Clinical characteristics of takotsubo cardiomyopathy in north america.

BACKGROUND: Takotsubo cardiomyopathy (TC) or transient left ventricular apical ballooning syndrome is an acute cardiac syndrome characterized by transient wall motion abnormalities extending beyond a single epicardial vessel in the absence of significant obstructive coronary artery disease. AIM: This study was to describe the clinical characteristics of TC in North America. MATERIALS AND METHODS: We identified 10 patients who met the Mayo Clinic criteria for TC using our Electronic Medical Records. We also conducted a systematic review of case series of TC that were done in North America by searching the MEDLINE database. We identified 11 case series that met our eligibility criteria. RESULTS: Our systematic review included 620 patients. Chest pain and ST segment elevation were the cardinal features of this syndrome, but the prevalence was lower than in the European and Asian cohort (50% and 39% as compared with 80% and 70%, respectively). Classic precipitating emotional or physical stress was described in > 80% of patients. Cardiac biomarkers were found to be elevated in >90% of our patients. CONCLUSIONS: TC is a worldwide problem and clinical presentation appears to be similar in North American, European, and Asian countries. However, fewer patients in our cohort presented with typical chest pain and electrocardiography (ECG) changes, which might suggest ethnic variations in the syndrome or perhaps a more aggressive diagnostic approach in North American countries.

Asthma treatment through the beta receptor: lessons from animal models.

Asthma is a significant health problem worldwide with a prevalence that continues to rise and for which there is no cure. Animal models have been used for decades to investigate the cause and cures of asthma, and while they do not always mimic many of the facets of this syndrome, mechanistic animal studies are still nevertheless very useful. Animal studies with beta-agonists suggest much broader and perhaps more important roles for beta-agonists since beta-agonists reduce aspects of inflammation and may affect structural remodeling. Studies using enantiomers of beta-agonists provide a confusing picture of the degree and mechanism of the deleterious effects of racemic mixtures and/or the S-enantiomer or other classes of beta-agonists. Neural mechanisms are implicated. The future holds a promise of even more insight into the mechanisms of the acute and chronic role of the beta-adrenoceptor, asthma therapeutics, in particular, beta-agonists that will lead to a better understanding of the pathogenesis and treatment of asthma.

Detrimental effects of albuterol on airway responsiveness requires airway inflammation and is independent of ß-receptor affinity in murine models of asthma.

BACKGROUND: Inhaled short acting ß2-agonists (SABA), e.g. albuterol, are used for quick reversal of bronchoconstriction in asthmatics. While SABA are not recommended for maintenance therapy, it is not uncommon to find patients who frequently use SABA over a long period of time and there is a suspicion that long term exposure to SABA could be detrimental to lung function. To test this hypothesis we studied the effect of long-term inhaled albuterol stereoisomers on immediate allergic response (IAR) and airway hyperresponsiveness (AHR) in mouse models of asthma. METHODS: Balb/C mice were sensitized and challenged with ovalbumin (OVA) and then we studied the IAR to inhaled allergen and the AHR to inhaled methacholine. The mice were pretreated with nebulizations of either racemic (RS)-albuterol or the single isomers (S)- and (R)-albuterol twice daily over 7 days prior to harvest. RESULTS: We found that all forms of albuterol produced a significant increase of IAR measured as respiratory elastance. Similarly, we found that AHR was elevated by albuterol. At the same time a mouse strain that is intrinsically hyperresponsive (A/J mouse) was not affected by the albuterol isomers nor was AHR induced by epithelial disruption with Poly-L-lysine affected by albuterol. CONCLUSIONS: We conclude that long term inhalation treatment with either isomer of albuterol is capable of precipitating IAR and AHR in allergically inflamed airways but not in intrinsically hyperresponsive mice or immunologically naïve mice. Because (S)-albuterol, which lacks affinity for the ß2-receptor, did not differ from (R)-albuterol, we speculate that isomer-independent properties of the albuterol molecule, other than ß2-agonism, are responsible for the effect on AHR.

Inhaled salmeterol and/or fluticasone alters structure/function in a murine model of allergic airways disease.

BACKGROUND: The relationship between airway structural changes (remodeling) and airways hyperresponsiveness (AHR) is unclear. Asthma guidelines suggest treating persistent asthma with inhaled corticosteroids and long acting beta-agonists (LABA). We examined the link between physiological function and structural changes following treatment fluticasone and salmeterol separately or in combination in a mouse model of allergic asthma. METHODS: BALB/c mice were sensitized to intraperitoneal ovalbumin (OVA) followed by six daily inhalation exposures. Treatments included 9 daily nebulized administrations of fluticasone alone (6 mg/ml), salmeterol (3 mg/ml), or the combination fluticasone and salmeterol. Lung impedance was measured following methacholine inhalation challenge. Airway inflammation, epithelial injury, mucus containing cells, and collagen content were assessed 48 hours after OVA challenge. Lungs were imaged using micro-CT. RESULTS AND DISCUSSION: Treatment of allergic airways disease with fluticasone alone or in combination with salmeterol reduced AHR to approximately naüve levels while salmeterol alone increased elastance by 39% compared to control. Fluticasone alone and fluticasone in combination with salmeterol both reduced inflammation to near naive levels. Mucin containing cells were also reduced with fluticasone and fluticasone in combination with salmeterol. CONCLUSIONS: Fluticasone alone and in combination with salmeterol reduces airway inflammation and remodeling, but salmeterol alone worsens AHR: and these functional changes are consistent with the concomitant changes in mucus metaplasia.

It's not all smooth muscle: non-smooth-muscle elements in control of resistance to airflow.

To achieve gas exchange, inspired air must pass through an intricate and dynamic tracheobronchial tree. The tree offers resistance to airflow, and increased resistance is the most important functional change in lung disease. Numerous mechanisms contribute to increased resistance by causing airway narrowing, closure, occlusion, and/or obliteration. Although airway smooth muscle (ASM) contraction and shortening are an important cause of increased resistance, non-ASM elements can also contribute. Nonmuscle elements can modify the amount of airway narrowing for any given level of ASM shortening and the amount of shortening for a given level of ASM activation. In this review, we outline the physiological basis for airflow resistance and describe how changes in the lung parenchyma, the airways, and their luminal contents can contribute to increased airflow resistance. A detailed understanding of the mechanisms and consequences of increased airway resistance is vital to our attempts to alleviate the enormous burden of suffering caused by obstructive lung diseases.

Development of allergen-induced airway inflammation in the absence of T-bet regulation is dependent on IL-17.

Dysfunctional expression of T-bet, a transcription factor that is critical for IFN-gamma production, has been implicated in the development of asthma. To investigate in detail the mechanisms responsible for exacerbated disease in the absence of T-bet expression, BALB/c wild-type (WT) and T-bet(-/-) mice were used in a murine model of OVA-induced allergic lung inflammation. Following OVA challenge, T-bet(-/-) mice displayed increased histological inflammation in the lungs as well as greater thickening of the bronchiole linings, increased numbers of eosinophils and neutrophils in the lung, and enhanced airway hyperresponsiveness, compared with WT mice. However, the production of Th2 cytokines in T-bet(-/-) mice did not appear to be significantly greater than in WT mice. Interestingly, a marked increase in the levels of the proinflammatory cytokine IL-17 was observed in T-bet(-/-) mice. Neutralization of pulmonary IL-17 in T-bet(-/-) mice by anti-IL-17 mAb treatment during OVA challenge resulted in decreased levels of neutrophilic infiltration into the airways and decreased airway inflammation, essentially reversing the development of allergic asthma development. These findings indicate that IL-17 is a key mediator of airway inflammation in the absence of T-bet. The results of this study suggest a possible target for therapeutic intervention of human asthma.

Radon awareness and mitigation in Vermont: a public health survey.

Radon exposure is associated with an increased incidence of lung cancer, and elevated levels may be found in as many as 1 out of 15 homes. The U.S. EPA recommends testing homes for radon and mitigating over the advisory level of 4 picocuries per liter (4 pCi L(-1), or 148 Bq m(-3)). A sample population from a list of Vermont residents who had tested their residence for radon through the Vermont Department of Health and who had elevated levels were mailed a survey to assess demographic characteristics, knowledge about radon, mitigation rates, types of mitigation, as well as barriers to mitigation. The response rate was 63%. Forty-three percent of respondents mitigated. Roughly half were not completely knowledgeable of radon based upon the ability to associate radon exposure with lung cancer risk. Reasons not to mitigate radon levels in homes were cost and lack of concern over elevated levels. A multivariate logistic regression analysis revealed factors associated with mitigating: an education level of college or higher (p = 0.02), concern that a high radon level would affect real estate value (p = 0.04), and home age less than 10 y (p = 0.05). In summary, less than half of Vermonters with elevated radon levels participating in the Department of Health program mitigated. We identify factors associated with radon mitigation that may lead to improved radon education and mitigation practice.