Faculty Bibliography

BACKGROUND: Malignant pleural effusion is a common complication of advanced malignancies. Indwelling tunneled pleural catheter (IPC) placement provides effective palliation but can be associated with complications, including infection. In particular, hematologic malignancy and the associated immunosuppressive treatment regimens may increase infectious complications. This study aimed to review outcomes in patients with hematologic malignancy undergoing IPC placement. METHODS: A retrospective multicenter study of IPCs placed in patients with hematologic malignancy from January 2009 to December 2013 was performed. Inclusion criteria were recurrent, symptomatic pleural effusion and an underlying diagnosis of hematologic malignancy. Records were reviewed for patient demographics, operative reports, and pathology, cytology, and microbiology reports. RESULTS: Ninety-one patients (mean +/- SD age, 65.4 +/- 15.4 years) were identified from eight institutions. The mean x SD in situ dwell time of all catheters was 89.9 +/- 127.1 days (total, 8,160 catheter-days). Seven infectious complications were identified, all of the pleural space. All patients were admitted to the hospital for treatment, with four requiring additional pleural procedures. Two patients died of septic shock related to pleural infection. CONCLUSIONS: We present, to our knowledge, the largest study examining clinical outcomes related to IPC placement in patients with hematologic malignancy. An overall 7.7% infection risk and 2.2% mortality were identified, similar to previously reported studies, despite the significant immunosuppression and pancytopenia often present in this population. IPC placement appears to remain a reasonable clinical option for patients with recurrent pleural effusions related to hematologic malignancy.

A patient with a history of lung adenocarcinoma, which was treated with chemoradiation, presented to our interventional pulmonology clinic for suspicion of recurrent lung cancer. The patient had a PET-avid right upper-lobe mass and subcarinal lymphadenopathy. We performed a curvilinear endobronchial ultrasound (CP-EBUS) with transbronchial needle aspiration (TBNA), followed by transbronchial EBUS-guided biopsies (TBB) of the subcarinal lymph node using miniforceps. The EBUS needle sheath was inserted over the needle through the bronchial wall and advanced into the lymph node. The EBUS-guided placement of the transbronchial sheath facilitated the miniforcep insertion and the performance of multiple transbronchial biopsies. Given success with this method, we further developed this technique in a second patient with a right lower-lobe mass. In an effort to obtain adequate tissue and minimize repeated efforts at miniforcep guidance into the lesion, we inserted a radial EBUS guide sheath through the curvilinear EBUS scope and guided it into the lesion using the miniforceps. We therefore used the radial sheath as a placeholder while obtaining repeated TBB using miniforceps as described. These modifications of previously described techniques allow for maximal and expeditious sampling of target lymph nodes and masses, with sufficient material obtained for histopathologic analysis.

Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from cystic fibrosis (CF) transmembrane conductance regulator(-/-) mice have impaired function, no study has investigated primary alveolar macrophages in adults with CF. CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infections. Serum and bronchoalveolar lavage (BAL) samples were obtained from eight CF subjects and eight healthy subjects. Macrophages were isolated from BAL fluid. We measured the ability of alveolar macrophages to kill Pseudomonas aeruginosa. Subsequently, macrophages were incubated with IGF-1 prior to inoculation with bacteria to determine the effect of IGF-1 on bacterial killing. We found a significant decrease in bacterial killing by CF alveolar macrophages compared with control subjects. CF subjects had lower serum and BAL IGF-1 levels compared with healthy control subjects. Exposure to IGF-1 enhanced alveolar macrophage macrophages in both groups. Finally, exposing healthy alveolar macrophages to CF BAL fluid decreased bacterial killing, and this was reversed by the addition of IGF-1, whereas IGF-1 blockade worsened bacterial killing. Our studies demonstrate that alveolar macrophage function is impaired in patients with CF. Reductions in IGF-1 levels in CF contribute to the impaired alveolar macrophage function. Exposure to IGF-1 ex vivo results in improved function of CF alveolar macrophages. Further studies are needed to determine whether alveolar macrophage function can be enhanced in vivo with IGF-1 treatment.