The Association of Severe Coronary Tortuosity and Non-Obstructive Coronary Artery Disease.

Background and Objectives: There is an increasing interest in the coronary tortuosity as a novel pathophysiological mechanism of ischemia in coronary artery disease without significant obstruction, but there are a lack of studies to confirm this relationship in the clinical setting. The aim of our study was to evaluate the association of severe coronary tortuosity and the potential role of coronary blood supply dominance in the appearance of myocardial ischemia in patients with non-obstructive coronary artery disease (non-CAD), compared to patients with obstructive coronary artery disease (CAD). Materials and Methods: The study enrolled 131 participants (71 male and 60 female), recruited among patients referred to cardiologists due to angina symptoms with ischemic alterations established by cardiac stress tests, as well as those admitted to the hospital for acute coronary syndrome. Results: Mean age of recruited patients was 61.6 (±10.1) years. According to the coronary angiography, they were divided into two groups: non-obstructive and obstructive CAD (77 and 54, respectively). There were significantly more women (61% vs. 24%, p < 0.001) in the non-CAD group. Both tortuous coronary arteries (50.6% vs. 14.8%, p < 0.001) and left coronary dominance (37.7% vs. 16.7%, p = 0.006) were more frequent in the non-CAD group compared to the CAD group. Female sex (OR = 17.516, p = 0.001), tortuous coronary arteries (OR = 7.962, p = 0.006) and left dominance of blood supply were significant predictors for non-CAD. Conclusions: Non-obstructive CAD is common among patients, especially women, who are referred for coronary angiography. Severe coronary artery tortuosity is the strongest independent predictor of non-obstructive CAD, followed by female gender and left coronary dominance.

Coronary Tortuosity Index vs. Angle Measurement Method for the Quantification of the Tortuosity of Coronary Arteries in Non-Obstructive Coronary Disease.

Coronary tortuosity has been recognized as a potential pathophysiological mechanism in the development of non-obstructive coronary artery disease (CAD). The aim of this study was to examine the role of two coronary tortuosity measurement methods in the detection of clinically significant coronary tortuosity. The study included 160 patients with angina symptoms and myocardial ischemia detected by cardiac stress tests in chronic settings and those diagnosed with acute coronary syndrome. After coronary angiography, tortuosity of coronary arteries was assessed by two methods, including measurement of tortuosity angles and calculating of tortuosity index. Significantly more tortuous coronary arteries were detected in the group with non-obstructive CAD (p < 0.01 for all three arteries), with significantly higher tortuosity index (TI) for all three coronary arteries in this group of patients, compared to patients with obstructive CAD. The highest TI for LCX was found in patients with lateral ischemia (p < 0.001) and for LAD in patients with anterior ischemia (p < 0.001). When measured by the angle method, the only association was found between LCX tortuosity and lateral ischemia (OR 4.9, p = 0.046). In conclusion, coronary tortuosity represents a pathophysiological mechanism for myocardial ischemia in non-obstructive CAD. The coronary tortuosity index could be a reliable and widely applicable tool for the quantification of coronary tortuosity.

Oxidative Stress in Ischemic Heart Disease.

One of the novel interesting topics in the study of cardiovascular disease is the role of the oxidation system, since inflammation and oxidative stress are known to lead to cardiovascular diseases, their progression and complications. During decades of research, many complex interactions between agents of oxidative stress, oxidation, and antioxidant systems have been elucidated, and numerous important pathophysiological links to na number of disorders and diseases have been established. This review article will present the most relevant knowledge linking oxidative stress to vascular dysfunction and disease. The review will focus on the role of oxidative stress in endotheleial dysfunction, atherosclerosis, and other pathogenetic processes and mechanisms that contribute to the development of ischemic heart disease.

Dynamics of exhaled breath temperature after smoking a cigarette and its association with lung function changes predictive of COPD risk in smokers: a cross-sectional study.

Exhaled breath temperature (EBT) is a biomarker of inflammation and vascularity of the airways already shown to predict incident COPD. This cross-sectional study was aimed to assess the potential of EBT in identifying "healthy" smokers susceptible to cigarette smoke toxicity of the airways and to the risk of developing COPD by analysing the dynamics of EBT after smoking a cigarette and its associations with their demographics (age, smoking burden) and lung function. The study included 55 current smokers of both sexes, 29-62 years of age, with median smoking exposure of 15 (10-71.8) pack-years. EBT was measured at baseline and 5, 15, 30, 45, and 60 min after smoking a single cigarette. Lung function was measured with spirometry followed by a bronchodilator test. To compare changes in EBT between repeated measurements we used the analysis of variance and the area under the curve (EBTAUC) as a dependent variable. Multivariate regression analysis was used to look for associations with patient characteristics and lung function in particular. The average (±SD) baseline EBT was 33.42±1.50 °C. The highest significant increase to 33.84 (1.25) °C was recorded 5 min after the cigarette was smoked (p=0.003), and it took one hour for it to return to the baseline. EBTAUC showed significant repeatability (ICC=0.85, p<0.001) and was significantly associated with age, body mass index, number of cigarettes smoked a day, baseline EBT, and baseline FEF75 (R2=0.39, p<0.001 for the model). Our results suggest that EBT after smoking a single cigarette could be used as early risk predictor of changes associated with chronic cigarette smoke exposure.

Inspiratory muscle strength affects anaerobic endurance in professional athletes.

To the best of our knowledge, little is known about the role of respiratory muscle strength and endurance on athlete performance in anaerobic conditions of maximal exertion. The aim of this cross-sectional study was therefore to examine the association between the strength/endurance of inspiratory muscles in a group of 70 healthy male professional athletes (team sports) and their ventilatory and metabolic parameters at the anaerobic threshold (second ventilatory threshold; VT2) and beyond it at maximum load during the cardiopulmonary exercise test (CPET) on a treadmill. Ventilatory parameters at VT2, at maximal effort, and their differences were tested for association with inspiratory muscle strength (PImax) and endurance (Tlim), measured as time to maintain inspiration at or above 80% of PImax. The difference in end-tidal oxygen tension (ΔPETO2) between VT2 and maximal effort was significantly associated with resting heart rate (HR) and systolic blood pressure (BP), PImax, and lean body mass (LBM) (r2=0.26, p=0.016; multivariate regression analysis). The difference in carbon dioxide output (ΔVCO2) was significantly associated with body mass index (BMI), resting HR, systolic BP, and PImax (r2=0.25, p=0.022; multivariate regression analysis). Our findings suggest that it is the inspiratory muscle strength and not endurance that affects the performance of professional athletes and that it should be tested and trained systematically.

Mood disorders in adult asthma phenotypes.

OBJECTIVE: Studies show high comorbidity of mood disorders in asthma. As asthma is a highly heterogeneous disease with different phenotypes it can be expected that there is a difference in this association with different asthma phenotypes. The aim of our cross-sectional study was to assess the association of specific asthma phenotypes with anxiety and/or depression and their impact on asthma control. METHODS: A cross-sectional study in 201 consecutive adult outpatients with asthma (≥18 years of age) was conducted. Each patient underwent physical examination, detailed medical history, Hospital Anxiety and Depression Scale, Asthma Control Questionnaire, Asthma Control Test, together with measurements of lung function and fraction of exhaled nitric oxide. Phenotypes were assessed using cluster analysis, and a multivariate analysis was used to identify associations of mood disorders with different phenotypes. RESULTS: Five asthma phenotypes were identified: allergic (AA, 43.8%), aspirin-exacerbated respiratory disease (AERD, 21.9%), late-onset (LOA, 18.9%), obesity-associated (OAA, 10.0%), and respiratory infections associated asthma (RIAA, 5.5%). A multivariate analysis showed a significant association of anxiety with LOA and comorbid hypertension (LOA, odds ratio (OR) = 2.12; hypertension, OR = 2.37, p = 0.012), and depression with AA, RIAA, hypertension, and ACQ score (AA, OR = 6.07; RIAA, OR = 4.73; hypertension, OR = 5.67; ACQ, OR = 1.87; p < 0.001). Comorbid anxiety/depression was associated with AA, LOA, RIAA, hypertension, and ACQ score (AA, OR = 10.15; LOA, OR = 2.98; RIAA, OR = 6.29; hypertension, OR = 5.15; ACQ, OR = 1.90; p < 0.001. CONCLUSION: Mood disorders were significantly associated with AA, LOA, and infection-associated asthma, together with comorbid hypertension and the level of asthma control.

What is safe enough - asthma in pregnancy - a review of current literature and recommendations.

BACKGROUND: Although asthma is one of the most serious diseases causing complications during pregnancy, half of the women discontinue therapy thus diminishing the control of the disease, mostly due to the inadequate education and fear of adverse events. Sadly, this is sometimes encouraged by insufficiently educated physicians. Since the incidence and the prevalence of asthma is increasing, it is important to arouse the importance of proper asthma therapy during pregnancy. Inadequate therapy, as well as interrupting or discontinuing therapy, may result in adverse perinatal outcomes for both mother and child. MAIN BODY: The main goal of asthma control during pregnancy is control of symptoms and prevention of exacerbations, same as in every asthmatic, but even more important. Maintaining optimal lung function, as well as regular daily activities, ensures maintenance of optimal fetal oxygenation. The therapy should be adapted depending on the frequency and severity of daily and nocturnal symptoms, demand for reliever therapy, by the limitations in everyday activities and the frequency of emergency asthma-related hospitalizations. Pre-conceptual education and therapy are very important and should be supported by an asthma action plan adjusted for the period of pregnancy. It is very important to note that most of the drugs used before pregnancy can be safely continued during pregnancy. Pharmacological and non-pharmacological therapy should be used in parallel. Pregnant women should be informed about the nature of the disease, therapy used during pregnancy, possible complications, avoidance of triggers, proper administration of therapy and, most important, why should the therapy be continued throughout the pregnancy on individual basis. Although drug treatment should be based on using drugs with less harm risk, if control of severe symptoms is needed to be achieved in order to protect both mother and child, any anti-asthmatic drug would have the beneficial benefit/harm ratio. CONCLUSION: There is no solid evidence that asthma treatment during pregnancy causes adverse outcomes for the mother and child but for many, especially new drugs, there is not enough data gathered. On the other hand, harmfulness of uncontrolled asthma during pregnancy is well documented so every effort should be put on preserving good control of asthma during pregnancy.

Long-term predictors of anxiety and depression in adult patients with asthma.

BACKGROUND: It is well established that anxiety and depression are associated with asthma, but there is limited evidence about the persistence of anxiety/depression in asthma. The aim of our study was to assess the long-term predictors of anxiety and depression in adult asthmatic patients. METHODS: A total of 90 adult asthma patients (63 women, age 18-50 years) with different levels of disease control (28 uncontrolled and 34 partially controlled) were assessed at baseline and at follow-up after 7 years for anxiety, depression and asthma control. The same work-up on both occasions included: demographics, living conditions, medical history (e.g. comorbidities, adherence and exacerbations), Hospital Anxiety and Depression Scale (HADS), Asthma Quality of Life Questionnaire (AQLQ), disease control and lung function. Persistence was defined as the HADS scores for anxiety and depression present at baseline and follow-up. RESULTS: The HADS results at follow-up visit showed 36 (40%) asthma patients with anxiety and 13 (14%) with depression, with the persistence of anxiety in 17 (19%) and of depression in 7 (8%) patients. Significant predictors of anxiety at follow-up were HADS and AQLQ results at baseline and several parameters of asthma control at follow-up (area under the curve AUC 0.917, 95% confidence interval CI 0.829-0.969, p < 0.001) and for depression AQLQ mood disorder domain, asthma control and lung function (AUC 0.947, 95% CI 0.870-0.986, p < 0.001). CONCLUSION: Anxiety and depression persist over years in some patients with asthma. The association between mood disorders and asthma suggests potential mutual treatability.

Early detection of COPD patients in GOLD 0 population: an observational non-interventional cohort study - MARKO study.

BACKGROUND: Main risk factor for the development of chronic obstructive pulmonary disease (COPD) is smoking, although only less than 1/3 of smokers develop clinically manifest COPD. COPD's progressive nature with high disability and mortality makes it plausible to detect it as early as possible thus allowing for an early intervention. The only tool for an early diagnosis that could be used on the global scale is spirometry, even though symptoms and deprivation of health related quality of life (HRQoL) precede relevant spirometric changes. Existing HRQoL questionnaires are too complicated or not developed for an early detection of COPD. The aim of our study was to develop a new simple HRQoL tool that will allow (alone or in combination with other markers) early detection of patients with COPD. METHODS: A multicenter prospective cohort study recruiting 500 subjects at risk for COPD (smokers/ex-smokers ≥20 pack-years, 40-65 years, both sexes, with no prior diagnosis of COPD) will be carried out in two phases: (1) cross-sectional - development and validation of a new questionnaire; and (2) prospective - follow-up of a cohort of patients at risk for COPD. Subjects were recruited by 25 GPs and assessed for COPD by dedicated pulmonologists in 7 hospital centers using a predefined protocol: HRQoL, history, physical, blood sampling, exhaled breath temperature (EBT), lung function, 6-min walk test (6MWT). Patients without COPD and those in GOLD stage 1 at initial assessment will be reassessed for disease progression by the same pulmonologist after 2 and 5 years. DISCUSSION: This is one of the first cohort studies attempting to establish the incidence of COPD in the pre-symptomatic stage before significant end organ damage. We intend to assess the validity, predictability and discriminative power ('healthy' smokers vs. pre-symptomatic phase in newly developed COPD) of newly developed HRQoL tool alone or in combination with other markers; EBT, lung function, 6MWT, genomics, transcriptomics, proteomics). We expect that the results of this study can improve our understanding of the development of COPD, identify some new underlying pathophysiological pathways, and offer to sensitive smokers/ex-smokers new preventive and early intervention measures thus improving the management of COPD. TRIAL REGISTRATION: Clinicaltrial.gov NCT01550679 retrospectively registered February 28, 2012.

Development and the initial validation of a new self-administered questionnaire for an early detection of health status changes in smokers at risk for chronic obstructive pulmonary disease (MARKO questionnaire).

AIM: To develop and do an initial validation of a new simple tool (self-administered questionnaire) that would be sensitive and specific enough to detect early changes in smokers leading to future development of chronic obstructive pulmonary disease (COPD). METHODS: 224 consecutive participants (50.9% women), with mean±standard deviation age of 52.3±6.7 years, 37.5±16.7 pack-years smoking history (85.8% active smokers), and no prior diagnosis of COPD were recruited. The MARKO questionnaire was self-administered twice; at the general practitioner's office and after 2-4 weeks at the tertiary care hospital. Participants were assessed for COPD by a pulmonologist after filling in a quality of life (QoL) questionnaires, history-taking, physical examination, lung function test, 6-minute walk test, and laboratory tests. They were divided into four subgroups: "healthy" smokers, symptomatic smokers, and smokers with mild and moderately severe COPD. RESULTS: Psychometric analyses indicated that the 18-item questionnaire had a very good internal consistency (Cronbach's alpha=0.91) and test-retest reliability for a four week period (c=0.89, 95% confidence interval [CI] 0.85-0.92, Lin's concordance). A significant correlations of MARKO scores were found with two QoL questionnaires; r=0.69 (P<0.001) and r=0.81 (P<0.001). Receiver operating characteristic curve analysis showed an area under the curve of 0.753 (95% CI 0.691-0.808, <0.001), with a sensitivity of 71.83% and specificity of 64.24% to discriminate "healthy" smokers from other subgroups. CONCLUSION: Based on psychometric analyses and high convergent validity correlation with already validated QoL questionnaires, the newly developed MARKO questionnaire was shown to be a reliable self-administered short health status assessment tool.

Exhaled Breath Temperature as a Novel Marker of Future Development of COPD: Results of a Follow-Up Study in Smokers.

Although only less than one-third of smokers develop COPD, early marker(s) of COPD development are lacking. The aim of this research was to assess the ability of an average equilibrium exhaled breath temperature (EBT) in identifying susceptibility to cigarette smoke so as to predict COPD development in smokers at risk. The study was a part of a multicenter prospective cohort study in current smokers (N = 140, both sexes, 40-65 years, ≥20 pack-years) with no prior diagnosis of COPD. Diagnostic workup includes history, physical, quality of life, hematology and highly sensitive CRP, EBT before and after smoking a cigarette, lung function with bronchodilator test, and 6-minute walk test. Patients without a diagnosis of COPD and in GOLD 1 stage at initial assessment were reassessed after 2 years. COPD was additionally diagnosed based on lower level of normal (LLN) lung function criteria. Utility of EBT for disease progression was analyzed using receiver operator curve (ROC) and logistic regression analyses. Change in EBT after smoking a cigarette at initial visit (ΔEBT) was significantly predictive for disease progression (newly diagnosed COPD; newly diagnosed COPD + severity progression) after 2 years (p < 0.05 for both). ΔEBT had an AUC of 0.859 (p = 0.011) with sensitivity of 66.7% and specificity of 98.1% for newly diagnosed COPD using LLN criteria. We conclude that EBT shows potential for predicting the future development of COPD in current smokers. This was best seen using LLN to diagnose COPD, adding further evidence to question the use of GOLD criteria for diagnosing COPD.

Asthma control in obesity-associated asthma phenotype in East Croatia.

AIM: To determine if obese asthmatics represent a distinct clinical phenotype than non-obese and the level of asthma control in obese asthmatics. METHODS: The study was conducted in the pulmonary clinic of the Department of Pulmonary Diseases, Osijek University Hospital Centre during 201, on 201 outpatients with asthma, who came to a regular examination. Each patient underwent a clinical examination with an extensive anamnesis and lung auscultation. During the examinationIanninternally made questionnaire, spirometry, fractional exhaled nitric oxide (FeNO), Asthma Control Test and Asthma Control Questionnaire were used to estimate the level of asthma control, wheread the Hospital Anxiety and Depression scale was used to estimate the presence of mood disorderd. RESULTS: The severity of asthma was increased in obese patients. There was no significant difference in the number and frequency of hospitalizations in obese compared to non-obese asthmatics. Non-obese asthmatics had more frequent visits to their general practitioner/Emergency medical services (GP/EMS) during the last month compared to obese asthmatics, which is a new finding inconsistent to any study conducted before. Obese asthmatics had more symptoms and had them almost every day. Lung function of obese asthmatic was worse compared to non-obese, especially in women. Values of exhaled nitric oxide showed no significant difference for obese asthmatics. No significant difference in intake of corticosteroids or combination therapy was found. Obese patients with asthma had more frequent and multiple comorbidities. CONCLUSION: Results confirmed that obese asthmatics represent a different phenotype of asthma, more severe and poorly controlled.

The prevalence and pulmonary consequences of anxiety and depressive disorders in patients with asthma.

The aim of this study was to determine the prevalence of anxiety and depression symptoms in outpatients with treated asthma and to determine the influence of anxiety and depression symptoms on lung function and asthma symptoms. The study was conducted in the pulmonary clinic of the Department of Pulmonary Diseases, Osijek University Hospital Centre, on 200 outpatients with asthma, aged 18-50 years, of which there were 65.5% women and 35.5% men. Each patient underwent a clinical examination with an extensive anamnesis and lung auscultation. The lung function was tested by spirometry. Demographic data and data on general and socioeconomic characteristics were evaluated using a questionnaire created internally for the purposes of this research, psychological status was assessed by HAD questionnaire, and Q test was used as a measure of asthma control. Based on the HAD questionnaire, 44.5% of asthma patients met the criteria for anxiety, and 24.5% of asthma patients met the criteria for depression. There was no significant correlation between asthma symptoms and the degree of anxiety or depression, while the pulmonary function of asthma patients negatively correlated with the degree of anxiety and depression. Pulmonary function in asthma patients with symptoms of anxiety and depression was significantly poorer than in asthma patients without anxiety and/or depression symptoms. The results show that among asthma patients there are large number of those who have symptoms of anxiety and depression. Asthma patients with symptoms of anxiety and depression have poorer lung function than patients with only asthma symptoms, however there is no significant correlation between the lung function and symptoms of asthma. We have confirmed that patients with anxiety symptoms visit general practitioners or EMS significantly more when compared to patients with depression symptoms.

Comparison of emotion recognition from facial expression and music.

The recognition of basic emotions in everyday communication involves interpretation of different visual and auditory clues. The ability to recognize emotions is not clearly determined as their presentation is usually very short (micro expressions), whereas the recognition itself does not have to be a conscious process. We assumed that the recognition from facial expressions is selected over the recognition of emotions communicated through music. In order to compare the success rate in recognizing emotions presented as facial expressions or in classical music works we conducted a survey which included 90 elementary school and 87 high school students from Osijek (Croatia). The participants had to match 8 photographs of different emotions expressed on the face and 8 pieces of classical music works with 8 offered emotions. The recognition of emotions expressed through classical music pieces was significantly less successful than the recognition of emotional facial expressions. The high school students were significantly better at recognizing facial emotions than the elementary school students, whereas girls were better than boys. The success rate in recognizing emotions from music pieces was associated with higher grades in mathematics. Basic emotions are far better recognized if presented on human faces than in music, possibly because the understanding of facial emotions is one of the oldest communication skills in human society. Female advantage in emotion recognition was selected due to the necessity of their communication with the newborns during early development. The proficiency in recognizing emotional content of music and mathematical skills probably share some general cognitive skills like attention, memory and motivation. Music pieces were differently processed in brain than facial expressions and consequently, probably differently evaluated as relevant emotional clues.