Implementation of the Baveno Classification in Obstructive Sleep Apnea and Its Correlation with Symptoms of Anxiety and Depression.

Background and Objectives: The Baveno classification represents a new approach to the assessment of the severity of OSA (Obstructive sleep apnea), which takes significant comorbidities into account: atrial fibrillation, arterial hypertension, heart failure, stroke, diabetes mellitus, and OSA symptoms expressed through the Epworth sleepiness scale (ESS). The authors believe that the Baveno classification facilitates a better stratification of patients with OSA and can be a good guide for deciding on the therapeutic approach and clinical monitoring of patients with OSA, compared to the AHI (apnea-hypopnea index) itself. The aim of this paper is to confirm the advantage of applying the Baveno classification to the evaluation of symptoms of anxiety and depression in the OSA patients compared to the application of the AHI as a single parameter. Materials and Methods: This research represents an observational retrospective study that was performed at the Pulmonology Clinic of the University Clinical Center in Kragujevac, Serbia. The study sample included 104 patients with diagnosed OSA. Patients were divided into four categories retrogradely according to the Baveno classification (A, B, C, and D). Statistical data processing was performed using the IBM SPSS Statistics version 25.0 program. Results: In our study, we proved that the Baveno classification is better at predicting the depressive disorder in OSA patients compared to the AHI itself, according to abnormal BDI-II (Beck Depression Inventory) score (value greater than ten) and HADS-D (Hospital anxiety and depression) scale (value greater than eight). The average AHI in the entire group of examined patients was 44.3 ± 19.8, while in category A the average AHI was 25.2 ± 10, in category B, 53.4 ± 20.6; in category C, 38.2 ± 18.5; and in category D, 48.1 ± 19.2. In the total sample, AHI did not correlate with the depressive episodes, but individually, the highest frequency of the depressive symptoms was precisely in the categories with the highest AHI (group D and B), where more than half of the subjects had an abnormal score. The frequency of the anxiety disorder (HADS-A) between the analyzed groups did not differ significantly, although the largest number of patients with significant anxiety were in category B, according to the Baveno classification. Conclusions: We proved that the Baveno classification is applicable in real life, and it is better at evaluating anxiety and depression using questionnaires and can identify new patients who need CPAP therapy, independently of other OSAS symptoms, primarily daytime sleepiness.

Risk factors for potential drug-drug interactions in patients with pneumonia.

OBJECTIVE: The goal of our study was to discover and analyze possible risk factors for and possible protective factors against the occurrence of potential drug-drug interactions (pDDIs) in a hospitalized patient with community-acquired pneumonia. MATERIALS AND METHODS: The central outcome was the incidence of pDDIs in patients with community-acquired pneumonia checked by Lexicomp and Micromedex interaction checkers. RESULTS: The most severe pDDIs (Consider therapy modification D/Avoid combination X/Major/Contraindicated) were found in 19 (20%) and 54 (58%) patients, according to Lexicomp and Micromedex, respectively. Patients with community-acquired pneumonia who were older, smokers, and with more prescribed drugs by more than a few independent prescribers had a higher risk to experience pDDIs. Possible protective factors were longer length of hospitalization, transfer from the Emergency Department, antiarrhythmic drugs as well as an anticoagulant therapy. CONCLUSION: In conclusion, community-acquired pneumonia patients with the above-mentioned factors should have their treatment more deeply monitored for pDDIs.

Cardiopulmonary Exercise Test in the Detection of Unexplained Post-COVID-19 Dyspnea.

There is emerging evidence of prolonged recovery in survivors of coronavirus disease 2019 (COVID-19), even in those with mild COVID-19. In this paper, we report a case of a 39-year-old male with excessive body weight and a history of borderline values of arterial hypertension without therapy, who was mainly complaining of progressive dyspnea after being diagnosed with mild COVID-19. According to the recent guidelines on the holistic assessment and management of patients who had COVID-19, all preferred diagnostic procedures, including multidetector computed tomography (CT), CT pulmonary angiogram, and echocardiography, should be conducted. However, in our patient, no underlying cardiopulmonary disorder has been established. Therefore, considering all additional symptoms our patient had beyond dyspnea, our initial differential diagnosis included anxiety-related dysfunctional breathing. However, psychiatric evaluation revealed that our patient had only a mild anxiety level, which was unlikely to provoke somatic complaints. We decided to perform further investigations considering that cardiopulmonary exercise test (CPET) represents a reliable diagnostic tool for patients with unexplained dyspnea. Finally, the CPET elucidated the diastolic dysfunction of the left ventricle, which was the most probable cause of progressive dyspnea in our patient. We suggested that, based on uncontrolled cardiovascular risk factors our patient had, COVID-19 triggered a subclinical form of heart failure (HF) with preserved ejection fraction (HFpEF) to become clinically manifest. Recently, the new onset, exacerbation, or transition from subclinical to clinical HFpEF has been associated with COVID-19. Therefore, in addition to the present literature, our case should warn physicians on HFpEF among survivors of COVID-19.

Does the Severity of Obstructive Sleep Apnea Have an Independent Impact on Systemic Inflammation?

Background and Objectives: This paper aims to show whether obstructive sleep apnea (OSA) severity increases the level of systemic inflammation markers regardless of body mass index (BMI) and body composition. Materials and Methods: In total, 128 patients with OSA were included in the study. Examinees were divided into two groups: one with mild OSA (apnea-hypopnea index (AHI) < 15) and one with moderate and severe OSA (AHI ≥ 15). Nutritional status was assessed using body mass index, body composition by dual X-ray absorptiometry. Systemic inflammation was assessed on the basis of plasma concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and serum level of C-reactive protein (CRP). Results: We found elevated mean values of the evaluated systemic inflammation markers (CRP, TNF-α, IL-6) in a group with AHI ≥ 15, although there was no statistical significance. Our research found a significant positive correlation with BMI (r = 0.633, p < 0.001), as well as with body fat percentage (r = 0.450, p = 0.024) and serum CRP values. Significant correlation was found between the plasma IL-6 concentration and body fat percentage (FM%) (r = 0.579, p = 0.003) and lean body mass (r = -0.501, p = 0.013). Multivariate regression analysis did not show any independent predictor (parameters of OSA, nutritional status, body composition) of the systemic inflammation markers. Conclusions: Neither one tested parameter (nutritional status and body composition) of the severity of OSA was identified as an independent prognostic factor for the severity of systemic inflammation in patients with OSA.

Effects of combustible cigarettes and heated tobacco products on immune cell-driven inflammation in chronic obstructive respiratory diseases.

Since long-term effects of heated tobacco products (HTP) on the progression of chronic obstructive pulmonary disease (COPD) are unknown, we used COPD mice model to compare immune cell-dependent pathological changes in the lungs of animals which were exposed to HTP or combustible cigarettes (CCs). We also performed intracellular staining and flow cytometry analysis of immune cells which were present in the blood of CCs and HTP users who suffered from immune cell-driven chronic obstructive respiratory diseases. CCs enhanced NLRP3 inflammasome-dependent production of inflammatory cytokines in lung-infiltrated neutrophils and macrophages and increased influx of cytotoxic Th1, Th2 and Th17 lymphocytes in the lungs of COPD mice. Similarly, CCs promoted generation of inflammatory phenotype in circulating leukocytes of COPD patients. Opposite to CCs, HTP favored expansion of immunosuppressive, IL-10-producing, FoxP3-expressing T, NK and NKT cells in inflamed lungs of COPD mice. Compared to CCs, HTP had weaker capacity to promote synthesis of inflammatory cytokines in lung-infiltrated immune cells. Significantly lower number of inflammatory neutrophils, monocytes, Th1, Th2 and Th17 lymphocytes were observed in the blood of patients who consumed HTP than in the blood of CCs users, indicating different effects of CCs and HTP on immune cells' phenotype and function.

Psychophysical and Social Functioning of Patients with Chronic Obstructive Lung Disease and Depression.

The relationship between depression and chronic obstructive pulmonary disease (COPD) is not fully understood. The comorbidity rate ranges from 18 to 84%, and depression is closely related to chronic inflammation, which affects how patients and the people around them perceive their condition. This study aims to examine the relationship between the psychophysical and social functioning of COPD patients who have been diagnosed with depression and the therapeutic benefits of selective serotonin reuptake inhibitors (SSRIs). This prospective study enrolled primary care patients diagnosed with COPD and depression. The entire period of this research was 3 years. The research was conducted at the Primary Health Center, Kragujevac, Serbia, in 87 patients for 8 weeks. The Hamilton Depression Scale (HAM-D) and Questionnaire for Quality of Life and Life Satisfaction Short Form (Q-LES-Q-SF) were used for psychiatric assessment. A positive correlation was found between the psychophysical and social functioning of the participants after 8 weeks of treatment with SSRIs. Based on the value of the phi correlation coefficient (phi = 0.5) obtained using the χ2 test, a large influence was observed in terms of life satisfaction and physical health (p < 0.05). In terms of physical functioning by gender, based on the value of the Pearson's coefficient (r) obtained with the χ2 test, it was shown that physical functioning was superior in the female respondents (p < 0.05). Treatment was found to improve depression in COPD after 8 weeks of therapy.

The functional consequences in severe and critical covid-19 survivors - A pilot study.

PURPOSE: To perform pulmonary function tests (PFT) in severe COVID-19 survivors one and five months after hospital discharge in order to assess the lung function, as well to identify clinical characteristics and PFT parameters associated with worse cardiopulmonary exercise testing (CPET). MATERIAL AND METHODS: A prospective study included 75 patients with severe form of COVID-19. PFT was conducted one and five months after hospital discharge, in addition to CPET in a second assessment. Patients with a previous history of chronic respiratory diseases were excluded from our study. RESULTS: One month after hospital discharge, all examined patients had diffusion lung capacity for carbon-monoxide(DLco%) below the 80% of predicted values (in mean 58%), with 40% of patients having a restrictive pattern (total lung capacity(TLC) < 80%). In a repeated assessment after five months, pathological DLco% persisted in 40% of patients, while all other PFT parameters were normal. CPET showed reduced maximum oxygen consumption during exercise testing (VO2peak%) values in 80% of patients (in mean 69%), and exercise ventilatory inefficiency in 60%. Patients with VO2peak < 60% had significantly lower values of examined PFT parameters, both one and five months after hospital discharge. Patients with VO2peak% ≥ 60% had a significantly higher increase after the second assessment for Forced expiratory volume in 1st second (FEV1%), Forced expiratory volume in 1st second and forced vital capacity ratio (FEV1/FVC), DLco% and Diffusion lung capacity for carbon monoxide corrected for alveolar volume (DLco/VA). CONCLUSION: Significant functional abnormalities, according to PFT and CPET, was present both one and five months in severe COVID-19 survivors, thus emphasizing the importance of a comprehensive follow-up including both resting and dynamic functional assessment in these patients.

Anthropometric Measurements and Admission Parameters as Predictors of Acute Respiratory Distress Syndrome in Hospitalized COVID-19 Patients.

Aim: We aimed to single out admission predictors of acute respiratory distress syndrome (ARDS) in hospitalized COVID-19 patients and investigate the role of bioelectrical impedance (BIA) measurements in ARDS development. Method: An observational, prospective cohort study was conducted on 407 consecutive COVID-19 patients hospitalized at the University Clinical Center Kragujevac between September 2021 and March 2022. Patients were followed during the hospitalization, and ARDS was observed as a primary endpoint. Body composition was assessed using the BMI, body fat percentage (BF%), and visceral fat (VF) via BIA. Within 24 h of admission, patients were sampled for blood gas and laboratory analysis. Results: Patients with BMI above 30 kg/m2, very high BF%, and/or very high VF levels were at a significantly higher risk of developing ARDS compared to nonobese patients (OR: 4.568, 8.892, and 2.448, respectively). In addition, after performing multiple regression analysis, six admission predictors of ARDS were singled out: (1) very high BF (aOR 8.059), (2) SaO2 < 87.5 (aOR 5.120), (3) IL-6 > 59.75 (aOR 4.089), (4) low lymphocyte count (aOR 2.880), (5) female sex (aOR 2.290), and (6) age < 68.5 (aOR 1.976). Conclusion: Obesity is an important risk factor for the clinical deterioration of hospitalized COVID-19 patients. BF%, assessed through BIA measuring, was the strongest independent predictor of ARDS in hospitalized COVID-19 patients.

COVID-19 vaccination acceptance, safety and side-effects in European patients with severe asthma.

Background: Vaccination is vital for achieving population immunity to severe acute respiratory syndrome coronavirus 2, but vaccination hesitancy presents a threat to achieving widespread immunity. Vaccine acceptance in chronic potentially immunosuppressed patients is largely unclear, especially in patients with asthma. The aim of this study was to investigate the vaccination experience in people with severe asthma. Methods: Questionnaires about vaccination beliefs (including the Vaccination Attitudes Examination (VAX) scale, a measure of vaccination hesitancy-related beliefs), vaccination side-effects, asthma control and overall safety perceptions following coronavirus disease 2019 (COVID-19) vaccination were sent to patients with severe asthma in 12 European countries between May and June 2021. Results: 660 participants returned completed questionnaires (87.4% response rate). Of these, 88% stated that they had been, or intended to be, vaccinated, 9.5% were undecided/hesitant and 3% had refused vaccination. Patients who hesitated or refused vaccination had more negative beliefs towards vaccination. Most patients reported mild (48.2%) or no side-effects (43.8%). Patients reporting severe side-effects (5.7%) had more negative beliefs. Most patients (88.8%) reported no change in asthma symptoms after vaccination, while 2.4% reported an improvement, 5.3% a slight deterioration and 1.2% a considerable deterioration. Almost all vaccinated (98%) patients would recommend vaccination to other severe asthma patients. Conclusions: Uptake of vaccination in patients with severe asthma in Europe was high, with a small minority refusing vaccination. Beliefs predicted vaccination behaviour and side-effects. Vaccination had little impact on asthma control. Our findings in people with severe asthma support the broad message that COVID-19 vaccination is safe and well tolerated.

The effects of respiratory exercises on partial pressures of gases and anxiety in the acute phase of COVID-19 infection.

INTRODUCTION: Respiratory exercise in post-COVID-19 significantly improves pulmonary function, exercise capacity and quality of life. Our study aimed to investigate the effect of respiratory exercise on partial pressures of oxygen, carbon dioxide and oxygen saturation in arterial blood and anxiety assessed by the GAD-7 scale in the acute phase of COVID-19 infection. METHODS: The study was conducted at the Clinical Center, Kragujevac, from June to July 2020. The study was a prospective clinical trial and included 62 patients with the acute-phase of COVID-19 infection (61.3% males, mean age 60.82 ± 11.72). The duration of the comprehensive pulmonary rehabilitation program was 14 days ± 2.28 days. Oxygen saturation and heart rate were determined by using the pulse oximeter, oxygen flow, and arterial blood gas analysis values by using the gas analyzer. The anxiety assessment was measured using the Generalized Anxiety Disorder (GAD-7). RESULTS: The values of oxygen saturation significantly differed before and after the respiratory exercise sessions (95.77 vs 98.02, respectively; p < .001). After the respiratory exercise program, significantly lower values of the GAD-7 scale were observed compared to the values before the respiratory exercise program (p = .049). A significant negative correlation was observed between oxygen saturation after respiratory exercise and age and presence of chronic obstructive pulmonary disease (ρ = -0.329; p = .013; ρ = -0.334; p = .009, respectively). GAD-7 score after respiratory exercise negatively correlated with chronic obstructive pulmonary disease and malignancy (ρ = -0.285; p = .025; ρ = -0.350; p = .005, respectively). CONCLUSION: The respiratory exercise program significantly improves oxygen saturation and anxiety levels in COVID-19 patients.

The Role of Bioelectrical Impedance Analysis in Predicting COVID-19 Outcome.

Background: Published data regarding the impact of obesity on COVID-19 outcomes are inconsistent. However, in most studies, body composition was assessed using body mass index (BMI) alone, thus neglecting the presence and distribution of adipose tissue. Therefore, we aimed to investigate the impact of body and visceral fat on COVID-19 outcomes. Methods: Observational, prospective cohort study included 216 consecutive COVID-19 patients hospitalized at University Clinical Center Kragujevac (Serbia) from October to December 2021. Body composition was assessed using the BMI, body fat percentage (%BF), and visceral fat (VF) via bioelectrical impedance analysis (BIA). In addition to anthropometric measurements, variables in the research were socio-demographic and medical history data, as well as admission inflammatory biomarkers. Primary end-points were fatal outcomes and intensive care unit (ICU) admission. Results: The overall prevalence of obesity was 39.3% according to BMI and 50.9% according to % BF, while 38.4% of patients had very high VF levels. After adjusting odds ratio values for cofounding variables and obesity-related conditions, all three anthropometric parameters were significant predictors of primary end-points. However, we note that % BF and VF, compared to BMI, were stronger predictors of both mortality (aOR 3.353, aOR 3.05, and aOR 2.387, respectively) and ICU admission [adjusted odds ratio (aOR) 7.141, aOR 3.424, and aOR 3.133, respectively]. Conclusion: Obesity is linked with COVID-19 mortality and ICU admission, with BIA measurements being stronger predictors of outcome compared to BMI use alone.

Diagnosis and treatment of adult asthma patients in Serbia: a 2022 experts group position statement.

INTRODUCTION: Asthma is the most common non-communicable chronic lung condition across all ages. Epidemiological data indicate that many asthma patients in Serbia remain undiagnosed and untreated. The implementation of recent global advances in asthma management is limited due to the lack of a systematic approach, drug availability and regulatory affairs. In addition, the global coronavirus disease pandemic has posed a significant challenge, particularly in resource-limited settings. AREAS COVERED: In this paper, we propose an algorithm for treating adult asthma patients in Serbia. We performed PubMed database search on published asthma clinical trials and guidelines from 1 January 2015 to 10 March 2020. The consensus process incorporated a modified Delphi method that included two rounds of e-mail questionnaires and three rounds of national asthma expert meetings. We focus on 1) objective diagnosis of asthma, 2) the implementation of up-to-date therapeutic options, and 3) the identification and referral of severe asthma patients to newly established severe asthma centers. EXPERT OPINION: Regional specificities and variations in healthcare systems require the adaptation of evidence-based knowledge. Practical, clinically oriented algorithms designed to overcome local barriers in healthcare delivery may facilitate timely and adequate asthma diagnosis and the local implementation of current advances in asthma management.

Admission Predictors of Mortality in Hospitalized COVID-19 Patients-A Serbian Cohort Study.

Background: Early prediction of COVID-19 patients' mortality risk may be beneficial in adequate triage and risk assessment. Therefore, we aimed to single out the independent morality predictors of hospitalized COVID-19 patients among parameters available on hospital admission. Methods: An observational, retrospective−prospective cohort study was conducted on 703 consecutive COVID-19 patients hospitalized in the University Clinical Center Kragujevac between September and December 2021. Patients were followed during the hospitalization, and in-hospital mortality was observed as a primary end-point. Within 24 h of admission, patients were sampled for blood gas and laboratory analysis, including complete blood cell count, inflammation biomarkers and other biochemistry, coagulation parameters, and cardiac biomarkers. Socio-demographic and medical history data were obtained using patients' medical records. Results: The overall prevalence of mortality was 28.4% (n = 199). After performing multiple regression analysis on 20 parameters, according to the initial univariate analysis, only four independent variables gave statistically significant contributions to the model: SaO2 < 88.5 % (aOR 3.075), IL-6 > 74.6 pg/mL (aOR 2.389), LDH > 804.5 U/L (aOR 2.069) and age > 69.5 years (aOR 1.786). The C-index of the predicted probability calculated using this multivariate logistic model was 0.740 (p < 0.001). Conclusions: Parameters available on hospital admission can be beneficial in predicting COVID-19 mortality.

The effect of the COVID-19 pandemic on severe asthma care in Europe: will care change for good?

Background: The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods: In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results: 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions: Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.

Obesity and sleep apnea as a significant comorbidities in COVID-19 - A case report.

In our paper we aimed to increase the awareness among physicians, concerning coronavirus disease 2019 (COVID-19) severity, especially in patients with specific underlying comorbidities. Obesity is the second most common condition in hospitalized COVID-19 patients. Furthermore it has a major role in the development of obstructive sleep apnoea (OSA), which is highly involved in a severe COVID-19 development and its serious outcomes. Even though obese OSA patients had an increased pulmonary embolism (PE) risk, there is no enough evidence to support the interaction between obesity and OSA regarding PE development in the setting of COVID-19. Our patient is a 45-year-old obese male with COVID-19, who was admitted to the intensive care unit (ICU) with acute respiratory failure requiring high-flow nasal oxygenation. Clinical, laboratory and diagnostic findings pointed on severe COVID-19 form, complicated with PE. After recovery, the diagnosis of OSA was established. With this case, we wanted to alert the physicians on comorbidities, such as obesity and OSA, while those conditions, to some extent, may contribute to worse COVID-19 clinical presentation.

Predicting Severity and Intrahospital Mortality in COVID-19: The Place and Role of Oxidative Stress.

SARS-CoV-2 virus causes infection which led to a global pandemic in 2020 with the development of severe acute respiratory syndrome. Therefore, this study was aimed at examining its possible role in predicting severity and intrahospital mortality of COVID-19, alongside with other laboratory and biochemical procedures, clinical signs, symptoms, and comorbidity. This study, approved by the Ethical Committee of Clinical Center Kragujevac, was designed as an observational prospective cross-sectional clinical study which was conducted on 127 patients with diagnosed respiratory COVID-19 viral infection from April to August 2020. The primary goals were to determine the predictors of COVID-19 severity and to determine the predictors of the negative outcome of COVID-19 infection. All patients were divided into three categories: patients with a mild form, moderate form, and severe form of COVID-19 infection. All biochemical and laboratory procedures were done on the first day of the hospital admission. Respiratory (p < 0.001) and heart (p = 0.002) rates at admission were significantly higher in patients with a severe form of COVID-19. From all observed hematological and inflammatory markers, only white blood cell count (9.43 ± 4.62, p = 0.001) and LDH (643.13 ± 313.3, p = 0.002) were significantly higher in the severe COVID-19 group. We have observed that in the severe form of SARS-CoV-2, the levels of superoxide anion radicals were substantially higher than those in two other groups (11.3 ± 5.66, p < 0.001) and the nitric oxide level was significantly lower in patients with the severe disease (2.66 ± 0.45, p < 0.001). Using a linear regression model, TA, anosmia, ageusia, O2 -, and the duration at the ICU are estimated as predictors of severity of SARS-CoV-2 disease. The presence of dyspnea and a higher heart rate were confirmed as predictors of a negative, fatal outcome. Results from our study show that presence of hypertension, anosmia, and ageusia, as well as the duration of ICU stay, and serum levels of O2 - are predictors of COVID-19 severity, while the presence of dyspnea and an increased heart rate on admission were predictors of COVID-19 mortality.

Risk factors for potential drug-drug interactions in patients with chronic obstructive pulmonary disease.

Potential drug-drug interactions (pDDIs) are especially frequent in patients with chronic obstructive pulmonary disease (COPD) who, if hospitalized, experience, on average 6.5 pDDIs on admission, and 7.2 on discharge. The aim of our study was to identify and analyze risk and/or protective factors for occurrence of pDDIs in hospitalized patients with COPD. Main outcome was occurrence of pDDIs in COPD patients ascertained by Medscape, Epocrates, and Micromedex interaction checkers. The most serious pDDIs (contraindicated/serious/major/use alternative) were found in 16 (22%), 8 (11%), and 35 (49%) patients, according to the Medscape, Epocrates, and Micromedex, respectively. The COPD patients who were prescribed more drugs (especially antiarrhythmic and anticoagulants), by several independent prescribers, and having more comorbidities, were more prone to experience a pDDI; the only protective factor against pDDIs was age of the patients. In conclusion, COPD patients with the abovementioned risk factors should have their therapy more intensely monitored for pDDIs.

Diagnosis and management of chronic obstructive pulmonary disease in Serbia: an expert group position statement.

In recent years, several national chronic obstructive pulmonary disease (COPD) guidelines have been issued. In Serbia, the burden of COPD is high and most of the patients are diagnosed at late stages. Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy is poorly implemented in real-life practice, as many patients are still prescribed inhaled corticosteroids (ICS)-containing regimens and slow-release theophylline. In this document, we propose an algorithm for treating COPD patients in Serbia based on national experts' opinion, taking into account global recommendations and recent findings from clinical trials that are tailored according to local needs. We identified four major components of COPD treatment based on country specifics: active case finding and early diagnosis in high-risk population, therapeutic algorithm for initiation and escalation of therapy that is simple and easy to use in real-life practice, de-escalation of ICS in low-risk non-exacerbators, and individual choice of inhaler device based on patients' ability and preferences. With this approach we aim to facilitate implementation of the recommendation, initiate the treatment in early stages, improve cost-effectiveness, reduce possible side effects, and ensure efficient treatment.

Influence of inhaler technique on asthma and COPD control: a multicenter experience.

BACKGROUND: The successful management of asthma and chronic obstructive pulmonary disease (COPD) mostly depends on adherence to inhalation drug therapy, the usage of which is commonly associated with many difficulties in real life. Improvement of patients' adherence to inhalation technique could lead to a better outcome in the treatment of asthma and COPD. OBJECTIVE: The aim of this study was to assess the utility of inhalation technique in clinical and functional control of asthma and COPD during a 3-month follow-up. METHODS: A total of 312 patients with asthma or COPD who used dry powder Turbuhaler were enrolled in this observational study. During three visits (once a month), training in seven-step inhalation technique was given and it was practically demonstrated. Correctness of patients' usage of inhaler was assessed in three visits by scoring each of the seven steps during administration of inhaler dose. Assessment of disease control was done at each visit and evaluated as: fully controlled, partially controlled, or uncontrolled. Patients' subjective perception of the simplicity of inhalation technique, disease control, and quality of life were assessed by using specially designed questionnaires. RESULTS: Significant improvement in inhalation technique was achieved after the third visit compared to the first one, as measured by the seven-step inhaler usage score (5.94 and 6.82, respectively; P<0.001). Improvement of disease control significantly increased from visit 1 to visit 2 (53.9% and 74.5%, respectively; P<0.001) and from visit 2 to visit 3 (74.5% and 77%, respectively; P<0.001). Patients' subjective assessment of symptoms and quality of life significantly improved from visit 1 to visit 3 (P<0.001). CONCLUSION: Adherence to inhalation therapy is one of the key factors of successful respiratory disease treatment. Therefore, health care professionals should insist on educational programs aimed at improving patients' inhalation technique with different devices, resulting in better long-term disease control and improved quality of life.

ECTOPIC ACTH SECRETION WITH CONCOMITANT HYPERAMYLASEMIA IN A PATIENT WITH SMALL CELL LUNG CARCINOMA: CASE REPORT.

Histologically confirmed small cell lung cancer associated with Cushing's syndrome and elevated amylase is rarely described in the literature. We present a case of a 63-year-old patient admitted to cardiology department due to shortness of breath, exhaustion, palpitations and nausea. Elevated values of troponin and electrocardiography suggested that he could have acute coronary syndrome. According to the radiologist's opinion, plane lung radiography was normal. Elevated level of amylase was found in both serum (3802 U/L, normal range 28-100) and urine (12012 U/L, normal range 0-450 U/L), as well as elevated sodium (156 mmol/L, normal range 137-147 mmol/L), hyperglycemia (12 mmol/L, normal range 3.8-6.1 mmol/L) and lowered serum potassium (1.7 mmol/L, normal range 3.5-5.3 mmol/L). Computerized tomography (CT) of the abdomen revealed a tumor of the left adrenal gland and enlargement of the right adrenal gland with normal structure of the pancreas. During hospitalization, the patient had blood while coughing and CT scan of the lungs showed a tumor 48x38x51 mm in size localized in the laterobasal segment of the left lung with mediastinal lymphadenopathy. He also had bilateral pleural effusions with signs of pulmonary embolism, which explained elevated troponin values. Biopsy confirmed microcellular lung carcinoma and tumor cells were diffusely positive for TTF-1 and focally for CK7, expressing markers of neuroendocrine differentiation (chromogranin +++, synaptophysin +++, NSE ++). Since neuroendocrine tumor was confirmed and the patient had low potassium and high glucose, hypercortisolism was suspected. High morning cortisol (1784 mmol/L, normal range 171-536) and unsuppressed ACTH (214 pg/L, < 60), as well as a high level of chromogranin (1339 µg/L, < 65) were determined. During hospital stay, the patient developed heart and respiratory failure and died in the second week of hospitalization.