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Introduction: Mepolizumab targets eosinophils in the treatment of asthma. The dose used for asthma is considerably lower than that used for treating eosinophilic granulomatosis with polyangiitis, a...

Anaphylaxis is a dramatic expression of systemic allergy. The lifetime prevalence of anaphylaxis is currently estimated at 0.05-2 % in the USA and ~3 % in Europe. Several population-specific studies have noted a rise in the incidence, particularly in the hospitalizations and ER visits due to anaphylaxis. The variable signs and symptoms that constitute the diagnostic criteria for anaphylaxis, the differences in diagnostic algorithms, and the limitations in the current coding systems have made summarizing epidemiologic data and comparing study results challenging. Nevertheless, across all studies, the most common triggers continue to be medications, food, and venom. Various risk factors for more severe reactions generally include older age, history of asthma, and having more comorbid diseases. Interesting seasonal, geographic, and latitude differences have been observed in anaphylaxis prevalence and incidence rates, suggesting a possible role of vitamin D and sun exposure in modifying anaphylaxis risk. While the incidence and prevalence of anaphylaxis appear to be increasing in certain populations, the overall fatality rate remains relatively low.

BACKGROUND The impact of dementia on hospitalization discharge dispositions (HDDs) in the United States has not been quantified, and dementia prevalence in various hospitalization categories has not been detailed in recent years. OBJECTIVE To characterize hospitalizations prevalent with dementia, and to examine the relationship between dementia and HDDs. DESIGN A retrospective cross-sectional study. SETTING 2000 to 2012 National Inpatient Sample databases. PATIENTS Hospitalizations in persons ≥65 years old assigned to 1 of 12 Diagnosis Related Groups (DRGs) with a high number of dementia patients. INTERVENTION None. MEASUREMENTS The databases were queried for 12 DRGs (versions 18/24). Predictor effects for dementia on HDD categories were modeled adjusting for other defined comorbidities/covariates using logistic regression. Adjusted predictor effects of dementia on HDD in the DRG groupings were determined. Dementia prevalence and trends were assessed. RESULTS Increasing proportions of dementia were noted in 4 DRGs studied. Dementia was strongly associated with being discharged to a nonhome setting. The most marked dementia effects were noted in DRGs 174 (gastrointestinal hemorrhage), 88 (chronic obstructive pulmonary disease), 182 (esophagitis/gastroenteritis), 138 (cardiac arrhythmias), 127 (congestive heart failure), and 89 (simple pneumonia and pleurisy), where there was at least a 76% reduction in the adjusted odds ratio (0.18–0.24) for home discharge. In contrast, DRGs 14 (stroke), 79 (respiratory infections/ inflammations), and 320 (kidney/urinary infections) had a smaller reduction in dementia-associated adjusted odds ratio (0.41–0.46) for home discharge. DRGs 79 and 320 had the highest proportions of dementia (>10%). CONCLUSIONS Dementia proportions in many hospitalization categories have increased. The variable effect of dementia on home discharge suggests that dementia has a differential influence on hospital discharge disposition depending on the DRG. These findings have implications for healthcare allocation and long-term care planning. Journal of Hospital Medicine 2015;10:586–591. © 2015 Society of Hospital Medicine

To examine the characteristics of United States hospitalizations that result in hospice transfers including the clinical and demographic features, and to determine distinctive factors associated with discharges to hospice (DTH).The National Inpatient Sample (NIS) databases for 2000-2009 were queried for hospitalizations which resulted in transfers to hospice and expiration in the hospital. Yearly totals, as well as demographic and clinical features were tabulated for DTH hospitalizations. These characteristics were also compared with hospitalizations that ended with expiration using multivariate regression.The number of DTH per year increased 15 fold from 27,912 in 2000 to 420,882 in 2009. The median hospital stay decreased, while the median age, proportion of sepsis disease related groups (DRGs), and proportion of Medicare hospitalizations increased. Lung, gastrointestinal, hepato-biliary, and brain cancer were consistently the most prevalent malignancy DRGs. However, the initial preponderance of hospitalizations with any diagnosis of cancer was diminished by the end of the study. The adjusted odds ratio (95%CI) for the prediction of DTH (compared to hospital death) by any diagnosis of cancer decreased from 3.61 (3.52-3.71) to 2.02 (2.00-2.04) from the years 2000-2009. Female gender, age, and chronic obstructive pulmonary disease were predictors of discharge to hospice, while congestive heart failure was inversely associated.Hospital discharges to hospice have increased over the past ten years, with a concomitant shift in clinical and demographic characteristics. A growing trend toward offering and adopting hospice care upon discharge from US hospitals will likely impact health care finance and quality of care measures.

Background. The ability to assess adequate reductions in immunoglobulin E (IgE) in allergic bronchopulmonary aspergillosis (ABPA) has been a concern with regards to omalizumab treatment. Objective. To describe the clinical course and serial measured IgE levels in two adult patients with elevated IgE levels, hypersensitivity to Aspergillus fumigatus, and bilateral bronchiectasis who were treated with omalizumab. Clinical Descriptions. Patient 1 met commonly used critieria for ABPA and had a more than 3-fold increase (from 702 to 2462 IU/ml) in measured IgE 4 months after starting omalizumab. Two years after starting omalizumab, the IgE level decreased to baseline (473 IU/ml) even when corticosteroids were discontinued. Patient 2 had near normalization of elevated IgE levels when treated with corticosteroids but IgE levels subsequently rose again to over 10,000 IU/ml. After reducing the IgE level to 586 IU/ml with higher corticosteroid doses, omalizumab was initiated. Twenty months after starting omalizumab, the measured IgE was 510 IU/ml. Based on published omalizumab treatment–associated total/free IgE ratios, the estimated free IgE levels for both patients after more than a year of omalizumab treatment was less than their pre–omalizumab treatment IgE levels. Conclusions. These data suggest that omalizumab can be beneficial in treating ABPA and that measured IgE levels can still be useful in this context. Noting the pattern of IgE levels associated with ABPA exacerbations and with corticosteroid treatment may help both with achieving an IgE level appropriate for omalizumab treatment and with the interpretation of measured IgE changes associated with omalizumab treatment.

Objective To describe clinical associations of delirium in hospitalized patients and relationships to on admission presentation. Design Retrospective analysis of an administrative hospitalization database 1998–2007. Setting Acute care hospitalizations in the New York State (NYS). Measurements Four categories of diagnosis related group (DRG) hospitalizations were extracted from a NYS administrative database: pneumonia, congestive heart failure, urinary tract/kidney infection (UTI), and lower extremity orthopedic surgery (LEOS) DRGs. These hospitalizations were examined for clinical associations with delirium coding both on and after admission. Results Delirium was coded in 0.8% of the cohort, of which an on admission diagnosis was present in 59%. On admission delirium was strongly associated with dementia (adjusted odds ratio 0, 95%CI 5.8–6.3) and with adverse drug effects (ADEs) (adjusted odds ratio 4.6, 95%CI 4.3, 5.0). After admission delirium was even more highly associated with ADEs (adjusted odds ratio 22.2, 95%CI 20.7–23.7). The UTI DRG category had the greatest proportion of on admission delirium. However after admission delirium was more common in the LEOS DRG category. Over time, there was a greater increase in delirium proportions in the UTI DRG category, and an overall increase in coding for encephalopathy states (potential alternative delirium descriptors). Conclusion ADEs play an important role in delirium regardless of whether or not it is present on admission. While the finding that most delirium hospitalizations presented on admission suggests that delirium impacts more as a clinical admitting determinant, in-hospital prevention strategies may still have benefit in targeted settings where after admission delirium is more frequent, such as patients with LEOS. Copyright © 2010 John Wiley & Sons, Ltd.

Although it is known that women have a higher prevalence of asthma than men, it is not known whether and/or how gender differences in asthma severity are affected by age. Asthma hospitalization rates were compared for men and women in New York State from 1990 through 2006 between the ages of 20 and 84. Female and male hospitalization rates were calculated and characterized for the different age intervals. The ratio between female to male hospitalization rates were compared for different age groups. While males showed an overall linear increase in hospitalization rates with increasing age, women had a steeper increase in hospitalization rates followed by a slowing beginning at the ages between 40-54. The ratio of the female to male hospitalization rates was maximal in this age interval, with a mean ratio of 2.41 compared to 1.97 in other ages. For each year, this female to male ratio was consistently higher for the age range between 40 to 54 than for other ages, and this difference remained when admissions associated obesity, tobacco dependence, and chronic non-asthmatic pulmonary disease were excluded. Differences between the hospitalization rates for men and women vary by age. The gender gap in hospitalization rates appears to be maximal between the ages of 40 and 54. This may reflect age related asthma prevalence and/or severity differences between men and women.

Background Although childhood hospitalizations for asthma are common, there are few detailed temporal and demographic descriptions of these hospitalizations. Objective To relate temporal patterns of asthma hospitalization in young children to admission age, sex, comorbid infection, and race. Methods Retrospective analysis of 151,391 New York State hospitalizations with a principal diagnosis of asthma between January 1, 1990, and December 31, 2004, in children younger than 5 years. Admission patterns across time were related to admission age, sex, race, and comorbid diagnoses of common infections. Results Although the overall hospitalization rate decreased, it was still 63.8 per 10,000 in 2004. Higher hospitalization rates were consistently observed in children younger than 3 years, African Americans, and boys. Fall increases and summer declines in overall monthly hospitalization rates and monthly median ages exemplified the seasonality observed in the study population. However, admissions with concomitant common infections peaked in the winter, not fall months. Sex did not affect the observed seasonality. Compared with white patients, African Americans not only manifested more than 3-fold higher hospitalization rates but also more repeated hospitalizations. Conclusions The concurrent cyclical increases in median age and monthly admissions suggest that seasonal factors affecting older children may relate to fall increases in asthma admissions. These fall peaks are not accounted for by recognizable concomitant common respiratory tract infections. Understanding the basis for these seasonal variations may lead to prevention strategies that could decrease asthma admissions. Asthma hospitalizations in young children continued to be highly prevalent in New York State, especially in African American patients.

Background The epidemiologic characteristics of angioedema have not been well described in the United States, especially regarding hospitalization patterns. This fact is particularly relevant given the increased use of angiotensin-converting enzyme inhibitors, a known cause of angioedema. Objective To profile hospital admissions for angioedema in New York State with respect to age, sex, race, comorbidities, and year. Methods A database of all acute hospitalizations in New York State was examined between 1990 and 2003. Patient admissions that had the principal admission diagnoses of angioedema and other acute allergic disorders (anaphylaxis, urticaria, or allergy unspecified) were extracted. Characteristics of angioedema admissions were tabulated and compared with those of other acute allergic disease admissions with respect to demographic variables and comorbidities. Results There were 6,775 hospitalizations for angioedema during the study period. The number of angioedema hospitalizations increased progressively from 293 in 1990 to 636 in 2003, which exceeded the number of hospitalizations for anaphylaxis that year. African Americans constituted 42% of the angioedema admissions despite being less than 16% of the state population. The increase in hospitalizations for angioedema was most marked in patients with a diagnosis of hypertension, and for each study year, patients admitted with angioedema were consistently older than those admitted with other allergic disorders. Conclusions Angioedema has become the most common nonasthmatic acute allergic disorder that results in hospitalization in New York State. The predilection for angioedema occurring in patients with hypertension suggests that angiotensin-converting enzyme inhibitor use may play a role in this trend.

While intensive chemotherapy is recommended for the treatment of non-HIV related adult small non-cleaved lymphoma (SNCL), including Burkitt's and Burkitt-like lymphoma, optimal treatment for patients with HIV-associated SNCL is not known. We assessed remissions and survival in a cohort of 44 consecutive HIV positive patients diagnosed with SNCL at our hospital between June 2000 and November 2001 using chart and pathology data. Median follow-up, survival and survival at the median follow-up time were 4.5 months, 4 months and 49% respectively. Of this cohort 39% were complete responders (CR) and 36% were long-term lymphoma-free survivors. Two patients relapsed from CR. Short course intensive chemotherapy (McMaster) was administered to 23 patients; 17 received less intensive conventional combination chemotherapy; and four received single-agent chemotherapy or no treatment. In the McMaster group, 38% (9/23) achieved CR with no relapses. Seven patients (30%) died of toxicity compared with one (6%) in the less intensively treated group. Of the stage I patients, 75% (6/8) achieved long-term CR with half being treated conventionally. Conventional chemotherapy may be curative for early stage HIV-SNCL. In advanced disease, McMaster chemotherapy was found to be associated with substantial early mortality but was curative in a significant number of patients.

The impact of dementia on hospitalization discharge dispositions (HDDs) in the United States has not been quantified, and dementia prevalence in various hospitalization categories has not been detailed in recent years.To characterize hospitalizations prevalent with dementia, and to examine the relationship between dementia and HDDs.A retrospective cross-sectional study.2000 to 2012 National Inpatient Sample databases.Hospitalizations in persons ≥65 years old assigned to 1 of 12 Diagnosis Related Groups (DRGs) with a high number of dementia patients.None.The databases were queried for 12 DRGs (versions 18/24). Predictor effects for dementia on HDD categories were modeled adjusting for other defined comorbidities/covariates using logistic regression. Adjusted predictor effects of dementia on HDD in the DRG groupings were determined. Dementia prevalence and trends were assessed.Increasing proportions of dementia were noted in 4 DRGs studied. Dementia was strongly associated with being discharged to a nonhome setting. The most marked dementia effects were noted in DRGs 174 (gastrointestinal hemorrhage), 88 (chronic obstructive pulmonary disease), 182 (esophagitis/gastroenteritis), 138 (cardiac arrhythmias), 127 (congestive heart failure), and 89 (simple pneumonia and pleurisy), where there was at least a 76% reduction in the adjusted odds ratio (0.18-0.24) for home discharge. In contrast, DRGs 14 (stroke), 79 (respiratory infections/ inflammations), and 320 (kidney/urinary infections) had a smaller reduction in dementia-associated adjusted odds ratio (0.41-0.46) for home discharge. DRGs 79 and 320 had the highest proportions of dementia (10%).Dementia proportions in many hospitalization categories have increased. The variable effect of dementia on home discharge suggests that dementia has a differential influence on hospital discharge disposition depending on the DRG. These findings have implications for healthcare allocation and long-term care planning.

Anaphylaxis-related deaths in the United States have not been well characterized in recent years.We sought to define epidemiologic features and time trends of fatal anaphylaxis in the United States from 1999 to 2010.Anaphylaxis-related deaths were identified by using the 10th clinical modification of the International Classification of Diseases system diagnostic codes on death certificates from the US National Mortality Database. Rates were calculated by using census population estimates.There were a total of 2458 anaphylaxis-related deaths in the United States from 1999 to 2010. Medications were the most common cause (58.8%), followed by "unspecified" (19.3%), venom (15.2%), and food (6.7%). There was a significant increase in fatal drug-induced anaphylaxis over 12 years: from 0.27 (95% CI, 0.23-0.30) per million in 1999 to 2001 to 0.51 (95% CI, 0.47-0.56) per million in 2008 to 2010 (P .001). Fatal anaphylaxis caused by medications, food, and unspecified allergens was significantly associated with African American race and older age (P .001). Fatal anaphylaxis to venom was significantly associated with white race, older age, and male sex (P .001). The rates of fatal anaphylaxis to foods in male African American subjects increased from 0.06 (95% CI, 0.01-0.17) per million in 1999 to 2001 to 0.21 (95% CI, 0.11-0.37) per million in 2008 to 2010 (P .001). The rates of unspecified fatal anaphylaxis decreased over time from 0.30 (95% CI, 0.26-0.34) per million in 1999 to 2001 to 0.09 (95% CI, 0.07-0.11) per million in 2008 to 2010 (P .001).There are strong and disparate associations between race and specific classes of anaphylaxis-related mortality in the United States. The increase in medication-related deaths caused by anaphylaxis likely relates to increased medication and radiocontrast use, enhanced diagnosis, and coding changes.

Protein-losing conditions can result from infectious, autoimmune, hypersensitivity, inflammatory, and mechanical etiologies. While various complications, such as edema, nutritional deficits, and end-organ disease, result from protein loss from the circulation, infectious complications that are noted in humoral immunodeficiency usually are not increased to the same extent, despite sometimes profound hypogammaglobulinemia. When properly diagnosed and managed, protein-losing conditions can be significantly ameliorated with both laboratory and clinical improvement.

Study Objective: Although the addition of H 2 blockers to H 1 antagonists has been promoted for use in anaphylaxis, there have been no large studies establishing the advantage of this approach in treating acute allergic syndromes. In this study we tested the hypothesis that combined H 1 and H 2 blockage results in improved outcomes in patients treated for acute allergic syndromes compared with treatment with H 1 blockade alone. Methods: In a randomized, double-blind, placebo-controlled trial, 91 adult patients with acute allergic syndromes were treated with either 50 mg of diphenhydramine and saline solution (control group) or with 50 mg of diphenhydramine and 50 mg of ranitidine (active group). These patients were treated with parenteral administration. Patients were recruited from an emergency department at an urban academic medical center. The primary endpoints were resolution of urticaria, angioedema, or erythema at 2 hours after protocol treatment. Areas of cutaneous involvement, heart rates, blood pressures, respiratory findings, and symptom scores were also assessed at baseline, 1 hour, and 2 hours. Results: There were significantly more patients without urticaria at 2 hours among the patients in the active group compared with those in the control group. Both groups had similar proportions of urticaria at baseline. Logistic regression models to predict resolution of urticaria, which accounted for baseline urticarial involvement, showed odds ratios in favor of the active group treatment. Similar findings were observed when the absence of both urticaria and angioedema was considered as the dependent variable. There was not a significant difference between the 2 groups with regard to the absence of erythema or angioedema (irrespective of the presence of urticaria) at 2 hours. Blood pressure and symptoms did not show differences between the 2 groups over time. Lower heart rates were observed 1 hour after treatment in the active treatment group (mean reduction 10 beats/min) compared with those found in the placebo group (mean reduction 6 beats/min). Conclusion: These data show that adding H 2 blockers to H 1 antagonists results in additional improvement of certain cutaneous outcomes for patients presenting with acute allergic syndromes. These findings favor the recommendation for using combined H 1 and H 2 antihistamines in acute allergic syndromes. [Lin RY, Curry A, Pesola GR, Knight RJ, Lee H-S, Bakalchuk L, Tenenbaum C, Westfal RE. Improved outcomes in patients with acute allergic syndromes who are treated with combined H 1 and H 2 antagonists. Ann Emerg Med. November 2000;36:462-468.]

Background: Emergency department visits for acute allergic reactions are common. Although the diagnosis and classification of these allergic reactions is primarily empiric, it is not always clear whether certain signs and symptoms constitute systemic mediator release syndromes, such as anaphylaxis, and thus may warrant more aggressive therapy or follow-up. Objective: We sought to determine associations between various clinical signs and symptoms with both plasma histamine levels and serum tryptase levels in adult patients presenting to an emergency department with acute allergic syndromes. The clinical correlates of raised β-tryptase levels were also investigated. Methods: Ninety-seven adult emergency department patients were prospectively studied by using a questionnaire, physical examination, and serum-plasma sampling. Plasma histamine and serum total and β-tryptase levels were determined. Clinical groupings were compared for mediator levels by using simple and multivariate analysis. Results: Elevated levels of plasma histamine (>10 nmol/L) and serum total tryptase (>15 ng/mL) were observed in 42 and 20 patients, respectively. Detectable β-tryptase (≥1 ng/mL) was observed in 23 patients, including 15 of the patients with elevated total tryptase levels. Suspected food allergy incidences and the duration of reaction were similar in patients with increased histamine levels and in patients with increased tryptase levels. Increased total tryptase levels, histamine levels, or both were observed in some patients who did not have airway, cardiovascular, or abdominal signs. Histamine levels correlated better with clinical signs than tryptase levels. Histamine elevations (>10 nmol/L) were observed more frequently in patients characterized by the following clinical signs in univariate analysis: the presence of urticaria, more extensive erythema, abnormal abdominal findings, and wheezing. Total tryptase increases were observed more frequently only in patients with urticaria. Histamine levels correlated with initial heart rates. In multivariate analysis the extent of urticaria was the best single predictor of plasma histamine levels and of either an elevated histamine or tryptase level. Detectable β-tryptase levels were observed in some patients who had neither elevated total tryptase nor elevated histamine levels. Unlike patients without detectable β-tryptase levels, patients who had detectable β-tryptase levels had a significant correlation between total tryptase and histamine levels ( P Conclusions: Raised histamine and, less commonly, raised tryptase levels are observed in almost 50% of patients presenting to emergency departments with acute allergic reactions. Some cases associated with systemic mediator release do not have classical features of severe anaphylaxis, such as hypotension or tachycardia. The lack of total tryptase elevations in many patients with elevated plasma histamine levels suggests basophil involvement. The clinical utility of β-tryptase determinations in the evaluation of acute allergic reactions needs further study. (J Allergy Clin Immunol 2000;106:65-71.)

Background We had previously observed that changes in nasal cytology were associated with specific clinical patterns in cross-sectional studies of allergy clinic patients. In the present study, we sought to determine whether specific cytologic changes occurred with antiinflammatory therapy in a controlled setting in a prospective manner. Objective To examine changes in nasal leukocytes and epithelial cells associated with topical beclomethasone treatment in allergic rhinitis patients. Specifically we tested the hypothesis that number of nasal leukocytes relative to epithelial cell numbers are altered by topical beclomethasone treatment. Methods Adult volunteers (n=26) with symptoms consistent with allergic rhinitis and positive aeroallergen skin tests were enrolled for treatment with either beclomethasone or placebo nasal spray. Sprays were allocated in a double-blind manner and were prescribed to be administered over a 2-week period. Baseline quality of life, nasal cytograms, and mucosal physical appearance scores were obtained at baseline and at the end of the treatment period. Changes in various nasal leukocytes and epithelial cell types were analyzed for association with active treatment using bivariate and multivariate analysis. Results Total leukocytes showed greater decreases with beclomethasone treatment than with placebo. Total epithelial cells on the other hand showed an increase with active treatment compared with placebo treatment. In multivariate analysis, the changes in both total leukocytes and total epithelial cells showed independent associations with beclomethasone treatment. Combining these two variables into a single leukocyte per epithelial ratio resulted in variable with values showing a significant decreases associated with beclomethasone treatment compared with placebo treatment ( P = .03). Conclusions The administration of topical corticosteroids results in decreases in total leukocytes and this decrease is of enhanced significance when adjusted for the quantities of associated epithelial cells. Further investigation relating to the quantities of total nasal leukocytes in inflammatory nasal diseases may be helpful in gauging disease activity and monitoring treatment modalities.

Study objective: Corticosteroids are thought to exert their physiologic effects in asthma over the course of several hours. In this study we tested the hypothesis that intravenous methylprednisolone improves airflow in a shorter time frame (2 hours) in adults with acute asthma. Methods: In a randomized, double-blind, placebo-controlled trial, 56 adult asthmatic patients with peak expiratory flow rates (PEFRs) less than 50% predicted after an initial albuterol aerosol treatment were studied. These patients were randomly assigned to treatment with either 125 mg of intravenous methylprednisolone or an equivalent volume of normal saline solution (placebo). Patients were also treated with identical schedules of nebulized ipratropium and albuterol. Patients were recruited from an emergency department at an urban academic medical center. The primary endpoints were changes in PEFR and in percent predicted PEFR over time. PEFRs were assessed at baseline and at 1 and 2 hours. Heart rate changes over time and the proportion of admissions in the 2 groups were also compared. Results: The increases in PEFR and percent predicted PEFR over time were both significantly greater in the methylprednisolone treatment group ( P =.002 and P =.005, respectively). The increases in geometric mean peak flow at 60 and 120 minutes were 79 and 96 L/min for the methylprednisolone group and 54 and 68 L/min for the placebo group. There was also a significantly different change in heart rates with time between the methylprednisolone and placebo groups ( P =.029), with the placebo group showing a moderate increase in heart rate over time. Although the proportion of patients admitted for status asthmaticus was less in the methylprednisolone treatment group (8/30) compared with the placebo group (10/26), this difference in proportions (–.118, 95% confidence interval –.363 to .127) was not significant. Conclusion: These data suggest that use of corticosteroids should be considered relatively early in the treatment of patients with acute asthma in whom initial bronchodilator therapy fails to produce an adequate response. [Lin RY, Pesola GR, Bakalchuk L, Heyl GT, Dow AM, Tenenbaum C, Curry A, Westfal RE: Rapid improvement of peak flow in asthmatic patients treated with parenteral methylprednisolone in the emergency department: A randomized controlled study. Ann Emerg Med May 1999;33:487-494.]

In many urban settings, a significant proportion of hospital services are directed toward HIV-related illnesses. Asthma, however, has long been associated with a high rate of hospitalization for patients with exacerbations of disease. It is therefore not surprising or unusual to encounter patients who have both HIV infection and asthma. To the allergist, HIV-infected patients have unique problems relating to hypersensitivity. To the HIV specialist, the differential diagnosis for obstructive pulmonary disease is crucial to establish for patients with bronchospasm of new onset. For any physician who treats patients with both disorders, an understanding of drug interactions is essential for proper management of patients, whose therapy is constantly being revised and updated. This article reviews special considerations in the diagnosis and treatment of patients with asthma and HIV infection.

Decreases in effective capillary blood flow during septic shock may be related to changes in neutrophil rheology which contribute to microvascular occlusion. The purpose of this study was to examine neutrophil deformability, adherence, and aggregation in patients with severe sepsis and septic shock. Neutrophils were isolated from six patients with septic shock (SS), 12 patients with severe sepsis (S), six noninfected critically ill patients (CINS), and nine normal volunteers (N). Neutrophil deformability was determined by examining filtration through 5-microm filters. Neutrophil aggregation was measured by aggregometry and leukergy. Neutrophil adherence was examined by assessing the binding of latex beads to neutrophils. Patients with S and SS demonstrated decreased neutrophil filterability of 27 +/- 2% and 16 +/- 5%, respectively (p0.01), in comparison with N subjects, 55 +/- 4% and CINS patients, 58 +/- 2%. Preincubation of neutrophils from S and SS patients with cytochalasin D significantly increased the percent filtration of neutrophils. Neutrophil aggregation, measured by aggregometry, was increased in SS patients, 16 +/- 4% (p0.01) compared with N subjects, 1 +/- 0.2% and CINS patients, 1 +/- 0.2%. Incubation of neutrophils of SS patients with anti-CD11/CD18 significantly increased the filtration of isolated neutrophils to 46 +/- 3% (p0.01) and decreased aggregation to 7 +/- 2%. Neutrophil adherence was not increased in S or SS patients. These observations suggest that neutrophil deformability is decreased in patients with S and SS. Increased leukoaggregation may also contribute to decreased filterability of neutrophils in SS patients. These mechanisms may play a role in impaired microvascular flow in septic shock.

Since angiotensin-converting enzyme (ACE) inhibitors became common treatments, there have been increasing reports of angioedema (AE). AE hospitalization (AEH) trend data in the new millennium are limited. This study calculates hospitalization rates for AEs and describes clinical characteristics of AEHs in the United States, especially as related to specific adverse drug effects (ADEs). The National Inpatient Samples 2000-2009 were queried for AEHs to calculate hospitalization rates and to examine for associations with specified ADEs, certain comorbidities, and demographic features. AEHs requiring intubation or tracheostomy were also examined for associations. There was a significant increase in the AEH rates (3.4 per 10(5) to 5.4 per 10(5)) over the study period (p < 0.0001) and the hospitalization rates for African Americans (AAs) were consistently higher. Throughout the study the proportions of AEH coding any ADEs, or an ADE due to a cardiovascular (CV) or antihypertensive (aHTN) drug increased over time. By 2009, 61.7% AEHs coded an ADE. Of these, 58.7% were caused by CV or aHTN drugs. In AEHs, having an ADE from a CV or aHTN medication had the strongest adjusted associations with hypertension and renal disease as well as with alcohol-related disorders. In AEHs, intubation/tracheostomy had the strongest ADE associations related to CV or aHTN medication (adjusted odds ratio, 1.4; 95% CI, 1.3, 1.6). AEHs continue to increase, but this can only be partially attributed to ACE inhibitor usage. Intubation/tracheostomy appears to be greater in AEHs with ADE due to CV/aHTN drugs. Alcohol-related disorders may have a role in ACE inhibitor-associated AEH.

OBJECTIVE To determine the relationships between cytokine concentrations and alterations in leukocyte functional antigen expression in sepsis. DESIGN Prospective, cross-sectional study. SETTING Respiratory, coronary, and medical intensive care units in a university hospital. PATIENTS Forty subjects consisting of: a) patients with severe sepsis, b) patients with sepsis, c) critically ill nonseptic patients, and d) normal controls. INTERVENTIONS None. MEASUREMENTS Plasma concentrations of interleukin (IL)-1 beta, IL-6, IL-8, IL-10, interleukin-1 receptor antagonist (IL-1Ra), and tumor necrosis factor (TNF)-alpha were determined by enzyme-linked immunosorbent assay (ELISA). Peripheral blood monocyte HLA-DR and CD14 expression and neutrophil CD11b expression were determined by flow cytometry. Measurements were taken within 24 hrs of admission to the intensive care unit and/or clinical presentation. MAIN RESULTS Significantly increased plasma IL-6, IL-8, IL-10, and TNF-alpha concentrations were observed in the severe sepsis group compared to normal controls. Increases in IL-1Ra were not significant. Monocyte HLA-DR expression, significantly decreased in patients with severe sepsis, was correlated both with IL-6 (p < .005) and IL-8 concentrations (p < .001). Both of these cytokines had close correlations to Acute Physiology and Chronic Health Evaluation (APACHE) II scores which were also correlated with monocyte HLA-DR. Neutrophil CD11b, which was increased in all infected patients, was significantly correlated with the ratio between IL-1 and IL-1Ra concentrations (p < .001). The percent of CD14+ monocytes was lowest in patients with severe sepsis and showed a significant covariate effect from IL-8 concentrations (p < .001). CONCLUSION These findings suggest that the expression of specific functional molecules on peripheral blood leukocytes is variably related to the net production of certain monokines in sepsis.

Hospitalization is a significant risk for the elderly (65 years or older) and is the largest component of U.S. health care spending accounting for more than 35% of health care dollars (Folland, Goodman, & Stano, 2001). It is estimated that by 2030, the number of elderly will be more than double to 70 million (Centers for Disease Control and Prevention [CDC], 2010). Because 20% of our future population will be elderly with many suffering from chronic diseases, health care and hospital costs for this group are expected to increase substantially (Lamont, Sampson, Matthias, & Kane, 1983). Compared with the general population and driving these predictions, the elderly have significantly higher rates of hospital admission and readmissions and are responsible for most hospitalization days and expenses (Parker, 2005; Victor, Healy, Thomas, & Seargeant, 2000). In the United States (Elixhauser, Yu, Steiner, & Bierman, 2000) and the United Kingdom (National Health Service Information Centre Hospital Episode Statistics, 2006), the elderly account for approximately 36% of hospital admissions; in Australia, they account for 52% (Karmel, Lloyd, & Hales, 2007). In addition to the frequency and expense of hospitalization during inpatient stays, many elderly experience deconditioning and functional decline that affects their future independence, autonomy, and quality of life (Covinsky et al., 2003; Creditor, 1993; Hoenig & Rubenstein, 1991). Published research shows that of 60 functionally independent individuals 75 years or older admitted to the hospital from their home for acute illness, 75% were no longer independent on discharge including 15% who were discharged to nursing homes (Creditor, 1993; Lamont et al., 1983). Reducing length of stay and aggressive discharge policies have become important features of the hospital experience, yet readmission following discharge has become a familiar and frustrating problem and may result from avoidable hospital, and/or community service failures (Colledge & Ford, 1994). Prior hospitalizations increase the probability of future hospitalizations and by identifying and managing patient-level risk factors for rehospitalization, patients' health care and quality of life would improve, whereas morbidity, mortality, costs, and the rate of future hospitalizations would decrease (Colledge & Ford, 1994; Creditor, 1993). Developing a predictive model for rehospitalization risk is one method to describe the factors associated with elderly rehospitalization, identify those at risk, and target individuals for appropriate preventive interventions (Blackman, Kamimoto, & Smith, 1999). Such a model may also predict hospital utilization costs more accurately allowing hospitals to better anticipate staffing and resource needs to efficiently serve elderly patients. However, research has shown that a risk factor must have a much stronger association with the outcome than we ordinarily see in etiologic and epidemiologic research if it is to provide a basis for prediction in individual patients. Despite the strong association between the risk factor and the outcome, it does not follow that the risk factor provides a basis for an effective prediction rule for individual patients (Ware, 2006). OBJECTIVES The purpose of this study is to identify demographic and clinical factors associated with nonelective, all-cause rehospitalization within 120 days of an index admission in the elderly. METHODOLOGY Our sampling frame included all patients 65 years or older admitted to Saint Vincent Catholic Medical Centers (SVCMC) of New York for nonelective admissions between June 21, 2003, and June 20, 2004. For all patients admitted more than once during the study period, we counted each admission as unique. To avoid the possibility of seasonal variation on our sample, we employed a random proportional stratified sampling strategy using the date of admission to stratify the sample by season. …

Since the 1999 US Food and Drug Administration (FDA) warning of renal failure/dysfunction associated with intravenous gammaglobulin (IVIg), there has been a movement towards developing safer, more convenient formulations. Until now, the scope of renal failure associated with IVIg, has not been well described. The FDA Adverse Event Reporting System (AERS) from 2004 through 2009 was examined for renal impairment reactions due to IVIg and associated demographic features, comorbidities and indications. Anaphylaxis cases associated with IVIg administration were used as a comparison group. There were 90 renal impairment cases associated with IVIg administration. Neuromuscular disorders (33/37%) and hematologic disorders (32/36%) were the predominant treatment indications. When reported anaphylaxis versus renal impairment due to IVIg was examined as a binary outcome in logistic regression modeling, renal impairment was predicted by sucrose presence, increasing age and non-hypogammaglobulinemic indications. Of the 34 hemodialysis cases, the excipient was known in 28 and all but 1 consisted of sucrose. IVIg containing sucrose was used in 33 of 48 nonhemodialysis cases. More hemodialysis cases also had diabetes mellitus. When the interval between renal impairment and the first IVIg infusion was determined, the renal impairment was reported by the second day in 43.3% of cases, and between 3 and 5 days in 41.7% of cases. Despite an evolution in clinical usage and formulations, renal impairment after IVIg administration continues to be reported. Sucrose as the excipient in IVIg plays a major role, but other factors are also important. These findings have implications in the management of patients treated with IVIg.

Study objectives: To compare bronchodilation, chronotropic effects, and side effects of the same dose of nebulized albuterol when given by either intermittent or continuous administration. Design: A randomized assignment of patients to one of the two methods of albuterol nebulization. Setting: Adult emergency department in an urban public hospital. Type of participants: Adult patients with acute exacerbations of asthma. Interventions: Administration of 30 mg albuterol given over 110 minutes by either continuous or intermittent aerosolization. Measurements: FEV 1 , forced vital capacity, heart rate, and systolic and diastolic blood pressures were measured immediately before treatment and then hourly for two hours. Side effects, symptoms, subsequent admission, and discharge also were noted. Main results: An overall significant decrease in heart rate was observed, indicating the lack of significant chronotropic effects with this dose of albuterol. Both treatments resulted in significant spirometric improvement without a significant treatment difference for the entire group. A difference, however, was found in the relative rates of FEV 1 improvement with the two treatments depending on whether patients had an initial FEV 1 less than or more than 50% predicted ( P = .05). A secondary analysis on patients with an initial FEV 1 less than percent predicted demonstrated a higher rate of percent predicted FEV 1 increase with the continuously nebulized albuterol group ( P = .03). Conclusion: This study demonstrates that albuterol can be given safely at this dose by either intermittent or continuous nebulization. Future studies should examine whether continuous nebulization has a reproducible advantage over intermittent nebulization in patients with more severe obstruction.

To evaluate the role of cellular activation markers and functional surface molecules in sepsis, specific immunophenotypes on peripheral blood leukocytes were studied in 40 subjects consisting of the following: (1) patients with septic shock; (2) patients with sepsis; (3) critically ill nonseptic patients; and (4) normal control subjects. These assays included phagocyte adhesion molecule CD11b expression, monocyte receptors HLA-DR and CD14, and lymphocyte activation markers IL-2R and HLA-DR. Patients with septic shock and sepsis had significantly increased neutrophil CD11b expression compared with normal subjects. Neutrophil HLA-DR expression did not significantly differ between groups. Monocytes from septic shock patients had significantly less HLA-DR expression than normal subjects and diere was a trend toward a lower proportion of gated monocytes that expressed CD14 in septic shock patients. Septic shock patients had no significant increases in IL-2R or HLA-DR expression on CD3 lymphocytes compared with control subjects, but they had significantly lower numbers of total, CD3, CD4, and CD8 lymphocytes and a higher prevalence of anergy. Septic shock patients manifested an increase in neutrophil CD11b expression that may play a role in organ injury. In contrast, a more specific decrease in monocyte expression of functional antigens is also observed in patients with septic shock that may have implications for immunologic defense mechanisms.

To study the feasibility of using high-dose continuously aerosolized albuterol aerosol in adults, seven adult asthmatic patients were treated eight times with 0.4 mg/kg/h albuterol delivered by continuous nebulization over 4 h. One patient withdrew at 3 h after supraventricular tachycardia developed. This subsided promptly on discontinuing albuterol therapy. Heart rate increases were observed in six of eight treatments and serum albuterol levels at the end of treatment were greater than 25.0 ng/ml in all but one treatment. A mean increase in heart rate of 16.3 percent was observed for the entire group. Of the treatments with elevated (> 25.0 ng/ml) serum albuterol levels, a significant cumulative increase in heart rate was observed with time. A significant improvement of FEV1 was observed (p = 0.0025) with a net increase of 36.8 percent. These data suggest that high-dose continuously aerosolized albuterol treatment in some adult asthmatics can result in markedly elevated serum albuterol levels and potential cardiac stimulation despite spirometric improvement.

Anaphylaxis incidence rates and time trends in the United States have been reported using different data sources and selection methods. Larger studies using diagnostic coding have inherent limitations in sensitivity and specificity. In contrast, smaller studies using chart reviews, including reports from single institutions, have better case characterization but suffer from reduced external validity due to their restricted nature. Increasing anaphylaxis hospitalization rates since the 1990s have been reported abroad. However, we report no significant overall increase in the United States. There have been several reports of increasing anaphylaxis rates in northern populations in the United States, especially in younger people, lending support to the suggestion that higher anaphylaxis rates occur at higher latitudes. We analyzed anaphylaxis hospitalization rates in comparably sized northern (New York) and southern (Florida) states and found significant time trend differences based on age. This suggests that the relationship of latitude to anaphylaxis incidence is complex.

The incidence and pattern of delirium recorded in a broad spectrum of American hospitalizations has not been well described. The National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project is an administrative database of hospitalizations in the US that affords an opportunity to examine for International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes relating to delirium. To examine the prevalence of delirium diagnoses and associated clinical factors, including adverse drug effects, in a broad spectrum of hospitalizations in the US. Delirium was grouped into three categories: drug-induced delirium, dementia-associated delirium, and non-dementia, non-drug (NDND). Hospitalizations during the years 1998–2005 in the NIS databases were examined. These databases represent samples of hospitalizations that allow for national prevalence estimates. ICD-9 codes for drug-induced, dementia-associated and NDND delirium were identified in the hospitalizations for each year. Delirium tremens was not considered in this classification, and paediatric and psychiatric admissions were excluded. Yearly prevalence for drug-induced, dementia-associated and NDND delirium were tabulated, and time trends were analysed with negative binomial regression. A hospitalization subset cohort with urinary tract/kidney infection, pneumonia, heart failure and lower extremity orthopaedic surgery diagnosis-related group categories was also analysed for clinical associations with the presence of the three categories of delirium using multinomial logistic regression. ICD-9 E codes (external causes of injury) constituting adverse drug effects were identified and considered as clinical predictors. Delirium was recorded in 1 269 185 (0.54%) non-psychiatric adult hospitalizations during the study years. Whereas the overall prevalence of dementia-associated delirium and NDND delirium decreased over time, drug-induced delirium prevalence increased (p

Background Anaphylaxis associated with omalizumab treatment is a growing concern. The broader context in which omalizumab-associated allergic reactions occur has not been well described. Objective To identify and characterize recently reported anaphylactic reactions associated with omalizumab administration. Methods The US Food and Drug Administration Adverse Event Reporting System reports between January 1, 2007, and June 30, 2008, were queried for new reactions primarily suspected to be due to omalizumab. Reaction characteristics were analyzed for a reaction descriptor of anaphylactic or anaphylactoid shock or reaction and for dermal, respiratory, cardiovascular, and gastrointestinal reaction descriptor terms that in combination could be interpreted as constituting anaphylaxis. Associated narratives for these reports were obtained and were examined further. Results There were 85 cases with an anaphylaxis descriptor and 33 cases without a descriptor of anaphylaxis but with multisystem allergic reactions (mostly respiratory and skin or mucosal) that were consistent with anaphylaxis. Of these 118 cases, 32 were after the first dose and 14 were after the second dose of omalizumab. Seventy-seven of the 118 cases were categorized as requiring hospital admission or prolongation, had life-threatening reactions, underwent treatment with epinephrine or corticosteroids, or had omalizumab treatment withheld or discontinued. Nineteen of the 118 reactions were described as occurring within 1 hour of omalizumab injection. Conclusions Allergic reactions to omalizumab continue to be reported. Some patients not labeled as having anaphylaxis have multisystem allergic reactions consistent with anaphylaxis, raising questions about the adequacy of the Food and Drug Administration categorizations. The characteristics of these patient reports point toward a spectrum of systemic allergic reactions associated with omalizumab use.

BACKGROUND: This study sought to define the incidence, economic impact, and nature of adverse drug effects (ADEs) related to antibiotics in pneumonia hospitalizations in the US. METHODS: Adult pneumonia hospitalizations were tabulated in statewide (New York) and national databases, respectively, from 2000 through 2005. The incidences of antibiotic related ADEs were determined by identifying antibiotic specific e-codes (external cause of injury codes). The modeled effect of the presence of antibiotic ADEs on length of stay (LOS) and total charges were also calculated. ADEs due to specific antibiotic classes, and the presence of certain cutaneous allergic and gastro-intestinal manifestations commonly attributable to ADEs, were tabulated. RESULTS: ADEs related to antibiotics were reported in a small but consistent proportion (0.45–0.6%) of pneumonia hospitalizations in both cohorts. The most common identifiable antibiotics class associated with ADEs was the cephalosporins followed by penicillins and quinolones. Over 60% of the ADEs were associated with reported dermal/allergic and gastro-intestinal manifestations. Multivariate analysis adjusting for co-morbid conditions and demographic factors showed that the presence of an antibiotic adverse drug effect was a significant independent predictor of greater LOS and higher total hospital charges. CONCLUSIONS: ADEs related to antibiotics can be identified by analyzing administrative hospitalization databases. For pneumonia, a common hospitalization diagnosis, there is a defined calculable impact and incidence of antibiotic associated adverse effects. This should be considered in planning hospitalization resource allocation and in developing equitable hospitalization reimbursements. Identifying the nature of antibiotic associated adverse effects may facilitate the development of stratagies for reducing these adverse effects. Journal of Hospital Medicine 2009;4:E7–E15. © 2009 Society of Hospital Medicine.

Results A 78-year-old female with end stage renal disease on hemodialysis via arteriovenous fistula, diabetes mellitus, hypertension, and hyperlipidemia was evaluated for recurrent fever and rash after receiving CM for a fistulogram. She had received prednisone prophylactically for reactions associated with ioxilan administration on two prior fistulograms. These reactions consisted of diffuse erythematous rash preceded by fever that started 2-4 hours after contrast administration and lasted several days. After receiving pretreatment with prednisone and diphenhydramine, she received her most recent dose of ioxilan (70 mL) for a fistulogram and developed fever and diffuse erythematous rash (2 and 4 hours post injection, respectively). The fever lasted 3 days and the rash subsequently desquamated involving the arms, trunk, neck and face. Her skin fully re-epithelialized 2 weeks later. She had negative skin prick tests and negative patch tests to ioxilan, iothalamate, and iohexol. She subsequently underwent challenge with 10 mL of intravenous iothalamate and was observed for 4 hours without incident. Later, she underwent fistulogram with iothalamate and tolerated it without adverse reactions. Conclusions Hypersensitivity reactions are generally much less common with non-ionic CM compared to older ionic CM. However, for DHRs, reaction rates between ionic CM and non-ionic CM are similar. Successful administration of different CM selected based on skin tests has been reported for patients with previous DHRs to specific CM. In our case, skin testing was non-diagnostic, and we hypothesized that the distinct chemical structures of these agents would make immunological cross-reactivity unlikely. Indeed this patient who was repeatedly reactive to the non-ionic lowosmolal CM ioxilan, subsequently tolerated the ionic hyperosmolal CM iothalamate. We conclude that different epitopes involved in DHRs to CM may be suggested based on differing chemical structure and ionicity. Further research is needed regarding both the cross-reactivity and cross-tolerance of various CM in DHRs, especially in CM skin-test negative patients.

The present study describes the cardiovascular responses to epinephrine (Epi) given into the arm, in adult patients with acute allergic reactions, and the differential responses to subcutaneous (SC) and intramuscular (IM) administration. Sixty-three adult patients were treated with Epi administered SC or IM after H1 and H2 receptor blockade. Heart rate and blood pressure (BP) were then measured for 20 minutes. Changes in heart rate and BP variables were analyzed. Pulse pressure and systolic BP showed increases with time. Diastolic BP also showed a modestly decreasing values over time. Heart rates did not change. Time-related changes between IM and SC Epi treatment were not observed. Sex influenced timed BP values and a significant sex by time effect was observed. In subset analysis, only male patients showed an overall time effect for BP variables, especially pulse pressure. In conclusion, adults with acute allergic syndromes treated with arm-injected Epi show a modest but definite increase in pulse pressure and systolic BP. This pattern is observed more in males. Heart rate and blood pressure differences between IM and SC arm-injected Epi treatments do not appear to be significant.

Molds have been linked epidemiologically to asthma as a key aeroallergen in several studies. Other allergens such as cockroach have been linked to asthma in New York City (NYC). To our knowledge, however, the pattern of mold hypersensitivity has never been examined systematically in the NYC area. Thus, we sought to determine the association between mold hypersensitivity and asthma in a large group of ambulatory patients evaluated for allergic disease for the years 1993 through 2001 at a single medical center. Serological testing for mold-specific immunoglobulin E (IgE) as well as IgE specific for other aeroallergens was performed and the associations between allergen-specific IgE and the presence of asthma were examined using bivariate and multivariate analysis. Factor analysis showed that three distinct groupings of aeroallergen-specific IgE existed within the panel of allergens used. Group 1 consisted of cat dander and dust mites (Dermatophagoides farinae). Group 2 consisted of tree, grass, and ragweed pollen. Group 3 consisted of the Deuteromycetes molds, Alternaria tenuis, Aspergillus fumigatus, and Cladosporium herbarum. Patients with asthma had a highly significant increase in the incidence of hypersensitivity to cat/dust mites and to the molds. Multivariate analysis showed that the presence of hypersensitivity to either A. tenuis or C. herbarum had a significant independent association with asthma after adjustment for cat/dust mite hypersensitivity and after adjustment for other clinical factors. On the other hand, pollen hypersensitivity was not associated independently with asthma. Mold hypersensitivity was strongly correlated with hypersensitivity to cat or dust mites in patients who did not have asthma but not in patients who did have asthma. In the NYC area, recent pollen and spore counts show that mold spores are measurable in at least 75% of the year. Thus it is conceivable that mold hypersensitivity plays a contributing and independent role in initiating or perpetuating the allergic response in patients with asthma in the New York area.

Testing for tree pollen hypersensitivity typically requires the use of several tree pollens. Identifying patterns of cross-sensitivity to tree pollens could reduce the number of trees used for testing. The goal of this study was to relate reported tree pollen levels to hypersensitivity patterns. Three hundred seventy-one allergy patients were tested serologically for hypersensitivity toward prevalent tree pollens in the surrounding New York area over the years 1993-2000. Specific tree pollens that were examined included oak (Quercus alba), birch (Betula verrucosa), beech (Fagus grandifolia), poplar (Populus deltoides), maple (Acer negundo), ash (Fraxinus americana), hickory (Carya pecan), and elm (Ulmus americana). Statistical analysis of the levels of hypersensitivity was performed to identify correlations and grouping factors. Pollen levels, obtained from published annual pollen and spore reports, were characterized and related to the prevalence of hypersensitivity for the various trees. The highest prevalence of hypersensitivity (scoreor = class 1) was for oak (34.3%), birch (32.9%), and maple (32.8%) tree pollens. Lower prevalences were observed for beech (29.6%), hickory (27.1%), ash (26%), elm (24.6%), and poplar (20.6%) trees. Significant correlations were observed between oak, birch, and beech radioallergosorbent test scores. Factor analysis identified two independent pollen groups with oak, birch, and beech consisting of one group and the other five tree pollens constituting the other group. Peak pollen counts clearly were highest for oak, birch, and maple trees. The peak pollen counts corresponded roughly to seropositivity prevalences for the tree pollens. When elm, poplar, and beech test scores were not used to identify patients who were allergic to tree pollens, only 1 of 106 patients with any positive tree radioallergosorbent test score was missed. It is concluded that in the New York City area, hypersensitivity to tree pollens most often is manifested with allergy to oak, birch, and maple tree pollens. Identifying beech, poplar, and elm hypersensitivity adds little toward identifying patients who are allergic to tree pollens. This may relate in part to cross-reactive epitopes. These data suggest that these three trees can be eliminated from testing with only a1% loss of sensitivity.

Background Elevations of interleukin 6 (IL-6) have been described in drug-induced anaphylaxis. Although IL-6 is well known to stimulate an acute phase response, profiling acute phase protein levels, such as C-reactive protein (CRP), has, to our knowledge, never been performed in patients with acute allergic reactions. Objective To examine the pattern of IL-6 and CRP levels in patients with acute allergic reactions and to relate these to relevant clinical and laboratory parameters. Methods Plasma CRP and serum IL-6 levels were determined in 85 adult emergency department patients. These patients had been previously studied with questionnaires, physical examinations, and histamine/tryptase levels. Clinical and historical features were related to CRP and IL-6 levels. CRP and IL-6 levels were also examined for relationships with histamine and tryptase levels. Results CRP and IL-6 levels were significantly correlated with one another in the study patients (Spearman ρ = 0.36, P = 0.0008). Similar to histamine levels, IL-6 levels were significantly correlated with the extent of erythema manifested by the study patients. The extent of erythema was independently predicted by both IL-6 and histamine levels. Histamine levels were negatively correlated with CRP levels (Spearman ρ = −0.32, P = 0.003). Unlike histamine levels, IL-6 and CRP did not show significant relationships with the extent or presence of urticaria/angioedema or the presence of wheezing. IL-6 levels were correlated with the duration of symptoms before serologic sampling. An inverse correlation was observed between IL-6 levels and mean arterial blood pressure. Multivariate modeling showed significant independent effects from mean arterial pressure, duration of symptoms, erythema extent, and age in predicting IL-6 levels. Tryptase levels were higher in patients whose IL-6 levels were >20 pg/mL. Conclusions CRP and IL-6 levels are not simple surrogate markers for histamine or tryptase release by mast cells or basophils in acute allergic reactions. Increasing IL-6 levels relate to greater erythema extent, lower mean arterial blood pressure, and a longer duration of symptoms. It would be interesting to speculate that CRP and IL-6 increases characterize a late-phase response in immediate hypersensitivity reactions. In this perspective, the inverse relationship between CRP and histamine levels could be explained. As histamine levels are waning, CRP levels are increasing. Timed studies for histamine and CRP/IL-6 levels in allergic reactions are necessary to confirm this hypothesis.

To identify characteristics associated with mortality in HIV-infected patients with bacteremia, 88 bacteremic episodes in 80 HIV-infected patients were prospectively identified over a 5-month period and observed for 30 days. Demographic, clinical, laboratory, and radiologic data were collected. Mean and median age was 41 years. Most study subjects were homosexual men. Median CD4 count was 20 cells/mm3. Gram-positive organisms predominated (65%). The most common source of bacteremia was intravascular catheters (45%). Overall mortality was 30%. A history of malignancy, three or more opportunistic infections, shock, low hemoglobin, source of bacteremia other than an intravascular catheter, resistance to therapy, and a second bacteremic episode during the study period, were all found to be independent predictors of mortality. In this cohort of HIV-infected patients, most of whom were severely immunosuppressed, several factors were found to be significantly and independently associated with mortality.

To examine the mechanisms contributing to decreased microvascular blood flow in cardiogenic shock by comparing patients with cardiogenic shock with critically ill controls and with patients with septic shock.Prospective, consecutive entry of patients meeting the criteria for septic shock, cardiogenic shock, and critical illness without coexisting infection or shock.University hospital, medical intensive care unit, coronary care unit, and respiratory care unit.Eight patients with cardiogenic shock secondary to acute myocardial infarction, six critically ill controls, and six patients with septic shock.Forearm blood flow was measured at rest and during reactive hyperemia by venous air plethysmography. Red cell deformability was determined by filtration. Leukocyte aggregation was detected by the leukergy test. Neutrophil CD11b/CD18 expression and soluble intercellular adhesion molecule-1 levels were also measured. In cardiogenic shock, forearm arterial resistance was significantly increased at rest and during reactive hyperemia compared with controls and patients with septic shock. The response to reactive hyperemia was attenuated in cardiogenic and septic shock patients, as measured by the absolute change in forearm blood flow from baseline, which was significantly less as compared with controls (p.01). The percent change in forearm blood flow during reactive hyperemia compared with forearm blood flow at rest was significantly lower in cardiogenic shock (60+/-10) and in septic shock (50+/-11) compared with controls at baseline (145+/-20; p.01). Red cell deformability was significantly decreased in cardiogenic shock (1.2+/-0.2 mL/min; p.05) and septic shock (1.1+/-0.2 mL/min; p.05), compared with controls (1.8+/-0.1 mL/min). Neutrophil CD11b/CD18 expression, leukergy, and serum intercellular adhesion molecule-1 levels in cardiogenic shock patients were not significantly different from controls.These data suggest that the response to reactive hyperemia is attenuated in cardiogenic shock. This appears to reflect increased vasoconstriction and an impaired capacity for vasodilation. Decreased erythrocyte deformability may also be important in limiting systemic microvascular flow. However, evidence supporting a role for neutrophil-endothelial cell interactions was not observed.

Background Nasal cytograms are useful in evaluating patients with inflammatory disease of the nose and paranasal sinuses. When mucosal samples are taken with curette and brush devices, significant numbers of non-leukocytic cells can also be analyzed. Objective To examine two specific morphologic variations in granule-containing epithelial cells in nasal samples obtained from allergy clinic patients and describe their clinical associations. These two cellular variants consisted of goblet cells, with coalesced granules usually displacing the nucleus, and discrete granular mucinous cells (DGMC), which show more discrete granules not displacing the nucleus. Methods Patients from an adult allergy clinic were studied prospectively for nasal mucosal cytology, historical clinical data, nasal physical findings, serum IgE levels, and aeroallergen-specific IgE. Proportions and absolute numbers of goblet cells and DGMC in the nasal mucosal samples were related to other data using simple and multivariate analyses. Results Both goblet cells and DGMC showed absolute number increases in patients with observable nasal secretions. Discrete granular mucinous cell decreases were also observed in patients with IgE levels greater than or equal to 200 IU/mL and in asthmatic patients. In non-asthmatic patients with nasal eosinophilia, a significantly greater proportion of DGMC was observed compared with other patients (19.8 +/− 11.9% versus 8.5 +/− 5.9%, P = .007), while asthmatics with nasal eosinophilia had mean DGMC quantities closer to that observed in patients without nasal eosinophilia. Increases in goblet cell numbers were observed in patients with specific IgE to aeroallergens compared with other patients (46.5 +/− 46.7 versus 27.0 +/− 23.9, P = .014). Multivariate analysis confirmed that (1) the presence of aeroallergen-specific IgE and (2) the presence of nasal eosinophilia in the absence of asthma were differentially associated with increases in goblet cells and DGMC, respectively. Conclusions Increases in nasal DGMC and goblet cells differentially relate to specific clinical patterns of nasal cellular inflammation and aeroallergen hypersensitivity. The nasal epithelial cell profile associated with nasal eosinophilia in asthmatics may differ from that observed in non-asthmatic nasal eosinophilia.

Study objective: The use of nebulized ipratropium in combination with β-agonists for the treatment of acute asthma in adults is controversial. We wished to test the hypothesis that combined aerosol treatment results in a greater rate of airflow improvement and a lower proportion of hospital admission in adults with acute asthma. Methods: In a randomized, double-blind, placebo-controlled trial, 55 adult asthmatic patients with peak expiratory flow rate (PEFR) less than 200 L/min were randomly assigned to nebulization treatment with albuterol alone (2.5 mg initial dose followed by 2 more doses at 20-minute intervals), or the same albuterol regimen plus ipratropium (.5 mg combined with the initial dose of albuterol only). Patients were recruited from an emergency department at an urban academic medical center. The primary endpoints were changes in PEFR and in percent predicted PEFR over time (ie, treatment by time effect). PEFRs were assessed at baseline and at 20-minute intervals for a 1-hour period. The proportion of admissions in the two groups were examined as secondary endpoints. Results: The increases in PEFR and percent predicted PEFR over time were both significantly greater in the combined ipratropium plus albuterol treatment group ( P ≤.001). In addition, the proportion of admitted patients was less in this group (3/27) than the proportion in the albuterol-only group (10/28). The 95% confidence interval for the absolute difference of 25% in the proportion admitted was 3% to 46%, P =.03. Most of the baseline clinical and historical features in the two groups were similar. Conclusion: These data suggest that ipratropium should be combined with initial albuterol nebulization in the ED treatment of acute asthma in adults, especially those with PEFRs less than 200 L/min. [Lin RY, Pesola GR, Bakalchuk L, Morgan JP, Heyl GT, Freyberg CW, Cataquet D, Westfal RE: Superiority of ipratropium plus albuterol over albuterol alone in the emergency department management of adult asthma: A randomized clinical trial. Ann Emerg Med February 1998;31:208-213.]