Severe Lung Function Impairment Research Articles

Race Adjustment of Pulmonary Function Tests in the Diagnosis and Management of COPD: A Scoping Review.

Increasing evidence suggests that the inclusion of self-identified race in clinical decision algorithms may perpetuate longstanding inequities. Until recently, most pulmonary function tests utilized separate reference equations that are race/ethnicity based. We assess the magnitude and scope of the available literature on the negative impact of race-based pulmonary function prediction equations on relevant outcomes in African Americans with COPD. We performed a scoping review utilizing an English language search on PubMed/Medline, Embase, Scopus, and Web of Science in September 2022 and updated it in December 2023. We searched for publications regarding the effect of race-specific vs race-neutral, race-free, or race-reversed lung function testing algorithms on the diagnosis of COPD and COPD-related physiologic and functional measures. Joanna Briggs Institute (JBI) guidelines were utilized for this scoping review. Eligibility criteria: The search was restricted to adults with COPD. We excluded publications on other lung disorders, non-English language publications, or studies that did not include African Americans. The search identified publications. Ultimately, six peer-reviewed publications and four conference abstracts were selected for this review. Removal of race from lung function prediction equations often had opposite effects in African Americans and Whites, specifically regarding the severity of lung function impairment. Symptoms and objective findings were better aligned when race-specific reference values were not used. Race-neutral prediction algorithms uniformly resulted in reclassifying severity in the African Americans studied. The limited literature does not support the use of race-based lung function prediction equations. However, this assertion does not provide guidance for every specific clinical situation. For African Americans with COPD, the use of race-based prediction equations appears to fall short in enhancing diagnostic accuracy, classifying severity of impairment, or predicting subsequent clinical events. We do not have information comparing race-neutral vs race-based algorithms on prediction of progression of COPD. We conclude that the elimination of race-based reference values potentially reduces underestimation of disease severity in African Americans with COPD.

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway.

Acute lung injury (ALI) is a severe pulmonary disease characterized by damage to the alveoli and pulmonary blood vessels, leading to severe impairment of lung function. Studies on the effect of capsaicin (8-methyl-N-geranyl-6-nonamide, CAP) on lipopolysaccharide (LPS)-induced ALI in bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B) are still limited. This study aimed to investigate the effect and specific mechanism by which CAP improves LPS-induced ALI. The present study investigated the effect of CAP and the potential underlying mechanisms in LPS-induced ALI in vitro and vivo via RNA sequencing, Western blotting (WB), quantitative real-time reverse transcription PCR (qRT‒PCR), enzyme-linked immunosorbent assay (ELISA), and transmission electron microscopy (TEM). The TRPV1 inhibitor AMG9810 and the AKT agonist SC79 were used to confirm the protective effect of the TRPV1/AKT axis against ALI. The autophagy agonist rapamycin (Rapa) and the autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin A1 (Baf-A1) were used to clarify the characteristics of LPS-induced autophagy. Our findings demonstrated that CAP effectively suppressed inflammation and autophagy in LPS-induced ALI, both in vivo and in vitro. This mechanism involves regulation by the TRPV1/AKT signaling pathway. By activating TRPV1, CAP reduces the expression of P-AKT, thereby exerting its anti-inflammatory and inhibitory effects on pro-death autophagy. Furthermore, prior administration of CAP provided substantial protection to mice against ALI induced by LPS, reduced the lung wet/dry ratio, decreased proinflammatory cytokine expression, and downregulated LC3 expression. Taken together, our results indicate that CAP protects against LPS-induced ALI by inhibiting inflammatory responses and autophagic death through the TRPV1/AKT signaling pathway, presenting a novel strategy for ALI therapy.

Impact of lag time on lung function impairment in pulmonary tuberculosis sequelae patients – A cross-sectional study

Background: Treatment completed pulmonary tuberculosis (PTB) patients are often left with permanent pulmonary function impairment. Lag time remains a major factor in determining the severity of the sequelae. Aims and Objectives: This study aims to assess the impact of lag time on PTB sequelae. Materials and Methods: A cross-sectional study was conducted during July 2019–December 2020. A total of 85 patients presenting with clinicoradiological features of PTB sequelae were recruited for the study and spirometry and diffusion capacity of lungs (DLCO) were done. They were divided into study groups based on lag time. The lag time (in days) was considered as primary explanatory variable. One-way ANOVA and Chi-square tests were used. coGuide V.1.0 was used for statistical analysis. Results: The mean lag time was 52.94 days in the study population. The mean duration of after treatment was 15.45 years in the study population. There was a statistically significant difference across study groups (classified based on the lag time) in lung function such as FVC%, FEV1, FEVI/FVC, MEF, DLCO, and duration of after treatment (P<0.05). Conclusion: The lag time from the development of symptom to the diagnosis of the disease has a significant impact on lung function impairment in PTB sequelae patients since the increase in lag time increases the severity of lung function impairment. Early identification and treatment may help in reducing the progression of lung function impairment.

Mechanisms of lung damage in tuberculosis: implications for chronic obstructive pulmonary disease.

Pulmonary tuberculosis is increasingly recognized as a risk factor for COPD. Severe lung function impairment has been reported in post-TB patients. Despite increasing evidence to support the association between TB and COPD, only a few studies describe the immunological basis of COPD among TB patients following successful treatment completion. In this review, we draw on well-elaborated Mycobacterium tuberculosis-induced immune mechanisms in the lungs to highlight shared mechanisms for COPD pathogenesis in the setting of tuberculosis disease. We further examine how such mechanisms could be exploited to guide COPD therapeutics.

Respiratory muscle metabolic activity on PET/CT correlates with obstructive ventilatory defect severity and prognosis in patients undergoing lung cancer surgery.

Respiratory muscle activity is increased in patients with chronic respiratory disease. 18 F-FDG-PET/CT can assess respiratory muscle activity. We hypothesized that respiratory muscles metabolism was correlated to lung function impairment and was associated to prognosis in patients undergoing lung cancer surgery based on the research question whether respiratory muscle metabolism quantitatively correlates with the severity of lung function impairment in patients? Does respiratory muscle hypermetabolism have prognostic value? Patients undergoing 18 F-FDG-PET/CT and pulmonary function tests prior to lung cancer surgery were identified. Maximum Standardized Uptake Value (SUVm) were measured in each respiratory muscle group (sternocleidomastoid, scalene, intercostal, diaphragm), normalized against deltoid SUVm. Respiratory muscle hypermetabolism was defined as SUVm >90th centile in any respiratory muscle group. Clinical outcomes were collected from a prospective cohort. One hundred fifty-six patients were included, mostly male [110 (71%)], 53 (34%) with previous diagnosis of COPD. Respiratory muscle SUVm were: scalene: 1.84 [1.51-2.25], sternocleidomastoid 1.64 [1.34-1.95], intercostal 1.01 [0.84-1.16], diaphragm 1.79 [1.41-2.27]. Tracer uptake was inversely correlated to FEV1 for the scalene (r=-0.29, p < 0.001) and SCM (r=-0.17, p=0.03) respiratory muscle groups and positively correlated to TLC for the scalene (r=0.17, p=0.04). Respiratory muscle hypermetabolism was found in 45 patients (28.8%), who had a lower VO2 max (15.4 [14.2-17.5] vs. 17.2 mL/kg/min [15.2-21.1], p=0.07) and poorer overall survival when adjusting to FEV1% (p < 0.01). Our findings show respiratory muscle hypermetabolism is associated with lung function impairment and has prognostic significance. 18 F-FDG/PET-CT should be considered as a tool for assessing respiratory muscle activity and to identify high-risk patients.

Severity of Lung Function Impairment Drives Transcriptional Phenotypes of COPD and Relates to Immune and Metabolic Processes.

This study sought to characterize transcriptional phenotypes of COPD through unsupervised clustering of sputum gene expression profiles, and further investigate mechanisms underlying the characteristics of these clusters. Induced sputum samples were collected from patients with stable COPD (n = 72) and healthy controls (n = 15). Induced sputum was collected for inflammatory cell counts, and RNA extracted. Transcriptional profiles were generated (Illumina Humanref-8 V2) and analyzed by GeneSpring GX14.9.1. Unsupervised hierarchical clustering and differential gene expression analysis were performed, and gene alterations validated in the ECLIPSE dataset (GSE22148). We identified 2 main clusters (Cluster 1 [n = 35] and Cluster 2 [n = 37]), which further divided into 4 sub-clusters (Sub-clusters 1.1 [n = 14], 1.2 [n = 21], 2.1 [n = 20] and 2.2 [n = 17]). Compared with Cluster 1, Cluster 2 was associated with significantly lower lung function (p = 0.014), more severe disease (p = 0.009) and breathlessness (p = 0.035), and increased sputum neutrophils (p = 0.031). Sub-cluster 1.1 had significantly higher proportion of people with comorbid cardiovascular disease compared to the other 3 sub-clusters (92.5% vs 57.1%, 50% and 52.9%, p < 0.013). Through supervised analysis we determined that degree of airflow limitation (GOLD stage) was the predominant factor driving gene expression differences in our transcriptional clusters. There were 452 genes (adjusted p < 0.05 and ≥2 fold) altered in GOLD stage 3 and 4 versus 1 and 2, of which 281 (62%) were also found to be significantly expressed between these GOLD stages in the ECLIPSE data set (GSE22148). Differentially expressed genes were largely downregulated in GOLD stages 3 and 4 and connected in 5 networks relating to lipoprotein and cholesterol metabolism; metabolic processes in oxidation/reduction and mitochondrial function; antigen processing and presentation; regulation of complement activation and innate immune responses; and immune and metabolic processes. Severity of lung function drives 2 distinct transcriptional phenotypes of COPD and relates to immune and metabolic processes.

Lung Stereotactic Body Radiation Therapy in a Patient with Severe Lung Function Impairment Allowed by Gallium-68 Perfusion PET/CT Imaging: A Case Report

Lung stereotactic body radiotherapy (SBRT) is increasingly proposed, especially for patients with poor lung function who are not eligible for surgery. However, radiation-induced lung injury remains a significant treatment-related adverse event in these patients. Moreover, for patients with very severe COPD, we have very few data about the safety of SBRT for lung cancer. We present the case of a female with very severe chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in one second (FEV1) of 0.23 L (11%), for whom a localized lung tumor was found. Lung SBRT was the only possible treatment. It was allowed and safely performed, based on a pre-therapeutic evaluation of regional lung function with Gallium-68 perfusion lung positron emission tomography combined with computed tomography (PET/CT). This is the first case report to highlight the potential use of a Gallium-68 perfusion PET/CT in order to safely select patients with very severe COPD who can benefit from SBRT.

Inducible Costimulator-C-X-C Motif Chemokine Receptor 3 Signaling is Involved in Chronic Obstructive Pulmonary Disease Pathogenesis.

BackgroundThe role of inducible costimulator (ICOS) signaling in chronic obstructive pulmonary disease (COPD) has not been fully elucidated.MethodsWe compared the percentages of ICOS+ T cells and ICOS+ regulatory T (Treg) cells in CD4+ T cells and CD4+CD25+FOXP3+ Tregs, respectively, in the peripheral blood of smokers with or without COPD to those in healthy controls. We further characterized their phenotypes using flow cytometry. To investigate the influence of ICOS signaling on C-X-C motif chemokine receptor 3 (CXCR3) expression in COPD, we evaluated the expression levels of ICOS and CXCR3 in vivo and in vitro.ResultsICOS expression was elevated on peripheral CD4+ T cells and CD4+ Tregs of COPD patients, which positively correlated with the severity of lung function impairment in patients with stable COPD (SCOPD), but not in patients with acute exacerbation of COPD (AECOPD). ICOS+CD4+ Tregs in patients with SCOPD expressed higher levels of coinhibitors, programmed cell death protein 1 (PD-1) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT), than ICOS−CD4+ Tregs, whereas ICOS+CD4+ T cells mostly exhibited a central memory (CD45RA−CCR7+) or effector memory (CD45RA−CCR7−) phenotype, ensuring their superior potential to respond potently and quickly to pathogen invasion. Furthermore, increased percentages of CXCR3+CD4+ T cells and CXCR3+CD4+ Tregs were observed in the peripheral blood of patients with SCOPD, and the expression level of CXCR3 was higher in ICOS+CD4+ T cells than in ICOS−CD4+ T cells. The percentage of CXCR3+CD4+ T cells was even higher in the bronchoalveolar lavage fluid than in matched peripheral blood in SCOPD group. Lastly, in vitro experiments showed that ICOS induced CXCR3 expression on CD4+ T cells.ConclusionsICOS signaling is upregulated in COPD, which induces CXCR3 expression. This may contribute to increased numbers of CXCR3+ Th1 cells in the lungs of patients with COPD, causing inflammation and tissue damage.

Short-Term Oxygen Therapy Outcomes in COPD

RationaleShort-term oxygen therapy (STOT) is often prescribed to allow patients with chronic obstructive pulmonary disease (COPD) to be discharged safely from hospital following an acute illness. This practice is widely accepted without being based on evidence.PurposeOur objective was to describe the characteristics and outcomes of patients with COPD who received STOT.Patients and MethodsThe study was a secondary analysis of the INOX trial, a 4-year randomised trial of nocturnal oxygen in COPD. The trial indicated that nocturnal oxygen has no significant effect on survival or progression to LTOT, allowing our merging of patients who received nocturnal oxygen and those who received placebo into a single cohort to study the predictors and outcomes of STOT regardless of the treatment received during the trial.ResultsAmong the 243 participants in the trial, 60 required STOT on at least one occasion during follow-up. Patients requiring STOT had more severe dyspnoea and lung function impairment, and lower PaO2 at baseline than those who did not. STOT was associated with subsequent LTOT requirement (hazard ratio [HR]: 4.59; 95% confidence interval [CI]: 2.98–7.07) and mortality (HR: 1.93; 95% CI: 1.15–3.24). The association between STOT and mortality was confounded by age, disease severity and comorbidities. Periods of STOT of more than one month and/or repeated prescriptions of STOT increased the probability of progression to LTOT (OR: 5.07; 95% CI: 1.48–18.8).ConclusionFollowing an acute respiratory illness in COPD, persistent hypoxaemia requiring STOT is a marker of disease progression towards the requirement for LTOT.

Impaired lung function and mortality in Eastern Europe: results from multi-centre cohort study

BackgroundThe association between impaired lung function and mortality has been well documented in the general population of Western European countries. We assessed the risk of death associated with reduced spirometry indices among people from four Central and Eastern European countries.MethodsThis prospective population-based cohort includes men and women aged 45–69 years, residents in urban settlements in Czech Republic, Poland, Russia and Lithuania, randomly selected from population registers. The baseline survey in 2002–2005 included 36,106 persons of whom 24,993 met the inclusion criteria. Cox proportional hazards models were used to estimate the hazard ratios of mortality over 11–16 years of follow-up for mild, moderate, moderate-severe and very severe lung function impairment categories.ResultsAfter adjusting for covariates, mild (hazard ratio (HR): 1.25; 95% CI 1.15‒1.37) to severe (HR: 3.35; 95% CI 2.62‒4.27) reduction in FEV1 was associated with an increased risk of death according to degree of lung impairment, compared to people with normal lung function. The association was only slightly attenuated but remained significant after exclusion of smokers and participants with previous history of respiratory diseases. The HRs varied between countries but not statistically significant; the highest excess risk among persons with more severe impairment was seen in Poland (HR: 4.28, 95% CI 2.14‒8.56) and Lithuania (HR: 4.07, 95% CI 2.21‒7.50).ConclusionsReduced FEV1 is an independent predictor of all-cause mortality, with risk increasing with the degree of lung function impairment and some country-specific variation between the cohorts.

Prevalence and severity of abnormal lung function among US former coal miners with and without radiographic coal workers’ pneumoconiosis

ObjectivesExamination of lung function abnormalities among coal miners has historically focused on actively working miners. This likely underestimates the true burden of chronic respiratory disease. The objective of this study...

Predicting Pulmonary Function From the Analysis of Voice: A Machine Learning Approach.

IntroductionTo self-monitor asthma symptoms, existing methods (e.g. peak flow metre, smart spirometer) require special equipment and are not always used by the patients. Voice recording has the potential to generate surrogate measures of lung function and this study aims to apply machine learning approaches to predict lung function and severity of abnormal lung function from recorded voice for asthma patients.MethodsA threshold-based mechanism was designed to separate speech and breathing from 323 recordings. Features extracted from these were combined with biological factors to predict lung function. Three predictive models were developed using Random Forest (RF), Support Vector Machine (SVM), and linear regression algorithms: (a) regression models to predict lung function, (b) multi-class classification models to predict severity of lung function abnormality, and (c) binary classification models to predict lung function abnormality. Training and test samples were separated (70%:30%, using balanced portioning), features were normalised, 10-fold cross-validation was used and model performances were evaluated on the test samples.ResultsThe RF-based regression model performed better with the lowest root mean square error of 10·86. To predict severity of lung function impairment, the SVM-based model performed best in multi-class classification (accuracy = 73.20%), whereas the RF-based model performed best in binary classification models for predicting abnormal lung function (accuracy = 85%).ConclusionOur machine learning approaches can predict lung function, from recorded voice files, better than published approaches. This technique could be used to develop future telehealth solutions including smartphone-based applications which have potential to aid decision making and self-monitoring in asthma.

Successful Pregnancy in a Cystic Fibrosis Patient with a Severe Impairment of Lung Function Receiving Elexacaftor-Tezacaftor-Ivacaftor

Successful Pregnancy in a Cystic Fibrosis Patient with a Severe Impairment of Lung Function Receiving Elexacaftor-Tezacaftor-Ivacaftor

Anxiety and Depression in Patients with Chronic Obstructive Pulmonary Disease in China: Results from the China Pulmonary Health [CPH] Study.

PurposeAnxiety and depression are often underdiagnosed and affect the prognosis of patients with chronic obstructive pulmonary disease (COPD). We analyzed data from the China Pulmonary Health (CPH) study to assess the prevalence of anxiety and depression in COPD patients and their relationship with disease severity.Patients and MethodsA total of 57,779 subjects aged 20 years or older were recruited in the CPH study. All participants were assessed using a standard questionnaire and underwent pulmonary function tests before and after the use of a bronchodilator in local health centers. The Hospital Anxiety and Depression Scale (HADS) questionnaire with a cutoff score of 8 was used to define anxiety and depression. The prevalence of anxiety and depression in patients of COPD were investigated. Multivariate logistic regression was used to investigate the effects of COPD and lung function on anxiety and depression.ResultsA total of 49,053 participants (20,661 men and 28,392 women) completed the questionnaire with reliable post-bronchodilator pulmonary function test results and were included in the final analysis, of which 4686 (9.55%) were diagnosed with COPD. Of the patients with COPD, 10.79% had anxiety, 13.65% had depression, and 7.08% had anxiety and depression concomitantly. In the multivariate logistic regression analysis, COPD was not significantly associated with anxiety, depression, or both. After adjusting for confounders in model 1, patients in the GOLD III–IV group had a significantly higher risk of anxiety, depression, and their coincidence. After further adjusting for respiratory symptoms in model 2, lung function impairment in the GOLD III–IV group was only significantly associated with a higher risk of depression or at least one of anxiety and depression.ConclusionAnxiety and depression are prevalent in patients with COPD in China. More severe lung function impairment is significantly associated with a higher risk of depression.

Impact of electronic cigarette ever use on lung function in adults aged 45–85: a cross-sectional analysis from the Canadian Longitudinal Study on Aging

ObjectiveTo describe the sociodemographic characteristics associated with e-cigarette ever use and to examine the impact of e-cigarette ever use on lung function impairment in an ageing population.DesignA cross-sectional analysis of...

Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge

Although plenty of data exist regarding clinical manifestations, course, case fatality rate, and risk factors associated with mortality in severe coronavirus disease 2019 (COVID-19), long-term respiratory and functional sequelae in survivors of COVID-19 are unknown. To evaluate the prevalence of lung function anomalies, exercise function impairment, and psychological sequelae among patients hospitalized for COVID-19, 4 months after discharge. This prospective cohort study at an academic hospital in Northern Italy was conducted among a consecutive series of patients aged 18 years and older (or their caregivers) who had received a confirmed diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection severe enough to require hospital admission from March 1 to June 29, 2020. SARS-CoV-2 infection was confirmed via reverse transcription-polymerase chain reaction testing, bronchial swab, serological testing, or suggestive computed tomography results. Severe COVID-19 requiring hospitalization. The primary outcome of the study was to describe the proportion of patients with a diffusing lung capacity for carbon monoxide (Dlco) less than 80% of expected value. Secondary outcomes included proportion of patients with severe lung function impairment (defined as Dlco <60% expected value); proportion of patients with posttraumatic stress symptoms (measured using the Impact of Event Scale-Revised total score); proportion of patients with functional impairment (assessed using the Short Physical Performance Battery [SPPB] score and 2-minute walking test); and identification of factors associated with Dlco reduction and psychological or functional sequelae. Among 767 patients hospitalized for severe COVID-19, 494 (64.4%) refused to participate, and 35 (4.6%) died during follow-up. A total of 238 patients (31.0%) (median [interquartile range] age, 61 [50-71] years; 142 [59.7%] men; median [interquartile range] comorbidities, 2 [1-3]) consented to participate to the study. Of these, 219 patients were able to complete both pulmonary function tests and Dlco measurement. Dlco was reduced to less than 80% of the estimated value in 113 patients (51.6%) and less than 60% in 34 patients (15.5%). The SPPB score was suggested limited mobility (score <11) in 53 patients (22.3%). Patients with SPPB scores within reference range underwent a 2-minute walk test, which was outside reference ranges of expected performance for age and sex in 75 patients (40.5%); thus, a total of 128 patients (53.8%) had functional impairment. Posttraumatic stress symptoms were reported in a total of 41 patients (17.2%). These findings suggest that at 4 months after discharge, respiratory, physical, and psychological sequelae were common among patients who had been hospitalized for COVID-19.

Association Between Routine Blood Biomarkers and Clinical Phenotypes and Exacerbations in Chronic Obstructive Pulmonary Disease.

IntroductionChronic obstructive pulmonary disease (COPD) is associated with increased lung and systemic inflammation. We aimed to identify associations between easy-to-obtain blood biomarkers and the frequency and severity of exacerbations.MethodsCross-sectional, multicentre study performed in four centres in Spain, Italy, Bulgaria, and Slovenia. Blood samples were obtained for blood cell count, C-reactive protein (CRP), alpha-1 antitrypsin (AAT) and fibrinogen analysis. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and eosinophil/basophil ratio (EBR) were calculated. Firstly, patients were divided into clinical phenotypes according to the Spanish guidelines of COPD, and secondly, patients were classified into 2 groups: non-exacerbators (≤1 ambulatory exacerbation in the previous year) and exacerbators (≥2 ambulatory exacerbations or 1 hospitalisation in the previous year). A multivariate stepwise logistic regression model was performed to identify laboratory parameters associated with exacerbators.ResultsA total of 355 patients with a mean age 66 years (SD=8.9) were included, and 64% were male. The mean FEV1% (forced expiratory volume in the first second) was 55% (SD=20%), and the mean COPD Assessment Test (CAT) score was 15.6 (SD=7.9). One hundred ninety-six (55.2%) patients were classified in the non-exacerbator group, and 159 (44.8%) were exacerbators. Patients in the exacerbators group presented lower haemoglobin levels (p=0.019) and ERB (p= 0.023) but higher CRP levels (p=0.001). In the multivariate analysis, females, higher levels of CRP, lower FEV1% and low EBR were independently related to exacerbators.ConclusionFemale sex, having a more severe impairment of lung function, higher CRP levels and a lower EBR are associated with an exacerbator phenotype in COPD.

Effect of different classes of obesity on the pulmonary functions among adult Egyptians: a cross-sectional study

IntroductionObesity is a common chronic disease, representing a major health hazard. Obesity has several delirious effects on the respiratory functions.Aim of the studyTo study the effect of obesity on pulmonary functions among our local population of obese adults and to assess the correlation between the severity of lung function impairment and the degree of obesity.Patients and methodsHealthy nonsmoker adult patients were recruited in our cross-sectional study. After full medical evaluation, measurement of height and weight, and calculation of BMI, patients underwent spirometry tests with measurement of forced expiratory volume in first second (FEV1), forced vital capacity (FVC), forced mid-expiratory flow, and peak expiratory flow rate. Then, they were classified according to their BMI into five groups.ResultsThe study included 293 patients divided into five groups according to their BMI. Significant statistical differences were noticed between nonobese patients and patients with classes II and III obesity regarding FVC, FEV1, and forced mid-expiratory flow, but no differences regarding peak expiratory flow rate and FEV1/FVC ratio. Overall, 28.9% of the total obese patients presented with restrictive pattern of spirometry, 2.8% with obstructive, and 2.4% with mixed patterns.ConclusionObesity of especially marked degrees with BMI of more than 35 kg/m2 negatively affects the spirometric parameters. Restrictive pattern was the commonest abnormality observed in the spirometry of obese patients.

BASELINE PERCENT PREDICTED FEV1 DOES NOT PREDICT A RESPONSE TO MEPOLIZUMAB IN PATIENTS WITH SEVERE EOSINOPHILIC ASTHMA: META-ANALYSIS FROM TWO PHASE 3 TRIALS

SESSION TITLE: Monday Electronic Posters 4 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: The MENSA (NCT01691521) and MUSCA (NCT02281318) trials showed that mepolizumab consistently reduced annualized asthma exacerbation rates in patients with severe eosinophilic asthma. There are several risk factors for exacerbations, including decreased pulmonary function. The effect of the approved dose of mepolizumab, 100 mg subcutaneous (SC), on exacerbations according to a patient’s baseline % predicted FEV1 has not been examined. METHODS: This post-hoc subgroup analysis investigated the annual rate of clinically significant exacerbations (requiring administration of systemic glucocorticoids for ≥3 days or an emergency department visit/hospitalization) in patients receiving mepolizumab or placebo according to baseline % predicted FEV1 at screening in 3 categories (≤ 60, > 60 – ≤ 80 and > 80%). Exacerbation rates in the meta-analysis were measured at week 32 for MENSA and week 24 for MUSCA. Analyses were performed using negative binomial regression and treatment differences combined across studies using fixed-effects inverse-variance weighted meta-analysis. RESULTS: Of the 936 patients, 489 (52%), 354 (38%) and 93 (10%) were identified as having a ≤ 60, > 60 – ≤ 80 and > 80% predicted FEV1 at screening, respectively. Clinically relevant reductions in exacerbation rates were observed in the meta-analysis with 100 mg SC mepolizumab versus placebo, in patients from all categories of obstruction (rate ratio [mepolizumab/placebo]: ≤ 60% predicted FEV1 is 0.51[95% confidence interval [CI]: 0.39,0.66]; > 60 - ≤ 80% predicted FEV1 is 0.39[95% CI: 0.26,0.58]; > 80% predicted FEV1 is 0.37[95% CI: 0.19,0.73]). There was a numerical trend of an increase in the proportion of patients not having a clinically significant exacerbation with mepolizumab treatment, compared to placebo, with increasing baseline lung function (odds ratio [mepolizumab v placebo]: ≤ 60% predicted FEV1 is 2.67[95% CI: 1.79,3.98]; > 60 - ≤ 80% predicted FEV1 is 3.18[95% CI: 1.92,5.28]; > 80% predicted FEV1 is 4.90[95% CI: 1.54,15.62]). CONCLUSIONS: Mepolizumab produced clinically relevant reductions in the exacerbation rate versus placebo in patients with severe eosinophilic asthma irrespective of baseline % predicted FEV1. This suggests that baseline airway obstruction is not a factor that predicts a response to mepolizumab although patients with less severe lung function impairment may experience increasing relative benefit. This is aligned with DREAM that showed in a covariate modelling analysis, baseline % predicted FEV1 did not predict a response to intravenous mepolizumab. CLINICAL IMPLICATIONS: This abstract provides health care professionals with clinically relevant information on the efficacy of mepolizumab in severe eosinophilic asthma patients stratified by severity of airflow obstruction. DISCLOSURES: Employee relationship with GSK Please note: >$100000 Added 03/15/2019 by Frank Albers, source=Web Response, value=Salary Employee relationship with GSK Please note: >$100000 Added 03/18/2019 by Eric Bradford, source=Web Response, value=Salary Employee relationship with GSK Please note: >$100000 Added 03/18/2019 by Eric Bradford, source=Web Response, value=Ownership interest Employee relationship with GSK Please note: $5001 - $20000 Added 03/13/2019 by Stephen Mallett, source=Web Response, value=Shares Speaker/Speaker's Bureau relationship with Novartis Please note: $1001 - $5000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Teva Please note: $1001 - $5000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Advisory Committee Member relationship with Astra Zeneca Please note: $5001 - $20000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Advisory Committee Member relationship with Glaxo SmithKline Please note: $1001 - $5000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Scientific Medical Advisor relationship with Boehringer Ingelheim Please note: $1001 - $5000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Consultant relationship with Vectura Please note: $5001 - $20000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Advisory Committee Member relationship with Sanofi Please note: $1001 - $5000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Employee relationship with GlaxoSmithKline Please note: >$100000 Added 03/07/2019 by Jared Silver, source=Web Response, value=Salary Employee relationship with GlaxoSmithKline (estimated stock ownership by time of Chest) Please note: $20001 - $100000 Added 03/07/2019 by Jared Silver, source=Web Response, value=stock Employee relationship with GSK Please note: >$100000 Added 03/07/2019 by Steven Smith, source=Web Response, value=Salary Employee relationship with GSK Please note: $5001 - $20000 Added 03/07/2019 by Steven Smith, source=Web Response, value=Stock Employee relationship with GlaxoSmithKline Please note: >$100000 Added 03/18/2019 by Steven Yancey, source=Web Response, value=Salary

Economic impact of delaying initiation with multiple-inhaler maintenance triple therapy in Spanish patients with chronic obstructive pulmonary disease.

PurposeGuidelines recommend the use of triple therapy with an inhaled corticosteroid (ICS), a long-acting β2 agonist (LABA) and a long-acting muscarinic antagonist (LAMA) to reduce the risk of future exacerbations in symptomatic COPD patients with a history of exacerbations. This study aimed to estimate COPD-related healthcare resource use and costs, and subsequent exacerbation rates, for patients initiating multiple-inhaler triple therapy (MITT) early (≤30 days) versus late (31–180 days) following an exacerbation, in a real-world clinical setting.Patients and methodsThis was an observational, longitudinal, retrospective study using electronic medical records from the Spanish database of the Red de Investigación en Servicios Sanitarios Foundation. Patients ≥40 years old with a confirmed COPD diagnosis who were newly prescribed MITT up to 180 days after an exacerbation between January 2013 and December 2015 were included. Patients were followed from the date of MITT initiation for up to 12 months to assess COPD-related health care resource use (routine and emergency visits, hospitalizations, pharmacologic treatment), exacerbation rate, and costs (€2017); these endpoints were compared between early versus late groups.ResultsThe study included 1280 patients who met selection criteria: mean age 73 years, 78% male, and 41% had severe/very severe lung function impairment. The proportion of patients initiating MITT early versus late was 61.6% versus 38.4%, respectively. There were no statistically significant differences in baseline characteristics between groups. During follow-up, health care resource consumption was lower in the early versus late group, especially primary care and ED visits, leading to lower total costs (€1861 versus €1935; P<0.05). In the follow-up period, 28.0% of the patients in the early group experienced ≥1 exacerbation versus 36.4% in the late group (P=0.002), with an exacerbation rate of 0.5 versus 0.6 per person per year (P=0.022), respectively.ConclusionInitiating MITT early (≤30 days after an exacerbation) may reduce health care costs and exacerbation rate compared with late MITT initiation.