Project description:Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the natural history of this chronic lung disorder. These events can be caused by a large number of infectious and noninfectious agents and are associated with an increased local and systemic inflammatory response. Their frequency and severity have been linked to progressive deterioration in lung function and health status. Infectious pathogens ranging from viral to atypical and typical bacteria have been implicated in the majority of episodes. Most therapeutic regimens to date have emphasized broad, nonspecific approaches to bronchoconstriction and pulmonary inflammation. Increasingly, therapy that targets specific etiologic pathogens has been advocated. These include clinical and laboratory-based methods to identify bacterial infections. Further additional investigation has suggested specific pathogens within this broad class. As specific antiviral therapies become available, better diagnostic approaches to identify specific pathogens will be required. Furthermore, prophylactic therapy for at-risk individuals during high-risk times may become a standard therapeutic approach. As such, the future will likely include aggressive diagnostic algorithms based on the combination of clinical syndromes and rapid laboratory modalities to identify specific causative bacteria or viruses.
Project description:BACKGROUND: There is a paucity of lung specific biomarkers to diagnose exacerbations of chronic obstructive pulmonary disease (COPD) and to track their progression. Surfactant protein D (SP-D) is a pulmonary collectin regulating the innate immunity of the lung and its serum expression is perturbed in COPD. However, it is not known whether serum levels change during exacerbations. We sought to determine whether serum SP-D levels are raised in COPD exacerbations. OBJECTIVES: To determine whether or not patients with exacerbations have elevated serum SP-D levels compared with asymptomatic controls, stable disease. STUDY DESIGN: case control study. METHODS: We measured serum SP-D levels from patients with stable COPD (n= 14), patients experiencing acute exacerbations (n=13) and in control subjects (n=54) using a specific immunoassay and compared the levels using analysis of variance. RESULTS: Serum SP-D levels were significantly increased in patients who experienced an acute exacerbation (227 +/- 120 ng/mL) compared to patients with stable disease (151 +/- 83 ng/mL) or control subjects (128 +/- 65 ng/mL; p=0.003). Serum SP-D levels were also found to be inversely related to various lung function parameters including FEV_{1}/FVC% predicted. CONCLUSIONS: Our study suggests that serum SP-D levels are increased in patients during exacerbations and may be a potential diagnostic biomarker for COPD exacerbations.
Project description:Mannose-binding lectin is a collectin involved in host defense against infection. Whether mannose-binding lectin deficiency is associated with acute exacerbations of chronic obstructive pulmonary disease is debated.Participants in a study designed to determine if azithromycin taken daily for one year decreased acute exacerbations had serum mannose-binding lectin concentrations measured at the time of enrollment.Samples were obtained from 1037 subjects (91%) in the trial. The prevalence of mannose-binding lectin deficiency ranged from 0.5% to 52.2%, depending on how deficiency was defined. No differences in the prevalence of deficiency were observed with respect to any demographic variable assessed, and no differences were observed in time to first exacerbation, rate of exacerbations, or percentage of subjects requiring hospitalization for exacerbations in those with deficiency versus those without, regardless of how deficiency was defined.In a large sample of subjects with chronic obstructive pulmonary disease selected for having an increased risk of experiencing an acute exacerbation of chronic obstructive pulmonary disease, only 1.9% had mannose-binding lectin concentrations below the normal range and we found no association between mannose-binding lectin concentrations and time to first acute exacerbation or frequency of acute exacerbations during one year of prospective follow-up.
Project description:Extracorporeal carbon dioxide removal (ECCO2R) has been proposed as an adjunctive intervention to avoid worsening respiratory acidosis, thereby preventing or shortening the duration of invasive mechanical ventilation (IMV) in patients with exacerbation of chronic obstructive pulmonary disease (COPD). This review will present a comprehensive summary of the pathophysiological rationale and clinical evidence of ECCO2R in patients suffering from severe COPD exacerbations.
Project description:BackgroundMany patients with chronic obstructive pulmonary disease (COPD) suffer from poor sleep quality. We hypothesized that poor sleep quality in otherwise stable patients predicted exacerbations in these patients.MethodsThis is a secondary analysis of the results of a previously published randomized trial of azithromycin in 1,117 patients with moderate to severe COPD who were clinically stable on enrollment. Sleep quality was measured using the Pittsburgh Sleep Quality Index. Other quality of life indices included the Medical Outcome Study 36-item Short Form Health Survey and the St Georges Respiratory Questionnaire. Outcomes included time to first exacerbation and exacerbation rate.ResultsSleep quality was "poor" (Pittsburgh Sleep Quality Index >5) in 53% of participants but was not related to age or severity of airflow obstruction. Quality of life scores were worse in "poor" sleepers than in "good" sleepers. Major classes of comorbid conditions, including psychiatric, neurologic, and musculoskeletal disease, were more prevalent in the "poor" sleepers. Unadjusted time to first exacerbation was shorter (190 versus 239 days) and exacerbation rate (1.7 versus 1.37 per year) was greater in the poor sleepers, but no differences were observed after adjusting for medications and comorbid conditions associated with poor sleep.ConclusionPoor sleepers had greater exacerbation rates than did good sleepers. This appeared to be due largely to them having more, or more severe, concomitant medical conditions and taking more medications.
Project description:Investigation of whole genome gene expression level changes of the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10, compared to the normal people and stable COPD patients. A five chip study using total RNA recovered from Peripheral Blood Mononuclear Cell of Peripheral Blood.Evaluating the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10 after the hospital admission, to compared with healthy controls or patients with stable COPD. Slides were scanned at 5 μm/pixel resolution using an Axon GenePix 4000B scanner (Molecular Devices Corporation) piloted by GenePix Pro 6.0 software (Axon). Scanned images (TIFF format) were then imported into NimbleScan software (version 2.5) for grid alignment and expression data analysis. Expression data were normalized through quantile normalization and the Robust Multichip Average (RMA) algorithm included in the NimbleScan software. The Probe level (*_norm_RMA.pair) files and Gene level (*_RMA.calls) files were generated after normalization.
Project description:BACKGROUND:Antimicrobial treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains controversial. In some cases AECOPD are caused by microorganisms that are resistant to treatments recommended by guidelines. Our aims were: 1) identify the risk factors associated with infection by microorganisms resistant to conventional treatment (MRCT), 2) Compare the clinical characteristics and outcomes of patients with AECOPD resulting from MRCT against those with AECOPD from other causes. METHODS:We prospective analysed a cohort of patients admitted with severe AECOPD (2009 to 2015) who were assigned to three groups: patients with MRCT (those patients with germs resistant to antibiotics recommended in guidelines), patients with microorganisms sensitive to conventional antimicrobial treatment (MSCT), and patients with negative microbiology results who had not previously received antibiotics. Multinomial logistic regression analyses were used to examine the associations between microbial aetiology groups and risk factors. The association between LOS and risk factors was also tested in simple and multiple analyses, and similar inclusion criteria were applied for the linear regression analysis. RESULTS:Of the 451 patients admitted, 195 patients (43%) were included. Respiratory cultures were positive in 86(44%) and negative in 109(56%). MRCT were isolated in 34 cases (40%) and MSCT in 52 (60%). Patients with MRCT had more AECOPD in the previous year, received more antibiotic treatment in the previous three months, had more severe disease, higher dyspnoea and a positive respiratory culture in the previous year (mainly for Pseudomonas aeruginosa). The following conditions were independent factors for MRCT isolation: non-current smoker (odds ratio [OR] 4.19 [95% confidence interval [CI] 1.29-13.67], p?=?0.017), ??2 AECOPD or???1 admission for AECOPD in the previous year (OR 4.13 [95% CI 1.52-11.17], p?=?0.005), C-reactive protein <?5 mg/dL; (OR 3.58 [95% CI 1.41-9.07], p?=?0.007). Mortality rates were comparable at 30-days, one year and 3 years; however, patients in the MRCT group had longer hospital stays. CONCLUSION:In conclusion, there are risk factors for resistant germs in AECOPD; however, the presence of these germs does not increase mortality. Patients with isolation of MRCT had longer length of stay.
Project description:INTRODUCTION:Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common reason for presentation to emergency departments (ED), but the management of these episodes is often heterogeneous regardless of their potential impact on short-term adverse outcomes. METHODS:This was a longitudinal, retrospective study of all patients >40 years old admitted to the ED of two Spanish teaching hospitals for an AECOPD between January 1st and May 31st, 2016. All data were collected from electronic medical records. The primary outcomes were patient treatment at discharge and 90-day mortality. Logistic regression was used to model the determinants of 90-day mortality. RESULTS:Of the 465 included patients, 56% were prescribed a 3-drug combination at hospital discharge, 22% a 2-drug combination, 19% a single drug, and 4% other or no treatment. Approximately 8% of patients died within 90 days after an AECOPD. Multivariate logistic models revealed that having more than 2 severe exacerbations within the last 12 months (OR (95% CI): 15.12 (4.22-54.22)) and being prescribed a single drug at discharge (OR (95% CI): 7.23 (2.44-21.38)) were the main determinants of 90-day mortality after an AECOPD. CONCLUSIONS:This study reflects the real-life heterogeneity in the pharmacological treatments prescribed after an ED admission for an AECOPD and suggests the potential impact of suboptimal inhaled treatment strategies on 90-day mortality rates.