Decreasing Attacks and Improving Quality of Life through a Systematic Management Program for Patients with Hereditary Angioedema.

INTRODUCTION: Prevention of attacks is a major goal in management of patients with hereditary angioedema (HAE). We aimed to investigate the effects of a systematic intervention for HAE patients. METHODS: Thirty-three patients with HAE with C1-inhibitor deficiency, belonging to a single family, participated in a management program coordinated by an allergist/immunologist. Angioedema attacks before intervention were ascertained by interviews and emergency room charts and recorded prospectively by patients or caregivers after enrollment. Mean number of attacks/month was compared at 12 months preintervention and 8 and 14 months within intervention. Patient-reported outcome instruments were used to assess quality of life, including HAE Quality of Life (HAE-QoL) questionnaire, psychological conditions, and work impairment, at baseline and 8 and 14 months within intervention. Data were stored in REDCap platform and analyzed by adjusted Bayesian models of double Poisson regression. RESULTS: Mean number of attacks/month significantly decreased (95% credible interval [CrI] excluding 0) from 1.15 preintervention to 0.25 and 0.23, 8 and 14 months within intervention, with mean decreases of -0.89 (95% CrI: -1.21 to -0.58) and -0.92 (95% CrI: -1.22 to -0.60), respectively. HAE-QoL scores showed mean total increases of 15.2 (95% CrI: 1.23-29.77) and 26 (95% CrI: 14.56-39.02) at 8 and 14 months within the study, as compared to baseline, revealing marked improvement in quality of life. Significant increase in role-emotional and reduction of depression, stress, and anxiety were observed at 14 months. CONCLUSION: A systematic approach integrating HAE-specific care with effective handling of psychological issues decreased the number of attacks and improved quality of life, targets for best practice in HAE.

Parasite Infections, Allergy and Asthma: A Role for Tropomyosin in Promoting Type 2 Immune Responses.

INTRODUCTION: The relationship of parasite infections and promotion or protection from allergy and asthma is controversial. Currently, over 1.5 billion people are infected with parasites worldwide, and Ascaris lumbricoides is the most frequent soil-transmitted helminth. OBJECTIVES: To evaluate the biological activity of recombinant A. lumbricoides tropomyosin and investigate IgE cross-reactive responses to tropomyosins by means of microarray methodology for the detection of sensitization to allergen components. METHODS: Forty patients 12-75 years of age (25 males) with asthma and/or rhinitis and 10 nonallergic control subjects participated in this study. All patients presented positive skin tests to cockroach extracts and underwent skin prick testing (SPT) with recombinant (r) tropomyosins rPer a 7 from Periplaneta americana and rAsc l 3 from A. lumbricoides, at 10 µg/mL. IgE to cockroach and parasite tropomyosins were measured by chimeric ELISA and ImmunoCAP-ISAC, and total IgE was quantitated by ImmunoCAP. Agreement of results was assessed by κ statistics. RESULTS: Recombinant A. lumbricoides showed biological activity, inducing positive skin tests in 50% patients with asthma and/or rhinitis. IgE to cockroach and parasite tropomyosins were detected in 55-62% of patients. There was good-to-excellent agreement of results of SPT and IgE measurements by ELISA and ImmunoCAP-ISAC, with κ indices of 0.66-0.95. No skin test reactivity or IgE antibodies to tropomyosins were found in nonallergic individuals. CONCLUSIONS: Our results suggest that IgE responses to tropomyosin from A. lumbricoides may enhance reactivity to homologous allergens upon exposure by inhalation or ingestion, promoting allergic reactions and asthma, or increasing the severity of these clinical conditions.

Acquired Angioedema due to C1 Inhibitor Deficiency Preceding Splenic Marginal Zone Lymphoma: Further Insights from Clinical Practice.

BACKGROUND: Acquired angioedema due to C1 inhibitor deficiency (AAE-C1-INH) is a very rare disease. In clinical practice, it may be difficult to differentiate AAE-C1-INH from hereditary angioedema due to C1-INH deficiency (HAE-C1-INH). In both conditions, patients are at an increased risk of death from asphyxiation due to upper airway obstruction. The association of AAE-C1-INH with lymphoproliferative and autoimmune diseases, and with presence of anti-C1-INH antibodies has been well documented, and treatment of the underlying condition may result in complete remission of angioedema. OBJECTIVES: To discuss the clinical evaluation, diagnosis, and treatment outcomes of AAE-C1-INH in the context of the care of 2 patients with recurrent isolated angioedema. METHODS: Two patients were followed up prospectively at our clinic. Measurements of C3, C4, C1-INH, and C1q levels were carried out by nephelometry, and the functional activity of C1-INH was determined by a chromogenic assay. Hematological investigation included morphological and immunophenotyping analysis of peripheral blood, bone marrow, and spleen histopathology. Sequencing of the 8 exons and adjacent intronic regions of the SERPING1 gene was performed using the Sanger method. RESULTS: Two patients were diagnosed with AAE-C1-INH associated with splenic marginal zone lymphoma during follow-up. CONCLUSIONS: Close follow-up, including detailed clinical history, physical examination, and laboratory tests, of our patients with AAE-C1-INH was essential for the early diagnosis and successful treatment of the lymphoproliferative disease, leading to the resolution of the angioedema attacks.

B lymphocyte-induced maturation protein 1 controls TH9 cell development, IL-9 production, and allergic inflammation.

BACKGROUND: The transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp-1) has a key role in terminal differentiation in various T-cell subtypes. However, whether Blimp-1 regulates TH9 differentiation and its role in allergic inflammation are unknown. OBJECTIVE: We aimed to investigate the role of Blimp-1 in TH9 differentiation and in the pathogenesis of allergic airway inflammation. METHODS: In vitro TH9 differentiation, flow cytometry, ELISA, and real-time PCR were used to investigate the effects of Blimp-1 on TH9 polarization. T cell-specific Blimp-1-deficient mice, a model of allergic airway inflammation, and T-cell adoptive transfer to recombination-activating gene 1 (Rag-1)-/- mice were used to address the role of Blimp-1 in the pathogenesis of allergic inflammation. RESULTS: We found that Blimp-1 regulates TH9 differentiation because deleting Blimp-1 increased IL-9 production in CD4+ T cells in vitro. In addition, we showed that in T cell-specific Blimp-1-deficient mice, deletion of Blimp-1 in T cells worsened airway disease, and this worsening was inhibited by IL-9 neutralization. In asthmatic patients CD4+ T cells in response to TGF-ß plus IL-4 increased IL-9 expression and downregulated Blimp-1 expression compared with expression in healthy control subjects. Blimp-1 overexpression in human TH9 cells inhibited IL-9 expression. CONCLUSION: Blimp-1 is a pivotal negative regulator of TH9 differentiation and controls allergic inflammation.

New Insights into Cockroach Allergens.

PURPOSE OF REVIEW: This review addresses the most recent developments on cockroach allergen research in relation to allergic diseases, especially asthma. RECENT FINDINGS: The number of allergens relevant to cockroach allergy has recently expanded considerably up to 12 groups. New X-ray crystal structures of allergens from groups 1, 2, and 5 revealed interesting features with implications for allergen standardization, sensitization, diagnosis, and therapy. Cockroach allergy is strongly associated with asthma particularly among children and young adults living in inner-city environments, posing challenges for disease control. Environmental interventions targeted at reducing cockroach allergen exposure have provided conflicting results. Immunotherapy may be a way to modify the natural history of cockroach allergy and decrease symptoms and asthma severity among sensitized and exposed individuals. The new information on cockroach allergens is important for the assessment of allergen markers of exposure and disease, and for the design of immunotherapy trials.

University and public health system partnership: A real-life intervention to improve asthma management.

OBJECTIVE: Asthma is under-diagnosed in many parts of the world. We aimed to assess the outcome of a capacitating program on asthma for non-specialist physicians and other healthcare professionals working in the public system in Ribeirão Preto, Brazil. METHODS: A group of 16 asthma specialists developed a one-year capacitating program in 11 healthcare clinics in the Northern District of the city, which included lectures on asthma, training on inhalation device use and spirometry, and development of an asthma management protocol. Researchers visited one health unit 2-4 times monthly, working with doctors on patients' care, discussing cases, and delivering lectures. Asthma education was also directed to the general population, focusing on recognition of signs and symptoms and long-term treatment, including production of educational videos available on YouTube. Outcome measures were the records of doctors' prescriptions of individual asthma medications pre- and post-intervention. RESULTS: Prior to the program, 3205 units of inhaled albuterol and 2876 units of inhaled beclomethasone were delivered by the Northern District pharmacy. After the one-year program, there was increase to 4850 units (51.3%) for inhaled albuterol and 3526 units (22.6%) for inhaled beclomethasone. The albuterol increase followed the recommendation given to the non-specialist doctors by the asthma experts, that every patient with asthma should have inhaled albuterol as a rescue medication, by protocol. No increase was observed in other districts where no capacitating program was conducted. CONCLUSION: A systematic capacitating program was successful in changing asthma prescription profiles among non-specialist doctors, with increased delivery of inhaled albuterol and beclomethasone.

Coagulation Factor XII Gene Mutation in Brazilian Families with Hereditary Angioedema with Normal C1 Inhibitor.

BACKGROUND: Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) is a rare disorder. Mutations of the gene encoding coagulation factor XII have been identified in a subset of patients with this condition. Our aim was to investigate mutations in the F12 gene in patients with HAE with normal C1-INH from Brazil. METHODS: We studied 5 Brazilian families with index female patients who presented with recurrent angioedema with normal C1-INH and C4 levels. Genomic DNA was isolated from whole blood and PCR was performed. Mutations were detected by the sequencing of exon 9 of the F12 gene and allelic discrimination. RESULTS: The c.983C>A (p.Thr328Lys) mutation was identified in 16 subjects, from 4 of the 5 families studied, including 8 patients with symptoms of HAE with normal C1-INH (87.5% women) and 8 subjects asymptomatic for HAE (25% women). Mean age at onset of symptoms among the FXII-HAE patients was 13.8 years (range 6-25 years). Recurrent abdominal pain (100%) and subcutaneous angioedema (87.5%) were the most frequent clinical presentations. Two patients presented with associated laryngeal edema. In keeping with previous observations in patients with both C1-INH-HAE and HAE with normal C1-INH, all 7 women with FXII-HAE reported triggering or worsening of symptoms upon intake of estrogen-containing oral contraceptives and/or pregnancy. CONCLUSIONS: We report for the first time in Brazil a mutation in the F12 gene as a likely cause of HAE with normal C1-INH in patients with recurrent attacks of angioedema and/or abdominal pain. A higher frequency of abdominal pain attacks and onset of symptoms at a younger age were observed among Brazilian patients when compared to those from other parts of the world.

Recombinant allergens for diagnosis of cockroach allergy.

Molecular cloning of cockroach allergens and their expression as recombinant proteins have allowed a better understanding of the mechanisms of cockroach allergic disease. Recombinant cockroach allergens have been used for skin testing or in vitro methods to measure IgE antibody levels in serum. Early studies evaluating selected U.S. patients revealed that a cocktail of four cockroach allergens, Bla g 1, Bla g 2, Bla g 4, and Bla g 5, would identify 95 % of cockroach allergic patients. More recent studies pointed to an important role of sensitization to tropomyosin among certain populations, and suggested that a cocktail of five allergens Bla g 1 and/or Per a 1, Bla g 2, Bla g 4, Bla g 5, and Bla g 7, and/or Per a 7, would be expected to diagnose 50- 64 % of cockroach-allergic patients worldwide. Variation in IgE reactivity profiles could be in part due to IgE responses to cross-reactive homologous allergens from different origins. The availability of purified natural or recombinant cockroach allergens provides the capacity to improve diagnosis of cockroach allergy and to develop novel forms of immunotherapy for cockroach-allergic patients.

Efficacy of recombinant allergens for diagnosis of cockroach allergy in patients with asthma and/or rhinitis.

BACKGROUND: Immunoglobulin E (IgE) reactivity to individual allergens among cockroach-allergic patients has revealed wide variability. The aim of this study was to assess the effectiveness of recombinant cockroach allergens for skin testing, and to determine sensitization profiles among cockroach-allergic patients living in Brazil. METHODS: Fifty-seven cockroach-allergic patients with asthma and/or rhinitis were recruited. Skin testing with recombinant (r) allergens from Periplaneta americana (rPer a 1 and rPer a 7) and Blattella germanica (rBla g 2, rBla g 4 and rBla g 5) were performed at 10 µg/ml and 5 µg/ml (rPer a 1). IgE antibodies to rPer a 7 and rPer a 1 were quantitated by ELISA. RESULTS: Of 57 patients tested, 3 (5.3%), 24 (42.1%), 4 (7%), 3 (5.3%) and 4 (7%) showed positive reactions to rPer a 1, rPer a 7, rBla g 2, rBla g 4 and rBla g 5, respectively. Twenty-eight patients (49.1%) had positive tests to at least one allergen. In keeping with skin test results, 31/57 patients (54.4%) and 5/55 patients (9%) had detectable IgE to rPer a 7 and rPer a 1, respectively. Levels of IgE to rPer a 7 were higher in patients with positive tests to rPer a 7 than those with negative tests (geometric mean 13.2 and 1.8 IU/ml, p < 0.05). There was good concordance of results of skin tests and measurements of serum IgE to rPer a 7. CONCLUSION: IgE reactivity to rPer a 7 (P. americana tropomyosin) was dominant among patients in Brazil. However, 50% of the patients did not present reactivity to any of the recombinant allergens tested.

Cockroach allergy: Understanding complex immune responses to develop novel therapies.

Cockroach allergy is associated with the development of asthma. The identification of cockroach allergens, which began in the 1990 s, is an ongoing process that has led to the current listing of 20 official allergen groups in the WHO/IUIS Allergen Nomenclature database. The function and structure of some of these allergens has been determined and define their natural delivery into the environment and their allergenicity. Analysis of antigenic determinants by X-ray crystallography and rational design of site-directed mutagenesis led to the identification of IgE binding sites for the design of molecules with reduced IgE reactivity and T cell modulatory capacity. New developments in recent years include component analyses of B and T cell reactivity and a recent cockroach immunotherapy trial, CRITICAL, that will contribute to understand the immune response to cockroach and to define future directions for cockroach allergy diagnosis and immunotherapy.

Efficacy of dupilumab for the treatment of severe skin disease in cytotoxic T lymphocyte antigen-4 insufficiency: A role of type 2 inflammation?

We report on the successful treatment of a severe, recalcitrant dermatitis caused by CTLA-4 insufficiency with dupilumab, raising the possibility of a role of type 2 immunity in clinical conditions associated with CTLA-4 insufficiency.

Type I and type IIb autoimmune chronic spontaneous urticaria: Using common clinical tools for endotyping patients with CSU.

Background: Mechanisms triggering the pathogenesis of chronic spontaneous urticaria (CSU) have been identified as type I autoallergic (which is associated with IgE antibodies against autoantigens) and type IIb autoimmune (which is driven by autoantibodies to FceR1 and/or IgE). Objective: Our aim was to define presumptive endotypes in patients with CSU by using tests amenable to use in routine clinical practice. Methods: A retrospective analysis of the medical records of 394 patients with CSU with or without chronic inducible urticaria or angioedema was performed. Patients were assigned to 1 of 4 groups as follows: (1) type I endotype of CSU, if they presented at least 1 of the following: allergic disease, total IgE level of at least 40UI/mL, and positive result of skin tests to inhalant allergen(s), (2) type IIb endotype of CSU, if they presented at least 1 of following: autoimmune disease, low total IgE level less than 40 IU/mL, positive autologous serum skin test result, positive for antinuclear antibodies in a titer of at least 1:160, and elevated level of anti-thyroid peroxidase, (3) overlap of type I/type IIb endotypes of CSU, if they presented with at least 1 marker of both type I and type IIb, and (4) non-type I/type IIb endotype of CSU, if they presented with none of the markers of type I or type IIb. Results: The mean age at onset of symptoms was 34 years; 82.2% of those with CSU were female, and angioedema and chronic inducible urticaria were found in 74.8% and 31.9% of patients, respectively. Of the patients with CSU, 38% presented with the type I endotype and 51% presented with type I/type IIb overlap, whereas 9% presented with the type IIb endotype and 2% presented with the non-type I/type IIb endotype. Eosinopenia was associated with type IIb and type I/type IIb overlap as opposed to the type I and non-type I/type IIb endotypes (P = .02). Conclusions: Most patients with CSU presented with features of the type 1 (autoallergic) endotype, whether associated with type IIb (autoimmune) endotype or not.

Pregnancy in Patients With Hereditary Angioedema and Normal C1 Inhibitor.

Background: HAE with normal C1 inhibitor (HAE-nC1-INH) has been identified as a bradykinin mediated angioedema. Estrogens are one of the main trigger factors. Pregnancy in HAE with C1 inhibitor deficiency showed variable course, however, few reports are available for HAE-nC1-INH. We evaluated the course of pregnancies in women diagnosed with HAE-nC1-INH. Methods: Women with diagnosis of HAE-nC1-INH according to the following criteria: clinical manifestations similar to HAE-C1-INH, normal biochemical evaluation and family history were included. A questionnaire about pregnancies was applied after consent. Genetic evaluation for known mutations was performed in all patients. Results: A total of 45 pregnancies occurring in 26 HAE-nC1-INH patients were evaluated (7/26 patients with F12 variant). Spontaneous abortion was reported in 8/45 (17.8%) pregnancies. Onset of attacks started before the pregnancy in 18/26 patients; during the pregnancy in 2/26; and after the pregnancy in 6/26. HAE attacks occurred in 24/37 pregnancies (64,7%): during the 1st trimester in 41.7%; 2nd trimester in 12.5%; 3rd trimester in 20.8%; 1st and 3rd trimesters in 4.2% and during the whole pregnancy in 20.8%. Among 15/18 patients who had attacks before pregnancy, symptoms persisted with worsening in 9/15; improvement in 4/15; no change in 1/15, and no response in 1/15. Conclusions: The occurrence of abortion in HAE-nC1-INH was similar to the expected for not affected women. The 1st trimester of the pregnancy was more symptomatic for HAE-nC1-INH women. Considering the strong relevance of estrogens in HAE-nC1-INH, pregnancy could worsen the course of disease.

Prevalence of the eosinophilic phenotype among severe asthma patients in Brazil: the BRAEOS study.

OBJECTIVE: To assess the prevalence of the eosinophilic and allergic phenotypes of severe asthma in Brazil, as well as to investigate the clinical characteristics of severe asthma patients in the country. METHODS: This was a cross-sectional study of adult patients diagnosed with severe asthma and managed at specialized centers in Brazil. The study was conducted in 2019. RESULTS: A total of 385 patients were included in the study. Of those, 154 had a blood eosinophil count > 300 cells/mm3 and 231 had a blood eosinophil count of ≤ 300 cells/mm3. The median age was 54.0 years, and most of the patients were female, with a BMI of 29.0 kg/m2 and a history of allergy (81.6%). The prevalence of patients with a blood eosinophil count > 300 cells/mm3 was 40.0% (95% CI: 35.1-44.9), and that of those with a blood eosinophil count > 300 cells/mm3 and a history of allergy was 31.9% (95% CI: 27.3-36.6). Age and BMI showed positive associations with a blood eosinophil count > 300 cells/mm3 (OR = 0.97, p < 0.0001; and OR = 0.96, p = 0.0233, respectively), whereas the time elapsed since the onset of asthma symptoms showed an increased association with a blood eosinophil count > 300 cells/mm3 (OR = 1.02, p = 0.0011). CONCLUSIONS: This study allowed us to characterize the population of severe asthma patients in Brazil, showing the prevalence of the eosinophilic phenotype (in 40% of the sample). Our results reveal the relevance of the eosinophilic phenotype of severe asthma at a national level, contributing to increased effectiveness in managing the disease and implementing public health strategies.

Measurement of IgE antibodies to shrimp tropomyosin is superior to skin prick testing with commercial extract and measurement of IgE to shrimp for predicting clinically relevant allergic reactions after shrimp ingestion.

BACKGROUND: Shrimp is a frequent cause of food allergy. Tropomyosin is the major allergen in shrimp, and it shares homology to tropomyosins from other crustaceans, dust mites, cockroach, and parasites. OBJECTIVE: The aim of this study was to determine the value of detection of IgE to shrimp tropomyosin in the diagnosis of shrimp allergy. METHODS: We have studied 35 patients with asthma, rhinitis, or both who were sensitized to Dermatophagoides pteronyssinus. All subjects underwent skin prick testing in addition to double-blind, placebo-controlled food challenges (DBPCFC); oral open challenges; or both with shrimp. Measurements of IgE to shrimp and shrimp tropomyosin were carried out by means of CAP and chimeric ELISA, respectively. RESULTS: Oral challenges confirmed the diagnosis of shrimp allergy in 7 patients. IgE measurement to shrimp tropomyosin was positive in 71.4% of the patients with shrimp allergy. Of the 28 patients without shrimp allergy, only 7.1% (2/28) had IgE to shrimp tropomyosin compared with 25% (7/28) who had IgE to shrimp and 35.7% (10/28) who had positive skin prick test responses to shrimp. Sensitivity was similar for all 3 methods (71.4%); in contrast, specificity of IgE to shrimp tropomyosin (92.8%) was greater than that of IgE to shrimp (75%) and skin prick testing (64.2%). With regard to diagnostic efficiency, measurement of IgE to shrimp tropomyosin was superior to measurement of IgE to shrimp and skin prick testing (88.5%, 74.2%, and 65.7%, respectively). CONCLUSION: Use of measurements of IgE to shrimp tropomyosin provided added value to the diagnosis of shrimp allergy.

Unnecessary Abdominal Surgeries in Attacks of Hereditary Angioedema with Normal C1 Inhibitor.

Hereditary angioedema (HAE) is an autosomal dominant disease mostly due to the deficiency of C1 inhibitor (C1-INH). HAE with normal C1-INH was first described in 2000 and associated with mutations in the coagulation factor XII in 2006. Both diseases are associated with high bradykinin production, resulting in increased vascular permeability. Gastrointestinal edema due to HAE can be misdiagnosed as acute abdomen and unnecessary surgical procedures may be performed. The present study evaluates the prevalence of surgical procedures and/or acute abdomen in HAE patients with the coagulation factor XII mutation. It is a retrospective study where patients were diagnosed with recurrent angioedema without urticaria, normal C1-INH levels, and positive family history of angioedema. All patients were evaluated for the known mutations located at exon 9 of the F12 gene. Medical records were evaluated and questionnaires were applied to 52 patients with normal C1-INH levels (age range 13-76 years; 47/52, 90.38% women; 5/52, 9.61% men). F12 mutation was present in 32/52 patients (61.5%). Acute abdominal pain was diagnosed in 16/52 (30.76%) patients, appendicitis in 9/16 (56.2%), and undetermined diagnosis in 7/16 (43.7%). Among patients diagnosed with acute abdominal pain, 13/16 (81.2%) underwent surgery and 3/16 (18.7%) improved without surgical intervention. We conclude that many HAE patients with coagulation factor XII mutation were misdiagnosed with acute abdomen and subjected to unnecessary invasive procedures. It is critical to disseminate information about this rare mutation in patients with otherwise normal C1-INH activity, in order to speed up diagnosis and avoid misconduct.

COVID-19, asthma, and biological therapies: What we need to know.

Managing patients with severe asthma during the coronavirus pandemic and COVID-19 is a challenge. Authorities and physicians are still learning how COVID-19 affects people with underlying diseases, and severe asthma is not an exception. Unless relevant data emerge that change our understanding of the relative safety of medications indicated in patients with asthma during this pandemic, clinicians must follow the recommendations of current evidence-based guidelines for preventing loss of control and exacerbations. Also, with the absence of data that would indicate any potential harm, current advice is to continue the administration of biological therapies during the COVID-19 pandemic in patients with asthma for whom such therapies are clearly indicated and have been effective. For patients with severe asthma infected by SARS-CoV-2, the decision to maintain or postpone biological therapy until the patient recovers should be a case-by-case based decision supported by a multidisciplinary team. A registry of cases of COVID-19 in patients with severe asthma, including those treated with biologics, will help to address a clinical challenge in which we have more questions than answers.

Respiratory infection, exposure to mouse allergen and breastfeeding: role in recurrent wheezing in early life.

BACKGROUND: Environmental factors may influence the development of allergen sensitization and asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life as a risk factor for recurrent wheezing. METHODS: One hundred and four infants from low-income families, at high risk of asthma, were enrolled at birth. Dust samples were collected from the bedding and bedroom floor within 6 months after birth. Recurrent wheezing was defined as 3 or more wheezing episodes in the past year. Endotoxin was determined by Limulus amebocyte lysate assay, and major indoor allergens were quantitated by ELISA in dust extracts. IgE antibodies were measured by ImmunoCAP at 30 months of age. RESULTS: At 30 months, 51 of the 99 infants who completed the study (51.5%) had recurrent wheezing. Respiratory infection was strongly associated with recurrent wheezing (OR 6.67, 95% CI 1.96-22.72), whereas exclusive breastfeeding for at least 1 month was a protective factor (OR 0.09, 95% CI 0.01-0.51). Exposure to high levels of mouse allergen was more frequent among non-recurrent wheezers, approaching significance (OR 0.12, 95% CI 0.01-1.13; p = 0.064). None of the children were sensitized to mouse. Sensitization to mite was found in 26/90 (28.8%) children, with no association with recurrent wheezing. CONCLUSION: Respiratory infection was strongly associated with recurrent wheezing in the first 30 months of life, in children at high risk of asthma, living in a socially deprived community in Brazil.

Cross-reactive IgE antibody responses to tropomyosins from Ascaris lumbricoides and cockroach.

BACKGROUND: Evidence indicates that infection with Ascaris lumbricoides may promote development of allergy and asthma. OBJECTIVE: To study the role of tropomyosin, a pan-allergen in invertebrates, in IgE responses to A lumbricoides. METHODS: Recombinant A lumbricoides and Periplaneta americana tropomyosins were expressed in Pichia pastoris. Levels of IgE to tropomyosins from A lumbricoides and P americana were determined by chimeric ELISA in sera from 119 children living in a parasite-endemic area and 112 patients with cockroach allergy from the allergy clinics. Presence of tropomyosin in A lumbricoides larvae at L3 stage was evaluated by immunofluorescence using mAb 1A6, directed against mite tropomyosin. Molecular modeling of P americana and A lumbricoides tropomyosins was performed by using the MODELLER program. RESULTS: A lumbricoides tropomyosin showed 69% to 98% sequence identity to tropomyosins from other invertebrates. The predicted structure of A lumbricoides tropomyosin was similar to that of P americana tropomyosin and showed the characteristic coiled-coil structure. Strong correlation was found for IgE antibodies to tropomyosins from A lumbricoides and P americana in sera from children living in a parasite-endemic area and from patients with cockroach allergy. Larvae of A lumbricoides reacted strongly with mAb 1A6. CONCLUSION: Tropomyosin induces IgE responses in A lumbricoides-infected children and in patients allergic to cockroach.