How Do Dual Long-Acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?

Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting ß2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaled corticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease.

Deep Benign Fibrous Histiocytoma of the Anterior Mediastinum Mimicking Malignancy.

The following report describes the case of a 43-year-old male smoker that was referred to the rapid access lung clinic with haemoptysis, chest pain, and axillary lymphadenopathy-a clinical picture that raised concern for a possible underlying malignancy. Preliminary investigations revealed elevated D-dimers, low-volume haemoptysis, and a normal chest X-ray, which lowered the index of suspicion. However, computed tomography (CT) pulmonary angiogram identified a right hilar mass, several parenchymal cysts, and a large mediastinal mass. In addition, a left-sided adrenal lesion was also discovered following CT abdomen pelvis, potentially indicating metastatic disease. Fortunately, a positron emission tomography scan failed to detect any metabolic activity in either the right hilar mass, left adrenal lesion or the anterior mediastinal mass. CT-guided biopsy identified the mediastinal mass as a low-grade spindle cell tumour. Due to its large size, the mass was surgically resected and confirmed to be a deep benign fibrous histiocytoma. The significance of this report is to highlight a clinical presentation suggestive of malignancy but actually resulting from a rare variant of a benign tumour. The constellation of regional lymphadenopathy, respiratory and gastrointestinal symptoms, lung cysts, an adrenal tumour, and a mediastinal mass appeared to suggest a progressive disease pattern more commonly associated with malignancy.

Hamman-Rich syndrome: a forgotten entity.

The following report outlines the case of a 76-year-old gentleman who presented to the hospital with acute interstitial pneumonitis, a rare and rapidly progressive type of idiopathic interstitial pneumonia. The patient initially presented with a three-week history of progressive shortness of breath and cough which was diagnosed as community acquired pneumonia. Treatment with oral antibiotics was unsuccessful resulting in re-presentation the following week with type one respiratory failure. Investigations revealed widespread inflammatory changes consistent with an acute inflammatory process. Intravenous steroids, antibiotics and antiviral medications were initiated before an urgent transfer to the intensive care unit was required for intubation. An open lung biopsy, in conjunction with the clinical picture, confirmed the diagnosis of acute interstitial pneumonitis. The significance of this report is to highlight the rapid and destructive clinical course of a rare type of pneumonitis, which initially presented as a routine and innocuous diagnosis in our patient.

End-Expiratory Volume and Oxygenation: Targeting PEEP in ARDS Patients.

INTRODUCTION: Changes in end-expiratory lung volume (∆EELV) in response to changes in PEEP (∆PEEP) have not been reported in mechanically ventilated patients with ARDS. The purpose of this study was to determine the utility of measurements of ∆EELV in determining optimal PEEP in ARDS patients. METHODS: Nine patients with ARDS were prospectively recruited. ∆EELV was measured using magnetometers during serial decremental PEEP trials. Changes in PaO2 (∆PaO2) were simultaneously measured. Static respiratory system compliance (CRS), ∆PaO2/∆PEEP, and ∆EELV/∆PEEP were calculated at each level of PEEP. RESULTS: For the group, ∆EELV decreased by 1.09 ± 0.13 L (mean ± SD) as PEEP was reduced from 20 to 0 cm H2O with the greatest changes in ∆EELV occurring over the mid range of the decremental PEEP curve. Optimal values for CRS, ∆EELV/∆PEEP, and ∆PaO2/∆PEEP could be identified for each patient and occurred at PEEP levels ranging from 10 to 17.5 cm H2O. There was a significant correlation (r = 0.712, p = 0.047) between ∆PaO2/∆PEEP and ∆EELV/∆PEEP. CONCLUSIONS: ∆EELV can be measured from a decremental PEEP curve. Since ∆EELV is highly correlated with ∆PaO2, measures of ∆PaO2/∆PEEP may provide a surrogate for measures of ∆EELV/∆PEEP. Combining measures of ∆EELV/∆PEEP with measures of CRS may provide a novel means of determining optimal PEEP in patients with ARDS.

The first reported case of Burkholderia contaminans in patients with cystic fibrosis in Ireland: from the Sargasso Sea to Irish Children.

BACKGROUND: Burkholderia contaminans is an emerging pathogen in the cystic fibrosis (CF) setting. Included in the Burkholderia cepacia complex (Bcc), B. contaminans is a Gram negative, motile, obligate aerobe previously classified as a pseudomonad. Previous reports have described B. contaminans isolation from patients in Portugal, Switzerland, Spain, Argentina and the USA. This, however, is the first report relating to B. contaminans affecting Irish patients with CF, initially detected in a paediatric setting. CASE PRESENTATION: Burkholderia contaminans was identified in the routine analysis of sputum from a fourteen year old boy, at his annual review and subsequently from the sputum from his 19 year old brother. RecA gene sequencing and pulsed field gel electrophoresis (PFGE) were unable to distinguish between the isolates, which demonstrated with susceptibility to ciprofloxacin, cotrimoxazole, meropenem, pipercillin/tazobactam and ceftazidime. Both isolates were resistant to aztreonam, with reduced susceptibility to tobramycin. Following treatment with intravenous meropenem and ceftazidime, oral ciprofloxacin and nebulised tobramycin for 6 weeks, sputum specimens from both patients were negative for B. contaminans. No other member of the local CF cohort proved positive. CONCLUSIONS: Bcc bacteria are associated with poor prognosis in CF and decreased life expectancy, specifically leading to a more rapid decline in lung function and, in some cases, to a fatal necrotizing pneumonia known as the "cepacia syndrome". Some species exhibit innate resistance to multiple antimicrobial agents and their transmission rate can be high in susceptible patients. In that context, we describe the first incidence of CF-related B. contaminans in Ireland and its successful eradication from two patients, one paediatric, using an aggressive antimicrobial regimen.

Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database.

OBJECTIVE: The Surviving Sepsis Campaign guidelines recommend obtaining a serum lactate measurement within 6 hours of presentation for all patients with suspected severe sepsis or septic shock. A lactate greater than 4 mmol/L qualifies for administration of early quantitative resuscitation therapy. We evaluated lactate elevation (with special attention to values > 4 mmol/L) and presence or absence of hypotension as a marker of clinical outcome. DESIGN AND SETTING: The Surviving Sepsis Campaign developed a database to assess the overall effect of the sepsis bundles as a performance improvement tool for clinical practice and patient outcome. This analysis focuses on one element of the Surviving Sepsis Campaign's resuscitation bundle, measuring serum lactate in adult severe sepsis or septic shock patients and its interaction with hypotension. This analysis was conducted on data submitted from January 2005 through March 2010. SUBJECTS: Data from 28,150 subjects at 218 sites were analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Unadjusted analysis of the 28,150 observations from the Surviving Sepsis Campaign database demonstrated a significant mortality increase with the presence of hypotension in conjunction with serum lactate elevation greater than 2 mmol/L. On multivariable analysis, only lactate values greater than 4 mmol/L, in conjunction with hypotension, significantly increased mortality when compared with the referent group of lactate values less than 2 mmol/L and not hypotensive. Mortality was 44.5% in patients with combined lactate greater than 4 mmol/L and hypotension when compared with 29% mortality in patients not meeting either criteria. CONCLUSIONS: Serum lactate was commonly measured within 6 hours of presentation in the management of severe sepsis or septic shock in this subset analysis of the Surviving Sepsis Campaign database in accordance with the Surviving Sepsis Campaign guidelines. Our results demonstrate that elevated lactate levels are highly associated with in-hospital mortality. However, only patients who presented with lactate values greater than 4 mmol/L, with and without hypotension, are significantly associated with in-hospital mortality and is associated with a significantly higher risk than intermediate levels (2-3 and 3-4 mmol/L). This supports the use of the cutoff of greater than 4 mmol/L as a qualifier for future clinical trials in severe sepsis or septic shock in patient populations who use quantitative resuscitation and the Surviving Sepsis Campaign bundles as standard of care.

A method for determining optimal mean airway pressure in high-frequency oscillatory ventilation.

BACKGROUND: "Optimal" mean airway pressure (MAP) during high-frequency oscillatory ventilation (HFOV) can be defined as the pressure that allows for maximal alveolar recruitment while minimizing alveolar overdistension. Choosing a MAP near or just below the point of maximal curvature (PMC) of the volume-pressure characteristics of the lung can serve as a guide to avoid overdistention during HFOV, while simultaneously preventing derecruitment. The purpose of this study was to assess whether optimal MAP at the PMC can be determined by using measures of PaO(2) in patients with acute respiratory distress syndrome (ARDS) undergoing HFOV. METHODS: We prospectively studied seven patients with ARDS who underwent HFOV after failed conventional ventilation. In addition, 11 healthy subjects were studied to validate measurements of changes in end-expiratory lung volume (∆EELV) using magnetometers. Using this validated method, plots of ∆EELV and MAP were constructed during decremental changes in MAP following a recruitment maneuver in seven ventilated patients with ARDS. The PMC was defined as the point where the slope of the ∆EELV versus MAP curve acutely changed. The MAP at the PMC was compared to that determined from plots of PaO(2) versus MAP. RESULTS: In the healthy cohort, measurements of ∆EELV obtained by magnetometry approximated the line of identity when compared to those obtained by spirometry. The MAP determined using either the ∆EELV or PaO(2) techniques were identical in all seven HFOV ventilated patients. Additionally, there was a significant correlation between the MAP associated changes in PaO2 and the MAP associated changes in ∆EELV (p < 0.001). CONCLUSIONS: The finding that MAP at the PMC is the same whether determined by measures of ∆EELV or PaO(2) suggest that bedside measures PaO(2) may provide an acceptable surrogate for measures of EELV when determining "optimal" MAP during HFOV.

Steps Ahead: Optimising physical activity in adults with cystic fibrosis: A pilot randomised trial using wearable technology, goal setting and text message feedback.

BACKGROUND: Regular participation in physical activity (PA) is encouraged for people with Cystic Fibrosis (CF). This study aimed to assess the effectiveness of an intervention using wearable technology, goal setting and text message feedback on PA and health outcomes in people with CF. METHODS: This was a pilot randomised trial conducted at University Hospital Limerick. Participants were randomly assigned to the intervention (INT) or active comparator (AC). The 12-week intervention consisted of wearable technology (Fitbit Charge 2) which was remotely monitored, and participants set step count goals. Participants were sent a one-way text message once a week over 12 weeks to positively reinforce and encourage PA participation. The AC group received the wearable technology alone. Follow up was assessed at 24 weeks. Outcomes assessed were PA, aerobic capacity, lung function, sleep, quality of life and wellbeing. RESULTS: Step count increased significantly for the INT group over 12 weeks when compared to the AC group (p=0.019). The INT group had a 28% week-to-week percentage change (Weeks 1-12), while the AC group reduced by 1%, p=0.023. Within group changes demonstrated that VO2 peak (ml/kg/min) significantly increased for the INT group at 12 weeks (24.4 ±7.65 to 26.13 ±7.79, p=0.003) but not at 24 weeks (24.45 ±7.05, p=0.776). There were no significant differences observed for VO2 peak (ml/kg/min) for the AC group. There was no significant effect on lung function, sleep, well-being, or quality of life for either group. CONCLUSIONS: A personalised PA intervention using wearable technology, goal setting and text message feedback increased PA and aerobic capacity in people with CF. Integration of this intervention into usual care may encourage regular PA participation for people with CF.

Genetic disruption of protein kinase Cδ reduces endotoxin-induced lung injury.

The pathogenesis of acute lung injury and acute respiratory distress syndrome is characterized by sequestration of leukocytes in lung tissue, disruption of capillary integrity, and pulmonary edema. PKCδ plays a critical role in RhoA-mediated endothelial barrier function and inflammatory responses. We used mice with genetic deletion of PKCδ (PKCδ(-/-)) to assess the role of PKCδ in susceptibility to LPS-induced lung injury and pulmonary edema. Under baseline conditions or in settings of increased capillary hydrostatic pressures, no differences were noted in the filtration coefficients (k(f)) or wet-to-dry weight ratios between PKCδ(+/+) and PKCδ(-/-) mice. However, at 24 h after exposure to LPS, the k(f) values were significantly higher in lungs isolated from PKCδ(+/+) than PKCδ(-/-) mice. In addition, bronchoalveolar lavage fluid obtained from LPS-exposed PKCδ(+/+) mice displayed increased protein and cell content compared with LPS-exposed PKCδ(-/-) mice, but similar changes in inflammatory cytokines were measured. Histology indicated elevated LPS-induced cellularity and inflammation within PKCδ(+/+) mouse lung parenchyma relative to PKCδ(-/-) mouse lungs. Transient overexpression of catalytically inactive PKCδ cDNA in the endothelium significantly attenuated LPS-induced endothelial barrier dysfunction in vitro and increased k(f) lung values in PKCδ(+/+) mice. However, transient overexpression of wild-type PKCδ cDNA in PKCδ(-/-) mouse lung vasculature did not alter the protective effects of PKCδ deficiency against LPS-induced acute lung injury. We conclude that PKCδ plays a role in the pathological progression of endotoxin-induced lung injury, likely mediated through modulation of inflammatory signaling and pulmonary vascular barrier function.

Evaluating the use of recombinant human activated protein C in adult severe sepsis: results of the Surviving Sepsis Campaign.

OBJECTIVE: The Surviving Sepsis Campaign developed guidelines for the administration of recombinant human activated protein C in adult severe sepsis. However, it is not clear how these impacted clinical practice or patient outcome. DESIGN AND SETTING: The Surviving Sepsis Campaign has developed an extensive database to assess the efficacy of the overall effect of its guidelines on clinical practice and patient outcome. From data submitted to the Surviving Sepsis Campaign database from January 2005 through March 2008, we evaluated data regarding the administration of recombinant human activated protein C in adult severe sepsis. SUBJECTS: Data from 15,022 subjects at 165 sites were analyzed. MEASUREMENTS AND MAIN RESULTS: Of patients with severe sepsis in the database, 1,009 of 15,022 (8%) received recombinant human activated protein C. Recombinant human activated protein C was administered within 24 hrs of the onset of sepsis in 76% (771 of 1009) of patients. Patients in North America (7.1%) and Europe (6.8%) were more likely to receive recombinant human activated protein C than patients in South America (4.2%, p<.001). After adjusting for covariates, the group that received recombinant human activated protein C had a significantly reduced associated hospital mortality (odds ratio 0.76, 95% confidence interval 0.66-0.86, p<.001). Comparing all the patients who received recombinant human activated protein C to those who did not receive recombinant human activated protein C, the reduction in the adjusted hospital mortality was only statistically significant in patients who had multiorgan dysfunction (odds ratio 0.82, 95% confidence interval 0.69-0.98, p=.027) vs. those who only had single organ dysfunction (odds ratio 0.78, 95% confidence interval 0.59-1.02, p=.072). However, in patients who received recombinant human activated protein C before 24 hrs there was a reduction in adjusted hospital mortality in patients with only one organ dysfunction (odds ratio 0.70, 95% confidence interval 0.51-0.9, p=.03) as well as patients with multiorgan dysfunction (odds ratio 0.78, 95% confidence interval 0.64-0.94 p=.012). There was a statistically significant increase over time in the percentage compliance with the institution of a recombinant human activated protein C administration policy from the first, second, and eighth quarters (47.4%, 46.2%, and 60.7%, respectively) (p<.001). There was also a statistically significant increase in the actual administration rates of recombinant human activated protein C over the same timeline (p<.001), with administration rates of recombinant human activated protein C reaching 9.2% in the last quarter. CONCLUSIONS: Recombinant human activated protein C use was associated with a significant improvement in hospital mortality in patients who participated in the Surviving Sepsis Campaign.

Accuracy of the ActivPAL and Fitbit Charge 2 in measuring step count in Cystic Fibrosis.

BACKGROUND: Physical activity (PA) is important in Cystic Fibrosis (CF) management. Fitness wearables are becoming increasingly popular as measurement tools of PA; however, the accuracy of these devices should first be evaluated. OBJECTIVE: The purpose of this study was to assess the accuracy of the ActivPAL and Fitbit Charge 2 as a measure of step count in Cystic Fibrosis. METHODS: Twenty-one participants were recruited from an adult CF Center in Ireland for a single session of testing. Participants walked for 5 min at five pre-determined speeds in a controlled testing environment (2, 2.5, 3, 3.5 and 4 miles per hour on a treadmill) and at three self-selected speeds in a corridor (slow, medium, and fast). They concurrently wore an accelerometer (ActivPAL) and fitness wearable (Fitbit Charge 2), and both were compared to visual observations. Step count is the outcome being assessed. RESULTS: The ActivPAL under-estimated step count by 0.63% across treadmill speeds and 1.1% across self-selected walking speeds. The Fitbit Charge 2 underestimated the step count by 2.97% across treadmill speeds and by 6.3% across self-selected walking speeds. Very strong correlations were found between the ActivPAL and visual observations (r: 0.93 to 0.99), while the Fitbit Charge 2 ranged from weak to very strong correlations when compared to visual observations (r: 0.34 to 0.84). CONCLUSION: The ActivPAL and Fitbit Charge 2 demonstrated acceptable validity for step count measurement in CF. These devices can be used for tracking PA during interventions in people with CF.

Physical Activity and Sedentary Behavior in Adults With Cystic Fibrosis: Association With Aerobic Capacity, Lung Function, Sleep, Well-Being, and Quality of Life.

BACKGROUND: Physical activity (PA) and sedentary behavior (SB) have marked impact on key prognostic indicators such as aerobic capacity and lung function in people with cystic fibrosis (CF) and may have associations with sleep, well-being, and health-related quality of life (HRQOL). METHODS: This observational study assessed PA, SB, aerobic capacity, spirometry, sleep, well-being, and HRQOL in adults with CF at University Hospital Limerick. PA and SB were assessed using an accelerometer that was worn for 7 days. A cardiopulmonary exercise test assessed aerobic capacity. Spirometry was performed according to American Thoracic Society guidelines. Well-being was measured by the AWESCORE, sleep quality by the Pittsburgh Sleep Quality Index (PSQI), and HRQOL using the CF Questionnaire-Revised. RESULTS: Thirty-three participants (13 males/20 females) were recruited. Mean age was 26.2 y (± 7.1 SD), with mean FEV1 72.9% of predicted (± 26.2 SD). Mean step count was 7,788 (± 3,583 SD). Over 75% of participants did not reach recommended PA targets (> 10,000 steps), with females being 25.5% less active than males. The PSQI indicated 48.5% of participants scored > 5, indicating poor sleep quality. Number of steps and SB demonstrated a moderate significant correlation with FEV1 (r = 0.45, P = .030; r = -0.37, P = .043, respectively) and sleep quality (r = -0.85, P < .001; r = 0.77, P < .001, respectively). [Formula: see text] peak expressed relative to body weight, and as a percentage of predicted, was significantly positively correlated with step count (r = 0.48, P = .007; r = 0.42, P = .02, respectively) but did not correlate with SB (P = .96). [Formula: see text] peak (L/min) strongly correlated with FEV1 (r = 0.75, P < .001). CONCLUSIONS: Most participants did not meet PA targets. PA levels correlated to aerobic capacity, FEV1, and self-reported sleep quality, and this should be considered in longitudinal studies and in PA interventions.

Diet quality in cystic fibrosis - associations with patient reported outcome measures and enablers and barriers to eating a healthy diet: A protocol paper for a mixed methods study.

Background: People with cystic fibrosis (PWCF) have increased energy requirements. However, in recent years concerns have emerged regarding the 'cystic fibrosis (CF) diet' in terms of reliance on energy-dense, nutrient poor foods, which tend to be higher in saturated fat, sugar, and salt. These foods lack essential nutrients and are aetiologically linked with diet-related chronic diseases. The aim is to explore habitual dietary intakes in PWCF and (i) assess adherence to CF dietary guidelines and population specific healthy eating guidelines; (ii) derive a diet quality score and the inflammatory potential for the average diet consumed by PWCF and assess associations with patient reported outcome measures; (iii) assess drivers for current consumption patterns and enablers and barriers to eating a healthy diet. Methods: The aim is to recruit between 100-180 PWCF. A mixed methods study will be performed. Using three-day food diaries and food frequency questionnaires, aims (i) and (ii) will be addressed. The Dietary Approaches to Stop Hypertension (DASH) score and Healthy Eating Index-International (HEI-I) will derive diet quality scores. The Dietary Inflammatory Index (DII®) will ascertain inflammatory potential of the diet. Validated questionnaires will be used to report health related quality of life measures. Online focus groups and semi-structured interview with PWCF will address aim (iii). Conclusions: It is timely to revise dietary priorities and targets for CF. However, a greater understanding of what adults with CF currently consume and what they require in terms of nutrition and dietary guidance into the future is needed. In doing so, this research will help to clarify nutrition priorities and simplify the dietary aspects of CF treatment, thereby supporting adherence.

Reducing mortality in severe sepsis and septic shock.

Severe sepsis is one of the most common reasons for critically ill patients to be admitted to an intensive care unit (ICU) and has very high associated morbidity and mortality. The Surviving Sepsis Campaign was initiated with the hope that mortality might be reduced by standardizing care informed by data from an increasing number of clinical trials. Important methods for reducing mortality identified by recent studies include aggressive fluid resuscitation, early goal-directed therapy (EGDT), early administration of antibiotics, and the administration of activated protein C to eligible patients.

Implementing a collaborative protocol in a sepsis intervention program: lessons learned.

The objective of this prospective cohort study was to see the effect of the implementation of a Sepsis Intervention Program on the standard processes of patient care using a collaborative approach between the Emergency Department (ED) and Medical Intensive Care Unit (MICU). This was performed in a large urban tertiary-care hospital, with no previous experience utilizing a specific intervention program as routine care for septic shock and which has services and resources commonly available in most hospitals. The study included 106 patients who presented to the ED with severe sepsis or septic shock. Eighty-seven of those patients met the inclusion criteria for complete data analysis. The ED and MICU staff underwent a 3-month training period followed by implementation of a protocol for sepsis intervention program over 6 months. In the first 6 months of the program's implementation, 106 patients were admitted to the ED with severe sepsis and septic shock. During this time, the ED attempted to initiate the sepsis intervention protocol in 76% of the 87 septic patients who met the inclusion criteria. This was assessed by documentation of a central venous catheter insertion for continuous SvO(2) monitoring in a patient with sepsis or septic shock. However, only 48% of the eligible patients completed the early goal-directed therapy (EGDT) protocol. Our data showed that the in-hospital mortality rate was 30.5% for the 87 septic shock patients with a mean APACHE II score of 29. This was very similar to a landmark study of EGDT (30.5% mortality with mean APACHE II of 21.5). Data collected on processes of care showed improvements in time to fluid administration, central venous access insertion, antibiotic administration, vasopressor administration, and time to MICU transfer from ED arrival in our patients enrolled in the protocol versus those who were not. Further review of our performance data showed that processes of care improved steadily the longer the protocol was in effect, although this was not statistically significant. There was no improvement in secondary outcomes, including total length of hospital stay, MICU days, and mortality. Implementation of a sepsis intervention program as a standard of care in a typical hospital protocol leads to improvements in processes of care. However, despite a collaborative approach, the sepsis intervention program was underutilized with only 48% of the patients completing the sepsis intervention protocol.

Echocardiographic evidence of pulmonary hypertension is associated with increased 1-year mortality in patients admitted with chronic obstructive pulmonary disease.

Pulmonary hypertension (PH) is associated with decreased overall survival in patients with chronic lung disease. The purpose of this study was to determine the effect of echocardiographic evidence of PH on 1-year survival in patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (COPD). This is a retrospective study of patients admitted to a respiratory intermediate care unit with COPD exacerbation between October 1, 2002 and September 30, 2004. All patients who had 2D echocardiograms and pulmonary function tests done within 12 months prior to hospital admission or during the admission were examined. Charts were reviewed for the following outcomes: length of hospital stay, need for mechanical ventilation, survival at discharge, and mortality over the next year. Data were analyzed using multiple logistic regression and p values calculated using Fisher's exact test. Forty-three patients met study entry criteria, and PH, defined as systolic right ventricular pressure greater than 45 mmHg, was found in 23 (53%). Sixteen of the 23 patients (70%) with PH died during the 1-year follow-up period compared to 5 of 20 (25%) patients with no PH (p = 0.0058). The effect of PH on survival was independent of age, forced expiratory volume in 1 s (FEV(1)), arterial pH, pCO(2), or pO(2) (p < 0.01). Echocardiographic evidence of PH is associated with increased 1-year mortality in patients admitted with COPD exacerbation. Further studies are needed to determine if PH is a cause of increased mortality in this population or an indicator of other cardiovascular disease.

Adenosine protected against pulmonary edema through transporter- and receptor A2-mediated endothelial barrier enhancement.

We have previously demonstrated that adenosine plus homocysteine enhanced endothelial basal barrier function and protected against agonist-induced barrier dysfunction in vitro through attenuation of RhoA activation by inhibition of isoprenylcysteine-O-carboxyl methyltransferase. In the current study, we tested the effect of elevated adenosine on pulmonary endothelial barrier function in vitro and in vivo. We noted that adenosine alone dose dependently enhanced endothelial barrier function. While adenosine receptor A(1) or A(3) antagonists were ineffective, an adenosine transporter inhibitor, NBTI, or a combination of DPMX and MRS1754, antagonists for adenosine receptors A(2A) and A(2B), respectively, partially attenuated the barrier-enhancing effect of adenosine. Similarly, inhibition of both A(2A) and A(2B) receptors with siRNA also blunted the effect of adenosine on barrier function. Interestingly, inhibition of both transporters and A(2A)/A(2B) receptors completely abolished adenosine-induced endothelial barrier enhancement. The adenosine receptor A(2A) and A(2B) agonist, NECA, also significantly enhanced endothelial barrier function. These data suggest that both adenosine transporters and A(2A) and A(2B) receptors are necessary for exerting maximal effect of adenosine on barrier enhancement. We also found that adenosine enhanced Rac1 GTPase activity and overexpression of dominant negative Rac1 attenuated adenosine-induced increases in focal adhesion complexes. We further demonstrated that elevation of cellular adenosine by inhibition of adenosine deaminase with Pentostatin significantly enhanced endothelial basal barrier function, an effect that was also associated with enhanced Rac1 GTPase activity and with increased focal adhesion complexes and adherens junctions. Finally, using a non-inflammatory acute lung injury (ALI) model induced by alpha-naphthylthiourea, we found that administration of Pentostatin, which elevated lung adenosine level by 10-fold, not only attenuated the development of edema before ALI but also partially reversed edema after ALI. The data suggest that adenosine deaminase inhibition may be useful in treatment of pulmonary edema in settings of ALI.

Steps Ahead: optimising physical activity in adults with cystic fibrosis: Study Protocol for a pilot randomised trial using wearable technology, goal setting and text message feedback.

Background: Physical activity (PA) and exercise are widely documented as key components in the management of cystic fibrosis (CF). In recent years there have been significant improvements in telehealth, in particular; fitness tracking, smartphone use and remote monitoring, all of which may have potential to impact on positive health outcomes in people with CF. The objective of this pilot randomised trial is to explore the potential efficacy of a fitness tracker, which is remotely monitored, combined with personalised text message feedback and goal setting, on lung function, aerobic capacity and PA in adults with CF. Secondary endpoints include quality of life, body composition and wellbeing. Methods: This is a pilot randomised trial which will be conducted at the University Hospital Limerick, Ireland. Participants will be randomised to the intervention or active comparator after their baseline assessment. The 12-week intervention will consist of a fitness tracker (Fitbit Charge 2) which is linked to an online monitoring system (Fitabase) for data collection purposes that enables the physiotherapist to remotely monitor participant data. The CF physiotherapist will set short- and long-term goals with participants and will send one-way text message feedback on Fitbit data and weekly progress. This message will consist of positive reinforcement and re-assess participant goals. The active comparator group will receive a fitness tracker which is also linked to Fitabase; however, no feedback will be provided to participants in this group. Both groups will be re-assessed at 12 weeks. After this point, both groups will continue with the Fitbit alone for a further 12 weeks. Both groups will be re-assessed at 24 weeks. Discussion: This is a novel concept which utilises modern technology, remote monitoring and personalised feedback to investigate the effect on health outcomes in people with CF.  Trial registration: ClinicalTrials.gov NCT03672058 (14/09/2018).