Biomedical subjects
Isabelle Tillie-Leblond
Publications and source records attributed to Isabelle Tillie-Leblond.
Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors.
BACKGROUND: Diagnosis of pulmonary embolism (PE) is difficult in patients with chronic obstructive pulmonary disease (COPD) and exacerbation. OBJECTIVE: To evaluate PE in patients with COPD and exacerbation of unknown origin and explore factors associated with PE. DESIGN: Prospective cohort study. SETTING: University-affiliated hospital in France. PATIENTS: 211 consecutive patients, all current or former smokers with COPD, who were admitted to the hospital for severe exacerbation of unknown origin and did not require invasive mechanical ventilation. MEASUREMENTS: Spiral computed tomography angiography (CTA) and ultrasonography within 48 hours of admission and assessment of the Geneva score. Patients were classified as PE positive (positive results on CTA or negative results on CTA and positive results on ultrasonography) or PE negative (negative results on CTA and negative results on ultrasonography or negative results on CTA and no recurrence of PE at follow-up 3 months later). RESULTS: 49 of 197 patients (25% [95% CI, 19% to 32%]) met the diagnostic criteria for PE. Clinical factors associated with PE were previous thromboembolic disease (risk ratio, 2.43 [CI, 1.49 to 3.94]), malignant disease (risk ratio, 1.82 [CI, 1.13 to 2.92]), and decrease in PaCO2 of at least 5 mm Hg (risk ratio, 2.10 [CI, 1.23 to 3.58]). A total of 9.2% (CI, 4.7% to 15.9%) of patients with a low-probability Geneva score received a diagnosis of PE. An exploratory analysis suggested that substituting malignant disease for recent surgery in the Geneva score might improve its performance in excluding PE in this sample who were more likely to have malignant disease than to have had recent surgery. However, this improvement seems insufficient to exclude PE with enough certainty to withhold therapy for low-risk patients on the basis of the modified score. LIMITATIONS: This study was done in only 1 center. Patients with COPD requiring invasive mechanical ventilation in the intensive care unit were not included. The upper bound of the 95% CI for the low probability of PE according to the Geneva score is too high to rule out PE. The classification of COPD exacerbation of unknown origin was based on the clinician's assessment, not on a standard evaluation for all patients. CONCLUSION: This study showed a 25% prevalence of PE in patients with COPD hospitalized for severe exacerbation of unknown origin. Three clinical factors are associated with the increased risk for PE. The Geneva score and the modified Geneva score should be prospectively evaluated in patients with COPD.
[Diagnosis of asthma in adult].
Asthma is underdiagnosed in France. Asthma can often be diagnosed on the basis of symptoms, help by specific questions useful to consider the diagnosis. Measurement of lung function is important, for diagnosis, evaluation of the reversibility, the variability and the severity of bronchial obstruction. Indeed, patient with asthma may have a poor recognition of their symptoms and a poor perception of bronchial obstruction. Peak expiratory flow meter is an important aid in the diagnosis of asthma but measurements do not always correlate with other measurements of lung function. Allergic status and risk factors must be identified to control environmental exposure.
Safety and effectiveness of gadolinium-enhanced multi-detector row spiral CT angiography of the chest: preliminary results in 37 patients with contraindications to iodinated contrast agents.
PURPOSE: To prospectively evaluate the safety and effectiveness of gadolinium-enhanced multi-detector row spiral computed tomographic (CT) angiography of the pulmonary circulation by using two gadolinium doses in patients with contraindications to iodinated contrast agents. MATERIALS AND METHODS: Study was approved by the Ethics Committee, and written informed consent was obtained. Thirty-seven patients (20 men, 17 women) with contraindications to iodinated contrast agents (allergic reactions, n = 27; impaired renal function, n = 10) underwent CT angiography of the pulmonary circulation in search of acute pulmonary embolism (n = 28) or for management of tumoral disease (n = 9). CT angiography was performed (a) with four-detector row (n = 19) or 16-detector row (n = 18) scanners; (b) at randomly assigned gadolinium doses of either 0.3 mmol per kilogram of body weight (n = 19) or 0.4 mmol/kg (n = 18); and (c) with a systematic evaluation of clinical and biologic tolerance of gadolinium. Comparison of percentages between group 1 and group 2 scans was performed with the chi2 or the Fisher exact test. An unpaired Wilcoxon rank sum test was used for numeric variables. P < .05 was considered to indicate a significant difference. RESULTS: The mean (+/- standard deviation) volume of gadopentetate dimeglumine administered in the overall study group was 48 mL +/- 9.6 (range, 29-65 mL). The level of maximal enhancement in the pulmonary arteries was significantly higher in group 2 than in group 1 (215.8 HU +/- 95 vs 141.3 HU +/- 44) (P = .02) and was maintained throughout the entire region of interest in a greater number of examinations in group 2 than in group 1 (n = 16 [89%] vs n = 2 [10.5%]) (P < .0001). The number of diagnostic CT angiograms was significantly higher in group 2 than in group 1 (n = 17 [94%] vs n = 13 [68%]) (P = .007). Significant but transient reduction of creatinine clearance was observed in one patient with preexisting moderate chronic renal failure (0.3 mmol/kg gadolinium dose). CONCLUSION: High-quality gadolinium-enhanced CT angiograms require the use of 16-detector row CT technology; the doses administered did not alter the renal function except transiently in one patient.
Costs of hospitalization for severe acute asthma of patients not treated according to guidelines and recommendations. French prospective study of 169 cases.
This prospective study of 169 adult patients hospitalized for severe acute asthma in four pneumology wards compared the incidence and costs of patients who were managed (group A) or not managed (group P) before hospitalization, according to the guidelines and international recommendations (11 criteria judged by experts). Ambulatory costs were calculated by questioning patients. Valuation of hospital costs was based DRGs weighted by length of stay. The incidence in group P patients was estimated at 70%; A patients were 14 years younger than those in group P and had less severe asthma. Their annual ambulatory care prior to hospitalization was less costly irrespective of age category or degree of severity (euro 685 vs. euro 1,145 in group A); their length of hospital stay was shorter (6.03 vs. 10.78 days), resulting in a lower cost of hospitalization (euro 2,820 vs. euro 4,843). In group P a specific education program based on increased understanding, compliance, self-management, and smoking cessation, particularly in young patients should lead to reductions in hospitalizations.
High-resolution computed tomography scan and airway remodeling in children with severe asthma.
BACKGROUND: Children with severe asthma have a significantly higher bronchial wall thickness (BWT) on high-resolution computed tomography scan than control children. OBJECTIVE: We sought to determine whether a BWT score correlates with markers of airway remodeling and inflammation. METHODS: In 37 children with severe asthma, we determined reticular basement membrane thickness; number of intraepithelial neutrophils and eosinophils on bronchial biopsy; IFN-gamma, IL-4, IL-5, and eosinophil cationic protein levels and IFN-gamma/IL-4 ratio on bronchoalveolar lavage specimen; and alveolar nitric oxide (NO) concentration and the maximum airway wall NO flux. RESULTS: The BWT score significantly correlated with reticular basement membrane thickening (r = 0.34; P = .04) and NO production by the airway wall (r = 0.45; P = .02). The correlation with the eosinophil cationic protein level was just significant (r = 0.40; P = .05), whereas there was no correlation with IFN-gamma/IL-4 ratio (r = -0.31; P = .08). The BWT score did not correlate with FEV(1) or forced expiratory flow at 25% to 75% of forced vital capacity. CONCLUSION: High-resolution computed tomography scan is a noninvasive technique that might be valuable for quantifying airway remodeling in children with severe asthma. The new generations of multislice computed tomography scanners will allow higher definition and lower radiation exposure and probably give a better assessment of airway remodeling and efficacy of treatment in children with asthma.
Both inflammation and remodeling influence nitric oxide output in children with refractory asthma.
BACKGROUND: Exhaled nitric oxide can be used to monitor airway inflammation in asthma. We hypothesized that the strong link between nitric oxide and inflammation may obscure a weaker link with airway remodeling. OBJECTIVE: The aim of this study was to determine whether airway remodeling influenced exhaled nitric oxide in 28 asthmatic children (median age [25th-75th], 11 [10-14] years old) with refractory asthma defined as airflow limitation and/or exacerbations despite high-dose inhaled steroids. METHODS: Multiple-flow analysis of exhaled nitric oxide was used to correlate alveolar nitric oxide concentration and maximal conducting airway nitric oxide output to pulmonary function tests, bronchoalveolar lavage, and bronchial biopsy findings. RESULTS: Nitric oxide measurements were related to inflammation and T(H)1/T(H)2 balance, that is, subepithelial eosinophilic infiltration and eosinophilic cationic protein and IFN-gamma/IL-4 ratio in bronchoalveolar lavage fluids. Nitric oxide measurements were also correlated with several parameters of airway remodeling: alveolar nitric oxide concentration with TGF-beta in bronchoalveolar lavage fluid (r = 0.42, P =.03) and maximal conducting airway nitric oxide output with reticular basement membrane thickness (r = 0.61, P =.0007) and tissue inhibitor of matrix metalloproteinases 1/matrix metalloproteinase 9 ratio in bronchoalveolar lavage fluid (r = 0.43, P =.04). Moreover, alveolar nitric oxide concentration was correlated with MEF(25-75) (r = 0.60, P =.02). CONCLUSIONS: These findings suggest that both subacute inflammation and remodeling influence nitric oxide output in refractory asthma.
Difficult asthma in children: an analysis of airway inflammation.
BACKGROUND: Difficult asthma in children displays distinct clinical patterns, and its physiopathology remains poorly understood. OBJECTIVE: To determine the characteristics of the bronchial inflammatory profile in children with difficult asthma. METHODS: We performed endobronchial biopsy and bronchoalveolar lavage in 28 children with persistent bronchial obstruction despite high doses of inhaled corticosteroids and regular treatment with long-acting beta(2)-agonists: 13 had persistent symptoms and 15 had few or no symptoms. RESULTS: The number of eosinophils (P =.03) and neutrophils (P =.04) in the epithelium was significantly higher in symptomatic children than in children with few symptoms. Reticular basement membrane thicknening was similar in both groups. IFNgamma levels (P =.03) and IFNgamma/IL-4 ratio (P =.01) were significantly higher in children with few symptoms. CONCLUSIONS: In symptomatic children, T(H)2-type inflammation was associated with the presence of activated eosinophils in the epithelium, whereas asthma in children with few symptoms was associated with an increase in T(H)1 cytokine levels. The high levels of IFNgamma suggest that this T(H)1 cytokine may modulate the local inflammatory response.
Chronic bronchial allergic inflammation increases alveolar liquid clearance by TNF-alpha -dependent mechanism.
Bronchial inflammation in allergic asthma is associated with active exudation from the bronchial tree into the interstitial space of both mucosa and submucosa. The aim of this study was to evaluate epithelial and endothelial permeability as well as alveolar fluid movement in a model of chronic allergic inflammation in Brown-Norway rats sensitized and challenged with ovalbumin (OA). Control groups were challenged with saline solution (C), and rats were immunized by OA but not challenged (Se). Lung sections showed a marked inflammatory infiltrate associated with perivascular and peribronchiolar edema in OA. To measure alveolar liquid clearance, a 5% bovine albumin solution with 1 microCi of (125)I-labeled human albumin was instilled into the air spaces. Alveolar-capillary barrier permeability was evaluated by intravascular injection of 1 microCi of (131)I-labeled albumin. Endothelial permeability was significantly increased in OA, from 0.08 +/- 0.01 in the C group to 0.19 +/- 0.03 in OA group (P < 0.05). Final-to-initial protein ratio was also statistically higher in OA (1.6 +/- 0.05) compared with C (1.38 +/- 0.03, P = 0.01) and Se groups (1.42 +/- 0.03, P = 0.04). Administration of anti-tumor necrosis factor-alpha antibodies within the instillate significantly decreased this ratio (1.32 +/- 0.08, P = 0.003 vs. OA). To conclude, we demonstrated a tumor necrosis factor-alpha-dependent increase in alveolar fluid movement in a model of severe bronchial allergic inflammation associated with endothelial and epithelial leakage.
CT angiography of pulmonary embolism in patients with underlying respiratory disease: impact of multislice CT on image quality and negative predictive value.
Our objective was to evaluate the impact of multislice CT (MSCT) on image quality and diagnostic value of spiral CT angiograms. Over an 8-month period (January 2000 to August 2000), 134 consecutive patients, including 55 patients with underlying lung disease, underwent MSCT (group 1). Image quality and diagnostic results of CT angiograms were compared with those obtained in 125 consecutive patients, including 58 patients with underlying lung disease, evaluated with thin-collimation single slice CT (SSCT; group 2) over a similar period of time (January 1999 to August 1999). A 3-month clinical follow-up was systematically obtained in all patients who were not anticoagulated in the two groups. For a significantly longer mean z-axis coverage, the mean duration of data acquisition was significantly shorter with MSCT. The frequency of examinations devoid of motion artifacts was significantly higher in group 1 than in group 2. In the absence of significant difference in the quality of vascular enhancement, mainly coded as good or excellent, the proportion of examinations interpretable down to the subsegmental arteries was higher in group 1 (57.5%) than in group 2 (13%) ( p<0.0001). The benefits of MSCT were more marked for patients with underlying respiratory disease and did not lead to a higher detection rate of peripheral pulmonary embolism. The negative predictive values of single-slice and multislice CT were 100 and 99%, respectively. Improvement in image quality on MSCT scans accounts for the improved diagnostic accuracy of CT angiography, in particular for patients with impaired respiratory function.
Involvement of the mannose receptor in the uptake of Der p 1, a major mite allergen, by human dendritic cells.
BACKGROUND: Immature dendritic cells (DCs) take up antigens in peripheral tissues and, after antigen processing, mature to efficiently stimulate T cells in secondary lymph nodes. In allergic airway diseases DCs have been shown to be involved in the induction and maintenance of a T(H)2-type profile. OBJECTIVE: The present study was undertaken to determine pathways of Der p 1 (a house dust mite allergen) uptake by human DCs and to compare Der p 1 uptake between DCs from patients with house dust mite allergy and DCs from healthy donors. METHODS: Monocyte-derived DCs (MD-DCs) were obtained from patients with house dust mite allergy (n = 13) and healthy donors (n = 11). Der p 1 was labeled with rhodamine. Der p 1 uptake by MD-DCs was analyzed by means of flow cytometry and confocal microscopy. RESULTS: Rhodamine- labeled Der p 1 was demonstrated to be taken up by MD-DCs in a dose-, time-, and temperature- dependent manner. The involvement of the mannose receptor (MR) in the Der p 1 uptake was demonstrated by using (1) inhibitors of the MR- mediated endocytosis (mannan and blocking anti-MR mAb), which inhibited the Der p 1 uptake from 40 % to 50 %, and (2) confocal microscopy showing the colocalization of rhodamine-labeled Der p 1 with FITC-dextran. Interestingly, compared with DCs from healthy donors, DCs from allergic patients expressed more MR and were more efficient in Der p 1 uptake. CONCLUSION: These results suggest that the MR could play a key role in the Der p 1 allergen uptake by DCs and in the pathogenesis of allergic diseases in dust mite -sensitive patients.
Risk of pulmonary embolism after a negative spiral CT angiogram in patients with pulmonary disease: 1-year clinical follow-up study.
PURPOSE: To evaluate the effect of pulmonary disease on diagnostic utility of spiral computed tomographic (CT) angiography in clinical practice. MATERIALS AND METHODS: Three hundred thirty-four patients, including 215 patients with pulmonary disease (group 1) and 119 patients with no history of respiratory disorder (group 2), were referred for thin-collimation CT angiography of the pulmonary circulation as the first-line diagnostic test. Patients with negative angiograms who had not received anticoagulation therapy and who could be clinically followed up at 3 months, 6 months, and 1 year were considered in the final study groups (n = 185); 135 patients had lung disease (group 3), and 50 patients had no history of a respiratory disorder (group 4). RESULTS: Between groups 3 and 4, no significant differences were found in the referral location, age, and risk factors. Confident evaluation of pulmonary arteries down to the subsegmental level was performed in 31 (23%) patients in group 3 and in 15 (30%) in group 4 (P =.5). Three episodes of acute pulmonary embolism (PE), all fatal, were diagnosed in group 3 patients; two cases occurred 14 days and one case occurred 6 months after the negative spiral CT scan. The negative predictive value of spiral CT angiography was 98% (175 of 178) in the study group in which follow-up was performed, with no significant difference between the values in groups 3 (98% [132 of 135]) and 4 (100% [50 of 50]). CONCLUSION: Underlying respiratory disease does not affect the negative predictive value of thin-collimation CT angiography, which appears to be a reliable tool in the work-up in this subgroup of patients with acute PE.
Usefulness of coronal reformations in the diagnostic evaluation of infiltrative lung disease.
PURPOSE: To evaluate the diagnostic accuracy of coronal thin sections as an alternative to transverse high-resolution computed tomography (HRCT) scans in the diagnostic approach to infiltrative lung disease (ILD) with multislice computed tomography (MSCT). MATERIALS AND METHODS: Fifty consecutive patients referred for suspicion of ILD underwent MSCT (collimation: 4 mm x 1 mm; pitch: 1.75; scan time: 0.5 seconds; 80 mA per slice) of the entire thorax. Two sets of lung images were systematically reconstructed: 1-mm thick transverse computed tomography (CT) scans (i.e., HRCT scans) (group 1) and 1-mm thick coronal images (group 2). Both series of images were obtained at 10-mm intervals and reconstructed with a high-spatial frequency algorithm. Two observers independently analyzed the overall image quality, the presence and distribution of CT features of ILD, and the diagnostic value of group 1 and group 2 lung images. RESULTS: Group 1 and group 2 images were coded as interpretable, with minimal respiratory artifacts in the lower lung zones in two cases (4%). Presence of abnormal lung infiltration was found in 38 patients in group 2 with concordant interpretation of group 1 images. No significant difference was found in the identification of CT features of ILD between group 2 and group 1 (nodules: 32% vs. 30%; lines: 14% vs. 16%; increased attenuation: 24% vs. 26%; fibrosis: 48% vs. 50%; distortion: 46% vs. 50%; and abnormal interfaces: 16% in both groups). Distribution of lung abnormalities in central, peripheral, anterior, and/or posterior lung zones was similarly recognized in group 2 and group 1. In patients with extensive lung infiltration, the vertical predominance of lung changes was more precisely assessed in group 2 (n = 12) than in group 1 (n = 4). For a mean coverage of 260 mm in this study group, the mean number of sections to be interpreted was significantly lower in group 2 (19 sections) than in group 1 (28 sections) (P < 0.01). CONCLUSION: Coronal sections allow a diagnostic approach to ILD as precise as that provided with HRCT scans, based on the interpretation of a significantly reduced number of images.