Publications by authors named "Igor Barjaktarevic"

Background: Evidence on trajectory of readmission rates post-hospitalization for COPD exacerbations and combined cardiopulmonary risk in the U.S. is sparse.

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Background: COPD phenotyping is an approach for developing tailored therapies. The eosinophilic phenotype is associated with exacerbation risk and response to specific treatments. This study evaluates the relationship between sputum and blood eosinophilia, hypothesizing that sputum eosinophil percentage (SpE%) better reflects disease severity and exacerbation risk than blood eosinophil counts (BEC).

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Rationale: Immunoglobulins (Ig) protect against pathogens frequently implicated in COPD exacerbations. We previously demonstrated an association of low-normal serum IgA and IgG concentrations with prospective exacerbation risk, but responsible mechanisms are undefined. Here, we examined associations of lower respiratory tract bacterial diversity to Ig levels in serum and bronchoalveolar lavage (BAL) and to the memory phenotypes of blood and BAL B cells.

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Background: Pulmonary emphysema occurs frequently in older adults, often without airflow limitation. Its presence predicts symptoms, respiratory hospitalizations and deaths, and all-cause mortality. Proteomics may provide further insights into emphysema pathogenesis and inform therapeutic targets.

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Rationale: Alpha-1 antitrypsin deficiency (AATD) is the most common genetic cause of chronic obstructive pulmonary disease (COPD), but considerable phenotypic variability exists among affected individuals who share disease-causing variants. Therefore, a multicenter longitudinal cohort study of 270 adult participants with PiZZ AATD will be established with a goal of examining how computed tomography (CT) imaging and serum and airway biomarkers can be used to explain differences in phenotypic manifestations and outcomes.

Methods: Study visits at enrollment, 18 months, and 36 months will obtain spirometry, patient-reported outcomes, and biosampling from blood, nasal mucosa, and sputum.

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Background: COPD is characterized by persistent inflammation that is responsible for remodeling the bronchovascular bundles (BVBs), which may lead to poor quality of life. Quantitative CT (QCT) scan textures of the lung can capture local disease patterns of inflammation and related respiratory morbidity.

Research Question: Are BVB textures, obtained from the adaptive multiple feature method, associated with systemic inflammation, morbidity, and mortality in COPD?

Study Design And Methods: We analyzed data from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS; n = 2,981) and the Genetic Epidemiology of COPD (COPDGene) study (n = 10,305).

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Discovering the biological basis of progression in chronic obstructive pulmonary disease (COPD), especially of rapid decline (RD) in forced expiratory volume in 1 second, is essential to the development of precision therapies. First, we sought to define baseline characteristics of RD (⩾100 ml/yr), relative to participants with stable-to-improved (S/I) status or with intermediate decline (D)-categories based on spirometric data from the Framingham Offspring cohort. Second, we sought to examine these categories as predictors of longitudinal COPD outcomes, adjusting for baseline characteristics.

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Quantifying functional small airway disease (fSAD) requires additional expiratory computed tomography (CT) scans, limiting clinical applicability. Artificial intelligence (AI) could enable fSAD quantification from chest CT scans at total lung capacity (TLC) alone (fSAD). To evaluate an AI model for estimating fSAD, compare it with dual-volume parametric response mapping fSAD (fSAD), and assess its clinical associations and repeatability in chronic obstructive pulmonary disease (COPD).

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Reliable data about the natural history of lung function decline in alpha-1 antitrypsin (AAT)-deficient Pi*MZ heterozygotes is largely missing. We hypothesized that, in adults with a tobacco smoking history, lung function deteriorates faster in Pi*MZ compared with the Pi*MM genotype. We identified 1,856 Pi*MM and 79 Pi*MZ participants with ⩾20 pack-years tobacco smoking history from the SPIROMICS (Subpopulations and Intermediate Outcomes Measures in COPD Study) cohort by DNA sequencing and followed them over a median of 4.

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Background: Studies suggest that the use of race-specific pulmonary function reference equations may obscure racial inequities in respiratory health. Whether removing race from the interpretation of pulmonary function would influence analyses of HIV and pulmonary function is unknown.

Setting: Pulmonary function measurements from 1067 men (591 with HIV) in the Multicenter AIDS Cohort Study and 1661 women (1175 with HIV) in the Women's Interagency HIV Study were analyzed.

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Hepatopulmonary syndrome (HPS), defined by the presence of pulmonary vascular dilatations that cause right-to-left transpulmonary shunting of venous blood with a consequential increase in the alveolar-arterial oxygen gradient, is a relatively frequent complication of chronic liver disease. While orthotopic liver transplantation (OLT) is indicated and often curative in HPS patients with end-stage liver disease (ESLD), little is known about the peri- and post-operative-period risks of CVA in OLT recipients with HPS. : We report a case series of five non-consecutive OLT recipients with HPS who developed ischemic and/or hemorrhagic CVAs during or shortly after OLT, raising concern that the risks of neurological complications remain increased even after OLT.

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Background: Lung computed tomography (CT) scan image registration is being used for lung function analysis such as ventilation. Given the high sensitivity of functional analyses to image registration errors, an image registration error scoring tool that can measure submillimeter image registration errors is needed.

Purpose: To propose an image registration error scoring tool, termed λ, whose spatial sensitivity can be used to quantify image registration errors in steep image gradient regions under realistic noise conditions.

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Among tobacco-exposed persons with preserved spirometry (TEPSs), we previously demonstrated that different lung volume indices-specifically, elevated total lung capacity (TLC) versus elevated ratio of functional residual capacity to TLC (FRC/TLC)-identify different lung disease characteristics in the COPDGene cohort. We sought to determine differential disease characteristics and trajectories associated with lung volume indices among TEPSs in the SPIROMICS cohort. We categorized TEPSs ( = 814) by tertiles (low, intermediate, and high) of TLC or residual volume-to-TLC ratio (RV/TLC) derived from baseline computed tomography images and then examined clinical and spirometric disease trajectories in mutually exclusive categories of participants with high TLC without high RV/TLC ([TLC]) versus high RV/TLC without high TLC ([RV/TLC]).

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Objectives: To differentiate invasive lepidic predominant adenocarcinoma (iLPA) from adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) of lung utilizing visual semantic and computer-aided detection (CAD)-based texture features on subjects initially diagnosed as AIS or MIA with CT-guided biopsy.

Materials And Methods: From 2011 to 2017, all patients with CT-guided biopsy results of AIS or MIA who subsequently underwent resection were identified. CT scan before the biopsy was used to assess visual semantic and CAD texture features, totaling 23 semantic and 95 CAD-based quantitative texture variables.

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Alpha-1 antitrypsin (AAT) deficiency is an autosomal codominant disorder caused by gene mutations. PI*Z and PI*S mutations commonly underlie this deficiency, but rarer homozygous PI* (Q0) mutations may result in a complete loss of AAT. Such rare mutations lead to severe AAT deficiency and early onset of lung disease.

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Article Synopsis
  • Researchers are investigating how artificial intelligence (AI) can help measure functional small airways disease (fSAD) in chronic obstructive pulmonary disease (COPD) using just one CT scan instead of the two traditionally required.
  • They studied over 2,500 participants and found strong correlations between the new AI method and existing measures of lung function, confirming its effectiveness.
  • The new AI technique for estimating fSAD proved to be more reliable and repeatable compared to standard methods, suggesting it could enhance clinical assessments of COPD.
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Article Synopsis
  • Exacerbations in COPD are serious events that can worsen lung function and impair quality of life, highlighting the need for effective medication to manage them.
  • Ensifentrine is a new drug that works as a dual inhibitor to reduce inflammation and open airways, and the study aimed to evaluate its effectiveness in reducing COPD exacerbation rates.
  • The analysis from two phase 3 trials involving nearly 1,000 patients showed that ensifentrine significantly reduced both the frequency and risk of severe COPD exacerbations compared to a placebo across various patient subgroups.
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The slope of decline in forced expiratory volume in 1 second (FEV) is commonly used to reflect the rate of disease progression for descriptive studies and therapeutic trials in chronic obstructive pulmonary disease (COPD). The frequency and duration of spirometric testing needed to report the true slope are unknown. We sought to define the minimum frequency and follow-up duration needed to accurately describe the annualized rate of FEV change among patients with moderate to very severe COPD.

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Article Synopsis
  • The SPIROMICS Study of Early COPD Progression (SOURCE) aims to investigate the biological reasons behind early-stage COPD in younger individuals who smoke, addressing a gap in current medical knowledge that hinders treatment development.
  • The study plans to enroll 649 participants aged 30-55 with a history of smoking, alongside 40 never-smoker controls, to collect comprehensive health data and analyze potential mechanisms of disease progression.
  • SOURCE seeks to use advanced imaging and biospecimen collection methods over three years to enhance understanding of COPD and contribute to better prevention and treatment strategies.
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Rationale: Identification and validation of circulating biomarkers for lung function decline in COPD remains an unmet need.

Objective: Identify prognostic and dynamic plasma protein biomarkers of COPD progression.

Methods: We measured plasma proteins using SomaScan from two COPD-enriched cohorts, the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene), and one population-based cohort, Multi-Ethnic Study of Atherosclerosis (MESA) Lung.

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Introduction: Chronic Bronchitis (CB) represents a phenotype of chronic obstructive pulmonary disease (COPD). While several definitions have been used for diagnosis, the relationship between clinical definitions and radiologic assessment of bronchial disease (BD) has not been well studied. The aim of this study was to evaluate the relationship between three clinical definitions of CB and radiographic findings of BD in spirometry-defined COPD patients.

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