Background In a subgroup of patients with severe interstitial lung disease (ILD) progressing despite conventional immunosuppression, rituximab, a B cell-depleting monoclonal antibody, may offer an effective rescue therapy. Methods Retrospective assessment of 50 patients with severe, progressive ILD (34 with connective tissue disease-associated ILD, 7 with fibrotic hypersensitivity pneumonitis, 3 with likely drug-induced ILD, the rest with miscellaneous ILD patterns, excluding idiopathic pulmonary fibrosis) treated with rituximab between 2010 and 2012. At the time of rituximab treatment, mean DLco was 25.5 % (±9.9%), and FVC was 49.1% (±17.6%). Change in pulmonary function tests compared to pre-rituximab levels, was assessed at six to twelve months post-treatment. Changes in lung function before and after treatment were analysed by Wilcoxon signed rank test. Results In contrast with a median decline in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) of 14.6% and 18.8% respectively in the six to twelve months prior to rituximab, analysis of paired pulmonary function data revealed a median improvement in FVC of 5.7% (p Conclusions In a subgroup of patients with severe, progressive ILD unresponsive to conventional immunosuppression, rituximab may offer a safe and effective therapeutic intervention. Future prospective, controlled trials are warranted to validate these findings.

https://erj.ersjournals.com/content/erj/42/Suppl_57/P5127.full.pdf

Rituximab in severe, treatment-refractory interstitial lung disease

Immunotherapy that includes programmed cell death-1 (PD-1), programmed cell death- ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors has revolutionized the therapeutic strategy in multiple malignancies. Although it has achieved significant breakthrough in advanced non-small cell lung cancer patients, immune-related adverse events (irAEs) including checkpoint inhibitor pneumonitis (CIP), are widely reported. As the particularly worrisome and potentially lethal form of irAEs, CIP should be attached more importance. Especially in non-small cell lung cancer (NSCLC) patients, the features of CIP may be more complicated on account of the overlapping respiratory signs compromised by primary tumor following immunotherapy. Herein, we included the previous relevant reports and comprehensively summarized the characteristics, diagnosis, and management of CIP. We also discussed the future direction of optimal steroid therapeutic schedule for patients with CIP in NSCLC based on the current evidence.

/pdf/immune-checkpoint-inhibitor-associated-pneumonitis-in-non-4lb5xpkqs3.pdf

Immune Checkpoint Inhibitor-Associated Pneumonitis in Non-Small Cell Lung Cancer: Current Understanding in Characteristics, Diagnosis, and Management

Immune-related adverse events associated with immune checkpoint inhibitors: An updated comprehensive disproportionality analysis of the FDA adverse event reporting system.

Background Interstitial lung disease (ILD) and its rapid progression (RP) are the main contributors to unfavourable outcomes of patients with idiopathic inflammatory myopathy (IIM). This study aimed to identify the clinical value of PET/CT scans in IIM-ILD patients and to construct a predictive model for RP-ILD. Methods Adult IIM-ILD patients who were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU), from 1 January 2017 to 31 December 2020 were reviewed. PET/CT scans and other characteristics of patients who met the inclusion and exclusion criteria were collected and analysed. Results A total of 61 IIM-ILD patients were enrolled in this study. Twenty-one patients (34.4%) developed RP-ILD, and 24 patients (39.3%) died during follow-up. After false discovery rate (FDR) correction, the percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P = 0.014), bilateral lung mean standard uptake value (SUVmean, P = 0.014) and abnormal mediastinal lymph node (P = 0.045) were significantly different between the RP-ILD and non-RP-ILD groups. The subsequent univariate and multivariate logistic regression analyses verified our findings. A "DLM" model was established by including the above three values to predict RP-ILD with a cut-off value of ≥ 2 and an area under the curve (AUC) of 0.905. Higher bilateral lung SUVmean (P = 0.019) and spleen SUVmean (P = 0.011) were observed in IIM-ILD patients who died within 3 months, and a moderate correlation was recognized between the two values. Conclusions Elevated bilateral lung SUVmean, abnormal mediastinal lymph nodes and decreased DLCO% were significantly associated with RP-ILD in IIM-ILD patients. The "DLM" model was valuable in predicting RP-ILD and requires further validation.

/pdf/the-lungs-were-on-fire-a-pilot-study-of-18f-fdg-pet-ct-in-1wqytraqf1.pdf

The lungs were on fire: a pilot study of 18F-FDG PET/CT in idiopathic-inflammatory-myopathy-related interstitial lung disease

Aim To investigate the risk factors for interstitial lung disease (ILD) and prognosis in patients with idiopathic inflammatory myopathy (IIM) Methods A retrospective longitudinal study was performed in patients diagnosed with IIM between January 2012 and December 2018 Results The study cohort included 91 men and 195 women who were classified as having dermatomyositis (DM, n = 183), polymyositis (PM, n = 77), or clinical amyopathic DM (CADM, n = 26) ILD was identified in 465% (n = 133) of patients with IIM The independent risk factors for ILD were age at disease onset, presence of anti-Ro-52 antibody, Gottron's papules, elevated serum immunoglobulin M levels and hypoalbuminemia Older age at disease onset, ILD, malignancy, and increased serum aspartate aminotransferase and neutrophil-to-lymphocyte ratio (NLR) were identified as the independent predictors for mortality, whereas elevated serum albumin level was associated with a better prognosis A total of 73 deaths (255%) occurred after a median follow-up time of 33 months Infection (493%) was the leading cause of death In the overall cohort, the 1-year, 5-year and cumulative survival rates were 832%, 742% and 694%, respectively The receiver operating characteristic curve indicated that the optimal cut-off value of NLR for predicting death in IIM was 611 Conclusion IIM patients have a poor prognosis with substantial mortality, especially in patients who have older age at onset, ILD, malignancy and higher NLR Close monitoring and aggressive therapies are required in patients having poor predictive factors

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1756-185X.14128

Analysis of risk factors of interstitial lung disease and mortality rates in Chinese patients with idiopathic inflammatory myopathy

OBJECTIVES Few studies have investigated the prognostic factors for idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) across different clinical/serological phenotypes. METHODS We conducted a retrospective analysis of patients diagnosed with IIM between January 2012 and December 2017. RESULTS Of the 760 IIM cases registered, 679 adult cases were included in this study. ILD was present in 508 cases, and the presence of ILD in the clinically amyopathic DM, DM and PM groups was 92.7, 73.6 and 55.1%, respectively (P   0.05). The prevalence of ILD in the melanoma differentiation-associated protein-5 (MDA-5)+-IIM group was higher than that in MDA-5--IIM group (97.8 vs 72.1%, P   0.05), although both were higher than that in PM group (13.2%, P = 0.01 and P   0.05), and both were lower than that in MDA5+ASA--IM-ILD group (33.7%, P < 0.05). CONCLUSION The prevalence of ILD in IIM and the prognosis of IIM-ILD patients may vary depending on the statuses of the ASA and MDA-5 antibodies.

Prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease: a retrospective study of 679 adult cases

Immune-related pneumonitis is an uncommon but potentially fatal immune-related adverse event in advanced non-small cell lung cancer (NSCLC) patients during treatment with anti-programmed cell death 1 (PD-1) and programmed cell death-ligand 1 (PD-L1). Underlying emphysema, interstitial lung disease (ILD), and previous radiation therapy for lung cancer might be factors precipitating immune-related pneumonitis. The incidence of immune-related pneumonitis is reported to be higher in those treated with PD-1 inhibitors than in those treated with anti-PD-L1 inhibitors. Early detection and diagnosis and appropriate management according to the severity are critical to improving the prognosis. The first-line physicians, including the primary responsible oncologists, family doctors, emergency physicians and NSCLC patients should be trained to identify and report symptoms of immune-related pneumonitis as early as possible. Multidisciplinary treatment teams involving clinicians (including ILD specialists and lung cancer specialists), radiologists and pathologists are recommended for the treatment of immune-related pneumonitis.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/ajco.13380

Programmed cell death 1 (PD-1)/PD-ligand 1(PD-L1) inhibitors-related pneumonitis in patients with advanced non-small cell lung cancer.

Objectives Anti-Ro-52 antibody positivity might be associated with the presence of interstitial lung disease (ILD) among patients with autoimmune features. However, the clinical significance of isolated anti-Ro-52 positivity (i.e., the presence of anti-Ro52 antibodies but the absence of anti-Ro60 antibodies; anti-Ro52+-Ro60-) in patients with ILD is not clear. Methods This is a prospective and observational study of Chinese ILD patients with isolated anti-Ro-52 positivity. According to their myositis-specific antibody (MSA) status, patients were split into groups, and their clinical and radiological features were compared. Results Of the 158 enrolled patients with ILD and isolated anti-Ro-52 positivity (isolated anti-Ro-52-ILD), there were 130 patients with a positive MSA status and 28 patients with a negative MSA status. Anti-synthetase antibodies (ASAs) were found in 61.5% of patients with MSA+ ILD, and anti-melanoma differentiated-associated protein 5 (MDA-5) antibodies were found in the remaining 38.5% of patients. The anti-nuclear antibody (ANA) pattern was associated with ASA and anti-MDA-5 positivity (χ2=70.7, P Conclusions Patients with isolated anti-Ro-52-ILD showed high positivity of MSA. Isolated anti-Ro-52 positivity with cytoplasmic ANA positivity was strongly associated with ASA+-ILD, while ANA negativity was associated with anti-MDA-5+-ILD.

Myositis specific antibodies are associated with isolated anti-Ro-52 associated interstitial lung disease

Clinical characteristics and prognostic analysis of Chinese dermatomyositis patients with malignancies.

Objectives: Long-term use of inhaled corticosteroids (ICS) was reported as a risk factor for patients with chronic obstructive pulmonary disease (COPD) complicated with nontuberculous mycobacterial lung disease (NTM-LD). But it was not reported often in China. Methods: We conducted a retrospective analysis of patients who were diagnosed with COPD and NTM-LD in our department from January 1(st) 2017 to December 31(th) 2018. Results: This study consisted of 10 male and 5 female patients with a mean age of (66±7) years. The detailed clinical data and radiological images were reviewed systemically. There were 4 current smokers (26.7%) and 6 past smokers (40%). All cases were current ICS users, with a mean duration of (27.3±9.7) months, ranging from 3 months to 61 months. Among them, 8 cases (53.3%) used inhaled fluticasone and 7 cases (46.7%) used inhaled budesonide. Aggravated coughing (15 cases, 100%), expectoration (15 cases, 100%) and dyspnea (10 cases, 66.7%) were the common clinical manifestations, although fever was only reported in 4 cases (26.7%). All cases showed normal white blood cell count and lymphocyte count, and some of them (7 cases, 46.7%) showed elevated erythrocyte sedimentation rate and C-reactive protein. Most of them (14 cases, 93.3%) had normal TB-SPOT results. Multiple focal bronchiectasis (9 cases, 60%) and significant emphysema (12 cases, 80%) were the common manifestations of basic high-resolution CT (HRCT) prior NTM infection. The occurrence of bronchiectasis (15 cases, 100%), "tree in bud" sign (12 cases, 80%) and tiny cavities (8 cases, 53.3%) were the common HRCT abnormalities for the NTM-LD cases. According to the 2007's NTM-LD diagnosis criteria, most of them (13 cases, 86.7%) were diagnosed with positive sputum samples at least twice, and 2 cases were diagnosed with positive CT-directed bronchial alveolar lavage fluid. NTM-PCR analysis was performed routinely for the isolated NTM samples to identify the NTM species. Mycobacterium avium complex (MAC) was the most common NTM species (8 cases, 53.3%). After treatment with proposed anti-NTM strategies, most cases improved (9 cases, 60%), and some of them (4 cases, 26.7%) were cured and a few cases (2 cases, 13.3%) relapsed. Conclusions: When COPD patients treated with ICS showed aggravated cough, expectation and/or dyspnea, and new occurrence of bronchiectasis and/or "tree in bud" sign in the recent HRCT, the differential diagnosis of NTM-LD should be considered. Respiratory samples should be arranged for NTM cultures and PCR analysis as soon as possible. Earlier antimicrobial strategies according to the identified NTM species would improve the clinical outcomes.

Yuxin Sun

Papers

Prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease: a retrospective study of 679 adult cases

Programmed cell death 1 (PD-1)/PD-ligand 1(PD-L1) inhibitors-related pneumonitis in patients with advanced non-small cell lung cancer.

Myositis specific antibodies are associated with isolated anti-Ro-52 associated interstitial lung disease

Clinical characteristics and prognostic analysis of Chinese dermatomyositis patients with malignancies.

The clinical analysis of chronic obstructive pulmonary disease patients complicated with nontuberculous mycobacterial pulmonary disease