Immunopathogenesis of Allergic Asthma: More Than the Th2 Hypothesis

Kim, You-Me; Jeon, Seong Gyu

doi:10.4168/aair.2013.5.4.189

Cited by 56 publications

(53 citation statements)

References 80 publications

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“…Downregulation of gene expression and decreasing the stability of lipid raft formation both result in decreased release of cytokines and chemokines [2]. This proinflammatory cytokines IL-4, IL-5, IL-6, IL-13 and TNF-α, trigger airway inflammation with different pathways [27]. IL-4 effects B cells with the production of IgE which is the important feature of mast cell activation and allergic inflammation, IL-5 increases the eosinophils production and IL-13 has a central role in IgE synthesis [28].…”

Section: Discussionmentioning

confidence: 99%

Influence of rosuvastatin treatment on airway inflammatory markers and health related quality of life domains in asthmatic patients

Yıldızeli¹,

Kocakaya²,

Balcan³

et al. 2017

Marmara Medical Journal

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Influence of rosuvastatin treatment on airway inflammatory markers and health related quality of life domains in asthmatic patientsAstımlı hastalarda rosuvastatin tedavisinin havayolu inflamatuvar belirteçleri ve yaşam kalitesi göstergeleri üzerine etkisi Sonuç: Bu çalışmada, astım hastalarında rosuvastatin 40mg ile 8 haftalık tedavi sonrasında periferik eosinofili, total IgE seviyesi, indükte balgamda inflamatuvar belirteçlerde anlamlı düzeyde azalma saptanmıştır. Yine SFT parametrelerinde düzelme izlenmiştir ancak buna karşın AKT ve QoL skorlarında değişim saptanmamıştır.Bu sonuçlara göre rosuvastatin tedavisinin astım hastaları üzerinde bir takım potensiyel anti-inflamatuar etkileri bulunmaktadır. Rosuvastatinin klinik etkilerinin saptanması için daha fazla sayıda randomize çalışmaya ihtiyaç vardır. Anahtar kelimeler: Astım, Havayolu inflamasyonu, Remodeling, Rosuvastatin, Statin ABSTRACT Objectives: Statins are lipid lowering agents which have pleiotropic and anti-inflammatory effects. Beneficial effects of statins have been shown in many inflammatory and asthmatic diseases. However, the results are still not consistent. The aim of this study is to determine the clinical and anti-inflammatory effects of rosuvastatin in asthmatic patients.Patients and Metods: A case control study among asthmatic patients was conducted. One hundred and thirty-six participants were screened. Seventy-four patients were eligible. Fifty-one patients have completed the trial. Twenty-five patients with blood levels of low-density-lipoprotein (LDL) above 130mg/dL, were treated with rosuvastatin 40mg for 8 weeks in addition to their standard treatment for asthma; 26 asthmatic patients were followed as control group. In both groups baseline and 8 th week evaluation were recorded including pulmonary function test (PFT), bronchial provocation test (PD20), induced sputum and serum inflammatory markers, asthma control test (ACT) and quality of life scores (QoL).Results: Statin group showed improvement in FEV1/FVC (pp) (85.8±11.1% vs 90.2±8.8% P<0.043), FEF 25-75 % (63.6±7.8 % vs 74.6±8.4 %, P<0.0001) and FEF25-75(L/sc) (3.51±0.4 vs 4.1±0.4 P<0.05) and no change was seen in non-statin group (P>0.05) at the end of the 8-week treatment. Treatment with rosuvastatin resulted in decreased sputum eosinophilia percentage (P<0.05); IL-6 and TNFalpha levels (P<0.05) however, bronchial challenge test, ACT and QoL domains did not change in both groups (P>0.05).Conclusion: An 8-week treatment with 40mg rosuvastatin in asthma decreased the peripheral eosinophilia, total IgE levels and inflammatory markers in the induced sputum samples. Beneficial effects in PFT have also been observed. However, ACT and QoL domains were not affected. The implication of this study is that rosuvastatin could potentially have anti-inflammatory effects on asthmatic airways. Prospective randomised trials to evalute the clinical effects of rosuvastatin are warranted.

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Section: Discussionmentioning

confidence: 99%

Influence of rosuvastatin treatment on airway inflammatory markers and health related quality of life domains in asthmatic patients

Yıldızeli¹,

Kocakaya²,

Balcan³

et al. 2017

Marmara Medical Journal

View full text Add to dashboard Cite

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“…Asthma is a complex and heterogeneous disease. Although asthma cannot be linked to a single pathogenic mechanism because of the complexity of the disease, one of its invariable characteristics is sustained allergic airway inflammation (32,33). The inflammation is probably initiated by inappropriate immune responses to certain Ags or irritants in the airway and persists as a result of abnormalities in immune homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment

Hong

Kwon

Moon

et al. 2016

The Journal of Immunology

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Recruitment and activation of dendritic cells (DCs) in the lungs are critical for Th2 responses in asthma, and CCL20 secreted from bronchial epithelial cells (BECs) is known to influence the recruitment of DCs. Because asthma is a disease that is closely associated with oxidative stress, we hypothesized that clusterin, an oxidative stress regulatory molecule, may have a role in the development of allergic airway inflammation. The aim of this study was to examine whether clusterin regulates CCL20 production from the BECs and the subsequent DC recruitment in the lungs. To verify the idea, clusterin knockout (Clu−/−), clusterin heterogeneous (Clu+/−), and wild-type mice were exposed intranasally to house dust mite (HDM) extract to induce allergic airway inflammation. We found that the total number of immune cells in bronchoalveolar lavage fluid and the lung was increased in Clu−/− and Clu+/− mice. Of these immune cells, inflammatory DCs (CD11b+CD11c+) and Ly6Chigh monocyte populations in the lung were significantly increased, which was accompanied by increased levels of various chemokines, including CCL20 in bronchoalveolar lavage fluid, and increased oxidative stress markers in the lung. Moreover, HDM-stimulated human BECs with either up- or downregulated clusterin expression showed that CCL20 secretion was negatively associated with clusterin expression. Interestingly, clusterin also reduced the level of intracellular reactive oxygen species, which is related to induction of CCL20 expression after HDM stimulation. Thus, the antioxidant property of clusterin is suggested to regulate the expression of CCL20 in BECs and the subsequent recruitment of inflammatory DCs in the airway.

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“…This inflammatory heterogeneity seems to correlate with the identification of a distinct cytokine profile [10,11]. These inflammatory profiles are mainly determined by the involvement of different T helper cell subsets, which contribute to the recruitment and activation of neutrophils [12,13]. Th1 and Th17 cells would be crucial for the development of neutrophilic inflammation in the airways, which may be related to corticosteroid resistance [14].…”

Section: Introductionmentioning

confidence: 99%

Significant Increase of IL-8 Sputum Levels in Treatment Resistant Severe Asthma Compared with Difficult to Treat Severe Asthma Patients

E¹

2014

J Genet Syndr Gene Ther

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The spectrum of severe asthma includes different groupings and phenotypes. World Health Organization proposes to differentiate two categories: difficult-to-treat-severe asthma (DTTSA) and treatment-resistant-severe asthma (TRSA). DTTSA includes controllable severe asthma and TRSA includes patient's not achieving adequate levels of control and persisting indicators of severity despite receiving and using maximum levels of inhaled medications. We hypothesized that granulocyte counts from sputum samples could differentiate pathogenic differences between both groups. We analyzed the number of sputum neutrophils and eosinophils in both categories of severe asthma patients admitted for an asthma exacerbation in a respiratory-based hospital. We also compared our results with mild to moderate asthma patients (MMA) and healthy controls (HC). We measured cytokines levels relevant to neutrophil recruitment (IL-8 and IL17-A) and inflammatory cytokines. We found a significant increase in neutrophil numbers in TRSA compared to DDTSA, MMA and HC; moreover, we detected a significant increase of IL-8 levels in sputum samples of TRSA patients. However we found no differences in exhaled FeNO and IL17-A levels among groups.This study shows that the sputum neutrophilic profile predominates in patients with TRSA, could be useful in distinguishing from DTTSA, and may provide insight into the pathogenic differences between both groups.

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Immunopathogenesis of Allergic Asthma: More Than the Th2 Hypothesis

Cited by 56 publications

References 80 publications

Influence of rosuvastatin treatment on airway inflammatory markers and health related quality of life domains in asthmatic patients

Influence of rosuvastatin treatment on airway inflammatory markers and health related quality of life domains in asthmatic patients

Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment

Significant Increase of IL-8 Sputum Levels in Treatment Resistant Severe Asthma Compared with Difficult to Treat Severe Asthma Patients

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