat increases the risk of chronic obstructive pulmonary disease (COPD) development. However, its potential effects on COPD evolution have not been tested. We aimed to assess the association between dietary intake of cured meat and risk of COPD readmission in COPD patients. 274 COPD patients were recruited during their first COPD admission between 2004 and 2006, provided information on dietary intake of cured meat during the previous 2 yrs, and were followed until December 31, 2007 (median follow-up 2.6 yrs). Associations between cured meat intake and COPD admissions were assessed using parametric regression survival-time models. Mean ± SD age was 68 ± 8 yrs, 93% of patients were male, 42% were current smokers, mean post-bronchodilator forced expiratory volume in 1 s (FEV(1)) was 53 ± 16% predicted, and median cured meat intake was 23 g · day(-1). After adjusting for age, FEV(1), and total caloric intake, high cured meat intake (more than median value) increased the risk of COPD readmission (adjusted HR 2.02, 95% CI 1.31-3.12; p=0.001). High cured meat consumption increases the risk of COPD readmission in COPD patients. The assessment of the effectiveness of healthy diet advice should be considered in the future.

Injury of peripheral muscles in smokers with chronic obstructive pulmonary disease.

Muscle injury has clinical relevance in diseased individuals because it is associated with muscle dysfunction in terms of decreased strength and/or endurance. This study was aimed at answering three questions: whether the presence of chronic obstructive pulmonary disease (COPD) is associated with peripheral muscle injury; whether muscle injury is associated with some of the relevant functional impairment in the muscles; and whether muscle injury can be solely justified by deconditioning. Twenty-one male COPD patients were eligible for the study. Seven healthy volunteers recruited from the general population were included as controls. Function of the quadriceps muscle was assessed through specific single-leg exercise (strength and endurance). Cellular (light microscopy) and subcellular (electron microscopy) techniques were used to evaluate muscle injury on biopsies from the vastus lateralis muscle. Signs of injury were found in muscles from both control and COPD patients, not only in cases showing severe airflow obstruction but also in the mild or moderate stages of the disease. Current smoking and presence of COPD were significantly associated with increased injury of the muscle as assessed by light and electron microscopy techniques. The authors conclude that peripheral muscle injury is evident in mild, moderate, and severe stages of COPD even in the absence of respiratory failure, hypercapnia, chronic steroid treatment, low body weight, or some coexisting disease. These findings support the theory that systemic factors with deleterious effect are acting on peripheral muscles of smokers with COPD, increasing the susceptibility of the muscle fibers to membrane and sarcomere injury.

Differences in health policies for drug availability in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension across Latin America.

Treatment for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in Latin America differs between countries, with regard to disease etiology, health insurance coverage, and drug availability. A group of experts from Latin America, met to share regional experiences and propose possible lines of collaboration. The available evidence, regional clinical practice data, and the global context of the proceedings of the 6th World Symposium on Pulmonary Hypertension, held in Nice, France, in February 2018, were analyzed. Here, we discuss some priority concepts identified that could guide transnational interaction and research strategies in Latin America: (1) despite being evidence-based, the 6th World Symposium on Pulmonary Hypertension proceedings may not be applicable in Latin American countries; (2) proactive identification and diagnosis of patients in Latin America is needed; (3) education of physicians and standardization of appropriate treatment for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension is vital; (4) our clinical experience for the treatment strategy for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension is based on drug availability in Argentina, Brazil, Colombia and México; (5) there are difficulties inherent to the consultation of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension, and access to treatment; (6) the importance of data generation and research of Latin American-specific issues related to pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension is highlighted.

Clinical Proof of Concept for Stabilization of Tracheostomy Tubes Using Novel DYNAtraq Device.

Introduction: Tracheostomy is one of the most common surgical strategies in intensive care units (ICU) and provides relevant clinical benefit for multiple indications. However, the complications associated with its use range from 5 to 40% according to different series. The risk of these complications could be reduced if fixation strategies and alignment of the tracheostomy tube with respect to the tracheal axis are improved. Aim: To build a functional device of technological innovation in respiratory medicine for the fixation and alignment of tracheostomy cannula (acronym DYNAtraq) and to evaluate its feasibility and safety in a pilot study in mechanically ventilated patients. Methods: Study carried out in four phases: (1) design engineering and functional prototyping of the device; (2) study of cytotoxicity and tolerance to the force of traction and push; (3) pilot study of feasibility and safety of its use in tracheostomized and mechanically ventilated patients; and (4) health workers satisfaction study. Results: The design of the innovative DYNAtraq device included, on the one hand, a connector with very little additional dead space to be inserted between the cannula and the ventilation tubes, and, on the other hand, a shaft with two supports for adhesion to the skin of the thorax with very high tolerance (several kilograms) to pull and push. In patients, the device corrected the malpositioned tracheostomy tubes for the latero-lateral (p < 0.001) and cephalo-caudal angles (p < 0.001). Its effect was maintained throughout the follow-up time (p < 0.001). The use of DYNAtraq did not induce serious adverse events and showed a 70% protective effect for complications (RR = 0.3, p < 0.001) in patients. Conclusion: DYNAtraq is a new device for respiratory medicine that allows the stabilization, alignment and fixation of tracheostomy tubes in mechanically ventilated patients. Its use provides additional benefits to traditional forms of support as it corrects misalignment and increases tolerance to habitual or forced movements. DYNAtraq is a safe element and can reduce the complications of tracheostomy tubes.

Effect of Antioxidants in the Treatment of COPD Patients: Scoping Review.

Chronic obstructive pulmonary disease (COPD) is a common, preventable, treatable lung disease characterized by persistent respiratory symptoms and airflow limitation and multiorgan impact. This affects the nutritional status of patients and requires multidimensional interventions including nutritional interventions according to individual metabolic needs. Our scoping review determined the effects of antioxidants in the treatment of COPD patients and their role in the decrease in the probability of exacerbations, hospital readmissions, and changes in lung function. The sources MEDLINE, LILACS, and Google Scholar were consulted and 19 studies were selected. The most indicated antioxidants are N-Acetylcysteine, vitamins E and D, and Zinc. Other antioxidants from plants or fruits extracts are also being investigated. The beneficial effect of antioxidants in stable or exacerbated patients is not clear, but theoretical and biological arguments of benefit justify lines of research that specify the impact on reducing oxidative stress and negative effects in COPD.

Invention and Pilot Study of the Efficacy and Safety of the SUPRAtube Device in Continuous Supraglottic Aspiration for Intubated and Mechanically Ventilated Patients.

BACKGROUND: Bronchoaspiration of content that accumulates in the supraglottic area (eg, saliva, gastroesophageal reflux) is a risk factor for ventilator-associated pneumonia. A continuous supraglottic suction system may decrease the risk of bronchoaspiration in these patients. OBJECTIVE: (1) Constructing a conceptual model and functional prototype of a continuous supraglottic suction device for use in humans; (2) defining functional characteristics in ex vivo swine head models; and (3) evaluating its efficacy and safety in mechanically ventilated patients. METHODS: Study conducted in three phases. First phase: definition of distances and diameters of the triangle determined by dental arch, posterior oropharynx and vallecula, and diameter of the oropharynx in axial projection; and identification of the declining area of supraglottic suction. Second phase: design engineering and functional prototype evaluated in ex vivo models. Third phase: evaluation of device use in terms of safety and efficacy in ventilated patients. RESULTS: We obtained a final functional model of the SUPRAtube device injected into PVC for medical use. Device effectiveness in in vitro simulation showed a high and fast suction capacity of liquid and thick volumes. Study of swine heads allowed to validate the shape, size and functional fenestration of the device. Study in intubated and mechanically ventilated patients showed a high supraglottic suction capacity and the absence of local adverse events during 72 (7-240) hours of continuous operation. CONCLUSION: Our study describes the process of conceptualization, design and production of a practical, safe, low-cost continuous supraglottic suction device without representing antibiotic pressure, which appears to be a new complementary preventive strategy for the standard management of intubated and mechanically ventilated patients.

[Chronic exposure to altitude. Clinical characteristics and diagnosis]. / Exposición crónica a la altura. Características clínicas y diagnóstico

Chronic exposure to altitude has been associated with hypobaric hypoxia in its inhabitants. Two entities have been associated with it, high altitude pulmonary hypertension and chronic mountain sickness. Its physiological and pulmonary circulation characteristics are described, as well as its clinical profile and diagnosis.

La exposición crónica a la altitud se ha asociado a hipoxia hipobárica en quienes la experimentan. Dos entidades se han asociado a la hipoxia hipobárica: la hipertensión pulmonar de la alta altitud y el mal de montaña crónico. Se describen sus características fisiológicas y de la circulación pulmonar, así como su perfil clínico y el diagnóstico.

Influence of pretransplantation restrictive lung disease on allogeneic hematopoietic cell transplantation outcomes.

We conducted a 15-year retrospective cohort study to determine the prevalence of restrictive lung disease before allogeneic hematopoietic cell transplantation (HCT), and to assess whether this was a risk factor for poor outcomes. A total of 2545 patients were eligible for the analysis. Restrictive lung disease was defined as a total lung capacity (TLC) < 80% of predicted normal. Chest x-rays and /or computed tomography (CT) scans were reviewed for all restricted patients to determine whether lung parenchymal abnormalities were unlikely or highly likely to cause restriction. Multivariate Cox proportional hazard and sensitivity analyses were performed to assess the relationship between restriction and early respiratory failure and nonrelapse mortality. Restrictive lung disease was present in 194 subjects (7.6%) before HCT. Among these cases, radiographically apparent abnormalities were unlikely to be the cause of the restriction in 149 subjects (77%). In unadjusted and adjusted analyses, the presence of pulmonary restriction was significantly associated with a 2-fold increase in risk for early respiratory failure and nonrelapse mortality, suggesting that these outcomes occurring in the absence of radiographically apparent abnormalities may be related to respiratory muscle weakness. These findings suggest that pulmonary restriction should be considered a risk factor for poor outcomes after transplantation.

Lung function and long-term complications after allogeneic hematopoietic cell transplant.

It is unknown if diminished pulmonary function early after allogeneic hematopoietic transplant is associated with poor long-term outcomes. The objective of this study was to determine if posttransplant lung function is associated with 5-year nonrelapse mortality (NRM) and the development of chronic graft-versus-host disease (cGVHD). Retrospective analysis was done for 2158 patients who had routine pulmonary function testing 60-120 days after transplant between 1992 and 2004. Cox regression was used to assess the hazard ratio for 5-year NRM. A second analysis assessed the hazard ratio for the development of cGVHD. Lung function score was the primary exposure, and was calculated according to forced expiratory volume in 1 second (FEV(1)) and carbon monoxide diffusion capapcity (DLCO). Individual pulmonary function parameters were secondary exposures. The primary outcomes were 5-year NRM and the development of cGVHD. Most patients had normal lung function following transplant. A higher lung function score, signifying greater impairment, was associated with an increased risk of mortality (category 1 hazard ratio [HR] 1.47 [1.17-1.85]; category 2 HR 3.38 [2.53-4.53]; category 3 HR 7.80 [4.15-14.68]). A similar association was observed for all individual pulmonary function parameters. Low FEV(1) was associated with the subsequent development of cGVHD (FEV(1) 70%-79% HR 1.26 [1.01-1.57]; 60%-69% HR 1.48 [1.10-2.01]; <60% HR 2.02 [1.34-3.05]). Models using either lung function score or individual pulmonary function parameters performed about equally well as judged by the C-statistic. Impaired lung function at day 80 posttransplant was associated with a higher risk of NRM. A low FEV(1) following transplant was associated with developing cGVHD within 1 year.

Factors affecting the relationship between psychological status and quality of life in COPD patients.

BACKGROUND: This study aims to (i) evaluate the association between anxiety and depressive symptoms and health-related quality of life (HRQoL); and (ii) identify the effect modifiers of this relationship in patients with chronic obstructive pulmonary disease (COPD). METHODS: A total of 337 clinically stable COPD patients answered the St. George's Respiratory Questionnaire (SGRQ) (assessing HRQoL) and the Hospital Anxiety and Depression Scale (HADS). Socio-demographic information, lung function, and other clinical data were collected. RESULTS: Most patients (93%) were male; they had a mean (SD) age of 68 (9) years and mild to very severe COPD (post-bronchodilator FEV1 52 (16)% predicted). Multivariate analyses showed that anxiety, depression, or both conditions were associated with poor HRQoL (for all SGRQ domains). The association between anxiety and total HRQoL score was 6.7 points higher (indicating a worse HRQoL) in current workers than in retired individuals. Estimates for patients with "both anxiety and depression" were 5.8 points lower in stage I-II than in stage III-IV COPD, and 10.2 points higher in patients with other comorbidities than in those with only COPD. CONCLUSIONS: This study shows a significant association between anxiety, depression, or both conditions and impaired HRQoL. Clinically relevant factors affecting the magnitude of this association include work status, COPD severity, and the presence of comorbidities.

Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.

BACKGROUND: Lung resection surgery further decreases exercise capacity and negatively affects respiratory muscle function in patients with non-small cell lung cancer (NSCLC). The best design for exercise interventions in these patients has not been determined yet. AIM: To assess the impact of aerobic exercise and high-intensity respiratory muscle training on patient outcomes following lung cancer resection surgery. DESIGN: Prospective, single-blind, pilot randomized controlled trial. SETTING: Outpatient cardiopulmonary rehabilitation unit of two university hospitals. POPULATION: Thirty-seven patients with NSCLC after tumor resection. METHODS: Patients were randomly assigned to exercise training or usual post-operative care. The training program consisted of aerobic exercises and high-intensity respiratory muscle training (24 supervised sessions, 3 per week, 8 weeks). Primary outcome was exercise capacity assessed with peak oxygen uptake (VO2peak) during cardiopulmonary exercise test. Secondary outcomes included changes in respiratory muscle strength, levels of serum insulin growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3), and quality of life assessed with the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) questionnaire. RESULTS: The 8-week training program was associated with significant improvement in VO2peak (2.13 mL/Kg/min [95%CI 0.06 to 4.20]), maximal inspiratory and expiratory pressures (18.96 cmH2O [95% CI 2.7 to 24.1] and 18.58 cmH2O [95% CI 4.0 to 33.1], respectively) and IGFBP-3 (0.61 µg/mL [%95 CI 0.1 to 1.12]). No significant differences were observed in the EORTC QLQ-C30. CONCLUSIONS: An 8-week exercise program consisting of aerobic exercise and high-intensity respiratory muscle training improved exercise capacity, respiratory muscle strength, and serum IGFBP-3 levels in NSCLC patients after lung resection. There was no impact on the other outcomes assessed. CLINICAL REHABILITATION IMPACT: A combination of aerobic exercise and respiratory muscle training could be included in the rehabilitation program of deconditioned patients with NSCLC after lung resection surgery.

[Activation of satellite cells in the intercostal muscles of patients with chronic obstructive pulmonary disease]. / Activación de células satélite en el músculo intercostal de pacientes con EPOC.

OBJECTIVE: The respiratory muscles of patients with chronic obstructive pulmonary disease (COPD) display evidence of structural damage in parallel with signs of adaptation. We hypothesized that this can only be explained by the simultaneous activation of satellite cells. The aim of this study was to analyze the number and activation of those cells along with the expression of markers of microstructural damage that are frequently associated with regeneration. PATIENTS AND METHODS: The study included 8 patients with severe COPD (mean [SD] forced expiratory volume in 1 second, 33% [9%] of predicted) and 7 control subjects in whom biopsies were performed of the external intercostal muscle. The samples were analyzed by light microscopy to assess muscle fiber phenotype, electron microscopy to identify satellite cells, and real-time polymerase chain reaction to analyze the expression of the following markers: insulin-like growth factor 1, mechano growth factor, and embryonic and perinatal myosin heavy chains (MHC) as markers of microstructural damage; Pax-7 and m-cadherin as markers of the presence and activation of satellite cells, respectively; and MHC-I, IIa, and IIx as determinants of muscle fiber phenotype. RESULTS: The patients had larger fibers than healthy subjects (54 [6] vs 42 [4] microm(2); P< .01) with a similar or slightly increased proportion of satellite cells, as measured by ultrastructural analysis (4.3% [1%] vs 3.7% [3.5%]; P>.05) or expression of Pax-7 (5.5 [4.1] vs 1.6 [0.8] arbitrary units [AU]; P< .05). In addition, there was greater activation of satellite cells in the patients, as indicated by increased expression of m-cadherin (3.8 [2.1] vs 1.0 [1.2] AU; P=.05). This was associated with increased expression of markers of microstructural damage: insulin-like growth factor 1, 0.35 (0.34) vs 0.09 (0.08) AU (P< .05); mechano growth factor, 0.45 (0.55) vs 0.13 (0.17) AU (P=.05). CONCLUSIONS: The intercostal muscles of patients with severe COPD show indirect signs of microstructural damage accompanied by satellite cell activation. This suggests the presence of ongoing cycles of lesion and repair that could partially explain the maintenance of the structural properties of the muscle.

Bispectral index in hypercapnic encephalopathy associated with COPD exacerbation: a pilot study.

BACKGROUND: Hypercapnic encephalopathy is relatively frequent in severe exacerbations of COPD (ECOPDs), with its intensity usually being evaluated through clinical scales. Bispectral index (BIS) is a relatively new technique, based on the analysis of the electroencephalographic signal, which provides a good approximation to the level of consciousness, having already been validated in anesthesia. OBJECTIVE: The objective of the study was to evaluate the utility of BIS in the assessment of the intensity of hypercapnic encephalopathy in ECOPD patients. PATIENTS AND METHODS: A total of ten ECOPD patients were included, and the level of brain activity was assessed using BIS and different scales: Glasgow Coma Scale, Ramsay Sedation Scale (RSS), and Richmond Agitation-Sedation Scale. The evaluation was performed both in the acute phase and 3 months after discharge. RESULTS: BIS was recorded for a total of about 600 minutes. During ECOPD, BIS values ranged from 58.8 (95% CI: 48.6-69) for RSS score of 4 to 92.2 (95% CI: 90.1-94.3) for RSS score of 2. A significant correlation was observed between values obtained with BIS and those from the three scales, although the best fit was for RSS, followed by Glasgow and Richmond (r=-0.757, r=0.701, and r=0.615, respectively; P<0.001 for all). In the stable phase after discharge, BIS showed values considered as normal for a wake state (94.6; 95% CI: 91.7-97.9). CONCLUSION: BIS may be useful for the objective early detection and automatic monitoring of the intensity of hypercapnic encephalopathy in ECOPD, facilitating the early detection and follow-up of this condition, which may avoid management problems in these patients.

Increased Urinary Erythropoietin Excretion in Severe Sleep Apnea-Hipoapnea Syndrome: The Effect of CPAP. / El síndrome de apneas-hipoapneas del sueño (SAHS) grave incrementa la excreción urinaria de eritropoyetina. Efecto del tratamiento con CPAP.

INTRODUCTION: Tissue hypoxia stimulates the production of erythropoietin (EPO), the main effect of which is, in turn, to stimulate erythropoiesis. Sleep apnea-hypopnea syndrome (SAHS) is an entity characterized by repeated episodes of hypoxemia during sleep. OBJECTIVE: To analyze whether hypoxemia stimulated increased urinary excretion of EPO, and if so, to evaluate if treatment with continuous positive airway pressure (CPAP) can inhibit this phenomenon. METHODS: We studied 25 subjects with suspected SAHS who underwent a polysomnography study (PSG). EPO levels in first morning urine (uEPO) and blood creatinine and hemoglobin were determined in all patients. Patients with severe SAHS repeated the same determinations after CPAP treatment. RESULTS: Twelve subjects were diagnosed with severe SAHS (mean ± SD, AHI 53.1 ± 22.7). Creatinine and hemoglobin levels were normal in all subjects. uEPO was 4 times higher in the SAHS group than in the control group (1.32 ± 0.83 vs. 0.32 ± 0.35 UI/l, p <.002). CPAP treatment reduced uEPO to 0.61 ± 0.9 UI/l (p <.02), levels close to those observed in healthy subjects. No dose-response relationship was observed between severity of PSG changes and uEPO values. CONCLUSIONS: Patients with severe SAHS show increased uEPO excretion, but this normalizes after treatment with CPAP.

Clinical outcomes of expiratory muscle training in severe COPD patients.

UNLABELLED: The most common symptoms in chronic obstructive pulmonary disease (COPD) patients are breathlessness and exercise limitation. Although both general and inspiratory muscle training have shown clinical benefits, the effects of specific expiratory muscle training remain controversial. OBJECTIVE: To investigate the effects of expiratory training on lung function, exercise tolerance, symptoms and health-related quality of life in severe COPD patients. METHODS: Sixteen patients (FEV(1), 28+/-8% pred.) were randomised to either expiratory muscle or sham training groups, both completing a 5-week programme (30 min sessions breathing through an expiratory threshold valve 3 times per week) (50% of their maximal expiratory pressure (MEP) vs. placebo, respectively). Lung function, exercise capacity (bicycle ergometry and walking test), and clinical outcomes (dyspnoea and quality of life (St. George Respiratory Questionnaire (SGRQ)) were evaluated both at baseline and following the training period. RESULTS: Although lung function remained roughly unchanged after training, exercise capacity, symptoms and quality of life significantly improved. The improvement in both walking distance and the SGRQ score significantly correlated with changes in MEP. CONCLUSION: Our results confirm that a short outpatient programme of expiratory training can improve symptoms and quality of life in severe COPD patients. These effects could be partially explained by changes in expiratory muscle strength.