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Oxidative stress and pulmonary function in the general population.

Studies have shown increased oxidative stress in patients with chronic airflow limitation; however, the population-based evidence for the association of oxidative stress with pulmonary function is limited. The authors analyzed the association of plasma thiobarbituric acid-reactive substances (TBARS), glutathione, glutathione peroxidase, and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox)-equivalent antioxidant capacity with forced expiratory volume in 1 second and forced vital capacity using data collected from 1996 to 2000 in a general population sample from western New York State (n = 2,346). After adjustment for covariates including smoking status, lifetime pack-years of smoking, education, weight, and eosinophils, multivariate analysis showed an inverse association of TBARS with forced expiratory volume in 1 second and forced vital capacity as the percentage of the predicted value (FEV1% and FVC%, respectively), positive associations of glutathione peroxidase with FEV1% and FVC%, and an inverse association of glutathione with FEV1% in men (p < 0.05). The associations of TBARS and glutathione peroxidase with FVC% in men remained statistically significant after adjustment for serum carotenoid levels. There were no statistically significant associations of oxidative stress with pulmonary function in women. These results suggest that oxidative stress may be associated with airflow limitation in men, and that gender differences may exist in the relation of oxidative stress to pulmonary function.

Biomarkers↗

High-resolution CT diagnosis of emphysema in symptomatic patients with normal chest radiographs and isolated low diffusing capacity.

To determine the prevalence of "nonobstructive" (impairment of gas transfer) emphysema in a select population of smokers with dyspnea, a retrospective study of patients with emphysema evident at high-resolution computed tomography (HRCT) was undertaken. Four hundred seventy HRCT studies were reviewed. In 47 cases, centrilobular emphysema was the dominant or sole parenchymal abnormality. Concomitant chest radiographs were available in 41 of these cases; 16 of the 41 lacked radiographic findings of emphysema. Among these 16 patients, pulmonary function testing revealed 10 to have normal flow rates (ratio of forced expiratory volume in 1 second to forced vital capacity and forced expiratory volume in 1 second greater than 80% predicted) and impaired gas transfer (single-breath carbon monoxide diffusing capacity [DLCOSB] less than 80% predicted). With the exclusion of one patient with congestive heart failure from the group of 10, the severity of emphysema at HRCT correlated inversely with DLCOSB (r = -.643). These results indicate that HRCT allows detection of emphysema in symptomatic patients when chest radiographs and pulmonary function tests are nondiagnostic.

Female↗

Spirometric reference equations for European females and males aged 65-85 yrs.

The aim of this study was to describe spirometric reference equations for healthy never-smoking European adults aged 65-85 yrs and to compare the predicted values of this sample with those from other studies including middle-aged and/or older adults. Reference equations and normal ranges for forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory volume in six seconds (FEV6), FEV1/FVC ratio and FEV1/FEV6 ratio were derived from a healthy subgroup of 458 subjects aged 65-85 yrs. Spirometry examinations followed the 1994 American Thoracic Society recommendations and the quality of the data was continuously monitored and maintained. Reference values and lower limits of normal were derived using a piecewise polynomial model with age and height as predictors. The reference values of FEV1 and FVC from the present study were higher than those given by prediction equations from the European Community for Coal and Steel. By contrast, use of prediction equations from Caucasian-American elderly subjects (Cardiovascular Health Study) consistently overpredicted FVC and FEV1 in females by 8.5 and 2.1%, respectively. In males, equations from the Cardiovascular Health Study overpredicted FVC by 2.8%, whilst underpredicting FEV1 by 2.5%. In conclusion, these results underscore the importance of using prediction equations appropriate to the origin, age and height characteristics of the subjects being studied.

Aged↗

Obstructive and restrictive spirometric patterns: fixed cut-offs for FEV1/FEV6 and FEV6.

The purpose of this study was to determine fixed cut-off points for forced expiratory volume in one second (FEV(1))/FEV(6) and FEV(6) as an alternative for FEV(1)/forced vital capacity (FVC) and FVC in the detection of obstructive and restrictive spirometric patterns, respectively. For the study, a total of 11,676 spirometric examinations, which took place on Caucasian subjects aged between 20-80 yrs, were analysed. Receiver-operator characteristic curves were used to determine the FEV(1)/FEV(6) ratio and FEV(6) value that corresponded to the optimal combination of sensitivity and specificity, compared with the commonly used fixed cut-off term for FEV(1)/FVC and FVC. The data from the current study indicate that FEV(1)/ FEV(6) <73% and FEV(6) <82% predicted can be used as a valid alternative for the FEV(1)/FVC <70% and FVC <80% pred cut-off points for the detection of obstruction and restriction, respectively. The statistical analysis demonstrated very good, overall, agreement between the two categorisation schemes. For the spirometric diagnosis of airway obstruction (prevalence of 45.9%), FEV(1)/FEV(6) sensitivity and specificity were 94.4 and 93.3%, respectively; the positive and negative predictive values were 92.2 and 95.2%, respectively. For the spirometric detection of a restrictive pattern (prevalence of 14.9%), FEV(6) sensitivity and specificity were 95.9 and 98.6%, respectively; the positive and negative predictive values were 92.2 and 99.3%, respectively. This study demonstrates that forced expiratory volume in one second/forced expiratory volume in six seconds <73% and forced expiratory volume in six seconds <82% predicted, can be used as valid alternatives to forced expiratory volume in one second/forced vital capacity <70% and forced vital capacity <80% predicted, as fixed cut-off terms for the detection of an obstructive or restrictive spirometric pattern in adults.

Adult↗

Effect of oral contraceptives on respiratory function.

The present study was carried out to assess the lung functions in oral contraceptive administered women. Lung function tests were carried out with Spirometer (Vitallograph Compact II). A significant increase in vital capacity (VC) was observed in these women as compared to normal control. There was also a significant decrease in forced expiratory volume in 1 sec./vital capacity (FEV1/VC%) and forced expiratory volume in 1 sec./forced vital capacity (FEV1/FVC%) among oral contraceptive administered women as compared to controls. Further, a significant increase in peak expiratory flow rate (PEF), reduction in forced expiratory flow rate (FEF75-85%) and FEF75% were observed among oral contraceptive administered women as compared to controls. The increase in VC and PEF might be due to the synthetic form of progesterone (progestins) present in oral contraceptive pills which causes hyperventilatory changes. Synthetic progesterone during luteal phase of menstrual cycle might increase the static and dynamic volumes of lung i.e. VC and PEF. But FEF75% showed a decrease which might be due to the lower neuromuscular coordination during breathing.

Adult↗

Smoking, socioeconomic status, and chronic respiratory disease.

Prevalence rates of chronic bronchitis and asthma and mean levels of ventilatory lung function were related to age, smoking habits, occupation, education, and income in 4,699 men and women living in Tecumseh, Michigan. The prevalence of chronic bronchitis was higher and mean levels of 1-sec forced expiratory volume were lower in cigarette smokers than in other men and women, and heavy smokers were affected more than light smokers. The prevalence of chronic bronchitis was higher and mean 1-sec forced expiratory volume was lower in blue collar workers than in white collar workers. Men and women with some college education had higher mean values for 1-sec forced expiratory volume than did those with less formal education, and the prevalence of chronic bronchitis was least among men with most education. Mean levels of 1-sec forced expiratory volume were slightly lower in those with the smallest incomes. There were no significant associations between the prevalence of asthma and smoking habits, occupation, education, or income. Most of the differences in the prevalence of chronic bronchitis and mean 1-sec forced expiratory volume in men and women of different occupational, educational, or income classes were due to differences in smoking habits. In comparison with smoking, poor occupational, educational, or economic circumstances had only a weak deleterious effect.

Adult↗

Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma: a multicenter, randomized, double-blind trial. Montelukast Clinical Research Study Group.

OBJECTIVES: To determine the clinical effect of oral montelukast sodium, a leukotriene receptor antagonist, in asthmatic patients aged 15 years or more. DESIGN: Randomized, multicenter, double-blind, placebo-controlled, parallel-group study. A 2-week, single-blind, placebo run-in period was followed by a 12-week, double-blind treatment period (montelukast sodium, 10 mg, or matching placebo, once daily at bedtime) and a 3-week, double-blind, washout period. SETTING/PATIENTS: Fifty clinical centers randomly allocated 681 patients with chronic, stable asthma to receive placebo or montelukast after demonstrating a forced expiratory volume in 1 second 50% to 85% of the predicted value, at least a 15% improvement in forced expiratory volume in 1 second (absolute value) after inhaled beta-agonist administration, a minimal predefined level of daytime asthma symptoms, and inhaled beta-agonist use. Twenty-three percent of the patients used concomitant inhaled corticosteroids. PRIMARY END POINTS: Forced expiratory volume in 1 second and daytime asthma symptoms. RESULTS: Montelukast improved airway obstruction (forced expiratory volume in 1 second, morning and evening peak expiratory flow rate) and patient-reported end points (daytime asthma symptoms, "as-needed" beta-agonist use, nocturnal awakenings) (P<.001 compared with placebo). Montelukast provided near-maximal effect in these end points within the first day of treatment. Tolerance and rebound worsening of asthma did not occur. Montelukast improved outcome end points, including asthma exacerbations, asthma control days (P<.001 compared with placebo), and decreased peripheral blood eosinophil counts (P<.001 compared with placebo). The incidence of adverse events and discontinuations from therapy were similar in the montelukast and placebo groups. CONCLUSIONS: Montelukast, compared with placebo, significantly improved asthma control during a 12-week treatment period. Montelukast was generally well tolerated, with an adverse event profile comparable with that of placebo.

Acetates↗

Long-term effects of metaproterenol in asthmatic children.

Oral metaproterenol was administered daily for 3 months to asthmatic children. The study was designed to determine whether chronic tolerance developed to this drug. Initial and final crossovers on the first 2 and the last 2 days of the investigation to a test dose of metaproterenol and placebo failed to show tolerance as indicated by improvement in lung volumes and dynamic mechanics of breathing after metaproterenol. Forced expiratory volume in 1 sec was the test most consistent in demonstrating bronchodilation; the action of metaproterenol. Forced expiratory volume in 1 sec was the test most consistent in demonstrating bronchodilation; the action of metaproterenol appeared to last at least 5 hours as measured by this test. T of distribution of ventilation, e.g., single- and multiple-breath nitrogen washout tests, were not consistently altered by metaproterenol. These tests did not appear to be sufficiently sensitive to detect improvement even when airway resistance decreased and forced expiratory volume in 1 sec increased toward the normal range.

Asthma↗

Ventilatory volumes, flow rates, transfer factor and its components (membrane component, capillary volume) in obese adults and children.

We have studied the ventilatory volumes, flow rates, transfer factor and its components (membrane component and capillary volume) in 19 women and 23 children with moderate obesity. The adults showed restrictive defects, but the pulmonary volumes of children were within normal range. Peak flow, flows at 75 and 50% forced expiratory volume, in two groups, normalized for the forced expiratory volume, did not differ between the two groups. The transfer factor was reduced in adults, because of reduction of the alveolar volume, the membrane component was low in both groups; transfer factor and membrane component normalized for functional residual capacity were not different between the two groups. The capillary volume was greater in children than adults, because the excess body weight was greater for the children. In simple obesity, the main alteration is the decrease of distensibility of the chest wall that becomes worse as time goes on and is the cause for the alterations in ventilatory volume, flow and transfer factor.

Adult↗

Use of technetium-99m tin colloid for sentinel lymph node identification in non-small cell lung cancer.

BACKGROUND: To test the reliability of sentinel lymph node identification in non-small cell lung cancer, sentinel nodes were localized with a radioactive colloid in patients undergoing surgery. METHODS: Forty-six patients with non-small cell lung cancer undergoing curative resection with mediastinal lymph node dissection were examined. The day before surgery, technetium-99m ((99m)Tc) tin colloid was injected into the peritumoral region. At operation, the radioactivity of the lymph nodes was counted with a handheld gamma counter before (in vivo) and after (ex vivo) dissection. Lymph nodes with an ex vivo radioactive count more than 10 times the background value were identified as sentinel nodes. The correlation between the in vivo and ex vivo results was examined. RESULTS: Lymphoscintigraphy revealed that it took longer than 6 hours for sufficient (99m)Tc tin colloid to reach the sentinel nodes. Sentinel nodes could be identified in 40 patients (87%). Patients whose sentinel nodes could not be identified had a significantly lower ratio of forced expiratory volume in 1 second to forced vital capacity than did those with identifiable sentinel nodes (P =.03). No false-negative sentinel nodes were detected in 14 patients with N1 or N2 disease (0%). In the hilar lymph node stations, the lobar lymph nodes were most frequently identified as sentinel nodes (as often as 85% of the time). Fourteen patients (35%) had sentinel nodes in the mediastinum, the distribution of which depended on the lobe. In vivo and ex vivo counting showed 88% concurrence for the identification of sentinel nodes in mediastinal lymph node stations. CONCLUSION: The identification of sentinel nodes with (99m)Tc tin colloid is a reliable method of establishing the first site of nodal metastasis in non- small cell lung cancer. Sentinel nodes could be hardly identified in patients with a low ratio of forced expiratory volume in 1 second to forced vital capacity because of such conditions as chronic obstructive pulmonary disease. In vivo identification of sentinel nodes in the mediastinum could be useful approach to guide mediastinal lymph node sampling or dissection.

Adult↗

Lung function in relation to intake of carotenoids and other antioxidant vitamins in a population-based study.

Accumulating evidence suggests that dietary antioxidant vitamins are positively associated with lung function. No evidence exists regarding whether dietary carotenoids other than beta-carotene are related to pulmonary function. In 1995--1998 the authors studied the association of forced expiratory volume in 1 second and forced vital capacity as the percentage of the predicted value (FEV(1)% and FVC%, respectively) after adjustment for height, age, gender, and race with the intakes of several carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, and lycopene) in a random sample of 1,616 men and women who were residents of western New York State, aged 35--79 years, and free from respiratory disease. They observed significant associations of lutein/zeaxanthin and vitamins C and E with FEV(1)% and FVC% using multiple linear regression after adjustment for total energy intake, smoking, and other covariates. When they analyzed all of these antioxidant vitamins simultaneously, they observed the strongest association of vitamin E with FEV(1)% and of lutein/zeaxanthin with FVC%. The differences in forced expiratory volume in 1 second and forced vital capacity associated with a decrease of 1 standard deviation of dietary vitamin E or lutein/zeaxanthin were equivalent to the influence of approximately 1--2 years of aging. Their findings support the hypothesis that carotenoids, vitamin C, and vitamin E may play a role in respiratory health and that carotenoids other than beta-carotene may be involved.

Adult↗

Performance of a new screening spirometer at a community health fair.

OBJECTIVE: Compare the results from a new screening spirometer (EasyOne) with the results from a standard laboratory spirometer (Vmax) approved by the American Thoracic Society. SETTING: A health fair at a community hospital. METHODS: We measured forced expiratory volume in the first second (FEV(1)) and forced expiratory volume in the first 6 seconds (FEV(6)). With the screening spirometer, good quality testing was achieved in 359 of 394 subjects (91%), and 115 subjects were also tested with the standard laboratory spirometer. The best test values for FEV(1) and FEV(6) were taken for 3 tests that agreed within 3%. FEV(6) was extrapolated from forced vital capacity on the printouts from the standard laboratory spirometer. RESULTS: Correlations between the screening spirometer results and the standard laboratory spirometer were excellent for FEV(1) (r = 0.93), FEV(6) (r = 0.96), and FEV(1)/FEV(6) (r = 0.72) (p = 0.001 for all comparisons). The 95% limits of agreement (mean difference between the 2 spirometers +/- 1.96 standard deviations) were: -0.18 and 0.69 for FEV(1); -0.24 and 0.81 for FEV(6); and -0.12 and 0.13 for FEV(1)/FEV(6). CONCLUSION: The new screening spirometer is suitable for clinical use.

Adult↗

Short-term effects of smoking cessation: benefit or penalty?

Eight of ten cigarette smokers successful in a smoking cessation group therapy program were examined, initially, and at six and 12 months postcessation. Examination included completion of a respiratory questionnaire and selective pulmonary function testing that included maximum expiratory flow volume curves, slope of phase 3 alveolar plateau, and closing volume. Two symptomatic subjects became symptom-free within six months postcessation. Results indicate a mean weight gain of 4.1 kg within 12 months (P less than 0.01), deterioration in mean forced expiratory volume in one second as percent of forced vital capacity (P less than 0.05), and deterioration in mean forced expiratory volume in three seconds as percent of forced vital capacity postcessation (P less than 0.05). Other tests derived from the maximum expiratory flow-volume curve, slope of phase 3, or closing volume showed no change. These results may be explained by a number of factors and may have implications for future studies.

Adult↗

Pulmonary function following mild respiratory tract infections ("common cold") in teenagers.

Ventilatory function--forced vital capacity (VC)--forced expiratory volume (in 1-sec forced expiratory flows) static lung volumes, closing volume, and phase III slope (single-breath N2 test) were compared in 94 children with and 436 children without a history of recent mild acute respiratory infection. Their age ranged from 10 to 16 years; subjects with symptoms on the day of the study were excluded. We found no difference in lung function between the two groups, with the exception of a slight (inconsistently significant) increase in closing volume (CV) and the CV/VC ratio. Although the influence of a persistent increase in interstitial lung pressure leading to early small airways closure cannot be ruled out, this isolated functional abnormality probably represents a spurious positive result, arising by chance when a large number of statistical tests are done.

Acute Disease↗

Evolution of pulmonary function during an acute exacerbation in hospitalized patients with cystic fibrosis.

Few objective criteria have been validated for serial clinical monitoring in patients with cystic fibrosis (CF) during pulmonary exacerbations. While pulmonary function tests (PFT) are often used to monitor clinical improvement, it is not known which test correlates most closely with clinical improvement. To answer this, we measured routine PFT in 58 patients with CF before, during, and at discharge after 2-3 week hospital admission in 71 episodes of pulmonary exacerbation. Patients with CF were discharged based on clinical, radiological, and laboratory criteria. In general, all PFTs improved at midadmission and improved further by discharge, at which time forced expiratory volume in 1 second (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75), vital capacity (VC), maximal voluntary ventilation (MVV), and oxygen saturation by pulse oximetry (SPO2) increased. The residual volume to total capacity ratio (RV/TLC) and the slope of phase 3 in the single breath N2 washout curve (SP3 N2) decreased. The change in SP3 N2 was significantly greater than in any other PFT (P < 0.01 vs. VC and FEV1; P < 0.02 vs. RV and P < 0.001 vs. SPO2). A calculated optimal cut-off value for SP3 N2 improvement was significantly more sensitive in identifying patient improvement at discharge than any other pulmonary function test (P = 0.005). We speculate that clinical improvement in patients with CF is closely linked to improved distribution of ventilation.

Acute Disease↗

Dumon silicone stents in obstructive tracheobronchial lesions: the Hong Kong experience.

The insertion of intraluminal stents is an effective method of relieving the distressing symptom of asphyxia in patients with obstructive lesions in the trachea and main-stem bronchi. We report our experience in the use of the studded Dumon silicone stent (Endoxane prosthesis; Axion, Aubagne, France). Between February 1994 and August 1996, 42 stents were placed in 30 patients. Of the 27 patients with a malignant stricture, 10 had carcinoma of the bronchus, 13 carcinoma of the esophagus, and 4 metastatic carcinoma involving the tracheobronchial tree. The benign lesions were made up of two tuberculous strictures and one suprastomal stenosis after tracheostomy. Stents were placed through a rigid bronchoscope with patients under general anesthesia. Postplacement assessment was performed with a 10-point, symptom-based visual analog scale. In eight less urgent cases, forced expiratory volume in 1 second and forced vital capacity were determined before and after surgery. The mean symptomatic improvement on the 10-point scale was 6.1 points, whereas the forced expiratory volume in 1 second (in the eight patients tested) improved by 75%, and the forced vital capacity improved by 54%. The median survival was 2 months for patients with carcinoma of the bronchus and 3 months for patients with carcinoma of the esophagus. Two patients with metastatic carcinoma and all of the patients with the benign lesions were alive and well after 12 months of follow-up. Insertion of the Dumon stent is a simple, safe, and effective method of countering the distressing symptoms arising from obstructive tracheobronchial lesions.

Adult↗

Pulmonary physiology in interstitial lung disease: recent developments in diagnostic and prognostic implications.

Pulmonary function changes in interstitial lung disease are characterized by loss of lung volume, increase in ratio of forced expiratory volume in 1 second to forced vital capacity, and decrease in carbon monoxide diffusion capacity. Recent developments in the assessment of respiratory mechanics in infiltrative lung disease have elucidated volume and flow dependence of lung and total respiratory resistance and elastance related to the viscoelastic properties of the respiratory system. A new, simple test of applying negative expiratory pressure at the mouth during tidal expiration can be used to generate expiratory flow-volume curves to detect flow limitation in patients with restrictive as well as obstructive disorders. This method is useful in patients who are weak, uncoordinated, or who cough during forced maneuvers. Poor prognostic signs in interstitial lung disease include male gender, paucity of lymphocytes on bronchoalveolar lavage, extensive radiographic infiltration, absence of cellular histologic findings on lung biopsy, presence of right-axis deviation, persistent or progressive decrease in lung volumes, and diffusion capacity of carbon monoxide.

Airway Resistance↗

Thirty-year cumulative incidence of chronic bronchitis and COPD in relation to 30-year pulmonary function and 40-year mortality: a follow-up in middle-aged rural men.

PURPOSE: To describe the 30-year cumulative incidence of chronic bronchitis and COPD in relation to smoking habits. The effect of chronic bronchitis on pulmonary function and mortality was also examined. METHODS: Middle-aged men belonging to two rural Finnish cohorts of the Seven Countries Study (n = 1,711 in 1959) were followed up for up to 40 years until 2000. Standard questionnaires were used to measure chronic bronchitis, and repeated spirometry was used to evaluate pulmonary function during the 30 years. Forty-year mortality data were examined. RESULTS: The cumulative incidence of chronic bronchitis and COPD was 42% and 32%, respectively, in continuous smokers, compared to 26% and 14% in ex-smokers and 22% and 12% in never-smokers. During the follow-up, subjects with chronic bronchitis had on average 252 mL (95% confidence interval, 211 to 293 mL) lower forced expiratory volume than those without it. The decrease in forced expiratory volume attributable to chronic bronchitis was most pronounced in those with persistent symptoms and in smokers. In subjects with chronic bronchitis, all-cause mortality was increased by a hazard ratio of 1.30 (95% confidence interval, 1.02 to 1.65). Smokers with chronic bronchitis who decreased their daily cigarette consumption increased their median life span by 2.4 years. CONCLUSIONS: The lifetime risk of chronic bronchitis among smokers is approximately two in five, and almost one half of smokers who have chronic bronchitis also acquire COPD. Chronic bronchitis is related to earlier death, also in never-smokers, probably partly through a rapid decline in pulmonary function.

Adult↗