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.

Subacute invasive pulmonary aspergillosis as a rare cause of pneumothorax in immunocompetent patient: brief report.

Subacute invasive pulmonary aspergillosis (IPA) represents a form of chronic pulmonary aspergillosis which affects immunocompetent individuals or mildly immunocompromised persons with underlying pulmonary disease. Pneumothorax can be a rare complication of subacute IPA due to a leakage of air from an air-filled lung cavitation into the pleural space. Herein, we report rare and unusual case of pneumothorax in a patient with pulmonary cavity infection. A 40-year-old woman was admitted to thoracic surgery due to complete pneumothorax of the left lung. She was active smoker with untreated chronic obstructive pulmonary disease (COPD). After thoracic drainage multiple cavity forms in the both lungs were noticed. Galactomannan antigen was positive in bronchoalveolar lavage as well as culture of Aspergillus fumigatus. Antifungal treatment by voriconazole was started and continued during 6 months with a favorable outcome. This case highlights that subacute IPA is a diagnose that should be considered in patients with end-stage COPD, low body mass index, or patient who developed pneumothorax. The results of our case show that voriconazole is a safe and effective treatment as primary or salvage therapy in subacute forms of IPA, irrespective of the immunological status of the patients.

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.

Questionable Reliability of Homocysteine as the Metabolic Marker for Folate and Vitamin B12 Deficiency in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: An increased homocysteine (Hcy) concentration may represent a metabolic marker of folate and vitamin B12 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hcy concentration in predicting folate or vitamin B12 deficiency in these patients. METHODS: A group of 50 COPD patients (28 males/22 females, age (χ̄±SD=49.0±14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and χ2 tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. RESULTS: Average (SD) concentrations of folate and vitamin B12 were 4.13 (2.16) µg/L and 463.6 (271.0) ng/L, whereas only vitamin B12 correlated with the Hcy level (P=-0.310 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R=0.279 (P=0.047)). The incidence of folate and vitamin B12 deficiency differed significantly (P=0.000 and P<0.000 for folate and vitamin B12 respectively), depending on the cutoff used for classification (4.4, 6.6 and 8.0 µg/L - folate; 203 and 473 ng/L - vitamin B12). ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B12 deficiency. CONCLUSION: Reliability of the Hcy concentration as a biomarker of folate or vitamin B12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.

Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?

INTRODUCTION: Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone. SUBJECTS AND METHODS: 50 unrelated patients (28 males/22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests. RESULTS: AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZMmalton, 1 ZQ0amersfoort), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, Mmalton and Q0amersfoort, the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063). CONCLUSION: There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone.

Anti-TNF treatment and miliary tuberculosis in Crohn's disease.

INTRODUCTION: Tumour necrosis factor alpha (TNFalpha) has a central role in the host immune response to mycobacterial infection.TNFalpha blockade may therefore result in reactivation of recent or remotely acquired infection. In reported mycobacterium tuberculosis infections, extra-pulmonary and disseminated tuberculosis (TB) was common, appeared rapidly, and if unrecognized, with fatal outcome. We present a female patient with miliary TB following treatment with infliximab for fistulizing Crohn's disease. CASE OUTLINE: Five years before admission, the patient was diagnosed with Crohn's disease, with inflammation limited to the terminal ileum and sigmoid colon and has been on azathioprine 100 mg/day for the last 10 months. Three months before admission to the hospital she developed an enterocutaneous fistula for which therapy with infliximab was started in addition to azathioprine therapy. A tuberculin skin test and a chest x-ray were performed prior to the first infusion with normal findings. She presented with a 6-week history of fever, weakness, weight-loss and a 2-week dry cough. Chest x-ray and computed tomography displayed remarkable bilateral hilar and mediastinal lymphadenopathy and uniformly distributed fine nodules throughout both lung fields varying in size from 2 to 3 mm, without any signs of cavitation. Since there were clinical and morphological signs that indicated miliary TB, the treatment with antituberculous therapy was started and six weeks later all of the symptoms completely resolved and the lesions visible on x-ray diminished. CONCLUSION: The clinical use of TNF-inhibitors is associated with increased risk of developing tuberculosis. Physicians should be aware of the increased risk of reactivation of TB among patients treated with anti-TNF agents and regularly look for usual and unusual symptoms of TB.

Asthma and chronic bronchitis symptoms among adult population of Belgrade.

INTRODUCTION: Over the last three decades the prevalence of respiratory diseases has been increasing worldwide thus increasing economic burden on the healthcare system. Recent studies have shown that the prevalence of asthma in West European countries ranges from 6-9%, while of chronic obstructive pulmonary diseases (COPD) is 8.0% worldwide. OBJECTIVE: The aim of the study was to estimate the prevalence of respiratory symptoms and smoking habits, and to assess the prevalence of asthma and chronic bronchitis among adults in Belgrade, Serbia. METHODS: To collect data we used a questionnaire based on the European Community Respiratory Health Survey (ECRHS) protocol, which was mailed to 10,208 randomly selected subjects. RESULTS: There were 58.3% of responders to our questionnaire. We noted a higher prevalence of respiratory symptoms in subjects who responded promptly. The majority of the respondents were current or former smokers (37.5% and 17.5% respectively) and 79.9% of them reported respiratory symptoms. The most frequent symptoms were longstanding cough (32.2%), sputum production (30.4%) and wheezing (30.3%). Asthma attacks were reported in 4.4% of cases and 5.6% of subjects were using asthma medications. The prevalence of respiratory symptoms increased with age. Women reported coughing, attacks of breathlessness and coughing, chest tightness by night, allergic rhinitis and chronic coughing, more frequently than men. Productive cough was more frequent in men. The prevalence of almost all symptoms was higher in smokers compared to nonsmokers. CONCLUSION: In Serbia there is a high prevalence of respiratory symptoms, asthma and chronic bronchitis smoking addiction.

Health related quality of life regarding to gender in sarcoidosis.

Evaluation of the health-related quality of life (HRQoL) in patients with respiratory diseases has been increasingly included into regular clinical studies, and HRQL in sarcoidosis has been evaluated since not a long ago. The aim of the study was to evaluate HRQoL in patients with sarcoidosis regarding gender differences, pre and after therapy. We investigated 202 pathohistologically verified sarcoidosis patients (154 female and 48 male) without comorbidities. HRQL was assessed by the disease-specific Sarcoidosis Health Questionnaire (SHQ), which contains 29 items, and cover three domains: everyday functioning, physical activities and emotional state. Total score, as well as the scores for each SHQ domains were calculated. HRQoL was estimated pre and after three months of therapy. At the study start, the lowest score value for the whole group was reported in SHQ emotional state domain (4.24), and the highest in domain of physical functioning (4.7). After three months, the lowest values were reported in domain of everyday activities, while the highest scores were found in emotional domain; all SHQ scores increased, but reached the statistical significance only in the everyday functioning and the physical activities domains. Analyzing mean SHQ scores in male and female sarcoidosis pts before therapy we found high statistically lower emotional and total score in female pts, as well as lower physical score. After the three months therapy we found high statistical difference in physical domain (i.e. women had lower physical score than men). Female sarcoidosis pts showed lower emotional, physical and total score before therapy. After the three-month therapy we found that women had lower physical score than men. SHQ showed good measurement properties both in the cross-sectional and longitudinal assessment of sarcoidosis patients.

[Contemporary approach to the immunology of tuberculosis]. / Savremeni pogled na imunologiju tuberkuloze.

The human immune response to tuberculosis (TB) is a complex reaction to infection and represents an interaction of various components of cellular immunity, including numerous chemokines and cytokines. Precise balance of these factors most likely has a large impact on the body's ability to successfully contain infection. Continuous evaluation of research results regarding immunology of TB should lead to substantial advances in approaches to treatment by immunomodulation and prevention of tuberculosis with more effective vaccines.