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The aims of this survey were to determine the prevalence of symptoms indicative of chronic bronchitis (CB) in the French adult population, to identify the role of risk factors for CB, and to assess rates of CB diagnosis and pulmonary function testing (PFT) in the presence of CB. A representative sample of 14,076 individuals aged > or = 25 yrs completed a self-administered questionnaire on symptoms, comorbidities, smoking history, sociodemographical data, and diagnosis and care by physicians. The prevalence of CB was 4.1% and the prevalence of chronic cough and/or expectoration was 11.7%. In individuals with comorbidity, these figures were 10.4% and 24.4%, respectively. Smoking was associated with an increased frequency of CB. In subjects with CB, 44.6% had PFT (spirometry or peak expiratory flow measurement), 24% were diagnosed as having CB, and 7.2% received care. Rates of diagnosis, PFT, and follow-up were lower in young individuals and in those without comorbidity. PFT and follow-up were less common in current smokers. Prevalence of chronic bronchitis in French adults is high and similar in magnitude to that of other industrialised countries. Comorbidities and tobacco smoking increase the frequency of chronic bronchitis symptoms. Chronic bronchitis is too infrequently diagnosed, investigated and cared for.

The choice of an aerosol delivery system depends on numerous factors such as the drug itself, the characteristics of the aerosol generator, the patient and his or her disease, the physician, and the clinical setting, notably an emergency situation or not. Some rules always apply: an ultrasonic nebulizer should not be used to aerosolize a drug suspension; whenever possible, the same type of aerosol generator should be used for all inhaled medications received by a given patient; for outpatients, education is a major factor to ensure treatment efficacy. When the deposition of the aerosolized drug is aimed at the terminal respiratory units, nebulizers that generate micronic aerosols should be chosen. When the deposition of the aerosolized drug is aimed at the conducting airways, the metered dose inhaler (MDI) is the first choice. However, the MDI is often ill-used, notably in children and elderly people. Therefore, other inhalation devices have been developed: spacers, dry-powder inhalers, breath-actuated MDIs and, more recently, piezo-electric devices. They have been shown to increase lung deposition of drugs in poor coordinators but they all have limitations, which may affect their clinical efficacy. These limitations include the cumbersome dimensions of spacers, the dependency of lung deposition of dry powders on the inspiratory flow rate, the need for reformulation of breath-actuated or not MDIs with CFC-free gases. Nebulization of drugs should be considered only when no portable device is available for the considered drug, or in case of failure of other forms of aerosol administration.

Several epidemiological studies suggest that exposure to house dust mite allergens plays a role in the pathogenesis of asthma. Since many of these allergens exhibit enzymatic properties, they may damage the airway epithelium. To characterize the effects of low doses of Dermatophagoides pteronyssinus on the airway epithelium, the effect of D. pteronyssinus on the epithelial bioelectric properties of tracheal fragments of non-sensitized Lewis rats was studied, using Ussing-type chamber technique. The addition of a crude D. pteronyssinus extract containing 20 microg mL(-1) of Der pI allergen in the presence of 1.5 mM dithiothreitol (DTT, an activator of cysteine proteases), induced a progressive increase in bioelectrical conductance (+12.0+/-1.5%, n=12, p<0.005), an index of epithelial permeability, without affecting the short circuit current (which reflects active ion transports). The D. pteronyssinus-induced increase in epithelial conductance was related to the cysteine-protease activity of the allergen since it was not observed in the absence of DTT (n=12), and was completely suppressed in the presence of 10 nM E-64, a specific inhibitor of cysteine proteases (n=12). D. pteronyssinus-induced increase in epithelial conductance could be entirely attributed to an increase in the paracellular conductance (+11.2+/-1.2%, n=8, p<0.01). There was no electrophysiological evidence of rupture in epithelial continuity, and no cell detachment was observed on microscopic examination. In conclusion, the cysteine protease activity of crude Dermatophagoides pteronyssinus extract is able to increase the epithelial paracellular conductance of rat tracheal tissues, even at relatively low doses that do not induce cell detachment or cell death.

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.

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.

We investigated the effects of tachykinins on the respiratory clearance of 99mTc-DTPA (RC-DTPA) in anesthetized and ventilated guinea pigs. We measured the change in RC-DTPA and in maximal pulmonary insufflation pressure (PIPmax) induced by substance P, neurokinin A, and capsaicin. Substance P, neurokinin A, and capsaicin increased both PIPmax and RC-DTPA in a concentration-dependent fashion. Substance-P- and capsaicin-induced increases in RC-DTPA were unaffected by pretreatment with atropine. Bilateral vagotomy attenuated substance-P-induced change in both RC-DTPA and PIPmax by approximately 70 and 50%, respectively. Capsaicin-induced change in RC-DTPA and PIPmax were slightly but not significantly reduced by bilateral vagotomy. The bronchodilator, salbutamol, dramatically reduced increase in RC-DTPA and in PIPmax induced by substance P, neurokinin A, and capsaicin, but it had no effect on increases in RC-DTPA and PIPmax generated by application of a positive end-expiratory pressure. We conclude that (1) tachykinins increase respiratory clearance to the solute, and (2) tachykinin-induced increase in RC-DTPA is not mediated by cholinergic neurotransmission but rather by the bronchoconstrictor effect of neuropeptides.

Pentamidine isethionate was administered by the tracheal route to control rats and immunodepressed rats with Pneumocystis carinii pneumonia (PCP). The serum concentration of pentamidine base 20 min after the administration was higher in the PCP rats (309 +/- 165 ng/ml) than in the control animals (71 +/- 36 mg/ml; p less than 0.001); 90 min after the injection the proportion of the pentamidine administered was lower in the right lung of the PCP rats (29 +/- 15%) than in the control rats (57 +/- 23%; p = 0.038); the proportion of pentamidine in the left kidney was higher in the PCP rats (14 +/- 4%) than in the control animals (4 +/- 2%; p less than 0.001). Respiratory clearance of 99mTc-DTPA, an index of the permeability of the respiratory epithelium, was higher in the PCP rats (1.84 +/- 0.42 %/min) than in the controls (0.44 +/- 0.11 %/min; p less than 0.001). We conclude that the more rapid diffusion of pentamidine from the alveolar lumen to the pulmonary circulation is explained by the increased alveolocapillary permeability as a result of pneumocystosis.

To investigate bronchial permeability in asthma, we measured the bronchial clearance of 113mIn-DTPA in seven asthmatics during and after an acute attack of asthma, seven asthmatics with chronic airflow limitation, and seven asthmatics without airflow limitation but with bronchial hyperresponsiveness to methacholine. We compared these results with those from seven normal subjects, seven patients with chronic bronchitis and bronchial infection, and seven patients with emphysema. An aerosol of 113mIn-DTPA was produced with a spinning disc to ensure a predominantly bronchial deposition of inhaled particles (6.3 microns MMAD). Radioactivity over the chest was recorded with a gamma-camera for 10 min after the subject inhaled the aerosol. Central regions of interest were selected, and the logarithm of the radioactivity was plotted against time; bronchial clearance of 113mIn-DTPA was calculated as the negative slope of the regression line. Clearance was substantially higher in asthmatics during their acute attacks than in all other groups (p less than 0.0001), and it decreased toward normal levels after recovery from the acute episode. The bronchial clearance of 113mIn-DTPA in all other groups did not differ from normal. We conclude that the bronchial clearance of 113mIn-DTPA is increased in asthmatics during attacks of asthma but in the stable state is not related either to bronchial hyperresponsiveness or to airflow limitation. Our findings are best explained by an increase in permeability of the bronchial mucosa of asthmatics during acute attacks.

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.

To investigate the relation between lung function and inflammation and fibrosis in patients with diffuse lung fibrosis, a study was made of untreated patients without appreciable airway obstruction (14 patients with cryptogenic fibrosing alveolitis and seven with pneumoconiosis). Quantitative assessment of inflammatory infiltration and fibrosis was carried out on open lung biopsy specimens and compared with lung volumes, carbon monoxide transfer factor (TLCO), TLCO corrected for alveolar volume (TLCO/VA), and arterial blood gases at rest and during exercise. The degree of fibrosis and the degree of cellular infiltration were positively correlated. Lung volumes and TLCO were correlated with the grades of fibrosis and cellular infiltration of alveoli; arterial blood gases during exercise tended to correlate with both fibrosis and infiltration (p less than 0.06). In contrast, morphological data were not correlated with gas exchange at rest or with TLCO/VA. It is concluded that, in untreated patients with diffuse lung fibrosis, lung volumes, TLCO, and arterial blood gases during exercise reflect the lung lesions, and that the pulmonary function tests used cannot discriminate between fibrosis and infiltration of the lung by inflammatory cells.

Respiratory epithelial clearance of 99mTc-DTPA (RC-Tc-DTPA) and pulmonary function tests (PFT) were determined at intervals of 6 or 12 months in 37 untreated, nonsmoking patients with sarcoidosis over a period of 6 to 36 months. PFT included the measurements of total lung capacity (TLC), vital capacity (VC), FEV1, and diffusing capacity for carbon monoxide. No difference was found between the respiratory clearance of 113mIn-DTPA (2.25 +/- 1.00%/min) and RC-Tc-DTPA (2.29 +/- 1.11%/min) in eight patients with pulmonary sarcoidosis. Pulmonary function decreased 15% or more in at least 2 function tests during 11 follow-up periods, but it remained stable during 47 follow-up periods. In patients whose lung function deteriorated, RC-Tc-DTPA increased to 3.51 +/- 1.55%/min; in contrast, in patients whose lung function remained stable, regardless of the initial values, RC-Tc-DTPA was normal (1.00 +/- 0.50%/min; p less than 0.001). In eight patients who were treated with corticosteroids, RC-Tc-DTPA decreased from 3.48 +/- 1.31%/min to 1.56 +/- 0.64%/min (p less than 0.001), and PFT improved. We conclude that in nonsmokers with pulmonary sarcoidosis, increased RC-Tc-DTPA is not related to dissociation of 99mTc from DTPA, RC-Tc-DTPA is increased when pulmonary function decreases, and, when increased, RC-Tc-DTPA decreases with corticosteroid therapy.

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.

To determine the separate influences of smoking and severe air-flow limitation on aerosol deposition and respiratory epithelial permeability, we studied 26 normal nonsmokers, 12 smokers without airway obstruction, 12 nonsmokers with chronic obstructive pulmonary disease (COPD), and 11 smokers with COPD. We aerosolized 99mTc-labeled diethylene triamine pentaacetic acid to particles approximately 1 micron activity median aerodynamic diameter. Levels of radioactivity were plotted semilogarithmically against time to calculate clearance as percent per minute. The distribution of radioactivity was homogeneous in control subjects and in smokers, but patchy in both groups with COPD. No difference was found between clearances of the control group (1.18 +/- 0.31% min-1), and nonsmoker COPD group (1.37 +/- 0.82% min-1), whereas values in smokers without COPD (4.00 +/- 1.70% min-1) and smokers with COPD (3.62 +/- 2.88% min-1) were significantly greater than in both nonsmoking groups. We conclude that (1) small particles appear to deposit peripherally, even with severe COPD; (2) respiratory epithelial permeability is normal in nonsmokers with COPD; (3) smoking increases permeability by a mechanism unrelated to air-flow limitation.

We assessed the effectiveness of various aerosol-generating systems. Taplin's settling method and Venticis generators had a lower efficiency (37.3 +/- 3.8% and 51.8 +/- 9.6%, respectively) than the Syntevent (88.8 +/- 6.9%, p less than 0.001), Cadema (89.8 +/- 9.9%, p less than 0.001) and Mefar (85.3 +/- 19.4%, p less than 0.001) generators. The Mass Median Aerodynamic Diameter of the particles produced by the Mefar nebulizer (2.05 +/- 0.27 micron) was larger than that of any other generators (p less than 0.001). The Syntevent (0.54 +/- 0.09 micron) generator produced smaller particles than the Mefar, Taplin (0.89 +/- 0.10 micron, p less than 0.01) and Venticis (0.79 +/- 0.06 micron, p less than 0.02) generators. Particles produced by the Cadema system (0.69 +/- 0.06 micron) were smaller than those generated by the Taplin system (p less than 0.05). We conclude: that the Syntevent, Mefar and Cadema aerosol generators are more efficient than the others, and that all the generators tested except the Mefar may be used for studies that depend on the peripheral deposition of small particles within the 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.

We performed bronchoalveolar lavage (BAL) in 120 subjects: 94 patients with sarcoidosis, 11 patients with idiopathic pulmonary fibrosis (IPF), and 15 normal volunteers. By counting cells and comparing the results with those from control subjects, we found a high percentage of lymphocytes in BAL fluid from all patients with sarcoidosis and a high percentage of neutrophils (NE) in BAL fluid from patients with IPF. In addition, we observed a significantly higher proportion of NE in the 14 patients with advanced sarcoidosis (i.e., fibrosis and bullous radiological patterns), than was seen in the 80 patients with early stages of involvement (i.e., bilateral hilar lymphadenopathy and/or pulmonary infiltrations) (p less than 0.001). The NE count exceeded the normal value of 3.5% in 9 of the 14 patients with advanced sarcoidosis but only in 1 of the 80 patients with early disease (p less than 0.001). We believe that advanced sarcoidosis is one of the conditions in which a simultaneous increase in both NE and lymphocytes in BAL fluid can be observed. The NE count in bronchoalveolar fluid in patients with sarcoidosis, as in patients with IPF, may indicate evolution of the granulomatous process toward pulmonary fibrosis. These phenomena point out the potential practical value of iterative BAL in patients with sarcoidosis in assessing the prognosis of their disease.

The concentration of angiotensin converting enzyme (ACE) and that of albumin (AIb) were assayed in the serum (SACE, SAlb) and in bronchoalveolar lavage fluid (LACE, LAlb). Three groups of patients were studied: 14 healthy volunteers (Group I), 45 patients with active sarcoidosis (Group II), and 7 patients with sarcoidosis in remission (Group III). The SACE in Group II (4,466 +/- 2,202 U/100 ml, mean +/- SD) was higher (p less than 0.001) than in Group I (2,470 +/- 547 U/100 ml) or in Group III (2,640 +/- 610 U/100 ml); LACE was higher in Group II (65.2 +/- 48.4 U/100 ml, p less than 0.001) than in Group I (21.1 +/- 14.7 U/100 ml), or in Group III (25.7 +/- 14.6 U/100 ml). The SAlb was found to be, respectively, 3,908 +/- 385 mg/100 ml, 3,982 +/- 965 mg/100 ml, and 3.613 +/- 222 mg/100 ml in Groups I, II, and III. The LAlb in Group II (8.2 +/- 6.2 mg/100 ml) was higher (p less than 0.01) than in Group I (2.5 +/- 1.4 mg/100 ml) or in Group III )4.1 +/- 1.0 mg/100 ml). The LACE in Group II increased with the number of alveolar lymphocytes, in nonsmokers (4 = + 0.56, df = 34, p less than 0.001) and in smokers (4 = + 0.88, df = 7, p less than 0.01). In the smokers in this group, LACE was higher with respect to the number of lymphocytes than in the nonsmokers. We conclude from this study (1) that the permeability of the alveolocapillary membrane to albumin and to ACE is increased in active pulmonary sarcoidosis, (2) that LACE increases during sarcoidosis and returns to normal when the disease is cured, and (3) that the concentration of ACE in alveolar fluid increases with tobacco use.

To investigate the relationships between the respiratory epithelial clearance of micronic aerosolized 99mTc-DTPA (RC-DTPA) and pulmonary function, serum angiotensin-converting enzyme (SACE), and lymphocytic alveolitis in patients with sarcoidosis, RC-DTPA was measured in 49 nonsmokers with pulmonary sarcoidosis and 38 normal nonsmokers. Pulmonary involvement was evaluated on chest roentgenograms (type O = normal, type I = hilar adenopathies, type II = hilar adenopathies associated with parenchymal shadows, type III = parenchymal shadows without adenopathy) and by pulmonary function tests. Serum angiotensin-converting enzyme was determined, and a bronchoalveolar lavage was performed for alveolar lymphocyte differential counting (Ly%). RC-DTPA was increased (greater than or equal to 1.96%/min) in 12 of 31 patients with type II or III involvement but was normal in all 18 patients with type O or I involvement (p = 0.002). Patients with increased RC-DTPA had low FVC, TLC, FEV1, and resting Pao2 (p less than 0.05); resting and exercise AaPo2 were increased (p less than 0.05), but RC-DTPA correlated negatively with FEV1 (p less than 0.01), Pao2 at rest (p less than 0.005), and DLCO (p less than 0.05) and positively with resting and exercise AaPO2 (p less than 0.01). In patients with increased RC-DTPA (42 +/- 17%), Ly% did not differ from Ly% in patients with normal RC-DTPA (34 +/- 16%). SACE was increased in patients with increased RC-DTPA (56 +/- 26 U/ml versus 38 +/- 16 U/ml; p = 0.007) and correlated positively with RC-DTPA (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin converting enzyme (ACE) was assayed both in serum (SACE) and in bronchoalveolar fluid lavage (LACE) in 14 healthy controls and in 45 patients with sarcoidosis with mediastinal and pulmonary involvement. Concentration of SACE was 4466 +/- 2202 U x 100 ml-1 (mean +/- SD) in sarcoidosis and 2470 +/- 547 U x 100 ml-1 (chi +/- SD) in sarcoidosis and 2470 +/- 547 U . 100 ml-1 in controls. Concentrations of LACE were 65.2 +/- 48.4 U . 100 ml-1 and 21.1 +/- 14.7 U . 100 ml-1 respectively in sarcoidosis and in controls. These results are in favor of an intraalveolar secretion of ACE in sarcoidosis. LACE could be a better criterium than SACE for the evaluation of the pulmonary activity of sarcoidosis.

We measured pulmonary tissue volume (Vt) and pulmonary capillary blood flow (Qc) by a rebreathing method using two soluble gases, acetylene (C2H2) and dimethyl ether (DME), in 32 normal subjects and 14 patients who had had pulmonary edema. In 18 of the normal subjects, studies were performed at three or more different rebreathing volumes (VA). To normalize for differences in body size, results were expressed as the ratio of Vt or VA to predicted total lung capacity (TLC). We found that 1) changes in VA/TLC had a significant effect on Vt/TLC and Qc measured with both gases, 2) the range of normal values for Vt was best defined by expressing the relationship between Vt/TLC and VA/TLC, 3) using this approach, many patients with clinically mild or inapparent pulmonary edema had abnormal values of Vt, and 4) when comparing mean values of C2H2 and DME in 82 simultaneous measurements at constant VA/TLC, Vt was significantly higher in 87% (71/82) and Qc in 63% (52/82) of the paired tests.

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.

To compare the prognostic value of the serum concentration of angiotensin converting enzyme (SACE) to that of pulmonary radiography, patients with mediastino-pulmonary sarcoidosis were followed over two years and then retrospectively placed in one of 2 groups, designated "cured" (CS) or "not cured" (NCS) on the basis of clinical and biologic criteria. The two groups were then compared with respect to the initial pulmonary radiologic image, and the initial SACE concentration. The initial SACE concentration (CS: 45.6 +/- 15.4 U . ml-1; NCS: 48.5 +/- 27.3 U . ml-1; means +/- SD) and the percentage of patients with elevated SACE (CS: 75%; NCS: 69%) did not differ significantly between the two groups; on the other hand, the percentage of patients with pulmonary nodules on their initial chest film was higher in the NCS group (50%) than in the CS group (21%; p less than 0.05). We conclude that pulmonary radiography is the more reliable prognostic criterion in mediastino-pulmonary sarcoidosis.

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.

To evaluate interactions between increased permeability of the pulmonary vasculature and increased hydrostatic pressure on lung fluid flux, we measured water and blood contents of five equally thick slices of in situ perfused dogs' lungs that had been vertically suspended and, after experimental manipulations, rapidly frozen. Measurements were made under four sets of conditions (4 dogs each): 1) control; 2) increased left atrial pressure (Pla), 25 cmH2O relative to the bottom of the lung; 3) oleic acid; and 4) oleic acid and increased Pla. Significant interactions on lung water content were found between 1) oleic acid and increased Pla (P less than 0.005) and 2) oleic acid and height of the slice of lung (P less than 0.003). Blood content was significantly affected by interactions between 1) oleic acid and height of the lung slice (P less than 0.001) and 2) increased Pla and height of the lung slice (P less than 0.001). We conclude that there are significant interactions between increased permeability and hydrostatic pressure that affect regional lung water content and intrapulmonary distribution of blood.

Croup and epiglottitis, which cause greater than normal negative inspiratory intrathoracic pressure (NIIP), have been associated with pulmonary edema. To examine the effects of increased NIIP per se on blood gases, hemodynamics, and lung water content, we carried out 2 types of experiments in 18 anesthetized dogs. Short-term, low-pressure experiments (6 control dogs and 6 dogs that generated intratracheal pressures of -12 cm H2O during inspiration for 3 h) and long-term, high-pressure experiments (6 dogs that generated -20 cm H2O during inspiration for 6 h). In the short-term, low-pressure experiments, animals made to generate negative inspiratory pressure differed from control dogs by demonstrating decreased pleural pressure (p less than 0.01), increased arterial PCO2 (p less than 0.05), and decreased minute volume (p less than 0.05); no differences occurred in hemodynamic data (pulmonary arterial, left atrial, and aortic pressures and cardiac index) and in extravascular lung water (indicator dilution and gravimetric analyses). Similarly, in the long-term, high-pressure dogs, arterial PCO2 increased (p less than 0.05) and lung water was normal by gravimetric analysis. We conclude that both 3 and 6 h of increased NIIP cause CO2 retention but have minimal effects on hemodynamics and lung fluid exchange.

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.

We developed a method for measuring an index of alveolar-capillary membrane permeability (PI) by aerosolizing a mixture of 99mTc-diethylenetriaminepentaacetic acid (Tc-DTPA) and 125I-antipyrine (I-AP) and injecting 111In-DTPA (In-DTPA). The I-AP was used to compute the quantity of Tc-DTPA delivered and the In-DTPA the quantity of Tc-DTPA in the body. The PI was the ratio of the uptake of Tc-DTPA per minute to the amount deposited at the end of aerosolization. In 14 anesthetized dogs we measured the volume of distribution of I-AP (0.54 +/- 0.034 l/kg body wt) and/or showed that the volumes of distribution of Tc-DTPA and In-DTPA were similar. We measured PI in four groups of dogs: control (n = 5), oleic acid (n = 5), hydrochloric acid (n = 6), and high left atrial pressure (n = 5). The PI increased significantly in both groups with acid-induced increased permeability compared with the control and high left atrial pressure groups, which did not differ from each other. We conclude that the aerosolization method is suitable for differentiating increased from normal permeability.