William J. Sheehan

The utility of forced expiratory flow between 25% and 75% of vital capacity in predicting childhood asthma morbidity and severity

Objectives. The forced expiratory volume in 1 second (FEV1) felt to be an objective measure of airway obstruction is often normal in asthmatic children. The forced expiratory flow between 25% and 75% of vital capacity (FEF25–75) reflects small airway patency and has been found to be reduced in children with asthma. The aim of this study was to determine whether FEF25–75 is associated with increased childhood asthma severity and morbidity in the setting of a normal FEV1, and to determine whether bronchodilator responsiveness (BDR) as defined by FEF25–75 identifies more childhood asthmatics than does BDR defined by FEV1. Methods. The Boston Children’s Hospital Pulmonary Function Test database was queried and the most recent spirometry result was retrieved for 744 children diagnosed with asthma between 10 and 18 years of age between October 2000 and October 2010. Electronic medical records in the 1 year prior and the 1 year following the date of spirometry were examined for asthma severity (mild, moderate, or severe) and morbidity outcomes for the three age, race, and gender-matched subgroups: Group A (n = 35) had a normal FEV1, FEV1/forced vital capacity (FVC), and FEF25–75; Group B (n = 36) had solely a diminished FEV1/FVC; and Group C (n = 37) had a normal FEV1, low FEV1/FVC, and low FEF25–75. Morbidity outcomes analyzed included the presence of hospitalization, emergency department visit, intensive care unit admission, asthma exacerbation, and systemic steroid use. Results. Subjects with a low FEF25–75 (Group C) had nearly 3 times the odds ratio (OR) (OR = 2.8, p < .01) of systemic corticosteroid use and 6 times the OR of asthma exacerbations (OR = 6.3, p > .01) compared with those who had normal spirometry (Group A). Using FEF25–75 to define BDR identified 53% more subjects with asthma than did using a definition based on FEV1. Conclusions. A low FEF25–75 in the setting of a normal FEV1 is associated with increased asthma severity, systemic steroid use, and asthma exacerbations in children. In addition, using the percent change in FEF25–75 from baseline may be helpful in identifying BDR in asthmatic children with a normal FEV1.

Pest and allergen exposure and abatement in inner-city asthma: A Work Group Report of the American Academy of Allergy, Asthma & Immunology Indoor Allergy/Air Pollution Committee

Our work group report details the importance of pest allergen exposure in inner-city asthma. We will focus specifically on mouse and cockroach exposure. We will discuss how exposure to these pests is common in the inner city and what conditions exist in urban areas that might lead to increased exposure. We will discuss how exposure is associated with allergen sensitization and asthma morbidity. Finally, we will discuss different methods of intervention and the effectiveness of these tactics.

Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial

IMPORTANCE Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed. OBJECTIVE To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institutes AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment. INTERVENTION Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n = 307) or matching placebo (n = 300), started early during each predefined RTI (childs signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12- through 18-month period. MAIN OUTCOMES AND MEASURES The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures. RESULTS A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P = .04; absolute risk for first RTI: 0.05 for azithromycin, 0.08 for placebo; risk difference, 0.03 [95% CI, 0.00-0.06]). Induction of azithromycin-resistant organisms and adverse events were infrequently observed. CONCLUSIONS AND RELEVANCE Among young children with histories of recurrent severe LRTIs, the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI. More information is needed on the development of antibiotic-resistant pathogens with this strategy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01272635.

Allergens in Urban Schools and Homes of Children with Asthma

To cite this article: Permaul P, Hoffman E, Fu C, Sheehan W, Baxi S, Gaffin J, Lane J, Bailey A, King E, Chapman M, Gold D, Phipatanakul W. Allergens in urban schools and homes of children with asthma. Pediatr Allergy Immunol 2012: 23: 543–549.

Mouse allergens in urban elementary schools and homes of children with asthma

BACKGROUND The association between allergens in schools and childhood asthma has not been well studied, particularly in the United States. OBJECTIVE To investigate allergen exposure in schools compared with homes with a specific focus on children with asthma. METHODS Dust samples were collected from 46 rooms in 4 urban elementary schools (northeastern United States) and from 38 student bedrooms. Samples were analyzed for cat (Fel d 1), dog (Can f 1), cockroach (Bla g 2), dust mites (Der f 1/Der p 1), and mouse urinary protein (MUP). Questionnaires identified students with physician-diagnosed asthma. RESULTS Cat and dog allergens were detectable in most school samples (96% and 78%, respectively), but at low levels. Cockroach allergen was detectable in only 11% of school samples. Mouse allergen was detectable in 89% of school samples, with 68% having MUP levels greater than 0.5 microg/g. In contrast, MUP was detectable in only 26% of bedroom samples. Matched classroom and home samples from 23 asthmatic students showed higher geometric mean MUP levels in the classroom vs the home (6.45 microg/g vs 0.44 microg/g, P < .001). However, there were lower geometric mean dust mite (Der f 1) levels in the classroom vs the home (0.04 microg/g vs 0.66 microg/g, P < .001). CONCLUSIONS There are significantly higher levels of MUP but lower levels of Der f 1 in schools vs homes. It is important to recognize that children with asthma may encounter varying levels of allergens in environments outside the home, such as schools.

Predicting food challenge outcomes for baked milk: role of specific IgE and skin prick testing

BACKGROUND Cows milk allergy is the most common food allergy in childhood. Many children with IgE-mediated cows milk allergy may tolerate baked milk products, but few data exist on predictors of outcomes of baked milk challenges. OBJECTIVE To determine the relation of milk protein allergen specific IgE (sIgE) levels and skin prick test (SPT) wheal size with baked milk challenge outcomes. METHODS A retrospective medical record review was conducted of 35 baked milk challenges. SPT results, sIgE levels, demographic characteristics, and food challenge results were analyzed. RESULTS Thirty-five children underwent open challenges to baked milk and 29 (83%) passed. Of those who failed, 3 (50%) passed the initial clinic challenge but developed symptoms to ongoing exposure at home, days to months later. One child who ultimately failed at home required epinephrine. Compared with those who passed, children who failed were younger (median age, 8.9 and 3.7 years, respectively; P = .02). Children with a milk SPT wheal less than 12 mm were more than 90% likely to pass a baked milk challenge, and no child with a milk SPT wheal less than 7 mm failed a baked milk challenge. We were also able to establish more than 90% predictive values for passing baked milk challenges with a casein SPT wheal of 9 mm, a milk sIgE level of 1.0 kU/L, and a casein sIgE level of 0.9 kU/L. CONCLUSION Most children allergic to cows milk tolerated baked milk. Milk protein SPT wheal may be more reliable than sIgE level in predicting outcomes of baked milk challenges. It is important to be aware of the possibility of late reactions to ongoing baked milk exposure.

Higher incidence of pediatric anaphylaxis in northern areas of the United States

To the Editor: Anaphylaxis is a severe allergic reaction that has a rapid course and can result in death.1 Similar to other allergic diseases, the incidence of anaphylaxis has increased over the past few decades.2-4 Recent estimates suggest a lifetime prevalence of 0.05% to 2.0%,5 with food allergy being the most common cause.2,6 One approach was to indirectly estimate the incidence of anaphylaxis by analyzing medication-dispensing data for epinephrine.7 Camargo et al8 used this method to demonstrate a north-south gradient of EpiPen (Dey L.P., Napa, Calif) prescriptions, with the highest rates found in northern states. Our study scrutinized the incidence of pediatric anaphylaxis with a specific focus on a north-south comparison. To do this, we analyzed a large national billing database of US pediatric hospitals for all patient encounters billed as anaphylaxis. Data for this study were obtained from the Pediatric Health Information System, an administrative database that contains administrative and billing data from a group of tertiary care pediatric hospitals in the United States that are affiliated with the Child Health Corporation of America (Shawnee Mission, Kan), a business alliance of children’s hospitals. We included all pediatric hospitals that contributed complete data from emergency department visits, inpatient admissions, and observation unit stays during a 5-year period from January 2003 to December 2007. There were 24 pediatric hospitals in 18 states across the United States that provided complete data during the entire study period. These hospitals were divided geographically at the line of 39°N latitude, extending roughly from Washington, DC, to Sacramento, California (see Fig E1 in this article’s Online Repository at www.jacionline.org). As determined by the US Geological Society (www.usgs.gov), cities with a degree of latitude greater than 39°N were considered northern cities (n = 11), and cities south of 39°N were considered southern cities (n = 13). FIG E1 Map of the United States divided into north and south. This represents a map of the United States divided geographically at the line of 39°N latitude. We considered hospitals in cities above this line to be northern hospitals and those below the ... We queried all cases in which the primary billing International Classification of Diseases, ninth revision, diagnosis code was specific for anaphylaxis. The diagnoses of anaphylaxis were classified by the type of anaphylaxis (see Table E1 in this article’s Online Repository at www.jacionline.org). We did not include cases in which an anaphylaxis code was secondary or in which the code was not specific for anaphylaxis. Thus we did not include sting anaphylaxis because the code 989.5 (“toxic effect of venom”) is not limited to or specific for anaphylaxis. We then used the Pediatric Health Information System database to calculate the total number of patient encounters at each of the hospitals during the study period. The number of anaphylaxis cases was divided by the total number of patient encounters to calculate an incidence (cases per 1,000 encounters). Incidences were calculated for each geographic region, each type of patient, and each coded type of anaphylaxis. Rates were compared, and rate ratios (RRs) with 95% CIs were calculated. Statistical significance was achieved with a 2-sided P value of less than .05, and analyses were performed with SPSS version 14 software (SPSS, Inc, Chicago, Ill). TABLE E1 International Classification of Diseases, ninth revision, codes evaluated to determine cases of anaphylaxis We identified 6,457 cases of anaphylaxis among 8,589,583 patient encounters over the 5-year period. This is an incidence of 0.75 cases per 1,000 patient encounters. The median age of the subjects with anaphylaxis was 4.1 years, with 53.8% being male. Across the country, the incidence increased 50% during our study period, from 0.64 cases per 1,000 encounters in 2003 to 0.96 cases per 1,000 encounters in 2007 (P < .001). The basic demographics of the cases of anaphylaxis are presented in Table I. Analysis of the northern hospital data revealed 3,704 cases of anaphylaxis among 4,199,103 patient encounters (rate of 0.88 cases per 1,000 encounters) compared with 2,753 cases of anaphylaxis among 4,390,480 patient encounters in the southern hospitals (rate of 0.63 cases per 1,000 encounters). Overall, this difference was statistically significant (RR, 1.41; 95% CI, 1.34-1.48; P < .001). Additionally, we compared degree of latitude with rate of anaphylaxis and found a statistically significant positive correlation (r = 0.555, P = .005). As seen in Table I, northern hospitals had statistically higher rates of anaphylaxis for all large subgroups of sex, race, and patient location. TABLE I Basic demographics of cases of anaphylaxis Overall, the most common cause of anaphylaxis was food induced (n = 2,082 [32.2%]). This was followed by anaphylaxis caused by immunization or serum (n = 1,800 [27.9%]), medication (n = 1,627 [25.2%]), and unspecified or “other” causes (n = 946 [14.7%]). The comparison of northern hospitals with southern hospitals according to each type of anaphylaxis is seen in Fig 1. Anaphylaxis cases caused by food, immunization or serum, and “other” were all more common in the northern hospitals. In particular, the incidence of food anaphylaxis was almost double in the north compared with that in the south (0.31 vs 0.17; RR, 1.81; 95% CI, 1.66-1.98; P < .001). There was no statistical difference in the rates of medication-induced anaphylaxis between the north and south (0.19 vs 0.19; RR, 1.02; 95% CI, 0.92-1.12; P = .73). FIG 1 Rates of anaphylaxis by type of anaphylaxis. Each bar represents the identified cases of anaphylaxis per 1,000 patient encounters. P values represent the comparison of rates in the north with rates in the south (χ2 test). This study is the first in the United States to evaluate the incidence of anaphylaxis on a national scale. Although we were unable to evaluate the true incidence in the general public, we were able to evaluate the rate of anaphylaxis cases per patient encounters at 24 hospitals in 18 states across the United States. We found a similar distribution of anaphylaxis as in previous studies,2,6 with food-induced cases being the most common. The median age of our cases was low (approximately 4 years), with a male predominance (53.8%). Although evaluated from a different perspective, our study also suggests higher rates of anaphylaxis in northern areas of the United States. Previous studies have used epinephrine distribution data, but instead, our study used primary billing diagnostic codes, thus eliminating prescription-writing bias. It has been suggested that this north-south gradient might be due to differences in vitamin D status. Although some studies have shown an inverse relationship between vitamin D status and risk of atopic illnesses,9 more studies are needed in this area. Additionally, future studies are needed to evaluate for a north-south gradient for other atopic illnesses, such as asthma, allergic rhinitis, and eczema. Of note, our study is representative of cases evaluated and treated at freestanding pediatric hospitals. As such, these hospitals are often referral centers providing tertiary care for all children in a certain city or state. It is difficult to assess how this might reflect incidence calculations for the general public. This might overestimate numbers if a large number of difficult anaphylaxis cases are referred to these hospitals. In contrast, it might underestimate incidence because anaphylaxis is an acute illness that is often treated immediately at local smaller hospitals. Also, our method of case identification by means of diagnostic billing codes might lead to errors in incidence calculation if anaphylaxis is inaccurately billed. However, both of these limitations occur in the north and south and should not affect the geographic comparison provided in our study.

The School Inner-City Asthma Study: Design, Methods, and Lessons Learned

Background. Children spend a significant amount of time in school. Little is known about the role of allergen exposure in school environments and asthma morbidity. Objectives. The School Inner-City Asthma Study (SICAS) is a National Institutes of Health (NIH)-funded prospective study evaluating the school/classroom-specific risk factors and asthma morbidity among urban children. Methods/results. This article describes the design, methods, and important lessons learned from this extensive investigation. A single center is recruiting 500 elementary school-aged children, all of whom attend inner-city metropolitan schools. The primary hypothesis is that exposure to common indoor allergens in the classroom will increase the risk of asthma morbidity in children with asthma, even after controlling for home allergen exposures. The protocol includes screening surveys of entire schools and baseline eligibility assessments obtained in the spring prior to the academic year. Extensive baseline clinical visits are being conducted among eligible children with asthma during the summer prior to the academic school year. Environmental classroom/school assessments including settled dust and air sampling for allergen, mold, air pollution, and inspection data are collected twice during the academic school year and one home dust sample linked to the enrolled student. Clinical outcomes are measured every 3 months during the academic school year. Conclusion. The overall goal of SICAS is to complete the first study of its kind to better understand school-specific urban environmental factors on childhood asthma morbidity. We also discuss the unique challenges related to school-based urban research and lessons being learned from recruiting such a cohort.

Exposures to Molds in School Classrooms of Children with Asthma

Students spend a large portion of their day in classrooms which may be a source of mold exposure. We examined the diversity and concentrations of molds in inner‐city schools and described differences between classrooms within the same school.

Role of specific IgE and skin-prick testing in predicting food challenge results to baked egg

Previous studies suggest that children with egg allergy may be able to tolerate baked egg. Reliable predictors of a successful baked egg challenge are not well established. We examined egg white-specific IgE levels, skin-prick test (SPT) results, and age as predictors of baked egg oral food challenge (OFC) outcomes. We conducted a retrospective chart review of children, aged 2-18 years, receiving an egg white-specific IgE level, SPT, and OFC to baked egg from 2008 to 2010. Fifty-two oral baked egg challenges were conducted. Of the 52 challenges, 83% (n = 43) passed and 17% (n = 9) failed, including 2 having anaphylaxis. Median SPT wheal size was 12 mm (range, 0-35 mm) for passed challenges and 17 mm (range, 10-30 mm) for failed challenges (p = 0.091). The negative predictive value for passing the OFC was 100% (9 of 9) if SPT wheal size was <10 mm. Median egg white-specific IgE was 2.02 kU/L (range, <0.35-13.00 kU/L) for passed challenges and 1.52 kU/L (range, 0.51-6.10 kU/L) for failed challenges (p = 0.660). Receiver operating characteristic (ROC) curve analysis for SPT revealed an area under the curve (AUC) of 0.64. ROC curve analysis for egg white-specific IgE revealed an AUC of 0.63. There was no significant difference in age between patients who failed and those who passed (median = 8.8 years versus 7.0 years; p = 0.721). Based on our sample, SPT, egg white-specific IgE and age are not good predictors of passing a baked egg challenge. However, there was a trend for more predictability with SPT wheal size.