Changes in bronchial inflammation during acute exacerbations of chronic bronchitis.

There are little data describing noncellular changes in bronchial inflammation during exacerbations of chronic bronchitis. The relationship between sputum colour and airway inflammation at presentation has been assessed during an exacerbation in patients with chronic bronchitis and a primary care diagnosis of chronic obstructive pulmonary disease. Sputum myeloperoxidase, neutrophil elastase, leukotriene B4 (LTB4), interleukin-8 (IL-8), sol:serum albumin ratio and serum C-reactive protein were measured in patients presenting with an exacerbation and mucoid (n = 27) or purulent sputum (n = 42). Mucoid exacerbations were associated with little bronchial or systemic inflammation at presentation, and sputum bacteriology was similar to that obtained in the stable state. Purulent exacerbations were associated with marked bronchial and systemic inflammation (p < 0.025 for all features) and positive sputum cultures (90%). Resolution was related to a significant reduction in LTB4 (p < 0.01), but no change in IL-8, suggesting that LTB4 may be more important in neutrophil recruitment in these mild, purulent exacerbations. In the stable state, IL-8 remained higher in patients who had experienced a purulent exacerbation (2p < 0.02). The presented results indicate that exacerbations of chronic bronchitis, defined by sputum colour, differ in the degree of bronchial and systemic inflammation. Purulent exacerbations are related to bacterial infection, and are associated with increased neutrophilic inflammation and increased leukotriene B4 concentrations.     

Sputum color as a marker of acute bacterial exacerbations of chronic obstructive pulmonary disease

We analyzed 795 sputa from 315 patients (233 males, mean age 69.3+/-8.8 years, mean number of exacerbations 2.52/patient) with acute exacerbations of moderate-to-severe chronic obstructive pulmonary disease (COPD) (mean steady-state FEV1 42.5+/-7.8% of predicted). 581/795 sputa were considered adequate. Sputum was analyzed by a quali-quantitative colorimetric scale allowing both color distinction and color degree of intensity. Quantitative culture was then performed (threshold: >10(6)CFU/mL). Samples were distinguished in mucoid (145) and purulent (436) sputa. Absence of bacterial growth was observed in 22% and 5% of mucoid and purulent sputa, respectively. Among mucoid sputa, Gram positive bacterial growth occurred more commonly compared to Gram negative and Pseudomonas aeruginosa/Enterobacteriaceae (56%, 24%, 20%, respectively). In purulent sputa, Gram positives were found in 38% of cases, Gram negatives in 38%, and P. aeruginosa/Enterobacteriaceae in 24%. We evaluated whether functional impairment (FEV1) orientates as to the infectious etiology of exacerbations. Significant differences were observed in the distribution of pathogens. Gram negative and P. aeruginosa/Enterobacteriaceae were isolated more frequently in the sputum when FEV1 was <35%. Our study indicates that purulent sputum is strongly associated with bacterial growth in COPD exacerbations. Deepening sputum color (from yellowish to brownish) was associated with increased yield of Gram negative and P. aeruginosa/Enterobacteriaceae.     

Exacerbations of COPD diagnosed in primary care: changes in spirometry and relationship to symptoms

The study objective was to assess spirometric changes during resolution of acute exacerbations of COPD diagnosed and treated in primary care and their relationship to clinical features. Spirometry was carried out on 101 patients with AECOPD presenting to a primary care physician on the day of presentation, days 5, 10-14, 28, and 56 after presentation and traces were analyzed including quality and reproducibility. Eighty-three patients produced at least one technically acceptable spirometer trace at presentation and 60 patients produced acceptable traces at all time points. The increase in FEV1 and VC occurred during the first 5 days after presentation, with a median increase in postbronchodilator FEV1 of 55 ml (IQR, -63 to 128, p = 0.003) and VC of 90 ml (IQR -78 to 308 ml, p < 0.001). The improvement in prebronchodilator values related to the bronchodilator reversibility at presentation and was strongest for VC (by day 28: r = 0.522, p < 0.001). Patients presenting with purulent sputum demonstrated improvements in FEV1 and VC but this was limited to FEV1 in those with mucoid sputum. The initial dyspnoea score related to the changes in spirometry. It is possible to obtain clinically useful spirometric traces in most patients presenting with an acute exacerbation in primary care. Some patients present with changes in sputum characteristics and cough without increased breathlessness. However, exacerbations characterized by increased breathlessness are associated with increases in airflow obstruction that may be influenced by sputum characteristics and/or changes in airway reactivity.     

C-Reactive Protein Levels Predict Bacterial Exacerbation in Patients With Chronic Obstructive Pulmonary Disease

BackgroundChronic obstructive pulmonary disease (COPD) causes a high rate of morbidity worldwide and predicting a bacterial cause of an exacerbation of COPD is difficult.MethodsIn this study, patient serum was obtained and C-reactive protein (CRP) levels were measured using an automated latex-enhanced turbidimetric assay. Sputum samples were obtained and evaluated microscopically. The relationship between CRP and the bacterial colonies in sputum in 81 patients with an exacerbation of COPD was assessed. Receiver operating characteristic (ROC) curves and the respective areas under the curve (AUCs) were calculated. Data from 64 patients with bacterial acute exacerbation of COPD (AECOPD) were compared with those of 37 patients with no documented bacterial AECOPD. Results categorized according to the nature of sputum as mucoid or purulent were also compared.ResultsHigh median CRP levels were observed in bacterial AECOPD compared with nonbacterial AECOPD. The ideal cutoff point for distinguishing patients with bacterial AECOPD from those with nonbacterial AECOPD was 19.65 mg/L (sensitivity, 78.18%; specificity, 84.61%; AUC, 0.832). In patients with mucoid sputum, the cutoff point was 15.21 mg/L and the area under the ROC curve 0.86, with a sensitivity of 81.5% and a specificity of 77.8%. Purulent sputum had a significantly higher CRP level than mucoid sputum, but with an AUC of only 0.617 (95% confidence interval, 0.49–0.74) to diagnosis bacterial AECOPD.ConclusionsIn adult patients with symptoms of AECOPD, an elevated serum CRP level of > 19.6 mg/L indicates bacterial exacerbation. In patients with AECOPD with mucoid sputum, an elevated CRP level of > 15.21 mg/L indicates bacterial infection, which may be a useful clinical marker for therapy of this disease.     

Optimal duration of IV and oral antibiotics in the treatment of thoracic actinomycosis

STUDY OBJECTIVE: IV antibiotic therapy for 2 to 6 weeks followed by 6 to 12 months of oral antibiotic therapy is usually recommended for the treatment of thoracic actinomycosis. The objective of this study was to evaluate the duration of IV and oral antibiotic therapy for thoracic actinomycosis. METHODS: We present a retrospective case series of 28 patients with thoracic actinomycosis as confirmed by histopathology from October 1994 through December 2003. RESULTS: After diagnosis of actinomycosis, 54% (15 of 28 patients) received antibiotic therapy alone. The duration of IV antibiotic therapy ranged from 0 to 18 days (median, 2 days; interquartile range [IQR], 0 to 3 days), and the duration of oral antibiotic treatment ranged from 76 to 412 days (median, 167 days; IQR, 142 to 214 days) in patients who received antibiotics alone. Combination surgical and antibiotic therapy occurred in 46% (13 of 28 patients). The duration of IV antibiotic therapy ranged from 3 to 17 days (median, 8 days; IQR, 5 to 13 days), and the duration of oral antibiotic therapy ranged from 0 to 534 days (median, 150 days; IQR, 3.5 to 289 days) in these patients. Clinical cures were achieved in 96% (27 of 28 patients). There was no clinical evidence of recurrence during follow-up period at our hospital (median, 23 months; IQR, 9 to 44 months) in 21 patients, excluding 7 patients who were transferred to referring hospitals after completion of antibiotic therapy (n = 6) or during antibiotic therapy (n = 1). CONCLUSIONS: Thoracic actinomycosis is best treated with individualized therapeutic modalities, depending on factors such as the initial burden of disease, the performance of resectional surgery, and the clinical and radiologic responses to therapy. The traditional recommendation of IV antibiotic therapy for 2 to 6 weeks followed by oral antibiotic therapy for 6 to 12 months is not always necessary for all thoracic actinomycosis patients.     

IgA subclasses in sputum from patients with bronchiectasis

The concentrations of IgA1 and IgA2 were measured in the serum and sputum from 27 clinically stable patients with bronchiectasis. Of the 27 patients, nine were regularly producing mucoid secretions, nine mucopurulent and nine purulent secretions. No significant differences were observed in serum IgA2 concentrations between the patient groups, although IgA1 concentrations were higher in the serum from the patients producing mucopurulent sputum than those producing mucoid or purulent sputum. The sputum concentrations of both IgA1 and IgA2 increased significantly with purulence. Furthermore, there was a significant increase in the proportion of IgA2 as the secretions became more purulent. The sputum concentrations of both IgA subclasses indicated significant local synthesis, with increased production (especially of IgA2) in the presence of inflammation due to infection.     

Correlation between cough frequency and airway inflammation in children with primary ciliary dyskinesia

Cough is common in airway disease. We measured cough frequency in children with primary ciliary dyskinesia (PCD), to determine how accurately families assess this symptom; and to assess the relationship between cough frequency and airway inflammation, measured using induced sputum and exhaled nitric oxide (eNO). Twenty stable PCD children (7 boys), median age 10.8 years (interquartile range (IQR), 9-14), and 10 healthy control children, median age 12 years (IQR, 10.5-12.7), were recruited. ENO was measured using a chemiluminescence analyzer, with sputum induction with 3.5% saline. PCD children underwent ambulatory cough monitoring. Sputum neutrophils were higher in PCD (median, 70.3%; IQR, 55.3-78%) compared to controls (median, 27%; IQR, 24.5-33%; P = 0.004); cough frequency was higher (median episodes, 19; IQR, 11-22.5) compared to healthy children (median episodes, 6.7; IQR, 4.1-10.5; P < 0.001). Forced expiratory volume in 1 sec (FEV(1) percent predicted) and eNO were lower in PCD (median, 63%; IQR, 57-85%; P < 0.0001); eNO (median, 7.1 ppb (IQR, 4.8-19.1 ppb) vs. 12.4 ppb (IQR, 10.3-17.3 ppb), P = 0.043). Parental scoring of day and night cough correlated with recorded cough (r = 0.930, P < 0.0001, daytime; r = 0.711 for nighttime, P = 0.002). Visual analogue score and cough episodes also correlated positively (r = 0.906; P < 0.0001). There was a positive correlation between cough frequency and sputum neutrophil count in PCD (Spearman's r = 0.693, P < 0.002), but not percent FEV(1) or eNO. Stable PCD children have increased cough frequency and neutrophilic airway inflammation. In conclusion, cough frequency correlated with sputum neutrophils but not with FEV1 or eNO.     

Tc2 response at the onset of COPD exacerbations

BACKGROUND: T lymphocytes and especially the subpopulations of CD8+ cells are believed to have a key role in COPD pathophysiology, but there are only few data regarding the role of these cells in COPD exacerbation. Aim: We aimed to study prospectively changes of CD8+ T-lymphocyte subpopulations in the sputum of COPD patients at the onset of mild exacerbations and at a stable condition in order to provide further insight in the pathophysiology of the disease. METHODS: Induced-sputum samples were collected from 24 COPD patients with median age of 52 years (interquartile range [IQR], 44 to 58 years) and FEV(1) percentage of predicted of 78.05% (IQR, 75.8 to 80.1%) at the onset of mild exacerbations not requiring hospitalization and when stable. Inflammatory cells and T-lymphocyte subpopulations (CD4+, CD8+, and cells producing interferon [IFN]-gamma or interleukin [IL]-4) were measured using flow cytometry and immunocytochemical methods. RESULTS: A significant increase in sputum CD8+ T lymphocytes (p < 0.0001) and significant decreases in CD4+ T lymphocytes as well as in CD4+/CD8+ (p = 0.0001) and CD8+IFN-gamma+/CD8+IL-4+ (p = 0.001), CD4+IFN-gamma+/CD4+IL-4+ (p = 0.0003) sputum cells ratios were found decreased at the onset of exacerbations compared to stable condition. The changes in T-lymphocyte subpopulations were not associated with smoking history, demographic characteristics, or disease severity. CONCLUSION: The findings of the present study suggest that CD8+ lymphocytes are increased and potentially polarized toward a Tc2 profile in the airways of COPD patients at the onset of COPD exacerbations with respect to stable condition. The clinical impact of the observed phenomenon requires further investigation.     

Airway and systemic inflammation and decline in lung function in patients with COPD

STUDY OBJECTIVES: Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1. There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1. PATIENTS AND DESIGN: A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8). At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3). RESULTS: During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr. Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 x 10(6) cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05). Patients with frequent exacerbations (> or = 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr). Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018). Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively. CONCLUSIONS: In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function.     

Safety of sputum induction during exacerbations of COPD

Sputum induction (SI) is considered to be a safe tool for assessing airway inflammation in stable patients with COPD, but little is known about its safety during exacerbations. We therefore assessed the safety of SI during COPD exacerbations. SI data from 44 COPD patients were assessed both in the stable phase and during exacerbation. The median FEV1 for the stable phase and exacerbation were 61% predicted (interquartile range [IQR], 49 to 74% predicted) and 51% predicted (IQR, 45 to 60% predicted), respectively. The median decrease in FEV(1) with SI during an exacerbation was 0.27 L (IQR, 0.17 to 0.40 L) vs 0.28 L (IQR, 0.22 to 0.44 L) during the stable phase (p = 0.03). The patients experienced the associated dyspnea well; no other adverse events occurred. All FEV1 values returned to within 90% of their initial value within 30 min. A larger decrease in FEV1 due to SI during an exacerbation was associated with the following parameters in the stable phase of disease: lower total sputum cell count (r = -0.37; p = 0.01); higher percentage of eosinophils (r = 0.33; p = 0.04); and a larger decrease in FEV1 after SI (r = 0.39; p = 0.03). In a multivariate analysis, the only independent association was with the larger decrease in FEV1 in the stable phase. We concluded that SI can be safely carried out in patients with mild-to-moderate COPD who experience an exacerbation, and this occurs with no greater risk than in stable patients with COPD.     

The role of piperacillin therapy in pulmonary exacerbations of cystic fibrosis: a controlled study

Piperacillin was evaluated as an antipseudomonas antibiotic in a double-blind controlled trial involving 18 pulmonary exacerbations of cystic fibrosis. Standard antibiotic treatment (flucloxacillin plus tobramycin) was compared with standard treatment plus intravenous piperacillin administered according to two regimens. No added benefit from piperacillin was demonstrable on the basis of improvement in symptoms, physical signs, weight gain, pulmonary function tests, radiologic signs, or sputum Pseudomonas bacterial counts. Some patients experienced sensitivity reactions to piperacillin. In vitro, piperacillin was a potent antibiotic against all beta-lactamase-producing mucoid strains of Pseudomonas aeruginosa; however, in spite of the fact that adequate serum antibiotic concentrations were achieved, sputum bacterial counts did not correlate with either the clinical status or the use of piperacillin therapy.     

Managing the older bronchitis patient

In this era of cost containment, it is not appropriate to obtain a complete blood cell count, Gram's stain of sputum, sputum culture, or blood cultures for elderly outpatients with an exacerbation of chronic bronchitis. For monitoring antibiotic therapy of infectious exacerbations, clinicians rely on the patient's observations that dyspnea is less severe, and that sputum volume is reduced and appears more mucoid than purulent. These criteria may be rudimentary, but they have withstood the test of time.     

Increased arginase activity in cystic fibrosis airways

RATIONALE: Airway nitric oxide concentrations are reduced in cystic fibrosis (CF). Arginases compete for L-arginine, the substrate of nitric oxide synthesis. OBJECTIVES: We hypothesized that increased arginase activity may be one factor contributing to nitric oxide deficiency in CF. MEASUREMENTS: We therefore studied sputum arginase activity, exhaled nitric oxide, and pulmonary function in patients with cystic fibrosis. RESULTS: Mean (+/- SEM) sputum arginase activity was significantly higher in patients admitted for pulmonary exacerbation compared with patients with stable disease (1.032 +/- 0.148 vs. 0.370 +/- 0.091 U/mg protein, p = 0.004). Fourteen days of intravenous antibiotic treatment resulted in significantly decreased sputum arginase activity in all patients (p = 0.0002). However, arginase activity was still significantly (p = 0.0001) higher in CF sputum after treatment for exacerbation compared with induced sputum from healthy control subjects (0.026 +/- 0.006 U/mg protein). Negative correlations were found for sputum arginase activity at admission with FEV1 (r = -0.41, p = 0.01), as well as changes in arginase activity with percent change in FEV1 during antibiotic therapy (r = -0.4, p < 0.01) in CF. Exhaled nitric oxide in CF was positively correlated to FEV1 (r = 0.34, p = 0.007), and in patients admitted for pulmonary exacerbation negatively correlated to sputum arginase activity (r = -0.45, p = 0.03). CONCLUSIONS: These data suggest that increased sputum arginase activity contributes to nitric oxide deficiency in CF lung disease and may be relevant in the pathogenesis of CF airway disease.     

Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients

The present study was undertaken to investigate the appearance and location of Pseudomonas aeruginosa in the cystic fibrosis (CF) lung and in sputum. Samples include preserved tissues of CF patients who died due to chronic P. aeruginosa lung infection prior to the advent of intensive antibiotic therapy, explanted lungs from 3 intensively treated chronically P. aeruginosa infected CF patients and routine sputum from 77 chronically P. aeruginosa infected CF patients. All samples were investigated microscopically using hematoxylin–eosin (HE), Gram and alcian‐blue stain, PNA FISH and immunofluorescence for alginate. Investigation of the preserved tissues revealed that prior to aggressive antibiotic therapy, P. aeruginosa infection and destruction of the CF lung correlated with the occurrence of mucoid (alginate) bacteria present in aggregating structures surrounded by pronounced polymorphonuclear‐leukocyte (PMN) inflammation in the respiratory zone (9/9). Non‐mucoid bacteria were not observed here, and rarely in the conductive zone (1/9). However, in the explanted lungs, the P. aeruginosa aggregates were also mucoid but in contrast to the autopsies, they were very rare in the respiratory zone but abundant in the sputum of the conductive zone (3/3), which also contained abundances of PMNs (3/3). Non‐mucoid and planktonic P. aeruginosa were also observed here (3/3). In conclusion, the present intensive antibiotic therapy of chronic P. aeruginosa infections, at the Copenhagen CF Centre, seems to restrain but not eradicate the bacteria from the conductive zone, whereas the remaining healthy respiratory zone appears to be protected, for a long period, from massive biofilm infection. This strongly suggests that the conductive zone serves as a bacterial reservoir where the bacteria are organized in mucoid biofilms within the mucus, protected against antibiotics and host defenses. Pediatr Pulmonol. 2009; 44:547–558. © 2009 Wiley‐Liss, Inc.     

Long-term outcomes of endoluminal gastroplication: a U.S. multicenter trial

BACKGROUND: Endoluminal gastroplication has shown promise for the treatment of GERD in short-term studies. Until now, long-term outcome data have been lacking. METHODS: A prospective, multicenter trial enrolled 85 patients with GERD to be treated with endoluminal gastroplication. Inclusion criteria were 3 or more heartburn or regurgitation episodes per week, >4.2% time in 24 hours with esophageal pH < 4, and dependency on antisecretory medications. Exclusion criteria were the presence of varices, achalasia, aperistalsis, or previous gastric resection. Patients underwent manometry, 24-hour pH monitoring, and symptom severity scoring before and after the procedure. Patient diaries were used to assess medication use and to estimate annual medication cost. RESULTS: At 1- and 2-year follow-up, patients had significant reductions in median heartburn symptom scores (72 at baseline [interquartile range (IQR) 90-48] vs. 4 at 12 months [IQR 43-0] and 16 at 24 months [IQR 53-3.5]; p < 0.0001 vs. baseline) and median regurgitation symptoms (2 at baseline [IQR 3-1] vs. 0 at 12 months (IQR 1-0) and 1 at 24 months [IQR 1-0]; p < 0.0001 vs. baseline). Of all patients, 59% and 52% showed heartburn symptom resolution at 12 and 24 months, respectively ( p < 0.0001 vs. baseline). Also, 83% and 77% had regurgitation symptom resolution at 12 and 24 months, respectively (p < 0.0001 vs. baseline). Proton pump inhibitor use also was significantly reduced at 12 and 24 months after the procedure. At 2-year follow-up, median annualized medication costs were reduced by 88% (1381 US dollars) (p < 0.0001). Endoluminal gastroplication significantly reduced the duration and the number of episodes of esophageal acid exposure (p < 0.0001 vs. baseline). Only 7 patients experienced adverse events. CONCLUSIONS: Endoscopic gastroplication is safe and effective, and is associated with symptom reductions in patients with GERD for at least 24 months.     

Up-regulation of thrombin activity induced by vascular endothelial growth factor in asthmatic airways

BACKGROUND: High expression of vascular endothelial growth factor (VEGF) induces subepithelial fibrosis associated with angiogenesis in patients with asthma. Thrombin is recognized as a new candidate mediating airway remodeling. Therefore, this study was designed to determine the role of up-regulated thrombin activity induced by VEGF on airway remodeling in patients with asthma. METHODS: Levels of biochemical parameters in induced sputum were examined in 21 asthmatic patients and 11 normal control subjects. RESULTS: Thrombin activity in induced sputum was significantly higher in asthmatic patients than in normal control subjects: median, 3.67 U/mL; range, 1.15 to 10.2 U/mL; vs median, 1.26 U/mL; range, 0.93 to 2.42 U/mL (p < 0.0001). In contrast, protein C activity in induced sputum was lower in asthmatic patients than in normal control subjects: median, 20%; range, 5 to 30%; vs 41%; range, 30 to 59% (p < 0.0001). VEGF level in induced sputum was positively correlated with thrombin activity in asthmatic patients (r = 0.55, p = 0.02), while inversely correlated with protein C activity (r = - 0.57, p = 0.01). Levels of basic fibroblast growth factor (bFGF), a major profibrotic factor, were also significantly higher in asthmatic patients than in normal control subjects. Moreover, thrombin activity was significantly correlated with bFGF level in asthmatic patients (r = 0.67, p = 0.003). CONCLUSIONS: Increase in VEGF level leads to up-regulation of thrombin activity in asthmatic airways, and this elevated thrombin activity induces elevation of bFGF level. It will become to be a new strategy of asthma therapy to attenuate thrombin activity for the regulation of airway remodeling.     

A large prospective study assessing injection site reactions, quality of life and preference in patients using the Biojector vs standard needles for enfuvirtide administration

OBJECTIVES: To determine the severity of injection site reactions (ISRs), patient quality of life (QoL) and preference when enfuvirtide is administered by the Biojector (Bioject, Medical Technologies, Inc., Tualatin, OR, USA) relative to standard needles. METHODS: A total of 201 HIV-positive patients on stable enfuvirtide-based therapy (n=184) or initiating such therapy (n=17) were evaluated prospectively after switching from standard needles to the Biojector system. Patients used needles for a minimum of 2 weeks prior to switching to the Biojector. Questionnaires to assess the incidence and severity of ISRs (31-item score) and QoL [Medical Outcomes Study HIV Health Survey (MOS-HIV)] were administered at baseline and following a minimum of 14 days of Biojector use. RESULTS: The median changes in ISR score and number of ISRs following a median of 1.0 month [interquartile range (IQR) 0.9, 1.3] of Biojector use were -3 (IQR -7, 1) and -1 (IQR -3, 1), respectively. The severity of pain (P<0.0001), induration (P<0.0001), pruritus (P<0.0001), nodules (P<0.0001) and erythema (P<0.0001) all decreased with the Biojector. Administration of enfuvirtide with the Biojector was associated with an improved patient QoL (P<0.0001), and was preferred by 72% of patients. CONCLUSIONS: Compared with needles, the Biojector was associated with a decreased severity of ISRs and improved QoL in patients taking enfuvirtide.     

Yield of sputum microbiological examination in patients hospitalized for exacerbations of chronic obstructive pulmonary disease with purulent sputum

BACKGROUND: Whether sputum microbiological examination should be performed systematically in hospitalized patients with chronic obstructive pulmonary disease (COPD) exacerbations remains unclear. OBJECTIVES: To assess the yield of sputum microbiological examination in COPD patients hospitalized in a medical ward for an acute exacerbation with purulent sputum. METHODS: Two hundred consecutive exacerbations in 118 patients were studied. Patients underwent sputum microbiological examination on admission and baseline lung function tests and CT scans were recorded. Factors associated with positive culture were analyzed. RESULTS: Sputum culture was positive (>or=10(7) CFU/ml) in 59% of samples, Haemophilus influenzae and Streptococcus pneumoniae being the most frequent pathogens. Factors associated with positive culture were bronchiectasis, long-term oxygen therapy and low FEV1. Pseudomonas spp. were found in 8.5% of all patients, who all had a FEV1<50% of predicted and were older. Only 25% of sputum samples satisfied all quality criteria. Sputum culture was positive in a high proportion of these samples (80.5%), but also in one half of samples with >25 leukocytes but >10 epithelial cells per field. Microbiological results induced a change in antibiotic therapy in 43.9% of cases with both quality criteria but also in 25.2% of cases with only one quality criterion. Finally, a predominant aspect after Gram stain was found in all positive samples. CONCLUSIONS: These data suggest that sputum microbiological examination with direct examination and leukocyte count should be performed routinely in patients hospitalized for COPD exacerbations with purulent sputum, especially when FEV1 is less than 50% predicted and in patients with bronchiectasis.     

CXCR3 and CCR5 chemokines in induced sputum from patients with COPD

BACKGROUND: COPD is associated with increased numbers of CD4(+) and CD8(+) lymphocytes and macrophages in the small airways and lung parenchyma. The chemokines regulating T-cell recruitment into the lung are unknown but may involve CXCR3 and CCR5 chemoattractants. The aims of this study were to determine the concentrations of CXCR3 chemokines CXCL9, CXCL10, CXCL11, and the CCR5 chemokine CCL5 in induced sputum from patients with COPD, smokers, and nonsmokers, and to examine the relationship between chemokine expression, inflammatory cells, and airway obstruction. METHODS: Differential cell counts were performed and concentrations of CXCL9, CXCL10, CXCL11, and CCL5 were measured in induced sputum from nonsmokers (n = 18), smokers (n = 20), and COPD patients (n = 35) using an enzyme-linked immunosorbent assay. RESULTS: Concentrations of CXCL9, CXCL10, CXCL11, and CCL5 were significantly increased in the sputum of patients with COPD when compared with nonsmokers but not smokers without obstruction: CXCL9 (median, 14.3 pg/mL; interquartile range [IQR], 6.5 to 99.3; vs median, 1.4 pg/mL; IQR, 0 to 10.4 [p < 0.001]; vs 8.5 pg/mL; IQR, 0 to 16.0, respectively); CXCL10 (16.9 pg/mL; IQR, 6.2 to 148.8; vs 3.7 pg/mL; IQR, 0 to 18.8 [p < 0.05]; vs 11.3 pg/mL; IQR, 3.7 to 46.7); CXCL11 (58.1 pg/mL; IQR, 34.5 to 85.3; vs 33.5 pg/mL; IQR, 23.2 to 49.7 [p < 0.05]; vs 49.8 pg/mL; IQR, 32.6 to 105.6); and CCL5 (59.9 pg/mL; IQR, 57.1 to 67.8; vs 33.5 pg/mL; IQR, 31.6 to 36.9 [p < 0.001]). CCL5 in sputum from smokers was also significantly increased compared with that from nonsmokers (median, 63.0 pg/mL; IQR, 60.8 to70.2; p < 0.001). There was a negative correlation between FEV(1) percentage of predicted, FEV(1)/FVC ratio, and percentage of macrophages, and all the chemokines analyzed. Neutrophil numbers correlated positively with the concentrations of chemokines. CONCLUSIONS: CXCR3 chemokines and CCL5 are increased in sputum from COPD patients compared with nonsmokers, and may be important in COPD pathogenesis.     

Thrombin generation in antiphospholipid syndrome

Our objective was to study acquired Activated Protein C (APC) resistance in patients with antiphospholipid antibodies (aPL) using a thrombin generation based assay. We compared patients with and without lupus (systemic lupus erythematosus, SLE). A parameter summarizing APC inhibition of thrombin generation with increasing APC concentrations (IC(50)-APC) was increased in all patient groups compared to controls: median values were 15.3 (interquartile range, IQR, 9.7 to 34.0) in patients with primary antiphospholipid syndrome (APS), 27.3 (IQR 23.5 to 43.5) in patients with SLE without APS, 64.1 (IQR 25.9 to 65.0) in patients with SLE/APS compared to 10.4 [IQR 8.5 to 15.8] in controls, respectively p = 0.003, p = 0.0001 and p = 0.0001. In conclusion, patients with SLE and primary APS displayed a hypercoagulable state characterized by APC resistance.