Background: Surfactant Protein D (SP-D) is a pattern recognition molecule belonging to the collectin family expressed in multiple human organ systems including the lungs. Previous studies have shown that SP-D concentrations in bronchoalveolar lavage samples decreases and serum concentrations increases in patients with asthma possibly attributable to a combination of induced SP-D synthesis and decreased air-blood barrier integrity. The aims of this study were to investigate if the serum level of SP-D and common variations in the SP-D gene were associated to asthma in adolescents and young adults. Methods: Prospective observational study including 449 adolescents and young adults (age 11-27 years) previously diagnosed with asthma during a two-year period from 2003 to 2005 (0-16 years). At follow-up from 2016 to 2017 314 healthy controls with no medical history of asthma were recruited. Serum SP-D was analyzed on samples obtained at baseline as well as samples obtained at follow-up. SP-D genotyping was performed for rs721917, rs2243639 and rs3088308. Results: No differences were found in mean levels of sSP-D and SFTPD genotype among subjects with current asthma, no current asthma and controls. Serum SP-D and SFTPD genotype were not associated to any clinical parameters of asthma. Furthermore, baseline sSP-D was not associated to asthma at follow-up. Conclusion: Serum surfactant protein D and common SP-D gene variants were not associated with asthma in Danish adolescents and young adults with mild to moderate asthma. Serum surfactant protein D did not demonstrate any value as a clinical biomarker of asthma.

Susanne Halken

and 3 more

To the EditorReply to Stefano Miceli SopoFirst of all we want to thank for giving us an opportunity to reply to this correspondence (1), acknowledging the correspondence authors important point about the recommendation of introducing well-cooked, but not raw or uncooked pasteurized hen’s egg as part of complementary feeding.We agree that the evidence-base is sparse, with just two trials about cooked egg contributing to the low to moderate certainty evidence in our review (2) and guideline (3). These studies were in different populations (4, 5). We highlighted these points in the guideline, and the subgroup analysis from the Perkin study (6) was used only as supporting material, and for estimating the amount of egg that could be used. It is correct that the Natsume study included infant at higher risk due to eczema, but that was the case for both groups, and outcome was assessed by controlled challenges as described in the systematic review (2).As set out in the guideline, the process took into account expert insight weighing up benefits and harms, costs, feasibility, standard practice and patient preferences, in addition to published evidence. Weighing up all of these factors, the task force decided that the potential benefits outweighed potential harms in the case of well-cooked egg. One relatively large study found a 29% absolute decrease in the proportion of high risk infants with egg allergy at 1 year when very small amounts of egg were introduced (RR 0.22, 95% CI 0.08 to 0.54) (4). And two trials found no adverse effects (4, 5). It is likely feasible for many families to introduce well-cooked egg as part of complementary feeding, including in baked goods. The potential benefits do not outweigh the harms for uncooked egg, so the task force did not suggest trying this approach.The task force included representatives from many countries and specialties, and followed a robust process when reviewing evidence and debating potential recommendations. As the correspondence authors note, this recommendation is in line with other key guidelines. Whilst the correspondence authors may not agree with specific recommendations, the process used to debate and vote on them was systematic and took into account perspectives from across the world, including those from organisations representing patients and their families. Furthermore, a public consultation process sought feedback prior to publication, which further reinforced consensus about this recommendation.As is the case with all guidelines, the EAACI food allergy prevention guideline provides suggestions for clinicians to consider, alongside the needs of individual patients and local contexts and customs. The guideline is not prescriptive and does not override clinical judgement ad individual circumstances. Given the lack of likely harm, the convenience of this approach and best available evidence to date, the task force stands by its suggestion that clinicians in countries where egg allergy is an issue discuss with families the potential and desire to introduce small amounts of well-cooked egg into the infant diet when appropriate as part of complementary feeding. This need not be from the beginning of complementary therapy and the amounts may be very small.The guideline suggests half of a well-cooked, small egg twice a week, which may be in the form of a hard-boiled egg, well-cooked egg pasta, bread or baked goods, for example (p. 850). There is no evidence of significant harm, and it is likely that infants in many parts of the world may be exposed to egg in their diet anyway. There is no need to avoid this to prevent egg allergy, and in the opinion of the EAACI task force, introducing it may have benefits.Susanne Halken, Professor a, ProfessorAntonella Maria Muraro b, ProfessorGraham Roberts c, ProfessorDebra de Silva d, ProfessorOn behalf of On behalf of the EAACI Prevention Guideline Task Forcea Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, DenmarkbDepartment of Women and Child Health, Food Allergy Referral Centre Veneto Region, Padua University Hospital, Padua, Italyc Clinical and Experimental Sciences and Human Development in Health, Faculty of Medicine, University of Southampton, Southampton, UK. NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, UKdThe Evidence Centre Ltd, London, UKReferencesStefano Miceli Sopo, Dario Sinatti, Francesco Mastellone, Giulia Bersani, Mariannita Gelsomino. Comment on Halken et al. Pediatr Allergy Immunol . 2022de Silva D, Halken S, Singh C, et al. Preventing food allergy in infancy and childhood: systematic review of randomised controlled trials. Pediatr Allergy Immunol . 2020;31(7):813-826Halken S, Muraro A, de Silva D, et al. EAACI guideline: Preventing the development of food allergy in infants and young children (2020 update). Pediatr Allergy Immunol. 2021;32(5):843-858.Natsume O, Kabashima S, Nakazato J, et al. Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. Lancet. 92 2017;389(10066):276-286.Perkin MR, Logan K, Tseng A, et al. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374(18):1733-1743.Perkin MR, Logan K, Bahnson HT, et al. Efficacy of the enquiring About Tolerance (EAT) study among infants at high risk of developing food allergy. J Allergy Clin Immunol. 2019;144(6):1606-1614.

Debra de Silva

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Background This systematic review used the GRADE approach to compile evidence to inform an anaphylaxis guideline from the European Academy of Allergy and Clinical Immunology (EAACI). Methods We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18,449 participants: 29 randomised controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarised narratively because studies were too heterogeneous to conduct meta-analysis. Results It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. Adrenaline is the cornerstone of first-line emergency management of anaphylaxis but, due to ethical constraints, little robust research has assessed its effectiveness . Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. Adrenaline prophylaxis prior to snake bite anti-venom may reduce anaphylaxis but the impact of prophylactic corticosteroids and antihistamines is uncertain. There was insufficient evidence about the impact of other anaphylaxis management strategies. Conclusions Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it.