Citations

ABSTRACT We present a case of disseminated Neosartorya pseudofischeri infection in a bilateral lung transplant patient with cystic fibrosis. The organism was originally misidentified from respiratory specimens as Aspergillus fumigatus using colonial and microscopic morphology. DNA sequencing subsequently identified the organism correctly as N. pseudofischeri .

Abstract Background: The EML4-ALK fusion gene is more frequently found in younger, never smoking patients with lung cancer. Meanwhile, never smokers exposed to secondhand tobacco smoke (SHS) during childhood are diagnosed at a younger age compared with never smoking patients with lung cancer who are not exposed. We, therefore, hypothesized that SHS, which can induce DNA damage, is associated with the EML4-ALK fusion gene. Methods: We compared the frequency of the EML4-ALK fusion gene among 197 never smoker patients with lung cancer with and without a history of exposure to SHS during childhood at Mayo Clinic. Results: The EML4-ALK fusion gene was detected in 33% of cases from never smokers with a history of SHS exposure during childhood, whereas 47% of never smoking lung cancer cases without a history of childhood SHS exposure tested positive for the fusion gene. Conclusions: The EML4-ALK fusion gene is not enriched in tumors from individuals exposed to SHS during childhood. Impact: These data suggest that childhood exposure to SHS is not a significant etiologic cause of the EML4-ALK fusion gene in lung cancer. Cancer Epidemiol Biomarkers Prev; 23(7); 1432–4. ©2014 AACR.

Abstract Extracellular cyclophilins have been well described as chemotactic factors for various leukocyte subsets. This chemotactic capacity is dependent upon interaction of cyclophilins with the cell surface signaling receptor CD147. Elevated levels of extracellular cyclophilins have been documented in several inflammatory diseases. We propose that extracellular cyclophilins, via interaction with CD147, may contribute to the recruitment of leukocytes from the periphery into tissues during inflammatory responses. In this study, we examined whether extracellular cyclophilin-CD147 interactions might influence leukocyte recruitment in the inflammatory disease allergic asthma. Using a mouse model of asthmatic inflammation, we show that 1) extracellular cyclophilins are elevated in the airways of asthmatic mice; 2) mouse eosinophils and CD4+ T cells express CD147, which is up-regulated on CD4+ T cells upon activation; 3) cyclophilins induce CD147-dependent chemotaxis of activated CD4+ T cells in vitro; 4) in vivo treatment with anti-CD147 mAb significantly reduces (by up to 50%) the accumulation of eosinophils and effector/memory CD4+ T lymphocytes, as well as Ag-specific Th2 cytokine secretion, in lung tissues; and 5) anti-CD147 treatment significantly reduces airway epithelial mucin production and bronchial hyperreactivity to methacholine challenge. These findings provide a novel mechanism whereby asthmatic lung inflammation may be reduced by targeting cyclophilin-CD147 interactions.

The balance between mitochondrial fission and fusion is crucial for mitochondria to perform its normal cellular functions. We hypothesized that cigarette smoke (CS) disrupts this balance and enhances mitochondrial dysfunction in the airway. In nonasthmatic human airway smooth muscle (ASM) cells, CS extract (CSE) induced mitochondrial fragmentation and damages their networked morphology in a concentration-dependent fashion, via increased expression of mitochondrial fission protein dynamin-related protein 1 (Drp1) and decreased fusion protein mitofusin (Mfn) 2. CSE effects on Drp1 vs. Mfn2 and mitochondrial network morphology involved reactive oxygen species (ROS), activation of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), protein kinase C (PKC) and proteasome pathways, as well as transcriptional regulation via factors such as NF-κB and nuclear erythroid 2-related factor 2. Inhibiting Drp1 prevented CSE effects on mitochondrial networks and ROS generation, whereas blocking Mfn2 had the opposite, detrimental effect. In ASM from asmatic patients, mitochondria exhibited substantial morphological defects at baseline and showed increased Drp1 but decreased Mfn2 expression, with exacerbating effects of CSE. Overall, these results highlight the importance of mitochondrial networks and their regulation in the context of cellular changes induced by insults such as inflammation (as in asthma) or CS. Altered mitochondrial fission/fusion proteins have a further potential to influence parameters such as ROS and cell proliferation and apoptosis relevant to airway diseases.

Context. —Patients with pneumothorax occasionally require limited lung resections to control persistent air leaks. In some patients, especially smokers, histopathologic findings suggest that a ruptured bulla or bleb caused the pneumothorax. Other patients only exhibit histopathologic changes related to the physical trauma of acute, and likely occult recurrent, peripheral lung injury in the setting of “spontaneous,” or idiopathic, lung rupture. Sometimes, pneumothorax occurs secondary to an underlying localized or diffuse parenchymal lung disease. A comprehensive description of the morphologic findings that may be seen in these specimens will help the surgical pathologist distinguish patients with more common and indolent occurrences of pneumothorax from those requiring additional workup or treatment. Objective. —To develop a diagnostic approach for surgical pathologists encountering lung specimens obtained in the context of pneumothorax repair. Data Sources. —Literature review and consultation experience of the authors. Conclusions. —Two general categories of histopathologic changes can be identified: (1) nonspecific changes, reflecting the lung's acute and chronic response to localized injury, and (2) changes suggesting an underlying lung disease that may have played an etiologic role in the development of pneumothorax. The latter changes are important to recognize because they may require additional workup or treatment of clinically occult lung disease. Difficulty arises when nonspecific histopathologic changes overlap with those of an underlying lung disease. Awareness of these diagnostic challenges and pitfalls, together with clinicoradiographic correlation, is essential in these situations and will help guide the surgical pathologist toward an accurate diagnosis and the appropriate management of clinically occult disease.

The newly proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) classification of lung adenocarcinoma has emphasized the prognostic significance of histological subtyping. In this study, 2 surgical pathologists reevaluated 49 consecutive cases of invasive primary pulmonary adenocarcinomas; histological subtyping was performed according to the IASLC/ATS/ERS classification. The 2 reviewers agreed on the predominant pattern in 23 out of 32 independently reviewed cases (71.9%, k = 0.628, 95% confidence interval = 0.442-0.815). Postconsensus, a complex glandular pattern consisting of fused, closely packed glands and cribriform architecture was identified in 9 of 49 (18%) cases. This pattern has a strong association with lymphovascular invasion (78%; P = .0091), high mitotic activity (89%), and higher tumor stage (78%). Frequent association of complex glandular pattern with poor prognostic factors and its overlap with acinar pattern warrant a more detailed description of this pattern in the classification system and a large-scale study to evaluate its prognostic significance.

Nanomedicine is a rapidly evolving field with high potential for developing novel research, diagnosis, and/or therapeutic approaches for lung diseases. However, for engineered nanomaterials to reach their true potential, there are still a number of unanswered questions regarding nanomaterial vs. tissue properties that dictate lung cellular uptake, distribution, and intracellular effects, and particle vs. tissue factors that determine toxicity vs. beneficial effects in the lung. Some of these key questions are highlighted in this Perspectives. Addressing these important issues will help improve nanoparticle design and enhance enthusiasm for more widespread use of nanotechnology in pulmonary medicine.