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.
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.
Induced-sputum samples were collected from 24 COPD patients with median age of 52 years (interquartile range [IQR], 44 to 58 years) and FEV1 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]- or interleukin [IL]-4) were measured using flow cytometry and immunocytochemical methods.
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-+/CD8+IL-4+ (p = 0.001), CD4+IFN-+/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.
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.
If descriptors of the sensation of breathlessness are able to differentiate between medical conditions, the language of breathlessness could potentially have a role in differential diagnosis. This study investigated whether the language used to describe the sensation of breathlessness accurately categorized older individuals with and without a prior diagnosis of COPD.
Using a parallel-group design, participants with and without a prior diagnosis of COPD volunteered words and phrases and endorsed up to three statements to describe their sensation of breathlessness. Cluster analysis (v-fold cross-validation) was applied, and subjects were clustered by their choice of words. Cluster membership was then compared to original group membership (COPD vs non-COPD), and predictive power was assessed.
Groups were similar for age and gender (COPD, n = 94; 48 men; mean age, 70 ± 10 years [± SD]; vs non-COPD, n = 55; 21 men; mean age, 69 ± 13 years) but differed significantly in breathlessness-related impairment, intensity, and quality of life (p < 0.0001). Cluster membership corresponded accurately with original group classifications (volunteered, 85%; and up to three statements, 68% agreement). Classification based on a single best descriptor (volunteered [62%] or endorsed [55%]) was less accurate for group membership.
Language used to describe the sensation of breathlessness differentiated people with and without a prior diagnosis of COPD when descriptors were not limited to a single best word or statement.
Continuous oxygen therapy is not recommended for emphysema patients who are not hypoxemic at rest, although it is often prescribed. Little is known regarding the clinical characteristics and survival of nonhypoxemic emphysema patients using continuous oxygen. Analysis of data from the National Emphysema Treatment Trial (NETT) offers insight into this population.
We analyzed demographic and clinical characteristics of 1,215 participants of NETT, stratifying by resting PaO2 and reported oxygen use. Eight-year survival was evaluated in individuals randomized to medical therapy.
At enrollment, 33.8% (n = 260) of participants nonhypoxemic at rest reported continuous oxygen use. When compared to nonhypoxemic individuals not using oxygen (n = 226), those using continuous oxygen had worse dyspnea, lower quality of life, more frequent exercise desaturation, and higher case-fatality rate. After adjusting for age, body mass index, and FEV1 percentage of predicted, the presence of exercise desaturation accounted for the differential mortality seen between these groups.
In the NETT, the use of continuous oxygen in resting nonhypoxemic emphysema patients was associated with worse disease severity and survival. The differential survival observed could nearly all be accounted for by the higher prevalence of exercise desaturation in those using continuous oxygen, suggesting that it is not a harmful effect of oxygen therapy contributing to mortality. It remains unclear whether continuous oxygen therapy improves survival in normoxic patients with exercise desaturation.
Clinicaltrials.gov Identifier: NCT00000606.
Prior case series have shown promising diagnostic sensitivity for CT scan-guided bronchoscopy.
This was a prospective randomized trial comparing CT scan-guided bronchoscopy vs conventional bronchoscopy for the diagnosis of lung cancer in peripheral lesions and mediastinal lymph nodes. All procedures were performed using a protocolized number of passes for forceps, transbronchial needles, and brushes. Cytologists and pathologists were blinded as to bronchoscopy type. Patients with negative results underwent open surgical biopsy (for nodules or lymph nodes) or were observed for ≥ 2 years if they had a nodule < 1 cm in size.
Fifty patients were enrolled into the study (CT scan-guided bronchoscopy, 26 patients; conventional bronchoscopy, 24 patients). Two patients, one from each arm, dropped out of the study. Ultimately, 36 patients were proven to have cancer, and 27 of these patients (75%) had their diagnosis made by bronchoscopy. The sensitivity for malignancy of CT scan-guided bronchoscopy vs conventional bronchoscopy for peripheral lesions was similar (71% vs 76%, respectively; p = 1.0). The sensitivity for malignancy of CT guided bronchoscopy vs conventional bronchoscopy for mediastinal lymph nodes was higher (100% vs 67%, respectively) but did not reach statistical significance (p = 0.26). On a per-lymph-node basis, there was a trend toward higher diagnostic accuracy with CT scan guidance (p = 0.09). The diagnostic yield was higher in larger lesions (p = 0.004) and when CT scanning confirmed target entry (p = 0.001).
We failed to demonstrate a significant difference between CT scan-guided bronchoscopy and conventional bronchoscopy for the diagnosis of lung cancer in peripheral lesions and mediastinal lymph nodes. Further study of improved steering methods combined with CT scan guidance for the diagnosis of lung cancer in peripheral lesions is warranted.
Interest in databases is growing to allow for outcomes research, assess health-care quality, and determine best practices and resource allocation, and they are increasingly considered as a tool to potentially tie reimbursement to outcome parameters. Little is known about resource use and risk-adjusted morbidity and mortality after therapeutic bronchoscopic interventions.
Data were extracted and reviewed from an ongoing prospective, multi-institutional outcomes database for therapeutic bronchoscopic interventions. All consecutive patients are entered into this database, and information on demographics, indications, procedures and anesthesia, comorbidities and general health status, urgency of intervention, morbidity and mortality to 30 days, increase in levels of care, and procedural resources is documented.
From December 2005 to May 2007, 554 therapeutic procedures were performed in four hospitals. Most procedures were done under general anesthesia (n = 362) and rigid bronchoscopy (n = 483), and the most common intervention was airway stent placement (n = 258). Forty-two percent of procedures were done urgently or emergently. Complications were common (19.8%), and 30-day mortality was 7.8%, correlating with underlying health status and urgency of intervention.
Prospective and ongoing data analysis for bronchoscopic procedures is feasible and valuable. Risk-adjusted and disease-specific outcomes can be documented and potentially used for quality assessment, benchmarking, and quality improvement initiatives. Appropriate use of resources and effect of interventions can be documented. Extending the number of participating centers as well as inclusion of quality of life tools and technical success are the next steps.
Data on patients with cancer who have a prolonged length of stay (LOS) in the ICU are scarce. The aim of the present study was to evaluate the characteristics and the outcomes of cancer patients with life-threatening complications with an ICU stay ≥ 21 days.
A cohort study performed at a 10-bed oncology medical-surgical ICU from May 2000 to December 2005. Prolonged ICU LOS was defined as an ICU stay ≥ 21 days.
During the period, 1,090 patients were admitted to the ICU and 163 patients (15%) had a prolonged ICU LOS. These patients, however, accounted for 48% (5,828/12,224) of the total ICU bed-days. The hospital and 6-month mortality rates were 50% and 60%, respectively, and similar to patients with ICU LOS < 21 days (51% and 61%, respectively). ICU-acquired events and complications were common, and the most frequent were infections (90%), mechanical ventilation (99%), and need for vasopressors (88%). The number of organ failures, older age, and poor performance status were the main outcome predictors. The median long-term follow-up after hospital discharge was 537 days (range, 193 to 1,119 days), and 29 patients (18%) were alive.
Fifteen percent of critically ill patients with cancer had a prolonged ICU LOS. Short- and long-term survival rates were reasonable, and the prognosis was better than expected a priori. In our opinion, the length of ICU admission per se should not be used in the clinical decisions regarding the continuation of treatment in these patients.
Traditionally, the positioning of central venous catheters (CVCs) outside the right atrium (RA) in patients receiving intensive care is determined by surrogate landmarks on bedside chest radiographs (CXRs). The validity of this method was examined by comparing readings of radiologists with the results of transesophageal echocardiography (TEE).
Prospective study at university hospital. Two hundred thirteen adults scheduled for cardiothoracic surgery were randomized to right or left internal jugular vein catheterization under ECG guidance. One senior radiologist and two radiologists in training independently read the CXRs, and determined whether the CVC tip ended in the RA and measured the vertical distance from the CVC tip to the carina (TC-distance).
Two hundred twelve CVC tips could be identified by TEE. Only left-sided CVCs (n = 5) ended in the upper RA (2.4%). Three of those patients were shorter than 160 cm. Specificity was 94% for senior radiologist, 44% for the first radiologist in training, and 60% for the second radiologist in training. The TC-distance of intraatrial catheters was 39, 55, 59, 80, and 83 mm, respectively. Thus, a TC-distance ≤ 55 mm ensured extraatrial tip position in four of five intraatrial CVCs (80%, p = 0.002). The TC-distance of extraatrial catheters ranged from – 26 to 102 mm.
Reading of a bedside CXR alone is not very accurate to identify intraatrial CVC tip position. TC-distance is a helpful marker, and its specificity is as good as that of an experienced radiologist if a cutoff value of 55 mm is chosen.
Acute lung injury (ALI) is a frequent complication of sepsis. It is unclear if a pulmonary vs nonpulmonary source of sepsis affects mortality in patients with sepsis-induced ALI.
Two hundred eighty-eight consecutive patients with sepsis-induced ALI from 14 ICUs at four hospitals in Baltimore, MD were prospectively classified as having a pulmonary vs nonpulmonary source of sepsis. Multiple logistic regression was conducted to evaluate the independent association of a pulmonary vs nonpulmonary source of sepsis with inpatient mortality.
In an unadjusted analysis, in-hospital mortality was lower for pulmonary vs nonpulmonary source of sepsis (42% vs 66%, p < 0.0001). Patients with pulmonary sepsis had lower acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, shorter ICU stays prior to the development of ALI, and higher lung injury scores. In the adjusted analysis, several factors were predictive of mortality: age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01 to 1.06), Charlson comorbidity index (OR, 1.15; 95% CI, 1.02 to 1.30), ICU length of stay prior to ALI diagnosis (OR, 1.19; 95% CI, 1.01 to 1.39), APACHE II score (OR, 1.07; 95% CI, 1.03 to 1.12), lung injury score (OR, 1.64; 95% CI, 1.11 to 2.43), SOFA score (OR, 1.15; 95% CI, 1.06 to 1.26), and cumulative fluid balance in the first 7 days after ALI diagnosis (OR, 1.06; 95% CI, 1.03 to 1.10). A pulmonary vs nonpulmonary source of sepsis was not independently associated with mortality (OR, 0.72; 95% CI, 0.38 to 1.35).
Although lower mortality was observed for ALI patients with a pulmonary vs nonpulmonary source of sepsis, this finding is likely due to a lower severity of illness in those with pulmonary sepsis. Pulmonary vs nonpulmonary source of sepsis was not independently predictive of mortality for patients with ALI.
ClinicalTrials.gov Identifier: NCT00300248.
Conflicting data exist regarding the effects of obstructive sleep apnea syndrome (OSAS) on cardiorespiratory fitness in morbidly obese individuals with normal resting left ventricular function.
Ninety-two morbidly obese subjects without any prior diagnosis of OSAS underwent cardiorespiratory fitness testing, two-dimensional echocardiography, and overnight polysomnography. Using the results of the polysomnogram, comparisons were made between subjects with (n = 42) and without (n = 50) OSAS.
Mean body mass index (BMI) for the study population (n = 92) was 48.6 ± 9.3 kg/m2 (± SD); mean age was 45.5 ± 9.8 years, and approximately 69% were female. Despite having a higher resting, exercise, and resting mean arterial pressures, the OSAS cohort had a maximum oxygen consumption that was lower than the cohort without OSAS (21.1 mL/kg/min vs 17.6 mL/kg/min; p < 0.001). There was no difference in BMI, age, gender, waist circumference, and neck circumference between those with and without OSAS. Differences were observed between the cohorts in systolic BP, diastolic BP, and heart rate during rest, exercise, and recovery periods. There was no difference in ejection fraction, diastolic dysfunction, and treadmill test duration between cohorts.
Morbidly obese individuals with OSAS demonstrate reduced cardiorespiratory fitness and differing hemodynamic responses to exercise testing as compared with their counterparts without this disorder. These data suggest chronic sympathetic nervous system activation negatively influences aerobic capacity in OSAS.
Therapy with inhaled corticosteroids (ICSs) decreases the risk of asthma exacerbations. Recent studies have suggested that ICS therapy also may decrease the risk of cardiovascular disease, and perhaps of all-cause mortality. We examined this hypothesis in a large, well-characterized cohort of asthmatic women.
In 1976, the Nurses' Health Study enrolled 121,700 registered nurses, who were 30 to 55 years of age. Participants were asked about "physician-diagnosed asthma" on biennial questionnaires. In 1998, asthmatic participants were sent a supplementary questionnaire on asthma diagnosis and management, including ICS use. Mortality was assessed through 2003, without knowledge of the 1998 (baseline) ICS status. The odds ratios (ORs) for death were adjusted for age, asthma severity, smoking, heart disease, cancer, stroke, aspirin, and statin use.
Among 2,671 eligible women (ie, those who responded to the 1998 supplement [85%], met criteria for persistent asthma, and had not received a prior diagnosis of COPD), 54% reported ICS use. Over the next 5 years, 87 women (3.3%) died (cardiovascular deaths, 22; cancer deaths, 31; other, 34 [including 4 from asthma]). Compared to asthmatic women who did not use ICSs, those receiving therapy with ICSs had lower all-cause mortality (OR, 0.58; 95% confidence interval [CI], 0.36 to 0.92). ICS users were at significantly lower risk of cardiovascular death (OR, 0.35; 95% CI, 0.13 to 0.93), but not of death from cancer (OR, 0.66; 95% CI, 0.32 to 1.38) or other causes (OR, 0.62; 95% CI, 0.30 to 1.27).
ICS use was associated with significantly lower cardiovascular and all-cause mortality in women with asthma. These observational data suggest that ICSs may indeed have antiinflammatory benefits beyond the airway, which is a possibility that merits further study.
Muscarinic receptor agonists increase water secretion from the acinar cells of respiratory, sweat, salivary, and lacrimal glands. Mice lacking the gene for aqueous water channel aquaporin (Aqp) 5 exhibit methacholine-induced bronchiolar hyperreactivity when compared to normal mice. Individuals with asthma also have enhanced airway responsiveness to methacholine and diminished airway hydration. Because Aqp5 in humans is also expressed in respiratory, sweat, salivary, and lacrimal glands, we hypothesized that those individuals with exercise-induced asthma and excessive bronchiolar reactivity should also have decreased muscarinic receptor-dependent sweat, salivary, and tear gland secretions.
Healthy, athletic subjects who are suspected of having exercise-induced bronchospasm were recruited, and FEV1 values were determined following provocative airway challenges with methacholine. Measurements of pilocarpine-induced sweat secretion were taken in 56 volunteers, and some additional subjects also had timed collections of saliva and tear production.
Subjects manifesting excessive airway reactivity demonstrated by exaggerated methacholine-induced reductions in FEV1 also had diminished values for pilocarpine-induced sweat secretion (n = 56; r = – 0.59; p < 0.0001). The rate of pilocarpine-stimulated sweat secretion in our subjects correlated highly with salivary flow rate (r = 0.69; p < 0.0001) and tearing rate (r = 0.86; p < 0.001).
Hyperhidrosis, sialorrhea, and excessive tearing are traits that may indicate a phenotype that predicts resistance to hyperactive airway diseases such as exercise-induced asthma in humans.
The optimal antithrombotic therapy strategy for atrial fibrillation (AF) patients who undergo percutaneous coronary intervention with stent implantation (PCI-S) is unknown. We assessed the safety of antithrombotic therapy strategies in AF patients with indication for oral anticoagulation (OAC) undergoing PCI-S.
We studied consecutive AF patients with indication for OAC who underwent PCI-S. We compared patients that received triple antithrombotic therapy (TT) [aspirin, clopidogrel, and coumadin] against other regimes (non-TT) after PCI-S. The primary end point was defined as the occurrence of major bleeding complications that were termed as early major bleeding (EMB) [≤ 48 h] or late major bleeding (LMB) [> 48 h]. Clinical follow-up was performed, and complications were recorded.
We studied 104 patients (mean age ± SD, 72 ± 8 years; 70% men); TT was used in 51 patients (49%). TT was associated with a higher incidence of LMB (21.6% vs non-TT, 3.8%; p = 0.006) but not of EMB (5.8% vs non-TT, 11.3%; p = 0.33). In multivariate analyses, glycoprotein (GP) IIb/IIIa inhibitor use (hazard ratio [HR], 13.5; 95% confidence interval [CI], 1.7 to 108.3; p = 0.014) and PCI-S of three vessels or left main artery disease (HR, 7.9; 95% CI, 1.6 to 39.2; p = 0.01) were independent predictors for EMB. TT use (HR, 7.1; 95% CI, 1.5 to 32.4; p = 0.012), the occurrence of EMB (HR, 6.7; 95% CI, 1.8 to 25.3; p = 0.005), and baseline anemia (HR, 3.8; 95% CI, 1.2 to 12.5; p = 0.027) were independent predictors for LMB. No differences in major cardiovascular events were observed in patients treated with TT vs non-TT (25.5% vs 21.0%; p = 0.53).
A high rate of major bleeding is observed in AF patients with indication for OAC undergoing PCI-S who receive TT. GP IIb/IIIa inhibitor use and multivessel/left main artery disease during PCI-S were independent predictors for EMB, while TT use, occurrence of EMB, and baseline anemia were independent predictors for LMB.
Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction that increases patient morbidity and mortality. The financial impact of HIT to an institution is thought to be significant. The objective of this study was to evaluate the financial impact of HIT.
A case-control study was employed. Case patients were identified as newly diagnosed HIT patients. Control subjects were matched by diagnosis-related group, primary diagnosis code, primary procedure code, and hospital admission date. The financial/decision support database of the hospital was queried to identify the matched control subjects, total cost, and reimbursement. The determination of financial impact included the total profit or (total loss) and the backfill effect (ie, the lost operating margin resulting from increased length of stay). Length of stay and mortality were compared.
Data from 22 case patients and 255 control subjects were analyzed. On average, HIT case patients incurred a financial loss of $14,387 per patient and an increase in length of stay of 14.5 days. When confining the analysis to only Medicare case patients (n = 17) and Medicare control subjects, case patients incurred a financial loss of $20,170 per case and an increase in length of stay of 15.8 days. Depending on the occupancy rate of the institution, additional financial loss could result from the backfill effect. Mortality was not significantly affected.
For an institution that sees 50 new cases of HIT per year, the projected annual financial impact ranges from approximately $700,000 to $1 million. Institutions with high bed occupancy rates may see an additional loss from the backfill effect.
Abnormal levels of soluble CD40 ligand (sCD40L) have been reported in patients with hypertension, coronary artery disease, diabetes mellitus, heart failure, and stroke, all of which are conditions that are associated with nonvalvular atrial fibrillation (AF). We hypothesized the following: (1) CD40 ligand (CD40L)-related indexes (ie, platelet surface expressed CD40L, the soluble fragment of CD40L [sCD40L], and the total amount of CD40L per platelet [pCD40L]) are elevated in patients with AF compared to control subjects; (2) these indexes correlate with soluble P-selectin (sP-selectin), which is an established platelet marker; and (3) these indexes differentiate "high-risk" from "low-risk" subjects.
We performed a case-control study of 121 AF patients, 71 "disease control subjects," and 56 "healthy control subjects." Peripheral venous levels of platelet surface-expressed CD40L were analyzed by flow cytometry, while levels of sCD40L, pCD40L, and sP-selectin were measured by enzyme-linked immunosorbent assay.
AF patients had significantly higher sCD40L levels compared to healthy control subjects (p = 0.042), with no difference in platelet surface CD40L and pCD40L levels. A positive correlation was noted between levels of sCD40L and pCD40L, and not with sP-selectin. CD40L-related indexes failed to distinguish between high-risk and low-risk AF patients. AF patients receiving optimal antithrombotic therapy had significantly lower pCD40L levels (p < 0.001) compared to control subjects. Optimized AF management also resulted in significant reductions in the levels of sCD40L (p = 0.023) and pCD40L (p < 0.001).
CD40L-related indexes are not useful in the risk stratification of AF patients, and abnormal sCD40L levels can be reduced by intense multifactorial risk management. While there is a significant, albeit modest, excess of platelet activation in AF patients (as measured by sCD40L levels) compared to healthy control subjects, this is not in excess of that seen in patients with underlying cardiovascular diseases.
Surfactant dysfunction has been implicated in both lung cancer and COPD. This study evaluated the relationship between surfactant protein D (SP-D) and the progression of bronchial dysplasia in heavy smokers.
SP-D and oxidized glutathione levels were determined in samples of BAL fluid from 71 ex-smokers and current heavy smokers who participated in a lung cancer chemoprevention study with inhaled budesonide therapy. Bronchoscopy with biopsies was performed at baseline and was repeated at 6 months. The primary end point was the progression of bronchial dysplasia over 6 months.
Log-normalized SP-D levels in BAL fluid were significantly associated with the progression of bronchial dysplasia. A 1-U decrease in log-normalized SP-D levels at baseline was associated with a 3.2-fold increase (95% confidence interval, 1.24 to 8.26) in the risk for progression. Reduced FEV1 also predicted the progression of bronchial dysplasia (p < 0.05). Additional reductions in BAL fluid SP-D levels over the 6 months further increased the risk of progression (odds ratio, 1.76 for a 1-U decrease in log-normalized SP-D levels in BAL fluid; p = 0.023). Thirty-seven percent of the variation in SP-D levels in BAL fluid was related positively to the subject's FEV1/FVC ratio, and inversely to their plasma C-reactive protein levels and number of pack-years of smoking.
Reduced SP-D expression in BAL fluid was associated with the progression of bronchial dysplasia. SP-D levels in BAL fluid may serve as a potential biomarker to identify smokers who are at risk of early lung cancer.
This study aimed to assess the utility of sputum examinations and chest radiographs (CXRs) in patients with extrapulmonary tuberculosis (XPTB) to detect pulmonary involvement of tuberculosis (TB).
We studied 72 XPTB patients who were managed through the TB Program, King County, WA, from January 2003 through November 2004.
The two most common sites of XPTB were the lymph nodes (36 [50%]) and pleura (12 [17%]). Thirty-five of 72 XPTB patients (49%) had abnormal CXR findings. Sputum was not obtained from 15 patients despite sputum induction. Of the 57 patients from whom sputum was collected, 30 (53%) had abnormal CXR findings, 5 (9%) had sputum smears that were positive for acid-fast bacilli, and 12 (21%) had sputum cultures that were positive for Mycobacterium tuberculosis. Weight loss was significantly associated with positive sputum culture findings in a multivariate analysis (odds ratio, 4.3; 95% confidence interval, 1.01 to 18.72; p = 0.049). There was no significant difference in the occurrence of positive sputum culture results between patients with abnormal CXR findings and those with normal CXR findings (7 of 30 patients [23%] vs 5 of 27 patients [19%], respectively; p = 0.656). Of 24 HIV-negative XPTB patients with normal CXR findings, 2 patients (8%) had positive sputum culture findings.
CXR results did not reliably differentiate XPTB patients with and without positive sputum culture findings. Some XPTB patients had positive sputum culture results despite normal CXR findings and negative HIV status. Weight loss in XPTB patients was associated with positive sputum culture results. Sputum examinations in XPTB patients, regardless of the CXR results, may identify potentially infectious cases of TB.
A study was undertaken to identify and weigh at the time of hospital discharge simple clinical variables that could predict short-term outcomes in patients with pneumonia.
In a prospective observational cohort study of 870 patients discharged alive after hospitalization for pneumonia, we collected oxygenation and vital signs on discharge and assessed mortality and readmission within 30 days. From the β-parameter obtained in a multivariate Cox proportional hazard regression model, a score was assigned to each predictive variable. The effects of instability at discharge on outcomes within 30 days thereafter were examined by adjusted models with use of the pneumonia severity index at hospital admission, the length of stay, the Charlson comorbidity index, or the preillness functional status.
Four variables related to a 30-day mortality rate from all causes were identified in the multivariate model; these included one major criterion (temperature >37.5°C) and three minor criteria (systolic BP < 90 mm Hg or diastolic BP < 60 mm Hg, respiratory rate > 24 breaths/min, and oxygen saturation < 90%). The developed score remained significantly associated with a higher risk-adjusted rate of death. Patients with a score ≥ 2 (one major criterion or two minor criteria) had a sixfold-greater risk-adjusted hazard ratio (HR) of death (HR, 5.8; 95% confidence interval, 2.5 to 13.1).
Four criteria of instability on discharge seem to be related to the mortality rate after discharge, but each of the factors must be weighed differently. The resulting score is a simple alternative that can be used by clinicians in the discharge process.
To evaluate the pathologic patterns, clinical features, and survival among subjects with scleroderma (ie, systemic sclerosis [SSc]) and clinically significant interstitial lung disease (ILD) evaluated at an ILD center.
Retrospective cohort study of all SSc patients who had been referred for further evaluation of ILD and had undergone surgical lung biopsy. Clinical data were abstracted by review of the medical record, and lung biopsy specimens were reviewed and classified according to current pathologic criteria.
All patients presented with significant respiratory symptoms. Twenty-two of 27 subjects had surgical lung biopsy-proven ILD, and 5 subjects had miscellaneous non-ILD patterns. Of those subjects with ILD, 64% (14 of 22 subjects) had a nonspecific interstitial pneumonia (NSIP) pathologic pattern (fibrotic NSIP, 13 subjects; cellular NSIP, 1 subject), and 36% (8 of 22 subjects) had the usual interstitial pneumonia (UIP) pattern. Subjects with NSIP were younger (median age, 42 vs 58 years, respectively; p = 0.003), but no differences were noted in pulmonary physiology (FVC: NSIP group, 52% predicted; UIP group, 65% predicted; p = 0.22; diffusing capacity of the lung for carbon monoxide: NSIP group, 40% predicted; UIP group, 42% predicted; p = 1.0). All patients had limited skin involvement. The Scl-70 antibody was absent among those assessed (NSIP group, 0 of 10 subjects; UIP group, 0 of 7 subjects). All patients were treated with cytotoxic therapy. The median survival time for those with NSIP was 15.3 years (5,596 days) compared with 3 years (1,084 days) for those with UIP (p = 0.07 [log-rank test]).
In SSc patients with limited cutaneous disease and clinically significant ILD, fibrotic NSIP and UIP are the predominant pathologic patterns. Those with the UIP pattern of disease had a trend toward shorter survival time.
Methods: In this double-blind, placebo-controlled pilot study, 19 subjects with inoperable CTEPH were randomly assigned to sildenafil or placebo for 12 weeks. The primary end point was change in 6-min walking distance (6MWD). Secondary end points included changes in World Health Organization (WHO) class, cardiopulmonary hemodynamics, quality of life (QOL) scores, and N-terminal pro brain natriuretic peptide (NT-proBNP). All subjects were transferred to open-label sildenafil at the end of the study and offered repeat assessment at 12 months.
Results: There were no significant differences between the two groups with respect to change in exercise capacity. However significant improvements were seen in WHO class and pulmonary vascular resistance (PVR). Seventeen subjects were eligible for reassessment at 12 months and demonstrated significant improvements in 6MWD, activity and symptom components of QOL, cardiac index, PVR, and NT-proBNP.
Conclusions: Although this pilot study was insufficiently powered to test the primary end point, it did suggest beneficial effects in favor of sildenafil in several secondary end points at both 3 months and 12 months. Further larger-scale trials of sildenafil in inoperable CTEPH are required to confirm these findings and potentially increase the treatment options available for this devastating disease.
Trial registration: The study protocol was registered with the UK National Research Register database (publication ID N0542136603).
]]>Methods: We searched the medical literature to identify prospective trials reporting on VTE prevention (either mechanical or pharmacologic). The rates of VTE and bleeding were our primary end points and were pooled using a random-effects model.
Results: We identified 30 studies reporting on 7,779 patients. There were 18 randomized controlled trials and 12 cohort studies. The results of pooled relative risks (RRs) showed LMWH and intermittent compression devices (ICDs) to be effective in reducing the rate of deep vein thrombosis (LMWH: RR, 0.60; 95% confidence interval [CI], 0.44 to 0.81; ICD: RR, 0.41; 95% CI, 0.21 to 0.78). Similar results were seen when pooled rates from all 30 trials were analyzed. In head-to-head trials, there was no statistical difference in the rate of intracranial hemorrhage (ICH) between therapy with LMWH and nonpharmacologic methods (RR, 1.97; 95% CI, 0.64 to 6.09). The pooled rates of ICH and minor bleeding were generally higher with heparin therapy than with non–heparin-based prophylactic modalities.
Conclusions: In a mixed neurosurgical population, LMWH and ICDs are both effective in the prevention of VTE. Sensitivity analyses have suggested that isolated high-risk groups, such as those with patients undergoing craniotomy for neoplasm, may benefit from a combination of prophylactic methods, suggesting the need for a more individualized approach to these patients.
]]>Methods: A retrospective review was performed on 70 consecutive patients with suspected acute PE over a 10-year period (from 1997 to 2006) who had been referred for pulmonary angiography and/or intervention. The criteria for study inclusion were patients who received CDI due to angiographically confirmed massive PE and hemodynamic shock (shock index, ≥ 0.9). CDI involved suction embolectomy and fragmentation with or without catheter thrombolysis.
Results: Twelve patients were treated with CDI. There were seven men and five women (mean age, 56 years; age range, 21 to 80 years). Seven patients (58%) were referred for CDI after failing systemic infusion with 100 mg of tissue plasminogen activator, and five patients (42%) had contraindications to systemic thrombolysis. Catheter-directed fragmentation and embolectomy were performed in all patients (100%). Additionally, catheter-guided thrombolysis was performed in eight patients (67%). Technical success was achieved in 12 of 12 cases (100%). There were no major procedural complications (0%). Significant hemodynamic improvement (shock index, < 0.9) was observed in 10 of 12 cases (83%). The remaining two patients (17%) died secondary to cardiac arrest within 24 h. Ten of 12 patients (83%) survived and remained stable until hospital discharge (mean duration, 20 days; range, 3 to 51 days).
Conclusion: In the setting of hemodynamic shock from massive PE, CDI is potentially a life-saving treatment for patients who have not responded to or cannot tolerate systemic thrombolysis.
]]>Methods: Following a screening visit, subjects entered a run-in period in which they received regular ipratropium. At randomization, patients were assigned to either tiotropium plus formoterol or salmeterol plus fluticasone. After 6 weeks of treatment, a 12-h lung function profile was obtained. The coprimary end points were FEV1 area under the curve for the time period 0 to 12 h (AUC0–12) and peak FEV1.
Results: A total of 729 patients were screened, and 605 patients were randomized and treated. A total of 592 patients (baseline FEV1, 1.32 ± 0.43 L/min [±SD]) were included in the analysis. After 6 weeks, the 12-h lung function profiles in the group receiving tiotropium plus formoterol were superior to those in the group receiving salmeterol plus fluticasone (mean difference in FEV1 AUC0–12, 78 mL [p = 0.0006]; mean difference in FVC AUC0–12, 173 mL, p < 0.0001). Also, peak responses were in favor of tiotropium plus formoterol (difference in peak FEV1, 103 mL [p < 0.0001]; difference in peak FVC, 214 mL [p < 0.0001]), as were FEV1 and FVC at each individual time point after dose (p < 0.05). Predose FVC was significantly higher with the bronchodilator combination, while predose FEV1 and rescue medication use did not differ significantly between groups. Both treatments were well tolerated.
Conclusions: Tiotropium plus formoterol was superior in lung function over the day compared to salmeterol plus fluticasone in patients with moderate COPD. Long-term studies in patients with severe COPD are warranted to assess the relative efficacy of different treatment combinations.
Trial registration: Clinicaltrials.gov Identifier: NCT00239421.
]]>Methods: We examined 167 patients who had been admitted to the hospital for acute exacerbation, and we followed them up for 2 years. We measured plasma C-terminal (CT) proET-1 and mid-regional (MR) proADM on hospital admission, after 14 to 18 days, and after 6 months. In addition to plasma CT proET-1 and MR proADM, we assessed with Cox regression univariate and multivariate analyses the predictive value of clinical, functional, and laboratory parameters on 2-year survival. We analyzed the time to death by Kaplan-Meier curves.
Results: Compared to recovery and stable state, CT-proET-1 and MR-proADM were significantly increased on hospital admission (p < 0.001 and p = 0.002, respectively). MR-proADM, but not CT-proET-1, was associated with increased in-hospital mortality (p = 0.049) and independently predicted 2-year survival (p = 0.017). ProADM plasma levels > 0.84 nmol/L on hospital admission increased the mortality risk within 2 years from 13 to 32% (p = 0.004). By contrast, age (p = 0.779), Charlson comorbidity score (p = 0.971), body mass index (p = 0.802), FEV1 percent predicted (p = 0.741), PA
Conclusions: This study shows that plasma proADM but not plasma proET-1 on admission to the hospital for acute exacerbation independently predicts survival, thus suggesting that this biomarker could be used to predict prognosis in patients with COPD.
]]>Methods: Physical activities in daily life (activity monitoring), pulmonary function (spirometry), exercise capacity (incremental cycle-ergometer testing and 6-min walk distance testing), muscle force (quadriceps and handgrip force, and inspiratory and expiratory maximal pressures), quality of life (chronic respiratory disease questionnaire), and functional status (pulmonary functional status and dyspnea questionnaire-modified version) were assessed at baseline, after 3 months of a multidisciplinary rehabilitation program, and at the end of a 6-month multidisciplinary rehabilitation program in 29 patients (mean [± SD] age, 67 ± 8 years; FEV1, 46 ± 16% predicted).
Results: Exercise capacity, muscle force, quality of life, and functional status improved significantly after 3 months of pulmonary rehabilitation (all p < 0.05), with further improvements in muscle force, functional status, and quality of life at 6 months. Movement intensity during walking improved significantly after 3 months (p = 0.046) with further improvements after 6 months (p = 0.0002). Walking time in daily life did not improve significantly at 3 months (mean improvement, 7 ± 35%; p = 0.21), but only after 6 months (mean improvement, 20 ± 36%; p = 0.008). No significant changes occurred in other activities or in the pattern of the time spent walking in daily life. Changes in dyspnea after the program were significantly related to changes in walking time in daily life (r = 0.43; p = 0.02).
Conclusion: If one aims at changing physical activity habits in the daily life of COPD patients, the contribution of long-lasting programs might be important.
]]>Design: A retrospective, single-center, observational cohort study.
Setting: Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital.
Patients: Adult patients requiring hospitalization with microbiologically confirmed VAP attributed to PARGNB.
Interventions: Retrospective data collection from automated hospital, microbiology, and pharmacy databases.
Measurements and main results: Seventy-six patients with VAP attributed to PARGNB were identified over a 5-year period. Nineteen patients (25.0%) died during hospitalization. Patients receiving their first dose of appropriate antibiotic therapy within 24 h of BAL sampling had a statistically lower 30-day mortality rate compared to patients receiving the first dose of appropriate therapy >24 h after BAL (17.2% vs 50.0%; p = 0.005). VAP due to Acinetobacter species was most often initially treated with an inappropriate antibiotic regimen, followed by S maltophilia and P aeruginosa (66.7% vs 33.3% vs 17.2%; p = 0.017). Overall, total hospitalization costs were statistically similar in patients initially treated with an inappropriate antibiotic regimen compared to an appropriate regimen ($68,597 ± $55,466 vs $86,644 ± $64,433; p = 0.390).
Conclusions: These data suggest that inappropriate initial antibiotic therapy of microbiologically confirmed VAP attributed to PARGNB is associated with greater 30-day mortality. High rates of VAP attributed to antibiotic-resistant bacteria (eg, Acinetobacter species) may require changes in the local empiric antibiotic treatment of VAP in order to optimize the prescription of appropriate initial therapy.
]]>Methods: We performed a retrospective study on 403 consecutive patients with a tracheostomy who had been admitted to an acute care unit specializing in weaning from mechanical ventilation between July 1, 2002, and December 31, 2005. Bronchoscopy reports were reviewed for evidence of tracheostomy tube malposition (ie, > 50% occlusion of lumen by tissue). The main outcome parameters were the incidence of tracheostomy tube malposition; demographic, clinical, and tracheostomy-related factors associated with malposition; clinical response to correct the malposition; the duration of mechanical ventilation; the length of hospital stay; and mortality.
Results: Malpositioned tracheostomy tubes were identified in 40 of 403 patients (10%). The subspecialty of the surgical service physicians who performed the tracheostomy was most strongly associated with malposition. Thoracic and general surgeons were equally likely to have their patients associated with a malpositioned tracheostomy tube, while other subspecialty surgeons were more likely (odds ratio, 6.42; 95% confidence interval, 1.82 to 22.68; p = 0.004). Malpositioned tracheostomy tubes were changed in 80% of cases. Malposition was associated with prolonged mechanical ventilation posttracheostomy (median duration, 25 vs 15 d; p = 0.009), but not with increased hospital length of stay or mortality.
Conclusion: Tracheostomy tube malposition appears to be a common and important complication in patients who are being weaned from mechanical ventilation. Surgical expertise may be an important factor that impacts this complication.
]]>Methods: We undertook a cross-sectional comparison of scores from two cough-specific health-related quality of life (HRQoL) questionnaires, the Leicester Cough Questionnaire (LCQ), and the Cough Quality of Life Questionnaire (CQLQ), together with a generic HRQoL measure, the EuroQol. Questionnaires were administered to and spirometry performed on 147 outpatients with chronic cough (n = 83), COPD (n = 18), asthma (n = 20), and bronchiectasis (n = 26).
Results: There was no significant difference in the LCQ and CQLQ total scores between groups (p = 0.24 and p = 0.26, respectively). Exploratory analyses of questionnaire subdomains revealed differences in psychosocial issues and functional impairment between the four groups (p = 0.01 and p = 0.05, respectively). CQLQ scores indicated that chronic coughers have more psychosocial issues than patients with bronchiectasis (p = 0.03) but less functional impairment than COPD patients (p = 0.04). There was a significant difference in generic health status across the four disease groups (p = 0.04), with poorest health status in COPD patients. A significant inverse correlation was observed between CQLQ and LCQ in each disease group (chronic cough r = – 0.56, p < 0.001; COPD r = – 0.49, p = 0.04; asthma r = – 0.94, p < 0.001; and bronchiectasis r = – 0.88, p < 0.001). There was no correlation between cough questionnaire scores and FEV1 in any group, although a significant correlation between EuroQol visual analog scale component and FEV1 (r = 0.639, p = 0.004) was observed in COPD patients.
Conclusion: Cough adversely affects health status across a range of common respiratory diseases. The LCQ and CQLQ can each provide important additional information concerning the impact of cough.
]]>Methods: Parents of children newly referred for chronic cough completed three questionnaires (Spence anxiety scale; depression, anxiety, and stress 21-item scale [DASS]; and burden of cough questionnaire) at enrollment. The last 79 parents also completed these questionnaires at follow-up.
Results: Median age of the 190 children recruited was 2.6 years. The number of medical consultations for coughing illness in the last 12 months was high: > 80% of children had ≥ 5 doctor visits and 53% had > 10 visits. At presentation, burden scores correlated to parental DASS scores when their child was coughing. Stress was the largest contributor to parents’ emotional distress. Parental anxiety and depression scores were within published norms. Scores on all three DASS subscales reduced significantly when the children ceased coughing. At follow-up, the reduction in burden scores was significantly higher in the "ceased coughing" group (n = 49) compared to the "still coughing" group (n = 32).
Conclusions: Chronic cough in children is associated with a high burden of recurrent doctor visits, parental stress, and worries that resolve when cough ceases. Parents of children with chronic cough did not have above-average anxiety or depression levels. This study highlights the need to improve the management of children with chronic cough, including clinicians being cognizant of the emotional distress of the parents.
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