Background: Despite multistep efforts, many asthma patients remain symptomatic. Anti-inflammatory activities of curcumin are shown. Aim of the study was to analyse the impact of curcumin add-on therapy on inflammatory parameters, lung function, disease control and quality of life in asthma patients. Subjects and methods: Three-months lasting study was done on 150 non-smokers with asthma, that were treated with stable, moderate dose of inhaled glucocorticoids (IGK) and divided into three groups (n=50 each): curcumin group (receiving curcumin 500 mg per os twice daily), placebo group (receiving placebo tablets) and control (non-intervention) group. Sputum eosinophils (sEo), blood eosinophils (bEo), high sensitive C-reactive protein (hsCRP), predicted forced expiratory volume in first second (FEV1%), Asthma Control Test (ACT) and mini Asthma Quality of Life Questionnaire (mAQLQ) were compared before and after study, as well as between groups. Results: Before study, all followed parameters were similar between groups. After study, FEV1%, ACT and AQLQ were improved in all groups, but these improvements were more prominent in curcumin group than in placebo and control. Additionally curcumin group only showed improvement in sEo, bEo and hsCRP. Furthermore, curcumin group showed more frequent clinically significant improvement in ACT score (change>3) and in mAQLQ score (change≥0.5) when compared to placebo and control. On the other side, after study FEV1%, ACT, mAQLQ, hsCRP, sEo and bEo were similarly distributed among placebo and control group. Conclusion: This is the first placebo controlled and single-blind study to suggest that add-on therapy with curcumin could improve lung function, disease control and quality of life in moderate partially controlled asthma. Future studies may benefit from a larger sample size, longer study duration, double blind design, different dose of curcumin and/or improvements in oral bioavailability.

Introduction: Although the skin prick test (SPT) is a reliable diagnostic tool in perennial allergic rhinitis (PER) for patients allergic to cats, the minimum necessary SPT wheal size required to distinguish cat sensitization from true allergy remains controversial. The cat nasal challenge test (cNCT) could be considered the gold standard for detecting true cat allergy. Aims: To assess the difference in the frequency of cNCT positivity between cat owners and non-owners and to determine an appropriate cut-off level for SPT wheal size in detecting positive cNCT in PER patients who are candidates for allergen immunotherapy (AIT) with cat allergen extracts. Subjects and Methods: cNCT in the form of a nasal spray was administered to 60 adult patients with PER, i.e., cat owners (n = 19) and cat non-owners (n = 41) with positive SPT to cat fur allergen (Diater, Spain). Subjective (total nasal symptom score [TNSS]) and objective measurements (peak nasal inspiratory flow [PNIF]) for assessment of nasal patency and nasal eosinophil count [NEo]) were used to assess the nasal response. Peak expiratory flow (PEF) was used as a safety parameter during cNCT. Results: No differences were obtained in SPT wheal size and cNCT positivity between cat owners and non-owners. Positive cNCT detecting true cat allergy could be predicted by a cat SPT wheal size > 6.5 mm with 71.11% sensitivity and 100% specificity. Conclusions: In adult patients with PER, the frequency of cat allergy was similar among cat owners and non-owners. A cat SPT wheal size ≥6.5 mm could be helpful in detecting true cat allergy by avoiding the demanding, time-consuming, and often unavailable cNCT when cat AIT is needed.

Aim To assess efficacy of omalizumab in moderate to severe asthma and notable factors affecting it, such as treatment compliance during the period of ten years. This retrospective, observational real life study is the first of this kind in the Gulf region and one of the worldwide rare long term omalizumab treatment studies. Methods The treatment for 35 patients started in 2008. Twenty patients (ongoing group) proceeded with treatment and were assessed annually until 2017. Reasons for treatment discontinuation in 15 patients (drop-out group) were also assessed. Results Before starting omalizumab the ongoing group of patients had history of ≥2 asthma exacerbations per year, which significantly decreased during the first year of the treatment (p<0.001), and for 14 (70%) patients ≤1 exacerbation stayed during the next 10 years. Since 2014 six (30%) patients had had ≥2 annual asthma exacerbations (p<0.05 in 2013; p<0.05 in 2014; p<0.001 in 2015; p<0.01 in 2016; p<0.001 in 2017). At the same time there was a significant drop in compliance index (CI) (p<0.0001). Conclusion To our knowledge this is the first 10-year study of compliance and effectiveness, which may help finalize some practical suggestions to improve CI in clinical practice and to note acceptable variation in CI. It is important to recognize factors that can possibly affect effectiveness of the treatment and identify the patients who will have the best benefit from a long term omalizumab treatment.

BACKGROUND: There is a lack of data related to real life, long-term safety, tolerability and compliance of omalizumab treatment in asthma patients beyond 6 years. AIM: Study aimed to assess safety, tolerability, compliance and all reasons for treatment discontinuation during 10 years on omalizumab. SUBJECT AND METHODS: This is a retrospective, observational study of uncontrolled asthma patients receiving omalizumab for the last 10 years. All data were collected from patients’ files (demographics, adverse events, comorbidities, compliance index, reasons for discontinuation of omalizumab). Reactions to omalizumab were classified as local and systemic, and their severity as mild, moderate or severe. Reactions were either immediate (minutes to hours after drug administration) or delayed (after days). Compliance to omalizumab, defined as Compliance index (CI), was calculated by comparing milligrams of given to milligrams of prescribed dose/ per year. RESULTS: Out of 35 patients receiving omalizumab, 15 drop out at different time points mostly due to treatment efficacy or appearance of new comorbidities. Patients who continue for the next ten years had mild to moderate adverse events related to omalizumab. There was no increased risk of severe adverse events during 10 years on omalizumab. Patient’s treatment tolerability, despite mild to moderate adverse events, is in favour of compliance. CONCLUSION: Compliance with omalizumab mildly decreased over 10 years but was not affected by severe adverse events of treatment or new comorbidities. Although, omalizumab is safe medicine appearance of new comorbidities has to be closely followed up.

SUMMARY – Multifocal motor neuropathy (MMN) is a chronic demyelinating neuropathy mainly characterized by multifocal distribution; affecting only motor nerve fibers of two or more peripheral nerves, with the absence of symptoms and signs of upper motor neuron; chronic, sometimes cascading progressive course; demyelination with partial block of motor conduction; immune-mediated pathogenesis and good response to intravenous immunoglobulin treatment (IVIG). The diagnosis of MMN is based on clinical, laboratory and electrophysiological characteristics. Steroids are ineffective in MMN and may lead to worsening of the disease. Similarly, therapeutic plasma exchange is negligibly effective in this neuropathy. However, more than 80% of patients with MMN experience improvement after IVIG. We present our three cases of MMN with positive response to IVIG.

Objective: To evaluate the long-term efficacy and safety of omalizumab in asthma in a real-life setting. Subjects and Methods: This 4-year observational study included 65 patients treated with omalizumab during clinic visits; treatment response was rated as excellent, good, and partial based on a modified physician’s Global Evaluation of Treatment Effectiveness (mGETE) scale of emergency room visits (ERV), hospitalization, use of oral corticosteroids, inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) dose, and short-acting β-agonist rescue. The following tests were done: forced expiratory volume in 1 s (FEV1) and the asthma control test (ACT). Measurements were performed 1 month before therapy and at 16 weeks, 1 year, and 4 years of treatment. Statistical analyses were done using the Wilcoxon signed-rank test, Spearman rank correlation, and McNemar χ2 test. Results: The dropout rate was 15 (18.5%): 8 nonresponders (10.0%); 2 patients died (2.5%), and 5 were lost to follow-up (6.25%). Treatment response was excellent in 35 (53.8%); good in 23 (35.4%), and partial in 7 patients (10.8%). The number of excellent responders increased from 35 (53.8%) at 16 weeks to 48 (73.8%) at the 4-year follow-up. The number of patients who did not require ERV improved from 0 to 59 (90.8%), and the lowest rate of hospitalization was 1 in year 4 (p < 0.001); patients who did not require courses of oral corticosteroids improved from 0 to 54 (83%). ICS/LABA dose significantly reduced from 65 (100%) to 25 (38.5%) after 4 years of treatment (p < 0.001); ACT scores significantly increased from 15 ± 3 at baseline to 23 ± 3 (p < 0.001) and FEV1 level from 55.6 ± 10.6 to 76.63 ± 10.34 at year 4. Conclusion: In this study, omalizumab therapy resulted in better asthma control, and was effective and well tolerated as an add-on therapy for patients with moderate-to-severe asthma.

Summary Introduction. Sensitization to cat allergens is common worldwide. Currently, there is a trend towards costly and often unavailable diagnostic analysis. Objectives. The aim is to assess the reliability of skin prick test (SPT) and serum specific IgE (ssIgE) to cat sensitization, by performing nasal challenge test (NCT) in a community with low cat ownership but common presence of stray cats. Patients and methods. Forty-one pa-tients with perennial allergic rhinitis (AR) who were mono or polysensitized (including cat) were included. We had 31 cat non-owners and 10 present cat owners. SPT (> 5 mm / diameter), ssIgE (≥ 0.70 IU/ml), nasal smear for eosinophil (Eo) and NCT were compared between groups. Outcomes included nasal challenge score, nasal Eo positivity, peak inspiratory and expiratory flow (PIF and PEF) 2 and 8 hours after the NCT, and were compared to baseline. Results. Baseline SPT wheal size and ssIgE level were similar in both groups. NCT positivity was more frequent in cat owners. The strongest nasal reaction was on the top concentration in both groups. Nasal Eo positivity in cat owners was higher before and 2 hours after NCT, but similar to non-owners at last measurement. NCT positive cat non-owners had bigger SPT wheal size than NCT negative non-owners, but smaller than NCT positive cat owners. In contrast to PEF, a significant fall in PIF was noticed in both groups. Mono and polysensitised patients showed similar NCT positivity. Conclusion. Stray cats may pose a relevant risk of developing perennial AR. Regardless of cat ownership status, SPT and ssIgE should be the first diagnostic tool. Nasal Eo and NCT seem to be good diagnostic tools in cat non-owners if diagnosis is elusive.

Introduction: The burden of stroke has been increasing worldwide, especially in developing countries. Very few data regarding epidemiology of stroke are available in Bosnia and Herzegovina (BH). Patients and methods: We undertook a retrospective hospital-based study in all hospitals existing in five cantons and one district of BH. The patients were recruited between January 1st, 2014, and December 31st, 2014, and only first-ever-in-lifetime strokes (FES) were included for evaluation. Results: A FES was diagnosed in 1479 patients (age 71.83 ± 11.703 years) during the study period. FES occurred in 709 men (47.9%; age 69.64 ±12.002 years) and 770 women (52.1%; age 73.85± 11.051 years). Stroke was categorized into ischemic stroke (IS), primary intracerebral hemorrhage (PICH), subarachnoid hemorrhage (SAH) and cerebral venous thrombosis (CVT), which was diagnosed in 84%, 12,2%, 3,4% and 0,4% cases respectively. Early 28-day case-fatality was 18.5 % for all patients and both sexes combined. Short-term case-fatality was significantly greater in women (P=0.007). Among all patients with FES, 87% had hypertension, 35% diabetes mellitus, 39% hypercholesterolemia and almost 25 % atrial fibrillation. Discussion: This is the first study that provides us with information on epidemiology of stroke in BH. More than 90% of patients had one or more modifiable risk factors and the number would be even higher if we included smoking. The early stroke case-fatality was lower than that observed in other low- to middle-income countries. Conclusion: All modifiable stroke risk factors, especially high blood pressure, should be understood as a major public health problem in BH and efforts should be focused on the primary prevention of stroke. Our emphasis is on the designing of a stroke register in BH for a better health planning.

Despite intensive treatment, considerable proportion of patients with asthma remains symptomatic. Anti-inflammatory activity of curcumin has been shown. Aim: analyse the impact of add-on therapy with curcumin in asthma patients on inflammatory parameters, lung function and asthma control. During 2 months, 100 non-smokers (46.8±12.4 years, F/M ratio 1.04) with moderate, partially controlled asthma were treated with moderate dose of inhaled glucocorticoids (IGK) with no changes in dose. Patients were divided into two groups (n=50): curcumin group receiving curcumin 500 mg per os twice daily and control group. Before study, sputum and blood eosinophils (Eo), blood neutrophils, high sensitive C-reactive protein (hsCRP), predicted forced expiratory volume in first second (FEV1%), Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ) were similar between groups. After study, in curcumin group blood Eo count and hsCRP decreased, and FEV1, ACT and AQLQ increased significantly (before vs. after study: Eo: 5.9±0.6 vs. 4.1±0.4; hsCRP: 4.2±0.3 vs. 3.4±0.2; FEV1%: 77.7±0.8 vs. 83.9±0.5; ACT: 14.5 (6,19) vs. 18 (14,21); AQLQ: 3.4±0.2 vs. 4.1±0.2). There was no change in the control group. Compared to control curcumin group showed significantly lower blood Eo and hsCRP and higher FEV1% (curcumin vs. control: Eo: 4.1±0.4 vs. 5.4±0.5; hsCRP: 3.4±0.2 vs. 4.0±0.3; FEV1%: 83.9±0.5 vs. 78.3± 0.8), and improved ACT and AQLQ (ACT change>3: 72% vs. 28%; AQLQ change>0.5: 54% vs. 32%) after study. Add-on therapy with curcumin in patients with moderate partially controlled asthma seems to improve response to IGK regarding lung function, asthma control and quality of life. Further placebo controlled trials are needed.

Background: Allergic rhinitis (AR) related to local weeds pollen sensitization (Chenopodiaceous family) is the most common cause of respiratory allergy in Kuwait. Local nasal accumulation of different cells typical of allergic inflammation is responsible for clinical symptoms of AR. Although nasal smear for Eosinophils (NSE) is one of the earliest included valuable test in diagnosis of AR, with time is underestimated. Aim: Explore possible correlation of natural pollen allergen stimulation with appearance and quantity of Eosinophils in nasal smear. Methods: A group of randomly selected patients with clinical history suggestive for seasonal AR (SAR), who came to Al Rashed Allergy Center in period from October 2014 to October 2015, obtain Nasal Smear for Eosinophils as a screening test before further diagnostic evaluation. Nasal samples were collected by passing a sterile swab, from each nasal cavity, along the medial surface of the inferior turbinate 2 to 3 times and the specimen smeared on a clear glass slide. Nasal smears were examined by light microscopy after staining with hematoxylin and eosin stain. Skin prick test is performed in all symptomatic patients with a battery of inhalant allergens that include local pollens. The control group was recruited, with their voluntary consent, from the medical stuff with a negative history of any allergic nasal symptoms. In this group we performed only nasal smear for Eosinophils. Air Biology Laboratory Kuwait provided us with daily pollen count. Results: From total 158 study participants, 132 had SAR symptoms and are divided in four groups. Fifth, control, group is non symptomatic. For 38.6% of symptomatic patients NSE were positive, while 45% of these patients have negative SPT. From 62.1% NSE negative patients, 37.8% have negative SPT. Our results showed expected positive correlation of NSE positive patients with pollen season in Kuwait, in SPT positive group. However, presence of Eosinophils in nasal smear was moderate to high also in patients with negative SPT during the highest peak of season, in contrast to control group. Conclusion: NES showed moderate sensitivity, relatively high specificity and importance as screening test in SPT negative patients. Evaluation of AR demand wide and improved diagnostic approach due to significant number of SPT negative patients with positive NSE based on natural allergen stimulation. Our results emphasize locale allergic response of nasal mucosa and importance of target organ diagnostic approach.