Chronic Asthma Research Articles

Multimorbidity and its Associated Factors in Korean Shift Workers: Population-Based Cross-Sectional Study.

Multimorbidity is a crucial factor that influences premature death rates, poor health, depression, quality of life, and use of health care. Approximately one-fifth of the global workforce is involved in shift work, which is associated with increased risk for several chronic diseases and multimorbidity. About 12% to 14% of wage workers in Korea are shift workers. However, the prevalence of multimorbidity and its associated factors in Korean shift workers are rarely reported. This study aimed to assess multimorbidity prevalence, examine the factors associated with multimorbidity, and identify multimorbidity patterns among shift workers in Korea. This study is a population-based cross-sectional study using Korea National Health and Nutrition Examination Survey data from 2016 to 2020. The study included 1704 (weighted n=2,697,228) Korean shift workers aged 19 years and older. Multimorbidity was defined as participants having 2 or more chronic diseases. Demographic and job-related variables, including regular work status, average working hours per week, and shift work type, as well as health behaviors, including BMI, smoking status, alcohol use, physical activity, and sleep duration, were included in the analysis. A survey-corrected logistic regression analysis was performed to identify factors influencing multimorbidity among the workers, and multimorbidity patterns were identified with a network analysis. The overall prevalence of multimorbidity was 13.7% (302/1704). Logistic regression indicated that age, income, regular work, and obesity were significant factors influencing multimorbidity. Network analysis results revealed that chronic diseases clustered into three groups: (1) cardiometabolic multimorbidity (hypertension, dyslipidemia, diabetes, coronary heart disease, and stroke), (2) musculoskeletal multimorbidity (arthritis and osteoporosis), and (3) unclassified diseases (depression, chronic liver disease, thyroid disease, asthma, cancer, and chronic kidney disease). The findings revealed that several socioeconomic and behavioral factors were associated with multimorbidity among shift workers, indicating the need for policy development related to work schedule modification. Further organization-level screening and intervention programs are needed to prevent and manage multimorbidity among shift workers. We also recommend longitudinal studies to confirm the effects of job-related factors and health behaviors on multimorbidity among shift workers in the future.

Expert consensus on the diagnosis and treatment of respiratory diseases exacerbated by nonsteroidal anti-inflammatory drugs （2024, Chengdu）

Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease （N-ERD） is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis （CRS）, asthma, and intolerance to cyclooxygenase 1 （COX-1） inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.

Low-Dose CT-derived Bronchial Parameters in Individuals with Healthy Lungs.

Background CT-derived bronchial parameters have been linked to chronic obstructive pulmonary disease and asthma severity, but little is known about these parameters in healthy individuals. Purpose To investigate the distribution of bronchial parameters at low-dose CT in individuals with healthy lungs from a Dutch general population. Materials and Methods In this prospective study, low-dose chest CT performed between May 2017 and October 2022 were obtained from participants who had completed the second-round assessment of the prospective, longitudinal Imaging in Lifelines study. Participants were aged at least 45 years, and those with abnormal spirometry, self-reported respiratory disease, or signs of lung disease at CT were excluded. Airway lumens and walls were segmented automatically. The square root of the bronchial wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10), luminal area (LA), wall thickness (WT), and wall area percentage were calculated. Associations between sex, age, height, weight, smoking status, and bronchial parameters were assessed using univariable and multivariable analyses. Results The study sample was composed of 8869 participants with healthy lungs (mean age, 60.9 years ± 10.4 [SD]; 4841 [54.6%] female participants), including 3672 (41.4%) never-smokers and 1197 (13.5%) individuals who currently smoke. Bronchial parameters for male participants were higher than those for female participants (Pi10, slope [β] range = 3.49-3.66 mm; LA, β range = 25.40-29.76 mm2; WT, β range = 0.98-1.03 mm; all P < .001). Increasing age correlated with higher Pi10, LA, and WT (r2 range = 0.06-0.09, 0.02-0.01, and 0.02-0.07, respectively; all P < .001). Never-smoking individuals had the lowest Pi10 followed by formerly smoking and currently smoking individuals (3.62 mm ± 0.13, 3.68 mm ± 0.14, and 3.70 mm ± 0.14, respectively; all P < .001). In multivariable regression models, age, sex, height, weight, and smoking history explained up to 46% of the variation in bronchial parameters. Conclusion In healthy individuals, bronchial parameters differed by sex, height, weight, and smoking history; male sex and increasing age were associated with wider lumens and thicker walls. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Emrich and Varga-Szemes in this issue.

ScRNA-seq profiling of human granulocytes reveals expansion of developmentally flexible neutrophil precursors with mixed neutrophil and eosinophil properties in asthma.

Neutrophils and eosinophils share common hematopoietic precursors and usually diverge into distinct lineages with unique markers before being released from their hematopoietic site, which is the bone marrow (BM). However, previous studies identified an immature Ly6g(+) Il-5Rα(+) neutrophil population in mouse BM, expressing both neutrophil and eosinophil markers suggesting hematopoietic flexibility. Moreover, others have reported neutrophil populations expressing eosinophil-specific cell surface markers in tissues and altered disease states, confusing the field regarding eosinophil origins, function, and classification. Despite these reports, it is still unclear whether hematopoietic flexibility exists in human granulocytes. To answer this, we utilized single-cell RNA sequencing (scRNA-seq) and CITE-seq to profile human BM and circulating neutrophils and eosinophils at different stages of differentiation and determine whether neutrophil plasticity plays role in asthmatic inflammation. We show that immature metamyelocyte neutrophils in humans expand during severe asthmatic inflammation and express both neutrophil and eosinophil markers. We also show an increase in tri-lobed eosinophils with mixed neutrophil and eosinophil markers in allergic asthma and that IL-5 promotes differentiation of immature blood neutrophils into tri-lobed eosinophilic phenotypes suggesting a mechanism of emergency granulopoiesis to promote myeloid inflammatory or remodeling response in patients with chronic asthma. By providing insights into unexpectedly flexible granulocyte biology and demonstrating emergency hematopoiesis in asthma, our results highlight the importance of granulocyte plasticity in eosinophil development and allergic diseases.

Healthy Mouth, Healthy Lungs: Novel Solutions for Preventing and Diagnosing Periodontal Disease in the Context of Chronic Respiratory Illness.

Chronic respiratory illnesses, such as chronic obstructive pulmonary disease and asthma, pose significant challenges to public health worldwide. Mounting evidence suggests a bidirectional relationship between respiratory health and oral health, with periodontal disease emerging as a potential risk factor for the development and exacerbation of respiratory conditions. This review paper explores the complex interplay between periodontal disease and chronic respiratory illness, highlighting the importance of oral health maintenance in promoting respiratory well-being. By examining recent advancements in the prevention and diagnosis of periodontal disease, particularly in the context of chronic respiratory conditions, this paper aims to elucidate novel solutions and strategies for improving oral health outcomes and respiratory outcomes simultaneously. Through a comprehensive analysis of the literature and emerging research trends, this review sheds light on the potential benefits and challenges of integrating oral health into the management of chronic respiratory illnesses and identifies opportunities for future research and clinical practice.

A Review on Concept of Malabar Nut

The plant is extremely valuable medicinally and is used to treat a wide range of illnesses, most commonly respiratory conditions such as chronic bronchitis, asthma, tb, and common cold symptoms.medicines are made from every component of the plant. This plant's primary chemical component, vasicine, has a number of therapeutic uses and is used into several ayurvedic formulas

Early Diagnosis and Treatment of COPD and Asthma — A Randomized, Controlled Trial

BackgroundMany persons with chronic obstructive pulmonary disease (COPD) or asthma have not received a diagnosis, so their respiratory symptoms remain largely untreated.MethodsWe used a case-finding method to identify adults in the community with respiratory symptoms without diagnosed lung disease. Participants who were found to have undiagnosed COPD or asthma on spirometry were enrolled in a multicenter, randomized, controlled trial to determine whether early diagnosis and treatment reduces health care utilization for respiratory illness and improves health outcomes. Participants were assigned to receive the intervention (evaluation by a pulmonologist and an asthma–COPD educator who were instructed to initiate guideline-based care) or usual care by their primary care practitioner. The primary outcome was the annualized rate of participant-initiated health care utilization for respiratory illness. Secondary outcomes included changes from baseline to 1 year in disease-specific quality of life, as assessed with the St. George Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better health status); symptom burden, as assessed with the COPD Assessment Test (CAT; scores range from 0 to 40, with lower scores indicating better health status); and forced expiratory volume in 1 second (FEV1).ResultsOf 38,353 persons interviewed, 595 were found to have undiagnosed COPD or asthma and 508 underwent randomization: 253 were assigned to the intervention group and 255 to the usual-care group. The annualized rate of a primary-outcome event was lower in the intervention group than in the usual-care group (0.53 vs. 1.12 events per person-year; incidence rate ratio, 0.48; 95% confidence interval [CI], 0.36 to 0.63; P<0.001). At 12 months, the SGRQ score was lower than the baseline score by 10.2 points in the intervention group and by 6.8 points in the usual-care group (difference, −3.5 points; 95% CI, −6.0 to −0.9), and the CAT score was lower than the baseline score by 3.8 points and 2.6 points, respectively (difference, −1.3 points; 95% CI, −2.4 to −0.1). The FEV1 increased by 119 ml in the intervention group and by 22 ml in the usual-care group (difference, 94 ml; 95% CI, 50 to 138). The incidence of adverse events was similar in the trial groups.ConclusionsIn this trial in which a strategy was used to identify adults in the community with undiagnosed asthma or COPD, those who received pulmonologist-directed treatment had less subsequent health care utilization for respiratory illness than those who received usual care. (Funded by Canadian Institutes of Health Research; UCAP ClinicalTrials.gov number, NCT03148210.)

Preparation and impregnation of deep eutectic solvents containing zileuton onto adsorbents to elicit the biopharmaceutical attributes

Deep eutectic solvent (DES) is a contemporary and eco-friendly solvent recently exploited to modulate the solubility of drugs. Herein, we developed DESs for an increment of solubility and bioavailability of zileuton (ZLT). ZLT is an anti-inflammatory drug categorized as an inhibitor of the enzyme 5-lipoxygenase commonly prescribed for treating chronic bronchial asthma. However, its therapeutic uses are limited owing to its poor water solubility. Several stable DESs were developed and assessed for viscosity, pH, and solubility. The DES comprising ChCl: EG (1:3) exhibits an excellent ZLT solubility (57.27 ± 0.14 mg/mL). The molecular and electrostatic interaction was assessed through a conductor-like screening model for real solvents (COSMO-RS). Further, 1H NMR analysis, FTIR, and digital microscopy were used to investigate the molecular transition in the chosen DES-ZLT. The DES in a liquid state possesses several drawbacks, such as instability, volatility, and dose precision. Therefore, a wet impregnation approach utilizing inert carriers such as Aerosil-200 and Avicel PH-102 was performed for the solidification of liquid DES. The solidified DES-ZLT was characterized by DSC and PXRD techniques and indicated the existence of ZLT in a highly dissolved state. Furthermore, solid DES-ZLT showed a significant increment in the dissolution studies, resulting in a 2.91 fold rise in oral bioavailability of ZLT. Hence, the presented study proves a well-organized and proficient development of a solid DES system to ameliorate the solubility and stability aspects of ZLT, which could provide the template for promising drugs that lack therapeutic effectiveness owing to solubility issues.

Narrative review on the spectrum of diseases prevalent among substance-addicted populations and their interconnected health dynamics

Substance addiction is a complex phenomenon characterized by the dysfunction of the brain's reward system and neuroplasticity, leading individuals to lose control over their behaviour. This review explores the diverse health implications of addiction, including its impact on liver diseases, cardiovascular conditions, respiratory issues, cancers, infectious diseases, gastrointestinal problems, and mental disorders. Heavy alcohol consumption, tobacco use, illicit drug abuse, and prescription drug misuse contribute significantly to these health burdens, affecting various organs and systems in the body. Respiratory issues arise from tobacco smoking, inhalation of illicit drugs, and volatile chemicals, causing chronic obstructive pulmonary disease, lung cancers, and bronchial asthma. Substance addiction is also linked to various cancers, particularly lung cancer from tobacco, oral cancers from tobacco and alcohol, and oesophageal cancers from alcohol and prescription drugs. Furthermore, addictive substances impair immunity, making individuals more susceptible to infectious diseases like pneumonia, tuberculosis, and HIV/AIDS, especially among injection drug users. The interconnected nature of substance addiction with mental health disorders, genetic factors, environmental influences, and social determinants underscores the need for comprehensive public health strategies. These strategies should encompass education, prevention programs, access to treatment and support services, harm reduction approaches, and destigmatization efforts to address substance addiction comprehensively and improve overall health outcomes for individuals and communities.

Efficient detection of nitric oxide a biomarker associated with COVID19 via N, P co-doped C60 fullerene: a computational study.

Coronavirus (COVID-19) is a novel respiratory viral infection, causing a relatively large number of deaths especially in people who underly lung diseases such as chronic obstructive pulmonary and asthma, and humans are still suffering from the limited testing capacity. In this article, a solution is proposed for the detection of COVID-19 viral infections through the analysis of exhaled breath gasses, i.e., nitric oxide, a prominent biomarker released by respiratory epithelial, as a non-invasive and time-saving approach. Here, we designed a novel and low-cost N and P co-doped C60 fullerene-based breathalyzer for the detection of NO gas exhaled from the respiratory epithelial cells. This breathalyzer shows a quick response to the detection of NO gas by directly converting NO to NO2 without passing any energy barrier (0kcal/mol activation energy). The recovery time of breathalyzer is very short (0.98 × 103s), whereas it is highly selective for NO sensing in the mixture of CO2 and H2O gasses. The study provides an idea for the synthesis of low-cost (compared to previously reported Au atom decorated nanostructure and metal-based breathalyzer), efficient, and highly selective N and P co-doped C60 fullerene-based breathalyzer for COVID-19 detection. The geometries of N and P-doped systems and gas molecules are simulated using spin-polarized density functional theory calculations.

Bronchom assuages airway hyperresponsiveness in house dust mite-induced mouse model of allergic asthma and moderates goblet cell metaplasia, sub-epithelial fibrosis along with changes in Th2 cytokines and chemokines.

Asthma is a common obstructive airway disease with an inflammatory etiology. The main unmet need in the management of asthma is inadequate adherence to pharmacotherapy, leading to a poorly-controlled disease state, necessitating the development of novel therapies. Bronchom is a calcio-herbal formulation, which is purported to treat chronic asthma. The objective of the current study was to examine the in-vivo efficacy of Bronchom in mouse model of allergic asthma. Ultra high performance liquid chromatography was utilized to analyze the phytocompounds in Bronchom. Further, the in-vivo efficacy of Bronchom was evaluated in House dust mite (HDM)-induced allergic asthma in mice. Mice were challenged with aerosolized methacholine to assess airway hyperresponsiveness. Subsequently, inflammatory cell influx was evaluated in bronchoalveolar lavage fluid (BALF) followed by lung histology, wherein airway remodeling features were studied. Simultaneously, the levels of Th2 cytokines and chemokines in the BALF was also evaluated. Additionally, the mRNA expression of pro-inflammatory and Th2 cytokines was also assessed in the lung along with the oxidative stress markers. Phytocompounds present in Bronchom included, gallic acid, protocatechuic acid, methyl gallate, rosmarinic acid, glycyrrhizin, eugenol, 6-gingerol and piperine. Bronchom effectively suppressed HDM-induced airway hyperresponsiveness along with the influx of leukocytes in the BALF. Additionally, Bronchom reduced the infiltration of inflammatory cells in the lung and it also ameliorated goblet cell metaplasia, sub-epithelial fibrosis and increase in α-smooth muscle actin. Bronchom decreased Th2 cytokines (IL-4 and IL-5) and chemokines (Eotaxin and IP-10) in the BALF. Likewise, it could also suppress the mRNA expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6 and IL-33), and IL-13. Moreover, Bronchom restored the HDM-induced diminution of endogenous anti-oxidants (GSH and SOD) and the increase in pro-oxidants (GSSG and MDA). Furthermore, Bronchom could also decrease the nitrosative stress by lowering the observed increase in nitrite levels. Taken together, the results of the present study data convincingly demonstrate that Bronchom exhibits pharmacological effects in an animal model of allergic asthma. Bronchom mitigated airway hyperresponsiveness, inflammation and airway remodeling evoked by a clinically relevant allergen and accordingly it possesses therapeutic potential for the treatment of asthma.

Efficacy of POWERbreathe Medic Plus device on maximal inspiratory pressure, functional capacity and quality of life in coronary artery bypass graft patients: A randomized controlled trial protocol

Coronary artery disease (CAD) is a prominent cause of illness and mortality worldwide, with a significant amount of coronary artery bypass graft (CABG) surgeries performed each year. It is a complicated technique that results in several clinical and functional issues. While CABG is an effective treatment, it comes with clinical and functional challenges, including reduced lung volume, maximal inspiratory and expiratory pressure, and thoracic mobility after surgery. Incisional pain has been associated with a decline in postoperative lung function; however, this resolves a month following surgery. There is no documented association between respiratory muscle strength and lung function after heart surgery. The POWERbreathe Medic Plus is intended for patients who have extremely weak breathing muscles as a result of illness, hospitalization, or existing respiratory health disorders such as Chronic Obstructive Pulmonary Disease (COPD) and asthma. To address these challenges, a study will investigate the efficacy of the POWERbreathe Medic Plus device in improving maximal inspiratory pressure, functional capacity, and quality of life in CABG patients. CTRI no. – CTRI/2023/04/052116 Link-https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODMxNTA=&amp;Enc=&amp;userName=CTRI/2023/04/052116 CTRI registration date – 28/04/2023

Clinical manifestations of EVALI in adolescents and the impact of e-cigarettes on the respiratory disease

In recent years there has been a significant increase in the popularity of electronic cigarettes among adolescents and young adults worldwide. E-cigarettes have reached the market without the extensive preclinical toxicology testing or long-term safety studies required for conventional therapeutics and medical devices. Their effectiveness as a smoking cessation intervention, their impact at the population level and whether they are less harmful than combustible tobacco products are highly controversial. Studies show measurable adverse biological effects on organ and cell health in humans, animals and in vitro. E-cigarette use also increases the risk of respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma. There is a serious risk of complications associated with e-cigarette use, such as EVALI (E-cigarette or Vaping Product Use-Associated Lung Injury) - serious lung damage associated with, especially for adolescents. This paper reviews the effects of e-cigarettes on respiratory health.

Using spirometry for screening and diagnosis of chronic respiratory diseases in primary health care: findings from a community health project in rural India

Background Chronic respiratory diseases (CRDs) such as Chronic obstructive pulmonary disease (COPD), Asthma and post-tuberculosis lung disease (PTLD) are a growing public health concern in India. Early diagnosis and management of CRDs require a good quality spirometry test, a technician to conduct spirometry and a chest physician to interpret the results. In India, these are not available at the primary care level. This study reports the feasibility of a large-scale CRD diagnosis and management program in primary care using a unique point-of-care spirometry solution, Briota PFT in a Box™. # Methods A community-based cross-sectional study was conducted among 15,602 adults in Dindori Taluka (subdivision), Nashik, Maharashtra state. This study was part of a holistic CRD diagnosis and management program SAVE™ (Spirometry Assisted Virtually Early). Make In India point of care solution Briota PFT in a Box™ was used. A House‐to‐house community-based assessment checklist (CBAC) survey, 4-parameter spirometry test, 15-parameter pre and post-bronchodilator spirometry test and a software-assisted medical examination by the medical officer at primary care were conducted. Software was used to generate CRD diagnosis and lung health score (LHS™). The diagnosis was verified by the chest physician. Confirmed diagnosed patients were provided treatment and offered a patient support program. Interviews were conducted with the patients, nurses, doctors and public health officials for understanding feasibility and documenting learning from program SAVE™. # Results Out of 15,602 adults surveyed, total 4,937 (31.6%) were identified as “CRD high risk”. 1231 participants based on medical examination, spirometry tests and software analysis were identified as CRD candidates by medical officers at primary care. 1154 participants out of 15,602 (7.4%) were confirmed diagnosed as CRD patients post independent evaluation by chest physicians. At the time of follow-up, 537 patients (75% of 712 patients enrolled in patient support program) reported improvement in symptoms and high satisfaction with the program. District health officer, Medical officers, nurses, Accredited Social Health Activist (ASHA) from the primary health care centers confirmed ease of use and feasibility of using Briota PFT in a Box™ in program SAVE™. Outcome and learning from program SAVE™ was documented and submitted to Ministry of Health and Family Welfare Government of India. # Conclusions CRD diagnosis and management in large scale settings in primary healthcare level using a point of care spirometry solution Briota PFT in a Box™ is highly feasible.

Abstract PO3-17-07: Real-world experience with trastuzumab deruxtecan in patients with breast cancer: 6 month-interim analysis of an all-patient postmarketing surveillance in Japan

Abstract Background: Trastuzumab deruxtecan (T-DXd) is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate. T-DXd has shown great efficacy in HER2-positive breast cancer, hence receiving approval in Japan in March 2020. In Japan, all-patient postmarketing surveillance (PMS) is underway to evaluate the risk of interstitial lung disease/pneumonitis (ILD/p) in patients with breast cancer treated with T-DXd. Due to the limited generalizability of results from clinical trials, there is a need for more information about ILD/p in a real-world setting. Herein we present an interim analysis of the large-scale all-patient PMS. Methods: This is an observational, multicenter, all-patient PMS (jRCT1080225197) with an observation period of 18 months that enrolled all patients treated with T-DXd for recurrent/advanced HER2-positive breast cancer. Patients who initiated T-DXd treatment between May 2020 (launch date of T-DXd) and May 2021 were included in the interim analysis to ensure the observation period of 6 months from the initial treatment of T-DXd. This interim analysis is based on safety data from the first 6 months of 1204 patients. Data collected includes baseline characteristics and information on ILD/p. All potential ILD/p (identified based on the AE terms) reported by physicians were adjudicated by an independent ILD adjudication committee. The incidence of ILD/p was calculated from adjudicated drug-related ILD/p. Results: The interim analysis set included 1204 patients with median age of 60 years. Three of the 1204 patients (0.2%) received T-DXd as a first-line treatment, 30 (2.5%) as second-line, 1159 (96.3%) as third- line or later treatment. At baseline, 105 (8.7%) of patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) 2 or greater, 8 (0.7%) had severe renal impairment (15≤ creatinine clearance (CLcr) &amp;lt; 30 mL/min), 4 (0.3%) had end-stage renal disease (CLcr &amp;lt; 15 mL/min), 5 (0.4%) had severe liver impairment (total bilirubin &amp;gt;4.5 mg/dL), and 32 (2.7%) had comorbid ILD/radiation pneumonitis. Those were defined as exclusion criteria in clinical trials of T-DXd. The median dose at the start of administration of T-DXd was 5.4 mg/kg (range:2.7-5.4). During the first 6 months from the initial treatment, T-DXd was discontinued in 403 (33.5%) of the 1204 patients. The most common reasons for discontinuation were disease progression in 232 (57.6%) of the discontinued 403 patients followed by ILD/p in 97 (24.1%) of the 403 patients. In the first 6 months, the incidence of all grade, grade ≥3, and grade 5 ILD/p were 8.2% (n=99), 1.7% (n=20) and 0.4% (n=5), respectively. The incidence of ILD/p stratified by baseline characteristics identified as potential risk factors of drug-related ILD/p is shown in Table. Conclusion: This is the first report demonstrating real-world experience with T-DXd in Japan. The interim analysis revealed useful information including patient and treatment profiles of T-DXd and the incidence of ILD/p during the first 6 months from the initial treatment in a real-world setting in Japan. The final analysis of the ongoing PMS is warranted for further evaluation. Incidence of interstitial lung disease/pneumonitis by patient baseline characteristics XX XX ILD/p: interstitial lung disease/pneumonitis, 95% CI: 95% confidence interval, CLCr: creatinine clearance using the Cockcroft-Gault equation * includes ILD/p, pulmonary fibrosis, radiation pneumonitis, chronic obstructive pulmonary disease, emphysema, and Asthma (Source: Powell CA, Modi S, Iwata H, et al. Pooled analysis of drug-related interstitial lung disease and/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies. ESMO Open 2022;7(4):100554) Citation Format: Junji Tsurutani, Hideki Mizutani, Ayumi Tanabe. Real-world experience with trastuzumab deruxtecan in patients with breast cancer: 6 month-interim analysis of an all-patient postmarketing surveillance in Japan [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-07.

Transcriptional profiling of primary human-skin derived mast cell activation by various MRGPRX2 agonists and inhibition with EVO756

Abstract Mas-related G-protein coupled receptor X2 (MRGPRX2) is a GPCR expressed predominantly by mast cells and has been implicated to play an important role in diseases such as chronic spontaneous urticaria, atopic dermatitis, and asthma. Cationic ligands, either endogenous or exogenous, can activate the receptor and induce IgE-independent mast cell activation, resulting in allergic responses and non-histaminergic itch. We have previously shown that EVO756, a novel small molecule antagonist of MRGPRX2, demonstrates potent, concentration dependent inhibition of MRGPRX2 mediated activation of transfected CHO-cells, ROSA and LAD2 mast cell lines, and primary human skin-derived mast cells. Furthermore, EVO756 does not affect mast cell viability. Here, we describe, for the first time, the transcriptional landscape of primary human skin-derived mast cells cultured in the presence of several MRGPRX2 agonists and analyze how the mast cell phenotype is altered in response to MRGPRX2 inhibition by EVO756.

Role of MNK/eIF4E pathway in CD4+ Th2 cytokine-induced lung fibrosis in chronic allergic asthma

Abstract Despite therapeutic advances in allergic asthma, the persistent challenge of airway remodeling still exists, necessitating further exploration. We aimed to investigate the influence of CD4+ Th2 cytokines on fibrosis associated with airway remodeling, with a focus on mesenchymal cell (MC) transformation. Using both human and mouse lung MCs, we investigated the pivotal role of MNK/eIF4E pathway in regulating fibrous protein expression driven by CD4+ Th2 cytokines. To assess this, we employed western blot and flow cytometry studies, while Luminex assays measured cytokine and chemokine secretion from activated lung MCs responding to Th2 cytokines. Treatment with Th2 cytokines significantly increased ATX expression in lung MCs, a response mitigated by the specific MNK1/2 inhibitor (eFT-508). Furthermore, this inhibitor not only abolished the phosphorylation of eIF4E but also reduced collagen levels within activated MCs induced by Th2 cytokines. Luminex assay results demonstrated a significant decrease in IL-6, CCL-2, and GM-CSF in the activated MCs upon inhibiting the MNK1/2 pathway. Additionally, eFT-508 exhibited a marked reduction in lymphocyte migration, utilizing the Boyden chamber transwell assay. Our study reveals that targeting the MNK/eIF4E pathway holds promise in mitigating airway remodeling associated with MCs fibrosis and provides valuable molecular insights for future therapeutic interventions related to fibrosis in the airway remodeling of allergic asthma.

Prevalence and predictors of polypharmacy in elderly patients discharged from a tertiary care teaching hospital in Swat, Pakistan: A retrospective cross-sectional study

Background: The use of polypharmacy in the elderly has been the subject of much consideration in recent years. However, its prevalence and risk factors are yet to be properly investigated in Pakistan. Objective: The study investigated the prevalence and risk factors of polypharmacy at discharge in Pakistan. Method: A retrospective cross-sectional study of elderly patients' medical profiles for the year 2021 was performed, and the profiles that met the inclusion criteria were included. Results: The total sample size was 800, and 51.9% of patients received polypharmacy at discharge. The authors found that the female gender (OR = 0.469) has comparatively less risk of receiving polypharmacy. Furthermore, patients with an increased length of stay and increased medication use in the hospital (OR 1.1295, OR = 17.189, respectively) have a high risk of receiving polypharmacy at discharge. Furthermore, patients diagnosed with peripheral vascular disease (OR = 4.689), cerebrovascular accident (OR = 2.764), chronic obstructive pulmonary disease (OR = 3.748), asthma (OR = 2.321), and diabetes mellitus (OR = 2.754) had higher risks of receiving polypharmacy. Conclusion: The study found a high prevalence of polypharmacy at discharge in Pakistan and identified several risk factors that could help to reduce polypharmacy by targeting vulnerable groups.

Investigating pulmonary neuroendocrine cells in human respiratory diseases with airway models.

Despite accounting for only ∼0.5% of the lung epithelium, pulmonary neuroendocrine cells (PNECs) appear to play an outsized role in respiratory health and disease. Increased PNEC numbers have been reported in a variety of respiratory diseases, including chronic obstructive pulmonary disease and asthma. Moreover, PNECs are the primary cell of origin for lung neuroendocrine cancers, which account for 25% of aggressive lung cancers. Recent research has highlighted the crucial roles of PNECs in lung physiology, including in chemosensing, regeneration and immune regulation. Yet, little is known about the direct impact of PNECs on respiratory diseases. In this Review, we summarise the current associations of PNECs with lung pathologies, focusing on how new experimental disease models, such as organoids derived from human pluripotent stem cells or tissue stem cells, can help us to better understand the contribution of PNECs to respiratory diseases.

Capacidad pronóstica del dimero D en la predicción de mortalidad en pacientes con el diagnóstico de COVID-19

Introduction: SARS-CoV-2 infection can increase the risk of thrombosis. Studies associate D-dimer levels with COVID-19 mortality. Objective: To determine the prognostic capacity of D-dimer in predicting COVID-19 mortality in patients hospitalized in the Intensive Care Unit. Methods: A retrospective cohort study was conducted at the Centro Médico Naval from January to July 2021. A total of 324 adult patients with RT-PCR confirmed COVID-19 were included. D-dimer levels were measured upon admission using coagulation turbidimetry (Sysmex CS-5100). Sociodemographic variables, comorbidities, and clinical data were analyzed. Statistical analysis was performed using SPSS version 26, employing Chi-square tests, Fisher's exact test, Mann-Whitney U test, ROC, and Cox regression. Results: A cut-off point of 1.40 µg/mL for D-dimer values was determined, with a sensitivity of 80.9%, specificity of 86.4%, and an area under the curve (AUC) of 0.916 (95% CI: 0.884 – 0.947; p=0.016) for predicting COVID-19 mortality. Additionally, patients with D-dimer values greater than or equal to 1.40 µg/mL had an increased risk of death (adjusted HR = 6.545; 95% CI: 3.867 – 11.077; p&lt;0.001), independent of age, diabetes mellitus, arterial hypertension, ischemic heart disease, cerebrovascular disease, atrial fibrillation, chronic obstructive pulmonary disease, asthma, cancer, and thrombocytopenia. Conclusion: This study showed that admission D-dimer levels represent a reliable biomarker in evaluating the prognosis of COVID-19 patients.