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.

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.

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.

An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features.

BACKGROUND: Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients. METHODS: Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients. RESULTS: All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema alone (p=0.001). The extent of emphysema in CPFE patients with TWCLs was greater than that in patients without such lesions. Honeycombing with emphysema was also observed in 11 CPFE patients. CONCLUSIONS: TWCLs were only observed in the CPFE patients. They were classified as lesions with coexistent fibrosing interstitial pneumonia and emphysema, and should be considered an important pathological and radiological feature of CPFE.

Interstitial lung changes and persistent COVID-19 in a patient with follicular lymphoma: A case report.

We herein report a case of interstitial lung changes in a patient with prolonged coronavirus disease 2019 (COVID-19) with follicular lymphoma receiving rituximab and bendamustine who recovered after treatment with a combination therapy consisting of corticosteroids and immunosuppressive agents. There is currently no treatment strategy for prolonged pneumonitis following COVID-19, which can be life-threatening for immunocompromised patients. Thus, further investigation is warranted.

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.

An analysis of the radiological factors associated with respiratory failure in COVID-19 pneumonia and the CT features among different age categories.

PURPOSE: To investigate CT patterns of COVID-19 pneumonia associated with respiratory failure (RF) focused on the distribution of lesions. MATERIALS AND METHODS: Eighty-five patients with COVID-19 pneumonia were reviewed. CT findings were classified as follows: Type A; patchy ground glass attenuation (GGA) with/without air-space consolidation, Type B; non-segmental GGA with/without air-space consolidation in both the central and peripheral lung portions especially with subpleural spare, and Type C; non-segmental GGA with/without air-space consolidation predominantly distributed in the peripheral lung portion without subpleural spare. We analyzed CT patterns and clinical factors associated with RF, including age categories. RESULTS: The number of patients with Type A, B and C was 31 (37%), 24 (28%) and 30 (35%), respectively. Type C and hypertension were independently associated with RF. On comparing between Types B and C, the frequency of traction bronchiectasis was higher in Type C than in Type B (P < 0.001). The ratio of Type C in patients ≥ 65 years old (66%) was higher than in patients < 40 years old (P < 0.001) and 40-49 years old (P = 0.001). CONCLUSION: The Type C, increasing with age, was associated with RF. Traction bronchiectasis in the lesion was more frequent in Type C than in Type B. Secondary abstract A lesion adjacent to the pleura and hypertension is associated with respiratory failure in patients with COVID-19. The frequency of a lesion adjacent to the pleura increased with age. The distribution of lesions is a useful parameter to predict respiratory failure.

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.

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.

Infection in Immunocompromised Hosts: Imaging.

Immunocompromised patients are encountered with increasing frequency in clinical practice. In addition to the acquired immunodeficiency syndrome (AIDS), therapy for malignant disease, and immune suppression for solid organ transplants, patients are now rendered immunosuppressed by advances in treatment for a wide variety of autoimmune diseases. The number of possible infecting organisms can be bewildering. Recognition of the type of immune defect and the duration and depth of immunosuppression (particularly in hematopoietic and solid organ transplants) can help generate a differential diagnosis. Radiologic imaging plays an important role in the detection and diagnosis of chest complications occurring in immunocompromised patients; however, chest radiography alone seldom provides adequate sensitivity and specificity. High-resolution computed tomography (CT) can provide better sensitivity and specificity, but even CT findings may be nonspecific findings unless considered in conjunction with the clinical context. Combination of CT pattern, clinical setting, and immunologic status provides the best chance for an accurate diagnosis. In this article, CT findings have been divided into 4 patterns: focal consolidation, nodules/masses, small/micronodules, and diffuse ground-glass attenuation/consolidation. Differential diagnoses are suggested for each pattern, adjusted for both AIDS and non-AIDS immunosuppressed patients.

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.

Features of usual interstitial pneumonia in patients with primary Sjögren׳s syndrome compared with idiopathic pulmonary fibrosis.

BACKGROUND: The different characteristics of usual interstitial pneumonia in patients with primary Sjögren׳s syndrome (UIP/pSS) compared with idiopathic pulmonary fibrosis (UIP/IPF) are not fully understood. This study aimed to compare characteristics, prognosis, and treatment responses in these patients. METHODS: Among 129 consecutive patients who underwent surgical lung biopsy to diagnose diffuse lung diseases at Kanagawa Cardiovascular and Respiratory Center between 1998 and 2002, we identified 10 and 19 patients with UIP/pSS and UIP/IPF, respectively. Baseline characteristics, chest high-resolution computed tomography (HRCT) and pathological findings, and the clinical course were compared between the two groups. Responses to immunosuppressive therapy were analyzed by comparing pulmonary function and clinical status before and one year after treatment initiation. RESULTS: More patients in the UIP/pSS group tended to be female and older than those in the UIP/IPF group (mean age, 68 years vs. 62 years). In addition, they more commonly exhibited enlarged mediastinal lymph nodes and bronchial wall thickening on HRCT. Pathologically, in the UIP/pSS group, interstitial inflammation, plasma cell infiltration, lymphoid follicles with germinal centers, cysts, bronchiolitis, and pleuritis were significantly more prominent, whereas smooth muscle hyperplasia and fibroblastic foci were milder (all P<0.05). The prognosis was better for UIP/pSS compared with UIP/IPF patients (P=0.01). In addition, immunosuppressive therapy provided better disease control for those with UIP/pSS (83%, 5/6) compared UIP/IPF (7%, 1/15). CONCLUSION: This study identified distinct clinical, radiological, and pathological characteristics of UIP/pSS compared with UIP/IPF. Immunosuppressive treatment could be a therapeutic option for UIP/pSS.

Pulmonary cryptococcosis in rheumatoid arthritis (RA) patients: comparison of imaging characteristics among RA, acquired immunodeficiency syndrome, and immunocompetent patients.

PURPOSE: The imaging characteristics of cryptococcosis in rheumatoid arthritis (RA) patients were analyzed by comparing them with those of acquired immunodeficiency syndrome (AIDS) and immunocompetent patients, and the imaging findings were correlated with pathological findings. METHODS: Two radiologists retrospectively compared the computed tomographic (CT) findings of 35 episodes of pulmonary cryptococcosis in 31 patients with 3 kinds of underlying states (10 RA, 12 AIDS, 13 immunocompetent), focusing on the nature, number, and distribution of lesions. The pathological findings of 18 patients (8 RA, 2 AIDS, 8 immunocompetent) were analyzed by two pathologists, and then correlated with imaging findings. RESULTS: The frequencies of consolidation and ground glass attenuation (GGA) were significantly higher, and the frequency of peripheral distribution was significantly lower in the RA group than in the immunocompetent group. Peripheral distribution was less common and generalized distribution was more frequent in the RA group than in the AIDS group. The pathological findings of the AIDS and immunocompetent groups reflected their immune status: There was lack of a granuloma reaction in the AIDS group, and a complete granuloma reaction in the immunocompetent group, while the findings of the RA group varied, including a complete granuloma reaction, a loose granuloma reaction and a hyper-immune reaction. Cases with the last two pathologic findings were symptomatic and showed generalized or central distribution on CT. CONCLUSION: Cryptococcosis in the RA group showed characteristic radiological and pathological findings compared with the other 2 groups.

Prognostic factors in interstitial lung disease associated with primary Sjögren's syndrome: a retrospective analysis of 33 pathologically-proven cases.

INTRODUCTION: Interstitial lung disease associated with primary Sjögren's syndrome (pSS-ILD) shows several patterns such as nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). Although UIP is a well-recognized prognostic determinant in idiopathic interstitial pneumonias, whether this is also the case in pSS-ILD is unclear. The objectives of this study were to evaluate the prognostic effect of UIP, and to identify the prognostic factors in pSS-ILD. METHODS: A retrospective review of medical records identified 33 consecutive patients with pathologically-proven pSS-ILD. Each patient was classified into each ILD pattern by multidisciplinary analysis. Baseline clinical-radiologic-pathologic characteristics and survival rates were compared between the ILD patterns. Finally, the prognostic factors in pSS-ILD were assessed by univariate and subsequent multivariate analyses using Cox's proportional hazards regression model. RESULTS: pSS-ILD patients were diagnosed with NSIP (n = 22) or UIP (n = 11). The median follow-up period was 110 months, and five-year survival rate was 87.3% in the total patient population. The prognosis of the UIP patients was not significantly different from that of the NSIP patients (NSIP to UIP, hazard ratio [HR]: 0.77, 95% confidence interval [CI]: 0.18-3.36, P = 0.73). Multivariate analysis identified PaCO2 (HR: 1.68 per 1 Torr increase, 95% CI: 1.24-2.28, P < 0.01), extent of reticular abnormality on high-resolution CT (HR: 4.17 per 1-grade increment, 95% CI: 1.18-14.73, P = 0.03), and severity of fibroblastic foci (HR: 9.26 per 1-grade increment, 95% CI: 1.74-49.35, P < 0.01) as prognostic factors in pSS-ILD. CONCLUSIONS: UIP in pSS-ILD was not related to poorer prognosis than NSIP. Assessment of detailed clinical-radiologic-pathologic findings is more important than distinguishing UIP to evaluate prognosis in this disease.

Imaging diagnosis of interstitial pneumonia with emphysema (combined pulmonary fibrosis and emphysema).

Based on clinical and radiological findings, Cottin defined combined pulmonary fibrosis and emphysema (CPFE) as pulmonary emphysema in the upper lungs and interstitial pneumonia in the lower lungs with various radiological patterns. Pathologic findings of CPFE probably corresponded with diffuse interstitial pneumonia with pulmonary emphysema, emphysema with fibrosis, and the combination of both. We described reported radiological findings of CPFE.

High-resolution computed tomography features of pulmonary chronic graft-versus-host disease following hematopoietic stem cell transplantation: histopathological correlation.

PURPOSE: The purposes of this study were to evaluate the development pattern in patients with multiple episodes of chronic graft-versus-host disease (cGVHD) and to analyze the computed tomography (CT) appearances of the pulmonary parenchymal injury and its relation to treatment response. MATERIALS AND METHODS: CT patterns from 41 episodes of cGVHD (25 patients) were evaluated retrospectively and classified into four groups: group 1, airway involvement; group 2, subpleural consolidation or ground glass opacity (GGO); group 3, peribronchovascular/periseptal GGO or consolidations; group 4, others. We analyzed the changing pattern of the CT appearance during multiple episodes and the relation between this CT pattern and response to treatment. RESULTS: None of the patients showed airway involvement (group 1) and pulmonary parenchymal injury patterns (group 2 and 3) simultaneously in one episode. The group 3 CT pattern was more resistant to treatment than that of group 2 (P < 0.05). The pathological basis of the group 3 CT pattern varied but was characterized by mural incorporation fibrosis. CONCLUSION: Pulmonary cGVHD affected either the airway or pulmonary parenchyma but did not affect both simultaneously in one episode. Of the four patterns, peribronchovascular GGO/consolidations (group 3 CT pattern) was the most resistant to treatment.