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Background: There is no existing reliable and practical method for predicting the prognosis of acute respiratory distress syndrome (ARDS). Objective: We aimed to clarify the association between the ROX index, which is calculated as the ratio of peripheral oxygen saturation divided by the fraction of inspired oxygen to the respiratory rate, and the prognosis of patients with ARDS under ventilator support. Methods: In this single-center retrospective cohort study from prospectively collected database, eligible patients were categorized into three groups based on ROX tertiles. The primary outcome was the 28-day survival, and the secondary outcome was 28-day liberation from ventilator support. We performed multivariable analysis using the Cox proportional hazards model. Results: Among 93 eligible patients, 24 (26%) patients died. The patients were divided into three groups according to the ROX index (< 7.4, 7.4–11, ≥ 11), with 13, 7, and 4 patients dying in the groups, respectively. A higher ROX index was associated with lower mortality; adjusted hazard ratios [95% CIs] for increasing tertiles of ROX index: 1[reference], 0.54[0.21–1.41], 0.23[0.074–0.72] (P = 0.011 for trend) and a higher rate of successful 28-day liberation from ventilator support; adjusted hazard ratios [95% CIs] for increasing tertiles of ROX index: 1[reference], 1.41[0.68–2.94], 2.80[1.42–5.52] (P = 0.001 for trend). Conclusions: The ROX index at 24 h after initiating ventilator support is a predictor of outcomes in patients with ARDS and might inform initiation of more advanced treatments. [ABSTRACT FROM AUTHOR]

Tobacco-specific nitrosamines (TSNAs) are a group of toxic substances specific to tobacco. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a tobacco-specific nitrosamine measurable in urine with a much longer half-life than cotinine. We aimed to examine the association between urinary tobacco-specific NNAL and HPV infection among American women. We used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2014 to collect details on their urinary NNAL, HPV infection status, and other essential variables. The association between dietary urinary NNAL and HPV infection status was analyzed by using a weighted multivariate logistic regression model, and stratified subgroup analysis. In total, 5197 participants aged 18–59 years were identified, with overall prevalence of high-risk and low-risk HPV infection of 22.0% and 19.1%, respectively. The highest quartile of NNAL(Q4) was more positively associated with low-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 1.83 (1.35,2.50), p<0.001). the highest quartile of NNAL(Q4) was more positively associated with high-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 2.20 (1.57,3.08), p < 0.001). In subgroup analyses, the positive correlation between urinary NNAL levels and low-risk HPV infection status was inconsistent in marital status and BMI (interaction p < 0.05). The positive association of urinary NNAL levels with high-risk HPV infection status was inconsistent in smoking and BMI. (interaction p < 0.05). Tobacco-specific NNAL levels positively correlate with high- and low-risk HPV. Future well-designed longitudinal studies are still needed to validate the effect of tobacco exposure on HPV infection by NNAL. [ABSTRACT FROM AUTHOR]

Background: Studies in general population reported a positive association between tobacco smoking and airflow obstruction (AFO), a hallmark of chronic obstructive pulmonary disease (COPD). However, this attempt was less addressed in silica dust-exposed workers. Methods: This retrospective cohort study consisted of 4481 silicotic workers attending the Pneumoconiosis Clinic during 1981–2019. The lifelong work history and smoking habits of these workers were extracted from medical records. Spirometry was carried out at the diagnosis of silicosis (n = 4177) and reperformed after an average of 9.4 years of follow-up (n = 2648). AFO was defined as forced expiratory volume in one second (FEV1)/force vital capacity (FVC) less than lower limit of normal (LLN). The association of AFO with smoking status was determined using multivariate logistics regression, and the effect of smoking cessation on the development of AFO was evaluated Cox regression. Results: Smoking was significantly associated with AFO (current smokers: OR = 1.92, 95% CI 1.51–2.44; former smokers: OR = 2.09, 95% CI 1.65–2.66). The risk of AFO significantly increased in the first 3 years of quitting smoking (OR = 1.23, 95% CI 1.02–1.47) but decreased afterwards with increasing years of cessation. Smoking cessation reduced the risk of developing AFO no matter before or after the confirmation of silicosis (pre-silicosis cessation: HR = 0.58, 95% CI 0.46–0.74; post-silicosis cessation: HR = 0.62, 95% CI 0.48–0.79). Conclusions: Smoking cessation significantly reduced the risk of AFO in the workers with silicosis, although the health benefit was not observed until 3 years of abstinence. These findings highlight the importance of early and long-term smoking cessation among silicotic or silica dust-exposed workers. [ABSTRACT FROM AUTHOR]

Evaluating variability and stability using measures for nonlinear dynamics may provide additional insight into the structure of the locomotor system, reflecting the neuromuscular system's organization of gait. This is in particular of interest when this system is affected by a respiratory disease and it's extrapulmonary manifestations. This study assessed stride-to-stride fluctuations and gait stability in patients with chronic obstructive pulmonary disease (COPD) during a self-paced, treadmill 6-minute walk test (6MWT) and its association with clinical outcomes. In this cross-sectional study, eighty patients with COPD (age 62±7y; forced expiratory volume in first second 56±19%predicted) and 39 healthy older adults (62±7y) were analyzed. Gait parameters including stride-to-stride fluctuations (coefficient of variation (CoV), predictability (sample entropy) and stability (Local Divergence Exponent (LDE)) were calculated over spatiotemporal parameters and center of mass velocity. Independent t-test, Mann-Whitney U test and ANCOVA analyses were conducted. Correlations were calculated between gait parameters, functional mobility using Timed Up and Go Test, and quadriceps muscle strength using dynamometry. Patients walked slower than healthy older adults. After correction for Speed, patients demonstrated increased CoV in stride length (F(1,116) = 5.658, p = 0.019), and increased stride length predictability (F(1,116) = 3.959, p = 0.049). Moderate correlations were found between mediolateral center of mass velocity LDE and normalized maximum peak torque (ρ = -0.549). This study showed that patients with COPD demonstrate alterations in stride length fluctuations even when adjusted for walking speed, highlighting the potential of nonlinear measures to detect alterations in gait function in patients with COPD. Association with clinical outcomes were moderate to weak, indicating that these clinical test are less discriminative for gait alterations. [ABSTRACT FROM AUTHOR]

Introduction: The interaction between smoking and asthma impairs lung function and increases airflow obstruction severity. The identification of smoking patterns in smokers with and without asthma is crucial to provide the best care strategies. The aims of this study are to estimate asthma frequency, describe asthma features, and characterize smoking in smokers attending smoking cessation units. Material and methods: We carried out a cross-sectional study in five smoking cessation units with different geographical distribution to estimate asthma frequency in smokers, characterize asthma features in smokers, as well as smoking in asthmatic smokers. Results: Asthma frequency among smokers was 18.6%. Asthmatic smokers presented high passive exposure, low smoking self-efficacy and will to quit smoking, as well as a high exacerbation frequency, severe symptoms, and frequent use of long-acting beta agonists, inhaled steroids, and short-acting beta agonists. Discussion: Smokers with asthma constitute a high-risk group with worsened evolution of pulmonary involvement. All smokers should be regularly screened for asthma. Effective smoking cessation strategies should be proposed to smokers with asthma in order to reverse the harmful effects of smoking on the airway, together with a comprehensive and integral approach. [ABSTRACT FROM AUTHOR]

Background: People experiencing asthma exacerbations are at increased risk of cardiovascular events. To better understand the relationship between asthma exacerbations and cardiovascular risk, this randomized case-control, cross-over controlled trial assessed the immediate systemic inflammatory and vascular responses to acutely induced pulmonary inflammation and bronchoconstriction in people with asthma and controls. Methods: Twenty-six people with asthma and 25 controls underwent three airway challenges (placebo, mannitol, and methacholine) in random order. Markers of cardiovascular risk, including serum C-reactive protein, interleukin-6, and tumor necrosis factor, endothelial function (flow-mediated dilation), microvascular function (blood-flow following reactive hyperemia), and arterial stiffness (pulse wave velocity) were evaluated at baseline and within one hour following each challenge. The systemic responses in a) asthma/control and b) positive airway challenges were analyzed. (ClinicalTrials.gov reg# NCT02630511) Results: Both the mannitol and methacholine challenges resulted in clinically significant reductions in forced expiratory volume in 1 second (FEV1) in asthma (-7.6% and -17.9%, respectively). Following positive challenges, reduction in FEV1 was -27.6% for methacholine and -14.2% for mannitol. No meaningful differences in predictors of cardiovascular risk were observed between airway challenges regardless of bronchoconstrictor response. Conclusion: Neither acutely induced bronchoconstriction nor pulmonary inflammation and bronchoconstriction resulted in meaningful changes in systemic inflammatory or vascular function. These findings question whether the increased cardiovascular risk associated with asthma exacerbations is secondary to acute bronchoconstriction or inflammation, and suggest that other factors need to be further evaluated such as the cardiovascular impacts of short-acting inhaled beta-agonists. [ABSTRACT FROM AUTHOR]

Background: The prevalence of multiple chronic conditions (MCC), defined as several coexisting chronic conditions, has increased with the aging of society. MCC is associated with poor outcomes, but most comorbid diseases in asthma patients have been evaluated as asthma-associated diseases. We investigated the morbidity of coexisting chronic diseases in asthma patients and their medical burdens. Methods: We analyzed data from the National Health Insurance Service-National Sample Cohort for 2002–2013. We defined MCC with asthma as a group of one or more chronic diseases in addition to asthma. We analyzed 20 chronic conditions, including asthma. Age was categorized into groups 1–5 (< 10, 10–29, 30–44, 45–64, and ≥ 65 years, respectively). The frequency of medical system use and associated costs were analyzed to determine the asthma-related medical burden in patients with MCC. Results: The prevalence of asthma was 13.01%, and the prevalence of MCC in asthmatic patients was 36.55%. The prevalence of MCC with asthma was higher in females than males and increased with age. The significant comorbidities were hypertension, dyslipidemia, arthritis, and diabetes. Dyslipidemia, arthritis, depression, and osteoporosis were more common in females than males. Hypertension, diabetes, COPD, coronary artery disease, cancer, and hepatitis were more prevalent in males than females. According to age, the most prevalent chronic condition in groups 1 and 2 was depression, dyslipidemia in group 3, and hypertension in groups 4 and 5. Older age, low income, and severe disability were independent risk factors for MCC in patients with asthma. The frequency of asthma-related medical system use and asthma-associated costs increased with increasing numbers of coexisting chronic diseases. Conclusion: Comorbid chronic diseases in asthma patients differed according to age and sex. The asthma-related-medical burdens were highest in patients with five or more chronic conditions and groups 1 and 5. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is considered a heterogenic syndrome with systemic effects, including muscle dysfunction. There is evidence of postural control impairments among individuals with COPD, partly related to muscle weakness. However, research is scarce regarding the other underlying systems of postural control, such as the visual, somatosensory and vestibular system. The aim was to compare postural control, as well as the motor and sensory systems, between individuals with and without COPD. Methods: Twenty-two participants with COPD (mean age 74.0 ±6.2 years) and 34 non-obstructive references (mean age 74.9 ±4.9 years) participated in this cross-sectional study. Postural control was assessed with center of pressure trajectory of postural sway in quiet as well as a limits of stability test, calculating mediolateral and anteroposterior amplitudes for each test. Assessment of function in the motor system included maximum hand grip strength, as well as maximum strength in muscles around the hip, knee and ankle joints. Visual acuity, pressure sensibility, proprioception, vestibular screening, and reaction time were also included. Data was compared between groups, and significant differences in postural control were further analyzed with an orthogonal projection of latent structures regression model. Results: There was a significantly increased sway amplitude in the mediolateral direction in quiet stance on soft surface with eyes open (p = 0.014) as well as a smaller anteroposterior amplitude in the limits of stability test (p = 0.019) in the COPD group. Regression models revealed that the mediolateral amplitude was related to visual acuity and the burden of tobacco smoking assessed as pack-years. Further, muscle strength associated with anteroposterior amplitude in limits of stability test in the COPD group, and with age and ankle dorsal flexion strength among the referents. Besides for lower ankle plantar flexion strength in the COPD group, there were however no significant differences in muscle strength. Conclusions: Individuals with COPD had a decreased postural control and several factors were associated with the impairments. The findings imply that the burden of tobacco smoking and reduced visual acuity relate to increased postural sway in quiet stance, and that muscle weakness is related to decreased limits of stability, among individuals with COPD. [ABSTRACT FROM AUTHOR]

Background: Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality after open abdominal surgery. Optimized perioperative lung expansion may minimize the synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction. This ongoing study will assess whether an anesthesia-centered bundle focused on perioperative lung expansion results in decreased incidence and severity of PPCs after open abdominal surgery. Methods: Prospective multicenter randomized controlled pragmatic trial in 750 adult patients with at least moderate risk for PPCs undergoing prolonged (≥2 hour) open abdominal surgery. Participants are randomized to receive either a bundle intervention focused on perioperative lung expansion or usual care. The bundle intervention includes preoperative patient education, intraoperative protective ventilation with individualized positive end-expiratory pressure to maximize respiratory system compliance, optimized neuromuscular blockade and reversal management, and postoperative incentive spirometry and early mobilization. Primary outcome is the distribution of the highest PPC severity by postoperative day 7. Secondary outcomes include the proportion of participants with: PPC grades 1–2 through POD 7; PPC grades 3–4 through POD 7, 30 and 90; intraoperative hypoxemia, rescue recruitment maneuvers, or cardiovascular events; and any major extrapulmonary postoperative complications. Additional secondary and exploratory outcomes include individual PPCs by POD 7, length of postoperative oxygen therapy or other respiratory support, hospital resource use parameters, Patient-Reported Outcomes Measurements (PROMIS®) questionnaires for dyspnea and fatigue collected before and at days 7, 30 and 90 after surgery, and plasma concentrations of lung injury biomarkers (IL6, IL-8, RAGE, CC16, Ang-2) analyzed from samples obtained before, end of, and 24 hours after surgery. Discussion: Participant recruitment for this study started January 2020; results are expected in 2024. At the conclusion of this trial, we will determine if this anesthesia-centered strategy focused on perioperative lung expansion reduces lung morbidity and healthcare utilization after open abdominal surgery. Trial registration: ClinicalTrial.gov NCT04108130. [ABSTRACT FROM AUTHOR]

Background: Barotrauma frequently occurs in coronavirus disease 2019. Previous studies have reported barotrauma to be a mortality-risk factor; however, its time-dependent nature and pathophysiology are not elucidated. To investigate the time-dependent characteristics and the etiology of coronavirus disease 2019-related-barotrauma. Methods and findings: We retrospectively reviewed intubated patients with coronavirus disease 2019 from March 2020 to May 2021. We compared the 90-day survival between the barotrauma and non-barotrauma groups and performed landmark analyses on days 7, 14, 21, and 28. Barotrauma within seven days before the landmark was defined as the exposure. Additionally, we evaluated surgically treated cases of coronavirus disease 2019-related pneumothorax. We included 192 patients. Barotrauma developed in 44 patients (22.9%). The barotrauma group's 90-day survival rate was significantly worse (47.7% vs. 82.4%, p < 0.001). In the 7-day landmark analysis, there was no significant difference (75.0% vs. 75.7%, p = 0.79). Contrastingly, in the 14-, 21-, and 28-day landmark analyses, the barotrauma group's survival rates were significantly worse (14-day: 41.7% vs. 69.1%, p = 0.044; 21-day: 16.7% vs. 62.5%, p = 0.014; 28-day: 20.0% vs. 66.7%, p = 0.018). Pathological examination revealed a subpleural hematoma and pulmonary cyst with heterogenous lung inflammation. Conclusions: Barotrauma was a poor prognostic factor for coronavirus disease 2019, especially in the late phase. Heterogenous inflammation may be a key finding in its mechanism. Barotrauma is a potentially important sign of lung destruction. [ABSTRACT FROM AUTHOR]

Objectives: To assess the incidence of barotrauma and its impact on mortality in COVID-19 patients admitted to ICU. Design: Single-center retrospective study of consecutive COVID-19 patients admitted to a rural tertiary-care ICU. The primary outcomes were incidence of barotrauma in COVID-19 patients and all-cause 30-day mortality. Secondary outcomes were the length of stay (LOS) in the hospital and ICU. Kaplan-Meier method and log-rank test were used in the survival data analysis. Setting: Medical ICU, West Virginia University Hospital (WVUH), USA. Patients: All adult patients were admitted to the ICU for acute hypoxic respiratory failure due to coronavirus disease 2019 between September 1, 2020, and December 31, 2020. Historical controls were ARDS patients admitted pre-COVID. Intervention: Not applicable. Measurements and main results: One hundred and sixty-five consecutive patients with COVID-19 were admitted to the ICU during the defined period, compared to 39 historical non-COVID controls. The overall incidence of barotrauma in COVID-19 patients was 37/165 (22.4%) compared to 4/39 (10.3%) in the control group. Patients with COVID-19 and barotrauma had a significantly worse survival (HR = 1.56, p = 0.047) compared to controls. In those requiring invasive mechanical ventilation, the COVID group also had significantly higher rates of barotrauma (OR 3.1, p = 0.03) and worse all-cause mortality (OR 2.21, p = 0.018). COVID-19 with barotrauma had significantly higher LOS in the ICU and the hospital. Conclusions: Our data on critically ill COVID-19 patients admitted to the ICU shows a high incidence of barotrauma and mortality compared to the controls. Additionally, we report a high incidence of barotrauma even in non-ventilated ICU patients. [ABSTRACT FROM AUTHOR]

Background: The available data to determine the chronic obstructive pulmonary disease (COPD) burden in Saudi Arabia are scarce. Therefore, this study closely examines and tracks the trends of the COPD burden in Saudi Arabia from 1990 to 2019 using the dataset of the Global Burden of Disease (GBD) 2019. Methods: This study used the GBD 2019 dataset to analyse the COPD prevalence, incidence, morbidity and mortality rates in the Saudi Arabian population from 1990 to 2019, stratified by sex and age. The age-standardised rate was used to determine the prevalence, incidence, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life years (DALYs) and deaths. Results: In 2019, an estimated 434,560.64 people (95% Uncertainty Interval (UI) 396,011.72–473,596.71) had COPD in Saudi Arabia, corresponding to an increase of 329.82% compared with the number of diagnosed people in 1990 [101,104.05 (95% UI 91,334.4–111,223.91)]. The prevalence rate of COPD increased by 49%, from 1,381.26 (1,285.35–1,484.96) cases per 100,000 in 1990 to 2,053.04 (1918.06–2194.29) cases per 100,000 in 2019, and this trend was higher in males than females. The incidence rate of COPD in 2019 was 145.06 (136.62–154.76) new cases per 100,000, representing an increase of 43.4% from the 1990 incidence rate [101.18 (95.27–107.86)]. In 2019, the DALYs rate was 508.15 (95% UI 434.85–581.58) per 100,000 population. This was higher in males than females, with a 14.12% increase among males. In 2019, YLLs contributed to 63.6% of DALYs due to COPD. The death rate due to COPD was 19.6 (95% UI 15.94–23.39) deaths per 100 000 in 2019, indicating a decrease of 41.44% compared with the death rate in 1990 [33.55 deaths per 100 000 (95% UI 25.13–47.69)]. In 2019, COPD deaths accounted for 1.65% (1.39–1.88) of the total of deaths in Saudi Arabia and 57% of all deaths caused by chronic respiratory diseases. Conclusion: Over the period 1990–2019, the prevalence and incidence of COPD in Saudi Arabia have been steadily rising. Even though COPD morbidity and death rates have been decreasing, they remain higher in men and older age. The holistic assessment and interventions with careful attention to optimising the community-based primary care management, such as screening for early diagnosis, smoking cessation programs and pulmonary rehabilitation, are likely to be the most successful strategies to reduce the burden of COPD in Saudi Arabia. [ABSTRACT FROM AUTHOR]

Background: Growing numbers of people with multimorbidity have a co-occurring mental health condition such as depression. Co-occurring depression is associated with poor patient outcomes and increased healthcare costs including unplanned use of secondary healthcare which may be avoidable. Aim: To summarise the current evidence on the association between depression and unplanned secondary healthcare use among patients with multimorbidity. Methods: We conducted a systematic review by searching MEDLINE, EMBASE, PsychINFO, Web of Science, CINAHL, and Cochrane Library from January 2000 to March 2021. We included studies on adults with depression and at least one other physical long-term condition that examined risk of emergency hospital admissions as a primary outcome, alongside emergency department visits or emergency readmissions. Studies were assessed for risk of bias using The National Institute of Health National Heart, Lung, and Blood Institute quality assessment tool. Relevant data were extracted from studies and a narrative synthesis of findings produced. Results: Twenty observational studies were included in the review. Depression was significantly associated with different outcomes of unplanned secondary healthcare use, across various comorbidities. Among the studies examining these outcomes, depression predicted emergency department visits in 7 out of 9 studies; emergency hospital admissions in 19 out of 20 studies; and emergency readmissions in 4 out of 4 studies. This effect increased with greater severity of depression. Other predictors of unplanned secondary care reported include increased age, being female, and presence of greater numbers of comorbidities. Conclusion: Depression predicted increased risk of unplanned secondary healthcare use in individuals with multimorbidity. The literature indicates a research gap in identifying and understanding the impact of complex multimorbidity combinations, and other patient characteristics on unplanned care in patients with depression. Findings indicate the need to improve planned care for patients with moderate-to-severe depression. We suggest regular reviews of care plans, depression severity monitoring and assessment of hospital admission risk in primary care settings. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD), the most common chronic respiratory disease worldwide, not only leads to the decline of pulmonary function and quality of life consecutively, but also has become a major economic burden on individuals, families, and society in China. The purpose of this meta-analysis was to explore the risk factors for developing COPD in the Chinese population that resides in China and to provide a theoretical basis for the early prevention of COPD. Methods: A total of 2457 cross-sectional, case-control, and cohort studies published related to risk factors for COPD in China were searched. Based on the inclusion and exclusion criteria, 20 articles were selected. Stata 11.0 was used for meta-analysis. After merging the data, the pooled effect and 95% confidence intervals (CIs) were calculated to assess the association between risk factors and COPD. Heterogeneity between studies was assessed using I2 and Cochran's Q tests. Begg's test was used to assess publication bias. Results: Exposure to particulate matter less than 2.5 μm in diameter (PM2.5) (pooled effect = 1.73; 95%CI: 1.16~2.58; P <0.01), smoking history (pooled effect = 2.58; 95%CI: 2.00~3.32; P <0.01), passive smoking history (pooled effect = 1.39; 95%CI: 1.03~1.87; P = 0.03), male sex(pooled effect = 1.70; 95%CI: 1.31~2.22; P <0.01), body mass index (BMI) <18.5 kg/m2 (pooled effect = 1.73; 95%CI: 1.32~2.25; P <0.01), exposure to biomass burning emissions (pooled effect = 1.65; 95%CI: 1.32~2.06; P <0.01), childhood respiratory infections (pooled effect = 3.44; 95%CI: 1.33~8.90; P = 0.01), residence (pooled effect = 1.24; 95%CI: 1.09~1.42; P <0.01), and a family history of respiratory diseases (pooled effect = 2.04; 95%CI: 1.53~2.71; P <0.01) were risk factors for COPD in the Chinese population. Conclusion: Early prevention of COPD could be accomplished by quitting smoking, reducing exposure to air pollutants and biomass burning emissions, maintaining body mass index between 18.5 kg/m2 and 28 kg/m2, protecting children from respiratory infections, adopting active treatments to children with respiratory diseases, and conducting regular screening for those with family history of respiratory diseases. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are bioactive particles that evoke beneficial responses in recipient cells. We identified a role for MSC-EV in immune modulation and cellular salvage in a model of SARS-CoV-2 induced acute lung injury (ALI) using pulmonary epithelial cells and exposure to cytokines or the SARS-CoV-2 receptor binding domain (RBD). Whereas RBD or cytokine exposure caused a pro-inflammatory cellular environment and injurious signaling, impairing alveolar-capillary barrier function, and inducing cell death, MSC-EVs reduced inflammation and reestablished target cell health. Importantly, MSC-EV treatment increased active ACE2 surface protein compared to RBD injury, identifying a previously unknown role for MSC-EV treatment in COVID-19 signaling and pathogenesis. The beneficial effect of MSC-EV treatment was confirmed in an LPS-induced rat model of ALI wherein MSC-EVs reduced pro-inflammatory cytokine secretion and respiratory dysfunction associated with disease. MSC-EV administration was dose-responsive, demonstrating a large effective dose range for clinical translation. These data provide direct evidence of an MSC-EV-mediated improvement in ALI and contribute new insights into the therapeutic potential of MSC-EVs in COVID-19 or similar pathologies of respiratory distress. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effects of statins and steroids on the risk of coronary artery disease (CAD) and stroke in patients with interstitial lung disease and pulmonary fibrosis (ILD-PF). Methods: We retrospectively enrolled patients with ILD-PF who were using statins (statin cohort, N = 11,567) and not using statins (nonstatin cohort, N = 26,159). Cox proportional regression was performed to analyze the cumulative incidence of CAD and stroke. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of CAD and stroke were determined after sex, age, and comorbidities, as well as the use of inhaler corticosteroids (ICSs), oral steroids (OSs), and statins, were controlled for. Results: Compared with those of patients without statin use, the aHRs (95% CIs) of patients with statin use for CAD and ischemic stroke were 0.72 (0.65–0.79) and 0.52 (0.38–0.72), respectively. For patients taking single-use statins but not ICSs/OSs, the aHRs (95% CIs) for CAD and ischemic stroke were 0.72 (0.65–0.79)/0.69 (0.61–0.79) and 0.54 (0.39–0.74)/0.50 (0.32–0.79), respectively. For patients using ICSs/OSs, the aHRs (95% CIs) for CAD and ischemic stroke were 0.71 (0.42–1.18)/0.74 (0.64–0.85) and 0.23 (0.03–1.59)/0.54 (0.35–0.85), respectively. Conclusions: The findings demonstrate that statin use, either alone or in combination with OS use, plays an auxiliary role in the management of CAD and ischemic stroke in patients with ILD-PF. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has presented emergency medical services (EMS) worldwide with the difficult task of identifying patients with COVID-19 and predicting the severity of their illness. The aim of this study was to investigate whether physiological respiratory parameters in pre-hospital patients with COVID-19 differed from those without COVID-19 and if they could be used to aid EMS personnel in the prediction of illness severity. Methods: Patients with suspected COVID-19 were included by EMS personnel in Uppsala, Sweden. A portable respiratory monitor based on pneumotachography was used to sample the included patient's physiological respiratory parameters. A questionnaire with information about present symptoms and background data was completed. COVID-19 diagnoses and hospital admissions were gathered from the electronic medical record system. The physiological respiratory parameters of patients with and without COVID-19 were then analyzed using descriptive statistical analysis and logistic regression. Results: Between May 2020 and January 2021, 95 patients were included, and their physiological respiratory parameters analyzed. Of these patients, 53 had COVID-19. Using adjusted logistic regression, the odds of having COVID-19 increased with respiratory rate (95% CI 1.000–1.118), tidal volume (95% CI 0.996–0.999) and negative inspiratory pressure (95% CI 1.017–1.152). Patients admitted to hospital had higher respiratory rates (p<0.001) and lower tidal volume (p = 0.010) compared to the patients who were not admitted. Using adjusted logistic regression, the odds of hospital admission increased with respiratory rate (95% CI 1.081–1.324), rapid shallow breathing index (95% CI 1.006–1.040) and dead space percentage of tidal volume (95% CI 1.027–1.159). Conclusion: Patients taking smaller, faster breaths with less pressure had higher odds of having COVID-19 in this study. Smaller, faster breaths and higher dead space percentage also increased the odds of hospital admission. Physiological respiratory parameters could be a useful tool in detecting COVID-19 and predicting hospital admissions, although more research is needed. [ABSTRACT FROM AUTHOR]

Background: Social and ecological differences in early SARS-CoV-2 pandemic screening and outcomes have been documented, but the means by which these differences have arisen are not well understood. Objective: To characterize socioeconomic and chronic disease-related mechanisms underlying these differences. Design: Observational cohort study. Setting: Outpatient and emergency care. Patients: 12900 Cleveland Clinic Health System patients referred for SARS-CoV-2 testing between March 17 and April 15, 2020. Interventions: Nasopharyngeal PCR test for SARS-CoV-2 infection. Measurements: Test location (emergency department, ED, vs. outpatient care), COVID-19 symptoms, test positivity and hospitalization among positive cases. Results: We identified six classes of symptoms, ranging in test positivity from 3.4% to 23%. Non-Hispanic Black race/ethnicity was disproportionately represented in the group with highest positivity rates. Non-Hispanic Black patients ranged from 1.81 [95% confidence interval: 0.91–3.59] times (at age 20) to 2.37 [1.54–3.65] times (at age 80) more likely to test positive for the SARS-CoV-2 virus than non-Hispanic White patients, while test positivity was not significantly different across the neighborhood income spectrum. Testing in the emergency department (OR: 5.4 [3.9, 7.5]) and cardiovascular disease (OR: 2.5 [1.7, 3.8]) were related to increased risk of hospitalization among the 1247 patients who tested positive. Limitations: Constraints on availability of test kits forced providers to selectively test for SARS-Cov-2. Conclusion: Non-Hispanic Black patients and patients from low-income neighborhoods tended toward more severe and prolonged symptom profiles and increased comorbidity burden. These factors were associated with higher rates of testing in the ED. Non-Hispanic Black patients also had higher test positivity rates. [ABSTRACT FROM AUTHOR]

Dexamethasone provides benefits in patients with coronavirus disease 2019 (COVID-19), although data regarding immunological profiles and viral clearance are limited. This study aimed to evaluate for differences in biomarkers among patients with severe COVID-19 who did and did not receive dexamethasone. We measured plasma biomarkers of lung epithelial/endothelial injury and inflammation in 31 patients with severe COVID-19 and in 13 controls. Changes in biomarkers and clinical parameters were compared during the 7-day period among COVID-19 patients, and also according to dexamethasone use. Thirty-two patients with severe COVID-19 who received mechanical ventilation (n = 6), high-flow nasal cannula (n = 11), and supplemental oxygen (n = 15) were analyzed. Relative to controls, patients with severe COVID-19 had significantly higher concentrations of biomarkers related to glycocalyx shedding (endocan and syndecan-1), endothelial injury (von Willebrand factor), and inflammation (soluble receptor for advanced glycation end-products [sRAGE] and interleukin-6). The 7-day decreases in biomarkers of endothelial injury (angiopoietin-2 [Ang-2] and intercellular adhesion molecule-1 [ICAM-1]) and sRAGE, but not in the biomarker of lung epithelial injury (surfactant protein D), were correlated with decreases in C-reactive protein and radiologic score at day 7. Twenty patients (63%) received dexamethasone, and the dexamethasone and non-dexamethasone groups differed in terms of disease severity. However, dexamethasone was associated marginally with increased SpO2/FiO2 and significantly with decreases in C-reactive protein and radiologic score after adjusting for baseline imbalances. Furthermore, the dexamethasone group exhibited a significant decrease in the concentrations of Ang-2, ICAM-1, soluble form of the Tie2 receptor (a biomarker of glycocalyx shedding), and sRAGE. Both groups exhibited a clinically insignificant increase in the cycle threshold value. Severe COVID-19 may be characterized by more severe endothelial injury and inflammation, and less severe lung epithelial injury. There is a possibility that dexamethasone improved severe COVID-19 and related endothelial injury without delaying viral clearance. [ABSTRACT FROM AUTHOR]

Objective: Failure of membrane oxygenator (MO) function of venovenous extracorporeal membrane oxygenators (VV ECMO) remains problematic. The development of device-induced coagulation disorder (COD) or worsened gas transfer (WGT) necessitates a system exchange. The aim was to correlate von Willebrand factor antigen (vWF:Ag) with the predisposition to MO failure and mortality. Methods: Laboratory parameters (inflammation, coagulation) and ECMO-related data from 31 VV ECMO patients were analyzed before and after the first MO exchange. Study groups were identified according to the exchange reasons (COD, WGT) and the extent of vWF:Ag (low, ≤425%; high, >425%). Results: vWF:Ag remained unchanged after system exchange. High vWF:Ag was associated with systemic endothelial activation of older and obese patients with elevated SOFA score, increased norepinephrine and higher requirement of continuous renal replacement therapy without an effect on MO runtime and mortality. Including the mechanism of MO failure (COD, WGT), various patient group emerged. COD/low vWF:Ag summarized younger and less critically ill patients that benefit mainly from ECMO by a significant improvement of their inflammatory and coagulation status (CRP, D-dimers, fibrinogen) and highest survival rate (91%). Instead, WGT/high vWF:Ag presented older and more obese patients with a two-digit SOFA score, highest norepinephrine, and aggravated gas transfer. They benefited temporarily from system exchange but with worst survival (33%). Conclusions: vWF:Ag levels alone cannot predict early MO failure and outcome in VV ECMO patients. Probably, the mechanism of clotting disorder in combination with the vWF:Ag level seems to be essential for clot formation within the MO. In addition, vWF:Ag levels allows the identification different patient populations In particular, WGT/high vWF:Ag represented a critically ill population with higher ECMO-associated mortality. [ABSTRACT FROM AUTHOR]

Background: A large body of evidence suggests that self-management interventions (SMIs) may improve outcomes in chronic obstructive pulmonary disease (COPD). However, accurate comparisons of the relative effectiveness of SMIs are challenging, partly due to heterogeneity of outcomes across trials and uncertainty about the importance of these outcomes for patients. We aimed to develop a core set of patient-relevant outcomes (COS) for SMIs trials to enhance comparability of interventions and ensure person-centred care. Methods: We undertook an innovative approach consisting of four interlinked stages: i) Development of an initial catalogue of outcomes from previous EU-funded projects and/or published studies, ii) Scoping review of reviews on patients and caregivers' perspectives to identify outcomes of interest, iii) Two-round Delphi online survey with patients and patient representatives to rate the importance of outcomes, and iv) Face-to-face consensus workshop with patients, patient representatives, health professionals and researchers to develop the COS. Results: From an initial list of 79 potential outcomes, 16 were included in the COS plus one supplementary outcome relevant to all participants. These were related to patient and caregiver knowledge/competence, self-efficacy, patient activation, self-monitoring, adherence, smoking cessation, COPD symptoms, physical activity, sleep quality, caregiver quality of life, activities of daily living, coping with the disease, participation and decision-making, emergency room visits/admissions and cost effectiveness. Conclusion: The development of the COPD COS for the evaluation of SMIs will increase consistency in the measurement and reporting of outcomes across trials. It will also contribute to more personalized health care and more informed health decisions in clinical practice as patients' preferences regarding COPD outcomes are more systematically included. [ABSTRACT FROM AUTHOR]

Mortality due to Covid-19 is highly associated with advanced age, owing in large part to severe lower respiratory tract infection. SARS-CoV-2 utilizes the host ACE2 receptor for infection. Whether ACE2 abundance in the lung contributes to age-associated vulnerability is currently unknown. We set out to characterize the RNA and protein expression profiles of ACE2 in aging human lung in the context of phenotypic parameters likely to affect lung physiology. Examining publicly available RNA sequencing data, we discovered that mechanical ventilation is a critical variable affecting lung ACE2 levels. Therefore, we investigated ACE2 protein abundance in patients either requiring mechanical ventilation or spontaneously breathing. ACE2 distribution and expression were determined in archival lung samples by immunohistochemistry (IHC). Tissues were selected from the specimen inventory at a large teaching hospital collected between 2010–2020. Twelve samples were chosen from patients receiving mechanical ventilation for acute hypoxic respiratory failure (AHRF). Twenty samples were selected from patients not requiring ventilation. We compared samples across age, ranging from 40–83 years old in the ventilated cohort and 14–80 years old in the non-ventilated cohort. Within the alveolated parenchyma, ACE2 expression is predominantly observed in type II pneumocytes (or alveolar type II / AT2 cells) and alveolar macrophages. All 12 samples from our ventilated cohort showed histologic features of diffuse alveolar damage including reactive, proliferating AT2 cells. In these cases, ACE2 was strongly upregulated with age when normalized to lung area (p = 0.004) or cellularity (p = 0.003), associated with prominent expression in AT2 cells. In non-ventilated individuals, AT2 cell reactive changes were not observed and ACE2 expression did not change with age when normalized to lung area (p = 0.231) or cellularity (p = 0.349). In summary, ACE2 expression increases with age in the setting of alveolar damage observed in patients on mechanical ventilation, providing a potential mechanism for higher Covid-19 mortality in the elderly. [ABSTRACT FROM AUTHOR]

Background: Data is lacking on outcomes among COPD patients in sub-Saharan Africa. The objective of the study was to assess the incidence and predictors of mortality among COPD patients enrolled in the Uganda Registry for Asthma and COPD. Research question: What is the Incidence and predictors of mortality among COPD patients in Uganda? Study design and methods: Individuals with a diagnosis of COPD at six hospitals in Uganda were enrolled into the registry, and followed every six months. Mortality was ascertained through post-mortem reports and verbal autopsies. Mortality rates (MR), mortality rate ratios (MRR), and hazard ratios (HR) were computed to assess associations between socio-demographic, behavioural, and clinical characteristics at enrolment into the registry and mortality up to two years after. Results: We enrolled 296 COPD patients. Median age was 60 years, and 51·3% were male. The overall mortality rate was 95·90 deaths/1000 person-years. COPD severity by post-bronchodilator FEV1 was the strongest risk factor for mortality. Compared to stage 1, adjusted hazard ratios were as follows for stage 4: 9·86 (95%CI: 1·70–57·14, p = 0·011), stage 3: 6·16 (95%CI: 1·25–30·32, p = 0·025), and stage 2: 1·76 (95%CI: 0·33–9·48, p = 0·51). Underweight patients had a higher incidence of mortality compared to normal weight patients (MRR: 3·47 (95%CI: 1·45–8·31, p = 0·0026). Conclusion: Among COPD patients in Uganda, two-year mortality is high, and disease severity at baseline was the strongest risk factor for mortality. Our findings suggest the need for early, accurate, diagnosis and management of COPD, to potentially improve survival. [ABSTRACT FROM AUTHOR]

Introduction: A large proportion of patients with COVID-19 develop acute kidney injury (AKI). While the most severe of these cases require renal replacement therapy (RRT), little is known about their clinical course. Methods: We describe the clinical characteristics of COVID-19 patients in the ICU with AKI requiring RRT at an academic medical center in New York City and followed patients for outcomes of death and renal recovery using time-to-event analyses. Results: Our cohort of 115 patients represented 23% of all ICU admissions at our center, with a peak prevalence of 29%. Patients were followed for a median of 29 days (2542 total patient-RRT-days; median 54 days for survivors). Mechanical ventilation and vasopressor use were common (99% and 84%, respectively), and the median Sequential Organ Function Assessment (SOFA) score was 14. By the end of follow-up 51% died, 41% recovered kidney function (84% of survivors), and 8% still needed RRT (survival probability at 60 days: 0.46 [95% CI: 0.36–0.56])). In an adjusted Cox model, coronary artery disease and chronic obstructive pulmonary disease were associated with increased mortality (HRs: 3.99 [95% CI 1.46–10.90] and 3.10 [95% CI 1.25–7.66]) as were angiotensin-converting-enzyme inhibitors (HR 2.33 [95% CI 1.21–4.47]) and a SOFA score >15 (HR 3.46 [95% CI 1.65–7.25). Conclusions and relevance: Our analysis demonstrates the high prevalence of AKI requiring RRT among critically ill patients with COVID-19 and is associated with a high mortality, however, the rate of renal recovery is high among survivors and should inform shared-decision making. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies suggest that occupational inhalant exposures trigger exacerbations of asthma and chronic obstructive pulmonary disease, but findings are conflicting. Methods: We included 7,768 individuals with self-reported asthma (n = 3,215) and/or spirometric airflow limitation (forced expiratory volume in 1 second (FEV1)/ forced expiratory volume (FVC) <0.70) (n = 5,275) who participated in The Copenhagen City Heart Study or The Copenhagen General Population Study from 2001–2016. Occupational exposure was assigned by linking job codes with job exposure matrices, and exacerbations were defined by register data on oral corticosteroid treatment, emergency care unit assessment or hospital admission. Associations between occupational inhalant exposure each year of follow-up and exacerbation were assessed by Cox regression with time varying exposure and age as the underlying time scale. Results: Participants were followed for a median of 4.6 years (interquartile range, IQR 5.4), during which 870 exacerbations occurred. Exacerbations were not associated with any of the selected exposures (high molecular weight sensitizers, low molecular weight sensitizers, irritants or low and high levels of mineral dust, biological dust, gases & fumes or the composite variable vapours, gases, dusts or fumes). Hazards ratios ranged from 0.8 (95% confidence interval: 0.7;1.0) to 1.2 (95% confidence interval: 0.9;1.7). Conclusion: Exacerbations of obstructive airway disease were not associated with occupational inhalant exposures assigned by a job exposure matrix. Further studies with alternative exposure assessment are warranted. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this article is to provide a detailed description of the Chikwawa lung health cohort which was established in rural Malawi to prospectively determine the prevalence and causes of lung disease amongst the general population of adults living in a low-income rural setting in Sub-Saharan Africa. Participants: A total of 1481 participants were randomly identified and recruited in 2014 for the baseline study. We collected data on demographic, socio-economic status, respiratory symptoms and potentially relevant exposures such as smoking, household fuels, environmental exposures, occupational history/exposures, dietary intake, healthcare utilization, cost (medication, outpatient visits and inpatient admissions) and productivity losses. Spirometry was performed to assess lung function. At baseline, 56.9% of the participants were female, mean age was 43.8 (SD:17.8) and mean body mass index (BMI) was 21.6 Kg/m2 (SD: 3.46) Findings to date: The cohort has reported the prevalence of chronic respiratory symptoms (13.6%, 95% confidence interval [CI], 11.9–15.4), spirometric obstruction (8.7%, 95% CI, 7.0–10.7), and spirometric restriction (34.8%, 95% CI, 31.7–38.0). Additionally, an annual decline in forced expiratory volume in one second [FEV1] of 30.9mL/year (95% CI: 21.6 to 40.1) and forced vital capacity [FVC] by 38.3 mL/year (95% CI: 28.5 to 48.1) has been reported. Future plans: The ongoing phases of follow-up will determine the annual rate of decline in lung function as measured through spirometry and the development of airflow obstruction and restriction, and relate these to morbidity, mortality and economic cost of airflow obstruction and restriction. Population-based mathematical models will be developed driven by the empirical data from the cohort and national population data for Malawi to assess the effects of interventions and programmes to address the lung burden in Malawi. The present follow-up study started in 2019. [ABSTRACT FROM AUTHOR]

The association between chronic obstructive pulmonary disease (COPD) and occupational exposures are less studied in Bangladeshi context, despite the fact that occupational exposures are serious public health concerns in Bangladesh. Therefore, this study aimed to evaluate this association considering demographic, health and smoking characteristics of Bangladeshi population. This was a hospital-based quantitative study including 373 participants who were assessed for COPD through spirometry testing. Assessment of occupational exposures was based on both self-reporting by respondents and ALOHA based job exposure matrix (JEM). Here, among the self-reported exposed group (n = 189), 104 participants (55%) were found with COPD compared to 23 participants (12.5%) in unexposed group (n = 184) that differed significantly (p = 0.00). Similarly, among the JEM measured low (n = 103) and high exposed group (n = 236), 23.3% and 41.5% of the participants were found with COPD respectively; compared to unexposed group (14.7%; n = 34), that differed significantly also (p = 0.00). Likewise, participants with longer self-reported occupational exposures (>8 years) showed significantly (p = 0.00) higher proportions of COPD (79.5%) compared to 40.4% in shorter exposure group (1–8 years). Similarly, significant (p = 0.00) higher cases of COPD were observed among the longer cumulative exposure years (>9 years) group than the shorter cumulative exposure years (1–9 years) group in JEM. While combining smoking and occupational exposure, the chance of developing COPD among the current, former and non-smokers of exposed group were 7.4, 7.2 and 12.7 times higher respectively than unexposed group. Furthermore, logistic analysis revealed that after adjustments for confounding risk factors, the chance of developing COPD among the self-reported exposure group was 6.3 times higher (ORs: 6.3, p = 0.00) than unexposed group; and JEM exposure group has odds of 2.8 and 1.1 respectively (p<0.05) for high and low exposures. Further studies are needed to reinforce this association between COPD and occupational exposure in Bangladesh. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the effects of combining the Simplified-Acute-Physiology-Score (SAPS) 2 or the SAPS 3 with Interleukin-6 (IL-6) or Procalcitonin (PCT) or C-Reactive Protein (CRP) concentrations for predicting in-hospital mortality. Material and methods: This retrospective study was conducted in an interdisciplinary 22-bed intensive care unit (ICU) at a German university hospital. Within an 18-month period, SAPS 2 and SAPS 3 were calculated for 514 critically ill patients that were admitted to the internal medicine department. To evaluate discrimination performance, the area under the receiver operating characteristic curves (AUROCs) and the 95% confidence intervals (95% CIs) were calculated for each score, exclusively or in combination with IL-6 or PCT or CRP. DeLong test was used to compare different AUROCs. Results: The SAPS 2 exhibited a better discrimination performance than SAPS 3 with AUROCs of 0.81 (95% CI, 0.76–0.86) and 0.72 (95% CI, 0.66–0.78), respectively. Overall, combination of the SAPS 2 with IL-6 showed the best discrimination performance (AUROC 0.82; 95% CI, 0.77–0.87), albeit not significantly different from SAPS2. IL-6 performed better than PCT and CRP with AUROCs of 0.75 (95% CI, 0.69–0.81), 0.72 (95% CI, 0.66–0.77) and 0.65 (95% CI, 0.59–0.72), respectively. Performance of the SAPS 3 improved significantly when combined with IL-6 (AUROC 0.76; 95% CI, 0.69–0.81) or PCT (AUROC 0.73; 95% CI, 0.67–0.78). Conclusions: Our analysis provided evidence that the risk stratification performance of the SAPS 3 and, to a lesser degree, also of the SAPS 2 can increase when combined with IL-6. A more accurate detection of aberrant or dysregulated systemic immunological responses (by IL-6) may explain the higher performance achieved by SAPS 3 + IL-6 vs. SAPS 3. Thus, implementation of IL-6 in critical care scores can improve prediction outcomes, especially in patients experiencing acute inflammatory conditions; however, statistical results may vary across hospital types and/or patient populations with different case mix. [ABSTRACT FROM AUTHOR]

Biomarkers can be used to assess smoking behaviour more accurately and objectively than self-report. This study assessed the association between cotinine (a biomarker of smoke exposure) and later e-cigarette use among a population who were unexposed to e-cigarettes in youth. Young people in the Avon Longitudinal Study of Parents and Children took part in the study. We observed associations between cotinine at 15 years (measured between 2006 and 2008 before the wide availability of e-cigarettes) and self-reported ever use of e-cigarettes at 22 (measured between 2014 and 2015 when e-cigarettes were widely available) using logistic regression. A range of potential confounders were adjusted for (age, sex, body mass index, alcohol use and passive smoke exposure). Additionally, we adjusted for the young people's self-reported smoking status/history to explore potential misreporting and measurement error. In a sample of N = 1,194 young people, cotinine levels consistent with active smoking at 15 years were associated with increased odds of e-cigarette ever use at 22 years (Odds Ratio [OR] = 7.24, 95% CI 3.29 to 15.93) even when self-reported active smoking status at age 16 (OR = 3.14, 95% CI 1.32 to 7.48) and latent classes of smoking behaviour from 14 to 16 (OR = 2.70, 95% CI 0.98 to 7.44) were included in the model. Cotinine levels consistent with smoking in adolescence were strongly associated with increased odds of later e-cigarette use, even after adjusting for reported smoking behaviour at age 16 and smoking transitions from 14 to 16. [ABSTRACT FROM AUTHOR]

This cross-sectional study of the general population of Telemark County, Norway, aimed to identify risk factors associated with poor asthma control as defined by the Asthma Control Test (ACT), and to determine the proportions of patients with poorly controlled asthma who had undergone spirometry, used asthma medication, or been examined by a pulmonary physician. In 2014–2015, the study recruited 326 subjects aged 16–50 years who had self-reported physician-diagnosed asthma and presence of respiratory symptoms during the previous 12 months. The clinical outcome measures were body mass index (BMI), forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), fractional exhaled nitric oxide (FeNO), immunoglobulin E (IgE) in serum and serum C-reactive protein (CRP). An ACT score ≤ 19 was defined as poorly controlled asthma. Overall, 113 subjects (35%) reported poor asthma control. The odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with poorly controlled asthma were: self-reported occupational exposure to vapor, gas, dust, or fumes during the previous 12 months (OR 2.0; 95% CI 1.1–3.6), body mass index ≥ 30 kg/m2 (OR 2.2; 95% CI 1.2–4.1), female sex (OR 2.6; 95% CI 1.5–4.7), current smoking (OR 2.8; 95% CI 1.5–5.3), and past smoking (OR 2.3; 95% CI 1.3–4.0). Poor asthma control was also associated with reduced FEV1 after bronchodilation (β –3.6; 95% CI –7.0 to –0.2). Moreover, 13% of the participants with poor asthma control reported no use of asthma medication, 51% had not been assessed by a pulmonary physician, and 20% had never undergone spirometry. Because these data are cross-sectional, further studies assessing possible risk factors in general and objectively measured occupational exposure in particular are needed. However, our results suggest that there is room for improvement with regards to use of spirometry and pulmonary physician referrals when a patient's asthma is inadequately controlled. [ABSTRACT FROM AUTHOR]

Incorporating expert knowledge at the time machine learning models are trained holds promise for producing models that are easier to interpret. The main objectives of this study were to use a feature engineering approach to incorporate clinical expert knowledge prior to applying machine learning techniques, and to assess the impact of the approach on model complexity and performance. Four machine learning models were trained to predict mortality with a severe asthma case study. Experiments to select fewer input features based on a discriminative score showed low to moderate precision for discovering clinically meaningful triplets, indicating that discriminative score alone cannot replace clinical input. When compared to baseline machine learning models, we found a decrease in model complexity with use of fewer features informed by discriminative score and filtering of laboratory features with clinical input. We also found a small difference in performance for the mortality prediction task when comparing baseline ML models to models that used filtered features. Encoding demographic and triplet information in ML models with filtered features appeared to show performance improvements from the baseline. These findings indicated that the use of filtered features may reduce model complexity, and with little impact on performance. [ABSTRACT FROM AUTHOR]

Background and objectives: Cardiovascular and respiratory diseases can frequently coexist. Understanding their link may improve disease management. We aimed at assessing the associations of chronic bronchitis (CB), asthma and rhinitis with cardiovascular diseases and risk factors in the general population. Methods: We used data collected in the Gene Environment Interactions in Respiratory Diseases study, an Italian multicentre, multicase-control study. Among 2463 participants (age 21–86, female 50%) who underwent standardized interviews, skin prick and lung function tests, we identified 254 cases of CB without airflow obstruction, 418 cases of asthma without CB, 959 cases of rhinitis alone, and 832 controls. The associations of respiratory diseases with reported cardiovascular risk factors (lifestyles, hypertension, dyslipidaemia), heart disorders (myocardial infarction, coronary thrombosis, angina, aorta or heart surgery) and intermittent claudication were estimated through relative risk ratios (RRR) by multinomial logistic regression models. Results: Compared to controls, CB cases were more likely to be heavy smokers, alcohol consumers, physically inactive, and to suffer from hypertension or dyslipidaemia; rhinitis cases were less obese but more likely to have hypertension. Asthma was significantly associated with current smoking. After adjusting for cardiovascular risk factors, heart disorders were associated with CB (RRR[95%CI]: 1.58[1.12–2.22]) and rhinitis (1.35[0.98–1.85]) and intermittent claudication was associated with CB (3.43[2.52–4.67]), asthma (1.51[1.04–2.21]) and rhinitis (2.03[1.34–3.07]). Conclusions: CB, asthma and rhinitis were associated with cardiovascular risk factors and diseases. In particular, CB shared with cardiovascular diseases almost all risk factors and was strongly associated with a higher risk of heart disorders and intermittent claudication. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) has high rates of mortality and multisystem morbidity. Pre-clinical data suggest that fibroblast growth factor 23 (FGF23) may contribute to pulmonary pathology, and FGF23 is associated with mortality and morbidity, including acute kidney injury (AKI), in non-ARDS cohorts. Here, we assess whether FGF23 is associated with AKI and/or mortality in a cohort of 161 pediatric ARDS patients. Plasma total (intact + C-terminal) FGF23 and intact FGF23 concentrations were measured within 24 hours of ARDS diagnosis (Day 1), and associations with Day 3 AKI and 60-day mortality were evaluated. 35 patients (22%) developed AKI by 3 days post-ARDS diagnosis, and 25 (16%) died by 60 days post-ARDS diagnosis. In unadjusted models, higher Day 1 total FGF23 was associated with Day 3 AKI (odds ratio (OR) 2.22 [95% confidence interval (CI) 1.62, 3.03], p<0.001), but Day 1 intact FGF23 was not. In a model adjusted for demographics and disease severity, total FGF23 remained associated with AKI (OR 1.52 [95% CI 1.02, 2.26], p = 0.039). In unadjusted models, both higher Day 1 total and intact FGF23 were associated with 60-day mortality (OR 1.43 [95% CI 1.07, 1.91], p = 0.014; and OR 1.44 [95% CI 1.02, 2.05], p = 0.039, respectively). In the adjusted model, only total FGF23 remained associated with 60-day mortality (OR 1.62 [95% CI 1.07, 2.45], p = 0.023). In a subgroup analysis of patients with Day 1 plasma IL-6 concentrations available, inflammation partially mediated the association between total FGF23 and AKI. Our data suggest both inflammation-dependent and inflammation-independent associations between total FGF23 and clinical outcomes in pediatric ARDS patients. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic obstructive pulmonary disease (COPD) are more likely to be readmitted than patients with other chronic medical conditions, yet knowledge regarding such readmissions is limited. We aimed to determine factors associated with readmission within 30 days of a COPD hospitalization or death with an emphasis on examining aspects of socioeconomic status and specific comorbidities. Methods: A population-based cohort study was conducted using health administrative data from Ontario, Canada. All hospitalizations for COPD between 2004 and 2014 were considered. The primary exposures were socioeconomic status as measured by residential instability (an ecologic variable), and comorbidities such as cardiovascular disease and cancer. Other domains of socioeconomic status were considered as secondary exposures. Logistic regression with generalized estimating equations was used to examine the effect of exposures, adjusting for other patient factors, on 30-day readmission or death. Results: There were 126,013 patients contributing to 252,756 index COPD hospitalizations from 168 Ontario hospitals. Of these hospitalizations, 19.4% resulted in a readmission and 2.8% resulted in death within 30 days. After adjusting for other factors, readmissions or death were modestly more likely among people with the highest residential instability compared to the lowest (OR 1.05, 95% CI 1.01–1.09). Comorbidities such as cardiovascular disease and cancer, as well as other aspects of low socioeconomic status also increased readmission or death risk. Interpretation: Socioeconomic status, measured in various ways, and many comorbidities predict 30-day readmission or death in patients hospitalized for COPD. Strategies that address these factors may help reduce readmissions and death. [ABSTRACT FROM AUTHOR]

Recent studies showed that physical and/or neuropsychiatric impairments significantly affect long-term mortality of ICU survivors. We conducted this study to investigate that simplified measurement of physical function and level of consciousness at hospital discharge by attending nurses could predict long-term outcomes after hospital discharge. A retrospective analysis of prospectively and retrospectively collected data of 246 patients who received medical ICU treatment was conducted. We grouped patients according to physical function and level of consciousness measured by the simplified method at hospital discharge as follow; group A included patients with alert mental and capable of walking or moving by wheel chairs; group B included those with alert mental and bed-ridden status; and Group C included those with confused mental and bed-ridden status. The two-year survival rate after hospital discharge was compared. Of 246 patients, 157 patients were included in the analysis and there were 103 survivors after two-year follow up. Compared to non-survivors, survivors were more likely to be younger (P = 0.026) and have higher body mass index (P = 0.019) and no malignant disease (P = 0.001). There were no statistically significant differences in treatment modalities including medication, use of medical devices, and physical therapy between the survivors and non-survivors. The analysis showed significant differences in survival between the groups classified by physical function (P < 0.001) and level of consciousness (P < 0.01). Multivariate analysis showed that survival rate was significantly lower among the patients in group C than in those in group B or group A (P < 0.001). Simplified method to assess physical function and level of consciousness at hospital discharge can predict long-term outcomes of medical ICU survivors. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate knowledge of secondhand smoke (SHS) risks, sources of information, and associated factors and behaviors among hospital staff. Methods: We conducted a cross-sectional survey using a 40-item self-administered questionnaire among 328 employees at a university hospital. The questions on representative diseases related to SHS were used to measure the degree of knowledge of SHS. Multiple regression analysis was used to determine the correlation between SHS knowledge scores and variables. Results: Females had better SHS knowledge scores than males, regardless of smoking status (p<0.05). SHS knowledge was positively correlated with cessation education in males, non-smokers, and the total sample (β = 3.950, 2.356, and 2.684, respectively, p<0.05). It was correlated with the experience of any SHS exposure-related symptoms in males, non-smokers, and the total sample (β = 3.950, 2.356, and 2.684, respectively, p<0.05) and discomfort when exposed to SHS in non-smokers and the total sample (β = 0.670 and 0.821, respectively, p<0.05). Conclusion: SHS knowledge is high among females, when hospital staff are educated about SHS risks, and when they have experienced any SHS exposure-related symptoms or felt uncomfortable when exposed to SHS. SHS risk education is an effective tool to increase SHS knowledge in hospital staff. [ABSTRACT FROM AUTHOR]

Background: Exercise capacity is an important feature in patients with COPD. Its impairment drives disability and dependency for daily activities performance. This study evaluated the six years change in exercise capacity in subjects with airflow obstruction and compared this to subjects without airflow obstruction, with and without a smoking history. Methods: Cardiopulmonary exercise tests (CPET) were repeatedly performed during a six years follow up period. Peak oxygen uptake (VO2peak), work rate (WRpeak), heart rate (HRpeak), minute ventilation (VEpeak), respiratory exchange ratio (RERpeak) and ventilatory reserve (VE/MVV) were collected as effort dependent outcomes. The slopes of oxygen uptake, ventilatory and mechanical efficiency (OUES, ΔVE/ΔVCO2 and ΔVO2/ΔWR) were collected as effort independent outcomes. Results: One hundred and thirty-eight subjects were included. Thirty-eight presented airflow obstruction (63±6 years, 74% men, FEV1 90±15%pred), 44 had a smoking history but no airflow obstruction (61±5 years, 61% men, FEV1 105±15%pred) and 56 had never smoked (61±7 years, 57% men, FEV1 117±18%pred). At baseline, the airflow obstruction group had slightly worse exercise capacity in comparison to the never smoking control group, in absolute terms and expressed as percentage of the predicted value (VO2peak = 27±5 versus 32±8 ml/min/kg, p<0.01; 112±29 versus 130±33%pred, p = 0.04). Most exercise variables showed a statistically significant yearly deterioration, with exception of VE/MVV, ΔVE/ΔVCO2 and ΔVO2/ΔWR. The yearly decline in VO2peak and OUES was not faster in subjects with airflow obstruction than in smoking and never smoking controls (VO2peak -67 (9) versus -76 (9) ml/min, p = 0.44 and versus -58 (9), p = 0.47; OUES -32 (11) versus -68 (10), p = 0.03 and versus -68 (13), p = 0.03). Conclusions: With exception of VO2peak, effort dependent variables deteriorated faster in subjects with airflow obstruction compared to never smoking controls. The deterioration of effort independent variables, however, was not accelerated in the airflow obstruction group compared to controls. [ABSTRACT FROM AUTHOR]

Introduction: ABO blood type A was reported to correlate with an increased risk of acute respiratory distress syndrome (ARDS) in white patients with severe sepsis and major trauma compared with patients with other blood types. Information regarding ABO phenotypes and major outcomes in patients with ARDS is unavailable. The primary aim was to determine the relationship between ABO blood type A and intensive care unit (ICU) mortality in patients with acute hypoxemic respiratory failure (AHRF). The secondary aim was to describe the association between ABO blood type A and ICU length of stay (LOS) in this study population. Methods: In a multicenter, retrospective cohort study, we collected the clinical records of patients admitted from January 2012 to December 2014 in five ICUs of Northern Italy. We included adult white patients admitted to the ICU who were diagnosed with AHRF requiring mechanical ventilation. Results: The electronic records of 1732 patients with AHRF were reviewed. The proportion of patients with ABO blood type A versus other blood types was 39.9% versus 60.1%. ICU mortality (25%) and ICU LOS (median [interquartile range], 5 [2–12] days) were not different when stratified by ABO blood type (ICU mortality, overall p value = 0.905; ICU LOS, overall p value = 0.609). SAPSII was a positive predictor of ICU mortality (odds ration [OR], 32.80; 95% confidence interval [CI], 18.80–57.24; p < 0.001) and ICU LOS (β coefficient, 0.55; 95% CI, 0.35–0.75; p < 0.001) at multivariate analyses, whereas ABO blood type did not predict ICU outcome when forced into the model. Conclusion: ABO blood type did not correlate with ICU mortality and ICU LOS in adult patients with AHRF who were mechanically ventilated. [ABSTRACT FROM AUTHOR]

Background: The relationship between chronic obstructive pulmonary disease (COPD) and periprocedural complications of percutaneous coronary interventions (PCIs) is influenced by several factors. We aimed to investigate the association between COPD, its complication type and rate in patients undergoing PCI. Methods: Data were prospectively collected using the Polish Cardiovascular Intervention Society national registry (ORPKI) on all PCIs performed in Poland between January 2015 and December 2016. COPD was present in 5,594 of the 221,187 patients undergoing PCI. We assessed the frequency and predictors of periprocedural complications in PCI. Results: Patients with COPD were elder individuals (70.3 ± 9.9 vs. 67 ± 10.8 years; p < 0.05). We noted 145 (2.6%) periprocedural complications in the COPD group and 4,121 (1.9%) in the non-COPD group (p < 0.001). The higher incidence of periprocedural complications in the COPD patients was mainly attributed to cardiac arrest (p = 0.001), myocardial infarctions (p = 0.002) and no-reflows (p < 0.001). COPD was not an independent predictor of all periprocedural complications. On the other hand, COPD was found to be an independent predictor of increased no-reflow risk (odds ratio [OR] 1.447, 95% CI 1.085–1.929; p = 0.01), and at the same time, of decreased risk of periprocedural allergic reactions (OR 0.117, 95% CI 0.016–0.837; p = 0.03). Conclusions: In conclusion, periprocedural complications of PCIs are more frequent in patients with COPD. COPD is an independent positive predictor of no-reflow and a negative predictor of periprocedural allergic reactions. [ABSTRACT FROM AUTHOR]

Background: Asthma is associated with an increased cardiovascular disease (CVD) risk in adults, but the impact of asthma and atopic conditions on CVD risk in children is less well established. We hypothesized that children in the Childhood Origins of Asthma (COAST) Cohort with asthma and atopic conditions would have early carotid arterial injury. Methods: The COAST study is a longitudinal birth cohort of children at increased risk of developing asthma. Children underwent ultrasonography measuring far wall right carotid bifurcation (RCB) and common carotid artery (RCCA) intima-media thickness (IMT; a measure of arterial injury). Multivariable linear regression models adjusted for age, gender, race, blood pressure, and body-mass index were used to assess associations of asthma and markers of arterial injury. Results: The 89 participants were a mean (standard deviation) 15.3 (0.6) years old and 42% were female; 28 asthmatics had atopic disease, 34 asthmatics were without other atopic disease, and 15 non-asthmatics had atopic disease. This study population was compared to 12 controls (participants free of asthma or atopic disease). Compared to controls (589 μm), those with atopic disease (653 μm, p = 0.07), asthma (649 μm, p = 0.05), or both (677 μm, p = 0.005) had progressively higher RCB IMT values (ptrend = 0.011). In adjusted models, asthmatic and/or atopic participants had significantly higher RCB IMT than those without asthma or atopic disease (all p≤0.03). Similar relationships were found for RCCA IMT. Conclusion: Adolescents with asthma and other atopic diseases have an increased risk of subclinical arterial injury compared to children without asthma or other atopic disease. [ABSTRACT FROM AUTHOR]

Neighborhood environments are considered crucial determinants of self-rated health. Previous research has documented a positive association between the quality of neighborhood environments and health status. However, the relationship between neighborhood environments and health status in East Asian countries has received far less attention. This study examined the relationship between the three main types of neighborhood environments (built, natural, and social) and self-rated health in Mainland China, Japan, and South Korea. It also compared the neighborhood effects on self-rated health across the three countries. Our analytical sample included 3,675, 2,390, and 1,500 respondents in China, Japan, and South Korea respectively from the 2010 East Asian Social Survey. Ordinal Logistic Regression models were estimated for each country and the country differences were tested. This study found that neighborhood built, natural and social environments are positively associated with self-rated health in China, Japan and South Korea. These effects vary somewhat by country, and neighborhood social environment has the strongest association with self-rated health in Japan, followed by South Korea and then China. The similar relationship between perceived neighborhood environments and self-rated health across the three countries underscores the prevalent impact of perceived neighborhood environments on health. The greater association between social environment and self-rated health in Japan suggests the greater need of community based support system in an aging society not only for the older people, but also for the general population, especially those who are living in poor neighborhood social environment. [ABSTRACT FROM AUTHOR]

Introduction: Chronic obstructive pulmonary disease (COPD) is a complex multi-component disorder characterized by progressive irreversible respiratory symptoms and extrapulmonary comorbidities, including anxiety-depression and mild cognitive impairment (MCI). However, the prevalence of these impairments is still uncertain, due to non-optimal screening methods. This observational cross-sectional multicentre study aimed to evaluate the prevalence of anxiety-depressive symptoms and MCI in COPD patients, identify the most appropriate cognitive tests to screen MCI, and investigate specific cognitive deficits in these patients and possible predictive factors. Materials and methods: Sixty-five stable COPD inpatients (n = 65, aged 69.9±7.6 years, mainly stage III–IV GOLD) underwent the following assessments: Hospital Anxiety and Depression Scale (HADS), Geriatric Depression Scale (GDS) or Beck Depression Inventory-II (BDI-II), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a complete neuropsychological battery (ENB-2) including different cognitive domains (attention, memory, executive functions, and perceptive and praxis abilities). Results: Moderate-severe anxiety was present in 18.5% of patients and depressive symptoms in 30.7%. The prevalence of MCI varied according to the test: 6.2% (MMSE), 18.5% (MoCA) and 50.8% (ENB-2). In ENB-2, patients performed significantly worse compared to Italian normative data on digit span (5.11±0.9 vs. 5.52±1.0, p = 0.0004), trail making test-B (TMT-B) (176.31±99.5 vs. 135.93±58.0, p = 0.004), overlapping pictures (26.03±8.9 vs. 28.75±8.2, p = 0.018) and copy drawing (1.370.6 vs. 1.61±0.5, p = 0.002). At logistic regression analysis, only COPD severity (p = 0.012, odds ratio, OR, 4.4 [95% CI: 1.4–14.0]) and anxiety symptoms (p = 0.026, OR 4.6 [1.2–17.7]) were significant and independent predictors of the deficit in copy drawing, which assesses visuospatial and praxis skills. Conclusion: Given the prevalence of neuropsychological impairments in COPD patients, the routine adoption in rehabilitation of screening tools for mood and cognitive function, including digit span, TMT-B and copy drawing, may be useful to detect psychosocial comorbidities and personalize the rehabilitative program. [ABSTRACT FROM AUTHOR]

Whether the association of work disability with obstructive sleep apnea (OSA) is mainly due to the disease, i.e. the number and frequency of apneas-hypoapneas, or to coexisting factors independent from the disease, is not well-established. In this study, we aim to evaluate work ability in a group of subjects undergoing OSA workup and to identify the major contributors of impaired work ability. In a cross-sectional study, we enrolled 146 consecutive subjects who have been working for the last five years and referred to the sleep disorders outpatients’ clinic of the University-Hospital of Ferrara, Italy, with suspected OSA. After completing an interview in which the Work Ability Index (WAI) and the Epworth Sleepiness Scale (ESS) questionnaires were administered to assess work ability and excessive daytime sleepiness, respectively, subjects underwent overnight polysomnography for OSA diagnosing and spirometry. Of the 146 subjects, 140 (96%) completed the tests and questionnaires and, of these, 66 exhibited work disability (WAI < 37). OSA was diagnosed (apnea-hypopnea index ≥ 5) in 45 (68%) of the 66 subjects. After controlling for confounders, a lower level of forced expiratory volume at 1 second (FEV1), [odds ratio 0.97 (95% CI 0.95–1.00)], older age [1.09 (95% CI 1.03–1.15)], excessive daytime sleepiness [3.16 (95% CI 1.20–8.34)] and a worse quality of life [0.96 (95% CI 0.94–1.00)], but not OSA [1.04 (95% CI 0.41–2.62)], were associated with work disability. Patients with a higher number of diseases, in which OSA was not included, and a lower quality of life had an increased probability of absenteeism in the previous 12 months. In subjects with suspected OSA, FEV1 can be an important predictor of work disability. [ABSTRACT FROM AUTHOR]

Rationale: Factors associated with one-year mortality after recovery from critical illness are not well understood. Clinicians generally lack information regarding post-hospital discharge outcomes of patients from the intensive care unit, which may be important when counseling patients and families. Objective: We sought to determine which factors among patients who survived for at least 30 days post-ICU admission are associated with one-year mortality. Methods: Single-center, longitudinal retrospective cohort study of all ICU patients admitted to a tertiary-care academic medical center from 2001–2012 who survived ≥30 days from ICU admission. Cox’s proportional hazards model was used to identify the variables that are associated with one-year mortality. The primary outcome was one-year mortality. Results: 32,420 patients met the inclusion criteria and were included in the study. Among patients who survived to ≥30 days, 28,583 (88.2%) survived for greater than one year, whereas 3,837 (11.8%) did not. Variables associated with decreased one-year survival include: increased age, malignancy, number of hospital admissions within the prior year, duration of mechanical ventilation and vasoactive agent use, sepsis, history of congestive heart failure, end-stage renal disease, cirrhosis, chronic obstructive pulmonary disease, and the need for renal replacement therapy. Numerous effect modifications between these factors were found. Conclusion: Among survivors of critical illness, a significant number survive less than one year. More research is needed to help clinicians accurately identify those patients who, despite surviving their acute illness, are likely to suffer one-year mortality, and thereby to improve the quality of the decisions and care that impact this outcome. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of disability. We aimed to analyse the impact of reduced pulmonary function on non-respiratory impairments and mobility activity limitations in an elderly population with COPD and to elucidate which specific limitations on mobility are related to reduced pulmonary function Methods: Cross-sectional study of 110 patients with COPD, recruited from public and university hospital. The effect of impaired pulmonary function on the risk of non-respiratory impairments and mobility limitations was analysed using validated measures, including: the 6-Minute Walk Test (6MWT), skeletal muscle strength, the Short Physical Performance Battery (SPPB), and self-reported mobility questionnaire. Multivariate analysis was used to control for confounders such as age, sex, height, education, and cigarette smoking. Results: Greater impairment of pulmonary function was associated with less distance walked during the 6MWT, poorer SPPB scores, and greater risk of self-reported mobility limitations (p<0.05). Lower forced expiratory volume in 1 s was also associated with a greater risk of limitations in carrying items under 10 pounds (4.54 kg), walking alone up and down a flight of stairs, and walking two or three neighbourhood blocks. There was no clear statistical relationship between pulmonary function impairment and skeletal muscle strength. Conclusions: Impaired pulmonary function was associated with the 6MWT score and limitations on performance-based and self-reported mobility activities, but not with skeletal muscle strength among elderly COPD patients. [ABSTRACT FROM AUTHOR]

The present study seeks to understand the determinants of land agricultural suitability in Malta before heavy mechanization. A GIS-based Logistic Regression model is built on the basis of the data from mid-1800s cadastral maps (cabreo). This is the first time that such data are being used for the purpose of building a predictive model. The maps record the agricultural quality of parcels (ranging from good to lowest), which is represented by different colours. The study treats the agricultural quality as a depended variable with two levels: optimal (corresponding to the good class) vs. non-optimal quality (mediocre, bad, low, and lowest classes). Seventeen predictors are isolated on the basis of literature review and data availability. Logistic Regression is used to isolate the predictors that can be considered determinants of the agricultural quality. Our model has an optimal discriminatory power (AUC: 0.92). The positive effect on land agricultural quality of the following predictors is considered and discussed: sine of the aspect (odds ratio 1.42), coast distance (2.46), Brown Rendzinas (2.31), Carbonate Raw (2.62) and Xerorendzinas (9.23) soils, distance to minor roads (4.88). Predictors resulting having a negative effect are: terrain elevation (0.96), slope (0.97), distance to the nearest geological fault lines (0.09), Terra Rossa soil (0.46), distance to secondary roads (0.19) and footpaths (0.41). The model isolates a host of topographic and cultural variables, the latter related to human mobility and landscape accessibility, which differentially contributed to the agricultural suitability, providing the bases for the creation of the fragmented and extremely variegated agricultural landscape that is the hallmark of the Maltese Islands. Our findings are also useful to suggest new questions that may be posed to the more meagre evidence from earlier periods. [ABSTRACT FROM AUTHOR]

Background: Bacterial meningitis is challenging to diagnose in infants, especially in the common setting of antibiotic pre-treatment, which diminishes yield of cerebrospinal fluid (CSF) cultures. Prior studies of diagnostic markers have not demonstrated sufficient accuracy. Interleukin-23 (IL-23), interleukin-18 (IL-18) and soluble receptor for advanced glycation end products (sRAGE) possess biologic plausibility, and may be useful as diagnostic markers in bacterial meningitis. Methods: In a prospective cohort study, we measured IL-23, IL-18 and sRAGE levels in CSF. We compared differences between infected and non-infected infants, and conducted receiver operating characteristic (ROC) analyses to identify individual markers and combinations of markers with the best diagnostic accuracy. Results: 189 infants <6 months, including 8 with bacterial meningitis, 30 without meningitis, and 151 with indeterminate diagnosis (due to antibiotic pretreatment) were included. CSF IL-23, IL-18 and sRAGE levels were significantly elevated in infants with culture proven meningitis. Among individual markers, IL-23 possessed the greatest accuracy for diagnosis of bacterial meningitis (area under the curve (AUC) 0.9698). The combination of all three markers had an AUC of 1. Conclusions: IL-23, alone and in combination with IL-18 and sRAGE, identified bacterial meningitis with excellent accuracy. Following validation, these markers could aid clinicians in diagnosis of bacterial meningitis and decision-making regarding prolongation of antibiotic therapy. [ABSTRACT FROM AUTHOR]

Despite advancements in ventilator technologies, lung supportive and rescue therapies, the outcome and prognostication in acute respiratory distress syndrome (ARDS) remains incremental and ambiguous. Metabolomics is a potential insightful measure to the diagnostic approaches practiced in critical disease settings. In our study patients diagnosed with mild and moderate/severe ARDS clinically governed by hypoxemic P/F ratio between 100–300 but with indistinct molecular phenotype were discriminated employing nuclear magnetic resonance (NMR) based metabolomics of mini bronchoalveolar lavage fluid (mBALF). Resulting biomarker prototype comprising six metabolites was substantiated highlighting ARDS susceptibility/recovery. Both the groups (mild and moderate/severe ARDS) showed distinct biochemical profile based on 83.3% classification by discriminant function analysis and cross validated accuracy of 91% using partial least squares discriminant analysis as major classifier. The predictive performance of narrowed down six metabolites were found analogous with chemometrics. The proposed biomarker model consisting of six metabolites proline, lysine/arginine, taurine, threonine and glutamate were found characteristic of ARDS sub-stages with aberrant metabolism observed mainly in arginine, proline metabolism, lysine synthesis and so forth correlating to diseased metabotype. Thus NMR based metabolomics has provided new insight into ARDS sub-stages and conclusively a precise biomarker model proposed, reflecting underlying metabolic dysfunction aiding prior clinical decision making. [ABSTRACT FROM AUTHOR]

Asthma is a chronic airway inflammation with a potential systemic impact. Atherosclerosis is a chronic inflammatory artery disease. The aim of our study was to prove if there is a correlation between the occurrence of asthma and increased atherosclerotic vessel disorders. Vessel status was compared between mild-to-moderate, severe allergic asthma and matched controls. Measurements of artery stiffness were calculated by central pulse wave velocity, ultrasonographic strain imaging and ankle-brachial index. Atherosclerotic plaque burden was assessed by colour-coded duplex sonography. Additionally, analysis of cardiovascular and asthma blood markers was conducted. Arterial stiffness expressed as an increased central pulse wave velocity and decreased circumferential and radial strains as well as the prevalence of media sclerosis were significantly higher among asthma patients compared to controls. Atherosclerotic plaque burden was relevantly increased in asthma groups vs. controls (severe asthma: 43.1%, mild-to-moderate asthma: 25.0%, control: 14.3% of study participants). Except for the elevated IgE and fibrinogen concentrations as well as leukocyte number there were no relevant differences in the blood parameters between the groups. Allergic asthma is associated with distinct atherosclerotic artery changes compared to the respectively matched control collective. The severity of asthma correlates with more pronounced pathological vessel alternations. [ABSTRACT FROM AUTHOR]

Background and purpose: Thoracic trauma remains to be a relevant injury to the polytraumatised patient. However, literature regarding how far changes in clinical guidelines for pre- and in-hospital trauma management and diagnostic procedures affect the outcome of multiple injured patients with severe chest injury during a long-term observation period is sparse. Methods: Multiple traumatised patients (age≥16y) documented in the TraumaRegister DGU® (TR-DGU) from January 1st 2005 to December 31st 2014 with severe chest trauma (AIS≥3) were included in this study. Demographic data, the pattern of injury, injury severity, radiographic emergency procedures, indication for intubation, duration of mechanical ventilation, emergency surgery, occurrence of complications and mortality were evaluated per year and over time. Results: A total of 16,773 patients were analysed. The use of whole body computer tomography increased (p<0.001), while the incidence of plain x-rays decreased (p<0.001). Furthermore, incidence of AISThorax = 3 graded injuries increased (p<0.001) while AISThorax = 4 decreased (p<0.001). Both, rate of patients being intubated at the time of ICU admission decreased (p<0.001) and the time of mechanical ventilation decreased (p<0.001). Additionally, need for emergency surgery, lung failure, sepsis, and multi organ failure all decreased (p<0.001). However, mortality remained unchanged. Interpretation: Severity of severe chest trauma and associated complications decreased while diagnostics and treatment improved over time. However, mortality remained unchanged. Our results are in line with those expected in the context of the incidence of CT diagnostics, which has increased parallel to the clinical outcome Thus, our data demonstrate a positive trend in the treatment of patients with severe chest trauma. [ABSTRACT FROM AUTHOR]