Chronic Obstructive Emphysema Research Articles

The PROgnostic ModEl for chronic lung disease (PRO-MEL): development and temporal validation

BackgroundPatients with chronic lung diseases (CLDs), defined as progressive and life-limiting respiratory conditions, experience a heavy symptom burden as the conditions become more advanced, but palliative referral rates are low and late. Prognostic tools can help clinicians identify CLD patients at high risk of deterioration for needs assessments and referral to palliative care. As current prognostic tools may not generalize well across all CLD conditions, we aim to develop and validate a general model to predict one-year mortality in patients presenting with any CLD.MethodsA retrospective cohort study of patients with a CLD diagnosis at a public hospital from July 2016 to October 2017 was conducted. The outcome of interest was all-cause mortality within one-year of diagnosis. Potential prognostic factors were identified from reviews of prognostic studies in CLD, and data was extracted from electronic medical records. Missing data was imputed using multiple imputation by chained equations. Logistic regression models were developed using variable selection methods and validated in patients seen from January 2018 to December 2019. Discriminative ability, calibration and clinical usefulness of the model was assessed. Model coefficients and performance were pooled across all imputed datasets and reported.ResultsOf the 1000 patients, 122 (12.2%) died within one year. Patients had chronic obstructive pulmonary disease or emphysema (55%), bronchiectasis (38%), interstitial lung diseases (12%), or multiple diagnoses (6%). The model selected through forward stepwise variable selection had the highest AUC (0.77 (0.72–0.82)) and consisted of ten prognostic factors. The model AUC for the validation cohort was 0.75 (0.70, 0.81), and the calibration intercept and slope were − 0.14 (-0.54, 0.26) and 0.74 (0.53, 0.95) respectively. Classifying patients with a predicted risk of death exceeding 0.30 as high risk, the model would correctly identify 3 out 10 decedents and 9 of 10 survivors.ConclusionsWe developed and validated a prognostic model for one-year mortality in patients with CLD using routinely available administrative data. The model will support clinicians in identifying patients across various CLD etiologies who are at risk of deterioration for a basic palliative care assessment to identify unmet needs and trigger an early referral to palliative medicine.Trial registrationNot applicable (retrospective study).

Citrullination, a novel post-translational modification of elastin, is involved in COPD Pathogenesis.

Elastin is an extracellular matrix protein (ECM) that supports elasticity of the lung, and in patients with chronic obstructive pulmonary disease (COPD) and emphysema, the structural changes that reduce the amount of elastic recoil, lead to loss of pulmonary function. We recently demonstrated that elastin is a target of peptidyl arginine deiminase (PAD) enzyme-induced citrullination, thereby leading to enhanced susceptibility of this ECM protein to proteolysis. The current study aimed to investigate the impact of PAD activity in vivo and furthermore assessed whether pharmacological inhibition of PAD activity protects against pulmonary emphysema. Using a Serpina1a-e knockout mouse model, previously shown to develop inflammation-mediated emphysema, we validated the involvement of PADs in airway disease. In line with emphysema development, intratracheal administration of lipopolysaccharide in combination with PADs provoked significant airspace enlargement (P < 0.001) and diminished lung function, including loss of lung tissue elastance (P = 0.0217) and increases in lung volumes (P = 0.0463). Intraperitoneal treatment of mice with the PAD inhibitor, BB-Cl-amidine, prevented PAD/LPS-mediated lung function decline and emphysema and reduced levels of citrullinated airway elastin (P = 0.0199). These results provide evidence for the impact of PADs on lung function decline, indicating promising potential for the future development of PAD-based therapeutics for preserving lung function in patients with COPD.

Current Practices for Severe Alpha-1 Antitrypsin Deficiency Associated COPD and Emphysema

Alpha-1 antitrypsin deficiency is a genetic disorder that can lead to chronic obstructive pulmonary disease and emphysema. Although it is the most well-studied genetic risk factor for emphysema, data is still scarce. Traditionally, medical therapy is similar to standard chronic obstructive pulmonary disease patients. Over the past several decades, enzyme augmentation therapy has emerged as a highly utilized alpha-1 antitrypsin-specific therapy. It has become the standard of care for severe alpha-1 antitrypsin deficiency despite unclear effects on a multitude of clinical outcomes. Significant data supports interventional therapies, including lung volume reduction surgery and bronchoscopic lung volume reduction, for chronic obstructive pulmonary disease patients without alpha-1 antitrypsin deficiency. These interventions have less robust data in the treatment of alpha-1 antitrypsin-induced chronic obstructive pulmonary disease. This review will explore the data regarding various treatment options for severe alpha-1 antitrypsin deficiency associated with chronic obstructive pulmonary disease and emphysema.

Molecular changes underlying pulmonary emphysema and chronic bronchitis in Chronic Obstructive Pulmonary Disease: An updated review.

The aim of this review is to update and synthesize the molecular mechanisms that lead to the heterogeneous effect on tissue remodeling observed in the two most important clinical phenotypes of chronic obstructive pulmonary disease (COPD), pulmonary emphysema (PE) and chronic bronchitis (CB). Clinical and experimental evidence suggests that this heterogeneous response to promote PE, CB, or both, is related to differentiated genetic, epigenetic, and molecular conditions. Specifically, a tendency toward PE could be related to a variant in the DSP gene, SIRT1 downregulation, macrophage polarization to M1, as well as the involvement of the noncanonical Wnt5A signaling pathway, among other alterations. Additionally, in advanced stages of COPD, PE development is potentiated by dysregulations in autophagy, which promotes senescence and subsequently cell apoptosis, through exacerbated inflammasome activation and release of caspases. On the other hand, CB or the pro-fibrotic phenotype could be potentiated by the downregulated activity of HDAC2, the activation of the TGF-β/Smad or Wnt/β-catenin signaling pathways, macrophage polarization to M2, upregulation of TIMP-1, and/or the presence of the epithelial-mesenchymal transition (EMT) mechanism. Interestingly, the upregulated activity of MMPs, especially MMP-9, is widely involved in the development of both phenotypes. Furthermore, MMP-9 and MMP-12 enhance the severity, perpetuation, and exacerbation of COPD, as well as the development of autoimmunity in this disease.

Zoster vaccine lowers stroke and myocardial infarction risk in chronic disease

Herpes zoster increases stroke and myocardial infarction (MI) risk. The objective of this study is to evaluate the impact of live attenuated zoster vaccination on stroke and MI risk in patients at-risk for zoster including persons with hypertension, diabetes mellites, obesity, hypercholesterolemia, chronic kidney disease, chronic obstructive pulmonary disease, emphysema, asthma, and chronic liver disease. Retrospective cohort study utilizing continuous de-identified claims data from the IBM MarketScan® Commercial Claims and Encounters Database (collected from 2005-2018) containing data for 200 million commercially insured Americans. Participants included 27,093 adults vaccinated against zoster with at least 5 years continuous enrollment, age and sex-matched 1:5 with unvaccinated controls. Odds ratios, risk difference, and number needed to treat (NNT) evaluated the effect of vaccination on stroke and MI while controlling for relevant comorbidities. Over five years, proportions of MI (1.29% vs 1.82%; p<0.05) and stroke (1.61% vs. 2.20%; p<0.05) were lower in vaccinated versus unvaccinated individuals respectively, controlling for age and sex, with greatest benefit for people with diabetes (stroke OR [95% Confidence Limits] 0.64 [0.58, 0.71], MI 0.63 [0.57, 0.71]). Although hypertension and chronic obstructive pulmonary disease (COPD) had highest odds of stroke and MI, vaccination still provided significant risk-reduction (Hypertension: stroke 0.75 [0.68, 0.83], MI 0.73 [0.65, 0.81]; COPD: stroke 0.75 [0.68, 0.83], MI 0.74 [0.66, 0.83]). Live attenuated zoster vaccination is associated with lower risk stroke and MI in adults with at-risk comorbidities, controlling for age and sex. Vaccination may provide cardiovascular benefits beyond zoster prevention.

Downregulation of Mirlet7 miRNA family promotes Tc17 differentiation and emphysema via de-repression of RORγt.

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the Mirlet7b/Mirlet7c2 cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the Mirlet7b/Mirlet7c2 cluster enhanced CD8+IL17a+ T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing Mirlet7g in T cells are resistant to Tc17 and CD4+IL17a+ T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of Mirlet7 in T cells. Overall, our findings shed light on the Mirlet7/RORγt axis with Mirlet7 acting as a molecular brake in the generation of Tc17 cells and suggest a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.

Downregulation of Mirlet7 miRNA family promotes Tc17 differentiation and emphysema via de-repression of RORγt

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the Mirlet7b/Mirlet7c2 cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the Mirlet7b/Mirlet7c2 cluster enhanced CD8+IL17a+ T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing Mirlet7g in T cells are resistant to Tc17 and CD4+IL17a+ T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of Mirlet7 in T cells. Overall, our findings shed light on the Mirlet7/RORγt axis with Mirlet7 acting as a molecular brake in the generation of Tc17 cells and suggest a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.

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.

Peripheral Blood Mononuclear Cell Gene Expression Associated with Pulmonary Microvascular Perfusion: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. The molecular mechanisms underlying these changes are poorly understood in patients, in part because of the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMCs) interact with the pulmonary endothelium. Objectives: To test the association between gene expression in PBMCs and pulmonary microvascular perfusion in COPD. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited two independent samples of COPD cases and controls with ⩾10 pack-years of smoking history. In both samples, pulmonary microvascular blood flow, pulmonary microvascular blood volume, and mean transit time were assessed on contrast-enhanced magnetic resonance imaging, and PBMC gene expression was assessed by microarray. Additional replication was performed in a third sample with pulmonary microvascular blood volume measures on contrast-enhanced dual-energy computed tomography. Differential expression analyses were adjusted for age, gender, race/ethnicity, educational attainment, height, weight, smoking status, and pack-years of smoking. Results: The 79 participants in the discovery sample had a mean age of 69 ± 6 years, 44% were female, 25% were non-White, 34% were current smokers, and 66% had COPD. There were large PBMC gene expression signatures associated with pulmonary microvascular perfusion traits, with several replicated in the replication sets with magnetic resonance imaging (n = 47) or dual-energy contrast-enhanced computed tomography (n = 157) measures. Many of the identified genes are involved in inflammatory processes, including nuclear factor-κB and chemokine signaling pathways. Conclusions: PBMC gene expression in nuclear factor-κB, inflammatory, and chemokine signaling pathways was associated with pulmonary microvascular perfusion in COPD, potentially offering new targetable candidates for novel therapies.

Body Composition after Endoscopic Lung Volume Reduction with Endobronchial Valves: A Prospective Study.

Patients with chronic obstructive pulmonary disease (COPD) and emphysema experience malnutrition and pulmonary cachexia. Endoscopic lung volume reduction (ELVR) with endobronchial valves has not only improved lung function, exercise capacity, and quality of life but also influenced body weight. Only a few data are available on body composition changes after ELVR. This single-center prospective study of patients with advanced COPD investigates body composition before and after endoscopic valve treatment using multifrequency bioelectrical impedance analysis (BIA). The following parameters were evaluated in addition to clinical data and routine tests: body weight, body mass index (BMI), basal metabolic rate, total body water, body fat, cell percentage, phase angle, intracellular water (ICW), extracellular water (ECW), extracellular mass (ECM), body cell mass (BCM), lean body mass (ECM + BCM), and fat-free mass index. A total of 23 patients (mean emphysema index 37.2 ± 7.5%, BMI 23.4 ± 4.3 kg/m2) experienced improvements in lung function and exercise capacity with ELVR. Complete lobar atelectasis was achieved in 39.1% of participants. A non-statistically significant increase in body weight and BMI was observed after ELVR (p = 0.111 and p = 0.102). BIA measurement revealed a worsening of phase angle, cell percentage and ECM/BCM and thus of body composition, but without statistical significance. This is mainly due to a statistically significant increase in ECM, ECW, and ICW (all p &lt; 0.001). ELVR demonstrated no beneficial changes in body composition, although patients tend to gain weight. A larger cohort is warranted to confirm these findings.

Terpenoids as Human Neutrophil Elastase (HNE) Inhibitors: A Comprehensive Review of Natural Anti-inflammatory Isoprenoids.

Human neutrophil elastase (HNE) is an enzyme that plays a key role in the body's inflammatory response. It has been linked to several diseases such as chronic obstructive pulmonary disease (COPD), emphysema, and cystic fibrosis. As potential treatments for these diseases, HNE inhibitors are of great interest. Metabolites derived from plants, particularly terpenoids such as β-caryophyllene found in black pepper and other plants, and geraniol present in several essential oils, are recognized as significant sources of inhibitors for HNE. Because of their ability to inhibit HNE, terpenoids are considered promising candidates for developing novel therapies to treat inflammatory conditions such as COPD and emphysema. Furthermore, nature can serve as an excellent designer, and it may offer a safer drug candidate for inhibiting HNE production and activity in the future. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were searched to get relevant and up-to-date literature on terpenoids as human neutrophil elastase inhibitors. This review focuses on the isolation, chemical diversity, and inhibition of human neutrophil elastase (HNE) of various terpenoids reported from natural sources up to 2022. A total of 251 compounds from various terpenoids classes have been reported. Further, it also provides a summary of HNE inhibitors and includes a thorough discussion on the structure-activity relationship.

The Type of Tobacco Consumption Habits &amp; Related Health Problem Among the Tobacco Users – A Retrospective Study

Background: Tobacco is the leading preventable cause of death in Bangladesh and worldwide. Tobacco use leads most common diseases affecting the heart and lungs. Smoking being a major risk factor for heart attacks, strokes, chronic obstruc-tive pulmonary disease (COPD), emphysema, and cancer. The aim of this study was to evaluate tobacco consump tion habits among users and identify associated health problems. Material &amp; Methods: This cross-sectional study was conducted in the Department of Health Education of National Institute of Preven-tive and Social Medicine, Dhaka, Bangladesh. Results: In total respondents who were adult male and female were included in the study. We found the Mean ± SD of age was 38.93 ±2.04. According to Sex, 89.30% were male and 10.70% were female and the majority 103.36% respondents of pattern of tobacco consumtion were smokless. 58.68% consumed Zarda, 54.67% cigarette, 27.34% Gul, 17.34% white tobacco, 8.67% Bidi, and rest of 3.34% consumed tobacco as various method. Tobacco con-sumption showed that a majority of knowledge of problem 50.67% were had cough and health problem the majori-ty 34.67% had dental pain. Conclusion: Health problem of tobacco use among the respondents they still consumed tobacco, so an effective awareness pro-gram to discourage the consumption of tobacco to protect people from the devastating consequences of tobacco usages for own and for the passive smoker.

Protective effect of oleo-gum resin of Commiphora wightii against elastase-induced chronic obstructive pulmonary disease-linked lung inflammation and emphysema: Isolation and identification of key bioactive phytoconstituent

Ethnopharmacological relevanceOleo-gum resin of Commiphora wightii (Arnott) Bhandari of family Burseraceae, commonly known as ‘guggul’, is a well known Ayurvedic drug used traditionally to treat various disorders including respiratory ailments. However, role of C. wightii in chronic obstructive pulmonary disease (COPD) is not known. AimThe present work was designed to investigate the protective potential of standardized C. wightii extract/and its fractions against elastase-induced COPD-linked lung inflammation and to identify key bioactive constituent(s). Material and methodsC. wightii oleo-gum resin extract was prepared using Soxhlet extraction technique and the resultant extract was standardized on basis of guggulsterone content using HPLC. The extract was partitioned by different solvents in increasing order of polarity. Standardized extract/its partitioned fractions were orally administered to male BALB/c mice 1 h prior to intra-tracheal instillation of elastase (1U/mouse). Anti-inflammatory effect was evaluated by analyzing inflammatory cells and myeloperoxidase activity in lungs. The various fraction(s) were subjected to column chromatography to isolate bioactive compound. Isolated compound was identified using 1H and 13C-NMR and analyzed for assessment of several inflammatory mediators using techniques like ELISA, PCR, and gelatin zymography. ResultsC. wightii extract attenuated elastase-induced lung inflammation in dose-dependent manner and Ethyl acetate fraction (EAF) provided maximum protection. EAF was subjected to column chromatography followed by assessment of bioactivity of each sub-fraction, ultimately leading towards isolation of two compounds i.e. C1 and C2. C1 seems to be the key active principle of C. wightii, as it displayed significant anti-inflammatory activity against elastase induced lung inflammation while C2 largely remains ineffective. C1 was identified as mixture of E− and Z-guggulsterone (GS). Reduction in the elastase induced lung inflammation by GS was associated with downregulation of expression of several COPD linked pro-inflammatory factors such as IL-6/TNF-α/IL-1β/KC/MIP-2/MCP-1/G-CSF as well as normalization of redox imbalance as indicated by levels of ROS/MDA/protein carbonyl/nitrite/GSH etc. Further, 21 days prolonged administration of GS (10 mg/kg b.wt; once daily) protected against elastase-induced emphysema by mitigating expression/activity of MMP-2/-9 and increasing TIMP-1 expression. ConclusionOverall, guggulsterone seems to be the key bioactive constituent responsible for exerting beneficial effects of C. wightii against COPD.

Fine and coarse particulate air pollution and hospital admissions for a wide range of respiratory diseases: a nationwide case-crossover study.

The associations between fine and coarse particulate matter (PM2.5 and PM2.5-10) air pollution and hospital admissions for full-spectrum respiratory diseases were rarely investigated, especially for age-specific associations. We aim to estimate the age-specific associations of short-term exposures to PM2.5 and PM2.5-10 with hospital admissions for full-spectrum respiratory diseases in China. We conducted an individual-level case-crossover study based on a nationwide hospital-based registry including 153 hospitals across 20 provincial regions in China in 2013-20. We applied conditional logistic regression models and distributed lag models to estimate the exposure- and lag-response associations. A total of 1 399 955 hospital admission records for various respiratory diseases were identified. The associations of PM2.5 and PM2.5-10 with total respiratory hospitalizations lasted for 4 days, and an interquartile range increase in PM2.5 (34.5 μg/m3) and PM2.5-10 (26.0 μg/m3) was associated with 1.73% [95% confidence interval (95% CI): 1.34%, 2.12%)] and 1.70% (95% CI: 1.31%, 2.10%) increases, respectively, in total respiratory hospitalizations over lag 0-4 days. Acute respiratory infections (i.e. pneumonia, bronchitis and bronchiolitis) were consistently associated with PM2.5 or PM2.5-10 exposure across different age groups. We found the disease spectrum varied by age, including rarely reported findings (i.e. acute laryngitis and tracheitis, and influenza) among children and well-established associations (i.e. chronic obstructive pulmonary disease, asthma, acute bronchitis and emphysema) among older populations. Besides, the associations were stronger in females, children and older populations. This nationwide case-crossover study provides robust evidence that short-term exposure to both PM2.5 and PM2.5-10 was associated with increased hospital admissions for a wide range of respiratory diseases, and the spectra of respiratory diseases varied by age. Females, children and older populations were more susceptible.

Clinical profile of disease-causing chronic airflow obstruction in tertiary care centre in Lucknow

Background: Chronic airflow obstruction (CAO) is a chronic lung condition that interferes with normal breathing. In common practice, CAO includes chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis, and emphysema. The present study was planned to be carried out in a tertiary care center to evaluate the profile of patients with chronic airflow obstruction with an aim to establish a cause-effect relationship between various disorders with chronic airflow obstruction. Aims and Objectives: The aim of the study was to find out the prevalence of different respiratory diseases among patients diagnosed as cases of chronic airflow obstruction and to evaluate the clinical and demographic profile of patients to find out risk factors and their role in etiology of chronic obstructive airflow. Materials and Methods: We studied demographic details of the patients, smoking history, biomass exposure, and tubercular history. All the patients were clinically examined and were subjected to pulmonary function assessment. The diagnosis of the patients was made on the basis of clinical features and outcome of spirometry. COPD was graded depending on post-bronchodilator FEV1% predicted as (GOLD, 2022). Results: Among patients with chronic airway obstruction, the number of patients diagnosed as COPD was highest (68%) followed by bronchial asthma (19%) and bronchectasis (13%). Among COPD population, 48% were smokers and 20% were non-smokers. Age of patients with bronchial asthma was significantly lower than that of other groups. In the present study, proportion of males diagnosed as COPD (NS) was significantly lower (P&lt;0.001) as compared to other groups. Conclusion: The findings in the present study highlighted that different types of CAO can affect a wide variety of population groups and share a number of risk factors; however, some demographic and clinical factors help in understanding the specific risks and type of disorder. A Change in environmental conditions and lifestyle can change the spectrum of CAO disorders.

Abstract P383: Trends in Multimorbidity Among U.S. Adults With and Without Hypertension, 1999-2000 to 2017-2020

Background: Most adults with hypertension have other chronic conditions. As obesity and diabetes are increasing among US adults, the prevalence of multimorbidity may have increased among US adults with hypertension. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) to assess the trend in multimorbidity among US adults (ages ≥ 20 years) with (n = 24,646) and without (n = 24,189) hypertension from 1999-2000 through 2017-March 2020. Hypertension was defined as systolic blood pressure ≥130 mm Hg, diastolic blood pressure ≥80 mm Hg, or use of antihypertensive medication. Multimorbidity was defined as the co-occurrence of ≥ 3 chronic conditions, not including hypertension. Chronic conditions were selected based on a framework from a US Health and Human Services report and data available in NHANES and included dyslipidemia, coronary heart disease, stroke, heart failure, diabetes, obesity, liver fibrosis, chronic kidney disease, asthma, lung disease (chronic obstructive pulmonary disease, emphysema, or chronic bronchitis), arthritis, hepatitis-C, cancer, and depression. Results: From 1999-2000 to 2017-2020, the age-adjusted mean number of chronic conditions increased from 2.4 to 3.0 among US adults with hypertension and from 1.9 to 2.2 among US adults without hypertension (Figure, top panel). During this period, the age-adjusted prevalence of multimorbidity increased from 42% to 56% among US adults with hypertension and from 32% to 34% among US adults without hypertension (Figure, bottom panel). In 2017-2020, after age, race/ethnicity, and sex adjustment, the mean difference in the number of chronic conditions among US adults with versus without hypertension was 0.70 (95% CI: 0.56 - 0.84). Multimorbidity was 1.50 (95% CI: 1.34 - 1.68) times more common among US adults with versus without hypertension. Conclusion: Multimorbidity has increased among US adults, and its prevalence is higher among adults with versus without hypertension.

Further evidence of a type 2 inflammatory signature in chronic obstructive pulmonary disease or emphysema

BackgroundThere is increasing recognition of a type 2 (T2) inflammatory pattern in a subset of patients with chronic obstructive pulmonary disease (COPD) or emphysema, characterized by blood and airway eosinophilia. The mechanism underlying this is not well established. The recognition that CD125 (interleukin [IL]-5 receptor alpha) is expressed on some lung neutrophils and eosinophils in patients with asthma led us to speculate that CD125 may also be expressed on lung neutrophils in patients with COPD or emphysema. ObjectiveTo interrogate the expression of CD125 on lung neutrophils (and, when present, eosinophils) in patients with COPD/emphysema and identify a meaningful biomarker to predict neutrophil CD125 expression, including other markers of T2 inflammation. MethodsWe obtained blood and bronchoalveolar lavage (BAL) samples from patients with physician-diagnosed COPD/emphysema undergoing a clinically indicated bronchoscopy. ResultsWe found that a highly variable percentage of BAL neutrophils indeed expressed surface CD125 (0%-78.7%), with obvious clustering of CD125high and CD125low patterns. No correlation was found with clinical characteristics, blood or BAL eosinophil or neutrophil counts, BAL cytokines, or BAL eosinophil CD125 expression. ConclusionWe conclude that, similar to asthma, lung neutrophils from patients with COPD display interleukin-5 receptor alpha (CD125) on their surface. This along with the frequent presence of IL-4 and IL-5 in airway fluid further suggests a possible role of the T2 pathway in contributing to COPD severity. Trial RegistrationClinicalTrials.gov Identifier: NCT03984799

Associations in Cigarette Smoking and Health Conditions by Race/Ethnicity Among a Diverse Sample of Patients Receiving Treatment in a Federally Qualified Health Care Setting in Chicago.

To examine the association of cigarette use and smoking-related health conditions by race/ethnicity among diverse and low-income patients at a federally qualified health center (FQHC). Demographics, smoking status, health conditions, death, and health service use were extracted from electronic medical data for patients seen between September 1, 2018, and August 31, 2020 (n=51,670). Smoking categories included everyday/heavy smoker, someday/light smoker, former smoker, or never smoker. Current and former smoking rates were 20.1% and 15.2%, respectively. Males, Black, White, non-partnered, older, and Medicaid/Medicare patients were more likely to smoke. Compared with never smokers, former and heavy smokers had higher odds for all health conditions except respiratory failure, and light smokers had higher odds of asthma, chronic obstructive pulmonary disease, emphysema, and peripheral vascular disease. All smoking categories had more emergency department visits and hospitalizations than never smokers. The associations between smoking status and health conditions differed by race/ethnicity. White patients who smoked had a greater increase in odds of stroke and other cardiovascular diseases compared with Hispanic and Black patients. Black patients who smoked had a greater increase in odds of emphysema and respiratory failure compared with Hispanic patients. Black and Hispanic patients who smoked had a greater increase in emergency care use compared with White patients. Smoking was associated with disease burden and emergency care and differed by race/ethnicity. Resources to document smoking status and offer cessation services should be increased in FQHCs to promote health equity for lower income populations.

Treatment of chronic obstructive pulmonary disease and emphysema

We summarized the available data on therapeutic, surgical and endoscopic treatment of chronic obstructive pulmonary disease and emphysema that may be used like a bridge to lung transplantation. Treatment of chronic obstructive pulmonary disease and emphysema is expensive. Certain limitations in lung transplantation make to create new methods of treatment of severe emphysema. However, one should be ready for possible complications and carefully select patients for certain treatment to avoid false negative results. Reducing costs or developing cheaper treatments is important for the future and availability of care. The risks and complications associated with surgical treatment of emphysema can make endoscopic surgery preferable for these patients, and this undoubtedly requires further research.

An Overview of Acute Bronchitis and Upper Respiratory Tract Infections

A variety of viruses and bacteria can cause upper respiratory tract infections. These cause a variety of patient diseases including acute bronchitis, the common cold, influenza, and respiratory distress syndromes. Defining most of these patient diseases is difficult because the presentations connected with upper respiratory tract infections commonly overlap and their causes are similar. Upper respiratory tract infections are characterized as self-limiting irritation and oedema of the upper respiratory tract, along with coughing and no evidence of pneumonia, in a patient without a background of chronic obstructive pulmonary disease, emphysema, or chronic bronchitis or any other disease that would contribute to their symptomology. A typical upper respiratory tract infection includes an organism directly invading the membrane of the upper respiratory tract. Acute bronchitis is a medical term that refers to a self-limiting pulmonary inflammation which is marked by cough but not pneumonia. It is believed that acute bronchitis is an inflammatory reaction to infectious diseases of the bronchial epithelium.