The inspiratory capacity/total lung capacity ratio as a predictor of survival in an emphysematous phenotype of chronic obstructive pulmonary disease.

BACKGROUND: Forced expiratory volume in 1 second (FEV1) grades severity of COPD and predicts survival. We hypothesize that the inspiratory capacity/total lung capacity (IC/TLC) ratio, a sensitive measure of static lung hyperinflation, may have a significant association with survival in an emphysematous phenotype of COPD. OBJECTIVES: To access the association between IC/TLC and survival in an emphysematous phenotype of COPD. METHODS: We performed a retrospective analysis of a large pulmonary function (PF) database with 39,050 entries, from April 1978 to October 2009. Emphysematous COPD was defined as reduced FEV1/forced vital capacity (FVC), increased TLC, and reduced diffusing capacity of the lungs for carbon monoxide (DLCO; beyond 95% confidence intervals [CIs]). We evaluated the association between survival in emphysematous COPD patients and the IC/TLC ratio evaluated both as dichotomous (≤25% vs >25%) and continuous predictors. Five hundred and ninety-six patients had reported death dates. RESULTS: Univariate analysis revealed that IC/TLC ≤25% was a significant predictor of death (hazard ratio [HR]: 2.39, P<0.0001). Median survivals were respectively 4.3 (95% CI: 3.8-4.9) and 11.9 years (95% CI: 10.3-13.2). Multivariable analysis revealed age (HR: 1.19, 95% CI: 1.14-1.24), female sex (HR: 0.69, 95% CI: 0.60-0.83), and IC/TLC ≤25% (HR: 1.69, 95% CI: 1.34-2.13) were related to the risk of death. Univariate analysis showed that continuous IC/TLC was associated with death, with an HR of 1.66 (95% CI: 1.52-1.81) for a 10% decrease in IC/TLC. CONCLUSION: Adjusting for age and sex, IC/TLC ≤25% is related to increased risk of death, and IC/TLC as a continuum, is a significant predictor of mortality in emphysematous COPD patients.

Reality bites: a case of severe rattlesnake envenomation.

Rattlesnake venoms can cause a wide range of adverse human health effects. However, with the availability of modern antivenin, toxicity can generally be minimized and controlled. We present a rare case of rattlesnake envenomation resulting in severe systemic effects and syndrome relapse. Management considerations and patient course are described in the context of the current literature.

Do faculty intensivists have better outcomes when caring for patients directly in a closed ICU versus consulting in an open ICU?

BACKGROUND: Intensivists have been associated with decreased mortality in several studies, but in one major study, centers with intensivist-staffed units reported increased mortality compared with controls. We hypothesized that a closed unit, in which a unit-based intensivist directly provides and coordinates care on all cases, has improved mortality and utilization compared with an open unit, in which individual attendings and consultants provide care, while intensivists serve as supervising consultants. METHODS: We undertook the retrospective study of outcomes in 2 intensive care units (ICUs)-a traditional open unit managed by faculty intensivists and a second closed unit overseen by the same faculty intensivists who coordinated the care on all patients in a large community hospital. PRIMARY OUTCOME: In-hospital mortality. SECONDARY OUTCOMES: Hospital length of stay (LOS), ICU LOS, and relative costs of hospitalization. RESULTS: From January 2006 to December 2007, we identified 2602 consecutive admissions to the 2 medical ICUs. Of all patients admitted to the closed and open units, 19.2% and 24.7%, respectively, did not survive (P < 0.001, adjusted for severity). Median hospital LOS was 10 days for the closed unit and 12 days for the open unit (P < 0.001). Median ICU LOS was 2.2 days for the closed unit and 2.4 days for the open unit (P = NS). The unadjusted cost index for the open unit was 1.11 relative to the closed unit (1.0) (P < 0.001). However, after adjusting for disease severity, cost differences were not significantly different. CONCLUSIONS: We observed significant reductions in mortality and hospital LOS for patients initially admitted to a closed ICU versus an open unit. We did not observe a significant difference in ICU LOS or total cost after adjustment for severity.

Carboxyhemoglobin and its correlation to disease severity in cirrhotics.

GOAL: To assess the correlation of serum carboxyhemoglobin (CO-Hb) to severity of liver disease as compared with Model for End Stage Liver Disease (MELD) score, Child Pugh score, and clinical parameters. BACKGROUND: There are 2 sources of carbon monoxide (CO) in humans, exogenous sources include those such as tobacco smoke and inhaled motor vehicle exhaust. The endogenous source is via the heme-oxygenase pathway, in which a heme molecule is broken down into biliverdin with release of an iron (Fe) and CO molecule. Normal serum CO-Hb levels in nonsmokers is 0% to 1.5% and 4% to 9% in smokers. Activity of the heme-oxygenase pathway may be increased in the cirrhotic patient, as measured indirectly by exhaled CO and serum CO-Hb. This may be due to alterations in vascular tone in the splanchnic circulation in cirrhotics that may lead to elevated CO production. One published study also showed that those with spontaneous bacterial peritonitis had higher levels of both CO and CO-Hb. The MELD score uses prothrombin time (INR), creatinine, and bilirubin in the prediction of short-term mortality in decompensated cirrhotics while awaiting liver transplant. Measurement of endogenous CO-Hb may correlate to severity of liver disease. STUDY: Retrospective analysis was done of 113 adult patients who were evaluated for liver transplantation between September 1996 and July 2003 and had pulmonary function testing with CO-Hb as part of their evaluation. We excluded any patients with a history of smoking. Clinical parameters used for comparison included grade of esophageal varices (n=75), spleen size (n=51) measured on abdominal ultrasound or computed tomography scan, aminotransferases, and disease duration. Serum CO-Hb levels were measured from whole blood, sent refrigerated to ARUP laboratories (Salt Lake City, UT) and analyzed via spectrophotometry. Bivariate analysis was performed by means of the Pearson product moment correlation. RESULTS: The mean CO-Hb level was 2.1%, which is higher than the expected normal population controls. No correlation was found, however, with MELD score, Child Turcotte Pugh score, or other biochemical or clinical measurements of disease severity. CONCLUSIONS: Although CO and CO-Hb production may be increased in the cirrhotic patient, in this study no correlation was found to disease severity as measured by the MELD score. Further studies are needed to assess the role of CO in other complications of cirrhosis including infection and circulatory dysfunction.

Improvement in serial cardiopulmonary exercise testing following enzyme replacement therapy in Fabry disease.

BACKGROUND: Fabry disease is an X-linked genetic disorder resulting in the accumulation of glycosphingolipids in various organs, leading to exercise intolerance and early mortality. Enzyme replacement therapy (ERT) has recently been approved for use in Fabry patients. GOALS OF STUDY: To assess baseline cardiopulmonary exercise characteristics in both invasive and noninvasive tests and to study the impact of ERT on exercise. METHODS: A total of 15 patients with Fabry disease underwent baseline cardiopulmonary exercise tests. Six patients were randomized 2:1 to receive either ERT or placebo. We performed serial cardiopulmonary exercise tests at baseline and every 3 months over a period of at least 18 months. The baseline test was compared to the last two exercise tests for each patient. RESULTS: Mean age was 32 years. Mean VO2max was 1.680 +/- 0.67 L/min and increased by 0.459 +/- 0.64 L/min in the patients receiving ERT. Mean VO2max was 1.462 +/- 0.25 L/min and decreased by 0.116 +/- 0.44 L/min in patients on placebo. Mean oxygen pulse (VO2/HR) increased by 1.71 with enzyme, but increased only 0.025 in patients taking placebo. Estimated stroke volume (SV) increased by 10 ml in patients on ERT. CONCLUSIONS: In this small cohort, exercise tolerance increased in patients receiving enzyme replacement therapy. Cardiopulmonary exercise testing is a useful test in measuring the response to therapy in Fabry disease patients.

Cardiopulmonary exercise testing in Fabry disease.

BACKGROUND: Fabry disease is a rare X-linked disorder that results from a deficiency in a lysosomal enzyme known as alpha-galactosidase A, with accumulation of globotriaosylceramide (Gl3). Early manifestations include angiokeratomas, acroparesthesias, and hypohidrosis and may progress to renal failure, cardiac dysfunction, and stroke. Patients exhibit decreased exercise tolerance and often complain of fatigue. OBJECTIVE: Our study evaluates the cardiopulmonary characteristics in a cohort of Fabry disease patients at rest and during exercise. METHODS: Thirty-nine patients with a diagnosis of Fabry disease underwent a health screening history and physical examination, an electrocardiogram, an echocardiogram, pulmonary function testing (spirometry), and a non-invasive cardiopulmonary exercise test. A control group was selected for comparison. RESULTS: Eighteen of the 39 Fabry patients (46%) exhibited a significant decrease in diastolic blood pressure (DBP) during exercise. The average decrease in DBP was 10 mm Hg. The maximum drop in DBP was 44 mm Hg. The drop in DBP was evident in 9 of the 24 female patients (38%). None of the control patients had a significant drop in DBP during exercise. CONCLUSIONS: Our finding of a significant decrease in DBP in patients with Fabry disease may explain deficits in exercise tolerance. It is notable that this abnormality is manifested in female patients, even though they are typically not as severely affected as males.

Airflow limitation and breathing strategy in congestive heart failure patients during exercise.

BACKGROUND: Congestive heart failure (CHF) patients experience dyspnea on exertion and therefore have decreased exercise tolerance. OBJECTIVE: This study explores the hypothesis that stable New York Heart Association (NYHA) class III CHF patients without a history of pulmonary disease exhibit airflow limitation with increasing exercise. METHODS: We characterized flow limitations and breathing reserves at baseline, during exercise before anaerobic threshold (pre-AT), and after anaerobic threshold (post-AT) in CHF patients and normal subjects. Data were collected in the form of maximal flow volume loops and subsequent tidal flow volume loops at baseline and during exercise. Expiratory flow limitation was expressed as percent of tidal volume that corresponded with overlap of the tidal flow volume loops and maximal flow volume loops during expiration. The area directly between the maximum flow volume loops and the tidal flow volume loops during the expiratory phase is expressed as expiratory flow volume reserve (EFVR). RESULTS: CHF patients experienced expiratory flow limitation during exercise (pre-AT and post-AT) that was significantly increased compared to baseline and to normal subjects at similar exercise levels (CHF, baseline 8.5 +/- 7, pre-AT 37 +/- 10, post-AT 38 +/- 8%, n = 9, p < 0.05). Both CHF patients and normal subjects increased EFVR during exercise, but only the normal subjects increased EFVR to a significantly different value at post-AT exercise levels (normal subjects, 9.5 +/- 2, 11 +/- 2, 32 +/- 4%, n = 7, p < 0.05). Both CHF patients and normal subjects increased end inspiratory lung volume (EILV) during exercise, but only the normal subjects significantly increased EILV at post-AT exercise levels (normal subjects, 49 +/- 4, 55 +/- 5, 76 +/- 4%, p < 0.05). Inspiratory capacity (IC)/forced vital capacity (FVC) ratios were increased in CHF patients compared to normal subjects. However, IC/FVC values did not change during exercise in either group. CONCLUSIONS: CHF patients cannot utilize their full respiratory capacity during exercise secondary to expiratory flow limitation and an inability to increase EILV and EFVR.

Grading the severity of obstruction in the presence of a restrictive ventilatory defect.

STUDY OBJECTIVES: No recommendation currently exists for grading the severity of airway obstruction in the presence of additional restriction. The grading of airway obstruction is currently based on the FEV(1) (American Thoracic Society [ATS] recommendations), while prior recommendations by the Intermountain Thoracic Society (ITS) graded the severity of obstruction based on the FEV(1)/FVC ratio. The objective was to compare the grading of airway obstruction using the percent predicted FEV(1) (ATS) with a confidence interval-based system (ITS), with particular focus on pulmonary functions in patients having both airway obstructions and restrictions. DESIGN: Retrospective analysis. SETTING: Tertiary medical center. PATIENTS: A retrospective analysis of 21,499 patient pulmonary function tests (PFTs) was performed. The predicted values of Crapo and coworkers were used. MEASUREMENTS AND RESULTS: The distribution of the severity of the obstruction was compared using the ATS and ITS methods for PFTs with normal, increased, or decreased total lung capacity (TLC). Analysis was performed using the chi(2) method. Of the 21,499 PFTs that were analyzed, TLC was measured in 28% (5,962 PFTs). In this cohort, 44% (2,619 PFTs) gave evidence of obstruction. Of these, 147 PFTs demonstrated additional restriction. While the ATS criteria graded 133 of these PFTs (90%) as being severe, the ITS criteria graded only 4 PFTs (3%) as severe (the severity distribution between the methods was significantly different [p < 0.01]). CONCLUSIONS: In view of the possible overestimation of the severity of obstruction in PFTs with concurrent restriction using the percentage of predicted FEV(1) values, consideration should be given to grading the severity of obstruction on the basis of the FEV(1)/FVC ratio in this specific subset of PFTs.