The Role of Postbiotics in Asthma Treatment.

In recent years, there has been abundant research concerning human microbiome and its impact on the host's health. Studies have shown that not only the commensal bacteria itself, but also postbiotics, understood as inanimate microorganisms, possibly with the presence of their components, may themselves have an effect on various elements of human physiology. In this review, we take a closer look at the specific ways in which postbiotics can alter immune response in allergic asthma, which is one of the most prevalent allergic diseases in today's world and a serious subject of concern. Through altering patients' immune response, not only to allergens but also to pathogens, postbiotics could have a significant role in lowering the number of asthma exacerbations. We suggest that more profound research should be undertaken in order to launch postbiotics into clinical standards of asthma treatment, given the greatly promising findings in terms of their immunomodulating potential.

Sensitization to Food and Aero-Allergens in Children with Coeliac Disease Assessed with the Use of a Multiplex Molecular Diagnostic Technique.

(1) Background. Coeliac disease (CD) often co-occurs with autoimmune conditions or genetic syndromes, but there are few studies on the co-existence of CD and immunoglobulin E (IgE)-mediated allergies. The purpose of this study was to assess sensitization to food and aero-allergens in pediatric patients with CD. (2) Methods. A multiplex ALEX®2 test was used to determine specific IgEs (sIgEs). (3) Results. The study included 108 children newly diagnosed with CD. Allergen extract- and/or allergen molecule-sIgEs were detected in 49.1% of children. Most children (41.5%) were sensitized to both inhalant and food allergens. The three most common aero-allergens (timothy pollen, ryegrass, silver birch) were molecules Phl p 1, Lol p 1, and Bet v 1. The most common food allergens (hazelnut, apple, and peanut) were Cor a 1, Mal d 1, and Ara h 8 molecules of the PR-10 subfamily. Patients were not sensitized to cereal allergens containing gluten. Spearman's rank correlation analysis of sensitized patients showed a significant positive relationship (r = 0.31) between the patients' age and the occurrence of positive sIgEs (≥0.3 kUA/L) for inhalant allergen molecules (p = 0.045). In sensitized patients, mainly symptoms of inhalant allergy were observed, such as hay fever, conjunctivitis, and bronchial asthma. (4) Conclusions. The current study indicates the co-occurrence of IgE sensitization to food and inhalant allergens in children with CD. The study highlights the need to take a closer look at the diagnosis of IgE-mediated allergy in patients with CD, which may help in their care and lead to a better understanding of the relationship between CD and IgE-mediated allergy.

Home Monitoring of Asthma Exacerbations in Children and Adults With Use of an AI-Aided Stethoscope.

PURPOSE: The advent of new medical devices allows patients with asthma to self-monitor at home, providing a more complete picture of their disease than occasional in-person clinic visits. This raises a pertinent question: which devices and parameters perform best in exacerbation detection? METHODS: A total of 149 patients with asthma (90 children, 59 adults) participated in a 6-month observational study. Participants (or parents) regularly (daily for the first 2 weeks and weekly for the next 5.5 months, with increased frequency during exacerbations) performed self-examinations using 3 devices: an artificial intelligence (AI)-aided home stethoscope (providing wheezes, rhonchi, and coarse and fine crackles intensity; respiratory and heart rate; and inspiration-to-expiration ratio), a peripheral capillary oxygen saturation (SpO2) meter, and a peak expiratory flow (PEF) meter and filled out a health state survey. The resulting 6,029 examinations were evaluated by physicians for the presence of exacerbations. For each registered parameter, a machine learning model was trained, and the area under the receiver operating characteristic curve (AUC) was calculated to assess its utility in exacerbation detection. RESULTS: The best single-parameter discriminators of exacerbations were wheezes intensity for young children (AUC 84% [95% CI, 82%-85%]), rhonchi intensity for older children (AUC 81% [95% CI, 79%-84%]), and survey answers for adults (AUC 92% [95% CI, 89%-95%]). The greatest efficacy (in terms of AUC) was observed for a combination of several parameters. CONCLUSIONS: The AI-aided home stethoscope provides reliable information on asthma exacerbations. The parameters provided are effective for children, especially those younger than 5 years of age. The introduction of this tool to the health care system might enhance asthma exacerbation detection substantially and make remote monitoring of patients easier.

Feedback systems in multi-dose dry powder inhalers.

Dry powder inhalers (DPIs) are a large, highly diverse group of inhalation devices. DPIs differentiate the process of measuring the dose of the drug and preparing the inhaler for use, but also the way of transmitting and the scope of feedback on the inhalation process that the user receives. The functioning of simple and technologically advanced systems of feedback on the inhalation process in the most commonly used multi-dose DPIs is discussed. All these DPIs have a dose counter. Only three DPIs - Novolizer®, Genuair® and NEXThaler® provide feedback to the patient in the form of auditory and visual signals confirming the correctness of the inhalation performed. This is important for the correct use of the inhaler, and thus for obtaining the expected therapeutic effects.

Influence of Physicochemical Properties of Budesonide Micro-Suspensions on Their Expected Lung Delivery Using a Vibrating Mesh Nebulizer.

The efficiency of lung drug delivery of nebulized drugs is governed by aerosol quality, which depends both on the aerosolization process itself but also on the properties of aerosol precursors. This paper determines physicochemical properties of four analogous micro-suspensions of a micronized steroid (budesonide, BUD) and seeks relationships between these properties and the quality of the aerosol emitted from a vibrating mesh nebulizer (VMN). Despite the same BUD content in all tested pharmaceutical products, their physicochemical characteristics (liquid surface tension, viscosity, electric conductivity, BUD crystal size, suspension stability, etc.) are not identical. The differences have a weak influence on droplet size distribution in the mists emitted from the VMN and on theoretical (calculated) regional aerosol deposition in the respiratory system but, simultaneously, there is an influence on the amount of BUD converted by the nebulizer to aerosol available for inhalation. It is demonstrated that the maximum inhaled BUD dose is below 80-90% of the label dose, depending on the nebulized formulation. It shows that nebulization of BUD suspensions in VMN is sensitive to minor dissimilarities among analogous (generic) pharmaceutics. The potential clinical relevance of these findings is discussed.

Effect of immunostimulation with bacterial lysate on the clinical course of allergic rhinitis and the level of γδT, iNKT and cytotoxic T cells in children sensitized to grass pollen allergens: A randomized controlled trial.

Background: There are many drugs for allergic rhinitis (AR), however, these drugs show variable clinical effectiveness and some side effects. Therefore, new methods of AR pharmacotherapy are being sought. Objectives: The objectives of this study were to evaluate the efficacy of polyvalent mechanical bacterial lysate (PMBL) therapy in improving the clinical course of grass pollen-induced AR (seasonal AR, SAR) in children and its effect on changes in the blood level of the γδT, iNKT and cytotoxic T cell subsets. Methods: Fifty children with SAR were enrolled in this study and were randomly assigned to either the PMBL group or the placebo group. The severity of SAR symptoms was assessed using the total nasal symptom score (TNSS) and visual analogue scale (VAS). During two visits (V1, V2), peak nasal inspiratory flow (PNIF) was measured and peripheral blood was collected for immunological analyses. The study also included 2 telephone contacts (TC1, TC2). Results: The severity of the nasal symptoms of SAR on the TNSS scale was revealed to have a significantly lower impact in the PMBL group vs the placebo group at measuring points TC1 and V2 (p = 0.01, p = 0.009, respectively). A statistically significantly lower mean severity of nasal symptoms of SAR on the VAS scale was recorded for children in the PMBL group compared to the placebo group at measuring points TC1, V2 and TC2 (p = 0.04, p = 0.04, p = 0.03, respectively). The compared groups do not show significant differences in terms of PNIF values at individual measuring points. There were no statistically significant changes in immune variables. For both groups, there was a statistically significant association between the level of Th1-like γδT cells and the severity of SAR symptoms expressed on the TNSS scale (p = 0.03) - the lower the level of Th1-like γδT cells, the higher the TNSS value. Conclusion: Administration of sublingual PMBL tablets during the grass pollen season proves to have a high efficacy in alleviating SAR symptoms in children sensitized to grass pollen allergens. Th1-like γδT cells may be used as potential markers for SAR severity in children. Clinical trial registration: ClinicalTrials.gov, identifier (NCT04802616).

IgE-Dependent Allergy in Patients with Celiac Disease: A Systematic Review.

In order to answer the question if an IgE-mediated allergy (A-IgE) may occur in subjects with celiac disease (CD), a systematic review was performed of available publications collected in the United States National Institute for Biotechnology Information/National Institutes of Health/National Library of Medicine/PubMed database up to 28 December 2022, with the use of the following keywords "allergy&celiac/coeliac", "sensitization&celiac/coeliac", and "anaphylaxis&celiac/coeliac" compared in the form of a conjunction. In total, the search returned 2013 publications from these keywords in any section of the article. As numerous review articles included the above-mentioned entries in the abstract, we decided to focus on the publications with the entries only in the title (n = 63). After rejecting studies unrelated to the topic, narrative reviews, book chapters, conference abstracts, symposium reports, letters to the editor, or non-English articles, 18 publications (6 observational original studies and 12 case reports describing a total of 15 cases of A-IgE developed after a diagnosis of CD) were included to this review. Our study is the first systematic review on allergy occurrence in CD patients. The analysis indicated that the possibility of a coexistence of A-IgE with any food and inhalant allergens in subjects diagnosed with CD should be considered. A sensitization to wheat was the most frequently described in subjects with CD. The clinical manifestation of A-IgE in CD was similar to that in subjects without CD; e.g., with possible atopic dermatitis, vomiting, urticaria, angioedema, or anaphylactic shock. Screening for allergies in subjects with CD should be considered, especially in those cases where symptoms persist after introducing a gluten-free diet. The elimination of wheat from the diet of patients with CD may lead to a loss of immune tolerance and to the development of sensitization, which may even manifest as anaphylaxis. In conclusion, although there are few studies assessing the occurrence of A-IgE in subjects with CD, they show the possibility of a coexistence of both diseases and the high clinical significance of this phenomenon, which indicates the need for further studies.

The Crosstalk between the Gut Microbiota Composition and the Clinical Course of Allergic Rhinitis: The Use of Probiotics, Prebiotics and Bacterial Lysates in the Treatment of Allergic Rhinitis.

Although massive progress in discovering allergic rhinitis (AR) aetiology has been made in recent years, its prevalence is still rising and it significantly impacts patients' lives. That is why further and non-conventional research elucidating the role of new factors in AR pathogenesis is needed, facilitating discoveries of new treatment approaches. One of these factors is the gut microbiota, with its specific roles in health and disease. This review presents the process of gut microbiota development, especially in early life, focusing on its impact on the immune system. It emphasizes the link between the gut microbiota composition and immune changes involved in AR development. Specifically, it elucidates the significant link between bacteria colonizing the gut and the Th1/Th2 imbalance. Probiotics, prebiotics and bacterial lysates, which are medications that restore the composition of intestinal bacteria and indirectly affect the clinical course of AR, are also discussed.

Promising Immunomodulatory Effects of Bacterial Lysates in Allergic Diseases.

In light of an escalating prevalence of allergic disorders, it is crucial to fully comprehend their pathophysiology and etiology. Such knowledge would play a pivotal role in the search for new therapeutic approaches concerning not only diseases' symptoms, but also their underlying causes. The hygiene hypothesis indicates a high correlation between limited exposure to pathogens in early childhood and the risk of developing allergic disorders. Bearing in mind the significance of respiratory and digestive systems' mucous membrane's first-line exposure to pathogens as well as its implications on the host's immune response, a therapy targeted at aforesaid membranes could guarantee promising and extensive treatment outcomes. Recent years yielded valuable information about bacterial lysates (BLs) known for having immunomodulatory properties. They consist of antigen mixtures obtained through lysis of bacteria which are the most common etiologic agents of respiratory tract infections. They interact with dendritic cells located in the mucous membranes of the upper respiratory tract and the gastrointestinal tract by toll-like receptors. The dendritic cells present acquired antigens resulting in innate immune response development on the release of chemokines, both stimulating monocytes and NK cells maturation and promoting polymorphonuclear neutrophil migration. Moreover, they influence the adaptive immune system by stimulating an increase of specific antibodies against administered bacterial antigens. The significance of BLs includes not only an anti-inflammatory effect on local infections but also restoration of Th1/Th2 balance, as demonstrated mainly in animal models. They decrease Th2-related cytokine levels (IL-4, IL-13) and increase Th1-related cytokine levels (IFN-γ). The reestablishment of the balance of the immune response leads to lowering atopic reactions incidence which, in addition to reduced risk of inflammation, provides the alleviation and improvement of clinical manifestations of allergic disorders. In this review, we hereby describe mechanisms of BLs action, considering their significant immunomodulatory role in innate immunity. The correlation between local, innate, and adaptive immune responses and their impact on the clinical course of allergic disorders are discussed as well. To conclude our review, we present up-to-date literature regarding the outcomes of BLs implemented in atopic dermatitis, allergic rhinitis, and asthma prevention and treatment, especially in children.

Perspectives for the Use of Bacterial Lysates for the Treatment of Allergic Rhinitis: A Systematic Review.

Bacterial lysates (BLs) are mixtures of bacterial antigens that have been used for many decades to minimize the risk of recurrent respiratory tract infections in both pediatric and adult populations. Research on the use of BLs is also conducted in allergology. Biomedical databases were searched for articles on the use of BLs in the treatment of allergic rhinitis (AR). After rejecting ineligible articles, six remaining reports were reviewed. Based on this review, it can be concluded that adding BL to standard therapy for seasonal or perennial AR reduces the severity of nasal symptoms and the need for antiallergic medications in both children and adults. Concurrently, these formulations have a high safety profile. An analysis of studies shows that the first effects of BLs therapy appear at the earliest 2-6 weeks after the start of treatment and persist at least 3 months after treatment.

Bronchodilator response after two methods of salbutamol nebulization in asthmatic children.

Introduction: Salbutamol is used in bronchodilator response testing (BDRT), which is an important diagnostic tool in bronchial obstructive diseases. Most available studies compare the bronchodilator response of salbutamol administered with a pressurized metered-dose inhaler and salbutamol in a nebulization solution. Aim: The spirometric evaluation of the bronchodilator response of two methods of salbutamol nebulization in asthmatic children. Material and methods: A randomized, open, comparative study was conducted in which 132 children with partially controlled asthma and current bronchial obstruction determined by spirometry were enrolled. BDRT was conducted using salbutamol solution administered with either a continuous jet nebulizer (CON) or a breath-actuated jet nebulizer (BAN). The BAN group received half the dose of the drug compared to the CON group, i.e. 2.5 mg. Changes in FEV1 and FEF25-75 after drug administration were calculated in relation to the baseline values. Results: The change in FEV1 after salbutamol administration was 16.9 ±9.7% in the BAN group and was statistically significantly higher than in the CON group (12.6 ±8.8%) (p = 0.026). The change in FEF25-75 was 37.7 ±23.2% in the BAN group and 32.7 ±25.5% in the CON group (p = 0.061). There were no statistically significant differences in the frequency of adverse events between the compared groups. Conclusions: Salbutamol inhaled from BAN results in a better bronchodilator response than twice the nominal dose of this drug inhaled from CON, which is due to the absence of drug loss during the expiratory phase and therefore greater pulmonary deposition.

Nasal carriage of Staphylococcus aureus in children with grass pollen-induced allergic rhinitis and the effect of polyvalent mechanical bacterial lysate immunostimulation on carriage status: A randomized controlled trial.

BACKGROUND: Numerous studies indicate that Staphylococcus aureus (S. aureus) colonizing the nasal cavity plays a role in the pathogenesis of allergic rhinitis (AR). This bacterium is able to produce a variety of toxins with superantigenic properties that can exacerbate allergic inflammation. OBJECTIVE: The objective of the study was to evaluate the ability of polyvalent mechanical bacterial lysate (PMBL) to eliminate S. aureus nasal carriage in children with grass pollen-induced AR. METHODS: This randomized, double-blind, placebo-controlled study included 80 children aged 5-17 years with seasonal AR (SAR). At the randomization visit and after 12 weeks of the study, a swab was taken from the region of the middle nasal meatus. Standard microbiology culture and identification techniques were used to analyze the swab contents. RESULTS: Nasal colonization by S. aureus was confirmed in 29 children (42%), with Moraxella catarrhalis in three participants (4.4%). Physiological flora was detected in 37 children. No statistically significant differences were observed between the two measurement points in both the PMBL and placebo groups with respect to the number of patients whose nasal swab cultures showed a growth of S. aureus (p = 1). Both groups also showed no significant changes in the mean number of S. aureus colonies in nasal swab cultures taken at baseline and after 12 weeks of the study (PMBL group p = .41; placebo group p = .16). CONCLUSION: Almost every second child with SAR is S. aureus nasal carrier. Sublingual administration of PMBL in children with grass pollen-induced AR did not affect S. aureus nasal colonization. Therefore, PMBL should not be used for the eradication of S. aureus from the nasal cavity.

A comparison of the costs of bronchodilator delivery methods in children with asthma exacerbations treated in hospital. The first Polish study in children.

INTRODUCTION: Recommended methods of administering bronchodilator drugs in children with asthma exacerbations in a hospital include the pressurized metered-dose inhaler (pMDI) and nebulization (NEB). These methods differ in clinical effectiveness, safety and, as some studies indicate, the cost of their use in a child. AIM: To calculate the direct costs of hospital therapy conducted with the use of short-acting ß2-agonist (SABA) or its combination with short-acting muscarinic antagonist (SAMA) administered via pMDI with valved holding chamber (VHC) versus the same drugs in NEB in children with asthma exacerbation. MATERIAL AND METHODS: A retrospective analysis of the costs of SABA (salbutamol) and SABA + SAMA (fenoterol + ipratropium bromide) inhalation therapy was performed. Based on the data obtained from the financial department, the pharmacy, and the sterilization department of the university hospital, the direct unit cost of the inhalation therapy in the child was calculated. RESULTS: The results of the analysis indicate that in a hospital setting the cost of one-time SABA or SABA + SAMA administration via pMDI+VHC is 1.5-2.4 times lower compared to NEB. The payer incurred the lowest costs during anti-obstructive treatment using SABA with pMDI + VHC (PLN 9.39 for one inhalation procedure). The working time of medical staff during the inhalation treatment is the component generating the highest cost for the hospital (up to 40% of direct costs). CONCLUSIONS: In hospital conditions, the supply of SABA or SABA + SAMA with the use of pMDI + VHC in a child with asthma exacerbation is more beneficial financially than the supply of the same drugs in NEB.

Polyvalent Mechanical Bacterial Lysate Administration Improves the Clinical Course of Grass Pollen-Induced Allergic Rhinitis in Children: A Randomized Controlled Trial.

BACKGROUND: Recent studies highlight the immunoregulatory potential of bacterial lysates, indicating their potential use in the prevention and treatment of allergic diseases. OBJECTIVE: To investigate the clinical efficacy of polyvalent mechanical bacterial lysates (PMBLs) in children with grass pollen-induced allergic rhinitis. METHODS: Seventy children with seasonal allergic rhinitis were enrolled to this study and were randomly assigned to the PMBL and placebo groups. Severity of seasonal allergic rhinitis symptoms was assessed by the total nasal symptom score, total ocular symptom score, and visual analogue scale. During 3 visits, peak nasal inspiratory flow was measured, and nasal smears for the presence of eosinophils and nasal lavage fluids for the presence of allergen-specific IgE against timothy grass pollen allergens were sampled. RESULTS: A statistically significant decrease in total nasal symptom score (P = .001), total ocular symptom score (P = .04), and visual analogue scale score for nasal and eye symptoms (P < .001 and P < .001, respectively) and an increase in peak nasal inspiratory flow (P = .04) were observed in the PMBL group versus the placebo group. During the grass pollen season, an increase and then a decrease in the number of eosinophils in nasal smears was observed in both groups; however, the number of eosinophils was significantly lower in the PMBL group versus the placebo group. No significant changes in allergen-specific IgE concentrations were observed in the PMBL group, whereas in the placebo group a statistically significant increase in allergen-specific IgE concentration was observed. CONCLUSIONS: Sublingual administration of PMBLs during the grass pollen season offers significant efficacy in alleviating seasonal allergic rhinitis symptoms in children sensitized to grass pollen allergens. PMBLs probably affect mucosal immunity, weakening the response of TH2 cells.

New guidelines for the treatment of seasonal allergic rhinitis.

The paper discusses the classification and forms of allergic rhinitis with a special focus on seasonal allergic rhinitis (SAR). The general principles of SAR management are presented, including the role of nasal glucocorticoids, nasal and oral antihistamines, and antileukotrienes. Based on the latest guidelines, the current rules for the selection of drugs in the therapy of SAR are given, paying special attention to the initial treatment. The aim of the paper is to present updated guidelines for the pharmacological management of patients with seasonal allergic rhinitis.