An Adult Case of Idiopathic Pulmonary Hemosiderosis Associated with Pulmonary Fibrosis and Emphysematous Change.

A 48-year-old woman was admitted to our hospital with acute respiratory failure. Chest computed tomography showed ground-glass opacity and patchy emphysematous lesions in both lungs. Corticosteroid therapy was effective; however, the disease worsened with the tapering of corticosteroids. Bronchoalveolar lavage revealed hemosiderin-laden macrophages, and video-assisted thoracic surgery showed diffuse interstitial fibrosis with diffuse alveolar hemorrhage (DAH). There was no evidence of vasculitis nor autoimmune diseases. This patient was diagnosed with idiopathic pulmonary hemosiderosis (IPH) that progressed to end-stage pulmonary fibrosis despite treatment. Autopsy demonstrated DAH with pulmonary fibrosis and emphysematous change, suggesting IPH-related pulmonary lesions.

Bronchiolitis obliterans syndrome associated with an immune checkpoint inhibitor in a patient with non-small cell lung cancer.

A 75-year-old woman was admitted to our hospital with progressive dyspnea 7 months after second-line treatment with pembrolizumab for advanced non-small cell lung cancer. Chest radiography revealed hyperinflation in both lung fields, and pulmonary function tests revealed severe obstructive dysfunction without bronchodilator reversibility. There were no identifiable causes such as infections or autoimmune diseases. Therefore, bronchiolitis obliterans syndrome associated with immune checkpoint inhibitors was clinically diagnosed. Pembrolizumab was discontinued, but the respiratory dysfunction was irreversible and resulted in death. Bronchiolitis obliterans syndrome is an extremely rare but potentially severe adverse event associated with immune checkpoint inhibitor-related lung disease.

Clinical features of idiopathic pleuroparenchymal fibroelastosis with progressive phenotype showing a decline in forced vital capacity.

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is heterogeneous, with some patients showing a progressive decline in forced vital capacity (FVC). However, the clinical features of these cases with progressive phenotypes remain unknown. METHODS: This retrospective study included 48 patients diagnosed with IPPFE who underwent longitudinal pulmonary function tests at our institution from 2005 to 2021. The progressive phenotype was defined as a relative decline of ≥10% in %FVC within two years from diagnosis of IPPFE, and its clinical features were evaluated. RESULTS: Of the 48 patients, 23 (47.9%) were classified as progressive IPPFE. They were significantly older with a higher rate of dyspnea, fine crackles on chest auscultation, lower-lobe usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography, and lower %FVC at diagnosis than non-progressive IPPFE. Additionally, progressive IPPFE had a significantly higher rate of long-term oxygen therapy requirement, the incidence of pneumothorax, and weight loss after diagnosis, which showed worse survival than non-progressive IPPFE. The relative decline in %FVC and weight loss showed a significant positive correlation. Multivariate analysis revealed that lower body mass index tended to predict early progression, and the coexistence of lower-lobe UIP pattern was significantly associated with early progression. A decline in %FVC was an independent poor prognostic factor in IPPFE. CONCLUSIONS: With a progressive decline in %FVC, IPPFE often has an advanced stage at diagnosis and lower-lobe UIP pattern and is associated with weight loss and worse survival.

Intra-abdominal Hemorrhage Due to Splenic Vein Aneurysm Rupture Caused by Invasive Aspergillosis during Treatment for Advanced Non-small-cell Lung Cancer.

A 71-year-old man was admitted for left-sided chest pain. He had a history of diabetes, treatment with epidermal growth factor receptor-tyrosine kinase inhibitor for advanced non-small-cell lung cancer, and corticosteroid treatment for underlying lung diseases. Chest computed tomography showed consolidations in the bilateral lower lobes, and Aspergillus fumigatus was detected by bronchoscopy. Invasive pulmonary aspergillosis was suspected, and antifungal therapy with voriconazole was initiated; however, the patient passed away suddenly. Autopsy revealed disseminated Aspergillus infection and intra-abdominal hemorrhage due to the rupture of a splenic vein aneurysm caused by Aspergillus necrotizing vasculitis, which was considered the cause of death.

Comparison of clinical utility between digital and analog drainage systems in patients with spontaneous pneumothorax.

BACKGROUND: Digital drainage systems can continuously and numerically monitor air leakage, which may lead to a shorter duration of drainage and hospitalization; however, the usefulness of digital drainage systems compared to that of analog drainage systems for patients with primary or secondary spontaneous pneumothorax remains unclear. METHODS: This retrospective study included 108 patients with spontaneous pneumothorax who were successfully treated with chest drainage alone at our institution. We compared the clinical efficacy of digital and analog chest drainage systems. RESULTS: From the study population, 68 patients were diagnosed with primary and the other 40 with secondary spontaneous pneumothorax. The analog drainage system was used in 44 patients, and the digital drainage system in 64 patients. Among patients with primary spontaneous pneumothorax, the digital group had a significantly shorter duration of chest drainage than the analog group (median 2 vs. 4 days; p = 0.001), but there was no significant difference in those with secondary spontaneous pneumothorax. Additionally, the length and cost of hospitalization in the digital group were significantly lower than those in the analog group for both patients with primary and secondary spontaneous pneumothorax. There was no significant difference in recurrence within 1 week after chest tube removal between the two groups, neither among patients with primary nor among those with secondary pneumothorax. CONCLUSIONS: Digital drainage system may be better than analog drainage system for patients with primary spontaneous pneumothorax who need chest drainage, but further research is needed on drainage system selection for those with secondary disease.

Sarcoid-like Granulomatous Lung Disease with Subacute Progression in Silicosis.

A 67-year-old man was admitted to our hospital with cough and fatigue. He had had long-term exposure to silica due to cement processing. Chest computed tomography showed bilateral centrilobular nodules, and hilar and mediastinal lymphadenopathy with calcification, suggesting chronic silicosis. Within a few months, these nodules enlarged, and bilateral patchy consolidations appeared. A lung biopsy revealed sarcoid-like granulomas with birefringent particles under polarized light without malignancy or infection. He was diagnosed with silicosis-associated sarcoid-like granulomatous lung disease, rather than sarcoidosis, according to the clinicopathological findings. His pulmonary manifestations improved after the discontinuation of silica exposure and combination therapy of corticosteroid and azathioprine.

Prognostic significance of bronchoalveolar lavage cellular analysis in patients with acute exacerbation of interstitial lung disease.

BACKGROUND: Acute exacerbation (AE) of interstitial lung disease (ILD) is an acute respiratory deterioration of unknown etiology, associated with high mortality. Currently, bronchoalveolar lavage (BAL) has been no longer required for the diagnosis of AE-ILD; however, the clinical utility of BAL fluid (BALF) cellular analysis in AE-ILD remains unclear. METHODS: A retrospective study of 71 patients who underwent BAL at our institution between 2005 and 2019 and were diagnosed with AE-ILD was conducted. We performed BALF cellular analysis and evaluated its prognostic significance. RESULTS: There were 26 patients with AE of idiopathic pulmonary fibrosis (IPF) and 45 with AE of non-IPF, including idiopathic interstitial pneumonias/non-IPF (n = 22), ILD associated with collagen tissue disease (n = 20) and fibrotic hypersensitivity pneumonia (n = 3). All patients were treated with high-dose corticosteroids, and the 90-day mortality after AE was 31%. Most patients showed a high percentage of lymphocytes and/or neutrophils in BALF regardless of the underlying ILD. There was a significant negative correlation between BALF neutrophils and the PaO2/FiO2 ratio, and patients with UIP pattern or diffuse AE pattern on HRCT had a significantly higher percentage of BALF neutrophils than those with other patterns. Multivariate analysis revealed that lower and higher percentage of lymphocytes and neutrophils, respectively, in BALF were independent poor prognostic factors for 90-day survival. BALF lymphocyte and neutrophil count ≥25% and <20%, respectively, predicted favorable survival after AE. CONCLUSIONS: Cellular analysis of BALF in AE-ILD is a potential biomarker for predicting prognosis after AE.

Significance of Brain Imaging for Staging in Patients With Clinical Stage T1-2 N0 Non-Small-Cell Lung Cancer on Positron Emission Tomography/Computed Tomography.

BACKGROUND: Routine positron emission tomography/computed tomography (PET/CT) has been recommended even for clinical stage I non-small-cell lung cancer (NSCLC). In spite of the progress in the screening procedure, and revisions to TNM classification, there is no evidence to support brain imaging screening of patients assessed with the current staging protocol including PET/CT. MATERIALS AND METHODS: We retrospectively investigated the frequency of extrathoracic metastasis in 466 consecutive patients with clinical stage T1-2 N0 NSCLC with the complete staging assessment comprised of thin-section CT, PET/CT, and brain contrast-enhanced magnetic resonance imaging between 2008 and 2016. All patients were reclassified according to the eighth edition of the tumor, node, and metastasis (TNM) classification. RESULTS: Among all patients, 70% of the tumors were pure solid and 30% had part-solid ground-glass opacity on thin-section CT, and 388 (83%) and 78 (17%) were classified into clinical stages T1 and T2, respectively. Eight patients (1.7%) had extrathoracic metastasis, including 3 (0.6%) with brain metastasis, and all showed pure-solid tumors. The frequency of extrathoracic and brain metastasis was 1.0% and 0.5% in 388 T1 patients, and 5.0% and 3.0% in 78 T2 patients. Although brain metastases were detected in 2 of 7 patients (29%) with PET/CT detectable extrathoracic metastases and 1 of 459 patients (0.2%) without PET/CT detectable extrathoracic metastasis, there were no neurologically asymptomatic brain metastases in patients with early-stage NSCLC confirmed by PET/CT. CONCLUSION: Routine screening of brain imaging is unnecessary in patients with early-stage NSCLC, assessed with the current staging protocol including PET/CT.

Endobronchial Lesions from Disseminated Mycobacterium avium Infection in a Patient with Anti-interferon-gamma Autoantibodies.

A 78-year-old man was admitted to our hospital with a fever and left chest pain. Computed tomography showed multiple lung nodules, narrowing of the right bronchus intermedius with mediastinal lymphadenopathy, and an osteolytic lesion. Bronchoscopic findings showed rapid progression of multiple polypoid lesions and the bronchial stenosis. A biopsy of the endobronchial lesions revealed non-necrotizing granulomatous inflammation, and a tissue culture identified Mycobacterium avium. An anti-human immunodeficiency virus antibody was negative. Finally, anti-interferon-gamma (IFN-γ) autoantibodies were detected, and the patient was diagnosed with disseminated nontuberculous mycobacterium infection with anti-IFN-γ autoantibodies. Antimycobacterial therapy was effective, and radiographic findings, including the endobronchial lesions, were resolved.

Prognosis after acute exacerbation in patients with interstitial lung disease other than idiopathic pulmonary fibrosis.

BACKGROUND: Acute exacerbation (AE) is recognized as a life-threatening condition with acute respiratory worsening in idiopathic pulmonary fibrosis (IPF). AE also occurs in fibrotic interstitial lung disease (ILD) other than IPF, including other types of idiopathic interstitial pneumonias (IIPs), ILD associated with collagen vascular disease (CVD-ILD), and chronic hypersensitivity pneumonia (CHP). However, the clinical impact after AE in those patients is still unclear. METHODS: A retrospective review of 174 consecutive first-episodes with AE of ILD in our institution from 2002 to 2016 was performed. AE was defined according to the revised definition and diagnostic criteria proposed by an international working group in 2016. Clinical characteristics, 90-day survival, and the requirement of long-term oxygen therapy (LTOT) after AE were evaluated in each underlying ILD. RESULTS: There were 102 patients with AE of IPF (AE-IPF) and 72 with AE of ILD other than IPF, including non-IPF IIPs (n = 29) and secondary ILD (n = 43) [CVD-ILD (n = 39), CHP (n = 4)]. In CVD-ILD, rheumatoid arthritis (n = 17) was most common. The 90-day mortality after AE was 57% in IPF, 29% in non-IPF IIPs, and 33% in secondary ILD. After AE, ILD other than IPF had a significantly better survival rate than IPF (P < 0.001). Among survivors, the rates of patients requiring LTOT after AE were 63% in IPF, 35% in non-IPF IIPs, and 46% in secondary ILD, respectively. CONCLUSIONS: AE of ILD other than IPF might have a better prognosis than AE-IPF, but both are fatal conditions that cause chronic respiratory failure.

Prognostic impact of an early marginal decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone.

BACKGROUND: Pirfenidone (PFD), an oral antifibrotic drug, is conditionally recommended for the treatment of idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the prognostic factors in IPF patients treated with PFD and clarify the clinical significance of marginal physiological changes after PFD therapy. METHODS: We retrospectively reviewed 96 consecutive IPF patients treated with PFD. The physiological evaluation was performed at 3-6 months after PFD therapy, and the findings were classified into three groups based on the presence of a 5% change in %forced vital capacity (%FVC): improved, stable, and worsened. The clinical characteristics and prognostic outcomes were compared among groups, and the prognostic factors were evaluated by Cox proportional hazards analysis. RESULTS: Of the 96 patients, 25 (26.0%) showed acute exacerbation (AE) and 40 (41.6%) died during the observation period (median, 17 months). Physiological responses could be evaluated in 80 patients and the findings were as follows: improved, 23%; stable, 36%; and worsened, 41%. Time to the first AE and the survival rate were significantly shorter and lower, respectively, in the worsened group than in the improved/stable group (P = 0.002, P < 0.001, respectively). The prognostic analysis revealed that low %FVC at baseline (hazard ratio [HR]: 0.973 [0.950-0.996]), use of supplemental oxygen (HR: 2.180 [1.041-4.622]), and a "worsened" status after PFD therapy (HR: 5.253 [2.541-11.400]) were significantly associated with a poor prognosis. CONCLUSIONS: An early marginal decline in FVC may be important for survival outcomes in PFD-treated IPF patients.

Clinical significance of lower-lobe interstitial lung disease on high-resolution computed tomography in patients with idiopathic pleuroparenchymal fibroelastosis.

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare form of idiopathic interstitial pneumonias (IIP) and may have other patterns of interstitial lung disease (ILD) in the lower lobe, such as usual interstitial pneumonia (UIP). However, the clinical significance of lower-lobe ILD in patients with IPPFE is unclear. METHODS: A retrospective review of 40 consecutive patients with clinically diagnosed IPPFE in our institution from 2005 to 2016 was conducted. The presence of lower-lobe ILD on high-resolution computed tomography (HRCT) was assessed and classified into UIP or non-UIP pattern according to a modification of diagnostic criteria for idiopathic pulmonary fibrosis. Clinical characteristics and prognostic factors were evaluated. RESULTS: Among the 40 patients with IPPFE, 21 (53%) had lower-lobe ILD, including 13 with UIP pattern and 8 with non-UIP pattern. Patients with IPPFE who had lower-lobe ILD had significantly older age, higher frequency of fine crackles, higher serum KL-6 level, lower residual volume (RV), and lower total lung capacity (TLC) than those without lower-lobe ILD. In addition, those with lower-lobe ILD, especially UIP pattern, had a significantly poorer survival than those without lower-lobe ILD (log-rank test; p = 0.014, p < 0.001, respectively). Multivariate Cox proportional hazards regression analysis revealed that low %forced vital capacity (%FVC) at baseline and coexistence of UIP pattern were significantly associated with poor prognosis in patients with IPPFE. CONCLUSIONS: The coexistence of lower-lobe ILD on HRCT, especially the UIP pattern, may predict poor survival in patients with IPPFE.

IgG4-related disease presenting with combined pulmonary fibrosis and emphysema (CPFE).

A 64-year-old man was admitted to our hospital with an abnormal chest shadow. The patient was a current-smoker and had a past illness of autoimmune pancreatitis with a high serum level of IgG4, 348 mg/dL. Chest CT showed upper-lobe emphysema, and lower-lobe reticulation with honeycombing, suggestive of combined pulmonary fibrosis with emphysema (CPFE). Surgical lung biopsy was revealed a usual interstitial pneumonia pattern with marked infiltration of IgG4-positive plasma cells. The patient was diagnosed with IgG4 related disease (IgG4-RD) presenting with CPFE. Pulmonary manifestation was improved by corticosteroid therapy. IgG4-RD may be an underlying condition in patient with CPFE.

Anti-PL-7 Antisynthetase Syndrome with Eosinophilic Pleural Effusion.

A 68-year-old woman was admitted to our hospital with fever and pleural effusion. Her thoracentesis showed eosinophilic pleural effusion (EPE) without any evidence of malignancy, infection, or trauma. Pleural biopsy revealed pleuritis and intercostal myositis. Characteristic skin manifestations, including Gottron's sign, interstitial lung disease, and pericardial effusion, appeared later in the clinical course. She was finally diagnosed with anti-PL-7 antisynthetase syndrome (ASS) based on the presence of anti-PL-7 antibody, and she fulfilled the diagnostic criteria for dermatomyositis. These clinical manifestations improved with immunosuppressive therapy. EPE might therefore be one of the characteristic features of anti-PL-7 ASS.