Variable Airflow Research Articles

Epidemiology and Immunopathogenesis of Virus Associated Asthma Exacerbations.

Asthma is a common airway disease, affecting millions of people worldwide. Although most asthma patients experience mild symptoms, it is characterized by variable airflow limitation, which can occasionally become life threatening in the case of a severe exacerbation. The commonest triggers of asthma exacerbations in both children and adults are viral infections. In this review article, we will try to investigate the most common viruses triggering asthma exacerbations and their role in asthma immunopathogenesis, since viral infections in young adults are thought to trigger the development of asthma either right away after the infection or at a later stage of their life. The commonest viral pathogens associated with asthma include the respiratory syncytial virus, rhinoviruses, influenza and parainfluenza virus, metapneumovirus and coronaviruses. All these viruses exploit different molecular pathways to infiltrate the host. Asthmatics are more prone to severe viral infections due to their unique inflammatory response, which is mostly characterized by T2 cytokines. Unlike the normal T1 high response to viral infection, asthmatics with T2 high inflammation are less potent in containing a viral infection. Inhaled and/or systematic corticosteroids and bronchodilators remain the cornerstone of asthma exacerbation treatment, and although many targeted therapies which block molecules that viruses use to infect the host have been used in a laboratory level, none has been yet approved for clinical use. Nevertheless, further understanding of the unique pathway that each virus follows to infect an individual may be crucial in the development of targeted therapies for the commonest viral pathogens to effectively prevent asthma exacerbations. Finally, biologic therapies resulted in a complete change of scenery in the treatment of severe asthma, especially with a T2 high phenotype. All available data suggest that monoclonal antibodies are safe and able to drastically reduce the rate of viral asthma exacerbations.

Immunometabolism in the pathogenesis of asthma.

Bronchial asthma is a heterogeneous disease characterised by chronic airway inflammation. A variety of immune cells such as eosinophils, mast cells, T lymphocytes, neutrophils and airway epithelial cells are involved in the airway inflammation and airway hyperresponsiveness in asthma pathogenesis, resulting in extensive and variable reversible expiratory airflow limitation. However, the precise molecular mechanisms underlying the allergic immune responses, particularly immunometabolism, remains unclear. Studies have detected enhanced oxidative stress, and abnormal metabolic progresses of glycolysis, fatty acid and amino acid in various immune cells, inducing dysregulation of innate and adaptive immune responses in asthma pathogenesis. Immunometabolism mechanisms contain multiple signalling pathways, providing novel therapy targets for asthma. This review summarises the current knowledge on immunometabolism reprogramming in asthma pathogenesis, as well as potential therapy strategies.

Causal Link between Human Blood Metabolites and Asthma: An Investigation Using Mendelian Randomization

Background: Asthma, a chronic inflammatory respiratory ailment, is characterized by variable airflow obstruction and heightened bronchial reactivity. Despite therapeutic advancements, a comprehensive comprehension of its underlying metabolic mechanisms remains elusive. Metabolomics has emerged as a powerful approach to investigating the complex connections between serum metabolites and disease pathogenesis. However, exploring the causal relationship between serum metabolites and asthma susceptibility demands meticulous examination to unveil potential therapeutic targets. Methods: Mendelian randomization (MR) approach was explored to investigate the potential causal associations between serum metabolites and asthma risk. The main analysis employed the inverse variance weighted method, supported by supplementary approaches such as MR-Egger, weighted median, weighted mode, and sample mode. To enhance the strength and credibility of our results, we conducted sensitivity analyses encompassing heterogeneity testing, assessment of horizontal pleiotropy, and leave-one-out analysis. Additionally, pathway enrichment analysis was performed to further elucidate the results. Results: We identified 18 known and 12 unknown metabolites with potential associations with asthma risk. Among known metabolites, seven exhibited protective effects (e.g., 4-acetamidobutanoate, allantoin, kynurenine, oxidized bilirubin*), while eleven were considered risk factors (e.g., ornithine, N-acetylornithine, alanine). Through the integration of four additional MR models and sensitivity analyses, we revealed a connection between 4-acetamidobutanoate and approximately 6% lower asthma risk (OR = 0.94, 95% CI: 0.90–0.98). Conclusions: Our MR analysis uncovered protective and risk-associated metabolites, alongside 12 unknown metabolites linked to asthma. Notably, 4-acetamidobutanoate demonstrated a nominal 6% reduction in asthma risk, highlighting its potential significance.

Review and perspective of clinical research involving chest tightness variant asthma in China

Chest tightness variant asthma (CTVA) was first reported and named by Chinese scholars in 2013. It is a new clinical type of asthma characterized by chest tightness as the only or primary symptom, without typical asthma manifestations such as recurrent wheezing and shortness of breath, and without wheezing sounds heard during lung auscultation. The overall epidemiological data on CTVA is currently unavailable. Its pathogenesis is similar to that of typical asthma, involving eosinophilic airway inflammation. Due to the lack of typical clinical manifestations, insufficient knowledge of this disease in some clinicians and some other reasons, CTVA is susceptible to misdiagnosis or missed diagnosis. Currently, the diagnostic criteria for CTVA are: chest tightness as the only or primary symptom, without typical asthma symptoms and signs such as wheezing and shortness of breath, and with any one of the objective indicators of variable airflow limitation. Effective anti-asthma treatment is required, and other diseases that cause chest tightness, such as cardiovascular, digestive, nervous, muscular, and mental diseases should be excluded. CTVA treatment follows that of typical asthma, but the specific treatment duration is uncertain and may require long-term management. Traditional Chinese medicine has shown some therapeutic effects on CTVA. Most CTVA patients have a good prognosis after active anti-asthma treatment. This paper analyzes and summarizes the research of CTVA in China from 2013 and provides new perspectives for further exploration of CTVA.

Summary of Korean Asthma Guideline.

Asthma is a chronic inflammatory airway disease that is characterized by variable airflow obstruction. The Korean Asthma Study Group of the Korean Academy of Tuberculosis and Respiratory Diseases has recently updated the Korean Asthma Guideline. This review summarizes the updated Korean Asthma Guideline. Asthma prevalence is increasing worldwide, and in Korea. Variable airflow obstruction can be confirmed by bronchodilator response or other tests, and should be established prior to the controller medication. A low-dose inhaled corticosteroid-formoterol is used to alleviate symptoms in all treatment step, and it can be used as a controller as well as reliever in steps 3-5. This approach is preferred, because it reduces the risk of severe exacerbations, compared to the use of short-acting β2-agonist as reliever. In severe asthma, phenotype/endotype based on the underlying inflammation should be evaluated. For type 2 severe asthma, the biologics should be considered.

A CONCEPTUAL STUDY TO EVALUATE THE EFFECT OF POUSHKARADI KASHAYA IN TAMAKA SWASA - BRONCHIAL ASTHMA

TamakaSwasa(Bronchial asthma) is a chronic disorder of Pranavaha Srotas that disturbs daily activities. It is caused by Pratiloma Gati of Vayu supported by Srothorodha produced by Kapha. It is well explained in all the classical texts of Ayurveda. The Udbhavasthana of Swasaroga is said as Amashaya in the classics. Bronchial Asthma, which can be compared with TamakaSwasa is a chronic inflammatory disease of the respiratory tract causing airway obstruction and variable airflow limitation. The prevalance of Asthma has increased over the past 30 years. Asthma is also a complex disease determined by the interaction between genetic and environmental factors. Modern synthetic drugs provide instant relief in these cases but tend to develop a number of adverse drug reactions. As this is a srotorodhavyadhi produced by Vata and Kapha, Drugs which are VataKapha Hara, UsnaVeerya, and VataAnulomana are prescribed in this condition. The polyherbal formulation Poushkaradi Kashaya mentioned in Sahasrayogam, Kashaya Prakarana in SwasakasaAdhikara is UshnaVeerya with KaphaVatha Hara and SwasaKasa Hara properties. Hence it will be effective in removing Kapharodha and causing Vatha Anulomana. Individual drugs in combination likePushkaramoola are antispasmodic, antiinflammatory, and antihistaminic.

Endobronchial hydatid cyst causing variable intrathoracic airflow limitation selectively during expiration acting as a ball valve.

The online version contains supplementary material available at 10.1007/s12055-023-01541-4.

Experimental study on the operating performance of the air source heat pump (ASHP) with variable outdoor airflow rate under the standard frosting condition

Frosting is a common phenomenon of the ASHP under the heating mode in winter, and the outdoor air flow rate flowing through the evaporator of the ASHP was always thought to be a major contributor. In order to validate its contribution, effects of outdoor fan airflow rate on the performance of air source heat pumps (ASHPs) were investigated under the winter heating condition. The experiment was conducted in a laboratory at the standard 2 °C air dry bulb temperature (DB)/ 1 °C air wet bulb temperature (WB) frosting condition, which enabled the analysis of the operating performance, frosting performance, and heating performance of the ASHP unit by changing the airflow rate of the outdoor fan. Results showed that as the airflow rate of the outdoor fan reduced from 100% to 36%, the operating performance decline and the elevated frosting-defrosting loss were observed. Meanwhile, both the frosting rate and the operating efficiency during frosting-defrosting cycles showed an increasing trend then followed by decreasing tendency. The maximum frosting rate and operating efficiency were 0.92 g/m2.min and 2.92, respectively, which were observed at 74% airflow rate of the outdoor fan of the ASHP unit. The observation implied the existence of the “minimum frosting suppression airflow rate”. At 36% airflow rate of the outdoor fan of the ASHP unit, however, the performance of the ASHP unit was attenuated greatly, with the frosting-defrosting efficiency loss coefficient of 0.47, the heating capacity and COP reduction by 51.5 and 38.8%, respectively. These findings provided significant references to the optimization of ASHPs performance with variable airflow rate of the outdoor fan under frosting conditions.

Improving production and prediction of the flow regimes, pressure drop, and void fraction in the perforated horizontal wellbore

This study aimed to investigate how oil production could be improved by experimenting with different distribution methods across multiple profiles. The authors tested five different profiles that included uniform radial airflow (explained in profile 1) and variable radial airflow (explained in profiles 2, 3, 4 and 5) in a perforated horizontal wellbore. In addition, the study predicted the behavior of total pressure drop, superficial mixture velocity and void fraction encountered in different flow patterns (bubble, slug, stratum and stratum wave flow). Flow patterns were predicted using ANSYS Fluent R3 with a borehole length of 3 m and an ID of 0.0381 m. This was designed with 12 perforations opening vertically at the wellbore with a phase angle of 180 and a perforation density of 4 shots per foot to simulate the complex flow in a horizontal wellbore. In the perforated section, there was a fluctuation in the behavior of the parameters, while in the non-perforated section, the behavior remained constant. The behavior of the total pressure drop, the superficial velocity mixtures and the void fraction were also reasonably uniform in profile 1 in the perforated section.In contrast, they were irregular in the other profiles. In profiles 2, 3, 4 and 5, the behavior of the mixture superficial velocity and void fraction was inverse to the total pressure drop. Note that all theoretically calculated pressure drop modes increased as the Reynolds number of the mixture increased. The liquid and air product increased with increasing Reynolds number of mixture flow in the profiles. In contrast, in profile 1, lower production was obtained through all flow patterns due to the influence of the mixture pressure and the friction factor. The Vogels method was used to calculate maximum production from the horizontal wellbore. The convergence between experimental and numerical results was good during all cases (flow patterns), with some difference in the static pressure drop behaviuor occurring during flow patterns (bubble, dispersed bubble and slug flow).

Comparative study of eosinophil count in peripheral blood, sputum and BAL fluid in patients of bronchial asthma

Bronchial Asthma is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation. Airflow limitation may later become persistent over the course of disease. To compare the findings of eosinophil counts in peripheral blood, induced sputum and bronchoalveolar lavage fluid in asthmatic patients and healthy individuals. This Case Control Cross sectional study was conducted among patients attending respiratory OPD at Sir Sunder Lal Hospital, BHU, Varanasi, with diagnosis of bronchial asthma (100) and healthy controls. Significant association was found between eosinophilic bronchial asthma and absolute eosinophil count (W = 1168.000, p = 0.020), total serum IgE (W = 1338.000, p = <0.001), BAL eosinophil count (χ2 = 94.589, p = <0.001), sputum eosinophil count (χ2 = 14.057, p = <0.001).

Simulation of a flat solar collector with thermal storage for drying food

This research addresses the numerical simulation of a working fluid, using specialized SolidWorks Flow Simulation Software, analyzing the behavior of a drying air in a flat solar collector with thermal energy storage. In addition, one of the main centers of computational study is the relationship between flow, air temperature at the outlet of the collector and efficiency; This study allows researchers a vision of the principles of the design of these technologies, especially if it focuses on the drying of food. Then, a proposal is made on the requirements to be taken into account for the sizing of collectors based on the requirements of the product to be dried. Among the results obtained, it is established that a correctly designed collector and under a variable air flow, based on the intensity of the irradiation in specific coordinates and location, can reach efficiencies close to 30% with temperatures close to 60 ° C, being ideal for injecting this fluid into a drying chamber, where the food to be dehydrated is available. For the selection of the volume of the material for energy storage, it is recommended to take the melting temperatures as a base, with a constant flow of air, it is normal that within the system, the temperature varies depending on the position, therefore it is recommending the application of materials with different melting temperatures, which are strategically located within the storage tank.

Whole Blood Expression Levels of Long Noncoding RNAs: HOTAIRM1, GAS5, MZF1-AS1, and OIP5-AS1 as Biomarkers in Adolescents with Obesity-Related Asthma

Asthma is a heterogeneous entity encompassing distinct endotypes and varying phenotypes, characterized by common clinical manifestations, such as shortness of breath, wheezing, and variable airflow obstruction. Two major asthma endotypes based on molecular patterns are described: type 2 endotype (allergic-asthma) and T2 low endotype (obesity-related asthma). Long noncoding RNAs (lncRNAs) are transcripts of more than 200 nucleotides in length, currently involved in many diverse biological functions, such as chromatin remodeling, gene transcription, protein transport, and microRNA processing. Despite the efforts to accurately classify and discriminate all the asthma endotypes and phenotypes, if long noncoding RNAs could play a role as biomarkers in allergic asthmatic and adolescent obesity-related asthma, adolescents remain unknown. To compare expression levels of lncRNAs: HOTAIRM1, OIP5-AS1, MZF1-AS1, and GAS5 from whole blood of Healthy Adolescents (HA), Obese adolescents (O), allergic asthmatic adolescents (AA) and Obesity-related asthma adolescents (OA). We measured and compared expression levels from the whole blood of the groups mentioned above through RT-q-PCR. We found differentially expressed levels of these lncRNAs between the groups of interest. In addition, we found a discriminative value of previously mentioned lncRNAs between studied groups. Finally, we generated an interaction network through bioinformatics. Expression levels of OIP5-AS1, MZF1-AS1, HOTAIRM1, and GAS5 in whole blood from the healthy adolescent population, obese adolescents, allergic asthma adolescents, and obesity-related asthma adolescents are differently expressed. Moreover, these lncRNAs could act as molecular biomarkers that help to discriminate between all studied groups, probably through molecular mechanisms with several genes and miRNAs implicated.

A remote and personalised novel approach for monitoring asthma severity levels from EEG signals utilizing classification algorithms

Asthma is a complex respiratory disorder in which structural changes in the conducting airway cause variable airflow limitation. The excessive narrowing of the airway lumen underlies the morbidity and the mortality that are attributable to the disease, which reduces quality of life in people of all ages. Monitoring of the disease progression to gather data continuously as an objective marker of morbidity and to support therapy is essential. Currently, patients with asthma are examined only a few times a year, which prevents continuous monitoring of the disease progression and any advance in precision medicine. Remote non-invasive monitoring tools will enable the collection of data with minimal effort from patients. To date, however, assessment and monitoring of asthma based on electroencephalogram (EEG) signals have not been studied. The objective of this research was to develop a general approach for identifying asthma severity levels based on EEG signals for personalised remote and non-invasive monitoring of patients with asthma. Simultaneous measurements of EEG and respiration motion signals were acquired from adults with suspected asthma, during the entire methacholine challenge test. The EEG segments were categorized into three classes, each representing a level of asthma severity based on participant’s spirometry score. Three artificial intelligence (AI) methodologies were designed and examined: the first aimed to identify a subject’s asthma severity levels based on their known data, the second based on mixed data comprising data from all subjects including the subject’s personal data, and the third methodology based on the datasets of all other subjects, reflecting a situation of a new patient. To overcome multi-subject variations in the third methodology, the probabilities of being at each one of the possible asthma severity levels in previous breathing cycles, as inputs for predictions of asthma severity levels in the current breathing cycle, was used. The classification was done based on ordinal and non-ordinal classification algorithms. In the first and second methodologies, an ensemble approach was also applied to enhance predictive performance. Good performance measures were obtained to identify asthma severity level using both the first and second methodologies, especially by the ensemble model and XGBoost classifier. In the third methodology, the combination of random forest and ordinal random forest in different stages of the methodology, yielded the best improvement in performance measures. The results of all three AI methodologies demonstrate that they may be employed for personalised home asthma monitoring and management that do not depend on patients exerting an effort.

Anatomical and histopathological approaches to asthma phenotyping

Asthma is typically characterized by variable respiratory symptoms and airflow limitation. Along with the pathophysiology and symptoms are immunological and inflammatory processes. The last decades research has revealed that the immunology of asthma is highly heterogeneous. This has clinical consequences and identification of immunological phenotypes is currently used to guide biological treatment. The focus of this review is on another dimension of asthma diversity, namely anatomical heterogeneity. Immunopathological alterations may go beyond the central airways to also involve the distal airways, the alveolar parenchyma, and pulmonary vessels. Also, extrapulmonary tissues are affected. The anatomical distribution of inflammation in asthma has remained relatively poorly discussed despite its potential implication on both clinical presentation and response to treatment. There is today evidence that a significant proportion of the asthma patients has small airway disease with type 2 immunity, eosinophilia and smooth muscle infiltration of mast cells. The small airways in asthma are also subjected to remodelling, constriction, and luminal plugging, events that are likely to contribute to the elevated distal airway resistance seen in some patients. In cases when the inflammation extends into the alveolar parenchyma alveolar FCER1-high mast cells, eosinophilia, type 2 immunity and activated alveolar macrophages, together with modest interstitial remodelling, create a complex immunopathological picture. Importantly, the distal lung inflammation in asthma can be pharmacologically targeted by use of inhalers with more distal drug deposition. Biological treatments, which are readily distributed to the distal lung, may also be beneficial in eligible patients with more severe and anatomically widespread disease.

Mapping knowledge structure and research of the biologic treatment of asthma: A bibliometric study.

Bronchial asthma (asthma) is a chronic inflammatory disease of the airways, involving a variety of cells and cellular components, that manifests clinically as recurrent episodes of wheezing, shortness of breath, with or without chest tightness or cough, airway hyperresponsiveness, and variable airflow limitation. The number of people with asthma has reached 358 million worldwide and asthma causes huge economic loss. However, there is a subset of patients who are not sensitive to existing drugs and the existing drugs have many adverse effects. Therefore, it's important to find new drugs for asthma patients. Publications related to biologics in asthma published from 2000 to 2022 were retrieved from Web of Science Core Collection. The search strategies were as follows: topic: TS=(biologic* OR "biologic* product*" OR "biologic* therap*" OR biotherapy* OR "biologic* agent*" OR Benralizumab OR "MEDI-563" OR Fasenra OR "BIW-8405" OR Dupilumab OR SAR231893 OR "SAR-231893" OR Dupixent OR REGN668 OR "REGN-668" OR Mepolizumab OR Bosatria OR "SB-240563" OR SB240563 OR Nucala OR Omalizumab OR Xolair OR Reslizumab OR "SCH-55700" OR SCH55700 OR "CEP-38072" OR CEP38072 OR Cinqair OR "DCP-835" OR DCP835 OR Tezspire OR "tezepelumab-ekko" OR "AMG-157" OR tezspire OR "MEDI-9929" OR "MEDI-19929" OR MEDI9929 OR Itepekimab OR "REGN-3500"OR REGN3500 OR "SAR-440340"OR SAR440340 OR Tralokinumab OR "CAT-354" OR Anrukinzumab OR "IMA-638" OR Lebrikizumab OR "RO-5490255"OR "RG-3637"OR "TNX-650"OR "MILR1444A"OR "MILR-1444A"OR"PRO301444"OR "PRO-301444"OR Pitrakinra OR altrakincept OR "AMG-317"OR"AMG317" OR Etokimab OR Pascolizumab OR "IMA-026"OR Enokizumab OR "MEDI-528"OR "7F3COM-2H2" OR 7F3COM2H2 OR Brodalumab OR "KHK-4827" OR "KHK4827"OR "AMG-827"OR Siliq OR Ligelizumab OR "QGE-031" OR QGE031 OR Quilizumab OR Talizumab OR "TNX-901" OR TNX901 OR Infliximab OR Etanercept OR "PRS-060") AND TS=asthma*. The document type was set to articles and review articles and the language restriction was set to English. Three different analysis tools including one online platform, VOS viewer1.6.18, and CiteSpace V 6.1.R1 software were used to conduct this bibliometric study. This bibliometric study included 1,267 English papers published in 244 journals from 2,012 institutions in 69 countries/regions. Omalizumab, benralizumab, mepolizumab, and tezepelumab in relation to asthma were the research hotspots in the field. This study systematically uncovers a holistic picture of existing literature related to the biologic treatment of asthma over the past 20 years. We consulted scholars in order to understand key information in this field from the perspective of bibliometrics, which we believe may greatly facilitate future research in this field.

Toward a Predict and Prevent Approach in Obstructive Airway Diseases

Asthma and chronic obstructive pulmonary disease (COPD) are currently diagnosed and treated after demonstration of variable airflow limitation and symptoms. Under this framework, undiagnosed and unchecked airway inflammation is associated with recurrent acute attacks, airway remodeling, airflow limitation, adverse effects of corticosteroids, and impaired quality of life, ultimately leading to the collection of side-effects termed 'people remodeling'. This one-size-fits-all, damage control approach aims to control symptoms and treat exacerbations rather than modify the underlying disease process. The advent of highly effective therapies targeting proximal drivers of airways inflammation calls for a paradigm shift; upstream-acting therapies offer potential to alter the disease course and achieve clinical remission. We propose moving away from downstream firefighting and towards a predict and prevent model, measuring inflammation and providing anti-inflammatory therapy early, without waiting for further clinical deterioration. Much in the same way that high blood pressure and cholesterol are used to predict and prevent heart attacks, in asthma elevated blood eosinophils and/or exhaled nitric oxide (FeNO) can be used to predict and prevent asthma attacks. We advocate also moving research further upstream by identifying patients with subclinical airways inflammation or disease who may be at risk of progressing to airflow limitation and associated morbidities and intervening early to prevent them. In summary, we call for a 'predict and prevent' approach in obstructive airways disease.

User’s Perception of Indoor Air Quality (IAQ) in Tall Office Buildings as the Cause of Symptoms of Sick Building Syndrome

The user’s assessment or perception of indoor air quality (IAQ) refers to an individual’s subjective assessment or perception of the quality of the air they breathe inside a particular building or space. This assessment or perception is very individual and can vary from one individual to another. This study aims to determine the IAQ felt by users of the Rectorate Building, State University of Malang, and its effect on Sick Building Syndrome (SBS) symptoms. This research is included in the quantitative research with the study population being all employees at the building, which has 215 people. The data collection technique in this study used the MM040NA questionnaire and the data analysis technique used was binary logistic regression analysis with the help of the IBM SPSS Statistics with crosstabs test. The results of this study indicate that all independent variables have no significant relationship with SBS symptoms experienced by respondents and all independent variables have a very weak correlation. In addition, from 80 respondents, 27 people (33.75%) experienced SBS and 53 people (66.25%) did not experience SBS. This shows that there is a SBS phenomenon in the building. The significance value for all independent variables is greater than the significance level value (>0.05). Furthermore, based on the test criteria, it is concluded that the variable airflow, high temperature, temperature change, low temperature, stale air, dry air, odor, air electrostatics, cigarette smoke, sound level, lighting, and air pollution have approximate significance values greater than 0.05 (null hypothesis was failed to be rejected). It is concluded that those variables have no significant relationship to the dependent variable (the SBS symptoms) experienced by the respondents.

Role of impulse oscillometry in diagnosis and follow-up in bronchial asthma.

Asthma is defined as a chronic inflammatory disorder of the airways, characterized by bronchial hyper-responsiveness and variable airflow obstruction, that is often reversible either spontaneously or with treatment. Impulse oscillometry is a newer diagnostic modality for asthma. It is based on the measurement of sound waves reflected by airway resistance. The aim of this article is to study the role of impulse oscillometry in diagnosis and follow-up of bronchial asthma. Fifty-five clinically diagnosed bronchial asthma patients were evaluated with spirometry and impulse oscillometry before and after 3 months of inhaled treatment. The sensitivity to diagnose and follow-up was compared using proper statistical tests. Impulse oscillometry was superior to spirometry in diagnosing bronchial asthma and also in accessing the treatment response after 3 months. Impulse oscillometry is superior in predicting bronchial asthma and its parameters are also more sensitive in accessing treatment response. It can replace spirometry as it is easy to perform and effort independent.

Neutrophil Extracellular Traps in Asthma: Friends or Foes?

Asthma is a chronic inflammatory disease characterized by variable airflow limitation and airway hyperresponsiveness. A plethora of immune and structural cells are involved in asthma pathogenesis. The roles of neutrophils and their mediators in different asthma phenotypes are largely unknown. Neutrophil extracellular traps (NETs) are net-like structures composed of DNA scaffolds, histones and granular proteins released by activated neutrophils. NETs were originally described as a process to entrap and kill a variety of microorganisms. NET formation can be achieved through a cell-death process, termed NETosis, or in association with the release of DNA from viable neutrophils. NETs can also promote the resolution of inflammation by degrading cytokines and chemokines. NETs have been implicated in the pathogenesis of various non-infectious conditions, including autoimmunity, cancer and even allergic disorders. Putative surrogate NET biomarkers (e.g., double-strand DNA (dsDNA), myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (CitH3)) have been found in different sites/fluids of patients with asthma. Targeting NETs has been proposed as a therapeutic strategy in several diseases. However, different NETs and NET components may have alternate, even opposite, consequences on inflammation. Here we review recent findings emphasizing the pathogenic and therapeutic potential of NETs in asthma.

Pharmacological OGG1 inhibition decreases murine allergic airway inflammation.

Background and aim: Allergic asthma is a complex inflammatory disease involving type 2 innate lymphoid cells, type 2T helper cells, macrophages, and eosinophils. The disease is characterized by wheezing, dyspnea, coughing, chest tightness and variable airflow limitation for which there is no cure and is symptomatically treated with inhaled corticosteroids and β2-agonists. Molecular mechanisms underlying its complex pathogenesis are not fully understood. However, 8-oxoguanine DNA glycosylase-1 (OGG1), a DNA repair protein may play a central role, as OGG1 deficiency decreases both innate and allergic inflammation. Methods: Using a murine ovalbumin (OVA) model of allergic airway inflammation we assessed the utility of an inhibitor of OGG1 (TH5487) in this disease context. Cytokines and chemokines, promoting immune cell recruitment were measured using a 23-multiplex assay and Western blotting. Additionally, immune cell recruitment to bronchi was measured using flow cytometry. Histological analyses and immunofluorescent staining were used to confirm immune cell influx and goblet cell hyperplasia of the airways. A PCR array was used to assess asthma-related genes in murine lung tissue following TH5487 treatment. Finally, airway hyperresponsiveness was determined using in vivo lung function measurement. Results: In this study, administration of TH5487 to mice with OVA-induced allergic airway inflammation significantly decreased goblet cell hyperplasia and mucus production. TH5487 treatment also decreased levels of activated NF-κB and expression of proinflammatory cytokines and chemokines resulting in significantly lower recruitment of eosinophils and other immune cells to the lungs. Gene expression profiling of asthma and allergy-related proteins after TH5487 treatment revealed differences in several important regulators, including down regulation of Tnfrsf4, Arg1, Ccl12 and Ccl11, and upregulation of the negative regulator of type 2 inflammation, Bcl6. Furthermore, the gene Clca1 was upregulated following TH5487 treatment, which should be explored further due to its ambiguous role in allergic asthma. In addition, the OVA-induced airway hyperresponsiveness was significantly reduced by TH5487 treatment. Conclusion: Taken together, the data presented in this study suggest OGG1 as a clinically relevant pharmacological target for the treatment of allergic inflammation.