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Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: closed (30 December 2020) | Viewed by 38305

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Prof. Dr. Luis Garcia-Marcos

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Guest Editor

Respiratory and Allergy Units, Arrixaca Children’s University Hospital, University of Murcia, 30120 Murcia, Spain
Interests: asthma; epidemiology; lung function; children
Special Issues, Collections and Topics in MDPI journals

Dr. Kostas N. Priftis

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Guest Editor

Paediatric Respiratory and Allergy Department, Paediatric Center of Athens, National and Kapodistrian University of Athens, Athens, Greece
Interests: asthma; allergic diseases; asthma management; lung diseases; spirometry; airway obstruction; pulmonary medicine
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

We are all aware that asthma is a public health issue worldwide as the condition is highly prevalent, frequently undiagnosed, often under- or ill-treated, and kills many people (more than malaria, in fact). Although there are good treatments and a plethora of guidelines and strategies, no dramatic advance has been performed in the past two decades. The affordability of even cheap treatment combinations in low- and middle-income countries is an important limitation for asthma control in those countries. However, even in high-income countries with access to the new monoclonal antibodies, the burden of the disease in terms of DALYs is enormous, especially in children. Furthermore, the costs for patients and/or health systems, both direct and indirect, is not negligible. As a way to overcome the paralysis in the era of personalized medicine, there is a need for a change of paradigm, in which the term ‘asthma’ is not the start and the end of the diagnostic pathway but succeeded by the question of ‘what sort of asthma is this patient suffering of’ in terms of airflow obstruction, airway inflammation, and infection. Under the light of those terms, the present Special Issue aims to put together all that we expect the asthmatic condition to be now and in the decades to come.

Prof. Luis Garcia-Marcos
Prof. Kostas N. Priftis
Guest Editors

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Keywords

Asthma
Definition
Epidemiology
Diagnosis
Treatment
Exacerbation
Phenotypes
Therapy adherence

Related Special Issue

Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments: Part II in Journal of Clinical Medicine (8 articles)

Published Papers (11 papers)

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Editorial

Jump to: Research, Review

3 pages, 198 KiB

Open AccessEditorial

What Is Asthma?

by Luis García-Marcos

J. Clin. Med. 2021, 10(6), 1282; https://doi.org/10.3390/jcm10061282 - 19 Mar 2021

Viewed by 2101

Abstract

Asthma is… [...] Full article

(This article belongs to the Special Issue Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments)

Research

Jump to: Editorial, Review

6 pages, 215 KiB

Open AccessArticle

Asthma-Like Features and Anti-Asthmatic Drug Prescription in Children with Non-CF Bronchiectasis

by Konstantinos Douros, Olympia Sardeli, Spyridon Prountzos, Angeliki Galani, Dafni Moriki, Efthymia Alexopoulou and Kostas N. Priftis

J. Clin. Med. 2020, 9(12), 4009; https://doi.org/10.3390/jcm9124009 - 11 Dec 2020

Cited by 3 | Viewed by 1666

Abstract

Bronchiectasis and asthma may share some characteristics and some patients may have both conditions. The present study aimed to examine the rationale of prophylactic inhaled corticosteroids (ICS) prescription in children with bronchiectasis. Data of children with radiologically established bronchiectasis were retrospectively reviewed. Episodes of dyspnea and wheezing, spirometric indices, total serum IgE, blood eosinophil counts, sensitization to aeroallergens, and air-trapping on expiratory CT scans, were recorded. The study included 65 children 1.5–16 years old, with non-CF bronchiectasis. Episodes of dyspnea or wheezing were reported by 22 (33.8%) and 23 (35.4%), respectively. Skin prick tests to aeroallergens (SPTs) were positive in 15 (23.0%) patients. Mosaic pattern on CT scans was observed in 37 (56.9%) patients. Dyspnea, presence of mosaic pattern, positive reversibility test, and positive SPTs were significantly correlated with the prescription of ICS. The prescription of ICS in children with bronchiectasis is more likely when there are certain asthma-like characteristics. The difficulty to set the diagnosis of real asthma in cases of bronchiectasis may justify the decision of clinicians to start an empirical trial with ICS in certain cases. Full article

(This article belongs to the Special Issue Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments)

17 pages, 1765 KiB

Open AccessCommunication

Global Asthma Network Phase I Surveillance: Geographical Coverage and Response Rates

by Philippa Ellwood, Eamon Ellwood, Charlotte Rutter, Virginia Perez-Fernandez, Eva Morales, Luis García-Marcos, Neil Pearce, M Innes Asher, David Strachan and on behalf of the GAN Phase I Study Group

J. Clin. Med. 2020, 9(11), 3688; https://doi.org/10.3390/jcm9113688 - 17 Nov 2020

Cited by 27 | Viewed by 3868

Abstract

Background—The Global Asthma Network (GAN) Phase I is surveying school pupils in high-income and low- or middle-income countries using the International Study of Asthma and Allergies in Childhood (ISAAC) methodology. Methods—Cross-sectional surveys of participants in two age groups in randomly selected schools within each centre (2015–2020). The compulsory age group is 13–14 years (adolescents), optionally including parents or guardians. Six to seven years (children) and their parents are also optional. Adolescents completed questionnaires at school, and took home adult questionnaires for parent/guardian completion. Children took home questionnaires for parent/guardian completion about the child and also adult questionnaires. Questions related to symptoms and risk factors for asthma and allergy, asthma management, school/work absence and hospitalisation. Results—53 centres in 20 countries completed quality checks by 31 May 2020. These included 21 centres that previously participated in ISAAC. There were 132,748 adolescents (average response rate 88.8%), 91,802 children (average response rate 79.1%), and 177,622 adults, with >97% answering risk factor questions and >98% answering questions on asthma management, school/work absence and hospitalisation. Conclusion—The high response rates achieved in ISAAC have generally been maintained in GAN. GAN Phase I surveys, partially overlapping with ISAAC centres, will allow within-centre analyses of time-trends in prevalence. Full article

(This article belongs to the Special Issue Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments)

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15 pages, 1106 KiB

Open AccessArticle

Longitudinal Asthma Patterns in Italian Adult General Population Samples: Host and Environmental Risk Factors

by Sara Maio, Sandra Baldacci, Marzia Simoni, Anna Angino, Stefania La Grutta, Vito Muggeo, Salvatore Fasola, Giovanni Viegi and on behalf of the AGAVE Pisa Group

J. Clin. Med. 2020, 9(11), 3632; https://doi.org/10.3390/jcm9113632 - 11 Nov 2020

Cited by 3 | Viewed by 1266

Abstract

Background: Asthma patterns are not well established in epidemiological studies. Aim: To assess asthma patterns and risk factors in an adult general population sample. Methods: In total, 452 individuals reporting asthma symptoms/diagnosis in previous surveys participated in the AGAVE survey (2011–2014). Latent transition analysis (LTA) was performed to detect baseline and 12-month follow-up asthma phenotypes and longitudinal patterns. Risk factors associated with longitudinal patterns were assessed through multinomial logistic regression. Results: LTA detected four longitudinal patterns: persistent asthma diagnosis with symptoms, 27.2%; persistent asthma diagnosis without symptoms, 4.6%; persistent asthma symptoms without diagnosis, 44.0%; and ex -asthma, 24.1%. The longitudinal patterns were differently associated with asthma comorbidities. Persistent asthma diagnosis with symptoms showed associations with passive smoke (OR 2.64, 95% CI 1.10–6.33) and traffic exposure (OR 1.86, 95% CI 1.02–3.38), while persistent asthma symptoms (without diagnosis) with passive smoke (OR 3.28, 95% CI 1.41–7.66) and active smoke (OR 6.24, 95% CI 2.68–14.51). Conclusions: LTA identified three cross-sectional phenotypes and their four longitudinal patterns in a real-life setting. The results highlight the necessity of a careful monitoring of exposure to active/passive smoke and vehicular traffic, possible determinants of occurrence of asthma symptoms (with or without diagnosis). Such information could help affected patients and physicians in prevention and management strategies. Full article

(This article belongs to the Special Issue Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments)

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8 pages, 948 KiB

Open AccessArticle

Preschool Asthma Symptoms in Children Born Preterm: The Relevance of Lung Function in Infancy

by Manuel Sanchez-Solis, Maria Soledad Parra-Carrillo, Pedro Mondejar-Lopez, Patricia W Garcia-Marcos and Luis Garcia-Marcos

J. Clin. Med. 2020, 9(10), 3345; https://doi.org/10.3390/jcm9103345 - 18 Oct 2020

Cited by 5 | Viewed by 1459

Abstract

Background: The aim of the study is to assess whether lung function of infants born preterm predicts wheezing in pre-school age. Methods: A survey of the core wheezing questionnaire of the International Study on Asthma and Allergy in Children was administered to parents of preterm newborns, to whom lung function tests were performed at a corrected age of six months, and who, at the time of the survey, were between three and nine years of age. Results: Low values of all lung function parameters measured, except FVC, were predictors of wheezing at some time in life, (FEV0.5 OR: 0.62 (95%CI 0.39; 0.995); FEV0.5/FVC OR: 0.73 (0.54; 0.99)) FEF75 OR: 0.60 [0.37; 0.93]; FEF25-75 OR: 0.57 (0.37; 0.89)); and of wheezing in the past year (FEV0.5 OR: 0.36 (0.17; 0.76); FEV0.5/FVC OR: 0.59 (0.38; 0.93); FEF75 OR: 0.38 [0.19; 0.76]; FEF25-75 OR: 0.35 (0.17; 0.70). In addition, FEV0.5/FVC values lower than the lowest limit of normality, were predictive of hospital admissions due to wheezing (OR: 3.07; (1.02; 9.25)). Conclusions: Limited lung function in infancy is predictive of both future wheezing and hospitalization for a wheezing episode. Full article

(This article belongs to the Special Issue Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments)

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10 pages, 662 KiB

Open AccessArticle

The Role of Airways 17β-Estradiol as a Biomarker of Severity in Postmenopausal Asthma: A Pilot Study

by Giulia Scioscia, Giovanna Elisiana Carpagnano, Donato Lacedonia, Piera Soccio, Carla Maria Irene Quarato, Luigia Trabace, Paolo Fuso and Maria Pia Foschino Barbaro

J. Clin. Med. 2020, 9(7), 2037; https://doi.org/10.3390/jcm9072037 - 29 Jun 2020

Cited by 13 | Viewed by 2241

Abstract

Background: Asthma severity differs according to gender; in adult women, there is higher prevalence and severity of asthma than in men, and it coincides with changes in sex hormones. Recently, a new phonotype of asthma has been identified that appears after menopause, and it may be associated with decreased estrogen levels. Our goal was to study the 17β-estradiol (E2) concentrations in the blood and airways of women affected by asthma onset after menopause, evaluating its possible role in the severity of the disease. Methods: We enrolled 33 consecutive women with a diagnosis of postmenopausal asthma, recruited from the outpatient pulmonary clinic: 18 with severe (SA) and 15 with mild-to-moderate (MMA) asthma. We also included 30 age-matched healthy menopausal women as controls (HS). All subjects enrolled underwent blood and sputum collection (IS), and E2 concentrations were determined in plasma and sputum supernatant samples using an enzyme-linked immunosorbent assay (ELISA) kit. Results: Significantly higher serum concentrations of E2 were found in postmenopausal SA compared to MMA and HS, respectively (33 ± 5.5 vs. 24 ± 6.63 vs. 7.79 ± 1.54 pg/mL, p < 0.05). Similar results were found in the IS: significantly higher levels of E2 were detected in patients with postmenopausal SA compared with MMA and HS, respectively (0.34 ± 0.17 vs. 0.26 ± 0.13 vs. 0.07 ± 0.06 pg/mL, p < 0.05). We found positive correlations between IS E2 concentrations and sputum neutrophil levels in SA group (ρ = 0.52, p < 0.05). Conclusions: Our findings showed the possibility to measure E2 in the airways, and it has increased in postmenopausal asthmatic patients, especially in those with SA. Airways E2 levels may serve as a suitable biomarker of postmenopausal SA to help to phenotype SA patients with neutrophil inflammation. Full article

(This article belongs to the Special Issue Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments)

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Review

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16 pages, 299 KiB

Open AccessReview

Use of Sublingual Immunotherapy for Aeroallergens in Children with Asthma

by Carlo Caffarelli, Carla Mastrorilli, Michela Procaccianti and Angelica Santoro

J. Clin. Med. 2020, 9(10), 3381; https://doi.org/10.3390/jcm9103381 - 21 Oct 2020

Cited by 8 | Viewed by 2605

Abstract

Asthma is a heterogeneous disease that in children is often allergen-driven with a type 2 inflammation. Sublingual immunotherapy represents an important progress in the use of personalized medicine in children with allergic asthma. It is a viable option for house dust mite-driven asthma and in subjects with the asthma associated with allergic rhinitis. The use and indications for isolated asthma caused by other allergens are still controversial owing to heterogeneity of commercially available products and methodological limitations of studies in children. Nevertheless, most studies and meta-analyses found the efficacy of sublingual immunotherapy. Sublingual immunotherapy is safe but cannot be recommended in children with uncontrolled asthma. Full article

(This article belongs to the Special Issue Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments)

16 pages, 618 KiB

Open AccessReview

Diet: A Specific Part of the Western Lifestyle Pack in the Asthma Epidemic

by Carmen Frontela-Saseta, Carlos A. González-Bermúdez and Luis García-Marcos

J. Clin. Med. 2020, 9(7), 2063; https://doi.org/10.3390/jcm9072063 - 01 Jul 2020

Cited by 9 | Viewed by 3030

Abstract

The Western lifestyle is a complex concept that includes the diet as the main axis of different factors which contribute to a detrimental effect on health, lower life expectancy and low quality-of-life. This type of diet is characterized by being high in calories, mainly provided by saturated fats, and rich in sugars that can lead to changes in immune cells and their responsiveness, by different mechanisms that have yet to be totally clarified. Inflammatory processes are perpetuated through different pathways, in which adipose tissue is a major factor. High fat stores in overweight and obesity accumulate energy but the endocrine function is also producing and releasing different bioactive compounds, adipokines, known to be pro-inflammatory and which play an important role in the pathogenesis of asthma. This review therefore explores the latest evidence regarding the adverse effect of the Western diet on adipose tissue inflammation and its causative effect on the asthma epidemic. Full article

(This article belongs to the Special Issue Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments)

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11 pages, 1945 KiB

Open AccessFeature PaperReview

Asthma/Rhinitis (The United Airway) and Allergy: Chicken or Egg; Which Comes First?

by John O. Warner

J. Clin. Med. 2020, 9(5), 1483; https://doi.org/10.3390/jcm9051483 - 14 May 2020

Cited by 7 | Viewed by 3881

Abstract

While allergy, asthma and rhinitis do not inevitably co-exist, there are strong associations. Not all those with asthma are allergic, rhinitis may exist without asthma, and allergy commonly exists in the absence of asthma and/or rhinitis. This is likely due to the separate gene/environment interactions which influence susceptibility to allergic sensitization and allergic airway diseases. Allergic sensitization, particularly to foods, and eczema commonly manifest early in infancy, and not infrequently are followed by the development of allergic rhinitis and ultimately asthma. This has become known as the “allergic march”. However, many infants with eczema never develop asthma or rhinitis, and both the latter conditions can evolve without prior eczema or food allergy. Understanding the mechanisms underlying the ontogeny of allergic sensitization and allergic disease will facilitate rational approaches to the prevention and management of asthma and allergic rhinitis. Furthermore, a range of new, so-called biological, therapeutic approaches, targeting specific allergy-promoting and pro-inflammatory molecules, are now in clinical trials or have been recently approved for use by regulatory authorities and could have a major impact on disease prevention and control in the future. Understanding basic mechanisms will be essential to the employment of such medications. This review will explain the concept of the united airway (rhinitis/asthma) and associations with allergy. It will incorporate understanding of the role of genes and environment in relation to the distinct but interacting origins of allergy and rhinitis/asthma. Understanding the patho-physiological differences and varying therapeutic requirements in patients with asthma, with or without rhinitis, and with or without associated allergy, will aid the planning of a personalized evidence-based management strategy. Full article

(This article belongs to the Special Issue Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments)

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15 pages, 3025 KiB

Open AccessReview

Which Child with Asthma is a Candidate for Biological Therapies?

by Andrew Bush

J. Clin. Med. 2020, 9(4), 1237; https://doi.org/10.3390/jcm9041237 - 24 Apr 2020

Cited by 14 | Viewed by 4212

Abstract

In asthmatic adults, monoclonals directed against Type 2 airway inflammation have led to major improvements in quality of life, reductions in asthma attacks and less need for oral corticosteroids. The paediatric evidence base has lagged behind. All monoclonals currently available for children are anti-eosinophilic, directed against the T helper (TH2) pathway. However, in children and in low and middle income settings, eosinophils may have important beneficial immunological actions. Furthermore, there is evidence that paediatric severe asthma may not be TH2 driven, phenotypes may be less stable than in adults, and adult biomarkers may be less useful. Children being evaluated for biologicals should undergo a protocolised assessment, because most paediatric asthma can be controlled with low dose inhaled corticosteroid if taken properly and regularly. For those with severe therapy resistant asthma, and refractory asthma which cannot be addressed, the two options if they have TH2 inflammation are omalizumab and mepolizumab. There is good evidence of efficacy for omalizumab, particularly in those with multiple asthma attacks, but only paediatric safety, not efficacy, data for mepolizumab. There is an urgent need for efficacy data in children, as well as data on biomarkers to guide therapy, if the right children are to be treated with these powerful new therapies. Full article

(This article belongs to the Special Issue Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments)

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10 pages, 1949 KiB

Open AccessReview

Effective Asthma Management: Is It Time to Let the AIR out of SABA?

by Alan Kaplan, Patrick D. Mitchell, Andrew J. Cave, Remi Gagnon, Vanessa Foran and Anne K. Ellis

J. Clin. Med. 2020, 9(4), 921; https://doi.org/10.3390/jcm9040921 - 27 Mar 2020

Cited by 28 | Viewed by 10729

Abstract

For years, standard asthma treatment has included short acting beta agonists (SABA), including as monotherapy in patients with mild asthma symptoms. In the Global Initiative for Asthma 2019 strategy for the management of asthma, the authors recommended a significant departure from the traditional treatments. Short acting beta agonists (SABAs) are no longer recommended as the preferred reliever for patients when they are symptomatic and should not be used at all as monotherapy because of significant safety concerns and poor outcomes. Instead, the more appropriate course is the use of a combined inhaled corticosteroid–fast acting beta agonist as a reliever. This paper discusses the issues associated with the use of SABA, the reasons that patients over-use SABA, difficulties that can be expected in overcoming SABA over-reliance in patients, and our evolving understanding of the use of “anti-inflammatory relievers” in our patients with asthma. Full article

(This article belongs to the Special Issue Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments)

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