Pierre-Yves Brillet

Progression of idiopathic pulmonary fibrosis: lessons from asymmetrical disease

Background In idiopathic pulmonary fibrosis (IPF) the distribution and spatial-temporal progression of fibrotic changes may be influenced by general or locoregional conditions. From this perspective, patients with asymmetrical disease (AIPF) may be unique. Methods This retrospective study included 32 patients (26 men, mean±SD age 69±7 years) with AIPF, as defined by an asymmetry ratio (most affected – least affected fibrosis score)/(most affected + least affected fibrosis score) >0.2. The global fibrosis score was the average of the right and left scores. Patients with AIPF were compared with 64 matched controls with symmetrical IPF. Results Patients with AIPF did not differ from controls in global fibrosis score and forced vital capacity, but carbon monoxide transfer factor was less decreased (52±19% vs 43±13%, p=0.009). The rate of gastro-oesophageal reflux and acute exacerbations was significantly higher in patients with AIPF (62.5% vs 31.3%, p=0.006 and 46.9% vs 17.2%, p=0.004, respectively). In patients with AIPF the right side was more likely to be involved (62.5%); the median asymmetry ratio was 0.5 (range 0.24–1). Although the global fibrosis score worsened significantly in all 23 patients with AIPF with serial high-resolution CT scans (p<0.0001), pulmonary fibrosis remained asymmetrical in all except three. During follow-up, 15 patients with AIPF experienced 18 acute exacerbations. The first episode was virtually unilateral, occurring in the most affected lung in 10 patients (66.7%). Survival was similar between patients with AIPF and controls. Conclusion AIPF may be related to locoregional factors including gastro-oesophageal reflux which may be responsible for both disease expansion and the occurrence of acute exacerbations.

Stage IV sarcoidosis: comparison of survival with the general population and causes of death

The objectives of this study were to compare the survival of sarcoid patients with pulmonary fibrosis with that of the general population and to determine the causes of death and the incidence of evolutive complications. This retrospective cohort included 142 sarcoid patients in radiographic stage IV (74 males; mean±sd age 48.1±12 yrs). Their survival was compared with that of the general French population, matched for the year and age at diagnosis of stage IV disease, sex and length of follow-up. Expected survival probabilities were calculated year-by-year on the basis of probabilities provided by official demographic data for France. Survival curves were based on the Kaplan–Meier method and compared using the log-rank test. During the follow-up period (7.1±4.8 yrs), pulmonary hypertension (PH) was observed in 29.7% of cases and aspergilloma in 11.3%. Long-term oxygen therapy was required in 12%. Survival was 84.1% at 10 yrs, which was worse than for the general population (p=0.013). 16 (11.3%) patients died from the following causes: refractory PH (n=5), chronic respiratory insufficiency (n=4), acute respiratory insufficiency (n=2), haemoptysis due to aspergilloma (n=1), heart sarcoidosis (n=1), nocardiosis (n=1) and unknown causes (n=2). Survival is significantly decreased in stage IV patients. 75% of fatalities are directly attributable to respiratory causes.

Acute Exacerbation of Idiopathic Pulmonary Fibrosis: Outcome and Prognostic Factors

Background: Acute exacerbation is a substantial cause of death in patients with idiopathic pulmonary fibrosis with poorly described prognostic factors. Objectives: To review the features associated with acute exacerbation of idiopathic pulmonary fibrosis and assess its prognostic factors. Methods: Thirty-seven occurrences of acute exacerbation of idiopathic pulmonary fibrosis were retrospectively reviewed in the medical records of 27 patients. Clinical presentation, radiographic studies, pulmonary function tests, laboratory data, treatment, and outcome were analyzed. Results: Acute exacerbation of idiopathic pulmonary fibrosis occurred more frequently between December and May (75.7%) than between June and November (24.3%) (p = 0.01). In-hospital mortality was 27% and median survival was 4.2 months (range 0.2–36.6). Significant differences between nonsurvivors and survivors included the time elapsed between their admission and the initiation of treatment for acute exacerbation (6 vs. 3.1 days, p = 0.04), lactate dehydrogenase levels at admission (801 vs. 544.6 IU/l, p = 0.002), impairment of the prior forced vital capacity (51.2 vs. 65%, p = 0.01) and diffusing capacity for carbon monoxide (21.7 vs. 34%, p = 0.01). Furthermore, the evolution of gas exchange in the first 10 days after the initiation of treatment was associated with in-hospital and long-term mortality. Conclusions: Acute exacerbations of idiopathic pulmonary fibrosis are more frequent during winter and spring. The time between admission and initiation of treatment is a new reported prognostic factor that should be investigated further. This finding highlights the need for a fast diagnostic approach that should probably be standardized. Early gas exchange modifications reflect the response to treatment and predict the prognosis.

CT findings in severe thoracic sarcoidosis

Severe thoracic sarcoidosis includes manifestations with significant clinical and functional impairment and a risk of mortality. Severe thoracic sarcoidosis can take on various clinical presentations and is associated with increased morbidity. The purpose of this article was to describe the CT findings in severe thoracic sarcoidosis and to explain some of their mechanisms. Subacute respiratory insufficiency is a rare and early complication due to a high profusion of pulmonary lesions. Chronic respiratory insufficiency due to pulmonary fibrosis is a frequent and late complication. Three main CT patterns are identified: bronchial distortion, honeycombing and linear opacities. CT can be helpful in diagnosing some mechanisms of central airway obstruction such as bronchial distortion due to pulmonary fibrosis or an extrinsic bronchial compression by enlarged lymph nodes. An intrinsic narrowing of the bronchial wall by endobronchial granulomatous lesions may be suggested by CT when it shows evidence of bronchial mural thickening. Pulmonary hypertension usually occurs in patients with end-stage pulmonary disease and is related to fibrotic destruction of the distal capillary bed and to the resultant chronic hypoxemia. Several other mechanisms may contribute to the development of pulmonary hypertension including extrinsic compression of major pulmonary arteries by enlarged lymph nodes and secondary pulmonary veno-occlusive disease. Aspergilloma colonization of a cavity is the main cause of hemoptysis in sarcoidosis. Other rare causes are bronchiesctasis, necrotizing bronchial aspergillosis, semi-invasive pulmonary aspergillosis, erosion of a pulmonary artery due to a necrotic sarcoidosis lesion, necrosis of parenchymal sarcoidosis lesions and specific endobronchial macroscopic lesions.

Pulmonary cavitary sarcoidosis: clinico-radiologic characteristics and natural history of a rare form of sarcoidosis.

Pulmonary cavitary lesions in the absence of concomitant comorbidities are an uncommon and often confusing manifestation of sarcoidosis. We retrospectively reviewed the clinical and high-resolution computed tomography (HRCT) characteristics and the natural history of a series of 23 patients with pulmonary cavitary lesions found on HRCT extracted from a large cohort of patients with pulmonary sarcoidosis. The estimated prevalence of cavitary sarcoidosis was 2.2%. Cavitary lesions developed in patients with severe and active sarcoidosis (serum angiotensin-converting enzyme [SACE] ≥2 times the upper limit of normal range: 63.6%). Twelve (52.2%) patients had evidence of radiographic stage IV, 9 of whom (75%) had persistently increased SACE. As found on HRCT, cavitary lesions were multiple in 21 patients (91.3%), including 5 patients with 10 or more cavities. The size of cavitary lesions was variable, with a median diameter of 20 mm (range, 11-100 mm). Follow-up was available for 20 patients with a median follow-up of 6.25 years (range, 6 months to 15 years). Seven patients (35%) experienced some type of complication related to cavitary lesions, including 6 episodes of hemoptysis in 5 patients and aspergilloma occurrence in 3 patients. As seen on HRCT, the evolution of the number and size of cavitary lesions was variable, with a complete resolution of the largest cavitary lesion in only 5 patients (25%). During follow-up, wall thickening was always associated with a further infectious complication. In summary, cavitary lesions are rare in pulmonary sarcoidosis and usually occur in active and severe sarcoidosis. Their evolution is unpredictable, and complications are frequent. Abbreviations: CT = computed tomography, HRCT = high-resolution computed tomography, RECIST = Response Evaluation Criteria in Solid Tumors, SACE = serum angiotensin-converting enzyme.

Granulomatosis-associated common variable immunodeficiency disorder: a case–control study versus sarcoidosis

The aim of the present study was to investigate to what extent interstitial lung disease (ILD) in common variable immunodeficiency disorder (CVID)-associated granulomatous disease (GD) is similar to pulmonary sarcoidosis 20 patients with CVID/GD were included in a retrospective study conducted by the Groupe Sarcoïdose Francophone. Medical records were centralised. Patients were compared with 60 controls with sarcoidosis. Clinical examination showed more frequent crackles in patients than controls (45% versus 1.7%, respectively; p<0.001). On thoracic computed tomography scans, nodules (often multiple and with smooth margins), air bronchograms and halo signs were more frequent in patients than controls (80% versus 42%, respectively; p=0.004) as well as bronchiectasis (65% versus 23%, respectively; p<0.001). The micronodule distribution was perilymphatic in 100% of controls and in 42% of patients (p<0.001). Bronchoalveolar lavage analysis showed lower T-cell CD4/CD8 ratios in patients than in controls (mean±sd 1.6±1.1 versus 5.3±4, respectively; p<0.01). On pathological analysis, nodules and consolidations corresponded to granulomatous lesions with or without lymphocytic disorders in most cases. Mortality was higher in patients than controls (30% versus 0%, respectively) and resulted from common variable immunodeficiency complications. ILD in CVID/GD presents a specific clinical picture and evolution that are markedly different from those of sarcoidosis.

Comparing algorithms for automated vessel segmentation in computed tomography scans of the lung: the VESSEL12 study

The VESSEL12 (VESsel SEgmentation in the Lung) challenge objectively compares the performance of different algorithms to identify vessels in thoracic computed tomography (CT) scans. Vessel segmentation is fundamental in computer aided processing of data generated by 3D imaging modalities. As manual vessel segmentation is prohibitively time consuming, any real world application requires some form of automation. Several approaches exist for automated vessel segmentation, but judging their relative merits is difficult due to a lack of standardized evaluation. We present an annotated reference dataset containing 20 CT scans and propose nine categories to perform a comprehensive evaluation of vessel segmentation algorithms from both academia and industry. Twenty algorithms participated in the VESSEL12 challenge, held at International Symposium on Biomedical Imaging (ISBI) 2012. All results have been published at the VESSEL12 website http://vessel12.grand-challenge.org. The challenge remains ongoing and open to new participants. Our three contributions are: (1) an annotated reference dataset available online for evaluation of new algorithms; (2) a quantitative scoring system for objective comparison of algorithms; and (3) performance analysis of the strengths and weaknesses of the various vessel segmentation methods in the presence of various lung diseases.

Imaging of sarcoidosis of the airways and lung parenchyma and correlation with lung function

Imaging has a prominent role in the assessment of sarcoidosis diagnosis and outcome, which are extremely variable. Chest radiography staging helps predict the probability of spontaneous remission, and stage IV is associated with higher mortality. However, the reproducibility of reading is poor and changes in radiography and lung function are inconsistently correlated, which may be problematic for the monitoring of disease and treatment response. Chest computed tomography (CT) makes a great diagnostic contribution in difficult cases. Bilateral hilar lymphadenopathy with peri-lymphatic micronodular pattern is highly specific for sarcoidosis. CT is important for the investigation of pulmonary complications, including aspergilloma and pulmonary hypertension. CT improves the yield of bronchoscopy for obtaining a positive endobronchial or transbronchial biopsy. CT findings may also discriminate between active inflammation and irreversible fibrosis, with occasional influence on therapeutic decisions. Three CT patterns of fibrotic sarcoidosis are identified, with different functional profiles: predominant bronchial distortion is associated with obstruction; honeycombing is associated with restriction and lower diffusing capacity of the lung for carbon monoxide; whereas functional impairment is relatively minor with linear pattern. The clinical impact of correlations between CT severity scores and functional impairment is uncertain, except for its utility elucidating the mechanisms of airflow limitation, which include bronchial distortion, peribronchovascular thickening, air-trapping and bronchial compression by lymphadenopathy.

Nonneoplastic Tracheal and Bronchial Stenoses

Nonneoplastic stenosis of proximal airways may result from longstanding intubations or tracheostomy, granulomatous infection, or systemic diseases such as relapsing polychondritis, amyloidosis, Wegeners granulomatosis, sarcoidosis, and inflammatory bowel disease. It also may be caused by saber sheath trachea, tracheobronchopathia osteoplastica, or broncholithiasis. An early diagnosis of the tracheal and bronchial stenosis has become possible with the advent of routine CT imaging. Multiplanar and volume rendering reformations after thin collimation MDCT acquisition help assess the location and extent of the stenosis and characterize the presence, distribution, and type of airway wall thickening. They also help surgeons and endoscopists to select adequate procedures and assess the response to treatment.

Patterns of pulmonary tuberculosis on FDG-PET/CT.

OBJECTIVE This study aims to describe patterns of pulmonary tuberculosis (TB) on FDG-PET/CT. METHODS All patients with a diagnosis of TB and who underwent FDG-PET/CT between January 2009 and June 2010 were included. Clinical, biological and imaging data were reviewed. TB was proven either on bacteriological or histopathological studies (n=13) or on a clinical and imaging basis (n=3). RESULTS Sixteen patients (11 men; median age 56, range 22-84 years) were included. Two distinct patterns were identified. In the lung pattern (9/16), patients had predominantly pulmonary symptoms (6/9 patients, 67%) with a parenchymal involvement: uptakes on lung consolidation ± cavitation surrounded by micronodules. Mediastino-hilar lymph nodes were slightly enlarged (15 mm, 10-27) with moderate uptake (3.9, 2.5-13.4). In the lymphatic pattern (7/16), patients had predominantly systemic symptoms (5/7 cases, 71%) and all had extra-thoracic involvement. Mediastino-hilar lymph nodes were more enlarged (30 mm, 18-35, p=0.03) and with higher uptake (6.8, 5.7-16.8, p=0.034) than in the lung pattern. CONCLUSION We identified two distinct patterns of pulmonary TB on FDG-PET/CT. The lung pattern related to a restricted and slight hypermetabolic infection and the lymphatic pattern related to a systemic and intense infection. Combined interpretation of PET and CT findings improves the specificity of images, especially for the lung pattern.