Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation. METHODS: The Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated. DISCUSSION: PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach. TRIAL REGISTRATION: The PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).

High-Flow Versus VenturiMask Oxygen Therapy to Prevent Reintubation in Hypoxemic Patients after Extubation: A Multicenter Randomized Clinical Trial.

Rationale: When compared with VenturiMask after extubation, high-flow nasal oxygen provides physiological advantages. Objectives: To establish whether high-flow oxygen prevents endotracheal reintubation in hypoxemic patients after extubation, compared with VenturiMask. Methods: In this multicenter randomized trial, 494 patients exhibiting PaO2:FiO2 ratio ⩽ 300 mm Hg after extubation were randomly assigned to receive high-flow or VenturiMask oxygen, with the possibility to apply rescue noninvasive ventilation before reintubation. High-flow use in the VenturiMask group was not permitted. Measurements and Main Results: The primary outcome was the rate of reintubation within 72 hours according to predefined criteria, which were validated a posteriori by an independent adjudication committee. Main secondary outcomes included reintubation rate at 28 days and the need for rescue noninvasive ventilation according to predefined criteria. After intubation criteria validation (n = 492 patients), 32 patients (13%) in the high-flow group and 27 patients (11%) in the VenturiMask group required reintubation at 72 hours (unadjusted odds ratio, 1.26 [95% confidence interval (CI), 0.70-2.26]; P = 0.49). At 28 days, the rate of reintubation was 21% in the high-flow group and 23% in the VenturiMask group (adjusted hazard ratio, 0.89 [95% CI, 0.60-1.31]; P = 0.55). The need for rescue noninvasive ventilation was significantly lower in the high-flow group than in the VenturiMask group: at 72 hours, 8% versus 17% (adjusted hazard ratio, 0.39 [95% CI, 0.22-0.71]; P = 0.002) and at 28 days, 12% versus 21% (adjusted hazard ratio, 0.52 [95% CI, 0.32-0.83]; P = 0.007). Conclusions: Reintubation rate did not significantly differ between patients treated with VenturiMask or high-flow oxygen after extubation. High-flow oxygen yielded less frequent use of rescue noninvasive ventilation. Clinical trial registered with www.clinicaltrials.gov (NCT02107183).

Physiologic effects of stress dose corticosteroids in in-hospital cardiac arrest (CORTICA): A randomized clinical trial.

Aim: Postresuscitation hemodynamics are associated with hospital mortality/functional outcome. We sought to determine whether low-dose steroids started during and continued after cardiopulmonary resuscitation (CPR) affect postresuscitation hemodynamics and other physiological variables in vasopressor-requiring, in-hospital cardiac arrest. Methods: We conducted a two-center, randomized, double-blind trial of patients with adrenaline (epinephrine)-requiring cardiac arrest. Patients were randomized to receive either methylprednisolone 40 mg (steroids group) or normal saline-placebo (control group) during the first CPR cycle post-enrollment. Postresuscitation shock was treated with hydrocortisone 240 mg daily for 7 days maximum and gradual taper (steroids group), or saline-placebo (control group). Primary outcomes were arterial pressure and central-venous oxygen saturation (ScvO2) within 72 hours post-ROSC. Results: Eighty nine of 98 controls and 80 of 86 steroids group patients with ROSC were treated as randomized. Primary outcome data were collected from 100 patients with ROSC (control, n = 54; steroids, n = 46). In intention-to-treat mixed-model analyses, there was no significant effect of group on arterial pressure, marginal mean (95% confidence interval) for mean arterial pressure, steroids vs. control: 74 (68-80) vs. 72 (66-79) mmHg] and ScvO2 [71 (68-75)% vs. 69 (65-73)%], cardiac index [2.8 (2.5-3.1) vs. 2.9 (2.5-3.2) L/min/m2], and serum cytokine concentrations [e.g. interleukin-6, 89.1 (42.8-133.9) vs. 75.7 (52.1-152.3) pg/mL] determined within 72 hours post-ROSC (P = 0.12-0.86). There was no between-group difference in body temperature, echocardiographic variables, prefrontal blood flow index/cerebral autoregulation, organ failure-free days, and hazard for poor in-hospital/functional outcome, and adverse events (P = 0.08->0.99). Conclusions: Our results do not support the use of low-dose corticosteroids in in-hospital cardiac arrest.Trial Registration:ClinicalTrials.gov number: NCT02790788 ( https://www.clinicaltrials.gov ).

Effect of Vitamin C on Clinical Outcomes of Critically Ill Patients With COVID-19: An Observational Study and Subsequent Meta-Analysis.

BACKGROUND: Whether vitamin C provides any benefit when administered in critically ill patients, including those with coronavirus disease (COVID-19), is controversial. We endeavored to estimate the effect of administration of vitamin C on clinical outcomes of critically ill patients with COVID-19 by performing an observational study and subsequent meta-analysis. METHODS: Firstly, we conducted an observational study of critically ill patients with laboratory-confirmed COVID-19 who consecutively underwent invasive mechanical ventilation in an academic intensive care unit (ICU) during the second pandemic wave. We compared all-cause mortality of patients receiving vitamin C ("vitamin C" group) or not ("control" group) on top of standard-of-care. Subsequently, we systematically searched PubMed and CENTRAL for relevant studies, which reported on all-cause mortality (primary outcome) and/or morbidity of critically ill patients with COVID-19 receiving vitamin C or not treatment. Pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO. RESULTS: In the observational study, baseline characteristics were comparable between the two groups. Mortality was 20.0% (2/10) in the vitamin C group vs. 47.6% (49/103; p = 0.11) in the control group. Subsequently, the meta-analysis included 11 studies (6 observational; five randomized controlled trials) enrolling 1,807 critically ill patients with COVID-19. Mortality of patients receiving vitamin C on top of standard-of-care was not lower than patients receiving standard-of-care alone (25.8 vs. 34.7%; RR 0.85, 95% CI 0.57-1.26; p = 0.42). CONCLUSIONS: After combining results of our observational cohort with those of relevant studies into a meta-analysis of data from 1,807 patients, we found that administration vitamin C as opposed to standard-of-care alone might not be associated with lower of mortality among critically ill patients with COVID-19. Additional evidence is anticipated from relevant large randomized controlled trials which are currently underway. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021276655.

The Role of Noninvasive Respiratory Management in Patients with Severe COVID-19 Pneumonia.

Acute hypoxemic respiratory failure is the principal cause of hospitalization, invasive mechanical ventilation and death in severe COVID-19 infection. Nearly half of intubated patients with COVID-19 eventually die. High-Flow Nasal Oxygen (HFNO) and Noninvasive Ventilation (NIV) constitute valuable tools to avert endotracheal intubation in patients with severe COVID-19 pneumonia who do not respond to conventional oxygen treatment. Sparing Intensive Care Unit beds and reducing intubation-related complications may save lives in the pandemic era. The main drawback of HFNO and/or NIV is intubation delay. Cautious selection of patients with severe hypoxemia due to COVID-19 disease, close monitoring and appropriate employment and titration of HFNO and/or NIV can increase the rate of success and eliminate the risk of intubation delay. At the same time, all precautions to protect the healthcare personnel from viral transmission should be taken. In this review, we summarize the evidence supporting the application of HFNO and NIV in severe COVID-19 hypoxemic respiratory failure, analyse the risks associated with their use and provide a path for their proper implementation.

High Flow Oxygen Therapy at Two Initial Flow Settings versus Conventional Oxygen Therapy in Cardiac Surgery Patients with Postextubation Hypoxemia: A Single-Center, Unblinded, Randomized, Controlled Trial.

In cardiac surgery patients with pre-extubation PaO2/inspired oxygen fraction (FiO2) < 200 mmHg, the possible benefits and optimal level of high-flow nasal cannula (HFNC) support are still unclear; therefore, we compared HFNC support with an initial gas flow of 60 or 40 L/min and conventional oxygen therapy. Ninety nine patients were randomly allocated (respective ratio: 1:1:1) to I = intervention group 1 (HFNC initial flow = 60 L/min, FiO2 = 0.6), intervention group 2 (HFNC initial flow = 40 L/min, FiO2 = 0.6), or control group (Venturi mask, FiO2 = 0.6). The primary outcome was occurrence of treatment failure. The baseline characteristics were similar. The hazard for treatment failure was lower in intervention group 1 vs. control (hazard ratio (HR): 0.11, 95% CI: 0.03-0.34) and intervention group 2 vs. control (HR: 0.30, 95% CI: 0.12-0.77). During follow-up, the probability of peripheral oxygen saturation (SpO2) > 92% and respiratory rate within 12-20 breaths/min was 2.4-3.9 times higher in intervention group 1 vs. the other 2 groups. There was no difference in PaO2/FiO2, patient comfort, intensive care unit or hospital stay, or clinical course complications or adverse events. In hypoxemic cardiac surgery patients, postextubation HFNC with an initial gas flow of 60 or 40 L/min resulted in less frequent treatment failure vs. conventional therapy. The results in terms of SpO2/respiratory rate targets favored an initial HFNC flow of 60 L/min.

Hospital Resources May Be an Important Aspect of Mortality Rate among Critically Ill Patients with COVID-19: The Paradigm of Greece.

For critically ill patients with coronavirus disease 2019 (COVID-19) who require intensive care unit (ICU) admission, extremely high mortality rates (even 97%) have been reported. We hypothesized that overburdened hospital resources by the extent of the pandemic rather than the disease per se might play an important role on unfavorable prognosis. We sought to determine the outcome of such patients admitted to the general ICUs of a hospital with sufficient resources. We performed a prospective observational study of adult patients with COVID-19 consecutively admitted to COVID-designated ICUs at Evangelismos Hospital, Athens, Greece. Among 50 patients, ICU and hospital mortality was 32% (16/50). Median PaO2/FiO2 was 121 mmHg (interquartile range (IQR), 86-171 mmHg) and most patients had moderate or severe acute respiratory distress syndrome (ARDS). Hospital resources may be an important aspect of mortality rates, since severely ill COVID-19 patients with moderate and severe ARDS may have understandable mortality, provided that they are admitted to general ICUs without limitations on hospital resources.

The combination of inspiratory muscle training and high-flow nasal cannula oxygen therapy for promoting weaning outcomes in difficult-to-wean patients: protocol for a randomised controlled trial.

BACKGROUND: According to the literature, 20-30% of intubated patients are difficult to wean off mechanical ventilation and have a prolonged intensive care unit (ICU) stay with detrimental effects on muscle strength, functional ability and quality of life. Inspiratory muscle training (IMT) via a threshold device has been proposed as an effective exercise for minimising the effects of mechanical ventilation on respiratory muscles of critically ill patients with prolonged weaning. In addition, high-flow nasal cannula (HFNC) oxygen has been proved to provide efficient support for both high- and low-risk patients after extubation, thus preventing re-intubation. MATERIAL AND METHODS: A randomised controlled trial was designed to assess the efficacy of combining IMT and HFNC as therapeutic strategies for patients with high risk for weaning failure. Once patients with prognostic factors of difficult weaning are awake, ventilated with support settings and cooperative, they will be randomised to one of the two following study groups: intervention group (IMT and HFNC) and control group (IMT and Venturi mask). IMT will start as soon as possible. Each allocated oxygen delivery device will be applied immediately after extubation. IMT intervention will continue until patients' discharge from ICU. The primary outcome is the rate of weaning failure. Secondary outcomes are maximal inspiratory and expiratory strength, endurance of respiratory muscles, global muscle strength, functional ability and quality of life along with duration of ventilation (days) and ICU and hospital length of stay. CONCLUSION: The present study could significantly contribute to knowledge of how best to treat patients with difficult weaning and high risk of re-intubation.

Lactate Kinetics Reflect Organ Dysfunction and Are Associated with Adverse Outcomes in Intensive Care Unit Patients with COVID-19 Pneumonia: Preliminary Results from a GREEK Single-Centre Study.

Coronavirus disease-19 (COVID-19) continues to be a health threat worldwide. Increased blood lactate is common in intensive care unit (ICU) patients; however, its association with outcomes in ICU COVID-19 patients remains currently unexplored. In this retrospective, observational study we assessed whether lactate is associated with outcomes in COVID-19 patients. Blood lactate was measured on ICU admission and thereafter daily up to day 14 in 45 patients with confirmed COVID-19 pneumonia. Acute physiology and chronic health evaluation (APACHE II) was calculated on ICU admission, and sequential organ failure assessment (SOFA) score was assessed on admission and every second day. The cohort was divided into survivors and non-survivors based on 28-day ICU mortality (24.4%). Cox regression analysis revealed that maximum lactate on admission was independently related to 28-day ICU mortality with time in the presence of APACHE II (RR = 2.45, p = 0.008). Lactate's area under the curve for detecting 28-day ICU mortality was 0.77 (p = 0.008). Mixed model analysis showed that mean daily lactate levels were higher in non-survivors (p < 0.0001); the model applied on SOFA scores showed a similar time pattern. Thus, initial blood lactate was an independent outcome predictor in COVID-19 ICU patients. The time course of lactate mirrors organ dysfunction and is associated with poor clinical outcomes.

Nasal high-flow oxygen versus noninvasive ventilation in acute exacerbation of COPD: protocol for a randomised noninferiority clinical trial.

BACKGROUND: Noninvasive ventilation (NIV) is considered as the first-line treatment for acute exacerbation of COPD (AECOPD) complicated by respiratory acidosis. Recent studies demonstrate a role of nasal high-flow oxygen (NHF) in AECOPD as an alternative treatment in patients intolerant to NIV or with contraindications to it. AIM: The study aimed to evaluate whether NHF respiratory support is noninferior compared to NIV in respect to treatment failure, defined as need for intubation or change to alternative treatment group, in patients with AECOPD and mild-to-moderate acute or acute-on-chronic hypercapnic respiratory failure. METHODS: We designed a multicentre, prospective, randomised trial on patients with AECOPD, who have pH<7.35 but >7.25 and P aCO2  >45 mmHg, in whom NIV is indicated as a first-line treatment. According to power analysis, 498 participants will be required for establishing noninferiority of NHF compared to NIV. Patients will be randomly assigned to receive NIV or NHF. Treatment will be adjusted to maintain S pO2 between 88%-92% for both groups. Arterial blood gases, respiratory variables, comfort, dyspnoea score and any pulmonary or extrapulmonary complications will be assessed at baseline, before treatment initiation, and at 1, 2, 4, 6, 12, 24, 48 h, then once daily from day 3 to patient discharge, intubation or death. CONCLUSION: Given the increasing number of studies demonstrating the physiological effects of NHF in COPD patients, we hypothesise that NHF respiratory support will be noninferior to NIV in patients with AECOPD and mild-to-moderate acute or acute on chronic hypercapnic respiratory failure.

Soluble Urokinase Plasminogen Activator Receptor: A Biomarker for Predicting Complications and Critical Care Admission of COVID-19 Patients.

The novel coronavirus infection has spread worldwide, causing a wide spectrum of clinical manifestations. Most patients develop moderate clinical illness, but a substantial number will experience severe pneumonia, which may rapidly progress to acute respiratory distress syndrome and multiple organ failure. In this population, soluble urokinase plasminogen activator receptor (suPAR) could serve as a quick triage test and independent marker of clinical severity, hospital and intensive care unit admission, complications, and mortality.

Nasal High Flow Use in COPD Patients with Hypercapnic Respiratory Failure: Treatment Algorithm & Review of the Literature.

Nasal high flow (NHF) therapy has recently gained attention as a new respiratory support system and is increasingly being utilized in every day clinical practice. Recent studies suggest that it may also be effective in patients with hypercapnia and suggest NHF as a possible alternative for patients who cannot tolerate standard noninvasive ventilation. The present review discusses the mechanisms of action that make NHF potentially suitable for chronic obstructive pulmonary disease (COPD) patients and evaluates the current evidence of NHF use for treatment of stable hypercapnic COPD patients as well as acute hypercapnic exacerbation of COPD. An algorithm is also proposed for the clinical application of NHF in patients with acute hypercapnic exacerbation of COPD, based on current literature.

Ethical challenges in resuscitation.

PURPOSE: A rapidly evolving resuscitation science provides more effective treatments to an aging population with multiple comorbidites. Concurrently, emergency care has become patient-centered. This review aims to describe challenges associated with the application of key principles of bioethics in resuscitation and post-resuscitation care; propose actions to address these challenges; and highlight the need for evidence-based ethics and consensus on ethical principles interpretation. METHODS: Following agreement on the article's outline, subgroups of 2-3 authors provided narrative reviews of ethical issues concerning autonomy and honesty, beneficence/nonmaleficence and dignity, justice, specific practices/circumstances such as family presence during resuscitation, and emergency research. Proposals for addressing ethical challenges were also offered. RESULTS: Respect for patient autonomy can be realized through honest provision of information, shared decision-making, and advance directives/care planning. Essential prerequisites comprise public and specific healthcare professionals' education, appropriate regulatory provisions, and allocation of adequate resources. Regarding beneficence/nonmaleficence, resuscitation should benefit patients, while avoiding harm from futile interventions; pertinent practice should be based on neurological prognostication and patient/family-reported outcomes. Regarding dignity, aggressive life-sustaining treatments against patients preferences should be avoided. Contrary to the principle of justice, resuscitation quality may be affected by race/income status, age, ethnicity, comorbidity, and location (urban versus rural or country-specific/region-specific). Current evidence supports family presence during resuscitation. Regarding emergency research, autonomy should be respected without hindering scientific progress; furthermore, transparency of research conduct should be promoted and funding increased. CONCLUSIONS: Major ethical challenges in resuscitation science need to be addressed through complex/resource-demanding interventions. Such actions require support by ongoing/future research.

Nasal high flow therapy: a novel treatment rather than a more expensive oxygen device.

Nasal high flow is a promising novel oxygen delivery device, whose mechanisms of action offer some beneficial effects over conventional oxygen systems. The administration of a high flow of heated and humidified gas mixture promotes higher and more stable inspiratory oxygen fraction values, decreases anatomical dead space and generates a positive airway pressure that can reduce the work of breathing and enhance patient comfort and tolerance. Nasal high flow has been used as a prophylactic tool or as a treatment device mostly in patients with acute hypoxaemic respiratory failure, with the majority of studies showing positive results. Recently, its clinical indications have been expanded to post-extubated patients in intensive care or following surgery, for pre- and peri-oxygenation during intubation, during bronchoscopy, in immunocompromised patients and in patients with "do not intubate" status. In the present review, we differentiate studies that suggest an advantage (benefit) from other studies that do not suggest an advantage (no benefit) compared to conventional oxygen devices or noninvasive ventilation, and propose an algorithm in cases of nasal high flow application in patients with acute hypoxaemic respiratory failure of almost any cause.

A Randomized Trial of the Amikacin Fosfomycin Inhalation System for the Adjunctive Therapy of Gram-Negative Ventilator-Associated Pneumonia: IASIS Trial.

BACKGROUND: Clinical failures in ventilator-associated pneumonia (VAP) caused by gram-negative bacteria are common and associated with substantial morbidity, mortality, and resource utilization. METHODS: We assessed the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS) for the treatment of gram-negative bacterial VAP in a randomized double-blind, placebo-controlled, parallel group, phase 2 study between May 2013 and March 2016. We compared standard of care in each arm plus 300 mg amikacin/120 mg fosfomycin or placebo (saline), delivered by aerosol twice daily for 10 days (or to extubation if < 10 days) via the investigational eFlow Inline System (PARI GmbH). The primary efficacy end point was change from baseline in the Clinical Pulmonary Infection Score (CPIS) during the randomized course of AFIS/placebo, using the subset of patients with microbiologically proven baseline infections with gram-negative bacteria. RESULTS: There were 143 patients randomized: 71 to the AFIS group, and 72 to the placebo group. Comparison of CPIS change from baseline between treatment groups was not different (P = .70). The secondary hierarchical end point of no mortality and clinical cure at day 14 or earlier was also not significant (P = .68) nor was the hierarchical end point of no mortality and ventilator-free days (P = .06). The number of deaths in the AFIS group was 17 (24%) and 12 (17%) in the placebo group (P = .32). The AFIS group had significantly fewer positive tracheal cultures on days 3 and 7 than placebo. CONCLUSIONS: In this trial of adjunctive aerosol therapy compared with standard of care IV antibiotics in patients with gram-negative VAP, the AFIS was ineffective in improving clinical outcomes despite reducing bacterial burden. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01969799; URL: www.clinicaltrials.gov.

Smoking and depression: Is smoking cessation effective?

Patients with depression tend to have a higher rate of smoking and an increased severity of nicotine dependence. It seems that common genetic and environmental factors may influence the bimodal relationship between smoking and depression. Nicotine has some positive reinforcing/rewarding effects that may affect people with mood disorders and smoking is also used as a ;relief medication' in order to ameliorate symptoms of depression, as it is already known that nicotine, which is the major psychoactive ingredient in tobacco, may act as an antidepressant. To date, the data regarding the difficulty in smoking cessation in depressed smokers are conflicting. Low confidence and self-esteem among this group of smokers are significant predictors of failure during smoking cessation attempt. In the most recently published guidelines for smokers with psychiatric comorbidities the suggestion is for combination treatment (counseling and pharmaceutical treatment) and prolongation of a therapeutic approach.

Body mass and fat-free mass indices in COPD: relation with variables expressing disease severity.

BACKGROUND: COPD primarily affects the lungs but also produces systemic consequences that are not reflected by the recent staging according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Body mass index (BMI) and fat-free mass index (FFMI) represent different aspects of nutrition abnormalities in COPD. We investigated whether BMI and FFMI could be related to parameters expressing airflow obstruction and limitation, exercise capacity, airway inflammation, and quality of life, and whether they would reflect the GOLD staging of the disease. METHODS: One hundred patients with clinically stable COPD equally classified into the five stages of the disease were evaluated for BMI, FFMI (measured by bioelectrical impedance analysis), airway obstruction and hyperinflation (FEV(1), FEV(1)/FVC, inspiratory capacity), exercise capacity (6-min walk distance [6MWD], Borg scale before and after 6MWD]), chronic dyspnea using the Medical Research Council (MRC) scale, airway inflammation (sputum differential cell counts, leukotriene B(4) in supernatant), and quality of life (emotional part of the chronic respiratory disease questionnaire). RESULTS: 6MWD was significantly associated with both BMI and FFMI values, while FFMI additionally presented significant correlations with MRC scale, percentage of predicted FEV(1), and FEV(1)/FVC ratio. No association was observed between the two nutritional indexes. BMI was not statistically different among patients in the five stages of COPD, while FFMI reflected the staging of the disease, presenting the highest values in stage 0. CONCLUSIONS: Nutritional status is mainly related to exercise capacity. FFMI seems to be more accurate in expressing variables of disease severity, as well as the current staging compared to BMI.