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Biomedical subjects

Frank C Sciurba

Publications and source records attributed to Frank C Sciurba.

At least 19 recordsLinked to original sources

Use of endobronchial valves for native lung hyperinflation associated with respiratory failure in a single-lung transplant recipient for emphysema.

Emphysema is a common indication for adult pulmonary transplantation. Double-lung transplantation is increasingly the preferred approach because severe posttransplant native lung hyperinflation (NLH) following single-lung transplantation may compromise allograft lung function. We describe successful emergency use of bronchoscopic lung volume reduction using endobronchial valves (EBVs) [Zephyr; Emphasys Medical; Redwood, CA] in a single-lung transplant recipient who was critically ill with ventilator dependence from complications of NLH and at excessive risk for lung volume reduction surgery or pneumonectomy. Following placement of 17 valves in all segments of the native lung, atelectasis of the native lung was accompanied by volume expansion of the allograft. Immediately following valve placement, peak airway pressure decreased and alveolar ventilation increased. The patient was subsequently weaned from mechanical ventilation. This report suggests the need for clinical trials to evaluate the effectiveness of EBVs in single-lung transplant recipients with less critical functional impairment associated with NLH.

Bronchoscopy↗

Variability of spirometry in chronic obstructive pulmonary disease: results from two clinical trials.

OBJECTIVE: Our goal is to determine short-term intraindividual biologic and measurement variability in spirometry of patients with a wide range of stable chronic obstructive pulmonary disease severity, using datasets from the National Emphysema Treatment Trial (NETT) and the Lung Health Study (LHS). This may be applied to determine criteria that can be used to assess a clinically meaningful change in spirometry. METHODS: A total of 5,886 participants from the LHS and 1,215 participants from the NETT performed prebronchodilator spirometry during two baseline sessions. We analyzed varying criteria for absolute and percent change of FEV(1) and FVC to determine which criterion was met by 90% of the participants. RESULTS: The mean +/- SD FEV(1) for the initial session was 2.64 +/- 0.60 L (75.1 +/- 8.8% predicted) for the LHS and 0.68 +/- 0.22 L (23.7 +/- 6.5% predicted) for the NETT. The mean +/- SD number of days between test sessions was 24.9 +/- 17.1 for the LHS and 85.7 +/- 21.7 for the NETT. As the degree of obstruction increased, the intersession percent difference of FEV(1) increased. However, the absolute difference between tests remained relatively constant despite the severity of obstruction (0.106 +/- 0.10 L). Over 90% of participants had an intersession FEV(1) difference of less than 225 ml irrespective of the severity of obstruction. CONCLUSIONS: Absolute changes in FEV(1) rather than percent change should be used to determine whether patients with chronic obstructive pulmonary disease have improved or worsened between test sessions.

Aged↗

Genetic association analysis of functional impairment in chronic obstructive pulmonary disease.

RATIONALE: Patients with severe chronic obstructive pulmonary disease (COPD) may have varying levels of disability despite similar levels of lung function. This variation may reflect different COPD subtypes, which may have different genetic predispositions. OBJECTIVES: To identify genetic associations for COPD-related phenotypes, including measures of exercise capacity, pulmonary function, and respiratory symptoms. METHODS: In 304 subjects from the National Emphysema Treatment Trial, we genotyped 80 markers in 22 positional and/or biologically plausible candidate genes. Regression models were used to test for association, using a test-replication approach to guard against false-positive results. For significant associations, effect estimates were recalculated using the entire cohort. Positive associations with dyspnea were confirmed in families from the Boston Early-Onset COPD Study. RESULTS: The test-replication approach identified four genes-microsomal epoxide hydrolase (EPHX1), latent transforming growth factor-beta binding protein-4 (LTBP4), surfactant protein B (SFTPB), and transforming growth factor-beta1 (TGFB1)-that were associated with COPD-related phenotypes. In all subjects, single-nucleotide polymorphisms (SNPs) in EPHX1 (p < or = 0.03) and in LTBP4 (p < or = 0.03) were associated with maximal output on cardiopulmonary exercise testing. Markers in LTBP4 (p < or = 0.05) and SFTPB (p = 0.005) were associated with 6-min walk test distance. SNPs in EPHX1 were associated with carbon monoxide diffusing capacity (p < or = 0.04). Three SNPs in TGFB1 were associated with dyspnea (p < or = 0.002), one of which replicated in the family study (p = 0.02). CONCLUSIONS: Polymorphisms in several genes seem to be associated with COPD-related traits other than FEV(1). These associations may identify genes in pathways important for COPD pathogenesis.

Aged↗

Computerized estimation of the lung volume removed during lung volume reduction surgery.

RATIONALE AND OBJECTIVES: This study was designed to develop an automated method for estimating lung volume removed during lung volume reduction surgery (LVRS) using computed tomography (CT). MATERIALS AND METHODS: The CT examinations of six patients who underwent bilateral LVRS were analyzed in this study. The resected lung tissue (right and left) was weighed during pathologic examination. An automated computer scheme was developed to estimate the lung volume removed using the CT voxel values and lung specimen weight. The computed fraction of lung volume removed was evaluated across a range of simulated surgical planes (ie, other than parallel to the CT image plane) and CT reconstruction kernels, and it was compared with the surgeons' postsurgical estimates. RESULTS: The computed fraction of the lung volume removed during LVRS was linearly correlated with the resected lung tissue weight (Pearson correlation = 0.697, P = .012). The computed fraction of lung volume removed ranged from 12.9% to 51.7% of the total lung volume. The surgeons' postsurgical estimates of lung volume removed ranged from 30% to 33%. The percent difference between the surgeons' estimates and the computed lung volume removed as a percentage of the surgeons' estimates ranged from -72.3% to 57.0% with mean absolute difference of 29.7% (+/-20.7). CONCLUSION: The preliminary findings of this study suggest that the proposed quantitative model should provide an objective measure of lung volume removed during LVRS that may be used to investigate the relationship between lung volume removed and outcome.

Absorptiometry, Photon↗

Long-term follow-up of patients receiving lung-volume-reduction surgery versus medical therapy for severe emphysema by the National Emphysema Treatment Trial Research Group.

BACKGROUND: The National Emphysema Treatment Trial defined subgroups of patients with severe emphysema in whom lung-volume-reduction surgery (LVRS) improved survival and function at 2 years. Two additional years of follow-up provide valuable information regarding durability. METHODS: A total of 1218 patients with severe emphysema were randomized to receive LVRS or medical treatment. We present updated analyses (4.3 versus 2.4 years median follow-up), including 40% more patients with functional measures 2 years after randomization. RESULTS: The intention-to-treat analysis of 1218 randomized patients demonstrates an overall survival advantage for LVRS, with a 5-year risk ratio (RR) for death of 0.86 (p = 0.02). Improvement was more likely in the LVRS than in the medical group for maximal exercise through 3 years and for health-related quality of life (St. George's Respiratory Questionnaire [SGRQ]) through 4 years. Updated comparisons of survival and functional improvement were consistent with initial results for four clinical subgroups of non-high-risk patients defined by upper-lobe predominance and exercise capacity. After LVRS, the upper-lobe patients with low exercise capacity demonstrated improved survival (5-year RR, 0.67; p = 0.003), exercise throughout 3 years (p < 0.001), and symptoms (SGRQ) through 5 years (p < 0.001 years 1 to 3, p = 0.01 year 5). Upper-lobe-predominant and high-exercise-capacity LVRS patients obtained no survival advantage but were likely to improve exercise capacity (p < 0.01 years 1 to 3) and SGRQ (p < 0.01 years 1 to 4). CONCLUSIONS: Effects of LVRS are durable, and it can be recommended for upper-lobe-predominant emphysema patients with low exercise capacity and should be considered for palliation in patients with upper-lobe emphysema and high exercise capacity.

Aged↗

Feasibility of retinoids for the treatment of emphysema study.

BACKGROUND: Retinoids promote alveolar septation in the developing lung and stimulate alveolar repair in some animal models of emphysema. METHODS: One hundred forty-eight subjects with moderate-to-severe COPD and a primary component of emphysema, defined by diffusing capacity of the lung for carbon monoxide (Dlco) [37.1 +/- 12.0% of predicted] and CT density mask (38.5 +/- 12.8% of voxels <- 910 Hounsfield units) [mean +/- SD] were enrolled into a randomized, double-blind, feasibility study at five university hospitals. Participants received all-trans retinoic acid (ATRA) at either a low dose (LD) [1 mg/kg/d] or high dose (HD) [2 mg/kg/d], 13-cis retinoic acid (13-cRA) [1 mg/kg/d], or placebo for 6 months followed by a 3-month crossover period. RESULTS: No treatment was associated with an overall improvement in pulmonary function, CT density mask score, or health-related quality of life (QOL) at the end of 6 months. However, time-dependent changes in Dlco (initial decrease with delayed recovery) and St. George Respiratory Questionnaire (delayed improvement) were observed in the HD-ATRA cohort and correlated with plasma drug levels. In addition, 5 of 25 participants in the HD-ATRA group had delayed improvements in their CT scores that also related to ATRA levels. Retinoid-related side effects were common but generally mild. CONCLUSIONS: No definitive clinical benefits related to the administration of retinoids were observed in this feasibility study. However, time- and dose-dependent changes in Dlco, CT density mask score, and health-related QOL were observed in subjects treated with ATRA, suggesting the possibility of exposure-related biological activity that warrants further investigation.

Aged↗

Physician and patient perceptions in COPD: the COPD Resource Network Needs Assessment Survey.

PURPOSE: Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in the United States, has received disproportionately little attention from physicians and institutions. National data are lacking on patient and physician perceptions of and patterns of care for COPD. METHODS: Linked surveys were administered to national samples of patients with COPD, primary care physicians, and pulmonologists to evaluate perceptions of COPD severity and quality of life, attitudes about COPD, health insurance barriers to COPD care, sources of information, and knowledge about COPD diagnosis and treatment. RESULTS: Overall, 1023 patients with COPD and 1051 primary care physicians and pulmonologists responded to the surveys. Despite experiencing significant symptoms and high health care use, the majority of patients were satisfied with their care. Eighty-eight percent of physicians agreed with the statement that COPD is a "self-inflicted" disease, and more than one third were nihilistic about the treatment of patients who continued to smoke. Patients and physicians reported that insurance problems impeded access to therapies. Patients were generally uninformed about COPD; 54% of primary care physicians were aware of any COPD guidelines. Both patient and physician surveys demonstrated continued confusion about the diagnosis of COPD and treatment choices. There was frequent use of regular oral steroids despite demonstrated lack of efficacy and under-use of pulmonary rehabilitation despite proven efficacy. CONCLUSIONS: Patients with COPD have a high prevalence of activity limitations. Although most physicians believed that proper treatment can slow progression, inadequate knowledge and poor adherence to practice guidelines, together with insurance impediments, negatively impact COPD care.

Adult↗

Emerging concepts in outcome assessment for COPD clinical trials.

The selection of appropriate, clinically meaningful outcome measures for chronic obstructive pulmonary disease (COPD) clinical trials is a complex issue. Functional exercise measures are more likely to adequately reflect the effect of novel and emerging interventions than traditional physiological measures such as forced expiratory volume in 1 second (FEV (1)). Nonetheless, among several exercise measures commonly used, the choice is not a simple issue and should be based upon rational as well as pragmatic issues. This is because important measurement properties (validity and responsiveness) can differ among exercise measures, among different interventions, and across degrees of disability. Furthermore, "free-living" daily activity measures may be more meaningful measures than these "in-lab" exercise measures for future clinical trials of COPD, although their reproducibility, validity, and responsiveness have not yet been adequately studied. Application of these and other emerging concepts in outcome assessment for COPD clinical trials will be examined.

Bronchodilator Agents↗

Improvements in symptom-limited exercise performance over 8 h with once-daily tiotropium in patients with COPD.

STUDY OBJECTIVES: We have previously shown that tiotropium at 18 mug reduces lung hyperinflation and dyspnea during exercise and improves exercise tolerance in patients with COPD. The present study was designed to gain further insight into the duration of improvements. DESIGN, PATIENTS, AND INTERVENTIONS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted in 261 COPD patients (mean age, 62.5 +/- 7.4 years [+/- SD]; 189 men and 72 women; mean FEV1, 1.2 +/- 0.4 L [43 +/- 12.7% predicted]). On day 0 (first dose), day 21, and day 42 of treatment, pulmonary function tests were performed before and 1 h 20 min after dosing, followed by a constant work rate cycle ergometry test (75% maximum work capacity) to symptom limitation at 2.25 h after dosing. On day 42, an additional constant work rate cycle ergometry test was performed at 8 h after dosing. RESULTS: Adjusted mean (+/- SE) endurance time (ET) on day 42 was 803 +/- 40 s (tiotropium), vs 568 +/- 42 s (placebo) at 2.25 h after dosing (primary end point; treatment difference, 236 +/- 58 s; p = 0.0001) and 665 +/- 40 s (tiotropium) vs 494 +/- 42 s (placebo) at 8 h after dosing (treatment difference, 171 +/- 58 s; p = 0.0035). Adjusted mean dyspnea intensity at isotime on day 42 was 4.60 +/- 0.16 Borg units (tiotropium), vs 5.65 +/- 0.16 Borg units (placebo) at 2.25 h after dosing (p < 0.001), and 5.54 +/- 0.17 Borg units (tiotropium) vs 6.51 +/- 0.18 Borg units (placebo) at 8 h after dosing (p < 0.001). Adjusted mean pre-exercise inspiratory capacity (IC) on day 42 was 2.41 +/- 0.03 L (tiotropium) vs 2.19 +/- 0.03 L (placebo) at 2.25 h after dosing (p < 0.001), and 2.31 +/- 0.03 L (tiotropium) vs 2.16 +/- 0.03 L (placebo) at 8 h after dosing (p < 0.001). The significant increase in IC with tiotropium compared with placebo was maintained throughout exercise. CONCLUSIONS: The present study confirms that tiotropium reduces lung hyperinflation at rest and during exercise, reduces exertional dyspnea, and improves symptom-limited exercise tolerance in COPD patients. Furthermore, this study shows that this improvement is present at 2.25 h and at 8 h after dosing after 6 weeks of treatment.

Aged↗

Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease.

To better understand the molecular basis of chronic obstructive pulmonary disease (COPD), we used serial analysis of gene expression (SAGE) and microarray analysis to compare the gene expression patterns of lung tissues from COPD and control smokers. A total of 59,343 tags corresponding to 26,502 transcripts were sequenced in SAGE analyses. A total of 327 genes were differentially expressed (1.5-fold up- or down-regulated). Microarray analysis using the same RNA source detected 261 transcripts that were differentially expressed to a significant degree between GOLD-2 and GOLD-0 smokers. We confirmed the altered expression of a select number of genes by using real-time quantitative RT-PCR. These genes encode for transcription factors (EGR1 and FOS), growth factors or related proteins (CTGF, CYR61, CX3CL1, TGFB1, and PDGFRA), and extracellular matrix protein (COL1A1). Immunofluorescence studies on the same lung specimens localized the expression of Egr-1, CTGF, and Cyr61 to alveolar epithelial cells, airway epithelial cells, and stromal and inflammatory cells of GOLD-2 smokers. Cigarette smoke extract induced Egr-1 protein expression and increased Egr-1 DNA-binding activity in human lung fibroblast cells. Cytomix (tumor necrosis factor alpha, IL-1beta, and IFN-gamma) treatment showed that the activity of matrix metalloproteinase-2 (MMP-2) was increased in lung fibroblasts from EGR1 control (+/+) mice but not detected in that of EGR1 null (-/-) mice, whereas MMP-9 was regulated by EGR1 in a reverse manner. Our study represents the first comprehensive analysis of gene expression on GOLD-2 versus GOLD-0 smokers and reveals previously unreported candidate genes that may serve as potential molecular targets in COPD.

Aged↗

The nature of small-airway obstruction in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major public health problem associated with long-term exposure to toxic gases and particles. We examined the evolution of the pathological effects of airway obstruction in patients with COPD. METHODS: The small airways were assessed in surgically resected lung tissue from 159 patients--39 with stage 0 (at risk), 39 with stage 1, 22 with stage 2, 16 with stage 3, and 43 with stage 4 (very severe) COPD, according to the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). RESULTS: The progression of COPD was strongly associated with an increase in the volume of tissue in the wall (P<0.001) and the accumulation of inflammatory mucous exudates in the lumen (P<0.001) of the small airways. The percentage of the airways that contained polymorphonuclear neutrophils (P<0.001), macrophages (P<0.001), CD4 cells (P=0.02), CD8 cells (P=0.038), B cells (P<0.001), and lymphoid aggregates containing follicles (P=0.003) and the absolute volume of B cells (P=0.03) and CD8 cells (P=0.02) also increased as COPD progressed. CONCLUSIONS: Progression of COPD is associated with the accumulation of inflammatory mucous exudates in the lumen and infiltration of the wall by innate and adaptive inflammatory immune cells that form lymphoid follicles. These changes are coupled to a repair or remodeling process that thickens the walls of these airways.

Aged↗

Association of chronic obstructive pulmonary disease severity and Pneumocystis colonization.

Factors modulating the variable progression of chronic obstructive pulmonary disease (COPD) are largely unknown, but infectious agents may play a role. Because Pneumocystis has previously been shown to induce a CD8(+) lymphocyte- and neutrophil-predominant response similar to that in COPD, we explored the association of the organism with accelerated disease progression. We examined Pneumocystis colonization rates in lung tissue obtained during lung resection or transplantation in smokers with a range of airway obstruction severity and in a control group with lung diseases other than COPD. Using nested polymerase chain reaction, Pneumocystis colonization was detected in 36.7% of patients with very severe COPD (Global Health Initiative on Obstructive Lung Disease [GOLD] Stage IV) compared with 5.3% of smokers with normal lung function or less severe COPD (Stages 0, I, II, and III) (p = 0.004) and with 9.1% of control subjects (p = 0.007). Colonized subjects exhibited more severe airway obstruction (median FEV(1) = 21% predicted versus 62% in noncolonized subjects, p = 0.006). GOLD IV was the strongest predictor of Pneumocystis colonization (odds ratio = 7.3, 95% confidence interval = 2.4-22.4, p < 0.001) and was independent of smoking history. We conclude that there is a strong association between Pneumocystis colonization and severity of airflow obstruction in smokers, suggesting a possible pathogenic link with COPD progression.

Aged↗

Physiologic similarities and differences between COPD and asthma.

The structural and physiologic findings in asthma and COPD appear, on average, and in the extremes of presentation, to be easily distinguished. A closer inspection of the literature reveals that significant overlap exists in individual patients with respect to airway wall thickening and low-attenuation parenchymal regions on CT scans, and in reversibility, airway hyperresponsiveness, lung diffusion, resting and dynamic hyperinflation, lung elastic recoil, exercise response, and a "pharmaceutical volume reduction" effect following therapy with bronchodilators. In particular, the subgroup of COPD patients having an airway-dominant phenotype becomes indistinguishable from asthmatic subjects with reversible disease that evolves into an incompletely reversible pattern.

Asthma↗

Size and morphology of the trachea before and after lung volume reduction surgery.

OBJECTIVE: The purpose of this investigation was to determine the effect of lung volume reduction surgery on measured tracheal features. MATERIALS AND METHODS: Twenty-four male and 19 female patients with emphysema underwent lung volume reduction surgery, pulmonary function testing, and repeated CT. The tracheal air column was segmented from axial images. The sagittal and coronal dimensions of the intrathoracic trachea were determined. Tracheal morphology was quantified using the tracheal (coronal and sagittal dimensions) and circularity indexes. The results were compared with pulmonary function test results. RESULTS: Morphologic appearance of the intrathoracic trachea was consistent before and 3 months after surgery. The group means of the tracheal length, mean area, and volume were 78.60 mm (+/- 16.88 mm), 283.84 mm(2) (+/- 61.47 mm(2)), and 22.59 cm(3) (+/- 7.69 cm(3)), respectively, before surgery and 67.53 mm (+/- 15.78 mm), 309.12 mm(2) (+/- 79.83 mm(2)), and 20.99 cm(3) (+/- 7.27 cm(3)), respectively, after surgery (p < 0.05). Mean tracheal indexes were 0.85 (+/- 0.11) before surgery and 0.82 (+/- 0.04) after surgery (p < 0.01). Mean circularity indexes were 0.91 (+/- 0.03) before surgery and 0.90 (+/- 0.04) after surgery (p < 0.05). The size of the trachea was significantly correlated with lung volume before and after surgery (p < 0.05). The changes in tracheal features and changes in pulmonary function were not correlated (p > 0.05), except for tracheal area (p < 0.05). CONCLUSION: Our data suggest that tracheal dimensions reflect the severity of emphysema as reflected by increased lung volumes. Tracheal features were poor predictors of changes in postsurgical pulmonary function parameters evaluated in this preliminary study.

Female↗

Medical management of chronic obstructive pulmonary disease.

Recent advances in the treatment of patients who have COPD include the development of long-acting bronchodilators, recognition of the benefits of ICS, and development of effective initiation and maintenance pulmonary rehabilitation programs. The focus on outcome parameters other than expiratory flow rates, such as symptoms, quality of life, exercise tolerance, and exacerbation frequency, might also allow effective development of novel disease-modifying agents.

Adrenal Cortex Hormones↗

Automated lung segmentation in X-ray computed tomography: development and evaluation of a heuristic threshold-based scheme.

RATIONALE AND OBJECTIVES: To develop and evaluate a reliable, fully-automated lung segmentation scheme for application in X-ray computed tomography. MATERIALS AND METHODS: The automated scheme was heuristically developed using a slice-based, pixel-value threshold and two sets of classification rules. Features used in the rules include size, circularity, and location. The segmentation scheme operates slice-by-slice and performs three key operations: (1) image preprocessing to remove background pixels, (2) computation and application of a pixel-value threshold to identify lung tissue, and (3) refinement of the initial segmented regions to prune incorrectly detected airways and separate fused right and left lungs. RESULTS: The performance of the automated segmentation scheme was evaluated using 101 computed tomography cases (91 thick slice, 10 thin slice scans). The 91 thick cases were pre- and post-surgery from 50 patients and were not independent. The automated scheme successfully segmented 94.0% of the 2,969 thick slice images and 97.6% of the 1,161 thin slice images. The mean difference of the total lung volumes calculated by the automated scheme and functional residual capacity plus 60% inspiratory capacity was -24.7 +/- 508.1 mL. The mean differences of the total lung volumes calculated by the automated scheme and an established, commonly used semi-automated scheme were 95.2 +/- 52.5 mL and -27.7 +/- 66.9 mL for the thick and thin slice cases, respectively. CONCLUSION: This simple, fully-automated lung segmentation scheme provides an objective tool to facilitate lung segmentation from computed tomography scans.

Image Processing, Computer-Assisted↗