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Total numbers of inflammatory cells ( panel A), eosinophils (panel B), and neutrophils ( panel C) in induced sputum of normal and asthmatic subjects. Symbols: normal ( open circles), mild asthma receiving occasional inhaled 2-agonist treatment (open triangles), moderate asthma requiring medium dose of inhaled corticosteroids to maintain control (closed diamonds), severe asthma despite high dose corticosteroid treatment (closed circles). Horizontal lines represent median values. *p 0.05; **p 0.01, ***p 0.001.
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Airway inflammation in severe asthma is not well characterized but may involve neutrophils. We have compared induced sputum profiles in patients with asthma of varying severity and normal control subjects. We have also measured exhaled nitric oxide (NO) as a noninvasive marker of inflammation. Asthma severity was based on clinical features before t...
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Context 1
... were no significant differences between the groups in terms of sputum volume and squamous epithelial cell and lym- phocyte numbers. Compared with normal subjects (Table 2), subjects with severe asthma had increases in total inflamma- tory cell count (p 0.01 ( Figure 1A), total eosinophil number (p 0.01) ( Figure 1B), and total neutrophil number (p 0.001) ( Figure 1C). Total eosinophil numbers were also greater in subjects with mild asthma (p 0.01) than in normal control subjects. Among asthmatic subjects, those with severe disease had more increases in total inflammatory cell count (p 0.05) and total neutrophil number (p 0.01) than did those with mild asthma. Total numbers of macrophages (Ta- ble 2) were not different between asthmatic and normal sub- jects. The proportion of macrophages (Table 2), however, was significantly lower in induced sputum of subjects with severe asthma than in either normal subjects (p .001) or subjects with mild asthma (p ...
Context 2
... were no significant differences between the groups in terms of sputum volume and squamous epithelial cell and lym- phocyte numbers. Compared with normal subjects (Table 2), subjects with severe asthma had increases in total inflamma- tory cell count (p 0.01 ( Figure 1A), total eosinophil number (p 0.01) ( Figure 1B), and total neutrophil number (p 0.001) ( Figure 1C). Total eosinophil numbers were also greater in subjects with mild asthma (p 0.01) than in normal control subjects. Among asthmatic subjects, those with severe disease had more increases in total inflammatory cell count (p 0.05) and total neutrophil number (p 0.01) than did those with mild asthma. Total numbers of macrophages (Ta- ble 2) were not different between asthmatic and normal sub- jects. The proportion of macrophages (Table 2), however, was significantly lower in induced sputum of subjects with severe asthma than in either normal subjects (p .001) or subjects with mild asthma (p ...
Context 3
... were no significant differences between the groups in terms of sputum volume and squamous epithelial cell and lym- phocyte numbers. Compared with normal subjects (Table 2), subjects with severe asthma had increases in total inflamma- tory cell count (p 0.01 ( Figure 1A), total eosinophil number (p 0.01) ( Figure 1B), and total neutrophil number (p 0.001) ( Figure 1C). Total eosinophil numbers were also greater in subjects with mild asthma (p 0.01) than in normal control subjects. Among asthmatic subjects, those with severe disease had more increases in total inflammatory cell count (p 0.05) and total neutrophil number (p 0.01) than did those with mild asthma. Total numbers of macrophages (Ta- ble 2) were not different between asthmatic and normal sub- jects. The proportion of macrophages (Table 2), however, was significantly lower in induced sputum of subjects with severe asthma than in either normal subjects (p .001) or subjects with mild asthma (p ...
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Citations
... To explore whether SCFAs can influence common neutrophilic asthma biomarkers, their main features, such as neutrophil influx into the lungs [22] and TNF-α [23], were replicated in our HDM-induced neutrophilic asthma model (Fig. 1a). In BALF, the HDM-treated group had significantly higher levels of total leukocyte infiltration ( Fig. 1b), neutrophils (Fig. 1c), monocytes and macrophages ( Fig. 1d), eosinophils (Fig. 1e), and lymphocytes ( Fig. 1f) than the control group. ...
... As previously demonstrated, the HDM group exhibited the main markers of cellular inflammation reported in asthmatics with poorly controlled symptoms such as neutrophil influx in BALF [22] and cytokines such as TNF-α [23], IL-17A [25], and IFN-γ [24]. Only one exposure of HDM in sensitization could be responsible for neutrophil infiltration in BALF. ...
Neutrophilic asthma is generally defined by poorly controlled symptoms and high levels of neutrophils in the lungs. Short-chain fatty acids (SCFAs) are proposed as nonpharmacological therapy for allergic asthma, but their impact on the neutrophilic asthma lacks evidence. SCFAs regulate immune cell responses and impact the inflammasome NLRP3, a potential pharmacological target for neutrophilic asthma. Here, we explored the capacity of SCFAs to mitigate murine-induced neutrophilic asthma and the contribution of NLRP3 to this asthma. The objective of this study is to analyze whether SCFAs can attenuate lung inflammation and tissue remodeling in murine neutrophilic asthma and NLRP3 contribution to this endotype. Wild-type (WT) C57BL6 mice orotracheally received 10 μg of HDM (house dust mite) in 80 μL of saline on days 0, 6–10. To explore SCFAs, each HDM group received 200 mM acetate, propionate, or butyrate. To explore NLRP3, Nlrp3 KO mice received the same protocol of HDM. On the 14th day, after euthanasia, bronchoalveolar lavage fluid (BALF) and lungs were collected to evaluate cellularity, inflammatory cytokines, and tissue remodeling. HDM group had increased BALF neutrophil influx, TNF-α, IFN-γ, IL-17A, collagen deposition, and mucus secretion compared to control. SCFAs distinctively attenuate lung inflammation. Only features of tissue remodeling were Nlrp3-dependent such as collagen deposition, mucus secretion, active TGF-β cytokine, and IMs CD206+. SCFAs greatly decreased inflammatory cytokines and tissue remodeling. Only tissue remodeling was dependent on NLRP3. It reveals the potential of SCFAs to act as an additional therapy to mitigate neutrophilic asthma and the NLRP3 contribution to asthma.
... Previous studies have suggested that neutrophil counts are associated with asthma exacerbations (36,37). Moreover, chemokines are related to neutrophilic and eosinophilic inflammation in asthmatic patients (38). ...
Background
Asthma is characterized by airway hyperresponsiveness, reversible airway obstruction, and chronic airway inflammation. It is the most common chronic disease in childhood. However, the diagnosis of childhood asthma remains challenging, and there is an urgent need to develop new diagnostic methods.
Methods
To identify biomarkers of asthma in children, we adopted the Orbitrap-based data-independent acquisition (DIA) mass spectrometry proteomics method to analyze the serum proteomic signatures of children with acute asthma and convalescent children.
Results
We identified 747 proteins in 46 serum samples and 50 differentially expressed proteins (DEPs) that distinguished between asthmatic and healthy children. Next, functional enrichment analysis of the DEPs was conducted, it was indicated that the DEPs were significantly enriched in immune-related and function terms and pathways. Furthermore, we performed statistical analysis and identified MMP14, ABHD12B, PCYOX1, LTBP1, CFHR4, APOA1, IGHG4, ANG and IGFALS proteins as the diagnostic biomarker candidates. Ultimately, a promising asthma diagnostic model for preschool children based on IGFALS was built and evaluated. The area under the curve (AUC) of the IGFALS model was 0.959.
Conclusions
In this study, the DIA proteome strategy was used and the largest number of proteins of asthmatic children serum proteomics was identified. The proteomics results showed that the DEPs play the central role of the inflammation-immune mechanism in asthma pathogenesis, suggesting that these proteins may be used in asthma diagnosis, prognosis, or therapy, and suggested biomarkers for asthma of preschool children. In conclusion, our results provide insight into the pathophysiology of asthma. We believe that the diagnostic model will facilitate clinical decision-making regarding asthma in preschool children.
... However, increasing evidence suggests that neutrophils can predominate in some cases, while some cases can be paucigranulocytic. 18,19 Th2 asthma is more responsive to corticosteroid therapy and other target therapies against Th2 activation molecules like IgE, IL-4, IL-5, etc. However, recent studies have found drugs like tezepelumab to be helpful in both Th2 and non-T2 asthma. ...
... [81][82][83] Higher sputum eosinophil count (>25%) and sputum neutrophil count may be present in the "exacerbationprone" patients because of the inability of the treatment to reduce inflammation in the airways. [84][85][86] Thus, only bronchodilators in the absence of ICSs will cause more harm than benefit. ICS has a key role in controlling eosinophilic inflammation and reducing exacerbations. ...
Bronchial asthma is the most common chronic lung disease in the obstructive airway disease category with the characteristic feature of "reversible" airflow obstruction. Despite an increase in awareness of risk factors, diagnosis, and treatment options available to treat bronchial asthma, more than half of cases received irrational treatment. Inadequate treatment is reasoning more morbidity and mortality of this easily treatable disease. Inhaled short-and long-acting bronchodilators, antimuscarinic agents, and inhaled corticosteroids (ICSs) are the cornerstone of the treatment of asthma and are categorized as "rescue and controller" role in disease management. Bronchodilators without ICSs are not recommended because of more harm than benefit in bronchial asthma. ICSs are the gold standard and the recommended treatment for asthma due to their anti-inflammatory and disease-modifying property labeled as "game changer role." Bronchodilators with ICSs will have added benefit of symptom control, improvement in quality of life, and decrease in exacerbation. Combo of bronchodilators with ICSs will decrease the overall cost of care in asthma by improving disease control and decrease in emergency room visits and hospitalizations in intensive care units due to exacerbations.
... 33 FeNO còn được xem như một "chỉ điểm của hen mất kiểm soát" 37 vì sự gia tăng FeNO và triệu chứng lâm sàng có thể xảy ra trước khi có sự thoái triển về tính đáp ứng của đường hô hấp, eosinophil trong đàm hay chức năng hô hấp trong đợt cấp bệnh hen do ngưng corticoid hít. 38,39 Tuy nhiên, đo lường FeNO tại một thời điểm có giá trị thấp hơn đo lường sự biến đổi của FeNO trong đánh giá hen mất kiểm soát. Jones và cộng sự nhận thấy sự thay đổi của FeNO theo thời gian có giá trị tiên đoán, độ nhạy và độ đặc hiệu trong việc tiên đoán hen mất kiểm soát cao hơn đo một lần duy nhất. ...
... IL-8 is a potent chemoattractant that regulates the activation and migration of neutrophils to the inflammation site through the high-affinity CXC motif chemokine receptor 2 (CXCR2) expressed on the surface of neutrophils. Increased levels of IL-8 in sputum have been reported in patients with neutrophilic asthma, which correlated with sputum neutrophil counts and increased in uncontrolled disease [65][66][67]. Studies have shown that neutrophils are also associated with allergic inflammation. ...
Asthma is a complex condition resulting from the interaction of genes and environment. Obesity is a risk factor to develop asthma and contributes to poor response to asthma therapy and severity. The aim of the study was to evaluate the effect of obesity on the expression levels of genes previously associated with severe asthma. Three groups of subjects were studied: non-obese asthmatics (NOA), obese asthma patients (OA), and non-asthmatic obese subjects (O). Previously reported overexpressed (IL-10, MSR1, PHLDA1, SERPINB2, and CD86) and underexpressed genes (CHI3L1, CPA3, IL-8, and PI3) in severe asthma were analyzed by RT-qPCR in peripheral blood mononuclear cells (PBMCs). In the overexpressed genes, obesity significantly decreased the expression of MSR1 and PHLDA1 and had no effects on CD86, IL-10, and SERPINB2. In underexpressed genes, obesity did not affect PI3, CHI3L1, and IL-8 and significantly reduced CPA3 expression. The results of this study show that obesity should be included among the known factors that can contribute toward modifying the expression of genes associated with asthma and, in particular, severe asthma.
... More than 50% of asthma is resulting from non-eosinophilic inflammation, in which neutrophilic inflammation is predominant [6,7]. Neutrophilic asthma (NA) is closely related to persistent, severe, and fatal asthma phenotypes [4,8]. Whereas the standard pharmacological treatment with corticosteroids represents the best therapeutic option for most asthmatic patients, NA remains poorly controlled by available therapies [2,4,9]. ...
... Compared to patients with mild asthma, more neutrophils were detected in the airways of severe asthmatics [7,8], suggesting that Peer review under responsibility of KeAi Communications Co., Ltd. neutrophils most likely play an important role in the pathophysiology of NA [4]. ...
... As well documented, severe asthma is insensitive to corticosteroids that are generally used for asthma treatment [2,4,9]. Increasing evidence has indicated that neutrophils and neutrophil-derived NETs can directly contribute to the initiation, progression, and exacerbation of severe asthma [2,[4][5][6][7][8]34]. Moreover, neutrophilic inflammation is closely associated with abnormal changes of macrophages, airway epithelial cells, and SMCs in the lungs, which are all responsible for the pathogenesis of asthma [2,3]. ...
Asthma is a serious global public health concern. Airway neutrophilic inflammation is closely related to severe asthma, for which effective and safe therapies remain to be developed. Here we report nanotherapies capable of simultaneously regulating multiple target cells relevant to the pathogenesis of neutrophilic asthma. A nanotherapy LaCD NP based on a cyclic oligosaccharide-derived bioactive material was engineered. LaCD NP effectively accumulated in the injured lungs of asthmatic mice and mainly distributed in neutrophils, macrophages, and airway epithelial cells after intravenous or inhalation delivery, thereby ameliorating asthmatic symptoms and attenuating pulmonary neutrophilic inflammation as well as reducing airway hyperresponsiveness, remodeling, and mucus production. Surface engineering via neutrophil cell membrane further enhanced targeting and therapeutic effects of LaCD NP. Mechanistically, LaCD NP can inhibit the recruitment and activation of neutrophils, especially reducing the neutrophil extracellular traps formation and NLRP3 inflammasome activation in neutrophils. Also, LaCD NP can suppress macrophage-mediated pro-inflammatory responses and prevent airway epithelial cell death and smooth muscle cell proliferation, by mitigating neutrophilic inflammation and its direct effects on relevant cells. Importantly, LaCD NP showed good safety performance. Consequently, LaCD-derived multi-bioactive nanotherapies are promising for effective treatment of neutrophilic asthma and other neutrophil-associated diseases.
... Several studies have demonstrated that NET levels were elevated in patients with severe asthma [23,42,45]. IL-8 is a potent NET inducer and has been found to be elevated in severe asthma [84][85][86]. Abnormally high levels of neutrophils, NE, and IL-8 were observed in patients with neutrophilic asthma [87]. Pham et al. reported that IL-8 induced neutrophil autophagy and NET production in patients with severe asthma [21]. ...
Neutrophils are important effector cells of the innate immune response that fight pathogens by phagocytosis and degranulation. Neutrophil extracellular traps (NETs) are released into the extracellular space to defend against invading pathogens. Although NETs play a defensive role against pathogens, excessive NETs can contribute to the pathogenesis of airway diseases. NETs are known to be directly cytotoxic to the lung epithelium and endothelium, highly involved in acute lung injury, and implicated in disease severity and exacerbation. This review describes the role of NET formation in airway diseases, including chronic rhinosinusitis, and suggests that targeting NETs could be a therapeutic strategy for airway diseases.
... Of further interest, an in vitro study found that FORM was more effective than salmeterol in suppressing neutrophilic activity [34]. Increased levels of neutrophils have been associated with severe asthma and asthma exacerbation [35][36][37]. FORM may thus have additional anti-inflammatory activity which could work synergistically with FP. However, further studies are warranted to fully understand the synergism of FP and FORM in asthma management. ...
Background:
Treatment guidelines for asthma management are derived almost exclusively from the results of controlled clinical trials undertaken in carefully selected patient populations; meaning that their outcomes may not reflect the true performance of treatments when used in general daily medical practice. The aim of this meta-analysis was to combine the results of observational studies investigating the fluticasone propionate/formoterol (FP/FORM) fixed-dose combination in real-world asthma patients.
Methods:
A systemic literature review was completed in March 2019 using the PubMed database. We identified 394 studies. Five studies, which included a total of 4756 patients treated with FP/FORM, were judged eligible and included in the meta-analysis.
Results:
The estimated severe asthma exacerbation rate was 11.47% (95% CI, 5.8 to 18.72%), calculated from the random effect model. A sensitivity analysis excluding 2 studies (one was an outlier, and the exacerbation rate for the studied treatment alone could not be determined in the other) showed a 7.04% rate of severe asthma exacerbations. The estimated relative risk of the incidence of severe asthma exacerbations was 0.323 (95% CI, 0.159 to 0.658). The estimated asthma control rate was 60.6% (95% CI, 55.7% to 65.6%). The odds of achieving asthma control significantly increased by FP/FORM compared with pre-study conditions (estimated odds ratio: 2.214 [95% CI, 1.292 to 3.795]; p < 0.001).
Conclusions:
The findings of this meta-analysis confirm the effectiveness of FP/FORM for the treatment of asthma patients in a real-world setting beyond the limitations of RCTs.
... In more severe cases of steroid-resistance, the cellular environment is characterized by airway inflammation induced by Th1/Th2 cytokine expression and neutrophil, with poorly reversible airflow obstruction [265][266][267]. In adults, elevated neutrophil counts in sputum are related to disease severity [268] and the persistence of symptoms [269]. These reports suggest an important role for neutrophils in asthma and their association with a more steroid-refractory subtype. ...
Reactive oxygen species, including singlet oxygen, play an important role in the onset and progression of disease, as well as in aging. Singlet oxygen can be formed non-enzymatically by chemical, photochemical, and electron transfer reactions, or as a byproduct of endogenous enzymatic reactions in phagocytosis during inflammation. The imbalance of antioxidant enzymes and antioxidant networks with the generation of singlet oxygen increases oxidative stress, resulting in the undesirable oxidation and modification of biomolecules, such as proteins, DNA, and lipids. This review describes the molecular mechanisms of singlet oxygen production in vivo and methods for the evaluation of damage induced by singlet oxygen. The involvement of singlet oxygen in the pathogenesis of skin and eye diseases is also discussed from the biomolecular perspective. We also present our findings on lipid oxidation products derived from singlet oxygen-mediated oxidation in glaucoma, early diabetes patients, and a mouse model of bronchial asthma. Even in these diseases, oxidation products due to singlet oxygen have not been measured clinically. This review discusses their potential as biomarkers for diagnosis. Recent developments in singlet oxygen scavengers such as carotenoids, which can be utilized to prevent the onset and progression of disease, are also described.
