Recommendations for asthma monitoring in children: A PeARL document endorsed by APAPARI, EAACI, INTERASMA, REG, and WAO.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

Food allergy across the globe.

The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of common food allergens during pregnancy and lactation and delaying the introduction of allergenic foods in children aged between 1 and 3 years. Recent guidelines for allergy prevention recommend consumption of a healthy and diverse diet without eliminating or increasing the consumption of allergenic foods during pregnancy or breast-feeding. Early introduction of allergenic foods is recommended by most guidelines for allergy prevention after a period of exclusive breast-feedng (6 months [World Health Organization] or 4 months [European Academy of Allergy and Clinical Immunology]). New diagnostics for FA have been developed with varied availability of these tests in different countries. Finally, the first oral immunotherapy drug for FA was approved by the US Food and Drug Administration and European Medicines Agency in 2020. In this review, we will address the global prevalence of FA, our current understanding of the causes of FA, and the latest guidelines for preventing, diagnosing, and treating FA. We will also discuss similarities and differences between FA guidelines.

Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multi-national cohort.

BACKGROUND: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 pandemic on childhood asthma outcomes. METHODS: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4 and 18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. RESULTS: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks, and hospitalizations due to asthma, in comparison with the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits, or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. CONCLUSION: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.

Breast milk interleukin-7 and thymic gland development in infancy.

PURPOSE: Interleukin-7 (IL-7) is known to be important for lymphocyte development. We sought to investigate the maternal breast milk IL-7 expression to explore its impact on thymus development in infants. METHODS: We conducted a prospective study on three groups of healthy infants classified into exclusively breast-fed (n = 19), formula-fed (n = 17) and mixed-fed (n = 19) infants. They were investigated at 2, 4 and 6 months of age for thymic indices by ultrasonography, T lymphocyte subsets enumeration by flowcytometry and breast milk IL-7 levels. RESULTS: Thymic indices were higher at the age of 2 and 6 months in the exclusively breast-fed infants (mean ± SD 22.4 ± 2.1, 26.2 ± 2.7 mm3, respectively) and mixed-fed infants (mean ± SD 22 ± 3.2, 25 ± 3.2, respectively) as compared to formula-fed infants (mean ± SD 17.9 ± 3.7, 21.6 ± 3.9 respectively); p < 0.001. In the exclusively breast-fed infants, IL-7 levels correlated positively to thymic indices and CD3+ T cell numbers at 2 months of age. Positive correlations were elicited in the mixed-fed group at 2, 4 and 6 months of age for thymic indices and at 6 months for CD3+ cells. CONCLUSION: Breast milk and/or its IL-7 content have a significant positive impact on thymic development. Our conclusions are limited by the sample size and short duration of follow-up. What is known is that breast milk has a trophic role in thymic development and contains IL-7. What is new is that there is positive correlation between breast milk IL-7 concentration and thymic development and lymphocyte output; variation of IL-7 levels with type of feeding (exclusive breast feeding/mixed breast and formula feeding) and with time postnatally.

Pediatric asthma: An unmet need for more effective, focused treatments.

BACKGROUND: Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. METHODS: A two-day, face-to-face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. RESULTS: These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non-steroid-based alternative therapies in patients <6 years of age. An increased focus on children is needed in the context of clinical practice guidelines for asthma; current pediatric practice relies mostly on extrapolations from adult recommendations. Furthermore, no uniform definition of pediatric asthma exists, which hampers timely and robust diagnosis of the condition in affected patients. CONCLUSIONS: There is a need for a uniform definition of pediatric asthma, clearly distinguishable from adult asthma. Furthermore, guidelines which provide specific treatment recommendations for the management of pediatric asthma are also needed. Clinical trials and real-world evidence studies assessing anti-immunoglobulin E (IgE) therapies and other monoclonal antibodies in children <6 years of age with asthma may provide further information regarding the most appropriate treatment options in these vulnerable patients. Early intervention with anti-IgE and non-steroid-based alternative therapies may delay disease progression, leading to improved clinical outcomes.

Allergy and immunology in Africa: Challenges and unmet needs.

The tremendous increase in allergy in the African continent cannot simply be explained by the change in public hygiene. There are many "prehygiene" communities with sewage-contaminated water supplies, helminth infestations, bare footedness, and poor housing, and still there is a high prevalence of allergic disease. Africans can be exposed to many risk factors facilitating severe asthma and wheezing, including airborne viruses, smoke, indoor dampness, cockroaches, and poor access to health care. Although the reporting on food allergy is inadequate to perform systematic reviews or meta-analyses, the available data suggest that food allergy is underdiagnosed. The rate of new HIV infections in high-prevalence settings in Africa remains unacceptably high. Although the annual number of new HIV infections in Sub-Saharan Africa has decreased lately, new HIV infections in the Middle East and North Africa region have increased; however, the current prevalence of 0.1% is still among the lowest globally. Africa is densely populated, and consanguineous mating is high in some areas of North and Sub-Saharan Africa. This allows for emergence of many autosomal recessive primary immunodeficiency diseases. There is urgent need for the establishment of primary immunodeficiency disease registries, stem cell transplantation facilities, and neonatal screening programs. To address these expanding problems and perform local cutting-edge research, Africans need to be empowered by motivated governments, dedicated funds, and compassionate scientific partnership.

Update on the use of immunoglobulin in human disease: A review of evidence.

Human immunoglobulin preparations for intravenous or subcutaneous administration are the cornerstone of treatment in patients with primary immunodeficiency diseases affecting the humoral immune system. Intravenous preparations have a number of important uses in the treatment of other diseases in humans as well, some for which acceptable treatment alternatives do not exist. We provide an update of the evidence-based guideline on immunoglobulin therapy, last published in 2006. Given the potential risks and inherent scarcity of human immunoglobulin, careful consideration of its indications and administration is warranted.

A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency.

BACKGROUND: The recombination-activating gene (RAG) 1/2 proteins play a critical role in the development of T and B cells by initiating the VDJ recombination process that leads to generation of a broad T-cell receptor (TCR) and B-cell receptor repertoire. Pathogenic mutations in the RAG1/2 genes result in various forms of primary immunodeficiency, ranging from T(-)B(-) severe combined immune deficiency to delayed-onset disease with granuloma formation, autoimmunity, or both. It is not clear what contributes to such heterogeneity of phenotypes. OBJECTIVE: We sought to investigate the molecular basis for phenotypic diversity presented in patients with various RAG1 mutations. METHODS: We have developed a flow cytometry-based assay that allows analysis of RAG recombination activity based on green fluorescent protein expression and have assessed the induction of the Ighc locus rearrangements in mouse Rag1(-/-) pro-B cells reconstituted with wild-type or mutant human RAG1 (hRAG1) using deep sequencing technology. RESULTS: Here we demonstrate correlation between defective recombination activity of hRAG1 mutant proteins and severity of the clinical and immunologic phenotype and provide insights on the molecular mechanisms accounting for such phenotypic diversity. CONCLUSIONS: Using a sensitive assay to measure the RAG1 activity level of 79 mutations in a physiologic setting, we demonstrate correlation between recombination activity of RAG1 mutants and the severity of clinical presentation and show that RAG1 mutants can induce specific abnormalities of the VDJ recombination process.

Pediatric asthma comorbidities: Global impact and unmet needs.

Real-world data on the range and impact of comorbid health conditions that affect pediatric asthma are scant, especially from developing countries. Lack of data hinders effective diagnosis, treatment, and overall management of these complex cases. We, hereby, describe the common pediatric asthma comorbid conditions in terms of evidence for association, potential mechanisms of impact on asthma control, and treatment benefit. Obesity, upper airway allergies, dysfunctional breathing, multiple sensitizations, depressive disorders, food allergy, and gastro-esophageal reflux are common associations with difficult-to-treat asthma. On the other hand, asthma symptoms and/or management may negatively impact the well-being of children through drug adverse effects, worsening of anaphylaxis symptoms, and disturbing mental health. Awareness of these ailments may be crucial for designing the optimum care for each asthmatic child individually and may ultimately improve the quality of life of patients and their families. A multidisciplinary team of physicians is required to identify and manage such comorbidities aiming to mitigate the over-use of asthma pharmacotherapy. Asthma research should target relevant real-world difficulties encountered at clinical practice and focus on interventions that would mitigate the impact of such comorbidities. Finally, policymakers and global healthcare organizations are urged to recognize pediatric asthma control as a healthcare priority and allocate resources for research and clinical interventions. In other words, global asthma control needs support by compassionate scientific partnership.

Updated grading system for systemic allergic reactions: Joint Statement of the World Allergy Organization Anaphylaxis Committee and Allergen Immunotherapy Committee.

There is a lack of consensus over the description and severity assignment of allergic adverse reactions to immunotherapy, although there seems to be a consensus at least in terms of using the World Allergy Organization (WAO) grading systems to describe local adverse events for Sublingual Immunotherapy (SLIT) and Systemic Allergic Reactions (SARs) to Subcutaneous Immunotherapy (SCIT) amongst the major national/regional allergy societies. In this manuscript, we propose a modification of the previous WAO Grading system for SARs, which aligns with the newly-proposed Consortium for Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions in Food Allergy (version 3.0). We hope this can facilitate a unified grading system appropriate to SARs due to allergen immunotherapy, independent of allergen and route of administration, and across clinical and research practice.

Unanswered questions on the use of biologics in pediatric asthma.

The emergence of biologic therapies for the management of asthma has been a revolutionary change in our capacity to manage this disease. Since the launch of omalizumab, several other biologics have been marketed or are close to being marketed, suggesting that a plethora of monoclonal antibodies can be expected in the coming years. This will facilitate the transition to the paradigm of personalized medicine, but on the other hand will decisively further complicate the choice of the most appropriate treatment, in the absence of reliable enough biological markers. For these reasons, along with the relatively short time of use with these treatments, there are recurrently arising questions for which there are not even moderately documented answers, and for which the only solution must be based, with all reservations, on the combination of indirect evidence and expertise. In this paper, we attempt to address such questions, providing relevant commentaries and considering the whole width of the evidence base.

Utility of biomarkers in the diagnosis and monitoring of asthmatic children.

Asthma imposes a heavy morbidity burden during childhood; it affects over 10% of children in Europe and North America and it is estimated to exceed 400 million people worldwide by the year 2025. In clinical practice, diagnosis of asthma in children is mostly based on clinical criteria; nevertheless, assessment of both physiological and pathological processes through biomarkers, support asthma diagnosis, aid monitoring, and further lead to better treatment outcomes and reduced morbidity. Recently, identification and validation of biomarkers in pediatric asthma has emerged as a top priority across leading experts, researchers, and clinicians. Moreover, the implementation of non-invasive biomarkers for the assessment and monitoring of paediatric patients with asthma, has been prioritized; however, only a proportion of them are currently included in the clinical practise. Although, the use of non-invasive biomarkers is highly supported in recent asthma guidelines for documenting diagnosis and supporting monitoring of asthmatic patients, data on the Pediatric population are limited. In the present report, the Pediatric Asthma Committee of the World Allergy Organization (WAO), aims to summarize and discuss available data for the implementation of non-invasive biomarkers in the diagnosis and monitoring in children with asthma. Information on the most studied biomarkers, including spirometry, oscillometry, markers of allergic sensitization, fractional exhaled nitric oxide, and the most recent exhaled breath markers and "omic" approaches, will be reviewed. Practical limitations and considerations based on both experts' opinion and critical review of the literature, on the utility of all "well-known" and newly introduced non-invasive biomarkers will be presented. A critical commentary on biomarkers' use in diagnosing and monitoring asthma during the COVID-19 pandemic, cost and availability of biomarkers in different settings and in developing countries, the differences on the biomarkers use between Primary Practitioners, Pediatricians, and Specialists and their role on the longitudinal aspect of asthma is provided.

WAO consensus on DEfinition of Food Allergy SEverity (DEFASE).

Background: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. Aim: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. Methods Phase 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. Phase 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from "strongly agree" to "strongly disagree". Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as "strongly agree" to "agree" after the second round. Based on feedback, 2 additional online voting rounds were conducted. Results: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. Conclusions: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice.

The role of environmental allergen control in the management of asthma.

Allergen exposure may exacerbate asthma symptoms in sensitized patients. Allergen reduction or avoidance measures have been widely utilized; however, there is ongoing controversy on the effectiveness of specific allergen control measures in the management of children with asthma. Often, allergen avoidance strategies are not recommended by guidelines because they can be complex or burdensome, although individual patients may benefit. Here we explore the potential for intervention against exposure to the major allergens implicated in asthma (ie, house dust mites, indoor molds, rodents, cockroaches, furry pets, and outdoor molds and pollens), and subsequent effects on asthma symptoms. We critically assess the available evidence regarding the clinical benefits of specific environmental control measures for each allergen. Finally, we underscore the need for standardized and multifaceted approaches in research and real-life settings, which would result in the identification of more personalized and beneficial prevention strategies.

Monovalent type 1 oral poliovirus vaccine in newborns.

BACKGROUND: In 1988, the World Health Assembly resolved to eradicate poliomyelitis. Although substantial progress toward this goal has been made, eradication remains elusive. In 2004, the World Health Organization called for the development of a potentially more immunogenic monovalent type 1 oral poliovirus vaccine. METHODS: We conducted a trial in Egypt to compare the immunogenicity of a newly licensed monovalent type 1 oral poliovirus vaccine with that of a trivalent oral poliovirus vaccine. Subjects were randomly assigned to receive one dose of monovalent type 1 oral poliovirus vaccine or trivalent oral poliovirus vaccine at birth. Thirty days after birth, a single challenge dose of monovalent type 1 oral poliovirus vaccine was administered in all subjects. Shedding of serotype 1 poliovirus was assessed through day 60. RESULTS: A total of 530 subjects were enrolled, and 421 fulfilled the study requirements. Thirty days after the study vaccines were administered, the rate of seroconversion to type 1 poliovirus was 55.4% in the monovalent-vaccine group, as compared with 32.1% in the trivalent-vaccine group (P<0.001). Among those with a high reciprocal titer of maternally derived antibodies against type 1 poliovirus (>64), 46.0% of the subjects in the monovalent-vaccine group underwent seroconversion, as compared with 21.3% in the trivalent-vaccine group (P<0.001). Seven days after administration of the challenge dose of monovalent type 1 vaccine, a significantly lower proportion of subjects in the monovalent-vaccine group than in the trivalent-vaccine group excreted type 1 poliovirus (25.9% vs. 41.5%, P=0.001). None of the serious adverse events reported were attributed to the trial interventions. CONCLUSIONS: When given at birth, monovalent type 1 oral poliovirus vaccine is superior to trivalent oral poliovirus vaccine in inducing humoral antibodies against type 1 poliovirus, overcoming high preexisting levels of maternally derived antibodies, and increasing the resistance to excretion of type 1 poliovirus after administration of a challenge dose. (Current Controlled Trials number, ISRCTN76316509.)

Peanut sensitization in a group of allergic Egyptian children.

BACKGROUND: There are no published data on peanut sensitization in Egypt and the problem of peanut allergy seems underestimated. We sought to screen for peanut sensitization in a group of atopic Egyptian children in relation to their phenotypic manifestations. METHODS: We consecutively enrolled 100 allergic children; 2-10 years old (mean 6.5 yr). The study measurements included clinical evaluation for site of allergy, possible precipitating factors, consumption of peanuts (starting age and last consumption), duration of breast feeding, current treatment, and family history of allergy as well as skin prick testing with a commercial peanut extract, and serum peanut specific and total IgE estimation. Children who were found sensitized to peanuts were subjected to an open oral peanut challenge test taking all necessary precautions. RESULTS: Seven subjects (7%) were sensitized and three out of six of them had positive oral challenge denoting allergy to peanuts. The sensitization rates did not vary significantly with gender, age, family history of allergy, breast feeding duration, clinical form of allergy, serum total IgE, or absolute eosinophil count. All peanut sensitive subjects had skin with or without respiratory allergy. CONCLUSIONS: Peanut allergy does not seem to be rare in atopic children in Egypt. Skin prick and specific IgE testing are effective screening tools to determine candidates for peanut oral challenging. Wider scale multicenter population-based studies are needed to assess the prevalence of peanut allergy and its clinical correlates in our country.

Harmonizing allergy care-integrated care pathways and multidisciplinary approaches.

There is a wide time gap between the publication of evidence and the application of new knowledge into routine clinical practice. The consequence is sub-optimal outcomes, particularly concerning for long-term relapsing/remitting conditions such as allergic diseases. In response, there has been a proliferation of published guidelines which systematically review evidence for the gold-standard management of most allergic disorders. However, this has not necessarily been followed by improved outcomes, partly due to a lack of coordination across the patient pathway. This has become known as the "second translational gap". A proposed solution is the development and implementation of integrated care pathways (ICPs) to optimize patient outcomes, with the notion that evidence-based medicine requires evidence-based implementation. ICP implementation is shown to improve short-term outcomes for acute conditions and routine surgery, including reduced length of hospital stay, improved documentation and improved patient safety. However, this improvement is not reflected in patient experience or patient-centered functional outcomes. The implementation of life-long, cost-effective interventions within comprehensive pathways requires a deep appreciation for complexity within allergy care. We promote an evidence-based methodology for the implementation of ICPs for allergic disorders in which all stakeholders in allergy care are positioned equally and encouraged to contribute, particularly patients and their caregivers. This evidence-based process commences with scoping the unmet needs, followed by stakeholder mapping. All stakeholders are invited to meetings to develop a common vision and mission through the generation of action/effect diagrams which helps build concordance across the agencies. Dividing the interventions into achievable steps and reviewing with plan/do/study/act cycles will gradually modify the pathway to achieve the best outcomes. While the management guidelines provide the core knowledge, the key component of implementation involves education, training, and support of all healthcare professionals (HCPs), patients and their caregivers. The pathways should define the level of competence required for each clinical task. It may be useful to leave the setting of care delivery or the specific HCP involved undefined to account for variable patterns of health service delivery as well as local socioeconomic, ethnic, environmental, and political imperatives. In all cases, where competence is exceeded, it is necessary to refer to the next stage in the pathway. The success and sustainability of ICPs would ideally be judged by patient experience, health outcomes, and health economics. We provide examples of successful programs, most notably from Finland, but recommend that further research is required in diverse settings to optimize outcomes worldwide.

Allergy education and training for physicians.

The increasing prevalence of allergic diseases has placed a significant burden on global healthcare and society as whole. This has necessitated a rapid development of "allergy" as a specialist area. However, as allergy is so common and, for most, relatively easy to diagnose and control, all clinicians need to have basic knowledge and competence  to manage  mild disease and recognize when referral is required. The allergology specialty has not yet been recognized in many countries and even where allergy is fully recognized as a specialty, the approach to training in allergy differs significantly. In the light of recent developments in allergy diagnosis and management, there is an urgent need to harmonize core competences for physicians, as well as the standardization of core principles for medical education and post-graduate training in allergy. All physicians and allied health professionals must appreciate the multidisciplinary team (MDT) approach to allergy, which is key to achieving the highest standards in holistic care. Due to worldwide variation in resources and personnel, some MDT roles will need to be absorbed by the treating physician or other healthcare professionals. We draw particular attention to the role of psychological input for all allergy patients, dietetic input in the case of food allergy and patient education to support all patients in the supported self-management of their condition on a daily basis. A strong appreciation of these multidisciplinary aspects will help physicians provide quality patient-centered care. We consider that harmonization of allergy components within undergraduate curricula is crucial to ensure all physicians develop the appropriate allergy-related knowledge and skills, particularly in light of inconsistencies seen in the primary care management of allergy. This review from the World Allergy Organization (WAO) Education and Training Committee also outlines allergy-related competences required of physicians working with allergic patients and provides recommendations to promote harmonization of allergy training and practice worldwide.

Management of asthma in childhood: study protocol of a systematic evidence update by the Paediatric Asthma in Real Life (PeARL) Think Tank.

INTRODUCTION: Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted. METHODS AND ANALYSIS: Standard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence. ETHICS AND DISSEMINATION: Ethics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank. PROSPERO REGISTRATION NUMBERS: CRD42020132990, CRD42020171624.