Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aerosol-derived airway morphometry (ADAM) and aerosol bolus dispersion (ABD) test are altered in patients with emphysema. We examined the diagnostic power of these aerosol methods in comparison with the noninvasive "gold-standard" HRCT in 50 consecutive patients with various lung diseases. The severity of airflow limitation was mild to moderate in the group of patients without emphysema and moderate to severe in the group of patients with HRCT-confirmed emphysema (FEV(1), 78 +/- 23% pred versus 53 +/- 33% pred; p < 0. 001). Among all lung function parameters under consideration ADAM showed the highest sensitivity and specificity for separating patients with emphysema from those without emphysema (area under the operating characteristics curve: p(ROC), 0.92), followed by ABD (p(ROC), 0.90), a marker for ventilation inhomogeneities. In patients with HRCT-confirmed macroscopic emphysema, peripheral air-space dimensions (EAD) at a relative volumetric lung depth V(pr) of 0.20 measured by ADAM were 155% larger, and bolus dispersion (ABD) at a lung depth of V(p) 600 ml was 53% larger than those observed in patients with other lung diseases (EAD = 0.84 +/- 0.53 mm versus 0.33 +/- 0.10 mm, p < 0.0001; ABD = 706 +/- 154 cm(3) versus 462 +/- 109 cm(3); p < 0.0001). EAD showed a significant correlation with the HRCT visual score (r = 0.78, p = 0.01). ABD showed weak significant correlations with all HRCT parameters under consideration (visual score, pixel density, mean lung density) (r = 0.45 to 0.66; p < 0.05). ADAM and ABD are powerful tools for the noninvasive diagnosis of macroscopic emphysema.
 ...
PMID:Noninvasive diagnosis of emphysema. Aerosol morphometry and aerosol bolus dispersion in comparison to HRCT. 1047 18

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evening at home showed no significant difference in decline of FEV(1) between treatment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed tomography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2.6 +/- 0.41 g/L/yr for placebo as compared with 1.5 +/- 0.41 g/L/yr for alpha(1)-antitrypsin infusion (p = 0.07). Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV(1) showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr.
 ...
PMID:A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy. 1055 7

Low single-breath diffusing capacity (DL(CO)) values are associated with anatomic emphysema, but the predictors of longitudinal change in DL(CO) over many years are unknown. Study subjects were adult participants in the longitudinal Tucson Epidemiology Study of Obstructive Lung Disease who had at least one DL(CO) measurement during either of two surveys 8 yr apart (n = 543). Smoking status was determined at each examination (current, former, or never smoker). Quitters were defined as those currently smoking at the baseline DL(CO) examination (1982-1983) and self-reported as no longer smoking at the follow-up exam (1990-1991). The longitudinal DL(CO) data were analyzed using repeated measures analysis; because of missing observations this was done using a saturated random effects model. The results showed that males had higher levels of DL(CO) than females, current smokers had significantly lower levels of DL(CO) than never smokers, but there was no difference in their mean slopes over time. Smoking history, assessed using pack-years of smoking, was associated with reduced DL(CO) levels, independent of whether current or ex-smokers. Males and females demonstrated equivalent rates of decline in DL(CO) that accelerated with increasing age, and mean DL(CO) declines were associated with declines in FEV(1) between surveys.
 ...
PMID:Predictors of longitudinal change in diffusing capacity over 8 years. 1058 1

We hypothesized that an altered effect of lung inflation on airway caliber may in part explain the isolated volume response to bronchodilators, i.e., an increase of forced vital capacity (FVC) without change in 1-s forced expiratory volume (FEV(1)). Small-airway caliber was measured by high-resolution computed tomography at functional residual capacity and total lung capacity in five chronic obstructive pulmonary disease patients with an isolated increase of FVC (FVC responders) and five with an increase of both FVC and FEV(1) (FVC-FEV(1) responders) after inhalation of salbutamol. In FVC-FEV(1) responders, the airway diameter increased with the cube root of increase in lung volume but was unchanged or even decreased in four of five FVC responders. FVC responders had more severe emphysema, as inferred from lung function and imaging studies, than FVC-FEV(1) responders. We speculate that longitudinal traction or space competition (Verbeken EK, Cauberghs M, and Van de Woestijne KP, J Appl Physiol 81: 2468-2480, 1996) are possible underlying mechanisms. We conclude that the isolated volume response to bronchodilators is associated with severe emphysema and likely results from an altered effect of lung inflation on airway caliber.
 ...
PMID:Mechanisms for isolated volume response to a bronchodilator in patients with COPD. 1084 10

Chronic obstructive pulmonary disease (COPD) is characterized by the presence of airflow obstruction caused by emphysema or airway narrowing, or both. Low attenuation areas (LAA) on computed tomography (CT) have been shown to represent macroscopic or microscopic emphysema, or both. However CT has not been used to quantify the airway abnormalities in smokers with or without airflow obstruction. In this study, we used CT to evaluate both emphysema and airway wall thickening in 114 smokers. The CT measurements revealed that a decreased FEV(1) (%predicted) is associated with an increase of airway wall area and an increase of emphysema. Although both airway wall thickening and emphysema (LAA) correlated with measurements of lung function, stepwise multiple regression analysis showed that the combination of airway and emphysema measurements improved the estimate of pulmonary function test abnormalities. We conclude that both CT measurements of airway dimensions and emphysema are useful and complementary in the evaluation of the lung of smokers.
 ...
PMID:Computed tomographic measurements of airway dimensions and emphysema in smokers. Correlation with lung function. 1098 37

We evaluated the ability of intravenous supplementation therapy with alpha(1)-antitrypsin (AAT) to reduce the rate of urinary excretion of desmosine (DES), a specific marker of elastin degradation, in eight men and four women with emphysema due to severe, congenital deficiency of AAT (range 17-69 mg/dl). Nine were former cigarette smokers, two were current smokers, and one reported never smoking; their mean age was 54 (SD 12) yr and their mean FEV(1) was 41 (18%) of predicted. Urinary DES was measured by isotope dilution and HPLC. Prior to the start of AAT supplementation, mean DES excretion was 13.0 (5.0) microg/g creatinine, 73% higher than in healthy nonsmokers. During 8 wk of supplementation therapy, mean urinary DES excretion was 13.0 (5.9) microg/g creatinine, unchanged from the baseline period (p = 0.85 by repeated measures ANOVA). We conclude that baseline levels of elastin degradation in emphysematous patients with severe AAT deficiency were abnormally high and that 8 wk of AAT supplementation therapy did not appreciably reduce the rate of elastin degradation. These findings raise the possibilities that protective levels of AAT in the lungs are insufficient or that elastin degradation in the lungs of these subjects is not dependent upon neutrophil elastase at this time.
 ...
PMID:Short-term supplementation therapy does not affect elastin degradation in severe alpha(1)-antitrypsin deficiency. The American-Italian AATD Study Group. 1111 16

Resting lung function is only weakly related to health status in chronic obstructive pulmonary disease, reflecting the multifactorial causes of impairment and the heterogeneous nature of the condition. The current study examined whether density mask analysis of high-resolution computed tomography (HRCT) or exercise capacity were better surrogates for health status in a well-defined, homogeneous group of patients with alpha(1)-antitrypsin deficiency (PiZ). Twenty-nine patients with predominantly lower zone emphysema on HRCT were studied. Exercise was assessed by incremental treadmill (V O(2) peak) and shuttle walking tests (ISWT) and health status by the St. George's Respiratory Questionnaire (SGRQ) and SF-36. Although lower zone expiratory HRCT was related to exercise capacity (rho = -0.64 and -0.63 for V O(2) peak and ISWT, respectively, p < 0.001), multiple regression analysis suggested that FEV(1) was a marginally better predictor (rho = -0.64 and -0.65, p < 0.001). HRCT also related significantly to health status (rho = -0.37 for SGRQ activity, p < 0.05), although again FEV(1) showed a stronger relationship (rho = -0.43, p = 0.01). However, exercise capacity was the best predictor of health status with the ISWT accounting for up to 55% of the variability seen in SGRQ total and up to 53% of the SF-36 domain scores (physical functioning). Although both HRCT and lung function relate to health status, exercise capacity is the best predictor of patients disability in these patients with predominantly lower zone emphysema.
 ...
PMID:Exercise capacity predicts health status in alpha(1)-antitrypsin deficiency. 1128 69

Physiological and radiological criteria are both used to identify candidates for LVRS. This study compares the predictive value of these screening techniques among patients with homogeneous (Ho) and heterogeneous (He) emphysema. Preoperative inspiratory lung conductance (G(Li)) during spontaneous breathing and quantitative radioisotope V/Q scan (QVQS) results were available for 48 of 50 patients undergoing bilateral LVRS for emphysema. Ho disease (n = 21) was defined by QVQS as an upper/lower perfusion ratio (ULPR) between 0.75 and1.25. G(Li) correlated with 6-mo improvement in FEV(1) (DeltaFEV(1)-6) (r = 0.53, p < 0.001) for the entire cohort, and for patients with both Ho (n = 21, r = 0.56, p = 0.015) and He disease (n = 27, r = 0.46, p = 0.017). ULPR correlated less well with DeltaFEV(1)-6 (n = 48, r = -0.38; p = 0.008) for the cohort, and was significantly correlated with outcomes only in the subgroup of patients with He disease (r = -0.40, p = 0.04). Multivariate regression demonstrated that by combining G(Li) and ULPR criteria, 33% of the DeltaFEV(1)-6 response could be accounted for. We conclude that both physiological and radiological criteria help identify appropriate candidates for LVRS. G(Li) best identifies patients with Ho emphysema who may benefit from surgery, but would be excluded on the basis of strictly radiological criteria. ULPR helps identify patients with He disease that improves with surgery, despite unfavorable G(Li).
 ...
PMID:Comparison of physiological and radiological screening for lung volume reduction surgery. 1131 37

Part of the functional benefit provided by lung volume reduction surgery (LVRS) may be related to improvement in respiratory muscle function resulting from changes in diaphragm dimension and configuration. To study these changes, we obtained 3D reconstructions of the muscle using spiral computed tomography in 11 patients with severe emphysema before and 3 mo after surgery, and in 11 normal subjects matched for sex, age, height, and weight. Bilateral LVRS was performed by thoracoscopy in eight patients and by sternotomy in three patients. Acquisitions were made in the supine posture at relaxed FRC, midinspiratory capacity, and TLC. On average, LVRS produced a 51 +/- 11% increase in FEV(1) and a 30 +/- 4% decrease in FRC. The total surface area of the diaphragm (A(di)) and of the zone of apposition (A(ap)) at FRC increased by 17 +/- 4% and 43 +/- 8%, respectively, but the surface area of the dome did not change. Compared with the values recorded in the normal subjects, postoperative values of A(di) and A(ap) at FRC were reduced by 11% (p < 0.05) and 24% (p < 0.005), respectively. The curvature of the dome increased at TLC in the left sagittal plane, but was otherwise unaffected by the procedure. We conclude that LVRS substantially increases A(di) and A(ap), but does not significantly improve diaphragm configuration at FRC.
 ...
PMID:Effects of lung volume reduction surgery for emphysema on diaphragm dimensions and configuration. 1131 27

Current datum more than 2 yr after lung volume reduction surgery (LVRS) for emphysema is limited. This prospective study evaluates pre-LVRS baseline and 5-yr results in 26 symptomatic patients (mean age 67 +/- 6 yr) (mean +/- SD) who underwent bilateral, targeted upper lobe stapled LVRS using video-assisted thoracoscopy. Baseline forced expiratory volume in 1 s (FEV(1)) was 0.7 +/- 0.2 L (mean +/- SD), 29 +/- 10% predicted. Following LVRS, with none lost to follow-up, mortality due to respiratory failure at 0.5, 1, 2, 3, 4, and 5 yr was 4%, 4%, 19%, 31%, 46%, and 58%, respectively. Increase above baseline for FEV(1) > 200 ml and/or FVC > 400 ml at 1, 2, 3, 4, and 5 yr post-LVRS was noted in 73%, 46%, 35%, 27%, and 8% of all patients; decrease in dyspnea grade >/= 1 in 88%, 69%, 46%, 27%, and 15%; and elimination of initial oxygen dependence in 18 patients in 78%, 50%, 33%, 22%, and 0%, respectively. Expiratory airflow improved due to the increase in both lung elastic recoil and small airway intraluminal caliber. Five patients decreased FEV(1) 141 +/- 60 ml/yr and FVC 102 +/- 189 ml/yr over 3.8 +/- 1.2 yr post-LVRS, similar to their pre-LVRS rate of decline. In the 11 patients who survived 5 yr, at 0.5-1.0 yr post-LVRS peak increase in FEV(1) was 438 +/- 366 ml, with a decline of 149 +/- 157 ml the following year and 78 +/- 59 ml/yr over 4.0-4.5 yr. Bilateral LVRS provided palliative clinical and physiological improvement in 9 of 26 patients at 3 yr, 7 at 4 yr, and 2 at 5 yr.
 ...
PMID:Lung function 5 yr after lung volume reduction surgery for emphysema. 1140 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>