Clinical Advances in Allergy and Asthma: Issues, Strategies, and Future Directions

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

Deadline for manuscript submissions: 25 July 2024 | Viewed by 14405

Special Issue Editor


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Guest Editor
1. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
2. Respiraotry Medicine Unit, ASST-Spedali Civili di Brescia, Brescia, Italy
Interests: asthma; airway remodelling; allergy; biological therapy; pulmonary function test; FeNO; airway hyperactivity; bronchodilation; methacholine; hypersensitivity

Special Issue Information

Dear Colleagues,

Asthma and allergic diseases are major clinical challenges in the modern medical landscape. Their clinical, economic, and social impact puts a strain on any national healthcare system and impairs patients’ quality of life. These are multifactorial pathologies with genetic and ambient triggering factors and unique pathophysiological underlying dynamics. Their different cellular, molecular, and clinical features make these diseases real medical enigmas that clinicians are called upon to decipher. The most common therapeutic strategies are based on inhalatory steroids, β2-agonists, muscarinic antagonists, oral anti-leukotrienes, and chromones. Until a few years ago, thermoplastic was the latest available therapeutic resource. However, the development of innovative and highly effective biological therapies with monoclonal antibodies (i.e., Anti-IgE, Anti-IL4Rα/IL13Rα1, Anti-IL5/IL5Rα) changed the therapeutic scene. However, many issues are still open, such as the long time elapsing between a proper diagnosis and adequate treatment or patients’ need to take numerous medications throughout the day.

The present special edition aims to describe the most up-to-date diagnostic and therapeutic evidence, discussed with a critical and multidisciplinary approach, and outline the most promising and challenging research perspectives for the future.

Dr. Laura Pini
Guest Editor

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Keywords

  • asthma
  • hypersensitivity
  • airway hyperactivity
  • allergic rhinitis
  • nasal polyposis
  • allergy

Published Papers (8 papers)

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Research

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13 pages, 921 KiB  
Article
Trends and Hospital Outcomes in HOSPITAL Admissions for Anaphylaxis in Children with and without Asthma in Spain (2016–2021)
by Javier De Miguel-Díez, Ana Lopez-de-Andres, Francisco J. Caballero-Segura, Rodrigo Jimenez-Garcia, Valentin Hernández-Barrera, David Carabantes-Alarcon, Jose J. Zamorano-Leon, Ricardo Omaña-Palanco and Natividad Cuadrado-Corrales
J. Clin. Med. 2023, 12(19), 6387; https://doi.org/10.3390/jcm12196387 - 06 Oct 2023
Viewed by 635
Abstract
(1) Background: To assess and compare the temporal trends in the incidence, characteristics and hospital outcomes among children with and without asthma who were hospitalized with anaphylaxis in Spain from 2016 to 2021, and identify the variables associated with severe anaphylaxis among children [...] Read more.
(1) Background: To assess and compare the temporal trends in the incidence, characteristics and hospital outcomes among children with and without asthma who were hospitalized with anaphylaxis in Spain from 2016 to 2021, and identify the variables associated with severe anaphylaxis among children with asthma. (2) Methods: An observational, retrospective study was conducted using a population-based database. The study population included pediatric patients with anaphylaxis. This population was stratified based on whether they had asthma. (3) Results: The number of hospital admissions was stable from 2016 to 2019, dropping in 2020 and raising to the highest number in 2021. A total of 60.63% of hospitalizations occurred in boys and the most common anaphylactic reactions were due to food consumption (67.28%), increasing over time. The in-hospital mortality (IHM) remained stable and under 1% in all the years studied. The incidence of anaphylaxis was 2.14 times higher in children with asthma than in those without asthma (IRR 2.14; 95% CI 1.87–2.44). Furthermore, it was 1.79 times higher in boys with asthma than in those without asthma (IRR 1.79; 95% CI 1.06–2.45) and 2.68 times higher in girls with asthma than in those without asthma (IRR 2.68; 95% CI 2.23–3.12). Asthma was not associated with severe anaphylaxis (OR 1.31; 95% CI 0.88–1.96). (4) Conclusions: The number of hospitalizations for anaphylaxis in children remained stable from 2016 to 2019, dropping in 2020 and recovering in 2021. IHM was low and remained stable during the study period. The incidence of hospitalizations for anaphylaxis was higher in asthmatic children than in non-asthmatics, but there were no differences in the occurrence of severe anaphylaxis among them. Full article
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12 pages, 1353 KiB  
Article
Switching to Dupilumab from Other Biologics without a Treatment Interval in Patients with Severe Asthma: A Multi-Center Retrospective Study
by Hisao Higo, Hirohisa Ichikawa, Yukako Arakawa, Yoshihiro Mori, Junko Itano, Akihiko Taniguchi, Satoru Senoo, Goro Kimura, Yasushi Tanimoto, Kohei Miyake, Tomoya Katsuta, Mikio Kataoka, Yoshinobu Maeda, Katsuyuki Kiura, Nobuaki Miyahara and Okayama Respiratory Disease Study Group (ORDSG)
J. Clin. Med. 2023, 12(16), 5174; https://doi.org/10.3390/jcm12165174 - 09 Aug 2023
Cited by 1 | Viewed by 2206
Abstract
Background: Dupilumab is a fully humanized monoclonal antibody that blocks interleukin-4 and interleukin-13 signals. Several large clinical trials have demonstrated the efficacy of dupilumab in patients with severe asthma. However, few studies have examined a switch to dupilumab from other biologics. Methods: This [...] Read more.
Background: Dupilumab is a fully humanized monoclonal antibody that blocks interleukin-4 and interleukin-13 signals. Several large clinical trials have demonstrated the efficacy of dupilumab in patients with severe asthma. However, few studies have examined a switch to dupilumab from other biologics. Methods: This retrospective, multi-center observational study was conducted by the Okayama Respiratory Disease Study Group. Consecutive patients with severe asthma who were switched to dupilumab from other biologics without a treatment interval between May 2019 and September 2021 were enrolled. Patients with a treatment interval of more than twice the standard dosing interval for the previous biologic prior to dupilumab administration were excluded. Results: The median patient age of the 27 patients enrolled in this study was 57 years (IQR, 45–68 years). Eosinophilic chronic rhinosinusitis (ECRS)/chronic rhinosinusitis with nasal polyp (CRSwNP) was confirmed in 23 patients. Previous biologics consisted of omalizumab (n = 3), mepolizumab (n = 3), and benralizumab (n = 21). Dupilumab significantly improved FEV1 (median improvement: +145 mL) and the asthma control test score (median improvement: +2). The overall response rate in patients receiving dupilumab for asthma as determined using the Global Evaluations of Treatment Effectiveness (GETE) was 77.8%. There were no significant differences in the baseline characteristics of the GETE-improved group vs. the non-GETE-improved group. ECRS/CRSwNP improved in 20 of the 23 patients (87.0%). Overall, 8 of the 27 patients (29.6%) developed transient hypereosinophilia (>1500/μL), but all were asymptomatic and able to continue dupilumab therapy. Conclusions: Dupilumab was highly effective for the treatment of severe asthma and ECRS/CRSwNP, even in patients switched from other biologics without a treatment interval. Full article
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20 pages, 1043 KiB  
Article
Etiologies of Acute Bronchiolitis in Children at Risk for Asthma, with Emphasis on the Human Rhinovirus Genotyping Protocol
by Ahmad R. Alsayed, Anas Abed, Mahmoud Abu-Samak, Farhan Alshammari and Bushra Alshammari
J. Clin. Med. 2023, 12(12), 3909; https://doi.org/10.3390/jcm12123909 - 08 Jun 2023
Cited by 5 | Viewed by 1455
Abstract
This research aims to determine acute bronchiolitis’ causative virus(es) and establish a viable protocol to classify the Human Rhinovirus (HRV) species. During 2021–2022, we included children 1–24 months of age with acute bronchiolitis at risk for asthma. The nasopharyngeal samples were taken and [...] Read more.
This research aims to determine acute bronchiolitis’ causative virus(es) and establish a viable protocol to classify the Human Rhinovirus (HRV) species. During 2021–2022, we included children 1–24 months of age with acute bronchiolitis at risk for asthma. The nasopharyngeal samples were taken and subjected to a quantitative polymerase chain reaction (qPCR) in a viral panel. For HRV-positive samples, a high-throughput assay was applied, directing the VP4/VP2 and VP3/VP1 regions to confirm species. BLAST searching, phylogenetic analysis, and sequence divergence took place to identify the degree to which these regions were appropriate for identifying and differentiating HRV. HRV ranked second, following RSV, as the etiology of acute bronchiolitis in children. The conclusion of the investigation of all available data in this study distributed sequences into 7 HRV-A, 1 HRV-B, and 7 HRV-C types based on the VP4/VP2 and VP3/VP1 sequences. The nucleotide divergence between the clinical samples and the corresponding reference strains was lower in the VP4/VP2 region than in the VP3/VP1 region. The results demonstrated the potential utility of the VP4/VP2 region and the VP3/VP1 region for differentiating HRV genotypes. Confirmatory outcomes were yielded, indicating how nested and semi-nested PCR can establish practical ways to facilitate HRV sequencing and genotyping. Full article
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11 pages, 771 KiB  
Article
Prevalence of Overweight and Obesity and Their Impact on Spirometry Parameters in Patients with Asthma: A Multicentre, Retrospective Study
by Abdullah A. Alqarni, Abdulelah M. Aldhahir, Rayan A. Siraj, Jaber S. Alqahtani, Hams H. Alshehri, Amal M. Alshamrani, Ahlam A. Namnqani, Lama N. Alsaidalani, Mohammed N. Tawhari, Omaima I. Badr and Hassan Alwafi
J. Clin. Med. 2023, 12(5), 1843; https://doi.org/10.3390/jcm12051843 - 25 Feb 2023
Cited by 8 | Viewed by 1893
Abstract
Introduction: Obesity is a common comorbidity in patients with asthma and has a significant impact on health and prognoses. However, the extent to which overweight and obesity impact asthma, particularly lung function, remains unclear. This study aimed to report on the prevalence of [...] Read more.
Introduction: Obesity is a common comorbidity in patients with asthma and has a significant impact on health and prognoses. However, the extent to which overweight and obesity impact asthma, particularly lung function, remains unclear. This study aimed to report on the prevalence of overweight and obesity and assess their impacts on spirometry parameters in asthmatic patients. Methods: In this multicentre, retrospective study, we reviewed the demographic data and spirometry results of all adult patients with confirmed diagnoses of asthma who visited the studied hospitals’ pulmonary clinics between January 2016 and October 2022. Results: In total, 684 patients with confirmed diagnoses of asthma were included in the final analysis, of whom 74% were female, with a mean ± SD age of 47 ± 16 years. The prevalence of overweight and obesity among patients with asthma was 31.1% and 46.0%, respectively. There was a significant decline in spirometry results in obese patients with asthma compared with patients with healthy weights. Furthermore, body mass index (BMI) was negatively correlated with forced vital capacity (FVC) (L), forced expiratory volume in one second (FEV1), forced expiratory flow at 25–75% (FEF 25–75%) L/s and peak expiratory flow (PEF) L/s (r = −0.22, p < 0.001; r = −0.17, p < 0.001; r = −0.15, p < 0.001; r = −0.12, p < 0.01, respectively). Following adjustments for confounders, a higher BMI was independently associated with lower FVC (B −0.02 [95% CI −0.028, −0.01, p < 0.001] and lower FEV1 (B −0.01 [95% CI −0.01, −0.001, p < 0.05]. Conclusions: Overweight and obesity are highly prevalent in asthma patients, and more importantly, they can reduce lung function, characterised mainly by reduced FEV1 and FVC. These observations highlight the importance of implementing a nonpharmacological approach (i.e., weight loss) as part of the treatment plan for patients with asthma to improve lung function. Full article
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13 pages, 1321 KiB  
Article
Association between Exposure to Selected Heavy Metals and Blood Eosinophil Counts in Asthmatic Adults: Results from NHANES 2011–2018
by Jun Wen, Mohan Giri, Li Xu and Shuliang Guo
J. Clin. Med. 2023, 12(4), 1543; https://doi.org/10.3390/jcm12041543 - 15 Feb 2023
Cited by 2 | Viewed by 1793
Abstract
(1) Background: Heavy metals are widely used and dispersed in the environment and people’s daily routines. Many studies have reported an association between heavy metal exposure and asthma. Blood eosinophils play a crucial role in the occurrence, progression, and treatment of asthma. However, [...] Read more.
(1) Background: Heavy metals are widely used and dispersed in the environment and people’s daily routines. Many studies have reported an association between heavy metal exposure and asthma. Blood eosinophils play a crucial role in the occurrence, progression, and treatment of asthma. However, there have thus far been few studies that aimed to explore the effects of heavy metal exposure on blood eosinophil counts in adults with asthma. Our study aims to discuss the association between metal exposure and blood eosinophil counts among asthmatic adults. (2) Methods: A total of 2026 asthmatic individuals were involved in our research from NHANES with metal exposure, blood eosinophils, and other covariates among the American population. A regression model, the XGBoost algorithm, and a generalized linear model (GAM) were used to explore the potential correlation. Furthermore, we conducted a stratified analysis to determine high-risk populations. (3) Results: The multivariate regression analysis indicated that concentrations of blood Pb (log per 1 mg/L; coefficient β, 25.39; p = 0.010) were positively associated with blood eosinophil counts. However, the associations between blood cadmium, mercury, selenium, manganese, and blood eosinophil counts were not statistically significant. We used stratified analysis to determine the high-risk group regarding Pb exposure. Pb was identified as the most vital variable influencing blood eosinophils through the XGBoost algorithm. We also used GAM to observe the linear relationship between the blood Pb concentrations and blood eosinophil counts. (4) Conclusions: The study demonstrated that blood Pb was positively correlated with blood eosinophil counts among asthmatic adults. We suggested that long-time Pb exposure as a risk factor might be correlated with the immune system disorder of asthmatic adults and affect the development, exacerbation, and treatment of asthma. Full article
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17 pages, 2138 KiB  
Article
Reduced Skeletal Muscle Mass Is Associated with an Increased Risk of Asthma Control and Exacerbation
by Shuwen Zhang, Xin Zhang, Ke Deng, Changyong Wang, Lisa G. Wood, Huajing Wan, Lei Liu, Ji Wang, Li Zhang, Ying Liu, Gaiping Cheng, Peter G. Gibson, Brian G. Oliver, Fengming Luo, Vanessa M. McDonald, Weimin Li and Gang Wang
J. Clin. Med. 2022, 11(23), 7241; https://doi.org/10.3390/jcm11237241 - 06 Dec 2022
Cited by 2 | Viewed by 1436
Abstract
Background: Skeletal muscle mass (SMM) has been suggested to be associated with multiple health-related outcomes. However, the potential influence of SMM on asthma has not been largely explored. Objective: To study the association between SMM and clinical features of asthma, including asthma control [...] Read more.
Background: Skeletal muscle mass (SMM) has been suggested to be associated with multiple health-related outcomes. However, the potential influence of SMM on asthma has not been largely explored. Objective: To study the association between SMM and clinical features of asthma, including asthma control and exacerbation, and to construct a model based on SMM to predict the risk of asthma exacerbation (AEx). Methods: In this prospective cohort study, we consecutively recruited patients with asthma (n = 334), classified as the SMM Normal group (n = 223), SMM Low group (n = 88), and SMM High group (n = 23). We investigated the association between SMM and clinical asthma characteristics and explored the association between SMM and asthma control and AEx within a 12-month follow-up period. Based on SMM, an exacerbation prediction model was developed, and the overall performance was externally validated in an independent cohort (n = 157). Results: Compared with the SMM Normal group, SMM Low group exhibited more airway obstruction and worse asthma control, while SMM High group had a reduced eosinophil percentage in induced sputum. Furthermore, SMM Low group was at a significantly increased risk of moderate-to-severe exacerbation compared with the SMM Normal group (relative risk adjusted 2.02 [95% confidence interval (CI), 1.35–2.68]; p = 0.002). In addition, a model involving SMM was developed which predicted AEx (area under the curve: 0.750, 95% CI: 0.691–0.810). Conclusions: Low SMM was an independent risk factor for future AEx. Furthermore, a model involving SMM for predicting the risk of AEx in patients with asthma indicated that assessment of SMM has potential clinical implications for asthma management. Full article
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11 pages, 1373 KiB  
Article
Exhaled Breath Analysis for Investigating the Use of Inhaled Corticosteroids and Corticosteroid Responsiveness in Wheezing Preschool Children
by Michiel A. G. E. Bannier, Sophie Kienhorst, Quirijn Jöbsis, Kim D. G. van de Kant, Frederik-Jan van Schooten, Agnieszka Smolinska and Edward Dompeling
J. Clin. Med. 2022, 11(17), 5160; https://doi.org/10.3390/jcm11175160 - 31 Aug 2022
Viewed by 1330
Abstract
Exhaled breath analysis has great potential in diagnosing various respiratory and non-respiratory diseases. In this study, we investigated the influence of inhaled corticosteroids (ICS) on exhaled volatile organic compounds (VOCs) of wheezing preschool children. Furthermore, we assessed whether exhaled VOCs could predict a [...] Read more.
Exhaled breath analysis has great potential in diagnosing various respiratory and non-respiratory diseases. In this study, we investigated the influence of inhaled corticosteroids (ICS) on exhaled volatile organic compounds (VOCs) of wheezing preschool children. Furthermore, we assessed whether exhaled VOCs could predict a clinical steroid response in wheezing preschool children. We performed a crossover 8-week ICS trial, in which 147 children were included. Complete data were available for 89 children, of which 46 children were defined as steroid-responsive. Exhaled VOCs were measured by GC-tof-MS. Statistical analysis by means of Random Forest was used to investigate the effect of ICS on exhaled VOCs. A set of 20 VOCs could best discriminate between measurements before and after ICS treatment, with a sensitivity of 73% and specificity of 67% (area under ROC curve = 0.72). Most discriminative VOCs were branched C11H24, butanal, octanal, acetic acid and methylated pentane. Other VOCs predominantly included alkanes. Regularised multivariate analysis of variance (rMANOVA) was used to determine treatment response, which showed a significant effect between responders and non-responders (p < 0.01). These results show that ICS significantly altered the exhaled breath profiles of wheezing preschool children, irrespective of clinical treatment response. Furthermore, exhaled VOCs were capable of determining corticosteroid responsiveness in wheezing preschool children. Full article
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11 pages, 673 KiB  
Systematic Review
Effects of Prenatal Paracetamol Exposure on the Development of Asthma and Wheezing in Childhood: A Systematic Review and Meta-Analysis
by Agnieszka Barańska, Wiesław Kanadys, Artur Wdowiak, Maria Malm, Agata Błaszczuk, Urszula Religioni, Anita Wdowiak-Filip and Małgorzata Polz-Dacewicz
J. Clin. Med. 2023, 12(5), 1832; https://doi.org/10.3390/jcm12051832 - 24 Feb 2023
Cited by 1 | Viewed by 2731
Abstract
The aim of the report was to evaluate whether in utero exposure to paracetamol is associated with risk towards developing respiratory disorders such as asthma and wheeze after birth. MEDLINE (PubMed), EMBASE and Cochrane Library databases were searched for articles published in English [...] Read more.
The aim of the report was to evaluate whether in utero exposure to paracetamol is associated with risk towards developing respiratory disorders such as asthma and wheeze after birth. MEDLINE (PubMed), EMBASE and Cochrane Library databases were searched for articles published in English to December 2021. The study involved 330,550 women. We then calculated the summary risk estimates and 95% CIs and plotted forest plots using random effect models (DerSimonian–Laird method) and fixed effect models. We also performed a systematic review of the chosen articles and a meta-analysis of studies based on the guidelines outlined in the PRISMA statement. Accordingly, maternal exposure to paracetamol during pregnancy was associated with a significant increased risk of asthma: crude OR = 1.34, 95% CI: 1.22 to 1.48, p < 0.001; and significant increased risk of wheeze: crude OR = 1.31, 95% CI: 1.12 to 1.54, p < 0.002. Results of our study confirmed that maternal paracetamol use in pregnancy is associated with an enhanced risk of asthma and wheezing in their children. We believe paracetamol should be used with caution by pregnant women, and at the lowest effective dose, and for the shortest duration. Long-term use or the use of high doses should be limited to the indications recommended by a physician and with the mother-to-be under constant supervision. Full article
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