Faculty of Medicine

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    Utility of exhaled nitric oxide in pediatric practice-review of literature.
    (Macedonian Association of Anatomists and Morphologists, 2019)
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    Popova, Gorica
    The field of interest for measurement of exhaled nitric oxide (NO) and nasal NO is significantly evolving over the last 25 years, with over 1000 publications published in that area. Inflammation of the airways is a central process in asthma and other lung disorders, but the monitoring of the inflammation has not been included in the current recommendations. The exhaled air contains volatile media such as nitric monoxide, carbon monoxide, ethane, pentane and non-volatile substances in the liquid phase in the exhalation, as a condensate (hydrogen peroxide). It is increasingly confirmed that the measurement of exhaled mediators in general, and especially NO, is a new way to monitor certain aspects of asthma, COPD and interstitial lung disease, which cannot be estimated with other methods, like lung function. In asthma, exhaled NO is recommended to be used as a marker for diagnosis, for monitoring the response of anti-inflammatory drugs, confirming the safety of therapy and predicting asthma exacerbation. Measurements of FeNO are easily performed, they are reproducible and technically less expensive than the analysis of induced sputum. In symptomatic patients, high FeNO levels (> 50 ppb), refer to significant eosinophilia in the airways, which will most likely respond to treatment with ICS. The current data provides support for the diagnostic use of FeNO in children with symptoms of asthma. For patients with chronic and/or severe asthma, FeNO levels are useful for determining whether eosinophilic inflammation of the airways is active or not. Both high (> 50ppb) and low (<25 ppb) levels of FeNO can be used to for predicting the outcome in patients with a definitive history of asthma who are currently in remission and who have stopped treatment with ICS.
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    Relationship between Vitamin D, Inflammation and Lung Function In Patients with Severe Uncontrolled Asthma
    (Scientific Foundation SPIROSKI, 2017-12-15)
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    Jovkovska-Kaeva, Biserka
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    Breskovska, Gorica
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    Goseva, Zlatica
    BACKGROUND:Recently epidemiological studies showed that low vitamin D is linked toairway hyperresponsiveness, decreasedlung function, poor asthma control, and steroid–resistant asthma.AIM:We investigatedtherelationshipbetween Vitamin D, inflammation with circulating IL-33 and lung function in 30 patients with severe uncontrolled asthma. MATERIALS AND METHODS:The study included 30 patients with severe uncontrolled asthma. In each of them were measured serum levels of IL-33 and Vitamin D by the ELISA method. The pulmonary function is measuredby basic spirometry parameters, FEV1. The results were statistically elaboratedaccording to the Pearson’s Correlation Tests. RESULTS:The results showed statistically insignificant correlation between Vitamin D and IL-33, and Vitamin D with FEV1 (Vit.D/IL-33; r=0.11323, p=0.551); (Vit.D/FEV1; r=-0.1005; p=0.597) Correlation between IL-33 and FEV1 is negative but statistically significant (IL-33/FEV1; r=-0.5248; p=0.003). CONCLUSION:Because there arelittle studies about the link between vitamin D and asthma, further research toclarify the mechanism how vitamin D control the activity of CD4+ T cells and the related Th2-type cytokines in the parthenogenesis of asthma.
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    Antibiotics use in relation to asthma in children
    (Wiley Blackwell, 2018-05)
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    Kimovska, M
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    Seckova, L
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    Background: Early-life antibiotic exposures have been reported to increase the risk of allergic diseases. The aim of the study was to examine the impact of current antibiotics use on asthma in schoolchildren in The Republic of Macedonia, as developing country with a high rate of antibiotics use and low prevalence of asthma. Method: Data from 2310 schoolchildren aged 5-15 years obtained through a parental-completed questionnaire in randomly selected primary schools in Skopje, the capital of Macedonia, in 2015/2016 was used. The frequency of antibiotics intake ≥3 and <3 times yearly vs never antibiotics intake for respiratory infections, in the last 12 months was correlated to current asthma-like symptoms and ever-diagnosed asthma after adjustment for confounding factors using multiple logistic regression. Results: 50.9% of the children used antibiotics currently and 21.0% out of them used antibiotics ≥3 times yearly. Current wheeze (W) was established in 6.5%, sleep-disturbing W in 3.6%, exercised-induced W in 1.7%, dry night cough apart from a cold in 12.2% and asthma in 2.3%. Current antibiotics use ≥3 times yearly was positively associated with current W (aOR: 13.37; 6.14-29.11; p < 0.001), sleep-disturbing W (aOR: 7.87; 3.34-18.57; p < 0.002), dry night cough (aOR: 3.80; 2.29-6.29; p <0.001), and diagnosed asthma (aOR: 5.68; 1.96-16.50; p = 0.001) while antibiotics use <3 times yearly was positively associated only with current W (p = 0.003) and dry night cough (p = 0.011). Conclusion: The results suggest an aggravating role of antibiotics use on asthma in school age thus further supporting the recommended restriction of antibiotics exposure.
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    Adaptation and validation of the pediatric asthma quality of life questionnaire in Macedonian children with asthma
    (2015-09)
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    Background: In order to better the control of asthma in the last decades, despit the use of clinical and pulmonary functional assessment, a lot of emphasis has been put on the assessment of quality of life (QL). The aim of the study was to evaluate the Macedonian version of the Pediatric Asthma Quality of Life Questionnaire (PAQLQ). Method: The study included 64 children with asthma from the ages ranging from 7 to 17 from a Macedonian nationality, treated in an ambulant or hospital facility within the University Children' s Hospital in Skopje in a time period of 2 years. The children were assess 3 times during a period of 3 months. To assess the control of the condition we used a Clinical Severity Score (CSS), and for the assessment of the QL we used the Macedonia version of the PAQLQ from Elizabeth Juniper which is contained od 23 questions organized into three domains: symptoms, activities and emotions. The results were analyzed with the appropriate statistical test. Result: There has been increase in the average values of the score of the PAQLQ, witch means better control of the asthma by the end of the 3 months. There was not a statistically significant difference (p>0,05) in the change of the QL and the age of the children with asthma in all the three domains and the overall score. Better scores on the PAQLQ were achieved by the children with persistent asthma, as well as the ones with better CSS. A significant correlation was determine between the assessed clinical parameters (asthma diary, FEV1, PEF and CCS) and the domain of activities, symptoms and overall score (p<0,05), and in the domain of emotions only in correlation to CSS (R=0,31). There was a significant improvement of all the scores of PAQLQ after the beginning of the anti-inflammatory therapy with ICS. According to CSS, at the end of the study all of the children were classified as stable (good QL), in contrast to beginning of the study witch was caracterized with 78% of stability. Conclusion: The Macedonian version of the PAQLQ shows exceptional validity, reliability, excellent responsiveness in the QL of the children with asthma. It can be used for the assessing of the condition, has good measurement properties for all children between 7 to 17, successfully assesses the effects of the anti-inflammatory therapy and achieves complete control of the condition. It is simple and easy for use and gives a new dimension to monitoring children with asthma.
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    Asthma Control Test™ in Assessment of Clinical Asthma Control
    (ID Design Press, 2009-12-01)
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    Tatjana Petrova
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    Snezana Risteska-Kuc
    Background. The goal of asthma treatment is to achieve and maintain control of the disease. Objective. To assess validity and reliability of Asthma Control TestTM (ACT) as a patient-based tool for quantifying the control of the disease in the subjects with persistent asthma. Methods. A cross-sectional study including 396 subjects with persistent asthma drown from a population of treated patients was performed. Evaluation of the examined subjects included completion of the ACT, spirometry, and asthma specialist rating of control. Results. The mean derived ACT score in all study subjects was 19.2±3.3. Prevalence of the study subjects with totally controlled (TC), well-controlled (WC) and not well-controlled (NWC) asthma by derived ACT score was 9.1%, 43.2% and 47.7%, respectively. Results from the spirometry showed that in 45% of the study subjects FEV1 value was less than 80%. Prevalence of the study subjects with TC, WC and NWC asthma by asthma specialist rating was 8.1%, 41.1% and 50.7%, respectively. A strong correlation between the derived ACT scores and asthma specialist rating of control was observed (r = 0.51, P = 0.000). Conclusion. Our data confirm the usefulness of the ACT as a valid and reliable screening tool for asthma control.
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    Exercise-related respiratory symptoms and exercise-induced bronchoconstriction in industrial bakers
    (Informa UK Limited, 2013)
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    In order to assess prevalence and characteristics of exercise-related respiratory symptoms (ERRS) and exercise-induced bronchoconstriction (EIB) in industrial bakery, the authors performed a cross-sectional study including 57 bakers and an equal number of office workers studied as a control. Evaluation of examined subjects included completion of a questionnaire, skin prick tests to common inhalant and occupational allergens, spirometry, and exercise and histamine challenge. The authors found a similar prevalence of ERRS and EIB in both bakers and controls. EIB was significantly associated with atopy, asthma, family history of asthma, and positive histamine challenge in either group, whereas in bakers it was closely related to sensitization to occupational allergens (p = .032). Bronchial reaction to exercise was significantly higher in bakers with EIB (25.7% vs 19.2%; p = .021). These findings suggest that occupational exposure in industrial bakery may accentuate bronchoconstrictive response to exercise.
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    Prevalence of the Respiratory Allergies among Adult Population in the City of Skopje in Relation to Climatic Change and Change in Pollen Micro Flora
    (Scientific Research Publishing, Inc., 2012)
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    Kendrovski, Vladimir
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    Milkovska, Snezana
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    Introduction: Climate change may have an impact of prevalence and severity of respiratory allergies causing changes in the concentrations, distribution, dispersion patterns, and allergenic potential of aeroallergens in the environment. Objective: To assess the prevalence of atopy, sensitization to common pollen allergens, and respiratory allergies (aller-gic rhinitis and asthma) among adult population in the city of Skopje in relation to changes in pollen distributions caused by climate change and particularly maximum temperature, in the period 1996-2010. Methods: Aeropalinologi-cal measurements in the city of Skopje were performed by volumetric method in the period 1996-2009. Serial cross-sectional studies on the prevalence of atopy, sensitization to common pollen allergens, allergic rhinitis and asthma in adults by standardized methodology were conducted in defined critical periods (1996, 2003, 2007/2008 and 2009/2010). Evaluation of examined subjects included completion of a questionnaire, skin prick tests (SPT) to common inhalant allergens, and lung function tests. Results: Data from aeropalinological measurements showed differences in the pollen concentrations, as well as in the duration of pollen season for some pollen types. The prevalence of atopics was similar in all critical periods, and the prevalence of sensitization to common pollen allergens was slightly higher in the last study than in the study performed in 1996. We registered increase in the prevalence of allergic rhinitis in the examined period (11.5% in 1996 to 17.4% in 2009/2010) followed by increase in the prevalence of rhinitics sensitized to common pollen allergens. The prevalence of allergic asthma was significantly higher in the study conducted in 2009/2010 than in the study conducted in 1996 (5.1% vs. 2.1%, P = 0.037) followed by slightly higher prevalence of asthmatics sensitized to common pollen allergens in the same period. Conclusions: Registered changes in the preva-lence of sensitization to common pollen allergens, as well as in the prevalence of subjects with respiratory allergies sen-sitized to these allergens, even statistically non-significant, indicate the need of further monitoring and investigation in order to assess the association between climate change with change in pollen micro flora and related allergic disorders.
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    RESPIRATORY SYMPTOMS, LUNG FUNCTION IMPAIRMENT, AND CHRONIC RESPIRATORY DISEASES AMONG CROP FARMERS: ASSESSMENT BY JOB EXPOSURE MATRICES
    (European Medical Group LTD, 2016-08)
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    Objective: To evaluate the prevalence of chronic respiratory symptoms, lung function impairment, and chronic obstructive respiratory diseases in crop farmers. Our objective is to then examine their relation to exposure duration, and to explore the usefulness of job exposure matrices as tools for exposure assessment, and predictors for respiratory health impairment. Methods: A cross-sectional study was performed, including 50 males (mean age: 45.4±10.7 years) employed as crop farmers (duration of exposure: 21.6±9.7 years) and 50 male office workers as a control group (mean age: 44.1±9.8 years) matched for age, smoking habits, and socioeconomic status. Methods of evaluating examined subjects included the completion of a questionnaire on respiratory symptoms in the last 12 months (cough, phlegm, dyspnoea, wheezing, chest tightness, and nasal symptoms), spirometry and histamine challenge (provocative concentration producing a 20% fall in forced expiratory volume in 1 second [FEV1]: ≤8 mg/mL), as well as use of job exposure matrices. Results: Crop farmers had a significantly higher prevalence of cough (29.4%), phlegm (16.7%), and wheezing (11.9%), than the control group (p<0.05). All spirometric parameters (forced vital capacity [FVC], FEV1, FEV1/FVC%, maximal expiratory flow (MEF) at 75%, 50%, and 25%) were lower in crop farmers compared to the control patients, but statistical significance was confirmed only for MEF at 25%, 50%, and 25–75% (p=0.021, p=0.011, and p=0.003, respectively). The prevalence of bronchial hyperresponsiveness, asthma, and chronic obstructive pulmonary disease was higher in crop farmers but without statistical significance. JEM were useful tools for exposure assessment and predictors of factors for asthma and COPD development. Conclusion: The results suggest that occupational exposure among crop farmers is associated with a higher prevalence of respiratory symptoms, lung function impairment, and a higher prevalence of chronic respiratory diseases.
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    Asthma and small airways
    (2016-10-29)
    Asthma is a chronic inflammatory disease of the airway characterized by episodic airway obstruction and increased bronchial responsiveness. The concept that inflammation is a major component of asthmatic pathology was establishe more than 100 years ago, but the attention had been focussed on the large asthmatic airways. That the distal airways and the lung parenchyma play a role in asthma has been suggested later. The distal airways have now been recognized as a predominant site of airflow obstruction in asthmatics. It is now accepted that in asthmatics, recruitment of inflammatory cells, in particular eosinophils and T cells, also occurs in the distal lung and the lung parenchyma.[In addition, in asthmatics there is an abundance of Th2-type cytokines and chemokines present at this distal site. The current therapeutic challenge is to develop better inhalation technologies to improve the delivery of anti-inflammatory agents to the lung periphery. This article aims to evaluate the pathological and physiological evidence presented in the literature to date, which outlines the contribution of the distal lung and the lung parenchyma to the pathophysiology of asthma.
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    LEUKOTRIENE RECEPTOR ANTAGONISTS IN MANAGING SEVERE UNCONTROLLED ASTHMA
    (European Medical Group, 2017-08-03)
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    Goseva, Zlatica
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    Gjorchev, Angelko