Clinical utility of thoracoscopy in elderly tuberculous pleurisy patients under local anesthesia.

INTRODUCTION: Diagnosing tuberculous pleurisy is important in Japan because it currently has a moderate tuberculosis prevalence. However, physicians often have difficulty making a diagnosis. It was reported that thoracoscopy under local anesthesia is useful for the diagnosis of tuberculous pleurisy, but there are no reports focusing on elderly patients. METHODS: In this study, the usefulness of thoracoscopy under local anesthesia was evaluated in elderly patients. Among 170 patients who underwent thoracoscopy under local anesthesia at our hospital during 11 years from January 2008 to December 2018, those aged 75 years or older (n = 75) were investigated retrospectively. RESULTS: A total of 55 patients underwent thoracoscopy under local anesthesia for detailed examination of pleural effusion of unknown cause. Of these, 18 were diagnosed as tuberculous pleurisy. The median age was 82 years (range: 75-92 years). The diagnosis of tuberculous pleurisy was made in 11 patients in whom Mycobacterium tuberculosis was detected and in four patients whose pathological findings indicated epithelioid granuloma accompanied by caseous necrosis. Clinical diagnosis was made in the remaining three patients based on thoracoscopic findings of the pleural cavity and a high level of adenosine deaminase in pleural fluid. No serious complications attributable to the examination were observed in any patient. CONCLUSIONS: Thoracoscopy under local anesthesia was useful for the diagnosis of tuberculous pleurisy in elderly patients, with useful information being also obtained for the treatment of tuberculosis.

A case of invasive pulmonary aspergillosis diagnosed by transbronchial lung biopsy during treatment for diabetic ketoacidosis in a type 1 diabetic patient.

Invasive pulmonary aspergillosis (IPA) patients with non-hematological malignancy are far less than with hematological malignancy patients. We encountered a very rare case of IPA in which type 1 diabetes was the only conceivable risk factor. Further, according to the diagnostic categories of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria for IPA, the frequency of proven diagnosis is very low. Here we report a proven IPA, which rapidly developed when the patient with type 1 diabetes was being treated for diabetic ketoacidosis, which was successfully treated with the combination therapy of voriconazole (VRCZ) and micafungin (MCFG), based on early diagnosis using bronchoscopy.

Impact of emphysema on sputum culture conversion in male patients with pulmonary tuberculosis: a retrospective analysis.

BACKGROUND: Although cigarette smoking may have a negative impact on the clinical outcome of pulmonary tuberculosis (PTB), few studies have investigated the impact of smoking-associated lung diseases. Emphysema is a major pathological finding of smoking-related lung damage. We aimed to clarify the effect of emphysema on sputum culture conversion rate for Mycobacterium tuberculosis (MTB). METHODS: We retrospectively studied 79 male patients with PTB confirmed by acid-fast bacillus smear and culture at Jikei University Daisan Hospital between January 2015 and December 2018. We investigated the sputum culture conversion rates for MTB after starting standard anti-TB treatment in patients with or without emphysema. Emphysema was defined as Goddard score ≥ 1 based on low attenuation area < - 950 Hounsfield Unit (HU) using computed tomography (CT). We also evaluated the effect on PTB-related CT findings prior to anti-TB treatment. RESULTS: Mycobacterial median time to culture conversion (TCC) in 38 PTB patients with emphysema was 52.0 days [interquartile range (IQR) 29.0-66.0 days], which was significantly delayed compared with that in 41 patients without emphysema (28.0 days, IQR 14.0-42.0 days) (p < 0.001, log-rank test). Multivariate Cox proportional hazards analysis showed that the following were associated with delayed TCC: emphysema [hazard ratio (HR): 2.43; 95% confidence interval (CI): 1.18-4.97; p = 0.015), cavities (HR: 2.15; 95% CI: 1.83-3.89; p = 0.012) and baseline time to TB detection within 2 weeks (HR: 2.95; 95% CI: 1.64-5.31; p < 0.0001). Cavities and consolidation were more often identified by CT in PTB patients with than without emphysema (71.05% vs 43.90%; p = 0.015, and 84.21% vs 60.98%; p = 0.021, respectively). CONCLUSIONS: This study suggests that emphysema poses an increased risk of delayed TCC in PTB. Emphysema detection by CT might be a useful method for prediction of the duration of PTB treatment required for sputum negative conversion.

Emphysematous change with scleroderma-associated interstitial lung disease: the potential contribution of vasculopathy?

BACKGROUND: Pulmonary emphysema combined with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) occurs more often in smokers but also in never-smokers. This study aimed to describe a new finding characterized by peculiar emphysematous change with SSc-associated ILD (SSc-ILD). METHODS: We conducted a retrospective review of 21 consecutive patients with SSc-ILD diagnosed by surgical lung biopsy and focused on the radio-pathological correlation of the emphysematous change. RESULTS: Pathological pulmonary emphysema (p-PE) with SSc-ILD was the predominant complication in 16 patients (76.2%) with/without a smoking history, of whom 62.5% were never-smokers. A low attenuation area (LAA) within interstitial abnormality on high-resolution computed tomography (HRCT) was present in 31.3%. Diffusing capacity of the lung for carbon monoxide (DLCO) was lower, disease extent on HRCT higher, and intimal/medial thickening in muscular pulmonary arteries more common in the patients with p-PE with SSc-ILD. However, forced vital capacity (FVC) was well preserved regardless of whether p-PE was observed. Most SSc-ILD patients had pulmonary microvasculature changes in arterioles (90.5%), venules (85.7%), and interlobular veins (81.0%). CONCLUSIONS: Pulmonary emphysematous changes (LAA within interstitial abnormalities on HRCT and destruction of fibrously thickened alveolar walls) are specific and novel radio-pathological features of SSc-ILD. Peripheral vasculopathy may help to destroy the fibrously thickened alveolar walls, resulting in emphysematous change in SSc-ILD.

Ultrasonic humidifier lung with a reversed halo sign: A case report.

The reversed halo sign was initially reported as a representative computed tomography scan finding of cryptogenic organizing pneumonia. Since then, however, it has been reported in various diseases and is now considered a nonspecific finding. However, there are no cases of humidifier lung with the reversed halo sign. An 82-year-old Japanese male patient presented with moving difficulties 48 days after starting darolutamide treatment for prostate cancer. He was admitted to the hospital due to acute pneumonia, which presented as bilateral extensive nonsegmental ground-glass opacities in the peripheral regions and extensive areas of ground-glass opacity with a circumferential halo of consolidation, with the reversed halo sign on computed tomography scan. After darolutamide discontinuation with the concomitant administration of antibiotics, the patient's pneumonia improved, and he was discharged from the hospital. However, within a few days, he was again admitted to the hospital due to pneumonia. He was found to have been using an ultrasonic humidifier at home and was then diagnosed with humidifier lung based on the bronchoscopy and provocative testing findings. Hence, ultrasonic humidifier lung should be considered as a differential diagnosis in patients presenting with the reversed halo sign, and a detailed medical history must be taken.

Association between serum ferritin level and decreased diffusion capacity 3 months after the onset of COVID-19 pneumonia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pneumonia can have prolonged sequelae and lead to respiratory dysfunction, mainly because of impaired diffusion capacity for carbon monoxide (DLCO). The clinical factors associated with DLCO impairment, including blood biochemistry test parameters, remain unclear. METHODS: Patients with COVID-19 pneumonia who underwent inpatient treatment between April 2020 and August 2021 were included in this study. A pulmonary function test was performed 3 months after onset, and the sequelae symptoms were investigated. Clinical factors, including blood test parameters and abnormal chest shadows on computed tomography, of COVID-19 pneumonia associated with DLCO impairment were investigated. RESULTS: In total, 54 recovered patients participated in this study. Twenty-six patients (48%) and 12 patients (22%) had sequelae symptoms 2 and 3 months after, respectively. The main sequelae symptoms at 3 months were dyspnea and general malaise. Pulmonary function tests showed that 13 patients (24%) had both DLCO <80% predicted value (pred) and DLCO/alveolar volume (VA) <80% pred, and appeared to have DLCO impairment not attributable to an abnormal lung volume. Clinical factors associated with impaired DLCO were investigated in multivariable regression analysis. Ferritin level of >686.5 ng/mL (odds ratio: 11.08, 95% confidence interval [CI]: 1.84-66.59; p = 0.009) was most strongly associated with DLCO impairment. CONCLUSIONS: Decreased DLCO was the most common respiratory function impairment, and ferritin level was a significantly associated clinical factor. Serum ferritin level could be used as a predictor of DLCO impairment in cases of COVID-19 pneumonia.

Impact of emphysema on the prognosis of Mycobacterium avium complex pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major comorbid disease of Mycobacterium avium complex pulmonary disease (MAC-PD). Emphysema is one of the main pathological findings in COPD, a risk factor for chronic pulmonary aspergillosis (CPA), and is associated with poor prognosis. We aimed to clarify the effect of emphysema on mortality in MAC-PD. METHODS: We retrospectively analyzed 203 patients with MAC-PD at The Jikei Daisan Hospital between January 2014 and December 2018. We investigated the mortality and CPA development rates after MAC-PD diagnosis in patients with or without emphysema. RESULTS: Multivariate Cox proportional hazards regression analysis showed the following negative prognostic factors in patients with MAC-PD: emphysema (hazard ratio [HR]: 11.46; 95% confidence interval [CI]: 1.30-100.90; P = 0.028); cavities (HR: 3.12; 95% CI: 1.22-7.94; P = 0.017); and low body mass index (<18.5 kg/m2) (HR: 4.62; 95% CI: 1.63-13.11; P = 0.004). The mortality and occurrence of CPA were higher in MAC-PD patients with than without emphysema (log-rank test, P < 0.0001 and P < 0.0001). CONCLUSION: Our study findings showed that emphysema detected by computed tomography was associated with an increased risk of CPA development and mortality in MAC-PD.

Solitary pulmonary nodule caused by pulmonary Mycobacterium lentiflavum infection.

An 82-year-old Japanese man who previously had descending colon cancer and underwent partial resection showed a growing solitary pulmonary nodule, suspected as lung cancer, on follow-up computed tomography. Thoracoscopic partial lobectomy was therefore performed. The surgical specimen showed granulomatous lesions with necrosis. Mass spectrometry was performed on the sputum specimen collected after surgery, which identified Mycobacterium lentiflavum infection. Antibiotics were not prescribed following surgery, and the patient has not experienced recurrence 2 years since the surgery. To our knowledge, this is the second case of solitary pulmonary nodule and the first case of M. lentiflavum infection treated via surgical resection.

Long-lasting response to afatinib that persisted after treatment discontinuation in a case of EGFR-mutated lung adenocarcinoma.

It is unknown whether tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGFR) can be discontinued in patients in whom EGFR-mutated lung cancer has well stabilised. We present a case of a 73-year-old Japanese woman with no history of smoking. Right pulmonary lower lobectomy, lymph node dissection and segmental resection of the right middle lobe were performed. Additionally, she underwent adjuvant chemotherapy for stage IIIB adenocarcinoma harbouring an EGFR exon 19 deletion. Afatinib was administered for liver metastases after 15 months. A complete response of metastatic disease was achieved for 2 years. However, afatinib was unavoidably discontinued due to splenectomy for the treatment of idiopathic thrombocytopenic purpura. Although afatinib was not resumed, due to the abscess formation as surgery complication, a drug-free complete response was sustained for over 18 months. The present case suggests that exceptional and durable responses to afatinib can be achieved in individual cases.

Pulmonary alveolar proteinosis developing during steroid treatment in a patient with organizing pneumonia in association with atypical chronic myeloid leukemia.

Organizing pneumonia (OP) and pulmonary alveolar proteinosis (PAP) are rare complications in patients with hematologic disorders. We herein report a case of PAP that developed during steroid treatment for OP in a patient with atypical chronic myeloid leukemia. Physicians should pay close attention to these complications in patients with hematologic malignancies.

Radiological images of interstitial pneumonia in mixed connective tissue disease compared with scleroderma and polymyositis/dermatomyositis.

OBJECTIVE: Little has been reported on the radiological and pathological findings of interstitial pneumonia in mixed connective tissue disease (MCTD). There may be possible difference in treatment response and prognosis between the imaging patterns of systemic sclerosis (SSc)-like and polymyositis/dermatomyositis (PM/DM)-like. The purpose of this study was to examine whether the radiological images of interstitial pneumonia in MCTD presented SSc-like or PM/DM-like pattern, and to assess whether the imaging patterns corresponded to clinical and pathological features. MATERIALS AND METHODS: This retrospective study included 29 patients with interstitial pneumonia who underwent surgical lung biopsy; 10 with SSc, 10 with PM/DM, and 9 with MCTD. High resolution computed tomography (HRCT) images were classified as SSc, PM/DM, or the other pattern by two radiologists independently without clinical information. The pathology of the lung specimens from MCTD patients were evaluated and compared with the imaging pattern. RESULTS: The concordance rate between clinical diagnosis and radiological pattern was 100% in SSc patients, and 80% in PM/DM patients. Among patients with MCTD, imaging patterns were classified as SSc pattern in 4 (MCTD-SSc), PM/DM pattern in 4 (MCTD-PM/DM) and other in one. The imaging patterns did not always correlate with the clinical findings in MCTD patients. Pathologically, plasma cell infiltration and organizing pneumonia were relatively more frequent in MCTD-PM/DM, and smooth muscle hyperplasia was relatively more frequent in MCTD-SSc. CONCLUSION: HRCT images in MCTD patients can be classified as SSc pattern or PM/DM pattern. MCTD-SSc and MCTD-PM/DM were corresponded to similar pathological findings of SSc and PM/DM.

Pathologically Proven Spontaneous Remission of IgG4-related Retroperitoneal Fibrosis.

Some forms of idiopathic retroperitoneal fibrosis (RF) have recently been considered to be a part of the spectrum of immunoglobulin G4 (IgG4)-related disease. This case report is the first description of a spontaneous remission in a patient with pathologically proven IgG4-related RF. Although the pathogenesis and long-term disease behavior of IgG4-related RF remains unknown, we believe that an initial assessment consisting of only careful monitoring might be one important strategy, especially in asymptomatic IgG4-related RF patients without nephropathy, while carefully monitoring these patients for the risk of recurrence.

A case of bilateral hilar and mediastinal lymphadenopathy developing during treatment for Mycobacterium avium complex.

We report a rare case of an immunocompetent patient with Mycobacterium avium complex (MAC) disease in which bilateral hilar lymphadenopathy developed during anti-MAC treatment. This case indicates that Propionibacterium acnes would be present and might be a cause of sarcoidosis even in patients with MAC.

Afatinib Therapy for Brain Metastases Aggravated by a Reduction in the Dose of Erlotinib Due to the Development of Hepatotoxicity.

We report an 80-year-old woman with EGFR-mutant lung adenocarcinoma with multiple brain metastases (BMs). All lesions including BM showed a successful resolution after initiating daily 150 mg erlotinib. However, a grade 2 bilirubin-increase developed, and it was necessary to reduce the dose of erlotinib to 50 mg every other day, which aggravated BM. Switching erlotinib to afatinib led to the resolution of BM without an increase in the bilirubin level. Our results indicate that afatinib is an important treatment option when erlotinib-induced hepatotoxicity develops, regardless of the patients' age. Particularly in those patients with BM, switching to afatinib may be preferable to reducing the dose of erlotinib.

Desquamative Interstitial Pneumonia Complicated with IgG4-related Lung Disease.

As an idiopathic interstitial pneumonia, desquamative interstitial pneumonia (DIP) is an uncommon form of interstitial lung disease and is considered to be a smoking- or dust inhalation-related interstitial pneumonia in the majority of cases. However, the details regarding immunoglobulin G4 (IgG4)-related lung disease remain unclear and controversial. We herein report the first case of DIP complicated with IgG4-related lung disease. Even if a patient has a smoking history, we emphasize the importance of exploring the association between DIP and IgG4-related lung disease to clarify the pathogenesis of these two disorders.

A 16-year Follow-up Case of Interstitial Pneumonia with Systemic Sclerosis-rheumatoid Arthritis Overlap Syndrome.

Interstitial pneumonia is a common and major comorbidity affecting the prognosis of patients with systemic sclerosis (SSc). However, there are few reported cases of SSc-rheumatoid arthritis (RA) overlap-associated interstitial pneumonia. We herein report a case in which the clinical behavior and histopathology of interstitial pneumonia with SSc-RA overlap syndrome was followed over a long clinical course. When clinicians are deciding on the treatment strategy for patients with SSc-RA overlap syndrome-associated interstitial pneumonia, a pathological examination of a surgical lung biopsy may be useful.

Serum KL-6 and surfactant protein-D as monitoring and predictive markers of interstitial lung disease in patients with systemic sclerosis and mixed connective tissue disease.

BACKGROUND: Interstitial lung disease (ILD) is frequent complication of systemic sclerosis (SSc) and mixed connective tissue disease (MCTD). The disease is heterogeneous, and its outcome is unpredictable. Some patients have severe and progressive deterioration of ILD, which is the leading cause of mortality. We aimed to determine whether serum levels of Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) correlate with SSc/MCTD-associated ILD activity. METHODS: We retrospectively analyzed the medical records of 40 patients with SSc/MCTD-associated ILD: 29 patients with SSc and 11 patients with MCTD. Measurement of serum KL-6 and SP-D levels, pulmonary function tests, and high-resolution computed tomography (HRCT) performed in parallel were reviewed. RESULTS: Serum KL-6 correlated positively with diffusing capacity of the lung for carbon monoxide (DLCO) (% predicted) and disease extent on HRCT, and the changes in serum levels of KL-6 were significantly related to the changes in forced vital capacity (FVC) in SSc/MCTD-associated ILD. On the other hand, multivariate logistic regression analyses with calculation of the area under the curve of the receiver-operating characteristic curve suggested that a higher serum level of SP-D was a significant predictor of FVC decline in SSc/MCTD-associated ILD. CONCLUSIONS: Our study suggests that serum KL-6 can be a useful monitoring tool of SSc/MCTD-associated ILD activity. In contrast, serum SP-D may be a significant predictor of potential FVC decline in the short term.

Low body surface area predicts hepatotoxicity of nintedanib in patients with idiopathic pulmonary fibrosis.

After the commercialization of nintedanib in Japan, a high incidence of hepatotoxicity resulting in treatment interruption was noted in idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib in our hospital. This study aimed to clarify the risk factors for hepatotoxicity of nintedanib. Sixty-eight consecutive cases of IPF newly treated with nintedanib at a dose of 150 mg twice daily from September 2015 to September 2016 were enrolled: 46 patients (67.6%) exhibited aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) elevation and 16 patients (23.5%) also had a Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2. Body surface area (BSA) was significantly lower in the CTCAE grade ≥2 group than in another group. A multivariate logistic regression analysis showed that the association between BSA and AST/ALT elevation with CTCAE grade ≥2 was statistically significant. Eight of 10 patients who resumed nintedanib at a reduced dose of 100 mg twice daily after interruption due to hepatotoxicity did not again develop AST/ALT elevation. In conclusion, a low BSA was associated with hepatotoxicity of nintedanib at a dose of 150 mg twice daily. It would be a good option for patients with a small physique to start nintedanib at a dose of 100 mg twice daily and then increase if possible after confirming its safety.

A case of severe arthralgia with malignant mesothelioma-associated hypertrophic osteoarthropathy.

Hypertrophic osteoarthropathy (HOA) is a rare syndrome characterized by the abnormal proliferation of dermato-osseous tissue. We report a rare case of malignant mesothelioma-associated HOA who suffered from refractory painful osteoarthropathy. HOA can be associated with malignant mesothelioma and that may be resistant to any treatment.

Clinical Features of Idiopathic Interstitial Pneumonia with Systemic Sclerosis-Related Autoantibody in Comparison with Interstitial Pneumonia with Systemic Sclerosis.

BACKGROUND: Patients with idiopathic interstitial pneumonias sometimes have a few features of connective tissue disease (CTD) and yet do not fulfil the diagnostic criteria for any specific CTD. OBJECTIVE: This study was conducted to elucidate the characteristics, prognosis, and disease behavior in patients with interstitial lung disease (ILD) associated with systemic sclerosis (SSc)-related autoantibodies. METHODS: We retrospectively analyzed medical records of 72 ILD patients: 40 patients with SSc (SSc-ILD) and 32 patients with SSc-related autoantibody-positive ILD but not with CTD (ScAb-ILD), indicating lung-dominant CTD with SSc-related autoantibody. RESULTS: Patients with SSc-ILD were predominantly females and non-smokers, and most had nonspecific interstitial pneumonia confirmed by high-resolution computed tomography (HRCT) and pathological analysis. However, about half of the patients with ScAb-ILD were male and current or ex-smokers. On HRCT analysis, honeycombing was more predominant in patients with ScAb-ILD than with SSc-ILD. Pathological analysis showed the severity of vascular intimal or medial thickening in the SSc-ILD patients to be significantly higher than that in the ScAb-ILD patients. Survival curves showed that the patients with ScAb-ILD had a significantly poorer outcome than those with SSc-ILD. CONCLUSION: Data from this study suggest that lung-dominant CTD with SSc-related autoantibody is a different disease entity from SSc-ILD.