Endothelial dysfunction and persistent inflammation in severe post-COVID-19 patients: implications for gas exchange.

BACKGROUND: Understanding the enduring respiratory consequences of severe COVID-19 is crucial for comprehensive patient care. This study aims to evaluate the impact of post-COVID conditions on respiratory sequelae of severe acute respiratory distress syndrome (ARDS). METHODS: We examined 88 survivors of COVID-19-associated severe ARDS six months post-intensive care unit (ICU) discharge. Assessments included clinical and functional evaluation as well as plasma biomarkers of endothelial dysfunction, inflammation, and viral response. Additionally, an in vitro model using human umbilical vein endothelial cells (HUVECs) explored the direct impact of post-COVID plasma on endothelial function. RESULTS: Post-COVID patients with impaired gas exchange demonstrated persistent endothelial inflammation marked by elevated ICAM-1, IL-8, CCL-2, and ET-1 plasma levels. Concurrently, systemic inflammation, evidenced by NLRP3 overexpression and elevated levels of IL-6, sCD40-L, and C-reactive protein, was associated with endothelial dysfunction biomarkers and increased in post-COVID patients with impaired gas exchange. T-cell activation, reflected in CD69 expression, and persistently elevated levels of interferon-ß (IFN-ß) further contributed to sustained inflammation. The in vitro model confirmed that patient plasma, with altered levels of sCD40-L and IFN-ß proteins, has the capacity to alter endothelial function. CONCLUSIONS: Six months post-ICU discharge, survivors of COVID-19-associated ARDS exhibited sustained elevation in endothelial dysfunction biomarkers, correlating with the severity of impaired gas exchange. NLRP3 inflammasome activity and persistent T-cell activation indicate on going inflammation contributing to persistent endothelial dysfunction, potentially intensified by sustained viral immune response.

Continuous Positive Airway Pressure Effect on Progression of Retinal Disease in Patients with Sleep Apnea and Nonproliferative Diabetic Retinopathy: A Randomized Clinical Trial.

Rationale: Obstructive sleep apnea (OSA) is associated with impaired glycemic control and a higher risk of vascular complications, such as diabetic retinopathy. However, the effect of apnea-hypopnea suppression on retinal disease progression is unclear. Objectives: To evaluate the efficacy and safety of continuous positive airway pressure (CPAP) for the reduction of retinal lesions in patients with non-proliferative diabetic retinopathy (NPDR) and OSA. Methods: This open-label, parallel-group, randomized controlled trial was conducted between October 2016 and February 2020 at a university hospital in Spain. The date of final follow-up was March 2, 2021. Eighty-three patients with OSA and mild to moderate NPDR receiving stable treatment were randomized to receive CPAP and usual care (43 patients with 79 available eyes) or usual care alone (40 patients with 67 available eyes) for 52 weeks. The primary outcomes were the change in the percentage of eyes with retinal exudates and the number of retinal microhemorrhages from baseline to week 52. We also assessed the effects of both interventions on retinal thickness by means of optical coherence tomography, serum concentrations of glycated hemoglobin, blood pressure, lipid concentrations, sleepiness, and quality of life. Results: Fifty-two weeks of CPAP treatment was associated with reductions from baseline in the percentage of eyes with hard exudates (overall difference, -21.7%; P = 0.035) and in optical coherence tomography indices of retinal edema, including central subfield thickness and cube volume. However, in patients who met prespecified criteria for CPAP adherence, treatment was also associated with a higher number of retinal microhemorrhages at 52 weeks (intergroup adjusted difference, 6.0 [95% confidence interval, 0.6-11.5]; P = 0.029), which was directly related to prescribed pressure levels. CPAP treatment also improved glycemic control, sleepiness, and general health-related quality of life. Conclusions: In patients with OSA and NPDR, long-term CPAP treatment in addition to usual care may result in slower progression of retinal disease, although it could also induce an increase in retinal microhemorrhages. Clinical trial registered with www.clinicaltrials.gov (NCT02874313).

Role of CD39 in COVID-19 Severity: Dysregulation of Purinergic Signaling and Thromboinflammation.

CD39/NTPDase1 has emerged as an important molecule that contributes to maintain inflammatory and coagulatory homeostasis. Various studies have hypothesized the possible role of CD39 in COVID-19 pathophysiology since no confirmatory data shed light in this regard. Therefore, we aimed to quantify CD39 expression on COVID-19 patients exploring its association with severity clinical parameters and ICU admission, while unraveling the role of purinergic signaling on thromboinflammation in COVID-19 patients. We selected a prospective cohort of patients hospitalized due to severe COVID-19 pneumonia (n=75), a historical cohort of Influenza A pneumonia patients (n=18) and sex/age-matched healthy controls (n=30). CD39 was overexpressed in COVID-19 patients' plasma and immune cell subsets and related to hypoxemia. Plasma soluble form of CD39 (sCD39) was related to length of hospital stay and independently associated with intensive care unit admission (adjusted odds ratio 1.04, 95%CI 1.0-1.08, p=0.038), with a net reclassification index of 0.229 (0.118-0.287; p=0.036). COVID-19 patients showed extracellular accumulation of adenosine nucleotides (ATP and ADP), resulting in systemic inflammation and pro-coagulant state, as a consequence of purinergic pathway dysregulation. Interestingly, we found that COVID-19 plasma caused platelet activation, which was successfully blocked by the P2Y12 receptor inhibitor, ticagrelor. Therefore, sCD39 is suggested as a promising biomarker for COVID-19 severity. As a conclusion, our study indicates that CD39 overexpression in COVID-19 patients could be indicating purinergic signaling dysregulation, which might be at the basis of COVID-19 thromboinflammation disorder.

Contribution of sleep characteristics to the association between obstructive sleep apnea and dyslipidemia.

OBJECTIVES/BACKGROUND: Little information is available about the association of obstructive sleep apnea (OSA) with atherogenic dyslipidemia and the contribution of sleep characteristics to lipid alterations. We compare dyslipidemia prevalence among non-apneic subjects and mild-severe OSA patients to identify the sleep characteristics that are independently associated with dyslipidemia and serum lipid levels in OSA patients. PATIENTS/METHODS: We recruited 809 consecutive patients who had been referred for polysomnography study by OSA suspicion. Anthropometric characteristics, body composition and comorbidities were recorded. Spirometry and 24-h ambulatory blood pressure monitoring were performed the same day of the sleep study. The day after attended polysomnography, fasting blood samples were drawn to measure the lipid profile. RESULTS: Dyslipidemia prevalence increased with the presence of OSA, from non-OSA subjects to mild, moderate and severe OSA patients (31%, 33%, 42% and 51%, respectively; p < 0.001). After adjusting for sex, age, body mass index and smoking habit, only severe OSA had an independent association with dyslipidemia when compared to non-OSA subjects (adjusted odds ratio 1.71, 95%CI 1.09 to 2.69, p = 0.019). In OSA patients, multivariate logistic regression identified active smoking, apnea-hypopnea index (AHI) and mean nocturnal saturation as variables independently associated with dyslipidemia. However, in these patients, arousal index, slow wave sleep duration and REM latency were also independently associated with cholesterol and low-density lipoprotein levels. CONCLUSIONS: The association between dyslipidemia and OSA is limited to severe patients, with high AHI and nocturnal hypoxemia. However, sleep fragmentation and increased sympathetic activity could also contribute to OSA-related lipid dysregulation.

[Palliative Sedation at the End of Life: A Comparative Study of Chronic Obstructive Pulmonary Disease and Lung Cancer Patients].

BACKGROUND: Although patients with chronic obstructive pulmonary disease (COPD) receive poor-quality palliative care, information about the use of palliative sedation (PS) in the last days of life is very scarce. OBJECTIVES: To compare the use of PS in hospitalized patients who died from COPD or lung cancer and identify factors correlating with PS application. METHODS: In a retrospective observational cohort study, from 1,675 patients died at a teaching hospital between 2013 and 2015, 109 patients who died from COPD and 85 from lung cancer were compared. Sociodemographic data, clinical characteristics, health care resource utilization, application of PS and prescribed drugs were recorded. RESULTS: In the last 6 months of life, patients who died from COPD had more hospital admissions due to respiratory causes and less frequent support by a palliative home care team (PHCT). Meanwhile, during their last hospitalization, patients who died from COPD had fewer do-not-resuscitate orders and were subjected to more intensive care unit admissions and cardiopulmonary resuscitation maneuvers. PS was applied less frequently in patients who died from COPD than in those who died from lung cancer (31 vs. 53%, p = 0.002). Overall, previous use of opioid drugs, support by a PHCT, and a diagnosis of COPD (adjusted odds ratio 0.48, 95% CI: 0.26-0.89, p = 0.020) were retained as factors independently related to PS. In COPD patients, only previous use of opioid drugs was identified as a PS-related factor. CONCLUSION: During their last days of life, hospitalized COPD patients receive PS less frequently than patients with lung cancer.

Small Airway Dysfunction Impairs Quality of Life Among Smokers With No Airflow Limitation. / La disfunción de las pequeñas vías aéreas deteriora la calidad de vida de fumadores sin limitación al flujo aéreo.

INTRODUCTION: Small airway dysfunction (SAD) caused by smoking contributes to the early onset of airflow limitation (AFL), although its impact on patients' perception of health is largely unknown. We aimed to evaluate the frequency of SAD in active smokers without AFL, and to compare health-related quality of life (HRQoL) of non-smokers, smokers without SAD, smokers with SAD, and smokers with AFL. METHODS: A total of 53 active smokers without AFL, 20 smokers with AFL, and 20 non-smokers completed the SF-36 and EuroQoL questionnaires and performed impulse oscillometry and spirometry. Pulmonary parenchymal attenuation was determined in inspiration and expiration. SAD was determined to exist when resistance at 5Hz (R5), the difference between R5 and R20, and reactance area (AX) exceeded the upper limit of normal. RESULTS: In total, 35.8% of smokers without AFL had SAD. No differences were detected in spirometric parameters or pulmonary attenuation between smokers with or without AFL and non-smokers. However, smokers with SAD had worse scores on HRQoL questionnaires than smokers without SAD or non-smokers, and scores compared to smokers with AFL were intermediate. R5 and X5 were identified as independent determinants of HRQoL in smokers without AFL. CONCLUSIONS: SAD is common in smokers without AFL, affecting one third of this population, and independently affecting their perception of health.

Hypermethylation of Anti-oncogenic MicroRNA 7 is Increased in Emphysema Patients.

INTRODUCTION: MicroRNA-7 (miR-7) has a suppressive role in lung cancer and alterations in its DNA methylation may contribute to tumorigenesis. As COPD patients with emphysema have a higher risk of lung cancer than other COPD phenotypes, we compared the miR-7 methylation status among smoker subjects and patients with various COPD phenotypes to identify its main determinants. METHODS: 30 smoker subjects without airflow limitation and 136 COPD patients without evidence of cancer were recruited in a prospective study. Clinical and functional characteristics were assessed and patients were classified into: frequent exacerbator, emphysema, chronic bronchitis and asthma COPD overlap (ACO). DNA collected from buccal epithelial samples was isolated and bisulfite modified. miR-7 methylation status was evaluated by quantitative methylation-specific polymerase chain reaction (qMSP). RESULTS: miR-7 Methylated levels were higher in COPD patients than in smokers without airflow limitation (23.7±12.4 vs. 18.5±8.8%, p=0.018). Among COPD patients, those with emphysema had higher values of methylated miR-7 (27.1±10.2%) than those with exacerbator (19.4±9.9%, p=0.004), chronic bronchitis (17.3±9.0%, p=0.002) or ACO phenotypes (16.0±7.2%, p=0.010). After adjusting for clinical parameters, differences between emphysematous patients and those with other phenotypes were retained. In COPD patients, advanced age, mild-moderate airflow limitation, reduced diffusing capacity and increased functional residual capacity were identified as independent predictors of methylated miR-7 levels. CONCLUSION: The increase of miR-7 methylation levels experienced by COPD patients occurs mainly at the expense of the emphysema phenotype, which might contribute to explain the higher incidence of lung cancer in these patients.

Static lung hyperinflation is an independent risk factor for lung cancer in patients with chronic obstructive pulmonary disease.

INTRODUCTION: Static hyperinflation, a hallmark characteristic of some patients with chronic obstructive pulmonary disease, is related to higher mortality and cardiovascular morbidity. However, information about its association with lung cancer is scarce. Our aim was to evaluate whether static hyperinflation is associated with future risk of lung cancer in COPD patients. METHODS: A cohort of 848 COPD patients recruited outside the hospital setting was monitored for an average period of 4.3 years, totaling 2858 person-years, regarding diagnosis of cancer of any origin or lung cancer. Static hyperinflation was defined by functional residual capacity measured by plethysmography greater than 120% of the predicted value. RESULTS: The incidence rates for cancer of any origin and lung cancer were 16.0 (95%CI, 15.1-17.8) and 8.7 (95%CI, 7.7-9.8) per 1000 patient-years, respectively. Among the patients with lung cancer, non-small cell lung cancer predominated (88%). In a stepwise multivariate Cox regression model, body mass index (BMI), pack-years, Charlson index, and postbronchodilator FEV1/FVC ratio were retained as independent predictors of cancer of any origin. In contrast, features associated with a future risk of lung cancer included older age, low BMI, increased pack-years and presence of static hyperinflation (adjusted hazard ratio: 4.617, 95%CI: 1.007-21.172, p = 0.049). CONCLUSION: In a general COPD outpatient population, static hyperinflation is an independent risk factor for the development of lung cancer, which might contribute towards justifying the excess mortality identified in COPD patients with hyperinflation.

Prediction of postoperative lung function after major lung resection for lung cancer using volumetric computed tomography.

OBJECTIVES: The study objectives were to assess the accuracy of volumetric computed tomography to predict postoperative lung function in patients with lung cancer in relation to anatomic segments counting and perfusion scintigraphy, to generate specific predictive equations for each functional parameter, and to evaluate accuracy and precision of these in a validation cohort. METHODS: We assessed pulmonary functions preoperatively and 3 to 4 months postoperatively after lung resection for lung cancer (n = 114). Absolute and relative lung volumes (total and upper/middle/lower) were determined using volumetric software analysis for staging thoracic computed tomography scans. Predicted postoperative function was calculated by segments counting, scintigraphy, and volumetric computed tomography. RESULTS: Volumetric computed tomography achieves a higher correlation and precision with measured postoperative lung function than segments counting or scintigraphy (correlation and intraclass correlation coefficients, 0.779-0.969 and 0.776-0.969; 0.573-0.887 and 0.552-0.882; and 0.578-0.834 and 0.532-0.815, respectively), as well as greater accuracy, determined by narrower agreement coefficients for forced vital capacity, forced expiratory volume in 1 second, lung diffusing capacity, and peak oxygen uptake. After validation in an independent cohort (n = 43), adjusted linear regression including volumetric estimation of decreased postoperative ventilation for postoperative lung function parameters explains 98% to 99% of variance. CONCLUSIONS: Volumetric computed tomography is a reliable and accurate method to predict postoperative lung function in patients undergoing lung resection that provides better accuracy than conventional procedures. Because lung computed tomography is systematically performed in the staging of patients with suspected lung cancer, this volumetric analysis might simultaneously provide the information necessary to evaluate operability.

Small airway dysfunction in smokers with stable ischemic heart disease.

BACKGROUND: A higher prevalence of airflow limitation (AL) has been described in patients with ischemic heart disease (IHD). Although small airway dysfunction (SAD) is an early feature of AL, there is little information about its occurrence in IHD patients. Our objective was to describe the prevalence of SAD in IHD patients, while comparing patient-related outcomes and future health risk among IHD patients with AL, SAD and normal lung function. METHODS: In 118 consecutive smoking patients with stable IHD, comorbidities, utilization of healthcare resources, current treatment, blood biochemistry and health status were recorded. SAD was evaluated by impulse oscillometry, and pre- and post-bronchodilator spirometry was performed. RESULTS: The prevalence of AL and SAD were 20.3 (95% CI, 13.1-27.6%) and 26.3% (95% CI, 18.3-34.2%), respectively. Compared to the normal lung function group, patients with SAD and without AL had lower spirometric values, poorer quality of life and higher levels of C-reactive protein (CRP), as well as increased cardiovascular risk and more vascular age. In patients with normal spirometry, the presence of SAD was independently associated with pack-years, HDL-cholesterol and CRP levels. CONCLUSION: In patients with IHD, the presence of SAD is common and that it is associated with reduced health status and increased future cardiac risk.

Identification of non-coding genetic variants in samples from hypoxemic respiratory disease patients that affect the transcriptional response to hypoxia.

A wide range of diseases course with an unbalance between the consumption of oxygen by tissues and its supply. This situation triggers a transcriptional response, mediated by the hypoxia inducible factors (HIFs), that aims to restore oxygen homeostasis. Little is known about the inter-individual variation in this response and its role in the progression of disease. Herein, we sought to identify common genetic variants mapping to hypoxia response elements (HREs) and characterize their effect on transcription. To this end, we constructed a list of genome-wide HIF-binding regions from publicly available experimental datasets and studied the genetic variability in these regions by targeted re-sequencing of genomic samples from 96 chronic obstructive pulmonary disease and 144 obstructive sleep apnea patients. This study identified 14 frequent variants disrupting potential HREs. The analysis of the genomic regions containing these variants by means of reporter assays revealed that variants rs1009329, rs6593210 and rs150921338 impaired the transcriptional response to hypoxia. Finally, using genome editing we confirmed the functional role of rs6593210 in the transcriptional regulation of EGFR. In summary, we found that inter-individual variability in non-coding regions affect the response to hypoxia and could potentially impact on the progression of pulmonary diseases.

Systemic inflammation and higher perception of dyspnea mimicking asthma in obese subjects.

BACKGROUND: There are a variable number of obese subjects with self-reported diagnosis of asthma but without current or previous evidence of airflow limitation, bronchial reversibility, or airway hyperresponsiveness (misdiagnosed asthma). However, the mechanisms of asthma-like symptoms in obesity remain unclear. OBJECTIVES: We sought to evaluate the perception of dyspnea during bronchial challenge and exercise testing in obese patients with asthma and misdiagnosed asthma compared with obese control subjects to identify the mechanisms of asthma-like symptoms in obesity. METHODS: In a cross-sectional study we included obese subjects with asthma (n = 25), misdiagnosed asthma (n = 23), and no asthma or respiratory symptoms (n = 27). Spirometry, lung volumes, exhaled nitric oxide levels, and systemic biomarker levels were measured. Dyspnea scores during adenosine bronchial challenge and incremental exercise testing were obtained. RESULTS: During bronchial challenge, patients with asthma or misdiagnosed asthma reached a higher Borg-FEV1 slope than control subjects. Moreover, maximum dyspnea and the Borg-oxygen uptake (V'O2) slope were significantly greater during exercise in subjects with asthma or misdiagnosed asthma than in control subjects. The maximum dyspnea achieved during bronchial challenge correlated with IL-1ß levels, whereas peak respiratory frequency, ventilatory equivalent for CO2, and IL-6 and IL-1ß levels were independent predictors of the Borg-V'O2 slope during exercise (r(2) = 0.853, P < .001). CONCLUSIONS: A false diagnosis of asthma (misdiagnosed asthma) in obese subjects is attributable to an increased perception of dyspnea, which, during exercise, is mainly associated with systemic inflammation and excessive ventilation for metabolic demands.

Prognostic Value of the Six-Second Spirometry in Patients with Chronic Obstructive Pulmonary Disease: A Cohort Study.

BACKGROUND: The six-second spirometry has been proposed as an alternative to diagnose airflow limitation, although its prognostic value in patients with chronic obstructive pulmonary disease (COPD) remains unknown. The purpose of this study was to determine the prognostic value of the postbronchodilator forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6 seconds (FEV6) ratio and FEV6 in COPD patients. METHODS AND FINDINGS: The study population consisted of 2,614 consecutive stable patients with COPD. The patients were monitored for an average period of 4.3 years regarding mortality, hospitalizations by COPD exacerbations, diagnosis of lung cancer, and annual lung function decline. The overall rate of death was 10.7 (95%CI: 8.7-12.7) per 1000 person-years. In addition to male gender, age and comorbidity, FEV6 (hazard ratio [HR]: 0.981, 95%CI: 0.968-0.003) and FEV1/FEV6 quartiles (lowest quartile (<74% pred.): HR 3.558, 95%CI: 1.752-7.224; and second quartile (74-84% pred.): HR 2.599, 95%CI: 1.215-5.561; versus best quartile (>0.89% pred.)) were independently associated with mortality, whereas FEV1 was not retained in the model. 809 patients (30.9%) had at least one hospital admission due to COPD exacerbation. In addition to sex, age, smoking and comorbidity, FEV1 and FEV1/FEV6 quartiles were independent risk factors of hospitalization. FEV6 was the only spirometric parameter independently related with lung function annual decline, while the FEV6 and FEV1/FEV6 quartiles were independent risk factors for lung cancer. CONCLUSIONS: In a general COPD outpatient population, airflow obstruction assessed by the FEV1/FEV6 is an independent risk factor for both death and hospitalization.

Exercise oxygen flow titration methods in COPD patients with respiratory failure.

We compare the adequacy of several titration procedures of oxygen flow in maintaining SpO(2) > 90% during the activities of daily life in patients with very severe COPD. Thirty-one very severe COPD patients undergoing oxygen-therapy were recruited. Three titration methods were randomly performed: (1) 6-min walking tests; (2) cycle-ergometer constant work-rate tests at a load equivalent to 12 ml/min/kg of oxygen uptake; (3) one single constant work-rate test at 40 W 12-h pulse-oximeter monitoring was performed on four consecutive days with the following oxygen flow during exercise: 1 l·min(-1) above the resting prescription (NOTT guidelines) and those established by the titration procedures. The time spent SpO(2) < 90% was higher for the titration based on NOTT and walking tests than for the oxygen flow established by the constant work-rate tests at 12 ml O(2)/min/kg (22.1 ± 18.7, 20.8 ± 19.5 and 6.7 ± 12.7%, respectively). As for the oxygen uptake-based titration, the simplified procedure (a single exercise test at 40 w) generates longer times spent SpO(2) < 90% and SpO(2) < 85%, although it maintains a SpO(2) > 90% for more 90% of the time. In COPD patients, exercise oxygen flow titrations by NOTT guidelines or walking tests do not allow a suitable oxygenation during the activities of daily life. Two more adequate alternative methods, based on constant work-rate tests, are proposed.

Prediction equations for single-breath diffusing capacity in subjects aged 65 to 85 years.

BACKGROUND: In senior subjects, diffusing capacity of the lung for carbon monoxide (Dlco) is interpreted using prediction equations derived from primarily younger adult populations. Our objectives were to provide reference equations for single-breath Dlco for a cohort of healthy, never-smoking, white, European adults between 65 and 85 years of age and to compare the predicted values of this sample with those from other studies involving middle-aged adults. METHODS: Reference equations were derived from a randomly selected sample from the general population of 431 healthy never smoker subjects aged 65 to 85 years (262 women and 169 men). Spirometry, lung volume determinations by plethysmography, and single-breath Dlco (corrected for hemoglobin) were performed following the American Thoracic Society/European Respiratory Society guidelines. Reference values and lower and upper limits of normal were derived using a piecewise polynomial model. RESULTS: In addition to age, our reference equations confirmed the height and body size dependence of Dlco and diffusing capacity for alveolar volume (Dlco/Va) in older subjects. Practically all of the reference values obtained by extrapolating reference equations of middle-aged adults underestimated the true diffusing capacity of the healthy elderly volunteers. Middle-aged reference equations underestimated Dlco by 2.1% to 22.3% in women and 2.8% to 37.8% in men. In addition, Dlco/Va was overestimated up to 18% and 39.8% in women and men, respectively, whereas other equations underestimated Dlco/Va up to 22.2% and 11.9% in women and men, respectively. CONCLUSIONS: These results underscore the importance of using prediction equations appropriate to the origin and age characteristics of the subjects being studied.

Dynamic hyperinflation, arterial blood oxygen, and airway oxidative stress in stable patients with COPD.

BACKGROUND: There is considerable evidence that oxidative stress is increased in patients with COPD, although little information is available about its relationship with the structural and functional alterations produced by COPD. In this study, we evaluated the relationship between 8-isoprostane in exhaled breath condensate (EBC) of stable patients with COPD and the main parameters of the disease (such as dyspnea), stages of severity, lung parenchyma densities, lung function impairment, and exercise tolerance in order to identify the predictors of airway oxidative stress. METHODS: In a cross-sectional study, we included 76 men with moderate to very severe COPD. 8-Isoprostane levels in EBC were measured by enzyme immunoassay. Regional lung densities were measured by lung densitometry with high-resolution CT scanning. Arterial blood gas levels, lung volumes, and diffusing capacity were determined. Patients performed a 6-min walk test and an incremental exercise test with measurement of breathing pattern and operating lung volumes. RESULTS: Significant severity-related differences in 8-isoprostane were identified according to the BMI, obstruction, dyspnea, and exercise (BODE) index. 8-Isoprostane levels were related to smoking intensity, lung densities in expiration, static lung volumes, PaO(2), diffusion capacity, distance walked in 6 min, peak oxygen uptake, and anaerobic threshold. Concentration of 8-isoprostane was higher in the 60 patients (79%) who developed dynamic hyperinflation than in the remaining 16 (21%) who did not. In a multivariate linear regression analysis using 8-isoprostane as a dependent variable, end-expiratory lung volume change and PaO(2) were retained in the prediction model (r(2) = 0.734, P < .001). CONCLUSIONS: In stable patients with COPD, oxygen level and dynamic hyperinflation are related to airway oxidative stress.