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A 72-year-old man was treated with prednisolone and cyclosporine A for idiopathic pulmonary fibrosis. A nodule with a diameter of 19 mm was found in the right lung and diagnosed as lung squamous cell carcinoma. Anti-cancer treatments were not performed because of the presence of advanced interstitial pneumonia and chronic respiratory failure. Cyclosporine A was tapered to avoid suppression of anti-tumor immunity, and pirfenidone was initiated. Within 2 months, the tumor had shrunk to 10 mm in diameter and remained regressed for 9 months. This is the first report of a non-hematologic solid organ tumor responding to the discontinuation of immunosuppressants.

A 44-year-old man developed coronavirus disease 2019 (COVID-19) pneumonia during immunochemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab for non-small cell lung cancer. Low-grade fever, followed by mild hypoxemia, and febrile neutropenia, were observed, and granulocyte colony-stimulating factor (G-CSF) was administered until the recovery of neutropenia, when he developed a high fever, severe hypoxemia, and hypotension accompanied by consolidation in the bilateral lungs. His conditions promptly improved after treatment including hydrocortisone and the primary and metastatic tumors remained regressed for 10 months without further treatment. Post-COVID-19 organizing pneumonia during cancer immunochemotherapy can be aggravated by immune-checkpoint inhibitors and G-CSF.

Unilateral absence of the pulmonary artery (UAPA) with or without other anomalies in the heart is a rare congenital malformation. A 55-year-old Filipino woman without a remarkable medical history was admitted to our hospital for hemoptysis. Contrast-enhanced chest computed tomography revealed the absence of the left pulmonary artery. Echocardiography and right heart catheterization showed no cardiac malformations or pulmonary hypertension. We diagnosed her with isolated left-sided UAPA and performed transarterial embolization of the left inferior phrenic artery. This resolved the hemoptysis, and there was no recurrence during the four-year follow-up period.

Post-bronchoscopy pneumonia can affect the prognosis of lung cancer patients. This prospective study examined the efficacy of prophylactic antibiotics for lung cancer patients at high-risk of post-bronchoscopy pneumonia, determined by our prediction score, using three risk factors: age 70 years or older, current smoking, and central tumors visualized on CT.Patients with lung cancer who underwent diagnostic bronchoscopy between June 2018 and March 2020 with a score of 2 points or higher were enrolled. Sulbactam/ampicillin was administered intravenously within one hour prior to bronchoscopy, followed by oral clavulanate/amoxicillin for three days. We used the data of lung cancer patients who underwent diagnostic bronchoscopy between April 2012 and July 2014 and exhibited a score of 2 or higher as the historical control.Post-bronchoscopy pneumonia occurred in none of the 24 patients in the prophylaxis group and in 17 of 144 patients in the control group, with no significant difference in the incidence of pneumonia between the two groups.Antibiotic prophylaxis can be effective and safe for the patients high-risk of post-bronchoscopy pneumonia. A multicenter prospective study to examine the effects of prophylactic antibiotics in high-risk patients is feasible with a modest number of participants.

An 82-year-old woman with a history of chronic thromboembolic pulmonary hypertension (CTEPH) presented with malaise, left facial nerve paralysis and the positive seroconversion of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA). She was diagnosed with ANCA-associated vasculitis (AAV). Administration of corticosteroids significantly improved her symptoms, with a decline in the serum MPOANCA level. Ten months later than the initial presentation, she developed an AAV exacerbation with lung infiltration and pericardial effusion, which improved with high-dose corticosteroid therapy. To date, a limited number of AAV cases concomitant with pulmonary hypertension have been reported. The case report presented herein suggests a potential role for CTEPH in the development of AAV.

Background People with human immunodeficiency virus (PWH) have an increased risk of developing chronic obstructive pulmonary disease (COPD). Methods We phenotyped lung macrophages in 4 subgroups—M1 (CD40+CD163−), M2 (CD40−CD163+), double positives (CD40+CD163+), and double negatives and (CD40−CD163−)—and we determined their phagocytic capacity in PWH with and without COPD. Results People with human immunodeficiency virus with COPD have more double-negative macrophages (84.1%) versus PWH without (54.3%) versus controls (23.9%) (P=.004) and reduced phagocytosis (P=.012). Double-negative macrophages had the worst phagocytic capacity (P Conclusions People with human immunodeficiency virus with COPD have an abundance of nonpolarized macrophages, which have poor phagocytic capacity and therefore predispose PWH to increased risk of disease progression.

Malignant pleural effusions (MPEs) deteriorate the quality of life in patients with advanced stages of cancer. Although vascular endothelial growth factor (VEGF) is known to be a key factor for MPE formation, it is not fully clarified whether there are other components related to its appearance.Pleural effusion and serum samples were collected from patients with MPEs of non-small cell lung cancer. Cellular analysis of pleural effusion was performed using fluorescence flow cytometry. The concentrations of 12 cytokines, chemokines, and growth factors in MPEs and serum samples were analyzed using the cytometric bead array method.Fifteen patients (median age: 70 years, 11 males) with non-small cell lung cancer (13 adenocarcinoma, 2 squamous cell carcinoma) were enrolled in this study. Concentrations of VEGF, interleukin (IL)-5, IL-6, IL-8, IL-12/IL-23p40, and C-C motif chemokine ligand (CCL) 2 were significantly higher in MPE than in serum. Pleural IL-5 levels correlated with malignant cell numbers in MPE. There was no factor related to the total amount of drained effusion or period of chest tube insertion.Production of six molecules were increased in the pleural cavity with MPE of non-small cell lung cancer. Complex interactions among these molecules may regulate MPE formation.

BackgroundAlthough development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years.MethodsFrom our hospital database, 1,699 patients, registered as lung cancer between 1stMar 2004 and 30thApr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13thFeb 2017.ResultsThere were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response.ConclusionsMultiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV.This study was retrospectively registered on 16thJun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).

BACKGROUND AND OBJECTIVES Chronic obstructive pulmonary disease (COPD) mainly develops after long-term exposure to cigarette or biomass fuel smoke, but also occurs in non-smokers with or without a history of asthma. We investigated the proportion and clinical characteristics of non-smokers among middle-aged to elderly subjects with airflow obstruction. METHODS We retrospectively analyzed 1,892 subjects aged 40-89 years who underwent routine preoperative spirometry at a tertiary university hospital in Japan. Airflow obstruction was defined as a forced expiratory volume in 1 second (FEV1)/forced vital capacity < 0.7 or as the lower limit of the normal. RESULTS Among 323 patients presenting with FEV1/forced vital capacity < 0.7, 43 had asthma and 280 did not. Among the non-asthmatic patients with airflow obstruction, 94 (34%) were non-smokers. A larger number of women than men with airflow obstruction had asthma (26% vs. 7.6%, p < 0.001), or were non-smokers among non-asthmatics (72% vs. 20%, p < 0.001). Non-asthmatic non-smokers, rather than non-asthmatic smokers, asthmatic non-smokers, and asthmatic smokers, exhibited better pulmonary function (median FEV1: 79% of predicted FEV1 vs. 73%, 69%, and 66%, respectively, p = 0.005) and less dyspnea on exertion (1% vs. 12%, 12%, and 28%, respectively, p = 0.001). Pulmonary emphysema on thoracic computed tomography was less common in non-smokers (p < 0.001). Using the lower limit of the normal to define airflow obstruction yielded similar results. CONCLUSIONS There are a substantial number of non-smokers with airflow obstruction compatible with COPD in Japan. In this study, airflow obstruction in non-smokers was more common in women and likelier to result in mild functional and pathological abnormalities than in smokers. Further studies are warranted to investigate the long-term prognosis and appropriate management of this population in developed countries, especially in women.

Background Exhaled volatile organic compounds (VOC) are being considered as biomarkers for various lungs diseases, including cancer. However, the accurate measurement of extremely low concentrations of VOC in expired air is technically challenging. We evaluated the clinical contribution of exhaled VOC measured with a new, double cold-trap method in the diagnosis of lung cancer. Methods Breath samples were collected from 116 patients with histologically confirmed lung cancer and 37 healthy volunteers (controls) after inspiration of purified air, synthesized through a cold-trap system. The exhaled VOC, trapped in the same system, were heat extracted. We analyzed 14 VOC with gas chromatography. Results The concentrations of exhaled cyclohexane and xylene were significantly higher in patients with lung cancer than in controls (p = 0.002 and 0.0001, respectively), increased significantly with the progression of the clinical stage of cancer (both p < 0.001), and decreased significantly after successful treatment of 6 patients with small cell lung cancer (p = 0.06 and 0.03, respectively). Conclusion Measurements of exhaled VOCs by a double cold-trap method may help diagnose lung cancer and monitor its progression and regression.

Patient: Male, 66 Final Diagnosis: Endobronchial hamartoma Symptoms: Fever Medication: — Clinical Procedure: Flexible bronchoscopy • surgical resection Specialty: Pulmonology Objective: Unusual clinical course Background: Post-obstructive pneumonia occurs in the presence of airway obstruction, usually caused by lung cancer. However, there are cases of bronchial obstruction due to benign origin such as foreign bodies and benign endobronchial tumors, which are often misdiagnosed. Case Report: A 66-year-old man was referred to our hospital due to high fever with abnormal shadow in the right lung. Chest computed tomography after a course of antibiotic treatment showed an intra-bronchial tumor obstructing the right upper bronchus. Part of the tumor was removed with flexible bronchoscopy, and histopathological examination revealed cartilage tissue but not fat or other components. Lobectomy of the right upper lobe of the lung was performed to make a definite diagnosis and prevent recurrent obstructive pneumonia. The resected tumor contained mature cartilage and fat tissues, and was diagnosed as endobronchial hamartoma. Conclusions: Benign endobronchial tumors such as hamartomas should be considered in the differential diagnosis of post-obstructive pneumonia.

Various volatile organic compounds (VOCs) are known to be toxic. Although exhaled VOC patterns change in obstructive sleep apnea (OSA) patients, individual VOC profiles are not fully determined. The primary outcome was VOC characterizations; secondary outcomes included their relationships with sleep and clinical parameters in OSA patients. We prospectively examined 32 OSA patients with an apnea-hypopnea index (AHI) ≥ 15 by full polysomnography, and 33 age- and sex-matched controls without obvious OSA symptoms. Nine severe OSA patients were examined before and after continuous positive airway pressure (CPAP) treatment. By applying a method which eliminates environmental VOC influences, exhaled VOCs were identified by gas chromatography (GC)-mass spectrometry, and their concentrations were determined by GC. Exhaled aromatic hydrocarbon concentrations (toluene, ethylbenzene, p-xylene, and phenylacetic acid) in the severe OSA groups (AHI ≥ 30) and exhaled saturated hydrocarbon concentrations (hexane, heptane, octane, nonane, and decane) in the most severe OSA group (AHI ≥ 60) were higher than those in the control group. Exhaled isoprene concentrations were increased in all OSA groups (AHI ≥ 15); acetone concentration was increased in the most severe OSA group. Ethylbenzene, p-xylene, phenylacetic acid, and nonane concentrations were increased according to OSA severity, and correlated with AHI, arousal index, and duration of percutaneous oxygen saturation (SpO2) ≤ 90%. Multiple regression analyses revealed these 4 VOC levels were associated with the duration of SpO2 ≤ 90%. Isoprene and acetone decreased after CPAP treatment. OSA increased some toxic VOCs, and some correlated with OSA severity. CPAP treatment possibly ameliorates these productions.

The incidence, risk factors, and consequences of pneumonia after flexible bronchoscopy in patients with lung cancer have not been studied in detail.We retrospectively analyzed the data from 237 patients with lung cancer who underwent diagnostic bronchoscopy between April 2012 and July 2013 (derivation sample) and 241 patients diagnosed between August 2013 and July 2014 (validation sample) in a tertiary referral hospital in Japan. A score predictive of post-bronchoscopy pneumonia was developed in the derivation sample and tested in the validation sample.Pneumonia developed after bronchoscopy in 6.3% and 4.1% of patients in the derivation and validation samples, respectively. Patients who developed post-bronchoscopy pneumonia needed to change or cancel their planned cancer therapy more frequently than those without pneumonia (56% vs. 6%, p0.001). Age ≥70 years, current smoking, and central location of the tumor were independent predictors of pneumonia, which we added to develop our predictive score. The incidence of pneumonia associated with scores=0, 1, and ≥2 was 0, 3.7, and 13.4% respectively in the derivation sample (p=0.003), and 0, 2.9, and 9.7% respectively in the validation sample (p=0.016).The incidence of post-bronchoscopy pneumonia in patients with lung cancer was not rare and associated with adverse effects on the clinical course. A simple 3-point predictive score identified patients with lung cancer at high risk of post-bronchoscopy pneumonia prior to the procedure.

We report a case of multifocal micronodular pneumocyte hyperplasia (MMPH) in a patient with tuberous sclerosis complex, in whom the lung nodules increased in the number and size over the course of 8 years. We diagnosed MMPH following a lung biopsy performed during video-assisted thoracic surgery. In most of the previously reported cases, the number and size of lung nodules is unchanged during the clinical course. Our case is the first report of progressive disease in pathologically proven MMPH.

Asthma and COPD, once regarded as distinct disease entities, often overlaps especially in the elderly and smokers. GINA/GOLD joint document 2014 has proposed a clinical entity of ACOS (asthma-COPD overlap syndrome) characterized by irreversible airflow limitation with clinical features of both asthma and COPD, although evidences for definite diagnosis and treatment are limited. ACOS includes several different phenotypes such as severe asthma with airway remodeling, incomplete airflow reversibility as a consequence of childhood asthma and smoking, eosinophilic phenotype of COPD, and so on. Considering the therapeutic modalities currently available for asthma and COPD, it is important to identify the patients who respond well to inhaled corticosteroids.

A 64-year-old man presented with diplopia, muscle weakness, a pulmonary nodule and mediastinal widening on a chest radiograph. He was diagnosed with clinical stage IIIA (T2aN2M0) lung cancer. His neurological symptoms worsened following the initiation of thoracic radiation therapy (60 Gy) and chemotherapy. A diagnosis of myasthenia gravis (MG) was confirmed with a repetitive nerve stimulation test that showed a waning pattern, and a positive edrophonium test, although neither anti-acetylcholine receptor antibodies nor anti-muscle-specific tyrosine kinase antibodies were detected. The ptosis and limb muscle weakness improved with prednisolone and acetylcholinesterase inhibitor treatment, and a partial response of the lung cancer to chemoradiotherapy was obtained. However, the ptosis and limb muscle weakness worsened again following a recurrence of the lung cancer. The herein described case, in which lung cancer and MG occurred and recurred simultaneously, suggests that MG can develop as a paraneoplastic syndrome of lung cancer.

Massive hemoptysis mostly arises from the bronchial arteries; however, bleeding can also occur from a lesion in injured pulmonary arteries, such as pulmonary artery aneurysm/pseudoaneurysm (PAA/PAP), during pulmonary infection.A 66-year-old man was admitted with a diagnosis of lung abscess in the right lower lobe that was complicated with pyothorax. Intravenous administration of antibiotics and thoracic drainage successfully controlled the infection and inflammation until day 16, when the patient began to exhibit hemoptysis and bloody pleural effusion. Enhanced computed tomography (CT) with multi-planer reconstruction (MPR) images showed a highly enhanced mass inside the abscess fed by the pulmonary artery, suggesting PAA/PAP. Pulmonary angiography confirmed PAA/PAP, and embolization with coils successfully stopped both the bleeding into the sputum and pleural effusion, with a collapsed aneurysm visible on chest CT scan.Clinicians should consider the possibility of PAA/PAP in the differential diagnosis of hemoptysis during the treatment of patients with lung abscess. MPR CT is helpful for the diagnosis of PAA/PAP and its feeding vessels.

We report 3 cases (all men, age: 69-81 years) of acute exacerbation of interstitial pneumonia (AEIP) that were successfully treated with a high-flow nasal cannula (HFNC), which delivers heated, humidified gas at a fraction of inspired oxygen (FIO2) up to 1.0 (100%). Oxygenation was insufficient under non-rebreathing face masks; however, the introduction of HFNC with an FIO2 of 0.7-1.0 (flow rate: 40 L/min) improved oxygenation and was well-tolerated until the partial pressure of oxygen in blood/FIO2 ratio increased (between 21 and 26 days). Thus, HFNC might be an effective and well-tolerated therapeutic addition to the management of AEIP.

A 79-year-old woman presented with unexplained hypoxia that became exacerbated by an upright posture (platypnea-orthodeoxia syndrome). A (99m)Tc-macroaggregated albumin pulmonary perfusion scan revealed a right to left shunt of 25.5% in the supine position and 32.3% in the sitting position. A dynamic CT scan and a transoesophageal echocardiogram confirmed the presence of a shunt across an atrial septal defect (ASD). A percutaneous transcatheter closure of the defect significantly improved the patient's blood oxygenation levels when she was in the upright position. An ASD should therefore be included in the differential diagnosis of platypnea-orthodeoxia syndrome, regardless of the patient's age.

The presence and severity of obstructive pulmonary diseases is important determinants of non-fatal and fatal postoperative complications. This study examined the characteristics of patients in need of perioperative drug therapy for obstructive pulmonary dysfunction.Among 2,358 surgical patients who, between September 2009 and February 2010, underwent spirometry at the Tokai University Hospital, the 333 whose forced expiratory volume in 1 second (FEV1) / forced vital capacity ratio was0.7 were studied retrospectively. Single and multiple variable logistic regression analyses were performed in search of predictors of need for drug therapy.Among the 230 men and 103 women (mean age = 68 ± 11 years) with obstructive pulmonary dysfunction, 108 (32%) received perioperative drug therapy with bronchodilators, inhaled corticosteroids or both. By multiple variable analysis, perioperative drug therapy was significantly correlated with a history of asthma and ever smoking, cough or sputum production, FEV150% predicted, and emphysema, independently of consultations with pulmonologists. In a decision tree analysis, FEV1 and smoking history were the independent predictors of perioperative drug therapy.Composite assessment of clinical history, respiratory symptoms, and pulmonary function is necessary for the efficient screening of the subjects who require perioperative drug therapy for obstructive pulmonary dysfunction.

A 61-year-old man was admitted for evaluation of an abnormal chest abnormal with progressive swelling in both hands, clubbing of all fingers and toes, and polyarthroceles. He was given a diagnosis of pulmonary hypertrophic osteoarthropathy (PHO) associated with primary lung cancer, and underwent an upper left lobectomy. Histopathological analysis revealed stage IIB adenocarcinoma of the lung with K-ras mutation, but with no evidence of epidermal growth factor receptor (EGFR). Postoperatively, his symptoms rapidly improved, and the preoperatively observed high levels of serum vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) decreased to normal levels after just 1 month. VEGF and IL-6 caused by the genetic mutation of K-ras might play a role in the pathogenesis of PHO with lung cancer.

We report a case of tuberculosis associated with hemophagocytic syndrome (HPS) which was complicated by treatment with infliximab for Crohn's disease. A 48-year-old woman was admitted because of fever, diarrhea and general malaise. Her condition did not improve with treatment for recurrence of Crohn's disease, and an abnormal shadow was pointed out on chest imaging. She was referred to our department and received a diagnosis of tuberculosis based on the results of smear and polymerase chain reaction examination of the sputum and bone marrow. HPS was suspected based on subsequent results such as hepatosplenomegaly, leukocytopenia, elevated ferritin, disseminated intravascular coagulation, hemophagocytosis of nucleated red cells, and leukocytes in the bone marrow. She was treated with antituberculous drugs, steroids and gamma globulin, and improved. A diagnosis of tuberculosis during the administration of infliximab therapy was very difficult because of atypical clinical symptoms and images e.g. the abscence of cavities or nodular shadows on her chest roentgenogram. To the best of our knowledge this case is the first report of tuberculosis associated with HPS, which was complicated by treatment with infliximab.