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Показатели, оцениваемые в фармакологических исследованиях ХОБЛ: от легочной функции до биомаркеров
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Body composition is an important measure of nutritional status in patients with chronic obstructive pulmonary disease (COPD). We generated a regression model for bioelectrical impedance (BI) by using deuterium dilution (²H2O) as a reference method in 32 COPD patients, aged 63 ± 9 y (x̄ ± SD), in stable pulmonary and cardiac condition. Height squared divided by resistance (Ht²/Res) correlated well with total body water (TBW) as measured by ²H2O (r = 0.93, P < 0.001, SEE = 1.9 L). The best-fitting regression equation to predict TBW comprised Ht²/Res and body weight (r² = 0.89, SEE = 1.8 L, P < 0.001). BI-predicted TBW was used to estimate BI-fat-free mass (FFM) that was compared with skinfold-thickness–based FFM predictions (Anthr-FFM). Relative to BI-FFM a significant overestimation of 4.4 ± 0.8 kg was found by Anthr-FFM. Our results suggest that BI is a useful measure of body composition in patients with severe COPD.
Eosinophilia has been reported during exacerbations of bronchitis, but the mechanisms of tissue recruitment of eosinophils are unclear. We quantified eosinophils and the concurrent expression of cytokines and chemokines probably responsible for the tissue eosinophilia in bronchial biopsies obtained from three groups of non-atopic subjects: (1) healthy nonsmokers (n = 7; FEV1 % predicted 108 +/- 4 [mean +/- SEM]); (2) nonasthmatic smokers with chronic bronchitis (CB) in a stable phase of their disease (n = 11; FEV1 % predicted: 75 +/- 5); and (3) nonasthmatic subjects with CB who sought medical advice for an exacerbation of their condition (n = 9; FEV1 % predicted: 61 +/- 8). We applied anti-EG2 antibody and immunostaining to detect and count eosinophils. We performed in situ hybridization to visualize and enumerate cells expressing the genes for interleukin (IL)-4 and IL-5 and the eosinophil chemokines eotaxin, monocyte chemoattractant protein (MCP)-4, or regulated on activation, normal T-cell expressed and secreted (RANTES). We confirmed an increase in EG2-positive eosinophils in patients with CB in exacerbation. We found messenger RNA (mRNA) positivity for IL-4 and IL-5 in CB, but the between-group differences were not statistically significant. However, the numbers of lymphomononuclear cells expressing eotaxin mRNA were significantly greater in the smokers with CB than in the healthy nonsmokers without CB (p < 0.01). Following an exacerbation, RANTES expression was upregulated and this chemokine was strongly expressed in both the surface epithelium and in subepithelial lymphomononuclear cells: only RANTES showed a significant positive correlation with the increasing number of EG2-positive cells (r = 0.51; p < 0.03). In conclusion, an allergic profile of inflammation can also occur in CB: the marked upregulation of RANTES in the epithelium and subepithelium most likely accounts for the increased eosinophilia associated with an exacerbation of bronchitis.
The National Emphysema Treatment Trial is a multicenter, randomized clinical trial of medical therapy vs medical therapy plus lung volume reduction surgery (LVRS) for the treatment of patients with severe bilateral emphysema. LVRS will he accomplished by bilateral nl stapled excision via median sternotomy or video-assisted thoracoscopic surgery. Every patient will complete 6 to 10 weeks of pulmonary rehabilitation prior to randomization anti will participate in a maintenance program of pulmonary rehabilitation after randomization, The primary outcome to be assessed by the trial is survival. Additional outcomes to be assessed are maximum exercise capacity, pulmonary function, oxygen requirement, distance walked in 6 min, quality of life, respiratory symptoms, and health-care utilization and costs, In addition, selected clinics will evaluate lung mechanics and respiratory muscle function, partial and maximal flow-volume curves, gas exchange during maximal exercise, and right heart function, The trial is targeted to enroll patients with severe emphysema who have no significant comorbid conditions; each patient will be randomized to one of the two treatment groups. The study duration is 4.5 years with a close-out period of 6 months.
Lung volumes are subdivided into static and dynamic lung volumes. Static lung volumes are measured by methods which are based on the completeness of respiratory manoeuvres, so that the velocity of the manoeuvres should be adjusted accordingly. The measurements taken during fast breathing movements are described as dynamic lung volumes and as forced inspiratory and expiratory flows.
### 1.1 Static lung volumes and capacities
The volume of gas in the lung and intrathoracic airways is determined by the properties of lung parenchyma and surrounding organs and tissues, surface tension, the force exerted by respiratory muscles, by lung reflexes and by the properties of airways. The gas volumes of thorax and lung are the same except in the case of a pneumothorax. If two or more subdivisions of the total lung capacity are taken together, the sum of the constituent volumes is described as a lung capacity. Lung volumes and capacities are described in more detail in § 2.
#### 1.1.1 Determinants
Factors which determine the size of the normal lung include stature, age, sex, body mass, posture, habitus, ethnic group, reflex factors and daily activity pattern. The level of maximal inspiration (total lung capacity, TLC) is influenced by the force developed by the inspiratory muscles (disorders include e.g. muscular dystrophy), the elastic recoil of the lung (disorders include e.g. pulmonary fibrosis and emphysema) and the elastic properties of the thorax and adjacent structures (disorders include e.g. ankylosis of joints). The level of maximal expiration (residual volume, RV) is determined by the force exerted by respiratory muscles (disorders include e.g. muscle paralysis), obstruction, occlusion and compression of small airways (disorders include e.g. emphysema) and by the mechanical properties of lung and thorax (disorders include diffuse fibrosis, kyphoscoliosis).
Assessing the total lung capacity is indispensable in establishing a restrictive ventilatory defect or in diagnosing abnormal lung distensibility, as may occur in patients …
This summary presents an overview of the entire document or the health practitioner, which is readily available online (www.copd-ats-ers, www.ersnet.org and www.thoracic.org). This summary does not include any reference to the patient document, which, due to its inherent characteristics, cannot be presented in a conventional format. The readers are encouraged to visit the website to access both full documents. The committee that developed this document fully understands that the field is rapidly changing and that individual components of this document need to be updated periodically as the need arises. However, the modular and flexible design allows for this to occur easier than ever before. The challenge for the future is to develop mechanisms to permit the updated flow of valid scientific information to reach all who need it.
The aim of this study was to assess the prognostic role of co-morbidity in severe chronic obstructive pulmonary disease (COPD), A cohort of 270 COPD patients, mean (+/-SD) age 67+/-9,,rs, consecutively discharged from a University Hospital after an acute exacerbation was studied, Mean (+/-SD) forced expiratory volume in one second (FEV1) was 34+/-16% of predicted and FEV1/ forced, vital capacity (FVC) was 40.5+/-13.8%, The most common co-morbid diseases,were: hypertension (28%), diabetes mellitus (14%), and ischaemic heart disease (10%). Clinical, electrocardiogram (EGG), and respiratory function data taken at the time of discharge were collected front the clinical records, The Charlson's index was used to quantify co-morbidity, Follow-up was conducted by means of telephone calls. Multivariate survival analysis was used to identify. the independent predictors of death, The median survival of the cohort was 3.1 yrs. Death was predicted by the following variables: age (hazard rate (HR) 1.04; 95% confidence intervals (95% Cl) 1.02-1.05), ECG signs of right ventricular hypertrophy (HR 1.76; 95% Cl 1.30-2.38), chronic renal failure (HR 1.79; 95% Cl 1.05-3.02), ECC signs of myocardial infarction or ischaemia (HR 1.42; 95% Cl 1.02-1.96), FEV1 <590 mL (HR 1.49; 95% CI 0.97-2.27). A scorebased upon these variables predicted mortality at 5 yrs with a sensitivity of 63% and a specificity of 77%. Selected co-morbid diseases and electrocardiogram signs of right ventricular hyertrophy. play a major prognostic role in advanced chronic obstructive pulmonary disease, The clinical assessment of patients with chronic obstructive pulmonary disease should include these important and easily measurable variables.
A ranked assessment of daily living (ADL) scale has been developed to assess activities which may be important to stroke patients who have been discharged home. A questionnaire incorporating 22 ADL activities in four sections was sent by post to 80 consecutively registered stroke patients. Gutmann scaling was carried out on the returned questionnaires, producing acceptable coefficients of reproducibility and scalability. The revised questionnaire was then sent to 20 stroke patients. The same patients were sent an identical questionnaire two weeks later. The overall level of agreement between the two assessments was satisfactory. The extended ADL scale could therefore be used as a postal questionnaire to assist in the follow-up of patients discharged home after a stroke. Due to the scaling properties of the assessment, patient's progress can be monitored and patients can also be compared on the basis of their scale score.
This is a unique, in-depth discussion of the uses and conduct of cost-effectiveness analyses (CEA) as decision-making aids in the health and medical fields. The product of over two years of deiberation by a multi-disciplinary Public Health Service appointed panel that included economists, ethicists, psychometricians, and clinicians, it explores cost-effectiveness in the context of societal decision-making for resource allocation purposes. It proposes that analysts include a “reference-case” analysis in all CEA’s designed to inform resource allocation and puts forth the most expicit set of guidelines (together with their rationale) ever outlined of the conduct of CEAs. Important theoretical and practical issues encountered in measuring costs and effectiveness, valuing outcomes, discounting, and dealing with uncertainty are examined in separate chapters. These discussions are complemented by additional chapters on framing and reporting of CEAs that aim to clarify the purpose of the analysis and the effective communication of its findings. Primarily intended for analysts in medicine and public health who wish to improve practice and comparability of CEAs, this book will also be of interest to decision-makers in government, managed care, and industry who wish to consider the roles and limitations of CEA and become familiar with criteria for evaluating these studies.
Quality of life (QOL) is how the individual perceives himself as having an impact on his physical-emotional integrity, functional capacity, and self-esteem. Quality of life assessment tools can be generic or specific. Generics evaluate various aspects of quality of life and health status, and can be useful for patients, regardless of disease or condition, and can also be used for healthy individuals. The Medical questionnaire Outcomes Study 36 (SF-36) is one of the main instruments used to assess the health-related quality of life. This study aimed to develop the first application software (APP) for assessing the quality of life in Portuguese. This is an experimental study, of analytical, observational, and transversal nature that seeks associations or correlations between variables of interest. The application was developed on the Unity Engine to facilitate port for Android and its graphical interface. The Sarcvida app contemplates the SF-36 questionnaire and the SARC-F+CC. The application has undergone structural and functional tests and the next step is the evaluation of the app by health professionals. Sarcvida app is composed of SF-36 QOL questionnaire, SARC-F+CC, and D-score. The application proved to be functional, corresponding to initial research expectations for the project. The app presented usability and functionality for the evaluation of QOL in the tests to which it has been submitted so far. In Brazil there are no applications composed of SF-36 QOL questionnaire, SARC-F+CC, and the D-score, therefore, this study is innovative, presenting the first Portuguese version available in the app. Besides, mobile technology developed here is a tool to help monitor patients by contributing health professionals in possible interventions for health promotion.KeywordsApplicationQuality of lifeBioengineering
Divided into three sections spanning the mechanisms of dyspnea, measurement and assessment strategies, and management techniques-this reference illustrates the impact of dyspnea on patients with chronic respiratory disease. With contributions by recognized experts on the topic, this handbook provides an abundance of practical information and recomm.
Background: Survival studies have consistently shown significantly greater mortality rates in underweight and normal-weight patients with chronic obstructive pulmonary disease (COPD) than in overweight and obese COPD patients.
Objective: To compare the contributions of low fat-free mass and low fat mass to mortality, we assessed the association between body composition and mortality in COPD.
Design: We studied 412 patients with moderate-to-severe COPD [Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) stages II–IV, forced expiratory volume in 1 s of 36 ± 14% of predicted (range: 19–70%). Body composition was assessed by using single-frequency bioelectrical impedance. Body mass index, fat-free mass index, fat mass index, and skeletal muscle index were calculated and related to recently developed reference values. COPD patients were stratified into defined categories of tissue-depletion pattern. Overall mortality was assessed at the end of follow-up.
Results: Semistarvation and muscle atrophy were equally distributed among disease stages, but the highest prevalence of cachexia was seen in GOLD stage IV. Forty-six percent of the patients (n = 189) died during a maximum follow-up of 5 y. Cox regression models, with and without adjustment for disease severity, showed that fat-free mass index (relative risk: 0.90; 95% CI: 0.84, 0.96; P = 0.003) was an independent predictor of survival, but fat mass index was not. Kaplan-Meier and Cox regression plots for cachexia and muscle atrophy did not differ significantly.
Conclusions: Fat-free mass is an independent predictor of mortality irrespective of fat mass. This study supports the inclusion of body-composition assessment as a systemic marker of disease severity in COPD staging.
Although current recommendations for spirometry require that the largest value of FEV1 and FVC should be taken from the largest values of different maneuvers, the validity of this approach was recently questioned. It has been suggested that selection of the maneuver with the largest peak flow or the maneuver with the largest FVC should be used for measurement of spirometric indices. The present analysis was therefore undertaken to determine which method of selection of spirometric maneuvers would give the least short-term variability in a clinical trial population. We examined the spirometry test sessions from 5,885 individuals with mild to moderate chronic airflow obstruction who were screened at two visits 24.9 +/- 17.1 d apart for entry into a multi-center clinical trial, the Lung Health Study. We compared eight potential selection methods for FEV1 and FVC. Using these different selection methods, the coefficient of variation ranged from 4.1 to 4.9% for FEV1 and from 3.5 to 5.7% for FVC. The average absolute difference between the two test sessions ranged from 110 to 123 ml for FEV1 and from 149 to 200 ml for FVC. Although all of the methods gave good results, the mean of the three highest values and the largest single value from all maneuvers provided the least short-term variability for both FEV1 and FVC. We therefore conclude that there is no reason to change the currently recommended selection methods for FEV1 and FVC.
To assist clinicians and researchers in choosing outcome measures for patients with chronic obstructive pulmonary disease attending routine outpatient clinics, a comparative assessment was undertaken of four questionnaires designed to reflect the patients' perception of their physical and emotional health in terms of their feasibility, validity, reliability, and responsiveness to health change. METHODS: Two condition specific questionnaires, the St George's Respiratory Questionnaire (SGRQ) and Guyatt's Chronic Respiratory Questionnaire (CRQ), and two generic questionnaires, the Short Form-36 Health Survey (SF-36) and Euroqol (EQ), were compared for their discriminative and evaluative properties. Spirometric tests and a walking test were also performed. One hundred and fifty six adults who were clinically judged to have COPD and who attended an outpatient chest clinic were assessed at recruitment and six and 12 months later. Patients were also asked whether their health had changed since their last assessment. RESULTS: Completion rates and consistency between items for dimensions of the SGRQ were lower than for dimensions of the other questionnaires. The distributions of responses were skewed for certain dimensions in all questionnaires except the CRQ. Validity was supported for all instruments insofar as patients' scores were associated with differences in disease severity. The generic questionnaires better reflected other health problems. All instruments were reliable over time. The condition specific questionnaires were more responsive between baseline and first follow up visit but this difference did not persist. While certain dimensions of the SF-36 were responsive to patient perceived changes, this did not apply to the derived single index of the EQ. The rating scale of the EQ, however, provided a quick and easy indicator of change. CONCLUSIONS: Evidence from this study supports the CRQ and the SF-36 as comprehensive outcome measures for patients with longstanding COPD.
At six centers, 203 patients with hypoxemic chronic obstructive lung disease were randomly allocated to either continuous oxygen (O2) therapy or 12-hour nocturnal O2 therapy and followed for at least 12 months (mean, 19.3 months). The two groups were initially well matched in terms of physiological and neuropsychological function. Compliance with each oxygen regimen was good. Overall mortality in the nocturnal O2 therapy group was 1.94 times that in the continuous O2 therapy group (P = 0.01). This trend was striking in patients with carbon dioxide retention and also present in patients with relatively poor lung function, low mean nocturnal oxygen saturation, more severe brain dysfunction, and prominent mood disturbances. Continuous O2 therapy also appeared to benefit patients with low mean pulmonary artery pressure and pulmonary vascular resistance and those with relatively well-preserved exercise capacity. We conclude that in hypoxemic chronic obstructive lung disease, continuous O2 therapy is associated with a lower mortality than is nocturnal O2 therapy. The reason for this difference is not clear.
Measurements of the single-breath carbon monoxide diffusing capacity (Dl) were obtained on a randomly selected sample representative of the white non-Mexican-American population of Tucson, Arizona. Methods of measurement followed the guidelines set forth in the ATS-sponsored Epidemiology Standardization Project. There were 228 healthy nonsmokers who had duplicate tests that met the criteria for being acceptable. On the basis of data from these subjects, reference equations were derived for Dl, alveolar volume (Va), and Dl/Va. The data demonstrate the effects of growth and development, height, and age on these variables. Because a significant proportion of women, but not of men, had low hematocrit values, an effect of hematocrit on Dl and Dl/Va could be demonstrated only in females in this population sample.
Background
Functional exercise capacity has been shownto be a strong predictor of survival following pulmonaryrehabilitation. This study evaluated whether questionnaire-ratedfunctional status is also predictive of survival.
Patientsand methods
Following pulmonary rehabilitation, patients withadvanced chronic lung disease were evaluated for survival, 6-min walkdistance, and questionnaire-rated functional status. The latter wasmeasured using the pulmonary functional status scale, which hassubscores of functional activities, psychological status, and dyspnea. Information on survival was available on 149 patients.
Results
The mean age was 69 years, and 45% of patientswere male. Eighty-nine percent had a diagnosis of COPD, and their, FEV1 was 37 ± 18% of predicted. Ninety-one (61%) weremarried. The 3-year survival for the group was 85%. Age, gender, bodymass index, and primary diagnosis were not related to survival. Variables strongly associated with increased survival followingpulmonary rehabilitation included a higher postrehabilitation, Functional Activities score, a longer postrehabilitation 6-min walkdistance, and being married (vs widowed, single, or divorced). Diseaseseverity variables associated with survival included an initialreferral to outpatient pulmonary rehabilitation, no supplemental oxygenrequirement, and a higher percent-predicted FEV1.
Conclusion
Indicators of functional status are strongpredictors of survival in patients with advanced lungdisease.
Only long-term home oxygen therapy has been shown in randomised controlled trials to increase survival in chronic obstructive pulmonary disease (COPD). There have been no trials assessing the effect of inhaled corticosteroids and long-acting bronchodilators, alone or in combination, on mortality in patients with COPD, despite their known benefit in reducing symptoms and exacerbations. The “TOwards a Revolution in COPD Health” (TORCH) survival study is aiming to determine the impact of salmeterol/fluticasone propionate (SFC) combination and the individual components on the survival of COPD patients.
TORCH is a multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Approximately 6,200 patients with moderate-to-severe COPD were randomly assigned to b.i.d. treatment with either SFC (50/500 µg), fluticasone propionate (500 µg), salmeterol (50 µg) or placebo for 3 yrs. The primary end-point is all-cause mortality; secondary end-points are COPD morbidity relating to rate of exacerbations and health status, using the St George's Respiratory Questionnaire. Other end-points include other mortality and exacerbation end-points, requirement for long-term oxygen therapy, and clinic lung function. Safety end-points include adverse events, with additional information on bone fractures.
The first patient was recruited in September 2000 and results should be available in 2006. This paper describes the “TOwards a Revolution in COPD Health” study and explains the rationale behind it.
We used a computed tomography (CT) scanner program (“density mask”) that highlights voxels within a given density range to quantitate emphysema by defining areas of abnormally low attenuation. We compared different density masks, mean lung attenuation, visual assessment of emphysema and the pathologic grade of emphysema in 28 patients undergoing lung resection for tumor. In each patient, a single representative CT image was compared with corresponding pathologic specimens of tissue. There was good correlation between the extent of emphysema as assessed by the density mask and the pathologic grade of emphysema. The optimal attenuation level to define areas of emphysema may vary in different scanners, but, once determined for a particular scanner, the density mask accurately assesses the extent of emphysema and eliminates interobserver and intraobserver variability. It has the added advantage of determining the exact percentage of lung parenchyma showing changes consistent with emphysema. (Chest 1988; 94:782-87)
Only long-term home oxygen therapy has been shown in randomised controlled trials to increase survival in chronic obstructive pulmonary disease (COPD). There have been no trials assessing the effect of inhaled corticosteroids and long-acting bronchodilators, alone or in combination, on mortality in patients with COPD, despite their known benefit in reducing symptoms and exacerbations. The "TOwards a Revolution in COPD Health" (TORCH) survival study is aiming to determine the impact of salmeterol/fluticasone propionate (SFC) combination and the individual components on the survival of COPD patients. TORCH is a multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Approximately 6,200 patients with moderate-to-severe COPD were randomly assigned to b.i.d. treatment with either SFC (50/500 mug), fluticasone propionate (500 mug), salmeterol (50 mug) or placebo for 3 yrs. The primary end-point is all-cause mortality; secondary end-points are COPD morbidity relating to rate of exacerbations and health status, using the St George's Respiratory Questionnaire. Other end-points include other mortality and exacerbation end-points, requirement for long-term oxygen therapy, and clinic lung function. Safety end-points include adverse events, with additional information on bone fractures. The first patient was recruited in September 2000 and results should be available in 2006. This paper describes the "TOwards a Revolution in COPD Health" study and explains the rationale behind it.
BACKGROUND—Pulmonary rehabilitation programmes improve the health of patients disabled by lung disease but their cost effectiveness is unproved. We undertook a cost/utility analysis in conjunction with a randomised controlled clinical trial of pulmonary rehabilitation versus standard care.
METHODS—Two hundred patients, mainly with chronic obstructive pulmonary disease, were randomly assigned to either an 18 visit, 6 week rehabilitation programme or standard medical management. The difference between the mean cost of 12 months of care for patients in the rehabilitation and control groups (incremental cost) and the difference between the two groups in quality adjusted life years (QALYs) gained (incremental utility) were determined. The ratio between incremental cost and utility (incremental cost/utility ratio) was calculated.
RESULTS—Each rehabilitation programme for up to 20 patients cost £12 120. The mean incremental cost of adding rehabilitation to standard care was £ -152 (95% CI -881 to 577) per patient, p=NS. The incremental utility of adding rehabilitation was 0.030 (95% CI 0.002 to 0.058) QALYs per patient, p=0.03. The point estimate of the incremental cost/utility ratio was therefore negative. The bootstrapping technique was used to model the distribution of cost/utility estimates possible from the data. A high likelihood of generating QALYs at negative or relatively low cost was indicated. The probability of the cost per QALY generated being below £0 was 0.64.
CONCLUSIONS—This outpatient pulmonary rehabilitation programme produces cost per QALY ratios within bounds considered to be cost effective and is likely to result in financial benefits to the health service.
To elucidate the effect of oxitropium bromide (OTB), an anticholinergic drug, on dyspnea and gas exchange during exercise in patients with chronic obstructive pulmonary disease (COPD), we performed the cycle exercise test on 19 patients with COPD (mean age, 72.0 ± 1.9 years; mean FEV1, 1.28 ± 0.07 L) before and after inhalation of OTB, 300 µg, or placebo, 300 in randomized fashion. Spirometry was performed immediately before and 30 min after inhalation of either OTB or placebo. Dyspnea during exercise was evaluated using the Borg scale (BS) and the slope of the regression between BS and oxygen uptake (V o2) during exercise (Borg scale slope: BSS). Arterial oxygen saturation (SaO2) was continuously monitored by pulse oximeter during and after exercise. We also measured the recovery time, which was defined as the time to recover decreases in SaO2 after exercise. After OTB, spirometric indices were improved (AFEV1 16.8 ± 0.9 percent) and maximal V˙o2 during exercise increased significantly (from 986 ± 46 ml/min to 1,156 ± 55 mil/min, p<0.01), but not after placebo. The maximal scores of BS and the BSS were significantly decreased after OTB, but not after placebo. Although the SaO2 at rest and during exercise did not differ with or without either OTB or placebo, the recovery time after OTB (77.3 ± 6.8 s) was significantly shorter than that before administration (98.4 ± 14.6 s) (p<0.01). We conclude that the inhaled OTB produces small but significant improvement both in dyspnea during exercise and in exercise performance in stable COPD and may contribute to improve the quality of life in some patients with COPD. However, gas exchange during exercise of COPD patients is little affected by OTB.
(Chest 1993; 103:1774-82)
We used a CT program “density mask” outlining areas with attenuation values less than —910 HU, to indicate areas of emphysema on a chest CT and to provide an overall percentage of lung involvement by emphysema. The “density mask” quantitation of emphysema was previously shown to correlate well with the pathologic assessment of emphysema in patients undergoing lung resection. We compared the CT quantitation of emphysema with mean lung density, overall lung volume on CT and pulmonary function tests in 85 patients. There was a significant correlation between the extent of emphysema on CT and FEV1/FVC percent of predicted, functional residual capacity percent predicted and Dsb percent predicted. Determination of the percentage of lung with areas of low attenuation by CT provides a useful method for quantitating emphysema in life and correlates significantly with pulmonary function tests.
(Cheat 1990; 97:315–321)
Objectives: To investigate the effectiveness of case finding of patients at risk of developing chronic obstructive pulmonary disease, whether the method is suitable for use in general practice, how patients should be selected, and the time required. Design: Cross sectional study. Setting: Two semirural general practices in the Netherlands. Participants: 651 smokers aged 35 to 70 years. Main outcome measures: Short standardised questionnaire on bronchial symptoms for current smokers, lung function with a spirometer, and the quality of the spirometric curve. Results: Of the 201 smokers not taking drugs for a pulmonary condition, 169 produced an acceptable curve (fulfilling American Thoracic Society criteria). Of these, 30 (18%, 95% confidence interval 12% to 24%) had a forced expiratory volume in one second (FEV 1 ) 1 v 2.50 (1.14 to 5.52)). Age was also a good predictor of obstruction; smokers over 60 with cough had a 48% chance of having an obstruction. The mean time needed for spirometry was four minutes. Detecting one smoker with an FEV 1 Conclusions: Trained practice assistants could check all patients who smoke for chronic obstructive pulmonary disease at little cost to the practice. Cough and age are the most important predictors of the disease. By testing one smoker a day, an average practice could identify one patient at risk a week.
In recent years, much attention has been given to the role of CT in detecting and quantitating pulmonary emphysema. We measured CT lung density in 45 patients undergoing a diagnostic work-up and compared this with pulmonary function tests. The CT lung densities measured with the sector method and with the whole lung method were very highly correlated with each other (r=0.96, p<O.0Ol), and measurements at TLC systematically gave a lower density than those at FRC (p<O.O0l). Also, CT density measurements at TLC and even more so at FRC correlated well with pulmonary function indices of airway obstruction and of hyperinflation, but not with indices that are considered more specific for emphysema (single breath Dco, static lung compliance) We conclude that CT lung density gives a good reflection of the degree of hyperinflation, le, enlargement of distal airways, but is not sensitive to detect whether or not this is associated with emphysema. (Chest 1992� 102:805-11)
A quantitative study was performed to assess the magnitude of the nonlinear partial volume effect (NLPVE) in computed tomography(CT) densitometry of polyethene foam and lung. This effect arises in materials having density variations on the scale of the sampling area of an individual CT‐detector element. It causes a systematic underestimation of the density determined with CT.Foam samples and a resected lung of a goat were imaged with high resolution (20 lp/mm) using a mammography system, and the observed optical density variation in the images was converted into a distribution of pathlengths that x rays penetrate within the solid component of the cellular material. The obtained pathlength distribution was used to calculate the transmission, as seen by a single detector in computed tomography. Comparison with the transmission through homogeneous material of the same thickness gave an estimate of the NLPVE. For the foams studied, the CT‐determined density was found to be too low by approximately 0.3%–0.5% due to this effect. Although these density errors are small, in calibrations of a CT scanner they may be of significance. For lung the underestimation of the density was less than 0.1%. These experimentally derived, NLPVE related CT‐density errors are 32%–84% of those calculated from a simple model of a cellular solid.
Objectives
COPD is a common and disabling disease that entails high costs for society. The objectives of this study were to measure the societal costs of COPD in Sweden, and to examine the relationship between severity of illness and costs.
Methods
The costs of COPD were examined using a well-defined and representative cohort of subjects with mild, moderate, and severe COPD. Regular telephone interviews regarding resource utilization were made to a cohort of 212 subjects with COPD derived from studies of the general population in Northern Sweden.
Results
The annual per capita cost for COPD in Swedish crowns (SEK) was estimated at SEK 13,418 (1,284 US dollars (USD); 1,448 euros (EUR). The direct and indirect costs were SEK 5,592 (42%) and SEK 7,828 (58%), respectively. A highly significant relationship was found between severity of disease and costs. Costs for severe disease were 3 times as high as costs for moderate disease and > 10 times as high as for mild disease. Large individual variations in the level of costs were found.
Conclusion
Assuming that the prevalence and treatment patterns are representative of Sweden as a whole, the total costs of COPD to society in 1999 were estimated at SEK 9.1 billion (USD 871 million; EUR 982 million). Subjects with mild disease (83%) accounted for 29%, while subjects with moderate disease (13%) accounted for 41% of the total costs. The subjects with severe disease (4%) accounted for the remainder (30%). Prevention, early diagnosis, and postponement of disease progression should have large monetary and policy implications.
The effects of broad-spectrum antibiotic and placebo therapy in patients with chronic obstructive pulmonary disease in exacerbation were compared in a randomized, double-blinded, crossover trial. Exacerbations were defined in terms of increased dyspnea, sputum production, and sputum purulence. Exacerbations were followed at 3-day intervals by home visits, and those that resolved in 21 days were designated treatment successes. Treatment failures included exacerbations in which symptoms did not resolve but no intervention was necessary, and those in which the patient's condition deteriorated so that intervention was necessary. Over 3.5 years in 173 patients, 362 exacerbations were treated, 180 with placebo and 182 with antibiotic. The success rate with placebo was 55% and with antibiotic 68%. The rate of failure with deterioration was 19% with placebo and 10% with antibiotic. There was a significant benefit associated with antibiotic. Peak flow recovered more rapidly with antibiotic treatment than with placebo. Side effects were uncommon and did not differ between antibiotic and placebo.
colon; Mean lung attenuation has been measured on computed tomography (CT) sections through the lung bases of 17 patients with no evidence of respiratory disease. Sections were obtained in inspiration and at neutral respiration together with spirometric measurement of lung volume changes. The normal range for mean attenuation including all phases of respiration is approximately -350 to -430 EMI units (EU) (air = -500). The range is narrower on inspiration than at neutral respiration. Mean attenuation in the posterior one-third of the lung base may be 100 EU greater than in the anterior one-third. This gradient is reduced but not abolished on inspiration. Reduction of attenuation with inspiration correlates inversely with increased lung volume and cross-sectional area. Anteroposterior attenuation gradients and regional changes of attenuation with breathing can be explained by preferential ventilation and perfusion of the dependent regions of the lung. When using CT to measure lung "density," the effects of breathing should be taken into account. The relevance of these observations to the detection of early diffuse lung disease is discussed. Index Terms: Computed tomography-Lungs, ventilation-Attenuation values.
PURPOSE: This study examines the association between lung function [percentage predicted FEV1 (forced expiratory volume in 1 s)] and respiratory symptoms (asthma, bronchitis, wheeze, dyspnea) and mortality from all causes; coronary heart disease, stroke, cancer, and respiratory disease in a cohort of 2100 men and 2177 women in the Busselton Health Study followed for 20–26 years for mortality.METHODS: A total of 840 men and 637 women died during the follow-up period, and Cox proportional hazards regression was used to assess the relationships between risk factors and mortality.RESULTS: Lung function was significantly and independently predictive of mortality from all causes, coronary heart disease, cancer, and respiratory disease in both men and women, and of mortality from stroke in women. There was evidence that, among men, the association was stronger in current and former smokers as compared to those who never smoked. After adjustment for age, smoking, lung function, coronary heart disease, blood pressure, treatment for hypertension, total cholesterol, body mass index, and alcohol consumption, dyspnea was significantly related to total mortality in men and women and to respiratory disease mortality in men, and asthma was significantly related to respiratory disease mortality in women.CONCLUSIONS: Lung function is associated with mortality from many diseases independent of smoking and respiratory symptoms. Although most respiratory symptoms are associated with smoking and lung function, after controlling for smoking and lung function, only dyspnea is associated with mortality from nonrespiratory causes.
Background and Objective: The aim of this study was to develop and validate two models to estimate the probabilities of frequent exacerbations (more than 1 per year) and admissions for chronic obstructive pulmonary disease (COPD) that can be used in a primary care setting. Methods: Information was obtained in a cross-sectional observational study on ambulatory COPD patients performed in 201 general practices located throughout Spain. The model for admissions included 713 cases, 499 for the developmental sample and 214 in the validation sample; the model for frequent exacerbations included 896 patients, 627 in the developmental sample and 269 in the validation model. Candidate variables to be included in both models were: age, sex, body mass index (BMI), FEV1 as percent predicted [FEV1 (% pred.)] , active smoking, chronic mucus hypersecretion (CMH) and significant comorbidity. Results: The admission model contained 2 readily obtainable variables: comorbidity (OR = 1.97; CI 95% = 1.24–3.14) and FEV1(% pred.) (OR = 0.72; 0.58–0.88, for every 10 units), and well calibrated in developmental and validation samples (goodness-of-fit tests: p = 0.989 and p = 0.720, respectively). The model for frequent exacerbations included 3 variables: age (OR = 1.21; 1.01–1.44; for every 10 years of increasing age), FEV1 (% pred.) (OR = 0.82; 0.70–0.96, for every 10 units) and CMH (OR = 1.54; 1.11–2.14) and also well calibrated (p = 0.411 and p = 0.340 in the developmental and validation samples, respectively). Conclusions: Our results suggest that FEV1 impairment explains part of the risk of frequent exacerbations and hospital admissions. Furthermore, CMH and increasing age are significantly associated with the risk of frequent exacerbations, but severity of exacerbations provoking hospital admissions is associated with the presence of significant comorbidity. These important and easily measurable variables contain valuable information for optimal management of ambulatory patients with COPD.
Background:
Neutrophil elastase (NE) is thought to be one of the key proteinases in the development of chronic obstructive pulmonary disease (COPD). Previously, we have shown that the NE-alpha1-proteinase inhibitor (NE-alpha1PI) complex in bronchoalveolar lavage (BAL) fluid was markedly elevated in asymptomatic smokers who had subclinical emphysema on CT scans. We proposed that excessive NE-alpha1PI complex in BAL fluid was a factor which might differentiate smokers who were developing emphysema from others.
Objective:
In this study, we addressed the question of whether elevated levels of the NE-alpha1PI complex in BAL fluid are linked to the accelerated decline in pulmonary functions in those subjects.
Methods:
We conducted a follow-up study to analyze the decline in FEV(1) for 4.3 years on average for 26 community-based volunteers who had received pulmonary function tests, CT scans and BAL. The levels of the NE-alpha1PI complex in BAL fluid and in plasma was measured.
Results:
Neither pulmonary function measurements nor the presence of emphysema on CT scans could predict the decline in FEV(1). The number of inflammatory cells in BAL fluid was also not an indicator of progression. By contrast, subjects with higher levels of the NE-alpha1PI complex in BAL fluid had a significantly accelerated decline in FEV(1) compared to those with lower levels.
Conclusion:
These data seem to support the hypothesis that NE in the lung is related to the onset and/or progression of COPD.