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.

Predictors of short-term LAMA ineffectiveness in treatment naïve patients with moderate to severe COPD.

BACKGROUND: No specific (only subgroup) recommendations for the use of long-acting muscarinic antagonists in chronic obstructive pulmonary disease (COPD) exist. The aim of this exploratory hypothesis generating study was to assess whether different phenotypic/endotypic characteristics could be determinants of the short-term ineffectiveness of the initial tiotropium bromide monotherapy in treatment naïve moderate to severe COPD patients. METHODS: A total of 51 consecutively recruited COPD patients were followed for 3 months after the initial evaluation and prescribed initial treatment (tiotropium). Short-term treatment ineffectiveness was assessed as a composite measure comprising COPD exacerbations, need for additional treatment, and no improvement in functional parameters, e.g. 6­min walking test (6MWT), body-mass index, airflow obstruction, dyspnea, and exercise (BODE) index and forced expiratory volume in 1 s (FEV1), and as single components. RESULTS: Treatment ineffectiveness was significantly associated with baseline hemoglobin level, COPD assessment test (CAT) score, modified Medical Research Council (mMRC) scale and BODE index (p = 0.002). Incident exacerbation during the follow-up was associated with baseline bronchoalveolar lavage fluid (BALF) alpha-amylase level and CAT score (p < 0.001), and change in treatment with leukocyte count, 6MWT desaturation and fatigue (p < 0.001). No improvement in 6MWT was associated with baseline CAT score, body mass index, mMRC, fatigue, 6MWT and BODE index (p = 0.002). No improvement in BODE index was associated with leukocyte count, serum interleukin 8 (IL-8) and BALF albumin levels (p < 0.001); and no improvement in FEV1 with CAT score, baseline vital capacity and BALF tumor necrosis factor alpha (TNF-alpha) level (p < 0.001). CONCLUSION: Our results suggest that there is a possibility to identify predictors of short-term tiotropium ineffectiveness in patients with moderate to severe COPD.

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.

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.

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.

Diagnostic accuracy of a pocket screening spirometer in diagnosing chronic obstructive pulmonary disease in general practice: a cross sectional validation study using tertiary care as a reference.

BACKGROUND: COPD-6™ is a lung function testing device for a rapid pre-spirometry testing to screen-out at-risk individuals not having COPD and indicating those at risk. The aim of this study was to validate COPD-6™ lung function testing (index test) in general practice in discriminating patients with COPD out of the population at risk - smokers/ex-smokers with no previous diagnosis of COPD, using measurements at tertiary care as reference standard. METHODS: Consecutive 227 subjects (115 women, 185 smokers/42 ex-smokers, ≥20 pack-years) with no previous diagnosis of COPD, aged 52.5 (SD 6.8) years from 26 general practitioners (GPs) were recruited, lung function tested with COPD-6™, referred to the tertiary institution for repeated COPD-6™ testing followed by spirometry with a bronchodilator (salbutamol), examination, and pulmonologist consultation for the diagnosis and severity of COPD. RESULTS: COPD was diagnosed in 43 subjects (18.9 %), with an AUC of 0.827 (95 % CI 0.769-0.875, P < 0.001) for the diagnosis of COPD when lung function was measured using COPD-6™ in GP's office with a specificity of 100 % (95 % CI, 97.95-100 %) but a very low sensitivity of 32.56 % (95 % CI, 20.49-47.48 %). Significant agreement for forced expiratory volume in 1 s measured at GP's office and at lung function lab was found (mean difference 0.01 L, p = 0.667) but not for other measured parameters (p < 0.001 for all). CONCLUSIONS: Our study results point out that active case finding in a population at risk for COPD should be instituted (almost 20 % of undiagnosed COPD). Based on our results lung function testing with COPD-6™ can substitute spirometry testing in cases where it is not readily available to the patient/physician taken into account that the traditional FEV1/FEV6 cutoff value of <0.7 is not the only criterion for diagnosis and/or further referral. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01550679 Registered 28 September 2014, retrospectively registered.

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.

[Risk assessment for sleep apnea syndrome and excessive daytime sleepiness in patients with chronic obstructive pulmonary disease]. / Procjena rizika za sindrom apneje u spavanju i prekomjerne dnevne pospanosti u bolesnika oboljelih od kronicne opstruktivne pluíne bolesti.

AIM: The objective of this study was to examine the risk of sleep apnea syndrome in patients with chronic obstructive pulmonary disease (COPD) and to determine correlation with the associated cardiovascular comorbidity in these patients. Chronic and occasional sleep disturbances represent a problem for millions of people worldwide. COPD is a multisystem disease and the leading cause of mortality and morbidity in the world. It is estimated that it will be the third cause of death in the world by 2020. Poor quality of sleep in patients with COPD occurs as a result of reduced oxygen saturation, hypercapnia, and the use of auxiliary respiratory muscles. METHODS: The study included 47 patients with COPD, examined at the Department of Pulmonology, Clinical Department of Internal Medicine, Osijek University Hospital Center in 2011. The respondents answered questions from the Croatian version of the Snoring, Tired, Observed, Pressure (STOP) questionnaire, which examines the risk of sleep apnea syndrome, and the Epworth Sleepiness Scale, which examines excessive daytime sleepiness. The respondents also provided data related to the current smoking status, bronchodilation therapy they apply at home, the associated cardiovascular comorbidity related to coronary heart disease (previous myocardial infarction, angina pectoris), cerebrovascular incident, diabetes, asthma, gastroesophageal reflux disease (GERD) and anxiety-depressive disorder. RESULTS: According to the STOP questionnaire, the risk of sleep apnea syndrome was recorded in 35 (74.5%) respondents. Patients at risk had a higher frequency of comorbidities such as hypertension, diabetes mellitus type 2 and GERD. Excessive daytime sleepiness was recorded in 14.9% of patients with COPD and the mean daytime sleepiness scored 4.76 points. In patients at a high risk according to the STOP questionnaire, the mean daytime sleepiness was 6.24 points versus 3.72 points in the group at a low risk. Snoring was present in 23 (49%), excessive tiredness in 27 (57%), and cessation of breathing during sleep in every other person in 4 cases (8.5% of patients). The t-test showed no significant differences in oxygen saturation, partial O2 and CO2 pressures between the groups of non-risk and high-risk patients according to the STOP questionnaire. CONCLUSION: For assessing the risk of sleep apnea syndrome in patients with COPD, the STOP questionnaire as a screening method has a significant role. Because of the high risk of sleep apnea syndrome in patients with COPD and considering the high level of associated cardiovascular comorbidity, it is necessary to perform polysomnography in patients at risk for timely detection and treatment of the syndrome, thus preventing its harmful consequences, with special reference to reduction of mortality in this population.

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.