M.R. Nelson

Adequacy of the epinephrine autoinjector needle length in delivering epinephrine to the intramuscular tissues

BACKGROUND Epinephrine injected by an autoinjector in the anterolateral aspect of the thigh is the standard of care in the emergency self-treatment of anaphylaxis. In the United States, the autoinjector EpiPen is widely used for the self-treatment of anaphylaxis. OBJECTIVE To investigate whether EpiPen autoinjector, with a needle length of 1.43 cm, is sufficient for intramuscular delivery of epinephrine in men and women. METHODS The distance from skin to muscle in the anterolateral aspect of the thigh was measured in 50 men and 50 women who had undergone computed tomography of the thighs for other medical reasons. For each individual, body mass index (BMI; a measure of weight in kilograms divided by the square of height in meters) was also calculated, and the individuals were classified as underweight (BMI, < 18.5), normal (BMI, 18.5-24.9), overweight (BMI, 25.0-29.9), and obese (BMI, > or = 30.0) using standard definition. RESULTS In the study participants the mean +/- SD distance from skin to muscle was 0.66 +/- 0.47 cm for men and 1.48 +/- 0.72 cm for women (P < .001). One man (obese at a BMI of 42.2) and 21 women (11 obese with a mean BMI of 35.2, 6 overweight with a mean BMI of 30.1, and 4 normal with a mean BMI of 24.5) had a greater distance from skin to muscle than the EpiPen needle length of 1.43 cm. CONCLUSION The distance from skin to muscle for the anterolateral aspect of the thigh is higher in women compared with men. This difference suggests that EpiPen may not deliver epinephrine to the intramuscular tissue in many women.

Safety and immunogenicity of an intranasal Shigella flexneri 2a Invaplex 50 vaccine

BACKGROUND Shigella flexneri 2a lipopolysaccharide 50 is a nasally delivered subunit vaccine consisting of a macromolecular complex composed of LPS, IpaB, IpaC and IpaD. The current study examined vaccine safety and immunogenicity across a dose range and the clinical performance of a new intranasal delivery device. METHODS Volunteers (N=36) were randomized to receive vaccine via the Dolphin™ (Valois of America, Congers, New York) intranasal spray device at one of three doses (240, 480, and 690 μg) on days 0, 14, and 28. Another group (N=8) received the 240 μg dose via pipette. Vaccine safety was actively monitored and antigen-specific humoral and mucosal immune responses were determined. RESULTS There were no serious adverse events and the majority of adverse events (98%) were mild. Antibody secreting cells (ASC), plasma, and mucosal immune responses to Shigella antigens were detected at all three dose levels with the 690 μg dose inducing the highest magnitude and frequency of responses. Vaccination with comparable doses of Invaplex 50 via the Dolphin™ resulted in higher plasma and ASC immune responses as compared to pipette delivery. CONCLUSION In this trial the S. flexneri 2a Invaplex 50 vaccine was safe, well-tolerated and induced robust levels of antigen-specific intestinal IgA and ASC responses. The spray device performed well and offered an advantage over pipette intranasal delivery.

Safety and immunogenicity of a Shigella flexneri 2a Invaplex 50 intranasal vaccine in adult volunteers.

Shigellosis is a leading cause of diarrhea worldwide prompting vaccine development. The Shigella flexneri Invaplex 50 is a macromolecular complex containing IpaB, IpaC, and LPS, formulated from an aqueous extract of virulent Shigella delivered via nasal administration. Preclinical vaccine testing demonstrated safety, immunogenicity and efficacy. An open-label dose-escalating phase 1 study evaluated a 3-dose (2-week intervals) regimen via nasal pipette delivery. Thirty-two subjects were enrolled into one of four vaccine dose groups (10, 50, 240, or 480 microg). The vaccine was well tolerated with minor short-lived nasal symptoms without evidence of dose effect. Antibody-secreting cell (ASC) responses were elicited at doses > or =50 microg with the highest IgG ASC, Invaplex 50 (100%) and S. flexneri 2a LPS (71%), as well as, serologic responses (43%) occurring with the 240 microg dose. Fecal IgA responses, Invaplex 50 (38.5%) and LPS (30.8%), were observed at doses > or =240 microg. The Invaplex 50 nasal vaccine was safe with encouraging mucosal immune responses. Follow-on studies will optimize dose, delivery mechanism and assess efficacy in a S. flexneri 2a challenge study.

Pollen aeroallergens in the Washington, DC, metropolitan area: a 10-year volumetric survey (1998-2007).

BACKGROUND Local aeroallergen surveys identify and establish patterns of prevalence for tree, grass, and weed species that enable the clinician to more effectively select allergens for skin testing and therapy. OBJECTIVES To determine peak pollination periods, atmospheric concentrations, and year-to-year variation for identified tree, weed, and grass aeroallergens and examine the influence of selected meteorological parameters. METHODS Atmospheric sampling for pollen aeroallergens was performed using a volumetric rotating-arm impaction sampler. The Spearman correlation coefficient was used to determine the relationship between daily counts and selected meteorological parameters. RESULTS Previous findings for area trees, conducted at a different location, are corroborated. Predominant pollen types include Quercus, Cupressaceae, Pinaceae, Morus, Betulaceae, Acer, Platanus, Fraxinus, Poaceae, and Ambrosia. Early flowering weeds (Rumex and Typha) and Poaceae overlap with peak tree season in April. Biphasic seasons are noted for Poaceae and Ulmus. Tree pollen accounts for 91.2%, weeds 3.8%, and grasses 3.2% of total annual pollen yield. Variation in overall pollen production is evident from year to year. High production years for some species are low for others. Cyclic pollinating patterns for Alnus, Betulaceae, and Fagus were observed. Grass and weed pollen correlated positively with maximum temperature and dew point; however, the results for individual tree species were variable. CONCLUSION The Washington, DC, metropolitan area is host to a variety of tree, weed, and grass species that produce copious amounts of pollen. Further investigation into year-to-year variation with respect to inherent cycling and meteorological influences is warranted.

Ovalbumin content of 2010-2011 influenza vaccines.

As regards patients 2 and 3, considering negative results of in vivo and in vitro tests as well as the fact that they had not experienced severe reactions, an open food challenge was performed to firmly establish the diagnosis. In accordance with Kanny et al, we administered increasing doses of sesame seeds (0.05, 0.5, 1, 5, and 10 g) every 30 minutes. Both patients experienced urticarial reactions: the first one 20 minutes after the dose of 0.5 g, the second 15 minutes after the dose of 1 g. Consequently, no oral provocation test with sesame oil was performed. We did not perform an oral provocation test in patient 1, because of the previous anaphylactic shock and positivity to SPTs with sesame seeds. Specific IgE was further analyzed by immunoblot experiments with an extract of sesame seeds and sesame oil (Fig 1). All patients’ sera (diluted 1:4 in PBS-Tween 0.5%) showed an IgE binding to several proteins of the oil bodies (membrane lipoproteins), such as oleosins (the band with molecular mass around 15-17 kDa). To our knowledge, these are the first cases of hypersensitivity to sesame diagnosed by a simple immediate-reading contact test with sesame oil. Because oleosins are hydrophobic and can not be solubilized in normal saline, a negative prick-to-prick test with crushed sesame seeds is not sufficient to exclude sesame allergy, especially in subjects in whom specific IgE is directed prevalently to liposoluble proteins. For this reason, patients with histories of adverse reactions to sesame should also be tested with an immediate-reading ‘‘contact test’’ with sesame oil, in which oleosins are anchored onto the surface by its central hydrophobic domain and can easily penetrate the skin. Negative results in SPTs with sesame oil can be explained by the fact that the oil drops were wiped away immediately after testing and there was not enough time to allow oil to penetrate into the skin. The data from Leduc et al and our data indicate that sensitization to oleosins can play an etiologic role in some subjects with immediate reactions to sesame products. Therefore, sensitization to oleosins might constitute a diagnostic problem in both adults and children. In effect, even though all our patients were adults, one of the patients described by Leduc et al was a 9-year-old girl. Few data exist on the allergenicity of other vegetable oils. The presence of oleosins has been shown in some of them. In peanut oil, for example, the allergenicity of oleosins has been established, even though commercially available, refined peanut oil has been proven to be well tolerated by most subjects with peanut allergy. In effect, the major refined oils are not thought to induce symptoms in susceptible individuals. There are commercial available crude and cold-pressed peanut oils that contain proteins. Sesame oil differs from the others because it is typically available as an unrefined, crude oil, which contains a significantly higher amount (3-13 mg/g) of proteins. Our immunoblot experiments detected serum-specific IgE to the oleosins contained in sesame oil. The sera of our patients also displayed a higher IgE-reactivity to other liposoluble proteins not yet characterized (Fig 1, D). Like oleosins, such lipoproteins are hydrophobic, and because they can not be solubilized in normal saline, they are not present in commercial extracts. Our data suggest that patients with histories of immediate reactions to sesame products and positive results in immediate-reading contact tests with sesame oil should be instructed to avoid all sesame products, including oil. However, further studies in larger samples are needed to confirm the usefulness of this immediate-reading contact test and to validate such advice. Cristiana Alonzi, MD Paolo Campi, MD Francesco Gaeta, MD Fernando Pineda, PhD Antonino Romano, MD

Adverse reactions to vaccines

Abstract(The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.)Immunization healthcare is becoming increasingly complex as the number and types of vaccines have continued to expand. Like all prescription drugs, vaccines may be associated with adverse events. The majority of these reactions are self-limited and not associated with prologned disability. The media, Internet and public advocacy groups have focused on potentially serious vaccine-associated adverse events with questions raised about causal linkages to increasing frequencies of diseases such as autism and asthma. Despite a lack of evidence of a causal relationship to a variety of vaccine safety concerns, including extensive reviews by the Institute of Medicine, questions regarding vaccine safety continue to threaten the success of immunization programs. Risk communication arid individual risk assessment is further challenged by the public health success of vaccine programs creating the perception that certain vaccines are no longer necessary or justified because of the rate reaction risk.There is a need for improved understanding of true vaccine contraindications and precautions as well as host factors and disease threat in order to develop a patient specific balanced treated, documented and reported through the VAERS system. The increasing complexity of vaccination health care has led the Center of Disease Control and Prevention (CDC) to identify Vaccine Safety Assessment and Evaluation as a potential new specialty.

Sublingual immunotherapy: A focused allergen immunotherapy practice parameter update

Matthew Greenhawt, MD, MBA, MSc; John Oppenheimer, MD; Michael Nelson, MD, PhD; Hal Nelson, MD; Richard Lockey, MD; Phil Lieberman, MD; Anna Nowak-Wegrzyn, MD; Anju Peters, MD; Charlotte Collins, JD; David I. Bernstein, MD; Joann Blessing-Moore, MD; David Khan, MD; David Lang, MD; Richard A. Nicklas, MD; Jay M. Portnoy, MD; Christopher R. Randolph, MD; Diane E. Schuller, MD; Sheldon L. Spector, MD; Stephen A. Tilles, MD; Dana Wallace, MD

Subcutaneous immunoglobulin therapy in an 11-year-old patient with common variable immunodeficiency and von Willebrand disease

BACKGROUND Subcutaneous immunoglobulin (SCIG) is an option for replacement therapy in patients with humoral immune deficiencies. OBJECTIVE To describe a patient with common variable immunodeficiency (CVID) and von Willebrand disease who tolerated immunoglobulin replacement via the subcutaneous route. METHODS An 11-year-old boy receiving monthly intravenous immunoglobulin (IVIG) since 5 years of age presented to an academic medical center after moving to the area. The patient also had a history of von Willebrand disease. He had started receiving IVIG because of recurrent infections and an absent IgG subclass 3. Further immunologic assessment revealed a normal B-cell count, decreased IgM level, and an abnormal response to bacteriophage phiX174. Given these findings and the lack of another cause, the patient was diagnosed as having CVID. Because of difficult intravenous access, a port was placed for IVIG administration in 1999. The initial port was removed because of infectious complications, and a second port was found to be distally displaced in the right atrium, requiring removal. RESULTS Continued difficulties with intravenous access and the potential complications with maintaining a long-term indwelling catheter prompted consideration of alternative methods for immunoglobulin administration. After removal of the port, the patient was prescribed weekly SCIG infusions. He tolerated the infusions well without bleeding complications related to the von Willebrand disease and was able to transition to home infusions. CONCLUSIONS SCIG was well tolerated by a pediatric patient with CVID and von Willebrand disease without any significant bleeding complications.

Determination of ranges for reporting pollen aeroallergen levels in the Washington, DC, metropolitan area

BACKGROUND Local aeroallergen monitoring provides useful information for the atopic patient and medical community. Currently, National Allergy Bureau (NAB) ranges are used for reporting pollen count levels in the Washington, DC, area. OBJECTIVE To determine standard range criteria (low, moderate, high, and very high) for the reporting of specific tree, grass, and weed aeroallergens representative of the Washington, DC, metropolitan region. METHODS Atmospheric sampling for pollen aeroallergens was performed using a volumetric rotating-arm impaction sampler (model 40 Rotorod, SDI Company, Plymouth Meeting, PA). The cumulative pollen count, over a 12-year period (1998-2009), was determined for specific pollen aeroallergens. Local ranges were developed using methodology previously employed to determine NAB ranges. A comparison was made between NAB and Washington, DC, area ranges. RESULTS The local median count, and low and moderate range criteria, are markedly lower than NAB range counts for tree, grass, and weed pollen. The NAB 99th percentile (high) count is significantly higher for grass and weed pollen but lower for tree pollen. Using new local range criteria, an increase was seen in the number of high days recorded for weed pollen (1,300%), grass pollen (258.6%), and tree pollen (11.8%). Previously, using NAB range criteria, no very high days were reported for grass and weed pollen over the 12-year period. CONCLUSION Washington, DC, ranges establish more relevant reporting standards for our local patient population and will allow for comparison with reporting levels developed for sampling locations nationwide as well as with other regional sites.

Effect of allergen immunotherapy practice parameters on cat extract prescribing patterns, 1993-2009.

BACKGROUND Cat extract allergen immunotherapy (AIT) is an effective treatment for cat allergy. The prescribed dose for cat AIT varies among prescribers, despite published data supporting an effective dose range. The original practice parameter published in December 1996 did not recommend a dose of cat allergen, but updates in January 2003 and September 2007 recommend cat extract dose ranges of 2,000 to 3,000 BAU and 1,000 to 4,000 BAU, respectively. OBJECTIVE To describe the prescribing patterns for cat AIT among practicing allergists in a large health care system and the effect of practice parameters on these patterns. METHODS A total of 27,788 prescriptions were analyzed to determine the date and amount of maintenance dose cat allergen prescribed. The data were subdivided into periods before and after the 3 published AIT practice parameters. RESULTS From January 2003 to September 2007, 1,810 prescriptions (18.0%) were written in the recommended range. From September 2007 to May 2009, 3,143 prescriptions (82.6%) were written in the recommended range. Cat AIT maintenance doses were 1,000 to 4,000 BAU 22.1% of the time before January 2003, 61.8% from January 2003 to September 2007, and 82.6% from September 2007 to May 2009. CONCLUSIONS In this large systemic evaluation of cat AIT prescribing patterns, maintenance dose recommendations in the AIT practice parameters were associated with changes in the prescribing patterns for cat AIT. Most prescriptions for cat AIT were inconsistent with recommended doses in the AIT practice parameters between 2003 and 2007. Dosing within recommended ranges improved after 2007, in part due to a widening of the recommended dose range.