Researchers from Duke University Medical Center, Durham, NC, have suggested that bariatric surgery can improve asthma management in type-2 high asthma with comorbid obesity, facilitated by normalisation of systemic procoagulant and pro-inflammatory mediators. However, they noted that a better understanding of attenuated coagulation parameters in the airway following bariatric surgery is needed to advance the knowledge of biomolecular pathways driving asthma pathobiology in patients with obesity. The findings were featured in the paper, ‘Imbalanced Coagulation in the Airway of Type-2 High Asthma with Comorbid Obesity’, published in Dovepress.
The authors explained that asthma is characterised by airway hyperresponsiveness (AHR), remodelling and inflammation resulting in moderate-to-severe respiratory symptoms. Asthma is a heterogeneous disease, with most patients categorised into two main endotypes: Type-2 high and Type-2 low. Type-2 high asthma patients with comorbid obesity are more likely to be hospitalised, use oral steroids, be admitted to the intensive care unit (ICU) and experience greater asthma severity through augmented small airway dysfunction and bronchial hyperresponsiveness - compared to lean Type-2 high asthma patients. Nevertheless, they noted that no longitudinal studies have investigated the effect of weight gain on Type-2 high asthma pathophysiology.
In this review, the authors sought to present current knowledge of the extrinsic coagulation pathway and regulatory effects of the coagulation cascade on asthma pathobiology in Type-2 high asthma patients with comorbid obesity. They hypothesize that the coagulation cascade may serve as a link between the influences of increased adiposity and diminished pulmonary function or AHR in asthma – and that bariatric surgery offers the potential to return patients to the normal coagulation processes and a decrease in inflammatory and procoagulant mediators following surgery and/or weight loss.
They state that several studies have reported bariatric surgery independently improves features of improper coagulation in patients with obesity, However, the impact of bariatric surgery on attenuated coagulation within the airway and in asthma is yet to be determined.
Nevertheless, a study of patients with comorbid obesity and asthma undergoing bariatric surgery showed a significant increase in asthma control, reduced medication usage and improved quality of life. However, further studies are needed to better understand the metabolic and cellular signalling mechanisms whereby bariatric surgery impacts features of asthma exacerbations and management.
In addition to improving asthma control, bariatric surgery corrects inflammatory cytokine and adipokine profiles, a significant decrease in mast cells 12 months post-operative, reduces CRP levels, significantly decreases 65 Serum levels of the co-initiator of the extrinsic coagulation cascade, FVII, 12 months after bariatric surgery, further reducing the pro-thrombotic potential.
Bariatric surgery also induces improvement in coagulation through normalised anti-coagulant and anti-fibrinolytic mediators, and circulating PC/APC levels were reported to have decreased one year post-surgery due to reduced thrombomodulin and thrombin potential.
The authors write epigenetic mechanisms may provide a link between bariatric surgery and improved coagulation profiles in patients with obesity, and DNA methylation is one possible molecular response following bariatric surgery and could be involved in reversing some of the detrimental effects of obesity.
However, although attenuated coagulation factors observed following bariatric surgery have been seen in systemic circulation, there are no studies investigating how these coagulation parameter profiles change in the airway following bariatric surgery.
“We hypothesise that bariatric surgery, unlike other pharmacological interventions, provides significant improvements in asthma control as seen through improved AHR, lung compliance, and normalized coagulant and inflammatory parameters. Future research will identify specific metabolic and cellular mechanisms whereby bariatric surgery influences airway coagulation and physiology and reveal potential applications to clinical care,” the researcher concluded. “A better understanding of bariatric surgery-induced metabolic and cellular mechanisms regulating mediators of the coagulation pathway, whether those mechanisms be weight loss-dependent or -independent, holds promise for the development of potential therapies to benefit all patients with Type-2 high asthma, not just those with comorbid obesity.”
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