Chronic Interstitial Pneumonia Research Articles

ORGANIZING PNEUMONIA: A RARE MANIFESTATION OF EARLY-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Systemic Lupus Erythematosus (SLE) affects lungs (30-50%) with pleurisy being the commonest manifestation. Interstitial Pneumonia (IP) related to SLE was found be less reported about 10% and Organizing Pneumonia (OP) type of IP was noted to be very rare (1). Here, we present a rare case of Organizing pneumonia manifesting in SLE CASE PRESENTATION: A 30-year-old female with history of left breast carcinoma status post bilateral mastectomy, adjuvant chemotherapy and radiation therapy completed in March 2019, sickle cell trait and SLE, first presented in January 2020 with dyspnea and cough. CT chest revealed bilateral lower lobe predominant consolidative opacities with air bronchogram and multifocal sub-pleural ground glass opacities throughout both the lungs [Fig 1A], she was treated for pneumonia. On next admission, she also complained of generalized myalgias/arthralgias and unresolving skin rashes on extremities and neck with topical steroids. No other system involvement except for proteinuria. ANA, ds-DNA and lupus anticoagulant were positive with elevated CRP. CT chest slightly worsened compared to previous CT [Fig 1B]. Bronchoscopy revealed normal gross appearance. RLL trans-bronchial biopsy pathology showed mild chronic interstitial inflammation, intra-alveolar macrophages and focal secondary organizing pneumonia with no specific features. She was started on Plaquenil and long-term low dose steroids that controlled her symptoms DISCUSSION: SLE commonly manifests as lung pathology varying from pleurisy (50%), lung parenchymal disease (10-15%) and pulmonary vascular hypertension (1,2). SLE induced IP commonly presents as Chronic IP (63.6%). The most common HRCT finding is unclassifiable and Nonspecific IP (NSIP) is shown to be the most common histopathology (1). Previous articles reported that pulmonary manifestations especially ILD and serositis usually present as a late manifestation or in SLE patients diagnosed at an older age (1,3,4) with no gender predominance. OP has a well-known association with connective tissue disorders like Rheumatoid Arthritis and Myositis but there are only a handful of cases of SLE reported in association with Bronchio-Obliterans Organizing Pneumonia (BOOP), and commonly seen in older women(1). In contrast our patient was young 30-year-old female who had isolated Organizing pneumonia identified as an early manifestation / initial presentation of SLE. Also, it is possible that OP resulted following a predisposing pulmonary insult in SLE – pneumonia and chest radiotherapy. It was noted from metanalysis that NSIP with OP was a favorable prognosis in patients with SLE compared to other histopathology (2,5) CONCLUSIONS: Though rare, Organizing Pneumonia can occur at any age of onset/ duration of SLE and early diagnosis and treatment with steroids and immunosuppression decreases morbidity and mortality from lung manifestations in SLE, given its favorable prognosis Reference #1: 1. Toyoda Y, Koyama K, Kawano H, Nishimura H, Kagawa K, Morizumi S, et al. Clinical features of interstitial pneumonia associated with systemic lupus erythematosus. Respir Investig. 2019;57(5):435–43. Reference #2: 2. Enomoto N, Egashira R, Tabata K, Hashisako M, Kitani M, Waseda Y, et al. Analysis of systemic lupus erythematosus-related interstitial pneumonia: a retrospective multicentre study. Sci Rep. 2019;9(1):1–11.v Reference #3: 5. Tselios K, Urowitz MB. Cardiovascular and Pulmonary Manifestations of Systemic Lupus Erythematosus. Curr Rheumatol Rev. 2017;13(3):206–18. DISCLOSURES: No relevant relationships by Rathnavali Katragadda, source=Web Response No relevant relationships by Vinod Khatri, source=Web Response No relevant relationships by Leela Krishna Vamsee Miriyala, source=Web Response No relevant relationships by Shanti Pittampalli, source=Web Response

Intranasal exposure of African green monkeys to SARS-CoV-2 results in acute phase pneumonia with shedding and lung injury still present in the early convalescence phase

We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.

The prognostic value of fixed time and self-paced walking tests in patients diagnosed with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic fibrosing interstitial pneumonia that has an unknown etiology. The natural history of the disease is characterized by a progressive decline in pulmonary function and overall health and well-being. The median survival time is between 2-3 years; however, the disease course is variable and unpredictable. The twelve-minute walking test (12MWT) and six-minute walking test (6MWT) are two fixed time tests that are commonly used in clinical practice. Our short and clinically oriented narrative review attempted to summarize current evidence supporting the use of fixed time, self-paced walking tests in predicting the outcome of patients diagnosed with IPF. A number of studies have justified that the 6MWT is a simple, cost-effective, well documented, fixed time, and self-paced walking test which is a valid and reliable measure of disease status and can also be used as a prognostic tool in patients with IPF. However, there is a need for dedicated and validated reference equations for this population of patients. It is also necessary to fill the knowledge gap about the role of the 12MWT. We hypothesize that it would be useful in evaluating patients that are in the early stages of the disease.

Serum levels of galectin-3 in idiopathic inflammatory myopathies: a potential biomarker of disease activity.

Galectin-3 is involved in various biological activities, including immune activations and fibrosis. Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases of unknown aetiology, often complicated by interstitial lung disease (ILD). The aim of this study was to evaluate the expression of galectin-3 in sera and tissues of patients with IIM and assess the associations of galectin-3 with patient characteristics and disease activity. Serum galectin-3 levels were significantly higher in IIM patients than in healthy controls. The serum galectin-3 levels positively correlated with serum levels of inflammatory markers and proinflammatory cytokines/chemokines and the Myositis Intention-to-Treat Activity Index. Stratification analysis revealed that patients with IIM-associated ILD (IIM-ILD) had significantly higher levels of serum galectin-3 than those without IIM-ILD. In addition, patients with acute/subacute interstitial pneumonia had significantly higher levels of serum galectin-3 than those with chronic interstitial pneumonia. Furthermore, serum galectin-3 levels in IIM-ILD patients correlated with the radiological assessments of parenchymal lung involvement and treatment response. Immunohistochemical analysis revealed that galectin-3 was expressed in inflammatory cells of myositis and dermatitis sections, whereas in ILD sections, galectin-3 was expressed in interstitial fibrosis and inflammatory cells. Galectin-3 may be involved in the pathogenesis of inflammatory and fibrotic conditions in IIM and can serve as a potential biomarker of disease activity, especially in patients with IIM-ILD.

Traditional Chinese medicine for the treatment of pulmonary fibrosis: A protocol for systematic review and meta-analysis of overview.

Background:Since December 2019, there have been many cases of viral pneumonia of unknown causes in Wuhan City, Hubei Province. During the period of novel coronavirus, according to the observation of limited autopsy and biopsy pathological results, pulmonary interstitial fibrosis appeared in some pathological changes of lung. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia with unknown etiology and pathological changes limited to the lung. At present, there is still a lack of reevaluation of systematic evaluation of traditional Chinese medicine treatment IPF. Therefore, a systematic re-evaluation of the systematic evaluation of traditional Chinese medicine in the treatment of pulmonary fibrosis may help to understand the effective treatment scheme of traditional Chinese medicine in the treatment of pulmonary fibrosis and provide more reliable evidence for the first-line clinicians to treat novel coronavirus.Methods:We will search 3 foreign electronic databases (Cochrane Library, Embase, PubMed) and 4 Chinese electronic databases (China National Knowledge Infrastructure [CNKI], WangFang Database, Chinese Biomedical Literature Database [CBM], and Chinese Scientific Journal Database [VIP]) to collect potential systematic reviews from their inceptions to February 2020. The language of publication is limited to Chinese or English. We will consider SRs and meta-analysis of Traditional Chinese Medicine for the Treatment of pulmonary fibrosis. Two reviewers will identify relevant studies, and then assess the methodological quality by assessment of multiple systematic reviews-2 tool. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) report checklist to assess the quality of reports included in the study. In order to better evaluate the systematic evaluation included in this research, risk of bias in systematic review tool is included in this research to evaluate the methodological quality. The quality of evidence of the included systematic reviews was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The Primary outcomes include: Clinical total effective rate, curative effect of TCM symptoms, pulmonary function and blood gas analysis.Results:The results of this study will be published in a peer-reviewed journal.Conclusions:We expect to obtain reliable evidence from systematic analysis of traditional Chinese medicine treatment of pulmonary fibrosis in an available and useful document.Registration number:INPLASY202060029

Clinical value of biomarkers in diagnosis and treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia characterized by progressive accumulation of fibroblastic foci and destruction of the alveolar structure. Due to an incomplete understanding of the mechanism of the occurrence and progression of IPF, currently no effective means have been available for its early screening or treatment. With a poor overall prognosis, the patients with IPF have a median survival of only 2-4 years. In recent years, several studies have confirmed that dozens of molecules are involved in the development of IPF and can be used as potential biomarkers. These biomarkers play important roles in early diagnosis (such as SP-D, MMP-7, and osteopontin), prognostic evaluation (such as telomerase length, KL-6, mtDNA, HSP-70, LOXL2, CXCL13, miRNA, ICAM-1, and CCL18), and guiding treatment of IPF (such as TOLLIP rs3750920 genotype, SAMS score, and SP-D), and also provide potential therapeutic targets (such as TERT, TERR, RTEC, and PARN).

Correlation of increased serum leucine-rich α2-glycoprotein levels with disease prognosis, progression, and activity of interstitial pneumonia in patients with dermatomyositis: A retrospective study.

ObjectiveTo investigate whether leucine-rich α2-glycoprotein (LRG) can be a biomarker for the disease activity, progression, and prognosis of interstitial pneumonia (IP) in patients with dermatomyositis (DM).MethodsCorrelations between the clinical findings and serum LRG levels were investigated in 46 patients with DM-IP (33 with acute/subacute IP [A/SIP] and 13 patients with chronic IP [CIP], including 10 fatal cases of IP).ResultsThe median serum LRG level of 18.4 (14.6–25.2) μg/mL in DM-IP patients was higher than that in healthy control subjects. The median levels of serum LRG at baseline and at 2 and 4 weeks after the initiation of treatment in the patients who died were significantly higher than those in the surviving patients (P = 0.026, 0.029, and 0.008, respectively). The median level of serum LRG in the DM-A/SIP patients was significantly higher than that in the DM-CIP patients (P = 0.0004), and that in the anti-MDA5-Ab-positive group was slightly higher than that in the anti-ARS-Ab-positive group. The serum LRG levels correlated significantly with the serum levels of LDH, C-reactive protein, ferritin, AaDO2, %DLco, and total ground-glass opacity score. The survival rate after 24 weeks in patients with an initial LRG level ≥ 17.6 μg/mL (survival rate: 40%) was significantly lower than that in patients with an initial LRG level < 17.6 μg/mL (100%) (P = 0.0009).ConclusionThe serum LRG level may be a promising marker of disease activity, progression, and prognosis in patients with DM-IP.

Characteristics of patients with chronic idiopathic interstitial pneumonia undergoing repeated respiratory-related hospitalizations: A retrospective cohort study.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease. Chronic idiopathic interstitial pneumonia (c-IIP) is a group of lung diseases consisting mainly of fibrotic IIPs, and IPF is a type of c-IIP. Some patients with c-IIP undergo respiratory-related hospitalizations (RHs). With the hypothesis that the characteristics of patients who undergo RHs are related to the number of hospitalizations, we reviewed and investigated the RHs of patients with c-IIP. We retrospectively examined the data of patients with c-IIP who were admitted to Kindai University Hospital between January 2008 and December 2018 for respiratory-related causes. During the study period, 243 patients with c-IIP were hospitalized a total of 544 times because of respiratory-related causes. The most common reasons for the first RH were acute exacerbation (48.1%) followed by pulmonary infection (32.5%). The most frequent reason for subsequent RHs was pulmonary infection. The in-hospital and 90-day mortality rate of patients with pulmonary infection increased with increasing numbers of RHs. Patients with multiple RHs had significantly worse long-term survival than patients hospitalized a single time. Pulmonary infection was the most frequent reason for repeated RHs. The proportion of all patients hospitalized for pulmonary infection at each RH increased with increasing numbers of RHs, along with the mortality rate of patients with pulmonary infections. Furthermore, repeated RHs were associated with poor survival.

U ne rémission « en peau de chagrin »

In systemic sclerosis, the presence of an anti-RNA polymerase III antibody (ARNpol3) is associated with an increased risk of cancer. The characteristic picture of this serotype includes severe diffuse cutaneous involvement, a high risk of renal scleroderma crisis and a 10year survival of only around 30%. Pulmonary involvement is less common. We report the case of a woman initially treated for drug-induced acute interstitial lung disease revealing chronic interstitial pneumonia with autoimmune features. The disease evolved in three stages with the occurrence of a rapidly progressive diffuse skin sclerosis with anti-ARNPol3antibodies in the context of ovarian cancer remission.

Multidisciplinary team approach on a case of bilateral interstitial pneumonia

Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by exposure to a wide variety of organic particles. In this article, we report a rare case of a 44-year-old male patient with cough and shortness of breath for more than 4 years and exacerbation for 1 month. The findings of lung computed tomography (CT) and pathology supported a diagnosis of chronic HP. The patient had a history of ulcerative colitis for 5 years, and used to take salazosulfapyridine more than 4 years since 2013. We organized domestic and foreign experts to discuss the diagnosis and treatment of this case. The final clinical diagnosis was chronic interstitial pneumonia [related to sulfasalazine or inflammatory bowel disease (IBD) itself], pulmonary infections. It is recommended to discontinuation of sulfasalazine and oral administration of glucocorticoids and required long-term follow-up.

Natural Autoantibodies in Chronic Pulmonary Diseases.

In autoantibody-mediated autoimmune diseases, pathogenic autoantibodies generated by a failure of central or peripheral tolerance, have different effects mediated by a variety of mechanisms. Interestingly, even non-autoimmune chronic diseases have a set of disease-specific natural autoantibodies that are maintained for a long time. Because most of these natural autoantibodies target intracellular proteins or long non-coding RNAs, they are speculated to be non-pathological and have some important as yet unrecognized physiological functions such as debris clearance. Recently, we revealed a set of disease-specific natural autoantibodies of chronic pulmonary diseases with unknown etiology by protein arrays that enable detection of specific autoantibodies against >8000 targets. Surprisingly, some of the targeted antigens of disease-specific autoantibodies were subsequently reported by other laboratories as strongly associated with the disease, suggesting that these antigens reflect the pathology of each disease. Furthermore, some of these autoantibodies that target extracellular antigens might modify the original course of each disease. Here, we review the disease-specific natural autoantibodies of chronic pulmonary diseases, including chronic fibrosing idiopathic interstitial pneumonias, sarcoidosis, and autoimmune pulmonary alveolar proteinosis, and discuss their utility and effects.

Pleuroparenchymal fibroelastosis-like lesions in patients with interstitial pneumonia diagnosed by multidisciplinary discussion with surgical lung biopsy

PurposeThe present study aimed to evaluate the significance of Pleuroparenchymal fibroelastosis (PPFE)-like lesions in predicting prognosis in patients with chronic interstitial pneumonia (IP). MethodThe present study enrolled 207 patients with IP in whom surgical lung biopsy was performed. Among the patients enrolled in the present study, 77 had idiopathic pulmonary fibrosis (IPF), 15 had nonspecific interstitial pneumonia (NSIP), 13 had chronic hypersensitivity pneumonitis (CHP), 41 had connective tissue disease (CTD), three had PPFE, and 58 had unclassifiable diagnosis. The incidence, characteristics, and thickness of PPFE-like lesions were evaluated in each patient with IP. Additionally, the influence of PPFE-like lesions on the prognosis was also determined. ResultsOf 207 patients, 160 (77.3 %) showed PPFE-like lesions. The frequency of PPFE-like lesions was similar in patients with IPF, NSIP, CHP, CTD, and unclassifiable diagnosis (79.5 %, 79.5 %, 73.2 %, 65.9 %, and 81 %, respectively); however, PPFE-like lesions were present in all patients with PPFE (p = 0.42). Consequently, there was no significant difference in the characteristics of PPFE-like lesions among patients with all forms of IP, except PPFE. PPFE-like lesions were not a significant predictor of prognosis (hazard ratio [HR], 1.16; 95 % confidence interval [CI], 0.64–2.10, p = 0.62); however, patients with PPFE-like lesions under the aortic arch had significantly poorer prognoses (HR, 2.70; 95 % CI, 1.66–4.39, p < 0.001). For craniocaudal extent comparison, patients with IPF with PPFE-like lesions below the level of the carina had significantly poorer prognoses than those without PPFE-like lesions (p = 0.001, overall survival 53.1 and 80.6, respectively). ConclusionPPFE-like lesions are common in patients with IP, and their characteristics were not significantly different among all forms of IP, except idiopathic PPFE. The broad extent of PPFE-like lesions is an important predictor of prognosis in patients with IPF.

Bioinformatics Analysis Identifies Potential Key Genes of Peripheral Blood Mononuclear Cell in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial pneumonia with progressive worsening of dyspnea and lung function. The etiology of IPF is unknown, and the pathogenesis remains unclear. Our study aimed to investigate the key genes of the peripheral blood mononuclear cell in IPF by bioinformatics analysis. Our study used the online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE28042 to identify differentially expressed genes (DEGs) between IPF patients and healthy controls. We performed the Gene Ontology (GO) and pathway enrichment analyses of genes for annotation, visualization, and integrated discovery. The STRING database constructed Protein-protein interaction (PPI) network analysis, and hub genes were identified by the CytoHubba plugin. Moreover, we used the receiver operating characteristic (ROC) curve to assess the diagnostic value of the hub genes. In total, 28 upregulated and 44 downregulated genes were identified in the differential expression analysis. The protein-protein interaction network (PPI) was established with 69 nodes and 68 edges. The top 10 hub genes were JUN, FOS, STAT3, SOCS3, JUNB, DUSP1, IL4, FCER1A, MS4A2, and CPA3. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched for the important module containing hub genes contained Fc epsilon RI signaling pathway, TNF signaling pathway, Jak-STAT signaling pathway, and MAPK signaling pathway. Additionally, the identified hub genes show high functional similarity and diagnostic value in IPF. Our study used bioinformatics analysis to provide new insight into the mechanisms underlying IPF. However, more experiments are needed to explore the relationships between the top 10 hub genes and IPF in the future.

A phase II study of atezolizumab for pretreated advanced/recurrent non-small cell lung cancer with idiopathic interstitial pneumonias: rationale and design for the TORG1936/AMBITIOUS study.

Background:Approximately 10% of patients with non-small cell lung cancer (NSCLC) are complicated with comorbid interstitial pneumonia (IP) with a poor prognosis. The pharmacotherapy for advanced lung cancer occasionally induces fatal acute exacerbation of pre-existing IP. Due to the lack of prospective studies, there is an urgent need to establish a safe and effective pharmacotherapy, especially for second-line or later settings. Atezolizumab, an anti-programmed cell death-ligand 1 antibody, is thought to be the safest candidate for second-line therapy among various immune checkpoint inhibitors. Moreover, compared with patients without IP, the patients with comorbid IP may have higher tumor mutation burden (TMB) or microsatellite instability (MSI), which are partly associated with a more favorable response to immune checkpoint inhibitors.Methods:The Thoracic Oncology Research Group 1936/AMBITIOUS study is an ongoing, multicenter, single-arm, phase II trial to assess the safety and efficacy of atezolizumab for pretreated advanced/recurrent patients with NSCLC complicated with idiopathic, chronic fibrotic IP with a forced vital capacity of >70%. The patients will receive atezolizumab (1200 mg, day 1) every 3 weeks until the discontinuation criteria are met. The primary end point of this study is the 1-year survival rate, and a sample size of 38 patients is set. As a translational research, we will perform the analysis of TMB, somatic mutations, and MSI for nucleic acids extracted from archival tumor samples.Discussion:Since there is no standard second-line or later therapy of advanced NSCLC with IP, the results of this study are expected to have a major impact on clinical practice.Trial registration:Japan Registry of Clinical Trials, jRCTs031190084, registered 26 August 2019 - retrospectively registered, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190084

Prognostic differences among patients with idiopathic interstitial pneumonias with acute exacerbation of varying pathogenesis: a retrospective study

BackgroundAcute exacerbation of chronic fibrosing idiopathic interstitial pneumonias (AE-IIPs) is associated with a high mortality rate. In 2016, an international working group proposed a revised diagnostic criteria for AE-IIPs, suggesting that it be classified as idiopathic or triggered. Many factors are known to trigger AE-IIPs, including surgery, infection, and drugs. However, it is unknown which AE-IIPs triggers have a worse prognosis. We aimed to investigate the prognosis of patients with various clinical types of AE-IIPs, particularly infection-triggered, non-infection triggered, and idiopathic AE-IIPs.MethodsWe retrospectively collected data from 128 chronic fibrosing IIPs (CF-IIPs) patients who were hospitalized by respiratory failure between April 2009 and March 2019 at Juntendo University Hospital. Among these patients, we evaluated 79 patients who developed AE-IIPs and 21 who developed pneumonia superimposed on CF-IIPs. Patients with AE-IIPs were classified into three types: idiopathic, infection-triggered, and non-infection-triggered AE-IIPs. We analyzed differences in patient characteristics, examination findings; level of serum markers, results of pulmonary function, and radiological findings, prior treatment for baseline CF-IIPs, and prognosis. We then evaluated the risk factor for early death (death within 30 days from the onset of AE-IIPs) associated with AE-IIPs.ResultsAmong the patients who developed AE-IIPs, 34 were characterized as having idiopathic, 25 were characterized as having infection-triggered, and 20 were categorized as having non-infection-triggered AE-IIPs. Survival time for pneumonia superimposed on IIPs was significantly longer than that for any AE-IIPs. Survival time for bacterial pneumonia superimposed on CF-IIPs was significantly longer than that for AE-IIPs (for each idiopathic and all triggered IIPs). Thereafter, survival time for infection-triggered was significantly longer than for idiopathic or non-infection-triggered AE-IIPs. The mortality rate was significantly lower in infection-triggered AE-IIPs than in other types of AE-IIPs. Furthermore, the incidence of infection-triggered AE-IIPs in winter was significantly higher than that in other seasons. Moreover, the clinical AE-IIPs types and radiological findings at AE-IIP onset were significant risk factors for AE-IIPs-induced early death.ConclusionsOur findings suggest that patients with infection-triggered AE-IIPs can expect a better prognosis than can patients with other clinical types of AE-IIPs.

Case Report of Diffuse Parenchymal Lung Disease with Non-Specific Interstitial Pneumonia Pattern and Good Response to Treatment

The diffuse parenchymal lung diseases (DPLDs) are a heterogeneous group of conditions affecting the pulmonary parenchyma (interstitial) and/or alveolar lumen. IPF (Idiopathic Pulmonary Fibrosis) is a chronic interstitial pneumonia of unknown causes. It is commonest form of DPLD but its treatment response is very poor. On the other hand, NSIP (Non-Specific Interstitial Pneumonia) can still be a variant of DPLD with better treatment response and prognosis. Here we discussed a young female with NSIP with good response to steroid. Faridpur Med. Coll. J. Jul 2018;13(2): 101-103

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

To assess inter-observer variability in identifying traction bronchiectasis on computed tomography (CT) using additional criteria for chronic fibrosing interstitial pneumonia. 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. 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). Inter-observer agreement in identifying traction bronchiectasis improves when using the additional criteria which specify chronic fibrosing interstitial pneumonia as the underlying disease.

Non-Perfused Brain and Retino-Dural Hemorrhage

10 cases of pneumonia causing cardiac arrest and non-perfused brain occurred at ages 40 days-30 months, in a medico-legal setting. In each deceased child, both the pneumonia and non-perfused brain were verified histologically. Upper respiratory infection and mouth-breathing accompanied the pneumonia, with ongoing choking on formula or food in three cases, and vomiting in an additional five cases. In eight of the 10 cases, the pre-terminal event was a quiet respiratory arrest while sleeping, or being carried in the arms. Adrenaline was given up to 7 times during CPR lasting 44±32 minutes, with up to 2 hours CPR and fall in body temp to &amp;lt;32°C. Mean survival was 1.9±1.5 days and heparin was given for organ donation in 3 cases. The lungs showed chronic interstitial pneumonia as described by Katzenstein, with superadded acute bronchiolo-alveolar infiltrates in two cases of aspiration. The court permitted recuts and cellular characterization of the interstitial cells in one case, revealing the infiltrate was ~40% histiocytes, 5% T or B cells, and ~50% vimentin+ mesenchymal cells. All brains showed features of non-perfused brain and retino-dural hemorrhage. The observed features of non-perfused brain were blurring of the gray-white junction, edema, gross friability, histologic pallor, closure of the microcirculation, patchy acidophilic neurons and recent demarcated pan-necrosis, and pituitary infarction in one patient where hypophysis was sampled. Normally, from birth to 30 months, cerebral blood flow increases to 55% of cardiac output, accompanying physical brain growth. Restoration of high cardiac output using adrenaline-CPR means that on resuscitation, re-routing of blood that can no longer go through the non-perfused brain detours through dura, face, scalp, eyes and optic nerve sheaths. The diversion of blood around non-perfused brain results in facial bruising and retino-dural hemorrhage that can be misinterpreted as head trauma, and a common inference of child abuse in the courts. In the present series from Australia, Canada and the USA, outcomes ranged from acquittal to life imprisonment.LEARNING OBJECTIVESThis presentation will enable the learner to:1.Investigate infant deaths including workup for interstitial pneumonia.2.Know cerebral blood flow changes in development, and cranial blood flow dynamics in non-perfused brain.

Effect of H2 treatment in a mouse model of rheumatoid arthritis‐associated interstitial lung disease

Rheumatoid arthritis (RA)‐associated interstitial lung disease (ILD), a primary cause of mortality in patients with RA, has limited treatment options. A previously established RA model in D1CC transgenic mice aberrantly expressed major histocompatibility complex class II genes in joints, developing collagen II‐induced polyarthritis and anti‐cyclic citrullinated peptide antibodies and interstitial pneumonitis, similar to those in humans. Molecular hydrogen (H2) is an efficient antioxidant that permeates cell membranes and alleviates the reactive oxygen species‐induced injury implicated in RA pathogenesis. We used D1CC mice to analyse chronic lung fibrosis development and evaluate H2 treatment effects. We injected D1CC mice with type II collagen and supplied them with H2‐rich or control water until analysis. Increased serum surfactant protein D values and lung densities images were observed 10 months after injection. Inflammation was patchy within the perilymphatic stromal area, with increased 8‐hydroxy‐2ʹ‐deoxyguanosine‐positive cell numbers and tumour necrosis factor‐α, BAX, transforming growth factor‐β, interleukin‐6 and soluble collagen levels in the lungs. Inflammatory and fibrotic changes developed diffusely within the perilymphatic stromal area, as observed in humans. H2 treatment decreased these effects in the lungs. Thus, this model is valuable for studying the effects of H2 treatment and chronic interstitial pneumonia pathophysiology in humans. H2 appears to protect against RA‐ILD by alleviating oxidative stress.

Acute exacerbation of chronic fibrosing interstitial pneumonia in patients receiving antifibrotic agents: incidence and risk factors from real-world experience

Background and objectiveHere, we present real-world data on the incidence and risk factors of acute exacerbation (AE) in patients with chronic fibrotic interstitial pneumonia (CFIP) treated with antifibrotic agents, which has been previously poorly documented.MethodsWe retrospectively examined clinical characteristics, incidence and risk factors of AE in a cohort of 100 patients with CFIP (n = 75, idiopathic pulmonary fibrosis [IPF]; n = 25, other conditions), all of whom received antifibrotic agents in a real-world setting.ResultsThe median follow-up was 17.4 months (interquartile range [IQR], 6.6 to 26.7 months). During the follow-up periods, 21 patients experienced AE after starting antifibrotic agents. The estimated 1-, 2-, and 3-year AE incidence rates were 11.4% (95% confidence interval [95%CI], 6.2–20.3%), 32% (95%CI, 20.7–47.4%), and 36.3% (95%CI 23.5–53.1%), respectively. Decreased baseline lung function (forced vital capacity and carbon monoxide diffusing capacity of the lung), existence of pulmonary hypertension estimated from an echocardiogram, higher Interstitial Lung Disease-Gender, Age, and Physiology (ILD-GAP) score, supplementary oxygen, and concomitant corticosteroid and proton-pump inhibitor (PPI) use upon starting the antifibrotic agent were risk factors of AE. Concomitant corticosteroid and PPI use and corticosteroid dose were risk factor of AE in a multivariate Cox regression hazard model adjusting for ILD-GAP score.ConclusionAE of CFIP is more common in patients with physiologically and functionally advanced disease under antifibrotic agents. Prudent use of corticosteroids and PPIs when initiating antifibrotic agents may be recommended. Further studies are warranted.