Fatal transfusion-associated graft-versus-host disease with concomitant immune hemolysis in a group A combat trauma patient resuscitated with group O fresh whole blood.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but well-established fatal complication of blood transfusion. It can occur in immunocompetent patients when they receive transfusions from human leukocyte antigen-haploidentical donors who have lymphocytes with antigens that are not recognized as foreign by the host, but that recognize the host's tissues as foreign. It is generally viewed as a T-cell-mediated process. Graft-induced immune hemolysis or passenger lymphocyte syndrome is a well-described complication of marrow or solid organ transplantation in which immune competent donor B cells produce alloantibodies to recipient red blood cell (RBC) antigens and cause hemolysis of the recipient's RBCs. It is generally considered as a separate process from GVHD, although it could be considered a type of GVHD. Despite the theoretical possibility of both a B-cell and T-cell component to TA-GVHD, detection of a humoral antibody in cases of acute TA-GVHD has not been described. We describe the clinical course and laboratory evaluation of a group A combat trauma patient who was acutely resuscitated with group O fresh whole blood and RBCs and group AB fresh-frozen plasma who experienced the onset of the clinical symptoms of TA-GVHD as well as the onset of hemolysis due to donor-derived anti-A in his plasma 11 days after transfusion.

Eucapnic voluntary hyperventilation is superior to methacholine challenge testing for detecting airway hyperreactivity in nonathletes.

INTRODUCTION: Response to eucapnic voluntary hyperventilation (EVH) has not been compared with methacholine challenge testing (MCCT) in nonathletes being evaluated for dyspnea on exertion. OBJECTIVE: To determine the airway response to EVH and MCCT in a population of nonathletes who exercise regularly but have symptoms with exertion. METHODS: We reviewed records for all patients with exercise symptoms who underwent both EVH and MCCT. Presenting symptoms, comorbid diseases, and results of bronchoprovocation (BP) testing were recorded. This study was approved by the institutional review board at our hospital. RESULTS: A total of 131 patients (mean age 32.3 ± 11.6, body mass index (BMI) 27.1 ± 4.7 kg/m(2), 59.5% male) had an EVH, MCCT, and clinical evaluation performed. Overall, 37 (28.2%) patients had positive BP testing and met criteria for exercise-induced bronchoconstriction (EIB). There were 32 (24.4%) patients with a positive EVH, compared with only 11 patients with a positive MCCT (8.4%). There were 26 patients (19.8%) who had a positive EVH but a negative MCCT, and correlation between the two tests was poor to moderate (r = 0.11-0.57). A complaint of chest pain and younger age were independent predictors for a positive EVH, whereas a history of tobacco use and a decreased FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) predicted a positive MCCT. A previous diagnosis of asthma was an independent predictor for a response to either test. Discussion. In a population of nonathletes who exercise regularly and have symptoms with exertion, EIB is common. Correlation between EVH and MCCT in this population is poor, and although the tests are somewhat complementary, a large percentage of patients had a negative MCCT but a positive EVH. CONCLUSIONS: EIB is common in nonathletes with exercise-induced symptoms, and EVH is the preferred test for this population. CLINICAL IMPLICATIONS: EIB is common in nonathletes who exercise regularly. In this population, MCCT will miss most patients with EIB, and MCCT and EVH show only poor-to-moderate correlation. CAPSULE SUMMARY: EVH has not been compared with MCCT in nonathletes without a diagnosis of asthma. Our study shows that the two tests are complementary in this population, but EVH is positive more often.

The impact of split-night versus traditional sleep studies on CPAP compliance.

BACKGROUND: Split-night polysomnography allows for the diagnosis of obstructive sleep apnea and titration of continuous positive airway pressure in a single study. However, there is concern that split-night studies do not provide sufficient time for optimal continuous positive airway pressure (CPAP) titration, which may lead to a poor initial experience with CPAP and potentially, worse adherence. Our goal was to determine whether CPAP use, after a split-night examination, is comparable to the use following separate diagnostic and titration studies. METHODS: We included consecutive patients presenting for follow-up 4-6 weeks after initiating CPAP therapy. Objective measures of CPAP use were recorded, and adherence to therapy was analyzed based on the initial method of diagnosis and titration-split-night versus dual-night study. RESULTS: A total of 400 patients (78% male, mean age 47 +/- 8 years) were included. Among the patients, 267 and 133 underwent split- and dual-night studies, respectively. The groups were similar at baseline; however, the average apnea-hypopnea index was significantly higher in the split-night group. Mean number of days between diagnosis and titration in the dual-night group was 80.5 days. There was no difference in therapeutic adherence between groups as measured by percentage of nights used (78.7% vs 77.5%; p = 0.42), hours per night used (3.9 vs 3.9; p = 0.95), or percentage of patients using continuous positive airway pressure for >4 hours per night for >70% of nights (52.9% vs 51.8%; p = 0.81). There was no difference in use after adjusting for severity of disease. CONCLUSIONS: Split-night polysomnography does not adversely affect short-term continuous positive airway pressure adherence in patients with obstructive sleep apnea.

Effects of a short course of eszopiclone on continuous positive airway pressure adherence: a randomized trial.

BACKGROUND: Adherence to short-term continuous positive airway pressure (CPAP) may predict long-term use. Unfortunately, initial CPAP intolerance may lead to poor adherence or abandonment of therapy. OBJECTIVE: To determine whether a short course of eszopiclone at the onset of therapy improves long-term CPAP adherence more than placebo in adults with obstructive sleep apnea. DESIGN: Parallel randomized, placebo-controlled trial from March 2007 to December 2008. Randomization, maintained and concealed centrally by pharmacy personnel, was computer-generated using fixed blocks of 10. Referring physicians, investigators, and patients were blinded to the treatment assignment until after the final data were collected. (ClinicalTrials.gov registration number: NCT00612157). SETTING: Academic sleep disorder center. PATIENTS: 160 adults (mean age, 45.7 years [SD, 7.3]; mean apnea-hypopnea index, 36.9 events/h [SD, 23]) with newly diagnosed obstructive sleep apnea initiating CPAP. INTERVENTION: Eszopiclone, 3 mg (n = 76), or matching placebo (n = 78) for the first 14 nights of CPAP. MEASUREMENTS: Use of CPAP was measured weekly for 24 weeks. Adherence to CPAP (primary outcome) and the rate of CPAP discontinuation and improvements in symptoms (secondary outcomes) were compared. Follow-up at 1, 3, and 6 months was completed by 150, 136, and 120 patients, respectively. RESULTS: Patients in the eszopiclone group used CPAP for 20.8% more nights (95% CI, 7.2% to 34.4%; P = 0.003), 1.3 more hours per night for all nights (CI, 0.4 to 2.2 hours; P = 0.005), and 1.1 more hours per night of CPAP use (CI, 0.2 to 2.1 hours; P = 0.019). The hazard ratio for discontinuation of CPAP was 1.90 (CI, 1.1 to 3.4; P = 0.033) times higher in the placebo group. Side effects were reported in 7.1% of patients and did not differ between groups. LIMITATIONS: Patients had severe obstructive sleep apnea treated at a specialized sleep center with frequent follow-up; results may not be generalizable to different settings. Patients' tolerance to CPAP and their reasons for discontinuation were not assessed. CONCLUSION: Compared with placebo, a short course of eszopiclone during the first 2 weeks of CPAP improved adherence and led to fewer patients discontinuing therapy.

The prevalence and impact of respiratory symptoms in asthmatics and nonasthmatics during deployment.

OBJECTIVE: The purpose of this study was to compare the prevalence, severity, and impact of respiratory symptoms in asthmatics and nonasthmatics during Operation Enduring Freedom and Operation Iraqi Freedom. METHODS: A survey was given to 1,250 active duty soldiers and Department of Defense contractors returning from Operation Enduring Freedom/Operation Iraqi Freedom. Subjects were asked about demographics, smoking habits, respiratory symptoms, and impact on job performance before and during deployment. Patients with a history of asthma were asked method of diagnosis, current symptoms, and asthma therapy. RESULTS: A total of 1,193 subjects returned the completed questionnaire (95% response rate). Mean age of respondents was 38 +/- 11 years, 83% (n = 977) were male, and 31% (n = 375) were past or present smokers. Sixty-one subjects (5%) reported a previous diagnosis of asthma. Both asthmatics and nonasthmatics had increased respiratory symptoms of wheezing, cough, sputum production, chest pain/tightness, and allergy symptoms during deployment compared to predeployment (p < 0.05 for all). When compared to nonasthmatics, asthmatic subjects reported more wheezing, sputum production, and chest pain/tightness during deployment (p < 0.0001, 0.05, 0.05 respectively), had more difficulty with military duties (p < 0.05), and were more likely to seek medical attention and receive duty restrictions (p < 0.0001). Twenty-six percent (n = 16) of asthmatics reported poor baseline symptom control, and this group had significantly increased symptoms, functional limitations, and health care utilization when compared to asthmatics who were symptom-controlled at baseline. CONCLUSIONS: Respiratory symptoms were common among both asthmatics and nonasthmatics during deployment. Differences in symptoms and health care utilization in this group of asthmatics were primarily due to subjects with poor baseline control.

Bacteria recovered from patients admitted to a deployed U.S. military hospital in Baghdad, Iraq.

The predominant bacteria and antimicrobial susceptibilities were surveyed from a deployed, military, tertiary care facility in Baghdad, Iraq, serving U.S. troops, coalition forces, and Iraqis, from August 2003 through July 2004. We included cultures of blood, wounds, sputum, and urine, for a total of 908 cultures; 176 of these were obtained from U.S. troops. The bacteria most commonly isolated from U.S. troops were coagulase-negative staphylococci, accounting for 34% of isolates, Staphylococcus aureus (26%), and streptococcal species (11%). The 732 cultures obtained from the predominantly Iraqi population were Klebsiella pneumoniae (13%), Acinetobacter baumannii (11%), and Pseudomonas aeruginosa (10%); coagulase-negative staphylococci represented 21% of these isolates. These differences in prevalence were all statistically significant, when compared in chi2 analyses (p < 0.05). Antimicrobial susceptibility testing demonstrated broad resistance among the Gram-negative and Gram-positive bacteria.

Bacteriology of war wounds at the time of injury.

Bacterial contamination of war wounds occurs either at the time of injury or during the course of therapy. Characterization of the bacteria recovered at the time of initial trauma could influence the selection of empiric antimicrobial agents used to prevent infection. In the spring of 2004, U.S. military casualties who presented to the 31st Combat Support Hospital in Baghdad, Iraq, with acute traumatic injuries resulting in open wounds underwent aerobic culture of their wounds to identify the bacteria colonizing the wounds. Forty-nine casualties with 61 separate wounds were evaluated. Wounds were located predominantly in the upper and lower extremities and were primarily from improvised explosive devices or mortars. Thirty wounds (49%) had bacteria recovered on culture, with 40 bacteria identified. Eighteen casualties (20 wounds) had undergone field medical therapy (irrigation and/or antimicrobial treatment); six of these had nine bacterial isolates on culture. Of the 41 wounds from 31 patients who had received no previous therapy, 24 grew 31 bacteria. Gram-positive bacteria (93%), mostly skin-commensal bacteria, were the predominant organisms identified. Only three Gram-negative bacteria were detected, none of which were characterized as broadly resistant to antimicrobial agents. The only resistant bacteria recovered were two isolates of methicillin-resistant Staphylococcus aureus (MRSA). Our assessment of war wound bacterioly soon after injury reveals a predominance of Gram-positive organisms of low virulence and pathogenicity. The presence of MRSA in wounds likely reflects the increasing incidence of community-acquired MRSA bacteria. These data suggest that the use of broad-spectrum antibiotics with efficacy against more resistant, Gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter spp., is unnecessary in early wound management.

Medical problems of detainees after the conclusion of major ground combat during Operation Iraqi Freedom.

After the conclusion of major ground combat operations during Operation Iraqi Freedom, the focus of the mission changed, although intense armed conflict continued. Included in this mission was management of security detainees, including provision of their medical care. We retrospectively reviewed the admission records identified at a short-term holding facility over 2 months and diagnoses of detainees admitted to a combat support hospital over 4 months as a health care service utilization statistics review. Six thousand six hundred thirty-one detainee encounters occurred at the short-term facility with approximately 45% of detainees reporting medical problems during each daily evaluation. Most frequent complaints were neurological (11%), gastrointestinal (10%), and respiratory (8%). Two hundred nineteen detainees' admission diagnoses were retrospectively reviewed from the combat support hospital, 98 (45%) due to gunshot or fragmentary injuries and 121 (55%) to other medical problems. Medical problems included cardiac (29%), gastrointestinal (17%), neurological (14%), musculoskeletal (11%), and pulmonary (6%) disease. Medical problems not traditionally dealt with in a combat theater, including management of transplant recipients, patients with cardiac valve replacement, and cancer patient, were also seen.

Inhalational exposure to nerve agents.

The respiratory system plays a major role in the pathogenesis of nerve agent toxicity. It is the major route of entry and absorption of nerve agent vapor, and respiratory failure is the most common cause of death follow-ing exposure. Respiratory symptoms are mediated by chemical irritation,muscarinic and nicotinic receptor overstimulation, and central nervous system effects. Recent attacks have demonstrated that most patients with an isolated vapor exposure developed respiratory symptoms almost immediately. Most patients had only mild and transient respiratory effects, and those that did develop significant respiratory compromise did so rapidly. These observations have significant ramifications on triage of patients in a mass-casualty situation, because patients with mild-to-moderate exposure to nerve agent vapor alone do not require decontamination and are less likely to develop progressive symptoms following initial antidote therapy. Limited data do not demonstrate significant long-term respiratory effects following nerve agent exposure and treatment. Provisions for effective respiratory protection against nerve agents is a vital consideration in any emergency preparedness or health care response plan against a chemical attack.

Racial discordance in spirometry comparing four commonly used reference equations to the National Health and Nutrition Examination Study III.

Diagnosing lung function abnormalities requires application of the appropriate reference equation for a given patient population. Current guidelines recommend the National Health and Examination Study III data set for evaluating patients in the United States. In Caucasian patients, relying on older reference equations, as opposed to those derived from the NHANES III data set, will often result in a different interpretation of a patient's spirometry. The present study assessed whether similar discordance would occur in African-American patients. A cross-sectional analysis of African-American patients undergoing spirometry testing at our hospital was performed. Patients were classified as normal, restricted, obstructed or mixed based upon the ATS/ERS guidelines, using Crapo, Knudson, Morris, Glindmeyer, and NHANES III prediction equations. Differences in classification were evaluated. 4463 subjects were identified, with a mean age of 49.6. Discordance in interpretation was most common when results from prediction equations by Morris, Knudson, and Glindmeyer were compared to NHANES III (24.6%, 26.4%, and 20.1%, respectively). Discordance was less common when comparing Crapo to NHANES III (12.8%). There was a tendency for Knudson, Morris and Glindmeyer to under classify restriction, and for Crapo, Morris, and Glindmeyer to over classify obstruction. There is significant discordance in interpretation when spirometry for African-American patients is referenced to equations published by Crapo, Morris, Knudson, and Glindmeyer, compared to NHANES III.

Clinical and polysomnographic predictors of short-term continuous positive airway pressure compliance.

BACKGROUND: Poor compliance and initial intolerance limit the effectiveness of continuous positive airway pressure (CPAP) in obstructive sleep apnea. Short-term compliance has been shown to predict long-term use. Unfortunately, few identified variables reliably predict initial CPAP tolerance and use. We sought to identify potential pretreatment variables that would predict short-term use of CPAP. METHODS: We performed a retrospective review assessing short-term CPAP compliance after 4 to 6 weeks of treatment. Consecutive patients initiating CPAP therapy were included. Demographic and polysomnographic variables were correlated with objective measures of CPAP use. The average hours per night and percentage of nights of CPAP use were correlated with each variable. Variables were also associated with good vs poor compliance, which we defined as > 4 h per night > 70% of nights. RESULTS: We included 400 consecutive patients (78% male; mean age, 47 +/- 8 years). Of the measured variables, only age (48 +/- 8 years vs 46 +/- 7 years, p = 0.02) and use of a sedative/hypnotic during CPAP titration (77% vs 57.6%, p < 0.0005) were associated with better compliance. Those receiving a sedative/hypnotic had longer sleep times (345 +/- 42 min vs 314 +/- 51 min, p < 0.0005) and greater sleep efficiency (84 +/- 9% vs 78 +/- 11%, p < 0.0005) during polysomnography. CPAP titrations were improved in those receiving sedative/hypnotics, achieving lower respiratory disturbance index on the final CPAP pressure (6 +/- 7 vs 10 +/- 11, p = 0.04). CONCLUSIONS: Of the measured variables, only age and a one-time use of sedative/hypnotics during polysomnography correlated with greater short-term CPAP compliance. Hypnotics facilitated better quality CPAP titrations. Reliable predictors of short-term CPAP use could help identify measures to improve long-term compliance.