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Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. We studied 674 consecutive adult patients who were prospectively enrolled in the French PAH registry (121 incident and 553 prevalent cases). Two survival analyses were performed. First, the cohort of 674 patients was followed for 3 yrs after study entry and survival rates described. Then, we focused on the subset with incident idiopathic, familial and anorexigen-associated PAH (n = 56) combined with prevalent patients who were diagnosed <3 yrs prior to study entry (n = 134). In the cohort of 674 patients, 1-, 2-, and 3-yr survival rates were 87% (95% CI 84-90), 76% (95% CI 73-80), and 67% (95% CI 63-71), respectively. In prevalent idiopathic, familial and anorexigen-associated PAH, 1-, 2-, and 3-yr survival rates were higher than in incident patients (p = 0.037). In the combined cohort of patients with idiopathic, familial and anorexigen-associated PAH, multivariable analysis showed that survival could be estimated by means of a novel risk-prediction equation using patient sex, 6-min walk distance, and cardiac output at diagnosis. This study highlights survivor bias in prevalent cohorts of PAH patients. Survival of idiopathic, familial and anorexigen-associated PAH can be characterised by means of a novel risk-prediction equation using patients' characteristics at diagnosis.

This study aims to describe the haemodynamic and survival characteristics of patients with pulmonary hypertension in the recently individualised syndrome of combined pulmonary fibrosis and emphysema. A retrospective multicentre study was conducted in 40 patients (38 males; age 68+/-9 yrs; 39 smokers) with combined pulmonary fibrosis and emphysema, and pulmonary hypertension at right heart catheterisation. Dyspnoea was functional class II in 15%, III in 55% and IV in 30%. 6-min walk distance was 244+/-126 m. Forced vital capacity was 86+/-18%, forced expiratory volume in 1 s 78+/-19%, and carbon monoxide diffusion transfer coefficient 28+/-16% of predicted. Room air arterial oxygen tension was 7.5+/-1.6 kPa (56+/-12 mmHg). Mean pulmonary artery pressure was 40+/-9 mmHg, cardiac index 2.5+/-0.7 L x min(-1) x m(-2) and pulmonary vascular resistance 521+/-205 dyn x s x cm(-5). 1-yr survival was 60%. Higher pulmonary vascular resistance, higher heart rate, lower cardiac index and lower carbon monoxide diffusion transfer were associated with shorter survival. Patients with combined pulmonary fibrosis and emphysema syndrome and pulmonary hypertension confirmed by right heart catheterisation have a dismal prognosis despite moderately altered lung volumes and flows and moderately severe haemodynamic parameters.

The characteristics of patients with rheumatoid arthritis (RA) who develop obliterative bronchiolitis characterised by severe airflow obstruction have been hitherto poorly investigated. A retrospective study of 25 patients with RA and functional evidence of obliterative bronchiolitis (forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) <50% and/or residual volume (RV)/total lung capacity (TLC) >140% predicted) was conducted. Patients (mean+/-SD age 64+/-11 yrs) included 17 never-smokers and eight ex-smokers (10.5+/-5.4 pack-yrs). The diagnosis of RA preceded respiratory symptoms in 88% of cases. Dyspnoea on exertion was present in all patients and bronchorrhea in 44%. High-resolution computed tomography findings included: bronchial wall thickening (96%), bronchiectasis (40%), mosaic pattern (40%), centrilobular emphysema (56%), and reticular and/or ground-glass opacities (32%). Pulmonary function tests showed: FEV(1) 41+/-12% pred, FEV(1)/FVC 49+/-14%, FVC 70+/-20% pred, RV 148+/-68% pred and RV/TLC 142+/-34% pred. Lung biopsy, available in nine patients, demonstrated constrictive, follicular and mixed bronchiolitis. Patients were followed for 48.2+/-49 months. Treatment was poorly effective. Chronic respiratory failure occurred in 40% of patients, and four patients died. Obliterative bronchiolitis associated with rheumatoid arthritis is a severe and under-recognised condition leading to respiratory failure and death in a high proportion of patients.

The priming of bronchiolitis obliterans organising pneumonia by radiation therapy (RT) to the breast is now a well recognised syndrome. This study describes the occurrence of chronic eosinophilic pneumonia following RT after surgery for breast cancer in five female patients, with a mean age of 68 yrs (range 49-77). All patients had a history of asthma and/or allergy. At the onset of eosinophilic pneumonia, all patients were symptomatic. Chest radiograph showed pulmonary infiltrates, unilateral and limited to the irradiated lung in three patients, and bilateral in two. Pulmonary opacities were migratory in one patient. All patients had blood eosinophilia >1.0 10(9) x L(-1) and/or eosinophilia >40% at bronchoalveolar lavage differential cell count. The median time interval between the end of radiation therapy and the onset of eosinophilic pneumonia was 3.5 months (range 1-10). All patients rapidly improved with oral corticosteroids without sequelae. Relapse occurred in two patients after treatment withdrawal. Priming of alveolitis by radiation therapy to the breast might promote either bronchiolitis obliterans organising pneumonia or chronic eosinophilic pneumonia, with the latter depending on genetic or acquired characteristics of patients and/or further stimulation that may trigger a T-helper cell type 2 form of lymphocyte response, especially in patients with asthma or other atopic manifestations.

This study investigated interstitial pneumonia associated with amyopathic dermatomyositis, dermatomyositis and polymyositis, paying particular attention to muscular and/or cutaneous manifestations and their chronology relative to lung involvement. Patients included four males and 13 females, aged 51.7+/-10.8 yrs, who had surgical lung biopsy. Diagnoses included dermatomyositis (10 patients), polymyositis (four patients) and amyopathic dermatomyositis (three patients). Solitary respiratory manifestations preceded the onset of any skin or muscle disease in four cases (24%). Reticular and ground glass opacities were the most frequent computed tomography (CT) findings. Pathological review showed nonspecific interstitial pneumonia (eleven, 65%; cellular, two; cellular and fibrotic, five; fibrotic, four), usual interstitial pneumonia (two), organising pneumonia (two), lymphocytic interstitial pneumonia (one), and unclassifiable interstitial pneumonia (one). Nonspecific interstitial pneumonia was the most common histological pattern of interstitial pneumonia in patients with amyopathic dermatomyositis (three of three) and in patients with respiratory symptoms as the initial clinical manifestation of the connective tissue disease (three of four). Survival at 5 yrs was 50%. This study shows the clinician should remain alert to potential muscular or cutaneous manifestations whenever a pathological diagnosis of nonspecific interstitial pneumonia is made.

Since idiopathic chronic eosinophilic pneumonia (ICEP) and asthma are frequently associated, their possible reciprocal influence on clinical presentation and evolution were investigated. The clinical and follow-up features of 53 cases of ICEP, of which 41 (77%) had asthma, were reviewed retrospectively. Asthma preceded the diagnosis of ICEP in 26 patients, was contemporaneous in eight patients, and developed 17 +/- 12 months after ICEP in seven patients. Presentation of ICEP was similar in asthmatics and nonasthmatics with the exception of a higher level of total immunoglobulin E in the former group. Patients with asthma at the time of diagnosis of ICEP were more likely to remain free of relapse of ICEP (56 versus 23%) and had a lower number of relapses per year of follow-up (median 0 versus 0.24). Moreover, they were treated more frequently with long-term inhaled corticosteroids (88 versus 31%) at last follow-up. Asthma got worse after the diagnosis of ICEP and frequently required long-term oral corticosteroids. To conclude, among patients with idiopathic chronic eosinophilic pneumonia, asthmatics have a lower frequency of relapse than nonasthmatics, possibly because of a higher use of inhaled corticosteroids. The occurrence of idiopathic chronic eosinophilic pneumonia in asthmatics is often associated with the development of severe asthma.

Respiratory bronchiolitis (RB) is defined by the accumulation of pigmented macrophages in the lumen and wall of respiratory and membranous bronchioles of smokers. The aim of this study was to determine whether spontaneous pneumothorax was associated with a high prevalence of RB. Seventy-nine consecutive patients who underwent a surgical procedure (thoracotomy or thoracoscopy) for recurrence or persistence of primary spontaneous pneumothorax despite thoracic drainage were studied retrospectively. RB was found in 70 of 79 (88.6%) smokers operated for spontaneous pneumothorax. Associated interstitial pathological abnormalities were present in 53 of 79 cases (67.1%). In nine patients, the pathological lesions were severe and resembled desquamative interstitial pneumonia. Emphysematous lesions were present in about one-third of the patients. Although the possible pathophysiological consequences of respiratory bronchiolitis remain speculative, this study demonstrates the high prevalence of this pathological abnormality in patients with pneumothorax requiring surgical treatment.

Four cases of lymphomatoid granulomatosis are reported, three of them involving the lung. Histological features included a true angiocentric and angiodestructive polymorphic cellular proliferation. This included histiocytes, plasma cells, many reactive T-cells and rare large, atypical cells which were of the B phenotype. Epstein-Barr virus was detected in the atypical cells by in situ hybridization in three cases, with expression of both latent membrane proteins (LMP)-1 and Epstein-Barr nuclear antigen-2 in two cases and expression of only LMP-1 in the third case. Expression of both of these proteins suggests a defect in the T-cell-mediated immunity and that Epstein-Barr virus is not only a silent passenger but may also be involved in the pathogenesis of the disease. This could have implications for therapy.

Pyothorax-associated lymphoma (PAL) is a newly-described entity developing several decades after artificial pneumothorax treatment for pulmonary or pleural tuberculosis. It is known to be associated with Epstein-Barr virus (EBV) with constant expression of the two latent membrane proteins: latent membrane protein (LMP)-1 and EBV-associated nuclear antigen (EBNA)-2. We are reporting three new cases of PAL. All of the tumours were of B-cell lineage and classified as large-cell diffuse lymphomas according to the International Working Formulation for the Classification of Lymphomas. The EBV genome was detected in two of the cases with LMP-1 and EBNA-2 expression. No EBV could be detected in the third case suggesting that different mechanisms may be involved in the pathogenesis of the disease. Body cavity-based high grade lymphomas (BCBL) represent a new disease, developing mainly in human immunodeficiency virus (HIV) infected patients: the tumoural cells often contain both human herpes virus (HHV)-8 (or Kaposi's sarcoma herpes virus) and EBV genomes, suggesting that these viruses might co-operate in the pathogenesis of the disease. The pleural location and the association of EBV have led to speculation that PAL could also be related to HHV-8 infection. However, no HHV-8 genome could be detected in any of the 14 tested cases already reported in the literature nor in the two cases we studied (one EBV-positive and one EBV-negative), suggesting that PAL and BCBL are two different entities.

A nationwide retrospective study of exogenous lipid pneumonia (ELP) was carried out to update the data on this disease, with emphasis on thoracic computed tomography (CT) scan and bronchoalveolar lavage (BAL) findings. The inclusion criteria were: 1) presence of abnormal imaging features compatible with the diagnosis of ELP; 2) presence of intrapulmonary lipids; and 3) exogenous origin of the lipid pneumonia. Forty four cases were included (20 males and 24 females; mean age 62 +/- 11 yrs), of which four were occupational (chronic inhalation of cutting mist or oily vapour in an industrial environment). Thirty of the 40 nonoccupational cases were related to aspiration of liquid paraffin used for the treatment of constipation. A condition possibly favouring oil aspiration or inhalation was present in 34 patients (77%), most commonly gastro-oesophageal reflux (n = 20) and neurological or psychiatric illness (n = 14). Fever (39%), weight loss (34%), cough (64%), dyspnoea (50%) and crepitations (45%) were the most frequent symptoms. BAL was performed in 39 cases: 23% had a lymphocytic alveolitis; 14% neutrophilic alveolitis; and 31% a mixed alveolitis (lymphocytic and neutrophilic). Alveolar consolidations (57%), ground glass opacities (39%), and alveolar nodules (23%) were the most common radiological abnormalities. The changes were bilateral (79%), predominant in the posterior and lower zones of the lobes concerned (74%), hypodense (71%), and spared the subpleural zones (52%). In 13 cases, hypodensity was retrospectively established on CT scan by the presence of a "positive angiogram". This sign may be of diagnostic value when the density measurement is either not possible or not reliable. In conclusion, this study provides an update of the clinical, biological and radiological profile of exogenous lipid pneumonia and, in particular, confirms the diagnostic benefit of computed tomography scan, which revealed bilateral and hypodense changes in a large majority of cases.

We report the case of a woman who presented with dyspnoea whilst taking minocycline for acne. Imaging features of bilateral patchy alveolar opacities suggested a diagnosis of bronchiolitis obliterans organizing pneumonia, which was confirmed by lung biopsy. The patient improved, partially, after stopping minocycline, and then completely on treatment with corticosteroids, without relapse when these where stopped 8 weeks later.

Patients at a single pulmonary centre who developed obstructive lung disease after bone marrow transplantation (BMT) and lung transplantation (LT) were studied, in order to compare the clinical expression of post-transplant obstructive lung disease (PTOLD) (bronchiolitis obliterans) in these two conditions, which have so far been studied separately. Nine out of 179 patients surviving more than 100 days after BMT (5%) and 9 out of 44 patients surviving more than 100 days after LT (20%) developed post-transplant obstructive lung disease. This was defined by an irreversible airflow obstruction, as characterized by a forced expiratory volume in one second divided by forced vital capacity (FEV1/FVC) of less than 70%, and a FEV1 of less than 70% of predicted value. The mean interval between transplantation and the diagnosis of post-transplant obstructive lung disease was 262 days and 217 days for BMT and LT patients, respectively. In all cases, pulmonary symptoms consisted of dyspnoea and progressively productive cough. Bronchial dilatation on high-resolution computed tomography scans was the main imaging feature present in both groups of patients at the onset of post-transplant obstructive lung disease. The mean FEV1/FVC ratio was 51 and 54% for BMT and LT patients, respectively. All BMT and LT patients had normal transfer coefficient. Clinical chronic graft-versus-host disease was present in all BMT patients before or concurrent with the onset of post-transplant obstructive lung disease, and all LT patients had presented at least one episode of acute lung rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

We report on two women presenting with cough and fever, 4 and 7 months, respectively, after starting breast radiation therapy following surgery for breast carcinoma. Chest roentgenogram and computed tomographic (CT) scan demonstrated alveolar opacities, initially limited to the pulmonary area next to the irradiated breast, but later migrating within both lungs. Intra-alveolar granulation tissue was found in transbronchial lung biopsies. Corticosteroid treatment resulted in dramatic clinical improvement, together with complete clearing of the pulmonary opacities on chest imaging. However, clinical and imaging relapses occurred when corticosteroids were withdrawn too rapidly; with further improvement when they were reintroduced. The reported cases clearly differ from radiation pneumonitis. They were fairly typical of cryptogenic organizing pneumonitis, also called idiopathic bronchiolitis obliterans organizing pneumonia, with the exception of the radiation therapy, partially affecting the lung, which had been performed within the previous months. Since focal radiation therapy involving the lung may induce diffuse bilateral lymphocytic alveolitis, we hypothesize that this may "prime" the lung to further injury, leading to cryptogenic organizing pneumonitis.

A 39 year old woman with severe primary biliary cirrhosis progressively developed exercise dyspnoea due to airflow obstruction. Sjögren's syndrome was not present. Bronchial and pulmonary biopsies demonstrated constrictive lymphocytic bronchitis/bronchiolitis, possibly a component of a generalized autoimmune process in this patient.

We report a patient with idiopathic hypereosinophilic syndrome presenting with bilateral eosinophilic pleural effusions. He also had erythema elevatum diutinum, a rare skin disease of the vasculitic type. No cardiomyopathy was present. Pleural effusions, skin lesions, and blood eosinophilia disappeared with prolonged corticosteroid treatment.

Gallium-67 citrate is known to localize within inflammatory sites. Gallium-67 scanning is used for the evaluation of lung inflammation (i.e. alveolitis) during interstitial lung diseases. We investigated 27 patients with cryptogenetic fibrosing alveolitis (n = 17) and hypersensitivity pneumonitis (n = 10) using gallium-67 lung scanning and lung function tests (forced vital capacity, diffusing capacity, resting and exercise blood gases). Investigations were performed before and after one year of methylprednisolone treatment. None of eight healthy volunteers had any abnormal gallium-67 uptake. In all patients with cryptogenetic fibrosing alveolitis an initial abnormal gallium-67 uptake was observed (mean fixation index: 163 +/- 18). In addition, analysis of lung function tests a year after initial evaluation showed that unchanged or improving patients presented initially with a lower gallium-67 index than patients with evidence of deterioration (153.9 +/- 23.7 vs 251.0 +/- 23.3.; p less than 0.01). Similarly, among patients with hypersensitivity pneumonitis the index was lower in unchanged or improving patients than in those with deterioration (74.9 +/- 22 vs 226.7 +/- 4.9; p less than 0.05). Thus gallium-67 scanning is useful in the management of cryptogenetic fibrosing alveolitis and hypersensitivity pneumonitis.