The hydroalcoholic extract of Nasturtium officinale reduces oxidative stress markers and increases total antioxidant capacity in patients with asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Asthma is a common chronic disease characterized by inflammation of the airways. One of the most devastating consequences of this inflammatory process is the production of reactive oxygen species responsible for oxidative stress. Nasturtium officinale commonly known as watercress has traditionally been applied in Iranian folk medicine to treat respiratory disorders and diseases mainly bronchitis and asthma. In accordance with these ethnopharmacological reports, through our previous in vivo experiment, we have confirmed significant effect of its hydroalcoholic extract in reducing lung inflammation and oxidative stress in an ovalbumin-induced asthmatic rat model. AIM OF THE STUDY: The aim of the present study was to investigate the anti-inflammatory and antioxidant effects of N. officinale hydroalcoholic extract (NOE) in patients with asthma, in order to confirm our findings of the previous performed in vivo study. MATERIAL AND METHODS: The NOE capsules (500 mg) were treated twice daily for 4 weeks as a supplementary treatment in a randomized, double-blind, and placebo-controlled trial in asthmatics. The primary outcome was Asthma Control Test score. The blood samples were taken at the beginning and end of the study. Then, the level of inflammatory markers, oxidative stress markers and antioxidant enzyme activity were measured. RESULTS: Treatment with NOE for one month caused a reduction in the levels of MDA, PCO and NO metabolite markers compared to the placebo group. In addition, FRAP levels as an indicator of total antioxidant capacity in the intervention group was significantly increased at the end of the treatment period compared to pre-treatment values. CONCLUSION: Findings demonstrated that NOE may have a therapeutic effect on asthma by improving oxidative stress. However, more studies are required to support these results. Moreover, bio-assay guided fractionation and isolation approach can be conducted to identify major bioactive compound/s.

Effects of total alkaloids from Alstonia scholaris (L.) R. Br. on ovalbumin-induced asthma mice.

ETHNOPHARMACOLOGICAL RELEVANCE: More than 300 million people worldwide suffer from asthma, a chronic respiratory inflammatory disease. Total alkaloids (TA) were extracted from the ethnic medicinal plant Alstonia solaris (L.) R.Br., which is used to treat respiratory diseases. They may be effective drugs for treating asthma, but research is still needed to determine their effectiveness and mechanism in treating asthma. AIM OF THE STUDY: To further understand TA's role in the treatment of asthma and to support the phase II trial of the drug. MATERIALS AND METHODS: In this study, we investigated the effects of TA in a mouse asthma model produced by Ovalbumin (OVA). H&E and PAS staining were used to observe the histopathological features of lung. airway hyperresponsiveness (AHR) was detected by ventilator; The expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and E-cadherin in the lungs was evaluated by IHC. The concentrations of Mucin5AC (MUC5AC), eotaxin, IL-4, IL-5, IL-9, IL-13, interferon (IFN)-γ, IL-6, IL-8, IL-17A, IL-33, IL-25, thymic stromal lymphopoietin (TSLP), monocyte chemoattractant protein 1 (MCP-1), leukotriene (LT) B4, LTC4, LTD4, LTE4 in bronchoalveolar lavage fluid (BALF) and total IgE (tIgE), OVA-Specific IgE (OVA-IgE) in serum were measured by ELISA. ILC2s and eosinophils were detected in lung tissue by flow cytometry. The gene expression levels of IL-33 and ST2 were detected by RT-qPCR. RESULTS: Administration of TA reduced pulmonary inflammatory symptoms, MUC5AC production in the BALF, and AHR. At the same time, TA inhibited eotaxin production and eosinophil recruitment. Moreover, TA significantly decreased Th2 and Th17 cytokines and increased Th1 cytokines, contributing to restore the balance between Th1 and Th2 and Th17 cytokines. TA may reduce ILC2s numbers by inhibiting IL-33, IL-25, and TSLP levels in BALF and IL-33/ST2 signaling in lung tissue. Finally, TA decreased tIgE, OVA-IgE, and MCP-1 levels and subsequently inhibited mast cell activation and leukotriene release. CONCLUSIONS: These findings imply that TA may be an effective immunoregulatory medication for the management and prevention of asthma.

A methanolic extract of Eclipta prostrata (L.) L. decreases inflammation in a murine model of chronic allergic asthma via inhibition of the NF-kappa-B pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrata (L.) L. is a medicinal plant used by many ethnic groups in Brazil to treat respiratory diseases, hepatitis and the bites of venomous animals. A methanolic extract of E. prostrata (MEEP), the major components of which are wedelolactone (WED) and demethylwedelolactone (DMW), exhibited anti-inflammatory activity in acute asthma models but the effects on lung inflammation and the mechanisms of action of MEEP in a chronic asthma model are not known. AIM OF THE STUDY: To study the effects of MEEP in vivo using a chronic ovalbumin (OVA)-induced allergic asthma model in mice. MATERIALS AND METHODS: The identities of WED and DMW in MEEP were confirmed and the concentrations determined by liquid chromatography and tandem mass spectrometry. Male Balb/c mice were sensitized and challenged with OVA and experimental animals were treated with MEEP (100, 250 or 500 mg/kg) while control animals were treated with dexamethasone (2 mg/kg) or normal saline. Bronchial hyperresponsiveness, total and differential cell counts in bronchoalveolar lavage (BAL), and the production of Th2 cytokines in lung homogenates were assessed. Lung inflammation and mucus production were evaluated by histological analysis while nuclear factor kappa-B (NF-κB) activation was assessed immunohistochemically. RESULTS: Concentrations of WED and DMW in MEEP were 5.12% and 1.04%, respectively. Treatments with MEEP (250 or 500 mg/kg) significantly decreased bronchial hyperresponsiveness, reduced total cell and eosinophil counts in BAL and IL-4 concentrations in lung homogenate, and inhibited NF-κB activation. Treatment with MEEP at 500 mg/kg reduced the level of IL-5 in lung homogenates but did not decrease IL-13 concentration or mucus production. CONCLUSIONS: MEEP attenuated bronchial hyperresponsiveness and decreased lung and airway inflammation in a chronic asthma model in mice. The mechanism of action involves inhibition of NF-κB activation, most likely associated with the presence of the coumestans WED and DMW. These results support the ethnopharmacological evidence for the use of E. prostrata against asthma and other respiratory inflammatory diseases.

Protective effects of Angelica decursiva Franchet & Savatier on allergic responses through enhancement of Nrf2 and suppression of NF-kB/MMP-9 in ovalbumin-exposed mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica decursiva Franchet & Savatier is a traditional medicinal plant used to treat asthma, cough, headache, pyrexia and thick phlegm in China, Japan and Korea. A. decursiva contains many types of coumarins, which can exert several pharmacological activities including anti-inflammatory and antioxidant properties for treating various diseases such as pneumonitis, atopic dermatitis, diabetes, and Alzheimer's disease. AIM OF THE STUDY: In this study, we analyzed the components of A. decursiva ethanol extract (ADE) by high performance liquid chromatography (HPLC) and investigated the therapeutic effects of ADE against allergic asthma using lipopolysaccharide (LPS) stimulated RAW264.7 cells and an ovalbumin (OVA)-exposed allergic asthma model. To elucidate the mechanism of action of ADE, we examined the protein expression through network pharmacological analysis. MATERIALS AND METHODS: To establish asthma model, the mice were sensitized on day 0 and 14 via intraperitoneal injection of OVA with aluminum hydroxide. The mice were inhaled with OVA using an ultrasonic nebulizer on day 21, 22 and 23. ADE (50 and 100 mg/kg) was administered to mice by oral gave form day 18-23. On day 24, airway hyperresponsiveness (AHR) was measured using flexivent. On day 25, the mice were sacrificed and collected bronchoalveolar lavage fluids (BALF), serum and lung tissue. In LPS-stimulated RAW264.7 cell, nitric oxide and cytokines were measured. Additionally, expression of nuclear factor erythroid-2-related factor (Nrf2) and suppression of nuclear factor (NF)-κB were detected using double-immunofluorescence. RESULTS: We detected the five coumarin components which included nodakenin, umbelliferon, (-)-marmesin (=nodakenetin), bergapten, and decursin, in ADE by high performance liquid chromatography. Treatment with ADE decreased the production of nitric oxide, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in LPS-stimulated RAW264.7 cells accompanied by the enhanced expression of nuclear factor erythroid-2-related factor (Nrf2) and suppression of nuclear factor (NF)-κB. In the asthma model, the administration of ADE reduced inflammatory cell count and airway hyperresponsiveness in OVA-exposed animals with decreased levels of IL-4, IL-13, and OVA-specific immunoglobulin E. These results were accompanied by the reduction of pulmonary inflammation and mucus secretion. Furthermore, ADE administration inhibited the expression of NF-κB and matrix metalloproteinase (MMP)-9 in OVA-exposed animals, which was consistent with the results of network pharmacological analysis. CONCLUSION: This study demonstrated that ADE effectively attenuated allergic inflammation induced by OVA inhalation through the enhancement of Nrf2 expression and suppression of NF-κB expression. Therefore, ADE may be a potential therapeutic agent for controlling asthma.

Daqing formula ameliorated allergic asthma and airway dysbacteriosis in mice challenged with ovalbumin and ampicillin.

ETHNOPHARMACOLOGICAL RELEVANCE: Asthma is a chronic airway inflammatory disease that can lead to several complications caused by bacterial infections. However, recurrent attacks of the disease require long-term use of antibiotics, resulting in lung dysbiosis and poor outcomes. Daqing Formula (DQF) is a well-known herbal medicine in Pharmacopoeia of China, which is widely used for various stimuli-induced lower respiratory diseases, including asthma, bronchitis, and pneumonia. Thus, it has been demonstrated to be a plant-derived broad-spectrum antibiotic for treating and preventing various acute and chronic respiratory diseases. AIM OF THE STUDY: This study evaluated the efficacy and possible mechanism of DQF on allergic asthma and airway dysbiosis. METHODS AND MATERIALS: The mice were co-challenged with ovalbumin and ampicillin to induce allergic asthma combined with airway dysbacteriosis. The populations of lung microbiota were detected by using 16s DNA sequencing. The levels of asthmatic markers in BALF were detected by ELISA. The levels of Th1/Th2 cytokines in splenic CD4+ cells of mice were analyzed by flow cytometry. The expressions of the GSK-3ß signaling pathway in the lung tissues of asthmatic mice and eosinophils were detected by western blotting assay. The inhibition of DQF on the production of pro-inflammatory cytokines in eosinophils of asthmatic mice. RESULTS: The results showed that treatment with DQF at 200-800 mg/kg doses significantly reduced the frequency of nasal rubbing and lung inflammation as well as the number of total cells, eosinophils, and macrophages in bronchoalveolar lavage fluid. It decreased the relative abundances of Streptococcus, Cuoriavidus, and Moraxella, increased Akkermansia and Prevotella_6 in lung tissues of asthmatic mice, and inhibited the growth of Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae and their resistant strains in vitro. Furthermore, DQF reduced the levels of eotaxin, TSLP, IL-4, IL-5, IL-25, and IL-33, but enhanced IFN-γ and IL-12 in BALF. It elevated the population of Th1 cells, inhibited eosinophil activation, and downregulated the expressions of p-GSK-3ß, p-p65, nuclear ß-catenin, and p-STAT3 in the lung tissues of asthmatic mice. CONCLUSIONS: The results revealed that DQF reduced airway inflammation, ameliorated lung dysbiosis, shifted the Th1/Th2 balance, and inhibited eosinophil activation in asthmatic mice, indicating its potential for severe asthma treatment.

Chemical constituents from the flowers of Inula japonica and their anti-inflammatory activity.

ETHNOPHARMACOLOGICAL RELEVANCE: The flowers of Inula japonica (Inulae Flos) can be used to treat cough and asthma and remove phlegm in traditional Chinese medicine (TCM). AIM OF THE STUDY: Our research aimed to obtain active components with the inhibition of inflammation and MUC5AC production to alleviate asthma symptoms from I. japonica. MATERIALS AND METHODS: These compounds were separated from the MeOH extract of Inulae Flos by column chromatography over silica gel, AB-8 macroporous resin column, MPLC, and semipreparative HPLC. Their structures were elucidated by detailed spectroscopic data analysis, ECD calculations, and chemical methods. NO production was determined to evaluate anti-inflammatory activity in RAW 264.7 cells. The expression of MUC5AC, IL-1ß, and IL-4 were measured in NCI-H292 cells by qRT-PCR. The anti-asthma activity assessments in vivo were performed through H & E and PAS staining, pulmonary function analysis, and cytokines determination by qRT-PCR or ELISA. The expression levels of PI3K, p-PI3K, AKT, p-AKT, MEK, p-MKE, ERK, p-MEK, and IL-1ß were analyzed through western blotting. RESULTS: One undescribed 1,10-seco-eudesmanolide derivative (1), two previously unreported 1,10-seco-eudesmanolide glycosides (2 and 3), and thirty-two known compounds (4-35) were obtained from Inulae Flos. Compound 11 had the most inhibitory effect against LPS-induced NO production in RAW 264.7 murine macrophages. Meanwhile, compound 11 also attenuated the increase in MUC5AC, IL-1ß, and IL-4 mRNA expression in NCI-H292 cells. The results of the animal experiment confirmed that compound 11 significantly ameliorated OVA-induced asthma in a murine model of allergic asthma demonstrated by elevated pulmonary function, reduced inflammatory cell infiltration and mucus production. In addition, compound 11 significantly inhibited the levels of OVA-specific IgE in serum, of IL-4 and IL-6 in BALF, and of MUC5AC, IL-1ß , IL-4, IL-5, IL-6 and IL-13 in lung tissue. Finally, compound 11 suppressed PI3K/AKT/MEK/ERK signaling pathway in lung tissue of mice. CONCLUSION: This study indicated that compound 11 might be a potential therapeutic candidate ameliorating airway inflammation and mucus hypersecretion via PI3K/AKT/MEK/ERK signaling pathway in allergic asthma.

[Omalizumab Treats Aspirin-Induced Asthma Complicated With Nasosinusitis and Otitis Media:Report of One Case].

Omalizumab,as a biological agent targeting IgE,is a recombinant humanized monoclonal antibody and the first targeted drug approved for treating moderate-to-severe bronchial asthma.By reviewing one case of aspirin-induced asthma complicated with nasosinusitis and otitis media,we discussed the value of omalizumab in the treatment of asthma and its complications,aiming to provide a reference for clinical practice.

The emerging roles of SUMOylation in pulmonary diseases.

Small ubiquitin-like modifier mediated modification (SUMOylation) is a critical post-translational modification that has a broad spectrum of biological functions, including genome replication and repair, transcriptional regulation, protein stability, and cell cycle progression. Perturbation or deregulation of a SUMOylation and deSUMOylation status has emerged as a new pathophysiological feature of lung diseases. In this review, we highlighted the link between SUMO pathway and lung diseases, especially the sumoylated substrate such as C/EBPα in bronchopulmonary dysplasia (BDP), PPARγ in pneumonia, TFII-I in asthma, HDAC2 in chronic obstructive pulmonary disease (COPD), KLF15 in hypoxic pulmonary hypertension (HPH), SMAD3 in idiopathic pulmonary fibrosis (IPF), and YTHDF2 in cancer. By exploring the impact of SUMOylation in pulmonary diseases, we intend to shed light on its potential to inspire the development of innovative diagnostic and therapeutic strategies, holding promise for improving patient outcomes and overall respiratory health.

The Association Between Urinary Concentrations of Organophosphate Metabolites and Asthma-Related Outcomes Among Schoolchildren From Informal Settlements.

Objectives: There is inconsistent evidence on the relationship between pesticide exposure and childhood respiratory outcomes in non-agricultural settings. This study investigated the association between organophosphate (OP) pesticide exposure and asthma-related outcomes in children residing in four informal settlements. Methods: The study was a longitudinal study of 590 schoolchildren, with a 12 months follow-up period. A standardised questionnaire adopted from the International Study of Asthma and Allergies in Childhood was administered to caregivers for child's respiratory symptoms and household characteristics. Spirometry and fractional-exhaled nitric oxide, including a phadiatop test (atopy status) and urinary dialkyl phosphate (DAP) metabolites were measured at baseline and follow-up. DAP metabolites included diethylphosphate (DEP) and dimethyl phosphate (DMP) measured at baseline and follow-up and dimethylthiophosphate (DMTP) measured only at baseline. Results: The mean ages of schoolchildren were 9.9 ± 0.91 years and the overal incidence proportions of new doctor diagnosed asthma was 2.2%. No consistent patterns of increased risk of asthma outcomes with increasing DAP concentrations was found in multivariate analysis. Conclusion: Future studies with longer follow-up periods and repeated OP biomonitoring are recommended.

Breathe easy: inhalational therapy for feline inflammatory airway disease.

PRACTICAL RELEVANCE: Feline inflammatory airway diseases, including (but not limited to) asthma, chronic bronchitis and bronchiectasis, are common and incurable disorders. These diseases require lifelong therapy and may result in substantial morbidity and, in some cases, mortality. Goals of therapy include reduction or resolution of clinical signs and the underlying pathologic processes driving those clinical signs. Inhalational therapy has the advantage of topical delivery of drugs to target tissues at higher doses with fewer systemic effects than oral medications. There are multiple options for delivery devices, and proper selection and training on the use of these devices - including acclimation of the cat to the device - can maximize therapeutic efficacy. AIM: As inhalational therapy is uncommonly used by many veterinarians and owners, this review article provides a foundation on the selection and use of devices and inhalant medications for specific feline inflammatory airway diseases. Cats present a unique challenge with respect to the use of inhalers, and easy-to-follow steps on acclimating them to the devices are provided. The review also discusses the mechanics of inhalational therapy and helps clarify why certain medications, such as albuterol (salbutamol), fluticasone or budesonide, are chosen for certain diseases. The ultimate aim is that the practitioner should feel more comfortable managing common airway diseases in cats. EVIDENCE BASE: In compiling their review, the authors searched the veterinary literature for articles in English that discuss inhalational therapy in cats, and which focus primarily on inhaled glucocorticoids and bronchodilators. While most literature on inhalational therapy in cats is based on experimental feline asthma models, there are some studies demonstrating successful treatment in cats with naturally occurring inflammatory airway disease.

Loke zupa decoction attenuates bronchial EMT-mediated airway remodelling in chronic asthma through the PI3K-Akt/HIF-1α signaling pathway.

CONTEXT: Loke zupa decoction (Lok) is a well-established classic Chinese folk remedy for asthma. OBJECTIVE: We sought to investigate the effect and mechanism of Lok on asthma airway remodelling and provide novel insights for the prevention and treatment of asthma. MATERIALS AND METHODS: For in vitro experiments, BEAS-2B cells were assigned into six groups: Control, TGF-ß1 (10 µM), TGF-ß1 + Lok-20, TGF-ß1 + Lok-40, TGF-ß1 + Lok-80 µg/mL and TGF-ß1 + SB431542 (5 µM). CCK8 and wound healing assays were performed. For in vivo experiments, 60 female BALB/c mice were randomly divided into 5 groups: Control, model, Lok-4.55, Lok-9.1, and DEX group. Lok was administrated by gavage during the challenge stage for 8 consecutive weeks (4.55 and 9.1 g/kg/day). We investigated airway inflammation and airway remodelling in the lungs and verified the activation status of EMT-related markers and the PI3K-Akt/HIF-1α signalling pathway. RESULTS: In vitro, Lok efficiently inhibited TGF-ß1-induced BEAS-2B cell proliferation ability (cell viability 165% vs. 105%) and migration (migration areas 85% vs. 35%) without affecting their normal growth (IC50 274.2 µg/mL at 48 h). In vivo, Lok effectively protected mice from asthma, as evidenced by decreased histological damage and level of cytokines in BALF (IL-4, IL-13 and TGF-ß1) by 17%-77%. Mechanistic research revealed that Lok reduced the levels of EMT-related molecules and significantly downregulated the PI3K-Akt/HIF-1α signalling pathway. DISCUSSION AND CONCLUSIONS: Our findings provide novel insights into the protective effect of Lok on asthma and the underlying mechanisms, providing a theoretical basis and potential treatment possibilities for this patient population.

Barriers to childhood asthma care in sub-Saharan Africa: a multicountry qualitative study with children and their caregivers.

OBJECTIVES: This study identifies barriers and provides recommendations to improve asthma care in children across sub-Saharan Africa, where qualitative data is lacking despite high rates. DESIGN: One of the aims of our National Institute for Health Research global health research group 'Achieving Control of Asthma in Children in Africa' was to use qualitative thematic analysis of transcribed audio recordings from focus group discussions (FGDs) to describe barriers to achieving good asthma control. SETTING: Schools in Blantyre (Malawi), Lagos (Nigeria), Durban (South Africa), Kampala (Uganda) and Harare (Zimbabwe). PARTICIPANTS: Children (n=136), 12-14 years with either asthma symptoms or a diagnosis and their caregivers participated in 39 FGDs. All were recruited using asthma control questions from the Global Asthma Network survey. RESULTS: There were four key themes identified: (1) Poor understanding, (2) difficulties experienced with being diagnosed, (3) challenges with caring for children experiencing an acute asthma episode and (4) suboptimal uptake and use of prescribed medicines. An inadequate understanding of environmental triggers, a hesitancy in using metred dose inhalers and a preference for oral and alternate medications were identified as barriers. In addition, limited access to healthcare with delays in diagnosis and an inability to cope with expected lifestyle changes was reported. Based on these findings, we recommend tailored education to promote access to and acceptance of metred dose inhalers, including advocating for access to a single therapeutic, preventative and treatment option. Furthermore, healthcare systems should have simpler diagnostic pathways and easier emergency access for asthma. CONCLUSIONS: In a continent with rapidly increasing levels of poorly controlled asthma, we identified multiple barriers to achieving good asthma control along the trajectory of care. Exploration of these barriers reveals several generalisable recommendations that should modify asthma care plans and potentially transform asthma care in Africa. TRIAL REGISTRATION NUMBER: 269211.

Determinants of Childhood Asthma: A Case Control Study from a Tertiary Care Hospital in Bengaluru, South India.

BACKGROUND: Childhood asthma is a common, and often serious, chronic disease with episodic exacerbations in infants and children. There is an increasing trend in the prevalence of childhood asthma in developing countries. Objectives: To identify the determinants of childhood asthma. METHODS: A case control study with 30 cases of childhood asthma and 30 gender- and aged-matched controls selected from the paediatric outpatient department and paediatric ward of a tertiary hospital. The primary caregiver was interviewed to capture sociodemographic details, prenatal and birth history, and history of exposure to environmental risk factors. Odds ratios with 95% confidence intervals were calculated to determine the strength of association between childhood asthma and independent co-variates, followed by subgroup multiple logistic regression analysis. RESULTS: We found that children with a parental history of allergy/atopy [OR=2.88 (1.94-4.27), P<0.001], residence in houses located in industrial areas [AOR=2.72 (2.6-323.1), P<0.001], exposure to incense at home [AOR=2.03 (1.14-29.42), P<0.001], or a history of allergic rhinitis [AOR=3.09 (2.22-243.25), P<0.001] had significantly higher odds of developing childhood asthma. CONCLUSION: Our study found that having homes located in industrial areas, burning incense at home, parental history of allergy, and history of allergic rhinitis in the child are determinants of childhood asthma. The findings from our study can be used to generate awareness regarding risk factors that are linked to childhood asthma.

[A clinical observational study on the preliminary effect of dupilumab in the treatment of severe asthma].

Objective: To investigate the effect and safety of dupilumab in the treatment of patients with severe asthma in a preliminary clinical observational study. Methods: This study retrospectively analyzed the clinical data of 20 patients with severe asthma who received dupilumab for 4-12 months between 2019 and 2022 at the First Hospital of Guangzhou Medical University, comparing pre-and post-treatment laboratory data, oral glucocorticoid dose (OCS), asthma control test (ACT) and adverse effects. The median age of the 20 patients was 48.5 (41.0-52.8) years, including 14 males and 6 females. The clinical data of 10 patients treated with other biologic agents were further analyzed to determine the reasons for switching to biologic drug treatment and the efficacy of dupilumab in these patients. Paired t-tests or Wilcoxon signed-rank tests were used for comparisons. Mann-Whitney analysis was used for inter-group comparison, and chi-square test or Fisher test was used for inter-group comparisons of count data. Results: A total of 20 patients were included in this study. All 20 severe asthma phenotypes were type 2 (T2)-high and completed at least the first 4 months of treatment, including 17 patients who completed 12 months of treatment. Among patients who completed 4 months of treatment, the asthma exacerbation score decreased from 1.0(0.3-1.0) episodes/4 months to 0.0(0.0-1.0) episodes/4 months, P<0.001, and FEV1/FVC increased from 58.4% (50.5%-69.0%) to 66.9% (59.6%-77.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 15 (75%) to 9 (45%), P<0.05. Among patients who completed 12 months of treatment, the asthma exacerbation score decreased from 1.0(0.5-1.0) episodes/4 months to 0.0 (0.0-0.0) episodes/4 months, P<0.01, and FEV1/FVC increased from 57.9% (49.6%-67.8%) to 72.7% (64.6%-78.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 13 (76%) to 6 (35%), P<0.01. In 10 patients with a history of previous biologic therapy, the most common reasons for switching to a biologic were a poor response to previous monoclonal antibodies (40%) and loss of control of asthma symptom control after discontinuation of monoclonal antibodies (30%). The remaining reasons were patients' uncontrolled symptoms of chronic rhinosinusitis (20%) and irregular or underdosed use of previous biologics (10%). After 4 months of switching to dupilumab, 10 patients experienced varying degrees of improvement in asthma control. Conclusions: The application of dupilumab for the treatment of T2-high severe asthma showed good efficacy and few adverse effects. Biologically targeted therapy is an important treatment approach to achieving better control of severe asthma.

[Adult asthma exacerbation: emergency room management]. / Exacerbation asthmatique chez l'adulte : prise en charge aux urgences.

Asthmatic exacerbations (AEs) are a frequent reason for emergency department visits. Management should be guided by the severity of the attack but should also focus on patient education and prevention of future exacerbations. This article summarizes current recommendations for the management of both simple and life-threatening AE. When the clinical evolution is favorable, and the patient no longer presents any criteria of severity or risk factors for decompensation, a return home can be considered, with appropriate treatment and the organization of outpatient follow-up. However, if the patient's prognosis is likely to be engaged, transfer to an intensive care unit should not be delayed, to ensure optimal care.

L'exacerbation asthmatique (EA) est un motif fréquent de consultation aux urgences. Sa prise en charge doit être guidée selon la sévérité de la crise mais doit également être axée sur l'éducation du patient et la prévention des récidives. Cet article résume les recommandations actuelles de prise en charge d'une EA autant pour les formes simples que sévères, engageant le pronostic vital. Lorsque l'évolution sous traitement est favorable et que le patient ne présente plus de critère de sévérité ou de facteur de risque de décompensation, un retour à domicile est envisageable avec un traitement adapté et l'organisation d'un suivi ambulatoire. Toutefois, lorsque le pronostic vital est susceptible d'être engagé, le transfert dans une unité de soins intensifs ne doit pas être retardé afin d'assurer une prise en charge optimale.

Construction of lncRNA-miRNA-mRNA regulatory network in severe asthmatic bronchial epithelial cells: A bioinformatics study.

Asthma is a chronic respiratory disease caused by environment-host interactions. Bronchial epithelial cells (BECs) are the first line of defense against environmental toxins. However, the mechanisms underlying the role of BECs in severe asthma (SA) are not yet fully understood. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been shown to play important roles in the regulation of gene expression in the pathogenesis of SA. In this study, bioinformatics was used for the first time to reveal the lncRNA-miRNA-mRNA regulatory network of BECs in SA. Five mRNA datasets of bronchial brushing samples from patients with SA and healthy controls (HC) were downloaded from the Gene Expression Omnibus (GEO) database. A combination of the Venn diagram and robust rank aggregation (RRA) method was used to identify core differentially expressed genes (DEGs). Protein-protein interaction (PPI) analysis of core DEGs was performed to screen hub genes. The miRDB, miRWalk, and ENCORI databases were used to predict the miRNA-mRNA relationships, and the ENCORI and starBase v2.0 databases were used to predict the upstream lncRNAs of the miRNA-mRNA relationships. Four core DEGs were identified: carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), interleukin-1 receptor type 2 (IL1R2), trefoil factor 3 (TFF3), and vascular endothelial growth factor A (VEGFA). These 4 core DEGs indicated that SA was not significantly associated with sex. Enrichment analysis showed that the MAPK, Rap1, Ras, PI3K-Akt and Calcium signaling pathways may serve as the principal pathways of BECs in SA. A lncRNA-miRNA-mRNA regulatory network of the severe asthmatic bronchial epithelium was constructed. The top 10 competing endogenous RNAs (ceRNAs) were FGD5 antisense RNA 1 (FGD5-AS1), metastasis associated lung adenocarcinoma transcript 1 (MALAT1), X inactive specific transcript (XIST), HLA complex group 18 (HCG18), small nucleolar RNA host gene 16 (SNHG16), has-miR-20b-5p, has-miR-106a-5p, hsa-miR-106b-5p, has-miR-519d-3p and Fms related receptor tyrosine kinase 1 (FLT1). Our study revealed a potential mechanism for the lncRNA-miRNA-mRNA regulatory network in BECs in SA.

Asthma, Airflow Obstruction, and Eosinophilic Airway Inflammation Prevalence in Western Kenya: A Population-Based Cross-Sectional Study.

Objectives: Determine the prevalence of airway disease (e.g., asthma, airflow obstruction, and eosinophilic airway inflammation) in Kenya, as well as related correlates of airway disease and health-related quality of life. Methods: A three-stage, cluster-randomized cross-sectional study in Uasin Gishu County, Kenya was conducted. Individuals 12 years and older completed questionnaires (including St. George's Respiratory Questionnaire for COPD, SGRQ-C), spirometry, and fractional exhaled nitric oxide (FeNO) testing. Prevalence ratios with 95% confidence intervals (CIs) were calculated. Multivariable models were used to assess correlates of airflow obstruction and high FeNO. Results: Three hundred ninety-two participants completed questionnaires, 369 completed FeNO testing, and 305 completed spirometry. Mean age was 37.5 years; 64% were women. The prevalence of asthma, airflow obstruction on spirometry, and eosinophilic airway inflammation was 21.7%, 12.3% and 15.7% respectively in the population. Women had significantly higher SGRQ-C scores compared to men (15.0 vs. 7.7). Wheezing or whistling in the last year and SGRQ-C scores were strongly associated with FeNO levels >50 ppb after adjusting for age, gender, BMI, and tobacco use. Conclusion: Airway disease is a significant health problem in Kenya affecting a young population who lack a significant tobacco use history.

Household adult smoking behaviors and prevalence of asthma in Greek schoolchildren: five surveys during 1998-2018.

OBJECTIVE: Environmental tobacco smoke exposure is a well-recognized risk factor for asthma development and poor asthma control in children. However, the relationship between changes in parental smoking habits over time and the prevalence of childhood asthma remains largely unknown. Our objective was to investigate the trends of parental smoking behaviors in relation to childhood wheeze/asthma rates over a 20-year period. SUBJECTS AND METHODS: A standardized questionnaire on household overall smoking and household indoor tobacco smoking (HITS) habits was distributed to 8-9-years-old school children in the context of five cross-sectional surveys conducted in 1998 (n=3,076), 2003 (n=2,725), 2008 (n=2,688), 2013 (n=2,554) and 2018 (n=2,648). RESULTS: The parental overall smoking and HITS rates have substantially decreased during the study period (p-for-trend<0.001). However, while HITS declined among the fathers of asthmatic and non-asthmatic children as well as among the mothers of non-asthmatic ones (p-for-trend<0.001), it remained unchanged in the case of the mothers of asthmatic participants (p-for-trend 0.283). The mothers of asthmatic children consistently reported more HITS than those of non-asthmatic participants, while prevalence changes of current wheeze/asthma over the surveillance period were in complete agreement with changes in maternal HITS (cross-correlation coefficient 0.918 at zero-year lag) but not with paternal smoking behaviors. CONCLUSIONS: Overall and indoor smoking rates of school children's adult family members declined substantially during the 1998-2018 period in Greece. However, no such trend was noted among mothers of asthmatic children, while temporal changes in maternal indoor smoking rates occurred in parallel with those of childhood asthma prevalence.

Should all asthma patients be switched to single maintenance and reliever therapy?

ABSTRACT: Recent data indicate that overuse of short-acting beta2-agonists (SABAs) results in an increased risk of asthma exacerbations and mortality. The use of inhaled corticosteroid-formoterol as both maintenance and reliever therapy has become a preferred regimen for asthma management. Clinicians should be aware of the pharmacology, dosing, and prescribing considerations regarding the use of budesonide-formoterol as the available combination in the United States.

Defining and Promoting Pediatric Pulmonary Health: Leveraging Patient Reported Outcomes.

Patient-reported outcomes are based on patient (or caregiver) descriptions without direct measurement by a health care provider. To capture patient-reported outcomes, various patient-reported outcome measures (PROMs) have been created. Using PROMs has been linked to improved patient satisfaction, patient-provider communication, and clinical outcomes in many pediatric fields. Despite a long-standing history of utilizing PROMs for the evaluation and management of childhood asthma, pediatric pulmonologists lag behind other pediatric subspecialists in the use of PROMs. During the National Heart, Lung, and Blood Institute's "Defining and Promoting Pediatric Pulmonary Health" workshop, critical knowledge gaps and research opportunities in the use of PROMs for childhood respiratory health were reviewed. In particular, PROMs can be employed as screening tools in the general population for the primary or secondary prevention of pediatric lung diseases. Incorporating these PROMs into the pediatric primary care setting would be especially impactful. In addition, the use of PROMs for the evaluation and management of asthma suggests that they can be applied to other childhood respiratory diseases. Ongoing multicenter studies or national consortia that study pediatric lung diseases could be leveraged to conduct research designed to develop, validate, and assess the utility of PROMs to assess childhood respiratory health. Harnessing the electronic health record will be critical for the successful adoption of PROMs in children with lung diseases. Ultimately, an integrative approach to systematically address numerous barriers at the level of the provider, patient, and health care system will be needed to attain this goal and achieve sustainability.