Risk factors for pleural effusion recurrence in patients with malignancy.

BACKGROUND AND OBJECTIVE: The main purpose of treatment in patients with malignant pleural effusion (MPE) is symptom palliation. Currently, patients undergo repeat thoracenteses prior to receiving a definitive procedure as clinicians are not aware of the risk factors associated with fluid recurrence. The primary objective of this study was to identify risk factors associated with recurrent symptomatic MPE. METHODS: Retrospective multicentre cohort study of patients who underwent first thoracentesis was performed. The primary outcome was time to fluid recurrence requiring intervention in patients with evidence of metastatic disease. We used a cause-specific hazard model to identify risk factors associated with fluid recurrence. We also developed a predictive model, utilizing Fine-Gray subdistribution hazard model, and externally validated the model. RESULTS: A total of 988 patients with diagnosed metastatic disease were included. Cumulative incidence of recurrence was high with 30% of patients recurring by day 15. On multivariate analysis, size of the effusion on chest X-ray (up to the top of the cardiac silhouette (hazard ratio (HR): 1.84, 95% CI: 1.21-2.80, P = 0.004) and above the cardiac silhouette (HR: 2.22, 95% CI: 1.43-3.46, P = 0.0004)), larger amount of pleural fluid drained (HR: 1.06, 95% CI: 1.04-1.07, P < 0.0001) and higher pleural fluid LDH (HR: 1.008, 95% CI: 1.004-1.011, P < 0.0001) were associated with increased hazard of recurrence. Negative cytology (HR: 0.52, 95% CI: 0.43-0.64, P < 0.0001) was associated with decreased hazard of recurrence. The model had low prediction accuracy. CONCLUSION: Pleural effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology were found to be risk factors for recurrence.

Improvement of constrictive bronchiolitis (bronchiolitis obliterans) after rituximab therapy in 2 patients with primary sjögren syndrome.

Constrictive bronchiolitis is one of the manifestations of small-airway involvement in primary Sjögren syndrome (SS) and is associated with fixed airflow obstruction despite treatment with bronchodilators, macrolides, corticosteroids, and corticosteroid-sparing agents. Reports have shown a beneficial effect of rituximab on interstitial lung disease associated with SS, but the effect of rituximab on constrictive bronchiolitis is unknown. Herein, we present 2 cases of patients with constrictive bronchiolitis associated with SS who experienced symptomatic improvement and stabilization of pulmonary function testing (PFT) after rituximab therapy. Lung function declined in one of the patients when B cells reconstituted, with improved PFT results on re-administration of rituximab. Our case reports suggest that B cells may be involved in the pathogenesis of SS-associated constrictive bronchiolitis. Therapy targeting B cells may therefore be helpful in treating this debilitating and refractory condition. Further research is warranted.

Hypercapnia Alters Alveolar Epithelial Repair by a pH-Dependent and Adenylate Cyclase-Mediated Mechanism.

Lung cell injury and repair is a hallmark of the acute respiratory distress syndrome (ARDS). Lung protective mechanical ventilation strategies in these patients may lead to hypercapnia (HC). Although HC has been explored in the clinical context of ARDS, its effect upon alveolar epithelial cell (AEC) wounding and repair remains poorly understood. We have previously reported that HC alters the likelihood of AEC repair by a pH-sensitive but otherwise unknown mechanism. Adenylate cyclase (AC) is an attractive candidate as a putative AEC CO2 sensor and effector as it is bicarbonate sensitive and controls key mediators of AEC repair. The effect of HC on AC activity and plasma membrane (PM) wound repair was measured in AEC type 1 exposed to normocapnia (NC, 40 Torr) or HC (80 Torr), ± tromethamine (THAM) or sodium bicarbonate (HCO3) ± AC probes in a micropuncture model of AEC injury relevant to ARDS. Intracellular pH and AC activity were measured and correlated with repair. HC decreased intracellular pH 0.56, cAMP by 37%, and absolute PM repair rate by 26%. Buffering or pharmacologic manipulation of AC reduced or reversed the effects of HC on AC activity (THAM 103%, HCO3 113% of NC cAMP, ns; Forskolin 168%, p < 0.05) and PM repair (THAM 87%, HCO3 108% of NC likelihood to repair, ns; Forskolin 160%, p < 0.01). These findings suggest AC to be a putative AEC CO2 sensor and modulator of AEC repair, and may have implications for future pharmacologic targeting of downstream messengers of the AC-cAMP axis in experimental models of ARDS.

Methylene Blue for Bronchopleural Fistula Localization.

A bronchopleural fistula (BPF) is a communication between the pleural space and the bronchial tree. BPFs are challenging to diagnose and are associated with a high morbidity and mortality. Sequential balloon occlusion is commonly used for localization of a BPF. We describe our experience with 4 cases of successful localization of the BPF by instillation of methylene blue into the pleural space through a pigtail catheter, with simultaneous bronchoscopic visualization of dye in the tracheobronchial tree. Two patients were treated with endobronchial valves and 3 had a surgical thoracic muscle flap placed.

Comparison of Programmed Death Ligand-1 Immunohistochemical Staining Between Endobronchial Ultrasound Transbronchial Needle Aspiration and Resected Lung Cancer Specimens.

BACKGROUND: In advanced non-small cell lung cancer (NSCLC), small biopsy specimens from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are often the only available material from cancer tissue for the analysis of programmed death ligand-1 (PD-L1) expression. We aim to assess the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PD-L1 expression at ≥ 1% and ≥ 50% on EBUS-TBNA samples compared with their corresponding surgically resected tumor. METHODS: We retrospectively reviewed all patients who underwent EBUS-TBNA followed by surgical resection of NSCLC between July 2006 and September 2016. Demographic information and periprocedural/surgical data were collected. The archived specimens were retrieved and assessed for PD-L1. A positive PD-L1 stain was defined using two separate cutoff points: ≥ 1% and ≥ 50% of tumor cell positivity. EBUS-TBNA aspirates were compared with the surgically resected specimen to calculate the sensitivity, specificity, PPV, and NPV. RESULTS: Sixty-one patients were included. For PD-L1 ≥ 1%, the sensitivity, specificity, PPV, and NPV were 72%, 100%, 100%, and 80%, respectively. For PD-L1 ≥ 50%, the sensitivity, specificity, PPV, and NPV were 47%, 93%, 70%, and 84%, respectively. The concordance rates for PD-L1 ≥ 1% and ≥ 50% were 87% and 82%, respectively. CONCLUSIONS: A PD-L1 cutoff of ≥ 1% on EBUS-TBNA has a strong correlation with resected tumor specimen. For PD-L1 ≥ 50%, there is a significant decrease in the sensitivity and PPV of EBUS-TBNA specimen when compared with resected tumor. When analyzing for PD-L1 expression using a cutoff of ≥ 50%, EBUS-TBNA specimens may misclassify the status of PD-L1.

Pulmonary Parenchymal Lymphoma Diagnosed by Bronchoscopic Cryoprobe Lung Biopsy.

A 51-year-old man presented with progressively worsening lung infiltrates and respiratory failure. Extensive investigations including bronchoscopy with bronchoalveolar lavage and conventional transbronchial forceps biopsies failed to establish the diagnosis. After transfer to our institution, he underwent repeat bronchoscopy with transbronchial cryobiopsy, which provided large, high-quality biopsy specimens establishing the diagnosis of parenchymal diffuse large B-cell lymphoma.

Fatal fulminant necrotizing pneumonia: a case report.

INTRODUCTION: Here we present the case of a patient with fatal pulmonary histoplasmosis who presented with extensive necrotizing and cavitating pneumonia. To the best of our knowledge, this case report is the first to describe this presentation in a patient with no known immunosuppression. CASE PRESENTATION: A 45-year-old Caucasian woman, a smoker from southeastern Minnesota, presented to our hospital with progressive dyspnea, fatigue and weight loss over the course of several months. Her medical history included type 2 diabetes mellitus, systemic hypertension and chronic opioid use for back pain. She did not have any recent travel history, and she had no unusual hobbies or risk factors for human immunodeficiency virus. When she was admitted to our intensive care unit, she was in hypoxic respiratory failure, thus we intubated her and placed her on mechanical ventilation. A computed tomographic scan of the chest revealed extensive areas of pulmonary necrosis with diffuse bilateral cavitation and lung destruction, which were especially prominent in the upper and middle lung fields. Bronchoalveolar lavage confirmed growth of Histoplasma capsulatum as the sole isolated pathogen. No other infectious agents were identified in blood, bronchoalveolar lavage, sputum or urine samples. Her condition worsened over the next 24 to 48 hours, with progressive multi-organ failure in spite of aggressive antibiotic and antifungal therapy. Her family elected to withdraw supportive care, and she died shortly thereafter. CONCLUSION: This case demonstrates a novel manifestation of histoplasmosis associated with extensive lung necrosis and cavitation. This report is of particular interest to pulmonologists and intensivists and underscores the importance of maintaining suspicion for mycotic disease in patients who have atypical presentations but live in an endemic area.

Influence of interstitial lung disease on outcome in systemic sclerosis: a population-based historical cohort study.

BACKGROUND: Interstitial lung disease (ILD) is a frequent complication of systemic sclerosis (SSc) and a major cause of SSc-related deaths. This study aimed to determine the influence of ILD on SSc in a population-based historical cohort study. The hypothesis was that patients with SSc who develop ILD have increased morbidity and mortality when compared with patients with SSc without ILD. METHODS: Using the record linkage system of the Rochester Epidemiology Project in Olmsted County, Minnesota, this study identified the incidence of SSc between 1980 and 2010 and point prevalence on December 31, 2010 and determined the progression of organ involvement and its influence on outcome. RESULTS: During the 30-year interval, we identified 64 incident cases of SSc: 57 women and seven men, median age 49.1 years (interquartile range [IQR], 39.8-67.6 years). There were 43 prevalent cases. ILD occurred in 19 cases, usually after the diagnosis of SSc (median, 2 years; IQR, 0-10 years), with only three cases occurring 6 to 24 months beforehand. Pulmonary arterial hypertension (PAH) was diagnosed in 14 cases, heart failure in 27 cases, and chronic kidney disease (CKD) in 21 cases. Seventeen patients died during the study period, with a median survival time after diagnosis of 22.9 years. ILD, PAH, and CKD were associated with an increased risk of death. CONCLUSIONS: The incidence of ILD associated with SSc was relatively low in this population-based cohort. ILD appeared to be a contributing factor to mortality. Other factors, including age, PAH, and CKD, were also associated with poor outcome.