Ras p21 protein levels in human plasma from patients with chronic obstructive pulmonary disease (COPD) compared with lung cancer patients and healthy controls

To explore the value of an increase in ras p21 proteins in plasma as a biomarker for the carcinogenic process or for the general disease state, we have directly analysed for ras p21 proteins, plasma samples from Polish human patients with chronic obstructive pulmonary disease (COPD). They were compared with appropriate controls and also with the Polish lung cancer patients previously examined before treatment [D. Anderson, J.A. Hughes, A. Cebulska-Wasilewska, E. Nizankowska, B. Graca, Ras oncoproteins in human plasma from lung cancer patients and healthy controls, Mutat. Res. 349 (1996) 121-126]. An elevated level of ras p21 proteins was considered to be greater than 2 standard deviations (SD) above the mean negative control values. Nine out of 20 COPD patients (mean age = 65.9 years) had increased ras p21 protein levels when compared with 20 age-matched (mean age = 62.4 years) controls of the present study with a mean + 2 SD of 0.70. Eighteen out of 40 lung cancer patients (mean age = 60.1 years) had increased ras p21 protein levels compared with their concurrent controls (mean age = 40.2 years) with a mean + 2 SD of 2.53. However when compared with the age-matched controls of this present study, there were 35 out of 40 (87.5%) with increased levels. When the COPD patients and lung cancer patients were compared with 101 historical controls (age range 25-76 years, of those whose age was recorded) from unexposed healthy populations from Poland, Estonia and Spain with a mean + 2 SD of 1.83, then 4 out of 20 (20%) COPD patients and 30 out of 40 (75%) lung cancer patients had increased levels. Whether using concurrent controls, age-matched controls or historical controls, the data would suggest that an increase in ras p21 protein levels in plasma from lung cancer patients could be a possible prognostic marker or biomarker for lung cancer. COPD patients when compared with historical controls or age-matched controls had lower ras p21 protein values than cancer patients. Their ras p21 protein values might also be a biomarker for cancer. It is possible that some of these COPD patients were in the process of developing cancer or perhaps would die from COPD before cancer develops. It cannot be ruled out that the increases could be a biomarker of exposure since many of the lung cancer patients and most of the COPD patients were smokers.     

Chronic respiratory insufficiency: evaluation, evolution, prognosis

Chronic respiratory failure (CRF) is a major cause of morbidity and mortality. It is estimated that in France at least 60,000 patients exhibit severe CRF and that about 15,000 patients die each year from CRF. Chronic obstructive pulmonary disease (COPD) (chronic obstructive bronchitis, emphysema and their association) is by far the first cause of CRF (90% of the cases). The clinical picture of CRF depends on the causal disease, but exertional dyspnea is observed in almost all patients. Pulmonary function testing allows to assess whether the ventilatory defect is obstructive (COPD), restrictive or mixed. Severe CRF is usually defined by a Pa02 < 55 mmHg, in a stable state of the disease, with or without hypercapnia (PaC02 > 45 mmHg). The two major complications of CRF are acute exacerbations of the disease, with clinical and gasometric worsening, and pulmonary hypertension which may lead with time to right heart failure. Prognosis is poor in CRF since the 5 year survival rate is of 50% in COPD patients. Under long-term oxygen therapy (LTOT) the survival rate has been somewhat improved, being of 60-65% at 5 years. The best prognostic indices in CRF complicating COPD are the level of FEV1, Pa02, PaC02, the level of pulmonary artery mean pressure (PAP) and age. In COPD patients under LTOT the best prognostic indices are PAP and age.     

Spirometrically controlled quantitative CT for assessing diffuse parenchymal lung disease

OBJECTIVE: Assessment of lung attenuation by CT reflects changes in the air-to-tissue ratio of the lung. We have analyzed the interdependence of intrathoracic gas volume, lung morphology, and functional disorder by high resolution CT (HRCT) to assess quantitative disease threshold in obstructive and restrictive diffuse lung disease. MATERIALS AND METHODS: Pulmonary HRCT was performed on 24 healthy volunteers, 11 patients with chronic obstructive pulmonary disease (COPD), and 16 patients with idiopathic lung fibrosis (IPF). HRCT measurement was standardized by taking three scans at the carina +/- 5 cm and by defining inspiration levels by percent vital capacity (VC) via spirometrically gating to the scanner. RESULTS: The mean lung density at 50% VC (DL50) for healthy subjects was -819 +/- 3.8 (mean +/- SEM) HU. In contrast, COPD DL50 was lower, averaging -861 +/- 6.4 HU, and the IPF DL50 was considerably higher (-731 +/- 17.7 HU), both significantly different (p < 0.001) compared with the control group. The accuracy of quantitative HRCT at different inspiration levels was evaluated by scanning the basal layer at 20, 50, and 80% VC. The control values were -747 +/- 5.6, -816 +/- 3.6, and -855 +/- 3.0 HU, respectively, which were significantly higher (p < 0.001) than those seen in COPD patients at 20 and 50% VC. Again, the IPF patients exhibited increased lung density (p < 0.001) at all inspiratory levels. Discrimination power was best among all cohorts at 20 and 50% VC. Position-dependent artifacts on lung density were quantified by the anteroposterior density gradient (APG). Irrespective of the underlying disease, APG at 50 and 80% VC was similar, but was up to twofold higher at 20% VC, indicating that quantitative estimates near RV may misrepresent mean lung density. CONCLUSION: Our data indicate that quantitative HRCT measurements should be performed not near full inspiration or expiration, but at an intermediate degree of lung inflation, e.g., 50% VC, for reasons of accuracy, intra- and intersubjective comparability, and feasibility. We conclude quantitative HRCT to be a sensitive tool for the evaluation of diffuse parenchymal lung disease.     

Altered rhodopsin regeneration in diabetic mice caused by acid conditions within the rod photoreceptors

BACKGROUND: We sought to describe changes in spirometric variables and lung volume subdivisions in healthy subjects and patients with chronic obstructive pulmonary disease (COPD) during moderate acute hypobaric hypoxia as occurs during air travel. We further questioned whether changes in lung function may associate with reduced maximum ventilation or worsened arterial blood gases. METHODS: Ambulatory patients with COPD and healthy adults comprised the study populations (n = 27). We obtained baseline measurements of spirometry, lung volumes and arterial blood gases from each subject at sea level and repeated measurements during altitude exposure to 8000 ft (2438 m) above sea level in a man-rated hypobaric chamber. RESULTS: Six COPD patients and three healthy subjects had declines in FVC during altitude exposure greater than the 95% confidence interval (CI) for expected within day variability (p < 0.05). Average forced vital capacity (FVC) declined by 0.123 +/- 0.254 L (mean +/- SD; 95% CI = -0.255, -0.020; p < 0.05) for all subjects combined. The magnitude of decline in FVC did not differ between groups (p > 0.05) and correlated with increasing residual volume (r = -0.455; <0.05). Change in maximum voluntary ventilation (MVV) in the COPD patients equaled -1.244 +/- 4.797 L x min(-1) (95% CI = -3.71, 1.22; p = 0.301). Decline in maximum voluntary ventilation (MVV) in the COPD patients correlated with decreased FVC (r = 0.630) and increased RV (r = -0.546; p < 0.05). Changes in spirometric variables for patients and controls did not explain significant variability in the arterial blood gas variables PaO2, PaCO2 or pH at altitude. CONCLUSIONS: We observed a decline in forced vital capacity in some COPD patients and normal subjects greater than expected for within day variability. Spirometric changes correlated with changes in reduced maximum voluntary ventilation in the patients but not with changes in resting arterial blood gases.     

Cellular mechanisms of adrenaline-stimulated anion secretion by the mouse endometrial epithelium

As freon is limited in its use as a generator for aerosol inhalation, powder particles are used as an alternative for inhalation therapy. The pulmonary deposition and clearance of inhaled powder particles was studied by positron emission tomography (PET) in ten patients with chronic obstructive pulmonary disease (COPD) and in five normal controls. The powder, 5 microm in mean diameter, was water soluble and labelled with 2-deoxy-2-[18F]-fluoro-D-glucose (18FDG). Powder inhalation was done with single deep inspiration from residual volume to total lung capacity. The initial deposition ratio in the right or left lung field to total inhaled dose, measured by an anteroposterior rectilinear scan, did not differ between normals and COPD patients. Ratios of radioactivity detected within the central and peripheral regions (the central to peripheral ratio) measured by the PET scan was not significantly different between COPD patients (4.8+/-2.6, mean+/-SD) and normals (2.6+/-0.8, mean+/-SD). However, the regional powder deposition in peripheral lung fields measured by the PET scan was significantly more uneven in COPD patients than in normal patients. The clearance rate of 18FDG, defined as the retention ratio of 18FDG activity to the initially deposited 18FDG at 60 and 120 min after inhalation, in the trachea, large bronchi or peripheral lung fields measured by tomographic scan showed a wider variation in COPD patients than in normals. To conclude, inhaled powder tended to be deposited more centrally and was distributed more unevenly in the peripheral lung in chronic obstructive pulmonary disease patients than in normals. This could be a limitation of powder inhalation used for therapy in chronic obstructive pulmonary disease patients.     

The relationship of perceived self-efficacy to quality of life in chronic obstructive pulmonary disease.

From a biomedical perspective, variations in the quality of life of chronic obstructive pulmonary disease (COPD) patients may be attributed to changes in pulmonary function, thus, an increase in lung function should be correlated with an increased score on a health-related quality-of-life measure. However, inconsistent results regarding correlations between various measures of pulmonary function and quality of life have been reported in the literature. The authors evaluated a social cognitive model of quality of life among persons with COPD by analyzing relationships among biomedical measures, self-efficacy measures, and quality-of-life measures in a recursive path model. Path analysis results indicated that the association of pulmonary function and symptoms with quality of life was mediated by perceived self-efficacy for functional activities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genotype of GB virus C/hepatitis G virus by molecular evolutionary analysis

We have determined that fractal analysis of the alveolar perimeter (Df) changes with aging in human lung tissue in twenty-nine patients, age range of 25 hours to 76 years, who died of non-respiratory related causes. There was a very significant difference (p = 0.0004) in Df between the young (less than 16 years old, N = 9, mean Df of 1.047 [0.01]) and adult (greater than 16 years old, N = 20, mean Df of 1.093 [0.013]) groups. Furthermore, there was a significant difference in Df between the Adult group and the group of patients who died of chronic obstructive pulmonary disease (COPD, N = 10) (p = 0.012). Additionally, the Df values for the COPD and cystic fibrosis (CF, N = 5) groups were virtually identical; 1.061 and 1.070, respectively. Regression analysis showed a significant (p = 0.0041) exponential relationship with a correlation coefficient of 0.59 between aging and Df. We have demonstrated that the correlation between Df and aging in humans is an exponential function and that the end-stage pulmonary diseases of COPD and CF decrease Df.     

Evolution of nocturnal pulse-oximetry results in patients with chronic obstructive pulmonary disease

The aim of this study was to evaluate if results of overnight pulse-oximetry (PO) change with time and progression of the disease. We studied 39 COPD patients. Majority of them (33 pts) were treated with long-term oxygen therapy (LTOT). Fifty pairs of PO were performed in the whole group separated from 1 to more than 3 years. Pulmonary function tests were performed at the same time as PO. Results of these tests showed progressive deterioration in the lung function-decrease of FEV1 and PaO2. Despite of that there were no statistically significant changes in any variable of PO in any studied group. This phenomenon is difficult to explain. It may resulted from the improvement in the cardiac output observed in COPD patient undergoing LTOT. May be that studied groups were not large enough or time of observation was too short to reveal differences. Stabilization of PO results in spite of deterioration in the lung function in COPD patients needs more studies.     

MRI evaluation of right ventricular pressure overload in chronic obstructive pulmonary disease

In chronic obstructive pulmonary disease (COPD), the development of pulmonary hypertension is common. This study was performed to assess the signs of right ventricular (RV) pressure overload and RV failure in COPD. In 8 COPD patients without primary cardiac disease, RV wall thickness, mass, and end-diastolic volume were measured by cardiac-triggered cine MRI. MR phase-contrast velocity quantification was used to measure stroke volume and the patterns of flow into and out of the RV. Data of patients were tested versus those of a control group matched for age (n = 8). Results showed that the RV wall thickness was increased (.6 +/- 0.1 vs 0.4 +/- 0.1 cm, P < .001). RV mass was increased (67 +/- 11 vs 57 +/- 5 g, P < .005). RV stroke volume was decreased (57 +/- 13 vs 71 +/- 13 ml, P < .01), but RV ejection fraction was not different. In the main pulmonary artery flow, the quotient of acceleration time divided by ejection time was decreased (33 +/- 5% vs 38 +/- 4%, P < .05), which is indicative of pulmonary hypertension. In conclusion, this MRI protocol provides a tool to assess the effects of RV pressure overload in COPD before heart failure has become manifest.     

Effects of extrinsic positive end-expiratory pressure on mechanically ventilated patients with chronic obstructive pulmonary disease and dynamic hyperinflation

OBJECTIVE: To examine the circulatory and respiratory effects of extrinsic positive end-expiratory pressure (PEEPe) in patients with chronic obstructive pulmonary disease (COPD) and dynamic hyperinflation during controlled mechanical ventilation. DESIGN: Different levels of PEEPe were applied randomly in mechanically ventilated patients with COPD and dynamic hyperinflation. SETTING: Respiratory Intensive Care Unit of a University Hospital. PATIENTS: 9 patients with acute respiratory failure and dynamic hyperinflation due to acute exacerbation of COPD. INTERVENTIONS: PEEPe 35%, 58% and 86% of intrinsic PEEP (PEEPi) were applied. MEASUREMENTS AND RESULTS: Using flow-directed pulmonary artery catheters hemodynamic measurements were obtained, while simultaneously lung volumes, airflows and airway pressures were recorded. In order to estimate alveolar pressures (Palv), rapid airway occlusions during passive expiration were also performed. At no level of PEEPe were significant changes in cardiac output, gas exchange variables, dead space, airways inflation resistances and respiratory system static end-inspiratory compliance observed. At high level of PEEPe central venous, mean pulmonary arterial and pulmonary capillary wedge pressures were increased significantly. All but one patient were flow-limited during passive expiration. PEEPe 86% of PEEPi caused a significant increase in end-expiratory lung volume and total PEEP. Iso-volume pressure-flow curves showed volume-dependence expiratory flow limitation in 2 patients, while in 8 patients volume-dependence of critical driving pressure (Palv-mouth pressure) that decreased flows was also observed. CONCLUSIONS: The effects of PEEPe on iso-volume flow and hence on lung mechanics and hemodynamics, depend on many factors, such as airways resistances, lung volumes and airway characteristics, making the patient response to PEEPe unpredictable.     

Patterns of hospitalization in elderly patients with asthma and chronic obstructive pulmonary disease

The purpose of this study was to describe the impact of asthma and chronic obstructive pulmonary disease (COPD) in the elderly on health care utilization. The Health Care Financing Administration (HCFA) file for the year 1984 through 1991 involving beneficiaries < or = 65 yr were searched for the diagnoses of asthma and COPD by ICD-9 codes. The study groups were created by determining the first admission for an exacerbation of either disease during each year from 1984 through 1991. Patients were identified by their social security number. The 1984 cohort consisted of 56,692 patients with asthma exacerbation and 162,899 with COPD exacerbation. The 1991 cohort consisted of 67,758 patients with asthma exacerbation and 131,974 patients with COPD exacerbation. In addition, the 1984 cohort was tracked by social security number for evidence of rehospitalization for either asthma or COPD through 1991. Length of hospitalization increased as patients grew older. The discharge rate to an independent living facility diminished as age increased. The use of convalescent and nursing homes or home health care after discharge more than doubled from 1984 through 1991. The utilization of health care resources by elderly patients with asthma and COPD is immense, both during hospitalization and after discharge.     

Efficacy, tolerability, and effects on quality of life of inhaled salmeterol and oral theophylline in patients with mild-to-moderate chronic obstructive pulmonary disease. SLMT02 Italian Study Group

The aims of management in mild-to-moderate stable chronic obstructive pulmonary disease (COPD) are to improve symptoms and quality of life (QOL), reduce decline in lung function, prevent and treat complications, increase survival while maintaining QOL, and minimize the adverse effects of treatment. Bronchodilator therapy is the keystone of improving COPD symptoms and functional capacity. The primary objective of this open-label study was to compare the efficacy and tolerability of salmeterol 50 microg BID administered by metered-dose inhaler versus oral, titrated, sustained-release theophylline BID, both given for 3 months to patients with a clinical history of chronic bronchitis. The secondary objectives of the study were to evaluate the safety profile of the two drugs for an additional 9-month period and to assess changes in QOL both within and between treatment groups, using the 36-Item Short Form (SF-36) Health Survey. One hundred seventy-eight outpatients (122 men, 56 women; mean age, 56 +/- 12.9 years; mean body weight, 76.1 +/- 11.8 kg) were randomized to the two treatment groups. Patients receiving salmeterol showed significant improvement in mean morning peak expiratory flow rate (16.56 L/min) over the 3-month period compared with patients receiving theophylline (P = 0.02). Salmeterol also significantly increased the percentage of symptom-free days and nights with no additional salbutamol requirement (P < 0.01). A significant difference was found between increases in forced expiratory volume in 1 second compared with baseline for salmeterol compared with theophylline throughout the initial 3-month period (0.13, 0.16, and 0.16 L at months 1, 2, and 3, respectively) and during the additional 9 months. The incidence of adverse events was similar in the two groups (salmeterol, 49.5%; theophylline, 49.4%), with a lower percentage of pharmacologically predictable adverse events in patients receiving salmeterol (4%) compared with those receiving theophylline (14.8%). Both drugs improved QOL, as measured by effects on the eight aspects of life experience analyzed by the SF-36 questionnaire. Salmeterol therapy was effective in more aspects, and the improvements seen in each were numerically greater than those seen with theophylline therapy. Statistically different changes between the two treatment groups were reported for physical functioning, changes in health perception, and social functioning (P = 0.02, P = 0.03, and P = 0.004, respectively). These data suggest that inhaled salmeterol 50 microg BID was more effective and better tolerated than oral, titrated theophylline and allowed better long-term control of airways obstruction and symptoms with improved lung function in patients with COPD.     

Effects of positive end-expiratory pressure on right ventricular function in COPD patients during acute ventilatory failure

OBJECTIVE: To examine the effects of external positive end-expiratory pressure (PEEP) on right ventricular function in chronic obstructive pulmonary disease (COPD) patients with intrinsic PEEP (PEEPi). DESIGN: Prospective study. SETTING: General intensive care unit in a university teaching hospital. PATIENTS: Seven mechanically ventilated flow-limited COPD patients (PEEPi = 9.7 +/- 1.3 cmH2O, mean +/- SD) with acute respiratory failure. INTERVENTION: Hemodynamic and respiratory mechanic data were collected at four different levels of PEEP (0-5-10-15 cmH2O). MEASUREMENTS AND RESULTS: Hemodynamic parameters were obtained by a Swan-Ganz catheter with a fast response thermistor. Cardiac index (CI) and end-expiratory lung volume (EELV) reductions started simultaneously when the applied PEEP was approximately 90% of PEEPi measured on 0 cmH2O (ZEEP). Changes in transmural intrathoracic pressure (PEEPi,cw) started only at a PEEP value much higher (120%) than PEEPi. The reduction in CI was related to a decrease in the right end-diastolic ventricular volume index (RVEDVI) (r = 0.61; p < 0.001). No correlation between CI and transmural right atrial pressure was observed. The RVEDVI was inversely correlated with PEEP-induced changes in EELV (r = -55; p < 0.001), but no with PEEPi,cw (r = -0.08; NS). The relationship between RVEDVI and right ventricular stroke work index, considered an index of contractility, was significant in three patients, i.e., PEEP did not change contractility. In the other patients, an increase in contractility seemed to occur. CONCLUSIONS: In COPD patients an external PEEP exceeding 90% of PEEPi causes lung hyperinflation and reduces the CI due to a preload effect. The reduction in RVEDVI seems related to changes in EELV, rather than to changes in transmural pressures, suggesting a lung/heart volume interaction in the cardiac fossa. Thus, in COPD patients, application of an external PEEP level lower than PEEPi may affect right ventricular function.     

Controlled expiration in mechanically-ventilated patients with chronic obstructive pulmonary disease (COPD)

In patients with severe chronic obstructive pulmonary disease (COPD), lung emptying may be affected by flow limitation. We tested the hypothesis that the airway compression leading to flow limitation can be counteracted by controlling the expiratory flow. The effects of an external resistor on lung emptying were studied in six patients with COPD, who were mechanically ventilated whilst sedated and paralysed. Respiratory mechanics were obtained during ventilatory support with and without the resistor. Airway compression was assessed using the interruptor method. For the study, a turbulent resistor was applied with the highest resistance level that did not increase the end-expiratory lung volume. At this resistance level, external positive end-expiratory pressure (PEEP) was generated in all patients. As total PEEP levels remained unchanged at both settings during the controlled expiration, the levels of intrinsic PEEP were significantly decreased from 0.96+/-0.30 to 0.53+/-0.19 kPa (mean+/-SD). Comparison of the expiratory flow-volume curves at both settings revealed that, during the controlled expiration, the flows were significantly decreased during the first 40% of the expired volume and significantly increased during the last 60%. As the end-expiratory lung volumes remained unchanged during both settings, these increments in flow indicated a decrease in effective resistance. Airway compression was observed during unimpeded expirations in all patients using the interruptor method. During the application of the resistor, airway compression was no longer detectable. In patients with chronic obstructive pulmonary disease receiving ventilatory support, the application of an external resistor could decrease effective expiratory resistance by counteracting airway compression, without increments in end-expiratory lung volume.     

The importance of serum IgE for level and longitudinal change in airways hyperresponsiveness in COPD

BACKGROUND: Airways hyperresponsiveness (AHR) is an important feature of patients with chronic obstructive pulmonary disease (COPD). Little is known about factors that modulate AHR in COPD. OBJECTIVE: To study these factors, we performed a long-term, double-blind, parallel intervention study in 58 male, non-allergic patients with COPD. METHODS: During a period of 2 years, patients were treated with inhaled budesonide (1600 microg/day), inhaled budesonide (1600 microg/day) plus oral prednisolone (5 mg/day), or placebo. PC20 histamine was measured at 4-monthly intervals. The influence of treatment, smoking, age, level of lung function, initial serum IgE level and peripheral blood eosinophils on level and longitudinal change of PC20 histamine was analysed. RESULTS: During follow-up, PC20 decreased in our group, and this decrease was not influenced by treatment. PC20 tended to decrease faster in current smokers than in ex-smokers. PC20 was significantly associated with pre-challenge FEV1 at each time point. Level nor decline of PC20 were significantly related to age. A higher initial serum IgE level was independently associated with a lower PC20. Moreover, a higher initial serum IgE level was associated with a slower annual decline of PC20, regardless of treatment, pre-challenge FEV1, and other modulating factors. No significant associations were found between initial blood eosinophils and level or decline of PC20. CONCLUSION: We conclude that AHR increases over time in non-allergic patients with COPD. Treatment with an inhaled corticosteroid alone or in combination with oral prednisolone does not change this increase. Our study suggests an important role for IgE in the course of the disease, since a higher initial serum IgE level predicts a more favourable course with regard to annual decline of PC20 histamine.     

A risk model approach to the prediction of fetal acidemia

OBJECTIVES: To compare clinical features, pulmonary function and high-resolution computed chest tomography (HRCT) findings of asthmatic patients with a component of incomplete reversibility of airflow obstruction (AIRAO) with those of patients with smoking-induced chronic obstructive pulmonary disease (COPD). METHODS: Thirteen patients with COPD (six males and seven females, mean age 59 years, mean smoking 50.5 pack-years) and 14 patients with AIRAO (six males and eight females, mean age 52 years) despite optimal treatment, with no significant smoking history (mean 1.5 pack-years) and no significant environmental exposure or any other respiratory disease, were studied. Patients had respiratory questionnaires, pulmonary function tests, allergy skin-prick tests and an HRCT to evaluate possible parenchymal or bronchial abnormalities. Eight patients in each group also had exercise tests. All patients were stable at the time of the study. RESULTS: As expected, atopy was more prevalent in AIRAO (n=13) than in COPD (n=1) patients. Mean forced expiratory volume in 1 s (FEV1) and forced vital capacity (percentage of predicted value) were 39% and 61%, respectively, in COPD patients and 49% and 71%, respectively, in AIRAO patients; FEV1 improved by 18% in COPD patients and and by 22% in AIRAO patients after use of inhaled salbutamol. Mean functional residual capacity was greater in COPD patients than in AIRAO patients (178% versus 144% of the predicted value), while the mean carbon monoxide diffusing capacity of the lungs (DLCO) was lower in COPD patients than in AIRAO patients (62% versus 89% of the predicted value). Exercise tolerance was similar in both groups, as were postexercise changes in arterial oxygen pressure (PaO2). Emphysematous changes were observed in COPD patients and AIRAO patients who had evaluable HRCTs (10 versus two patients, although very mild in asthma), bronchial dilations (zero versus six patients), bronchial wall thickening (two versus eight patients) and an acinar pattern (one versus five patients). Mean thickness of the large airway wall to outer diameter (intermediary bronchus) ratio was 0.176 in COPD and 0.183 in AIRAO (P>0.05). CONCLUSIONS: Asthma may lead to physiological features similar to COPD but may be distinguished by demonstrating a preserved DLCO and a higher ratio of airway to parenchymal abnormalities on HRCT scan.     

A 5-year evaluation of ceramic inlays (CEREC)

BACKGROUND: The aim of this study was to evaluate the morbidity and mortality attributable to smoking. MATERIAL AND METHODS: A transversal study was performed in a reference population of residents of the province of Granada (Spain). The number of deaths in 1985, the number of patients admitted to public hospitals in 1987 and a sample of out patients in 1989 were gathered from the National Institute of Statistics and hospital registries, and a prospective collection from out patient clinics was also carried out. The diseases studied included: oropharyngeal, esophageal, pancreatic, laryngeal, lung, bladder and kidney carcinomas, ischemic cardiopathy, cerebrovascular stroke, peripheral arteriopathy and chronic obstructive lung disease (COPD). Statistical analysis was performed by populational etiologic fraction and the chi square test. RESULTS: Four point five percent of the total number of annual hospital admissions, 6.3% of the out patients, 15.9% of the mortality and 12.0% of the total number of potential years of life lost (TPYLL) were estimated to be attributable to smoking in individuals over the age of 15 years in the province of Granada. The most frequent causes of morbidity attributable to smoking were COPD and ischemic cardiopathy, and with regards to mortality, ischemic cardiopathy (28.5%), COPD (21.6%) and lung cancer (17.5%). Higher percentages were observed in males than in females and in the group from 46 to 65 years of age. CONCLUSIONS: Smoking is not only responsible for an important percentage of deaths, but also leads to premature death and a reduction in the quality of life which is translated into an excess of health care costs. Since the impact of smoking becomes particularly evident from 46 to 65 years of age, smoking prevention should be centered on the early years of life.     

Stretching

BACKGROUND: It has recently been reported that total daily energy expenditure (TDE) is increased in patients with chronic obstructive pulmonary disease (COPD) and it was hypothesised that these patients may have a decreased mechanical efficiency during activities. The purpose of the present study was to measure the mechanical efficiency of submaximal leg exercise, and to characterise patients with a potentially low efficiency in terms of body composition, resting energy expenditure, lung function, and symptom limited exercise performance. METHODS: Metabolic and ventilatory variables were measured breath by breath during submaximal cycle ergometry exercise performed at 50% of symptom limited achieved maximal load in 33 clinically stable patients with COPD (23 men) with forced expiratory volume in one second (FEV1) of 40 (12)% predicted. Net mechanical efficiency was calculated adjusting for resting energy expenditure (REE). RESULTS: Median mechanical efficiency was 15.5% and ranged from 8.5% to 22.7%. Patients with an extremely low mechanical efficiency (< 17%, n = 21) demonstrated an increased VO2/VE compared with those with a normal efficiency (median difference 4.7 ml/l, p = 0.005) during submaximal exercise. There was no difference between the groups differentiated by mechanical efficiency in blood gas tensions at rest, airflow obstruction, respiratory muscle strength, hyperinflation at rest, resting energy expenditure or body composition. There was a significant difference in total airways resistance (92% predicted, p = 0.03) between the groups differentiated by mechanical efficiency. CONCLUSIONS: It is concluded that many patients with severe COPD have decreased mechanical efficiency. Furthermore, based on the results of this study it is hypothesised that an increased oxygen cost of breathing during exercise contributes to the decreased mechanical efficiency.     

An analysis of the outcomes of treatment of small cell lung cancer in the elderly

BACKGROUND: Many cases of small cell lung cancer will occur in the elderly population but optimal management of the disease in this age group remains uncertain. AIMS: To evaluate treatment of small cell lung cancer in the elderly in Australia and to compare treatment received and outcomes with those of younger patients. To draw insights from these observations into the optimal management of small cell lung cancer in the elderly. METHODS: A retrospective review of treatment charts and case notes for 51 elderly patients and 102 younger patients was undertaken. RESULTS: Elderly patients had similar baseline parameters with respect to disease stage and performance status. Elderly patients were mostly treated uniformly with combination chemotherapy, but suffered more dose reductions than younger patients. Benefits of chemotherapy were seen even in patients with poor performance status. Despite the dose reductions, response rates and survival times for elderly patients were usually similar to younger patients. CONCLUSIONS: Combination chemotherapy is beneficial to elderly patients with small cell lung cancer. Optimal therapy for the elderly may be different from that for younger patients and should be defined through prospective randomised clinical trials.