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)

FEV(1) is fundamental to the diagnosis and staging of chronic obstructive pulmonary disease. In emphysema, airflow obstruction usually coexists with impairment of gas exchange, but discordance is not infrequent. We hypothesized that variations in the distribution of emphysema would be associated with functional differences and therefore account for discordant physiology. We used quantitative computed tomography to assess emphysema severity and distribution in 119 subjects with alpha1-antitrypsin deficiency (PiZ phenotype) and grouped them according to distribution pattern. In the 102 subjects with emphysema, 65 had a predominantly basal pattern ("basal"), but 37 (36%) had greater involvement of the upper regions ("apical"). Subjects from each group were matched for total volume of emphysema and age, and matched pairs analysis was used to relate emphysema distribution to clinical phenotype. Basal distribution was associated with greater impairment of FEV(1) (mean difference, 9.9% predicted; 95% confidence interval, 3.8 to 16.0; p = 0.002) but less impairment of gas exchange (Pa(O(2)) mean difference, 0.5 kPa, 0.03 to 0.1; p = 0.016) and alveolar-arterial oxygen gradient (mean difference, 0.7 kPa; 0.2 to 1.2; p = 0.007) than the apical distribution. Emphysema distribution correlated with physiologic discordance (r = -0.409, p < 0.001). The use of single physiologic parameters as a surrogate measure of emphysema severity may introduce systematic bias in the staging of subjects with emphysema.
 ...
PMID:Pattern of emphysema distribution in alpha1-antitrypsin deficiency influences lung function impairment. 1530 34

We examined small airway morphometry from resected lung specimens in 25 patients with severe emphysema undergoing lung volume reduction surgery (LVRS) and correlated their pathologic findings to changes in FEV(1) 6 months after LVRS. Patients were classified into two groups: responders had a more than 12% and a more than 200-ml change in FEV(1) at 6 months, and nonresponders had 12% or less and/or 200 ml or less change in FEV(1). Epithelial height (EH) and perimeters and areas of peribronchial smooth muscle, epithelium, and subepithelial space were measured quantitatively. The degrees of interstitial fibrosis, vascular sclerosis, goblet cell hyperplasia, squamous metaplasia, chronic inflammation, peribronchial fibrosis, and bullous disease were assessed semiquantitatively. Despite similar baseline characteristics, nonresponders had a greater EH (0.045 vs. 0.035 mm, p = 0.025), greater EH adjusted for basement membrane perimeter (0.040 vs. 0.011, p = 0.016), greater epithelial area adjusted for basement membrane area (0.561 vs. 0.499, p = 0.040), and less bullous disease (1.7 vs. 2.6, p = 0.011) compared with responders. We found a linear relationship between percentage change in FEV(1) and bullous disease and inverse relationships between percentage change in FEV(1) and interstitial fibrosis, goblet cell hyperplasia, peribronchial fibrosis, and vascular sclerosis. We conclude that small airway morphometry and lung histopathology in patients with severe emphysema have an important influence on changes in FEV(1) 6 months after LVRS.
 ...
PMID:Small airway morphometry and improvement in pulmonary function after lung volume reduction surgery. 1547 94

The term chronic obstructive pulmonary disease (COPD) is mainly characterised by an irreversible obstructive airway obstruction, that in most cases, is secondary to tobacco exposure. Management of the disease includes an assessment of severity, and measures to decrease FEV decline, to treat bronchial obstruction, to improve exercise tolerance and to correct abnormal gas exchange. Treatment not only requires drug therapy, but also respiratory rehabilitation, surgery of emphysema, and psychosocial support. In this way, a global strategy, adapted to the severity of COPD, can be proposed.
 ...
PMID:[Management of stable COPD]. 1549 96

Severe alpha(1)-antitrypsin (AAT) deficiency is an inherited disorder that leads to the development of emphysema in smokers at a relatively young age; most are disabled in their forties. Emphysema is caused by the protease-antiprotease imbalance when smoking-induced release of neutrophil elastase in the lung is inadequately inhibited by the deficient levels of AAT, the major inhibitor of neutrophil elastase. This protease-antiprotease imbalance leads to proteolytic damage to lung connective tissue (primarily elastic fibers), and the development of panacinar emphysema. AAT replacement therapy, most often applied by weekly intravenous infusions of AAT purified from human plasma, has been used to partially correct the biochemical defect and raise the serum AAT level above a theoretically protective threshold level of 0.8 g/L. A randomized controlled clinical trial was not considered feasible when purified antitrypsin was released for clinical use. However, AAT replacement therapy has not yet been proven to be clinically effective in reducing the progression of disease in AAT-deficient patients. There was a suggestion of a slower progression of emphysema by computed tomography (CT) scan in a small randomized trial. Two nonrandomized studies comparing AAT-deficient patients already receiving replacement therapy with those not receiving it, and a retrospective study evaluating a decline in FEV(1) before and after replacement therapy, suggested a possible benefit for selected patients. Because of the lack of definitive proof of the clinical effectiveness of AAT replacement therapy and its cost, we recommend reserving AAT replacement therapy for deficient patients with impaired FEV(1) (35-65% of predicted value), who have quit smoking and are on optimal medical therapy but continue to show a rapid decline in FEV(1) after a period of observation of at least 18 months. A randomized placebo-controlled trial using CT scan as the primary outcome measure is required. Screening for AAT deficiency is recommended in patients with chronic irreversible airflow obstruction with atypical features such as early onset of disease or disability in their forties or fifties, or positive family history, and in immediate family members of patients with AAT deficiency.
 ...
PMID:Emphysema in alpha1-antitrypsin deficiency: does replacement therapy affect outcome? 1572 45

Alpha-1 antitrypsin (AAT) is a protein that prevents enzymes such as elastin from degrading normal host tissue. Individuals who are deficient in AAT (those with levels < 11 micromol/L) are at risk for developing such clinical manifestations as emphysema, cirrhosis, panniculitis, and anticytoplasmic neutrophilic antibody (C-ANCA)-positive vasculitis (Wegener's granulomatosis). Estimates suggest that 75 to 85% of those with severe deficiency of AAT will develop emphysema. Smoking appears to be the most important risk factor for the development of emphysema among AAT deficient persons. Severe deficiency of AAT also seems to be associated with a shorter lifespan. Among smokers, mild to moderate reductions in AAT levels may be associated with a more rapid decline in lung function. Diagnosis of AAT deficiency is made by measuring serum levels of AAT and, if reduced, an effort should then be made to identify the genetic abnormality responsible for the reduction. A recent evidence-based review has offered testing recommendations for AAT deficiency and includes the recommendation that all patients with COPD be tested for AAT deficiency. Augmentation with an intravenous form of purified pooled human plasma has been shown to increase the serum levels of AAT among deficient patients and its use appears to impact the rate of forced expiratory volume in 1 second (FEV (1)) decline and overall survival; to date, no confirmatory, large, prospective, randomized trials are available.
 ...
PMID:A review of alpha-1 antitrypsin deficiency. 1608 34

Many patients with severe chronic obstructive pulmonary disease (COPD) experience incapacitating breathlessness and exercise limitation. Multiple surgical techniques have been utilized to achieve resection of giant, localized bullae with documented short-term benefit in pulmonary function and dyspnea in highly selected patients. The poorest long-term outcome has been noted in those with greater degrees of emphysema in the remaining lung, greater underlying chronic bronchitis, and a bulla occupying less than one third of the hemithorax, particularly if compressed normal lung is not evident. Lung volume reduction surgery (LVRS) in the absence of giant bullae has become more widely accepted in selected patients. Bilateral LVRS procedures appear to result in greater short-term improvement than unilateral LVRS, whereas physiological benefits appear similar with video-assisted thoracoscopy (VATS) or median sternotomy (MS) techniques. Improvement in dyspnea and health status after LVRS has been documented and appears to be better preserved over longer-term follow-up than physiological improvement. Clear direction has been provided in identifying optimal candidates for bilateral LVRS; patients with a postbronchodilator forced expiratory volume in 1 second (FEV (1)) < or = 20% predicted and a diffusing capacity for carbon monoxide (DL (CO)) < or = 20% predicted or homogeneous emphysema exhibit a much higher mortality with LVRS than with medical management. Patients with upper-lobe predominant emphysema and a low postrehabilitation exercise tolerance exhibited a decreased risk of mortality after LVRS. Patients with non-upper lobe predominant emphysema on high-resolution computed tomography (HRCT) and a high postrehabilitation exercise capacity exhibit an increased risk of death after LVRS. Patients with upper lobe predominant emphysema and a high postrehabilitation exercise capacity or patients with non-upper lobe predominant emphysema and a low postrehabilitation exercise capacity do not have a survival advantage or disadvantage, whereas those with upper lobe predominant emphysema treated surgically are more likely to improve their exercise capacity after surgery. Lung transplantation is an option for a more limited number of patients. Consistent short-term spirometric improvement after both single- and double-lung transplant has been documented. Long-term results of lung transplantation are limited by significant complications that impair survival; an approximately 80% 1-year, 50% 5-year, and 35% 10-year survival has been reported. Bronchiolitis obliterans is the most important long-term complication of lung transplantation resulting in decreased pulmonary function. In general, a COPD patient can be considered an appropriate candidate for transplantation when the FEV (1) is below 25% predicted and/or the paCO (2) is > or = 55 mm Hg.
 ...
PMID:Surgical therapy for chronic obstructive pulmonary disease. 1608 35

The NETT study assessed the benefits of lung volume reduction surgery (LVRS) versus medical treatment. However, data is available only on the early outcome of LVRS (24 months). We evaluate the factors affecting the outcome at one-year and up to 6 years after LVRS. Thirty-seven patients underwent LVRS. Thirty-five patients, who survived the operation for at least one-year, were followed up to 6 years. Patients' laboratory, clinical and scintigraphic data before surgery were reviewed retrospectively, and follow-up at one-year and at the end of data collection. Successful LVRS with improvement of FEV(1)30% at one-year was observed in 13 of 35 patients. Five of these patients had initial FEV(1) values of <20% of the predicted. The group of patients with improvement was younger as compared to the 22 patients without improvement (P<0.005). The younger age group used less supplemental oxygen and had a PDiff of >23%. Combinations of age under 60 years and PDiff >23% were a favorable factor (P<0.002) for successful LVRS. Thirty-four patients were followed up to 6 years. Fifteen of the 34 patients (44.1%) remained well. Use of supplemental oxygen before surgery, and FEV(1) improvement of 30% at one-year after surgery were good prognostic factors. We concluded that the long-term success of LVRS is affected by non-dependence on oxygen supplementation before surgery, and the one-year post-surgical improvement of FEV(1) (30%). Based on our findings, the subgroup of patients below 60 years old with severe disease (FEV(1)<20%) and heterogeneous upper lobe emphysema (Pdiff>23%) has improved outcome.
 ...
PMID:Short- and long-term outcome of lung volume reduction surgery. The predictive value of the preoperative clinical status and lung scintigraphy. 1630 93

Chronic obstructive pulmonary disease (COPD) is often misdiagnosed as asthma, leading to inappropriate treatment and suboptimal patient outcomes. As part of a prospective study of patients with a history consistent with obstructive lung disease, we compared prior diagnostic labels with a study diagnosis based on spirometric results. We enrolled persons 40 years of age or older with prior diagnoses or medications consistent with obstructive lung disease. Patients were recruited via random mailing to primary care practices in Aberdeen, Scotland, and Denver, Colorado. Prior diagnoses of chronic bronchitis or emphysema (CBE) and asthma were reported by the subjects. Participants underwent pre- and post-bronchodilator spirometry. A study diagnosis of COPD was defined using post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) < 0.70. Spirometric examination was complete in 597 patients, of whom 235 (39.4%) had a study diagnosis of COPD. Among subjects with a spirometry-based study diagnosis of COPD, 121 (51.5%) reported a prior diagnosis of asthma without concurrent CBE diagnosis, 89 (37.9%) reported a prior diagnosis of CBE, and 25 (10.6%) reported no prior diagnosis of obstructive lung disease. Despite the availability of consensus guideline diagnostic recommendations, diagnostic confusion between COPD and asthma appears common. Increased awareness of the differences between the two conditions is needed to promote optimal patient management and treatment.
 ...
PMID:Misdiagnosis of COPD and asthma in primary care patients 40 years of age and over. 1644 70

We have evaluated the relationship between pulmonary function tests (PFT), thorax high resolution computed tomography (HRCT) images and quantitative ventilation-perfusion (V/Q) scintigraphic studies in 16 male patients (mean age 65.6 +/- 5.5 years) with chronic obstructive pulmonary disease (COPD). The mean forced vital capacity (FVC) value of the patient group was 2352 +/- 642 mL (65.4 +/- 15.8%), whereas mean forced expiratory volume in one second (FEV(1)) was found to be 1150 +/- 442 mL (40.8 +/- 14.9%). The ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA) was 3.17 +/- 0.88 mL/min/mmHg/L, and the mean partial oxygen (PaO(2)) and carbon dioxide (PaCO(2)) pressures were 68.5 +/- 11.04 mmHg and 38.9 +/- 5.8 mmHg respectively. For each patient, thorax HRCT and V/Q scintigraphic images of both lungs were divided into upper, mid and lower zones during examination. Visual scoring for the assessment of emphysema on thorax HRCT were used and images were graded from mild to severe (< or = 25% - > or = 76%). Emphysema scores were found to be higher on upper zones with accompanying lowest V/Q ratios. DLCO/VA, DLCO, total emphysema scores, and individual emphysema scores of the upper, mid and lower zones were found to be correlated. As a conclusion, it can be stated that emphysematous changes in COPD patients are more apparent in the upper lung zones, which also have the lowest V/Q ratios.
 ...
PMID:The relationship between pulmonary function tests, thorax HRCT, and quantitative ventilation-perfusion scintigraphy in chronic obstructive pulmonary disease. 1645 33

Recent guidelines define chronic obstructive pulmonary disease (COPD) as a preventable and treatable disease characterized by airflow limitation and systemic consequences. Airflow limitation in COPD worsens over years as assessed by the forced expiratory volume in one second (FEV(1)). Regardless, while it is likely that cardiovascular and other systemic components also worsen as COPD progresses, there are no accepted or validated outcomes to measure such pathophysiologic changes as they relate to COPD disease progression. It is clear that health status in COPD is more closely related to levels of patients' physical functional capacity than it is to changes in FEV(1). Furthermore, the relative contributions of pathoanatomic changes such as small airways fibrosis and pulmonary emphysema to declining airflow remain unknown. These features may even progress at different rates in the same individuals. Although stopping smoking is the only intervention shown to alter the relentless progression of COPD, the resultant slowing of FEV(1) decline takes several years to evince and requires at least 1,000 subjects to demonstrate annual therapeutic benefits of as little as 20 ml. The FEV(1) cannot distinguish between peribronchiolar fibrosis and emphysema and it is feasible that, as techniques are developed and validated, lung imaging methodologies may become important and sensitive outcomes measures of time- and age-dependent lung structural changes in COPD. The development of biomarkers of lung damage, pulmonary inflammation, and systemic disease will be essential to our further understanding of the natural history of COPD and the discovery of new, effective treatments for its progression.
 ...
PMID:Chronic obstructive pulmonary disease: linking outcomes and pathobiology of disease modification. 1663 98


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