Pulmonary & Respiratory Medicine

Prostate cancer is the most common type of malignancy in males in many parts of the world. Prostate adenocarcinoma is both second leading cause of cancer and cancer death in the North American males. Of the patients who are detected with prostate cancer, about 10-20% of them are found to have metastatic cancer on presentation. Prostate cancer commonly metastasizes to the bones; vertebrae, ribs, long bones and the skull. Metastasis to pleura is extremely uncommon. We present a case of prostate cancer metastasizing to pleura. The purpose of this report is to remind physicians of this rare occurrence. This case also highlights that pleural fluid cytology can be negative repeatedly even though pleural surface has multiple metastatic nodules.

We report a 45 year old male with right sided pleural mesothelioma who received neoadjuvant chemotherapy prior to a right extrapleural pneumonectomy followed by adjuvant chemotherapy. The patient became tumor free and remained in remission for 19 months following which he developed a lymphangitic spread over the contralateral lung. His diagnosis was confirmed by a bronchoscopic transbronchial biopsy of the left lung. The patient died from progressive respiratory failure over a period of three months. Such a relapse with an aggressive and fatal lymphangitic spread is rarely seen and reported in malignant pleural mesothelioma. Discussion and review of the literature are provided. Mesothelioma is still considered, worldwide, a rare cancer of the serosal membranes. It typically involves the pleural cavity but other reported sites include the peritoneum, pericardium and Tunica vaginalis of the testis. The usual progression of the mesothelioma is coalescence of multiple, small nodules into large masses that invade, entrap and destroy the affected organ by direct extension and invasion. We report an unusual case of relapsing mesothelioma, recurring in an aggressive and fatal form, after 19 months of remission.

Limited information is available comparing the efficacy and safety of Short-Acting β2-agonists (SABAs) versus long-acting β2-agonists (LABAs) for maintenance therapy in Chronic Obstructive Pulmonary Disease (COPD). The objective of this research was to conduct a systematic literature review and evaluate COPD-related outcomes in a meta-analysis. The literature review identified randomized clinical trials of LABAs and SABAs as maintenance therapy in adults with stable COPD. PubMed/Medline, Embase, and the Cochrane Library were searched for reports published between January 1, 1990 and July 16, 2010. Only studies of at least 2 weeks in duration were included. Few studies directly comparing LABAs and SABAs were expected; therefore, studies with placebo or ipratropium were included for a potential indirect-comparison. A total of 938 studies were identified with 62 meeting all inclusion criteria. Only one study directly compared outcomes for LABA versus SABA. This study reported significantly better airflow and greater reduction in symptoms for the LABA treatment. Twelve studies evaluated a SABA with a shared common comparator, but indirect metaanalysis was not tenable due to different outcome variables. The efficacy and safety of LABAs and SABAs in patients with COPD has been demonstrated, but only LABAs have supporting data for maintenance treatment. In usual clinical care, SABAs appear to be used in place of LABAs for long-term therapy, despite the lack of any empirical support. This review supports the current evidence-based guidelines that recommend LABAs for maintenance therapy in adults with stable COPD and reserves SABAs for use as rescue medications.

Background: Plasma levels of Clara cell protein (CC16) and Surfactant Protein D (SP–D) are elevated in patients with Acute Lung Injury or Acute Respiratory Distress Syndrome (ALI/ARDS). We investigated the relation between these biomarkers and clinical outcome scores from mechanically ventilated patients at risk for lung injury.

Methods: Data from all 150 patients enrolled in a previously reported preventive randomized controlled trial, comparing a 10 ml/kg with a 6 ml/kg tidal volume strategy in patients without ALI/ARDS at the onset of mechanical ventilation, were used. CC16 and SP–D levels were measured in plasma samples at baseline and on day 2 and 4 after initiation of the mechanical ventilation protocol. The relation between CC16 and SP–D levels and development of ALI/ARDS (North American European Consensus Conference (NAECC) criteria), and of the following clinical scores: lung injury score, Sequential Organ Failure Assessment (SOFA) score, and oxygenation index, was investigated using multivariate regression analysis.

Results: Plasma CC16 and SP–D levels increased after 4 days in patients who developed acute lung injury (NAECC criteria). At all time points the plasma CC16 level was significantly correlated with the lung injury score, SOFA score and oxygenation index. The highest correlations were observed on day 2 (standardized coefficient, β=0.38; β=0.54; and β=0.40; P<0.001 for all, respectively). The systemic SP–D level was correlated with these scores only on day 4 (β=0.29; β=0.26; and β=0.33; P<0.05 for all, respectively).

Conclusion: Plasma CC16 and SP–D levels may be used to monitor the extent of lung injury in mechanically ventilated intensive care unit patients.

This report presents a 25 year old female with a history of exertional dyspnea since the age of three. She was wrongly diagnosed and managed as bronchiectasis although she had had no productive cough or recurrent infection. At the age of 23, because of her dyspnea she was referred to a pneumologist for the first time. High resolution computed tomography and open lung biopsy was performed at that time. High resolution computed tomography showed diffuse thin walled cysts and pathologic results also confirmed lymphangioleiomyomatosis as her definite diagnose. She was treated with sirolimus and progesterone for two years which resulted in significant increase in oxygen saturation. However, no change was seen in forced expiratory volume at first second.

Background: Outpatient treatment is an increasingly used option in Community-Acquired Pneumonia (CAP). Risk factors for deterioration and subsequent hospitalization are poorly characterized.

Material and Methods: A prospective study was conducted to assess risk factors associated with hospitalization of CAP-patients initially treated in an outpatient setting. Clinical history, severity of disease, physical examination findings, laboratory test results, initial treatment and outcome were prospectively documented in both groups. Data derived from a multicenter prospective study initiated by the German competence network for communityacquired pneumonia CAPNETZ. The network includes 10 clinical centers representing hospital and outpatient facilities from all levels of health care. 5431 patients with CAP were screened for inclusion. 1517 of these patients were initially treated as outpatients and included. 1403 patients were treated exclusively in an outpatient setting, 114 (8.1%) were hospitalized after initial outpatient treatment.

Results: Compared to patients treated exclusively in an outpatient setting patients with subsequent hospitalization had a significantly higher 28-day mortality rate (4.2% vs. 0.2%, p=<0.001), advanced mean age (56.7 vs. 50.9 years, p=<0.05), and a higher CRB-65 score. However 53.3% of subsequently admitted patients had CRB-65=0, and 23% had CRB-65=1 with age >65 years as the only risk factor. Cerebrovascular disease, chronic kidney disease and diabetes mellitus were overrepresented in this patient group. In addition, cephalosporin monotherapy was identified as independent risk factor for hospitalization.

Conclusion: In ambulatory CAP patients subsequent hospitalization was observed mainly in low CRB-65 risk classes and was associated with comorbidities and the choice of initial therapy

A 32 yr old female clinically and radiographically diagnosed as tuberculosis initially not responding to anti tuberculous treatment was later on Diagnosed as classical Wegener’s granulomatosis basing on tissue biopsy, c-ANCA, along with other systemic manifestations posing a diagnostic challenge.

Background: IKK-2 activity is essential for cytokine mediated NFκB activation and subsequent expression of a wide variety of inflammatory genes. To investigate the role of IKK-2 signalling in lung epithelium we have developed a knock out mouse in which we have specifically deleted the IKK-2 gene in lung epithelial cells.

Materials and Methods: IKK-2 KO mice and littermate control animals were challenged with either nebulised Lipopolysaccharide (LPS) or with Cigarette Smoke Extract (CSE). Cytokines and inflammatory cells were assessed in Bronchoalveolar Lavage Fluid (BALF) and tissue inflammatory cells, markers of apoptosis and general pathology assessed histologically.

Results: BALF neutrophils were reduced by 63% at 4 hours and 67% at 8 hours following LPS challenge in the IKK-2 KO animals (P<0.001). Immunocytochemical analysis showed no difference in neutrophil numbers within pulmonary tissue between the groups or any evidence of increased apoptosis. BALF neutrophils were also reduced below control values in the IKK-2 KO mice in response to CSE compared to littermates animals (P<0.005).

Conclusion: Mice lacking IKK-2 in the pulmonary epithelium recruit fewer neutrophils into the airways in response to both LPS and CSE challenge, suggesting that the epithelium participates in airway inflammatory neutrophil recruitment in response to inflammatory challenge.