Improvement of asthma control in adult patients using extrafine inhaled beclomethasone/formoterol fixed combination as maintenance therapy as well as maintenance and reliever therapy - CONTROL study.

INTRODUCTION: Extrafine formulation of beclomethasone/formoterol fixed combination (BDP/F pMDI HFA) is approved for both fixed maintenance and maintenance and reliever therapy (MART) of asthma, and recent data has proven that BDP/F pMDI HFA maintenance and reliever therapy is an effective alternative to other regimens. OBJECTIVE: This study aimed to assess the level of asthma control in a real-life setting in adult patients using extrafine BDP/F pMDI HFA fixed combination in a pressurized metered-dose inhaler (pMDI) as fixed maintenance dosing as well as maintenance and maintenance and reliever therapy. Additionally, we examined patients' satisfaction with the inhaler device and compliance with therapy as essential factors determining asthma control. METHODS: This multicenter prospective non-interventional observational study lasted 4 months with 3 patient visits. We used the Asthma Control Questionnaire 7 (ACQ-7) to evaluate the degree of asthma control and Morisky Medication Adherence Scale (MMAS-4) to assess compliance. A self-developed questionnaire was used to assess satisfaction with the inhaler device. RESULTS: 2179 patients using BDP/F pMDI HFA fixed combination as maintenance and reliever therapy or BDP/F pMDI HFA as maintenance therapy and SABA (short-acting beta2-agonist) as a reliever for at least 2 months were included. During the prospective follow-up, we observed an upward trend in the FEV1% (forced expiratory volume in 1 s) predicted values, improvement in the control of symptoms as indicated by a decline in the mean ACQ-7 score was noted (1.62 at Visit 1 vs. 1.21 at Visit 2 vs. 0.94 at Visit 3, p < 0.001) and increase in patients' compliance (the number of patients that reported forgetting at times to take their medication was reduced from 49.7 % to 27.1 %, p < 0.001). At the same time, we noted a reduction in the number of as-needed doses used for symptom relief (p < 0.001). Most patients were satisfied with the pMDI, considered it easy and convenient to use, and preferred it to a dry powder inhaler (p < 0.001). CONCLUSIONS: The use of extrafine BDP/F pMDI HFA as maintenance as well as reliever therapy seems to be associated with increased asthma control and better compliance to therapy.

Comparison of the effects of active and passive smoking of tobacco cigarettes, electronic nicotine delivery systems and tobacco heating products on the expression and secretion of oxidative stress and inflammatory response markers. A systematic review.

OBJECTIVES: This work attempts to summarize current knowledge on the effects of active and passive smoking of cigarettes, electronic nicotine delivery systems and tobacco heating products on the expression and secretion of oxidative stress and inflammatory response mediators, and on their possible impact on chronic obstructive pulmonary disease development. MATERIALS AND METHODS: The literature was searched by the terms: 'smoking', 'active smoking', 'passive smoking', 'main-stream smoke', 'side-stream smoke', 'secondhand smoke', 'cigarette' 'THP', 'tobacco heating product', 'ENDS', 'electronic nicotine delivery system', 'e-cigarette', 'electronic cigarette', oxidative stress', inflammatory response' and 'gene expression'. RESULTS: Cigarette smoking (active and passive) induces oxidative stress and inflammatory response in the airways. We present the effect of active smoking of e-cigarettes (EC) and heat-not-burn (HnB) products on the increased expression and secretion of oxidative stress and inflammatory response markers. However, there is only a limited number of studies on the effect of their second-hand smoking, and those available mainly describe aerosol composition. DISCUSSION: The literature provides data which confirm that active and passive cigarette smoking induces oxidative stress and inflammatory response in the airways and is a key risk factor of COPD development. Currently, there is a limited number of data about ENDS and THP active and passive smoking effects on the health of smokers and never-smokers. It is particularly important to assess the effect of such products during long-term use by never-smokers who choose them as the first type of cigarettes, and for never-smokers who are passively exposed to their aerosol.

Anti-fibrotic effect of ciglitazone in HRV-induced airway remodelling cell model.

Fibrosis is an important phenomenon as it can occur early in the pathogenesis of asthma; it may be associated with disease severity and resistance to therapy. There is a strong evidence that infection caused by human rhinovirus (HRV) contributes to remodelling process, but there is lack of studies clearly explaining this pathway. Synthetic peroxisome proliferator-activated receptor (PPAR) γ presents immunomodulatory and anti-inflammatory features. In this study, we examined immunomodulatory properties of ciglitazone - PPAR-γ agonist, in development and modulation of airway remodelling. Epithelial cells (NHBE) and two lines of fibroblasts (WI-38, HFL1) were stimulated with ciglitazone and rhinovirus. The expression of genes related to airway remodelling process were analysed in the cells; moreover NF-κB, c-Myc and STAT3 were silenced in order to estimate potential pathways involved. Ciglitazone decreased mRNA expression of MMP-9 and TGF-ß. It also modified the expression of α-SMA and collagen after rhinovirus infection. Transcription factors knockdown altered the levels of expression. The results suggest possible anti-fibrotic activity of PPAR-γ agonist in human airway cells. Ciglitazone has been shown to be dependent on NF-κB- and STAT3-related pathways, thus, the PPAR-γ agonist may have therapeutic potential for the treatment of airway remodelling in asthma.

Relationship between vitamin D and asthma from gestational to adulthood period: a meta-analysis of randomized clinical trials.

BACKGROUND: Despite numerous studies investigating vitamin D, its impact on asthma is still unknown. The aim of our meta-analysis is to analyze the vitamin D supplementation influence on asthma prevention and treatment ranging from gestational to adulthood period. METHODS: Fifteen randomized clinical trials were included after database search. Studies contained the analyzed endpoints: the number of asthma and wheezing occurrence in gestational and infantile periods, the change of childhood/adult asthma control test score and forced expiratory volume in one second (FEV1) in childhood and adulthood periods. Random effects model was used to calculate effect sizes. RESULTS: Supplementation by women during pregnancy period decreased the wheezing occurrence in their children by 23% (RR = 0.77; 95% CI [0.64; 0.92]; p < 0.0049, I2 = 0%); whereas had no effect on given asthma parameters during the infantile period. Moreover, vitamin D administration had negative effect on the FEV1 change in children (MD = -3.84; 95% CI [-7.68; -0.01]; p = 0.0497; I2 = 95%), but had positive effect on the change of ACT score in adults (MD = 1.80; 95% CI [0.12; 3.49]; p = 0.0359; I2 = 99%). CONCLUSIONS: Our meta-analysis showed the varying results depending on patient's life period. It is important to further investigate the role of vitamin D supplementation in asthma management.

New Data on Anti-Inflammatory and Wound Healing Potential of Transgenic Senna obtusifolia Hairy Roots: In Vitro Studies.

Asthma is an inflammatory disease whose etiology remains unclear. Its characteristics encompass a wide range of clinical symptoms, inflammatory processes, and reactions to standard therapies. Plants produce a range of constitutive products and secondary metabolites that may have therapeutic abilities. The aim of this study was to determine the effects of Senna obtusifolia transgenic hairy root extracts on virus-induced airway remodeling conditions. Three cell lines were incubated with extracts from transformed (SOA4) and transgenic (SOPSS2, with overexpression of the gene encoding squalene synthase 1) hairy roots of Senna obtusifolia in cell lines undergoing human rhinovirus-16 (HRV-16) infection. The effects of the extracts on the inflammatory process were determined based on the expression of inflammatory cytokines (IL-8, TNF-α, IL-1α and IFN-γ) and total thiol content. The transgenic Senna obtusifolia root extract reduced virus-induced expression of TNF, IL-8 and IL-1 in WI-38 and NHBE cells. The SOPSS2 extract reduced IL-1 expression only in lung epithelial cells. Both tested extracts significantly increased the concentration of thiol groups in epithelial lung cells. In addition, the SOPPS2 hairy root extract yielded a positive result in the scratch test. SOA4 and SOPPS2 Senna obtusifolia hairy root extracts demonstrated anti-inflammatory effects or wound healing activity. The SOPSS2 extract had stronger biological properties, which may result from a higher content of bioactive secondary metabolites.

Comparison of effects of tobacco cigarettes, electronic nicotine delivery systems and tobacco heating products on miRNA-mediated gene expression. A systematic review.

OBJECTIVES: This work attempts to summarize current knowledge on the effects of cigarettes, electronic nicotine delivery systems and tobacco heating products on miRNA-mediated gene expression regulation and on their possible impact on smoking-related respiratory disease development. MATERIALS AND METHODS: Literature search by terms combination: 'smoking', 'cigarette' 'THP', 'tobacco heating product', 'ENDS', 'electronic nicotine delivery system', 'e-cigarette', electronic cigarette' and 'miRNA-mediated gene expression' has been performed from October 2021 to February 2022. In this systematic review all relevant literature, including clinical trials, cellular and animal-based studies were included. RESULTS: Cigarette smoke (CS) significantly altered transcriptome, including miRNAs expression profile. MiRNA-mediated gene expression is mentioned as one of the mechanisms associated with smoking-related respiratory disease development. Differential expression of miRNAs was reduced in aerosol from e-cigarettes (EC) and tobacco heating products (THP) when compared to CS. However, there was a significant alteration of some miRNAs expression when compared to air-controls in both EC and THP. DISCUSSION: CS negatively affects transcriptome and miRNA-mediated gene expression regulation because of a huge number of hazardous substances which predispose to smoking-related diseases. Despite the reduced effect of ENDS and THP on miRNAs profile compared to CS, differences in expression of miRNAs when compared to air-control were observed, which may be harmful to never-smokers who may perceive such alternative smoking products as non-hazardous. To clearly indicate the role of ENDS and THP in the alteration of miRNA-mediated gene expression and the development of smoking-related respiratory diseases associated with this mechanism, more long-term studies should be performed in the future.

Compositional differences between gut microbiota of adult patients with asthma and healthy controls.

Introduction: Asthma is a complex and multifactorial disorder, with severe public health implications. Over the last several years, our knowledge in the field of human gut microbiota has expanded and allowed us to understand its crucial role in the development of many diseases. Aim: To analyse the nature of human gut microbiota patterns among patients with asthma compared to healthy controls. Material and methods: Composition of the complex gut microbiota was analysed in faecal samples from 13 asthma patients and 7 healthy volunteers using Next-Generation Sequencing technology (NGS). The Kruskal-Wallis Analysis of Variance (ANOVA) and Mann-Whitney tests were used to compare the above two groups of subjects. Results: The composition of the gut microbiota of asthma patients differed from that of healthy volunteers at each of the analysed levels (p < 0.05). Compared to healthy individuals, bacterial diversity was significantly lowered among the asthma group, which is the evidence of gut microbiota depletion in asthma patients. The analysis of beta diversity showed that the gut community compositions of asthma are widely dispersed in contrast to the tight clustering observed in the control group. Finally, the similarity index was found to be lower in the inter-group comparison than in the intra-group comparison, which confirmed changes in the gut microbial composition in the asthmatic group. Conclusions: The study revealed significant differences in the human gut microbiome composition between asthma patients and the healthy control group.

Curcumin modulates airway remodelling-contributing genes-the significance of transcription factors.

Bronchial epithelial cells and fibroblasts play an essential role in airway remodelling, due to their protective and secretory functions. There are many studies proving that infection caused by human rhinovirus may contribute to the process of airway remodelling. The beneficial properties of curcumin, the basic ingredient of turmeric, have been proved in many studies. Therefore, the aim of this study was the evaluation of curcumin immunomodulatory properties in development of airway remodelling. Fibroblasts (WI-38 and HFL1) and epithelial cells (NHBE) were incubated with curcumin. Additionally, remodelling conditions were induced with rhinovirus (HRV). Airway remodelling genes were determined by qPCR and immunoblotting. Moreover, NF-κB, c-Myc and STAT3 were silenced to analyse the pathways involved in airway remodelling. Curcumin reduced the expression of the genes analysed, especially MMP-9, TGF-ß and collagen I. Moreover, curcumin inhibited the HRV-induced expression of MMP-9, TGF-ß, collagen I and LTC4S (p < 0.05). NF-κB, c-Myc and STAT3 changed their course of expression. Concluding, our study shows that curcumin significantly downregulated gene expression related to the remodelling process, which is dependent on NF-κB and, partially, on c-Myc and STAT3. The results suggest that the remodelling process may be limited and possibly prevented, however this issue requires further research.

COVID-19 vaccination efficacy in numbers including SARS-CoV-2 variants and age comparison: a meta-analysis of randomized clinical trials.

BACKGROUND: New vaccines are being developed to fight the ongoing COVID-19 pandemic. In our study we compared the efficacy of COVID-19 vaccines to prevent COVID-19-related infections and mortality. METHODS: 17 randomized clinical trials of COVID-19 vaccines were included after search in databases. We compared COVID-19 vaccines based on symptomatic and severe infections, number of deaths and hospitalizations related to COVID-19. Also, we analyzed the efficacy of COVID-19 against different variants of SARS-CoV-2 as well as according to different age groups. Random effects model using Mantel-Haenzeal method was used to pool relative risk (RR). RESULTS: Our meta-analysis shows that full vaccination could decrease not only the risk of symptomatic or severe COVID-19, the risk of hospitalization and death caused by COVID-19. COVID-19 vaccines were also effective against variants of SARS-CoV-2 (RR = 0.36; 95% CI [0.25; 0.53], p < 0.0001). However, efficacy of vaccination varied in COVID-19 variant-dependent manner. Moreover, the analysis in different age groups showed that COVID-19 vaccines had the similar results: the risk was slightly lower in adults compared to elderly cohort [Formula: see text] 65 years): (RR = 0.16, 95% CI [0.11; 0.23]) and (RR = 0.19, 95% CI [0.12; 0.30]), respectively. CONCLUSIONS: Data obtained from clinical trials of COVID-19 vaccines looks promising, in order to fully investigate efficacy of the vaccines further clinical examination is required especially considering new SARS-CoV-2 variants.

COVID-19 mortality rate determinants in selected Eastern European countries.

BACKGROUND: The COVID-19 pandemic has caused increased mortality worldwide. We noticed a tendency for higher number of deaths in Eastern European countries. Therefore, we decided to investigate whether any common factor that might be responsible for the increased COVID-19 mortality exists. METHODS: In our cross-sectional study, we conducted the correlation and multiple regression analysis using R basing on the data gathered in publicly available databases. In the analysis, we included variables such as: number of deaths, number of new cases, number of hospitalizations, number of ICU (intensive care units) patients, number of vaccinations, number of boosters, number of fully vaccinated individuals, stringency index, number of reported COVID-19 variant cases, and number of flights. Additionally, we analyzed the influence of population density and median age in particular European countries on total number of COVID-19 deaths. Analyzed data represents periods from start of the COVID-19 pandemic in particular Eastern European Countries: Bulgaria, Croatia, Czech Republic, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia and Slovenia, while as the end of the study the day of January 31, 2022 is considered. Results were considered statistically significant at p < 0.05. RESULTS: Our study showed that mortality rate reflects the number of COVID-19 cases (e.g. for Poland was 0.0058, p < 0.001), number of hospitalized patients (e.g. for Poland 0.0116, p < 0.001), and patients in intensive care (e.g. for Slovakia 0.2326, p < 0.001). Stringency index corresponding to level of introduced restrictions and vaccination can affect the mortality rate of COVID-19 in a country-dependent manner: e.g. for Romania 0.0006, p < 0.001; whereas in Lithuania - 0.0002, p < 0.001. Moreover, occurrence of B.1.1.7 and B.1.617.2 variants increased COVID-19 mortality rates. CONCLUSION: Our analysis showed that crucial factor for decreasing mortality is proper healthcare joined by accurate restriction policy. Additionally, our study shows that COVID-19 vaccination proven successful in COVID-19 mortality prevention.

The risk of anaphylaxis behind authorized COVID-19 vaccines: a meta-analysis.

BACKGROUND: A serious allergic reaction that may occur in response to medical products is anaphylaxis, which potentially can lead to anaphylactic shock. In the light of recent COVID-19 pandemic, much public attention had been paid to the severe allergic reactions occurring after COVID-19 vaccination. Therefore, in our study we would like to investigate the risk of authorized COVID-19 vaccines to induce anaphylactic reaction, anaphylactoid reaction, anaphylactic shock and anaphylactoid shock. METHODS: We searched databases, such as PubMed, Web of Science and Embase and found eight articles about the incidence of anaphylactic and anaphylactoid reactions. Also, we used data from four databases from Canada, the U.S., the European Union and the United Kingdom. To calculate effect sizes, we used random effects model with inverse variance method. The risk ratio with 95% confidence interval were used for dichotomous outcomes. Statistical analysis was prepared in R. Results were considered statistically significant at p < 0.05. RESULTS: The most cases of anaphylactic reaction, anaphylactoid reaction, anaphylactic shock and anaphylactoid shock were reported in female aged 18-85 years after BNT162b2 vaccine according to data from the EU. Analyzed COVID-19 vaccines can cause the anaphylaxis/anaphylactic reaction with risk of 106.99 (95% CI [39.95; 286.57], p < 0.0001, I2 = 59%), whereas the anaphylactoid reaction, anaphylactic and anaphylactoid shocks with risk of 113.3 (95% CI [28.11; 456.53], p < 0.0001), 344.2 (95% CI [85.77; 1381.39], p < 0.0001), 14.9, 95% CI [1.96; 112.79], p = 0.009), respectively. CONCLUSIONS: Our meta-analysis shows that the risk of anaphylactic reaction, anaphylactoid reaction, anaphylactic shock and anaphylactoid shock do not occur only after mRNA COVID-19 vaccines. Therefore, vaccination centers should be prepared to render assistance in the event of a reaction in all cases.

Does Vitamin D Work Synergistically with Anti-Asthmatic Drugs in Airway Remodeling?

Vitamin D is commonly known for its properties of airway remodeling inhibition. Due to this, we decided to analyze the action of calcitriol with anti-asthmatic drugs in airway remodeling. The HFL1 cell line was treated with calcitriol, beclomethasone 17-propionate, montelukast sodium, LTD4 and TGF-ß in different combinations. Real-time PCR was used to analyzed the expression of ACTA2, CDH-1, Vimentin, ADAM33, MMP-9 and CysLTR1 on the mRNA level, whereas Western blot was used to analyze gene expression on the protein level. One-way analysis variants, the Kruskal-Wallis test, Student's t-test or Welch's t-test were used for statistical analysis. Concerning the results, pre-treatment with calcitriol increased the inhibitory effect of beclomethasone 17-propionate and montelukast sodium on the expression of ACTA2 (p = 0.0072), Vimentin (p = 0.0002) and CysLTR1 (p = 0.0204), and 1,25(OH)2D3 had an influence on the effects of beclomethasone 17-propionate and montelukast sodium and of CDH1 expression (p = 0.0076). On the protein level, pre-treatment with calcitriol with beclomethasone 17-propionate and montelukast sodium treatment decreased ACTA2 expression in comparison to the LT (LTD4 and TGF-ß) control group (p = 0.0191). Hence, our study not only confirms that vitamin D may inhibit airway remodeling, but also shows that vitamin D has a synergistic effect with anti-asthmatic drugs.

Relaxin Affects Airway Remodeling Genes Expression through Various Signal Pathways Connected with Transcription Factors.

Fibrosis is one of the parameters of lung tissue remodeling in asthma. Relaxin has emerged as a natural suppressor of fibrosis, showing efficacy in the prevention of a multiple models of fibrosis. Therefore, the aim of this study was to analyze the aptitudes of relaxin, in the context of its immunomodulatory properties, in the development of airway remodeling. WI-38 and HFL1 fibroblasts, as well as epithelial cells (NHBE), were incubated with relaxin. Additionally, remodeling conditions were induced with two serotypes of rhinovirus (HRV). The expression of the genes contributing to airway remodeling were determined. Moreover, NF-κB, c-Myc, and STAT3 were knocked down to analyze the pathways involved in airway remodeling. Relaxin decreased the mRNA expression of collagen I and TGF-ß and increased the expression of MMP-9 (p < 0.05). Relaxin also decreased HRV-induced expression of collagen I and α-SMA (p < 0.05). Moreover, all the analyzed transcription factors­NF-κB, c-Myc, and STAT3­have shown its influence on the pathways connected with relaxin action. Though relaxin requires further study, our results suggest that this natural compound offers great potential for inhibition of the development, or even reversing, of factors related to airway remodeling. The presented contribution of the investigated transcription factors in this process additionally increases its potential possibilities through a variety of its activity pathways.

Pharmacist's recommendations of over-the-counter treatments for the common cold - analysis of prospective cases in Poland.

BACKGROUND: Common cold is a frequent illness in northern hemisphere between late autumn and early spring. Patients suffering from it frequently turn to pharmacists instead of physicians in order to receive medical advice and treatment. We studied its treatment advised by pharmacists in Poland, as well as evidence for the efficacy of their recommendations by utilizing a self-developed questionnaire and a study of existing literature. METHODS: The data were collected by 27 pharmacists who worked in four large network community pharmacies in Lodz, Poland. The study took place from December 2019 to February 2020. Data were recorded only if the patient asked for pharmacy counselling for over-the counter (OTC) products due to common cold self-diagnosis and a product was sold. Pharmacists' recommendations were compared with the results of a literature review of best evidence to determine appropriateness of the pharmacists' decisions. RESULTS: In four out of five cases the pharmacists recommended products contained paracetamol. In addition, in one out of three patient encounters they advised nasal decongestant, inosines and/or OTC mucolytics. There was a significant relationship between fever and recommendation frequency of some analgesics, inosines, mucolytics and sore throat products (OR > 1, p < 0.05); rhinorrhea and recommendation frequency of paracetamol, inosines, anti-histamines and alpha-mimetics (OR > 1, p < 0.05); cough and recommendation frequency of paracetamol, inosines, mucolytics and sore throat products (OR > 1, p < 0.05); and fatigue and recommendation frequency of paracetamol, acetylsalicylic acid, inosines and sore throat products (OR > 1, p < 0.05). The pharmacist recommendations were based on patients' symptoms, product price, pharmaceutical company promotion and the financial incentive. In many cases their recommendations were not in line with current best practice recommendations. CONCLUSIONS: Our study suggests that the most common rationale for pharmacist recommendation on anti-common cold treatment was to take a "shotgun" approach. Pharmacists commonly made recommendations for products that lack strong evidence for efficacy (i.e. anti-viral agents) and are potentially unnecessary, based on presentation of the symptom. Reasons for this situation include lack of training, lack of time to evaluate the patient, lack of awareness of evidence as well as drug company marketing and financial incentives (i.e. fulfilling sale plans and target sale bonuses). TRIAL REGISTRATION: The study was a non-interventional, observational research trial. The study registration was not required.

Wide-Range Effects of 1,25(OH)2D3 on Group 4A Phospholipases Is Related to Nuclear Factor κ-B and Phospholipase-A2 Activating Protein Activity in Mast Cells.

INTRODUCTION: Phospholipases are enzymes that occur in many types of human cells, including mast cells, and play an important role in the molecular background of asthma pathogenesis, and the development of inflammation NF-κB activities that affect numerous biological processes has been reported in many inflammatory diseases including asthma. Vitamin D is a widely studied factor that affects many diseases, including asthma. The aim of this study is to assess the influence of 1,25-(OH)2D3 on regulation of chosen phospholipase-A2 (PLA2) expression-selected inflammation mediators. METHODS: LUVA mast cells were stimulated with 1,25(OH)2D3, and inhibitors of NF-κB p65 and ubiquitination. Expression analysis of phospholipases (PLA2G5, PLA2G10, PLA2G12, PLA2G15, PLA2G4A, PLA2G4B, PLA2G4C, PLAA, NF-κB p65, and UBC) was done utilizing real-time PCR and Western blot. Eicosanoid (LTC4, LXA4, 15[S]-HETE, and PGE2) levels and sPLA2 were also measured. RESULTS: We found that 1,25(OH)2D3 decreased the expression of PLA2G5, PLA2G15, PLA2G5,UBC, and NF-κB p65 but increased expression of PLAA and PLA2G4C (p < 0.05). Moreover, the expression of PLA2G5 and PLA2G15 decreased after inhibition of NF-κB p65 and UBC. Increased levels of released LXA4 and 15(S)-HETE, decreased levels of LTC4, and sPLA2s enzymatic activity in response to 1,25(OH)2D3 were also observed. Additionally, NF-κB p65 inhibition led to an increase in the LXA4 concentration. CONCLUSION: Future investigations will be needed to further clarify the role of 1,25(OH)2D3 in the context of asthma and the inflammatory process; however, these results confirm a variety of effects which can be caused by this vitamin. 1,25(OH)2D3-mediated action may result in the development of new therapeutic strategies for asthma treatment.

Menthol additives to tobacco products. Reasons for withdrawing mentholated cigarettes in European Union on 20th may 2020 according to tobacco products directive (2014/40/EU).

Menthol, which is a natural cyclic monoterpene alcohol with a minty smell, is one of the main constituents of essential oils that naturally occur in some aromatic plants, such as Mentha × piperita L. This natural compound shows many biological properties, such as anesthetic, analgesic, antibacterial and antifungal, immunomodulating, and skin penetration-enhancing. It is added to a variety of goods, such as food, oral-care products, OTC products, cosmetics, and tobacco products. Menthol is not just a simple flavoring agent, especially when it comes to tobacco products. Its ability to 'mask' the negative effects of nicotine and its additional positive sensory effects makes it the most common additive in such products. For the customers, mentholated tobacco products may be mistakenly perceived as less harmful for health, which may increase their consumption. However, as the evidence shows, menthol cigarettes are no safer than conventional cigarettes and may lead to more frequent disease exacerbation during prolonged exposure to smoke from such products. In addition, because of its complex interactions with nicotine, menthol may affect smoking behavior and may increase addiction to nicotine. For those reasons, the European Union banned flavored cigarettes (whose sale size reached more than 3% of the total tobacco product market) by implementing the Tobacco Products Directive (2014/40/EU) on 20th May 2020. While the menthol ban was based on health concerns, the ultimate effect on consumers, regarding potential quitting, is yet to be determined.

IQOS - a heat-not-burn (HnB) tobacco product - chemical composition and possible impact on oxidative stress and inflammatory response. A systematic review.

Objectives: This work attempts to summarize current knowledge about IQOS, the heat-not-burn tobacco products, their chemical composition and possible impact on oxidative stress and inflammatory response.Materials and Methods: The literature search was performed between January and April 2019 by a combination of terms: 'IQOS smoking', 'IQOS cigarette', 'I quit original smoking cigarette', 'heat-not-burn products', 'HnB tobacco products'.Results: The aim of IQOS system is to minimalize the exposure of its smokers to dangerous substances present in cigarette smoke and to lower the probability of development of tobacco-related diseases. As current studies suggest, this new heat-not-burn tobacco product emits significantly lower concentrations of tar, carbonyls, VOCs, CO, free radicals or nitrosamines when compared to conventional cigarette, and thus it may reduce health risk for smokers. However, it does not eliminate this risk of development of tobacco-related diseases.Discussion: For conventional tobacco smokers the IQOS products may be an alternative option, which helps to reduce exposure to hazardous and potentially hazardous constituents. However, for never-smokers using the IQOS cigarettes may develop an addiction or increase exposition to some substances, which may increase probability of tobacco-related diseases. Moreover, emission of unexpected substances depends on device cleaning strategy and puff regiments.Conclusions: There is only limited data about IQOS effect on smokers' health. The future investigation, especially comparison with healthy never-smokers or study of chronic exposure to IQOS, is needed.

Clinical profile of chronic bronchial asthma patients in Poland: results of the PROKSAL study.

INTRODUCTION: Asthma is a complex condition characterized by the presence of chronic inflammation in the lower respiratory tract resulting in many disturbing symptoms. The study of the clinical profile of the population with asthma allows us to understand a trend of a specific disease taking into account several indicators and its clinical characteristics. AIM: Evaluation of the clinical profile of patients with chronic bronchial asthma in Poland. MATERIAL AND METHODS: The study included 10400 adult patients, of both sexes, diagnosed with chronic bronchial asthma who started therapy based on inhaled glucocorticosteroids accompanied by salmeterol, and 52 allergists. The examination was performed in a doctor's surgery. Standardized questionnaire interviews were used in order to carry out the procedure. RESULTS: The age of the patients ranged from 18 up to 97 years. Most of them suffer from overweight and obesity. 45.3% of the patients smoked cigarettes or declared to be passive smokers. Current asthma control was poor: over 56% of the patients suffered from diurnal symptoms more often than twice a week, almost 55% from nocturnal symptoms, in 72% of the patients' physical activity was limited, whereas 57% required immediate treatment. Most commonly used drugs were inhaled glucocorticosteroids and short acting ß2-mimetics. After treatment change, fewer patients suffered from asthma symptoms. CONCLUSIONS: Adjusting the therapy according to the current guidelines and to the patient's needs helps to improve asthma control.

Comparison of an automated microfluidic immunoassay technology (BioIC, lab-on-chips) and ImmunoCAP assay. Lab-on-chips as a tool for specific IgE (sIgE) detection.

INTRODUCTION: The measurement of clinically important specific IgE (sIgE) antibody is pivotal for both diagnosis and management of allergy. Two methods may be distinguished depending on the number of antigens tested simultaneously: singleplex and multiplex. BioIC is a multiplex, advanced, automated microfluidic immunoassay system enabling simultaneous sIgE measurement against multiple allergens. ImmunoCAP is a singleplex assay for sIgE detection and gold standard method for diagnosis of allergy. AIM: To compare and validate the diagnostic capability of a multiplex sIgE assay - BioIC assay with a singleplex ImmunoCAP assay. MATERIAL AND METHODS: Using both BioIC assay and ImmunoCAP assay, the sIgE level in serum samples from 20 allergic disease patients with respect to 33 allergens (16 inhalant allergens, 16 food allergens and 1 contact allergen) was measured. Receiver operating characteristic (ROC) area under the curve (AUC), qualitative and semi-quantitative comparisons were performed to compare both sIgE measurement methods using statistical analyses. RESULTS: ROC AUC analysis showed similar sensitivity and specificity of BioIC assay and ImmunoCAP assay. In qualitative analysis, the negative and positive agreements were 100% equal for each allergen. Spearman's rank correlation coefficients identified very high positive correlations between two assays for all tested allergens (p < 0.001). CONCLUSIONS: The BioIC showed agreement with ImmunoCAP assay. Sensitivity and specificity of both assays are similar, thus they showed similar diagnostic performance. However, careful interpretation of obtained results is necessary in clinical applications because of methodological differences between these two systems.

Efficacy and safety of topical calcineurin inhibitors for the treatment of atopic dermatitis: meta-analysis of randomized clinical trials.

INTRODUCTION: Calcineurin inhibitors, novel topical immunomodulators, may constitute a superior alternative for glucocorticosteroids in atopic dermatitis (AD) topical treatment. AIM: Determination of efficacy and safety of each topical calcineurin inhibitor (TCI) formulation, 0.3% or 0.1% tacrolimus and 1% pimecrolimus, for the treatment of moderate to severe AD in comparison with glucocorticosteroids. MATERIAL AND METHODS: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, GREAT database, trials registers and reference lists were searched up to February 2018. Randomised controlled trials of TCI, compared to corticosteroids (TCS), reporting efficacy or safety outcomes were selected. Quality of trials and evidence of each outcome were evaluated according to Cochrane Collaboration recommendations and tools. The primary outcomes were physician's global assessment of improvement and occurrence of adverse events (AEs). RESULTS: Fourteen trials involving 7376 children and adults with AD were included. Calcineurin inhibitors were significantly more effective than various potency TCS, neither least potent to lower mid-strength nor mid-strength to potent TCS (RR = 1.24, 95% CI: 1.06-1.44). The major AEs were skin burning and pruritus, their incidence was higher in TCI treatment (RR = 3.32, 95% CI: 2.90-3.80; RR = 1.59, 95% CI: 1.34-1.80). CONCLUSIONS: Calcineurin inhibitors seem to be more effective and contrarily they elicit more AEs than TCS.