Asthma: Current Perspectives on Phenotypes, Endotypes, and Treatable Traits

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

Deadline for manuscript submissions: closed (31 August 2019) | Viewed by 88790

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Special Issue Editor

Department of Pulmonary Medicine and Intensive Care Unit, Nationaland Kapodistrian University of Athens, 11527 Athens, Greece
Interests: cytokines; asthma; COPD; ICU
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Asthma is a common complex and heterogeneous respiratory disease with an increasing prevalence in developed countries. Asthma is a disease consisting of different phenotypes that are driven by different mechanistic pathways (endotypes). The recognition of these phenotypes and endotypes is central to asthma management entailing prognostic and therapeutic implications. It is acknowledged that despite optimal treatment, many patients are poorly controlled, highlighting the need for phenotype guided treatments. In this context, the emergence of novel therapies (monoclonal antibody therapy, bronchial thermoplasty) pave the way for personalised asthma therapy. A better understanding of disease pathogenesis may enable the identification of biomarkers, mediators, novel therapeutic targets, and treatable traits. Further molecular phenotyping or endotyping of asthma will be necessary to tailor new therapeutic strategies. The present Special Issue on Asthma aims to provide the current knowledge on phenotypes and endotypes in appreciating and managing the heterogeneous condition that is asthma.

Dr. Nikoletta Rovina
Guest Editor

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Keywords

  • Asthma
  • Pathophysiology
  • Biomarkers
  • Mediators
  • Phenotypes
  • Endotypes
  • Biologics
  • Precision medicine

Published Papers (13 papers)

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Research

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13 pages, 1188 KiB  
Article
Longitudinal Relationships between Asthma-Specific Quality of Life and Asthma Control in Children; The Influence of Chronic Rhinitis
by Dillys van Vliet, Brigitte A. Essers, Bjorn Winkens, Jan W. Heynens, Jean W. Muris, Quirijn Jöbsis and Edward Dompeling
J. Clin. Med. 2020, 9(2), 555; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020555 - 18 Feb 2020
Cited by 2 | Viewed by 1909
Abstract
Managing pediatric asthma includes optimizing both asthma control and asthma-specific quality of life (QoL). However, it is unclear to what extent asthma-specific QoL is related to asthma control or other clinical characteristics over time. The aims of this study were to assess in [...] Read more.
Managing pediatric asthma includes optimizing both asthma control and asthma-specific quality of life (QoL). However, it is unclear to what extent asthma-specific QoL is related to asthma control or other clinical characteristics over time. The aims of this study were to assess in children longitudinally: (1) the association between asthma control and asthma-specific QoL and (2) the relationship between clinical characteristics and asthma-specific QoL. In a 12-month prospective study, asthma-specific QoL, asthma control, dynamic lung function indices, fractional exhaled nitric oxide, the occurrence of exacerbations, and the use of rescue medication were assessed every 2 months. Associations between the clinical characteristics and asthma-specific QoL were analyzed using linear mixed models. At baseline, the QoL symptom score was worse in children with asthma and concomitant chronic rhinitis compared to asthmatic children without chronic rhinitis. An improvement of asthma control was longitudinally associated with an increase in asthma-specific QoL (p-value < 0.01). An increased use of β2-agonists, the occurrence of wheezing episodes in the year before the study, the occurrence of an asthma exacerbation in the 2 months prior to a clinical visit, and a deterioration of lung function correlated significantly with a decrease in the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) total score (p-values ≤ 0.01). Chronic rhinitis did not correlate with changes in the PAQLQ score over 1 year. The conclusion was that asthma control and asthma-specific QoL were longitudinally associated, but were not mutually interchangeable. The presence of chronic rhinitis at baseline did influence QoL symptom scores. β2-agonist use and exacerbations before and during the study were inversely related to the asthma-specific QoL over time. Full article
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10 pages, 1092 KiB  
Article
Evolution of Airway Inflammation in Preschoolers with Asthma—Results of a Two-Year Longitudinal Study
by Paraskevi Xepapadaki, Paraskevi Korovessi, Claus Bachert, Susetta Finotto, Tuomas Jartti, John Lakoumentas, Marek L. Kowalski, Anna Lewandowska-Polak, Heikki Lukkarinen, Nan Zhang, Theodor Zimmermann and Nikolaos G. Papadopoulos
J. Clin. Med. 2020, 9(1), 187; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9010187 - 09 Jan 2020
Cited by 10 | Viewed by 3278
Abstract
Fractional exhaled nitric oxide (FeNO) is a non-invasive marker for eosinophilic airway inflammation and has been used for monitoring asthma. Here, we assess the characteristics of FeNO from preschool to school age, in parallel with asthma activity. A total of 167 asthmatic children [...] Read more.
Fractional exhaled nitric oxide (FeNO) is a non-invasive marker for eosinophilic airway inflammation and has been used for monitoring asthma. Here, we assess the characteristics of FeNO from preschool to school age, in parallel with asthma activity. A total of 167 asthmatic children and 66 healthy, age-matched controls were included in the 2-year prospective PreDicta study evaluating wheeze/asthma persistence in preschool-aged children. Information on asthma/rhinitis activity, infections and atopy was recorded at baseline. Follow-up visits were performed at 6-month intervals, as well as upon exacerbation/cold and 4–6 weeks later in the asthmatic group. We obtained 539 FeNO measurements from asthmatics and 42 from controls. At baseline, FeNO values did not differ between the two groups (median: 3.0 ppb vs. 2.0 ppb, respectively). FeNO values at 6, 12, 18 and 24 months (4.0, CI: 0.0–8.6; 6.0, CI: 2.8–12.0; 8.0, CI: 4.0–14.0; 8.5, CI: 4.4–14.5 ppb, respectively) increased with age (correlation p ≤ 0.001) and atopy (p = 0.03). FeNO was non-significantly increased from baseline to the symptomatic visit, while it decreased after convalescence (p = 0.007). Markers of disease activity, such as wheezing episodes and days with asthma were associated with increased FeNO values during the study (p < 0.05 for all). Age, atopy and disease activity were found to be important FeNO determinants in preschool children. Longitudinal and individualized FeNO assessment may be valuable in monitoring asthmatic children with recurrent wheezing or mild asthma. Full article
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13 pages, 1279 KiB  
Article
Mitochondrial Function in Peripheral Blood Mononuclear Cells (PBMC) Is Enhanced, Together with Increased Reactive Oxygen Species, in Severe Asthmatic Patients in Exacerbation
by Carole Ederlé, Anne-Laure Charles, Naji Khayath, Anh Poirot, Alain Meyer, Raphaël Clere-Jehl, Emmanuel Andres, Frédéric De Blay and Bernard Geny
J. Clin. Med. 2019, 8(10), 1613; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8101613 - 03 Oct 2019
Cited by 15 | Viewed by 3440
Abstract
Asthma is a chronic inflammatory lung syndrome with an increasing prevalence and a rare but significant risk of death. Its pathophysiology is complex, and therefore we investigated at the systemic level a potential implication of oxidative stress and of peripheral blood mononuclear cells’ [...] Read more.
Asthma is a chronic inflammatory lung syndrome with an increasing prevalence and a rare but significant risk of death. Its pathophysiology is complex, and therefore we investigated at the systemic level a potential implication of oxidative stress and of peripheral blood mononuclear cells’ (PBMC) mitochondrial function. Twenty severe asthmatic patients with severe exacerbation (GINA 4–5) and 20 healthy volunteers participated at the study. Mitochondrial respiratory chain complexes activities using different substrates and reactive oxygen species (ROS) production were determined in both groups by high-resolution respirometry and electronic paramagnetic resonance, respectively. Healthy PBMC were also incubated with a pool of plasma of severe asthmatics or healthy controls. Mitochondrial respiratory chain complexes activity (+52.45%, p = 0.015 for VADP) and ROS production (+34.3%, p = 0.02) were increased in asthmatic patients. Increased ROS did not originate mainly from mitochondria. Plasma of severe asthmatics significantly increased healthy PBMC mitochondrial dioxygen consumption (+56.8%, p = 0.031). In conclusion, such asthma endotype, characterized by increased PMBCs mitochondrial oxidative capacity and ROS production likely related to a plasma constituent, may reflect activation of the immune system. Further studies are needed to determine whether increased PBMC mitochondrial respiration might have protective effects, opening thus new therapeutic approaches. Full article
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13 pages, 1904 KiB  
Article
Virus-Induced Asthma/Wheeze in Preschool Children: Longitudinal Assessment of Airflow Limitation Using Impulse Oscillometry
by George N Konstantinou, Nikolaos G Papadopoulos, Emmanouel Manousakis and Paraskevi Xepapadaki
J. Clin. Med. 2019, 8(9), 1475; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8091475 - 16 Sep 2019
Cited by 9 | Viewed by 3313
Abstract
Several researchers have assessed the utility of Impulse Oscillometry System (IOS) in diagnosing and evaluating the severity of respiratory diseases in childhood, but none has investigated the impact of the fluctuations of IOS parameters in an individualized manner. In this two-year prospective study, [...] Read more.
Several researchers have assessed the utility of Impulse Oscillometry System (IOS) in diagnosing and evaluating the severity of respiratory diseases in childhood, but none has investigated the impact of the fluctuations of IOS parameters in an individualized manner. In this two-year prospective study, we aimed to longitudinally evaluate changes in airflow limitation and bronchodilator responsiveness in steroid-naïve four- to six-year-old children during a virus-induced wheezing episode, with IOS pulmonary resistance parameters set at 5 (R5) and 20 (R20) Hz. Moreover, feasibility and reproducibility, in addition to the diagnostic properties of these parameters were examined. Lung function was assessed every six weeks (baseline), within the first 48 h following an acute wheezing episode (Day 0), after 10, and after 30 days. Forty-three out of 93 recruited children (4.5 ± 0.4 years old) experienced a wheezing episode during the study period. All children were able to perform the IOS effort in an acceptable and highly reproducible manner. R5 and R20 fluctuated independently of atopy, age, height, and weight. On Day 0, R5 values were significantly lower than the respective baseline values and returned to individual baseline levels within 10 days. Post-bronchodilation R5 values were similar to the baseline ones, reflecting a reversible airway obstruction on Day 0. Response to bronchodilation (ΔR5) was significantly more pronounced on Day 0. ΔR5 values lower than −20.5% had a sensitivity of 70% and a specificity of 76% and could accurately identify up to 75% of the examined preschoolers. This study provides evidence in favor of the objective utility of IOS as an easy, highly reproducible, and sensitive technique to assess clinically significant fluctuations and bronchodilation responses suggestive of airflow limitation. Reference values although necessary are suboptimal, utilizing the personal best values as personal reference is useful and reliable. Full article
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16 pages, 5593 KiB  
Article
Increased Ratio of Matrix Metalloproteinase-9 (MMP-9)/Tissue Inhibitor Metalloproteinase-1 from Alveolar Macrophages in Chronic Asthma with a Fast Decline in FEV1 at 5-Year Follow-up
by Fu-Tsai Chung, Hung-Yu Huang, Chun-Yu Lo, Yu-Chen Huang, Chang-Wei Lin, Chih-Chen He, Jung-Ru He, Te-Fang Sheng and Chun-Hua Wang
J. Clin. Med. 2019, 8(9), 1451; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8091451 - 12 Sep 2019
Cited by 20 | Viewed by 3506
Abstract
Chronic asthma is associated with progressive airway remodeling, which may contribute to declining lung function. An increase in matrix metalloproteinases-9 (MMP-9)/tissue inhibitor metalloproteinase-1 (TIMP-1) may indicate airway inflammation and bronchial injury. Bronchial biopsy specimens and alveolar macrophages (AMs) were obtained from patients with [...] Read more.
Chronic asthma is associated with progressive airway remodeling, which may contribute to declining lung function. An increase in matrix metalloproteinases-9 (MMP-9)/tissue inhibitor metalloproteinase-1 (TIMP-1) may indicate airway inflammation and bronchial injury. Bronchial biopsy specimens and alveolar macrophages (AMs) were obtained from patients with asthma under regular treatment with inhaled corticosteroids or combination therapy and normal subjects (n = 10). Asthmatics included those with a slow forced expiratory volume in one second (FEV1) decline (<30 mL/year, n = 13) and those with a fast FEV1 decline (≥30 mL/year, n = 8) in 5-year follow-up. Immunostaining expression of MMP-9 and TIMP-1 was detected in airway tissues. MMP-9 and TIMP-1 was measured from AMs cultured for 24 h. After the 5-year treatment, the methacholine airway hyperresponsiveness of the slow FEV1 decline group was decreased, but that of the fast FEV1 decline group was increased (PC20, provocative concentration causing a 20% decrease in FEV1, 3.12 ± 1.10 to 1.14 ± 0.34 mg/dL, p < 0.05). AMs of asthma with a fast FEV1 decline released a higher level of MMP-9 (8.52 ± 3.53 pg/mL, p < 0.05) than those of a slow FEV1 decline (0.99 ± 0.20 pg/mL). The MMP-9/TIMP ratio in the fast FEV1 decline group (0.089 ± 0.032) was higher than that of the slow FEV1 decline group (0.007 ± 0.001, p < 0.01). The annual FEV1 decline in 5 years was proportional to the level of MMP-9 (r = 57, p < 0.01) and MMP-9/TIMP-1 ratio (r = 0.58, p < 0.01). The airways of asthma with greater yearly decline in FEV1 showed an increased thickness of submucosa and strong expression of MMP-9. An increase in MMP-9 and MMP-9/TIMP-1 in airways or AMs could be indicators of chronic airway inflammation and contribute to a greater decline in lung function of patients with chronic asthma. Full article
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23 pages, 3495 KiB  
Article
The Enhanced Adhesion of Eosinophils Is Associated with Their Prolonged Viability and Pro-Proliferative Effect in Asthma
by Andrius Januskevicius, Ieva Janulaityte, Virginija Kalinauskaite-Zukauske, Reinoud Gosens and Kestutis Malakauskas
J. Clin. Med. 2019, 8(9), 1274; https://doi.org/10.3390/jcm8091274 - 22 Aug 2019
Cited by 8 | Viewed by 3683
Abstract
Before eosinophils migrate into the bronchial lumen, they promote airway structural changes after contact with pulmonary cells and extracellular matrix components. We aimed to investigate the impact of eosinophil adhesion to their viability and pro-proliferative effect on airway smooth muscle (ASM) cells and [...] Read more.
Before eosinophils migrate into the bronchial lumen, they promote airway structural changes after contact with pulmonary cells and extracellular matrix components. We aimed to investigate the impact of eosinophil adhesion to their viability and pro-proliferative effect on airway smooth muscle (ASM) cells and pulmonary fibroblasts during different asthma phenotypes. A total of 39 individuals were included: 14 steroid-free non-severe allergic asthma (AA) patients, 10 severe non-allergic eosinophilic asthma (SNEA) patients, and 15 healthy control subjects (HS). For AA patients and HS groups, a bronchial allergen challenge with Dermatophagoides pteronysinnus was performed. Individual combined cells cultures were prepared between isolated peripheral blood eosinophils and ASM cells or pulmonary fibroblasts. Eosinophil adhesion was measured by evaluating their peroxidase activity, cell viability was performed by annexin V and propidium iodide staining, and proliferation by Alamar blue assay. We found that increased adhesion of eosinophils was associated with prolonged viability (p < 0.05) and an enhanced pro-proliferative effect on ASM cells and pulmonary fibroblasts in asthma (p < 0.05). However, eosinophils from SNEA patients demonstrated higher viability and inhibition of pulmonary structural cell apoptosis, compared to the AA group (p < 0.05), while their adhesive and pro-proliferative properties were similar. Finally, in the AA group, in vivo allergen-activated eosinophils demonstrated a higher adhesion, viability, and pro-proliferative effect on pulmonary structural cells compared to non-activated eosinophils (p < 0.05). Full article
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Review

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32 pages, 2104 KiB  
Review
Lung Microbiome in Asthma: Current Perspectives
by Konstantinos Loverdos, Georgios Bellos, Louiza Kokolatou, Ioannis Vasileiadis, Evangelos Giamarellos, Matteo Pecchiari, Nikolaos Koulouris, Antonia Koutsoukou and Nikoletta Rovina
J. Clin. Med. 2019, 8(11), 1967; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8111967 - 14 Nov 2019
Cited by 44 | Viewed by 6981
Abstract
A growing body of evidence implicates the human microbiome as a potentially influential player actively engaged in shaping the pathogenetic processes underlying the endotypes and phenotypes of chronic respiratory diseases, particularly of the airways. In this article, we specifically review current evidence on [...] Read more.
A growing body of evidence implicates the human microbiome as a potentially influential player actively engaged in shaping the pathogenetic processes underlying the endotypes and phenotypes of chronic respiratory diseases, particularly of the airways. In this article, we specifically review current evidence on the characteristics of lung microbiome, and specifically the bacteriome, the modes of interaction between lung microbiota and host immune system, the role of the “lung–gut axis”, and the functional effects thereof on asthma pathogenesis. We also attempt to explore the possibilities of therapeutic manipulation of the microbiome, aiming at the establishment of asthma prevention strategies and the optimization of asthma treatment. Full article
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27 pages, 1148 KiB  
Review
Targeting NLRP3 Inflammasome Activation in Severe Asthma
by Efthymia Theofani, Maria Semitekolou, Ioannis Morianos, Konstantinos Samitas and Georgina Xanthou
J. Clin. Med. 2019, 8(10), 1615; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8101615 - 04 Oct 2019
Cited by 67 | Viewed by 8744
Abstract
Severe asthma (SA) is a chronic lung disease characterized by recurring symptoms of reversible airflow obstruction, airway hyper-responsiveness (AHR), and inflammation that is resistant to currently employed treatments. The nucleotide-binding oligomerization domain-like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome is an intracellular [...] Read more.
Severe asthma (SA) is a chronic lung disease characterized by recurring symptoms of reversible airflow obstruction, airway hyper-responsiveness (AHR), and inflammation that is resistant to currently employed treatments. The nucleotide-binding oligomerization domain-like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome is an intracellular sensor that detects microbial motifs and endogenous danger signals and represents a key component of innate immune responses in the airways. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent release of the pro-inflammatory cytokines IL-1β and IL-18 as well as pyroptosis. Accumulating evidence proposes that NLRP3 activation is critically involved in asthma pathogenesis. In fact, although NLRP3 facilitates the clearance of pathogens in the airways, persistent NLRP3 activation by inhaled irritants and/or innocuous environmental allergens can lead to overt pulmonary inflammation and exacerbation of asthma manifestations. Notably, administration of NLRP3 inhibitors in asthma models restrains AHR and pulmonary inflammation. Here, we provide an overview of the pathophysiology of SA, present molecular mechanisms underlying aberrant inflammatory responses in the airways, summarize recent studies pertinent to the biology and functions of NLRP3, and discuss the role of NLRP3 in the pathogenesis of asthma. Finally, we contemplate the potential of targeting NLRP3 as a novel therapeutic approach for the management of SA. Full article
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24 pages, 646 KiB  
Review
The Co-Existence of Obstructive Sleep Apnea and Bronchial Asthma: Revelation of a New Asthma Phenotype?
by Angeliki Damianaki, Emmanouil Vagiakis, Ioanna Sigala, Athanasia Pataka, Nikoletta Rovina, Athina Vlachou, Vasiliki Krietsepi, Spyros Zakynthinos and Paraskevi Katsaounou
J. Clin. Med. 2019, 8(9), 1476; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8091476 - 16 Sep 2019
Cited by 20 | Viewed by 5214
Abstract
Bronchial asthma (BA) and obstructive sleep apnea (OSA) are common respiratory obstructive diseases that may coexist. It would be interesting to study the possible influence of that coexistence on both diseases. Until now, reviews focused mainly on epidemiology. The aim of this study [...] Read more.
Bronchial asthma (BA) and obstructive sleep apnea (OSA) are common respiratory obstructive diseases that may coexist. It would be interesting to study the possible influence of that coexistence on both diseases. Until now, reviews focused mainly on epidemiology. The aim of this study was to review the literature in relation to epidemiology, pathophysiology, consequences, screening of patients, and treatment of the coexistence of OSA and BA. We pooled studies from the PubMed database from 1986 to 2019. OSA prevalence in asthmatics was found to be high, ranging from19% to 60% in non-severe BA, reaching up to 95% in severe asthma. Prevalence was correlated with the duration and severity of BA, and increased dosage of steroids taken orally or by inhalation. This high prevalence of the coexistence of OSA and BA diseases could not be a result of just chance. It seems that this coexistence is based on the pathophysiology of the diseases. In most studies, OSA seems to deteriorate asthma outcomes, and mainly exacerbates them. CPAP (continuous positive airway pressure) treatment is likely to improve symptoms, the control of the disease, and the quality of life in asthmatics with OSA. However, almost all studies are observational, involving a small number of patients with a short period of follow up. Although treatment guidelines cannot be released, we could recommend periodic screening of asthmatics for OSA for the optimal treatment of both the diseases. Full article
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24 pages, 333 KiB  
Review
Severe Eosinophilic Asthma
by Agamemnon Bakakos, Stelios Loukides and Petros Bakakos
J. Clin. Med. 2019, 8(9), 1375; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8091375 - 02 Sep 2019
Cited by 75 | Viewed by 7496
Abstract
Asthma is a heterogeneous disease with varying severity. Severe asthma is a subject of constant research because it greatly affects patients’ quality of life, and patients with severe asthma experience symptoms, exacerbations, and medication side effects. Eosinophils, although at first considered insignificant, were [...] Read more.
Asthma is a heterogeneous disease with varying severity. Severe asthma is a subject of constant research because it greatly affects patients’ quality of life, and patients with severe asthma experience symptoms, exacerbations, and medication side effects. Eosinophils, although at first considered insignificant, were later specifically associated with features of the ongoing inflammatory process in asthma, particularly in the severe case. In this review, we discuss new insights into the pathogenesis of severe asthma related to eosinophilic inflammation and the pivotal role of cytokines in a spectrum that is usually referred to as “T2-high inflammation” that accounts for almost half of patients with severe asthma. Recent literature is summarized as to the role of eosinophils in asthmatic inflammation, airway remodeling, and airway hypersensitivity. Major advances in the management of severe asthma occurred the past few years due to the new targeted biological therapies. Novel biologics that are already widely used in severe eosinophilic asthma are discussed, focusing on the choice of the right treatment for the right patient. These monoclonal antibodies primarily led to a significant reduction of asthma exacerbations, as well as improvement of lung function and patient quality of life. Full article
44 pages, 3923 KiB  
Review
Acute Severe Asthma in Adolescent and Adult Patients: Current Perspectives on Assessment and Management
by Eirini Kostakou, Evangelos Kaniaris, Effrosyni Filiou, Ioannis Vasileiadis, Paraskevi Katsaounou, Eleni Tzortzaki, Nikolaos Koulouris, Antonia Koutsoukou and Nikoletta Rovina
J. Clin. Med. 2019, 8(9), 1283; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8091283 - 22 Aug 2019
Cited by 31 | Viewed by 20761
Abstract
Asthma is a chronic airway inflammatory disease that is associated with variable expiratory flow, variable respiratory symptoms, and exacerbations which sometimes require hospitalization or may be fatal. It is not only patients with severe and poorly controlled asthma that are at risk for [...] Read more.
Asthma is a chronic airway inflammatory disease that is associated with variable expiratory flow, variable respiratory symptoms, and exacerbations which sometimes require hospitalization or may be fatal. It is not only patients with severe and poorly controlled asthma that are at risk for an acute severe exacerbation, but this has also been observed in patients with otherwise mild or moderate asthma. This review discusses current aspects on the pathogenesis and pathophysiology of acute severe asthma exacerbations and provides the current perspectives on the management of acute severe asthma attacks in the emergency department and the intensive care unit. Full article
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12 pages, 1279 KiB  
Review
Early Airway Pathological Changes in Children: New Insights into the Natural History of Wheezing
by Matteo Bonato, Mariaenrica Tiné, Erica Bazzan, Davide Biondini, Marina Saetta and Simonetta Baraldo
J. Clin. Med. 2019, 8(8), 1180; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8081180 - 07 Aug 2019
Cited by 12 | Viewed by 3613
Abstract
Asthma is a heterogeneous condition characterized by reversible airflow limitation, with different phenotypes and clinical expressions. Although it is known that asthma is influenced by age, gender, genetic background, and environmental exposure, the natural history of the disease is still incompletely understood. Our [...] Read more.
Asthma is a heterogeneous condition characterized by reversible airflow limitation, with different phenotypes and clinical expressions. Although it is known that asthma is influenced by age, gender, genetic background, and environmental exposure, the natural history of the disease is still incompletely understood. Our current knowledge of the factors determining the evolution from wheezing in early childhood to persistent asthma later in life originates mainly from epidemiological studies. The underlying pathophysiological mechanisms are still poorly understood. The aim of this review is to converge epidemiological and pathological evidence early in the natural history of asthma to gain insight into the mechanisms of disease and their clinical expression. Full article
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11 pages, 486 KiB  
Review
Acid-Base Disturbances in Patients with Asthma: A Literature Review and Comments on Their Pathophysiology
by Ioannis Vasileiadis, Emmanouil Alevrakis, Sevasti Ampelioti, Dimitrios Vagionas, Nikoletta Rovina and Antonia Koutsoukou
J. Clin. Med. 2019, 8(4), 563; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8040563 - 25 Apr 2019
Cited by 17 | Viewed by 15941
Abstract
Asthma is a common illness throughout the world that affects the respiratory system function, i.e., a system whose operational adequacy determines the respiratory gases exchange. It is therefore expected that acute severe asthma will be associated with respiratory acid-base disorders. In addition, the [...] Read more.
Asthma is a common illness throughout the world that affects the respiratory system function, i.e., a system whose operational adequacy determines the respiratory gases exchange. It is therefore expected that acute severe asthma will be associated with respiratory acid-base disorders. In addition, the resulting hypoxemia along with the circulatory compromise due to heart–lung interactions can reduce tissue oxygenation, with a particular impact on respiratory muscles that have increased energy needs due to the increased workload. Thus, anaerobic metabolism may ensue, leading to lactic acidosis. Additionally, chronic hypocapnia in asthma can cause a compensatory drop in plasma bicarbonate concentration, resulting in non-anion gap acidosis. Indeed, studies have shown that in acute severe asthma, metabolic acid-base disorders may occur, i.e., high anion gap or non-anion gap metabolic acidosis. This review briefly presents studies that have investigated acid-base disorders in asthma, with comments on their underlying pathophysiology. Full article
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