Vlasis Polychronopoulos

Apoptosis in lung injury and fibrosis

Pulmonary fibrosis is characterised by fibroblast accumulation and alveolar epithelium denudation. Increased apoptosis of alveolar epithelial cells and decreased apoptosis of fibroblasts may play an important role in the pathogenesis of disease. Inflammatory cells can modulate apoptosis of other cell types, both by removal of apoptotic debris and by cytokine production, thus preserving a pro-fibrotic environment. In the present review, some of the mechanisms by which apoptosis may contribute to the pathogenesis of idiopathic pulmonary fibrosis are described.

Cryptogenic and Secondary Organizing Pneumonia: Clinical Presentation, Radiographic Findings, Treatment Response, and Prognosis

BACKGROUND Organizing pneumonia (OP) is a distinct clinical and pathologic entity. This condition can be cryptogenic (COP) or secondary to other known causes (secondary OP). In the present study, we reviewed the features associated with COP and secondary OP in patients from two teaching hospitals. METHODS The medical records of 61 patients with biopsy-proven OP were retrospectively reviewed. Forty patients were diagnosed with COP and 21 patients with secondary OP. The clinical presentation, radiographic studies, pulmonary function tests (PFTs), laboratory data, BAL findings, treatment, and outcome were analyzed. RESULTS The mean age at presentation was 60.46 ± 13.57 years. Malaise, cough, fever, dyspnea, bilateral alveolar infiltrates, and a restrictive pattern were the most common symptoms and findings. BAL lymphocytosis was observed in 43.8% of patients with OP. The relapse rate and mortality rate after 1 year of follow-up were 37.8% and 9.4%, respectively. The in-hospital mortality was 5.7%. The clinical presentation and radiographic findings did not differ significantly between patients with COP and secondary OP. A mixed PFT pattern (obstructive and restrictive physiology) and lower blood levels of serum sodium, serum potassium, platelets, albumin, protein, and pH were observed among patients with secondary OP. Higher blood levels of creatinine, bilirubin, Paco₂, and BAL lymphocytes were also more common among patients with secondary OP. There were no differences in the relapse rate or mortality between patients with COP and secondary OP. The 1-year mortality correlated with an elevated erythrocyte sedimentation rate, low albumin, and low hemoglobin levels. CONCLUSIONS The clinical and radiographic findings in patients with COP and secondary OP are similar and nonspecific. Although certain laboratory abnormalities are more common in secondary OP and can be associated with worse prognosis, they are likely due to the underlying disease. COP and secondary OP have similar treatment response, relapse rates, and mortality.

Acute exacerbations of interstitial lung diseases.

Purpose of review This review aims to highlight recent advances in pathogenesis, clinical presentation and treatment of interstitial lung diseases (ILDs). Recent findings Acute exacerbation is increasingly recognized as a major complication in the course of idiopathic pulmonary fibrosis. It is precipitated by a variety of intrinsic and extrinsic factors. Moreover, acute exacerbation is an apparently equally frequent event in hypersensitivity pneumonitis and collagen–vascular diseases associated ILDs, especially the rheumatoid pulmonary fibrosis. Treatment of acute exacerbations is unsatisfactory and prognosis extremely poor. Summary In a critically ill patient proper recognition of an acute exacerbation and of the underlying chronic ILD is warranted because treatment approach varies with the type of ILD. Advances in the understanding of the pathogenesis and treatment of this ‘idiopathic’ phenomenon are reviewed.

Prognostic value of C-reactive protein in parapneumonic effusions.

Background and objective:  Parapneumonic effusions (PPE) that require drainage are referred to as complicated parapneumonic effusions (CPPE). Following resolution of these effusions, residual pleural thickening (RPT) may persist. We hypothesize that the concentrations of CRP in pleural fluid (CRPpf) and serum (CRPser) can be used to identify CPPE and to predict RPT.

Expression of bcl-2 Protein in Bronchoalveolar Lavage Cell Populations from Patients with Idiopathic Pulmonary Fibrosis

OBJECTIVE To investigate changes in the expression of the antiapoptotic protein bcl-2 in bronchoalveolar lavage fluid (BALF) cell populations in patients with idiopathic pulmonary fibrosis (IPF). STUDY DESIGN Ten patients with IPF underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) in the area of maximal radiographic shadowing (based on high-resolution computed tomography findings). Results were compared with those of 10 normal people in the control group. Cellular bcl-2 expression was identified using an immunoperoxidase staining method. RESULTS A statistically significant (P < .001) increase in the expression of bcl-2 in BALF neutrophils and eosinophils was observed in patients with IPF as compared with controls. BAL macrophages exhibited only a slight (statistically insignificant) increase in bcl-2 expression in IPF patients. No bcl-2 expression was observed in BAL lymphocytes from IPF patients in contrast to the control group. CONCLUSION The overexpression of bcl-2 on BALF neutrophils and eosinophils, cells that characterize the special cellular profile of alveolitis in IPF, could be one of the pathophysiologic mechanisms of this disease.

Respiratory and lower limb muscle function in interstitial lung disease.

Growing evidence suggests that respiratory and limb muscle function may be impaired in patients with interstitial lung disease (ILD). Importantly, muscle dysfunction could promote dyspnoea, fatigue and functional limitation all of which are cardinal features of ILD. This article examines the risk factors for skeletal muscle dysfunction in ILD, reviews the current evidence on overall respiratory and limb muscle function and focuses on the occurrence and implications of skeletal muscle dysfunction in ILD. Research limitations and pathways to address the current knowledge gaps are highlighted.

Decreased Apoptotic Rate of Alveolar Macrophages of Patients with Idiopathic Pulmonary Fibrosis

Introduction. Increased apoptosis of epithelial cells and decreased apoptosis of myofibroblasts are involved in the pathogenesis of IPF. The apoptotic profile of alveolar macrophages (AMs) in IPF is unclear. Aim. To investigate whether AMs of patients with IPF exhibit a different apoptotic profile compared to normal subjects. Methods. We analyzed, by immunohistochemistry, the expression of the apoptotic markers fas, fas ligand , bcl-2, and bax in AM obtained from bronchoalveolar lavage fluid (BALF) of 20 newly diagnosed, treatment-naive IPF patients and of 16 controls. Apoptosis of AM was evaluated by Apoptag immunohistochemistry. IPF patients received either interferon-g and corticosteroids or azathioprine and corticosteroids for six months. Results. BALF AMs undergoing apoptosis were significantly less in IPF patients. No difference was found in the expression of fas or fas ligand, bcl-2 and bax between IPF and control group. No difference was found between the respiratory function parameters of the two treatment groups after six months. A positive correlation was found between the number of bcl-2 positive stained macrophages and DLCO after treatment. Conclusions. The decreased apoptotic rate of AM of patients with IPF is not associated with decreased expression of apoptosis mediators involved in the external or internal apoptotic pathway.

A Case of Tracheal Hamartoma Resected with Loop Electrocautery

The authors report on the case of a 67-year-old man with longstanding breathlessness, which was eventually attributed to a fixed mass in the upper third of the trachea causing upper airway obstruction. The lesion was amenable to loop electrocautery resection via flexible bronchoscopy that led to prompt resolution of patient symptoms. Biopsy was consistent with tracheal hamartoma, an exceedingly rare benign tracheal tumor. All the cases of tracheal hamartomas in the literature to date, the application of electrocautery and other methods of interventional bronchoscopy for resection of selected tracheal tumors are discussed.

How can autoantibodies predict the long-term outcome of patients with interstitial lung disease? Results from a retrospective cohort study

OBJECTIVES This study aimed to investigate whether positive serum autoantibodies (AAbs) have any impact on survival and time evolution of radiological findings and pulmonary function indices in patients with interstitial lung disease (ILD). PATIENTS AND METHODS Ninety four patients with regular clinical, functional and high resolution computed tomography (HRCT) imaging follow-up for at least 12 consecutive months and complete testing for a panel of AAbs most commonly associated with ILD were enrolled in this retrospective two-center study. Eligible patients were divided into two groups based on the presence [ILD/AAb(+)] (n = 69) or absence [ILD/AAb(-)] (n = 25) of positive serum AAbs. All-cause mortality and longitudinal indicators of ILD progression such as a sustained decrease from baseline in absolute measurements of forced vital capacity (FVC) of ≥10% or single-breath diffusion capacity (DLCOSB) of ≥15% were the primary study endpoints. DLCOSB < 40% predicted on at least two consecutive measurements and progression of HRCT findings were our secondary endpoints. Kaplan-Meier (K-M) survival analysis and multivariate Cox proportional-hazards (PH) model were used to evaluate the prognostic significance of positive AAbs in the outcome of patients with ILD. RESULTS ILD/AAb(+) patients were predominantly female (71% vs 32%), were significantly younger (54.8 ± 14.6 vs 66.8 ± 10.1 years), and had longer duration of follow-up (78.1 ± 53.1 vs 41.6 ± 26.7 months), compared with ILD/AAb(-) patients (p < .01 for each comparison). Baseline measurements of FVC (% pred.) and DLCOSB (% pred.) did not differ significantly between the two groups. At the end of follow-up, mortality rates and the percentage of patients with a sustained FVC decrease were lower in the ILD/AAb(+) group (p < .05 for each comparison). With the exception of DLCOSB < 40% pred., ILD/AAb(+) patients had a longer median time-to-event for each of the other studied outcomes (p < .01 for each K-M analysis). In addition, Cox PH models adjusted for age, smoking status, baseline pulmonary function tests and morphological pattern of ILD remained statistically significant in favor of the ILD/AAb(+) group (p < .05 for each comparison). CONCLUSIONS AAb(+) patients with ILD seem to have a more favorable prognosis regarding all-cause mortality, long-term deterioration in lung function parameters and progression of HRCT findings than their AAb (-) counterparts.