Acute Interstitial Pneumonia Research Articles

Computed tomography patterns and clinical outcomes of radiation pneumonitis in non-small-cell lung cancer patients.

Radiation pneumonitis (RP) is not an uncommon complication in lung cancer patients undergoing radiation therapy (RT) and symptomatic RP can affect their quality of life. To investigate the CT findings of RP in non-small cell lung cancer (NSCLC) patients and their relationship with clinical outcomes. We reviewed data from 240 NSCLC patients who underwent RT between 2014 and 2022. CT findings of RP were evaluated for parenchymal abnormalities and distribution, which were then classified into three patterns: localized pneumonia (LP), cryptogenic organizing pneumonia (COP), and acute interstitial pneumonia (AIP). Clinical outcomes of RP were evaluated based on Common Terminology Criteria for Adverse Events (CTCAE) grade. Of the 153 patients, 135 developed RP. The most common pattern was LP (n = 78), followed by COP (n = 30) and AIP (n = 25). Among the three CT patterns, CTCAE grade and days between the start of RT and the onset of RP (RT-RP days) were statistically significantly different (p < 0.05). The patients with AIP patterns exhibited higher CTCAE grade, and fewer RT-RP days compared to those with non-AIP patterns (p < 0.05). In these patients, lung-to-lung metastasis and underlying interstitial lung abnormality were observed more frequently (p < 0.05). Underlying pulmonary fibrosis, the AIP pattern, and higher CT extent scores were more frequently observed in higher CTCAE grade group (p < 0.001). In multiple regression analysis, age, bilateral distribution, RT-RP days, and CT extent score ≥3 were independent predicting factors for higher CTCAE grade. RP in NSCLC patients can be classified into LP, COP, and AIP patterns and they exhibit different severities in clinical outcomes.

High-Resolution CT Patterns of Anti-PD1 Checkpoint Inhibitor-Related Pneumonitis in Patients With Lung Cancer.

Lung cancer has the highest morbidity and mortality in the world, and immunotherapies have been developed for this disease in recent years. However, activation of the immune system can cause immune-related adverse events (irAEs), and checkpoint inhibitor-related pneumonitis (CIP), can be the most severe and fatal. But few reports have systematically examined the spectrum of imaging findings of this condition. Therefore, the objective of this paper is to investigate the high-resolution computed tomography (HRCT) characteristics of CIP in patients with lung cancer. To investigate the HRCT characteristics of CIP in patients with lung cancer. HRCT patterns in 41 lung cancer patients who developed CIP after treatment with immune checkpoint inhibitors were retrospectively characterized by interstitial lung disease classification, and their severity was graded. Specific HRCT characteristics related to CIP were identified. There are 4 types of immunotherapy-induce pneumonitis patterns (organizing pneumonia OP 19 cases, nonspecific interstitial pneumonia NSIP 8 cases, acute interstitial pneumonia AIP 7 cases, 7 cases of undetermined type) and image grade (13 cases of grade 1, 17 cases of grade 2, 11 cases of grade 3, 0 cases of grade 4) were identified. Spatial distribution characteristics of these lesions were noted (17 cases predominantly distributed in tumor-containing lobes, 6 cases predominantly distributed in non-tumor-containing lobes, and no specific predilection in 18 cases). Specific CT imaging features found in CIP included, in the order of prevalence, the following: ground glass opacities (38 cases), subpleural/vertical line (37 cases), interstitial thickening around the bronchovascular bundles (36 cases), reticulation (34 cases), fine reticular shadow (31 cases), consolidation (31 cases), small cystic shadow (24 cases, may not having honeycombing), small nodules (17 cases), bronchiectasis (15 cases), honeycombing (11 cases), mosaic sign (11 cases), and pleural effusion (18 cases). HRCT of CIP predominantly manifests as ground glass opacities, reticulation, subpleural/vertical line, interstitial thickening around the bronchovascular bundle, and consolidation.

Antihelical erythema/papules as a potential risk factor for acute and subacute interstitial pneumonia in MDA5+ dermatomyositis: A retrospective cohort study

Antihelical erythema/papules as a potential risk factor for acute and subacute interstitial pneumonia in MDA5+ dermatomyositis: A retrospective cohort study

Pulmonary manifestations of VEXAS syndrome with acute interstitial pneumonia and diffuse alveolar hemorrhage: a case report and literature review

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an emerging adult-onset systemic autoinflammatory disorder affecting multiple organ systems. While lung involvement is common in this syndrome, literature regarding specific patterns is sparse. In this report, we present a case description of a patient with VEXAS syndrome who presented at the emergency department on two separate occasions with acute interstitial pneumonia (AIP) and diffuse alveolar hemorrhage (DAH). A literature review with a comparison of our observed findings to the general findings of VEXAS syndrome, AIP, and DAH is provided. This report underscores the rarity of specific pulmonary manifestations associated with VEXAS syndrome, contributing valuable insight to the limited literature available on this topic.

Acute Lupus Pneumonitis with Cytomegalovirus Co-infection in Patients with Lupus Nephritis

Introduction: Most patients with systemic lupus erythematosus (SLE) show signs of pulmonary involvement. The clinical manifestations of Lupus Pneumonitis are the similar to those of acute interstitial pneumonia. The use of cyclophosphamide in lupus nephritis (LN) is associated with high CMV titers. Ganciclovir is the main choice of therapy for CMV pneumonia infection. Case presentation: A 19-year-old female with previous history of lupus nephritis presented with worsening dyspnea, productive cough with yellowish sputum and hemoptysis. Following physical, laboratory and radiological examinations, the patient was diagnosed with acute lupus pneumonitis, with a differential diagnosis of pneumonia infection. During treatment in the intensive care unit (ICU), she was put on ventilator and received routine hemodialysis due to pulmonary edema. She was given intravenous antibiotics before the culture results came out, but there was no clinical improvement. Once the culture results returned negative, the antibiotics were discontinued and IV pulse methylprednisolone was started. There was significant clinical, radiological, and laboratory improvements. After discharge, the patient experienced hemoptysis again due to CMV pneumonia infection and was given ganciclovir therapy with satisfactory results. Conclusion: In patients with advanced LN and pulmonary involvement, distinguishing between infection and SLE flares may be challenging, which can cause dilemma in diagnosis and treatment decisions. Adequate oxygenation with ventilator, hemodialysis, and administration of ganciclovir and mycophenolic acid provides significant improvements in patient care.

Epidemiological factors associated with gross diagnosis of lung pathologies in feedlot mortalities

Bronchopneumonia (BP) and acute interstitial pneumonia (AIP) are commonly identified lung pathologies in feedlot cattle at treatment or death. Bronchopneumonia with an interstitial pneumonia (BIP) was recently described as an emerging lung pathology. Due to recent introduction of BIP diagnosis, little is known about epidemiological factors associated with this pa­thology and if it differs from AIP and BP. This study aimed to identify epidemiological factors associated with BIP, AIP and BP at necropsy.

Determining frequency of common pulmonary gross and histopathological findings in feedyard fatalities

Pulmonary disease is often associated with morbidity and mortality in feedlot cattle. The most common syndromes in­clude bronchopneumonia, acute interstitial pneumonia, and bronchopneumonia with an interstitial pneumonia. Systemic necropsy is a useful diagnostic tool to collect information to enhance decision making about the health and management of feedlot cohorts. The study objective was to utilize gross nec­ropsy and histopathology to determine the frequency of pul­monary lesions associated with 3 major syndromes and the agreement between gross and histopathological diagnoses. Furthermore, we assessed the consistency of classifying his­topathologic lesions from 4 different lung lobe samples taken from an individual case.

Fatal acute interstitial pneumonia induced by radiotherapy alone.

Fatal acute interstitial pneumonia induced by radiotherapy alone.

Abstract B179: 2-Deoxy-D-glucose (2-DG) combination with ketogenic diet induces sedation and hypothermia in mice that becomes lethal

Abstract Introduction. The term “ketogenic” was coined for the diet that specifically consists of a 4:1 ratio of fats to proteins. 2-Deoxy-d-glucose (2-DG) is a synthetic glucose analog that potently inhibits glycolysis. It has been hypothesized that 2-DG in combination with KD, should improve the anticancer effects of either therapeutic approach. The therapeutic benefit of such a combination was supported by studies of Voss et al. (Int J Mol Sci, 2018. 19(8): PMC6121440), showing that continued combination of KD and anti-glycolytic therapy is feasible, and KD increased tolerance to 2-DG. However, in contrast to this report, our preliminary studies revealed a dose-dependent reduction in the survival of mice of receiving inhibition of glycolysis (2-DG) and KD. The objective of this study was to assess the toxic limitation of the combination of glycolysis inhibition and ketogenic diet. Methods. CD-1 mice were maintained on either a standard diet (SD) or a ketogenic diet (KD). Some groups were treated with of 2-DG at 1.5 g/kg via the oral or intraperitoneal route or vehicle. For temperature monitoring, the animals were implanted subcutaneously with a temperature microchip UCT-2112. Body temperature was recorded manually for each mouse using a contactless, handheld URH-1HP receiver. Alternatively, for continuous monitoring of the body temperature, the UID Mouse Matrix was used. Mice exhibiting treatment-related toxicity symptoms, such as prolonged hypothermia or laborious breathing, and euthanized following blood collection for hematology and serum chemistry analysis. Key organs were also collected for histopathology analysis. Results. Previously, we reported that 2-DG reduces the survival of mice maintained on KD (median survival 9 days p=0.0022), while it is well tolerated by mice receiving regular chow (no deaths reported). Here, we report that the administration of 2-DG induces transient sedation and hypothermia. CBC analysis revealed that the number of platelets in the KD + 2-DG group was significantly decreased compared to the SD + 2-DG group and the KD + vehicle group (p&amp;lt;0.001). The reduction of platelets was associated with a two- to three-fold increase of LDH in the KD + 2-DG group. Histopathological analysis of the lung tissue revealed the presence of diffuse congestion in blood vessels and dilation of the alveolar capillaries consistent with interstitial pneumonia. Similarly, degenerative and congestive hepatic parenchyma was observed in animals treated with 2-DG and KD. Preliminary experiments involving supplementation of 2-DG-treated animals with D-glucose or D-mannose failed to provide a rescue effect. Conclusion. A highly reproducible, dose-dependent toxicity leading to rapid death of treated animals maintained on KD was observed following 2-DG administration, while the same doses appeared to be safe in mice fed a standard diet. The toxic effects induced by the combination treatment included acute thrombocytopenia and acute interstitial pneumonia; however, delineation of the exact mechanism of toxicity requires additional studies. Citation Format: Rafal Zielinski, Moises Martinez Castillo, Damian Grybowski, Krzysztof Grela, Roberto Cardenas-Zuniga, Izabela Fokt, Stanislaw Skora, Gerardo Ramirez, Waldemar Priebe. 2-Deoxy-D-glucose (2-DG) combination with ketogenic diet induces sedation and hypothermia in mice that becomes lethal [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B179.

Histopathological pulmonary lesions in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques experimentally infected with wild-type severe acute respiratory syndrome coronavirus 2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a viral pneumonia characterized by acute interstitial pneumonia and diffuse alveolar damage in humans. Non-human primates (NHPs) are widely used as preclinical animal models for vaccine development against SARS-CoV-2. However, the pathological changes in NHPs have been described only in selected facets and inconsistent nomenclature is used, making it difficult to interpret and compare the outcomes between studies. Here, we present a standardized methodology for histopathological evaluation of experimental infection outcomes in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques. Evaluation criteria for vascular and epithelial changes in the early (3 days post infection [dpi]) and late (21 dpi) phases of the infection were developed, and a four-grade classification encompassing all the histopathological lung lesions was established. The grades of histopathological lung lesions were higher at 3 dpi compared with 21 dpi in both species of macaques, and there were no statistically significant differences in the grades between the two species at 3 dpi and 21 dpi. This study contextualized the pathological SARS-CoV-2 presentation and standardized the terminology and grading scale for lesion severity to facilitate histopathological examination in the macaque model. By referring to the standardized histopathological criteria and grades proposed here, comparable results with high reproducibility can be obtained in future studies of pathogenicity.

The anti-inflammatory effects of NaCl with KCl as a potent graphene exfoliator in a patients with interstitial pneumonia by epithelial-mesenchymal transition

A 72-year-old man with normal pressure hydrocephalus to our hospital with a history of productive cough, sputum, fever, dyspnea combined with nasal cannula oxygen therapy, chest radiography, vital signs: Total leukocyte count of 11800/cmm and Erythrocyte Sedimentation Rate (ESR) 53 mm in the first hour using Westergren method, C-reactive protein (CRP) 11.2 mg/dl [1]. The intravenous infusion of a solution consisting of 250mL normal saline with of potassium chloride (KCl) over 6 h , vitamin C intake with supportive care resulted in recovery, intramuscular injections of the graphene previously [2,3]. After the injection, ESR, CRP was 40-1.91 and segmental neutrophil was 79.6%. Alveolar epithelial cells underwent Epithelial-Mesenchymal Transition (EMT) in the progression of Acute Interstitial Pneumonia (AIP). AIP is characterized by acute respiratory prodrome including sore throat, headache, cough, dyspnea, and often fever with abrupt onset and short duration . AIP was defined Diffuse Alveolar Damage (DAD). The pathologic progress of DAD three phases: acute exudative phase, characterized by interstitial edema, hyaline membrane, and acute interstitial inflammation accumulation; proliferative phase,characterized by in alveolar spaces; and fibrotic phase,characterized by enlarged fibrotic septa and laminated intra-alveolar fibrosis. Epithelial-mesenchymal transition defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype [4].

Clinical Features and Outcomes of the Association of Co-Infections in Children with Laboratory-Confirmed Influenza during the 2022-2023 Season: A Romanian Perspective.

The 2022-2023 influenza season in Romania was characterized by high pediatric hospitalization rates, predominated due to influenza A subtypes (H1N1) pdm09 and H3N2. The lowered population immunity to influenza after the SARS-CoV-2 pandemic and the subsequent stoppage of influenza circulation, particularly in children who had limited pre-pandemic exposures, influenced hospitalization among immunosuppressed children and patients with concurrent medical conditions who are at an increased risk for developing severe forms of influenza. This study focused on the characteristics of influenza issues among pediatric patients, as well as the relationship between different influenza virus types/subtypes and viral and bacterial co-infections, as well as illness severity in the 2022-2023 season after the SARS-CoV-2 pandemic. We conducted a retrospective clinical analysis on 301 cases of influenza in pediatric inpatients (age ≤ 18 years) who were hospitalized at the National Institute of Infectious Diseases "Prof. Dr. Matei Balș" IX Pediatric Infectious Diseases Clinical Section between October 2022 and February 2023. The study group's median age was 4.7 years, and the 1-4 year age group had the highest representation (57.8%). Moderate clinical forms were found in 61.7% of cases, whereas severe versions represented 18.2% of cases. Most of the complications were respiratory (acute interstitial pneumonia, 76.1%), hematological (72.1%, represented by intra-infectious and deficiency anemia, leukopenia, and thrombocytopenia), and 33.6% were digestive, such as diarrheal disease, liver cytolysis syndrome, and the acute dehydration syndrome associated with an electrolyte imbalance (71.4%). Severe complications were associated with a risk of unfavorable evolution: acute respiratory failure and neurological complications (convulsions, encephalitis). No deaths were reported. We noticed that the flu season of 2022-2023 was characterized by the association of co-infections (viral, bacterial, fungal, and parasitic), which evolved more severely, with prolonged hospitalization and more complications (p < 0.05), and the time of use of oxygen therapy was statistically significant (p < 0.05); the number of influenza vaccinations in this group was zero. In conclusion, co-infections with respiratory viruses increase the disease severity of the pediatric population to influenza, especially among young children who are more vulnerable to developing a serious illness. We recommend that all people above the age of six months should receive vaccinations against influenza to prevent the illness and its severe complications.

Trastuzumab Deruxtecan‒Related Interstitial Lung Disease/Pneumonitis: Computed Tomography Imaging Patterns to Guide Diagnosis and Management

PURPOSE Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate approved for the treatment of several advanced cancers; however, severe or fatal interstitial lung disease/pneumonitis can occur. We characterized the computed tomography (CT) patterns of T-DXd‒related pneumonitis as a marker for its clinical severity. MATERIALS AND METHODS Ninety patients with advanced cancers who developed T-DXd‒related pneumonitis in two completed single-arm clinical trials were included. Three radiologists independently characterized the CT patterns of pneumonitis at diagnosis, for analyses of those patterns' relationships with clinical severity and pneumonitis outcome. RESULTS T-DXd‒related pneumonitis most commonly presented with cryptogenic organizing pneumonia (COP) pattern, observed in 65 patients (72%), followed by a newly identified COP/hypersensitivity pneumonitis (HP) pattern (13%), acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) pattern (11%), and HP pattern (3%). A subset of cases with COP pattern demonstrated an atypical distribution with upper and peripheral lung involvement (6/65; 9%). CT patterns were associated with Common Terminology Criteria for Adverse Events severity grades of pneumonitis, with the AIP/ARDS pattern having higher grades compared with others ( P &lt; .0001). Fatal pneumonitis was more common in the AIP/ARDS pattern than in others ( P = .005). The onset of pneumonitis was earlier in the AIP/ARDS pattern compared with others (median time to onset: at 17.9 v 32.7 weeks of therapy; P = .019). Pneumonitis was treated by withholding T-DXd with or without corticosteroids in most patients (78/90; 87%). CONCLUSION T-DXd‒related pneumonitis most commonly demonstrated a COP pattern, with a subset having an atypical distribution. The AIP/ARDS pattern was indicative of severe, potentially fatal pneumonitis, and requires immediate clinical attention to mitigate serious adverse events.

Epidemiological Factors Associated with Gross Diagnosis of Pulmonary Pathology in Feedyard Mortalities.

Respiratory disease continues to be the major cause of mortality in feedyard cattle, with bronchopneumonia (BP) and acute interstitial pneumonia (AIP) as the two most common syndromes. Recent studies described a combination of these pathological lesions with the presence of AIP in the caudodorsal lungs and BP in the cranioventral lungs of necropsied cattle. This pulmonary pathology has been described as bronchopneumonia with an interstitial pneumonia (BIP). The epidemiological characteristics of BIP in U.S. feedyard cattle are yet to be described. This study's objectives were to describe the agreement between feedyard clinical and necropsy gross diagnosis and to characterize epidemiological factors associated with four gross pulmonary diagnoses (AIP, BIP, BP, and Normal pulmonary tissue) observed during feedyard cattle necropsies. Systemic necropsies were performed at six feedyards in U.S. high plains region, and gross pulmonary diagnoses were established. Historical data were added to the dataset, including sex, days on feed at death (DOFDEATH), arrival weight, treatment count, and feedyard diagnosis. Generalized linear models were used to evaluate epidemiological factors associated with the probability of each pulmonary pathology. Comparing feedyard clinical diagnosis with gross pathological diagnosis revealed relatively low agreement and the frequency of agreement varied by diagnosis. The likelihood of AIP at necropsy was higher for heifers than steers and in the 100-150 DOFDEATH category compared with the 0-50 DOFDEATH (p = 0.05). The likelihood of BIP increased after the first treatment, whereas the DOFDEATH 0-50 category had a lower likelihood compared with the 150-200 category (p = 0.05). These findings highlight the importance of necropsy for final diagnosis and can aid the development of future diagnosis and therapeutic protocols for pulmonary diseases.

Acute interstitial pneumonia post-COVID infection complicated by secondary bacterial pnuemonia

64-year-old lady presented to emergency with dyspnoea, fever, cough and green sputum production for the previous week. She had tested positive for SARS-cov-2 two weeks prior to the onset of these symptoms. Investigations including a Chest X-Ray (CXR) (Figure 1a) confirmed a lower respiratory tract infection

Imaging Features of Idiopathic Interstitial Lung Diseases.

Idiopathic interstitial pneumonias (IIPs) are a group of diffuse parenchymal lung diseases of unclear etiology and are distinguished from diffuse parenchymal lung diseases of known cause, such as connective tissue disease-related interstitial lung diseases or hypersensitivity pneumonitis by history, physical exam, imaging, serologic testing, and, when necessary, histopathology. The 2013 American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines are the most widely accepted classification of IIPs and include the following diagnoses: idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, idiopathic lymphocytic interstitial pneumonia, idiopathic pleuro-parenchymal fibroelastosis, respiratory bronchiolitis-interstitial lung disease, and desquamative interstitial pneumonia. The gold standard for diagnosis of IIP involves multidisciplinary discussion among pulmonologists, radiologists, and pathologists. The focus of this review will be to discuss the imaging features of the most common IIPs and the role of multidisciplinary discussion as the gold standard for diagnosis.

Comparison between of fuzzy partial H-transform and fuzzy partial Laplace transform in x-ray images processing of acute interstitial pneumonia

Comparison between of fuzzy partial H-transform and fuzzy partial Laplace transform in x-ray images processing of acute interstitial pneumonia

Lung pathology of natural Babesia rossi infection in dogs.

A proportion of Babesia rossi infections in dogs are classified as complicated and one of the most lethal complications is acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Most dogs that die succumb within 24 hours of presentation. The pulmonary pathology caused by B. rossi in dogs has not been described. The aim of this study was to provide a thorough macroscopic, histological and immunohistochemical description of the lung changes seen in dogs naturally infected with B. rossi that succumbed to the infection. Death was invariably accompanied by alveolar oedema. Histopathology showed acute interstitial pneumonia characterised by alveolar oedema and haemorrhages, with increased numbers of mononuclear leucocytes in alveolar walls and lumens. Intra-alveolar polymerised fibrin aggregates were observed in just over half the infected cases. Immunohistochemistry showed increased numbers of MAC387- and CD204-reactive monocyte-macrophages in alveolar walls and lumens, and increased CD3-reactive T-lymphocytes in alveolar walls, compared with controls. These histological features overlap to some extent (but far from perfectly) with the histological pattern of lung injury referred to as the exudative stage of diffuse alveolar damage (DAD) as is quite commonly reported in ALI/ARDS.

Serum Progranulin Level Might Differentiate Non-IPF ILD from IPF.

Diagnosing interstitial lung disease (ILD) can be a challenging process. New biomarkers may support diagnostic decisions. Elevated serum progranulin (PGRN) levels have been reported in liver fibrosis and dermatomyositis-associated acute interstitial pneumonia. Our aim was to assess the role of PGRN in the differential diagnosis of idiopathic pulmonary fibrosis (IPF) and other ILDs. Serum levels of PGRN were measured by enzyme-linked immunosorbent assay in stable IPF (n = 40), non-IPF ILD (n = 48) and healthy controls (n = 17). Patient characteristics, lung function, CO diffusion (DLCO), arterial blood gases, 6-min walk test, laboratory parameters and high-resolution (HR)CT pattern were assessed. In stable IPF, PGRN levels did not differ from healthy controls; however, serum PGRN levels were significantly higher in non-IPF ILD patients compared to healthy subjects and IPF (53.47 ± 15.38 vs. 40.99 ± 5.33 vs. 44.66 ± 7.77 ng/mL respectively; p < 0.01). The HRCT pattern of usual interstitial pneumonia (UIP) was associated with normal PGRN level, while for non-UIP patterns, significantly elevated PGRN level was measured. Elevated serum PGRN levels may be associated with non-IPF ILD, especially non-UIP patterns and might be helpful in cases of unclear radiological patterns in the differentiation between IPF and other ILDs.

Acute interstitial pneumonia image enhancement using fuzzy partial transforms

Acute interstitial pneumonia image enhancement using fuzzy partial transforms