Elizabeth A. Erwin

Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing.

Abstract Background Viral respiratory tract infections and atopy are associated with attacks of wheezing during childhood. However, information about the relationship between viral infections and atopy among children whose attacks of wheezing lead to hospitalization is unclear. Objective To evaluate the prevalence of viral respiratory tract pathogens among infants and children hospitalized for wheezing and to analyze the results in relation to the patients age, atopic characteristics, and season of admission. Methods This was a case-control study of children (age 2 months to 18 years) admitted for wheezing to the University of Virginia Medical Center over a period of 12 months. Children without wheezing were enrolled as controls. Nasal secretions were evaluated for viral pathogens by using cultures, PCR tests, and antigen detection. Total IgE and specific IgE antibody to common aeroallergens was measured in serum. Results Seventy percent of children hospitalized for wheezing before age 3 years (n=79) were admitted between December and March, whereas 46% of children age 3 to 18 years (n=54) were hospitalized between September and November. Among children younger than 3 years, viral pathogens were detected in 84% (66/79) of wheezing children and 55% (42/77) of controls (P < .001). Respiratory syncytial virus was the dominant pathogen during the winter months, but rhinovirus was more common during other months. Total serum IgE levels were generally low, and values from wheezing and control subjects overlapped considerably. Among children 3 years and older, 61% (33/54) of subjects admitted for wheezing tested positive for virus (predominantly rhinovirus), compared with 21% (12/56) of controls (P < .001). The total serum IgE values among wheezing children (geometric mean, 386 IU/mL; 95% CI, 259-573) were substantially elevated compared with those of controls (geometric mean, 38 IU/mL; 95% CI, 26-56; P < .001). A significantly higher percentage of wheezing children compared with controls was sensitized to at least 1 of the inhaled allergens tested: 84% (36/43) compared with 33% (15/45; P < .001). The atopic characteristics of wheezing children who tested positive or negative for virus were similar. Conclusions Viral infections were the dominant risk factor for wheezing among children hospitalized before 3 years of age. By comparison, a large majority of the wheezing children age 3 to 18 years had striking atopic characteristics that may be critical as a risk factor for hospitalization and an adverse response to viral infections, especially infections caused by rhinovirus.

Is the hygiene hypothesis still a viable explanation for the increased prevalence of asthma

The hygiene hypothesis states that a reduced exposure to allergens in early life is solely implicated in the growing propensity for allergy sensitization. Important elements of the hypothesis include helminth infection, exposure to endotoxins, exposure to pets and growing up on a farm. However, the hygiene hypothesis alone does not provide an adequate explanation for the observed increase in allergic disease. For example, in North American inner cities, asthma is increasing among children who live in very poor housing, which might be assumed to be somewhat dirty. In order to explain the increase in asthma, we need to take a broader view and also consider alterations related to the adoption of a western lifestyle. It has been suggested that lifestyle changes related to obesity (e.g. a change in diet) are associated with asthma. Other changes include a progressive decrease in physical activity. This lifestyle factor seems to correlate best with the recent increase in asthma. Clearly, the link between physical activity and asthma needs to be investigated in more detail.

Serum IgE measurement and detection of food allergy in pediatric patients with eosinophilic esophagitis

BACKGROUND Although associated allergies are common and the mechanism may include long-term exposure to allergens, measurement of serum specific IgE levels has not been studied in pediatric eosinophilic esophagitis (EE). OBJECTIVE To compare the results of serum IgE testing, patch testing, and epicutaneous skin testing to measure allergic sensitization in pediatric patients with EE. METHODS In a cross-sectional study of 53 pediatric patients with EE, relevant history was obtained by questionnaire, and patch testing to foods was performed. Food and inhalant sensitivities were also assessed using skin prick testing and serum specific IgE measurement. Streptavidin CAP was used to measure specific IgE to cross-reactive carbohydrate determinants and Helicobacter pylori. RESULTS The overall prevalence of food and inhalant sensitization was 80%, with higher total IgE levels in sensitized vs nonsensitized patients (median, 150 vs 13 IU/mL; P < .001). For foods, serum IgE measurement detected more positive results than did skin prick testing. Specific IgE to milk was most common (43%). Inhalants were implicated as frequently as were foods. In keeping with this, 32% of patients had a cluster of multiple sensitivities that included pollens, soy, grains, peanut, and tree nuts and had higher total IgE levels (P = .001). Patch test results were interpreted as positive in 39% of patients (rye, wheat, and soy were the most common). CONCLUSIONS Most, but not all, patients with EE are highly atopic individuals with frequent allergic sensitivities. Thus, serum IgE measurement of low-titer IgE antibody may be useful in identifying relevant food sensitivities and in distinguishing subgroups of patients with EE, making a more directed approach to food avoidance possible.

Prospective, comparative effectiveness trial of cow's milk elimination and swallowed fluticasone for pediatric eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease in which food antigens play a key role. Current therapeutic options are limited to long-term steroid medication and dietary elimination of multiple foods, each of which is challenging. Our objective was to compare single food elimination of cows milk to swallowed fluticasone in pediatric EoE patients. This is a prospective, comparative effectiveness trial of newly diagnosed EoE patients (ages 2-18 years) treated with swallowed fluticasone (n = 24) or elimination of cows milk (n = 20). The dual outcome measures of repeat esophageal biopsy (6-8 weeks) and change in Pediatric Quality of Life Inventor (PedsQL) EoE Module and Symptoms Scales were used to assess response to treatment. After 6-8 weeks of treatment, peak esophageal eosinophil counts decreased to below the threshold of 15 eosinophils/high-power field in 64% of patients treated with cows milk elimination and 80% of patients treated with swallowed fluticasone (P = 0.4). Mean PedsQL EoE Module total scores (69 vs. 82; P < 0.005) and Total Symptoms scores (58 vs. 75; P = 0.001) showed significant improvement with cows milk elimination. Among children treated with swallowed fluticasone, mean PedsQL EoE Module total scores (64 vs. 75; P < 0.05) and Total Symptoms scores (58 vs. 69; P < 0.01) were also significantly improved after 6-8 weeks of therapy. Removal of cows milk from the diet is an effective single food elimination treatment for pediatric patients with EoE as assessed by statistically significant histologic and symptomatic improvement. Cows milk elimination may be more desirable for EoE patients who do not want to take chronic, long-term steroid medications.

Environmental Factors Influencing Allergy and Asthma

Despite the strong and consistent association between immediate hypersensitivity, allergy, asthma and exposure, there is still controversy about the role inhaled allergen plays and about the timing of events related to sensitization. However, IgE antibodies are essential for the asthmatic response and the symptoms are much more closely associated with IgE antibodies to perennial than to seasonal allergens. Although there have been many changes in our environment, none of these alone explains the consistency or the scale of the rise in asthma over the 40 years between 1960 and 2000.

IgE Antibody Detection and Component Analysis in Patients with Eosinophilic Esophagitis

BACKGROUND Although IgE antibodies to cows milk and wheat are common in patients with eosinophilic esophagitis (EoE), titers are low and responses to diet are not dependent on having IgE antibodies. OBJECTIVE To better define specific IgE antibody responses to foods, focusing on those foods that appear to play a role in EoE. METHODS Adult (n = 46) and pediatric (n = 51) patients with EoE were recruited for skin prick testing and serum measurement (whole and diluted) of IgE antibodies specific for aeroallergens, food extracts, and component allergens by ImmunoCAP. Immuno Solid-phase Allergen Chip analysis was also used to measure the specificity of IgE antibodies to 112 allergen molecules. RESULTS In adults and children, there was a higher prevalence of sensitization to food extracts by ImmunoCAP than by skin prick testing. Using Immuno Solid-phase Allergen Chip to assess the specificity of IgE antibodies to 112 allergen molecules, we found that results for food allergens were mostly negative. In contrast, ImmunoCAP assays for specific milk allergens gave positive IgE antibody results in 31 of 34 sera. The correlations between specific IgE antibody to Bos d 4 or Bos d 5 and milk extract were strong (R = 0.89 and 0.76, respectively; P < .001). The evidence that IgE antibodies to foods were directed at minor components of the extracts was further supported by measurements on diluted sera. CONCLUSIONS The IgE responses in cows milk-sensitized patients with EoE are frequently to whey proteins Bos d 4 and Bos d 5, minor components of the extract. These IgE assays may be able to identify the proteins that are relevant to EoE even though IgE is not the primary mechanism.

The indoor air and asthma: the role of cat allergens

Purpose of review The objective is to discuss recent progress in our understanding of the role of the indoor environment in asthma, focusing on the special role of cat allergens. Recent findings Sensitization to Fel d 1 is the dominant event in inhalant responses to cat; however, there are also IgE responses to the lipocalin (Fel d 4), to cat albumin (Fel d 2), and to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) on cat IgA (Fel d 5w) and other molecules. The dose response and routes of sensitization for these allergens are now thought to be diverse. It is important to remember that exposure outside a house with a cat is sufficient to cause sensitization. Furthermore, the only solid evidence about a role in asthma relates to Fel d 1. Recently, it has been shown that tolerance associated with early exposure to cats can persist to age 18 and that IgE to alpha-gal (on cat IgA) is not related to asthma. In addition, a recent study of anti-IgE reinforces the evidence that IgE antibodies to indoor allergens make a major contribution to asthma severity. Summary Exposure to Fel d 1 in a home with a cat is far higher than the levels necessary to induce an allergic (IgE antibody) response. In keeping with that, children may develop tolerance, which can be long-lived. In addition, there is increasing evidence that IgE antibodies to an inhalant allergen, such as Fel d 1, dust mite, or cockroach, are causally related to lung inflammation and asthma.

Allergens, sources, particles, and molecules: Why do we make IgE responses?

Allergens are foreign proteins or glycoproteins that are the target of IgE antibody responses in humans. The relationship between subsequent exposure and the allergic symptoms is often or usually obvious; however, there is increasing evidence that in asthma, atopic dermatitis and some forms of food allergy the induction of symptoms is delayed or chronic. The primary exposure to inhaled allergens is to the particles, which are capable of carrying allergens in the air. Thus, the response reflects not only the properties of the proteins, but also the biological properties of the other constituents of the particle. This is best understood in relation to the mite fecal particles in which the contents include many different immunologically active substances. Allergic disease first became a major problem over 100 years ago, and for many years sensitization to pollens was the dominant form of these diseases. The rise in pediatric asthma correlates best with the move of children indoors, which started in 1960 and was primarily driven by indoor entertainment for children. While the causes of the increase are not simple they include both a major increase in sensitization to indoor allergens and the complex consequences of inactivity. Most recently, there has also been an increase in food allergy. Understanding this has required a reappraisal of the importance of the skin as a route for sensitization. Overall, understanding allergic diseases requires knowing about the sources, the particles and the routes of exposure as well as the properties of the individual allergens.

Epidemiological analysis of chronic rhinitis in pediatric patients.

Background Nonallergic rhinitis is a poorly understood entity, especially among pediatric patients. Objective The objective of this study was to identify clinical features that may distinguish phenotypes of allergic and nonallergic patients and to evaluate the usefulness of current diagnostic modalities. Methods We reviewed medical records for 151 pediatric patients with perennial rhinitis, evaluated in a multidisciplinary allergy and otolaryngology clinic. Results obtained by standard history, validated sinus and Nasal Quality of Life Survey (SN-5), epicutaneous allergy testing, acoustic rhinometry, and sinus CT were compared. Results Nasal congestion was the most frequent primary presenting complaint (62%). Among subjects having a positive allergy test, associated eye symptoms were more frequent (p = 0.01) and responses to the SN-5 allergic domain were higher (p = 0.02). Sinus CT scores were similar among allergic and nonallergic subjects (median 7 and 8, respectively) and did not correlate with symptom scores (p = 0.6). Among nonallergic subjects, quality of life ratings weakly correlated with sinus CT scores (r = 0.4; p = 0.05). By rhinometry, absolute mean cross-sectional area was similar among allergic (0.32 cm 2 ) and nonallergic (0.36 cm 2 ) subjects and did not correlate with symptom scores (p = 0.8 for allergic and p = 0.6 for nonallergic subjects). Distinct groups of nonallergic patients including those with prominent conjunctival pruritus (n = 24), frequent cold symptoms (n = 3), and chronic sinus disease (n = 2) were observed. Conclusion It is difficult to distinguish allergic and nonallergic rhinitis in patients with perennial disease, but associated eye symptoms and questionnaire responses are predictive of allergy. Acoustic rhinometry and sinus CT suggest that physical obstruction and sinus disease are not related to nasal symptoms including, surprisingly, the sensation of congestion.

Serum vitamin D levels in a cohort of adult and pediatric patients with eosinophilic esophagitis

BACKGROUND Vitamin D deficiency has been associated with increased risk for severe asthma, challenge-proven food allergy, and severe atopic dermatitis. Vitamin D levels have not been reported in patients with eosinophilic esophagitis (EoE). OBJECTIVE To determine levels of 25-hydroxyvitamin D in a cohort of patients with EoE. METHODS Total serum 25-hydroxyvitamin D was measured using liquid chromatography with tandem mass spectroscopy in adults (n = 35) and children (n = 34) with EoE. Results were compared with patient demographics, EoE-specific disease parameters, markers of sensitization, and features of severity using multivariable logistic regression. RESULTS The median vitamin D level was 28.9 ng/mL. Patients with insufficient vitamin D (<30 ng/mL) were older (median 25.5 vs 16.2 years) and had a higher body mass index (median 25.2 vs 19.8 kg/m(2)). Peak median esophageal eosinophil counts were not significantly different for vitamin D insufficient and sufficient patient groups; however, higher vitamin D levels correlated with higher histologic eosinophil counts (R = 0.61, P = .03). Although there were no statistical differences in total IgE or levels of specific IgE between patients with vitamin D insufficiency and those with sufficiency, a positive skin prick test reaction to peanut was more common in patients who had vitamin D insufficiency (adjusted odds ratio 7.57, P = .009). Vitamin D insufficiency was not associated with surrogate markers of severity (dilation in adults or hospitalization or emergency visits in children). CONCLUSION In these patients with EoE, vitamin D levels were low overall (median <30 ng/mL). The only marker of sensitization associated with insufficient vitamin D in these patients with EoE was a positive skin prick test reaction to peanut.