Interstitial lung disease preceding primary biliary cirrhosis in a male patient.

A 47-year-old male was admitted with subacute onset of dry cough and fever. Chest tomography demonstrated multifocal areas of consolidation and ground glass attenuation. Cytological analysis of bronchoalveolar lavage revealed lymphocytosis and eosinophilia and anatomopathological exam of transbronchial cryobiopsy showed poorly formed non-caseous granulomas associated to interstitial lympho-plasmocitary infiltrate. The diagnosis of idiopathic granulomatous lung disease (GLD) was assumed and the patient started oral prednisolone, presenting clinical, functional and radiological improvement. Two years later, the patient was diagnosed with primary biliary cirrhosis (PBC). At this time, it was possible to associate GLD with the autoimmune hepatobiliary disease. Clinical, epidemiological and pathological aspects of this uncommon case of interstitial lung disease as first presentation of PBC in a male patient are discussed.

Infection and immunity on a chip: a compartmentalised microfluidic platform to monitor immune cell behaviour in real time.

Cells respond to their environments and self-organise into multicellular assemblies with dedicated functions. The migratory and homing response of cells to soluble ligands can be studied by using different techniques, but for real time studies of complex multicellular self-organisation, novel and simpler systems are required. We fabricated a flexible open access microsystem and tested the design by studying cell recruitment from an immune cell reservoir towards an infectious compartment. The two compartments were connected by a network of bifurcated microchannels allowing diffusion of signalling molecules and migration of cells. Bacterial filters were incorporated in the design to prevent bacteria and activated cells from entering the network, permitting migration only from the recruitment reservoir. The fabricated microsystem allows real-time continuous monitoring of cellular decision-making based on biologically produced gradients of cytokines and chemokines. It is a valuable tool for studying cellular migration and self-organisation in relation to infections, autoimmunity, cancer, stem cell homing, and tissue and wound repair.

The effect of anticoagulant therapy for idiopathic pulmonary fibrosis in real life practice.

BACKGROUND: IPF is a common form of interstitial lung disease for which there is no effective therapy and usually results in death. Two previous contradictory studies showed anticoagulant therapy  to be associated with both improved and worsened survival, respectively. OBJECTIVE: The objective of this retrospective cohort study was to evaluate the effect of anticoagulant therapy on the survival and disease progression of patients with idiopathic pulmonary fibrosis (IPF) in real clinical practice. METHODS: We compared the clinical characteristics, time to disease progression, incidence of acute exacerbation, and survival of 25 (20%) IPF patients receiving anticoagulant therapy to the remaining 97 IPF patients not receiving anticoagulant therapy. In addition we conducted a sensitivity analysis using as comparator a group of 25 patients matched by age, sex, functional impairment, cardiac comorbidities and pulmonary hypertension. RESULTS: Patients on anticoagulant therapy had a worse 1- and 3-year survival (84% and 53% versus 89% and 64% in the non-anticoagulant group, respectively), a difference that persisted after adjusting for age and comorbidities (hazard ratio 3.1 - 95% confidence interval, 1.4 to 7.0; p=0.006) and after comparison with the matched group (adjusted HR=4.8, 95% CI: 1.8-12.8; p=0.002). IPF patients on anticoagulant therapy had a shorter interval to disease progression ( 0.7 years versus 1.6 years, adjusted HR 2.2 -95% CI, 0.96 to 5.1; p=0.063) confirmed also in the analysis with matched subgroups (HR=2.7 (95% CI: 1.2-6.5); p=0.023). The incidence of acute exacerbations did not differ in the two groups (22% versus 23%). Two patients (8%) experienced anticoagulant treatment related complications and included an episode of hemorrhagic shock. CONCLUSION: In this retrospective study patients treated with anticoagulants had a worse survival and a shorter interval to disease progression. This support the recent finding that warfarin worsen the respiratory status and survival of IPF patients.

Diagnostic role of rapid on-site cytologic examination (ROSE) of broncho-alveolar lavage in ALI/ARDS.

BACKGROUND: While bronchoscopy should be considered in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in which the cause cannot be determined from history or clinical and laboratory data, there are no studies about the utility of rapid on-site examination (ROSE) of broncho-alveolar lavage for identification, as early as possible, of the pathological condition underlying the onset of this condition. The aim of this prospective, observational study was to evaluate the diagnostic role of ROSE of BAL in ALI/ARDS. METHODS: 71 patients with ALI/ARDS underwent bronchoalveolar lavage, and one part of the sample was examined with ROSE. The on-site report was categorized as diagnostic (specific diagnosis), presence of atypical reactive type II pneumocytes with no further comments or not diagnostic. RESULTS: ROSE of bronco-alveolar lavage yielded 29 (41%) specific diagnoses, revealed typical features of diffuse alveolar damage without a specific diagnosis in 28 patients (39%) and did not reveal a specific diagnosis in the remaining 14 cases (20%). CONCLUSIONS: The results of this study show that, in patients with ALI/ARDS, bronchoalveolar lavage with ROSE is diagnostic in 40% of cases: ROSE may therefore spare lung biopsies and improve the prognosis of patients with ARDS (immunocompetent or not) as therapy could be started or modified at a very early phase.

Catamenially recurring pneumothorax with partial liver herniation: a particular view.

Few cases of catamenial pneumothorax with complete or partial diaphragmatic hernias are reported in the literature. We present herein the case of a 38-year-old woman affected by recurrent right-sided spontaneous pneumothorax during menstrual periods. CT scan revealed normal lung parenchyma and multiple diaphragmatic nodes suspected for endometrial implants. The patient underwent right thoracoscopy and the presence of multiple diaphragmatic perforations of the tendinous part was observed as well as partial hepatic hernia. Through a video-assisted procedure, pleural biopsies and diaphragmatic plication containing the tendinous part with total pleural abrasion and talc pleurodesis were performed. No endometrial implants were found on histologic examination of pleural biopsies. The surgical procedure was uneventful and totally successful. On the basis of the clinical data and endoscopic view, we consider our case as catamenially recurring pneumothorax.

Pulmonary features of Birt-Hogg-Dubé syndrome: cystic lesions and pulmonary histiocytoma.

BACKGROUND: to describe clinical, radiologic and pathologic features of lung lesions in Birt-Hogg-Dubè syndrome (BHDS) (MIM 135150). METHOD: review of 12 patients of BHDS from 3 unrelated Italian families evaluated at GB Morgagni Hospital, Forlì, from 2005 to 2010. RESULTS: mean age (±SD) at diagnosis was 44.6 (±16) years, 8 (66%) were male. All three index cases presented with a history of recurrent pneumothorax and/or cystic lung lesions evaluated by CT scan request by referring pulmonary physicians, none were diagnosed to have BHDS at the time of initial pulmonary evaluation. One of the three cases was a middle-aged female patient with a clinical phenotype indistinguishable from lymphangioleiomyomatosis (LAM), characterized by cystic lung lesions and kidney angiomyolipoma. In one case of BHDS presenting with recurrent pneumothorax and a solitary lung nodule, surgical lung resection revealed a pulmonary histiocytoma. In one case a novel mutation of BHD gene was detected (c.771 del, exon 7). CONCLUSIONS: BHDS is associated with cystic lung disease largely under-recognized by pulmonary physicians and can mimic LAM and may be associated with lung tumor, pulmonary histiocytoma. In one case we found a novel mutation in exon 7, c.771 del (ref.seq. NM_144997.5) never reported before.

Idiopathic nonspecific interstitial pneumonia: an interstitial lung disease associated with autoimmune disorders?

Recent evidence suggests that idiopathic nonspecific interstitial pneumonia (iNSIP) is a distinct clinical entity amongst other idiopathic interstitial pneumonias, and some data seem to suggest a possible pathogenetic role of autoimmunity. The aim of the present study was to assess if iNSIP might represent an early lung manifestation of an autoimmune disease. After initial review of cases found in the medical records database by searching for the term "NSIP" (n = 63), 37 iNSIP cases were identified, and were re-evaluated using a dynamic integrated multidisciplinary approach. 27 cases with iNSIP were selected for the study. Mean ± sd age at first respiratory symptom was 54.2 ± 8 yrs, 70% were females, and 59% were never-smokers. At follow-up (mean ± sd 59.7 ± 29 months, range 12-138 months), autoimmune diseases occurred in 14 (52%) patients, with seven (26%) cases of autoimmune thyroiditis, six (22%) of undifferentiated connective tissue disease and three (11%) of connective tissue disease. Patients developing autoimmune diseases were older and more frequently never-smoking females. In >50% of patients diagnosed with iNSIP, evidence of autoimmune diseases develops within 2 yrs, suggesting a probable link between the clinical entity of iNSIP and autoimmune disorders.

Diffuse alveolar damage.

Diffuse alveolar damage (DAD) is a characteristic histopathologic pattern that has time dependent findings: intraalveolar and interstitial oedema, and hyaline membranes in the acute phase, myofibroblastic accumulation in the alveolar spaces and type II alveolar cell proliferation in the proliferative phase and fibrosis in the more advanced phases. The diagnosis of DAD is sometimes feasible on small specimens obtained by transbronchial lung biopsy or on cytological slides. Surgical lung biopsy is rarely needed.

Endobronchial ultrasound in Dieulafoy's disease of the bronchus: an additional application of EBUS.

Dieulafoy's disease is a rare vascular malformation represented by an abnormally enlarged submucosal arterial vessel. This malformation is mostly found in gastrointestinal tract causing spontaneous bleeding although a few cases have been described in the bronchial tree. Recognizing Dieulafoy's malformation is crucial for the bronchoscopist in order to avoid biopsy that can lead to a massive hemoptysis, sometimes fatal. In this case report we show the clinical utility of endobronchial ultrasound (EBUS) in the evaluation of bronchial alteration suspicious for Dieulafoy's malformation.

The role of transbronchial lung biopsy for the diagnosis of diffuse drug-induced lung disease: a case series of 44 patients.

At present, no studies have evaluated the role of bronchoscopic transbronchial lung biopsy (TBLB) in the diagnosis of diffuse drug-induced lung disease (DILD), and there is no consensus for a definite diagnostic workup approach for this rare clinical entity. The aim of the present study was to evaluate the clinical usefulness of TBLB in diffuse DILD. This study was a retrospective analysis of patients with diffuse DILD, who underwent bronchoscopy. The role of TBLB was assessed to determine whether the histological results are useful for the final diagnosis. Over a 5-yr period, 44 patients underwent bronchoscopy, and all had a bronchoalveolar lavage (BAL). Thirty-three of the 44 patients underwent TBLB (75%), and the results of TBLB were diagnostically helpful in 25 (75.7%) of the procedures. No histopathologic abnormality was identified in 6 (18%) of the 33 patients. In 2 patients (6%) the obtained samples were not adequate, since no lung parenchyma was obtained. No severe complications related to bronchoscopic procedures occurred. In conclusion, TBLB is a safe procedure, and is diagnostically helpful in the majority of cases of patients with diffuse DILD. Histological data obtained by TBLB further corroborate clinical, laboratory, radiologic and BAL results for a definitive diagnosis of diffuse DILD.

The value of transbronchial lung biopsy using jumbo forceps via rigid bronchoscope in diffuse lung disease.

BACKGROUND: Transbronchial lung biopsy (TBLB) is a valuable procedure used to obtain a parenchymal specimen in the evaluation of diffuse lung infiltrates. Large forceps are expected to result in larger specimens and improve diagnostic yield. AIM: The objective of this study was to evaluate diagnostic yield of TBLB using large modified flexible gastroenterological forceps ("Jumbo forceps") compared with 'normal' flexible forceps via rigid bronchoscopy in patients with diffuse parenchymal lung disease (DPLD). METHODS: The study was a prospective analysis of 95 patients who underwent fluoroscopy guided TBLB over a two year period. Patients with a lung mass or solitary lung nodule undergoing TBLB were excluded. The larger and small forceps were used in a random sequence to avoid a reduction in diagnostic yield of the second series of biopsies related to possible bleeding by first series of biopsies. To minimize the consequence of haemorrhage, we performed every rigid bronchoscopy, placing a non inflated Fogarty balloon and a rigid aspirator (diameter 4 mm) in lobar bronchus near the biopsy segment. The Fogarty balloon has been inflated in case of bleeding. After the bleeding was controlled we continued to operate up to the biopsy segment. RESULTS: Diagnostic yield of TBLB using Jumbo forceps was significantly higher than using normal flexible forceps via rigid bronchoscopy in patients with DPLD (p = 0.001). In 74 out of 95 patients (78%) the diagnosis was placed with Jumbo forcep while the smaller forcep was diagnostic in 62 out of 95 patients (65%). Large forceps obtained significantly more tissue than the small forceps; the biopsy specimen taken with normal forcep measured in average 1.4 x 1.0 mm and the larger biopsy taken with jumbo forcep measured in average 2.5 x 1.9 mm (p < 0.005). CONCLUSION: The use of large biopsy forceps to perform TBLB via rigid bronchoscope can significantly increase diagnostic yield in the pathological diagnosis of diffuse infiltrative lung disease.

Diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory disease, well recognised in Japan and principally affecting the respiratory bronchioles, causing a progressive suppurative and severe obstructive respiratory disorder. If left untreated, DPB progresses to bronchiectasis, respiratory failure and death. It was first described in the early 1960s. Subsequently, in 1969, the disease was named DPB to distinguish it from chronic bronchitis. "Diffuse" refers to the distribution of the lesions throughout both lungs, and "pan-" refers to the involvement of inflammation in all layers of the respiratory bronchioles. The distinctive imaging and histological features, the coexisting sinusitis, and the isolation of Haemophilus influenzae and Pseudomonas aeruginosa in the sputum enhance disease recognition. Histologically, DPB is characterised by chronic inflammation, localised mainly in the respiratory bronchioles and adjacent centrilobular regions, with characteristic interstitial accumulation of foamy histiocytes, neutrophils and lymphocyte infiltration. Neutrophils and T-lymphocytes, particularly CD8+ cells, together with the cytokines interleukin-8 and macrophage inflammatory protein-1, are believed to play key roles in the development of DPB. A significant improvement in the prognosis of this potentially fatal disease has been recently reported thanks to the use of long-term therapy with macrolide antibiotics, the effect of which is attributed to an anti-inflammatory and immunoregulatory action.