Lung Fixation under Constant Pressure for Evaluation of Emphysema in Mice.

Emphysema is a significant feature of chronic obstructive pulmonary disease (COPD). Studies involving an emphysematous mouse model require optimal lung fixation to produce reliable histological specimens of the lung. Due to the nature of the lung's structural composition, which consists largely of air and tissue, there is a risk that it collapses or deflates during the fixation process. Various lung fixation methods exist, each of which has its own advantages and disadvantages. The lung fixation method presented here utilizes constant pressure to enable optimal tissue evaluation for studies using an emphysematous mouse lung model. The main advantage is that it can fix many lungs with the same condition at one time. Lung specimens are obtained from chronic cigarette smoke-exposed mice. Lung fixation is performed using specialized equipment that enables the production of constant pressure. This constant pressure maintains the lung in a reasonably inflated state. Thus, this method generates a histological specimen of the lung that is suitable to evaluate cigarette smoke-induced mild emphysema.

Usual Interstitial Pneumonia Pattern in the Lower Lung Lobes as a Prognostic Factor in Idiopathic Pleuroparenchymal Fibroelastosis.

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare interstitial pneumonia that is characterized by stiffness in both the upper lobes and pleura, which is evident on high resolution computed tomography (HRCT) of the chest. However, prognostic factors for IPPFE have not been identified yet. OBJECTIVE: We aimed to investigate the clinical prognostic factors affecting survival in patients with IPPFE. METHODS: Between April 2009 and September 2017, we enrolled 36 patients who were clinically diagnosed with IPPFE, using HRCT. These patients were classified as either short survival (dead within 12 months from the diagnosis of IPPFE) or long survival (survived for greater than 12 months) groups. We retrospectively analyzed the clinical characteristics, serum markers, pulmonary function test results, and HRCT findings. RESULTS: Twelve patients were classified into the short survival and 24 were categorized into long survival categories. At the time of diagnosis, the incidence of coexistence of a usual interstitial pneumonia (UIP) pattern in the lower lobes on HRCT in the short survival was significantly higher than that in the long survival. Multivariate analysis revealed that a UIP pattern in the lower lobes on HRCT was the only independent variable for poor prognosis. The median survival time from diagnosis in patients with IPPFE was 24 months. Of these patients with IPPFE, the survival time with a UIP pattern was significantly shorter than in those without a UIP pattern. CONCLUSION: Our findings suggest that a UIP pattern in the lower lobes at the time of diagnosis was an independent prognostic factor for IPPFE.

Regional heterogeneity in response of airway epithelial cells to cigarette smoke.

BACKGROUND: Cigarette smoke (CS) exposure causes an abnormal inflammatory response, which can result in chronic obstructive pulmonary disease (COPD). Previous studies show that this disorder predominantly occurs in peripheral or small-airway areas, whereas the same condition has not been identified in the larger airways during the course of COPD. However, the different biochemical and genetic alterations occurring in response to CS exposure among airway epithelial cells from different sites in the lungs have not been fully investigated. METHODS: Human small airway epithelial cells (SAECs) and normal human bronchial epithelial cells (NHBEs) were exposed to CS extract (CSE), and microarray analysis was used to determine gene- and protein-expression profiles and identify alterations following CSE exposure in both cell types. An in vivo smoking experiment was also performed to confirm differential responses to CS between sites in the lung. RESULTS: Microarray analysis of SAECs and NHBEs following 24 h of CSE exposure showed that inflammatory related pathways and terms, including the tumor necrosis factor-signaling pathway, were overrepresented, especially in SAECs. Clustering analysis highlighted prostaglandin-endoperoxide synthase-2 [also known as cyclooxygenase (COX)-2] as a gene specifically upregulated in SAECs, with COX-2 mRNA and protein expression significantly elevated by CSE exposure in SAECs (3.1- and 3.1-fold, respectively), but not in NHBEs. Furthermore, time-course analysis of COX-2 expression revealed earlier increases in SAECs compared with NHBEs following CS exposure. Short-term exposure of mouse lungs to CS was found to predominantly induce COX-2 expression in the small airway. CONCLUSIONS: The small airway is more susceptible to CSE than the large airway and could be the initial site of development of CS-related respiratory diseases, such as COPD.

A Case of a Pregnant Woman Diagnosed as Having ALK-rearranged Lung Adenocarcinoma.

A 28-year-old woman who was 34 weeks pregnant was admitted with complaints of cough and blood-stained sputum. After delivery of the baby at 37 weeks gestation, computed tomography and magnetic resonance imaging revealed a tumor in the right lung and a 15-mm brain metastasis. A diagnosis of lung adenocarcinoma was made, cT4N3M1b (stage IV disease) by pleural fluid cytology. Additional testing for anaplastic lymphoma kinase (ALK) fusion protein showed a strongly positive result, which was then confirmed by fluorescence in situ hybridization. The patient was started on treatment with alectinib, and the tumor and brain metastasis had almost vanished by 2 months after the start of this treatment. In the literature, there are 59 reports of lung cancer diagnosed during pregnancy, including two cases of cancer with expression of ALK fusion protein and five cases showing epidermal growth factor receptor mutation. The type of mutation should be taken into consideration while selecting for the appropriate therapeutic strategy.

Hydrogen-rich pure water prevents cigarette smoke-induced pulmonary emphysema in SMP30 knockout mice.

Chronic obstructive pulmonary disease (COPD) is predominantly a cigarette smoke (CS)-triggered disease with features of chronic systemic inflammation. Oxidants derived from CS can induce DNA damage and stress-induced premature cellular senescence in the respiratory system, which play significant roles in COPD. Therefore, antioxidants should provide benefits for the treatment of COPD; however, their therapeutic potential remains limited owing to the complexity of this disease. Recently, molecular hydrogen (H2) has been reported as a preventive and therapeutic antioxidant. Molecular H2 can selectively reduce hydroxyl radical accumulation with no known side effects, showing potential applications in managing oxidative stress, inflammation, apoptosis, and lipid metabolism. However, there have been no reports on the efficacy of molecular H2 in COPD patients. In the present study, we used a mouse model of COPD to investigate whether CS-induced histological damage in the lungs could be attenuated by administration of molecular H2. We administered H2-rich pure water to senescence marker protein 30 knockout (SMP30-KO) mice exposed to CS for 8 weeks. Administration of H2-rich water attenuated the CS-induced lung damage in the SMP30-KO mice and reduced the mean linear intercept and destructive index of the lungs. Moreover, H2-rich water significantly restored the static lung compliance in the CS-exposed mice compared with that in the CS-exposed H2-untreated mice. Moreover, treatment with H2-rich water decreased the levels of oxidative DNA damage markers such as phosphorylated histone H2AX and 8-hydroxy-2'-deoxyguanosine, and senescence markers such as cyclin-dependent kinase inhibitor 2A, cyclin-dependent kinase inhibitor 1, and ß-galactosidase in the CS-exposed mice. These results demonstrated that H2-rich pure water attenuated CS-induced emphysema in SMP30-KO mice by reducing CS-induced oxidative DNA damage and premature cell senescence in the lungs. Our study suggests that administration of molecular H2 may be a novel preventive and therapeutic strategy for COPD.

Lung metastases from cutaneous adenoid cystic carcinoma 23 years after initial treatment.

Cutaneous adenoid cystic carcinoma (CACC) is an extremely rare neoplasm of head and neck region, and is characterized by propensity for local recurrence and perineural invasion. Late distant metastases occur usually to lungs. Although patients with lung metastases from CACC cannot be cured, long-term survival may be possible due to its slow-growing malignancy. We report a case of a 69-year-old female with lung metastases from CACC 23 years after initial surgery of scalp nodule.

Loxoprofen-induced interstitial pneumonia: a case report.

BACKGROUND: Loxoprofen is a nonsteroidal anti-inflammatory drug used in the treatment of many diseases. However, there are no case reports about loxoprofen-induced pneumonia. We have encountered a rare case of loxoprofen-induced pneumonia. CASE PRESENTATION: We report the case of a 71-year-old Japanese woman who was initially treated with loxoprofen for fever. She was admitted to our hospital because of worsening of her symptoms, including fever and dyspnea. Her symptoms improved after treatment with ceftriaxone. Seven days after admission, she again developed high fever. She was again treated with loxoprofen and levofloxacin. However, acute respiratory failure developed after initiation of loxoprofen treatment. Chest computed tomography showed peribronchovascular consolidation. She was diagnosed with loxoprofen-induced pneumonia for which she was administered steroids. After treatment, her dyspnea and radiological findings improved. CONCLUSIONS: The findings in this case report reveal an association between treatment with a nonsteroidal anti-inflammatory drug and pneumonia. This rare case was diagnosed after accidental retreatment with loxoprofen. This is the first report of loxoprofen-induced pneumonia.