Interstitial pneumonia associated with MPO-ANCA: Clinicopathological features of nine patients

SummaryMyeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) is a well known marker for small vessel vasculitis. Recent reports have demonstrated that interstitial pneumonia (IP) may rarely be associated with serum MPO-ANCA. Yet, little is known about the histological features.We reviewed surgical lung biopsy from nine patients with IP of uncertain etiology with serum MPO-ANCA.There was a male predominance (6:3) with a median age of 62.1. Histologically, eight patients presented with a usual interstitial pneumonia (UIP) pattern of pulmonary fibrosis, frequently accompanied by areas of nonspecific interstitial pneumonia (NSIP) pattern. One patient showed diffuse alveolar damage (DAD), and two patients showed mixture of UIP and DAD reflecting acute exacerbation of UIP. Microscopic honeycomb cysts were common, but fibroblastic foci were inconspicuous. The most frequent additional findings were small airway disease (9/9), and lymphoid follicles (7/9). Neither capillaritis nor vasculitis was seen in any of our cases. Three patients had microscopic hematuria, but none progressed to microscopic polyangiitis during the follow up. Mortality rate was 44% (median follow up 39.1 months).IP associated with MPO-ANCA showed characteristic histology dominated by UIP pattern. Vasculitis was not identified in our cohort, but small airways disease and lymphoid follicles were present in most cases. IP associated with MPO-ANCA may be a histologically distinctive disease from idiopathic pulmonary fibrosis. Mortality was relatively high and life threatening acute exacerbation may occur

Programmed death (PD)-1/PD-ligand 1 blockade mediates antiangiogenic effects by tumor-derived CXCL10/11 as a potential predictive biomarker

Immune checkpoint inhibitor (ICI) programmed death (PD)-1/PD-ligand 1 (PD-L1) blockade has been approved for various cancers. However, the underlying antitumor mechanisms mediated by ICIs and the predictive biomarkers remain unclear. We report the effects of anti-PD-L1/PD-1 Ab in tumor angiogenesis. In syngeneic mouse models, anti-PD-L1 Ab inhibited tumor angiogenesis and induces net-like hypoxia only in ICI-sensitive cell lines. In tumor tissue and serum of ICI-sensitive cell line-bearing mice, interferon-γ (IFN-γ) inducible angiostatic chemokines CXCL10/11 were upregulated by PD-L1 blockade. In vitro, CXCL10/11 gene upregulation by IFN-γ stimulation in tumor cell lines correlated with the sensitivity of PD-L1 blockade. The CXCL10/11 receptor CXCR3-neutralizing Ab or CXCL11 silencing in tumor cells inhibited the antiangiogenic effect of PD-L1 blockade in vivo. In pretreatment serum of lung carcinoma patients receiving anti-PD-1 Ab, the concentration of CXCL10/11 significantly correlated with the clinical outcome. Our results indicate the antiangiogenic function of PD-1/PD-L1 blockade and identify tumor-derived CXCL10/11 as a potential circulating biomarker of therapeutic sensitivity

Recognition of Connective Tissue Disease-Related Interstitial Pneumonia Based on Histological Score—A Validation Study of an Online Diagnostic Decision Support Tool

Objectives: to evaluate the number of cases of idiopathic pulmonary fibrosis (IPF) that included histological features of connective tissue disease (CTD) and to check whether they demonstrated the clinical features of CTD, using a previously reported CTD-interstitial pneumonia (IP) index that histologically differentiates CTD-associated and idiopathic IP. Methods: patients diagnosed with IPF following video-assisted thoracoscopic biopsy through multidisciplinary team diagnosis between 2014 and 2017 were selected. Pathological observation was made by four pathologists who scored eight observational items needed for the CTD-IP index. Cases determined as CTD, by the CTD-IP index, were extracted, and their clinical features were compared. Results: a total of 94 cases of IPF were identified, of which 20 were classified into the CTD group using the CTD-IP index with reasonable interobserver agreement (k = 0.76). Cases pathologically classified into the CTD group were significantly associated with female sex, non-smoking history, autoantibody positivity, and CTD symptoms (p = 0.01, 0.03, 0.01, and 0.04, respectively). Conclusions: patients with IPF with pathological findings of CTD showed clinical characteristics similar to those of patients with CTD

Histologic factors associated with nintedanib efficacy in patients with idiopathic pulmonary fibrosis

Background Histopathologic factors predictive of nintedanib efficacy in idiopathic pulmonary fibrosis have not been studied. We aimed to describe the characteristics, focusing on histopathology, of idiopathic pulmonary fibrosis patients who did and did not respond to nintedanib. Methods This study retrospectively examined the clinicoradiopathologic features of 40 consecutive patients with surgical lung biopsy-confirmed idiopathic pulmonary fibrosis treated with nintedanib. Additionally, we compared the histopathologic scoring of 21 microscopic features between patients with functional or radiological progression and those with non-progression during 12 months of treatment. Results The histopathologic evaluation showed edematous changes in the interlobular septum as the only histologic finding observed more frequently in patients with both functional and radiological progression than in those without (58% vs. 14%, P = 0.007 and 50% vs. 0%, P = 0.003, respectively). Regarding per-year change, patients with edematous changes in the interlobular septum showed greater progression in median changes in spared area (-12%, interquartile range: [-25%-5%], vs. -3% [-7%-0%], P = 0.004) and reticular shadow (7% [3%-13%], vs. 0% [0%-5%], P = 0.041) on computed tomography. Functional and radiological progression-free survival were shorter in patients with edematous changes in the interlobular septum than in those without (6.6 months, 95% confidence interval: [5.9-25.3], vs. event <50%, [12.1-Not available], P = 0.0009, and 6.1 months, [5.2-6.6] vs. 14.5 months [7.8-not available], P<0.0001). Conclusions Edematous changes in the interlobular septum may indicate poor nintedanib efficacy in idiopathic pulmonary fibrosis. Further studies are needed to validate these findings and address the mechanism behind ECIS

Acute exacerbation of idiopathic pulmonary fibrosis triggered by Aspergillus empyema

Acute exacerbation (AE) is a severe and life-threatening complication of idiopathic pulmonary fibrosis (IPF). In 2016, the definition and diagnostic criteria for AE-IPF were updated by an international working group. The new definition includes any acute, clinically significant respiratory deterioration (both idiopathic and triggered events) characterized by evidence of new widespread alveolar abnormality in patients with IPF. There are no currently proven beneficial management strategies for idiopathic and triggered AE-IPF. This is the first report describing AE-IPF triggered by Aspergillus empyema, which was improved by a combination of corticosteroid, systemic antifungal therapy, local antifungal therapy, and additional pharmacological therapies. Future research may reveal optimal strategies for both idiopathic and triggered AE-IPF. Keywords: Idiopathic pulmonary fibrosis, Acute exacerbation, AE-IPF, Triggered AE, Aspergillus infectio

A Pilot Study of Transbronchial Biopsy Using Endobronchial Ultrasonography with a Guide Sheath in the Diagnosis of Peripheral Pulmonary Lesions in Patients with Interstitial Lung Disease

The occurrence of interstitial lung disease (ILD) with peripheral pulmonary lesions (PPLs) is closely linked to the development of lung cancer. Yet, the best diagnostic approach for identifying PPLs in patients with ILD remains elusive. This study retrospectively investigated the application of transbronchial biopsy (TBB) using endobronchial ultrasonography with a guide sheath (EBUS-GS) to the effective and safe diagnosis of PPLs when compared with conventional TBB. The study sample included a consecutive series of 19 patients with ILD who underwent conventional TBB or TBB using EBUS-GS at Tosei General Hospital between 1 April 2013 and 31 October 2015. The two techniques were compared based on diagnostic yield and associated complications. The diagnostic yield of EBUS-GS TBB was significantly higher than that of conventional TBB (p = 0.009), especially for small lesions (&le;20 mm), lesions located in the lower lobes, lesions with a positive bronchus sign, and lesions visible by chest radiography (p = 0.010, p = 0.022, p = 0.006, and p = 0.002, respectively). There were no significant differences in complication rates. Therefore, EBUS-GS is an effective alternative for the diagnosis of PPLs in patients with ILD, without additional complications

Endobronchial Ultrasonography with a Guide Sheath Transbronchial Biopsy for Diagnosing Peripheral Pulmonary Lesions within or near Fibrotic Lesions in Patients with Interstitial Lung Disease

In patients with interstitial lung disease (ILD), the most frequent locations of lung cancer are within or near fibrotic lesions. However, the diagnostic yield for peripheral pulmonary lesions (PPLs) within or near fibrotic lesions using endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS-GS TBB) may be unsatisfactory compared to that for PPLs distant from fibrotic lesions because of the difficulty in reaching the lesions. Our objectives were to evaluate the yield for PPLs using EBUS-GS TBB according to the proximity of PPLs to fibrotic lesions and to determine factors affecting the yield for PPLs. We retrospectively investigated 323 consecutive lesions using EBUS-GS TBB between 1 November 2014 and 31 December 2016. We identified PPLs with ILD in such lesions. PPLs with ILD were divided into PPLs within or near fibrotic lesions which met the criterion of PPLs, and of fibrotic lesions overlapping each other (PPLs-FL) and those distant from fibrotic lesions, which met the criterion of PPLs and the area of fibrotic lesion not overlapping each other (PPLs-NFL). Of the 323 lesions, 55 were included (31 PPLs-FL and 24 PPLs-NFL). The diagnostic yield for PPLs-FL was significantly lower than for PPLs-NFL (45.2% vs. 83.3%, p = 0.004). Multivariate analysis revealed that PPLs-NFL (odds ratio (OR) = 7.509) and a probe position within the lesion (OR = 4.172) were significant factors affecting diagnostic yield. Lesion’s positional relation to fibrotic lesions and the probe position were important factors affecting the successful diagnosis via EBUS-GS TBB in these patients

Acute exacerbation of IPF following diagnostic bronchoalveolar lavage procedures

SummaryBackgroundsBronchoalveolar lavage (BAL) is generally regarded as a safe diagnostic procedure. However, acute exacerbation after BAL is increasingly recognized as a specific complication for patients with idiopathic pulmonary fibrosis (IPF). So far little is known about the correlation between BAL and acute exacerbation of IPF (AE-IPF).MethodsA cohort of 112 IPF patients at a single institution was analyzed retrospectively. We defined BAL-related AE-IPF as development of AE-IPF within 30 days after the procedure. The incidence rate of AE-IPF per person-month during the post-BAL period was compared with that after the post-BAL period. The relative risk was estimated as the former rate divided by the latter. We also reviewed the previous literature.ResultsFour AE-IPF cases occurred during the 201 person-month post-BAL period. The risk of AE-IPF was significantly elevated within 30 days after BAL (rate ratio = 4.12; 95% CI = 1.03–12.2). None of the 111 initial BAL procedures were followed by AE-IPF within a month. In a post hoc analysis, the relative risk of developing AE after second or later BAL procedures was estimated to be considerably higher (rate ratio = 9.10; 95% CI = 2.27–26.98).Twelve cases of BAL-induced AE-IPF were found in our study and in the literature review. Among them, nine showed moderate to severe functional impairment, and eight had either findings of leukocytosis, positive C-reactive protein, or neutrophilia in BAL.ConclusionsThese results suggest that IPF patients should be carefully monitored after BAL, especially those with functional impairment or active inflammation