Interstitial Pneumonia In Patients Research Articles

MUC5B rs35705950 Promoter Variant Is Associated with Usual Interstitial Pneumonia in Patients with Antisynthetase Syndrome

Background: The presence of the rs35705950 variant in the MUC5B gene promoter is a critical genetic risk factor in idiopathic pulmonary fibrosis (IPF). It has been associated with usual interstitial pneumonia (UIP) in several interstitial lung diseases (ILDs). In antisynthetase syndrome (ASSD), most high-resolution computed tomography (HRCT) patterns are inflammatory, but up to 13% have UIP, leading to a worse prognosis. Methods: This single-center study included 60 patients with ASSD-ILD. We investigated whether carrying the MUC5B rs35705950 promoter variant was associated with UIP. To estimate the strength of the association between the genotype of the MUC5B rs35705950 promoter variant and the fibrotic pattern we used the odds ratio (cOR), and to assess the effect of confounding variables (age, evolution time, and sex), we performed a logistic regression to obtained the adjusted odds ratio (aOR). Results: The GT genotype of the MUC5B rs35705950 promoter variant is associated with up to a 4-fold increased risk of UIP (cOR 5.0, 95% CI 1.13–22.10), and the effect was even maintained after adjusting for potentially confounding variables such as sex, age, and time to progression (aOR 5.2, 95% CI 1.04–25.89). Conclusions: our study supports the role of MUC5B rs35705950 in ASSD-ILD with UIP. It reinforces that this polymorphism in our population could have a similar genetic basis to that already described in other ILDs that present predominantly fibrotic patterns.

Assessing the diagnostic utility of serum tumor markers for lung cancer detection in patients with interstitial pneumonia.

The prevalence of lung cancer among individuals afflicted with interstitial pneumonia (IP) stands at approximately 20%. The early detection of lung cancer via chest computed tomography (CT) surveillance proves challenging in IP patients. Our investigation sought to identify a potential biomarker capable of providing early indications of the presence of lung tumors in such patients. We examined the attributes of serum tumor markers, imaging characteristics, and histological findings in individuals diagnosed with IP, both with and without concurrent lung cancer. 106 patients diagnosed with IP were included in the study, comprising 36 individuals with concurrent lung cancer and 70 patients solely diagnosed with IP. Serum concentrations of CEA and CA12-5 were notably elevated in IP patients with lung cancer, compared to those with IP alone. Logistic regression analyses revealed that, in comparison to IP patients within the first quartile of CEA levels, the relative risk of developing lung cancer associated with IP escalated by 4.0-fold, 3.1-fold, 11.0-fold, and 13.3-fold in the second, third, fourth, and fifth quartiles, respectively. Upon controlling for gender and age, statistical significance in risk was observed solely for the fourth and fifth quartiles. Receiver operating characteristic (ROC) curve analysis conducted in patients diagnosed with ILD-CA identified a CEA cutoff point of 6.9ng/mL, demonstrating sensitivities of 61.1% and specificities of 78.5%. The area under the curve was calculated as 0.7(95% CI: 0.63-0.81). The serum levels of CEA were notably elevated in IP patients with concurrent lung cancer in contrast to those who were just suffering from IP. The heightened serum CEA levels correlate with an escalated risk of cancer occurrence among IP patients, suggesting that serum CEA levels could potentially serve as an indicative marker for the presence of cancer in IP patients.

Deleterious impact of trivial to severe interstitial pneumonia and emphysema on mortality and acute exacerbation of interstitial pneumonia in patients with lung cancer: a retrospective cohort study

BackgroundInterstitial pneumonia and emphysema may complicate patients with lung cancer. However, clinical significance of trivial and mild pulmonary abnormalities remains unclear. In this study, we aimed to investigate whether trivial and mild interstitial pneumonia and emphysema, in addition to their advanced forms, impact the prognosis and lead to acute exacerbation of interstitial pneumonia (AEIP) in patients with lung cancer.MethodsThis retrospective cohort study was conducted at a tertiary hospital and included patients with lung cancer. Computed tomography images were evaluated using the interstitial lung abnormality (ILA) score for interstitial pneumonia, which included no ILA, equivocal ILA, ILA, interstitial lung disease (ILD), and the Goddard score for emphysema. Cox analyses were performed using the ILA and Goddard scores as the main explanatory variables, adjusting for multiple covariates.ResultsAmong 1,507 patients with lung cancer, 1,033 had no ILA, 160 had equivocal ILA, 174 had ILA, and 140 had ILD. In total, 474 patients (31.5%) exhibited interstitial pneumonia and 638 (42.3%) showed emphysema. The log-rank trend test showed that survival probability was significantly better in patients with no ILA, followed by those with equivocal ILA, ILA, and ILD (P < 0.001). After adjustment, the ILA and Goddard scores remained significant variables for increased hazard ratios (HR) for mortality: no ILA (HR, 1.00: reference), equivocal ILA (HR, 1.31; 95% confidence interval [CI], 1.18–1.46; P < 0.001), ILA (HR, 1.71; 95% CI, 1.39–2.12; P < 0.001), ILD (HR, 2.24; 95% CI, 1.63–3.09; P < 0.001), and Goddard score (HR, 1.03; 95% CI, 1.01–1.06; P < 0.010). Moreover, both scores were associated with increased cause-specific HRs for AEIP.ConclusionOur results revealed that approximately one-third of patients with lung cancer had interstitial pneumonia when incorporating trivial and mild cases. Because interstitial pneumonia and emphysema, ranging from trivial to severe, significantly impact mortality and AEIP in patients with lung cancer, we should identify even trivial and mild cases of these pulmonary abnormalities among patients with lung cancer in addition to the advanced ones.

Histopathological aspects of usual interstitial pneumonia in patients with systemic connective tissue diseases.

Five cases of patients with systemic connective tissue diseases (CTD) who developed connective tissue disease-associated interstitial lung disease (CTD-ILD) with progressive pulmonary fibrosis (PPF) are reported here. Unspecified ILD was diagnosed using high-resolution computed tomography (HRCT). Histologically, all cases were usual interstitial pneumonia (UIP) with findings of advanced (3/5) to diffuse (2/5) fibrosis, with a partially (4/5) to completely (1/5) formed image of a honeycomb lung. The fibrosis itself spread subpleurally and periseptally to more central parts (2/5) of the lung, around the alveolar ducts (2/5), or even without predisposition (1/5). Simultaneously, there was architectural reconstruction based on the mutual fusion of fibrosis without compression of the surrounding lung parenchyma (1/5), or with its compression (4/5). The whole process was accompanied by multifocal (1/5), dispersed (2/5), or organized inflammation in aggregates and lymphoid follicles (2/5). As a result of continuous fibroproduction and maturation of the connective tissue, the alveolar septa thickened, delimiting groups of alveoli that merged into air bullae. Few indistinctly visible (2/5), few clearly visible (1/5), multiple indistinctly visible (1/5), and multiple clearly visible (1/5) fibroblastic foci were present. Among the concomitant changes, areas of emphysema, bronchioloectasia, and bronchiectasis, as well as bronchial and vessel wall hypertrophy, and mucostasis in the alveoli and edema were observed. The differences in the histological appearance of usual interstitial pneumonia associated with systemic connective tissue diseases (CTD-UIP) versus the pattern associated with idiopathic pulmonary fibrosis (IPF-UIP) are discussed here. The main differences lie in spreading lung fibrosis, architectural lung remodeling, fibroblastic foci, and inflammatory infiltrates.

Acute exacerbation predicting poor outcomes in idiopathic interstitial pneumonia and advanced lung cancer patients undergoing cytotoxic chemotherapy

Effective treatment for advanced lung cancer and idiopathic interstitial pneumonia (IIP) remains an unmet medical need. The relationship between chemotherapy’s effectiveness in advanced lung cancer and the risk of acute exacerbation of IIP is poorly investigated. There is limited evidence that patients who experience an acute exacerbation of IIPs during cytotoxic chemotherapy have poorer outcomes than those who do not. Among 1004 patients with advanced lung cancer and IIPs enrolled in our published multi-centre retrospective study from 110 Japanese institutions, 708 patients (male: female, 645:63; mean age, 70.4) received first-line chemotherapy. The occurrence of chemotherapy-triggered acute exacerbations of IIPs and overall survival (OS) were analysed. The OS between groups of patients with and without the occurrence of acute exacerbation was compared at four landmark time points (30, 60, 90, and 120 days), starting from the first-line chemotherapy, using the landmark method. The incidence of acute exacerbation in patients who received first-line chemotherapy with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was more frequent in NSCLC patients than in SCLC (4.2% vs 12.6%; odds ratio [OR]: 3.316; 95% confidence interval [CI] 1.25–8.8). Median survival time was 9.9 months (95% CI 9.2–10.7). Patients who experienced acute exacerbation had significant worse survival outcomes than those who did not at various time points (30 days, hazard ratio [HR]: 5.191, 95% CI 2.889–9.328; 60 days, HR: 2.351, 95% CI 1.104–5.009; 90 days, HR: 2.416, 95% CI 1.232–4.739; and 120 days, HR: 2.521, 95% CI 1.357–4.681). Acute exacerbation during first-line chemotherapy can predict poor survival.Trial Registration number: UMIN000018227.

Radiological and histopathological features and treatment response by subtypes of interstitial pneumonia with autoimmune features: A prospective, multicentre cohort study

BackgroundPatients with idiopathic interstitial pneumonia (IIP) have a favourable prognosis when they have interstitial pneumonia with autoimmune features (IPAF). However, precise IPAF-related findings from high-resolution computed tomography (HRCT) and lung histopathological specimens and the treatment response have not been fully determined. Therefore, this study was conducted to evaluate the relationship between findings on HRCT or lung histopathological specimens and the progression of interstitial pneumonia in patients with IPAF. MethodsThis multicentre cohort study prospectively enrolled consecutive patients with IIP. At the diagnosis of IIP, we systematically evaluated 74 features suggestive of connective tissue diseases and followed them up. HRCT, lung specimens, serum antibodies, and the clinical course were also evaluated. ResultsAmong 222 patients with IIP, 26 (11.7%) fulfilled the IPAF criteria. During a median observation period of 36 months, patients with IPAF showed better survival than those without IPAF (p = 0.034). While histopathological findings were not related to IPAF, nonspecific interstitial pneumonia (NSIP) with organizing pneumonia (OP) overlap was the most prevalent HRCT pattern (p < 0.001) and the consolidation opacity was the most common radiological finding in IPAF (p = 0.017). Furthermore, in patients with IPAF, the diagnosis of COP or NSIP with OP overlap was associated with a higher increase in %FVC in 1 year than in those with idiopathic pulmonary fibrosis, NSIP, or unclassifiable IIP (p = 0.002). ConclusionsThis study shows the presence of consolidation opacity on HRCT and the diagnosis of COP or NSIP with OP overlap are associated with IPAF and its favourable treatment response in patients with IPAF.

Artificial intelligence for segmentation and classification of lobar, lobular, and interstitial pneumonia using case-specific CT information.

Pneumonia can be anatomically classified into lobar, lobular, and interstitial types, with each type associated with different pathogens. Utilizing artificial intelligence (AI) to determine the anatomical classifications of pneumonia and assist in refining the differential diagnosis may offer a more viable and clinically relevant solution. This study aimed to develop a multi-classification model capable of identifying the occurrence of pneumonia in patients by utilizing case-specific computed tomography (CT) information, categorizing the pneumonia type (lobar, lobular, and interstitial pneumonia), and performing segmentation of the associated lesions. A total of 61 lobar pneumonia patients, 60 lobular pneumonia patients, and 60 interstitial pneumonia patients were consecutively enrolled at our local hospital from June 2020 and May 2022. All selected cases were divided into a training cohort (n=135) and an independent testing cohort (n=46). To generate the ground truth labels for the training process, manual segmentation and labeling were performed by three junior radiologists. Subsequently, the segmentations were manually reviewed and edited by a senior radiologist. AI models were developed to automatically segment the infected lung regions and classify the pneumonia. The accuracy of pneumonia lesion segmentation was analyzed and evaluated using the Dice coefficient. Receiver operating characteristic curves were plotted, and the area under the curve (AUC), accuracy, precision, sensitivity, and specificity were calculated to assess the efficacy of pneumonia classification. Our AI model achieved a Dice coefficient of 0.743 [95% confidence interval (CI): 0.657-0.826] for lesion segmentation in the training set and 0.723 (95% CI: 0.602-0.845) in the test set. In the test set, our model achieved an accuracy of 0.927 (95% CI: 0.876-0.978), precision of 0.889 (95% CI: 0.827-0.951), sensitivity of 0.889 (95% CI: 0.827-0.951), specificity of 0.946 (95% CI: 0.902-0.990), and AUC of 0.989 (95% CI: 0.969-1.000) for pneumonia classification. We trained the model using labels annotated by senior physicians and compared it to a model trained using labels annotated by junior physicians. The Dice coefficient of the model's segmentation improved by 0.014, increasing from 0.709 (95% CI: 0.589-0.830) to 0.723 (95% CI: 0.602-0.845), and the AUC improved by 0.042, rising from 0.947 to 0.989. Our study presents a robust multi-task learning model with substantial promise in enhancing the segmentation and classification of pneumonia in medical imaging.

Pneumocystis jirovecii with high probability detected in bronchoalveolar lavage fluid of chemotherapy-related interstitial pneumonia in patients with lymphoma using metagenomic next-generation sequencing technology

BackgroundPrevious studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF).MethodsFifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared.ResultsOf the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids.ConclusionOur findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive.

Impact of partial pressure of arterial oxygen and radiologic findings on postoperative acute exacerbation of idiopathic interstitial pneumonia in patients with lung cancer.

To establish accurate diagnostic criteria and predictors of treatment response for postoperative acute exacerbation (AE) in patients with lung cancer and idiopathic interstitial pneumonia (IIP). Among 93 patients with IIP who underwent surgery for lung cancer, suspected postoperative AE developed in 20 (21.5%). Patients were divided into a progressive AE group, comprising patients with bilateral alveolar opacities and decreasing PaO2 ≥ 10mmHg (n = 5); an incipient AE group, comprising patients with unilateral alveolar opacities and decreasing PaO2 ≥ 10mmHg (n = 10); and an indeterminate AE group, comprising patients with alveolar opacities but decreasing PaO2 < 10mmHg (n = 5). The progressive AE group had significantly higher 90-day mortality (80%) than the incipient AE group (10%, P = 0.017) or the indeterminate AE group (0%, P = 0.048). Bilateral opacities may indicate advanced AE and poor prognosis, whereas unilateral opacities may indicate an early stage of AE and a good prognosis. PaO2 < 10mmHg may indicate conditions other than AE. In patients with lung cancer and IIP, decreasing PaO2 and HRCT findings may allow for the initiation of rapid and accurate treatment strategies for postoperative AE.

Clinical Characterization and Predictive Factors for Progression in a Cohort of Patients with Interstitial Lung Disease and Features of Autoimmunity: The Need for a Revision of IPAF Classification Criteria.

Background and Objectives: The "interstitial pneumonia with autoimmune features" (IPAF) criteria have been criticized because of the exclusion of usual interstitial pneumonia (UIP) patients with a single clinical or serological feature. To classify these patients, the term UIPAF was proposed. This study aims to describe clinical characteristics and predictive factors for progression of a cohort of interstitial lung disease (ILD) patients with at least one feature of autoimmunity, applying criteria for IPAF, specific connective tissue diseases (CTD), and a definition of UIPAF when possible. Methods: We retrospectively evaluated data on 133 consecutive patients with ILD at onset associated with at least one feature of autoimmunity, referred by pulmonologists to rheumatologists from March 2009 to March 2020. Patients received 33 (16.5-69.5) months of follow-up. Results: Among the 101 ILD patients included, 37 were diagnosed with IPAF, 53 with ILD-onset CTD, and 11 with UIPAF. IPAF patients had a lower prevalence of UIP pattern compared to CTD-ILD and UIPAF patients (10.8% vs. 32.1% vs. 100%, p < 0.01). During the follow-up, 4 IPAF (10.8%) and 2 UIPAF (18.2%) patients evolved into CTD-ILD. IPAF patients presented features not included in IPAF criteria, such as sicca syndrome (8.1%), and were more frequently affected by systemic hypertension (p < 0.01). Over one year, ILD progression (greater extent of fibrosis on HRCT and/or decline in PFTs) was less frequent in the IPAF group compared to CTD-ILD and UIPAF (32.3% vs. 58.8% vs. 72.7, p = 0.02). A UIP pattern and an IPAF predicted a faster (OR: 3.80, p = 0.01) and a slower (OR: 0.28, p = 0.02) ILD progression, respectively. Conclusions: IPAF criteria help identify patients who might develop a CTD-ILD, even though a single clinical or serological feature is respected. Future revisions of IPAF criteria should include sicca syndrome and separate UIP-pattern into a different definition (UIPAF), given its association with a different prognosis, independently from ILD classification.

Pathophysiological conditions induced by SARS-CoV-2 infection reduce ACE2 expression in the lung.

SARS-CoV-2 infection causes a variety of physiological responses in the lung, and understanding how the expression of SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), and its proteolytic activator, transmembrane serine protease 2 (TMPRSS2), are affected in patients with underlying disease such as interstitial pneumonia will be important in considering COVID-19 progression. We examined the expression of ACE2 and TMPRSS2 in an induced usual interstitial pneumonia (iUIP) mouse model and patients with IPF as well as the changes in whole-lung ACE2 and TMPRSS2 expression under physiological conditions caused by viral infection. Histopathological and biochemical characteristics were analyzed using human specimens from patients with IPF and precision-cut lung slices (PCLS) from iUIP mouse model showing UIP with honeycombing and severe fibrosis after non-specific interstitial pneumonia. ACE2 expression decreased with acute lung inflammation and increased in the abnormal lung epithelium of the iUIP mouse model. ACE2 is also expressed in metaplastic epithelial cells. Poly(I:C), interferons, and cytokines associated with fibrosis decreased ACE2 expression in PCLS in the iUIP model. Hypoxia also decreases ACE2 via HIF1α in PCLS. Antifibrotic agent, nintedanib attenuates ACE2 expression in invasive epithelial cells. Patients with IPF are at a higher risk of SARS-CoV-2 infection due to the high expression of ACE2. However, ACE2 and TMPRSS2 expression is decreased by immune intermediaries, including interferons and cytokines that are associated with viral infection and upon administration of antifibrotic agents, suggesting that most of the viral infection-induced pathophysiological responses aid the development of resistance against SARS-CoV-2 infection.

Development of an Artificial Intelligence Model for Analyzing the Relationship between Imaging Features and Glucocorticoid Sensitivity in Idiopathic Interstitial Pneumonia.

High-resolution CT (HRCT) imaging features of idiopathic interstitial pneumonia (IIP) patients are related to glucocorticoid sensitivity. This study aimed to develop an artificial intelligence model to assess glucocorticoid efficacy according to the HRCT imaging features of IIP. The medical records and chest HRCT images of 150 patients with IIP were analyzed retrospectively. The U-net framework was used to create a model for recognizing different imaging features, including ground glass opacities, reticulations, honeycombing, and consolidations. Then, the area ratio of those imaging features was calculated automatically. Forty-five patients were treated with glucocorticoids, and according to the drug efficacy, they were divided into a glucocorticoid-sensitive group and a glucocorticoid-insensitive group. Models assessing the correlation between imaging features and glucocorticoid sensitivity were established using the k-nearest neighbor (KNN) algorithm. The total accuracy (ACC) and mean intersection over union (mIoU) of the U-net model were 0.9755 and 0.4296, respectively. Out of the 45 patients treated with glucocorticoids, 34 and 11 were placed in the glucocorticoid-sensitive and glucocorticoid-insensitive groups, respectively. The KNN-based model had an accuracy of 0.82. An artificial intelligence model was successfully developed for recognizing different imaging features of IIP and a preliminary model for assessing the correlation between imaging features and glucocorticoid sensitivity in IIP patients was established.

Different Lung Parenchyma Quantification Using Dissimilar Segmentation Software: A Multi-Center Study for COVID-19 Patients.

Background: Chest Computed Tomography (CT) imaging has played a central role in the diagnosis of interstitial pneumonia in patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can be used to obtain the extent of lung involvement in COVID-19 pneumonia patients either qualitatively, via visual inspection, or quantitatively, via AI-based software. This study aims to compare the qualitative/quantitative pathological lung extension data on COVID-19 patients. Secondly, the quantitative data obtained were compared to verify their concordance since they were derived from three different lung segmentation software. Methods: This double-center study includes a total of 120 COVID-19 patients (60 from each center) with positive reverse-transcription polymerase chain reaction (RT-PCR) who underwent a chest CT scan from November 2020 to February 2021. CT scans were analyzed retrospectively and independently in each center. Specifically, CT images were examined manually by two different and experienced radiologists for each center, providing the qualitative extent score of lung involvement, whereas the quantitative analysis was performed by one trained radiographer for each center using three different software: 3DSlicer, CT Lung Density Analysis, and CT Pulmo 3D. Results: The agreement between radiologists for visual estimation of pneumonia at CT can be defined as good (ICC 0.79, 95% CI 0.73–0.84). The statistical tests show that 3DSlicer overestimates the measures assessed; however, ICC index returns a value of 0.92 (CI 0.90–0.94), indicating excellent reliability within the three software employed. ICC was also performed between each single software and the median of the visual score provided by the radiologists. This statistical analysis underlines that the best agreement is between 3D Slicer “LungCTAnalyzer” and the median of the visual score (0.75 with a CI 0.67–82 and with a median value of 22% of disease extension for the software and 25% for the visual values). Conclusions: This study provides for the first time a direct comparison between the actual gold standard, which is represented by the qualitative information described by radiologists, and novel quantitative AI-based techniques, here represented by three different commonly used lung segmentation software, underlying the importance of these specific values that in the future could be implemented as consistent prognostic and clinical course parameters.

A Handcrafted Radiomics-Based Model for the Diagnosis of Usual Interstitial Pneumonia in Patients with Idiopathic Pulmonary Fibrosis.

The most common idiopathic interstitial lung disease (ILD) is idiopathic pulmonary fibrosis (IPF). It can be identified by the presence of usual interstitial pneumonia (UIP) via high-resolution computed tomography (HRCT) or with the use of a lung biopsy. We hypothesized that a CT-based approach using handcrafted radiomics might be able to identify IPF patients with a radiological or histological UIP pattern from those with an ILD or normal lungs. A total of 328 patients from one center and two databases participated in this study. Each participant had their lungs automatically contoured and sectorized. The best radiomic features were selected for the random forest classifier and performance was assessed using the area under the receiver operator characteristics curve (AUC). A significant difference in the volume of the trachea was seen between a normal state, IPF, and non-IPF ILD. Between normal and fibrotic lungs, the AUC of the classification model was 1.0 in validation. When classifying between IPF with a typical HRCT UIP pattern and non-IPF ILD the AUC was 0.96 in validation. When classifying between IPF with UIP (radiological or biopsy-proved) and non-IPF ILD, an AUC of 0.66 was achieved in the testing dataset. Classification between normal, IPF/UIP, and other ILDs using radiomics could help discriminate between different types of ILDs via HRCT, which are hardly recognizable with visual assessments. Radiomic features could become a valuable tool for computer-aided decision-making in imaging, and reduce the need for unnecessary biopsies.

Radiographic Progression and Survival of the Different HRCT Patterns of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a peculiar (typical) HRCT pattern, but biopsy can demonstrate usual interstitial pneumonia in patients with atypical patterns. It is unknown how progression pattern varies among different radiographic presentations of IPF. We sought to investigate the longitudinal radiographic evolution and survival of typical and non-typical patterns. One-hundred-twenty-three patients diagnosed with IPF in 2 tertiary referral hospitals were included in the study. Longitudinal evolution of non-typical patterns was considered. The HRCT visual fibrosis score was used as a reliable evaluation tool of disease progression. HRCTs were scored by 2 senior chest radiologists with ILD expertise. The primary endpoint was the evolution of the presentation pattern to probable or typical. The secondary endpoint was lung transplant (LTx)-free survival from the time of diagnosis. Average interval between HRCTs was 16±5 months; average follow-up after the 2nd HRCT was 17±11 months. Four out of 45 (8.9%) patients with probable pattern "evolved" to a typical pattern of IPF, while 5 out of 31 (16.1%) with indeterminate/alternative pattern "evolved" to probable pattern. An average HRCT fibrosis score increase of 9±11% was observed with typical (n=49), 6±5% with probable (n=43) and 7±8% (n=31) with indeterminate/alternative presentation pattern. LTx-free survival and lung function declines did not show any difference related to presentation HRCT patterns. The evolution of a non-typical UIP pattern to a typical one is infrequent. All presentation HRCT patterns of IPF evolve in similar way and are associated with comparable survival time.[/sc].

Incidence and Characteristics of CD20 Monoclonal Antibody-Induced Interstitial Pneumonitis

Background:CD20 monoclonal antibody therapy is the backbone of treatment for B-cell non-Hodgkin lymphoma. Several studies have described an association between the use of rituximab and non-infectious interstitial pneumonitis, with estimates ranging from 3.9% to 8.4%. 1-3 However, several novel CD20 monoclonal antibodies have been introduced in the past decade, with obinutuzumab gaining FDA approval in 2013, ofatumumab first approved in 2014, and rituximab/hyaluronidase human approved as a subcutaneous route of rituximab in 2017. While the use of these agents has rapidly increased in clinical practice, the incidence of pneumonitis with these agents is not well known. Thus, we have performed a retrospective review of patients with B cell lymphoma treated with CD20 monoclonal antibody therapy to determine the incidence and characteristics of pneumonitis with these novel agents.Methods:We evaluated all patients at the University of North Carolina at Chapel Hill with B-cell lymphoma who were treated with CD20 monoclonal antibody therapy from 2014 to 2020. We performed individual chart review to verify the presence of interstitial pneumonitis, as defined by presence of respiratory symptoms (cough, dyspnea, fever, chest pain) in addition to imaging findings (pulmonary opacity on chest X-ray and/or ground glass opacities on chest computed tomography (CT)) without alternative cause (CHF with pulmonary edema, COPD flare, infectious cause including bacterial, fungal or viral pneumonia/bronchitis). We extracted demographic data, comorbid conditions, tobacco use history, and timing of pneumonitis related to CD20 monoclonal antibody exposure. We determined rates of pneumonitis based on agent and chemotherapy backbone.Results:We identified 18 cases of chart-confirmed interstitial pneumonitis over a six-year period, out of 2,207 patients treated with CD20-monoclonal antibody therapy. Seven (39%) were current or former smokers, with a median of 30 pack-years smoked. Five (29%) had a history of hypersensitivity reaction to rituximab infusion. Pneumonitis developed after a median of 4 cycles, and 16 days from the most recent CD20 monoclonal antibody infusion. Ten (56%) had diffuse large B-cell lymphoma, 4 (22%) had mantle cell lymphoma, and 1 (6%) each had follicular lymphoma, chronic lymphocytic leukemia, hairy cell leukemia, and Waldenstrom's macroglobulinemia. Eight cases (44%) occurred among patients being treated with R-CHOP, 2 (11%) were treated with BR, 2 (11%) were receiving single agent rituximab, although several other regimens were represented. Most cases occurred in patients being treated with infusional rituximab, but the rate remained quite low (14/1654, 0.8%). Four occurred in patients receiving subcutaneous rituximab hycela out of 167 treated patients (2.4%), less than prior estimates of pneumonitis with monoclonal antibody therapy. Most cases of pneumonitis were treated with steroids (n=15, 83%), although none required infliximab or anti-TNF agents, and no cases of pneumonitis were fatal. Most notably, we did not identify any cases of pneumonitis among patients treated with ofatumumab (n=51) or obinutuzumab (n=58).Conclusion:This retrospective review reinforced the safety of novel anti-CD20 agents, with low rates of interstitial pneumonitis among patients treated with infusional or subcutaneous rituximab. Cases that did occur were effectively treated with steroids, and there were no fatalities associated with pneumonitis. Ofatumumab and obinutuzumab were not associated with any cases of interstitial pneumonitis.Bibliography1. Katsuya H, Suzumiya J, Sasaki H, et al. Addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy has a high risk of developing interstitial pneumonia in patients with non-Hodgkin lymphoma. Leuk Lymphoma. 2009;50(11):1818-1823. doi:10.3109/104281909032587802. Salmasi G, Li M, Sivabalasundaram V, et al. Incidence of pneumonitis in patients with non-Hodgkin lymphoma receiving chemoimmunotherapy with rituximab. Leuk Lymphoma. 2015;56(6):1659-1664. doi:10.3109/10428194.2014.9630753. Liu X, Hong X-N, Gu Y-J, Wang B-Y, Luo Z-G, Cao J. Interstitial pneumonitis during rituximab-containing chemotherapy for non-Hodgkin lymphoma. Leuk Lymphoma. 2008;49(9):1778-1783. doi:10.1080/10428190802270886 [Display omitted] DisclosuresGrover: Novartis: Consultancy; Genentech: Research Funding; ADC: Other: Advisory Board; Kite: Other: Advisory Board; Tessa: Consultancy. Dittus: BeiGene: Other: Advisory Board; Seattle Genetics: Research Funding; AstraZeneca: Research Funding; Genentech: Research Funding.

Fibrotic extracellular matrix induces release of extracellular vesicles with pro-fibrotic miRNA from fibrocytes

RationaleExtracellular vesicles (EVs) are small lipid vesicles, and EV-coupled microRNAs (miRNAs) are important modulators of biological processes. Fibrocytes are circulating bone marrow-derived cells that migrate into the injured lungs and...

Surgical treatment for patients with idiopathic pulmonary fibrosis and lung cancer: postoperative acute exacerbation of idiopathic pulmonary fibrosis and outcomes.

Postoperative exacerbation of interstitial pneumonia in patients with interstitial lung disease and lung cancer has emerged as a serious problem. Therefore, we need to determine the risk factors for the development of postoperative exacerbation of interstitial pneumonia in this population. There are several subtypes of interstitial lung disease, which may lead to confusion about the treatment of patients with interstitial lung disease and lung cancer. Among the idiopathic forms of interstitial lung disease, we focused on idiopathic pulmonary fibrosis (IPF) and reviewed the surgical treatments used for patients with IPF and lung cancer.

A retrospective study on the efficacy of Ninjin’yoeito on fatigue in patients with interstitial pneumonia

IntroductionFatigue, caused by dyspnea associated with progression of interstitial pneumonia (IP), can negatively affect patients' quality of life (QOL). Ninjin’yoeito (NYT), a Chinese herbal medicine, is prescribed for general symptoms of fatigue and for fatigue associated with various respiratory diseases. However, there is a lack of integrated research on the effects of NYT in patients with IP. Therefore, we retrospectively investigated the efficacy of NYT in patients with IP and fatigue. Materials and methodsFrom the IP patients who had taken NYT, 19 who met the following inclusion criteria were included: (1) age of ≥20 years, (2) fatigue, and (3) history of NYT administration. The primary endpoint was fatigue, which was assessed using the Chalder Fatigue Scale (CFS). The secondary endpoints were loss of appetite and dyspnea, which were evaluated using the Simplified Nutritional Appetite Questionnaire (SNAQ) and modified Medical Research Council (mMRC) scores, respectively. All items were measured before and after 12 weeks of NYT administration. ResultsIn the enrolled 19 patients (male, 12; female, 7; mean age, 65.8 ± 12.7 years), the underlying diseases were idiopathic pulmonary fibrosis (n = 8), idiopathic pleuroparenchymal fibroelastosis (n = 5), connective tissue disease-related interstitial pneumonia (n = 2), chronic hypersensitivity pneumonitis (n = 3), and nonspecific interstitial pneumonia (n = 1). The CFS score decreased from 17.1 ± 6.8 before administration to 13.4 ± 5.7 after administration of NYT (p = 0.0389). The SNAQ score did not change markedly. The median mMRC score decreased from 3 to 2, however, the difference was not significant. ConclusionMany subtypes of IP are progressive, and a cure cannot be expected in cases of irreversible lung fibrosis. Therefore, a multifaceted approach to improve and maintain the QOL is needed in addition to the standard of care. This study showed that NYT can improve fatigue and help maintain the QOL in IP patients.

Patients with Terminal Interstitial Pneumonia Require Comparable or More Palliative Pharmacotherapy for Refractory Dyspnea than Patients with Terminal Lung Cancer.

Background: Dyspnea is a severe symptom of terminal-stage interstitial pneumonia (IP). We commonly use continuous morphine or midazolam for terminal refractory dyspnea.Objective: We aimed to determine whether there is a difference in the use of continuous morphine and midazolam for terminal dyspnea between IP patients and lung cancer (LC) patients.Design: This is a single-center retrospective study.Setting/Subjects/Measurements: We retrospectively examined the clinical records of IP and LC patients who had died in our hospital. These patients were divided into the IP and LC groups to compare the use of morphine and midazolam.Results: Continuous morphine was administered to 50.0% of those in the IP group and 38.0% of those in the LC group for terminal dyspnea. There was no difference in the effect at six hours after morphine initiation between the two groups, but the concomitant use of continuous midazolam and morphine was more common in the IP group than in the LC group. The dose of continuous midazolam was significantly higher in the IP group than in the LC group, and the survival time after morphine initiation was significantly shorter in the IP group.Conclusions: The efficacy of continuous morphine administration for terminal dyspnea in IP patients was similar to that in LC patients for a short time after initiation, but just before death, more patients in the IP group required concomitant use of midazolam and morphine. Thus, IP patients require comparable or more palliative treatment than LC patients.