[The gap between the high impact and low awareness of COPD in the population]. / Sujets à risque de BPCO en population générale: disproportion entre la fréquence des symptômes, leur perception et la connaissance de la maladie.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is markedly under-diagnosed, which may relate to under-reporting of symptoms and poor awareness of the disease. METHODS: A survey was conducted in a sample of the French general population aged 40-75 years (n=2758) to assess respiratory symptoms and level of knowledge of the disease in subjects with or at-risk of COPD (n=860, 31%). RESULTS: The high frequency of dyspnoea (MRC dyspnoea grade > or =1: 40%) contrasted with that of subjects spontaneously reporting respiratory problems (9%). Among these, 72% reported limitations in daily-life activities but only 14% considered that they were severely affected by their respiratory status. A very low proportion of subjects knew the term COPD (8%) and only 66% of these associated COPD with a respiratory disease. CONCLUSIONS: There is a wide gap between the high number of subjects at risk of COPD in the general population and the frequency of breathlessness in these subjects on one hand, and the poor knowledge of the disease, poor perception of symptoms, and under-diagnosis and under-use of spirometry on the other. Increasing awareness of COPD in the population is needed.

[Arterial and venous thrombosis in lung cancer]. / Thrombose artérielle et veineuse et cancer bronchique.

We report the case of a 61-year old man in whom a deep venous thrombosis was the presenting feature of disseminated lung carcinoma. A few days later, an arterial thrombosis occurred necessitating amputation. Within a few weeks, the lung cancer progressed dramatically and the patient died. While the association between venous thrombosis and cancer is well known, the relationship between cancer and arterial thrombosis has been less explored. This observation allows discussion of the pathophysiological and clinical aspects of this association, as well as the implications for patient care.

Impact of chronic airflow obstruction in a working population.

Data on the individual and collective impact of chronic airflow obstruction at a population level are scarce. In a nationwide survey, dyspnoea, quality of life and missed working days were compared between subjects with and without spirometrically diagnosed chronic airflow obstruction. Subjects aged > or =45 yrs were recruited in French health prevention centres (n = 5,008). Results of pre-bronchodilator spirometry and questionnaires (European Community Respiratory Health Survey-derived questionnaire and European quality of life five-dimension questionnaire) were collected. Adequate datasets were available for 4,764 subjects aged 60+/-10 yrs (only 2% were aged > or =80 yrs). The prevalence of airflow obstruction (forced expiratory volume in one second/forced vital capacity of <0.70) was 7.5%. The vast majority (93.9%) of cases had not been diagnosed previously. Health status was significantly influenced by dyspnoea. Both were associated with the number of missed working days. Despite mild-to-moderate severity, subjects with chronic airflow obstruction exhibited more dyspnoea, poorer quality of life and higher numbers of missed working days (mean 6.71 versus 1.45 days.patient(-1).yr(-1) in patients without airflow obstruction, for the population with no known heart or lung disease). In conclusion, even mild-to-moderate airflow obstruction is associated with an impaired health status, which represents an additional argument in favour of early detection in chronic obstructive pulmonary disease.

[Follow-up criteria for community acquired pneumonias and acute exacerbations of chronic obstructive pulmonary disease]. / Critères du suivi évolutif des pneumonies aiguës communautaires et des exacerbations aiguës de bronchopneumopathie chronique obstructive.

The follow-up of Community Acquired Pneumonias (CAP) and Acute Exacerbations of Chronic Obstructive Pulmonary Diseases (AECOPD) differs with the setting of care, but overall calls upon the same investigations as the initial evaluations. In the event of initial ambulatory care, the evaluation is carried out primarily on clinical data, at the 2 or 3rd day for the CAP, at the 2nd to 5th day for the AECOPD. In the event of unfavourable evolution, or from the start in the most severe cases, the follow-up is carried out in hospital; clinical evaluation is readily daily, and all the more frequent that the clinical condition is worrying because of the severity or risk factors. The investigations will be limited to those initially abnormal in the event of favourable evolution; on the contrary, unfavourable evolution can justify new investigations which depend on clinical characteristics. Remotely, i.e. 4 to 8 weeks later, must be checked the return at the baseline clinical state, a chest X-ray (CAP), spirometry and arterial blood gas (AECOPD), even bronchoscopy and thoracic CT-scan.

Incidence and prognostic value of respiratory events in acute leukemia.

Acute respiratory failure and infectious pneumonia are the major causes of death during induction chemotherapy of acute leukemia. However, the causes, incidence and prognostic value of all respiratory events (REs) occurring in this context have never been assessed prospectively. We recruited 65 consecutive patients with newly diagnosed acute leukemia into a 1-year prospective study (December 2000-November 2001) to evaluate the incidence and prognostic value of these events. REs were frequent: 38 were recorded in 30 patients. There was a significant relationship between REs and pre-existing respiratory disease and/or smoking. REs were caused by infection in 34% of cases, by an established cause other than infection in 42% and had an undetermined cause in 24%. Poor early outcome (death within 45 days of starting induction chemotherapy) in patients experiencing an RE was independently associated with a >25/min respiratory rate (P=0.003) and the nonachievement of complete remission (CR) (P<0.0001). Predictors of overall survival in the entire patient population were the absence of CR (P<0.0001), REs (P=0.02) and a > or =2 performance status (P=0.03). In conclusion, REs are frequent during induction chemotherapy of acute leukemia and represent an independent prognostic factor of poor outcome, regardless of their cause.

[The place of routine immediate non-invasive ventilation following pulmonary resection in preventing pulmonary complications in patients with COPD (POPVNI Trial)]. / Intérêt de la ventilation non invasive (VNI) systématique en post-opératoire immédiat d'une résection pulmonaire pour prévenir les complications pulmonaires chez les patients BPCO (essai POPVNI).

BACKGROUND: Respiratory complications are common following pulmonary resection and cause a significant mortality. The use of non-invasive ventilation (NIV) in acute respiratory insufficiency (ARI) is now well recognised. The prophylactic use of NIV in the absence of ARI and/or hypercapnia may be equally justified for the physiological benefits expected in the post-operative period following pulmonary surgery. The aim of our study therefore is to evaluate the effectiveness of NIV in the prevention of pulmonary complications in the immediate post-operative care of patients with moderate and severe COPD. METHODS: It will be a multicentre, prospective, randomised, parallel, open ended study of patients with moderate and severe COPD admitted to hospital for pulmonary resection. EXPECTED RESULTS: To determine whether the setting up of NIV immediately post-operatively reduces the incidence of acute respiratory events (acute respiratory insufficiency) and to identify any sub-groups who receive greater benefit from NIV. This study should establish the place of NIV in the immediate post operative care following pulmonary resection.

[Economic burden of COPD: the SCOPE study]. / Impact economique de la BPCO en France: etude SCOPE.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major health problem. Few data about COPD economic burden are available. METHODS: SCOPE was an observational economical retrospective and prospective study conducted in France in 2001, by 114 general practitioners (GPs) and 57 lung specialists. The aim was to describe the burden of COPD patients and to estimate the annual cost according to severity stages. Health resource utilization was collected by questionnaires over a 12-month period for 285 patients. RESULTS: It was a cost-of-illness analysis. COPD patients followed by a lung specialist were more severe than patients followed by a GP and had a higher level of medical resource consumption. The COPD disease and its complications explained 66% of the total cost. The main cost drivers were inpatient care (35%, or 1509,9 euros/year/patient) and prescription medications (31%, or 1340,6 euros/year/patient). The direct total cost varied according to COPD severity on account of inpatient care and respiratory assistance. DISCUSSION: This study confirmed the economic burden of COPD in France. Actions allowed to slow down the disease's evolution and to anticipate the exacerbation could reduce the cost.

Multiple pulmonary arterial aneurysms in Behcet's disease and Hughes-Stovin syndrome.

Four case studies of patients with angiographically documented pulmonary arterial aneurysms are presented. In two cases, Behcet's disease was diagnosed; one case corresponded to the syndrome described by Hughes and Stovin, that is, venous thrombosis especially of the vena cava accompanied by singular or multiple pulmonary arterial aneurysms in young patients; and the last case could best be described as an association of the two. Our observations lead us to question the existing notions concerning the relationship between Behcet's disease and Hughes-Stovin syndrome-the clinical, angiographic and histologic aspects of the vascular manifestations are comparable. Typically the two diseases run similar courses with death resulting frm the rupture of the aneurysms and massive hemoptysis. These case studies cast certain doubts as to the effectiveness of the corticosteroid treatment usually prescribed. Finally, we suggest that Hughes-Stovin syndrome might be, in fact, a manifestation of Behcet's disease.

Effects of smoking on bronchial clearance of technetium-99m-DTPA and indium-113m-DTPA.

UNLABELLED: In asymptomatic smokers, epithelial permeability in the distal lung regions is increased. To date, the effect of smoking on the epithelial permeability in proximal lung regions is still debated. The measurement of bronchial clearance of inhaled radiolabeled diethylene-triaminepentaacetic acid (BC-DTPA) can be used to assess epithelial permeability of proximal bronchi, but there are two potential limitations to this method: in vivo breakdown of 99mTc-DTPA in smokers and mucociliary transport of DTPA. METHODS: Eight nonsmokers and eight asymptomatic smokers were studied. We used a spinning disk system to generate an aerosol of large particles of 99mTc-DTPA or 113mIn-DTPA (MMAD 6.3 microns). To measure the bronchial clearance of 99mTc-DTPA and 113mIn-DTPA, we analyzed the perihilar regions of the lung. To determine the contribution of mucociliary transport, we measured the activity over a tracheal region of interest (ROI) in eight nonsmokers. RESULTS: Technetium-99m-DTPA bronchial clearance did not differ in smokers (1.16 +/- 0.54%/min; mean +/- s.d.) or nonsmokers (1.29 +/- 0.51%/min; ns). The 113mIn-DTPA bronchial clearances in nonsmokers (1.24 +/- 0.51%/min) and in smokers (1.01 +/- 0.66%/min) were similar to the 99mTc-DTPA bronchial clearances (ns). In the tracheal ROI, we found no increase in activity. CONCLUSION: In smokers, BC-DTPA was not increased compared to nonsmokers. In contrast to distal lung regions, there was no evidence of breakdown of the 99mTc-DTPA complex in the proximal regions of smokers' lungs. Mucociliary clearance does not significantly contribute to BC-DTPA.

Respiratory clearance of aerosolized radioactive solutes of varying molecular weight.

To determine the influence of varying molecular weight (mol wt) on respiratory clearance of aerosolized solutes, we studied eight radiopharmaceuticals, each administered to four dogs: sodium 99mTc pertechnetate (TcO4), 99mTc glucoheptonate ([99mTc]GH), 51Cr-ethylenedinitrotetraacetate ([51Cr]EDTA), 99mTc diethylenetriaminepentaacetate ([99mTc] DTPA), 111In diethylenetriaminepentaacetate ([111In]DTPA), 67Ga desferoxaminemesylate ([67Ga]DFOM), 99mTc dextran ([99mTc]DX) and 111In transferrin ([111In]TF). After aerosolization (0.8 m MMD, 2.4 GSD), clearance was determined for 30 min and then corrected by intravenous injection for nonairspace radioactivity. In-TF clearance (0.11 +/- 0.10%/min) was lower than TcO4 (6.32 +/- 0.62%/min), [99mTc]GH (1.50 +/- 0.37%/min), [51Cr]EDTA (2.38 +/- 1.02%/min), [99mTc]DTPA (3.51 +/- 0.40%/min), [111In]DTPA (2.35 +/- 0.42%/min), [67Ga] DFOM (1.99 +/- 0.49%/min) and [99mTc]DX (1.81 +/- 0.75%/min) clearances (p less than 0.001). TcO4 clearance was higher than others (p less than 0.001). Technetium binding to DX was unsatisfactory; aerosolization caused unbinding from DTPA. We conclude that respiratory clearance of large mol wt solutes within 30 min is negligible and, that clearance of molecules between 347-5,099 daltons differs greatly, suggesting that binding and/or intrapulmonary retention affect transfer.

Cardiorespiratory arrest following peak expiratory flow measurement during attack of asthma.

We report two episodes of cardiorespiratory arrest immediately after measurement of peak expiratory flow in two young asthmatic subjects during an attack of asthma. Various mechanisms could be involved, particularly airway inflammation.

Respiratory symptoms and peak expiratory flow in survivors of the Nyos disaster.

In August 1986, gases from the Nyos volcanic lake killed 1,746 persons in northwestern Cameroun, but 1,500 others living in the affected area survived. Gas emanations contained carbon dioxide, sulfur dioxide, and hydrogen sulfide. The objective of this study was to evaluate the delayed respiratory consequences of the inhalation of such volcanic gases. Two groups of subjects living in the same area, exposed (Nyos group; n = 381) or not exposed (control group; n = 128) to Nyos gases, were evaluated with a short questionnaire and by measurement of peak expiratory flow (PEF, percent predicted) in March 1991. Eleven percent of the subjects smoked, more often men than women (23% vs 4%; p < 0.001). In the whole population (exposed and unexposed), smoking was associated with a 3.6-fold increase in the frequency of cough (p < 0.001) and with a 6-fold increase in the frequency of sputum production (p < 0.005), but not with a decrease in PEF. There was no difference in the frequency of dyspnea, cough, sputum production, and PEF between Nyos and control groups. We conclude that 55 months after the emanation of gases from Nyos volcanic lake, there was no difference in respiratory symptoms, and PEF between survivors who inhaled volcanic gases and control subjects, whereas smoking was associated with cough and sputum production.

Metered-dose inhaler to deliver methacholine in bronchial provocation testing: a pilot study.

BACKGROUND: Nonspecific bronchial provocation tests may be simplified by the use of hand-held devices to deliver methacholine. OBJECTIVE: To study the feasibility of using a metered-dose inhaler (MDI) to administer methacholine in bronchial provocation tests, and the ability of such a device to diagnose bronchial hyperresponsiveness (BHR) accurately. METHODS: In an open randomized crossover pilot study, we compared the provocative dose that induces a 20% fall in FEV1 (PD20 FEV1) obtained with the methacholine MDI with that obtained using a conventional nebulizer in 20 hyperresponsive and 20 nonhyperresponsive subjects. The MDI delivers 400 doses of 100 microg of methacholine, and was used via a spacer. Bronchial hyperresponsiveness (BHR) was defined as a PD20 FEV1 <2,000 microg with the conventional test using the nebulizer. The tests were performed in each subject in a randomized order, 1 to 7 days apart. RESULTS: Of the subjects who had a nebulizer PD20 FEV1 <2,000 microg, all but one had an MDI PD20 FEV1 <800 microg. When 800 microg was taken as the threshold for the diagnosis of BHR with the MDI test, the accuracy of this test to diagnose BHR was 97.5%, and the two tests were highly concordant for the diagnosis of BHR (Pearson chi2, 36.19; p<0.0001). CONCLUSION: A hand-held device may be suitable for delivery of methacholine during bronchial provocation tests, if these results are confirmed in large samples.

Value of clinical, functional, and oximetric data for the prediction of obstructive sleep apnea in obese patients.

OBJECTIVE: To evaluate the diagnostic value of clinical features, pulmonary function testing, blood gas tensions, and oximetric data for case finding of obstructive sleep apnea (OSA) before polysomnography (PSG) in a series of consecutive overweight patients. METHODS: We studied a population of 102 consecutive patients referred by an obesity clinic for suspected OSA, in whom body mass index was > or = 25 kg/m(2). The following tests were performed: clinical score (CS), pulmonary function tests (PFTs), measurement of arterial blood gas tensions, nocturnal oximetry, and full-night PSG. RESULTS: Six of 34 women and 34 of 68 men had OSA, defined by an apnea-hypopnea index > or = 15. CS and the cumulative time spent below 80% arterial oxygen saturation (SaO(2)) were higher, and PaO(2), minimal SaO(2), and mean nocturnal SaO(2) (mSaO(2)) were lower in OSA patients than in non-OSA patients. Logistic regression showed that sex, CS, and the ratio of FEV(1) over forced expiratory volume in 0.5 s (an index of upper airway obstruction on flow-volume curves) and mSaO(2), expressed as categorical variables, were independent predictors of OSA. None of these individual variables had a satisfactory diagnostic value for the diagnosis of OSA. A logistic regression model including sex and all continuous variables would have allowed us to predict the presence or absence of OSA confidently in 72.5% of the population, in whom the positive predictive value of the model was 94% and the negative predictive value was 90%. CONCLUSION: In obese patients referred to a respiratory sleep laboratory and evaluated by CS, PFTs, arterial blood gases, and oximetry, no individual sign or symptom may accurately predict the presence or absence of OSA. Provided that it is validated in prospective studies, a logistic regression model using these variables may be useful for the prediction of OSA.

Blood vessel invasion in resected non small cell lung carcinomas is predictive of metastatic occurrence.

Prognosis of patients with non small cell lung cancer (NSCLC) remains difficult to assess, even after adjustment for pathological stage. Prognostic value of numerous biological markers has been evaluated, with conflicting results. Data of 86 patients with NSCLC treated by surgery were collected with clinical characteristics, histopathological data including tumor differentiation and status of blood and lymphatic vessel invasion and evaluation by immunohistochemistry of Rb, Bcl-2 and Ki-67 expression. Prognostic values for overall survival (OS) and event-free survival (EFS) were analyzed by the log tank test and the multivariable Cox model. Using univariable analyses, pT, pN, poor differentiation or large cell subtype were associated with a poor OS, while lymphatic and/or blood vessel invasion were associated with a short EFS. None of the molecular markers had a significant prognostic value for either outcome. In multivariable analyses, only stage remained of prognostic value for OS. Interestingly, the presence of blood vascular invasion in the tumor was significantly predictive for subsequent metastatic occurrence in stages I and II. This feature might, therefore, be relevant for administration of adjuvant therapy in completely resected NSCLC.

Rebreathing lung tissue volume of sheep with normal and edematous lungs.

To determine the accuracy of measurements of lung tissue volume (Vlt) by rebreathing acetylene in normal and edematous lungs, we compared gravimetric values of total lung weight (Ql) and extravascular lung water (Qwl) with Vlt in anesthetized control sheep (C) and sheep with hydrostatic pulmonary edema (HPE) or oleic acid-induced permeability pulmonary edema (PPE), five animals each. In eight additional sheep we determined that acetylene solubility in blood (0.117 +/- 0.010 ml X 100 ml-1 X Torr-1) differed significantly from that in lung-blood homogenates (0.095 +/- 0.009 ml X 100 ml-1 X Torr-1, P = 0.0017). The latter value was used in all calculations. In C, Vlt was 194% of Qwl and 98% of Ql; in HPE, Vlt was 144% of Qwl and 87% of Ql; and in PPE, Vlt was 112% of Qwl and 77% of Ql. We conclude that when the lungs are normal, Vlt reasonably measures Ql not Qwl. However in both HPE and PPE, Vlt progressively underestimates Ql and cannot differentiate between increased blood volume and increased Qwl.

Pulmonary clearance of three aerosolized solutes in oleic acid-induced lung injury.

We studied the effects of oleic acid (OA) on pulmonary clearance of three aerosolized radioactive solutes: 99mTc-diethylenetriamine pentaacetate (99mTc-DTPA), 67Ga-desferoxamine (67Ga-DFOM), and 111In-transferrin (111In-TF). Either 0.09 ml/kg OA or an equivalent volume of 0.9% NaCl (controls) was administered intravenously to 48 anesthetized, paralyzed dogs. Each animal received one aerosolized solute either 60 min after (protocol A) or 30 min before (protocol B) the infusion of OA or NaCl. In protocol A clearances of all three solutes were similar in OA and control animals. In contrast, in protocol B clearances of all three solutes increased significantly during OA infusion; during the next 60 min clearances of 99mTc-DTPA and 67Ga-DFOM returned to control values but 111In-TF remained increased. We conclude that 1) in OA-induced permeability edema pulmonary clearance of aerosolized solutes is increased when the aerosol is delivered 30 min before but not 60 min after injury, and 2) increased clearance persists only for large molecules, presumably because smaller molecules cross injured epithelium quickly and completely. These phenomena are best explained by a nonhomogeneous distribution of OA-induced injury.

Factors affecting tissue volume measurements in normal and edematous dog lungs.

To characterize further some of the factors affecting lung tissue soluble-gas rebreathing volume (Vlt), we determined the solubility of acetylene in blood and lung tissue, the influence of the presence of pulmonary edema on tissue solubility, the effects of varying tidal volume (VT), and the tissue volume actually measured in two groups of six anesthetized paralyzed dogs: controls (C) and oleic acid-induced pulmonary edema (OA). Each animal's solubility was used to compute Vlt for comparison with gravimetric lung weight (Ql) and extravascular lung water content (Qwl). Solubility at 37.5 degrees C in blood (0.125 ml X 100 ml-1 X Torr-1) exceeded that in lung tissue (P less than 0.005): C = 0.118 and OA = 0.112 ml X 100 ml-1 X Torr-1 (NS). Vlt, expressed as %Ql, increased with increasing VT (20, 35, and 50 ml/kg) in OA (62.2, 78.9, and 94.7%, respectively, P less than 0.0001) but not in C (92.4, 94.4, and 99.3%, respectively). We conclude that solubility differs in blood and lung tissue but not in normal and edematous lungs, Vlt is not affected by VT in normal dogs but is in those with pulmonary edema, and Vlt measures Ql rather than Qwl.

Regional respiratory clearance of aerosolized 99mTc-DTPA: posture and smoking effects.

We studied 10 healthy nonsmokers and 8 healthy smokers, in both the upright and supine position, to investigate whether regional differences in respiratory clearance of technetium-99m-labeled diethylenetriamine pentaacetic acid 99mTc-DTPA (RC-DTPA) existed and to assess the influence of posture and smoking on the regional RC-DTPA. RC-DTPA was assessed by the lung clearance rates (%/min) of aerosolized 99mTc-DTPA (0.8 micron MMD; 2.4 GSD), using data corrected for recirculating radioactivity, in the upper (zone 1), middle (zone 2), and lower (zone 3) posterior lung fields. In nonsmokers, RC-DTPA in zone 1 was faster than in zone 2 or 3 in both the upright (P less than 0.001) and supine positions (P less than 0.0). No effect was produced by changes in posture on the regional RC-DTPA. In smokers, RC-DTPA was increased in all zones compared with the nonsmokers (P = 0.004), with a further increase in RC-DTP in zone 1 in the upright posture compared with the other regions (P less than 0.001). We conclude that in nonsmokers regional RC-DTPA is faster in zone 1 than in other zones, and this is not related to recirculation of radioactivity; posture does not modify the regional RC-DTPA of nonsmokers; smoking increases RC-DTPA in all zones and more in zone 1 in the upright posture.

The burden of COPD in France: results from the Confronting COPD survey.

Chronic obstructive pulmonary disease (COPD) is an obstructive lung disorder characterized by progressive airflow limitation that is not reversible or only partially reversible, including chronic bronchitis and emphysema. Confronting COPD in North America and Europe was the first large-scale international survey to attempt to quantify the country-specific burden of the disease, collecting data on clinical outcomes, healthcare resource utilization, and lost productivity, from patients and physicians in France and seven other countries. The economic analysis of the French survey results showed that patients with COPD required considerable utilization of healthcare resources, with annual direct costs estimated at Euro 530 per patient In addition, COPD-related illness or disability prevented many patients from working, with an estimated annual indirect cost of Euro 1078 per patient The survey suggested underdiagnosis and undertreatment of COPD by healthcare professionals, and patients reported poor symptom control. The cost of unscheduled care (Euro 151) was almost double the cost of scheduled visits to healthcare professionals (Euro 82). This suggests that improving the long-term management of chronic symptoms by healthcare professionals could reduce the burden of disease. As in other countries, the clinical management of COPD in France may be improved by following guideline recommendations for COPD treatment. These include smoking cessation at all stages of the disease, regular treatment of chronic symptoms with bronchodilators in dyspnoeic patients, and pulmonary rehabilitation. The results of the survey also showed that the societal cost of COPD was considerably greater in patients with severe disease (Euro 2882) compared with mild COPD (Euro 289). This suggests that interventions that could help delay the progression of COPD to the advanced stages of the disease (such as smoking cessation) could be of economic benefit.