Introduction: Takotsubo cardiomyopathy or stress cardiomyopathy is a syndrome of transient left ventricular (LV) dysfunction mimicking myocardial infarction, but lacking obstruction of coronary artery disease (CAD) or acute plaque rupture. A characteristic differentiation from CAD is that regional motional abnormality extends beyond a territory perfused with a single epicardial coronary artery. Clinically, it is characterized by apical ballooning of the LV due to due to depression of mid and apical segments, with hyperkinesis of cardiac basal walls. Women are affected more than men, predominantly in the postmenopausal age. Case Report: A 54-year-old Caucasian female with a history of COPD, hypertension, uncontrolled diabetes mellitus, hyperlipidemia, depression and ongoing tobacco use presented with complaints of worsening shortness of breath two days prior to admission. She denied chest pain, worsened cough, palpitations, nausea or vomiting. On examination, she was in distress and anxious, with labored breathing. Upon examining the chest, decreased air entry was present in both lung fields with bibasilar wheezing. Initial lab tests showed mild respiratory acidosis, with pH of 7.24, pCO2 of 47.4 and pO2 of 65. Troponins on the day of admission was Soon after admission, she started complaining of severe right neck pain. Repeat EKG revealed localized lateral J point, anteroseptal q waves and 4mm ST-segment elevation in leads V3 and V4 reciprocal changes and without chest pain. Repeat troponins were slightly elevated to 0.42 ng/ml and CK-MB was elevated to 20.2 ng/ml. A transthoracic echocardiogram showed regional abnormalities in left ventricle with the apex, mid to distal septum and the anterior part of septum was akinetic. Discussion: Takotsubo cardiomyopathy presents in 1 to 2 percent of troponin-positive acute coronary syndrome (ACS) with various clinical manifestations and various outcomes. Some patients have favorable outcomes based on their clinical performance and extent of cardiac muscle involvement. As in the case we presented, this syndrome can be entirely idiopathic, without a definitive underlying cause. Supportive management while hospitalized and early identification of complications improve the prognosis.

Over 1.1 billion people smoke worldwide despite the association of smoking with numerous diseases including chronic obstructive pulmonary disease (COPD). The decline in lung function observed in COPD patients is thought to be related to smoke-induced inflammation. COPD patients are also at increased risk of acquiring lung bacterial infections that are associated with exacerbations, characterized by worsened disease symptoms and inflammation. The focus of this thesis is on how cigarette smoke impacts bacterial-host interactions and bacterial community interactions to promote infection and disease. In chapter 3.1, we sought to understand how cigarette smoke primed the lungs towards an amplified inflammatory response to bacterial infection reflective of COPD exacerbations that accelerate disease progression. We present a novel finding that exacerbated neutrophilia elicited by nontypeable Haemophilus influenzae (NTHi) lung challenge in smoke-exposed mice occurred dependent on IL-1α. Smokers and patients with COPD are additionally at increased risk of acquiring bacterial infection that may be related to impaired containment of nasally colonizing pathogens. In chapter 3.2, we found that cigarette smoke predisposed mice to invasive pneumococcal disease (IPD) following nasal pneumococcal colonization associated with attenuated nasal inflammatory responses. To our knowledge, this is the first study to describe the progression from asymptomatic nasal pneumococcal colonization to the development of IPD in the context of cigarette smoking. It has been suggested that smokers have higher rates of pathogen colonization as a consequence of cigarette smoke-induced nasal microbiome dysbiosis. The last study in chapter 3.3 advanced knowledge in the field by testing this hypothesis. We observed that cigarette smoke alone did not alter the mouse nasal microbiome and concluded that microbiome dysbiosis observed in smokers likely occur as a consequence of nasal pathogen colonization. Overall, work presented in this thesis advanced our understanding of how cigarette smoking alters bacterial-host interactions to promote infection and disease. / Thesis / Doctor of Philosophy (PhD) / Over 1.1 billion people smoke worldwide and can develop chronic obstructive pulmonary disease (COPD), a serious inflammatory disease compromising lung function. Additionally, smokers and COPD patients have higher rates of bacterial infection. The goal of this thesis is to understand how smoking impacts our ability to combat infection. Lung infection in COPD patients causes exacerbation, with worsened disease symptoms. Using mouse models, we learned how smoking causes increased lung inflammation following bacterial infection, contributing to damage reflective of COPD exacerbations, and identified a potential intervention. We elucidated smokers may have increased infections due to impaired immune responses in the nose, a major pathogen entry point. It is thought smoking reduced beneficial bacteria that counter pathogen acquisition in the nose. We confirmed smoking did not impact these bacteria, directing research focus towards other ways smokers acquire pathogens. Overall, this thesis advanced knowledge and will help efforts to control disease in smokers.