Rapid growth of primary pulmonary meningioma with hemoptysis.

While lung cancer is the predominant neoplasm causing hemoptysis, rare benign neoplasms can also be associated with hemoptysis. A 60-year-old woman presented with cough and hemoptysis. Chest computed tomography revealed an oval-shaped, well-circumscribed solitary mass (10 cm in size) in the right lower lobe, which had grown rapidly over the past year. The presence of intramass air bubbles and a surrounding halo of ground-glass opacities suggested the hemorrhagic rupture of a circumscribed hematoma into the surrounding lung tissue. Subsequent right lower lobectomy revealed a well-demarcated hematoma; its wall consisted of nonatypical spindle tumor cells, which were histologically diagnosed as meningioma. No meningioma was observed in the central nervous system, leading to the diagnosis of primary pulmonary meningioma. This case highlights PPM as a rare benign tumor (World Health Organization grade 1) capable of rapid development due to intratumoral hemorrhage, presenting with hemoptysis.

Bronchoscopic visualization of the inner cavity caused by Pasteurella multocida infection.

We report a 69-year-old man who presented to our hospital with cough and sputum production. He had been in close contact with six domestic cats. He had a smoking history of 40 pack-years and had been in close contact with six domestic cats. A chest computed tomography scan revealed multiple consolidations with cavities in both lung fields. Pasteurella multocida was cultured from his sputum. On bronchoscopic evaluation, the flexible bronchoscope was navigated through the right middle lobe bronchus, which opened inside the cavity, allowing visualization of a spider-web-appearing architecture consisting of many cord-like lung tissues loosely adherent to the cavity lumen. Using these findings, a diagnosis of cavity formation was made secondary to Pasteurella multocida infection. Pasteurella infection should be considered as a cause of a lung cavity in patients with chronic lung disease. History taking regarding animal exposure is important for its diagnosis.

Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system in vitro.

Fenofibrate (FF) is a peroxisome proliferator- activated receptor (PPAR)-α agonist that is widely used for the treatment of hyperlipidemia. It has been shown to have pleiotropic actions beyond its hypolipidemic effect. FF has been shown to exert a cytotoxic effect on some cancer cells when used at higher than clinically relevant concentrations; on the other hand, its cytoprotective effect on normal cells has also been reported. The present study assessed the effect of FF on cisplatin (CDDP) cytotoxicity to lung cancer cells in vitro. The results demonstrated that the effect of FF on lung cancer cells depends on its concentration. FF at ≤50 µM, which is a clinically achievable blood concentration, attenuated CDDP cytotoxicity to lung cancer cells, whereas FF at ≥100 µM, albeit clinically unachievable, had an anticancer effect. The mechanism of FF attenuation of CDDP cytotoxicity involved PPAR-α-dependent aryl hydrocarbon receptor (AhR) expression, which in turn stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and antioxidant production, resulting in lung cancer cell protection from CDDP-evoked oxidative damage. In conclusion, the present study revealed that FF, at clinically relevant concentrations, attenuated CDDP cytotoxicity to lung cancer cells by enhancing the antioxidant defense system through activation of a pathway that involves the PPAR-α-PPAR response element-AhR xenobiotic response element-Nrf2-antioxidant response element. These findings suggested that concomitant use of FF with CDDP may compromise the efficacy of chemotherapy. Although the anticancer property of FF has recently attracted much attention, concentrations that exceed clinically relevant concentrations are required.

Pulmonary miliary sarcoidosis masquerading the reactivation of tuberculosis 30 years later.

Key Clinical Message: Sarcoidosis may occur after treatment with pulmonary tuberculosis and requires differential diagnosis from tuberculosis reactivation. Miliary sarcoidosis should be promptly differentiated from miliary tuberculosis associated with high mortality. Abstract: Clinical, histological, and radiological similarities between sarcoidosis and tuberculosis render differential diagnosis challenging. The association between these two diseases has long been discussed, although the coexistence or subsequent occurrence of tuberculosis and sarcoidosis is rare. We report a case of miliary sarcoidosis that developed 30 years after tuberculous pleurisy treatment. Sarcoidosis may occur after treatment with pulmonary tuberculosis and requires differential diagnosis from tuberculosis reactivation. Although miliary sarcoidosis is uncommon, it should be promptly differentiated from miliary tuberculosis associated with high mortality. This study reignites the debate on the causal association between tuberculosis and sarcoidosis.

Black pleural effusion caused by a pancreaticopleural fistula secondary to chronic alcoholic pancreatitis exacerbation accompanying COVID-19.

Pancreaticopleural fistula should be considered in alcohol abusers with pleural effusion, which can exhibit a black color.

Effect of roflumilast on airway remodeling in asthmatic mice exposed to or not exposed to cigarette smoke: Comparison with the effect of dexamethasone.

Cigarette smoking constitutes a risk factor for severe asthma, which is frequently linked to remodeling of the airways. Appropriate drug treatment for smokers with asthma is uncertain because many smokers with asthma are less sensitive to glucocorticoid treatment than non-smokers with asthma. The purpose of this study was to compare the anti-airway remodeling effects of dexamethasone (Dex) and roflumilast (Rof), a selective phosphodiesterases-4 inhibitor, in smoking and non-smoking mice with asthma. BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with OVA for two weeks, either with or without concurrent exposure to cigarette smoke (CS). Dex (1 mg/kg body weight), Rof (5 mg/kg body weight), or vehicle alone was given orally to the mice once daily. To assess the histopathological effects of airway remodeling, lung tissue sections were obtained. Repeated OVA challenges resulted in fibrosis, goblet cell hyperplasia, and thickening of the airway but not the smooth muscle layer. The presence of CS did not have an impact on the degree of airway remodeling brought on by repeated OVA challenges. In mice repeatedly exposed to OVA either with or without CS, Dex treatment reduced the remodeling alterations. In these mice group, the Rof Treatment had a less significant impact than the Dex treatment. Dex was still more effective than Rof at reducing airway remodeling in asthmatic smoking mice. According to the current study's findings, Dex effectively prevented airway remodeling in a two-week asthma model in mice exposed to CS or not. In contrast, we found that Rof had little to no inhibitory effect of Rof on the airway in our mouse model of asthma, whether or not it had been exposed to CS. We were unable to find solid proof to support CS-induced steroid resistance to treat airway remodeling.

Neurogenic pulmonary edema caused by right insular cortex infarction.

We report a case of neurogenic pulmonary edema (NPE) caused by middle cerebral artery infarction involving the right insular cortex. Hyperactivity of the insular cortex, which regulates sympathetic function, can cause NPE. The NPE should be considered in the differential diagnosis of dyspneic patients with insular cortex infarction.

Subcutaneous abscess due to empyema necessitans caused by Porphyromonas gingivalis in a patient with periodontitis.

Empyema necessitans is a rare empyema complication characterized by an extension of empyema out of the pleural space into the subcutaneous tissues of the chest wall. We herein report a case of empyema necessitans that presented as a subcutaneous chest wall abscess caused by Porphyromonas gingivalis (P. gingivalis), an important anaerobic periodontal pathogen, in a 74-year-old woman with periodontitis. The patient was admitted to our hospital with a painful soft tissue mass in the chest wall extending from a subpleural lung abscess associated with empyema. Exploratory percutaneous puncture and aspiration of the chest wall mass yielded foul-smelling chocolate-colored pus, which was found to be caused due to infection with P. gingivalis. Treatment with antibacterials resulted in a relapse of empyema necessitans requiring a second admission 1 month later. An additive treatment with surgical open drainage and decortication of the subcutaneous abscess successfully cured the abscess. Physicians must be aware of emphysema necessitans as an etiology of a chest wall mass and should consider periodontitis as a source of infection.

Acute respiratory distress syndrome relapsing in 10 months with an initial manifestation of polymyositis.

Autoimmune disorders are an important cause of acute respiratory distress syndrome (ARDS). We report a case of a patient with steroid-responsive ARDS that relapsed in 10 months with an initial manifestation of seronegative polymyositis. ARDS associated with polymyositis may develop earlier than myopathy and may relapse later.

A case of nonislet cell tumor hypoglycemia associated with malignant mesothelioma requiring a multifaceted approach for optimal glycemic control.

Nonislet tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome characterized by refractory hypoglycemia, which often requires multifaceted therapy. We reported a case of a patient with pleural malignant mesothelioma and developed NICTH, for which chemotherapy, glucocorticoids, and nutrition were given to achieve optimal glycemic control.

A case of humidifier lung with a difficult differential diagnosis from COVID-19.

Acute respiratory illnesses that presented with diffuse ground-glass opacities (GGOs) on chest computed tomography (CT) scan suggest the diagnosis of coronavirus disease 2019 (COVID-19). However, many other diseases show similar CT findings, which often offer a difficult differential diagnosis. Here, we report a case of humidifier lung, a rare phenotype of hypersensitivity pneumonitis (HP), which mimicked COVID-19. A 71-year-old man was admitted because of dyspnea and diffuse GGOs found on chest CT scan. Although COVID-19 was initially suspected, his symptoms rapidly improved by the next day. A medical interview revealed that he had started using an ultrasonic humidifier 1 month ago. A high-resolution CT (HRCT) scan showed ill-defined centrilobular nodules and mosaic attenuation, which are typical of HP but atypical of COVID-19. The inhalation challenge test confirmed the diagnosis of humidifier lung. History-taking of humidifier use and a precise HRCT interpretation are helpful to differentiate it from COVID-19.

Fenofibrate inhibits TGF-ß-induced myofibroblast differentiation and activation in human lung fibroblasts in vitro.

Fenofibrate (FF), a peroxisome proliferator-activated receptor-alpha (PPAR-α) agonist and a lipid-lowering agent, can decrease experimental pulmonary fibrosis. However, the mechanisms underlying the antifibrotic effect of FF remain unknown. Hence, this study was conducted to evaluate the effects of FF on transforming growth factor-beta (TGF-ß)-induced myofibroblast differentiation and activation in lung fibroblasts. The results showed that FF inhibited alpha-smooth muscle actin (α-SMA) and connective tissue growth factor expression, collagen production, cell motility, SMAD3 phosphorylation and nuclear translocation, and metabolic reprogramming in TGF-ß-exposed cells. The inhibitory effect of FF did not decrease with the addition of a PPAR-α antagonist. Moreover, the inhibitory effect given by FF could not be reproduced with the addition of an alternative PPAR-α agonist. FF inhibited mitochondrial respiration. However, rotenone, a complex I inhibitor, did not suppress TGF-ß-induced myofibroblast differentiation. Furthermore, the TGF-ß-induced nuclear reduction of protein phosphatase, Mg2+ /Mn2+ -dependent 1A (PPM1A), a SMAD phosphatase, was inhibited by FF. These results showed that FF suppressed TGF-ß-induced myofibroblast differentiation and activation independent of PPAR-α activation and impaired mitochondrial respiration. In conclusion, this study provides information on the effects of FF on anti-TGF-ß mechanisms.

Differential effects of dexamethasone and roflumilast on asthma in mice with or without short cigarette smoke exposure.

Appropriate drug treatment for smoking asthmatics is uncertain because most smokers with asthma are less sensitive to treatment with glucocorticoids compared with non-smokers with asthma. We hypothesized that roflumilast (Rof), a selective phosphodiesterases-4 inhibitor regarded as an add-on therapy for chronic obstructive pulmonary disease, might be more effective than glucocorticoids for improving asthma in smokers. To investigate this hypothesis, we compared the therapeutic effects of dexamethasone (Dex) and Rof in a mouse model of ovalbumin-induced asthma with or without concurrent cigarette smoke (CS) exposure for 2 weeks. We found that recurrent asthma attacks increased lung tissue resistance. CS exposure in asthmatic mice decreased the central airway resistance, increased lung compliance, and attenuated airway hyper-responsiveness (AHR). CS exposure in asthmatic mice also increased the number of neutrophils and macrophages in the bronchoalveolar fluid. Treatment with Dex in asthmatic mice without CS exposure reduced airway resistance, AHR and airway eosinophilia. In asthmatic mice with CS exposure, however, Dex treatment unexpectedly increased lung tissue resistance and restored AHR that had been otherwise suppressed. Dex treatment in asthmatic mice with CS exposure inhibited eosinophilic inflammation but conversely exacerbated neutrophilic inflammation. On the other hand, treatment with Rof in asthmatic mice without CS exposure reduced airway resistance and airway eosinophilia, although the inhibitory effect of Rof on AHR was unremarkable. In asthmatic mice with CS exposure, Rof treatment did not exacerbate lung tissue resistance but modestly restored AHR, without any significant effects on airway inflammation. These results suggest that CS exposure mitigates sensitivity to both Dex and Rof. In asthmatic mice with CS exposure, Dex is still effective in reducing eosinophilic inflammation but increases lung tissue resistance, AHR and neutrophilic inflammation. Rof is ineffective in improving lung function and inflammation in asthmatic mice with CS exposure. This study did not support our initial hypothesis that Rof might be more effective than glucocorticoids for improving asthma in smokers. However, glucocorticoids may have a detrimental effect on smoking asthmatics.

Differential diagnosis of relapsing polychondritis from asthma by 18-fluoro-2-deoxyglucose positron emission tomography and computed tomography.

About a half of all patients with relapsing polychondritis show airway involvement, which is a major cause of morbidity and mortality from this disease. FDG-PET/CT is useful in the differential diagnosis of relapsing polychondritis from asthma.

Anti-cancer strategy targeting the energy metabolism of tumor cells surviving a low-nutrient acidic microenvironment.

OBJECTIVE: Tumor cells experience hypoxia, acidosis, and hypoglycemia. Metabolic adaptation to glucose shortage is essential to maintain tumor cells' survival because of their high glucose requirement. This study evaluated the hypothesis that acidosis might promote tumor survival during glucose shortage and if so, explored a novel drug targeting metabolic vulnerability to glucose shortage. METHODS: Cell survival and bioenergetics metabolism were assessed in lung cancer cell lines. Our in-house small-molecule compounds were screened to identify those that kill cancer cells under low-glucose conditions. Cytotoxicity against non-cancerous cells was also assessed. Tumor growth was evaluated in vivo using a mouse engraft model. RESULTS: Acidosis limited the cellular consumption of glucose and ATP, causing tumor cells to enter a metabolically dormant but energetically economic state, which promoted tumor cell survival during glucose deficiency. We identified ESI-09, a previously known exchange protein directly activated by cAMP (EAPC) inhibitor, as an anti-cancer compound that inhibited cancer cells under low-glucose conditions even when associated with acidosis. Bioenergetic studies showed that independent of EPAC inhibition, ESI-09 was a safer mitochondrial uncoupler than a classical uncoupler and created a futile cycle of mitochondrial respiration, leading to decreased ATP production, increased ATP dissipation, and fuel scavenging. Accordingly, ESI-09 exhibited more cytotoxic effects under low-glucose conditions than under normal glucose conditions. ESI-09 was also more effective than actively proliferating cells on quiescent glucose-restricted cells. Cisplatin showed opposite effects. ESI-09 inhibited tumor growth in lung cancer engraft mice. CONCLUSIONS: This study highlights the acidosis-induced promotion of tumor survival during glucose shortage and demonstrates that ESI-09 is a novel potent anti-cancer mitochondrial uncoupler that targets a metabolic vulnerability to glucose shortage even when associated with acidosis. The higher cytotoxicity under lower-than-normal glucose conditions suggests that ESI-09 is safer than conventional chemotherapy, can target the metabolic vulnerability of tumor cells to low-glucose stress, and is applicable to many cancer cell types.