FEV1 performance among patients with acute asthma: results from a multicenter clinical trial

OBJECTIVE: To determine the ability of patients seen for acute asthma exacerbations in the emergency department (ED) to perform good-quality FEV(1) measurements. METHODS: Investigators from 20 EDs were trained to perform spirometry testing as part of a clinical trial that included standardized equipment with special software-directed prompts. Spirometry was done on ED arrival and 30 min, 1 h, 2 h, and 4 h later, and during follow-up outpatient visits. MEASUREMENTS: Study performance criteria differed from American Thoracic Society (ATS) guidelines because of the population acuity and severity of illness as follows: ability to obtain acceptable FEV(1) measures (defined as two or more efforts with forced expiratory times >/= 2 s and time to peak flow < 120 ms or back-extrapolated volume < 5% of the FVC) and reproducibility criteria (two highest acceptable FEV(1) values within 10% of each other). RESULTS: Of the 620 patients (age range, 12 to 65 years), > 90% met study acceptability criteria on ED arrival and 74% met study reproducibility criteria. Mean initial FEV(1) was 38% of predicted. Spirometry quality improved over time; by 1 h, 90% of patients met study acceptability and reproducibility criteria. Patients with severe airway obstruction (FEV(1) < 25% of predicted) were initially less likely to meet quality goals, but this improved with time. The site was also an independent predictor of quality. CONCLUSION: When staff are well trained and prompt feedback regarding adequacy of efforts is given, modified ATS performance goals for FEV(1) tests can be met from most acutely ill adolescent and adult asthmatics, even within the first hour of evaluation and treatment for an asthma exacerbation.     

Cardiac involvement in patients with sarcoidosis: diagnostic and prognostic value of outpatient testing

BACKGROUND: Cardiac sarcoidosis (CS) causes substantial morbidity and sudden death. Early diagnosis and risk stratification are warranted. METHODS: Ambulatory patients with sarcoidosis were interviewed to determine whether they experienced palpitations, syncope, or presyncope, and were evaluated with ECG, Holter monitoring, and echocardiography (transthoracic echocardiogram [TTE]). Those with symptoms or abnormal results were studied with cardiac MRI (CMRI) or positron emission tomography (PET) scanning. The diagnosis of CS was based on abnormalities detected by these imaging studies. Patients with CS were referred for risk stratification by electrophysiology study (EPS). RESULTS: Among the 62 patients evaluated, the prevalence of CS was 39%. Patients with CS had more cardiac symptoms than those without CS (46% vs 5%, respectively; p < 0.001), and were more likely to have abnormal Holter monitoring findings (50% vs 3%, respectively; p < 0.001) and TTE findings (25% vs 5%, respectively; p = 0.02). The degree of pulmonary impairment did not predict CS. Two of the 17 patients who underwent EPS had abnormal test findings and received implantable cardioverter-defibrillators. No patients died, had ventricular arrhythmias that triggered defibrillator therapy, or had heart failure develop during almost 2 years of follow-up. This diagnostic approach was more sensitive than the established criteria for identifying CS. CONCLUSION: CS is common among patients with sarcoidosis. A structured clinical assessment incorporating advanced cardiac imaging with PET scanning or CMRI is more sensitive than the established criteria for the identification of CS. Sarcoidal lesions seen on CMRI or PET scanning do not predict arrhythmias in ambulatory patients with preserved cardiac function, who appear to be at low risk for short-term mortality.     

Clinical utility of the QuantiFERON TB-2G test for elderly patients with active tuberculosis

OBJECTIVE: To evaluate the response to the QuantiFERON-TB-2 Gold (QFT-2G) test (Cellestis Ltd; Carnegie, VIC, Australia) in elderly patients with active tuberculosis (TB) to determine whether the QFT-2G test might be a feasible method for diagnosing TB infection in this group of patients. METHODS: The subjects were 30 elderly patients with active TB and 100 younger patients with active TB. The QFT-2G test results were analyzed in relation to combined and separate responses to early secretory antigenic target 6-kD (ESAT-6) protein and culture filtrate protein 10 (CFP-10) antigens. RESULTS: Of the 30 elderly patients with active TB, 27% had a positive tuberculin skin test (TST) result and 77% had a positive QFT-2G test result. Of the 100 younger patients with active TB, 70% had a positive TST result and 87% had a positive QFT-2G test result. Although there was no significant difference between the two patient groups in the positive rate for the QFT-2G test results (p = 0.185), there was a significant difference in the rates of positive TST results between the elderly and younger patients (p = 0.012). The positive test result rate for both ESAT-6 and CFP-10 antigens in the elderly patients (17%) was significantly lower than that in younger patients (37%; p = 0.038). There was an indeterminate result for the QFT-2G test in five elderly patients, and this might have been related to the presence of lymphocytopenia due to underlying disease. A negative result on the QFT-2G test was detected in two elderly patients, and this might have been related to the severity of the active TB. CONCLUSION: We confirmed that the QFT-2G test might be a more useful method of diagnosing TB infection than the TST for elderly patients if peripheral lymphocyte counts have been preserved.     

Health-related quality of life trajectories among adults with tuberculosis: differences between latent and active infection

BACKGROUND: Tuberculosis (TB) remains a public health threat with significant annual impacts on morbidity and mortality. However, few studies have examined the impact of active and latent TB infection (LTBI) on health-related quality of life (HRQL). METHODS: Patients with recently diagnosed active TB or LTBI patients were administered the Short Form-36 (SF-36) and the Beck depression inventory (DI) at baseline, 3 months, and 6 months. Mixed-effect linear regression was used to compare the trajectory of HRQL over time in the two patient groups after adjusting for potential confounders. Ordinal logistic regression was used to determine the relationship between changes in HRQL of at least the minimal important difference. RESULTS: One hundred four active TB and 102 LTBI patients participated. At baseline, participants with active TB had significantly lower SF-36 mean domain and component scores (4 to 12 points lower, p < 0.03) and higher mean Beck DI scores (4 points higher, p < 0.0001) when compared to LBTI participants. In the responder analysis, those with active TB were associated with reporting improved scores at 6 months of at least the minimal important difference in vitality (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.3 to 5.6), role physical (OR, 3.1; 95% CI, 1.4 to 6.5), mental component score (OR, 3.2; 95% CI, 1.5 to 6.9), social functioning (OR, 11.1; 95% CI, 3.8 to 33), and role emotional (OR, 2.7; 95% CI, 1.2 to 6.0). CONCLUSIONS: Active TB patients had large improvements in most HRQL domains by 6 months. However, when compared to LTBI participants and US norms, HRQL was still low at completion of therapy.     

Pleural tuberculosis in the United States: incidence and drug resistance

BACKGROUND: Pleural tuberculosis (TB) should be considered in any patient with a lymphocytic pleural effusion. The diagnostic approach is under debate. Knowledge of pleural TB epidemiology would be beneficial. To help clarify pleural TB epidemiology, we analyzed US national TB surveillance data for 1993 to 2003. METHODS: We compared pleural TB to pulmonary TB (where each was reported as the major site of TB disease, and no additional sites of disease were reported). Applicable statistical tests were performed; p < 0.05 was considered to be significant. RESULTS: From 1993 through 2003, 7,549 cases of pleural TB and 156,779 cases of pulmonary TB were reported (in 2003: pleural TB, 536 cases; pulmonary TB, 10,551 cases). The annual proportion of pleural TB was relatively stable (median rate, 3.6%; range, 3.3 to 4.0%) compared to that for pulmonary TB, which steadily decreased (average annual decrease, 0.9%; p < 0.01). Pleural TB occurred significantly more often than pulmonary TB among persons >/= 65 years old (30.4% vs 23.3%, respectively; p < 0.01), and it occurred significantly less often among children < 15 years old (1.8% vs 6.1%, respectively; p < 0.01) and persons 45 to 64 years old (22.9% vs 27.9%, respectively; p < 0.01). Pleural TB patients (63.4%) were born slightly more often in the United States than were pulmonary TB patients (60.9%; p < 0.01). Drug-resistance patterns of pleural TB broadly reflected those of pulmonary TB. However, isolates from pleural TB patients were less often resistant to at least isoniazid (6.0% vs 7.8%, respectively; p < 0.01) and to at least one first-line TB drug (9.9% vs 11.9%, respectively; p < 0.01) compared with pulmonary TB patients. CONCLUSIONS: Knowledge of pleural TB demographic, clinical, and drug-resistance patterns may assist clinicians in making diagnostic and therapeutic decisions.     

Clinical outcome of patients with upper-extremity deep vein thrombosis: results from the RIETE Registry

BACKGROUND: There is little information on the clinical outcome of patients with upper-extremity deep vein thrombosis (DVT). METHODS: RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute DVT or pulmonary embolism (PE). In this analysis, we analyzed the demographic characteristics, treatment, and 3-month outcome of all patients with DVT in the arm. RESULTS: Of the 11,564 DVT patients enrolled, 512 patients (4.4%) had arm DVT. They presented less often with clinically overt PE (9.0% vs 29%; odds ratio, 0.24; 95% confidence interval [CI], 0.18 to 0.33) than those with lower-limb DVT, but their 3-month outcome was similar. Of the 512 patients with arm DVT, 196 patients (38%) had cancer and 228 patients (45%) had catheter-related DVT. During follow-up, those with cancer DVT had an increased incidence of major bleeding (4.1% vs 0.9%; odds ratio, 4.4; 95% CI, 1.2 to 21), recurrent venous thromboembolism (6.1% vs 2.8%; odds ratio, 2.2; 95% CI, 0.91 to 5.6; p = 0.04), and death (22% vs 3.5%; odds ratio, 7.8; 95% CI, 4.0 to 16). Thirty patients had the composite event of recurrent DVT, symptomatic PE, or major bleeding. They were significantly older, more often had cancer, and presented more frequently with symptomatic PE on hospital admission. On multivariate analysis, only cancer patients with arm DVT had an increased risk for the composite event (odds ratio, 3.0; 95% CI, 1.4 to 6.4). CONCLUSIONS: At presentation, patients with arm DVT have less often clinically overt PE than those with lower-limb DVT, but their 3-month outcome is similar. Among patients with arm DVT, those with cancer have the worse outcome.     

Detailed analysis of the radiographic presentation of Mycobacterium kansasii lung disease in patients with HIV infection

BACKGROUND: Published criteria for the diagnosis of Mycobacterium kansasii lung disease require the presence of clinical symptoms, positive microbiologic results, and radiographic abnormalities. In patients with HIV infection, the radiographic findings of M kansasii lung disease are not well described. METHODS: Medical records and chest radiographs of all patients with HIV infection and at least one respiratory specimen culture positive for M kansasii at San Francisco General Hospital between December 1989 and July 2002 were reviewed. RESULTS: Chest radiographic results were abnormal in 75 of 83 patients (90%) included in the study. Radiographic abnormalities were diverse, with consolidation (66%) and nodules (42%) as the most frequent findings. The mid or lower lung zones were involved in 89% of patients. The pattern of radiographic abnormalities did not differ based on acid-fast bacilli smear status, the presence or absence of coexisting pulmonary infections, or CD4+ T-lymphocyte count. In multivariate Cox regression analysis, cavitation was the only radiographic abnormality independently associated with mortality (hazard ratio, 4.8; 95% confidence interval, 1.2 to 19.6). CONCLUSION: Patients with HIV infection and M kansasii lung disease present with diverse radiographic patterns, most commonly consolidation and nodules predominantly located in the mid and lower lung zones. This finding is in contrast to the upper-lobe cavitary presentation described in patients without HIV infection. Although rare, the presence of cavitary disease in patients with HIV infection and M kansasii independently predicts worse outcome. The diversity in the radiographic presentation of M kansasii lung disease implies that clinicians should obtain sputum mycobacterial culture samples from any patient with HIV infection and an abnormal chest radiograph finding.     

Risk of progression to active tuberculosis among foreign-born persons with latent tuberculosis

BACKGROUND: Increased risk for tuberculosis (TB) disease has been identified in foreign-born persons in the United States, particularly during the first 5 years after their arrival in the United States. This could be explained by undetected TB disease at entry, increased prevalence of latent TB infection (LTBI), increased progression from LTBI to TB, or a combination of these factors. METHODS: We performed a cluster analysis of TB cases in Boston and a case-control study of risk factors for TB with an unclustered isolate among Boston residents with LTBI to determine whether such persons have an increased risk for reactivation of disease. RESULTS: Of 321 case patients with TB seen between 1996 and 2000, 133 isolates were clustered and 188 were not. In multivariate analysis, foreign birth was associated with an unclustered isolate (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2 to 3.8; p < 0.01), while being a close contact of a TB case was negatively associated (OR, 0.22; 95% CI, 0.07 to 0.73; p = 0.02). When 188 TB patients with unclustered isolates were compared to 188 age-matched control subjects with LTBI, there was no association between the occurrence of TB and foreign birth (OR, 0.71; 95% CI, 0.42 to 1.3); among foreign-born persons, there was no association between the occurrence of TB and being in the United States 相似文献   

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.     

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.     

Diagnosing tuberculosis infection in the 21st century: new tools to tackle an old enemy

The century-old tuberculin skin test (TST) was until recently the only means of diagnosing latent tuberculosis infection (LTBI). Recent advances in mycobacterial genomics and human cellular immunology have resulted in two new blood tests that detect tuberculosis infection by measuring in vitro T-cell interferon (IFN)-gamma release in response to two unique antigens that are highly specific for Mycobacterium tuberculosis but absent from bacille Calmette-Guérin (BCG) vaccine and most nontuberculous mycobacteria. One assay, the enzyme-linked immunospot (ELISpot) [T-SPOT.TB; Oxford Immunotec; Oxford, UK] enumerates IFN-gamma-secreting T cells, while the other assay measures IFN-gamma concentration in supernatant by enzyme-linked immunosorbent assay (ELISA) [QuantiFERON-TB Gold; Cellestis; Carnegie, Australia]. A large and growing clinical evidence base indicates that both tests are more specific than the skin test because they are not confounded by prior BCG vaccination. In active tuberculosis, ELISA has similar sensitivity to the skin test, while ELISpot is significantly more sensitive. Current cross-sectional evidence suggests that for diagnosis of LTBI, sensitivity of ELISA is similar to TST, while ELISpot appears more sensitive. High specificity will enable clinicians to avoid unnecessary preventive treatment in BCG-vaccinated persons without infection who commonly have false-positive TST results. High sensitivity could enable accurate targeting of preventive treatment to patients with infection at the highest risk of progression to active tuberculosis who frequently have false-negative TST results due to impaired cellular immunity. However, longitudinal studies are needed to define the predictive value of positive blood test results for progression to tuberculosis.     

Cytokine and chemokine expression profiles in response to Mycobacterium tuberculosis stimulation are altered in HIV-infected compared to HIV-uninfected subjects with active tuberculosis

Mycobacterium tuberculosis (Mtb) infects nearly 2 million people annually and is the most common cause of death in HIV-infected individuals. Tuberculosis (TB) diagnostics cater to HIV-uninfected individuals in non-endemic countries, are expensive, slow, and lack sensitivity for those most affected. Patterns of soluble immune markers from Mtb-stimulated immune cells are not well defined in HIV co-infection. We assessed immune differences between HIV-infected and HIV-uninfected individuals with active TB utilizing IFNγ-based QuantiFERON^®-TB Gold In-Tube (QFT) testing in Nairobi, Kenya. Excess QFT supernatants were used to measure cytokine and chemokine responses by a 17-plex bead array. Mtb/HIV co-infected participants were significantly less likely to be QFT+ (47.2% versus 84.2% in the HIV-uninfected group), and demonstrated lower expression of all cytokines except for IFNα2. Receiver operator characteristic analyses identified IL-1α as a potential marker of co-infection. Among HIV-infected individuals, CD4+ T cell count correlated weakly with the expression of several analytes. Co-expression analysis highlighted differences in immune profiles between the groups. These data suggest that there is a unique and detectable Mtb-specific immune response in co-infection. A better understanding of Mtb immunology can translate into much needed immunodiagnostics with enhanced sensitivity in HIV-infected individuals, facilitating their opportunity to obtain live-saving treatment.