Intimal enlargement of pulmonary arteries is an early change in chronic obstructive pulmonary disease (COPD). The cellular and extracellular components that are involved in this enlargement are unknown. The present study was designed to characterize the structural changes occurring in pulmonary muscular arteries in the initial disease stages.Lung specimens from patients with moderate COPD (n=8; forced expiratory volume in one second (FEV1), 66¡10% predicted) and smokers without airflow obstruction (n=7; FEV1, 86¡6% pred), were investigated by histochemistry to characterize extracellular matrix proteins and by immunohistochemistry to identify intrinsic cells of the vascular wall.In both COPD patients and smokers, the majority of cells present in the enlarged intimas were stained by specific smooth muscle cell (SMC) markers. No staining with endothelial or fibroblast markers was shown. A proportion of SMCs did not stain with desmin, suggesting cellular heterogeneity in this population. Elastin was the most abundant extracellular matrix protein and collagen was seen in a lower proportion. The amount of collagen was related to the intimal thickness (pv0.001).The findings demonstrated smooth muscle cell proliferation, as well as elastin and collagen deposition, in the thickened intimas of pulmonary arteries in moderate chronic obstructive pulmonary disease patients and smokers, suggesting that these abnormalities may originate at an early stage in cigarette smoke-induced respiratory disease.

Background-A study was undertaken to assess the diagnostic value of diVerent clinical criteria and the impact of microbiological testing on the accuracy of clinical diagnosis of suspected ventilator associated pneumonia (VAP). Methods-Twenty five deceased mechanically ventilated patients were studied prospectively. Immediately after death, multiple bilateral lung biopsy specimens (16 specimens/patient) were obtained for histological examination and quantitative lung cultures. The presence of both histological pneumonia and positive lung cultures was used as a reference test. Results-The presence of infiltrates on the chest radiograph and two of three clinical criteria (leucocytosis, purulent secretions, fever) had a sensitivity of 69% and a specificity of 75%; the corresponding numbers for the clinical pulmonary infection score (CPIS) were 77% and 42%. Non-invasive as well as invasive sampling techniques had comparable values. The combination of all techniques achieved a sensitivity of 85% and a specificity of 50%, and these values remained virtually unchanged despite the presence of previous treatment with antibiotics. When microbiological results were added to clinical criteria, adequate diagnoses originating from microbiological results which might have corrected false positive and false negative clinical judgements (n = 5) were countered by a similar proportion of inadequate diagnoses (n = 6). Conclusions-Clinical

To investigate whether endothelial dysfunction of pulmonary arteries (PA) is present in patients with mild chronic obstructive pulmonary disease (COPD) and to what extent it is related to the morphological abnormalities of PA, we studied 41 patients who underwent lung resection. Patients were divided into the following groups: nonsmokers ( n = 7), smokers with normal lung function ( n = 13), and COPD ( n = 21). Endothelium-dependent relaxation mediated by nitric oxide was evaluated in vitro in PA rings exposed to cumulative concentrations of acetylcholine (ACh) and ADP. Structural abnormalities of PA were assessed morphometrically. PA of COPD patients developed lower maximal relaxation in response to ADP than both nonsmokers and smokers ( P < 0.05 each) and a trend to reduced relaxation in response to ACh ( P = 0.08). Maximal relaxation to ADP correlated with the degree of airflow obstruction ( r = 0.48, P < 0.01). Morphometrical analysis of PA revealed thicker intimas, especially in small arteries, in both smokers and COPD compared with nonsmokers ( P < 0.05 each). We conclude that endothelial dysfunction of PA is already present in patients with mild COPD. In these patients, as well as in smokers with normal lung function, small arteries show thickened intimas, suggesting that tobacco consumption may play a critical role in the pathogenesis of pulmonary vascular abnormalities in COPD.

Endothelial dysfunction and intimal thickening have been shown in pulmonary arteries (PA) of patients with mild chronic obstructive pulmonary disease (COPD). To investigate whether an inflammatory process related to tobacco smoking might be involved in the development of pulmonary vascular abnormalities in COPD, we characterized the inflammatory cell infiltrate and the endothelium-dependent relaxation in PA of 39 patients who underwent lung resection, divided into three groups: "nonsmokers" (n ϭ 7); "smokers," with normal lung function (n ϭ 12); and "COPD" (n ϭ 20). Endothelium-dependent relaxation was assessed in vitro by exposing PA rings to adenosine diphosphate (ADP). Inflammatory cell types were identified by immunohistochemistry. PA of COPD patients Structural and functional abnormalities of the pulmonary circulation are common features in the wide spectrum of chronic obstructive pulmonary disease (COPD). Dysfunction of the pulmonary endothelium, which is associated with an impaired release of endothelium-derived nitric oxide (NO), may play a critical role in the remodeling of pulmonary vessels in COPD. Endothelial dysfunction in pulmonary arteries was initially shown in end-stage COPD patients undergoing lung transplantation by Dinh-Xuan and coworkers (1). In a recent study we observed that endothelial dysfunction may also be present in pulmonary arteries of patients with mild COPD (2). However, whereas in end-stage COPD chronic severe hypoxemia may account for the impairment of the endothelial function (1), the mechanisms of such an impairment in patients with milder degrees of disease, who are not hypoxemic, are unknown.Several studies performed in lungs of patients with mild COPD have shown apparent abnormalities in the structure of the pulmonary muscular arteries, in most cases consisting of the thickening of the intimal layer (3-5). Interestingly, the intensity of the intimal thickening has been shown to correlate with the severity of the inflammatory infiltrate in small airways (5, 6), suggesting that an inflammatory process might also account for the structural abnormalities of the pulmonary artery wall. Indeed, inflammation has been shown to be involved in the pathogenesis of some forms of pulmonary hypertension (7) and also in the remodeling of systemic vessels (8). Accordingly, we hypothesized that the structural abnormalities and the endothelial dysfunction shown in pulmonary arteries of patients with mild COPD could be related to an inflammatory process.Cigarette smoking causes an inflammatory reaction in the airways of patients with COPD. Whereas in both asymptomatic smokers and patients with COPD the nature and characteristics of the inflammatory reaction in central and peripheral airways (9-14), as well as in alveolar septa (15), have been thoroughly evaluated, little is known about the degree, nature, and evolution of the inflammatory infiltrate in pulmonary arteries of COPD patients.The present study, results of which have been given in abstract form (16), was therefore addressed to inves...

Morphologic changes in pulmonary muscular arteries may modify the mechanisms that regulate the pulmonary vascular tone and contribute to maintaining an adequate ventilation-perfusion (VA/Q) matching in patients with chronic obstructive pulmonary disease (COPD). To analyze the relationships between the abnormalities of pulmonary muscular arteries and the degree of VA/Q inequality, and to assess the effect of these abnormalities on the changes in VA/Q relationships induced by oxygen breathing, we studied a group of patients with mild COPD undergoing resective lung surgery. According to the degree of airflow obstruction and the increase in VA/Q mismatch produced by 100% O2 breathing (delta logSD Q), patients were divided into three groups: (A) patients with normal lung function, (B) patients with airflow obstruction and a high response to oxygen (delta logSD Q > 0.4), and (C) patients with airflow obstruction and a low response to oxygen (delta logSD Q < 0.4). Pulmonary arteries in Groups B and C showed narrower lumens and thicker walls than in Group A. These morphologic changes were produced mainly by an enlargement of the intimal layer and were more pronounced in Group C than in Group B. The assessment of intimal area as a function of artery diameter showed that the increase in intima in Group C took place predominantly in arteries with small diameters (< 500 microns). The mean intimal area on each subject correlated with both the PaO2 value (r = -0.46, p < 0.05) and the overall index of VA/Q mismatching (r = 0.51, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the accuracy of clinical parameters for the diagnosis of ventilator-associated (VA) pneumonia, as well as the diagnostic value of several invasive techniques, such as protected specimen brush (PSB), bronchoalveolar lavage (BAL), fiberoptic bronchial aspirates (FBAS), and percutaneous lung needle aspiration (PLNA), we compared the results of these techniques with the histopathology of immediate postmortem pulmonary biopsies, considered the "gold standard" reference test. We studied 30 mechanically ventilated patients (age 52 +/- 21 yr; mechanical ventilation period 9 +/- 7 days) who died in an intensive care unit. All patients received prior antibiotic treatment. The following procedures were performed immediately after death: bilateral PSB, BAL, FBAS, and PLNA, as well as bilateral minithoracotomies to obtain pulmonary biopsies as close as possible to the area sampled with the other techniques. According to the histopathology 18 patients had pneumonia and 12 did not. The presence of fever (sensitivity 55%, specificity 58%), purulent secretions (sensitivity 83%, specificity 33%), and chest radiograph infiltrates (sensitivity 78%, specificity 42%) could not differentiate in all instances presence from absence of pneumonia. Quantitative bacterial cultures of lung biopsies using 10(3) cfu/g as a cutoff point had low sensitivity (40%) and low specificity (45%) and could not differentiate the histologic absence or presence of pneumonia. Considering the histopathology of pulmonary biopsies as a gold standard, we found the following sensitivities for PSB, BAL, FBAS, and PLNA: 36, 50, 44, and 25%. The specificities were 50, 45, 48, and 79%, respectively. The sensitivities and specificities of different invasive techniques are much lower than those reported in clinical studies.(ABSTRACT TRUNCATED AT 250 WORDS)

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The diagnosis of pulmonary candidiasis is still controversial. We undertook a prospective study on 25 non-neutropenic, mechanically ventilated (> 72 h) patients who died in our ICU with the aim of assessing the incidence and significance of the isolation of Candida species from quantitative cultures of immediate postmortem lung biopsies and different respiratory sampling techniques. Immediate postmortem respiratory samples (endotracheal aspirate, protected specimen brush [PSB], bronchoalveolar lavage [BAL], blind biopsies [average 14/patient], and bilateral bronchoscopically guided biopsies [two per patient]) were taken from all patients. Lung tissue specimens were histologically examined. Respiratory samples were classified as having Candida or otherwise. Ten (40%) patients had at least one pulmonary biopsy yielding Candida spp. Among these 10 patients with Candida isolates, only two had definite pulmonary candidiasis. A total of 470 microorganisms were isolated from 280 of 375 (77%) lung biopsy samples in all 25 patients. Candida species represented 9% (n = 40) of the isolates, corresponding to 10 patients (40%). In the 10 patients in whom Candida species was isolated from pulmonary biopsies, this was always associated with the isolation of the same microorganism from one of the sampling methods. Quantitative cultures of Candida species from different sampling methods correlated well among each other but could not discriminate the presence from absence of Candida pneumonia. A logistic regression model adjusted for the presence of antibiotics, days of antibiotic treatment, mechanical ventilation period, age, ARDS, parenteral nutrition, and gender did not show any independent risk factor for developing positive pulmonary samples for Candida species. The incidence of Candida isolation from pulmonary biopsies in critically ill mechanically ventilated, non-neutropenic patients who die is high (40%). However, the incidence of definite Candida pneumonia was 8%. We also found that Candida colonization is uniform throughout the different lung regions, and that the presence of Candida in respiratory samples, independently of quantitative cultures, is not a good marker of Candida pneumonia in critically ill, non-neutropenic, non-AIDS patients.