Volume 123, Issue 2 , Pages 333-334, February 2009
The Editors' Choice
Article Outline
- Less allergy at age 5 years in cesarean-born children receiving probiotics
- How well are US emergency departments taking care of asthmatic patients?
- Prostatic kallikrein—a new major dog allergen
- Why are peanuts so allergenic?
- A BAFF affirmation
- Airway smooth muscle hyperplasia in asthma—a consequence of fibrocyte recruitment?
- Copyright
Less allergy at age 5 years in cesarean-born children receiving probiotics
Decreased environmental microbial exposure in early childhood is associated with more allergic disease later. Infants developing allergies have a different fecal flora, with less lactobacilli and bifidobacteria. Probiotic supplementation of mothers in late pregnancy and of their infants meant decreased allergies until age 2 years, but long-term effects remain unresolved. In this issue, Kuitunen et al (p 335) report a double-blind, placebo-controlled study randomizing 1223 mothers with infants at high risk for allergy to receive a probiotic mixture of 4 bacteria or placebo during the last month of pregnancy and their infants from birth until age 6 months. Infants also received a prebiotic galacto-oligosaccharide or placebo. Cumulative incidence of allergic diseases (eczema, food allergy, allergic rhinitis, and asthma) and IgE sensitization was evaluated at age 5 years. Although an allergy-preventive effect had continued at age 2 years, none emerged that extended to 5 years in the total cohort. Cesarean-delivered children administered probiotics, however, developed IgE-associated allergic disease markedly less frequently. These children—deprived of the massive microbial load during vaginal delivery and showing marked deviation in their fecal bacteria (see Figure)—may benefit the most from probiotic supplementation. The high incidence of C-section worldwide strengthens the impact of this observation.
Fecal bifidobacteria in cesarean- and vaginally delivered children (∗P = .036).
How well are US emergency departments taking care of asthmatic patients?
Little is known about quality of acute asthma care in US emergency departments (EDs). In this issue of the Journal, the study by Tsai et al (p 354) aimed to determine concordance of ED management with National Institutes of Health (NIH) asthma guidelines, to identify ED characteristics predictive of higher guideline concordance, and to assess whether guideline concordance was associated with reduced hospital admissions. The authors conducted a retrospective chart review study of acute asthma as part of the National Emergency Department Safety Study. This study was performed by the Emergency Medicine Network (www.emnet-usa.org) and included 4053 asthmatic patients in 63 urban EDs between 2003 and 2006. The authors found that concordance of emergency asthma care with the NIH guidelines was moderate, with a mean ED concordance score of 71 (see Figure). They also found geographic variations in the quality of asthma care, with lower concordance in the South. Finally, patients who received perfect guideline-concordant care had a 46% reduction in the risk of hospital admission in comparison with others. The authors encourage implementation of quality improvement efforts. Greater adherence to asthma guideline recommendations would likely improve patient outcomes.
Distribution of emergency department composite guideline concordance scores.
Prostatic kallikrein—a new major dog allergen
The quest for elusive dog allergens takes a leap ahead in this issue of the Journal, and with a special twist to the story. Mattsson et al (p 362) report prostatic kallikrein as a novel and major dog allergen. The protein was isolated from dog urine and its identity established by N-terminal sequencing and mass spectrometry. The new allergen, designated Can f 5, is shown to also be present in dogs' dander, thus allowing its dispersion and airway entry in the same way as other dog dander allergens. Among 37 subjects with dog allergy studied, 26 displayed IgE binding to Can f 5, and in 14 of those, no sensitization to the previously known dog allergens Can f 1-3 was detected. Interestingly, Can f 5 shares significant homology with human prostate specific antigen (PSA). PSA has been implicated as a culprit in a rare condition among women, vaginal hypersensitivity to semen. IgE sensitization to PSA has been demonstrated in such cases, and Mattsson et al now demonstrate cross-reactivity between Can f 5 and PSA. This finding raises the possibility of an association between Can f 5 sensitization and female hypersensitivity reactions to human semen.
Why are peanuts so allergenic?
Peanuts and tree nuts commonly cause food allergy that persists into adulthood and are the most frequent cause of lethal food allergy in the United States. In contrast, milk- and egg-associated food allergy is typically less severe and rarely persists into adulthood. Khodoun et al (p 342) demonstrate that peanut and tree nut extracts, unlike milk and egg white, induce shock when injected into unimmunized mice (see Figure) that are first made highly susceptible to histamine and platelet-activating factor (PAF). Peanut extract induces shock by directly activating complement with production of C3a, which stimulates macrophages and basophils to produce PAF and mast cells to produce histamine. This mechanism acts synergistically with IgE-dependent mast cell activation to cause particularly severe anaphylaxis, even when peanut extract is administered orally. This synergy could explain why peanuts are such potent inducers of severe anaphylaxis; in addition, the ability of complement activation products to enhance antibody responses may explain why peanuts are so allergenic. The ability of peanuts to induce C3a production in both mouse and human plasma suggests that complement stabilizers and PAF antagonists might be useful for prophylaxis in peanut-allergic patients; furthermore, identification of the peanut component(s) that activates complement might facilitate engineering of less allergenic peanuts.
Peanut and cashew extracts induce shock (hypothermia) in nonimmune mice.
A BAFF affirmation
Local B-cell activation in the airways is an important event in mucosal immunity. Although local production of immunoglobulins, especially IgE, plays a role in allergic diseases such as asthma and allergic rhinitis, the mechanisms of local B-cell activation and IgE production are not fully understood. Kato et al (p 369) investigated the local production of B cell–activating factor of the TNF family (BAFF), a factor that activates B lymphocytes, after segmental allergen challenge of allergic subjects. They found elevated BAFF in bronchoalveolar lavage (BAL) fluid taken from allergen-challenged sites (see Figure) and show that it was probably synthesized locally. The local concentration of BAFF at allergen-challenged sites was strongly correlated with the numbers of infiltrating cells, such as lymphocytes, neutrophils, and eosinophils, but not resident macrophages. BAFF levels were also correlated with the appearance of 2 other B cell–activating cytokines, IL-6 and IL-13. The authors conclude that exposure to antigen induces local production of BAFF and other B cell–stimulating cytokines in the airways. This study provides a novel insight into the mechanism of local activation of B cells and production of immunoglobulins such as IgA and IgE in airway inflammatory diseases.
BAFF production in BAL fluid after segmental allergen challenge.
Airway smooth muscle hyperplasia in asthma—a consequence of fibrocyte recruitment?
Airway smooth muscle hyperplasia is a hallmark of asthma, associated with disease severity and persistent airflow obstruction. There is increasing evidence that fibrocytes migrate to the airway in asthma. Saunders et al (p 376) have enumerated the fibrocyte number in bronchial biopsies and blood from subjects with mild-severe refractory asthma and healthy controls and show for the first time an increase in the number of fibrocytes in the airway smooth muscle-bundle in asthma of all severities and in the lamina propria in severe asthmatics. In addition, there is an increased number of fibrocytes in peripheral blood in severe refractory disease, which corroborates a recent study showing a higher percentage of circulating fibrocytes in asthmatics with chronic airflow obstruction. This suggests that in addition to recruitment to the airway, there is an increase in the bone marrow production of peripheral blood fibrocytes, as observed for other progenitor cells. In vitro investigations into the mechanism driving fibrocyte migration show that airway smooth muscle augments fibrocyte migration in part mediated by platelet-derived growth factor. Thus, fibrocyte recruitment contributes to airway remodeling in asthma. There is a pressing need to further our understanding of fibrocyte biology, as this may present novel therapeutic targets for the asthma.
PII: S0091-6749(08)03538-0
doi:10.1016/j.jaci.2008.12.1118
© 2009 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Volume 123, Issue 2 , Pages 333-334, February 2009
