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RISS 인기검색어
- 검색키워드
- 저자 : ( Parameswaran Nair ) (검색결과 6 건)
- 무료
- 기관 내 무료
- 유료
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Biomarkers, biologics, and bio-imaging to manage severe asthma
( Parameswaran Nair ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.-
A fundamental principle in the management of severe asthma is to identify the components of the airway disease that contribute to the severity. The airway luminal inflammatory (ie bronchitic) component can be identified by applying new “omics” platforms such as proteomics, transcriptomics, or metabolomics. Simple sputum quantitative cytometry provides just as useful information that can be applied to clinical practice. The lecture will focus on the utility of biomarkers of airway inflammation (sputum cytometry and omics technology, FeNO, novel imaging including functional MRI and airway CT) to identify the inflammatory component in the airways of patients with severe asthma and how this could be applied in routine clinical practice to choose the appropriate monoclonal antibody therapy, particularly against IL-5 and IL4. The lecture will address the various predictors of success and failures of anti-IL5 therapies, including issues with inadequate dosing, the relevance of airway autoimmune responses, and the modulating effect of innate immune cells such as NK cells and macrophages on IL-5R-targeted ADCC. The utility of measurement of airway hyper-responsiveness and the assessment of the so-called non-T2 inflammation will also be discussed, and illustrated using clinical case scenarios.
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Novel insights from sputum inflammometry to manage COPD exacerbations
( Parameswaran Nair ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.-
Quantitative sputum cytometry helps to assess the nature of bronchitis associated with exacerbations of COPD. This is not assessed in most clinical trials that evaluate the effectiveness of strategies to prevent or to treat exacerbations. While up to a quarter of exacerbations may be associated with raised eosinophil numbers, vast majority of exacerbations are associated with neutrophilic bronchitis that may indicate airway infections. While eosinophilia may be a predictor of response to corticosteroids (both oral and inhaled), the limited efficacy of anti-IL5 therapies would suggest that eosinophils may not directly contribute to those exacerbations. However, they may contribute to airspace enlargement in patients with COPD through various mechanisms involving IL-13 and MMP pathways. The absence of eosinophils may help to limit the unnecessary use of corticosteroids. The presence of neutrophiia could prompt an investigation for the specific pathogens in the airway. In addition, sputum measurements may also provide insights into mechanisms of susceptibility to airway infections. Iron within sputum macrophages, identified by hemosiderin staining (and by more direct quantification) may impair macrophage functions while low levels of immunoglobulins in sputum may also contribute to airway infections. Assessment of sputum at the time of exacerbations thus would help to customize treatment and treat current exacerbations and reduce the future risk of exacerbations.
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Autoimmune Responses in Severe Asthma
Manali Mukherjee,Parameswaran Nair 대한천식알레르기학회 2018 Allergy, Asthma & Immunology Research Vol.10 No.5
Asthma and autoimmune diseases both result from a dysregulated immune system, and have been conventionally considered to have mutually exclusive pathogenesis. Autoimmunity is believed to be an exaggerated Th1 response, while asthma with a Th2 underpinning is congruent with the well-accepted Th1/Th2 paradigm. The hypothesis of autoimmune involvement in asthma has received much recent interest, particularly in the adult late-onset non-atopic patients (the “intrinsic asthma”). Over the past decades, circulating autoantibodies against diverse self-targets (beta-2-adrenergic receptors, epithelial antigens, nuclear antigens, etc.) have been reported and subsequently dismissed to be epiphenomena resulting from a chronic inflammatory condition, primarily due to lack of evidence of causality/pathomechanism. Recent evidence of ‘granulomas’ in the lung biopsies of severe asthmatics, detection of pathogenic sputum autoantibodies against autologous eosinophil proteins (e.g., eosinophil peroxidase) and inadequate response to monoclonal antibody therapies (e.g., subcutaneous mepolizumab) in patients with evidence of airway autoantibodies suggest that the role of autoimmune mechanisms be revisited. In this review, we have gathered available reports of autoimmune responses in the lungs, reviewed the evidence in the context of immunogenic tissue-response and danger-associated molecular patterns, and constructed the possibility of an autoimmune-associated pathomechanism that may contribute to the severity of asthma.
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( Carmen Venegas ),( Nan Zhao ),( Terence Ho ),( Parameswaran Nair ) 대한결핵 및 호흡기학회 2020 Tuberculosis and Respiratory Diseases Vol.83 No.3
Quantitative sputum cytometry facilitates in assessing the nature of bronchitis associated with exacerbations of chronic obstructive pulmonary disease (COPD). This is not assessed in most clinical trials that evaluate the effectiveness of strategies to prevent or to treat exacerbations. While up to a quarter of exacerbations may be associated with raised eosinophil numbers, the vast majority of exacerbations are associated with neutrophilic bronchitis that may indicate airway infections. While eosinophilia may be a predictor of response to corticosteroids (oral and inhaled), the limited efficacy of anti-interleukin 5 therapies would suggest that eosinophils may not directly contribute to those exacerbations. However, they may contribute to airspace enlargement in patients with COPD through various mechanisms involving the interleukin 13 and matrix metalloprotease pathways. The absence of eosinophils may facilitate in limiting the unnecessary use of corticosteroids. The presence of neutrophiia could prompt an investigation for the specific pathogens in the airway. Additionally, sputum measurements may also provide insight into the mechanisms of susceptibility to airway infections. Iron within sputum macrophages, identified by hemosiderin staining (and by more direct quantification) may impair macrophage functions while the low levels of immunoglobulins in sputum may also contribute to airway infections. The assessment of sputum at the time of exacerbations thus would facilitate in customizing treatment and treat current exacerbations and reduce future risk of exacerbations.
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