Association of Airway Eosinophilia with Small Airway Dysfunction in Patients with Mild and at Risk for COPD.
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ABSTRACT:
SUBMITTER: Abdo M
PROVIDER: S-EPMC9212784 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
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Association of Airway Eosinophilia with Small Airway Dysfunction in Patients with Mild and at Risk for COPD.
Abdo Mustafa M Pedersen Frauke F Trinkmann Frederik F Herth Felix J F FJF Rabe Klaus F KF Kirsten Anne-Marie AM Watz Henrik H
International journal of chronic obstructive pulmonary disease 20220617
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Project description:The associations between airway eosinophilia, measured in sputum or peripheral blood, and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are inconsistent. We therefore aimed to determine the association between eosinophilia in bronchoalveolar lavage (BAL) fluid and AECOPD in a clinical cohort. We analyzed differential cell counts from baseline BAL fluid in participants in the DISARM clinical trial (Clinicaltrials.gov #NCT02833480) and classified participants by the presence or absence of BAL eosinophilia (>1% of total leukocytes). We determined the association between BAL eosinophilia and AECOPD over 1 year of follow-up using negative binomial regression and Cox proportional hazards test. N = 63 participants were randomized, and N = 57 had BAL differential cell counts available. Participants with BAL eosinophilia (N = 21) had a significantly increased rate of acute exacerbations (unadjusted incidence rate ratio (IRR) 2.0, p = 0.048; adjusted IRR 2.24, p = 0.04) and a trend toward greater probability of acute exacerbation (unadjusted hazard ratio (HR) 1.74, p = 0.13; adjusted HR 2.3, p = 0.1) in the year of follow-up compared to participants without BAL eosinophilia (N = 36). These associations were not observed for BAL neutrophilia (N = 41 participants), BAL lymphocytosis (N = 27 participants) or peripheral blood eosinophilia at various threshold definitions (2%, N = 37; 3%, N = 27; 4%, N = 16). BAL may therefore be a sensitive marker of eosinophilic inflammation in the distal lung and may be of benefit for risk stratification or biomarker-guided therapy in COPD.
| S-EPMC9220207 | biostudies-literature
Project description:IntroductionIn patients with chronic obstructive pulmonary disease (COPD), small airway dysfunction (SAD) is a key element and a functional consequence of the pathology. The exact role of SAD as a specific 'pharmacological target' represents an important research topic. Our objective was to ascertain whether an extra-fine formulation of beclomethasone dipropionate/formoterol fumarate (BDP/FF) NEXThaler® 100/6 μg b.i.d. could improve SAD and, consequently, the quality of life of COPD patients.MethodsWe enrolled COPD patients with severe airflow obstruction and at least one moderate exacerbation in the previous year, having started treatment with BDP/FF NEXThaler® for no more than 1 week. Patients underwent three visits: at the start of the treatment (V1), 6 weeks (V2), and 12 weeks later (V3). At each visit, we evaluated the fall in resistance from 5 to 20 Hz (R5-R20) and residual volume/total lung capacity (RV/TLC) ratio by impulse oscillometry, spirometry, and plethysmography. The COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) questionnaire were also administered to assess the disease's impact on quality of life.ResultsWe enrolled 43 COPD patients (mean age 69 years, FEV1 43%). R5-R20 significantly changed from baseline [0.23 ± 0.09 kPa/(l/s)] to V2 [0.16 ± 0.09 kPa/(l/s)] and V3 [0.16 ± 0.08 kPa/(l/s)] (p < 0.05). Clinical status was also significantly improved compared to baseline; in fact, CAT score changed from an average baseline value of 13-6 and 4 (V2 and V3, respectively) (p < 0.05). A correlation was found between CAT percentage change values and the corresponding ones of R5-R20 (r = - 0.329, p = 0.045) and RV/TLC (r = 0.354, p = 0.029).ConclusionsIn COPD patients, treatment with BDP/FF extra-fine formulation improved functional parameters related to small airway disease as well as the disease impact on health status.Trial registrationClinicalTrials.gov identifier, NCT04421742.
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Project description:Eosinophilia is a marker of corticosteroid responsiveness and risk of exacerbation in asthma; although it has been linked to submucosal matrix deposition, its relationship with other features of airway remodelling is less clear.The aim of this study was to investigate the relationship between airway eosinophilia and airway remodelling.Bronchial biopsies from subjects (n = 20 in each group) with mild steroid-naïve asthma, with either low (0-0.45 mm(-2)) ) or high submucosal eosinophil (23.43-46.28 mm(-2) ) counts and healthy controls were assessed for in vivo epithelial damage (using epidermal growth factor receptor staining), mucin expression, airway smooth muscle (ASM) hypertrophy and inflammatory cells within ASM.The proportion of in vivo damaged epithelium was significantly greater (P = 0.02) in the high-eosinophil (27.37%) than the low-eosinophil (4.14%) group. Mucin expression and goblet cell numbers were similar in the two eosinophil groups; however, MUC-2 expression was increased (P = 0.002) in the high-eosinophil group compared with controls. The proportion of submucosa occupied by ASM was higher in both asthma groups (P = 0.021 and P = 0.046) compared with controls. In the ASM, eosinophil and T-lymphocyte numbers were higher (P < 0.05) in the high-eosinophil group than both the low-eosinophil group and the controls, whereas the numbers of mast cells were increased in the high-eosinophil group (P = 0.01) compared with controls.Submucosal eosinophilia is a marker (and possibly a cause) of epithelial damage and is related to infiltration of ASM with eosinophils and T lymphocytes, but is unrelated to mucus metaplasia or smooth muscle hypertrophy.
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Project description:BackgroundRecent years, idiopathic pulmonary fibrosis (IPF) is thought to be a disease of alveoli as well as small airways. This study aimed to demonstrate the clinical feature, predictor, and prognosis of small airway dysfunction (SAD) in Chinese patients with IPF.MethodsWe enrolled 416 patients with IPF who hospitalized in Beijing Chao-Yang Hospital from 2000 to 2014 in this study, and the follow-up ended at December 2016. We collected demographic information, clinical examination results, spirometry results, HRCT results, and blood gas results during the study. Logistic regression analysis was used to identify the predictor for SAD. The COX proportional hazard model was used to analysis the prognosis effect of SAD.ResultsAmong all the participants, 165 (39.66%) patients had SAD. FEV1 (% predicted) and FEV3/FVC were significantly associated with SAD in patients with IPF. IPF patients with lower FEV1 (% predicted, OR 30.04, 95% CI 9.61-93.90) and FEV3/FVC (OR 77.76, 95% CI 15.44-391.63) had increased risk for SAD. Patients with SAD were associated with significantly increased risk of mortality in patients with IPF (HR 1.73, 95% CI 1.02-2.92), as well as in IPF patients without other pulmonary comorbidities (COPD, emphysema, and asthma).ConclusionsSpirometry-defined SAD was like 40% in patients with IPF. Lower FEV1 (% predicted) and FEV3/FVC were main predictors for SAD. IPF patients with SAD showed poorer prognosis.
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Project description:Biomass and functional small airway disease http://ow.ly/gXu730abpKu.
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Project description:In this cohort of 3084 patients hospitalized for acute exacerbation of COPD (AECOPD), we found that 17% had blood eosinophilia (≥300 cells/μL); the use of an alternative cut-off level (≥2%) demonstrated that 40% had elevated eosinophil count. Patients with eosinophilia had higher frequency of readmission for AECOPD during 1-year follow-up period. This is the first study to investigate the prevalence of eosinophilia among inpatients with AECOPD--the population with the highest morbidity and health-care utilization.
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Project description:BackgroundLittle attention has been paid to the pathophysiological changes in the natural history of chronic obstructive pulmonary disease (COPD). The destructions of the small airways were visualized on thoracic micro-computed tomography scan. We investigated whether small airway inflammation (SAI) was the risk for the development of COPD.MethodsA total of 1062 patients were enrolled and analyzed in the study. The partitioned airway inflammation was determined by exhaled nitric oxide (NO) of FnNO, FeNO50, FeNO200, and calculated CaNOdual. Both FeNO200 and CaNOdual were compared to detect the promising predictor for peripheral airway/alveolar inflammation in COPD. The correlation between exhaled NO and white cell classification was evaluated to determine the inflammation type during the development of COPD.ResultsExhaled NO levels (FnNO, FeNO50, FeNO200, and CaNOdual) were the highest in the COPD group compared with all other groups. Furthermore, compared with controls, exhaled NO levels (FeNO50, FeNO200, and CaNOdual) were also significantly higher in the emphysema, chronic bronchitis, and smoking groups. FeNO200 was found to be a promising predictor for peripheral airway/alveolar inflammation (area under the curve [AUC] of the receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.841) compared with CaNOdual (AUC ROC = 0.707) in COPD. FeNO200 was the main risk factor (adjusted odds ratio, 2.191; 95% CI, 1.797-2.671; p = 0.002) for the development of COPD. The blood eosinophil and basophil levels were correlated with FeNO50 and FeNO200.ConclusionThe complete airway inflammations were shown in COPD, whereas SAI was the main risk factor for the development of COPD, which might relate to eosinophil and basophil levels.
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Project description:BackgroundMany asthmatic patients exhibit sputum eosinophilia associated with exacerbations. Benralizumab targets eosinophils by binding IL-5 receptor α, inducing apoptosis through antibody-dependent cell-mediated cytotoxicity.ObjectivesWe sought to evaluate the safety of benralizumab in adults with eosinophilic asthma and its effects on eosinophil counts in airway mucosal/submucosal biopsy specimens, sputum, bone marrow, and peripheral blood.MethodsIn this multicenter, double-blind, placebo-controlled phase I study, 13 subjects were randomized to single-dose intravenous placebo or 1 mg/kg benralizumab (day 0; cohort 1), and 14 subjects were randomized to 3 monthly subcutaneous doses of placebo or 100 or 200 mg of benralizumab (days 0, 28, and 56; cohort 2). Cohorts 1 and 2 were consecutive.ResultsThe incidence of adverse events was similar between groups. No serious adverse events related to benralizumab occurred. In cohort 1 intravenous benralizumab produced a median decrease from baseline of 61.9% in airway mucosal eosinophil counts (day 28; placebo: +19.6%; P = .28), as well as an 18.7% decrease (day 21) in sputum and a 100% decrease (day 28) in blood counts. Eosinophils were not detectable in bone marrow of benralizumab-treated subjects (day 28, n = 4). In cohort 2 subcutaneous benralizumab demonstrated a combined (100 + 200 mg) median reduction of 95.8% in airway eosinophil counts (day 84; placebo, 46.7%; P = .06), as well as an 89.9% decrease (day 28) in sputum and a 100% decrease (day 84) in blood counts.ConclusionSingle-dose intravenous and multiple-dose subcutaneous benralizumab reduced eosinophil counts in airway mucosa/submucosa and sputum and suppressed eosinophil counts in bone marrow and peripheral blood. The safety profile supports further development. Additional studies are needed to assess the clinical benefit in asthmatic patients.
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Project description:BackgroundAging has been evidenced to bring about some structural and functional lung changes, especially in COPD. However, whether aging affects SAD, a possible precursor of COPD, has not been well characterized.ObjectiveWe aimed to comprehensively assess the relationship between aging and SAD from computed tomography, impulse oscillometry, and spirometry perspectives in Chinese.MethodsWe included 1859 participants from ECOPD, and used a linear-by-linear association test for evaluating the prevalence of SAD across various age subgroups, and multivariate regression models for determining the impact of age on the risk and severity of SAD. We then repeated the analyses in these subjects stratified by airflow limitation.ResultsThe prevalence of SAD increases over aging regardless of definitional methods. After adjustment for other confounding factors, per 10-yrs increase in age was significantly associated with the risk of CT-defined SAD (OR 2.57, 95% CI 2.13 to 3.10) and the increase in the severity of air trapping (β 2.09, 95% CI - 0.06 to 4.25 for LAA-856), airway reactance (β - 0.02, 95% CI - 0.04 to - 0.01 for X5; β 0.30, 95% CI 0.13 to 0.47 for AX; β 1.75, 95% CI 0.85 to 2.66 for Fres), as well as the decrease in expiratory flow rates (β - 3.95, 95% CI - 6.19 to - 1.71 for MMEF%predicted; β - 5.42, 95% CI - 7.88 to - 2.95 for FEF50%predicted) for SAD. All these associations were generally maintained in SAD defined by IOS or spirometry. After stratification of airflow limitation, we further found that the effect of age on LAA-856 was the most significant among almost all subgroups.ConclusionsAging is significantly associated with the prevalence, increased risk, as well as worse severity of SAD. CT may be a more optimal measure to assess aging-related SAD. The molecular mechanisms for the role of aging in SAD need to be explored in the future. Trial registration Chinese Clinical Trial Registry ChiCTR1900024643. Registered on 19 July 2019.
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Project description:The principal determining factors influencing the development of the airway disease and emphysema components of chronic obstructive pulmonary disease (COPD) have not been clearly defined. Genetic variability in COPD patients might influence the varying degrees of involvement of airway disease and emphysema. Therefore, we investigated the genetic association of single nucleotide polymorphisms (SNPs) in COPD candidate genes for association with emphysema severity and airway wall thickness phenotypes. Polymorphisms in six candidate genes were analysed in 379 subjects of the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study with quantitative chest computed tomography (CT) data. Genetic association with per cent of lung area below -950 HU (LAA950), airway wall thickness, and derived square root wall area (SRWA) of 10-mm internal perimeter airways were investigated. Three SNPs in EPHX1, five SNPs in SERPINE2 and one SNP in GSTP1 were significantly associated with LAA950. Five SNPs in TGFB1, two SNPs in EPHX1, one SNP in SERPINE2 and two SNPs in ADRB2 were associated with airway wall phenotypes in NETT. In conclusion, several COPD candidate genes showed evidence for association with airway wall thickness and emphysema severity using CT in a severe COPD population. Further investigation will be required to replicate these genetic associations for emphysema and airway wall phenotypes.
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