Impact of residual pulmonary obstruction on the long-term outcome of patients with pulmonary embolism.

The impact of residual pulmonary obstruction on the outcome of patients with pulmonary embolism is uncertain.We recruited 647 consecutive symptomatic patients with a first episode of pulmonary embolism, with or without concomitant deep venous thrombosis. They received conventional anticoagulation, were assessed for residual pulmonary obstruction through perfusion lung scanning after 6 months and then were followed up for up to 3 years. Recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension were assessed according to widely accepted criteria.Residual pulmonary obstruction was detected in 324 patients (50.1%, 95% CI 46.2-54.0%). Patients with residual pulmonary obstruction were more likely to be older and to have an unprovoked episode. After a 3-year follow-up, recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension developed in 34 out of the 324 patients (10.5%) with residual pulmonary obstruction and in 15 out of the 323 patients (4.6%) without residual pulmonary obstruction, leading to an adjusted hazard ratio of 2.26 (95% CI 1.23-4.16).Residual pulmonary obstruction, as detected with perfusion lung scanning at 6 months after a first episode of pulmonary embolism, is an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension.

Pulmonary Infarction: An Often Unrecognized Clinical Entity.

Pulmonary infarction occurs in nearly one-third of the patients with acute pulmonary embolism. Infarcts are still often mistaken for pneumonia or lung cancer because of the deeply rooted belief that they ought to be triangular in shape. In reality, the apical portion of an embolized region is spared from infarction thanks to sufficient collateral blood flow. Infarcts are always arranged peripherally along the surface of the visceral pleura (costal, diaphragmatic, mediastinal, or interlobar). Their free margin is sharp and convex toward the hilum, casting a semicircular or cushion-like density on chest radiography or computed tomography (CT). Focal areas of hyperlucency within the infarction are often seen on CT. Clinical presentation is nonspecific. Pleuritic chest pain, either isolated or in combination with abrupt dyspnea, is the most frequent presenting symptom, whereas hemoptysis is much rarer. Recent data indicate that younger age, increasing body height, and active cigarette smoking are independent predictors of infarction in the setting of acute pulmonary embolism. Correct recognition of pulmonary infarction is fundamental because pleural-based consolidations suggestive of infarction may be the first manifestation of pulmonary embolism.

Initial non-invasive in vivo sensing of the lung using time domain diffuse optics.

The in vivo diagnosis and monitoring of pulmonary disorders (caused for example by emphysema, Covid-19, immature lung tissue in infants) could be effectively supported by the non-invasive sensing of the lung through light. With this purpose, we investigated the feasibility of probing the lung by means of time-resolved diffuse optics, leveraging the increased depth (a few centimeters) attained by photons collected after prolonged propagation time (a few nanoseconds). We present an initial study that includes measurements performed on 5 healthy volunteers during a breathing protocol, using a time-resolved broadband diffuse optical spectroscopy system. Those measurements were carried out across the spectral range of 600-1100 nm at a source-detector distance of 3 cm, and at 820 nm over a longer distance (7-9 cm). The preliminary analysis of the in vivo data with a simplified homogeneous model revealed a maximum probing depth of 2.6-3.9 cm, suitable for reaching the lung. Furthermore, we observed variations in signal associated with respiration, particularly evident at long photon propagation times. However, challenges stemming from both intra- and inter-subject variability, along with inconsistencies potentially arising from conflicting scattering and absorption effects on the collected signal, hindered a clear interpretation. Aspects that require further investigation for a more comprehensive understanding are outlined.

Perfusion SPECT in patients with suspected pulmonary embolism.

PURPOSE: Ventilation/perfusion tomography (V/PSPECT), with new interpretation criteria and newer tracers for ventilation imaging, has markedly improved the diagnostic yield in acute pulmonary embolism (PE). Here, we evaluated the diagnostic performance of perfusion SPECT (PSPECT) without ventilation imaging. METHODS: We studied 152 patients with clinically suspected PE who had been examined with both V/PSPECT and multidetector computed tomographic angiography (MD-CTA). The diagnosis or exclusion of PE was decided by the referring clinician based on both the V/PSPECT and/or MD-CTA findings in combination with the clinical findings. PSPECT images were retrospectively examined by a physician with experience in the interpretation of planar perfusion scans who was blinded to clinical, V/PSPECT and MD-CTA data. PSPECT images were interpreted without the aid of chest radiography. All the patients who were deemed to have PE were given anticoagulant therapy. RESULTS: Of the 152 patients, 59 (39%) received a final diagnosis of PE, and 19 (32%) had associated cardiopulmonary diseases such as pneumonia, COPD, or left heart failure. PSPECT correctly identified 53 (90%) of the 59 patients with PE. The specificity was 88 of 93 (95%). None of the PSPECT images was rated nondiagnostic. PSPECT yielded an overall diagnostic accuracy of 93% (95% confidence interval, CI, 87-96%). At the observed PE prevalence of 39 %, the positive and negative predictive values of PSPECT were 91% (95% CI, 80-97%) and 94% (95% CI, 86-97%), respectively. CONCLUSION: In managing critically ill patients, PSPECT might be a valid alternative to V/PSPECT or MD-CTA since it was able to identify most patients with PE with a low false-positive rate and no inconclusive results.

Prognostic value of alveolar volume in systolic heart failure: a prospective observational study.

BACKGROUND: Ventilatory impairment is known to occur in patients with heart failure (HF). Alveolar volume (VA) is measured by the dilution of an inert gas during a single breath-hold maneuver. Such measurement is sensitive to ventilatory disturbances. We conducted a prospective, observational study to establish the prognostic value of VA in systolic HF. METHODS: We studied 260 consecutive patients who were hospitalized for systolic HF. All patients were evaluated under stable clinical conditions, before hospital discharge. Lung function studies included spirometry and determination of the lung diffusing capacity for carbon monoxide (DLCO) by the single-breath method. We also measured the cardiothoracic ratio on frontal chest radiographs, and the circulating levels of N-terminal pro-hormone of B-type natriuretic peptide (NT-proBNP). The hazard ratio (HR) of death was estimated with Cox regression, and the percentiles of survival time with Laplace regression. For survival analysis, VA was categorized as < 80% (n = 135), or ≥ 80% of the predicted value (n = 125). RESULTS: Follow-up had a median duration of 2.7 years (interquartile range, 1.1 to 4.2 years). The crude mortality rate was 27% in the whole sample, 36% in patients with VA < 80%, and 16% in those with VA ≥ 80%. The HR of death was 2.3-fold higher in patients with VA < 80% than in those with VA ≥80% (p = 0.002). After adjusting for age, New York Heart Association class III-IV, cardiothoracic ratio >0.5, NT-proBNP, persistent atrial fibrillation, DLCO, COPD comorbidity, use of beta-blockers and angiotensin converting enzyme inhibitors, the HR decreased to 1.9 but remained statistically significant (p = 0.039). Two percent of the patients with VA < 80% died about 0.9 years earlier than those with VA ≥ 80% (p = 0.033). The difference in survival time at the 20th percentile was 0.8 years. CONCLUSIONS: VA is a significant, independent predictor of reduced survival in patients with systolic HF.

The thrombophilic pattern of different clinical manifestations of venous thromboembolism: a survey of 443 cases of venous thromboembolism.

Although pulmonary embolism (PE) and deep vein thrombosis (DVT) share many risk factors, it is uncertain whether thrombophilic abnormalities may impact differently on the development of these two clinical manifestations of venous thromboembolism (VTE). To give further insight into this issue, we estimated the association of PE with different types of thrombophilia and evaluated whether these abnormalities have a different prevalence in patients presenting with PE, alone or associated with DVT, as compared with those with isolated DVT. In this study 443 consecutive patients with a first episode of VTE and 304 matched healthy controls underwent laboratory screening for thrombophilia, including natural anticoagulants, factor V Leiden and prothrombin G20210A polymorphisms, antiphospholipid antibodies, homocysteine, factor VIII, and lipoprotein(a). Of the 443 patients, 224 patients had isolated DVT, 144 had combined DVT/PE, and 75 had isolated PE. At least one thrombophilic abnormality was detected in 72.8% of DVT, 66% of DVT/EP, and 60% of isolated PE patients. A high prevalence of hyperhomocysteinemia and elevated lipoprotein(a) levels was found in all patients with no significant differences among the three groups. The prevalence of prothrombin G20210A polymorphism and of elevated factor VIII levels was significantly higher in patients with DVT and DVT/PE than in controls, but not in those with isolated PE, whereas factor V Leiden polymorphism was associated with isolated DVT but not with DVT/PE or isolated PE. In conclusion, the thrombophilic burden seems different in isolated PE versus DVT with or without PE, suggesting that PE may encompass a different pathophysiological process of thrombosis to DVT.

The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study.

BACKGROUND: Genetic factors are known to contribute to COPD susceptibility and these factors are not fully understood. Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease. Genome-wide association studies in combination with expression profiling have identified a number of new candidates including IREB2. A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility. METHODS: We have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls. Genotype information was obtained for seven SNPs in the IREB2 gene, and for four SNPs in the TGFbeta1 gene. Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated. The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre. RESULTS: Our data replicate the association of IREB2 SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053. No significant associations were identified for TGFbeta1. CONCLUSIONS: These studies have therefore confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis.

Soluble receptor for advanced glycation end products in COPD: relationship with emphysema and chronic cor pulmonale: a case-control study.

BACKGROUND: The receptor for advanced glycation end products (RAGE) is a multiligand signal transduction receptor that can initiate and perpetuate inflammation. Its soluble isoform (sRAGE) acts as a decoy receptor for RAGE ligands, and is thought to afford protection against inflammation. With the present study, we aimed at determining whether circulating sRAGE is correlated with emphysema and chronic cor pulmonale in chronic obstructive pulmonary disease (COPD). METHODS: In 200 COPD patients and 201 age- and sex-matched controls, we measured lung function by spirometry, and sRAGE by ELISA method. We also measured the plasma levels of two RAGE ligands, N-epsilon-carboxymethyl lysine and S100A12, by ELISA method. In the COPD patients, we assessed the prevalence and severity of emphysema by computed tomography (CT), and the prevalence of chronic cor pulmonale by echocardiography. Multiple quantile regression was used to assess the effects of emphysema, chronic cor pulmonale, smoking history, and comorbid conditions on the three quartiles of sRAGE. RESULTS: sRAGE was significantly lower (p = 0.007) in COPD patients (median 652 pg/mL, interquartile range 484 to 1076 pg/mL) than in controls (median 869 pg/mL, interquartile range 601 to 1240 pg/mL), and was correlated with the severity of emphysema (p < 0.001), the lower the level of sRAGE the greater the degree of emphysema on CT. The relationship remained statistically significant after adjusting for smoking history and comorbid conditions. In addition, sRAGE was significantly lower in COPD patients with chronic cor pulmonale than in those without (p = 0.002). Such difference remained statistically significant after adjusting for smoking history, comorbidities, and emphysema severity. There was no significant difference in the plasma levels of the two RAGE ligands between cases and controls. CONCLUSIONS: sRAGE is significantly lower in patients with COPD than in age- and sex-matched individuals without airflow obstruction. Emphysema and chronic cor pulmonale are independent predictors of reduced sRAGE in COPD.

The incidence of recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension following a first episode of pulmonary embolism.

PURPOSE OF REVIEW: Pulmonary embolism is the most serious complication of venous thromboembolism, with an elevated case/fatality rate. Patients who survived a first episode of pulmonary embolism should be evaluated for the risk of recurrence and of chronic thromboembolic pulmonary hypertension (CTEPH). RECENT FINDINGS: The risk of recurrence is higher in patients with unprovoked pulmonary embolism than in those with transient risk factors. Persistent risk factors, such as active cancer and antiphospholipid antibodies, are associated with high risk of recurrence. Recently, elevated D-dimer levels after discontinuation of therapy have been identified as a risk factor for recurrence. CTEPH is characterized by intravascular organization of emboli and occurs in 0.5-1% of cases. Some patients with CTEPH have impaired fibrinolysis, likely due to a structural abnormality of fibrin or fibrin clot. Echocardiography often reveals signs of pulmonary hypertension. This should be confirmed by direct measurement of pulmonary artery pressures at right heart catheterization. SUMMARY: CTEPH patients should receive life-long anticoagulation for preventing recurrent pulmonary embolism. Pulmonary endarterectomy is the treatment of choice for patients with proximal pulmonary vascular occlusion. Patients with predominantly distal pulmonary vascular occlusion are candidates for pharmacological treatment. All patients with unprovoked pulmonary embolism should be evaluated for long-term anticoagulation.

Fibrin resistance to lysis in patients with pulmonary hypertension other than thromboembolic.

RATIONALE: Reportedly, fibrin isolated from patients with chronic thromboembolic pulmonary hypertension (CTEPH) is resistant to lysis. Persistence of regions within the fibrin beta chain, which mediate cell signaling and migration, could trigger the organization of pulmonary thromboemboli into chronic intravascular scars. OBJECTIVES: Ascertain whether fibrin resistance to lysis occurs in patients with pulmonary hypertension (PAH) other than CTEPH, and in those with prior pulmonary embolism (PE) and no pulmonary hypertension. METHODS: Fibrinogen was purified from 96 subjects (17 with CTEPH, 14 with PAH, 39 with prior PE, and 26 healthy control subjects) and exposed to thrombin to obtain fibrin clots. Plasmin-mediated cleavage of fibrin beta chain was assessed hourly over a 6-hour period by polyacrylamide gel electrophoresis. Fibrin band intensity was measured by densitometry of stained gels. Data were normalized to the band intensity of the undigested protein. MEASUREMENTS AND MAIN RESULTS: By 1 hour of digestion, fibrin band intensity had decreased by a median of 25% (interquartile range [IQR], 20 to 27%) in control subjects, and by 15% (IQR, 11 to 18%) in patients with prior PE (P < 0.0001). The 1-hour median reduction in band intensity was 2% (IQR, 1 to 3%) in CTEPH, and 4% (IQR, 2 to 7%) in PAH (P < 0.0001 vs. control subjects and PE). The decline in fibrin band intensity remained significantly different among the four groups up to 6 hours (P < 0.0001). CONCLUSIONS: Fibrin resistance to lysis occurs in pulmonary hypertension other than CTEPH and, to a smaller extent, in patients with prior PE and no pulmonary hypertension.

Association of MMP-2 polymorphisms with severe and very severe COPD: a case control study of MMPs-1, 9 and 12 in a European population.

BACKGROUND: Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis of the pathogenesis of COPD. These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease--antiprotease imbalance theory for the cause of COPD. Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies. METHODS: To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations. We used logistic regression to adjust for age, gender, centre and smoking history. RESULTS: Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV. CONCLUSIONS: Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94). The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129). This implicates haplotypes of MMP-12 as modifiers of disease severity.

Incidence of recurrent venous thromboembolism and of chronic thromboembolic pulmonary hypertension in patients after a first episode of pulmonary embolism.

After a first episode of pulmonary embolism (PE), two major problems need to be considered: risk of recurrence when anticoagulation is stopped, and risk of chronic thromboembolic pulmonary hypertension (CTPH). We followed prospectively consecutive patients who survived a first episode of PE, with or without deep vein thrombosis, to assess the incidence of venous thromboembolism (VTE) recurrences and of symptomatic and asymptomatic CTPH. After 3-6 months of oral anticoagulant therapy (OAT) patients underwent transthoracic echocardiography for measuring transtricuspid (rV-rA) gradient. When rV-rA gradient was >35 mmHg further evaluations were performed to rule in or out CTPH. During follow-up patients who developed persistent dyspnea were re-evaluated. In patients who underwent OAT withdrawal D-dimer (DD), prothrombin fragment 1 + 2 (F1 + 2), and thrombophilia were evaluated one month after warfarin discontinuation. Overall, 239 patients, 118 males, median age 59(16-89) years, were followed up for a median time of 36(9-192) months. Nine patients had rV-rA gradient >30 mmHg and ≤35 mmHg, and one of 37 mmHg. Among patients with normal rV-rA gradient, one developed persistent dyspnea 55 months after the first event and CPTH was confirmed. Among 206 patients who stopped OAT, 23(11.2%) had VTE recurrence, 11 PE(48%). Elevated DD and F1 + 2 levels after stopping OAT were significantly associated with recurrence. None of patients with recurrent VTE had elevated rV-rA gradient. In our series the incidence of CTPH after a first episode of PE was 0.4%. VTE recurrence and elevated DD and F1 + 2 levels seemed not to be related to the development of CTPH.

Simple and accurate prediction of the clinical probability of pulmonary embolism.

RATIONALE: Clinical probability assessment is a fundamental step in the diagnosis of pulmonary embolism. OBJECTIVES: To develop a predictive model for pulmonary embolism based on clinical symptoms, signs, and the interpretation of the electrocardiogram. METHODS: The model was developed from a database of 1,100 patients with suspected pulmonary embolism, of whom 440 had the disease confirmed by angiography or autopsy findings. It was validated in an independent sample of 400 patients with suspected pulmonary embolism (71% were inpatients). Easy-to-use software was developed for computing the clinical probability on palm computers and mobile phones. MEASUREMENTS AND MAIN RESULTS: The model comprises 16 variables of which 10 (older age, male sex, prolonged immobilization, history of deep vein thrombosis, sudden-onset dyspnea, chest pain, syncope, hemoptysis, unilateral leg swelling, electrocardiographic signs of acute cor pulmonale) are positively associated, and 6 (prior cardiovascular or pulmonary disease, orthopnea, high fever, wheezes, or crackles on chest auscultation) are negatively associated with pulmonary embolism. In the validation sample, 165 (41%) of 400 patients had pulmonary embolism confirmed by angiography. The prevalence of pulmonary embolism was 2% when the predicted clinical probability was slight (0 to 10%), 28% when moderate (11 to 50%), 67% when substantial (51 to 80%), and 94% when high (81 to 100%). There was no significant difference between inpatients and outpatients with respect to the prevalence of pulmonary embolism in the four probability categories. CONCLUSIONS: The proposed model is simple and accurate, and it may aid physicians when assessing the clinical probability of pulmonary embolism.

Sensitivity and specificity of perfusion scintigraphy combined with chest radiography for acute pulmonary embolism in PIOPED II.

UNLABELLED: We used the archived Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) data and images to test the hypothesis that reading perfusion scans with chest radiographs but without ventilation scans, and categorizing the perfusion scan as "pulmonary embolism (PE) present" or "PE absent," can result in clinically useful sensitivity and specificity in most patients. METHODS: Patients recruited into PIOPED II were eligible for the present study if they had a CT angiography (CTA) or digital subtraction angiography (DSA) diagnosis, an interpretable perfusion scan and chest radiographs, and a Wells' score. Four readers reinterpreted the perfusion scans and chest radiographs of eligible patients. Two readers used the modified PIOPED II criteria and 2 used the Prospective Investigative Study of Pulmonary Embolism Diagnosis (PISAPED) criteria. The chest radiographs were read as "normal/near normal," "abnormal," or "nondiagnostic," and the perfusion scans were read as "PE present," "PE absent," or "nondiagnostic." The primary analysis used a composite reference standard: the PIOPED II DSA result or, if there was no definitive DSA result, CTA results that were concordant with the Wells' score as defined in PIOPED II (CTA positive and Wells' score > 2, or CTA negative and Wells' score < 6). RESULTS: The prevalence of PE in the sample was 169 of 889 (19%). Using the modified PIOPED II criteria, the sensitivity of a "PE present" perfusion scan was 84.9% (95% confidence interval [CI], 80.1%-88.8%), and the specificity of "PE absent" was 92.7% (95% CI, 91.1%-94.1%), excluding "nondiagnostic" results, which occurred in 20.6% (95% CI, 18.8%-22.5%). Using PISAPED criteria, the sensitivity of a "PE present" perfusion scan was 80.4% (95% CI, 75.9%-84.3%) and the specificity of "PE absent" was 96.6% (95% CI, 95.5%-97.4%), whereas the proportion of patients with "nondiagnostic" scans was 0% (95% CI, 0.0%-0.2%). CONCLUSION: Perfusion scintigraphy combined with chest radiography can provide diagnostic accuracy similar to both CTA and ventilation-perfusion scintigraphy, at lower cost and with lower radiation dose. With modified PIOPED II criteria, a higher proportion of scans were nondiagnostic than with CTA, and with PISAPED criteria none were nondiagnostic.

Matrix metalloproteinase-2 protein in lung periphery is related to COPD progression.

BACKGROUND: There is increasing evidence that matrix metalloproteinases (MMPs) may contribute to the pathogenesis of COPD, but their role in humans is not completely understood. We performed this study to quantify the expression of MMP-2 in a population of COPD patients at different stages of severity. METHODS: We collected surgical specimens from 46 subjects, as follows: 10 smokers with severe COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage III-IV); 13 smokers with mild/moderate COPD (GOLD stage I-II); 12 control smokers; and 11 nonsmoking control subjects. We quantified MMP-2 expression in alveolar macrophages, alveolar walls, peripheral airways, and pulmonary arterioles by immunohistochemistry. RESULTS: In all compartments, MMP-2 expression was increased both in smokers with severe COPD and in smokers with mild/moderate COPD compared to control smokers and nonsmokers (p < 0.05 for all comparisons). Only in alveolar macrophages was MMP-2 expression increased in smokers with severe COPD compared to smokers with mild/moderate COPD (p = c0.002). Moreover, MMP-2 expression was inversely related to values of FEV1/FVC ratio (p < 0.0001; r = -0.71) and Pao2 (in millimeters of Hg) [p = 0.005; r = -0.49], and was positively related to emphysema score (p = 0.01; r = 0.65) and residual volume percent predicted (p = 0.04; r = 0.49). A stepwise increase in the total number of alveolar macrophages was observed in the four groups of subjects examined, with the highest value in those with severe COPD. CONCLUSION: This study shows that MMP-2 expression in the lung periphery progressively increases as lung function worsens and the degree of emphysema increases. These results suggest that MMP-2 may be a key mediator of the mechanisms leading to lung tissue remodeling and inflammation in patients with severe COPD.

Computer-aided diagnosis of emphysema in COPD patients: neural-network-based analysis of lung shape in digital chest radiographs.

Several abnormalities of the shape of lung fields (depression and flattening of the diaphragmatic contours, increased retrosternal space) are indicative of emphysema and can be accurately imaged by digital chest radiography. In this work, we aimed at developing computational descriptors of the shape of the lung silhouette able to capture the alterations associated with emphysema. We analyzed two-sided digital chest radiographs from a sample of 160 patients with chronic obstructive pulmonary disease (COPD), 60 of which were affected by emphysema, and from 160 subjects with normal lung function. Two different description schemes were considered: a first one based on lung-silhouette curvature features, and a second one based on a minimal-polyline approximation of the lung shape. Both descriptors were employed to recognize alterations of the lung shape using classifiers based on multilayer neural networks of the feed-forward type. Results indicate that pulmonary emphysema can be reliably diagnosed or excluded by using digital chest radiographs and a proper computational aid. Two-sided chest radiographs provide more accurate discrimination than single-view analysis. The minimal-polyline approximation provided significantly better results than those obtained from curvature-based features. Emphysema was detected, in the entire dataset, with an accuracy of about 90% (sensitivity 88%, specificity 90%) by using the minimal-polyline approximation.

Bayes pulmonary embolism assisted diagnosis: a new expert system for clinical use.

BACKGROUND: The diagnosis of pulmonary embolism demands flexible decision models, both for the presence of clinical confounders and for the variability of local diagnostic resources. As Bayesian networks fully meet this requirement, Bayes Pulmonary embolism Assisted Diagnosis (BayPAD), a probabilistic expert systems focused on pulmonary embolism, was developed. METHODS: To quantitatively validate and improve BayPAD, the system was applied to 750 patients from a prospective study done in an Italian tertiary hospital where the true pulmonary embolism status was confirmed using pulmonary angiography or ruled out with a lung scan. The proportion of correct diagnoses made by BayPAD (accuracy) and the correctness of the pulmonary embolism probabilities predicted by the model (calibration) were calculated. The calibration was evaluated according to the Cox regression-calibration model. RESULTS: Before refining the model, accuracy was 88.6%. Once refined, accuracy was 97.2% and 98%, respectively, in the training and validation samples. According to Cox analysis, calibration was satisfactory, despite a tendency to exaggerate the effect of the findings on the probability of pulmonary embolism. The lack of some investigations (like Spiral computed tomographic scan and Lower limbs doppler ultrasounds) in the pool of available data often prevents BayPAD from reaching the diagnosis without invasive procedures. CONCLUSIONS: BayPAD offers clinicians a flexible and accurate strategy to diagnose pulmonary embolism. Simple to use, the system performs case-based reasoning to optimise the use of resources available within a particular hospital. Bayesian networks are expected to have a prominent role in the clinical management of complex diagnostic problems in the near future.

Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. While cigarette smoking is a major cause of COPD, only 15% of smokers develop the disease, indicating major genetic influences. The most widely recognized candidate gene in COPD is SERPINA1, although it has been suggested that SERPINA3 may also play a role. To detect cryptic genetic variants that might contribute to disease, we identified 15 SNP haplotype tags from high-density SNP maps of the two genes and evaluated these SNPs in the largest case-control genetic study of COPD conducted so far. For SERPINA1, six newly identified haplotypes with a common backbone of five SNPs were found to increase the risk of disease by six- to 50-fold, the highest risk of COPD reported to date. In contrast, no haplotype associations for SERPINA3 were identified.