Significance of pulmonary arterial pressure and diffusion capacity of the lung as prognosticator in patients with idiopathic pulmonary fibrosis

STUDY OBJECTIVES: To evaluate the long-term clinical course of patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension. DESIGN: Prospective analysis of consecutive IPF patients undergoing initial workup with right-heart catheterization (RHC) and pulmonary function testing (PFT). Pulmonary arterial pressure (PAP) and diffusion capacity of the lung for carbon monoxide (Dlco) were focused on. SETTING: University hospital. PATIENTS: Seventy-eight patients with IPF (67 men, 11 women; diagnosis by pathology, n = 59; clinical diagnosis, n = 19) had been followed up after initial workup for a maximum of 14 years. MEASUREMENTS AND RESULTS: RHC data on 61 patients and PFT data on 52 patients were available. Five-year survival rates were 62.2% in the normal-PAP group (mean PAP < 17 mm Hg, n = 37) and 16.7% in the high-PAP group (mean PAP > 17 mm Hg, n = 24) [p < 0.001]; 70.4% in the preserved-Dlco group (percentage of predicted > 40%, n = 27) and 20.0% in the low-Dlco group (percentage of predicted < 40%, n = 25) [p < 0.001]; and 82.6% in group 1 (normal PAP and preserved Dlco, n = 23) and 15.6% in group 2 (high PAP, low Dlco, or both, n = 32) [p < 0.0001]. The relative risks of mortality within 5 years after RHC were 2.20 (95% confidence interval [CI], 1.40 to 3.45) in the high-PAP group, 2.70 (95% CI, 1.46 to 4.99) in the low-Dlco group, and 4.85 (95% CI, 1.97 to 11.97) in group 2. CONCLUSION: Dlco was a critical factor for evaluating disease status and prognosis, and PAP status provided feasible information in the initial workup of IPF patients.     

Intensive smoking cessation intervention reduces mortality in high-risk smokers with cardiovascular disease

PURPOSES: To compare an intensive smoking cessation intervention against usual care in hospitalized high-risk smokers with acute cardiovascular disease. METHODS: A total of 209 hospitalized smokers were randomized to the intensive intervention (n = 109) or to usual care (n = 100). Usual care consisted only of counseling and printed educational material provided prior to hospital discharge. Intensive treatment consisted of a minimum of 12 weeks of behavior modification counseling and individualized pharmacotherapy provided at no cost to the participant. Smoking status in all subjects was confirmed biochemically (ie, by measuring expired carbon monoxide) at 3, 6, 12, and 24 months after randomization. Outcomes included point prevalence and continuous abstinence smoking cessation rates, hospitalizations, and all-cause mortality. RESULTS: At each follow-up interval, point prevalence and continuous abstinence smoking cessation rates were significantly greater in the intensive-treatment group compared to the usual-care group. At 24 months, continuous abstinence smoking cessation rates were 33% in the intensive-treatment group and 9% in the usual-care group (p < 0.0001). Over the 2-year follow-up period, 41 patients in the usual-care group were hospitalized compared to 25 patients in the intensive-treatment group (relative risk reduction [RRR], 44%; 95% confidence interval [CI], 16 to 63%; p = 0.007). The all-cause mortality rate was 2.8% in the intensive-treatment group and 12.0% in the usual-care group (RRR, 77%; 95% CI, 27 to 93%; p = 0.014). The absolute risk reduction in mortality was 9.2% with a number needed to treat of 11. CONCLUSION: Hospitalized smokers, especially those with cardiovascular disease, should undergo treatment with a structured intensive cessation intervention. The duration of the initial treatment should be 3 months.     

A clinical model to estimate the pretest probability of lung cancer in patients with solitary pulmonary nodules

BACKGROUND: Estimating the clinical probability of malignancy in patients with a solitary pulmonary nodule (SPN) can facilitate the selection and interpretation of subsequent diagnostic tests. METHODS: We used multiple logistic regression analysis to identify independent clinical predictors of malignancy and to develop a parsimonious clinical prediction model to estimate the pretest probability of malignancy in a geographically diverse sample of 375 veterans with SPNs. We used data from Department of Veterans Affairs (VA) administrative databases and a recently completed VA Cooperative Study that evaluated the accuracy of positron emission tomography (PET) scans for the diagnosis of SPNs. RESULTS: The mean (+/- SD) age of subjects in the sample was 65.9 +/- 10.7 years. The prevalence of malignant SPNs was 54%. Most participants were either current smokers (n = 177) or former smokers (n = 177). Independent predictors of malignant SPNs included a positive smoking history (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.6 to 23.6), older age (OR, 2.2 per 10-year increment; 95% CI, 1.7 to 2.8), larger nodule diameter (OR, 1.1 per 1-mm increment; 95% CI, 1.1 to 1.2), and time since quitting smoking (OR, 0.6 per 10-year increment; 95% CI, 0.5 to 0.7). Model accuracy was very good (area under the curve of the receiver operating characteristic, 0.79; 95% CI, 0.74 to 0.84), and there was excellent agreement between the predicted probability and the observed frequency of malignant SPNs. CONCLUSIONS: Our prediction rule can be used to estimate the pretest probability of malignancy in patients with SPNs, and thereby facilitate clinical decision making when selecting and interpreting the results of diagnostic tests such as PET imaging.     

Racial differences in cancer risk among relatives of patients with early onset lung cancer

BACKGROUND: Relatives of patients with early onset lung cancer are at increased risk for lung cancer, and this risk varies by race. This study evaluates whether first-degree relatives of patients with early onset lung cancer are at increased risk for cancer at sites other than lung. METHODS: Family histories were ascertained from 673 lung cancer patients < 50 years of age identified from the Metropolitan Detroit Surveillance, Epidemiology and End Results program, and 773 age-, race-, and sex-matched control subjects were obtained via random-digit dialing. Data were collected for 3,556 case relatives (mothers, fathers, and siblings) and 3,943 control relatives, and unconditional logistic regression models using generalized estimating equations were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among case relatives, African Americans were 2.44-fold more likely to have head and neck cancers and 1.86-fold more likely to have any tobacco-related cancer compared to white case relatives (95% CI, 1.04 to 5.69% and 95% CI, 1.25 to 2.76, respectively). African-American case relatives were at increased risk for head and neck cancers (OR, 13.42; 95% CI, 1.65 to 109.01), all tobacco-related cancers (OR, 3.77; 95% CI, 2.16 to 6.55), tobacco-related cancers other than lung (OR, 4.10; 95% CI, 1.56 to 10.79), and cancer at any site (OR, 1.45, 95% CI, 1.04 to 2.02) compared to African-American control relatives. CONCLUSIONS: These results can be used to counsel family members of patients with early onset lung cancer, and suggest target populations for preventive strategies, including smoking cessation and appropriate screening.     

Prevalence and reversibility of pulmonary dysfunction in refractory systemic lupus: improvement correlates with disease remission following hematopoietic stem cell transplantation

AIM: To report the prevalence and reversibility of pulmonary function test (PFT) abnormalities among systemic lupus erythematosus (SLE) patients, refractory to therapy, undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Thirty-four SLE patients received 200 mg/kg cyclophosphamide and 90 mg/kg equine antithymocyte globulin followed by HSCT. PFTs were performed prior to, at 6 months, and yearly following HSCT. RESULTS: The prevalence of significant PFT abnormalities was high (97%). Low FEV(1) and FVC occurred in 26 of 34 patients (76%). A significant abnormality in diffusion capacity of the lung for carbon monoxide (Dlco) occurred in 26 of 32 individuals able to complete Dlco testing (81%). Dlco 18 months after HSCT. Five of 28 patients had a normal entry FVC; for each, the FVC remains normal. Of the 23 patients with an abnormal baseline FVC, 18 have improved, 15 completely and 3 partially. Eight of these 18 patients also have improved Dlco. The two patients with a diagnosis of SLS and one patient with SLE-related pulmonary hypertension improved in both parameters. Only 5 of 23 patients with an abnormal FVC did not improve. Each of these five patients retained active lupus in spite of HSCT. CONCLUSION: The prevalence of lung impairment among SLE patients requiring long-term immune suppression is high. Following HSCT, pulmonary impairments can improve, which is sustained if disease control is sustained.     

Effect of mycophenolate mofetil on pulmonary function in scleroderma-associated interstitial lung disease

OBJECTIVE: We sought to determine the effectiveness of mycophenolate mofetil (MMF) in scleroderma- associated interstitial lung disease (SSc-ILD). METHODS: We retrospectively identified patients who met criteria for systemic sclerosis, had evidence of SSc-ILD on chest CT, received > 1 g/d of MMF for >or= 6 months, and had pulmonary function data available. Vital capacity (VC) and diffusion capacity of the lung for carbon monoxide (Dlco) at treatment onset were compared with VC and Dlco values 12 months before and 12 months after treatment onset. Twelve-month values were imputed from regression lines generated using all VC and Dlco measurements made in the 24-month period either prior to or following treatment onset. RESULTS: Among 13 patients who met inclusion criteria, MMF was associated with a significant improvement in VC (mean, + 159 mL; confidence interval [CI], + 30 to + 289 mL; and + 4% of the predicted normal value; CI, + 2 to + 7%) after 12 months of treatment. In contrast, patients had a significant decrease in VC (mean, - 239 mL; CI, - 477 to - 0.5 mL; and - 5% of the predicted normal value; CI, - 11 to - 0.3%) in the 12 months prior to MMF treatment. Dlco did not change significantly during MMF treatment (mean, + 1% of the predicted normal value; CI, - 2 to + 5%) but decreased significantly in the 12 months prior to treatment (mean, - 5% of the predicted normal value; CI, - 10 to - 1%). CONCLUSION: These retrospective data suggest MMF improves VC in patients with SSc-ILD.     

Glutathione S-transferase P1 and lung function in patients with alpha1-antitrypsin deficiency and COPD

BACKGROUND: The glutathione S-transferase P1 (GSTP1) gene is involved in detoxification of electrophilic substances of tobacco smoke. A polymorphism at nucleotide 315 of this gene alters its enzymatic activity. OBJECTIVE: We analyzed the association between the variability in the GSTP1 gene and impairment in lung function in smokers with and without alpha(1)-antitrypsin (AAT) deficiency and COPD.Population and method: The study population consisted of 99 patients with smoking-related COPD and 69 patients with AAT deficiency; 198 healthy volunteers provided the frequency of the different polymorphisms in the general population. GSTP1 genotyping was performed by a real-time polymerase chain reaction amplification assay. RESULTS: The frequency (0.28) of the 105Val polymorphism was identical in COPD patients and the general population. However, the frequency was significantly increased (0.44) in patients with AAT deficiency (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.17 to 3.72 compared to control subjects; and OR, 2.41; 95% CI, 1.27 to 4.59 compared to COPD). FEV(1) percentage of predicted was significantly impaired in AAT-deficient carriers of 105Val. This effect was not observed in COPD patients. CONCLUSIONS: These findings suggest that the frequency of the GSTP1 105Val polymorphism is increased in patients with AAT deficiency. Globally, GSTP1 genotypes, age, and tobacco smoking explained 41% of total FEV(1) percentage of predicted variability in patients with AAT deficiency. The modulatory role of GSTP1 in lung disease has only been observed in smokers lacking AAT.     

Bone mineral density improvement after lung volume reduction surgery for severe emphysema

BACKGROUND: In patients with severe emphysema, bone mineral density (BMD) is reduced and the risk of osteoporosis is increased. STUDY OBJECTIVES: To identify the impact of lung volume reduction surgery on BMD. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS AND INTERVENTIONS: Forty emphysematous patients, all receiving oral steroid therapy, underwent bilateral lung volume reduction surgery. Thirty similar patients, who refused the operation, followed a standard respiratory rehabilitation program. MEASUREMENTS: All subjects were evaluated pretreatment and 12 months posttreatment for respiratory function, nutritional status, and bone-related biochemical parameters. BMD was assessed by dual-energy radiograph absorptiometry. RESULTS: After surgery, we observed significant improvements in respiratory function (FEV1, + 18.8% [p < 0.01]; residual volume [RV], -29.6% [p < 0.001]; diffusing capacity of the lung for carbon monoxide [Dlco], + 21.6% [p < 0.01]) nutritional parameters (fat-free mass, + 6.0% [p < 0.01]), levels of bone-related hormones (free-testosterone, + 20.5% [p < 0.01]; parathormone, -11.2% [p < 0.01]), bone turnover markers (osteocalcin, -12.7% [p < 0.05]; bone-alkaline-phosphatase, -14.0% [p < 0.05]; beta-crosslaps, -33.6% [p < 0.001]), BMD (lumbar, + 8.8% [p < 0.01]; femoral, + 5.5% [p < 0.01]), and T-score (lumbar, + 21.0% [p < 0.01]; femoral, + 12.4% [p < 0.01]) with reduction in osteoporosis rate (50 to 25%). Nineteen patients who had undergone surgery were able to discontinue treatment with oral steroids. These subjects showed a more significant improvement in BMD (lumbar, + 9.6%; femoral, + 6.8%; p < 0.001) and T-score (lumbar, + 27.3%; femoral, + 14.3%; p < 0.001). The remaining 21 patients who had undergone surgery experienced significant improvement compared to respiratory rehabilitation subjects despite continued therapy with oral steroids (BMD: lumbar, + 4.5% vs -0.7%, respectively [p < 0.01]; femoral, + 2.7% vs -1.1%, respectively [p < 0.05]; T-score: lumbar, + 14 vs -2.1, respectively [p < 0.01]; femoral, + 7.4 vs -2.7, respectively [p < 0.01]). The increase in lumbar BMD was correlated with the surgical reduction of RV (p = 0.02) and with the increase in Dlco (p = 0.01) and fat-free mass (p = 0.01). CONCLUSIONS: Lung volume reduction surgery significantly improves BMD compared to respiratory rehabilitation therapy, even in patients requiring oral steroids. The increase in BMD correlates with RV, Dlco, and fat-free mass, suggesting that the restoration of respiratory dynamics, gas exchange, and nutritional status induces improvement in bone metabolism and mineral content.     

Is the Mortality Higher in the Pulmonary vs the Extrapulmonary ARDS?: A Metaanalysis

BACKGROUND AND AIM: ARDS can occur from the following two pathogenetic pathways: a direct pulmonary injury (ARDSp); and an indirect injury (ARDSexp). The predisposing clinical factor can influence the pathogenesis and clinical outcome of ARDS. This metaanalysis was aimed at evaluating whether there is any difference in mortality between the two groups. METHODS: We searched the MEDLINE, EMBASE, and CINAHL databases for relevant studies published from 1987 to 2007, and included studies that have reported mortality in the two groups of ARDS. We calculated the odds ratio (OR) and 95% confidence interval (CI) to assess mortality in patients with ARDSp vs patients with ARDSexp and pooled the results using three different statistical models. RESULTS: Our search yielded 34 studies. In all, the studies involved 4,311 patients with 2,330 patients in the ARDSp group and 1,981 patients in the ARDSexp group. The OR of mortality in ARDSp group compared to the ARDSexp group was 1.11 (95% CI, 0.88 to 1.39), as determined by the random-effects model; 1.04 (95% CI, 0.92 to 1.18), as determined by the fixed-effects model; and 1.04 (95% CI, 0.92 to 1.18), as determined by the exact method, indicating that mortality is similar in the two groups. The mortality was no different whether the studies were classified as prospective (OR, 1.15; 95% CI, 0.87 to 1.51) or retrospective (OR, 1.01; 95% CI, 0.61 to 1.69); small (OR, 1.11; 95% CI, 0.77 to 1.60) or large (OR, 1.1; 95% CI, 0.82 to 1.49); or observational (OR, 1.10; 95% CI, 0.82 to 1.49) or interventional (OR, 0.97; 95% CI, 0.79 to 1.19). There was methodological and statistical heterogeneity (I(2), 50.9%; 95% CI, 21.3 to 66.2%; chi(2) statistic, 67.22; p = 0.0004). CONCLUSIONS: The results of this study suggest that there is no difference in mortality between these two groups. Further studies should focus on specific etiologies within the subgroups rather than focusing on the broader division of ARDSp and ARDSexp.     

Endoscopic ultrasound-guided fine-needle aspiration for non-small cell lung cancer staging: A systematic review and metaanalysis

BACKGROUND: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a minimally invasive alternative technique for mediastinal staging of non-small cell lung cancer. A metaanalysis was performed to estimate the diagnostic accuracy of EUS-FNA for staging mediastinal lymph nodes (N2/N3 disease) in patients with lung cancer. METHODS: Relevant studies were identified using Medline (1966 to November 2005), CINAHL, and citation indexing. Included studies used histology or adequate clinical follow-up (> 6 months) as the "gold standard," and provided sufficient data for calculating sensitivity and specificity. Summary receiver operating characteristic curves metaanalysis was performed to estimate the pooled sensitivity and specificity. RESULTS: In 18 eligible studies, EUS-FNA identified 83% of patients (95% confidence interval [CI], 78 to 87%) with positive mediastinal lymph nodes (pooled sensitivity) and 97% of patients (95% CI, 96 to 98%) with negative mediastinal lymph nodes (pooled specificity). In eight studies that were limited to patients who had abnormal mediastinal lymph nodes seen on CT scans, the sensitivity was 90% (95% CI, 84 to 94%) and the specificity was 97% (95% CI, 95 to 98%). In patients without abnormal mediastinal lymph nodes seen on CT scans (four studies), the pooled sensitivity was 58% (95% CI, 39 to 75%). Minor complications were reported in 10 cases (0.8%). There were no major complications. CONCLUSIONS: EUS-FNA is a safe modality for the invasive staging of lung cancer that is highly sensitive when used to confirm metastasis to mediastinal lymph nodes seen on CT scans. In addition, among lung cancer patients with normal mediastinal adenopathy seen on CT scans, despite lower sensitivity, it has the potential to prevent unnecessary surgery in a large proportion of cases missed by CT scanning.     

Timeliness of care in veterans with non-small cell lung cancer

BACKGROUND: Timeliness is an important dimension of quality of care for patients with lung cancer. METHODS: We reviewed the records of consecutive patients in whom non-small cell lung cancer (NSCLC) had been diagnosed between January 1, 2002, and December 31, 2003, at the Veterans Affairs Palo Alto Health Care System. We used multivariable statistical methods to identify independent predictors of timely care and examined the effect of timeliness on survival. RESULTS: We identified 129 veterans with NSCLC (mean age, 67 years; 98% men; 83% white), most of whom had adenocarcinoma (51%) or squamous cell carcinoma (30%). A minority of patients (18%) presented with a solitary pulmonary nodule (SPN). The median time from the initial suspicion of cancer to treatment was 84 days (interquartile range, 38 to 153 days). Independent predictors of treatment within 84 days included hospitalization within 7 days (odds ratio [OR], 8.2; 95% confidence interval [CI], 2.9 to 23), tumor size of > 3.0 cm (OR, 4.8; 95% CI, 1.8 to 12.4), the presence of additional chest radiographic abnormalities (OR, 3.0; 95% CI, 1.1 to 8.5), and the presence of one or more symptoms suggesting metastasis (OR, 2.6; 95% CI, 1.1 to 6.2). More timely care was not associated with better survival time (adjusted hazard ratio, 1.6; 95% CI, 1.3 to 1.9). However, in patients with SPNs, there was a trend toward better survival time when the time to treatment was < 84 days. CONCLUSIONS: The time to treatment for patients with NSCLC was often longer than recommended. Patients with larger tumors, symptoms, and other chest radiographic abnormalities receive more timely care. In patients with malignant SPNs, survival may be better when treatment is initiated promptly.     

A Registry-Based Randomized Trial Comparing Radial and Femoral Approaches in Women Undergoing Percutaneous Coronary Intervention: The SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women) Trial

ObjectivesThis study sought to determine the effect of radial access on outcomes in women undergoing percutaneous coronary intervention (PCI) using a registry-based randomized trial.BackgroundWomen are at increased risk of bleeding and vascular complications after PCI. The role of radial access in women is unclear.MethodsWomen undergoing cardiac catheterization or PCI were randomized to radial or femoral arterial access. Data from the CathPCI Registry and trial-specific data were merged into a final study database. The primary efficacy endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding or vascular complications requiring intervention. The primary feasibility endpoint was access site crossover. The primary analysis cohort was the subgroup undergoing PCI; sensitivity analyses were conducted in the total randomized population.ResultsThe trial was stopped early for a lower than expected event rate. A total of 1,787 women (691 undergoing PCI) were randomized at 60 sites. There was no significant difference in the primary efficacy endpoint between radial or femoral access among women undergoing PCI (radial 1.2% vs. 2.9% femoral, odds ratio [OR]: 0.39; 95% confidence interval [CI]: 0.12 to 1.27); among women undergoing cardiac catheterization or PCI, radial access significantly reduced bleeding and vascular complications (0.6% vs. 1.7%; OR: 0.32; 95% CI: 0.12 to 0.90). Access site crossover was significantly higher among women assigned to radial access (PCI cohort: 6.1% vs. 1.7%; OR: 3.65; 95% CI: 1.45 to 9.17); total randomized cohort: (6.7% vs. 1.9%; OR: 3.70; 95% CI: 2.14 to 6.40). More women preferred radial access.ConclusionsIn this pragmatic trial, which was terminated early, the radial approach did not significantly reduce bleeding or vascular complications in women undergoing PCI. Access site crossover occurred more often in women assigned to radial access. (SAFE-PCI for Women; NCT01406236)     

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.     

Chronic interstitial pneumonia in silicosis and mix-dust pneumoconiosis: its prevalence and comparison of CT findings with idiopathic pulmonary fibrosis

BACKGROUND: Increased prevalence of chronic interstitial pneumonia (CIP) is reported in dust-exposed subjects. We investigated the prevalence of CIP in silicosis and mixed-dust pneumoconiosis and sought morphologic differences of CIP between the pneumoconiosis and idiopathic pulmonary fibrosis (IPF). METHODS: We reviewed CT scans of 243 silicosis and mixed-dust pneumoconiosis patients to identify any cases of parenchymal lung lesions showing a CIP pattern, and compared the CT findings with those of 62 patients with IPF. Two observers independently scored CT images and classified the CT pattern as typical or not typical for IPF. Differences were sought between the groups using a nonparametric test, Fisher exact test, and a logistic regression analysis. A radiopathologic correlation was performed in 11 pneumoconiosis patients. RESULTS: Twenty-eight patients (11.5%) showed CIP on CT. Seven patients (25%) showed a pattern not typical of IPF, while the remaining patients showed a pattern typical of IPF, 11 of which were confirmed pathologically. The extent of fibrosis did not differ between the groups; however, patients with pneumoconiosis showed less traction bronchiectasis (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.08 to 0.48; p < 0.001), more subpleural homogeneous attenuation (OR, 2.56; 95% CI, 1.55 to 4.23; p < 0.001), and fibrosis was more randomly distributed (OR, 315.38; 95% CI, 4.68 to 21244.63; p = 0.007). Pathologically, subpleural homogeneous attenuation corresponded to dense fibrosis often with abundant silicotic nodules. CONCLUSIONS: Prevalence of CIP in pneumoconiosis was approximately 12% on CT. One fourth of patients showed an atypical IPF pattern, and the others showed a typical IPF pattern.     

Power spectral analysis of EEG activity during sleep in cigarette smokers

BACKGROUND: Research on the effects of cigarette smoking on sleep architecture is limited. The objective of this investigation was to examine differences in sleep EEG between smokers and nonsmokers. METHODS: Smokers and nonsmokers who were free of all medical comorbidities were matched on different factors, including age, gender, race, body mass index, and anthropometric measures. Home polysomnography was conducted using a standard recording montage. Sleep architecture was assessed using visual sleep-stage scoring. The discrete fast Fourier transform was used to calculate the EEG power spectrum for the entire night within contiguous 30-s epochs of sleep for the following frequency bandwidths: delta (0.8 to 4.0 Hz); theta (4.1 to 8.0 Hz); alpha (8.1 to 13.0 Hz); and beta (13.1 to 20.0 Hz). RESULTS: Conventional sleep stages were similar between the two groups. However, spectral analysis of the sleep EEG showed that, compared to nonsmokers, smokers had a lower percentage of EEG power in the delta-bandwidth (59.7% vs 62.6%, respectively; p < 0.04) and higher percentage of EEG power in alpha-bandwidth (15.6% vs 12.5%, respectively; p < 0.001). Differences in the EEG power spectrum between smokers and nonsmokers were greatest in the early part of the sleep period and decreased toward the end. Subjective complaints of lack of restful sleep were also more prevalent in smokers than in nonsmokers (22.5% vs 5.0%, respectively; p < 0.02) and were explained, in part, by the differences in EEG spectral power. CONCLUSIONS: Cigarette smokers manifest disturbances in the sleep EEG that are not evident in conventional measures of sleep architecture. Nicotine in cigarette smoke and withdrawal from it during sleep may contribute to these changes and the subjective experience of nonrestorative sleep.     

Granulocyte chemotactic activity in exhaled breath condensate of healthy subjects and patients with COPD

BACKGROUND: Several chemoattractants have been measured in exhaled breath condensate (EBC) from patients with COPD. The aim of this study was to compare the eosinophil and neutrophil chemotactic activity contained in EBC from healthy subjects and patients with COPD. METHODS: EBC collected using a commercially available condenser (EcoScreen; Erich Jaeger Viasys; Hoechberg, Germany) was compared in 45 COPD patients and 65 healthy subjects. EBC chemotactic activity for eosinophils and neutrophils was assessed using microchambers (Boyden; Neuro Probe; Cabin John, MD). Chemotactic index (CI) was used to evaluate cell migration. RESULTS: EBC from patients with COPD (CI, 2.21 +/- 0.16 [mean +/- SEM]) and healthy subjects (CI, 1.67 +/- 0.11) displayed significant neutrophil chemotactic activity (p < 0.0001 for both), which was however higher in patients with COPD (p < 0.001). Healthy smokers had a significantly raised CI for neutrophils by comparison with healthy nonsmokers (p < 0.01) and ex-smokers (p < 0.05). Likewise, current COPD smokers tended to have greater neutrophil CI than COPD who stopped smoking (p = 0.08). COPD ex-smokers had raised chemotactic activity by comparison with healthy ex-smokers (p < 0.05). Anti-interleukin-8 (10(-6) g/mL) antibodies reduced neutrophil chemotactic activity by 35.2% (p < 0.05). EBC also contained significant eosinophil chemotactic activity in healthy subjects (CI, 1.68 +/- 0.09; p < 0.0001) and patients with COPD (CI, 1.23 +/- 0.07; p < 0.01), with a significantly lower CI in patients with COPD as compared to healthy subjects (p < 0.001). Smoking did not influence eosinophil chemotactic activity in healthy subjects or patients with COPD. CONCLUSIONS: Current smoking favors neutrophil chemotactic activity. As compared to healthy subjects, EBC from patients with COPD displays a skewed chemotactic activity toward neutrophils vs eosinophils.     

Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients

BACKGROUND: Transfusion has long been identified as a risk factor for acute lung injury (ALI)/ARDS. No study has formally evaluated the transfusion of specific blood products as a risk factor for ALI/ARDS in critically ill medical patients. METHOD: In this single-center retrospective cohort study, 841 consecutive critically ill patients were studied for the development of ALI/ARDS. Patients who received blood product transfusions were compared with those who did not, in univariate and multivariate propensity analyses. RESULTS: Two hundred ninety-eight patients (35%) received blood transfusions. Transfused patients were older (mean [+/- SD] age, 67 +/- 17 years vs 62 +/- 19 years; p < 0.001) and had higher acute physiologic and chronic health evaluation (APACHE) III scores (74 +/- 32 vs 58 +/- 23; p < 0.001) than those who had not received transfusions. ALI/ARDS developed more commonly (25% vs 18%; p = 0.025) in patients exposed to transfusion. Seventeen patients received massive RBC transfusions (ie, > 10 U of blood transfused within 24 h), of whom 13 also received fresh-frozen plasma (FFP) and 11 received platelet transfusions. When adjusted for the probability of transfusion and other ALI/ARDS risk factors, any transfusion was associated with the development of ALI/ARDS (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.24 to 3.75). Among those patients receiving individual blood products, ALI/ARDS was more likely to develop in patients who received FFP transfusions (OR, 2.48; 95% CI, 1.29 to 4.74) and platelet transfusions (OR, 3.89; 95% CI, 1.36 to 11.52) than in those who received only RBC transfusions (OR, 1.39; 95% CI, 0.79 to 2.43). CONCLUSION: Transfusion is associated with an increased risk of the development of ALI/ARDS in critically ill medical patients. The risk is higher with transfusions of plasma-rich blood products, FFP, and platelets, than with RBCs.     

Lung CT densitometry in systemic sclerosis: correlation with lung function, exercise testing, and quality of life

BACKGROUND: To ascertain if analysis of lung density histograms in thin-section CT was more reproducible than visual assessment of lung changes in systemic sclerosis (SSc), and if such density histogram parameters as mean lung attenuation (MLA), skewness, and kurtosis could more closely reflect pulmonary function as well as exercise and quality of life impairment. METHODS: The intraoperator and interoperator reproducibility of visual and densitometric lung CT analysis in 48 SSc patients examined with CT were evaluated by means of weighted kappa statistics. Univariate and multivariate regression analyses were applied to evaluate the relationship of visual and densitometric CT measurements with functional parameters including functional residual capacity (FRC), FVC, FEV(1), diffusion capacity of the lung for carbon monoxide (Dlco), 6-min walking testing (6MWT), and health-related quality of life questionnaire (QLQ) parameters. RESULTS: The intraoperator and interoperator reproducibility of MLA (intraobserver weighted kappa = 0.97; interobserver weighted kappa = 0.96), skewness (intraobserver weighted kappa = 0.89; interobserver weighted kappa = 0.88), and kurtosis (intraobserver weighted kappa = 0.89; interobserver weighted kappa = 0.88) were higher than those of visual assessment (intraobserver weighted kappa = 0.71; interobserver weighted kappa = 0.69). In univariate analysis, only densitometric measurements were correlated with some exercise and QLQ parameters. In multivariate analysis, MLA (square regression coefficient corrected [R(2)c] = 0.70), skewness (R(2)c = 0.78), and kurtosis (R(2)c = 0.77) were predicted by FRC, FVC, Dlco, 6MWT, and QLQ parameters, while visual assessment was associated only with FRC and FVC (R(2)c = 0.40). CONCLUSIONS: In SSc, densitometric analysis is more reproducible than visual assessment of lung changes in thin-section CT and more closely correlated to pulmonary function testing, 6MWT, and QLQ. Density histogram parameters may be useful for cross-sectional and longitudinal studies of lung involvement in SSc.     

Falsely elevated international normalized ratio values in patients undergoing anticoagulation therapy: a descriptive evaluation

BACKGROUND: Elevated international normalized ratio (INR) values have been linked to bleeding complications; however, elevated INR values are not always physiologic and can be falsely increased. This study describes the rate of falsely elevated INRs and characteristics predictive of falsely elevated INRs. METHODS: This cross-sectional study was conducted among adult patients receiving anticoagulation therapy monitored by a centralized anticoagulation service during January 2000 through December 2004 (n = 29,536). Prevalence rates of all elevated (ie, value >/= 10), falsely elevated, and truly elevated INRs were calculated. Multivariate logistic regression was performed to identify predictors of falsely elevated INRs among elevated INRs. RESULTS: Of the 556,998 INRs included in the analysis, 793 INRs (prevalence, 0.14%; 95% confidence interval [CI], 0.10 to 0.19%), 53 INRs (prevalence, 0.01%; 95% CI, < 0.01 to 0.03%), and 740 INRs (prevalence, 0.13%; 95% CI, 0.09 to 0.18%) were elevated, falsely elevated, and truly elevated, respectively. The strongest independent predictor of a falsely elevated INR was a patient undergoing hemodialysis at the time of the elevated INR (adjusted odds ratio, 9.60; 95% CI, 4.96 to 18.58; p < 0.001). A low target INR was the only other factor found to be an independent predictor of a falsely elevated INR. CONCLUSIONS: Although INR values >/= 10.0 occur infrequently, patients presenting with such values can present a challenge to the anticoagulation provider. Anticoagulation providers should be particularly vigilant for falsely elevated INRs when monitoring patients undergoing hemodialysis.     

The presence of pneumococcal bacteremia does not influence clinical outcomes in patients with community-acquired pneumonia: results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort study

BACKGROUND: It remains unknown whether pneumococcal bacteremia increases the risk of poor outcomes in hospitalized patients with community-acquired pneumonia (CAP). The objective of this study was to investigate whether the presence of pneumococcal bacteremia influences the clinical outcomes of hospitalized patients with CAP. METHODS: We performed secondary analyses of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP and pneumococcal bacteremia, and patients with CAP and negative blood culture findings. To identify the effect of pneumococcal bacteremia on patient outcomes, we modeled all-cause mortality and CAP-related mortality using logistic regression analysis, and time to clinical stability and length of hospital stay using Cox proportional hazards models. RESULTS: We studied 125 subjects with pneumococcal bacteremic CAP and 1,847 subjects with nonbacteremic CAP. The multivariable regression analysis revealed a lack of association of pneumococcal bacteremic CAP and time to clinical stability (hazard ratio, 0.87; 95% confidence interval [CI], 0.7 to 1.1; p = 0.25), length of hospital stay (hazard ratio, 1.14; 95% CI, 0.91 to 1.43; p = 0.25), all-cause mortality (odds ratio [OR], 0.68; 95% CI, 0.36 to 1.3; p = 0.25), and CAP-related mortality (OR, 0.86; 95% CI, 0.35 to 2.06; p = 0.73). CONCLUSIONS: Pneumococcal bacteremia does not increase the risk of poor outcomes in patients with CAP. Factors related to severity of disease are confounders of the association between pneumococcal bacteremia and poor outcomes. This study indicates that the presence of pneumococcal bacteremia by itself should not be a contraindication for deescalation of therapy in clinically stable hospitalized patients with CAP.