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Abnormal ventilation scans in middle-aged smokers. Comparison with tests of overall lung function.

We have assessed the uniformity of regional ventilation during tidal breathing using continuous inhalation of krypton-81m in 43 male, lifelong nonsmokers and 46 male, current cigarette smokers (mean daily consumption 24.1 cigarettes/day) between 44 and 61 yr of age and with mild or no respiratory symptoms. All subjects had normal chest radiographs. The results of the ventilation scans were compared with tests of overall lung function (spirometry, maximal expiratory flow-volume curves, and single-breath N2 test). Diffuse abnormalities of the ventilation scan were found in 19 (41%) of the 46 smokers but in none of the nonsmokers. Focal abnormalities were found in 7 smokers and 3 nonsmokers. Smokers showed the expected abnormalities in overall lung function (reduced FEV1 and VC, increased single-breath N2 slope, and closing volume), but in individual smokers there was only a weak relation between the severity of abnormality of overall lung function and an abnormal ventilation scan. Abnormal scans could be found when overall lung function was normal and were not invariably found when significant abnormalities in FEV1/VC or N2 slope were present. There was no relation between the presence of chronic expectoration and an abnormal scan. The prognostic significance of an abnormal ventilation scan in such smokers remains to be established.

Adult↗

Lung function changes in teenage carpet weavers.

Lung function was measured with a Microlab 3500 Spirometer in 17 teenage carpet weavers, their 17 non weaving sisters and 13 age/sex matched controls in a carpet making community in Gwalior in late 2001. All subjects were asymptomatic. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and mid-expiratory flow rate (MEF) were expressed as percentages of expected values for the subjects age and height using prediction equations for healthy North-Indian girls (FVC% FEV1% and MEF%). There was no significant difference in FVC% FEV1% or FEV1/FVC ratio between the 3 groups but weavers had a significantly lower mean MEF% than their sisters (p< 0.01 by paired "t" test) and the age-matched control group (p< 0.002 by "t" test). The reduction in MEF% was correlated with duration of employment (Spearmans correlation = 0.5 with p < 0.05).

Adolescent↗

Lung function impairment in long-term survivors of Hodgkin's disease.

BACKGROUND: Treatment of Hodgkin's disease (HD) involves radiation and chemotherapy, modalities known to cause lung injury. PATIENTS AND METHODS: In Norway, between 1980 and 1988, 129 patients aged less than 50 years at the time of diagnosis, had curative treatment with thoracic radiation alone or combined-modality therapy for supradiaphragmatic HD. We have examined 116 (90%) of these patients by interview, chest X-ray and lung function tests, 5-13 years after treatment. RESULTS: Nearly 30% of the patients had dyspnoea on exertion and associated reductions in total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and gas transfer (TLCO) (p < 0.05). Radiographic evidence of no, slight or moderate fibrosis occurred in 32%, 54% and 14% of the patients, respectively. Moderate fibrosis was associated with reductions in FVC, FEV1 and TLCO (p < 0.05). Radiation plus chemotherapy containing bleomycin-anthracyclines (median cumulative bleomycin dose 120 mg) was associated with decreases in FVC and TLCO (p < 0.05). In the multivariate analysis, chemotherapy with bleomycin-anthracyclines was the only significant predictor for lung function impairment. CONCLUSION: More than five years after therapy, respiratory symptoms and reduction in lung function were diagnosed in nearly one-third of otherwise healthy HD survivors.

Adolescent↗

Dyspnea in patients with chronic obstructive pulmonary disease: does dyspnea worsen longitudinally in the presence of declining lung function?

OBJECTIVE: To determine the direction and rate of change in the symptom of dyspnea in patients with chronic obstructive pulmonary disease (COPD) whose lung function has worsened over time. DESIGN: Secondary analysis of a longitudinal data set. SETTING: Outpatient clinic. PATIENTS: Thirty-four medically stable male subjects with chronic obstructive pulmonary disease studied for 5.3 +/- 3.5 years, with a mean reduction in FEV1 over the period studied of 330.9 +/- 288.0 mL. Subjects were 63.3 +/- 5.5 years of age at entry into the study. OUTCOME MEASURES: Dyspnea and functional status scores were obtained using the Pulmonary Functional Status and Dyspnea Questionnaire. RESULTS: There was no significant difference in reports of dyspnea from the beginning to the end of the study, despite significant reductions in lung function. Of all activities studied, dyspnea when raising arms overhead was the only activity showing a relationship to the slope of change in FEV1 %. CONCLUSION: These findings suggest that, although patients with chronic lung disease experience varying degrees of deterioration in lung function longitudinally, there is no evidence that they report worsening of dyspnea in tandem with these physiologic changes. In this study, patient ratings of dyspnea longitudinally were not directly linked to changes in lung impairment.

Disease Progression↗

Relevant and redundant lung function parameters in discriminating asthma from COPD.

A relevant set of lung function parameters, derived from spirometry, flow-volume curves, diffusion capacity and bodyplethysmography, to discriminate asthma from COPD was established via logistic regression analysis. All new patients, referred to the outpatient clinic and later defined as asthma or COPD, underwent extensive lung function testing with reversibility testing. Logistic regression was used to calculate the probability to be a COPD or asthma patient. Selection of relevant parameters was done via 1] forward-, 2] backward-, 3] stepwise selection and 4] the best score method. All four methods were supplemented by bootstrapping to obtain a validated selection and estimation of the logistic regression parameters. The area under the ROC curve (mean+/-sd) for respectively the forward, backward, stepwise and best score selection method is 0.9348+/-0.0115, 0.9346+/-0.0115, 0.9348+/-0.0115 and 0.9296+/-0.0121. The TLCO, VA and the postdilator MEF50, VC and PEF were selected as the most relevant parameters in discriminating asthma from COPD: they appeared most often as relevant discriminators in 500 bootstrapped samples: TLco was present in all bootstrapped samples and VA, postdilator MEF50, VC and PEF in resp. 70.8%, 46.2%, 42.8% and 36.8%. Bodyplethysmography derived parameters turned out to be of limited value. Diffusion capacity testing and spirometry/flow-volume curve after administration of bronchodilators are the methods of choicewhen having to chose between asthma or COPD.

Adult↗

Lung function in patients with diabetes mellitus.

Lung function was assessed in 35 nonsmoking adults with insulin dependent diabetes mellitus and 34 matched control subjects. The tests included spirometry, lung volumes, CO transfer factor and maximum respiratory pressures. Additionally, in subjects under 35 years of age (20 patients and 18 controls) measurements of CO transfer factor were obtained during exercise at three different workloads. Random blood glucose and glycosylated haemoglobin were measured and each patient's diabetic history was recorded. The total lung capacity (TLC) in the patients was lower than those recorded for the controls (P less than 0.05) but there were no significant differences in respiratory muscle strength between the groups. In the young group of patients (less than 35 years) the transfer factor for CO (TLCO) was similar but the volume corrected transfer coefficient (KCO) was higher at rest than in the controls (P less than 0.02). The KCO remained high in these patients during exercise. The older patients (greater than 35 years) showed a lower TLCO (P less than 0.01) with a similar KCO to the controls. The association of a reduction in TLC and higher KCO in the young patients suggests an extrapulmonary mechanism of lung volume restriction. This is not attributable to muscle weakness but might be due to limited expansion of the rib cage. In older patients any tendency for KCO to rise may be masked by disease-related changes in the pulmonary microvasculature.

Adult↗

Lung function after bilateral lower lobe lung volume reduction surgery for alpha1-antitrypsin emphysema.

This study explores the mechanism(s) of airflow limitation following lung volume reduction surgery (LVRS) in patients with emphysema due to homozygous alpha1-antitrypsin (AT) deficiency. Bilateral targeted lower lobe stapled LVRS using video thoracoscopy was performed in six patients (five males) aged 61+/-9 yrs (mean+/-SD) with alpha1-AT emphysema. Two patients received only a 6-month follow-up. However, four patients, at 22, 24, 27 and 36 months post-LVRS, noted relief from dyspnoea and increased walk tolerance. At 27+/-6 months (mean+/-SD) post-LVRS, their forced expiratory volume in one second improved only from 30+/-2% of the predicted value (mean+/-SEM) before surgery to 33+/-1% pred after surgery. Yet, total lung capacity (TLC) decreased from 151+/-13 to 127+/-10% pred; diffusing capacity increased from 35+/-9 to 59+/-9% pred; and vital capacity increased from 68+/-10 to 88+/-5% pred. In three patients, static lung elastic recoil at TLC increased from 1.1+/-0.15 to 1.2+/-0.10 kPa. Using flow/pressure curves, the mechanism for expiratory airflow limitation pre-LVRS and the improvement noted post-LVRS could be primarily accounted for by the initial loss and subsequent increase in lung elastic recoil. Bilateral lung volume reduction surgery provides modest physiologic improvement for 2-3 yrs in patients with alpha1-antitrypsin emphysema due to increases in lung elastic recoil.

Dyspnea↗

Lung functions after intravenous or intraperitoneal administration of perfluorooctyl bromide (PFOB) or perfluorotributylamine (FTBA) emulsions.

The biomechanical and oxygen transfer functions of lungs of animals administered intravenous or intraperitoneal fluorocarbon emulsions containing either perfluorotributylamine or perfluorooctyl bromide 4 to 7 days earlier were tested in a porcine and a canine model. Lung fluorocarbon content was measured by 19F NMR spectroscopy. The existence of fluorocarbon in the lung tissue produced no measurable effects on lung compliance variables in vivo or ex vivo nor on steady state oxygen transfer from air to blood over a wide range of inspired oxygen partial pressures.

Animals↗

Assessment of the results of glottis-dilating operations using lung function tests.

Our aim was to obtain an objective evaluation of the airway before and after glottis-dilating operations utilizing lung function tests. The charts of 109 patients who underwent either reversible or irreversible glottis-dilating operations by Lichtenberger were reviewed. 64 nonselected cases of these patients, all with irreversible glottis-dilating operations, were studied. Lung function tests that were performed were body-pletysmography, forced inspiratory volume (FIV1), forced expiratory volume (FEV1), peak inspiratory flow rate (PIF), peak expiratory flow rate (PEF) and resistance of the airways (RAW). The FEV1, FIV1, PEF and PIF all improved following irreversible glottis-dilating operations. The RAW was remarkably decreased post-operatively as compared to pre-operatively. In conclusion, the airways of patients undergoing irreversible glottis-dilation operations improved moderately to well following such surgeries. Lung function tests are an objective means of evaluating the airway before and after surgery.

Glottis↗

Lung function at one month of age as a risk factor for infant respiratory symptoms in a high risk population.

BACKGROUND: Abnormal premorbid lung function is a risk factor for subsequent wheezing in children with one or no atopic parent. This study was undertaken to establish whether early lung function in high risk infants (both parents atopic) was a risk factor for respiratory symptoms in infancy and to examine the influence of maternal asthma, smoking, and allergen exposure during pregnancy on any association. METHODS: Infants were recruited from the NAC Manchester Asthma and Allergy Study cohort at birth. Partial forced expiratory flow volume technique under sedation was carried out to determine maximal flow at FRC (V'maxFRC). Children were followed prospectively and parents completed a standard respiratory questionnaire at one year of age. RESULTS: Sixty nine term infants (34 boys; 88% mothers non-smokers; no household pets) underwent respiratory function testing. Size adjusted V'maxFRC was significantly lower in infants who had recurrent wheeze during the first year of life (mean 1.3 ml/s/cm, 95% CI 0.99 to 1.60) than in those who did not (mean 2.03 ml/s/cm, 95% CI 1.71 to 2.36; p=0.01). V'maxFRC was also significantly lower in infants who had recurrent cough symptoms. In multivariate regression analysis, when adjusted for age at test, sex, maternal asthma, smoking and maternal mattress Der 1 levels, a lower size adjusted V'maxFRC score remained strongly associated with wheezing (OR 0.37, 95% CI 0.18 to 0.77, p=0.007). Maternal smoking also remained an independent risk factor (OR 29.85, 95% CI 2.46 to 362.5, p=0.008). CONCLUSION: Significantly diminished lung function was present in high risk infants who subsequently wheezed and coughed. This was independent of maternal exposure to mite allergen, asthma, and smoking during pregnancy.

Cough↗

Relation between severity of mitral valve disease and results of routine lung function tests in non-smokers.

The effects of mitral valve disease on lung function have been studied in 26 non-smoking patients by relating values for lung volumes and carbon monoxide transfer factor (TLCO) to various indices of cardiac function measured at catheterisation. In general, more severe mitral disease was associated with greater abnormalities of lung function. Reductions of the one-second forced expiratory volume, vital capacity, TLCO and transfer coefficient, and increase in residual volume were all significantly related to the severity of mitral valve disease. In addition, the cardiothoracic ratio, measured radiographically, showed an inverse correlation with both vital capacity and total lung capacity. Although some of the consequences of mitral valve disease on lung function resemble those of primary airway disease, useful distinguishing points are the relative normality of the forced expiratory ratio and the absence of an increase in total lung capacity.

Adult↗

Lung function and airway inflammation in rats following exposure to combustion products of carbon-graphite/epoxy composite material: comparison to a rodent model of acute lung injury.

Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the lavage fluid. Increased MIP-2 levels also preceded the maximum neutrophil infiltration. The differences in the time-course and primary site of TNF-alpha, MIP-2, and IFN-gamma expression; and the differences in the temporal relationship between their expression and infiltration of inflammatory cells may have accounted for the differences in lung function between paraquat treated and ACM smoke exposed animals.

Animals↗

Glutathione S-transferase variants and their interaction with smoking on lung function.

We studied glutathione S-transferase (GST) polymorphisms in 1,098 whites with the lowest (n = 544, FEV(1) % predicted mean +/- SEM = 62.6 +/- 0.1) and the highest (n = 554, FEV(1) % predicted mean +/- SEM = 91.8 +/- 0.1) lung function at the beginning of the Lung Health Study. Homozygosity for GSTP1 105Val was significantly more frequent in the low- than in the high-function group (13.2 vs. 9.3%) (odds ratio = 1.69, 95% confidence interval [CI] = 1.11-2.61, p = 0.016), after adjustment for confounding variables. Subjects with 105Val homozygotes had higher rates of lung function decline in the high-function group (p = 0.017). The frequencies of GSTM1, GSTT1 null genotypes were similar between the high- and low-function groups, but subjects with the GSTT1 null genotype had a faster decline of lung function in the low-function group (p = 0.032). In addition, there was a significant interaction of GSTT1 genotype and pack-years on lung function. When comparing individuals with GSTT1 null genotype with wild type, the adjusted odds ratio was 3.49 (95% CI, 1.48-8.39, p = 0.005) in mild smokers (< or = 25 pack years). We conclude that GST genotypes are risk factors for rapid decline or low lung function in smokers with mild to moderate airflow obstruction.

Acyltransferases↗

Extended therapy with ipratropium is associated with improved lung function in patients with COPD. A retrospective analysis of data from seven clinical trials.

OBJECTIVE: Bronchodilators are routinely used in the long-term therapy of patients with COPD. These drugs are generally evaluated for their short-term bronchodilatory effects. Long-term and short-term benefits, however, are not necessarily equivalent. We evaluated, therefore, the effects of extended therapy with inhaled bronchodilators in patients with COPD. DESIGN: Data were obtained from seven clinical trials in which ipratropium was compared with a beta-agonist over a 90-day treatment interval. This comprised all the available data from clinical trials performed for registration of ipratropium and included 1,445 evaluable patients. Results of pulmonary function tests were evaluated prior to and after short-term administration of bronchodilator both before and after the 90-day treatment period. In addition, data were analyzed after stratification for smoking status and for lung function. RESULTS: Long-term therapy with ipratropium resulted in improvement in baseline (ie, before short-term administration of bronchodilator) FEV1 (28 mL; p < 0.01) and FVC (131 mL; p < 0.01), while long-term therapy with beta-agonist resulted in no significant change in FEV1 (1-mL decline; p > 0.2) or in FVC (20-mL improvement; p > 0.2). The improvement in baseline function in the ipratropium-treated patients was most marked in ex-smokers (average duration of abstinence, 9 years). Short-term administration of ipratropium following the 90-day treatment interval resulted in similar response in average FEV1 (6 mL more improvement after the extended therapy; p > 0.2) and an increased response in average FVC (44 mL more improvement after extended therapy; p < 0.01). In contrast, extended therapy with beta-agonist resulted in significantly less response to the short-term administration of beta-agonist for both FEV1 (49 mL less response; p < 0.0001) and FVC (74 mL less response; p < 0.0001). Assessed as the percentage of patients who achieved a 15% improvement in lung function, most patients responded to both treatments both before and after extended therapy. There was, however, a significant decline in the number of patients who responded after extended therapy, and this was more marked for the beta-agonist treated group. CONCLUSION: Long-term benefits of bronchodilator therapy appear to differ from short-term effects. Extended administration of ipratropium appears to be associated with improved baseline lung function and perhaps with improvement in the response to acute bronchodilation. Extended administration of beta-agonist, in contrast, appears to have little effect on baseline lung function, but may decrease response to acute bronchodilation.

Adrenergic beta-Agonists↗

Unilateral lung function. Comparison of the lateral position test with radionuclide ventilation-perfusion studies.

Twenty-seven patients underwent studies of unilateral lung function by the lateral-position test (LPT) and by computer-analyzed radionuclide imaging of ventilation and perfusion. The patients were divided into two groups, symmetric or asymmetric, on the basis of the physical examination of the chest and the chest radiograph. In patients with symmetry, the estimate of unilateral lung function by the LPT and isotopic estimates for unilateral lung volume, unilateral distribution of tidal volume, and unilateral perfusion, agreed within 2 percent, 4 percent, and 3 percent, respectively. In patients with asymmetry, the differences were 9 percent, 8 percent, and 13 percent. In settings of marked unilateral ventilation-perfusion imbalance, the LPT primarily reflected ventilation. Prediction of unilateral ventilatory function based upon the LPT and spirometric measurements agreed closely with unilateral ventilation determined isotopically by 133xenon, even in the presence of chronic obstructive lung disease. Our results confirm that the LPT provides valid information about unilateral lung function.

Adult↗