The multimorbidity of asthma and rhinitis: from epidemiologic data to molecular traits

RESUMO: Introdução e Objetivos: A asma afeta a vida de várias centenas de milhões de pessoas de todas as idades, em todo o mundo. Apesar dos avanços nas últimas décadas, a asma e a sua inerente multimorbilidade permanecem um ónus significativo para as pessoas com a doença, para as suas famílias e para a sociedade e economia da saúde. Um número elevado de questões permanece por responder, abrangendo vários aspetos da doença, relacionados com lacunas no conhecimento científico atual, desde a epidemiologia à fisiopatologia e aos cuidados prestados à pessoa com asma. O objetivo principal desta dissertação foi contribuir para a abordagem de algumas destas questões relativas à asma e a sua associação com a rinite. Em particular, os trabalhos originais visavam: (1) estimar a prevalência de asma em Portugal e analisar a sua associação com a rinite em grupos populacionais particularmente vulneráveis e sobre os quais há carência de dados a nível internacional - crianças e idosos; (2) identificar características para um reconhecimento precoce de asma, através de fenótipos clínicos multidimensionais de sibilância recorrente em idade pré-escolar, estabelecidos “sem hipóteses pré-definidas" e relacionados com a persistência de asma na adolescência; (3) analisar a associação entre parâmetros funcionais respiratórios das vias aéreas superiores e inferiores, em conjunto com a avaliação subjetiva do controlo da rinite alérgica e da asma, em crianças em idade escolar; (4) explorar estratégias inovadoras para identificar características metabólicas associadas ao fenótipo de asma e rinite alérgica em crianças, em amostras colhidas de forma não invasiva. Métodos: Esta dissertação baseou-se em três tipos de estudos: 1. Estudos transversais, baseados na população nacional, de cidadãos que viviam em Portugal, tendo sido aplicados questionários por entrevista, usando procedimentos padronizados, para a obtenção de dados epidemiológicos relativos à asma e à rinite. Para o estudo pediátrico, foram analisados os dados de todos os indivíduos com idade inferior a 18 anos que participaram no estudo INAsma (estudo por entrevista telefónica, de base populacional, nacional, para estimar a prevalência de asma em Portugal). O estudo dirigido aos idosos foi desenhado para estimar a prevalência de rinite em adultos com 65 anos ou mais, residentes em Portugal continental, tendo sido os dados colhidos por entrevista direta; 2. Estudo prospetivo de coorte de crianças com idade inferior a 7 anos com sibilância recorrente, avaliadas sistematicamente em pontos de tempo específicos, até 13 anos de seguimento. Foram desenvolvidos modelos de regressão logística multivariável para persistência de asma na adolescência, com base em respostas a questionários e resultados de testes cutâneos por picada. Os fenótipos clínicos foram identificados por análise de agrupamento das variáveis (cluster), selecionadas com base na análise de regressão logística, e comparados a respeito da persistência de asma, uso de tratamentos de controlo e avaliação funcional respiratória em idade escolar e na adolescência; 3. Estudo transversal, caso-controlo, de crianças em idade escolar, com rinite alérgica e asma, e crianças saudáveis (amostra emparelhada para a idade e género), avaliadas no que diz respeito a: - Análise laboratorial funcional respiratória, i.e., avaliações sequenciais do débito inspiratório máximo nasal (PNIF) antes e após a aplicação de vasoconstritor tópico nasal, e espirometria com prova de broncodilatação. O teste de controlo da rinite alérgica e da asma para crianças (CARATkids) foi utilizado para a avaliação subjetiva do controlo destas doenças. As associações entre os parâmetros de avaliação funcional respiratória e de controlo subjetivo foram analisadas usando modelos de regressão linear múltipla. - Análise laboratorial analítica por espectroscopia de ressonância magnética nuclear (NMR) para análise metabolómica não dirigida das amostras de urina e saliva de cada criança. Os dados espectroscópicos e clínicos foram analisados estatisticamente, incluindo abordagens multivariável e univariável. Adicionalmente foram colhidas amostras de condensado de ar exalado (EBC) de voluntários, em conjunto com amostras de ar ambiente da sala de colheitas. As amostras colhidas foram analisadas por NMR, com comparação dos espectros resultantes.Resultados: A prevalência estimada de asma ativa em crianças foi de 8,4% (intervalo de confiança a 95% (95%CI) 6,6%-10,7%). As prevalências estimadas de rinite e de asma diagnosticada por médico em idosos foram 29,8% (95CI% 28,4%-31,3%) e 10,9% (95%CI 9,9%-11,9%), respetivamente. Foi encontrada uma associação forte entre asma e rinite a nível populacional, tanto nas crianças (odds-ratio (OR) 5,2, 95%CI 3,1-8,9), como nos idosos (OR variando de 8,3 95%CI 6,1-11,4 na rinite intermitente ligeira, a 39,9 95%CI 27,5-58,0 na rinite persistente moderada-grave). No estudo de coorte, a presença de atopia e de rinite em idade pré-escolar foram fatores de risco independentes para a persistência de asma na adolescência (OR 11,8 95%CI 4,0-34,6 e OR 10,4 95%CI 3,7-29,1, respetivamente). Foram identificados três fenótipos de sibilância em idade pré-escolar, que foram preditivos para a persistência de asma, uso de medicamentos de controlo e parâmetros funcionais respiratórios em idade escolar e na adolescência. A multimorbilidade, em particular a presença de rinite, com ou sem atopia, associou-se a um pior prognóstico. Na avaliação funcional nasal e pulmonar, observaram-se correlações entre os valores de PNIF pré e pós-vasoconstritor e do débito expiratório máximo instantâneo (PEF) e volume expiratório forçado no primeiro segundo (FEV1), pré e pós-broncodilatação, observado independentemente da presença de rinite e asma. O melhor modelo de regressão linear múltipla para o PNIF incluiu as variáveis PEF, idade e género. Em crianças com rinite alérgica e asma, não foi encontrada associação entre o PNIF e a pontuação no questionário CARATkids, exceto no que diz respeito à obstrução nasal auto-reportada. A análise metabolómica não dirigida em amostras de saliva e urina mostrou um subconjunto de áreas do espetro de NMR significativamente diferente nas crianças com rinite alérgica e asma, em comparação com crianças saudáveis. Alguns metabolitos que contribuíram para estas áreas do espetro foram identificados: arginina, taurina, citrato e aspartato (na saliva), e quinolinato, butirato, pantotenato, gluconato, pseudouridina e lisina (na urina). Observou-se uma correlação entre parâmetros espirométricos e a concentração urinária dos metabolitos quinolinato, butirato e pantotenato, enquanto a dos metabolitos quinolinato, gluconato e pseudouridina estava correlacionada com os níveis de óxido nítrico no ar exalado (FeNO). Observou-se uma associação entre a presença de sensibilização alergénica múltipla e as concentrações urinárias de quinolinato e salivares de citrato e aspartato. O perfil metabólico do EBC foi semelhante à composição espectral do ar ambiente. Discussão e Conclusões: Estes estudos epidemiológicos foram os primeiros de base populacional nacional que reportaram a prevalência de sintomas de asma em todas as idades pediátricas, bem como de sintomas de rinite, sua classificação e associação com asma em idosos. Os resultados reforçaram a asma como uma doença comum em crianças e em idosos, frequentemente associada a rinite. Em crianças com sibilância recorrente em idade pré-escolar, a presença de multimorbilidade, particularmente rinite com ou sem atopia associada, tende a prever um pior prognóstico no que respeita à persistência de asma e compromisso da função respiratória em idade escolar e na adolescência. Estes resultados apoiam a necessidade de uma abordagem integrada da rinite e da asma, desde idades precoces. Para a avaliação funcional respiratória global, o PNIF pode constituir uma medida objetiva complementar à avaliação subjetiva do controlo da rinite alérgica e da asma, em crianças em idade escolar. Os resultados sugerem que na interpretação dos valores do PNIF nesta faixa etária, os valores do PEF devem idealmente ser considerados, para além da idade e do género. A análise metabolómica exploratória de amostras de urina e saliva revelou subconjuntos de áreas do espectro de NMR associadas à rinite alérgica e asma em crianças, gerando novas hipóteses que necessitam de análises suplementares. Os resultados obtidos na análise do perfil metabólico do EBC reforçaram a importância do controlo do ar ambiente durante a colheita de amostras e a necessidade de procedimentos analíticos que permitam distinguir a presença de compostos exógenos nas amostras de EBC. Em resumo, os resultados apresentados nesta dissertação adicionam evidência para uma avaliação global integrada da asma em conjunto com a rinite, tanto na prática clínica, como na investigação. Prevemos que a avaliação funcional nasal possa ser generalizada na prática clínica, numa abordagem global funcional das vias aéreas. O conjunto de metabolitos identificados na análise exploratória metabolómica estimula a continuação dos estudos nesta área para validação dos resultados, seguida da identificação das moléculas/vias metabólicas responsáveis pelas diferenças encontradas, o seu papel na fisiopatologia da rinite alérgica e asma e, por fim, como potenciais (novos) alvos terapêuticos.ABSTRACT: Introduction and Aims: Worldwide and across all age groups, asthma affects the lives of several hundred million people. In spite of the advances over the last decades, asthma and its multimorbidity continue to impart a significant onus on individuals with the disease, their families and society and also on health economies. A high number of unmet needs remain to be resolved, related to gaps in current scientific knowledge covering many aspects of asthma, from epidemiology and pathophysiology to patient care. The main objective of this dissertation was to contribute to address some of these existing unmet needs in asthma and its link with rhinitis. In particular, the original work aimed to (1) estimate nationwide asthma prevalence and analyze its association with rhinitis in particularly vulnerable and internationally data-lacking population groups – the children and the elderly; (2) unveil features for an early recognition of asthma, identifying multidimensional “hypothesis-free” early childhood wheezing clinical phenotypes related to asthma persistence in adolescence; (3) analyze the association between nasal and lower airway function, together with the subjective evaluation of allergic rhinitis and asthma concurrent control in children; (4) explore innovative strategies to uncover “unbiased” differentiating metabolic features of childhood allergic rhinitis and asthma multimorbidity in non-invasively collected samples. Methods: This dissertation was based on three types of studies: 1. Cross-sectional, population-based, nationwide surveys of citizens living in Portugal, applied by interview using standardized procedures, to collect epidemiological data related to asthma and rhinitis and to analyze the association between these two conditions. For the pediatric study, data from all individuals aged below 18 years who participated in the INAsma study (population-based, all-age, nationwide telephone interview study to estimate asthma prevalence in Portugal) was analyzed. The elderly-targeted study was originally designed to estimate rhinitis prevalence in individuals aged 65 years or above living in mainland Portugal and the data was collected by direct face-to-face interview; 2. Prospective cohort study of children aged below 7 years with recurrent wheezing, systematically evaluated at specific time-points, up to 13 years of follow-up. Multivariable logistic regression models for persistent asthma in adolescence were developed based on questionnaires and skin prick tests data. Clinical phenotypes were identified by cluster analysis of variables selected with the logistic regression analysis, and compared for predicting asthma prevalence, use of control treatments and lung function in childhood and adolescence; 3. Cross-sectional, case-control study of school-aged children with allergic rhinitis and asthma multimorbidity and healthy children (matched for age and gender), evaluated with respect to: a. Respiratory functional laboratorial assessments, i.e., sequential assessments of peak nasal inspiratory flow (PNIF) before and after nasal decongestion and spirometry with bronchodilation test. The Control of Allergic Rhinitis and Asthma Test for children (CARATkids) was used for these diseases concurrent subjective control evaluation. Associations between objective and subjective scores were investigated by multiple linear regression models. b. Analytical laboratorial study using untargeted metabolomics analysis by nuclear magnetic resonance (NMR) spectroscopy of urine and saliva samples collected from each child. Spectroscopic and clinical data were subjected to statistical analysis including multivariable and univariable approaches. Additionally, exhaled breath condensate (EBC) samples were collected from volunteers, together with room air samples, which were analyzed by NMR spectroscopy. The resulting spectra were compared.Results: The estimated prevalence of current asthma in children was 8.4% (95% confidence interval (CI) 6.6%-10.7%). The prevalence of rhinitis and of physician-diagnosed asthma in the elderly were estimated to be 29.8% (95%CI 28.4%-31.3%) and 10.9% (95%CI 9.9%-11.9%), respectively. A strong association between asthma and rhinitis at the population-level was found both in children (odds-ratio (OR) 5.2, 95%CI 3.1-8.9) and in the elderly (OR varying from 8.3, 95%CI 6.1-11.4 in mild intermittent rhinitis to 39.9, 95%CI 27.5-58.0 in moderate-severe persistent rhinitis). In the cohort study, atopy and rhinitis at preschool-age were independent risk factors for asthma persistence in adolescence (OR 11.8, 95%CI 4.0-34.6, and OR 10.4, 95%CI 3.7-29.1, respectively). Three distinct early childhood wheezing phenotypes were identified, which were predictive of asthma persistence, use of control treatments and lung function in school-age and adolescence. Multimorbidity, particularly rhinitis, with or without associated atopy, tended to predict a worse prognosis. In the nasal and lung function study, baseline and decongested PNIF correlated with baseline and post-bronchodilation peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) in school-aged children, observed independently of rhinitis and asthma diagnosis. The best linear regression model for PNIF included the variables PEF, age and gender. In children with allergic rhinitis and asthma, no association was found between PNIF and CARATkids scores, except for nasal obstruction self-report. Untargeted metabolomics analysis of saliva and urine samples revealed a subset of the spectral areas significantly different in the children with allergic rhinitis and asthma, compared to healthy controls. Some metabolites contributing to these variables were identified: arginine, taurine, citrate and aspartate (in saliva), and quinolinate, butyrate, pantothenate, gluconate, pseudouridine and lysine (in urine). Urinary quinolinate, butyrate and pantothenate concentrations correlated with spirometric parameters, while quinolinate, gluconate and pseudouridine concentrations correlated with exhaled nitric oxide (FeNO) levels. Urinary quinolinate and salivary citrate and aspartate were associated with multiple allergenic sensitization. The EBC metabolic profile was found to be highly comparable to the ambient air spectral composition. Discussion and Conclusions: These were the first population-based nationwide epidemiologic studies reporting asthma symptoms prevalence among all pediatric ages, and rhinitis prevalence, its classification and association with asthma in the elderly. Our results further support that asthma is a common disease in children and the elderly, frequently associated with rhinitis. In early childhood, the presence of multimorbidity, particularly rhinitis with or without associated atopy, tended to predict a worse prognosis of recurrent wheezing regarding asthma persistence and impaired lung function in later childhood and adolescence. These results reinforce the need for a global, integrated care pathway in asthma and rhinitis, since early ages. In this integrated assessment, PNIF may provide complementary objective information to subjective concurrent control assessment of allergic rhinitis and asthma in school-aged children. The results suggested that PEF values should ideally be considered, besides age and gender, when interpreting PNIF values in this age group. Exploratory metabolomics revealed differentiating subsets of NMR spectral features in saliva and urine associated with allergic rhinitis and asthma multimorbidity in children, generating hypotheses to be further analyzed. The results obtained in the EBC metabolic profile analysis reinforced the importance of ambient air controls during samples collection and the need for analytical procedures to distinguish exogenously originated metabolites in EBC. In summary, the results presented in this dissertation added compelling information for an integrated, global assessment of asthma together with rhinitis, in clinical practice and in research. We foresee the clinical general application of nasal and lung function evaluation in a global airways assessment strategy. The differentiating subsets of metabolites found in exploratory metabolomics analysis stimulate further studies in order to validate our findings, followed by the identification of molecules/metabolic pathways involved, its role in allergic rhinitis and asthma pathophysiology and ultimately the potential as (novel) therapeutic targets

A Literature Review

Even though respiratory viruses are one of the most common triggers for asthma exacerbations, not all of these viruses affect patients equally. There is no strong evidence supporting that patients with asthma have a higher risk of becoming seriously ill from coronavirus disease 2019 (CO-VID-19), although recent reports from the USA and the UK suggest that asthma is much more common in children and adults with mild to severe COVID-19 than has previously been reported in Asia and in Europe. As in previous severe acute respiratory syndrome (SARS) outbreaks, patients with asthma, especially children, appear to be less susceptible to the coronavirus with a low rate of asthma exacerbations. A different expression of viral receptors and T2 inflammation can be responsible for different outcomes. Future studies focused on asthma and on other allergic disorders are needed to provide a greater understanding of the impact of underlying asthma and allergic inflammation on COVID-19 susceptibility and disease severity. However, for the moment, it is crucial that asthmatic patients maintain their controller medication, from inhaled corticosteroids to biologics, without making any dose adjustments on their own or stopping the medication. New data are emerging daily, rapidly updating our understanding of this novel coronavirus.publishersversionpublishe

Relationship with inflammatory and clinical phenotypes and prognostic implications

Bronchial asthma is a chronic disease that affects individuals of all ages. It has a high prevalence and is associated with high morbidity and considerable levels of mortality. However, asthma is not a single disease, and multiple subtypes or phenotypes (clinical, inflammatory or combinations thereof) can be detected, namely in aggregated clusters. Most studies have characterised asthma phenotypes and clusters of phenotypes using mainly clinical and inflammatory parameters. These studies are important because they may have clinical and prognostic implications and may also help to tailor personalised treatment approaches. In addition, various metabolomics studies have helped to further define the metabolic features of asthma, using electronic noses or targeted and untargeted approaches. Besides discriminating between asthma and a healthy state, metabolomics can detect the metabolic signatures associated with some asthma subtypes, namely eosinophilic and non-eosinophilic phenotypes or the obese asthma phenotype, and this may prove very useful in point-of-care application. Furthermore, metabolomics also discriminates between asthma and other “phenotypes” of chronic obstructive airway diseases, such as chronic obstructive pulmonary disease (COPD) or Asthma–COPD Overlap (ACO). However, there are still various aspects that need to be more thoroughly investigated in the context of asthma phenotypes in adequately designed, homogeneous, multicentre studies, using adequate tools and integrating metabolomics into a multiple-level approach.publishersversionpublishe

Current perspectives

The increasing knowledge of the mechanisms involved in metabolism is shifting the paradigms by which the pathophysiology of many pulmonary diseases is understood. Metabolic dysfunction is recognized in obesity-associated asthma, but other metabolic conditions have been shown to be independently related to asthma. Novel insights have also recently been brought by metabolomics in this filed. The purpose of this review is to discuss current perspectives regarding metabolic dysfunction in asthma, from obesity-related asthma to other metabolic conditions and the role of current pharmacological therapeutic strategies and lifestyle interventions. Obesity is a well-recognized risk factor for asthma across the lifespan, which is generally associated with poorer response to current available treatments, rendering a more severe, refractory disease status. Besides the epidemiological and clinical link, untargeted metabolomics studies have recently supported the obesity-associated asthma phenotype at the molecular level. Not only obesity-related, but also other aspects of metabolic dysregulation can be independently linked to asthma. These include hyperinsulinemia, dyslipidemia and hypertension, which need to be taken into account, even in the non-obese patient. Untargeted metabolomics studies have further highlighted several other metabolic pathways that can be altered in asthma, namely regarding oxidative stress and systemic inflammation, and also suggesting the importance of microbiota in asthma pathogenesis. Considering the reduced response to corticosteroids, other pharmacologic treatments have been shown to be effective regardless of body mass index. Non-pharmacologic treatments (namely weight reduction and dietary changes) may bring substantial benefit to the asthmatic patient. Taken together, this evidence points towards the need to improve our knowledge in this filed and, in particular, to address the influence of environmental factors in metabolic dysfunction and asthma development. Personalized medicine is definitely needed to optimize treatment, including a holistic view of the asthmatic patient in order to set accurate pharmacologic therapy together with dietary, physical exercise and lifestyle interventions.publishersversionpublishe

innovation through design

Background: Asthma affects the lives of hundred million people around the World. Despite notable progresses in disease management, asthma control remains largely insufficient worldwide, influencing patients' wellbeing and quality of life. Poor patient handling of inhaling devices has been identified as a major persistent problem that significantly reduces inhaled drugs' efficacy and is associated with poor adherence to treatment, impairing clinical results such as asthma control and increasing disease-related costs. We herein review key research and development (R&D) innovation in inhaler devices, highlighting major real-world critical errors in the handling and inhalation technique with current devices and considering potential solutions. Furthermore, we discuss current evidence regarding breath-triggered inhalers (BTI). Main body: The two most common significant problems with inhalers are coordinating actuation and inhalation with pressurized metered-dose inhalers (pMDIs), and the need to inhale forcibly with a dry powder inhaler. BTI R&D plans were designed to overcome these problems. Its newest device k-haler® has several other important features, generating a less forceful aerosol plume than previous pMDIs, with efficient drug delivery and lung deposition, even in patients with low inspiratory flow. The local and systemic bioavailability of fluticasone propionate and formoterol (FP/FORM) administered via k-haler® has been shown to be therapeutically equivalent when administered via the previous FP/FORM pMDI. This device requires very few steps and has been considered easy to use (even at first attempt) and preferred by the patients in a randomized crossover study. In our country, FP/FORM k-haler is available without additional costs compared to FP/FORM pMDI. All devices continue to require education and regular checking of the correct inhalation technique. Conclusion: BTI R&D can bring advantage over current available inhalers, avoiding the two most common identified critical errors in inhalation technique. K-haler® BTI is currently available, without an increased cost, and approved for adolescents and adults with asthma in whom treatment with inhaled combined therapy with long-acting beta2-agonists and corticosteroids is indicated. Its attractive and practical design to facilitate its use has been awarded. K-haler® represents added value through innovation to fulfill actual asthma patient needs, thus with potential relevant impact in asthma management and effective control.publishersversionpublishe

Lower airway flow influences peak nasal inspiratory flow in school-aged children*

Background: Rhinitis and asthma frequently coexist. Peak nasal inspiratory flow (PNIF) objectively evaluates nasal obstruction. Lower airway flow’s impact on PNIF has seldom been analysed in children. We aimed to study the associations between PNIF and: (1)forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) in children with allergic rhinitis and asthma and healthy controls; (2)allergic rhinitis and asthma control subjective evaluation. Methods: Sequential assessments of PNIF before and after nasal decongestion and spirometry with bronchodilation test were performed in 65 children (6-12 years) with allergic rhinitis and asthma, and 24 gender, age-matched healthy controls. The Control of Allergic Rhinitis and Asthma Test in children (CARATkids) was used for control assessment. Associations were investigated by multiple linear regression models. Results: Baseline and decongested PNIF correlated with baseline and post-bronchodilation FEV1 and PEF, observed independently of rhinitis and asthma diagnosis. The best model for PNIF included PEF, age and gender. No association was found between PNIF and CARATkids scores, except for nasal obstruction self-report. Conclusion: In school-aged children, besides age and gender, PEF values should ideally be known to interpret PNIF values. PNIF can be complementary to subjective control assessment in children with allergic rhinitis and asthma.publishersversionpublishe

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

IntroductionClinical 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 analysisStandard 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 disseminationEthics 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.</p

For a patient with severe asthma, every day may be his last World Asthma Day

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Asthma and the Coronavirus Disease 2019 Pandemic: A Literature Review

Even though respiratory viruses are one of the most common triggers for asthma exacerbations, not all of these viruses affect patients equally. There is no strong evidence supporting that patients with asthma have a higher risk of becoming seriously ill from coronavirus disease 2019 (CO-VID-19), although recent reports from the USA and the UK suggest that asthma is much more common in children and adults with mild to severe COVID-19 than has previously been reported in Asia and in Europe. As in previous severe acute respiratory syndrome (SARS) outbreaks, patients with asthma, especially children, appear to be less susceptible to the coronavirus with a low rate of asthma exacerbations. A different expression of viral receptors and T2 inflammation can be responsible for different outcomes. Future studies focused on asthma and on other allergic disorders are needed to provide a greater understanding of the impact of underlying asthma and allergic inflammation on COVID-19 susceptibility and disease severity. However, for the moment, it is crucial that asthmatic patients maintain their controller medication, from inhaled corticosteroids to biologics, without making any dose adjustments on their own or stopping the medication. New data are emerging daily, rapidly updating our understanding of this novel coronavirus