John B. Hagan

Common variable immunodeficiency: a new look at an old disease

Primary immunodeficiencies comprise many diseases caused by genetic defects primarily affecting the immune system. About 150 such diseases have been identified with more than 120 associated genetic defects. Although primary immunodeficiencies are quite rare in incidence, the prevalence can range from one in 500 to one in 500 000 in the general population, depending on the diagnostic skills and medical resources available in different countries. Common variable immunodeficiency (CVID) is the primary immunodeficiency most commonly encountered in clinical practice, and appropriate diagnosis and management of patients will have a significant effect on morbidity and mortality as well as financial aspects of health care. Advances in diagnostic laboratory methods, including B-cell subset analysis and genetic testing, coupled with new insights into the molecular basis of immune dysfunction in some patients with CVID, have enabled advances in the clinical classification of this heterogeneous disease.

Incidence and Temporal Trends of Primary Immunodeficiency: A Population-Based Cohort Study

OBJECTIVE: To determine the incidence and temporal trends of primary immunodeficiency diseases (PIDs) and examine whether an association exists between delayed diagnosis and increased morbidity. PATIENTS AND METHODS: We performed a historical cohort study to describe the epidemiology of PIDs in Olmsted County, Minnesota, during a 31-year period from January 1, 1976, through December 31, 2006, using the Rochester Epidemiology Project. Incidence and trends over time, presence of comorbid conditions, and trends in management were determined. RESULTS: During the 31-year study period, 158 new cases of PIDs were diagnosed, with an overall incidence rate of 4.6 per 100,000 person-years. The rate of PIDs from 2001 through 2006 (10.3 per 100,000 person-years) was nearly 5 times higher than that from 1976 through 1980 (2.4 per 100,000 person-years). The associations between continuous variable(s) and categorical outcome(s) were assessed by using the Wilcoxon rank sum test. Longer delay in diagnosis was significantly associated with recurrent sinusitis (P<.001), recurrent pneumonia (P=.03), and subsequent treatment with immunoglobulins (P<.001). On the basis of Kaplan-Meier survival estimates, the proportion of patients surviving at 10 years after diagnosis was 93.5% (95% confidence interval, 85.9%-97.1%). However, older age at diagnosis was significantly associated with mortality (P=.01). CONCLUSION: This is one of the first population-based studies to examine the temporal trends of PIDs. The incidence of PIDs increased markedly between 1976 and 2006. In this cohort, a delay in diagnosis was common and was associated with increased morbidity. Despite substantial morbidity, most patients with PIDs can expect a normal life span.

Evaluation of National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network criteria for the diagnosis of anaphylaxis in emergency department patients

BACKGROUND Diagnostic criteria were proposed at the Second Symposium on the Definition and Management of Anaphylaxis convened by the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN). Validation is needed before these criteria can be widely adapted into clinical practice. OBJECTIVE Our aim was to retrospectively assess the diagnostic accuracy of the NIAID/FAAN criteria for the diagnosis of anaphylaxis in emergency department (ED) patients. METHODS A retrospective cohort study of ED patients presenting from April to October 2008 was conducted. Patients given a diagnosis of an allergic reaction or anaphylaxis and a subset of patients with related diagnoses were included. Electronic medical records were reviewed and data were abstracted to determine whether the NIAID/FAAN criteria were met. Records were also independently reviewed in a blinded fashion by 2 experienced attending allergists. Final diagnosis by allergists was considered the reference standard. RESULTS Of 214 patients, 86 (40.2%) met the NIAID/FAAN criteria for anaphylaxis. Allergists gave 61 (28.5%) patients diagnoses of anaphylaxis, 59 (96.7%) of whom satisfied the NIAID/FAAN criteria. The interrater agreement between allergists was substantial (κ = 0.77). The test characteristics of the NIAID/FAAN criteria were as follows: sensitivity, 96.7% (95% CI, 88.8% to 99.1%); specificity, 82.4% (95% CI, 75.5% to 87.6%); positive predictive value, 68.6% (95% CI, 58.2% to 77.4%); negative predictive value, 98.4% (95% CI, 94.5% to 99.6%); positive likelihood ratio, 5.48; and negative likelihood ratio, 0.04. CONCLUSIONS These results suggest that the NIAID/FAAN criteria are highly sensitive but less specific and are likely to be useful in the ED for the diagnosis of anaphylaxis.

Antihypertensive medication use is associated with increased organ system involvement and hospitalization in emergency department patients with anaphylaxis

BACKGROUND Risk factors for increased anaphylaxis severity are poorly understood. Angiotensin-converting enzyme (ACE) inhibitors have been associated with severe anaphylactic reactions in patients with hymenoptera venom allergy. Studies evaluating the association between beta-blockers and severe anaphylaxis have been conflicting. OBJECTIVE To evaluate the association between antihypertensive medication use and increased anaphylaxis severity. METHODS We included emergency department anaphylaxis patients aged 18 years and older. Markers of severe anaphylaxis were defined as (1) syncope, hypotension, or hypoxia; (2) signs and symptoms involving 3 or more organ systems; and (3) hospitalization. Antihypertensive medications evaluated included beta-blockers, ACE inhibitors, calcium channel blockers, angiotensin receptor blockers, and diuretics. Simple and multiple logistic regression analyses were conducted to estimate the association between antihypertensive medication use and markers of increased anaphylaxis severity. RESULTS Among 302 patients with anaphylaxis, 55 (18%) had syncope, hypoxia, or hypotension, 57 (19%) required hospitalization, and 139 (46%) had 3 or more organ system involvement. After adjusting for age, gender, suspected trigger, and preexisting lung disease, beta-blocker, ACE-inhibitor, diuretic, or antihypertensive medication use in aggregate remained associated with both 3 or more organ system involvement and need for hospital admission. The adjusted associations between antihypertensive medication use in aggregate and 3 or more organ system involvement yielded an odds ratio of 2.8 (95% CI, 1.5-5.2; P=.0008) and with hospitalization an odds ratio of 4.0 (95% CI, 1.9-8.4; P=.0001). CONCLUSIONS In emergency department anaphylaxis patients, antihypertensive medication use is associated with increased organ system involvement and increased odds of hospital admission, independent of age, gender, suspected trigger, or preexisting lung disease.

Anaphylaxis in emergency department patients 50 or 65 years or older

BACKGROUND Anaphylaxis is a potentially life-threatening allergic reaction commonly managed in the emergency department (ED). Data describing patients 50 or 65 years or older with anaphylaxis are limited. OBJECTIVE To describe the presentation and management of patients with anaphylaxis who were 50 or 65 years or older and to compare these findings with those of younger patients. METHODS A consecutive cohort study of patients presenting to an ED with approximately 80,000 visits per year was conducted. Patients who met diagnostic criteria for anaphylaxis from April 2008 to June 2010 were included. Data were collected on suspected causes, signs and symptoms, management, ED disposition, and follow-up. RESULTS The study included 220 patients. Food was the most common suspected cause of anaphylaxis for patients younger than 50 (42.2%) or 65 years (38.5%) but was much less common in patients 50 (14.8%, P < .001) or 65 years or older (14.3%, P = .01). Cardiovascular symptoms were more likely to occur in older patients (≥50 years old, 55.6% vs 30.1%, P < .001; ≥65 years old, 64.3% vs 32.3%, P = .002). Patients 50 or 65 years or older were less likely to be dismissed home directly from the ED (≥50 years old, 35.2% vs 56.6%, P = .006; ≥65 years old, 32.1% vs 54.2%, P = .03) and were less likely to be prescribed self-injectable epinephrine (≥50 years old, 40.7% vs 63.3%, P = .004; ≥65 years old, 32.1% vs 61.5%, P = .003). CONCLUSIONS In ED patients presenting with anaphylaxis, age of 50 or 65 years or older is associated with a decreased likelihood of food-induced anaphylaxis, increased likelihood of experiencing cardiovascular symptoms, decreased dismissal to home directly from the ED, and decreased prescriptions for self-injectable epinephrine.

Outcomes of Allergy/Immunology Follow-Up After an Emergency Department Evaluation for Anaphylaxis

BACKGROUND Anaphylaxis guidelines currently recommend referring patients with anaphylaxis seen in the emergency department (ED) to an allergist for follow up. OBJECTIVE The objective of our study was to evaluate outcomes of allergy/immunology follow-up after an ED visit for anaphylaxis. METHODS A retrospective health records review was conducted from April 2008 to August 2012. Charts were reviewed independently by 2 allergists to determine outcomes. Descriptive statistics with corresponding 95% CIs were calculated. RESULTS Among 573 patients seen in the ED who met anaphylaxis diagnostic criteria, 217 (38%) had a documented allergy/immunology follow-up. After allergy/immunology evaluation, 16 patients (7% [95% CI, 5%-12%]) had anaphylaxis ruled out. Among those with an unknown ED trigger (n = 74), 24 (32% [95% CI, 23%-44%]) had a trigger identified; and, among those who had a specific suspected ED trigger (n = 143), 9 (6% [95% CI, 3%-12%]) had a trigger identified in a category other than the one suspected in the ED, and 28 (20% [95% CI, 14%-27%]) had an unknown trigger. Thus, there were a total of 77 patients (35% [95% CI, 29%-42%]) who had an alteration in the diagnosis of anaphylaxis or trigger after allergy/immunology evaluation. Four patients (2% [95% CI, 0.7%-4.6%]) were diagnosed with a mast cell activation disorder, and 13 patients (6% [95% CI, 4%-10%]) underwent immunotherapy or desensitization. CONCLUSION Overall, 35% of the patients with suspected anaphylaxis in the ED had an alteration in the diagnosis or suspected trigger after allergy/immunology evaluation. These results underscore the importance of allergy/immunology follow-up after an ED visit for anaphylaxis.

Inhibition of interleukin-5 mediated eosinophil viability by fluticasone 17-propionate : comparison with other glucocorticoids

Inhaled glucocorticoids are commonly employed to treat patients with asthma. Eosinophils are important effector cells in the pathogenesis of asthma, and, in vitro, glucocorticoids modulate eosinophil viability.

Three-dimensional volumetric computed tomographic scoring as an objective outcome measure for chronic rhinosinusitis: clinical correlations and comparison to Lund-Mackay scoring.

We aimed to test the hypothesis that three‐dimensional (3D) volume‐based scoring of computed tomography (CT) images of the paranasal sinuses was superior to Lund‐Mackay CT scoring of disease severity in chronic rhinosinusitis (CRS). We determined correlation between changes in CT scores (using each scoring system) with changes in other measures of disease severity (symptoms, endoscopic scoring, and quality of life) in patients with CRS treated with triamcinolone.

The risk of asthma exacerbation after reducing inhaled corticosteroids: A systematic review and meta-analysis of randomized controlled trials

Asthma guidelines suggest reducing controller medications when asthma is stable.

A multifaceted intervention for patients with anaphylaxis increases epinephrine use in adult emergency department.

BACKGROUND Studies have documented inconsistent emergency anaphylaxis care and low compliance with published guidelines. OBJECTIVE To evaluate anaphylaxis management before and after implementation of an emergency department (ED) anaphylaxis order set and introduction of epinephrine autoinjectors, and to measure the effect on anaphylaxis guideline adherence. METHODS A cohort study was conducted from April 29, 2008, to August 9, 2012. Adult patients in the ED who were diagnosed with anaphylaxis were included. ED management, disposition, self-injectable epinephrine prescriptions, allergy follow-up, and incidence of biphasic reactions were evaluated. RESULTS The study included 202 patients. The median age of the patients was 45.3 years (interquartile range, 31.3-56.4 years); 139 (69%) were women. Patients who presented after order set implementation were more likely to be treated with epinephrine (51% vs 33%; odds ratio [OR] 2.05 [95% CI, 1.04-4.04]) and admitted to the ED observation unit (65% vs 44%; OR 2.38 [95% CI, 1.23-4.60]), and less likely to be dismissed home directly from ED (16% vs 29%, OR 0.47 [95% CI, 0.22-1.00]). Eleven patients (5%) had a biphasic reaction. Of these, 5 (46%) had the biphasic reaction in the ED observation unit; 1 patient was admitted to the intensive care unit. Six patients (55%) had reactions within 6 hours of initial symptom resolution, of whom 2 were admitted to the intensive care unit. CONCLUSIONS Significantly higher proportions of patients with anaphylaxis received epinephrine and were admitted to the ED observation unit after introduction of epinephrine autoinjectors and order set implementation. Slightly more than half of the biphasic reactions occurred within the recommended observation time of 4 to 6 hours. Analysis of these data suggests that the multifaceted approach to changing anaphylaxis management described here improved guideline adherence.