Asthma Is A Risk Factor Of Human And Experimental Abdominal Aortic Aneurysms

Objective:Asthma and abdominal aortic aneurysms(AAA) both involve inflammation.Patients with asthma exhibit increased plasma Ig E and accumulation of eosinophils,lymphocytes,macrophages, and mast cells in the bronchi and alveoli, whereas patients with AAA harbor macrophages, lymphocytes, and neutrophils in the arterial wall. It remains unknown whether one disease serves as a risk factor of the other. Our aim is to prove a new link between the allergic and AAA and to explore new evidence for the prevention and screening of AAA and r AAA.Methods:DNRP: Population-based nationwide case-control study included all patients with ruptured AAA(r AAA) and age- and sex-matched AAA controls without rupture in Denmark from 1996-2012. VIVA: Subgroup study of participants from the population-based randomized Viborg vascular screening trial. Asthmatic patients were categorized by hospital diagnosis, bronchodilator use, and the recorded use of other anti-asthma prescription medications. Logistic regression models was fitted to determine whether asthma was associated with the risk of r AAA in DNRP, and an independent risk of having an AAA at screening in the VIVA trial.Results:From the DNRP study, asthma diagnosed with less than one year or six months before the index date increased the risk of AAA rupture before(odds ratio OR=1.60,2.12) and after(OR=1.51, 2.06) adjusting for AAA comorbidities. Use of bronchodilators elevated the risk of AAA rupture from ever use to within 90 days from the index date, before(OR=1.10~1.37) and after(OR=1.10~1.31) adjustment.Patients prescribed anti-asthma drugs also showed an increased risk of rupture before(OR=1.12~1.79) and after(OR=1.09~1.48) the same adjustment. In the VIVA trial,anti-asthma medication showed increased risk of AAA before(OR=1.45) or after adjustment for smoking(OR=1.45) or other risk factors(OR=1.46).Conclusions:Recent active asthma increased risk of AAA and AAA-rupture. These findings document and furnish novel links between airway disease and AAA, two common diseases that share inflammatory aspects.Objective:Asthma and abdominal aortic aneurysms(AAA) both involve inflammation. Our previous results demonstrated that patients with asthma have increased risk of developing AAA or experiencing aortic rupture. This study tests the development of one disease on the progression of the other and explores the underlying machnisms.Methods:Ovalbumin sensitization and challenge in mice developed asthma. Subcutaneous infusion of angiotensin II(Ang-II) to mice produced AAA. This study included six experiments with different combinations of asthma and AAA models to test theinteractions between asthma and AAAs in Apoe–/– mice: To produce asthma and AAA at the same time; at the meantime mice also received anti-Ig E antibody treatment; to produce asthma first followed by producing AAA; These three protocols tested whether development of asthma affected AAA formation and whether asthma promotes AAA formation via increase Ig E production; to produce AAA first, and then induce asthma; and to produce asthma only, as a control. These two protocols tested whether consequent asthma exacerbated pre-established AAA and whether pre-existing AAA affected airway allergic response development; finally to produce asthma in peri-aortic Ca Cl2 injury-induced AAA.Results:Simultaneous productions of asthma in AAA mice doubled abdominal aortic diameters, increased macrophage and mast cell content, arterial media smooth muscle cell(SMC) loss, cell proliferation, and angiogenesis in AAA lesions. Asthma also increased plasma Ig E, reduced plasma IL5, and increased bronchioalveolar total inflammatory cell and eosinophil accumulation. Intraperitoneal administration of an anti-Ig E antibody suppressed AAA lesion formation and reduced lesion inflammation,plasma Ig E, and bronchioalveolar inflammation. Pre-establishment of asthma also increased AAA lesion size and lesion accumulation of macrophage and mast cell, and media SMC loss, increased plasma Ig E, reduced plasma IL5, IL13, and TGF-?, and increased bronchioalveolar inflammation. Consequent production of asthma also doubled lesion size of pre-established AAA and increased lesion mast cell and T-cell accumulation, media SMC loss, lesion cell proliferation and apoptosis, plasma Ig E,and bronchioalveolar inflammation. In peri-aortic Ca Cl2 injury-induced AAA in mice,production of asthma also increased AAA formation, lesion inflammation, plasma Ig E, and bronchioalveolar inflammatory cell accumulation.Conclusion:This study suggested a pathologic link between asthma and AAA. Production of one disease aggravates the progression of the other.