Supranormal lung function: Prevalence, associated factors and clinical manifestations across the lifespan.

BACKGROUND AND OBJECTIVE: It is now well established that there are different life-long lung function trajectories in the general population, and that some are associated with better or worse health outcomes. Yet, the prevalence, clinical characteristics and risk factors of individuals with supranormal FEV1 or FVC values (above the upper-limit of normal [ULN]) in different age-bins through the lifetime in the general population are poorly understood. METHOD: To address these questions, we investigated the prevalence of supranormal FEV1 and FVC values in the LEAD (Lung, hEart, sociAl and boDy) study, a general population cohort in Austria that includes participants from 6 to 82 years of age. RESULTS: We found that: (1) the prevalence of supranormal pre-bronchodilator FEV1 and FVC values was 3.4% and 3.1%, respectively, and that these figures remained relatively stable through different age-bins except for participants >60 years., in whom they increased (5.0% and 4.2%, respectively). Approximately 50% of supranormal individuals had both increased FEV1 and FVC values; (2) supranormal spirometric values were consistently accompanied by higher static lung volumes and lower specific airway resistance through the lifespan, indicating better overall lung function; and (3) multivariate regression analysis identified that female sex, higher muscle mass (FFMI), less diabetes and fewer respiratory symptoms were consistently associated with supranormal FEV1 and FVC values. CONCLUSION: Supranormal FEV1 and/or FVC values occur in about 3% of the general population in different age bins and are associated with better health markers.

Prevalence of restrictive lung function in children and adults in the general population.

BACKGROUND: Restrictive lung function (RLF) is characterized by a reduced lung expansion and size. In the absence of lung volume measurements, restriction can be indirectly assessed with restrictive spirometric patterns (RSP) by spirometry. Prevalence data on RLF by the golden standard body plethysmography in the general population are scarce. Therefore, we aimed to evaluate the prevalence of RLF and RSP in the general population by body plethysmography and to determine factors influencing RLF and RSP. METHODS: Pre-bronchodilation lung function data of 8891 subjects (48.0% male, age 6-82 years) have been collected in the LEAD Study, a single-centered, longitudinal, population-based study from Vienna, Austria. The cohort was categorized in the following groups based on the Global Lung Initiative reference equations: normal subjects, RLF (TLC < lower limit of normal (LLN)), RSP (FEV1/FVC ≥ LLN and a FVC < LLN), RSP only (RSP with TLC ≥ LLN). Normal subjects were considered those with FEV1, FVC, FEV1/FVC and TLC between LLN and ULN (upper limit of normal). RESULTS: The prevalence of RLF and RSP in the Austrian general population is 1.1% and 4.4%. Spirometry has a positive and negative predictive value of 18.0% and 99.6% to predict a restrictive lung function. Central obesity was associated with RLF. RSP was related to smoking and underweight. CONCLUSIONS: The prevalence of true restrictive lung function and RSP in the Austrian general population is lower than previously estimated. Our data confirm the need for direct lung volume measurement to diagnose true restrictive lung function.

Effects of Dynamic Hyperinflation on Left Ventricular Diastolic Function in Healthy Subjects - A Randomized Controlled Crossover Trial.

Objective: Diastolic dysfunction of the left ventricle is common in patients with chronic obstructive pulmonary disease (COPD). Dynamic hyperinflation has been suggested as a key determinant of reduced diastolic function in COPD. We aimed to investigate the effects of induced dynamic hyperinflation on left ventricular diastolic function in healthy subjects to exclude other confounding mechanisms associated with COPD. Design: In this randomized controlled crossover trial (NCT03500822, https://www.clinicaltrials.gov/), we induced dynamic hyperinflation using the validated method of expiratory resistance breathing (ERB), which combines tachypnea with expiratory resistance, and compared the results to those of tachypnea alone. Healthy male subjects (n = 14) were randomly assigned to the ERB or control group with subsequent crossover. Mild, moderate, and severe hyperinflation (i.e., ERB1, ERB2, ERB3) were confirmed by intrinsic positive end-expiratory pressure (PEEPi) using an esophageal balloon catheter. The effects on diastolic function of the left ventricle were measured by transthoracic echocardiographic assessment of the heart rate-adjusted transmitral E/A-ratio and E/e'-ratio. Results: We randomly assigned seven participants to the ERB group and seven to the control group (age 26 [24-26] vs. 24 [24-34], p = 0.81). Severe hyperinflation decreased the E/A-ratio compared to the control condition (1.63 [1.49-1.77] vs. 1.85 [0.95-2.75], p = 0.039), and moderate and severe ERB significantly increased the septal E/e'-ratio. No changes in diastolic function were found during mild hyperinflation. PEEPi levels during ERB were inversely correlated with the E/A ratio (regression coefficient = -0.007, p = 0.001). Conclusions: Our data indicate dynamic hyperinflation as a determinant of left ventricular diastolic dysfunction in healthy subjects. Therapeutic reduction of hyperinflation might be a treatable trait to improve diastolic function in patients with COPD.

Induction of dynamic hyperinflation by expiratory resistance breathing in healthy subjects - an efficacy and safety study.

NEW FINDINGS: What is the central question of this study? The study aimed to establish a novel model to study the chronic obstructive pulmonary disease (COPD)-related cardiopulmonary effects of dynamic hyperinflation in healthy subjects. What is the main finding and its importance? A model of expiratory resistance breathing (ERB) was established in which dynamic hyperinflation was induced in healthy subjects, expressed both by lung volumes and intrathoracic pressures. ERB outperformed existing methods and represents an efficacious model to study cardiopulmonary mechanics of dynamic hyperinflation without potentially confounding factors as present in COPD. ABSTRACT: Dynamic hyperinflation (DH) determines symptoms and prognosis of chronic obstructive pulmonary disease (COPD). The induction of DH is used to study cardiopulmonary mechanics in healthy subjects without COPD-related confounders like inflammation, hypoxic vasoconstriction and rarefication of pulmonary vasculature. Metronome-paced tachypnoea (MPT) has proven effective in inducing DH in healthy subjects, but does not account for airflow limitation. We aimed to establish a novel model incorporating airflow limitation by combining tachypnoea with an expiratory airway stenosis. We investigated this expiratory resistance breathing (ERB) model in 14 healthy subjects using different stenosis diameters to assess a dose-response relationship. Via cross-over design, we compared ERB to MPT in a random sequence. DH was quantified by inspiratory capacity (IC, litres) and intrinsic positive end-expiratory pressure (PEEPi, cmH2 O). ERB induced a stepwise decreasing IC (means (95% CI): tidal breathing: 3.66 (3.45-3.88), ERB 3 mm: 3.33 (1.75-4.91), 2 mm: 2.05 (0.76-3.34), 1.5 mm: 0.73 (0.12-1.58) litres) and increasing PEEPi (tidal breathing: 0.70 (0.50-0.80), ERB 3 mm: 11.1 (7.0-15.2), 2 mm: 22.3 (17.1-27.6), 1.5 mm: 33.4 (3.40-63) cmH2 O). All three MPT patterns increased PEEPi, but to a far lesser extent than ERB. No adverse events during ERB were noted. In conclusion, ERB was proven to be a safe and efficacious model for the induction of DH and might be used for the investigation of cardiopulmonary interaction in healthy subjects.

The European COPD audit : Adherence to guidelines, readmission risk and hospital care for acute exacerbations in Austria.

OBJECTIVE: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are the major reason for COPD hospitalization and increased risk for readmissions. The organizational structure of Austrian hospitals provides the opportunity to investigate the impact of specialized respiratory care compared to general care on adherence to guidelines and readmission in AECOPD. METHODS: The data from the European COPD audit, a prospective observational non-interventional cohort trial were analyzed. In total, 823 patients admitted due to AECOPD in 26 hospitals (specialized respiratory care vs. general care) within Austria were included. Patients characteristics and outcomes (length of stay, readmission rate, and mortality) were analyzed in relation to hospital resources (personnel and equipment) and adherence to international guidelines. RESULTS: Patients admitted to general care had more comorbidities (Charlson comorbidity index: 2.6 ± 1.7 vs. 2.0 ± 1.4; p < 0.05) and a shorter length of stay (10.7 ± 7.8 days vs. 12.0 ± 10.2 days; p < 0.05). Patients admitted to specialized respiratory care more often underwent blood gas analysis and non-invasive ventilation (98.4% vs. 81.5% and 68.6% vs. 26.7%, p < 0.01; respectively). In multivariate analysis, the risk for AECOPD readmission was lower (odds ratio, OR 0.72 [0.51;0.91]; p < 0.05) in patients admitted to specialized respiratory care. CONCLUSION: A greater adherence to COPD guidelines with respect to blood gas analysis and non-invasive ventilation and decreased AECOPD readmission risk was observed for patients admitted to specialized respiratory care. Adherence to guidelines may have the potential to decrease COPD readmission rates.

The LEAD (Lung, Heart, Social, Body) Study: Objectives, Methodology, and External Validity of the Population-Based Cohort Study.

BACKGROUND: The Lung, hEart, sociAl, boDy (LEAD) Study (ClinicalTrials.gov; NCT01727518; http://clinicaltrials.gov) is a longitudinal, observational, population-based Austrian cohort that aims to investigate the relationship between genetic, environmental, social, developmental and ageing factors influencing respiratory health and comorbidities through life. The general working hypothesis of LEAD is the interaction of these genetic, environmental and socioeconomic factors influences lung development and ageing, the risk of occurrence of several non-communicable diseases (respiratory, cardiovascular, metabolic and neurologic), as well as their phenotypic (ie, clinical) presentation. METHODS: LEAD invited from 2011-2016 a random sample (stratified by age, gender, residential area) of Vienna inhabitants (urban cohort) and all the inhabitants of six villages from Lower Austria (rural cohort). Participants will be followed-up every four years. A number of investigations and measurements were obtained in each of the four domains of the study (Lung, hEart, sociAl, boDy) including data to screen for lung, cardiovascular and metabolic diseases, osteoporosis, and cognitive function. Blood and urine samples are stored in a biobank for future investigations. RESULTS: A total of 11.423 males (47.6%) and females (52.4%), aged 6-80 years have been included in the cohort. Compared to governmental statistics, the external validity of LEAD with respect to age, gender, citizenship, and smoking status was high. CONCLUSIONS: In conclusion, the LEAD cohort has been established following high quality standards; it is representative of the Austrian population and offers a platform to understand lung development and ageing as a key mechanism of human health both in early and late adulthood.

Long-term outcomes after acute hypercapnic COPD exacerbation : First-ever episode of non-invasive ventilation.

BACKGROUND: Non-invasive ventilation (NIV) is used to treat acute hypercapnic respiratory failure (AHRF) in patients with chronic obstructive pulmonary disease (COPD); however, long-term outcomes following discharge are largely unknown. This study aimed to characterize long-term outcomes and identify associated markers in patients with COPD after surviving the first episode of HRF requiring NIV. METHODS: This study retrospectively analyzed 122 patients, mean age 62 ± 8 years, 52% female and forced expiratory volume in 1 s (FEV1) predicted 30 ± 13%, admitted with an acute hypercapnic exacerbation of COPD and receiving a first-ever NIV treatment between 2000 and 2012. RESULTS: A total of 40% of the patients required hospital readmission due to respiratory reasons within 1 year. Persistent hypercapnia leading to the prescription of domiciliary NIV, older age and lower body mass index (BMI) were risk factors for readmission due to respiratory reasons. Survival rates were 79% and 63% at 1 and 2 years after discharge, respectively. A shorter time to readmission and recurrent hypercapnic failure, lower BMI and acidemia on the first admission, as well as hypercapnia at hospital discharge were correlated with a decreased long-term survival. CONCLUSION: Patients with COPD surviving their first episode of AHRF requiring NIV are at high risk for readmission and death. Severe respiratory acidosis, chronic respiratory failure and a lower BMI imply shorter long-term survival.

Phenotypes of COPD in an Austrian population : National data from the POPE study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) represents a major global health problem; however, there are no data regarding clinical phenotypes of these patients in Austria. METHODS: This was an analysis from the Austrian cohort of the cross-sectional Phenotypes of COPD in Central and Eastern Europe (POPE) study, which was offered to patients with stable COPD in a real-life setting. Patients were recruited at 5 different outpatient facilities in 3 different provinces in Austria. All consecutive patients aged ≥40 years with a diagnosis of COPD confirmed by a post-bronchodilator forced expired volume in 1 s/forced vital capacity (FEV1/FVC) ratio <0.7 during a stable state (≥4 weeks without exacerbation or worsening of any relevant comorbidities) were considered eligible. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analyses of differences in patient characteristics, symptom load, comorbidities, and pharmacological treatment. RESULTS: Among 283 patients fulfilling the inclusion criteria, 49.5% were considered non-exacerbators, 21.6% were classified as exacerbators with chronic bronchitis, 21.2% exacerbators without chronic bronchitis, and 7.8% were patients with an asthma-COPD overlap. Exacerbators had significantly higher prevalence of symptoms, lower lung function and exercise capacity, and a higher prevalence of comorbidities, such as heart failure and depression, compared with the other patient phenotypes. A large majority of patients with stable COPD in this cohort received inhaled triple therapy, irrespective of exacerbation history. CONCLUSIONS: There were significant differences in COPD outcome measures between predefined phenotypes of COPD in this study. The majority of patients with stable COPD in this Austrian population were not treated according to current COPD guidelines. While non-exacerbators appear to have been overtreated, patients with an asthma-COPD overlap appear to have been undertreated.

Increased brachial intima-media thickness is associated with circulating levels of asymmetric dimethylarginine in patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased cardiovascular risk. However, the mechanisms for this association are yet unclear. The aim of this study was to investigate the relationship between brachial intima-media thickness (B-IMT), an independent predictor of cardiovascular risk, systemic inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in patients with COPD and respective controls. METHODS: The study sample consisted of 60 patients with stable COPD, free from overt cardiovascular disorders, as well as 20 smoking and 20 nonsmoking controls. Ultrasound assessment of B-IMT, spirometry, venous blood sampling for quantification of inflammatory markers and ADMA levels were carried out, and individual cardiovascular risk was calculated via the Framingham risk score. RESULTS: Patients with COPD showed significantly higher B-IMT compared to smoking (P=0.007) and nonsmoking controls (P=0.033). COPD patients with elevated B-IMT had a twofold increased calculated 10-year risk for cardiovascular events compared to those below the recommended cutoff (P=0.002). B-IMT was significantly associated with systemic inflammation (interleukin-6 [IL-6]; r=0.365, P=0.006) and ADMA (r=0.331, P=0.013) in COPD. Multivariate linear regression revealed male sex and ADMA as independent predictors of B-IMT in this study sample. CONCLUSION: B-IMT is significantly increased in patients with COPD and is associated with systemic inflammation and ADMA levels.

An update on the efficacy of endobronchial valve therapy in the management of hyperinflation in patients with chronic obstructive pulmonary disease.

Lung volume reduction surgery has been shown to be effective in patients with heterogeneous emphysema, but is also associated with a relatively high perioperative morbidity and mortality. Accordingly, several novel and potentially less invasive methods for bronchoscopic lung volume reduction have been developed. Endobronchial valve (EBV) therapy is one such therapeutic approach in patients with advanced emphysema. It has been the most widely studied technique over the past years and represents an effective treatment option for patients with severe heterogeneous upper- or lower-lobe-predominant emphysema. The choice of EBV therapy largely depends on the distribution of emphysema and the presence or absence of interlobar collateral ventilation. Adequate patient selection and technical success of valve implantation with the intention of lobar exclusion are predictive factors for positive outcomes. This review attempts to highlight the milestones in the development of bronchoscopic lung volume reduction with one-way valve implantation over the past few years.

Tobacco addiction and smoking cessation in Austrian migrants: a cross-sectional study.

OBJECTIVE: Recent observations revealed substantial differences in smoking behaviour according to individuals' migration background. However, smoking cessation strategies are rarely tailored on the basis of a migration background. We aimed to determine whether smoking behaviour and preferences for smoking cessation programmes differ between Austrian migrant smokers and Austrian smokers without a migration background. STUDY DESIGN: Cross-sectional study. SETTING: Recruitment and interview were performed at public places in Vienna, Austria. PARTICIPANTS: The 420 smokers included: 140 Bosnian, 140 Turkish migrant smokers of the first or second generation, as well as 140 Austrian smokers without a migration background. METHODS: We cross-sectionally assessed determinants of smoking behaviour and smoking cessation of every participant with a standardised questionnaire. PRIMARY OUTCOME MEASURE: The Fagerström Test for Nicotine Dependence. SECONDARY OUTCOME MEASURES: Determinants of smoking behaviour, willingness to quit smoking and smoking cessation. RESULTS: Nicotine addiction expressed via the Fagerström score was significantly higher in smokers with a migration background versus those without (Bosnian migrant smokers 4.7 ± 2.5, Turkish migrant smokers 4.0 ± 2.0, Austrian smokers without a migration background 3.4 ± 2.3, p<0.0001). Bosnian and Turkish migrant smokers described a greater willingness to quit, but have had more previous cessation trials than Austrian smokers without a migration background, indicating an increased demand for cessation strategies in these study groups. They also participated in counselling programmes less often than Austrian smokers without a migration background. Finally, we found significant differences in preferences regarding smoking cessation programmes (ie, preferred location, service offered in another language besides German, and group rather than single counselling). CONCLUSIONS: We found significant differences in addictive behaviour and cessation patterns between smokers with and without a migration background. Our results indicate a strong demand for adjusting cessation programmes to the cultural background.

Effectiveness and safety of ciclesonide in the treatment of patients with persistent allergic or non-allergic asthma in medical practice (Data from a non-interventional study conducted in Austria).

BACKGROUND: Effectiveness and safety profile of ciclesonide in the treatment of persistent allergic or non-allergic asthma was evaluated in real-life setting in Austria. METHODS: Prospective, single-arm, 3-month observational, non-interventional, open-label cohort study in patients with persistent asthma (with or without allergic component) of any severity grade was conducted. Patients were either treatment naïve or switched to treatment with ciclesonide and had an indication for treatment with inhaled corticosteroids. RESULTS: In all, 307 patients (50.8% female; mean age, 45.7 years) were prescribed ciclesonide. After 3 months of observation, the percentage of patients with daily symptoms had declined from 33.2 to 3.9%, night-time symptoms from 21.8 to 5.2%, physical activity limitations from 73.9 to 24.4%, and rescue medication usage from 70.0 to 45.9%. The mean total Asthma Control Questionnaire (ACQ) score was 2.32 ± 1.14 at the first and 1.08 ± 0.88 at the final visit. The number of patients with well-controlled asthma (ACQ score < 1) increased considerably from 11.0% at baseline to 52.2% at study end. Clinically important mean improvements were observed in the total self-assessed Asthma Quality of Life score and all four domain scores. The mean forced expiratory volume in 1 s (FEV1) increased by 0.3 L from 2.60 ± 0.87 L to 2.89 ± 0.86 L, and the mean FEV1% predicted increased from 75.1 ± 15.4% to 83.7 ± 14.9%. Incidence of adverse drug reactions (ADRs) was low (4 ADRs in 3 of 307 patients, or 1.0%). CONCLUSION: This study confirmed the effectiveness and safety of ciclesonide under routine conditions in Austria. Improvements in symptom control, lung function, and quality of life were observed. Ciclesonide was well tolerated.

Insulin resistance may contribute to vascular dysfunction in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at an increased cardiovascular risk; however, the underlying mechanisms for this relationship are ill defined. Altered glucose metabolism may increase cardiovascular risk via impaired endothelial function. METHODS: We conducted a longitudinal pilot study to assess the interrelationship between systemic vascular function, glucose metabolism, and lung function in patients with COPD. Eighteen non-smoking patients with stable moderate-to-severe COPD [67 % male; median (first to third quartiles) Forced Expiratory Volume in 1 second (FEV1) % predicted: 38 % (28-55 %); body mass index: 26 kg/m(2) (24-28 kg/m(2))] free from cardiovascular risk factors were evaluated. Systemic vascular function was assessed by means of flow-mediated dilation technique of the brachial artery. Laboratory measurements included fasting blood glucose levels, circulating concentrations of insulin, C-reactive protein, and fibrinogen. Homeostatic model assessment of insulin resistance (HOMA-IR) was determined. Measurements were performed at baseline and were repeated after 12 months. RESULTS: Flow-mediated dilation significantly decreased from 13.5 % (11-15 %) at baseline to 9.8 % (6-12 %; p = 0.002) at the follow-up visit, whereas both fasting blood glucose concentrations and HOMA-IR increased from 94 mg/dl (86-103 mg/dl) to 102 mg/dl (94-111 mg/dl; p = 0.027) and from 1.2 (0.8-2.1) to 1.7 (1.2-3.0; p = 0.023), respectively. There was a significant relationship between changes in endothelial function and changes in fasting serum glucose (r = - 0.483, p = 0.009), HOMA-IR (r = - 0.441, p = 0.019), and FEV1 (r = 0.336, p = 0.05). CONCLUSION: Altered glucose metabolism may be associated with progression of endothelial dysfunction in patients with COPD.

Prevalence and prognosis of COPD in critically ill patients between 1998 and 2008.

The epidemiology of chronic obstructive pulmonary disease (COPD) in critically ill patients is largely unknown. The aims of the study were: 1) to determine whether COPD, either as the cause of intensive care unit (ICU) admission or as a comorbid condition, is an independent risk factor for increased morbidity and mortality; and 2) to investigate time trends in proportion and outcome of acute respiratory failure in patients with COPD admitted to ICUs. Prospectively recorded data from 194 453 adults consecutively admitted to 87 Austrian ICUs over a period of 11 years (1998-2008) were retrospectively analysed. COPD was present in 8.6% of all patients. The risk-adjusted mortality of patients with COPD was higher than in patients without COPD. The presence of COPD was an independent risk factor for increased mortality and was associated with prolonged mechanical ventilation and prolonged weaning. During the course of the 11 years, the proportion of acute respiratory failure due to COPD increased by about two-thirds, and the use of noninvasive ventilation within the COPD cohort more than doubled. Simultaneously, the risk-adjusted mortality of patients with COPD improved. In critically ill patients, the presence of COPD is increasing and is an independent risk factor for mortality and morbidity.

Sleep profile and symptoms of sleep disorders in patients with stable mild to moderate chronic obstructive pulmonary disease.

BACKGROUND: Sleep problems associated with chronic obstructive pulmonary disease may have an important impact on quality of life and health outcome measures in patients. The aim of this study was to prospectively assess differences in symptom profile and polysomnographic parameters in patients with stable mild to moderate COPD and age, gender, and body-mass-index matched controls without airflow obstruction. METHODS: The Sleep Disorders Questionnaire was administered to both patients and controls prior to clinical and polysomnographic evaluation. Responses obtained from the questionnaire were used to construct four independent symptom scales: sleep apnea, periodic limb movement syndrome, psychiatric sleep disorder, and narcolepsy. Associations between each diagnostic scale and sleep parameters were considered by means of multiple analyses of covariance. RESULTS: Fifty-two patients with mild-to-moderate COPD (age 62±8 years, BMI 29±7 kg/sqm) and 52 age, gender, and body-weight matched controls without COPD were studied. Patients with COPD had overall lower sleep efficiency, a lower total sleep time, and lower mean overnight oxygen saturation compared to controls. Patients with COPD were significantly more likely to report symptoms such as insomnia and difficulty in initiating and maintaining sleep, resulting in overall higher psychiatric sleep disorder scale scores in patients compared with controls. Minimum oxygen saturation was an independent predictor for all symptom scales. After correcting for potentially confounding factors, including pack/years of smoking, total sleep time, sleep efficiency, arousal index, mean and minimum oxygen saturation, and apnea-hypopnea-index, the between group-differences for both the periodic limb movement and psychiatric sleep disorder scale scores remained statistically significant. CONCLUSIONS: We observed significant differences in both quantity and quality of sleep between patients with stable mild to moderate chronic obstructive pulmonary disease and respective controls.

Long-term non-invasive ventilation in COPD after acute-on-chronic respiratory failure.

BACKGROUND: COPD patients who remain hypercapnic after acute respiratory failure requiring mechanical ventilation have a poor prognosis. Long-term nocturnal non-invasive ventilation (NIV) may be beneficial for these patients. We hypothesized that stable patients on long-term NIV would experience clinical worsening after withdrawal of NIV. METHODS: We included 26 consecutive COPD patients (63 ± 6 years, 58% male, FEV(1) 31 ± 14% predicted) who remained hypercapnic after acute respiratory failure requiring mechanical ventilation. After a six month run-in period, during which all patients received NIV, they were randomised to either continue (ventilation group, n = 13) or to stop NIV (withdrawal group, n = 13). The primary endpoint was time to clinical worsening defined as an escalation of mechanical ventilation. RESULTS: All patients remained stable during the run-in period. After randomisation the withdrawal group had a higher probability of clinical worsening compared to the ventilation group (p = 0.0018). After 12 months, ten patients (77%) in the withdrawal group, but only two patients (15%) in the ventilation group, experienced clinical worsening (p = 0.0048). Six-minute walking distance increased in the ventilation group. CONCLUSION: COPD patients who remain hypercapnic after acute respiratory failure requiring mechanical ventilation may benefit from long-term NIV.

Prediction and uncertainty source analysis of the spatial and temporal disturbance from off-road vehicular traffic in a complex ecosystem.

Vehicle use during military training activities results in soil disturbance and vegetation loss. The capacity of lands to sustain training is a function of the sensitivity of lands to vehicle use and the pattern of land use. The sensitivity of land to vehicle use has been extensively studied. Less well understood are the spatial patterns of vehicle disturbance. Since disturbance from off-road vehicular traffic moving through complex landscapes varies spatially, a spatially explicit nonlinear regression model (disturbance model) was used to predict the pattern of vehicle disturbance across a training facility. An uncertainty analysis of the model predictions assessed the spatial distribution of prediction uncertainty and the contribution of different error sources to that uncertainty. For the most part, this analysis showed that mapping and modeling process errors contributed more than 95% of the total uncertainty of predicted disturbance, while satellite imagery error contributed less than 5% of the uncertainty. When the total uncertainty was larger than a threshold, modeling error contributed 60% to 90% of the prediction uncertainty. Otherwise, mapping error contributed about 10% to 50% of the total uncertainty. These uncertainty sources were further partitioned spatially based on other sources of uncertainties associated with vehicle moment, landscape characterization, satellite imagery, etc.