Pilot study investigating diagnostic utility of serum MMP-1 and TGF-β1 in asthma in ‘real world’ clinical practice in India

2021 ◽  
pp. jclinpath-2020-206821
Author(s):  
Aswani Prabha ◽  
Komarla Sundararaja Lokesh ◽  
S K Chaya ◽  
B S Jayaraj ◽  
Sowmya Malamardi ◽  
...  
Keyword(s):  
Pilot Study ◽  
Severe Asthma ◽  
Predictive Value ◽  
Transforming Growth Factor ◽  
Persistent Asthma ◽  
Performance Characteristics ◽  
Therapeutic Monitoring ◽  
Moderate Asthma ◽  
Severe Persistent Asthma ◽  
Tgf Β1

AimsAt a tissue level, matrix metalloproteinase-1 (MMP-1) and transforming growth factor-beta 1 (TGF-β1) contribute to allergic airway inflammation, tissue remodelling and disease severity in asthma via different pathways. Their peripheral blood levels and role in diagnosis and therapeutic monitoring has not been adequately explored. We investigated the association between MMP-1 and TGF-β in moderate and severe persistent asthma and evaluated their performance characteristics by constructing receiver operating characteristic curves.MethodsSerum MMP-1 and TGF-β1 were measured using ELISA in 75 adults; moderate persistent asthma (n=25), severe persistent asthma (n=25) and healthy community controls (n=25). Severity of asthma was determined as per Global Initiative for Asthma guidelines. Subjects were followed up for 3 months and treatment responsiveness was assessed by spirometry and symptom response.ResultsSerum MMP-1 and TGF-β1 were significantly elevated in asthmatics compared with controls (p<0.0001 and p<0.01). While serum MMP-1 was elevated in severe asthma compared with moderate asthma (p<0.05), TGF-β1 was lower in severe asthma compared with moderate asthma (p<0.05). The performance characteristics of serum MMP-1 and TGF-β1 were promising in this cohort with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 82%, 100%, 100% and 99% and 62%, 100%, 100% and 97.8%, respectively; sensitivity of MMP-1 being superior.ConclusionThis pilot study showed that serum MMP-1 and TGF-β1 levels are elevated in chronic asthma and may serve as a useful adjunct in differentiating moderate from severe asthma. A large multicentre study in well characterised cohort of asthmatics is warranted to investigate their role in diagnosis and therapeutic monitoring.

scholarly journals Regulation of IL-17A and implications for TGF-β1 comodulation of airway smooth muscle remodeling in severe asthma

2019 ◽  
Vol 316 (5) ◽  
pp. L843-L868 ◽  
Author(s):  
Jon M. Evasovic ◽  
Cherie A. Singer
Keyword(s):  
Smooth Muscle ◽  
Airway Inflammation ◽  
Severe Asthma ◽  
Airway Smooth Muscle ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
High Dose ◽  
Persistent Symptoms ◽  
Immune Factors ◽  
Tgf Β1

Severe asthma develops as a result of heightened, persistent symptoms that generally coincide with pronounced neutrophilic airway inflammation. In individuals with severe asthma, symptoms are poorly controlled by high-dose inhaled glucocorticoids and often lead to elevated morbidity and mortality rates that underscore the necessity for novel drug target identification that overcomes limitations in disease management. Many incidences of severe asthma are mechanistically associated with T helper 17 (TH17) cell-derived cytokines and immune factors that mediate neutrophilic influx to the airways. TH17-secreted interleukin-17A (IL-17A) is an independent risk factor for severe asthma that impacts airway smooth muscle (ASM) remodeling. TH17-derived cytokines and diverse immune mediators further interact with structural cells of the airway to induce pathophysiological processes that impact ASM functionality. Transforming growth factor-β1 (TGF-β1) is a pivotal mediator involved in airway remodeling that correlates with enhanced TH17 activity in individuals with severe asthma and is essential to TH17 differentiation and IL-17A production. IL-17A can also reciprocally enhance activation of TGF-β1 signaling pathways, whereas combined TH1/TH17 or TH2/TH17 immune responses may additively impact asthma severity. This review seeks to provide a comprehensive summary of cytokine-driven T cell fate determination and TH17-mediated airway inflammation. It will further review the evidence demonstrating the extent to which IL-17A interacts with various immune factors, specifically TGF-β1, to contribute to ASM remodeling and altered function in TH17-driven endotypes of severe asthma.

Overview of severe asthma, with emphasis on pediatric patients: a review for practitioners

2021 ◽  
pp. jim-2020-001752
Author(s):  
Arabelle Abellard ◽  
Andrea A Pappalardo
Keyword(s):  
Risk Factors ◽  
Health Disparities ◽  
Severe Asthma ◽  
Pediatric Population ◽  
Asthma Management ◽  
Persistent Asthma ◽  
Individual Characteristics ◽  
Severe Persistent Asthma ◽  
The Usa ◽  
Life Threatening

Asthma is the most common life-threatening chronic disease in children. Although guidelines exist for the diagnosis and treatment of asthma, treatment of severe, pediatric asthma remains difficult. Limited studies in the pediatric population on new asthma therapies, complex issues with adolescence and adherence, health disparities, and unequal access to guideline-based care complicate the care of children with severe, persistent asthma. The purpose of this review is to provide an overview of asthma, including asthma subtypes, comorbidities, and risk factors, to discuss diagnostic considerations and pitfalls and existing treatments, and then present existing and emerging therapeutic approaches to asthma management. An improved understanding of asthma heterogeneity, clinical characteristics, inflammatory patterns, and pathobiology can help further guide the management of severe asthma in children. More studies are needed in the pediatric population to understand emerging therapeutics application in children. Effective multimodal strategies tailored to individual characteristics and a commitment to address risk factors, modifiers, and health disparities may help reduce the burden of asthma in the USA.

scholarly journals Still Fighting for Breath: a patient survey of the challenges and impact of severe asthma

2018 ◽  
Vol 4 (4) ◽  
pp. 00076-2018 ◽  
Author(s):  
Paraskevi Katsaounou ◽  
Mikaela Odemyr ◽  
Otto Spranger ◽  
Michael E. Hyland ◽  
Claus Kroegel ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Online Survey ◽  
Persistent Asthma ◽  
Patient Survey ◽  
Management Support ◽  
Daily Lives ◽  
Global Initiative For Asthma ◽  
Severe Persistent Asthma ◽  
Global Initiative ◽  
The Impact

We conducted a large global survey, Still Fighting for Breath, in patients with severe persistent asthma, 10 years after the Fighting for Breath survey to assess the impact of disease on patients' lives and to determine if control and management have changed in recent years.Data were collected from 1333 adults (aged >18 years) and caregivers of children (aged 6–17 years) with severe persistent asthma from nine countries through an online survey conducted in 2016 by GfK.A decade after the first survey, our results showed that the impact of severe asthma has not changed significantly and a high proportion of patients with severe asthma remain inadequately controlled. A large discrepancy was observed between the proportion of patients who perceived their asthma to be well controlled (42%) and the proportion of patients who reported to be well controlled as per the Global Initiative for Asthma (GINA) assessment (6%). Although most patients perceived their asthma to be controlled, many experienced frequent symptoms that affected their daily lives.Thus, there is a need for improved management (support and strategies) of patients with severe persistent asthma and improved coordination of efforts that would enable these patients to achieve better disease control.

Predictive value of HLA variants for Graves' disease recurrence - pilot study in Czech patients

2018 ◽  
Author(s):  
Daniela Vejrazkova ◽  
Josef Vcelak ◽  
Eliska Vaclavikova ◽  
Marketa Vankova ◽  
Petra Lukasova ◽  
...  
Keyword(s):  
Pilot Study ◽  
Predictive Value ◽  
Disease Recurrence ◽  
Graves Disease

The Safety and Efficacy of Mupirocin Topical Spray for Burn Wound Healing in A Rat Model

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Sritharadol Rutthapol ◽  
Chunhachaichana Charisopon ◽  
Kumlungmak Sukanjana ◽  
Buatong Wilaiporn ◽  
Dechraksa Janwit ◽  
...  
Keyword(s):  
Wound Healing ◽  
Matrix Metalloproteinase ◽  
Rat Model ◽  
Transforming Growth Factor ◽  
Immunohistochemical Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Burn Wound ◽  
Safety And Efficacy ◽  
Burn Wound Healing ◽  
Tgf Β1

ABSTRACT This study evaluated the effect of mupirocin topical spray on burn wound healing in a rat model. Fifteen male Sprague Dawley rats were used to create full-thickness burns on the rat dorsum using a cylindrical stainless steel rod. The rats were topically treated with normal saline solution (NSS), mupirocin spray, ointment, and solution. The wound size and morphological evaluation were investigated by photographs and clinical criterions for wound healing. The histology was observed by hematoxylin and eosin (HandE) staining assay. The immunohistochemical study was evaluated by detection of transforming growth factor-beta 1 (TGF-β1), and the ratio of matrix metalloproteinase-9 to the tissue inhibitor of matrix metalloproteinase-1 (MMP-9/TIMP-1) was quantified using the enzyme-linked immunosorbent assay (ELISA) assay. A complete healing was observed at 28 days in all treatments. Mupirocin formulations accelerated the wound healing faster than NSS in size. However, the clinical criteria indicated a desirable skin appearance in the mupirocin spray and ointment treated groups. The histological evaluations showed no differences between the treatments while the immunohistochemical study revealed that all treatments reduced the level of TGF-β1 over time, particularly on day 28 in the mupirocin spray and ointment treated groups. The MMP-9/TIMP-1 ratio was significantly lower in the mupirocin spray and ointment treated groups than in the NSS and mupirocin solution groups. This study shows the safety and efficacy in the use of mupirocin topical spray. The topical mupirocin spray is an alternative suitable for development as a human topical anti-infective and wound protection spray.

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