Risk factors for COPD exacerbations in inhaled medication users: the COPDGene study biannual longitudinal follow-up prospective cohort.

BackgroundDespite inhaled medications that decrease exacerbation risk, some COPD patients experience frequent exacerbations. We determined prospective risk factors for exacerbations among subjects in the COPDGene Study taking inhaled medications.Methods2113 COPD subjects were categorized into four medication use patterns: triple therapy with tiotropium (TIO) plus long-acting beta-agonist/inhaled-corticosteroid (ICS ± LABA), tiotropium alone, ICS ± LABA, and short-acting bronchodilators. Self-reported exacerbations were recorded in telephone and web-based longitudinal follow-up surveys. Associations with exacerbations were determined within each medication group using four separate logistic regression models. A head-to-head analysis compared exacerbation risk among subjects using tiotropium vs. ICS ± LABA.ResultsIn separate logistic regression models, the presence of gastroesophageal reflux, female gender, and higher scores on the St. George's Respiratory Questionnaire were significant predictors of exacerbator status within multiple medication groups (reflux: OR 1.62-2.75; female gender: OR 1.53 - OR 1.90; SGRQ: OR 1.02-1.03). Subjects taking either ICS ± LABA or tiotropium had similar baseline characteristics, allowing comparison between these two groups. In the head-to-head comparison, tiotropium users showed a trend towards lower rates of exacerbations (OR = 0.69 [95 % CI 0.45, 1.06], p = 0.09) compared with ICS ± LABA users, especially in subjects without comorbid asthma (OR = 0.56 [95% CI 0.31, 1.00], p = 0.05).ConclusionsEach common COPD medication usage group showed unique risk factor patterns associated with increased risk of exacerbations, which may help clinicians identify subjects at risk. Compared to similar subjects using ICS ± LABA, those taking tiotropium showed a trend towards reduced exacerbation risk, especially in subjects without asthma.Trial registrationClinicalTrials.gov NCT00608764, first received 1/28/2008

Study of filtration mechanics and sampling techniques, phase II Technical summary report, 1 Jan. - 31 Dec. 1965

Contaminant capacity at constant flow rate of pleated wire cloth filter element for testing wide range of silica impuritie

Red Footed Tortoises in Captivity

This is where the abstract of this record would appear. This is only demonstration data

C-reactive protein does not opsonize early apoptotic human neutrophils, but binds only membrane-permeable late apoptotic cells and has no effect on their phagocytosis by macrophages

BACKGROUND: It has been reported that C-reactive protein (CRP) binds both leukocyte FcγRIIA (CD32) and the plasma membrane of apoptotic cells. Since FcγRIIA becomes functionally enabled during neutrophil apoptosis, we sought to determine whether CRP bound to apoptotic neutrophils via FcγRIIA. METHODS: We prepared directly labelled CRP and demonstrated that it was essentially free of IgG. We looked for evidence of CRP binding to intact, membrane impermeable apoptotic human neutrophils and to FcγRIIA-transfected Jurkat cells. We examined the functional consequences of incubation with CRP upon phagocytosis of apoptotic cells by human monocyte-derived macrophages. RESULTS: We could not detect binding of purified soluble CRP to classical early apoptotic human neutrophils or to FcγRIIA-transfected Jurkat cells. In contrast, membrane-permeable late apoptotic neutrophils exhibited strong CRP binding, which comprised both Ca(2+)-dependent and heparin-inhibitable Ca(2+)-independent components. However, there was no effect of CRP binding upon phagocytosis of late apoptotic neutrophils by macrophages. CONCLUSION: Potential apoptotic cell opsonins such as CRP may bind only to intracellular structures in cells with leaky membranes that have progressed to a late stage of apoptosis

Understanding the impact of chronic obstructive pulmonary disease exacerbations on patient health and quality of life

Exacerbations of chronic obstructive pulmonary disease (COPD) represent a significant clinical problem, and are associated with decreased lung function, worsening quality of life and decreased physical activity levels, with even a single exacerbation having detrimental effects. The occurrence of COPD exacerbations can also have a considerable impact on healthcare costs and mortality rates, with over one-fifth of patients hospitalized for a COPD exacerbation for the first time dying within one year of discharge. This highlights the need for COPD exacerbations to be a major focus in clinical practice. Furthermore, the substantial effect that COPD exacerbations can have on patient mental health should not be underestimated. Despite their clinical importance, COPD exacerbations are poorly recognized and reported by patients, and improving patient understanding and reporting of exacerbations to ensure prompt treatment may minimize their deleterious effects. Renewed focus on improving current clinical practice with support from evidence-based guidelines is required. This also raises a challenge to payors, healthcare systems and government policies to do more to tackle the considerable outstanding burden of COPD exacerbations

New Spirometry Indices for Detecting Mild Airflow Obstruction.

The diagnosis of chronic obstructive pulmonary disease (COPD) relies on demonstration of airflow obstruction. Traditional spirometric indices miss a number of subjects with respiratory symptoms or structural lung disease on imaging. We hypothesized that utilizing all data points on the expiratory spirometry curves to assess their shape will improve detection of mild airflow obstruction and structural lung disease. We analyzed spirometry data of 8307 participants enrolled in the COPDGene study, and derived metrics of airflow obstruction based on the shape on the volume-time (Parameter D), and flow-volume curves (Transition Point and Transition Distance). We tested associations of these parameters with CT measures of lung disease, respiratory morbidity, and mortality using regression analyses. There were significant correlations between FEV1/FVC with Parameter D (r = -0.83; p < 0.001), Transition Point (r = 0.69; p < 0.001), and Transition Distance (r = 0.50; p < 0.001). All metrics had significant associations with emphysema, small airway disease, dyspnea, and respiratory-quality of life (p < 0.001). The highest quartile for Parameter D was independently associated with all-cause mortality (adjusted HR 3.22,95% CI 2.42-4.27; p < 0.001) but a substantial number of participants in the highest quartile were categorized as GOLD 0 and 1 by traditional criteria (1.8% and 33.7%). Parameter D identified an additional 9.5% of participants with mild or non-recognized disease as abnormal with greater burden of structural lung disease compared with controls. The data points on the flow-volume and volume-time curves can be used to derive indices of airflow obstruction that identify additional subjects with disease who are deemed to be normal by traditional criteria

Efficacy and safety of once-daily fluticasone furoate/vilanterol (100/25 mcg) versus twice-daily fluticasone propionate/salmeterol (250/50 mcg) in COPD patients

SummaryBackgroundFluticasone furoate/vilanterol (FF/VI) is an inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA), recently approved as once-daily maintenance therapy for COPD. We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol (FP/SAL).MethodsThree 12 week studies comparing FF/VI and FP/SAL were conducted. Patients aged ≥40 years with moderate-to-very severe COPD were randomized to receive double-blind, double-dummy FF/VI 100/25 mcg once-daily, or FP/SAL 250/50 mcg twice-daily for 12 weeks following a 2 week placebo run-in period. The primary endpoint of each study was change from baseline trough in 0–24 h weighted mean FEV1 (wmFEV1) on Day 84. Safety was also assessed.ResultsIn Study 1 (HZC113109) (intent-to-treat n: FF/VI = 260; FP/SAL = 259), the increase from baseline in 0–24 h wmFEV1 was significantly greater with FF/VI than FP/SAL (Δ80 mL, P < 0.001). In Study 2 (HZC112352) (intent-to-treat n: FF/VI = 259; FP/SAL = 252) and Study 3 (RLV116974) (intent-to-treat n: FF/VI = 412; FP/SAL = 416), the increase from baseline in 0–24 h wmFEV1 was not significantly greater with FF/VI than FP/SAL (Δ29 mL, P = 0.267; Δ25 mL, P = 0.137). The treatment difference was statistically but not clinically significant in a pooled analysis (Δ41 mL, P < 0.001). Pooled adverse events (FF/VI 27%; FP/SAL 28%) and serious adverse events (FF/VI 2%; FP/SAL 3%) were similar between treatments.ConclusionsOur data suggest that once-daily FF/VI 100/25 mcg provides FEV1 improvement in COPD that is at least comparable with that conferred by twice-daily FP/SAL 250/50 mcg, although interpretation is limited by differences in individual study outcomes. The safety profiles of FF/VI 100/25 mcg and FP/SAL 250/50 mcg are similar.Clinical trial registrationclinicaltrials.gov: NCT01323634; NCT01323621; NCT01706328. GlaxoSmithKline study codes: HZC113109; HZC112352; RLV116974

Formal Verification of a Rover Anti-collision System

In this paper, we integrate inductive proof, bounded model checking, test case generation and equivalence proof techniques to verify an embedded system. This approach is implemented using Systerel Smart Solver (S3) toolset. It is applied to verify properties at system, software, and code levels. The verification process is illustrated on an anti-collision system (ARP for Automatic Rover Protection) implemented on-board a rover. Focus is placed on the verification of safety and functional properties and the proof of equivalence between the design model and the generated code