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Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease.
Bourbeau J; Rouleau MY; Boucher S McGill University Health Centre, McGill University, Montreal, Canada.
Thorax (England) Jun 1998, 53 (6) p477-82
BACKGROUND: Inhaled corticosteroids are known to be beneficial for patients with asthma, but their role in treating patients with stable chronic obstructive pulmonary disease (COPD) remains controversial. A study was undertaken to determine whether inhaled corticosteroids are of functional benefit in patients who did not show improvement with a trial of oral corticosteroids.
METHODS: In phase I patients with stable COPD were given a two week course of oral placebo followed by two weeks of prednisone 40 mg per day in a single blind manner to distinguish between responders and non-responders to oral corticosteroids. In phase II a double blind, randomised, parallel group trial of inhaled budesonide 1600 micrograms per day versus placebo was carried out in 79 nonresponders to oral corticosteroids. The primary outcome measure was forced expiratory volume in one second (FEV1), and secondary outcome measures were exercise capacity, dyspnoea with exertion, quality of life, peak expiration flow rate, and respiratory symptoms.
RESULTS: Randomisation allocated 39 subjects to inhaled corticosteroids and 40 to placebo. There was no difference in the change in FEV1 from baseline between the treatment and placebo groups; mean difference -12 ml (95% CI -88 to 63) at three months and -4 ml (95% CI -95 to 87) at six months. The proportion of patients with a 15% or greater improvement was no higher among those receiving inhaled corticosteroids than in the placebo group at any of the follow up visits. Changes in secondary outcomes were also no different.
CONCLUSIONS: Inhaled corticosteroids, even at high doses, were of no physiological or functional benefit in these patients with advanced COPD.
Risk factors associated with glucocorticoid-induced adverse effects in children with severe asthma.
Covar RA, Leung DY, McCormick D, Steelman J, Zeitler P, Spahn JD. Ira J. and Jacqueline Neimark Laboratory of Clinical Pharmacology in Pediatrics, Divisions of Clinical Pharmacology, Denver, CO, USA.
J Allergy Clin Immunol 2000 Oct;106(4):651-9
BACKGROUND: Although high-dose inhaled glucocorticoids (GCs) with or without chronically administered oral GCs are often used in children with severe persistent asthma, the adverse effects associated with their use have not been well-described in this patient population.
OBJECTIVE: We sought to determine the GC-induced adverse effects profile of older children with severe persistent asthma. METHODS: A chart review of 163 consecutive children 9 years of age or older admitted to National Jewish for difficult to control asthma was done.
RESULTS: The population studied consisted mostly of adolescents (mean +/- SD age, 14.4 +/- 2.1 years) with severe asthma receiving high-dose inhaled GC therapy (1675 +/- 94 microg/d) and averaging 6 systemic GC bursts per year. 50% required chronic oral GC therapy. GC-associated adverse effects were common and included hypertension (88%), cushingoid features (66%), adrenal suppression (56%), myopathy (50%), osteopenia (46%), growth suppression (39%), obesity and hypercholesterolemia (30%), and cataracts (14%). Height standard deviation scores of -0.44, -1.22, and -0.93 for those receiving intermittent, alternate day, and daily oral GCs, respectively, were smaller (less suppressed) than published values from the same institution before inhaled GC therapy (standard deviation scores of -1.26, -1.91, and -1.95, respectively). Osteopenia was strongly associated with growth suppression (odds ratio, 5.6; confidence interval, 2.7-11.8; < 0001) and was found to be more common in female than male subjects, even after correcting for short stature (42% vs 18%, < 006).
CONCLUSIONS: GC-associated adverse effects are still unacceptably common among children with severe asthma, even in those not receiving chronically administered oral GC therapy yet receiving high-dose inhaled GCs. Therefore close monitoring and proper intervention are warranted, especially in female subjects, who appear to be at greater risk for osteopenia. There is clearly a need to consider alternative therapy or earlier intervention. The magnitude of growth suppression, while still a problem, appeared to be less severe with the addition of inhaled GC therapy. This observation suggests that high-dose inhaled GC therapy, by affording better asthma control and allowing less use of systemic therapy, has attenuated the growth-suppressive effects of poorly controlled asthma.
Retinoic acid as a therapy for emphysema?
DeLuca LM, Ross SA Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892-4255, USA.
Nutr Rev 1997 Aug;55(8):307-8
In concert with its action as a morphogen during embryonal development, retinoic acid appears to be able to regenerate lung alveoli in an experimental model of elastase-induced emphysema in rats, thereby inhibiting manifestation of the disease. The application to humans is now an interesting possibility.
Does lung transplantation prolong life? A comparison of survival with and without transplantation.
Geertsma A; Ten Vergert EM; Bonsel GJ; de Boer WJ; van der Bij W Office for Medical Technology Assessment, University Hospital Groningen, The Netherlands. a.geertsma@mta.azg.nl
J Heart Lung Transplant (United States) May 1998, 17 (5) p511-6
BACKGROUND: Because of the assumed beneficial effect of lung transplantation on survival, controlled trials to assess the therapeutic benefit of lung transplantation are considered to be unethical. Therefore other methods must be used to provide control data. In this study the effect of lung transplantation on survival for patients with end-stage pulmonary disease was analyzed, with waiting list survival rates used as control data.
METHODS: The analysis was based on 157 consecutive patients who were put on the waiting list of the Dutch lung transplantation program during the period November 1990 to January 31, 1996, of whom 76 underwent transplantation. Following the principles of control group estimation as set out in the context of heart transplantation, a stepwise approach was used to arrive at a multivariate time-dependent Cox regression model. The following prognostic variables were included in the analyses: age, forced expiratory volume in 1 second, partial pressure of carbon dioxide, partial pressure of oxygen, and diagnosis.
RESULTS: The 1- and 2-year waiting list survival rates were 78% and 58%, respectively. The 1- and 2-year transplantation survival rates (i.e., survival from placement on the waiting list, including posttransplantation survival) were 79% and 64%, respectively. The multivariate time-dependent Cox analysis showed that lung transplantation reduced the risk of dying by 55% (95% confidence interval, 3% to 79%). For patients with emphysema the risk of dying was estimated to be 77% lower than for patients with other diagnoses (96% confidence interval, 50% to 89%).
CONCLUSIONS: With Cox regression, adjusting for age, forced expiratory volume in 1 second, partial pressure of carbon dioxide, partial pressure of oxygen, and diagnosis, lung transplantation showed a statistically significant effect on survival in selected patients with end-stage pulmonary disease.
The risk of cataract among users of inhaled steroids.
Jick SS, Vasilakis-Scaramozza C, Maier WC. Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, MA 02421, USA.
Epidemiology 2001 Mar;12(2):229-34
Prolonged exposure to inhaled corticosteroids among adults over 49 years old has been reported to increase cataract risk. Small-scale studies of inhaled steroid users suggest that no increased risk for children and young adults exists. To describe cataract risk among people with asthma who use inhaled corticosteroids relative to patients with asthma with no history of corticosteroid use, we conducted a retrospective observational cohort study of patients identified from the United Kingdom-based General Practice Database with a nested case-control analysis. Relative to patients who do not use corticosteroids, all inhaled corticosteroid users were at a marginally increased risk of cataract (RR = 1.3). Among individuals 40 years of age or older, the risk ratio increased with use of increasing numbers of inhaled corticosteroid prescriptions after controlling for diabetes mellitus, hypertension, and smoking history. This trend was not evident in those under age 40.
Oxidants/antioxidants and chronic obstructive pulmonary disease: pathogenesis to therapy.
MacNee W. ELEGI/Colt Laboratories, Department of Medical and Radiological Sciences, Wilkie Building, University of Edinburgh, Medical School, Teviot Place, Edinburgh EH8 9AG, UK.
Novartis Found Symp 2001;234:169-85; discussion 185-8
There is now considerable evidence for an increased oxidant burden in smokers, particularly in those smokers who develop chronic obstructive pulmonary disease (COPD), as shown by increased markers of oxidative stress in the airspaces, breath, blood and urine. The presence of increased oxidative stress is a critical feature in the pathogenesis of COPD, since it results in inactivation of antiproteinases, airspace epithelial injury, mucus hypersecretion, increased sequestration of neutrophils in the pulmonary microvasculature, and gene expression of pro-inflammatory mediators. The sources of the increased oxidative stress in patients with COPD derive from the increased burden of oxidants present in cigarette smoke, or from the increased amounts of reactive oxygen species released from leukocytes, both in the airspaces and in the blood. Antioxidant depletion or deficiency in antioxidants also contributes to oxidative stress. The development of airflow limitation is related to dietary deficiency of antioxidants and hence dietary supplementation may be a beneficial therapeutic intervention in this condition. Oxidative stress also has a role in enhancing the airspace inflammation, which occurs in smokers and patients with COPD through the activation of redox-sensitive transcriptions factors such as NF-kappa B and AP-1, which regulate the genes for pro-inflammatory mediators and protective antioxidant gene expression. Antioxidants that have good bioavailability or molecules that have antioxidant enzyme activity are therefore therapies that not only protect against the direct injurious effects of oxidants, but also may fundamentally alter the inflammatory events which have a central role in the pathogenesis of COPD.
A pilot study of all-trans-retinoic acid for the treatment of human emphysema.
Mao JT, Goldin JG, Dermand J, Ibrahim G, Brown MS, Emerick A, McNitt-Gray MF, Gjertson DW, Estrada F, Tashkin DP, Roth MD. Pulmonary and Critical Care Medicine, UCLA School of Medicine, Los Angeles, CA 99095-1690, USA.
Am J Respir Crit Care Med 2002 Mar 1;165(5):718-23
Emphysema results from progressive destruction of alveolar septae and was considered irreversible until all-trans-retinoic acid (ATRA) was shown to reverse anatomic and physiologic signs of emphysema in a rat model. To evaluate the feasibility of ATRA as a clinical therapy, 20 patients with severe emphysema were enrolled into a randomized, double-blind, placebo-controlled pilot study. Participants included 16 male and 4 female former smokers, two with alpha(1)-antitrypsin deficiency. Patients were treated with either 3 mo of ATRA (50 mg/m(2)/d) or 3 mo of placebo, followed by a 3-mo crossover phase. Plasma drug levels were followed and outcome measures included serial pulmonary function tests, blood gases, lung compliance, computed tomography (CT) imaging, and quality of life questionnaires. In general, treatment was well tolerated and associated with only mild side effects including skin changes, transient headache, hyperlipidemia, transaminites, and musculoskeletal pains. Plasma drug levels varied considerably between subjects and decreased significantly over time in 35% of the participants. Physiologic and CT measurements did not change appreciably in response to therapy. We conclude that ATRA is well tolerated in patients with emphysema, and trials evaluating higher doses, longer treatment, or different dosing schedules are feasible.
Postnatal treatment with retinoic acid increases the number of pulmonary alveoli in rats.
Massaro GD, Massaro D Lung Biology Laboratory, Georgetown University School of Medicine, Washington, District of Columbia 20007, USA.
Am J Physiol 1996 Feb;270(2 Pt 1):L305-10
Dexamethasone, a glucocorticosteroid hormone, inhibits the formation of alveoli; retinoids and glucocorticosteroid hormones can be mutually antagonistic. These observations led us to test the hypothesis that the administration of retinoic acid to postnatal rats would prevent the low alveolar number and the low body mass-specific gas-exchange surface area (Sa) produced by treatment with dexamethasone. We used serial lung sections to distinguish alveoli from alveolar ducts and stereological procedures that allow quantitation of alveoli uninfluenced by their size, shape, or distribution. Treatment with retinoic acid prevented the low number of alveoli and the low body mass-specific Sa caused by treatment with dexamethasone. In otherwise untreated rats, retinoic acid caused a 50% increase in the number of alveoli, but without an increase in Sa, suggesting the action of a regulatory mechanism to prevent unneeded Sa. These findings provide the first experimental support for the possibility that, in individuals with too few alveoli for adequate gas exchange, treatment with a pharmacological agent may provide preventative or remedial therapy.
[Mechanism of short-term improvement in exercise tolerance after lung volume reduction surgery for severe emphysema]
Matsuzawa Y; Kubo K; Fujimoto K; Eda S; Hanaoka M; Yamazaki Y; Kobayashi T; Sekiguchi M; Yamanda T; Haniuda M First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Nihon Kokyuki Gakkai Zasshi (Japan) Apr 1998, 36 (4) p323-9
To investigate the mechanism of short-term improvement in exercise tolerance after lung volume reduction surgery (LVRS) for severe emphysema, we performed six-minute walk tests and pulmonary-function tests, and studied their correlation before and 3-to-5 months after LVRS in 7 patients with severe emphysema who underwent bilateral lung reduction via median sternotomy. Results of the tests showed a 59% increase in the 1-second forced expiratory volume (FEV1), a 25% reduction in the functional residual capacity (FRC), a 49% increase in the maximum voluntary ventilation (MVV), and a 20% increase in the distance walked in 6 minutes (6 MD). The degree of improvement in 6 MD correlated significantly with the degree of improvement in FEV1 (r = 0.97, < 0.01), in FRC (r = 0.86, < 0.05), and in MVV (r = 0.87, < 0.05), and did not correlate with the degree of improvement in pulmonary gas exchange. These results support the hypothesis that an increase in lung elastic recoil after targeted emphysematous resection reduces airflow limitation, and thus leads to a short-term improvement in exercise tolerance after LVRS.
Outcome of Medicare patients with emphysema selected for, but denied, a lung volume reduction operation.
Meyers BF; Yusen RD; Lefrak SS; Patterson GA; Pohl MS; Richardson VJ; Cooper JD Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Ann Thorac Surg (United States) Aug 1998, 66 (2) p331-6
BACKGROUND: Lung volume reduction operation shows promise in relieving symptoms and improving function in highly selected patients with emphysema . Withdrawal of Medicare funding for patients selected for operation by standard criteria created a matched control group with which to compare lung volume reduction recipients.
METHODS: A retrospective study was done comparing 22 volume reduction candidates denied operation with 65 contemporaneous and comparable volume reduction recipients. Baseline physiologic characteristics were compared and longitudinal measures of pulmonary function were followed up for 24 months.
RESULTS: Patients denied operation were similar to volume reduction recipients in all baseline measurements. Patients denied operation experienced a progressive worsening of their function, whereas volume reduction patients experienced sustained improvements . Absolute survival to date is 82% for the surgical group and 64% for the medical group.
CONCLUSIONS: The improvement seen in volume reduction patients cannot be attributed to the effects of patient selection or preoperative and postoperative rehabilitation.
Reduced platelet glutathione peroxidase activity and serum selenium concentration in atopic asthmatic patients.
Misso NL, Powers KA, Gillon RL, Stewart GA, Thompson PJ. Department of Medicine, University of Western Australia, Queen Elizabeth II Medical Centre, Perth, Australia.
Clin Exp Allergy 1996 Jul;26(7):838-47
BACKGROUND: Asthmatic inflammation results in increased oxygen free radical generation and assessment of the activity of the selenium (Se) dependent anti-oxidant enzyme, glutathione peroxidase (GSH-Px) in asthma may therefore be important. OBJECTIVE: To test the hypothesis that reduced GSH-Px activity and Se intake contribute to asthmatic inflammation, platelet and whole blood GSH-Px activities and serum and whole blood Se concentrations were measured and compared in atopic and non-atopic asthmatic patients and non-asthmatic control subjects. METHODS: GSH-Px activities of whole blood and isolated platelets were assessed in 41 asthmatic patients (33 atopic) and 41 age- and sex-matched non-asthmatic subjects (15 atopic) by spectrophotometric assay based on the oxidation of NADPH. Se concentrations were determined by semi-automated fluorimetric assay. RESULTS: Mean (+/-SD) platelet GSH-Px activity was lower in asthmatic (89.5 +/- 45.7 mumol NADPH oxidized min-1 g-1 of protein) than in non-asthmatic subjects (109.9 +/- 41.9; P = 0.038) and in atopic (89.7 +/- 45.1, n = 48) compared with non-atopic subjects (113.7 +/- 40.9, n = 34; P = 0.016). Mean whole blood GSH-Px activity was also lower in atopic (12.2 +/- 5.2 mumol NADPH oxidized min-1 g-1 of Hb) than in non-atopic subjects (14.5 +/- 4.2; P = 0.038). In non-asthmatic subjects, the mean whole blood GSH-Px activity was lower in men (9.9 +/- 3.5) than in women (14.5 +/- 3.7; P = 0.0004) and was positively correlated with age (r = 0.51; P = 0.0006). Mean serum Se was lower in asthmatic (1.07 +/- 0.12 mumol/L) than in non-asthmatic subjects (1.16 +/- 0.31; P = 0.036). Using multiple linear regression, asthma was an independent predictor of decreased platelet GSH-Px after gender, age and serum Se were taken into account (P = 0.048) while atopy was a significant predictor of low whole blood GSH-Px independent of asthma, gender, age and whole blood Se (P = 0.033). CONCLUSIONS: In addition to Se status, atopy, gender and age all appear to influence GSH-Px activity, although the relative importance of these factors may differ in asthmatic and non-asthmatic populations. It seems likely that the reduced activity of this enzyme in platelets and blood may reflect mechanisms associated with the pathogenesis and severity of asthma.
Improved lung function and quality of life following increased elastic recoil after lung volume reduction surgery in emphysema.
Norman M; Hillerdal G; Orre L; Jorfeldt L; Larsen F; Cederlund K; Zetterberg G; Unge G Department of Thoracic Physiology, Karolinska Hospital, Stockholm, Sweden.
Respir Med (England) Apr 1998, 92 (4) p653-8
Lung volume reduction surgery for severe emphysema with removal of 20-30% of the most destroyed parts of the lung parenchyma has been reported to improve lung function substantially. Increased elastic recoil has been suggested as one underlying mechanism for the improvement . Fourteen patients, seven men and seven women with a mean age of 62 years, who underwent bilateral lung volume reduction surgery have been followed up for 3 months. We here report the data on quality of life, lung function and elastic recoil. FEV1.0 increased by a mean of 26% from 0.581 to 0.731 (< 0.01). The mean TLC was reduced by 16% from 8.91 to 7.51 (< 0.001). The level of hyperinflation decreased as implied by a reduction in the ratio of RV to TLC from 0.70 to 0.60 (< 0.001). The pulmonary elastic recoil improved, with an increase in the transpulmonary pressure at maximal inspiration (PelTLC) from 0.95 kPa to 1.35 kPa (< 0.05) and an average increase in the coefficient of retraction PelTLC/TLC) from 0.12 kPa l-1 to 0.19 kPa l-1 (< 0.01). The resting PaO2 increased from a mean of 8.7 kPa to 9.8 kPa (< 0.01). The patients reported a high degree of subjective improvement according to the St. George's Respiratory Questionnaire and the working capacity on a bicycle increased by 26% from a mean of 38 W to 48 W (< 0.01). The promising short-term results of lung volume reduction surgery for severe emphysema appear to be related to improved pulmonary elastic recoil.
Assessment of vitamin A status in chronic obstructive pulmonary disease patients and healthy smokers.
Paiva SA, Godoy I, Vannucchi H, Favaro RM, Geraldo RR, Campana AO. Department of Internal Medicine, Faculty of Medicine of Botucatu UNESP, Brazil.
Am J Clin Nutr 1996 Dec;64(6):928-34
The relation between vitamin A status and the degree of lung airway obstruction was examined in a cross-sectional study of 36 male subjects aged 43-74 y who were assigned to five groups as follows: healthy nonsmokers (n = 7), healthy smokers (n = 7), mild chronic obstructive pulmonary disease (COPD-mild) patients (n = 9), COPD-moderate-severe patients (n = 7), and COPD-moderate-severe patients with exacerbation (+ex; n = 6). Smoking habits, pulmonary function tests, energy-protein status were assessed; serum concentrations of retinyl esters, retinol, retinol binding protein, and transthyretin and relative dose responses were measured. In addition, 12 male smokers aged 45-61 y with mild COPD were randomly assigned to two groups for a longitudinal study: six subjects consumed vitamin A (1000 RE/d; COPD-vitamin A) and six subjects received placebo for 30 d. Lowered serum retinol concentrations were found in the COPD-moderate-severe and COPD-moderate-severe+ex groups. Measurements of vitamin A status in healthy smokers and in COPD-mild patients were not different from those in healthy nonsmokers. The improvement of pulmonary function test results after vitamin A supplementation [mean increase for 1-s forced expiratory volume (FEV1) = 22.9% in the COPD-vitamin A group] may support the assumption of a local (respiratory) vitamin A deficiency in patients with this disease.
The effects of nebulised isotonic saline and terbutaline on breathlessness in severe chronic obstructive pulmonary disease (COPD).
Poole PJ, Brodie SM, Stewart JM, Black PN. Department of Medicine, Faculty of Medicine and Health Sciences, University of Auckland, NZ.
Aust N Z J Med 1998 Jun;28(3):322-6
BACKGROUND: There is anecdotal evidence that nebulised saline relieves breathlessness at rest in patients with severe chronic obstructive pulmonary disease (COPD). It is unclear whether nebulised beta agonists are any more effective than nebulised saline in relieving breathlessness at rest in these individuals. AIM: To compare the effects of nebulised saline and nebulised terbutaline on breathlessness at rest in patients with severe COPD. METHODS: We studied 18 patients with severe COPD with a mean age of 71.1 years, forced expiratory volume in 1 second (FEV1) of 0.58 L and vital capacity (VC) of 1.59 L, in a randomised, double-blind, crossover trial. The subjects received three doses of nebulised saline on one study day, and three doses of nebulised terbutaline (cumulative dose 10 mg) on the other. Breathlessness was measured using Likert and Visual Analogue Scales (VAS). RESULTS: Both treatments led to a significant improvement in breathlessness on VAS and Likert scales but there was no significant difference in breathlessness scores for saline compared with terbutaline. There was a small but significant increase in FEV1 with terbutaline of 74 mL, but no change with saline. CONCLUSIONS: A saline aerosol has no effect on lung function but reduces breathlessness at rest in subjects with severe COPD. Nebulised saline may be considered as an adjunct to the use of nebulised bronchodilators for the treatment of breathlessness in patients with COPD.
Systemic oxidative stress in asthma, COPD, and smokers
Rahman I.; Morrison D.; Donaldson K.; MacNee W. Respiratory Medicine Unit, Department of Medicine, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW United Kingdom
American Journal of Respiratory and Critical Care Medicine (USA), 1996, 154/4 I (1055-1060)
An imbalance between oxidants and antioxidants is proposed in smokers and in patients with airways diseases. We tested this hypothesis by measuring the Trolox equivalent antioxidant capacity (TEAC) of plasma and the levels of products of lipid peroxidation as indices of overall oxidative stress. The plasma TEAC was markedly reduced (0.66 plus or minus 0.07 mmol/L; mean plus or minus SEM; n = 11), with increased levels of lipid peroxidation products, in healthy chronic smokers as compared with healthy nonsmokers (1.31 plus or minus 0.10 mmol/L, n = 14, < 0.001), an effect that was exaggerated in those who had smoked 1 h before the study. Plasma TEAC was also low in patients presenting with acute exacerbations of chronic obstructive pulmonary disease (COPD) (0.46 plus or minus 0.10 mmol/L, n = 20, < 0.001) or asthma (0.61 plus or minus 0.05 mmol/L, n = 9, < 0.01) with increases in plasma lipid peroxidation products. There was a negative correlation between superoxide anion release by stimulated neutrophils and plasma antioxidant capacity (r = -0.73, < 0.001) in patients with acute exacerbations of COPD. The profound decrease in TEAC was associated with a decreased plasma protein sulfhydryl concentrations in acute exacerbations of COPD but not in smokers or in asthmatic subjects. Therefore smoking, acute exacerbations of COPD, and asthma are associated with a marked oxidant/antioxidant imbalance in the blood, associated with evidence of increased oxidative stress. The decreased antioxidant capacity in plasma may result from different mechanisms in these conditions.
The antioxidative defense in asthma.
Tekin D, Sin BA, Mungan D, Misirligil Z, Yavuzer S. Department of Physiology, Faculty of Medicine, University of Ankara, Turkey.
J Asthma 2000 Feb;37(1):59-63
Asthma is a disease characterized by chronic airway inflammation. Generation of oxygen free radicals by activated inflammatory cells produces many of the pathophysiologic changes associated with asthma and may contribute to its pathogenesis. However, the activities of antioxidant enzymes and their relation with asthma have not been well defined. This study was performed to examine the activities of major intracellular antioxidants in mild asthmatic patients. Twelve asymptomatic mild asthmatic patients who never used any antiasthma medication and 13 age- and sex-matched healthy control subjects were selected. The activities of erythrocyte antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione-peroxidase (GSH-Px) were measured spectrophotometrically. The mean SOD activity of asthmatic patients was found to be significantly lower than that of the controls (< 0.05). There was no significant difference in CAT and GSH-Px activities between patients and controls (< 0.05). Although the mechanisms underlying the association between asthma and antioxidant system are unclear, according to our findings, decreased antioxidant protection may contribute to the pathogenesis of mild asthma.
Lung volume reduction surgery for emphysema. A review.
Sabanathan A; Sabanathan S; Shah R; Richardson J Department of Cardio-Thoracic Surgery, Bradford Royal Infirmary, UK.
J Cardiovasc Surg (Torino) (ITALY) Apr 1998, 39 (2) p237-43
Lung volume reduction surgery is emerging as a promising treatment option for selected patients with severe, debilitating end-stage emphysema refractory to medical management. Lung volume reduction surgery involves the removal of space occupying severely diseased, slowly ventilating and hyperexpanded lung, thus allowing the better conserved adjoining lung parenchyma to expand into the vacated space and function effectively. The operation can be accomplished by unilateral or bilateral thoracoscopy, thoracotomy or median sternotomy. The most emphysematous areas are excised using stapling or laser techniques or both. This review summarises the results of lung volume reduction surgery performed by various operative techniques. Results indicate that in the majority of patients improvement occurs in subjective dyspnoea and objective pulmonary function while oxygen and steroid dependence are reduced or eliminated at the cost of acceptable mortality and morbidity. Even though bilateral procedures produced much greater improvement, it is emphasized that it is the lung resection and not the operative approach that is critical to the success of the operation. Regardless of the technique used, the surgical treatment of emphysema is palliative in nature. (61 Refs.)
Vitamin D binding protein variants and the risk of COPD.
Schellenberg D; Pare PD; Weir TD; Spinelli JJ; Walker BA; Sandford AJ Respiratory Health Network of Centres of Excellence, University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.
Am J Respir Crit Care Med (United States) Mar 1998, 157 (3 Pt 1) p957-61
Although the development of chronic obstructive pulmonary disease (COPD) in smokers shows genetic susceptibility, only alpha1-antitrypsin deficiency has been identified as a definite genetic risk factor. There have been three previous studies in which associations between Gc-globulin phenotypes and COPD have been investigated. Although some data suggest an association, the were inconclusive. Because smoking is the major risk factor for COPD, it may have been a confounding factor in previous studies. We have investigated Gc-globulin genotypic frequencies among 75 COPD patients and 64 nonobstructed controls. Both groups had significant smoking histories: pack-years (mean +/- SD) of 52 +/- 30 and 48 +/- 27, respectively. The results show that homozygosity for the Gc2 allele is protective against COPD (OR = 0.17, 95% CI = 0.03 to 0.83). There were no differences between genotypes for lung elastic recoil values or for the level of upstream airway resistance. Gc-globulin can enhance complement (C5a)-mediated neutrophil chemotaxis. Because neutrophils play a role in parenchymal destruction and airway inflammation, we examined whether Gc-globulin's ability to enhance neutrophil chemotaxis varied with genotype. We found no difference among genotypes with respect to neutrophil chemotaxis suggesting that the protective effect of the Gc2 allele is mediated through a different mechanism. |