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We determined prognostic implications of acute lung injury (ALI) and organizing pneumonia (OP), including timing relative to transplantation, in a multicenter lung recipient cohort. We sought to understand clinical risks that contribute to development of ALI/OP. We analyzed prospective, histologic diagnoses of ALI and OP in 4786 lung biopsies from 803 adult lung recipients. Univariable Cox regression was used to evaluate the impact of early (≤90 days) or late (90 days) posttransplant ALI or OP on risk for chronic lung allograft dysfunction (CLAD) or death/retransplantation. These analyses demonstrated late ALI/OP conferred a two- to threefold increase in the hazards of CLAD or death/retransplantation; there was no association between early ALI/OP and these outcomes. To determine risk factors for late ALI/OP, we used univariable Cox models considering donor/recipient characteristics and posttransplant events as candidate risks. Grade 3 primary graft dysfunction, higher degree of donor/recipient human leukocyte antigen mismatch, bacterial or viral respiratory infection, and an early ALI/OP event were significantly associated with increased late ALI/OP risk. These data from a contemporary, multicenter cohort underscore the prognostic implications of ALI/OP on lung recipient outcomes, clarify the importance of the timing of these events, and identify clinical risks to target for ALI/OP prevention.

BACKGROUND: Peanut allergy affects 1% to 2% of European children. Early introduction of peanut into the diet reduces allergy in high-risk infants.OBJECTIVE: We aimed to determine the optimal target populations and timing of introduction of peanut products to prevent peanut allergy in the general population.METHODS: Data from the Enquiring About Tolerance (EAT; n = 1303; normal risk; 3-year follow-up; ISRCTN14254740) and Learning Early About Peanut Allergy study (LEAP; n = 640; high risk; 5-year follow-up; NCT00329784) randomized controlled trials plus the Peanut Allergy Sensitization (PAS; n = 194; low and very high risk; 5-year follow-up) observational study were used to model the intervention in a general population. Peanut allergy was defined by blinded peanut challenge or diagnostic skin prick test result.RESULTS: Targeting only the highest-risk infants with severe eczema reduced the population disease burden by only 4.6%. Greatest reductions in peanut allergy were seen when the intervention was targeted only to the larger but lower-risk groups. A 77% reduction in peanut allergy was estimated when peanut was introduced to the diet of all infants, at 4 months with eczema, and at 6 months without eczema. The estimated reduction in peanut allergy diminished with every month of delayed introduction. If introduction was delayed to 12 months, peanut allergy was only reduced by 33%.CONCLUSIONS: The preventive benefit of early introduction of peanut products into the diet decreases as age at introduction increases. In countries where peanut allergy is a public health concern, health care professionals should help parents introduce peanut products into their infants' diet at 4 to 6 months of life.

Rationale: Acute rejection, manifesting as lymphocytic inflammation in a perivascular (acute perivascular rejection [AR]) or peribronchiolar (lymphocytic bronchiolitis [LB]) distribution, is common...

The histopathologic diagnosis of acute allograft injury is prognostically important in lung transplantation with evidence demonstrating a strong and consistent association between acute rejection (AR)(1–7), acute lung injury (ALI)(8, 9) and the subsequent development of chronic lung allograft dysfunction (CLAD). The pathogenesis of these allograft injuries however, remains poorly understood. CXCL9 and CXCL10 are CXC chemokines induced by interferon-γ and act as potent chemoattractants of mononuclear cells. We hypothesized that these chemokines are involved in the mononuclear cell recruitment associated with AR and ALI. We further hypothesized that the increased activity of these chemokines could be quantified as increased levels in the bronchoalveolar lavage fluid. In this prospective multicenter study, we evaluate the incidence of histopathologic allograft injury development during the first-year post-transplant and measure bronchoalveolar CXCL9 and CXCL10 levels at the time of the biopsy. In multivariable models, CXCL9 levels were 1.7-fold and 2.1-fold higher during AR and ALI compared with “normal” biopsies without histopathology. Similarly, CXCL10 levels were 1.6-fold and 2.2-fold higher during these histopathologies, respectively. These findings support the association of CXCL9 and CXCL10 with episodes of AR and ALI, and provide potential insight into the pathogenesis of these deleterious events.

Background Nasal allergen challenge (NAC) could be a means to assess indication and/or an outcome of allergen-specific therapies, particularly for perennial allergens. NACs are not commonly conducted in children with asthma and cockroach NACs are not well established. This study's objective was to identify a range of German cockroach extract doses that induce nasal symptoms and to assess the safety of cockroach NAC in children with asthma. Methods Ten adults (18-37 years) followed by 25 children (8-14 years) with well-controlled, persistent asthma and cockroach sensitization underwent NAC with diluent followed by up to 8 escalating doses of cockroach extract (0.00381 -11.9 mcg/mL Bla g 1). NAC outcome was determined by Total Nasal Symptom Score (TNSS) and/or sneeze score. Cockroach allergen-induced T cell activation and IL-5 production were measured in peripheral blood mononuclear cells. Results 67% (6/9) of adults and 68% (17/25) of children had a positive NAC at a median response dose of 0.120 mcg/mL [IQR 0.0380-0.379 mcg/mL] of Bla g 1. Additionally, three children responded to diluent alone, and did not receive any cockroach extract. Overall, 32% (11/34) were positive with sneezes alone, 15% (5/34) with TNSS alone, and 21% (7/34) with both criteria. At baseline, NAC responders had higher cockroach-specific IgE (p=0.03), lower cockroach-specific IgG/IgE ratios (children, p=0.002), and increased cockroach-specific IL-5-producing T lymphocytes (p=0.045). The NAC was well tolerated. Conclusion We report the methodology of NAC development for children with persistent asthma and cockroach sensitization. This NAC could be considered a tool to confirm clinically relevant sensitization and to assess responses in therapeutic studies.

For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population.We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160.Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755-5005) for peanut oral immunotherapy versus 5 mg (0-105) for placebo (p0·0001). After avoidance, 20 (21%, 95% CI 13-30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10-28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0-2755) for peanut oral immunotherapy and 0 mg (0-55) for placebo (p0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy.In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy.National Institute of Allergy and Infectious Disease, Immune Tolerance Network.

Introduction There is no detailed comparison of allergen-specific immunoglobulin responses following sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT). Objective We sought to compare nasal and systemic timothy grass pollen (TGP)-specific antibody responses during 2 years of SCIT and SLIT and 1 year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial. Methods Nasal fluid and serum were obtained yearly (per-protocol population, n = 84). TGP-specific IgA1, IgA2, IgG4, IgG, and IgE were measured in nasal fluids by ELISA. TGP-specific IgA1, IgA2, and Phleum pratense (Phl p)1, 2, 4, 5b, 6, 7, 11, and 12 IgE and IgG4 were measured in sera by ELISA and ImmunoCAP, respectively. Results At years 2 and 3, TGP-IgA1/2 levels in nasal fluid were elevated in SLIT compared with SCIT (4.2- and 3.0-fold for IgA1, 2.0- and 1.8-fold for IgA2, respectively; all P Conclusions The observed induction of IgA1/2 in SLIT and IgG4 in SCIT suggest key differences in the mechanisms of action.

Background Nonpharmacologic interventions for asthma management rely on identification and mitigation of important asthma triggers. Cockroach exposure is strongly associated with asthma morbidity. It is also associated with stress, another risk factor for asthma. Despite high prevalence of both in vulnerable populations, the impact of joint exposure has not been examined. Methods Participants included 173 children with asthma in New Orleans, Louisiana. Cockroach exposure was based on visual inspection using standard protocols. Caregiver stress was measured using Cohen’s 4-item Perceived Stress Scale. Outcomes included unscheduled clinic or emergency department (ED) visits, hospitalization, and pulmonary function. Multivariable logistic regression was performed to assess independent effects of the exposure on the outcome and effect modification was examined in stratified analysis based on stress. Path analysis to explore the mediation effect by stress was performed using a probit link with parameters based on Bayes’ method with non-informative priors. Results Adjusting for stress and other covariates, cockroach exposure was associated with unscheduled clinic/ED visits (aOR = 6.2; 95% CI 1.8, 21.7). Positive associations were also found for hospitalization and FEV1

Background The direct-instillation nasal allergen challenge (NAC) and the environmental exposure chamber (EEC) are 2 methods of conducting controlled allergen provocations. The clinical and biological comparability of these methods has not been thoroughly investigated. Objective We sought to compare clinical and immunologic responses to cat allergen in NAC versus EEC. Methods Twenty-four participants were randomized to receive either NAC followed by a 2-day challenge in an EEC or a 2-day challenge in an EEC followed by NAC. Challenges were separated by 28-day washout periods. We measured total nasal symptom scores, peak nasal inspiratory flow, nasal (0-8 hours) and serum cytokines, serum antibodies, peripheral blood antigen-specific T lymphocytes, and gene expression in nasal scrapings. The primary outcome was the total nasal symptom score area under the curve for the first 3 hours after allergen exposure in NAC or after initiation of exposure in EEC. Results Both challenges increased IL-5 and IL-13 in nasal fluids and serum and resulted in altered nasal cell expression of gene modules related to mucosal biology and transcriptional regulation. Changes in gene modules, more so than cytokine measurements, showed significant associations with total nasal symptom score and peak nasal inspiratory flow. Overall, EEC exposure generated larger responses and more early terminations compared with NAC. Although the 2 challenges did not correlate in symptom magnitude or temporality, striking correlations were observed in cytokine levels. Conclusions Although clinical outcomes of NAC and EEC were temporally different and nonequivalent in magnitude, immunologic responses were similar. Selection of a particular allergen challenge method should depend on considerations of study objectives and cost.

BACKGROUND: Staphylococcus aureus has been implicated in the pathophysiology of eczema, allergic rhinitis, asthma, and food allergy. S aureus is a marker of more severe eczema, which is a risk factor for food sensitization/allergy. Therefore it might be that the association between S aureus and food allergy in eczematous patients is related to eczema severity.OBJECTIVE: We sought to investigate the association of S aureus colonization with specific IgE (sIgE) production to common food allergens and allergies in early childhood independent of eczema severity. We additionally determined the association of S aureus colonization with eczema severity and persistence.METHODS: In Learning Early About Peanut Allergy (LEAP) study participants eczema severity was assessed, and skin/nasal swabs were cultured for S aureus. Sensitization was identified by measuring sIgE levels. Peanut allergy was primarily determined by means of oral food challenge, and persistent egg allergy was primarily determined by using skin prick tests.RESULTS: Skin S aureus colonization was significantly associated with eczema severity across the LEAP study, whereas at 12 and 60 months of age, it was related to subsequent eczema deterioration. Skin S aureus colonization at any time point was associated with increased levels of hen's egg white and peanut sIgE independent of eczema severity. Participants with S aureus were more likely to have persistent egg allergy and peanut allergy at 60 and 72 months of age independent of eczema severity. All but one of the 9 LEAP study consumers with peanut allergy (9/312) were colonized at least once with S aureus.CONCLUSION: S aureus, independent of eczema severity, is associated with food sensitization and allergy and can impair tolerance to foods. This could be an important consideration in future interventions aimed at inducing and maintaining tolerance to food allergens in eczematous infants.

Streszczenie Wstep Wczesne wprowadzenie do diety orzeszkow ziemnych jest skuteczną strategią zapobiegania alergii na orzeszki ziemne u niemowląt z grupy wysokiego ryzyka; jednakze wykonalnośc oraz wplyw na rozwoj fizyczny i stan odzywienia są nieznane. Cel Staraliśmy sie ocenic wykonalnośc wprowadzenia orzeszkow ziemnych do diety u niemowląt i badaliśmy ich wplyw na rozwoj fizyczny i stan odzywienia do uzyskania przez dzieci wieku 60 miesiecy. Metody W badaniu LEAP ( Learning Early About Peanut Allergy ) 640 niemowląt z atopią w wieku od 4 do 11 miesiecy zostalo losowo wlączonych do grupy spozywającej orzeszki (6 g bialka orzeszkow ziemnych na tydzien) lub grupy unikającej spozywania orzeszkow do osiągniecia wieku 60 miesiecy. Spozycie orzeszkow i praktyki dotyczące karmienia byly oceniane za pomocą kwestionariusza. Przyjmowanie pokarmow oceniano za pomocą prospektywnych dzienniczkow. Pomiary antropometryczne byly zbierane podczas kazdej wizyty w czasie trwania badania. Wyniki Orzeszki ziemne zostaly z powodzeniem wprowadzone do diety i byly spozywane do czasu ukonczenia 60. miesiąca zycia, ze średnim tygodniowym spozyciem bialka orzeszkow ziemnych wynoszącym 7,5 g (przedzial miedzykwartylowy, 6,0–9,0 g/tydz.) w grupie dzieci spozywającej orzeszki w porownaniu do 0 g w grupie dzieci unikających orzeszkow. Wprowadzenie orzeszkow ziemnych do diety niemowląt karmionych piersią nie wplynelo na dlugośc okresu karmienia piersią. Podczas zadnej z wizyt nie zaobserwowano roznic pomiarow antropometrycznych lub wartości energetycznej pomiedzy obiema grupami. Regularne spozywanie orzeszkow ziemnych prowadzilo do roznic w diecie. Dieta dzieci spozywających orzeszki byla bogatsza w tluszcze, podczas gdy dzieci unikające orzeszkow spozywaly wiecej weglowodanow; roznice byly wieksze dla gornych kwartyli grupy spozywającej orzeszki ziemne. Spozycie bialek bylo stale w obu grupach. Wnioski Wprowadzenie orzeszkow ziemnych do diety niemowląt z wysokim ryzykiem alergii na orzeszki ziemne okazalo sie wykonalne i nie wplynelo na dlugośc okresu karmienia piersią, a takze nie wplynelo negatywnie na rozwoj fizyczny lub stan odzywienia. Rownowage kaloryczną osiągnieto w obu grupach poprzez rozne spozycie tluszczow i weglowodanow, przy czym rownowaga bialkowa zostala zachowana.

Purpose Frailty is gaining increased recognition in the evaluation of lung transplant (LTx) candidates. The Fried Frailty Phenotype (FFP) index has been the most commonly used instrument and is associated with pre- and post-transplant morbidity and mortality. A novel, alternative approach to assessing frailty is the Cumulative Deficits Frailty Index (CFI), which evaluates health deficits across multiple domains that may aid in refining candidacy evaluation. As a preliminary assessment, we aimed to understand the distribution of frailty scores among LTx candidates and assess agreement between the FFP and the CFI. Methods This was a prospective, multi-center study of a subset of participants in the Clinical Trials in Organ Transplantation-20 cohort who completed both the FFP and CFI assessments pre-transplant. FFP was characterized using 5 criteria (unintentional weight loss, grip strength, energy levels, gait speed and physical activity), with FFP frailty defined (≥3 criteria frail; 1-2 pre-frail; and 0 not frail). The CFI was comprised of 40 health items abstracted from medical records with frailty defined as >10/40 (score of 0.25) deficits. Agreement between total FFP and CFI scores was assessed using Cohen's Kappa statistic and we also evaluated the distribution of CFI scores by each sub-component of the FFP. Results The cohort was comprised of 124 LTx candidates (median age 62 years, 56% male, median LAS 39) with 57% having restrictive lung disease. 11 (9%) LTx candidates were frail on the FFP, whereas 85 (69%) were pre-frail (grouped as non-frail). The median CFI score for the cohort was 0.23 (IQR 0.15-0.28) with 48 (39%) deemed frail. 79 (64%) had matching frail and non-frail statuses between the indices with agreement assessed as poor [Kappa 0.11 95% CI (-0.02 to 0.24)]. The median CFI scores were more concordant with FFP domains of weight loss [Frail FFP: 0.26 (IQR 0.20-0.29) vs. Not Frail FFP: 0.21 (0.15-0.28)], physical activity [0.25 (0.21-0.28) vs. 0.21 (0.15-0.28)], and gait speed [0.25 (0.19-0.33) vs. 0.21 (0.15-0.28)], but not with grip strength or energy levels. Conclusion In this multi-center study, agreement between frailty indices was poor suggesting the CFI potentially captures a different construct than FFP. The study is ongoing evaluating the prognostic utility of these indices with early post-transplant outcomes.

Purpose The occurrence of acute allograft injuries remains one of the most important factors responsible for the development of early chronic lung allograft dysfunction. We and others have previously demonstrated a consistent association between acute lung injury (ALI), acute perivascular rejection (AR) and lymphocytic bronchiolitis (LB) and the subsequent development of CLAD. However, the pathogenesis of these allograft injuries remains poorly understood. CXCL9, CXCL10, and CXCL11 are CXC chemokines induced by interferon-γ and act as potent chemoattractants of mononuclear cells (e.g., activated T-cells and NK cells). We hypothesized that episodes of ALI, AR and LB would be associated with increased activity of these CXCR3 chemokines, as measured in the BAL at the time of the injury. Methods The study cohort consisted of the first 200 lung transplant recipients enrolled in Clinical Trials in Organ Transplantation-20 (NCT02631720), a prospective multi-center observational study collecting serial clinical data and biologic samples from 5 North American transplant centers. Recipients received a median (Q1,Q3) of 5 (3, 6) bronchoscopies during the first-year post-transplant. Transbronchial biopsies (TBBXs) with no histopathologic evidence of allograft injury were classified as “healthy”. BALF CXCL9, CXCL10 and CXCL11 mean fluorescence intensities (MFIs) were measured using luminex bead assays. To evaluate differences in CXCR3 chemokine levels between allograft injuries and healthy biopsies, multivariable linear mixed effects models were constructed taking into account repeated measurements from recipients. Results There were 844 TBBXs with 249(30%) episodes of allograft injury observed. There were 173(20%) episodes of AR, 30(4%) episodes of LB and 42(5%) episodes of ALI. Biopsies with AR, LB or ALI were associated with significant elevations in all three chemokines compared with healthy biopsies (p Conclusion We demonstrate for the first time in a multicenter study, CXCR3 chemokine elevations during episodes of acute allograft injury. These findings support the association of CXCR3 chemokines during episodes of AR, LB and ALI, and may potentially offer novel therapeutic targets to prevent and treat these deleterious events.

Purpose Diagnosis of CLAD after lung transplantation (LT) requires sustained decline in lung function and exclusion of other etiologies for the decline. The limitations of relying primarily on pulmonary function test (PFT) decline to define CLAD onset for large cohort studies are not well characterized. Using a large, prospective, multicenter cohort of LT recipients, we sought to implement a rigorous approach to identify and confirm CLAD using automated analysis of serial PFT trajectory combined with local site adjudication to rule out exclusionary conditions. Methods The CTOT-20 cohort consists of 803 adult first LT recipients enrolled between 2015 and 2018 from 5 North American centers. PFT data transfers occurred monthly from sites to the data coordinating center, which applied an automated process using SAS code to identify potential CLAD in subjects who survived at least 90 days and had at least 5 PFTs. Potential CLAD cases, defined by sustained PFT decline per ISHLT definition, were sent to the local site to either identify alternative reasons for the decline or confirm CLAD. The site adjudication process included systematic assessment of clinical findings, bronchoscopy, microbiology, pathology, and radiographic information. Results 746 subjects were included in the analysis and had on average 18.9 (range 5-77) PFTs. Potential CLAD was identified a total of 379 times in 195 subjects based on PFT decline. CLAD was confirmed by the local site PI in 108/195 subjects (55.4%) and the mean time to CLAD onset was 14.8 (range 3.6-39.6) months. CLAD was confirmed even less frequently during earlier timepoints (28% in months 0-6, 43% in months 7-12, and 52% in months 13-18). The most frequent concurrent conditions excluding CLAD diagnosis were active infection (34.4%), airways stenosis (16.0%), pleural effusion/disease (14.9%), and acute rejection (14.1%). Conclusion Utilizing an automated approach to identify potential CLAD supplemented by local site adjudication, we found that the majority of potential CLAD qualifying events by PFT decline had evident alternative explanations. Our results indicate that CLAD adjudication utilizing a broad spectrum of clinical information is critical. This approach was used effectively across multiple centers and provides a robust strategy that can be leveraged in future multicenter CLAD studies.

BACKGROUND: Early introduction of dietary peanut in high-risk infants with severe eczema, egg allergy, or both prevented peanut allergy at 5 years of age in the Learning Early About Peanut Allergy (LEAP) study. The protective effect persisted after 12 months of avoiding peanuts in the 12-month extension of the LEAP study (LEAP-On). It is unclear whether this benefit is allergen and allergic disease specific.OBJECTIVE: We sought to assess the effect of early introduction of peanut on the development of allergic disease, food sensitization, and aeroallergen sensitization.METHODS: Asthma, eczema, and rhinoconjunctivitis were diagnosed based on clinical assessment. Reported allergic reactions and consumption of tree nuts and sesame were recorded by questionnaire. Sensitization to food allergens and aeroallergens was determined by means of skin prick testing and specific IgE measurement.RESULTS: A high and increasing burden of food allergen and aeroallergen sensitization and allergic disease was noted across study time points; 76% of LEAP participants had at least 1 allergic disease at 60 months of age. There were no differences in allergic disease between LEAP groups. There were small differences in sensitization and reported allergic reactions for select tree nuts, with levels being higher in the LEAP consumption group. Significant resolution of eczema and sensitization to egg and milk occurred in LEAP participants and was not affected by peanut consumption.CONCLUSION: Early consumption of peanut in infants at high risk of peanut allergy is allergen specific and does not prevent the development of other allergic disease, sensitization to other food allergens and aeroallergens, or reported allergic reactions to tree nuts and sesame. Furthermore, peanut consumption does not hasten the resolution of eczema or egg allergy.

Purpose Despite the importance of AR and LB in lung recipients, the incidence and associated clinical factors have not been prospectively studied in a contemporary cohort. We used a multicenter lung transplant cohort to describe the incidence of AR and LB over the first posttransplant year, examine concurrent histology at the time of an AR/LB event, and determine recipient factors associated with AR or LB. Methods The cohort was drawn from CTOT-20 (NCT02631720), an observational study collecting prospective clinical outcome data on lung recipients at 5 North American centers. The first 200 enrolled, transplanted subjects with ≥1 lung biopsy within the first posttransplant year were included. Recipients were managed according to center-specific clinical care practices. Descriptive statistics were used to summarize AR or LB events and concurrent histology. Univariate Cox modeling was used to evaluate the impact of select recipient factors on the time to first occurrence of AR or LB. Results 1007 biopsies were performed over the first posttransplant year in this cohort. 56% and 17% of patients experienced at least one AR or LB episode, respectively. Rates of minimal and mild AR and minimal LB were similar on for cause vs. surveillance biopsies. While a majority of LB events were concurrent with AR, AR events generally occurred in isolation or were concurrent with non-rejection histopathology. Univariate analyses suggested a protective effect of induction immunosuppression on the risk for AR. We also observed a significant decrease in the hazard of AR and LB in bilateral, as compared to single, lung recipients (Figure). Conclusion We observed a higher incidence of AR than that reported by the ISHLT registry. This may, in part, be attributed to the practice of surveillance biopsies in all CTOT-20 centers. While the impact of induction on AR risk is consistent with ISHLT data, the novel association between transplant type and AR/LB will be further validated over extended cohort follow up using multivariable approaches.

Purpose ALI and OP are histologic patterns of lung damage associated with poor long-term outcomes after lung transplantation. Yet the incidence of ALI and OP and associated clinical factors remain poorly understood. Methods The cohort was drawn from CTOT-20 (NCT02631720), a multicenter prospective lung transplant cohort study. The first 200 enrolled, transplanted subjects with ≥ 1 lung biopsy in the first year after transplant were included. Descriptive statistics were used to summarize ALI or OP events in the 1007 biopsies performed over the first posttransplant year in this cohort. Univariate Cox regression models were used to evaluate the impact of recipient factors on the time to first ALI or OP event. Time independent covariates included age, sex, native disease, transplant type, use of induction immunosuppression, type of primary maintenance immunosuppression, HLA mismatch, and grade 3 primary graft dysfunction (PGD) within 72 hours. Time dependent covariates included a positive fungal, bacterial, mycobacterial, or respiratory viral organism on a respiratory specimen and development of a donor specific antibody. Results Forty-eight patients (24%) experienced at least one ALI event over the first posttransplant year (max 4 per patient). Similarly, 50 patients (25%) experienced at least one OP event (max 3 per patient). The median time to first ALI event was 44 (IQR 24,90) days while the time to first OP was somewhat longer at 92 (IQR 35,203) days. Both ALI and OP were identified slightly more often on for cause vs. surveillance biopsies. The majority of ALI and OP events were not concurrent with other histologic findings, such as acute rejection. Cox analyses identified PGD (HR 2.27, p=0.01) and cyclosporine-based maintenance therapy (HR 2.15, p=0.01) as risk factors for ALI. Analyses for the outcome of OP also implicated PGD (HR 1.97, p=0.03) and cyclosporine maintenance (HR 2.59, p Conclusion OP and ALI are common patterns of lung allograft injury. We identified clinical risk factors for ALI and OP that are potentially modifiable. Ongoing analyses will validate these risks over extended cohort follow up using multivariable approaches. As such, this work may identify strategies to mitigate ALI and OP and improve lung recipient outcomes.

Purpose Lung transplant improves health-related quality of life (HRQL) for many recipients. However, with increasing lung disease severity and higher acuity candidates, it is not clear the early trajectory of improvement and the specific early clinical factors that might be associated with this improvement. Understanding post transplant HRQL trajectories and clinical factors that influence those trajectories is an unmet need. Methods As part of a prospective multi center cohort study, lung transplant recipients completed the Short Form-36 (SF-36) and the St George's Respiratory Questionnaire (SGRQ) pre-transplant and at 1, 3, 6, 9 and 12 months post-transplant. A longitudinal repeated measures linear mixed model was constructed with separate slopes prior to and post day 91 due to evidence of time-varying associations. The impact of key clinical factors on HRQL changes was modeled in secondary analyses. Results For the SF-36 physical component score and all SGRQ domains, lung transplant recipients had large improvements in the first 3 months post-transplant that remained mostly stable over the remainder of the first year. In particular, younger patients, patients with cystic fibrosis and patients with worse pre-transplant HRQL had the greatest improvements in the early period after transplant. The mean SF-36 mental component score was in the normal range pre-transplant and remained stable post-transplant. Conclusion Lung transplant recipients have dramatic and sustained improvement in HRQL by SF-36 and SGRQ domains with the greatest improvements evident within 3 months that may differ by age, native lung disease pre-transplant HRQL.

Background Early introduction of peanut is an effective strategy to prevent peanut allergy in high-risk infants; however, feasibility and effects on growth and nutritional intake are unknown. Objective We sought to evaluate the feasibility of introducing peanut in infancy and explore effects on growth and nutritional intake up to age 60 months. Methods In the Learning Early About Peanut Allergy trial, 640 atopic infants aged 4 to 11 months were randomly assigned to consume (6 g peanut protein per week) or avoid peanut until age 60 months. Peanut consumption and early feeding practices were assessed by questionnaire. Dietary intake was evaluated with prospective food diaries. Anthropometric measurements were taken at all study visits. Results Peanut was successfully introduced and consumed until 60 months, with median peanut protein intake of 7.5 g/wk (interquartile range, 6.0-9.0 g/wk) in the consumption group compared with 0 g in the avoidance group. Introduction of peanut in breast-feeding infants did not affect the duration of breast-feeding. There were no differences in anthropometric measurements or energy intakes between groups at any visits. Regular peanut consumption led to differences in dietary intakes. Consumers had higher intakes of fat and avoiders had higher carbohydrate intakes; differences were greatest at the upper quartiles of peanut consumption. Protein intakes remained consistent between groups. Conclusions Introduction of peanut proved feasible in infants at high risk of peanut allergy and did not affect the duration of breast-feeding nor impact negatively on growth or nutrition. Energy balance was achieved in both groups through variations in intakes from fat and carbohydrate while protein homeostasis was maintained.

Background In a randomized trial, the early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. In this follow-up study, we investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanut-consumption group), as compared with those who had avoided peanuts (peanut-avoidance group). Methods: At the end of the primary trial, we instructed all the participants to avoid peanuts for 12 months. The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age. Results: We enrolled 556 of 628 eligible participants (88.5%) from the primary trial; 550 participants (98.9%) had complete primary-outcome data. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], PConclusions: Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longer-term effects are not known. (Funded by the National Institute of Allergy and Infectious Diseases and others; LEAP-On ClinicalTrials.gov number, NCT01366846 .).

Background: Dust mite allergens can induce allergic sensitization and exacerbate asthma symptoms. Although dust mite reduction and control strategies exist, few asthmatics employ them. Objectives: We examined whether an in-home test kit, which quantifies dust mite allergen levels, resulted in behavioral changes in implementation and maintenance of mite reduction strategies and helped reduce allergen levels in homes of dust mite-sensitive children. Methods: We enrolled 60 households of children aged 5–15 with parent-reported dust mite allergy into a randomized controlled trial. Intervention homes (N = 30) received educational material about reducing dust mites and test kits at 1, 2, 5 and 8 months. Control homes (N = 30) received only educational material. At baseline, 6 and 12 months, study staff visited all homes, collected dust samples from three locations and obtained information about parents’ mite reduction behaviors by questionnaire. Allergen concentrations (Der f 2/Der p2) in dust were assessed by immunoassays. After adjusting for visit and location, allergen concentrations in intervention and control homes were compared using mixed effects model analysis. Results: In the intervention homes, allergen concentrations in the child’s bedroom and living room floors were significantly reduced over time compared to control homes. Although not all location-specific differences in allergen concentrations were statistically significant, combining data across locations, there was a differential reduction in allergen concentrations in the intervention group versus the control group (p = 0.02). Conclusion: The use of in-home test kits along with education may beneficially influence behaviors and attitudes toward dust mite reduction strategies and help reduce residential dust mite allergen levels.

Allergic asthma is a complex disease characterized by eosinophilic pulmonary inflammation, mucus production and reversible airway obstruction. Exposure to indoor allergens is a risk factor for asthma, but this disease is also associated with high household levels of total and particularly Gram-negative bacteria. The ability of bacterial products to act as adjuvants suggests they might promote asthma by priming allergic sensitization to inhaled allergens. In support of this idea, house dust extracts (HDEs) can activate antigen-presenting dendritic cells (DCs) in vitro and promote allergic sensitization to inhaled innocuous proteins in vivo. It is unknown which microbial products provide most of the adjuvant activity in HDEs. A screen for adjuvant activity of microbial products revealed that the bacterial protein flagellin (FLA) stimulated strong allergic airway responses to an innocuous inhaled protein, ovalbumin (OVA). Moreover, Toll-like receptor 5 (TLR5), the mammalian receptor for FLA, was required for priming strong allergic responses to natural indoor allergens present in HDEs. In addition, individuals with asthma have higher serum levels of FLA-specific antibodies as compared to nonasthmatic individuals. Together, these findings suggest that household FLA promotes the development of allergic asthma by TLR5-dependent priming of allergic responses to indoor allergens.

BACKGROUND: Bedroom allergen exposures contribute to allergic disease morbidity because people spend considerable time in bedrooms, having close contact with allergen reservoirs. OBJECTIVE: We investigated participant and housing characteristics, including sociodemographic, regional and climatic factors, associated with bedroom allergen exposures in a nationally representative sample of the US population. METHODS: Data were obtained from National Health and Nutrition Examination Survey (NHANES) 2005–2006. Information on participant and housing characteristics was collected by questionnaire and environmental assessments. Concentrations of 8 indoor allergens (Alt a 1, Bla g 1, Can f 1, Fel d 1, Der f 1, Der p 1, Mus m 1, and Rat n 1) in dust vacuumed from nearly 7,000 bedrooms were measured by immunoassays. Exposure levels were classified as elevated based on percentile (75(th)/90(th)) cut-offs. We estimated the burden of exposure to multiple allergens and used multivariable logistic regression to identify independent predictors for each allergen and household allergen burden. RESULTS: Almost all participants (>99%) had at least one and 74.2% had 3–6 allergens detected. Over 2/3 of participants (72.9%) had at least one allergen and 18.2% had ≥3 allergens exceeding elevated levels. Although exposure variability showed significant racial/ethnic and regional differences, high exposure burden to multiple allergens was most consistently associated with the presence of pets and pests, living in mobile homes/trailers, older and rental homes, and in non-metropolitan areas. CONCLUSIONS: Exposure to multiple allergens is common. Despite highly variable exposures, bedroom allergen burden is strongly associated with the presence of pets and pests. CLINICAL IMPLICATIONS: In the general US population, exposure to indoor allergens varies by sociodemographic and housing characteristics; however, exposure patterns show sociodemographic differences when compared to sensitization patterns.

Background Although pets are found in more than 50% of US homes, the effect of pet allergen exposure on asthma morbidity in the US population is not well documented. Objective To determine the effect of dog and cat allergen exposures on asthma morbidity in the US population. Methods The National Health and Nutrition Examination Survey is a representative sample of civilian US population. Data on asthma, dog and cat allergen levels in bedroom dust, as well as specific IgE to dog and cat were analyzed for all participants 6 years or older. Results Pets are common in the United States, with more that 50% of households having a dog or a cat or both. The prevalence of allergic sensitization in the National Health and Nutrition Examination Survey population was similar for dog and cat, with both being approximately 12%. Among those who were sensitized, exposure to elevated levels of pet allergens was associated with an increased prevalence of asthma and asthma attacks. Indeed, 44.2% of the asthma attacks were attributable to exposure to high levels of dog allergen in the bedroom among patients with asthma sensitive to dog and 30.3% were attributable to cat allergen exposure among the comparable cat-sensitive and exposed group. Projecting these results to the US population indicates more than 1 million increased asthma attacks each year for the dog-sensitive and exposed group and more than 500,000 increased asthma attacks for the cat-sensitive and exposed population of patients with asthma. Conclusions Exposure to elevated levels of dog and cat allergens among those sensitized individuals with asthma is associated with excess asthma attacks. Reducing pet allergen exposures has the potential for a significant decrease in asthma morbidity.

The effects of atopic and nonatopic asthma phenotypes on asthma morbidity are unclear. Moreover, asthma morbidity in patients without atopy might be mediated by immunoglobulin E (IgE).To determine differences in morbidity in patients with asthma with and without atopy in a population of inner-city adolescents with asthma and to assess the impact of total IgE (tIgE) in this population.Data were obtained from 546 inner-city adolescents in the Asthma Control Evaluation study. A positive skin prick test reaction to 14 aeroallergens and specific IgE to 5 aeroallergens determined atopic status. High (≥75th percentile) and low (≤25th percentile) tIgE levels were categorized. Asthma control (Asthma Control Test) and asthma severity (Composite Asthma Severity Index [CASI]) were measured at multiple time points over 1 year. Fractional exhaled nitric oxide (FeNO) and measurements of morbidity also were collected. Multivariable and repeated measures analyses modeled the relation between atopic status and morbidity.Baseline CASI scores increased 0.90 point (P.05) and FeNO increased 0.85 natural logarithmic unit (P.001) in participants with vs without atopy. Repeated measures analyses showed consistent results. Participants without atopy and increased tIgE had FeNO 0.73 natural log unit higher (P.01) than low tIgE and a nonsignificant increase in CASI. The CASI score and FeNO levels were higher for high than for low tIgE in participants with atopy.In this population, participants with atopic asthma had worse asthma severity and higher FeNO compared with those with nonatopic asthma, but no difference in control. In all participants, higher tIgE indicated worse severity and higher FeNO. In this population, asthma severity and FeNO might be mediated by IgE in the 2 asthma phenotypes.

Exposure to indoor allergens represents a significant risk factor for allergies and asthma in several parts of the world. In Mexico, few studies have evaluated indoor allergens, including cat, dog, and mouse allergens and the factors that predict their presence. This study evaluates the main environmental and household predictors of high prenatal allergen levels and multiple allergen exposures in a birth cohort from Mexico City. A cross-sectional study was conducted as part of a birth cohort study of 1094 infants recruited during pregnancy and followed until delivery. We collected dust samples in a subset of 264 homes and assessed environmental factors. Der p 1, Der f 1, dust mite group 2, Fel d 1, Can f 1, Rat n 1, Mus m 1, and Bla g 2 concentrations in dust samples were measured using immunoassays. To define detectable allergen levels, the lowest limits of detection for each allergen were taken as cutoff points. Overall allergen exposure was considered high when four or more allergens exceeded detectable levels in the same household. Logistic regression was used for predictive models. Eighty-five percent of homes had at least one allergen in dust over the detection limit, 52.1% had high exposure (four or more allergens above detectable limits), and 11.7% of homes had detectable levels for more than eight allergens. Der p 1, Der p 2, Mus m 1, and Fel d 1 were the most frequent allergens detected. Each allergen had both common and distinct predictors. The main predictors of a high multiple allergen index were the size of the home, pesticide use, mother's age, mother as homemaker, and season. Increased indoor environmental allergen exposure is mainly related to sociodemographic factors and household cleaning.

The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, and peanut allergy is becoming apparent in Africa and Asia. We evaluated strategies of peanut consumption and avoidance to determine which strategy is most effective in preventing the development of peanut allergy in infants at high risk for the allergy.We randomly assigned 640 infants with severe eczema, egg allergy, or both to consume or avoid peanuts until 60 months of age. Participants, who were at least 4 months but younger than 11 months of age at randomization, were assigned to separate study cohorts on the basis of preexisting sensitivity to peanut extract, which was determined with the use of a skin-prick test--one consisting of participants with no measurable wheal after testing and the other consisting of those with a wheal measuring 1 to 4 mm in diameter. The primary outcome, which was assessed independently in each cohort, was the proportion of participants with peanut allergy at 60 months of age.Among the 530 infants in the intention-to-treat population who initially had negative results on the skin-prick test, the prevalence of peanut allergy at 60 months of age was 13.7% in the avoidance group and 1.9% in the consumption group (P0.001). Among the 98 participants in the intention-to-treat population who initially had positive test results, the prevalence of peanut allergy was 35.3% in the avoidance group and 10.6% in the consumption group (P=0.004). There was no significant between-group difference in the incidence of serious adverse events. Increases in levels of peanut-specific IgG4 antibody occurred predominantly in the consumption group; a greater percentage of participants in the avoidance group had elevated titers of peanut-specific IgE antibody. A larger wheal on the skin-prick test and a lower ratio of peanut-specific IgG4:IgE were associated with peanut allergy.The early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00329784.).

Background Exposure to the fungus Alternaria alternata is a risk factor for asthma. Few studies have examined Alternaria exposures in indoor environments. Objective We examined whether exposure to A alternata in US homes was associated with asthma-related outcomes. Methods The data for this study were collected as part of the National Survey of Lead and Allergens in Housing. This cross-sectional study surveyed a nationally representative sample of 831 housing units inhabited by 2456 individuals in 75 different locations throughout the United States. An interviewer-administered questionnaire obtained information on demographics, household characteristics, and occupants' health status. Exposure to A alternata was assessed by measuring concentrations of A alternata antigens in vacuumed dust samples using a polyclonal anti– A alternata antibody assay. Dust samples were collected from a bed, a sofa, or a chair, and from bedroom, living room, and kitchen floors. Results Lifetime prevalence of doctor-diagnosed asthma was 11.2%, and 6.9% of the study subjects reported active asthma symptoms in the past 12 months. The prevalence of current symptomatic asthma increased with increasing Alternaria concentrations in US homes; higher levels of A alternata antigens increased the odds of having asthma symptoms in the past year (relative to the lowest tertile, adjusted odds ratio was 1.52, 95% CI, 0.90-2.55 for the 2nd tertile; and 1.84, 95% CI, 1.18-2.85 for the 3rd tertile). Conclusion Exposure to A alternata in US homes is associated with active asthma symptoms. Clinical implications Measures that reduce indoor exposure to A alternata may help control asthma exacerbations.

Background Alternaria alternata is one of the most common fungi associated with allergic disease. However, Alternaria exposure in indoor environments is not well characterized. Objective The primary goals of this study were to examine the prevalence of Alternaria exposure and identify independent predictors of Alternaria antigen concentrations in US homes. Methods Data for this cross-sectional study were obtained from the National Survey of Lead and Allergens in Housing. A nationally representative sample of 831 housing units in 75 different locations throughout the United States completed the survey. Information on housing and household characteristics was obtained by questionnaire and environmental assessments. Concentrations of A alternata antigens in dust collected from various indoor sites were assessed with a polyclonal anti- Alternaria antibody assay. Results Alternaria antigens were detected in most (95% to 99%) of the dust samples. The geometric mean concentration, reflecting the average Alternaria concentration in homes, was 4.88 μg/g (SEM, 0.13 μg/g). In the multivariable linear regression analysis, the age of the housing unit, geographic region, urbanization, poverty, family race, observed mold and moisture problems, use of dehumidifier, and presence of cats and dogs were independent predictors of Alternaria antigen concentrations. Less frequent cleaning and smoking indoors also contributed to higher Alternaria antigen levels in homes. Conclusion Exposure to A alternata antigens in US homes is common. Antigen levels in homes are influenced not only by regional factors but also by residential characteristics. Preventing mold and moisture problems, avoiding smoking indoors, and regular household cleaning may help reduce exposure to Alternaria antigens indoors.

Background: Clinically relevant reductions in exposure to cockroach allergen, an important risk factor for asthma in inner-city households, have proven difficult to achieve in intervention trials. Objective: This study investigated a method for the abatement of cockroach allergen in low-income, urban homes. The goal was to reduce mean Bla g 1 concentrations below the previously proposed thresholds for allergic sensitization and asthma morbidity. Methods: A prerandomized, nonmasked trial with 16 intervention and 15 control homes was conducted. Study inclusion was based on 50 to 500 cockroaches trapped in a 3-day period. The interventions consisted of occupant education, placement of insecticide bait, and professional cleaning. Vacuumed dust and multiple swab samples were collected at 0, 1, 2, 4, and 6 months in intervention homes and at 0 and 6 months in control homes. Room maps containing cockroach and allergen data were used to guide and monitor the interventions. Results: From 0 to 6 months among intervention homes, geometric mean Bla g 1 concentrations (U/g dust) decreased from 633 to 24 on kitchen floors (96% reduction), from 25 to 4.3 on living room floors/sofas (83% reduction), from 46 to 7.3 on bedroom floors (84% reduction), and from 6.1 to 1.0 in bedroom beds (84% reduction). These reductions, with the exception of that on the bedroom floor ( P = .06), were statistically significant relative to changes in control homes. Conclusions: Substantial reductions in cockroach allergen levels can be achieved in inner-city homes. In this study, allergen levels were reduced below the sensitization threshold (2 U/g) in beds, arguably the most relevant site for exposure, and below the asthma morbidity threshold (8 U/g) on bedroom floors and living room floors/sofas. The level on kitchen floors, although reduced 96%, remained above the asthma morbidity threshold. Future studies will test the intervention's effectiveness in asthma prevention trials. (J Allergy Clin Immunol 2003;112:339-45.)

Importance Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment. Objective To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up. Design, Setting, and Participants A randomized double-blind, placebo-controlled, 3–parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015. Interventions Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation). Main Outcomes and Measures Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Results Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95% CI, 5.23 to 6.88) at pretreatment and 4.81 (95% CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was −0.18 (95% CI, −1.25 to 0.90; [ P = .75]). Conclusions and Relevance Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up. Trial Registration clinicaltrials.gov Identifier:NCT01335139; EudraCT Number: 2010-023536-16

Background Allergic sensitization is an important risk factor for the development of atopic disease. The National Health and Nutrition Examination Survey (NHANES) 2005-2006 provides the most comprehensive information on IgE-mediated sensitization in the general US population. Objective We investigated clustering, sociodemographic, and regional patterns of allergic sensitization and examined risk factors associated with IgE-mediated sensitization. Methods Data for this cross-sectional analysis were obtained from NHANES 2005-2006. Participants aged 1 year or older (n = 9440) were tested for serum specific IgEs (sIgEs) to inhalant and food allergens; participants 6 years or older were tested for 19 sIgEs, and children aged 1 to 5 years were tested for 9 sIgEs. Serum samples were analyzed by using the ImmunoCAP System. Information on demographics and participants' characteristics was collected by means of questionnaire. Results Of the study population aged 6 years and older, 44.6% had detectable sIgEs, whereas 36.2% of children aged 1 to 5 years were sensitized to 1 or more allergens. Allergen-specific IgEs clustered into 7 groups that might have largely reflected biological cross-reactivity. Although sensitization to individual allergens and allergen types showed regional variation, the overall prevalence of sensitization did not differ across census regions, except in early childhood. In multivariate modeling young age, male sex, non-Hispanic black race/ethnicity, geographic location (census region), and reported pet avoidance measures were most consistently associated with IgE-mediated sensitization. Conclusions The overall prevalence of allergic sensitization does not vary across US census regions, except in early life, although allergen-specific sensitization differs based on sociodemographic and regional factors. Biological cross-reactivity might be an important but not the sole contributor to the clustering of allergen-specific IgEs.

Background The National Health and Nutrition Examination Survey (NHANES) 2005-2006 was the first population-based study to investigate levels of serum total and allergen-specific IgE in the general US population. Objective We estimated the prevalence of allergy-related outcomes and examined relationships between serum IgE levels and these outcomes in a representative sample of the US population. Methods Data for this cross-sectional analysis were obtained from NHANES 2005-2006. Study subjects aged 6 years and older (n = 8086) had blood taken for measurement of total IgE and 19 specific IgE levels against common aeroallergens, including Alternaria alternata , Aspergillus fumigatus , Bermuda grass, birch, oak, ragweed, Russian thistle, rye grass, cat dander, cockroach, dog dander, dust mite ( Dermatophagoides farinae and Dermatophagoides pteronyssinus) , mouse and rat urine proteins, and selected foods (egg white, cow's milk, peanut, and shrimp). Serum samples were analyzed for total and allergen-specific IgE by using the Pharmacia CAP System. Information on allergy-related outcomes and demographics was collected by questionnaire. Results In NHANES 2005-2006, 6.6% reported current hay fever, and 23.5% had current allergies. Allergy-related outcomes increased with increasing total IgE levels (adjusted odds ratios for a 10-fold increase in total IgE level of 1.86 [95% CI, 1.44-2.41] for hay fever and 1.64 [95% CI, 1.41-1.91] for allergies). Increased levels of plant-, pet-, and mold-specific IgE contributed independently to allergy-related symptoms. The greatest increase in odds was observed for hay fever and plant-specific IgE (adjusted odds ratio, 4.75; 95% CI, 3.83-5.88). Conclusion In the US population self-reported allergy symptoms are most consistently associated with increased levels of plant-, pet-, and mold-specific IgE.

d a r e ( t d Exposure and sensitization to indoor allergens are important risk factors for asthma.While the role of indoor allergen exposure in the development of allergic sensitization and the onset of asthma remains a subject of controversy, there is strong evidence that indoor allergens play a key role in exacerbation of existing asthma, particularly in sensitized individuals. In this supplement to the American Journal of Preventive Medicine, Crocker and coworkers advocate for a multi-trigger, multicomponent, home-based environmental intervention for the reduction of morbidity in asthmatic children and adolescents. This is appropriate guidance when dealing with the general population; however, inner-city asthmatic children, especially those who are sensitive and exposed to cockroach allergen, may experience greater benefit from a highly effective, single-component intervention that specifically targets cockroach allergen. Asthma morbidity is a significant public health concern, especially in inner-city populations. The National Cooperative Inner-City Asthma Study (NCICAS) demonstrated that asthma morbidity was strongly associated with the presence of a positive skin test and high allergen exposure. In particular, sensitization and exposure to ockroach allergen was shown to be one of the major risk actors for severe asthma. Asthma morbidity was highest in children with both a positive skin-test response to cockroach and a high exposure (defined as 8 units of cockroach allergen per gram of dust [U/g]) in the bedroom. Detectable levels of cockoach allergen were found in 85% of the bedrooms tested, nd 50% of the bedrooms had levels 2 U/g, the proosed threshold for allergic sensitization. Correspondngly, a study of children in Boston showed that cockoach allergen exposure in the family room was a redictor of two or more episodes of wheeze in the first ear of life. The risk of asthma from exposure to cockroach allergen is not limited to children. Indeed, a recent study showed that sensitization to cockroach allergenwas

Background Alternaria alternata -derived allergenic materials are causes of human disease. Several immunoassays exist to quantify these materials. Objective To compare methods for evaluating Alternaria content. Methods Four methods, including 1 monoclonal antibody (MAb)-based assay specific for recombinant Alt a 1, 1 MAb-based assay for chromatographically purified Alt a 1, 1 polyclonal antibody (PAb)-based assay for chromatographically purified Alt a 1, and 1 PAb-based assay for whole Alternaria extract, were evaluated. Environmental samples collected as part of the National Survey of Lead and Allergens in Housing were examined. Alternaria spore counts were determined in dust by observation. Results The MAb-based assay for recombinant Alt a 1 detected Alternaria in few samples (25%); the PAb-based assay for whole Alternaria proteins detected antigen in 97% of the samples. The PAb- and MAb-based assays for purified Alt a 1 detected antigen in 100% of the samples. There was a significant positive correlation between the 2 assays directed against purified Alt a 1. There was a positive correlation between the PAb-based assay for whole Alternaria and the PAb-based assay for Alt a 1. Nearly all the dust samples contained Alternaria spores, and there was a strong positive correlation between counts and all assays. Conclusion Because of the multifaceted nature of Alternaria , the disparities between methods for quantifying Alternaria , the cross-reactivity between fungal allergens, and the documented genetic promiscuity of this fungus, enzyme immunoassays using PAbs against a range of Alternaria proteins will probably produce the most reliable estimation of overall Alternaria exposure in house dust.

Background The hygiene hypothesis contends that fewer opportunities for infection have led to increases in the prevalences of asthma and other allergic diseases. Objective This study evaluated the association between asthma, wheeze, and hay fever and antibodies to 2 oral bacteria associated with periodontal disease. Methods Data were obtained from the Third National Health and Nutrition Examination Survey. Serum levels of IgG antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were quantified by enzyme-linked immunoassays in 9385 subjects age 12 years and older. The outcomes were current asthma, wheeze, and hay fever. Odds ratios (ORs) representing a 1–log-unit increase in IgG concentrations were estimated with logistic regression. ORs were adjusted for 8 confounders and weighted to represent the US population. Results For each disease outcome, geometric mean antibody concentrations were higher in persons without the disease outcome than with the disease outcome. For a 1–log-unit increase in P gingivalis antibody concentration, adjusted ORs were 0.41 (95% CI, 0.20-0.87) for asthma, 0.43 (0.23-0.78) for wheeze, and 0.45 (0.23-0.93) for hay fever. For A actinomycetemcomitans, those ORs were 0.56 (0.19-1.72), 0.39 (0.17-0.86), and 0.48 (0.23-1.03), respectively. Conclusion Consistent with the hygiene hypothesis, higher concentrations of IgG antibodies to P gingivalis were significantly associated with lower prevalences of asthma, wheeze, and hay fever, and higher concentrations of IgG antibodies to A actinomycetemcomitans were significantly associated with a lower prevalence of wheeze. Clinical implications Colonization of the oral cavity by bacteria and other microbes might play a protective role in the etiology of allergic disease.

Background With 63% of US children under 5 years of age in regular child care, day-care facilities could be an important source of exposure to indoor allergens. Objective This study examined levels of 7 indoor allergens in 89 day-care facilities in 2 North Carolina counties. Methods At each facility, a questionnaire was administered, observations were made, and vacuumed dust samples were collected from carpeted and noncarpeted areas of one room. Allergen concentrations were measured with antibody-based ELISAs. Results Each allergen was detected in a majority of facilities (52% to 100%). Geometric mean concentrations were 5.19 μg/g for Alternaria alternata , 2.06 μg/g for Can f 1, 1.43 μg/g for Fel d 1, 0.21 U/g for Bla g 1, 0.20 μg/g for Der p 1, 0.10 μg/g for Der f 1, and 0.01 μg/g for Mus m 1. Concentrations for 5 of the 7 allergens were not statistically different from concentrations found in southern US homes sampled in the National Survey of Lead and Allergens in Housing. In rooms with carpet and hard-surfaced flooring, levels of A alternata , Can f 1, Der f 1, Der p 1, and Fel d 1 were statistically higher on carpet. Conclusions In this survey of day-care facilities in North Carolina, detectable levels of indoor allergens were commonly found. For many young children and day-care staff, day-care facilities might be a source of clinically relevant exposures to indoor allergens.

Studies of indoor allergen exposures are often limited by the cost and logistics of sending technicians to homes to collect dust. In this study we evaluated the feasibility of having subjects collect their own dust samples. The objectives were to compare allergen concentrations between subject- and technician-collected samples and to examine the sample return rate. Using a dust collection device and written instructions provided to them by mail, 102 subjects collected a combined dust sample from a bed and bedroom floor. Later the same day, a technician collected a side-by-side sample. Dust samples were weighed and analyzed for the cat allergen Fel d 1 and the dust mite allergen Der p 1. Fifty additional subjects who were enrolled by telephone were mailed dust collection packages and asked to return a dust sample and questionnaire by mail. A technician did not visit their homes. Correlations between subject- and technician-collected samples were strong for concentrations of Fel d 1 (r = 0.88) and Der p 1 (r = 0.87). With allergen concentrations dichotomized at lower limits of detection and clinically relevant thresholds, agreements between methodologies ranged from 91 to 98%. Although dust weights were correlated (r = 0.48, p < 0.001), subjects collected lighter samples. Among the group of 50 subjects, 46 returned a dust sample and completed questionnaire. The median number of days to receive a sample was 15. With some limitations, subject-collected dust sampling appears to be a valid and practical option for epidemiologic and clinical studies that report allergen concentration as a measure of exposure.

Background In the first 6 months of this previously published, randomized trial, the combined intervention of occupant education, insecticide bait application, and professional cleaning significantly reduced cockroach numbers and Bla g 1 allergen levels in inner-city homes. Objective This continuation study investigated whether the cockroach allergen reductions achieved by month 6 could be maintained through month 12 with insecticide application alone. Methods Because we had agreed to place insecticide bait in control homes at the conclusion of the first study, intervention and control homes were treated with insecticide bait at months 6 and 9. No other intervention was conducted in either arm. Vacuumed dust and swab samples were collected at month 12. Twenty-one of the 31 original homes completed the 12-month study. Results Among the original intervention homes, Bla g 1 concentrations remained essentially unchanged from months 6 to 12. However, among the crossed-over control homes, the geometric mean Bla g 1 concentrations (Units per gram of dust) decreased from 287 to 14.4 for kitchen floors (95% reduction), from 28.8 to 5.6 for living room floors/sofas (81% reduction), from 26.7 to 4.7 for bedroom floors (82% reduction), and from 7.2 to 2.4 for beds (67% reduction). At month 12, Bla g 1 concentrations did not significantly differ between intervention and crossed-over control homes ( P > .64 at each location). Similar results were seen for the allergen Bla g 2. Conclusions Reductions in cockroach allergen concentrations achieved through the combined intervention of occupant education, insecticide application, and professional cleaning can be maintained with continued cockroach control. Surprisingly, and in contrast to other studies, insecticide application alone significantly lowered allergen concentrations in the crossed-over control homes. This unexpected result is being tested further in another randomized trial.