Use of DECAF scoring system to facilitate early discharge in acute exacerbation of COPD patients: a quality improvement project at a district general hospital.

INTRODUCTION: DECAF is a scoring tool that can predict severity in patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Previous research has shown AECOPD patients with DECAF scores of 0-1 are candidates for early discharge. METHODS: Plan, do, study, act (PDSA) methodology was used. Patients with AECOPD and a DECAF score of 0-1 were included. Notes were retrospectively reviewed for patients for DECAF score, length of stay, 30-day re-admission and 30-day mortality (PDSA cycle 1). A framework to facilitate early discharge for patients was subsequently established. Awareness was increased through teaching sessions, posters and targeted emails. To evaluate our improvements, the same parameters were collected prospectively (PDSA cycle 2). RESULTS: DECAF score was assessed for no patients in PDSA cycle 1 (n=20) but was assessed for all patients in PDSA cycle 2 (n=14). Hospital stay was significantly decreased in PDSA cycle 2 (mean 0.29±0.45 days) compared with PDSA cycle 1 (mean 3.71±2.69 days; difference p<0.00001). Thirty-day re-admission and 30-day mortality was not significantly different between two groups. CONCLUSION: DECAF protocol is safe and feasible in the district general hospital setting and can facilitate early discharge for patients with low severity AECOPD without any worrisome effects.

EGF-induced bronchial epithelial cells drive neutrophil chemotactic and anti-apoptotic activity in asthma.

Chronic damage and repair of the bronchial epithelium are features of asthma. We have previously reported that ex vivo stimulation of normal bronchial epithelial cells with epidermal growth factor (EGF), a key factor of epithelial repair, enhances the mechanisms of neutrophil accumulation, thereby promoting neutrophil defences during acute injury but potentially enhancing inflammation in chronic airway diseases. We have now sought to (i) determine whether this EGF-dependent pro-neutrophil activity is increased in asthma, where EGF and its epithelial receptor are over-expressed, and (ii) elucidate some of the mechanisms underlying this asthmatic epithelial-neutrophil interaction. Primary bronchial epithelial cells (PBEC) from healthy subjects, mild asthmatics and moderate-to-severe asthmatics (Mod/Sev) were stimulated with EGF, a model that mimics a repairing epithelium. Conditioned culture media (EGF-CM) were assessed for neutrophil chemotactic and anti-apoptotic activities and inflammatory mediator production. EGF induced the epithelium to produce soluble mediators with neutrophil chemotactic (p<0.001) and pro-survival (p = 0.021) activities which were related to the clinical severity of asthma (trend p = 0.010 and p = 0.009, respectively). This was associated with enhanced IL-6, IL-8, GM-CSF and TNF-α release, and cytokine-neutralising experiments using EGF-CM from Mod/Sev asthmatics demonstrated a role for GM-CSF in neutrophil survival (p<0.001). Pre-treatment of neutrophils with specific inhibitors of the myeloid-restricted class I phosphatidylinositol-3-OH kinase (PI(3)K) isoforms showed that the EGF-CM from Mod/Sev asthmatics depended on the γ (p<0.021) but not δ isoforms, while neutrophil survival required multiple class I PI(3)Ks. The EGF-induced chemotactic, but not pro-survival activity, involved RhoA signaling in neutrophils (p = 0.012). EGF whose activity is upregulated in asthma induces ex vivo the epithelium from asthmatic patients to produce pro-neutrophil activities; these are related to asthma severity and, in moderate-to-severe asthmatics, involves class IB PI(3)Kγ signaling, providing a potential therapeutic target for neutrophilic forms of asthma.

Identification of lipocalin and apolipoprotein A1 as biomarkers of chronic obstructive pulmonary disease.

RATIONALE: Much effort is being made to discover noninvasive biomarkers of chronic airway disease that might enable better management, predict prognosis, and provide new therapeutic targets. OBJECTIVES: To undertake a comprehensive, unbiased proteomic analysis of induced sputum and identify novel noninvasive biomarkers for chronic obstructive pulmonary disease (COPD). METHODS: Induced sputum was obtained from patients with COPD with a spectrum of disease severity and from control subjects. Two-dimensional gel electrophoresis and mass spectrometric identification of differentially expressed proteins were first applied to induced sputum from patients with GOLD stage 2 COPD and healthy smoker control subjects. Initial results thus obtained were validated by a combination of immunoassays (Western blotting and ELISA) applied to a large subject cohort. The biomarkers were localized to bronchial mucosa by immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: Of 1,325 individual protein spots identified, 37 were quantitatively and 3 qualitatively different between the two groups (P < 0.05%). Forty protein spots were subjected to tandem mass spectrometry, which identified 15 separate protein species. Seven of these were further quantified in induced sputum from 97 individuals. Using this sequential approach, two of these potential biomarkers (apolipoprotein A1 and lipocalin-1) were found to be significantly reduced in patients with COPD when compared with healthy smokers. Their levels correlated with FEV(1)/FVC, indicating their relationship to disease severity. CONCLUSIONS: A potential role for apolipoprotein A1 and lipocalin-1 in innate defense has been postulated previously; our discovery of their reduction in COPD indicates a deficient innate defense system in airway disease that could explain increased susceptibility to infectious exacerbations.