Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: Comparison with different sputum phenotypes.

BACKGROUND: According to induced sputum cell count, four different asthma phenotypes have been recognized (eosinophilic, neutrophilic, mixed and paucigranulocytic). The aim of this study was to detect functional and inflammatory characteristics of patients with paucigranulocytic asthma. METHODS: A total of 240 asthmatic patients were categorized into the four phenotypes according to cell counts in induced sputum. All patients underwent pulmonary function tests, and measurement of fraction of exhaled nitric oxide (FeNO). The levels of IL-8, IL-13 and eosinophilic cationic protein (ECP) were also measured in sputum supernatant. Treatment, asthma control and the presence of severe refractory asthma (SRA) were also recorded. RESULTS: Patients were categorized into the four phenotypes as follows: eosinophilic (40%), mixed (6.7%), neutrophilic (5.4%) and paucigranulocytic (47.9%). Although asthma control test did not differ between groups (P=.288), patients with paucigranulocytic asthma had better lung function (FEV1 % pred) [median (IQR): 71.5 (59.0-88.75) vs 69.0 (59.0-77.6) vs 68.0 (60.0-85.5) vs 80.5 (69.7-95.0), P=.009] for eosinophilic, mixed, neutrophilic and paucigranulocytic asthma, respectively, P=.009). SRA occurred more frequently in the eosinophilic and mixed phenotype (41.6% and 43.7%, respectively) and less frequently in the neutrophilic and paucigranulocytic phenotype (25% and 21.7%, respectively, P=.01). FeNO, ECP and IL-8 were all low in the paucigranulocytic, whereas as expected FeNO and ECP were higher in eosinophilic and mixed asthma, while IL-8 was higher in patients with neutrophilic and mixed asthma (P<.001 for all comparisons). Interestingly, 14.8% of patients with paucigranulocytic asthma had poor asthma control. CONCLUSION: Paucigranulocytic asthma most likely represents a "benign" asthma phenotype, related to a good response to treatment, rather than a "true" phenotype of asthma. However, paucigranulocytic patients that remain not well controlled despite optimal treatment represent an asthmatic population that requires further study for potential novel targeted interventions.

Sputum interleukin-13 as a biomarker for the evaluation of asthma control.

BACKGROUND: Asthma control refers to the extent to which the manifestations of asthma have been reduced or eradicated by treatment. Interleukin-13 (IL-13) has a central role in Th2 response and serves as a possible therapeutic target in uncontrolled asthma. Fraction of exhaled nitric oxide (FeNO) and sputum eosinophils have modest performance in the evaluation of asthma control. OBJECTIVE: To assess the diagnostic performance of sputum IL-13 for the evaluation of asthma control and furthermore to investigate the performance of sputum eosinophils and FeNO. METHODS: One hundred and seventy patients with asthma were studied. All subjects underwent assessment of asthma control by asthma control test (ACT), lung function tests, FeNO measurement and sputum induction for cell count identification and IL-13 measurement in supernatants. RESULTS: IL-13 (pg/mL) levels in sputum supernatant differed significantly among patients with well-controlled asthma and those with not well-controlled asthma [median IQR 78 (66-102) vs. 213 (180-265), P < 0.001]. Receiver operating characteristic (ROC) analysis showed that, for the whole study population, the diagnostic performance of IL-13 was superior to both sputum eosinophils and FeNO levels [area under the curve (AUC) 0.92, 95% CI 0.87 to 0.95 vs. AUC 0.65, 95% CI 0.58 to 0.72 vs. AUC 0.65, 95% CI 0.55 to 0.72, respectively]. CONCLUSION: The diagnostic performance of sputum IL-13 was superior to both sputum eosinophils and FeNO levels for the identification of well-controlled asthma. Sputum IL-13 levels could serve as a useful biomarker for asthma control assessment.

Sputum and BAL Clara cell secretory protein and surfactant protein D levels in asthma.

Clara cell secretory protein (CC16) is associated with Th2 modulation. Surfactant protein D (SPD) plays an important role in surfactant homeostasis and eosinophil chemotaxis. We measured CC16 and SPD in sputum supernatants of 84 asthmatic patients and 12 healthy controls. In 22 asthmatics, we additionally measured CC16 and SPD levels in BAL and assessed smooth muscle area (SMA), reticular basement membrane (RBM) thickness, and epithelial detachment (ED) in bronchial biopsies. Induced sputum CC16 and SPD were significantly higher in patients with severe asthma (SRA) compared to mild-moderate and healthy controls. BAL CC16 and SPD levels were also higher in SRA compared to mild-moderate asthma. CC16 BAL levels correlated with ED, while SPD BAL levels correlated with SMA and RBM. Severity represented a significant covariate for these associations. CC16 and SPD levels are upregulated in SRA and correlate with remodeling indices, suggesting a possible role of these biomarkers in the remodeling process.

Alpha1-antitrypsin deficiency in Greece: Focus on rare variants.

PURPOSE: A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. AIM: to investigate genotype and clinical profile of Greeks with AATD. METHODS: Symptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. RESULTS: Included are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5-58.5) years, AAT-levels 0.20(0.08-0.26) g/L, FEV1(%predicted) 41.5(28.8-64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with MHeerlen (M1Ala/M1Val); p.(Leu65Pro) with MProcida; p.(Lys241Ter) with Q0Bellingham; p.(Leu377Phefs*24) with Q0Mattawa (M1Val) and Q0Ourem (M3); p.(Phe76del) with MMalton (M2), MPalermo (M1Val), MNichinan (V) and Q0LaPalma (S); p.(Asp280Val) with PLowell (M1Val); PDuarte (M4), YBarcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0GraniteFalls, Q0Saint-Etienne, Q0Amersfoort(M1Ala), MWürzburg, NHartfordcity and one novel-variant (c.1A>G) named Q0Attikon.Heterozygous included PI*MQ0Amersfoort(M1Ala), PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). CONCLUSION: Genotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis. In the future the detection of rare genotypes may add to personalize preventive and therapeutic measures.

Levels of prostaglandin E(2) and Cysteinyl-leukotrienes in sputum supernatant of patients with asthma: the effect of smoking.

BACKGROUND: Smoking is associated with worse asthma outcomes and may modify airway inflammation. Such modification may be mediated through an effect on prostaglandin E(2) (PGE(2)) and cysteinyl leukotrienes (Cyst-LTs). OBJECTIVE: We aimed to determine the levels of both PGE(2) and Cyst-LTs in sputum supernatants of patients with asthma and to investigate the effect of smoking habit as well as their associations with inflammatory cells, bronchial hyperresponsiveness (BHR) and lung function. METHODS: Ninety-eight patients to asthma (47 smokers) and 40 healthy subjects (20 smokers) were studied. All subjects underwent sputum induction for cell count identification, PGE(2) and Cyst-LTs levels measurement in supernatants, pulmonary function tests and BHR to methacholine. RESULTS: Patients with asthma had significantly higher levels of both Cyst-LTs and PGE(2) in sputum supernatants compared to healthy subjects [median (interquartile ranges) 432 (287, 575) vs. 91.5 (73.5, 111) pg/mL and 654 (456,789) vs. 117.5 (92,157) pg/mL, respectively, P < 0.001 for both comparisons]. Smoking asthmatics had significantly higher Cyst-LTs and PGE(2) levels compared to non-smoking asthmatics. Cyst-LTs levels in sputum supernatant of smoking asthmatics presented a significant positive association with sputum eosinophils, while PGE(2) levels were positively associated with sputum neutrophils. CONCLUSIONS: The increased concentrations of PGE(2) and Cyst-LTs in sputum supernatants of smoking asthma are consistent with an up-regulation of these two mediators in this specific phenotype of asthma. Furthermore, Cyst-LTs are associated with eosinophilic inflammation, while PGE(2) is associated with the presence of neutrophilic inflammation in smoking asthma.

Sleep apnea as a comorbidity in obese psoriasis patients: a cross-sectional study. Do psoriasis characteristics and metabolic parameters play a role?

BACKGROUND: Psoriasis is associated with a variety of comorbidities such as obesity and cardiovascular disease. OBJECTIVE: In a cross-sectional study, we explored whether obstructive sleep apnea and hypopnea syndrome (OSAHS) is associated with psoriasis characteristics and metabolic parameters. METHODS: Thirty-five patients with chronic plaque psoriasis underwent a nocturnal polysomnography study and were analysed for Apnoea-Hypopnoea Index to assess OSAHS severity and Framigham score to predict the absolute risk of coronary artery disease at 10 years. The association of OSAHS with psoriasis was examined according to psoriasis characteristics (PASI and DLQI scores, disease duration and previous use of systemic treatments), metabolic parameters (Body Mass Index - BMI, waist to hip ratio - WHR, lipid profile) and other comorbidities (obesity, hypertension, arthritis and cardiovascular disease). RESULTS: There was no correlation between psoriasis characteristics and OSAHS. Psoriasis patients with OSAHS presented more frequent snoring and lower sleep quality compared with those without OSAHS. In univariate analyses, OSAHS was associated with increased BMI and hypertension in psoriasis patients. In multivariable logistic regression models, there was statistically significant evidence that only BMI and hypertension were associated with increased risk of OSAHS, adjusting for psoriasis characteristics, age and gender. Presence of metabolic syndrome, WHR, and smoking were not significant risk factors for OSAHS. In subgroup analyses, OSAHS correlated with duration of psoriasis (>8 years) in women (P = 0.021) and with Framigham score in men (P = 0.035). CONCLUSION: OSAHS may be a comorbidity in obese psoriasis patients with hypertension. Treatment with continuous positive airway pressure and weight loss interventions should be initiated.

Increased levels of angiopoietins 1 and 2 in sputum supernatant in severe refractory asthma.

BACKGROUND: Airway and vascular remodeling may play a prominent role in the clinical severity of severe refractory asthma (SRA). Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. OBJECTIVE: We aimed to determine the levels of angiopoietins in sputum supernatants of patients with SRA and to investigate the possible associations with mediators and cells involved in both the inflammatory and the vascular remodeling processes. METHODS: Thirty-eight patients with SRA, 35 patients with moderate asthma, and 20 healthy subjects were studied. All participants underwent lung function tests, bronchial hyperresponsiveness assessment and sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-ß1, Cys-LTs, MMP-2, IL-13, ECP, and IL-8 measurement in supernatants. Airway vascular permeability (AVP) index was also assessed. RESULTS: Ang-1 (ng/ml) and Ang-2 (pg/ml) levels were significantly elevated in patients with SRA compared with patients with moderate asthma and control subjects [median, interquartile ranges: 30 (17-39) vs 7.5 (5-11) vs 4.7 (3.8-5.9) respectively, P < 0.001; and 506 (400-700) vs 190 (146-236) vs 96 (89-120) respectively, P < 0.001]. Regression analysis showed a significant positive association between Ang-2 and AVP index, MMP-2, Ang-1, and VEGF in SRA. A weak association was also observed between Ang-1 and sputum eosinophils% in SRA. CONCLUSION: Our results indicate that both angiopoietins levels are higher in SRA compared with moderate asthma and healthy subjects. In SRA, Ang-2 is associated with mediators involved in both the inflammatory and the vascular remodeling processes.

Telomere length across different UIP fibrotic-Interstitial Lung Diseases: a prospective Greek case-control study.

INTRODUCTION: Short telomeres are recognized as risk factor for idiopathic pulmonary fibrosis (IPF). We aimed to assess the role of telomere length (TL) in fibrotic-Interstitial Lung Diseases (f-ILDs) associated with a usual interstitial pneumonia (UIP) pattern as well as in IPF acute exacerbation (IPF-AE). AIM AND METHODS: TL was measured from peripheral white blood cells using a multiplex quantitative polymerase chain reaction in consecutive patients with f-ILDs, all presenting UIP pattern in the high-resolution chest-computed-tomography and compared to age-matched healthy controls. RESULTS: Seventy-nine individuals were included (mean age 69.77 ±â€¯0.72 years); 24 stable IPF, 18 IPF-AE, 10 combined pulmonary fibrosis and emphysema, 7 Rheumatoid arthritis-UIP-ILDs and 20 controls. TL in all patients was significantly shorter compared to controls [mean T/S ratio (SE) 0.77 (±0.05) vs 2.26 (±0.36), p < 0.001] as well as separately in each one of f-ILD subgroups. IPF-AE patients presented significantly shorter TL compared to stable IPF (p = 0.029). Patients with IPF and shorter than the median TL (0-0.72) showed reduced overall survival (p = 0.004). T/S < 0.72 was associated with increased risk for IPF-AE (OR = 30.787, 95% CI: 2.153, 440.183, p = 0.012) independent of age, gender, smoking and lung function impairment. A protective effect of TL was observed, as it was inversely associated with risk of death both in UIP-f-ILDs (HR = 0.174, 95%CI: 0.036, 0.846, p = 0.030) and IPF patients (HR = 0.096, 95%CI: 0.011, 0.849, p = 0.035). CONCLUSIONS: Shorter TL characterizes different UIP f-ILDs. Although no difference was observed in TL among diverse UIP subgroups, IPF-AE presented shorter TL compared to stable IPF. Reduced overall survival and higher hazard ratio of death are associated with shorter TL in IPF.

Ambient air pollution and respiratory health effects in mail carriers.

Mail carriers represent an occupational group suffering from respiratory symptoms and lung function impairment. Although environmental conditions may play role, information on the effects of air pollution exposure in this population is lacking. The present study was conducted in Athens, Greece, in order to investigate the adverse effects of long-term air pollution exposure on respiratory outcomes in mail carriers. A total of 226 mail carriers and 73 office employees were enrolled. Information on respiratory symptoms, medical, occupational, residential and smoking history was obtained through a questionnaire. Flow-volume curves were performed in the workplace using a portable spirometer. Individualised personal exposure assessment has been applied based on long-term residential and occupational subject history linked with geographical air pollution distribution. Furthermore, personal measurements were obtained for forty-one mail carriers using NO(2) and O(3) passive samplers, assuming that current air pollution exposure is sufficiently representative of long-term, previous exposure to make a plausible link with current health status. The analysis based on exposures estimated on the basis of residential and work addresses showed that the most exposed to PM(10) postal workers have rhinitis at a higher rate (OR=1.67, 95% CI: 1.01-2.75). In mail carriers there is indication that those exposed to higher concentrations of Omicron(3) or PM(10) have a greater possibility to present rhinitis (OR=1.63, 95% CI: 0.93-2.88 and OR=1.70, 95% CI: 0.96-3.03, respectively). The effect of O(3) on rhinitis became even more apparent in the analysis based on exposures assessed by personal measurements (OR=6.74, 95% CI: 1.24-36.55). Exposure to NO(2) was significantly associated with decrements in lung function. For office employees the exposure to air pollutants was not associated to any adverse respiratory outcome. Our findings suggest that air pollution is a contributing factor for the occurrence of rhinitis and lung function impairment in mail carriers.

Exhaled breath condensate in patients with asthma: implications for application in clinical practice.

Exhaled breath condensate (EBC) analysis, a rather appealing and promising method, can be used to evaluate conveniently and non-invasively a wide range of molecules from the respiratory tract, and to understand better the pathways propagating airway inflammation. A large number of mediators of inflammation, including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, prostanoids, nitrogen oxides, peptides and cytokines, have been studied in EBC. Concentrations of such mediators have been shown to be related to the underlying asthma and its severity and to be modulated by therapeutic interventions. Despite the encouraging positive results to date, the introduction of EBC in everyday clinical practice requires the resolution of some methodological pitfalls, the standardization of EBC collection and finally the identification of a reliable biomarker that is reproducible has normal values and provides information regarding the underlying inflammatory process and the response to treatment. So far, none of the parameters studied in EBC fulfils the aforementioned requirements with one possible exception: pH. EBC pH is reproducible, has normal values, reflects a significant part of asthma pathophysiology and is measurable on-site with standardized methodology although some methodological aspects of measurement of pH in EBC (e.g. the effect of ambient CO(2), sample de-aeration, time for pH measurement) require further research. However, EBC pH has not been evaluated prospectively as a guide for treatment, in a manner similar to exhaled NO and sputum eosinophils. EBC represents a simple and totally non-invasive procedure that may contribute towards our understanding of asthma pathophysiology. Besides the evaluation of new biomarkers, the standardization of the already existing procedures is warranted for the introduction of EBC in clinical practice.

Cirrhosis-related intrathoracic disease. Imaging features in 1038 patients.

BACKGROUND/AIMS: To describe imaging features of cirrhosis-related intrathoracic disease. METHODOLOGY: Chest CTs of 1038 cirrhotic patients (mean age 53 yrs; range, 17-79) were evaluated for: bronchoarterial ratio (BAR), arteriovenous malformations, interstitial opacities, emphysema, and pleural effusions. Lymphangiography, pulmonary angiography, cardiac ultrasound and scintigraphy were selectively performed. RESULTS: Mean BAR was 0.83+/-0.19. In two patients with hepatopulmonary syndrome (HPS), mean BAR was 0.55. HRCT detected interstitial lung opacities in 15 patients. Signs of fibrosis were seen in 7 (only two associated to biliary cirrhosis) and interstitial edema in 8. Accurate pattern recognition was achieved in 10/15 cases (66.6%). Of the 93 patients with emphysema only one had documented alpha1-AT deficiency (1.08%). Multiple type 1 vascular dilatations were visualized in two patients with HPS. Hepatic hydrothorax was present in 49 patients (4.72%); right-sided in 34 (69.4%), bilateral in 9 (18.4%) and left-sided in 6 (12.2%). Hepatic chylothorax was confirmed in 3 patients. Lymphangiography demonstrated the site of leakage and the engorged thoracic duct. CONCLUSIONS: CT can identify intrathoracic pathology associated with liver disease. Decreased BAR is highly specific for HPS. However, a multimodality approach is necessary to depict cases of liver origin.

Imaging of thoracic Wegener's granulomatosis: the computed tomographic appearance.

PURPOSE: Computed tomography (CT) can play a major role in the examination of patients with diffuse infiltrative disorders of the lung. CT patterns of thoracic Wegener's granulomatosis were retrospectively evaluated in this study. The CT appearance was compared with imaging obtained by conventional plain roentgenograms. PATIENTS AND METHODS: Fourteen patients with Wegener's granulomatosis seen during the last 5 years are described. Conventional chest roentgenograms and CT scans from these patients are reviewed. RESULTS: The most frequent manifestation found in the lungs of patients with Wegener's granulomatosis was that of rounded opacities with or without cavitation. This was observed in 7 of 14 patients. Relatively unexpected was the frequent occurrence of bronchovascular bundle cuffing with a quite constant and characteristic bronchocentric distribution. This finding was observed in 5 of 14 patients. Vasculitis sign was demonstrated in 2 of 14 patients. Widespread acinar infiltrates, usually confluent, were common and were seen in 5 of 14 of our patients; in 2 of the patients, these infiltrates were due to diffuse pulmonary hemorrhage. Tracheal stenosis was the cause of sudden acute respiratory failure that was observed in one patient. Pleural disease was present in 3 of 14 patients. Hilar and mediastinal lymphadenopathy was observed in one patient. An interstitial pattern was observed in 3 of 14 patients. CONCLUSIONS: We conclude that an extremely wide spectrum of radiologic findings may be observed in this disease. In 14 patients we found 11 different roentgenographic manifestations; moreover, in 8 patients it was possible to describe more than 1 radiologic manifestation at the same time or during the course of the disease. This observation is not surprising, if we consider the wide variability and broad spectrum of pathologic features in pulmonary Wegener's granulomatosis. Because conventional roentgenograms failed in a great number of cases to visualize the exact pattern and the extent of thoracic involvement, we believe that CT is particularly helpful for the assessment of pulmonary involvement in Wegener's granulomatosis.

Round atelectasis and Metsovo lung.

Round (helical) atelectasis is one of the benign sequelae of occupational asbestos exposure. Environmental asbestos exposure does not differ from occupational in its pleural manifestations, but to our knowledge, round atelectasis has not been reported yet. In the present study, we present the clinical and radiologic findings of five individuals with round atelectasis. They were all born in the Metsovo area, northwest Greece, where environmental exposure to asbestos (tremolite) has been documented. All five had negative evaluation for malignancy. In addition, they have been followed up for one to four years and four of them are in good health, thus confirming round atelectasis as a benign, nonpremalignant condition. The fifth patient died of malignant pleural mesothelioma two years later, while the previously detected round atelectasis remained unchanged. We therefore consider that his mesothelioma was not related to the round atelectasis, although both were certainly related to the same environmental asbestos exposure.

Orthodeoxia in amiodarone-induced acute reversible pulmonary damage.

A case of acute reversible pulmonary damage from amiodarone is described. Pulmonary infiltrates had a basal predominance. The histopathologic picture was that of acute alveolitis. Orthodeoxia was evident on blood gas analysis; the PaO2 was 73 mm Hg on recumbency, and the PaO2 was 57 mm Hg in the upright position. Partial arterial resaturation was evident on exercise (PaO2, 64 mm Hg).

Pneumothorax as a first manifestation of sarcoidosis.

Pneumothorax is a rare manifestation of sarcoidosis, occurring usually late in the course of the disease. We report five cases of pneumothorax as a presenting manifestation of sarcoidosis. In two patients, thoracotomy showed extensive pleural infiltration by noncaseating granulomas. High-resolution CT scans showed cavitated subpleural nodules and subpleural bullae in one case. These findings support that necrosis of subpleural granulomas or rupture of a subpleural bullae, or both, are the mechanisms of pneumothorax in sarcoidosis. Three patients with a lung function impairment were treated with oral corticosteroids. One nontreated patient died due to progression of the disease.

Diagnostic and prognostic significance of squamous cell carcinoma antigen in non-small cell lung cancer.

Squamous cell carcinoma antigen (SCC-Ag) is a glycoprotein secreted by non-small cell lung tumours (NSCLC). This study investigated the diagnostic and prognostic significance of SCC-Ag in NSCLC. Receiver operating characteristic (ROC) curve analysis was used to test the diagnostic performance of the SCC-Ag and determine the optimal threshold value in a group of 100 NSCLC patients undergoing surgery and 50 age matched healthy controls. This threshold was then prospectively validated in a group of 53 patients and 49 healthy controls. The prognostic significance of the preoperative SCC-Ag level and its postoperative decrease were tested using univariate and multivariate proportional hazard models. The area under the ROC curve was 0.71+/-0.04, and the best cutoff value was 1.4 ng/ml. This discriminated patients in the validation group, with a sensitivity of 0.55 and a specificity of 1.0. The hazard ratio was 0.144 (95% CI 0.074-0.281) for the postoperative decrease in the SCC Ag, and 5.823 (3.299-10.278) for the preoperative SCC Ag level. Multivariate analysis revealed that only disease stage and patients' age are strong prognostic factors for survival. In conclusion, the SCC-Ag serum level has moderate diagnostic role in NSCLC. Both the preoperative SCC-Ag level and its postoperative decrease have prognostic significance, yet inferior to the disease stage and the patient's age.

Fibrosing mediastinitis causing rapidly progressive dyspnea, pulmonary edema and death in a 16 yr old male.

Idiopathic fibrosing mediastinitis is a rare entity involving more severely the more compliant structures within the mediastinum. In this report a rare case of simultaneous involvement of both the superior vena cava (SVC) and pulmonary veins is described in a 16--year old male with progressive dyspnea on exertion, cough and a three months' history of blood--tinged sputum. Physical examination and imaging studies revealed signs of pulmonary venous hypertension (PVH) and SVC stenosis. Fibrosing mediastinitis was confirmed by multiple biopsy samples.