Noah Lechtzin

Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis

CONTEXTnThe prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the respiratory tract of individuals with cystic fibrosis (CF) has increased dramatically; however, its impact on outcomes in CF is unclear. Because the time between infection with bacteria in CF and death can be decades, observational studies with long periods of follow-up are well suited to address the current gap in knowledge.nnnOBJECTIVEnTo determine whether isolation of MRSA from the respiratory tract of CF patients is associated with worse survival compared with patients who never have a culture positive for MRSA.nnnDESIGN, SETTING, AND PARTICIPANTSnCohort study of 19,833 CF patients aged 6 to 45 years seen at centers accredited by the Cystic Fibrosis Foundation in the United States. Patients entered between January 1996 and December 2006 and were followed up through December 2008. Cox regression models with time-varying covariates were used to compare survival between CF patients with and without respiratory tract MRSA.nnnMAIN OUTCOME MEASUREnTime from age at entry until age at death from any cause.nnnRESULTSnIn 137,819 patient-years of observation (median, 7.3 years/patient), 2537 CF patients died and 5759 patients had MRSA detected. The mortality rate was 18.3 deaths (95% confidence interval [CI], 17.5-19.1) per 1000 patient-years in patients without MRSA and 27.7 deaths (95% CI, 25.3-30.4) per 1000 patient-years in those with MRSA. Among those with MRSA, the attributable risk percentage of death associated with MRSA was 34.0% (95% CI, 26.7%-40.4%). The unadjusted hazard ratio associated with MRSA was 1.47 (95% CI, 1.32-1.62). After adjustment for time-varying covariates associated with severity of illness, MRSA remained associated with a higher risk of death (1.27; 95% CI, 1.11-1.45).nnnCONCLUSIONnDetection of MRSA in the respiratory tract of CF patients was associated with worse survival.

Persistent methicillin-resistant Staphylococcus aureus and rate of FEV1 decline in cystic fibrosis.

RATIONALEnThe prevalence in cystic fibrosis (CF) of respiratory cultures with methicillin-resistant Staphylococcus aureus (MRSA) has dramatically increased over the last 10 years, but the effect of MRSA on FEV(1) decline in CF is unknown.nnnOBJECTIVESnTo determine the association between MRSA respiratory infection and FEV(1) decline in children and adults with CF.nnnMETHODSnThis was a 10-year cohort study using the Cystic Fibrosis Foundation patient registry from 1996-2005. We studied individuals who developed new MRSA respiratory tract infection. Repeated-measures regression was used to assess the association between MRSA and FEV(1) decline, adjusted for confounders, in individuals aged 8-21 years and adults (aged 22-45 yr). Two different statistical models were used to assess robustness of results.nnnMEASUREMENTS AND MAIN RESULTSnThe study cohort included 17,357 patients with an average follow-up of 5.3 years. During the study period, 1,732 individuals developed new persistent MRSA infection (> or =3 MRSA cultures; average, 6.8 positive cultures) and were subsequently followed for an average of 3.5 years. Even after adjustment for confounders, rate of FEV(1) decline in individuals aged 8-21 years with persistent MRSA was more rapid in both statistical models. Their average FEV(1) decline of 2.06% predicted/year was 43% more rapid than the 1.44% predicted/year in those without MRSA (difference, -0.62% predicted/yr; 95% confidence interval, -0.70 to -0.54; P < 0.001). Effect of MRSA on FEV(1) decline in adults was not clinically significant.nnnCONCLUSIONSnPersistent infection with MRSA in individuals with CF between the ages of 8 and 21 years is associated with a more rapid rate of decline in lung function.

Vancomycin-Resistant and Vancomycin-Susceptible Enterococcal Bacteremia: Comparison of Clinical Features and Outcomes

Vancomycin-resistant Enterococcus (VRE) is a major nosocomial pathogen. We collected clinical and laboratory data on 93 hospitalized adults with VRE bacteremia and 101 adults with vancomycin-susceptible enterococcal (VSE) bacteremia. Risk factors for VRE bacteremia included central venous catheterization, hyperalimentation, and prolonged hospitalization prior to the initial blood culture. VRE-infected patients were less likely to have undergone recent surgery or have polymicrobial bacteremia, suggesting a pathogenesis distinct from traditional VSE bacteremia. Prior exposure to metronidazole was the only significant pharmacologic risk factor for VRE bacteremia. Animal studies suggest metronidazole potentiates enterococcal overgrowth in the gastrointestinal tract and translocation into the bloodstream. An increasing APACHE II score was the major risk factor for death in a multivariate analysis, with VRE status being of only borderline significance.

Hospitalization in amyotrophic lateral sclerosis Causes, costs, and outcomes

Objective: As ALS progresses, extensive supportive care is required, including multidisciplinary outpatient care and hospitalization. The authors studied the causes, health care utilization, and outcomes for hospitalized patients with ALS. Methods: With use of the 1996 Nationwide Inpatient Sample, an administrative database representing 20% of U.S. hospitals, 1,600 hospitalizations in patients with ALS were identified and compared with 5,364,728 non-ALS hospitalizations. Results: The most common concurrent diagnoses in patients with ALS were dehydration and malnutrition (574 patients, 36%), pneumonia (507 patients, 32%), and respiratory failure (398 patients, 25%). Only 38% of patients with ALS were discharged to home without home health care compared with 73% of patients with non-ALS. Fifteen percent of patients with ALS died in the hospital compared with 3% of non-ALS patients. The average length of hospital stay and charges were greater for patients with ALS than for non-ALS patients (8.4 days and

Tricuspid Annular Plane Systolic Excursion Is a Robust Outcome Measure in Systemic Sclerosis-associated Pulmonary Arterial Hypertension

19,810 for ALS patients and 5.4 days and

High-frequency chest wall oscillation in ALS An exploratory randomized, controlled trial

11,924 for non-ALS patients). Mortality was significantly associated with emergency room admission (versus nonemergency admission; OR = 1.60), increasing age (per year; OR = 1.03), respiratory failure (OR = 3.37), and pneumonia (OR = 2.02) (p < 0.01 for all comparisons). Conclusions: Patients with ALS have lengthy and costly hospital admissions, a high in-hospital mortality rate, and few routine discharges. Recognition of the issues that precipitate hospitalization may allow development of preventive strategies.

Comparison of 21-Gauge and 22-Gauge Aspiration Needle in Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: Results of the American College of Chest Physicians Quality Improvement Registry, Education, and Evaluation Registry

Objective. The tricuspid annular plane systolic excursion (TAPSE) strongly reflects right ventricular (RV) function and predicts survival in idiopathic pulmonary arterial hypertension (PAH). But its role in systemic sclerosis (SSc)-associated PAH has not been established. Our objective was to validate the TAPSE in the assessment of RV function and prediction of survival in SSc-PAH. Methods. Fifty consecutive patients with SSc-PAH who underwent echocardiography with TAPSE measurement within 1 h of clinically indicated right heart catheterization were followed prospectively. The relationship between TAPSE and measures of RV function and measures of survival was assessed. Results. The majority of the cohort were women in New York Heart Association class III/IV with severe PAH (mean cardiac index 2.4 ± 0.8 l/min/m2). RV function was significantly impaired (mean cardiac index 2.1 ± 0.7 vs 2.9 ± 0.8 l/min/m2; p < 0.01) and RV afterload was significantly greater (mean pulmonary vascular resistance 11.1 ± 5.1 vs 5.8 ± 2.5 Wood units; p < 0.01) in subjects with a TAPSE ≤ 1.7 cm. The proportion surviving in the low TAPSE group was significantly lower [0.56 (95% CI 0.37–0.71) and 0.46 (95% CI 0.28–0.62) vs 0.87 (95% CI 0.55–0.96) and 0.79 (95% CI 0.49–0.93), 1- and 2-year survival, respectively]. TAPSE ≤ 1.7 cm conferred a nearly 4-fold increased risk of death (HR 3.81, 95% CI 1.31–11.1, p < 0.01). Conclusion. TAPSE is a robust measure of RV function and strongly predicts survival in patients with PAH-SSc. Future studies are needed to identify the responsiveness of TAPSE to PAH-specific therapy and to assess its diagnostic utility in PAH-SSc.

Ambrisentan and Tadalafil Up-front Combination Therapy in Scleroderma-associated Pulmonary Arterial Hypertension

Objectives: To evaluate changes in respiratory function in patients with ALS after using high-frequency chest wall oscillation (HFCWO). Methods: This was a 12-week randomized, controlled trial of HFCWO in patients with probable or definite ALS, an Amyotrophic Lateral Sclerosis Functional Rating Scale respiratory subscale score ≤11 and ≥5, and forced vital capacity (FVC) ≥40% predicted. Results: We enrolled 46 patients (58.0 ± 9.8 years; 21 men, 25 women); 22 used HFCWO and 24 were untreated. Thirty-five completed the trial: 19 used HFCWO and 16 untreated. HFCWO users had less breathlessness (p = 0.021) and coughed more at night (p = 0.048) at 12 weeks compared to baseline. At 12 weeks, HFCWO users reported a decline in breathlessness (p = 0.048); nonusers reported more noise when breathing (p = 0.027). There were no significant differences in FVC change, peak expiratory flow, capnography, oxygen saturation, fatigue, or transitional dyspnea index. When patients with FVC between 40 and 70% predicted were analyzed, FVC showed a significant mean decrease in untreated patients but not in HFCWO patients; HFCWO patients had significantly less increased fatigue and breathlessness. Satisfaction with HFCWO was 79%. Conclusion: High-frequency chest wall oscillation was well tolerated, considered helpful by a majority of patients, and decreased symptoms of breathlessness. In patients with impaired breathing, high-frequency chest wall oscillation decreased fatigue and showed a trend toward slowing the decline of forced vital capacity.

Optimizing Endobronchial Ultrasound for Molecular Analysis. How Many Passes Are Needed

BACKGROUNDnEndobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure originally performed using a 22-gauge (22G) needle. A recently introduced 21-gauge (21G) needle may improve the diagnostic yield and sample adequacy of EBUS-TBNA, but prior smaller studies have shown conflicting results. To our knowledge, this is the largest study undertaken to date to determine whether the 21G needle adds diagnostic benefit.nnnMETHODSnWe retrospectively evaluated the results of 1,299 patients from the American College of Chest Physicians Quality Improvement Registry, Education, and Evaluation (AQuIRE) Diagnostic Registry who underwent EBUS-TBNA between February 2009 and September 2010 at six centers throughout the United States. Data collection included patient demographics, sample adequacy, and diagnostic yield. Analysis consisted of univariate and multivariate hierarchical logistic regression comparing diagnostic yield and sample adequacy of EBUS-TBNA specimens by needle gauge.nnnRESULTSnA total of 1,235 patients met inclusion criteria. Sample adequacy was obtained in 94.9% of the 22G needle group and in 94.6% of the 21G needle group (P = .81). A diagnosis was made in 51.4% of the 22G and 51.3% of the 21G groups (P = .98). Multivariate hierarchical logistic regression showed no statistical difference in sample adequacy or diagnostic yield between the two groups. The presence of rapid onsite cytologic evaluation was associated with significantly fewer needle passes per procedure when using the 21G needle (P < .001).nnnCONCLUSIONSnThere is no difference in specimen adequacy or diagnostic yield between the 21G and 22G needle groups. EBUS-TBNA in conjunction with rapid onsite cytologic evaluation and a 21G needle is associated with fewer needle passes compared with a 22G needle.

Pulmonary Arterial Hypertension: MR Imaging-derived First-Pass Bolus Kinetic Parameters Are Biomarkers for Pulmonary Hemodynamics, Cardiac Function, and Ventricular Remodeling

BACKGROUNDnScleroderma-associated pulmonary arterial hypertension (SSc-PAH) is a rare disease characterized by a very dismal response to therapy and poor survival. We assessed the effects of up-front combination PAH therapy in patients with SSc-PAH.nnnMETHODSnIn this prospective, multicenter, open-label trial, 24 treatment-naive patients with SSc-PAH received ambrisentan 10 mg and tadalafil 40 mg daily for 36 weeks. Functional, hemodynamic, and imaging (cardiac magnetic resonance imaging and echocardiography) assessments at baseline and 36 weeks included changes in right ventricular (RV) mass and pulmonary vascular resistance as co-primary endpoints and stroke volume/pulmonary pulse pressure ratio, tricuspid annular plane systolic excursion, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide as secondary endpoints.nnnRESULTSnAt 36 weeks, we found that treatment had resulted in significant reductions in median (interquartile range [IQR]) RV mass (28.0 g [IQR, 20.6-32.9] vs. 32.5 g [IQR, 23.2-41.4]; P < 0.05) and median pulmonary vascular resistance (3.1 Wood units [IQR, 2.0-5.7] vs. 6.9 Wood units [IQR, 4.0-12.9]; P < 0.0001) and in improvements in median stroke volume/pulmonary pulse pressure ratio (2.6 ml/mm Hg [IQR, 1.8-3.5] vs. 1.4 ml/mm Hg [IQR 8.9-2.4]; P < 0.0001) and mean ( ± SD) tricuspid annular plane systolic excursion (2.2 ± 0.12 cm vs. 1.65 ± 0.11 cm; P < 0.0001), 6-minute walk distance (395 ± 99 m vs. 343 ± 131 m; P = 0.001), and serum N-terminal pro-brain natriuretic peptide (647 ± 1,127 pg/ml vs. 1,578 ± 2,647 pg/ml; P < 0.05).nnnCONCLUSIONSnUp-front combination therapy with ambrisentan and tadalafil significantly improved hemodynamics, RV structure and function, and functional status in treatment-naive patients with SSc-PAH and may represent a very effective therapy for this patient population. In addition, we identified novel hemodynamic and imaging biomarkers that could have potential value in future clinical trials. Clinical trial registered with www.clinicaltrials.gov (NCT01042158).