Preliminary results in tracheal replacement using stented aortic matrices for primary extensive tracheal cancer.

Objective: Recent studies have demonstrated the feasibility and favorable long-term results of tracheobronchial replacement using stented cryopreserved aortic allografts. We propose to investigate the outcomes of this emerging technique in the subgroup of patients with extensive tracheal cancer. Methods: This study was based on 13 patients with primary extensive tracheal cancer extracted from the prospective registry TRITON-01 (ClinicalTrials.gov Identifier: NCT04263129), which included 40 patients in total. We analyzed early and late outcomes in this subset of patients. Results: From March 2019 to September 2022, 13 patients were included in the study. There were 9 female and 4 male patients, with a mean age of 53.9 years [36-71 years]. They had tracheal replacement for extended adenoid cystic carcinoma (n = 11), squamous cell carcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). A venovenous extracorporeal membrane oxygenation was used in the 6 last cases. The mean length of resection was 81 mm [50-120 mm]. There was no 30-day postoperative mortality. A complete resection (R0) was achieved in 11 patients. The main late complications consisted of tracheal granulomas related to the stent and requiring repeated bronchoscopies (n = 9), pneumonia (n = 3), airway infection (n = 1), bronchoesophageal fistula (n = 1), mechanical stent obstruction requiring change (n = 2), and mediastinitis treated by antibiotics, drainage, and omentoplasty (n = 1). With a maximal follow-up of 3 years and 7 months, cancer recurrence was observed in 2 patients. All patients were alive at last follow-up except 2 (84.6%). Conclusions: Airway replacement using stented CAA represents a feasible and promising solution for extensive tracheal cancer.

Airway replacement using stented aortic matrices: Long-term follow-up and results of the TRITON-01 study in 35 adult patients.

Over the past 25 years, we have demonstrated the feasibility of airway bioengineering using stented aortic matrices experimentally then in a first-in-human trial (n = 13). The present TRITON-01 study analyzed all the patients who had airway replacement at our center to confirm that this innovative approach can be now used as usual care. For each patient, the following data were prospectively collected: postoperative mortality and morbidity, late airway complications, stent removal and status at last follow-up on November 2, 2021. From October 2009 to October 2021, 35 patients had airway replacement for malignant (n = 29) or benign (n = 6) lesions. The 30-day postoperative mortality and morbidity rates were 2.9% (n = 1/35) and 22.9% (n = 8/35) respectively. At a median follow-up of 29.5 months (range 1-133 months), 27 patients were alive. There have been no deaths directly related to the implanted bioprosthesis. Eighteen patients (52.9%) had stent-related granulomas requiring a bronchoscopic treatment. Ten among 35 patients (28.6%) achieved a stent free survival. The actuarial 2- and 5-year survival rates (Kaplan-Meier estimates) were respectively 88% and 75%. The TRITON-01 study confirmed that airway replacement using stented aortic matrices can be proposed as usual care at our center. Clinicaltrials.gov Identifier: NCT04263129.

Case Report: Laryngotracheal Post-Intubation/Tracheostomy Stenosis in COVID-19 Patients.

Introduction: The novel Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), has spread rapidly to become a major global public health emergency since March 2020. Laryngotracheal stenosis (LTS) has been observed more frequently since the onset of the COVID-19 pandemic. Methods: All patients referred to our 24/7 Airway Diseases Center for laryngotracheal post-intubation/tracheostomy stenosis from May 2020 to May 2021were evaluated retrospectively. Patient data on comorbidities, diagnosis, type of procedures, lengths of ICU stay and invasive mechanical ventilation, medical treatment, and the severity of illness were recorded. Results: This case series included nine patients (five women and four men), with a mean age of 52.9 years, most with a BMI >30, all with a severe illness revealed by the Simplified Acute Physiology Score (SAPS) II >31. From May 2020 to May 2021, 21 procedures were performed on seven patients, consisting of bronchoscopic rigid interventions, T-tube Montgomery tracheostomy, and one cricotracheal resection with end-to-end anastomosis. Histologic examination of tracheal biopsies showed an inflammatory state of the airway mucosa. Two patients only had medical therapy. Discussion and Conclusions: Pneumonia caused by SARSCoV-2 can lead to severe acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation. The time of intubation, the drugs used, the prone position, comorbidities (diabetes, obesity), and the inflammatory state of the upper airways linked to the viral infection, predispose to an increased tendency to stenosis and its recurrence. A conservative approach with medical and endoscopic treatment should be preferred in case of persistence of local airways inflammation. Further studies with a larger sample of patients will help to a better understanding of the disease, reduce the prevalence, and improve its treatment.

Endobronchial Seeding of Squamous Lung Carcinoma with Mediastinal Lymph Involvement Node after EBUS: A Case Report.

In locally advanced non-small-cell lung cancer (NSCLC), mediastinal staging is the cornerstone of the therapeutic decision and echoendoscopy is the most practiced exam to assess the lymph node involvement. We describe a rare case of endobronchial involvement by cells originating from a metastatic lymph node after endobronchial ultrasound (EBUS). A 64-year-old man was diagnosed with a squamous cell lung cancer with mediastinal nodal involvement proven by EBUS. The patient received neoadjuvant chemotherapy with partial response and was scheduled for a lobectomy. Before surgery, a fibroscopy was performed which demonstrated a 1-cm polypoid lesion settled on the internal face of the main right bronchus corresponding to the EBUS puncture site. The histological analysis confirmed tumoral cell in this lesion. The patient was rejected for surgery and undergo chemoradiation. This case highlights the need for a careful endoscopic control before surgical resection in case of prior positive EBUS followed by an interval of time.

Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. METHODS: In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov, NCT02460588. FINDINGS: Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI -3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89-4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12-6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13-0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. INTERPRETATION: In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. FUNDING: Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014-502), Roche Pharmaceuticals.

Diagnosis Yield and Safety of Surgical Biopsy in Interstitial Lung Diseases: A Prospective Study.

BACKGROUND: Surgical lung biopsy is essential in the diagnostic algorithm of interstitial lung disease (ILD) of unknown cause. Safety concerns have been recently reiterated. This study prospectively assessed the yield of diagnosis and safety of video-assisted thoracoscopic surgical lung biopsy (VATS-LB) for ILD diagnosis. METHODS: This prospective study, conducted in 6 ILD-referral Paris hospitals, included 103 patients with ILD. VATS-LB was proposed after initial multidisciplinary discussion. A final diagnosis was made after the procedure, during a second multidisciplinary discussion. The main outcome was to determine the final diagnoses and their proportion after VATS-LB. Other outcomes were the percentage of change in diagnosis and treatment propositions after VATS-LB and adverse events during 3 months after the operation, postoperative pulmonary function, quality of life, and pain. RESULTS: A definite diagnosis was reached in 87 patients (84.4%), and 16 remained unclassifiable (15.6%). After VATS-LB, the hypothesized diagnosis changed in 65 patients (63.1%) and treatment changed in 41 patients (39.8%). One patient died of acute exacerbation. In-hospital complications were predicted by a shorter preoperative 6-minute walking test distance and by forced vital capacity lower than 77%. Postoperative quality of life was not modified at 3 months, whereas forced vital capacity decreased slightly. Postoperative neuropathic pain was revealed in 5% of patients at 1 month and in 2% at 3 months. CONCLUSIONS: VATS-LB dramatically changed preoperative hypothetical diagnoses and treatment in ILD of unknown cause, with good patient survival in ILD referral centers.

Gender Differences in Idiopathic Pulmonary Fibrosis: Are Men and Women Equal?

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by a male predominance. The aim of the study was to explore gender differences in a well-designed French multicentre prospective IPF cohort (COhorte FIbrose, COFI) with a 5-year follow-up. Methods: Between 2007 and 2010, 236 patients with incident IPF were included in COFI. Gender characteristics were compared using a t-test, Chi-squared test and ANOVA, as appropriate. Survival analyses were performed. Results: Fifty-one (22%) females and 185 (78%) males with an average age at diagnosis of 70.1 ± 9.20 and 67.4 ± 10.9 years, respectively, were included in the cohort. Women were significantly less exposed to tobacco smoke [never n = 32 (62.7%) vs. n = 39 (21.1%), p < 0.001] and to occupational exposure [n = 7 (13.7%) vs. n = 63 (34.1%), p = 0.012]. Baseline forced vital capacity, % of predicted (FVC%) was significantly better in women compare to men (83.0% ± 25.0 v. 75.4% ± 18.7 p = 0.046). At presentation honeycombing and emphysema on CT scan were less common in women [n = 40 (78.4%) vs. n = 167 (90.3%) p = 0.041] and [n = 6 (11.8%) vs. n = 48 (25.9%) p = 0.029], respectively. During follow-up fewer women were transplanted compared to men [n = 1 (1.96%) vs. n = 20 (10.8%) p = 0.039]. Medians of survival were comparable by gender [31 months (CI 95%: 28-40) vs. 40 months (CI 95%: 33-72) p = 0.2]. After adjusting for age and FVC at inclusion, being a woman was not associated to a better survival. Conclusions: Women appear to have less advanced disease at diagnosis, maybe due to less exposure history compare to men. Disease progression and overall survival remains comparable regardless gender, but women have less access to lung transplantation.

Elective extra corporeal membrane oxygenation for high-risk rigid bronchoscopy.

The use of extracorporeal membrane oxygenation for high-risk rigid bronchoscopy has been reported in few urgent cases. We report our experience with this approach which was planned electively in five cases on 202 procedures (2.5%). It was proposed because of the potential inability to ventilate the lungs using conventional techniques due to extensive tracheobronchial lesions or the risk of major intraoperative bleeding related to disease characteristics. There were no intraoperative complications and postoperative course was favourable in all patients. With a maximum follow-up of 3 years and 7 months, all patients are alive with no tracheostomy despite major morbidities.

The place of high-resolution computed tomography imaging in the investigation of interstitial lung disease.

INTRODUCTION: High-resolution computed tomography (HRCT) has revolutionized the diagnosis, prognosis and in some cases the prediction of therapeutic response in interstitial lung disease (ILD). HRCT represents an essential second step to a patient's clinical history, before considering any other investigation, including lung biopsy. Areas covered: This review describes the current place of HRCT in the diagnosis, prognosis and monitoring of ILD. It also lists some perspectives for the near future. Expert commentary: Since the 1980s, HRCT and its interpretation have improved, the diagnosis value of patterns, and the integration of bio-clinical elements to HRCT have been better standardized. The interobserver agreement has been investigated, allowing a better use of some limits in the interpretation of various signs. It not only takes into account one particular predominant sign, but the combination of patterns and the distribution of findings. Thanks to HRCT, the range of diagnoses and their probability are more accurately identified. The contribution of HRCT has been optimized during the multidisciplinary discussion that a difficult diagnosis calls for. HRCT quantification of the extent of diffuse lung disease becomes possible and is linked to prognosis. In the future, artificial intelligence may significantly modify the practice of radiology.

Sarcoidosis, inorganic dust exposure and content of bronchoalveolar lavage fluid: the MINASARC pilot study.

Inhalation of mineral dust was suggested to contribute to sarcoidosis. We compared the mineral exposome of 20 sarcoidosis and 20 matched healthy subjects. Bronchoalveolar lavage (BAL) samples were treated by digestion-filtration and analyzed by transmission electron microscopy. The chemical composition of inorganic particles was determined by energy-dispersive X-ray (EDX) spectroscopy. Dust exposure was also assessed by a specific questionnaire. Eight sarcoidosis patients and five healthy volunteers had a high dust load in their BAL. No significant difference was observed between the overall inorganic particle load of each group while a significant higher load for steel was observed in sarcoidosis patients (p=0.029). Moreover, the building activity sub-score was significantly higher in sarcoidosis patients (p=0.018). These results suggest that building work could be a risk factor for sarcoidosis which could be considered at least in some cases as a granulomatosis caused by airborne inorganic dust. The questionnaire should be validated in larger studies. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 327-332).

Outcome and prognostic factors in a French cohort of patients with myositis-associated interstitial lung disease.

Interstitial lung disease (ILD) is a common form of extramuscular involvement in patients with polymyositis/dermatomyositis and is associated with poor prognosis. This study was designed to describe the long-term outcome of myositis-associated ILD. This retrospective observational study was conducted in 48 consecutive patients. Two groups defined according to outcome were compared to determine prognostic factors: a "severe" group (vital capacity [VC] < 50 % or carbon monoxide transfer factor [TLCO] < 35 % or death or lung transplantation) and a "nonsevere" group (other patients). The study population comprised 31 women and 17 men with a median age of 49.5 ± 13.6 years. Mean PFT results at the onset of ILD were 56.9 ± 23.1 % pred. for VC and 42.1 ± 16.6 % pred. for TLCO. Median (range) follow-up was 65 (2-204) months. Three patients (6.4 %) died. At last follow-up, 19 patients were classified in the "severe" group and 27 patients were classified in the "nonsevere" group. Two patients lost to follow-up after less than 12 months were excluded from this analysis. Multivariate analysis identified two independent prognostic factors: VC at onset of ILD [OR 0.95 (95 % CI 0.90-0.99)] and myopathic changes on electromyography [OR 5.76 (95 % CI 1.10-30.3)]. Patients treated in our pulmonology department for myositis-associated ILD had severe initial PFT results but a low mortality rate. Independent prognostic factors at presentation were initial VC and myopathic changes on electromyography. This study highlights the need for studies focusing on the correlation between muscle and lung pathogenic mechanisms.

Management of sarcoidosis in clinical practice.

Sarcoidosis is a systemic disease of unknown cause with very diverse presentation, outcome, severity and need for treatments. While some presentations may be very typical, for many patients, the presentation is nonspecific, with shared associations with other diseases at times being by far more frequent or misleading, which can be a cause of significant delay and often several consultations before a diagnosis of sarcoidosis can be confirmed. This is particularly the case when pulmonary manifestations are in the forefront. The diagnosis relies on three well-known criteria. In clinical practice, these criteria are not easily implemented, particularly by physicians without expertise in sarcoidosis, which can lead to a risk of either under- or over-diagnosis. Qualifying the presentation according to sarcoidosis diagnosis is essential. However, it is often not easy to classify the presentation as typical versus compatible or compatible versus inconsistent. Further investigations are needed before any other hypothesis is to be considered. It is important to detect events and to determine whether or not they are indicative of a flare of sarcoidosis. Eventually, treatment needs to be related to the correct indications. The evaluation of the efficacy and safety of treatments is crucial. To address such issues, we present five emblematic cases that illustrate this.

Human lung fibroblasts may modulate dendritic cell phenotype and function: results from a pilot in vitro study.

In human lung fibrotic lesions, fibroblasts were shown to be closely associated with immature dendritic cell (DC) accumulation. The aim of the present pilot study was to characterize the role of pulmonary fibroblasts on DC phenotype and function, using co-culture of lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and from control patients, with a DC cell line MUTZ-3. We observed that co-culture of lung control and IPF fibroblasts with DCs reduced the expression of specific DC markers and down-regulated their T-cell stimulatory activity. This suggests that pulmonary fibroblasts might sustain chronic inflammation in the fibrotic lung by maintaining in situ a pool of immature DCs.

Pulmonary Sarcoidosis.

Sarcoidosis is a systemic disease, with lung involvement in almost all cases. Abnormal chest radiography is usually a key step for considering diagnosis. Lung impact is investigated through imaging; pulmonary function; and, when required, 6-minute walk test, cardiopulmonary exercise testing, or right heart catheterization. There is usually a reduction of lung volumes, and forced vital capacity is the most accurate parameter to reflect the impact of pulmonary sarcoidosis with or without pulmonary infiltration at imaging. Various evolution patterns have been described. Increased risk of death is associated with advanced pulmonary fibrosis or cor pulmonale, particularly in African American patients.

Pulmonary hypertension complicating sarcoidosis.

Pulmonary hypertension is a challenging complication of sarcoidosis, which reported rates of prevalence largely depend on the advancement of pulmonary disease. About 6% of unselected sarcoidosis patients suffer from PH. Although destruction of the distal capillary bed and resultant hypoxemia are important, the mechanisms of sarcoidosis-PH are multifactorial, including specific vasculopathy, local increased vasoreactivity, extrinsic compression of pulmonary vessels and portal hypertension. As a result, a proportion of patients exhibit "out of proportion" PH, i.e. more severe than expected from functional impairment (mean PAP>35-40mmHg). The sarcoidosis vasculopathy prevails in the venous side, reflecting the spreading of granulomatous process, and can cause pulmonary veno-occlusive disease. The responsibility of left-heart dysfunction is probably underestimated by echocardiography. There is no validated screening algorithm for the detection of sarcoidosis-PH but recent studies have underlined the role of right heart catheterisation to exclude post-capillary PH. PH carries a poor prognosis in sarcoidosis patients, with a significantly increased morbidity and mortality. Management of sarcoidosis-PH mainly relies on supportive therapy (supplemental oxygen and diuretics as needed) and lung transplantation in otherwise eligible patients. Rare cases of sarcoidosis-PH with nonfibrotic pulmonary disease respond to corticosteroids. Data on the efficacy and safety of PAH agents are scarce and discrepant. Further controlled trials are warranted and should integrate the concept of disproportionate PH in their design.

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.

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.

Cardiac sarcoidosis.

Cardiac involvement is undeniably one of the most challenging issues in sarcoidosis. Although autopsy studies reveal heart lesions in 20 to 30% of sarcoid patients, fewer than 5% suffer from clinical disease. Cardiac sarcoidosis (CS) has a predilection for the myocardium, but the pericardium and endocardium may also be affected. CS manifestations are various and most frequently include the following: (1) aberrations of atrioventricular or intraventricular conduction, either silent or symptomatic; (2) ventricular arrhythmias; (3) subacute congestive heart failure; and (4) sudden death. CS must be detected in all sarcoid patients by means of detailed medical history, physical examination, and resting electrocardiogram (ECG) at first evaluation and during follow-up. In patients with suspected CS, further investigations are aimed at evaluating diagnosis and cardiac consequences. Unfortunately, no gold standard exists that would allow CS diagnosis with a level of confidence. Endomyocardial biopsy is an invasive procedure that lacks sensitivity. Patients need, at a minimum, specialized cardiologic advice, echocardiography, and 24-hour ambulatory ECG. Other diagnostic tools include thallium, technetium, and gallium scintigraphy, and more recently, 18F-fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance (CMR). The respective role of these new imaging tools in the diagnostic approach remains to be defined. CMR has the advantage of not exposing patients to radiation, but it is not feasible in those with cardiac devices. In Western countries, heart involvement accounts for 13 to 25% of sarcoidosis-related deaths, and it is the leading cause of mortality in Japan. The main prognostic indicators are New York Heart Association functional class, left ventricular enlargement, and sustained ventricular tachycardia. Treatment is based on systemic corticosteroids with an initial dose between 30 mg/day and 1 mg/kg/day (which is usually maintained for at least 24 months), specific cardiologic agents, and the placement of a pacemaker or implantable cardiac defibrillator in case of an atrioventricular block or severe intractable ventricular arrhythmias. Cardiac transplantation is exceptionally required.

A role for dendritic cells in bleomycin-induced pulmonary fibrosis in mice?

RATIONALE: Lung dendritic cells (DCs) have been shown to accumulate in human fibrotic lung disease, but little is known concerning a role for DCs in the pathogenesis of fibrotic lung. OBJECTIVES: To characterize lung DCs in an in vivo model of bleomycin-induced pulmonary fibrosis in mice. METHODS: We characterized the kinetics and activation of pulmonary DCs during the course of bleomycin-induced lung injury by flow cytometry on lung single-cell suspensions. We also characterized the lymphocytes accumulating in bleomycin lung and the chemokines susceptible to favor the recruitment of immune cells. MEASUREMENTS AND MAIN RESULTS: We show, for the first time, that increased numbers of CD11c(+)/major histocompatibility complex class II(+) DCs, including CD11b(hi) monocyte-derived inflammatory DCs, infiltrate the lung of treated animals during the fibrotic phase of the response to bleomycin. These DCs are mature DCs expressing CD40, CD86, and CD83. They are associated with increased numbers of recently activated memory T cells expressing CD44, CD40L, and CD28, suggesting that fully mature DCs and Ag-experienced T cells can drive an efficient effector immune response within bleomycin lung. Most importantly, when DCs are inactivated with VAG539, a recently described new immunomodulator, VAG539 treatment attenuates the hallmarks of bleomycin lung injury. CONCLUSIONS: These findings identify lung DCs as key proinflammatory cells potentially able to sustain pulmonary inflammation and fibrosis in the bleomycin model.