Chronic Airway Research Articles

Oxygen and mechanical stretch in the developing lung: risk factors for neonatal and pediatric lung disease.

Chronic airway diseases, such as wheezing and asthma, remain significant sources of morbidity and mortality in the pediatric population. This is especially true for preterm infants who are impacted both by immature pulmonary development as well as disproportionate exposure to perinatal insults that may increase the risk of developing airway disease. Chronic pediatric airway disease is characterized by alterations in airway structure (remodeling) and function (increased airway hyperresponsiveness), similar to adult asthma. One of the most common perinatal risk factors for development of airway disease is respiratory support in the form of supplemental oxygen, mechanical ventilation, and/or CPAP. While clinical practice currently seeks to minimize oxygen exposure to decrease the risk of bronchopulmonary dysplasia (BPD), there is mounting evidence that lower levels of oxygen may carry risk for development of chronic airway, rather than alveolar disease. In addition, stretch exposure due to mechanical ventilation or CPAP may also play a role in development of chronic airway disease. Here, we summarize the current knowledge of the impact of perinatal oxygen and mechanical respiratory support on the development of chronic pediatric lung disease, with particular focus on pediatric airway disease. We further highlight mechanisms that could be explored as potential targets for novel therapies in the pediatric population.

Phaeanthus vietnamensis Ban Ameliorates Lower Airway Inflammation in Experimental Asthmatic Mouse Model via Nrf2/HO-1 and MAPK Signaling Pathway.

Asthma is a chronic airway inflammatory disease listed as one of the top global health problems. Phaeanthus vietnamensis BÂN is a well-known medicinal plant in Vietnam with its anti-oxidant, anti-microbial, anti-inflammatory potential, and gastro-protective properties. However, there is no study about P. vietnamensis extract (PVE) on asthma disease. Here, an OVA-induced asthma mouse model was established to evaluate the anti-inflammatory and anti-asthmatic effects and possible mechanisms of PVE. BALB/c mice were sensitized by injecting 50 μg OVA into the peritoneal and challenged by nebulization with 5% OVA. Mice were orally administered various doses of PVE once daily (50, 100, 200 mg/kg) or dexamethasone (Dex; 2.5 mg/kg) or Saline 1 h before the OVA challenge. The cell infiltrated in the bronchoalveolar lavage fluid (BALF) was analyzed; levels of OVA-specific immunoglobulins in serum, cytokines, and transcription factors in the BALF were measured, and lung histopathology was evaluated. PVE, especially PVE 200mg/kg dose, could improve asthma exacerbation by balancing the Th1/Th2 ratio, reducing inflammatory cells in BALF, depressing serum anti-specific OVA IgE, anti-specific OVA IgG1, histamine levels, and retrieving lung histology. Moreover, the PVE treatment group significantly increased the expressions of antioxidant enzymes Nrf2 and HO-1 in the lung tissue and the level of those antioxidant enzymes in the BALF, decreasing the oxidative stress marker MDA level in the BALF, leading to the relieving the activation of MAPK signaling in asthmatic condition. The present study demonstrated that Phaeanthus vietnamensis BÂN, traditionally used in Vietnam as a medicinal plant, may be used as an efficacious agent for treating asthmatic disease.

Severe asthma and biologics: managing complex patients.

Bronchial asthma is a chronic airway inflammatory disease of the respiratory tract that varies in terms of clinical presentations (phenotypes) and distinct underling pathophysiological mechanisms (endotypes). The definition of phenotype/endotype is crucial tak-ing into account the availability of novel biologic agent dedicated to patients who do not respond to conventional therapies. Although patients suffering from type 2 severe asthma significantly benefit from treatment with biologics no responders patients have been identified. Comorbidities increase the symptoms of asthma and complicate the overall management of the disease. The assessment and treatment of comorbidities is a crucial step and they the appropriate management may improve asthma symptoms and morbidity. Among comorbidities certainly chronic rhinosinusit with nasal polyps, obesity, bronchiectasis and immune defects represent a group of clinical conditions that negatively impact on asthma control despite a correct treatment. Although asthma is frequently characterized by an increase of blood eosinophils that releasing mediators and cytokines are involved in the inflammatory processes of airways wall, in patients with very high blood eosinophil levels it is opportune to be very careful in discerning whether it is a case of isolated severe eosinophilic asthma or a case of asthma in EGPA disease. In addition, hypereosinophilia can be the consequence of specific biological treatment as in the case of dupilumab. In this paper we have outlined the clinical features of those patients with severe asthma in which the management of the disease can be more complex.

Strain stiffening retards growth instability in residually stressed biological tissues

Soft biological tissues often exhibit notable strain stiffening under increasing stretch, and this can have significant effects on tissue growth and morphological development, such as causing symmetry breaking in growing airways and leading to mucosal folding and airway hyperresponsiveness. To investigate the role of strain stiffening and the multifactorial control in growth and remodeling, we consider a growing tubular structure with strain-stiffening effects caused by increased and tightened collagen. In addition, we employ the nonlinear hyperelastic Gent model and initial stress symmetry theory to include the coupling effects of differential growth and initial residual stress. Results show that for strain stiffening that takes place at higher strain (Jm>21), the maximum critical growth ratio matches that obtained using neo-Hookean model calculations. Meanwhile, for biological tissues that exhibit strain stiffening under moderate strain conditions (0.46<Jm<21), the strain-stiffening effect delays significantly the onset of growth instability. When strain stiffening takes place at very low strains (Jm<0.46), stiff biological tissues can prevent growth instability, resulting in a smooth hyperelastic cylindrical tubular structure, and the epithelial tissue remains stable at all growth stages without forming any unstable morphology. Our results suggest that strain stiffening can induce retardation instability during biological growth and remodeling, but airway remodeling can incorporate this effect by increasing wall stiffness and reducing obstruction. This highlights the importance of considering the impact of strain stiffening on biological growth and remodeling, which can inform the development of effective clinical interventions for chronic inflammatory airway diseases.

Assessment of Fitness for Air travel in Patients with Pulmonary Diseases

During air travel, increasing hypoxia with altitude ascent is a potentially serious problem for patients with hypoxemic chronic airway obstruction (CAO). Travel by air is the most popular way of transport nowadays &amp; estimated that each year worldwide, more than 3 billion passengers travel by air &amp; 736 million in the United States alone. For most passengers, even those with respiratory disease, air travel is safe and comfortable. Some patients with COPD &amp;other Chronic Lung diseases may be at risk but, with screening, these patients can be identified and most of them can travel safely with supplemental oxygen. Some patients with chronic lung disease may have mild hypoxemia at sea level but during air travel in a hypobaric hypoxic environment, compensatory pulmonary mechanisms may be inadequate despite normal sea-level oxygen requirements. In addition, compensatory cardiovascular mechanisms may be less effective in some patients who are unable to increase cardiac output. Air travel also presents an increased risk of venous thromboembolism. It's estimated that, almost 1 medical emergency for every 600 flights. Respiratory symptoms accounted for 12% of all these in-air emergencies.&#x0D; Pulse Volume 12-14 2020-2022 p.16-21

T-helper cells and their cytokines in pathogenesis and treatment of asthma.

Prosperous advances in understanding the cellular and molecular mechanisms of chronic inflammation and airway remodeling in asthma have been made over the past several decades. Asthma is a chronic inflammatory disease of the airways characterized by reversible airway obstruction that is self-resolving or remits with treatment. Around half of asthma patients are "Type-2-high" asthma with overexpression of type 2 inflammatory pathways and elevated type 2 cytokines. When stimulated by allergens, airway epithelial cells secrete IL-25, IL-33, and TSLP to derive a Th2 immune response. First ILC2 followed by Th2 cells produces a series of cytokines such as IL-4, IL-5, and IL-13. TFH cells control IgE synthesis by secreting IL-4 to allergen-specific B cells. IL-5 promotes eosinophil inflammation, while IL-13 and IL-4 are involved in goblet cell metaplasia and bronchial hyperresponsiveness. Currently, "Type-2 low" asthma is defined as asthma with low levels of T2 biomarkers due to the lack of reliable biomarkers, which is associated with other Th cells. Th1 and Th17 are capable of producing cytokines that recruit neutrophils, such as IFN-γ and IL-17, to participate in the development of "Type-2-low" asthma. Precision medicine targeting Th cells and related cytokines is essential in the management of asthma aiming at the more appropriate patient selection and better treatment response. In this review, we sort out the pathogenesis of Th cells in asthma and summarize the therapeutic approaches involved as well as potential research directions.

The mouse model of chronic asthma: Airway remodelling and disease exacerbation by somatic antigen of Echinococcus granulosus.

There is now sufficient evidence to support an inverse association between helminth infection and secreted products with allergic/autoimmune disorders. Accordingly, several experimental studies have shown that Echinococcus granulosus infection and hydatid cyst compounds are able to suppress immune responses in allergic airway inflammation. This is the first study on effects of somatic antigens of E. granulosus on chronic allergic airway inflammation in BALB/c mice. Mice in OVA group were intraperitoneally (IP) sensitized with OVA/Alum. Subsequently, were challenged by nebulizing of OVA 1%. The treatment groups received somatic antigens of protoscoleces on the specified days. Mice in PBS group were received PBS in both sensitization and challenge. The effects of somatic products on development of chronic allergic airway inflammation were evaluated by examining histopathological changes, the recruitment of inflammatory cells in the bronchoalveolar lavage, cytokines production in the homogenized lung tissue, and total antioxidant capacity in serum. Our findings show that the co-administration of somatic antigens of protoscoleces simultaneously with the development of asthma intensifies allergic airway inflammation. The identification of effective components involved in exacerbation of allergic airway inflammation manifestations will be a crucial approach to understanding the mechanism of these interactions.

The oral bacteriomes of patients with allergic rhinitis and asthma differ from that of healthy controls.

Allergic rhinitis and asthma are two of the most common chronic respiratory diseases in developed countries and have become a major public health concern. Substantial evidence has suggested a strong link between respiratory allergy and upper airway dysbacteriosis, but the role of the oral bacteriota is still poorly understood. Here we used 16S rRNA massive parallel sequencing to characterize the oral bacteriome of 344 individuals with allergic rhinitis (AR), allergic rhinitis with asthma (ARAS), asthma (AS) and healthy controls (CT). Four of the most abundant (>2%) phyla (Actinobacteriota, Firmicutes, Fusobacteriota, and Proteobacteria) and 10 of the dominant genera (Actinomyces, Fusobacterium, Gemella, Haemophilus, Leptotrichia, Neisseria, Porphyromonas, Prevotella, Streptococcus, and Veillonella) in the oral cavity differed significantly (p ≤ 0.03) between AR, ARAS or AS and CT groups. The oral bacteriome of ARAS patients showed the highest intra-group diversity, while CT showed the lowest. All alpha-diversity indices of microbial richness and evenness varied significantly (p ≤ 0.022) in ARAS vs. CT and ARAS vs. AR, but they were not significantly different in AR vs. CT. All beta-diversity indices of microbial structure (Unifrac, Bray-Curtis, and Jaccard distances) differed significantly (p ≤ 0.049) between each respiratory disease group and controls. Bacteriomes of AR and ARAS patients showed 15 and 28 upregulated metabolic pathways (PICRUSt2) mainly related to degradation and biosynthesis (p < 0.05). A network analysis (SPIEC-EASI) of AR and ARAS bacteriomes depicted simpler webs of interactions among their members than those observed in the bacteriome of CT, suggesting chronic respiratory allergic diseases may disrupt bacterial connectivity in the oral cavity. This study, therefore, expands our understanding of the relationships between the oral bacteriome and allergy-related conditions. It demonstrates for the first time that the mouth harbors distinct bacteriotas during health and allergic rhinitis (with and without comorbid asthma) and identifies potential taxonomic and functional microbial biomarkers of chronic airway disease.

Chronic airway epithelial hypoxia exacerbates injury in muco-obstructive lung disease through mucus hyperconcentration.

Unlike solid organs, human airway epithelia derive their oxygen from inspired air rather than the vasculature. Many pulmonary diseases are associated with intraluminal airway obstruction caused by aspirated foreign bodies, virus infection, tumors, or mucus plugs intrinsic to airway disease, including cystic fibrosis (CF). Consistent with requirements for luminal O2, airway epithelia surrounding mucus plugs in chronic obstructive pulmonary disease (COPD) lungs are hypoxic. Despite these observations, the effects of chronic hypoxia (CH) on airway epithelial host defense functions relevant to pulmonary disease have not been investigated. Molecular characterization of resected human lungs from individuals with a spectrum of muco-obstructive lung diseases (MOLDs) or COVID-19 identified molecular features of chronic hypoxia, including increased EGLN3 expression, in epithelia lining mucus-obstructed airways. In vitro experiments using cultured chronically hypoxic airway epithelia revealed conversion to a glycolytic metabolic state with maintenance of cellular architecture. Chronically hypoxic airway epithelia unexpectedly exhibited increased MUC5B mucin production and increased transepithelial Na+ and fluid absorption mediated by HIF1α/HIF2α-dependent up-regulation of β and γENaC (epithelial Na+ channel) subunit expression. The combination of increased Na+ absorption and MUC5B production generated hyperconcentrated mucus predicted to perpetuate obstruction. Single-cell and bulk RNA sequencing analyses of chronically hypoxic cultured airway epithelia revealed transcriptional changes involved in airway wall remodeling, destruction, and angiogenesis. These results were confirmed by RNA-in situ hybridization studies of lungs from individuals with MOLD. Our data suggest that chronic airway epithelial hypoxia may be central to the pathogenesis of persistent mucus accumulation in MOLDs and associated airway wall damage.

GliSODin® prevents airway inflammation by inhibiting T-cell differentiation and activation in a mouse model of asthma.

Asthma is a chronic inflammatory airway disease characterized by a prevailing type 2 inflammation, airway hyperresponsiveness, and mucus hypersecretion and is driven by various factors among which oxidative molecules, called reactive oxygen species (ROS), play a major role. Superoxide dismutases (SODs) are enzymes that constitute the first line of defense against ROS. Melon SOD-gliadin, which is known as GliSODin®, is commonly used as a nutritional supplement that has proven antioxidant properties. In this study, we evaluated the efficacy and mechanism of action GliSODin® in the treatment of allergic asthma. House dust mite (HDM)-induced asthmatic mice were orally exposed to GliSODin®, and airway hyperresponsiveness, lung inflammation, in vitro T-cell polarization, in vivo T-cell reactivation, and blood immunoglobulin were investigated. GliSODin® reduced airway hyperresponsiveness, lung innate and adaptive immune response, and HDM-specific IgE production. Coculturing CD4+ T-cell with HDM-sensitized dendritic cells and GliSODin® reduced T-cell polarization into Th2 and Th17 cells. Moreover, adoptively transferred CD4+ T cells from asthmatic mice exhibited a reduced reactivation of Th2 and Th17 cells following stimulation with HDM plus GliSODin®. GliSODin® abrogates asthma features and reduces CD4+ T-cell polarization and reactivation. Taken together, these data suggest that GliSODin® could be used for the management of asthma symptoms.

Baseline reticular basement membrane morphology is related to subsequent spirometry deterioration in pediatric chronic airway inflammation: a follow-up study.

Reticular basement membrane (RBM) thickening may occur in children with allergic bronchial asthma (BA), cystic fibrosis (CF), and primary ciliary dyskinesia (PCD). Its functional consequences remain unknown. We investigated the relationship between baseline RBM thickness and subsequent spirometry. In our cohort follow-up study, patients aged 3-18 yr with BA, CF, and PCD and controls underwent baseline lung clearance index (LCI) measurement, spirometry, and endobronchial biopsy sampling. Total RBM and collagen IV-positive layer thickness were measured. Trends in forced vital capacity (FVC), forced expired volume in 1 s (FEV1), and FEV1/FVC were analyzed during follow-up, and their relationship to baseline characteristics was studied using univariate analysis and multiple regression models. Complete baseline data were available in 19 patients with BA, 30 patients with CF, 25 patients with PCD, and 19 controls. The RBM was thicker in patients with BA (6.33 ± 1.22 μm), CF (5.60 ± 1.39 μm), and PCD (6.50 ± 1.87 μm) than in controls (3.29 ± 0.55 μm) (all P < 0.001). The LCI was higher in patients with CF (15.32 ± 4.58, P < 0.001) and PCD (10.97 ± 2.46, P = 0.002) than in controls (7.44 ± 0.43). The median follow-up times were 3.6, 4.8, 5.7, and 1.9 years in patients with BA, CF, PCD, and controls, respectively. The z-scores of FEV1 and FEV1/FVC deteriorated significantly in all groups except in controls. In patients with CF and PCD, trends in FEV1 z-scores correlated with baseline LCI and RBM; in BA, it correlated with collagen IV. In multiple regression models, RBM morphology and ventilation inhomogeneity could predict up to 84.4% of variability in spirometry trends. In conclusion, baseline LCI value and RBM morphology may predict trends in subsequent spirometry.NEW & NOTEWORTHY This paper deals with the relationship between reticular basement membrane (RBM) morphology at baseline and follow-up spirometry in children with asthma, cystic fibrosis, and primary ciliary dyskinesia. For the first time, to our knowledge, the possibility to predict subsequent lung function development using selected baseline characteristics (reticular basement membrane morphology from endobronchial biopsy and ventilation inhomogeneity from nitrogen multiple breath washout test) is proposed. Corresponding predictive models are presented.

Economic impact of a more extensive use of FENO testing on the Italian population with asthma

BackgroundAsthma is a common chronic inflammatory airway affecting over 260 million people worldwide, and characterized, in the large majority of cases, by the so-called “type 2 inflammation”. Fractional exhaled nitric oxide (FENO) testing is noninvasive point-of-care tool to assess type 2 inflammation and therefore improve asthma management. It has been suggested to determine eligibility for a specific biologic therapy and predict likelihood to respond. The aim of this study was to estimate the overall economic impact of an extensive use of FENO testing on the Italian population with asthma, including extra costs of testing and savings generated by more appropriate prescriptions, increased adherence and lower frequency of exacerbations.MethodsA cost of illness analysis was firstly performed to estimate the yearly economic burden from the National Healthcare Service (NHS) perspective in Italy of the management of asthmatic patients with standard of care (SOC) according to the application of GINA (Global Initiative for Asthma) guidelines; then, we evaluated the changes in the economic burden in patient management by introducing FENO testing into clinical practice. The cost items considered were: visits/exams, exacerbations, drugs, management of adverse events caused by short-term oral corticosteroids use. Efficacy of FeNO test and SOC is based on literature evidence. Costs refer to published data or Diagnosis Related Group/outpatient tariffs.ResultsConsidering one asthma visit every 6 months, the total yearly cost for the management of patients with asthma in Italy is 1,599,217,876€ (409.07€ per patient), while for FENO testing strategy this figure is 1,395,029,747€ (356.84€ per patient). An increased utilization rate of FENO testing from 50 to 100% of patients may lead to savings for the NHS from about 102 to 204 million € compared to SOC.ConclusionsOur study showed that FeNO testing strategy may improve the management of asthmatic patients leading to significant savings for the NHS.

Identification of autoantigens and their potential post-translational modification in EGPA and severe eosinophilic asthma.

The chronic airway inflammation in severe eosinophilic asthma (SEA) suggests potential autoimmune aetiology with unidentified autoantibodies analogous to myeloperoxidase (MPO) in ANCA-positive EGPA (eosinophilic granulomatosis with polyangiitis). Previous research has shown that oxidative post-translational modification (oxPTM) of proteins is an important mechanism by which autoantibody responses may escape immune tolerance. Autoantibodies to oxPTM autoantigens in SEA have not previously been studied. Patients with EGPA and SEA were recruited as well as healthy control participants. Autoantigen agnostic approach: Participant serum was incubated with slides of unstimulated and PMA-stimulated neutrophils and eosinophils, and autoantibodies to granulocytes were identified by immunofluorescence with anti-human IgG FITC antibody. Target autoantigen approach: Candidate proteins were identified from previous literature and FANTOM5 gene set analysis for eosinophil expressed proteins. Serum IgG autoantibodies to these proteins, in native and oxPTM form, were detected by indirect ELISA. Immunofluorescence studies showed that serum from patients with known ANCA stained for IgG against neutrophils as expected. In addition, serum from 9 of 17 tested SEA patients stained for IgG to PMA-stimulated neutrophils undergoing NETosis. Immunofluorescent staining of eosinophil slides was evident with serum from all participants (healthy and with eosinophilic disease) with diffuse cytoplasmic staining except for one SEA individual in whom subtle nuclear staining was evident. FANTOM5 gene set analysis identified TREM1 (triggering receptor expressed on myeloid cells 1) and IL-1 receptor 2 (IL1R2) as eosinophil-specific targets to test for autoantibody responses in addition to MPO, eosinophil peroxidase (EPX), and Collagen-V identified from previous literature. Indirect ELISAs found high concentrations of serum autoantibodies to Collagen-V, MPO, and TREM1 in a higher proportion of SEA patients than healthy controls. High concentrations of serum autoantibodies to EPX were evident in serum from both healthy and SEA participants. The proportion of patients with positive autoantibody ELISAs was not increased when examining oxPTM compared to native proteins. Although none of the target proteins studied showed high sensitivity for SEA, the high proportion of patients positive for at least one serum autoantibody shows the potential of more research on autoantibody serology to improve diagnostic testing for severe asthma. ClinicalTrials.gov, identifier, NCT04671446.

WS18.01 Impact of elexacaftor/tezacaftor/ivacaftor therapy on sputum metabolomics in adult cystic fibrosis

Background: Adults with cystic fibrosis (CF) suffer from chronic inflammation, infection, and airway obstruction, and often have enhanced sputum production. Although CF transmembrane conductance regulator modulator therapies such as elexacaftor-tezacaftor-ivacaftor (ETI) confer lung function gains in patients with CF, their impact on inflammation and infection is not fully understood. CF sputum contains metabolites and proteins that reflect inflammation. We hypothesized the impact of ETI therapy on CF airway inflammation would be mirrored by changes in the sputum metabolome.

Twenty years of changes in the definition of early chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease that affects the quality of life of nearly one-tenth of the global population. Due to irreversible airflow obstruction and progressive lung function decline, COPD is characterized by high mortality and disability rates, which imposes a huge economic burden on society. In recent years, the importance of intervention in the early stage of COPD has been recognized and the concept of early COPD has been proposed. Identifying and intervening in individuals with early COPD, some of whom have few or no symptoms, might halt or reverse the progressive decline in lung function, improve the quality of life, and better their prognosis. However, understanding of early COPD is not yet well established, and there are no unified and feasible diagnostic criteria, which complicates clinical research. In this article, we review evolution of the definition of early COPD over the past 20 years, describe the changes in awareness of this concept, and propose future research directions.

Prolonged inflammatory resolution in allergic asthma relates to dysfunctional interactions between neutrophils and airway epithelium

BackgroundAllergic asthma is a heterogeneous disorder involving chronic airway inflammation, reversible airflow limitation, and tissue remodeling, causing chronic airflow limitation. Most of the asthma research has been focused on elucidating the proinflammatory pathways underlying disease pathogenesis. Paradoxically, the necessity of appropriate termination and resolution of inflammation has not been recognized until recently. The latter has led to the concept of chronic inflammation developing as a result of lack of specific “stop” signals for the inflammatory process. ObjectiveTo investigate the interaction between neutrophils and airway epithelium during inflammatory resolution in patients with allergic asthma. MethodsAn in vitro scratch assay with cultured epithelial cells, based on live-imaging microscopy, was used to evaluate regeneration and the influence of neutrophils on resolution. Epithelial cells and autologous neutrophils were derived from healthy donors and patients with allergic asthma. Supernatants and cells were collected for enzyme-linked immunosorbent assay and transcriptional analyses at the end of the experiment. ResultsHealthy epithelial cells regenerated faster than epithelial cells from patients with allergic asthma. Autologous neutrophils improved the regeneration of healthy epithelial cells but not asthmatic epithelial cells. Interleukin (IL)-8 and β-catenin were down-regulated in healthy epithelial cells after resolution, but not in allergic asthmatic epithelial cells. ConclusionThe prolonged duration of inflammation in the respiratory tract in patients with allergic asthma could be due to the impaired healing pattern of epithelial cells and their compromised interactions with the neutrophils.

Effects of in-house and commercial extracts of the allergenic mite Tyrophagus putrescentiae on murine and human cell responses.

Mites are among the major sources of domestic and occupational allergens worldwide, and continuous exposure to these allergens leads to chronic airway inflammation. One of the most allergenic species is the storage mite Tyrophagus putrescentiae (Schrank). Protein extracts are produced from this mite for tests that help the clinical diagnosis (via prick test), treatment, and monitoring of disease progression in patients who had positive results for allergic reactions. Therefore, the aim of the present study was to evaluate the cell viability of RAW 264.7 and L929 cells when exposed to in-house raw protein extracts of T. putrescentiae compared to a commercial product, as well as quantify TNF-α secretion by RAW 264.7. Additionally, this study quantified the effect of these extracts in IgE secretion in total blood of people affected by this mite. The study found similarity between the in-house extract and the commercial extract as they had equivalent TNF-α secretion. Additionally, viabilities of RAW 264.7 and L929 exposed to the in-house extract were compatible with viabilities of cells exposed to the commercial extract, with no cytotoxicity at the concentrations tested. Results corroborated the hypothesis that the extract produced in-house would be equivalent to the commercial extract in allergic patients when the IgE was quantified. This study is the first to show the cytotoxicity of T. putrescentiae extracts, and to provide a quantitative analysis of TNF-α and IgE.

Clinical, paraclinical, and genetic profile of patients with cystic fibrosis from Colombian Caribbean

BackgroundCystic fibrosis (CF) is a serious autosomal recessive disorder. Early diagnosis, comorbidity prevention, and control are cornerstones for a quality life and for improving life expectancy. In Colombian Caribbean, where there is a genetically admixed population, CF is an orphan disease affecting children and adults, and it remains a challenging issue to be addressed carefully. This work describes the genetic, clinical, and paraclinical profiles of CF patients from Cartagena de Indias, Colombia. MethodsThirty-six patients were included in the study. The subjects were identified and evaluated through the Regional Program for CF patients. CFTR gene mutations, anthropometric parameters, microbiological infections, and pulmonary function were analyzed. Data on demographic parameters, pharmacological treatments, and comorbidities were reported. Frequency and percentages were established for the categorical variables and mean or median for the quantitative variables. In addition, comparisons were made by sex. ResultsThe average age of the patients was 11.9 ± 5.3 years and the median age at diagnosis was 14 months. 55.5% were women and 44.5% were men. The mean values for weight, height, and body mass index were 35 ± 17.6 kg, 139.9 ± 28 cm, and 16.5 ± 2.9 kg/m2, respectively. The clinical manifestations that occurred more frequently were steatorrhea (65.4%) and recurrent pneumonia (46.2%). Chronic airway infection with Pseudomonas aeruginosa was identified in 71.4% of the cases and the p.F508del mutation was found in 47.2% of the subjects. ConclusionThe current profile of CF patients from the Colombian Caribbean showed some concerning features, such as nutritional status; however, progress in early diagnosis and clinical follow-up could contribute to improve the general conditions of patients. It is necessary to continue efforts to increase the life expectancy and quality of life of the patients.

ЭВОЛЮЦИЯ ПРЕДСТАВЛЕНИЙ О РОЛИ ХРОНИЧЕСКОГО ВОСПАЛЕНИЯ КАК КЛЮЧЕВОГО ЗВЕНА В ПАТОГЕНЕЗЕ БРОНХИАЛЬНОЙ АСТМЫ

ntroduction. Asthma is considered as a heterogeneous disease. Recently, the pathophysiological mechanisms of chronic airway inflammation development have been established. However, the evolution of understanding the asthma pathogenesis is a matter of great interest. Aim. Based on literature review, our aim was to provide the key milestones in the formation of modern understandings in asthma etiology and pathogenesis. Material and methods. We searched across PubMed and eLibrary.ru databases to identify articles published in 1900-2022, using the keywords ‘bronchial asthma’, ‘history’, ‘pathogenesis’, ‘eosinophilic inflammation’, ‘endotypes’, ‘biomarkers’, ‘innate lymphoid cells’ and ‘Th2 lymphocytes’. Results and discussion. Since ancient times scientists were interested in the mechanisms of asthma development. ‘Asthma’ derived from Greek word that means ‘shortness of breath’ and ‘suffocation’. In the Middle Ages, science was scholasticism oriented, so the understandings of asthma were based only on observational studies, and the works of Hippocrates and Galen were considered irrefutable. Subsequently, in Modern times observational studies were supported by experiments and that gave the opportunity to study the asthma pathogenesis. Since the 20th century studies on identifying the roles of heredity, sensitization and mechanisms of airway inflammation have flourished and that led to the identification of asthma endotypes and phenotypes. Recent trends in the understanding of pathogenesis at molecular levels provided a personalized approach to asthma treatment. Conclusion. Thus, accumulated clinical observational and experimental data gained new insights into asthma pathogenesis and led to the development of biologics for the management of asthma. This study was funded by grant from Kazan State Medical University N2/22-10 (02.08.2022).

P273 Chronic airway infection and resistance pattern in children and adults with cystic fibrosis in Oman. A single centre cross sectional study

To assess the pattern of airway bacterial growth among cystic fibrosis (CF) patients in Oman, and to identify possible risk factors for the hypothesize early Pseudomonas aeruginosa (PA) acquisition among these children.