Luís Miguel Borrego

EAACI food allergy and anaphylaxis guidelines: managing patients with food allergy in the community

The European Academy of Allergy and Clinical Immunology (EAACI) Food Allergy and Anaphylaxis Guidelines, managing patients with food allergy (FA) in the community, intend to provide guidance to reduce the risk of accidental allergic reactions to foods in the community. This document is intended to meet the needs of early‐childhood and school settings as well as providers of non‐prepackaged food (e.g., restaurants, bakeries, takeaway, deli counters, and fast‐food outlets) and targets the audience of individuals with FA, their families, patient organizations, the general public, policymakers, and allergists. Food allergy is the most common trigger of anaphylaxis in the community. Providing children and caregivers with comprehensive information on food allergen avoidance and prompt recognition and management of allergic reactions are of the utmost importance. Provision of adrenaline auto‐injector devices and education on how and when to use these are essential components of a comprehensive management plan. Managing patients at risk of anaphylaxis raises many challenges, which are specific to the community. This includes the need to interact with third parties providing food (e.g., school teachers and restaurant staff) to avoid accidental exposure and to help individuals with FA to make safe and appropriate food choices. Education of individuals at risk and their families, their peers, school nurses and teachers as well as restaurant and other food retail staff can reduce the risk of severe/fatal reactions. Increased awareness among policymakers may improve decision‐making on legislation at local and national level.

EAACI position paper for practical patch testing in allergic contact dermatitis in children

Allergic contact dermatitis (ACD) in children appears to be on the increase, and contact sensitization may already begin in infancy. The diagnosis of contact dermatitis requires a careful evaluation of a patients clinical history, physical examination, and skin testing. Patch testing is the gold standard diagnostic test.

New reference ranges for interpreting forced expiratory manoeuvres in infants and implications for clinical interpretation: a multicentre collaboration

The raised volume rapid thoracoabdominal compression (RVRTC) technique is commonly used to obtain full forced expiratory manoeuvres from infants, but reference equations derived from ‘in-house’ equipment have been shown to be inappropriate for current commercially available devices. Aim To explore the impact of equipment differences on RVRTC outcomes, derive robust equipment-specific RVRTC reference ranges and investigate their potential clinical impact on data interpretation. Method RVRTC data from healthy subjects using Jaeger BabyBody or the ‘Respiratory Analysis Software Program, RASP’ systems were collated from four centres internationally. Data were excluded if gestational age <37 weeks or birth weight <2.5 kg. Reference equations for RVRTC outcomes were constructed using the LMS (lambda–mu–sigma) method, and compared with published equations using data from newborn screened infants with cystic fibrosis (CF). Results RVRTC data from 429 healthy infants (50.3% boys; 88% white infants) on 639 occasions aged 4–118 weeks were available. When plotted against length, flows were significantly higher with RASP than Jaeger, requiring construction of separate equipment-specific regression equations. When comparing results derived from the new equations with those from widely used published equations based on different equipments, discrepancies in forced expiratory volumes and flows of up to 2.5 z-scores were observed, the magnitude of which increased with age. According to published equations, 25% of infants with CF fell below the 95% limits of normal for FEV0.5, compared with only 10% when using the new equations. Conclusions Use of equipment-specific prediction equations for RVRTC outcomes will enhance interpretation of infant lung function results; particularly during longitudinal follow-up.

Characterization of B cells in healthy pregnant women from late pregnancy to post-partum: a prospective observational study

BackgroundB cells play a role in pregnancy due to their humoral and regulatory activities. To our knowledge, different maturational stages (from transitional to memory) of circulating B cell subsets have not yet been characterized (cell quantification and phenotype identification) in healthy pregnant women. Thus, the objective of our study was to characterize these subsets (as well as regulatory B cells) from late pregnancy to post-partum and to compare them with the circulating B cells of non-pregnant women.MethodsIn all of the enrolled women, flow cytometry was used to characterize the circulating B cell subsets according to the expression of IgD and CD38 (Bm1-Bm5 classification system). Regulatory B cells were characterized based on the expression of surface antigens (CD24, CD27, and CD38) and the production of IL-10 after lipopolysaccharide stimulation.ResultsCompared to the absolute counts of B cells in the non-pregnant women (n = 35), those in the pregnant women (n = 43) were significantly lower (p < 0.05) during the 3rd trimester of pregnancy and on delivery day (immediately after delivery). The percentages of these cells on delivery day and at post-partum were significantly lower than those in the non-pregnant women.In general, the absolute counts and percentages of the majority of the B cell subsets were significantly lower in the 3rd trimester of pregnancy and on delivery day than in the non-pregnant women. However, these counts and percentages did not differ significantly between the post-partum and the non-pregnant women.The most notable exceptions to the above were the percentages of naïve B cells (which were significantly higher in the 3rd trimester and on delivery day than in the non-pregnant women) and of CD24hiCD38hi regulatory B cells (which were significantly higher in the post-partum than in the non-pregnant women).ConclusionAccording to our study, the peripheral B cell compartment undergoes quantitative changes during normal late pregnancy and post-partum. Such findings may allow us to better understand immunomodulation during human pregnancy and provide evidence that could aid in the development of new strategies to diagnose and treat pregnancy-associated disturbances. Our findings could also be useful for studies of the mechanisms of maternal responses to vaccination and infection.

Bronchodilator responsiveness using spirometry in healthy and asthmatic preschool children

Objective To assess repeatability and reproducibility of spirometry measurements, and bronchodilator responsiveness (BDR), in healthy 3–6-year-old preschool children and those with asthma. Design Spirometry was performed before and 20 minutes after administering either inhaled placebo (for repeatability) or 400 μg salbutamol (for BDR) on two separate occasions (reproducibility) 3–23 days apart in asthmatic preschoolers and healthy controls. Settings Lung Function Laboratory, Hospital de Dona Estefania, Lisbon. Participants Healthy preschool children and those with physician-diagnosed asthma, recruited from local Health Clinics and Outpatient Clinic. Main outcome measures Paired measurements of forced expired volume in 0.75 s (FEV0.75) and forced mid-expiratory flows (FEF25–75). Results Technically successful baseline results were obtained in 86% of children assessed. Paired data were obtained in 43 asthmatic and 22 controls (median (range) age: 5.1 (3.4–6.8) years). Baseline FEV0.75 was significantly lower in asthmatic children (mean (SD): 90 (15)% predicted) than in controls (102 (13) % predicted; p<0.001). Within-occasion coefficient of repeatability following placebo was similar in both groups, being 10.4% in asthma and 13.2% in controls for FEV0.75. Following bronchodilator, FEV0.75 increased significantly more in asthmatic preschoolers (mean (SD): 15.0 (12) %) than in controls (4.5 (5) %; p<0.001), with no significant difference between groups post-bronchodilator. Between-occasion variability was similar to within-day repeatability in controls, but almost twice as high in asthmatic children. Conclusions BDR can be assessed reliably using FEV0.75 in wheezy preschoolers, provided within-subject variability and responsiveness in health are taken into consideration.

Validation of Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) - a prospective multicenter study

Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) is the first questionnaire that assesses simultaneously allergic rhinitis and asthma control in children. It was recently developed, but redundancy of questions and its psychometric properties were not assessed. This study aimed to (i) establish the final version of the CARATKids questionnaire and (ii) evaluate its reliability, responsiveness, cross‐sectional validity, and longitudinal validity.

Exequibilidade do estudo funcional respiratório em idade pré-escolar na prática clínica

INTRODUCTION The assessment of respiratory function in preschool children, which has recently been attracting considerable interest, has several methodological particularities. Whether this is feasible in clinical practice with large groups of patients still needs to be investigated. AIM To assess the feasibility of pulmonary function testing in preschool children in clinical practice, and report the degree of success achieved according to age. METHODS Retrospective analysis of lung function tests performed in children from 2 to 6 years old at the respiratory function laboratory of CUF Descobertas Hospital between September 2006 and August 2011. Whole-body pletismography without occlusion for specific airway resistance (sRaw) assessment and animated spirometry were performed using the equipment Jaeger 4.65 (Viasys Healthcare), before and after 400 μg of inhaled salbutamol via a spacer device. The research fulfilled international criteria (ATS/ERS) for acceptability and reproducibility. RESULTS Of 1,239 lung function tests performed, 1,092 (88%) had acceptable and reproducible criteria for spirometry (children with a mean age of 4.3±0.91 years; 60.7% male), and 979 (79%) for sRaw measurement. We were able to report FEV(1) in 801 (65%) tests (children with a mean age of 4.5±0.89 years). In 23 (2%) tests it was only possible to report FEV(0.5) (children with a mean age of 3.5±0.67 years) and in 268 (22%) only FEV(0.75) (children with a mean age of 4.0±0.89 years). CONCLUSION Spirometry and sRaw assessment in preschool children can be used in clinical practice, with an increasing success rate as children get older. Reporting maneuvers of 0.5 or 0.75 seconds facilitates spirometric evaluation in a larger number of children.

Regulatory T and B cells in asthmatic women: variations from pregnancy to postpartum Treg and Breg: pregnancy to postpartum.

BACKGROUND AND OBJECTIVE Allergic asthma and rhinitis are common in pregnancy. The immune mechanisms underlying the effects of asthma on pregnancy and vice versa are not completely understood. The aim of this study was to investigate changes in regulatory T and B cells in asthmatic women from late pregnancy to postpartum. METHODS Four groups of women were enrolled for this study: asthmatic (n=23) and healthy (n=43) third trimester-pregnant women and asthmatic (n=33) and healthy (n=35) nonpregnant women. Pregnant women were also evaluated postpartum (>6 weeks after delivery). Blood samples were taken from each woman and flow cytometry was used to characterize circulating regulatory T cells (Tregs) and regulatory B cells (Bregs). Foxp3 expression was assessed in CD4DimCD25Hi Tregs. RESULTS Tregs did not vary significantly from pregnancy to postpartum in asthmatic or healthy women, but CD24HiCD38Hi Bregs decreased in pregnancy and increased significantly postpartum. Foxp3 expression in Tregs was also impaired during pregnancy in both asthmatic and healthy women, but recovered postpartum. Asthmatic pregnant women had higher Foxp3 expression levels than healthy pregnant women (P=.007), probably due to the use of control medication. CONCLUSIONS Women with controlled asthma showed variations in regulatory cell subsets during pregnancy and postpartum. A similar pattern was observed for Foxp3 expression and CD24HiCD38Hi Bregs during this period, corroborating the interaction between Tregs and Bregs in immune responses. Considering the immunomodulatory potential of these immune mediators, more studies are needed to evaluate their relationship with asthma and rhinitis complications in pregnancy.

Ultrarush schedule of subcutaneous immunotherapy with modified allergen extracts is safe in paediatric age.

Background Traditional subcutaneous immunotherapy up dosing with allergenic extracts has been shown to be associated with frequent adverse reactions. In recent studies it has been demonstrated that using modified extracts, namely allergoids, it is a safe and effective procedure particularly on accelerated schedules. However data assessing its safety in paediatric age is scarce. Objective To evaluate the safety profile in paediatric population of using modified allergen extracts, in an ultrarush schedule, to reach the maintenance dose in the first day. Methods We included children undergoing treatment with subcutaneous immunotherapy during a five-year period, using modified aeroallergen extracts, depigmented, polymerized with glutaraldehyde and adsorbed on aluminium hydroxide using an ultrarush induction phase. The type of adverse reactions during the ultrarush protocol was recorded. Results We studied 100 paediatric patients (57 males) with a mean age of 11.6 years (5 to 18 years; standard deviation, 3.3), all with moderate to severe persistent rhinitis, with or without allergic conjunctivitis, asthma and atopic eczema, sensitized to mites and/or pollens. All reached the maintenance dose of 0.5 mL in the first day, except 1 child. During the ultrarush protocol the total number of injections was 199. There were 21 local adverse reactions in 11 patients, 11 immediate and 10 delayed; from those, had clinical relevance 1 immediate and 4 delayed. Systemic reactions were recorded in 2 cases, both immediate and mild. Conclusion The ultrarush protocol, without premedication, was a safe alternative to be used in paediatric age during the induction phase of subcutaneous immunotherapy using allergoid depigmented extracts.

Pregnancy alters the circulating B cell compartment in atopic asthmatic women, and transitional B cells are positively associated with the development of allergy manifestations in their progeny

Maternal atopy is a risk factor for allergy. B cells are poorly studied in reproduction and atopy. We aimed to assess how pregnancy affects B cells in atopic women and whether B cells relate to allergic manifestations in offspring.