Search Results (143)

Background: Yellow fever vaccination is recommended for travelers visiting endemic regions in South America and Africa. The live-attenuated vaccine (Stamaril^®, Sanofi Pasteur) is produced in embryonated chicken eggs and contains residual ovalbumin, posing a challenge for individuals with egg protein allergy. Case Presentation: We report the case of a 35-year-old male disaster relief worker with confirmed egg protein allergy and moderate sensitization but no history of anaphylaxis. Under normal circumstances, a statement confirming that vaccination is not possible would be sufficient for entry. However, due to his work-related duties and the relevant guidelines from his employer, there was an urgent need for vaccination despite his egg protein allergy. A comprehensive allergy work-up including skin prick testing, serum-specific IgE, and oral provocation testing revealed a moderate allergy without systemic reactions. Intervention: Following informed consent and risk assessment, a fractional dose (0.1 mL) of the reconstituted yellow fever vaccine was administered under close monitoring. The patient developed a localized dermal reaction without systemic symptoms. Post-vaccination neutralization testing confirmed seroconversion indicating protective immunity. Discussion: Although yellow fever vaccination is considered contraindicated in individuals with severe egg protein allergy, the literature supports its cautious use in selected cases. Fractional dosing has emerged as an effective dose-sparing strategy. Studies show that even in egg protein-allergic individuals, adverse events are rare. Conclusions: In this case, a fractional yellow fever vaccination was safe and an effective option for an egg-allergic individual in a high-risk occupational setting, supporting a personalized approach based on clinical risk assessment and current evidence. Full article

Background: Oral food challenge (OFC) remains the gold standard for diagnosing food allergy; however, it is time-consuming and associated with the risk of allergic reactions. The identification of reliable biomarkers capable of predicting OFC outcomes could improve patient selection and reduce the number of OFCs required in clinical practice. Among the most widely used biomarkers are skin prick tests (SPTs) and serum-specific IgE (sIgE) measurements, including component-resolved diagnostics. However, their diagnostic utility, as well as the comparability of different diagnostic platforms, remains incompletely defined in cow’s milk (CM) and hen’s egg (HE) allergy. Methods: We retrospectively analyzed results of diagnostic tests obtained in children undergoing OFCs to baked milk, raw milk, baked egg, and boiled egg. Diagnostic performance of SPTs to either allergen extracts or native food allergens, as well as sIgE measured using ImmunoCAP and ALEX2 platforms, was evaluated using receiver operating characteristic (ROC) analysis and logistic regression models. Results: Diagnostic performance varied across allergy phenotypes. SPTs to native food allergens demonstrated good discriminative capacity for raw milk and boiled egg allergy, whereas SPTs to standardized extracts showed limited diagnostic utility overall. In baked milk allergy, casein-sIgE measured by ImmunoCAP demonstrated the best diagnostic performance. In raw milk allergy, α-lactalbumin-sIgE measured using ALEX2 platform and β-lactoglobulin-sIgE measured by ImmunoCAP showed greater diagnostic relevance than casein-sIgE. In boiled egg allergy, SPT to raw egg yolk demonstrated the highest diagnostic value. In baked egg allergy, ovalbumin-sIgE measured using the ALEX2 platform showed the best performance, while ovomucoid-sIgE did not demonstrate clear superiority. ALEX2 showed good concordance with ImmunoCAP despite systematic differences in absolute sIgE values. Combined multivariable models provided only modest improvements over single predictors and did not achieve sufficient accuracy to replace OFCs. Conclusions: SPTs to either allergen extracts or native food allergens, as well as sIgE measurements, demonstrate moderate and heterogeneous utility in predicting OFC outcomes for CM and HE allergy. Although ALEX2 and ImmunoCAP showed comparable overall performance, platform-specific interpretation may be required. OFC remains indispensable for definitive diagnosis. Full article

Food allergy is an increasingly prevalent global health condition characterized by immune-mediated reactions to dietary antigens and a substantial clinical burden. Growing understanding of IgE-mediated mechanisms has highlighted the central role of type 2 inflammation, effector-cell activation, and impaired immune regulation. These advances have prompted the development of disease-modifying therapies beyond allergen avoidance. This narrative review summarizes recent advances in the therapeutic management of IgE-mediated food allergy. A structured PubMed search was performed to identify clinical trials, randomized studies, and meta-analyses published within the last five years. Both allergen-specific and non-allergen-specific interventions were evaluated. Current evidence supports oral immunotherapy as the most effective strategy for increasing reaction thresholds and inducing desensitization in peanut, milk, and egg allergies. However, safety concerns remain, and sustained unresponsiveness after treatment discontinuation is achieved inconsistently. Sublingual and epicutaneous immunotherapy show improved safety but lower efficacy. Modified allergen approaches, including baked milk and processed peanut products, may improve tolerability and facilitate immune modulation in selected patients. Biologic therapies, particularly anti-IgE agents, demonstrate efficacy both alone and when combined with immunotherapy. Emerging approaches include peptide vaccines, DNA immunization, microbiome-targeted interventions, and early dietary modulation. These strategies may improve durable immune tolerance through personalized, mechanism-based therapeutic approaches. Future progress will depend on optimizing safety, identifying predictive biomarkers, and integrating multimodal approaches to achieve durable immune tolerance. Full article

Background: Egg allergy is one of the most common food allergies in early childhood and is traditionally managed through strict avoidance diets, which may negatively affect nutrition and quality of life. Early oral immunotherapy (OIT) may represent an alternative therapeutic strategy; however, controlled studies in children younger than two years remain limited. Methods: We conducted a prospective observational study using historical controls. Thirty-one children younger than two years with IgE-mediated egg allergy underwent OIT using pasteurized liquid egg white (maximum dose: 30 mL; 3300 mg protein). Twelve children managed with an avoidance diet served as the historical control group. Outcomes included desensitization rates, adverse reactions, and longitudinal changes in skin prick test (SPT) wheal diameters, serum-specific IgE (sIgE), specific IgG4 (sIgG4), and sIgE/total IgE ratios. Results: At six months, 29/31 children (93.5%) in the OIT group did not experience allergic reactions after ingestion of any egg preparation, compared with none in the historical control group (p < 0.001). In the control group, 7/12 children (58.3%) continued to react to less-cooked egg preparations, whereas 5/12 (41.7%) remained reactive to all forms of eggs. During the induction phase, 24/31 OIT-treated children (77.4%) experienced mild adverse reactions, predominantly isolated cutaneous or gastrointestinal symptoms, and no patient required intramuscular adrenaline administration. In contrast, allergic reactions occurred in 11/12 controls, including anaphylaxis in 6/12 (50.0%) patients (p = 0.0301). The OIT group demonstrated significant reductions in SPT wheal diameters, sIgE levels, and sIgE/total IgE ratios (all p < 0.001), accompanied by increased sIgG4 levels. Conclusions: Early OIT with pasteurized egg white in children younger than two years with IgE-mediated egg allergy was associated with high desensitization rates, favorable short-term safety outcomes, and significant immunological changes. These findings support the potential role of early active intervention as an alternative to exclusive avoidance strategies in infants with egg allergy. Full article

Background: Measles has re-emerged in recent years as a public health concern in the context of insufficient vaccination coverage. Some children experience significant delays in receiving, or refuse to take, the measles, mumps and rubella (MMR) vaccination, often due to concerns related to hen’s egg allergy (HEA). Methods: In this study, we retrospectively assessed the safety of MMR vaccination (Priorix^®, GlaxoSmithKline, Belgium) in patients with HEA hospitalised at our clinic. Detailed medical histories were collected, along with skin prick tests and measurements of specific IgE against milk and egg proteins or extracts. The study included 39 patients with a mean age of 19 months, of whom 15 had previously experienced an anaphylactic reaction after egg ingestion. Results: None of these patients experienced a systemic reaction to vaccination. One patient developed a generalised maculopapular rash, which resolved after a single dose of an antihistamine. Vaccination was postponed in 63% of patients, with the longest delay extending to 113 months. Conclusions: Severe adverse reactions following MMR vaccination in patients with HEA are generally rare and are outweighed by the risks associated with natural infection and its complications. Effective communication of vaccine safety data and strengthening public trust in healthcare professionals are crucial. Full article

Background: Egg proteins are among the most common triggers of allergic reactions. This study aimed to evaluate whether changes in the protein source in hen diets may influence the immunoreactivity of eggs and recognize the ELISA limits in egg allergen detection. Methods: This study used eggs from laying hens fed various feeds (including soy and lupin). Determinations of selected allergens were performed using the immunoenzymatic ELISA method. Results: Studies have shown that including legumes in hens’ diets reduces egg immunoreactivity. The highest detected reactivity using a commercial test for the immunoreactivity of egg albumen was twice as high in whites from hens fed the control diet, and this result was most likely due to the Gal d 1 and Gal d 3 detection. Still, the use of this diet reduced the lysozyme (Gal d 4) content in the egg white by approximately 10%. The applied method did not allow for Gal d 5 determination in the tested eggs. The results of the immunoreactivity of the studied eggs with anti-soy and anti-lupine antibodies were outside the limits of detection. Conclusions: The obtained results confirm that the studied allergen content in eggs can be modified by nutritional factors. Full article

Background: Food allergy (FA) is an increasing public health concern with significant implications for child health and quality of life. Early introduction of allergenic foods has been shown to reduce the risk of food allergy development; however, maternal awareness and adherence to these recommendations remain inconsistent. This study aimed to assess maternal awareness and practices regarding the timing of allergenic food introduction among mothers residing in Makkah, Saudi Arabia. Methods: A descriptive cross-sectional study was conducted between November 2023 and March 2024 involving parents of children aged younger than 48 monthsin the Makkah region. Data were collected via a self-administered electronic questionnaire distributed through social media platforms. Results: A total of 391 parents participated. Parent-reported food allergy was identified in 11.3% of children, while 14.6% had eczema. Early introduction (<12 months) was more common for egg (43.3%) and wheat (71.1%) compared to peanut (28.9%), tree nuts (30.9%), sesame (30.9%), and seafood (28.9%). A considerable proportion of children had not been introduced to key allergenic foods even after 36 months, particularly peanuts (45.3%) and sesame (42.2%). Children with eczema were significantly more likely to have early introduction of egg (p = 0.035), tree nuts (p = 0.046), and seafood (p = 0.031). Similarly, children with a family history of food allergy had higher early introduction rates of tree nuts (55.3% vs. 44.0%, p = 0.043) and seafood (62.3% vs. 49.1%, p = 0.019). Only 25.8% of mothers were aware that early introduction might prevent food allergies, and just 22% reported receiving professional advice to introduce allergenic foods early. Conclusions: Maternal awareness regarding the timely introduction of allergenic foods in Makkah remains limited, with delayed introduction persisting beyond 36 months for several high-risk allergens. These findings underscore the need for targeted educational interventions and improved counseling by healthcare providers. Full article

Food allergies arise when environmental factors, lifestyle choices, and genetic predispositions affect the integrity of the gut epithelial barrier. Under healthy conditions, gut microbiota supports intestinal tight junction integrity and promotes immune tolerance to dietary allergens. Disruption of this microbiota increases susceptibility to epithelial barrier leakage, thereby enabling food allergens to penetrate the bloodstream from the gut and leading to allergic sensitization. Restoring gut homeostasis through allergen-specific immunotherapy (AIT), executed via oral termed as oral immunotherapy (OIT), skin as subcutaneous immunotherapy (SCIT), or under the tongue in the form of sublingual immunotherapy (SLIT), remains a promising yet complex and multifaceted approach. In parallel, probiotics offer a simpler alternative to reinforce epithelial barrier function, restore cellular homeostasis, mitigate allergy symptoms, and represent the probiotics-based OIT. Recently, several bioengineering strategies have been developed toward enriching gut microbiota, such as using additives such as carbohydrates, polyphenols, and probiotics. While generic probiotics have shown efficacy, their undefined dosages and administration protocols pose challenges for clinical standardization in the form of OIT. Emerging developments include recombinant probiotics engineered to express the specific allergen in a controlled manner inside the gut. However, safety concerns regarding their clinical application remain under active discussion. This review highlights various bioengineering strategies to enhance the probiotic capacity, address safety considerations, and explore future prospects for managing food allergies. Full article

Background/Objectives: As an escalating global health challenge, food allergies impose substantial burdens on the physical and psychological well-being of pediatric populations, profoundly compromising their quality of life. Given the marked geographical heterogeneity in allergen distribution patterns, this epidemiological investigation systematically characterizes prevalent pediatric food allergens sensitization patterns in Southwest China, yielding critical region-specific data to inform targeted prevention strategies and clinical management protocols. Methods: A cohort of 36,399 pediatric participants (age <18 years) underwent hospital-based testing for allergen-specific immunoglobulin E (sIgE) reactivity against 10 regionally prevalent food allergens, utilizing a semi-quantitative, immunocapture-based, and enzyme-linked immunosorbent assay. Results: Of the 36,399 children whose food allergen sensitization profiles were analyzed, 48.12% (n = 17,514) demonstrated elevated sIgE reactivity in response to at least one tested allergen, with milk and eggs emerging as the predominant allergenic triggers. Age-stratified analyses identified preschool age (≤6 years) as the critical window for food sensitization, demonstrating peak IgE reactivity to major allergens, including milk, peanuts, soybeans, shrimp, eggs, wheat, and beef. Male subjects exhibited significantly higher sensitization rates to peanuts, soybeans, crustaceans and wheat compared to females (p < 0.05), underscoring the importance of sex-based considerations in allergy prevention strategies. Conclusions: Milk and eggs emerge as the dominant food allergens that cause sensitization in Chengdu’s pediatric population. Age- and sex-dependent vulnerabilities were identified, with younger children and male participants demonstrating higher sensitization rates than their counterparts. These age-stratified and male-predominant sensitization patterns provide a scientific foundation for public health initiatives. Full article

Background: The pathophysiological mechanism of eosinophilic esophagitis (EoE) is complex and is still being investigated. We believe that there is a group of patients with eosinophilic esophagitis which could be differentiated as having an allergic phenotype who exhibit a sensitization profile (aeroallergens, panallergens, foods and specific IgG4 levels) with significant differences compared to patients with conventional allergic disease without associated eosinophilic esophagitis and healthy controls. Method: We measured the prevalence of sensitization to aeroallergens, foods and panallergens by means of molecular diagnostic techniques (ImmunoCAP^TM ISAC) and determined the levels of specific IgG4 against foods and eosinophilic-derived neurotoxin (EDN) (ImmunoCAP technology) in patients with EoE of an allergic phenotype to study whether there are statistically significant differences with respect to the control groups (patients with different allergic pathologies without EoE and healthy patients without documented allergies). The total number of patients under study was 118, distributed among the different study groups. The case group (Allergic phenotype EoE patients) had 48 subjects. The food and respiratory allergy control groups had 30 subjects each. Finally, we included 10 in the healthy control group. Results: We were able to identify statistically significant differences when comparing levels of food-specific IgG4. Milk, egg, wheat, nuts, soy, cod, and Pru p3/LTP stood out. We did not observe significant differences in relation to sensitization to aeroallergens, foods, or panallergens. We also did not observe differences in EDN levels. Conclusions: We present a study in which statistically significant differences in IgG4 levels were observed in response to different types of food, comparing patients with eosinophilic esophagitis of allergic phenotype (case group) against subjects with allergic pathology without EoE and healthy subjects (control groups). Determining whether the detected foods are clinically relevant or not in these patients would be fundamental to establishing their usefulness as a treatment alternative in our patients. Full article

Background: Skin prick testing (SPT) and serum egg white–specific IgE (sIgE) support oral food challenge (OFC) decisions in suspected egg allergy, but the incremental value of histamine-normalized SPT indices remains uncertain. Methods: In this single-center retrospective study, 105 egg-sensitized children underwent clinically indicated OFC. Commercial egg white SPT, prick-to-prick testing with fresh egg white, histamine controls, and serum egg white–specific IgE were assessed. Discriminatory performance was evaluated by ROC analysis, and independent predictors of OFC positivity were identified using multivariable logistic regression. Results: OFC was positive in 23 of 105 children (21.9%). Egg white SPT wheal diameter, the prick-to-histamine ratio, and serum egg white–specific IgE (sIgE) levels were significantly higher in OFC-positive patients (all p < 0.001). ROC analysis demonstrated moderate-to-good discrimination for both sIgE (AUC = 0.767) and the prick-to-histamine ratio (AUC = 0.786), without clear superiority of normalized indices. In multivariable logistic regression analysis, only absolute egg white SPT wheal diameter (adjusted OR 1.41 per 1 mm increase; 95% CI 1.13–1.77) and serum egg white–specific IgE level (adjusted OR 31.86 per 100 kUA/L increase; 95% CI 1.60–636.15) remained independent predictors of OFC positivity. Conclusions: Absolute egg white SPT wheal diameter and serum sIgE independently predict OFC outcomes in egg-sensitized children. Histamine-normalized indices did not provide added value over wheal size alone. These findings support a probabilistic, context-based use of test results to inform selective OFC planning rather than replace OFC. Full article

Background/Objectives: Food allergy (FA) is a substantial health burden in children. FA is often associated with malnutrition and malabsorption, due to restrictive food avoidance diets, which can significantly impair the patient’s and their family’s quality of life. To this date, population-based data combining sensitization and clinical allergy remain limited. This study aimed to assess the patterns of sensitization rates to food and food allergy prevalence rates in Croatian children and to evaluate differences according to age, sex, and region of origin. Materials and Methods: In this cross-sectional study, 1948 preschool and school-aged children from three Croatian regions (Zagreb, Dalmatia, and Slavonia) were included. Participants underwent skin prick testing to common food and inhalant allergens. Data on personal and family medical history were collected using questionnaires and medical records. FA prevalence was evaluated using self-reported data in school-aged children and physician-diagnosed FA data in preschool children. Results: Overall, 41% of participants were sensitized to at least one allergen, while 13% were sensitized to at least one food allergen. Tree nuts—particularly hazelnut—were the most common food-derived sensitizers, followed by hen’s egg, cow’s milk, and fish. Boys exhibited higher total sensitization rates than girls (44.2% vs. 37.5%; p = 0.001), higher food allergen sensitization rates (14.7% vs. 11.4%; p = 0.037), and higher total polysensitization rates (30.7% vs. 22.6%; p < 0.001). School-aged children showed higher total sensitization (44.8% vs. 33.4%; p < 0.001) and polysensitization rates (29.8% vs. 20.5%; p < 0.001) than preschool children, while sensitization to food allergens did not differ between age groups. Food allergen sensitization rates differed by region, with higher prevalence in Zagreb compared with Dalmatia and Slavonia (p = 0.0055), whereas total sensitization rates did not differ regionally. The agreement between sensitization and self-reported FA among school-aged children was low (κ = 0.22; p < 0.001), as was the agreement between sensitization and physician-diagnosed FA in preschool children (κ = 0.13; p < 0.001), despite high specificity in both analyses (95% and 99%%, respectively). Conclusions: Allergic sensitization is common among Croatian children, but it poorly predicts clinically relevant food allergy. These findings highlight the multifactorial nature of allergen sensitization in children and emphasize the need for improvements in diagnostic pathways, targeted prevention strategies, and continued surveillance to optimize allergy prevention and management in children. Full article

Atopic allergy is rising globally and placing a significant strain on healthcare systems, yet the understanding of the underpinning mechanisms of allergic sensitization remains incomplete. Extracellular vesicles (EVs) have recently emerged as important mediators of immune modulation, due to their diverse cargo, and therefore may play a mechanistic role in allergic sensitization development. Thus, this study investigated whether EVs released by activated dendritic cells (DCs) contribute to allergic sensitization of the common egg allergen, ovalbumin (OVA). DCs were generated from human monocytes cultured with GM-CSF and IL-4, then stimulated with LPS and/or OVA. EVs were subsequently isolated using size-exclusion chromatography and added to freshly isolated naive T cells at defined time points. T cell responses were then analyzed using spectral flow cytometry. The results highlight that EVs derived from LPS or LPS + OVA-stimulated DCs enhanced IL-4 production and reduced IFN-γ production in naive T cells from egg-allergic donors, indicating a shift toward a Th2 profile. In healthy donors, LPS-induced DC EVs also suppressed IFN-γ expression. Notably, EVs alone were insufficient to activate T cells without CD3/CD28 co-stimulation, suggesting that EVs may function as a “third signal” shaping T cell polarization. These findings highlight a potential role for DC-derived EVs in initiating allergic sensitization. Full article

Background: Presence of milk, fruits, eggs, fish, nuts and wheat antigens in the amniotic fluid is described in the literature. Studies show a contradictory relationship between maternal exposure to allergens and early sensitization of the fetus to allergens. Hemochorionic type of the human placenta allows for easier transfer of nutrients and antibodies from the mother’s blood to the fetal circulation through the direct contact of maternal blood with the fetal chorion. During the third trimester of pregnancy, immunoglobulin G (IgG) is actively transferred through the placenta into the fetal via neonatal FcRN receptor (FcRN). In addition, monomeric immunoglobulin E (IgE) cannot cross the placenta Aim: The objective of our study is to track intrauterine sensitization to essential food proteins at birth in umbilical cord blood in mothers with established peripheral blood eosinophilia and in their infants using allergen-specific IgE and IgG. Methods: An observational study was carried out in a cohort of 22 mothers with eosinophilia and their babies. Differences in expression between groups were assessed. Blood samples were collected to determine serum IgE and IgG specific to a set of inhalant and food allergens. Results: We did not find a significant correlation between specific IgE to cow’s milk (p = 0.857), egg white (p = 0.926) and egg yolk (p = 0.096) in umbilical cord blood and maternal blood samples taken immediately before birth. Spearman’s correlation of the specific IgE and IgG in umbilical cord blood showed no dependence between the two variables. In contrast, statistical analysis showed that maternal eosinophilia in peripheral blood could be a risk factor for the development of allergy in the offspring (χ², p = 0.0347). However, given the small number of patients, this claim needs to be confirmed with further studies. Conclusions: Due to the functional immaturity of the developing immune system of the fetus, the generation and maintenance of an independent immune response to allergens are incomplete. Maternal IgG (specific) passes to the baby and high maternal IG to a specific allergen reduces babies IgE production. In addition, low maternal specific IgG may promote IgE production in the baby under the influence of microenvironmental factors (cytokine background). The main limitation of our study is the small number of patients. Further research is needed in this direction to clarify the mechanisms and risk factors for early sensitization in newborns. Full article

Background: Oral food challenges (OFCs) are still the reference standard for confirming food allergy, yet the influence of previous anaphylaxis on challenge outcomes remains uncertain. Patients with a history of anaphylaxis are often considered at higher risk, which may affect the clinical decision-making process. This study aimed to identify predictors of OFC failure stratified by a history of anaphylaxis, given that prior investigations have predominantly considered anaphylaxis as an overall risk factor, without delineating distinct risk factor profiles according to anaphylaxis history. Methods: We conducted a retrospective evaluation of standard-of-care pediatric OFCs to cow’s milk and hen’s egg white. Eligible children had suspected or confirmed IgE-mediated allergy to cow’s milk protein (CMP) or hen’s egg white protein (HEWP) and were stratified by the presence or absence of previous anaphylaxis to the challenged food. Clinical data were compared between groups. Open OFCs were conducted under inpatient supervision with full emergency support. Logistic regression models were used to assess the relationship between comorbidities, specific IgE (sIgE) concentrations and OFC outcomes. Receiver operating characteristic (ROC) analysis evaluated diagnostic accuracy of sIgE concentrations in predicting OFC outcomes. Results: The analysis included 192 pediatric patients undergoing OFCs: 106 to CMP and 86 to HEWP. Six challenges (3.1%) were inconclusive, giving 186 valid results. The overall OFC failure rate was 32.3%. Patients with a past history of anaphylaxis more frequently underwent cow’s milk challenges (p = 0.01). Atopic dermatitis was a more common comorbidity in those without prior anaphylaxis (p = 0.04), regardless of the trigger. In hen’s egg challenges, children with a history of anaphylaxis reacted to significantly lower cumulative doses (p = 0.03) than patients without. Atopic dermatitis was identified as a predictor of OFC failure in children without prior anaphylaxis (p = 0.02), and asthma as a borderline predictor in those with previous systemic reactions (p = 0.05). Specific IgE concentrations correlated with OFC outcomes across allergens, with casein-sIgE showing the highest discriminative performance (AUC = 0.81) in children without previous anaphylaxis. Conclusions: Atopic dermatitis and asthma were identified as potential risk factors influencing OFC outcomes, depending on the patient’s history of anaphylaxis. The predictive accuracy of sIgE was different in groups stratified by presence of prior anaphylaxis, and the relationship between sIgE concentration and clinical reactivity was not identical across the two subpopulations. Casein-sIgE showed the highest diagnostic accuracy in children without previous severe reactions to CMP. Presence of anaphylactic reactions in the past is an important consideration when selecting children for OFCs to CMP and HEWP, since it delineates distinct risk factors for challenge failure in these patient populations. Full article