Antonella Fossi

Bronchoalveolar lavage fluid protein composition in patients with sarcoidosis and idiopathic pulmonary fibrosis : a two-dimensional electrophoretic study

We used two‐dimensional (2‐D) electrophoresis to analyze the protein composition of fluid recovered by bronchoalveolar lavage (BALF) from patients with sarcoidosis and idiopathic pulmonary fibrosis, two forms of interstitial lung disease with different cellular composition and cytokine profile in BALF. They are also characterized by different pathogenesis and clinical evolution, idiopathic pulmonary fibrosis being less favorable than sarcoidosis due to rapidly progressive pulmonary fibrosis. Thirty‐eight proteins or protein fragments, never previously assigned in BALF samples, were identified by various methods including mass fingerprinting of tryptic digests. Comparison of the BALF protein maps of the two groups of patients showed 32 spots with statistically significant disease‐related variations in relative abundance. In sarcoidosis we found an increase in the amount of several plasma proteins, while in idiopathic pulmonary fibrosis we observed a statistically significant increase in low‐molecular‐weight proteins, many of which are involved in inflammatory processes (such as MIF and calgranulin) or antioxidant response (such as antioxidant peroxysomal enzyme and thioredoxin peroxidase 2). 2‐D electrophoresis allowed us to identify new BALF proteins and to characterize protein composition in patients with sarcoidosis and idiophatic pulmonary fibrosis. Comparison of the gels of the two diseases showed that they differ in BALF protein profiles as they do in type of immune response.

Impact of interstitial lung disease on short-term and long-term survival of patients undergoing surgery for non-small-cell lung cancer: analysis of risk factors

OBJECTIVES The study aimed to determine the impact of interstitial lung disease (ILD) on postoperative morbidity, mortality and long-term survival of patients with non-small-cell lung cancer (NSCLC) undergoing pulmonary resection. METHODS We performed a retrospective chart review of 775 consecutive patients who had undergone lung resection for NSCLC between 2000 and 2009. ILD, defined by medical history, physical examination and abnormalities compatible with bilateral lung fibrosis on high-resolution computed tomography, was diagnosed in 37 (4.8%) patients (ILD group). The remaining 738 patients were classified as non-ILD (control group). We also attempted to identify the predictive factors for early and late survival in patients with ILD following pulmonary resection. RESULTS There was no significant difference between the two groups in terms of age (69 vs 66 years), sex (79 vs 72% male), smoking history (93 vs 90% smokers), forced expiratory volume in 1 s % of predicted (89 vs 84%), predicted values of forced vital capacity (FVC)% (92 vs 94%), types of surgical resection and histology. Patients with ILD had a higher incidence of postoperative acute respiratory distress syndrome (ARDS; 13 vs 1.8%, P < 0.01) and higher postoperative mortality (8 vs 1.4%, P < 0.01). The overall 5-year survival rate was 52% in the ILD and 65% in the non-ILD patients, respectively (P = 0.019). In the ILD group, at the median follow-up of 26 months (range 4-119), 19 (51%) patients were still alive and 18 (49%) had died in the ILD group. The major cause of late death was respiratory failure due to the progression of fibrosis (n = 7, 39%). In the ILD group, lower preoperative FVC% (mean 77 vs 93%, P < 0.01) and lower diffusing capacity of the lung for carbon monoxide (DLCO%; 47 vs 62%; P < 0.01) were significantly associated with postoperative ARDS. CONCLUSIONS In conclusion, major lung resection in patients with NSCLC and ILD is associated with an increased postoperative morbidity and mortality. Patients with a low preoperative FVC% should be carefully assessed prior to undergoing surgery, particularly in the presence of a lower DLCO%. Long-term survival is significantly lower when compared with patients without ILD, but still achievable in a substantial subgroup. Thus, surgery can be offered to properly selected patients with lung cancer and ILD, keeping in mind the risk of respiratory failure during the evaluation of such patients.

Quality of life, anxiety and depression in Sarcoidosis

OBJECTIVES This study sought to evaluate the quality of life and the presence of psychiatric disorders in patients with sarcoidosis. METHODS Data were collected from 80 consecutive outpatients with sarcoidosis presenting to the Sarcoidosis Center of the Respiratory Diseases Division at the University of Siena, Italy. RESULTS Forty-four percent of the subjects endorsed at least one psychiatric DSM-IV axis I diagnosis. Specifically, 25% of subjects met the criteria for Major Depressive Disorder, 6.3% for Panic Disorder, 6.3% for Bipolar Disorder, 5% for Generalized Anxiety Disorder and 1.3% for Obsessive Compulsive Disorder. Statistically significant correlations were found between Forced Expiratory Volume in the first second (FEV(1)), Forced Vital Capacity (FVC) and several domains of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) questionnaire. Subjects with multi-systemic involvement, with asthenia and with a more severe radiographic stage and subjects receiving steroids, reported a poorer quality of life. CONCLUSIONS Sarcoidosis is associated with a high rate of psychiatric comorbidity and may contribute to a poorer quality of life. A referral for a psychiatric or psychological evaluation and counseling should be considered for many of the sarcoidosis patients.

Assessment of cardiac involvement in sarcoidosis by echocardiography.

The main objective of this study is to determine the prevalence of left ventricular systolic and diastolic dysfunction in patients with chronic sarcoidosis without clinical evidence of heart disease. The study includes 69 chronic sarcoidosis patients, 30 diagnosed by organ biopsy and 39 by clinical history, chest X-ray, high resolution computerized tomography (HRCT) and bronchoalveolar lavage (BAL), without suspected cardiac involvement. The control group consisted of 26 subjects selected from a population of hospital workers. The examination includes 12-lead ECG and echocardiographic examination. The results show that there were no differences in atrial size, left ventricular diameters, wall thickness, left ventricular ejection fraction or endocardial fractional shortening between the sarcoid group and controls. Signs of diastolic dysfunction were found in 33 (55%) patients, however, this group was significantly older than the others and had marginally higher blood pressure. Sarcoid patients had lower midwall fractional shortening (mFS) than controls; patients with diastolic dysfunction also had lower mFS but the difference was not significant. In conclusion, the results demonstrated an absence of left ventricular systolic dysfunction, evaluated by traditional echocardiographic methods, in our chronic sarcoidosis patients and an apparent absence of any relation between left ventricular diastolic dysfunction and sarcoidosis. Lower mFS was found among patients, particularly those with a long history of sarcoidosis. Further analysis is required to evaluate the significance of this index as a potential marker of heart involvement in chronic sarcoidosis.

Right single-lung transplantation for pulmonary alveolar microlithiasis

A 64-year old woman with pulmonaryalveolar microlithiasis underwent a right single-lung transplantation in 2008. She recovered uneventfully. We report two images (Figs 1 and 2) obtained at her 5-year follow-up visit. At present, she leads an independent and active life. Her last forced expiratory volume in 1st second and forced vital capacity were 96 and 91% of predicted, respectively.

Severe Acute Graft Versus Host Disease After Lung Transplant: Report of a Case Successfully Treated With High Dose Corticosteroids

Acute graft vs host disease is an uncommon and usually fatal complication of lung transplant for which no effective therapy exists. All 8 patients with grade 3 to 4 acute graft vs host disease after lung transplantation described in literature died within 208 days. We report a patient with grade 3 to 4 acute graft vs host disease after bilateral lung transplantation who was successfully treated with high-dose corticosteroids after basiliximab and extracorporeal photopheresis were unsuccessful.

Eosinophilic cationic protein in bronchoalveolar lavage fluid of lung transplant patients

Figure 2 ECP concentrations in BAL of patients with acute/ chronic rejection or infection and controls. Figure 1 ECP concentrations in BAL of lung transplant patients compared to sarcoidosis patients, Langerhans cell histiocytosis patients and controls. Elena Bargagli, Chiara Madioni*, Antje Prasse, Antonella Fossi, Rita Filippi, Nicola Bianchi, Luca Voltolini, Joachim Muller-Quernheim and Paola Rottoli 1 Respiratory Diseases Section, Department of Clinical Medicine and Immunology, Siena University, Siena, Italy 2 Thoracic Surgery Section, Department of Heart, Vessel and Thorax, Siena University, Siena, Italy 3 Department of Pneumology, University Hospital Freiburg, Freiburg, Germany

Diffuse panbronchiolitis in a patient with common variable immunodeficiency: a casual association or a pathogenetic correlation?

Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory disease that seems to have an immunological pathogenesis and that causes a severe progressive suppurative and obstructive respiratory disorder. Common variable immunodeficiency (CVID) is the most common serious primary immunodeficiency and it is often associated with respiratory diseases. Herein, we describe a case of DPB in a 41-year-old man affected by CVID. We examined the patient’s lungs, focusing on the characteristics of the inflammatory cells and of the foamy macrophagic nodules typical of DPB. Immunohistochemical typing of the lymphocytic infiltrate showed that B-cells were almost absent, matching the immunological profile of CVID. The case described is the first case reported in the literature of DPB in a patient affected by CVID. Moreover it seems to confirm the correlation between an immunodeficiency status and the development of DPB and provides more information on the accumulation of nodules of foamy macrophages in DPB.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5310709471138338.

Quetiapine in post-transplant acute mania/bipolar disorder NOS.

There is no medication specifically approved for the treatment of bipolar disorder not otherwise specified (BD-NOS), substance-induced mood disorders and mood disorders due to a general medical condition. We report the case of a man whose post-transplant BD-NOS was treated successfully with quetiapine. Mr G, a 58-year-old man with cystic fibrosis and no history of psychiatric disorders, as documented by a pre-transplant SCID evaluation, received lung transplantation in December 2004. The patient underwent the post-transplant course with no medical or psychiatric complications until 6 wk after the transplant, when he developed decreased need for sleep, euphoria, irritability, grandiosity, pressured speech, flights of ideas, increased sexual drive, mystical and grandiose delusions. His symptoms led him to a poor adherence to the post-transplant immunosuppressant treatment and to other …

Bronchial stenosis following lung transplant: an innovative approach with a modified endobronchial emphysema valve

To the Editor, Airway complications (AC) after lung transplant (LT) are relative common and include bronchial stenosis (BS), suture dehiscence, granulation tissue, bronchomalacia, and fistula. BS is the commonest complication; management is wideranging and different endobronchial approaches have been proposed. We report a 61-years old man who underwent a bilateral LT for chronic obstructive pulmonary disease (COPD) at our Institution and 16 weeks after developed a BS. At time of diagnosis pulmonary function tests showed a FEV1 drop (212%) and bronchoscopy revealed the presence of a stenosis of the right lower lobe bronchus after apical segmental subdivision (3 mm of diameter and 4 mm of length)— peripheral bronchial structures appeared patent. Any previous bronchoscopies did not show any alterations of bronchial canalization or early sign of stenosis. Before BS occurrence, 5 weeks after LT, the patient experienced an acute rejection episode (A3 grade) promptly treated with pulsed steroid therapy and with complete remission. Several balloon dilations (Cordis Powerflex® Pro 6 mm diameter) were performed but stenosis always recurred. Six months after BS diagnosis a stent placement was proposed and, due to the particular localization and extension, we implanted a modified endobronchial valve designed for emphysema treatment (Pulmonx Zephyr® 4.0 endobronchial valve). In particular, we removed central silicon flaps maintaining the device structure intact (Figure 1). By flexible bronchoscope, the modified valve was placed at stenosis level using a flexible delivery catheter with no complications (Figure 2). No more bronchial dilations were necessary and 12-month follow-up showed a complete BS stabilization with unmodified valve patency, adequate fluids clearance, and pulmonary ventilation. Unfortunately, the patient developed bronchiolitis obliterans syndrome (BOS) and he died 28 months after LT. The last CT scan, 15 days before the exitus, still showed valve patency and adequate placement. Several risk factors have been identified to AC development, in particular donor/recipient factors, surgical technique, infections, and immunosuppressant therapy seem to be the most determinant. Early acute rejection episodes, as our patient experienced, have also been associated to BS development. BS is the commonest AC (prevalence range from 1.6% to 32%); more frequently the stenosis involves bronchial anastomosis, although distal localizations to segmental and subsegmental bronchi, as in the present case, have been reported. Therapeutic approaches depend on the severity and the localization of the stenosis; dilation and ablation are commonly repeatedly performed to gain stabilization. Nevertheless, recurrent BS may benefit of stenting procedures. Different stents (SEMS, silicon, hybrid, and biodegradable stents) have been proposed, but no single method has demonstrated clear superiority and procedure decision mainly depends to single institutions and operators experience. Some complex BS even need open surgical approaches.