A retrospective study on radiological findings of diffuse pleural thickening with benign asbestos pleural effusion in Japanese cases.

The requirement for compensation for diffuse pleural thickening in benign asbestos pleural effusion include five computed tomography findings of organized pleural effusion: [1] heterogeneity in the pleural effusion, [2] declined chest capacity, [3] "crow's feet" sign at the pleura, [4] immobilization of effusion volume, and [5] air in the effusion. Pleural effusion is diagnosed as organized, immobilized, and in the state of diffuse pleural thickening if at least three of these items are fulfilled, ([1] and [3] compulsory + one of the remaining items). This retrospective study investigated whether the requirement to confirm no organized pleural effusion changes after a follow-up of >3 months were available for cases fulfilling three of the five items; i.e., the confirmation of only [2] with [1] and [3]. Of 302 cases recognized by the Japanese laws, 105 cases with diffuse pleural thickening with organized effusion were enrolled. The number of subjects who fulfilled the diagnostic requirement for organized pleural effusion was confirmed. Eight subjects had a full score of 5 points, 82 subjects scored 4 points, and only 15 subjects scored 3 points. Furthermore, no changes were observed in the organized pleural effusion volume after a follow-up of >3 months.

2020 guide for the diagnosis and treatment of interstitial lung disease associated with connective tissue disease.

The prognosis of patients with connective tissue disease (CTD) has improved significantly in recent years, but interstitial lung disease (ILD) associated with connective tissue disease (CTD-ILD) remains a refractory condition, which is a leading cause of mortality. Because it is an important prognostic factor, many observational and interventional studies have been conducted to date. However, CTD is a heterogeneous group of conditions, which makes the clinical course, treatment responses, and prognosis of CTD-ILD extremely diverse. To summarize the current understanding and unsolved questions, the Japanese Respiratory Society and the Japan College of Rheumatology collaborated to publish the world's first guide focusing on CTD-ILD, based on the evidence and expert consensus of pulmonologists and rheumatologists, along with radiologists, pathologists, and dermatologists. The task force members proposed a total of 27 items, including 7 for general topics, 9 for disease-specific topics, 3 for complications, 4 for pharmacologic treatments, and 4 for non-pharmacologic therapies, with teams of 2-4 authors and reviewers for each item to prepare a consensus statement based on a systematic literature review. Subsequently, public opinions were collected from members of both societies, and a critical review was conducted by external reviewers. Finally, the task force finalized the guide upon discussion and consensus generation. This guide is expected to contribute to the standardization of CTD-ILD medical care and is also useful as a tool for promoting future research by clarifying unresolved issues.

CT classification of acute myeloid leukemia with pulmonary infiltration.

PURPOSE: To characterize and categorize the CT findings of pulmonary leukemic infiltration (PLI) in patients with acute myeloid leukemia (AML). MATERIALS AND METHODS: Among 435 patients with AML, 20 patients with PLI were retrospectively selected, and clinical characteristics and CT findings were analyzed. PLI was categorized into four patterns according to CT findings: type A, multiple nodules and/or masses; type B, bilateral perihilar airspace opacities (GGA or consolidation) without any nodules or masses; type C, mixture of type A and B; and type D, PLI without visible abnormal lung opacity. The difference in overall survival among four CT patterns was also examined. RESULTS: The frequency of complex karyotypes was higher in AML patients with PLI than in whole AML patients. Percentages of patients with CT findings of type A, B, C, and D were 35%, 20%, 35%, and 10%, respectively. There was a clear difference in the localization of opacities according to the type of infiltrates, i.e., nodules/masses were mainly detected in the lower/peripheral portion. Conversely, GGA was mainly located in the upper/central portion. The median overall survival from diagnosis of PLI was 262 days (range 12-1148). The CT pattern was not significantly associated with survival (p = 0.3), with the exception of patients with type C tending to have significantly better outcomes compared to patients with type B (p = 0.05). CONCLUSION: This classification can contribute in accurate non-invasive diagnosis and possibly in the estimation of prognosis.

Intractable diffuse pulmonary diseases: Manual for diagnosis and treatment.

This manual has been compiled by a joint production committee with the Diffuse Lung Disease Assembly of the Japanese Respiratory Society (JRS) to provide a practical manual for the epidemiology, diagnosis, and treatment of intractable diffuse pulmonary diseases. The contents are based upon the results of research into these diseases by the Diffuse Pulmonary Diseases Study Group (principal researcher: Sakae Homma) supported by the FY2014-FY2016 Health and Labor Sciences Research Grant on Intractable Diseases. This manual focuses on: 1) pulmonary alveolar microlithiasis, 2) bronchiolitis obliterans, and 3) Hermansky-Pudlak Syndrome with interstitial pneumonia. As these are rare/intractable diffuse lung diseases (2 and 3 were first recognized as specified intractable diseases in 2015), there have not been sufficient epidemiological studies made, and there has been little progress in formulating diagnostic criteria and severity scales; however, the results of Japan's first surveys and research into such details are presented herein. In addition, the manual provides treatment guidance and actual cases for each disease, aiming to assist in the establishment of future modalities. The manual was produced with the goal of enabling clinicians specialized in respiratory apparatus to handle these diseases in clinical settings and of further advancing future research and treatment.

Pirfenidone plus inhaled N-acetylcysteine for idiopathic pulmonary fibrosis: a randomised trial.

BACKGROUND: A randomised controlled trial in Japan showed that inhaled N-acetylcysteine monotherapy stabilised serial decline in forced vital capacity (FVC) in some patients with early idiopathic pulmonary fibrosis (IPF). However, the efficacy and tolerability of combination therapy with an antifibrotic agent and inhaled N-acetylcysteine are unknown. METHODS: This 48-week, randomised, open-label, multicentre phase 3 trial compared the efficacy and tolerability of combination therapy with pirfenidone plus inhaled N-acetylcysteine 352.4 mg twice daily with the results for pirfenidone alone in patients with IPF. The primary end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide (D LCO) and 6-min walk distance (6MWD), progression-free survival (PFS), incidence of acute exacerbation, and tolerability. RESULTS: 81 patients were randomly assigned in a 1:1 ratio to receive pirfenidone plus inhaled N-acetylcysteine (n=41) or pirfenidone (n=40). The 48-week rate of change in FVC was -300 mL and -123 mL, respectively (difference -178 mL, 95% CI -324--31 mL; p=0.018). Serial change in D LCO, 6MWD, PFS and incidence of acute exacerbation did not significantly differ between the two groups. The incidence of adverse events (n=19 (55.9%) for pirfenidone plus N-acetylcysteine; n=18 (50%) for pirfenidone alone) was similar between groups. CONCLUSIONS: Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF.

Treatment and relapse of interstitial lung disease in nivolumab-treated patients with non-small cell lung cancer.

Nivolumab, a human monoclonal antibody against programmed death-1, is approved for the treatment of non-small cell lung cancer (NSCLC). Although nivolumab is generally well tolerated, it can cause interstitial lung disease (ILD), a rare but potentially fatal immune-related adverse event. Currently, there are limited data available on the treatment of nivolumab-induced ILD and its outcome. This retrospective cohort study based on a post-marketing study described the treatment of nivolumab-induced ILD and its outcome in NSCLC patients in Japan through the assessment of clinical and chest imaging findings by an expert central review committee. Treatment details for patients who experienced a relapse of ILD were also analyzed. Of the 238 patients identified as having nivolumab-induced ILD, 37 patients died of ILD. Corticosteroids were used in 207 (87.0%) patients. Of those, 172 (83.1%) patients responded well and survived and 35 (16.9%) died (most died during corticosteroid treatment). A total of nine patients experienced a relapse; at the time of relapse, four patients were taking nivolumab. Of those who were receiving corticosteroids at the time of relapse, three of four patients were taking low doses or had nearly completed dose tapering. All patients (except one, whose treatment was unknown) received corticosteroids for the treatment of relapse, but one patient died. Patients with NSCLC who experience nivolumab-induced ILD are treated effectively with corticosteroids, and providing extra care when ceasing or reducing the corticosteroid dose may prevent relapse of ILD.

Radiographic features and poor prognostic factors of interstitial lung disease with nivolumab for non-small cell lung cancer.

Nivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This postmarketing study evaluated the poor prognostic factors of ILD in nivolumab-treated patients with non-small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an expert central review committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground-glass opacity (peritumoral-GGO). Poor prognostic factors were identified by univariate and multivariate Cox regression analysis. Of the 238 patients with nivolumab-induced ILD, 37 died. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia-like (53.4%), faint infiltration pattern/acute hypersensitivity pneumonia-like (20.2%), diffuse alveolar damage (DAD)-like (10.9%), and nonspecific interstitial pneumonia-like (6.3%). The main poor prognostic factors identified were DAD-like pattern (highest hazard ratio: 10.72), ≤60 days from the start of nivolumab treatment to the onset of ILD, pleural effusion before treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal change in C-reactive protein (CRP) levels. Of the 37 deaths due to ILD, 17 had DAD-like radiographic pattern, three had peritumoral-GGO, and five had a change in radiographic pattern from non-DAD at the onset to DAD-like. Patients with NSCLC who develop ILD during nivolumab treatment should be managed carefully if they have poor prognostic factors such as DAD-like radiographic pattern, onset of ILD ≤60 days from nivolumab initiation, pleural effusion before nivolumab treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal changes in CRP levels.

Real-World Evaluation of Factors for Interstitial Lung Disease Incidence and Radiologic Characteristics in Patients With EGFR T790M-positive NSCLC Treated With Osimertinib in Japan.

INTRODUCTION: Using real-world Japanese postmarketing data, we characterized interstitial lung disease (ILD) development during the second- or later-line osimertinib treatment for EGFR mutation-positive NSCLC. Retrospective radiologic image evaluation of patients developing ILD was also performed. METHODS: Patients who had ILD events reported as an adverse drug reaction by their physicians and who were assessed as having developed ILD as assessed by an ILD expert committee in Japan were included. RESULTS: Among 3578 patients, 252 ILD events were reported in 245 patients (6.8%) by their attending physicians. The median (range) time to the first onset of ILD after osimertinib treatment initiation was 63.0 (5-410) days, and 29 patients with a fatal outcome were reported. The ILD expert committee assessed 231 of 3578 patients (6.5%) as having ILD. A previous history of nivolumab therapy (adjusted OR: 2.84; 95% confidence interval: 1.98-4.07) and a history or concurrence of ILD (3.51; 2.10-5.87) were identified as factors potentially associated with ILD onset during osimertinib treatment. In patients who had received a previous nivolumab treatment, the number and proportion of patients developing ILD were highest for patients who discontinued nivolumab treatment within the first month before initiating osimertinib; trends for decreasing incidence and proportion were observed, with an increasing duration between the end of nivolumab treatment and the initiation of osimertinib treatment. CONCLUSIONS: The frequency of ILD was consistent with the known osimertinib safety profile in the Japanese population. A history or concurrence of ILD and history of previous nivolumab therapy are factors potentially associated with ILD onset during osimertinib treatment.

CT of invasive pulmonary aspergillosis (IPA) in cases with hematologic malignancy: Comparison of CT features in the group classified by the severity of neutropenia and underlying disease.

PURPOSE: To identify differences in the radiological findings of invasive pulmonary aspergillosis (IPA) among patients classified by severity of neutropenia, and differences in underlying disease. MATERIALS AND METHODS: We retrospectively reviewed computed tomography (CT) scans from the time of the diagnosis of IPA in 83 hematological malignancy patients with probable or proven IPA according to the EORTC-MSG criteria. We evaluated CT findings (radiological pattern, number of lesions, distribution, and presence of low attenuation area [LAA]), and compared the radiological findings of patients classified by degree of neutropenia with two different indicators (neutrophil count at the onset, and c-d-index) and underlying disease. RESULTS: Neutropenia at the onset of IPA was associated with an increased frequency of LAA (p < 0.05), especially in FN (p < 0.01). Cases with a c-d-index of ≧5500 showed an increased incidence of the angio-invasive pattern. In contrast, cases with a c-d-index of 0 showed an increased incidence of the airway-invasive pattern (p < 0.05). The airway-invasive pattern was more frequent in cases with MM, while the angio-invasive pattern was more frequent in cases with AML (p < 0.01). Lower-predominant distribution was more frequent and random distribution was less frequent in cases with AML, random distribution was more frequent and lower-predominant distribution was less frequent in cases with ALL, and upper-predominant distribution was more frequent in cases with MDS (p < 0.05). CONCLUSIONS: CT features of IPA vary according to the degree of neutropenia and underlying disease.

Real-world use of osimertinib for epidermal growth factor receptor T790M-positive non-small cell lung cancer in Japan.

OBJECTIVE: Adverse drug reactions (ADRs) during real-world osimertinib use were investigated in Japan. METHODS: Patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer treated with second-line or later oral osimertinib per the Japanese package insert (80 mg once daily) were included. Data were collected between 28 March 2016 and 31 August 2018. RESULTS: The median observation period in the safety analysis population (n = 3578) was 343.0 days. ADRs (defined as adverse events whose causality to osimertinib could not be denied by the attending physicians or manufacturer) were reported in 58.1% (2079/3578) of patients. ADRs of interstitial lung disease events were reported in 6.8% (245/3578; Grade ≥ 3, 2.9% [104/3578]) of patients, of whom 29 (11.8%) died (0.8% of patients overall). ADRs of QT interval prolonged, liver disorder and haematotoxicity were reported in 1.3% (45/3578; Grade ≥ 3, 0.1% [5/3578]), 5.9% (212/3578; Grade ≥ 3, 1.0% [35/3578]) and 11.4% (409/3578; Grade ≥ 3, 2.9% [104/3578]) of patients, respectively. In the efficacy analysis population (n = 3563), 119 (3.3%) patients had complete responses, 2373 (66.6%) had partial responses and 598 (16.8%) had stable disease. The objective response rate was 69.9%; disease control rate was 86.7%; and median progression-free survival (PFS) was 12.3 months. At 6 and 12 months, PFS rates were 77.4% (95% confidence interval [CI], 75.9-78.9) and 53.2% (95% CI, 51.3-55.1) and overall survival rates were 88.3% (95% CI, 87.2-89.4) and 75.4% (95% CI, 73.8-77.0), respectively. CONCLUSIONS: These data support the currently established benefit-risk assessment of osimertinib in this patient population.

Acute exacerbation of idiopathic interstitial pneumonias related to chemotherapy for lung cancer: nationwide surveillance in Japan.

BACKGROUND: Chemotherapy-induced acute exacerbation (AEx) of idiopathic interstitial pneumonias (IIPs) seriously compromises the success of treatment of Japanese lung cancer patients. Here, we conducted a nationwide surveillance to clarify the risk of AEx and compare it with the survival benefit of chemotherapy for this population. METHODS: Advanced nonsmall cell lung cancer (NSCLC) or small cell lung cancer (SCLC) patients with IIPs were retrospectively analysed. For the surveillance of first-line chemotherapy in 2009, we gathered clinical data from 396 patients who received chemotherapy at 19 institutions between January 1990 and July 2009. In a consecutive retrospective study in 2012, we analysed data from 278 patients from 17 institutions who received second-line chemotherapy between April 2002 and March 2012. RESULTS: Of the 396 patients analysed, 13.1% developed chemotherapy-related AEx. Combination chemotherapies of carboplatin plus paclitaxel (CP) or carboplatin plus etoposide (CE) were frequently used as first-line treatments. The lowest incidence of AEx was 3.7% in CE, followed by 8.6% in CP. In the retrospective study, 16.2% of the 278 patients developed a second-line chemotherapy-related AEx. The overall response rate by second-line chemotherapy was 7.4% in NSCLC and 25.7% in SCLC. The median overall survival from second-line and first-line chemotherapy was 8.0 and 14.3 months in NSCLC, and 8.7 and 16.0 months in SCLC, respectively. CONCLUSION: Combination chemotherapies consisting of CP or CE are candidates for standard first-line treatments for patients with advanced lung cancer accompanied by IIP. Second-line chemotherapy should be considered for patients remaining fit enough to receive it.

High-resolution CT features distinguishing usual interstitial pneumonia pattern in chronic hypersensitivity pneumonitis from those with idiopathic pulmonary fibrosis.

PURPOSE: Radiologic diagnosis of chronic hypersensitivity pneumonitis (CHP) presenting a usual interstitial pneumonia (UIP) pattern is challenging. The aim of this study was to identify the high-resolution CT (HRCT) findings which are useful to discriminate CHP-UIP from idiopathic pulmonary fibrosis (IPF). MATERIALS AND METHODS: This study included 49 patients with well-established bird-related CHP-UIP, histologically confirmed, and 49 patients with IPF. Two groups of observers independently assessed HRCT, evaluated the extent of each abnormal HRCT finding. When their radiological diagnosis was CHP-UIP, they noted the HRCT findings inconsistent with IPF. RESULTS: Correct CT diagnoses were made in 79% of CHP-UIP and 53% of IPF. Although no apparent difference was seen in the extent of each HRCT finding, upper or mid-lung predominance, extensive ground-glass abnormality, and profuse micronodules were more frequently pointed out as inconsistent findings in CHP-UIP than IPF (p = 0.007, 0.010, 0.001, respectively). On regression analysis, profuse micronodules [OR 13.34 (2.85-62.37); p = 0.001] and upper or mid-lung predominance of findings [OR 2.86 (1.16-7.01); p = 0.022] remained as variables in the equation. CONCLUSION: In this cohort, some IPF cases were misdiagnosed as CHP-UIP. Profuse micronodules and upper or mid-lung predominance are important clues for the differentiation of CHP-UIP from IPF.

Computed Tomography Images of Fibrotic Pulmonary Sarcoidosis Leading to Chronic Respiratory Failure.

BACKGROUND: There is currently no consensus on the morphology of severe fibrotic pulmonary sarcoidosis, and we examined computed tomography (CT) findings and progression. METHODS: We analyzed findings in 10 consecutive patients (three men, seven women) with pulmonary sarcoidosis requiring oxygen therapy for chronic respiratory failure, who were extracted from >2500 sarcoidosis patients (three hospitals, 2000-2018). Patients with comorbidities causing chronic respiratory failure were excluded. RESULTS: Predominant findings were consolidations along the bronchovascular bundles comprising 'central-peripheral band', traction bronchiectasis, peripheral cysts/bullae, and upper lobe shrinkage. Traction bronchiectasis arose from opacities comprising 'central-peripheral band'. Clustering of traction bronchiectasis at the distal side formed honeycomb lung-like structures in three patients. Upper lobe shrinkage progressed in seven patients together with progression of consolidations, 'central-peripheral band', traction bronchiectasis clusters, and cysts, while patients without shrinkage included two patients with severe multiple cysts without traction bronchiectasis. Restrictive ventilatory impairment developed in most patients. Pulmonary hypertension (PH) was detected radiologically in five patients, and chronic progressive pulmonary aspergillosis (CPPA) in four patients. CONCLUSIONS: During progression, consolidations comprising 'central-peripheral band' progressed together with traction bronchiectasis clusters and peripheral cysts, resulting in upper lobe shrinkage. This may lead to respiratory failure with possible complications such as PH and CPPA.

Inter-observer agreement in identifying traction bronchiectasis on computed tomography: its improvement with the use of the additional criteria for chronic fibrosing interstitial pneumonia.

PURPOSE: To assess inter-observer variability in identifying traction bronchiectasis on computed tomography (CT) using additional criteria for chronic fibrosing interstitial pneumonia. METHODS: Seven experts categorized CT image set representing 39 patients into three groups on the basis of the presence of traction bronchiectasis, using a three-point scale: 3-definitely/probably yes; 2-possibly yes; and 1-definitely/probably no. This scale served as a reference standard. The image set included cases of chronic fibrosing interstitial pneumonia, non-interstitial lung disease, and difficult-to-determine cases. Forty-eight observers similarly assessed the same image set, first according to the Fleischner Society definition, and second with additional criteria, in which traction bronchiectasis was observed exclusively in chronic fibrosing interstitial pneumonia. The agreement level between the reference standard and each observer's evaluation in each session was calculated using weighted kappa values which were compared between the two sessions using a paired t test. RESULTS: The mean weighted kappa value for all observers was significantly higher in the second reading session (mean 0.75) than in the first reading session (mean 0.62) (p < 0.001). CONCLUSION: Inter-observer agreement in identifying traction bronchiectasis improves when using the additional criteria which specify chronic fibrosing interstitial pneumonia as the underlying disease.

Radiologic features of pneumonitis associated with nivolumab in non-small-cell lung cancer and malignant melanoma.

Aim: To assess the clinical features/imaging characteristics of pneumonitis reported during nationwide nivolumab postmarketing surveillance in Japan. Patients & methods: Clinical and radiological data were collected from pneumonitis cases reported during/after nivolumab treatment for melanoma or non-small-cell lung cancer. The expert central review committee evaluated each case. Results: Among 144 cases analyzed, 91 (63.2%) had radiological patterns considered typical for drug-induced pneumonitis and 53 (36.8%) patients had previously unobserved patterns with one or more atypical features, including 23 cases (16.0%) with ground glass opacity confined to the area around the tumor (peritumoral infiltration). A higher proportion of patients with (vs without) peritumoral infiltration had an antitumor response to nivolumab. Conclusion: Images of nivolumab-induced pneumonitis showed previously unobserved radiological patterns.

Criteria for the diagnosis of idiopathic pleuroparenchymal fibroelastosis: A proposal.

BACKGROUND: Physicians have few opportunities to perform surgical lung biopsy (SLB) to diagnose idiopathic pleuroparenchymal fibroelastosis (IPPFE). Therefore, diagnostic criteria for IPPFE that do not require SLB must be established. Herein, we propose diagnostic criteria for IPPFE with and without SLB. METHODS AND RESULTS: The diagnostic criteria for IPPFE with SLB are histological, based on computed tomography (CT) lesions compatible with PPFE, predominantly in the upper lobes. The three diagnostic criteria for IPPFE without SLB are as follows: (1) radiologically possible IPPFE (a radiological criterion confirming CT lesions in both lung apexes, regardless of the lower lobe lesions); (2) radiologically probable IPPFE (also a radiological criterion, but mandatory to confirm chest radiograph findings of bilateral upward shift of the hilar structures and/or CT findings of volume loss of the upper lobes); (3) radiologically and physiologically probable IPPFE. Our data from 41 patients with IPPFE and 97 with idiopathic pulmonary fibrosis (IPF) showed that the percentage of the predicted values of the ratio of residual volume to total lung capacity (RV/TLC %pred.) ≥115% and body mass index (BMI) ≤20 kg/m2 plus RV/TLC %pred. ≥80% performed well for discriminating IPPFE from IPF. These parameters were thus added to criterion (3). CONCLUSIONS: We have proposed diagnostic criteria for IPPFE in patients with and without SLB. Both imaging criteria and physiological criteria using RV/TLC and BMI successfully discriminate IPPFE from chronic IIPs when SLB cannot be performed.

Distinctive clinicopathological features of adenocarcinoma in situ and minimally invasive adenocarcinoma of the lung: A retrospective study.

OBJECTIVES: The aim of this study was to investigate distinguishing clinicopathological features, in addition to histological invasiveness, in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) of the lung. MATERIALS AND METHODS: Patients with lung adenocarcinoma who underwent surgery at our hospital between 2007 and 2014 were reviewed, focusing on computed tomography (CT) images, operative procedures and clinical outcomes, histopathology, Ki-67 immunostaining, and EGFR-mutation status. EGFR mutations were examined using a peptide nucleic acid-locked nucleic acid PCR clamp method. Group comparisons were investigated by Mann-Whitney U or Fisher's exact tests. RESULTS: Of 629 patients with lung adenocarcinoma who underwent surgery, 91 (14%) of 103 AIS (n = 34) or MIA (n = 69) tumors were reviewed. The ratio of male to female patients with MIA compared to AIS was significantly higher (p < 0.02). Of 103 tumors, 99 (96%) were non-mucinous. By CT, 74% of AIS appeared as pure ground-glass nodules and 75% of MIAs as part-solid ground-glass nodules. Pathological tumor diameters and Ki-67 labeling index (LI) values were significantly greater for MIAs compared to AIS (p < 0.001 for both). A Ki-67 LI of ≥2.8% indicated the presence of an MIA rather than an AIS. EGFR mutations were more frequently detected in MIAs (33/69, 48%) than AIS (9/34, 26%; p = 0.055). The ratio of exon 19 deletions to exon 21 missense mutations in MIAs tended to be higher than those in AIS (p = 0.06). Patients did not experience a local recurrence or metastasis after AIS and MIAs were removed by wedge resection, segmentectomy or lobectomy. Five-year recurrence-free survival rates were 100%. CONCLUSION: Despite similar surgical outcomes for AIS and MIAs, we found differences in terms of gender, tumor diameters, CT findings, Ki-67 LI and a subset of EGFR mutations, highlighting the validity of classifying the two subtypes.

Association between chronic bacterial airway infection and prognosis of bronchiolitis obliterans syndrome after hematopoietic cell transplantation.

Bronchiolitis obliterans syndrome (BOS) is a rare pulmonary complication of hematopoietic stem cell transplantation (HSCT) with high mortality. Chronic bacterial airway infection (CAI) causes exacerbation and progression of several airway diseases, and bacterial airway colonization was shown to be associated with BOS after lung transplantation.We assessed the association between CAI and clinical course in patients with BOS after HSCT. This retrospective study included 910 patients undergoing allogeneic HSCT between 2005 and 2013 at our institution. BOS diagnosis was reevaluated according to the 2014 US National Institutes of Health criteria. Sputum and bronchial lavage culture results, pulmonary function, and survival were compared between patients with and without CAI.Median follow-up was 974.5 (261.5-2748.5) days. BOS was diagnosed in 27 (3.0%) patients, including 18 males. Median age at BOS diagnosis was 45 (40.5-58) years. Nine patients had ≥2 positive sputum cultures for bacteria or one positive bronchial lavage culture for nontuberculous mycobacteria (CAI+), whereas 9 patients had negative sputum/bronchial lavage culture or only one positive sputum culture (CAI-). Median change in forced expiratory volume in 1 s within 6 months after BOS diagnosis and overall survival were significantly worse in CAI+ patients than in CAI- patients (-250 vs +260 mL, P = .002, and 1340 days vs not reached, P = .04, respectively). No other factors including patient demographics or transplant protocol affected prognosis. There were no differences in clinical characteristics of patients with and without CAI, except for the time from transplantation to BOS diagnosis (214 vs 768 days for CAI+ and CAI-, respectively; P = .02).CAI was associated with worse outcomes in patients with BOS after HSCT. Further prospective studies should assess the association between the airway microbiome and changes in pulmonary function after HSCT to improve prognosis.

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.