Search Results (19)

Background: Human metapneumovirus (hMPV) is a respiratory pathogen that causes illness ranging from mild upper respiratory tract infections to severe pneumonia, particularly in individuals with comorbidities. Fatal cases of hMPV-induced hemorrhagic pneumonia are rare and likely under-reported. Diagnosis is often delayed due to overlapping symptoms with other respiratory viruses and the rapid progression of the disease. Case presentation: We report the case of a 55-year-old man with a complex medical history, including liver cirrhosis and diabetes mellitus, who developed acute viral pneumonia. Initial symptoms appeared three days before a sudden clinical deterioration marked by shortness of breath, hemoptysis, and respiratory failure. A nasopharyngeal swab taken on the third day of illness tested positive for hMPV by qRT-PCR. The patient died the following day. Postmortem molecular testing confirmed hMPV in lung tissue and alveolar contents. Autopsy revealed bilateral hemorrhagic pneumonia with regional lymphadenopathy. Histopathological examination showed alveolar hemorrhage, multinucleated cells, neutrophilic infiltration, activated autophagy in macrophages, and numerous cytoplasmic eosinophilic viral inclusions. Conclusions: This is the first documented case of fatal hMPV pneumonia in Armenia. It highlights the potential severity of hMPV in adults with chronic health conditions and emphasizes the need for timely molecular diagnostics. Postmortem identification of characteristic viral inclusions may serve as a cost-effective histopathological marker of hMPV-associated lung pathology. Full article

The hospital-at-home (HaH) model offers hospital-level care within patients’ homes and has proven effective for managing conditions such as pneumonia. The point-of-care ultrasonography (PoCUS) is a key diagnostic tool in this model, especially when traditional imaging modalities are unavailable. This review explores how PoCUS can be optimized to manage pneumonia in HaH settings, focusing on its diagnostic accuracy in patients with comorbidities, differentiation from mimickers, and role in assessing disease severity. Pulmonary comorbidities, such as heart failure and interstitial lung disease (ILD), can complicate lung ultrasound (LUS) interpretation. In heart failure, combining lung, cardiac, and venous assessments (e.g., IVC collapsibility, VExUS score) improves diagnostic clarity. In ILD, distinguishing chronic changes from acute infections requires attention to B-line patterns and pleural abnormalities. PoCUS must differentiate pneumonia from conditions such as atelectasis, lung contusion, cryptogenic organizing pneumonia, eosinophilic pneumonia, and neoplastic lesions—many of which present with similar sonographic features. Serial LUS scoring provides useful information on pneumonia severity and disease progression. Studies, particularly during the COVID-19 pandemic, show correlations between worsening LUS scores and poor outcomes, including increased ventilator dependency and mortality. Furthermore, LUS scores correlate with inflammatory markers and gas exchange metrics, supporting their prognostic value. In conclusion, PoCUS in HaH care requires clinicians to integrate multi-organ ultrasound findings, clinical context, and serial monitoring to enhance diagnostic accuracy and patient outcomes. Mastery of LUS interpretation in complex scenarios is crucial to delivering personalized, high-quality care in the home setting. Full article

Interstitial lung diseases (ILD) represent a diverse group of disorders that primarily affect the pulmonary interstitium and, less commonly, involve the alveolar and vascular epithelium. Overlapping clinical, radiological and histopathological features make proper classification difficult, requiring multiple complementary methodologies, including flow cytometry of bronchoalveolar lavages (BAL). This retrospective study analyzed BAL flow cytometry data from 1074 real-life patients, quantifying alveolar macrophages, CD4/CD8 lymphocytes, neutrophils, eosinophils, and CD1a+ Langerhans cells, with the aim of evaluating its diagnostic utility in ILD and pulmonary infection. Clustering and logistic regression analyses identified seven distinct leukocyte profiles: lymphocytic (associated with hypersensitivity pneumonitis, cryptogenic organizing pneumonia, and lymphocytic interstitial pneumonia), sarcoidosis, macrophagic (including nonspecific interstitial pneumonia, desquamative interstitial pneumonitis, pneumoconiosis, and unclassifiable ILD), neutrophilic (including usual interstitial pneumonia, respiratory bronchiolitis ILD, and acute interstitial pneumonia), infectious diseases, eosinophilic ILD, and Langerhans cell histiocytosis. The estimated leukocyte profiles were associated with different overall survival (OS) outcomes. Neutrophilic profiles, both infectious and non-infectious, correlated with poorer OS, particularly in patients without pulmonary fibrosis. Furthermore, corticosteroids and other immunosuppressive therapies did not show significant OS differences across leukocyte profiles. Although the gold standard in BAL cytology continues to be cytopathology, these results support BAL flow cytometry as a rapid and reliable complementary tool to aid in the classification of interstitial lung diseases based on immune cell profiles, providing valuable predictive information and contributing to personalized therapeutic approaches. Full article

Background and Objectives: Eosinophilic lung diseases (ELD) encompass disorders with an abnormally high number of polymorphonuclear eosinophils in the lungs. Presentation severity can range from low-grade fever and cough to life-threatening acute respiratory distress syndrome (ARDS). Due to the rarity of these conditions, no large sample studies have been performed to assess the characteristics of patients with pulmonary eosinophilia. Materials and Methods: Patients admitted with a diagnosis of pulmonary eosinophilia between the years 2016 and 2020 were extracted from the largest inpatient US database, the Nationwide Inpatient Sample (NIS). Patients under the age of eighteen and those with diabetic ketoacidosis were excluded. Baseline demographic characteristics and medical comorbidities were evaluated for individuals admitted with pulmonary eosinophilia depending on intubation requirement. The primary outcomes included in-hospital mortality, intubation, and length of stay (LOS). Results: 3784 records were extracted, among which 384 patients required intubation. Patients who required intubation had higher rates of in-hospital mortality (23.9% vs. 1.2% p < 0.0001%) and a significantly more prolonged hospital stay (19 days vs. 6 days p < 0.001) compared to patients who did not need intubation. Factors associated with mortality in the intubated group included increasing age (OR: 1.022, 95% CI 1.002–1.042), duration of intubation superior to 96 h (OR: 2.705, 95% CI 1.235–5.927), and AKI (OR: 2.964, 95% CI 1.637–5.366). Conclusions: Our findings suggest that ELD patients requiring intubation experience significantly higher rates of in-hospital mortality, acute kidney injury, deep venous thrombosis, and ARDS. Full article

Background: Eosinophilic pneumonias denote a rare condition, wherein infiltrating eosinophilic granulocytes accumulate within the lung parenchyma. Although eosinophilic pneumonias may be idiopathic, they are also associated with secondary causes. More than 110 medications have been linked to eosinophilic pneumonia, including several antidepressants. This review presents an analysis of case reports of eosinophilic pneumonia correlated to antidepressants. Objectives: The objectives of this study are to provide a contemporary overview of the literature delineating eosinophilic pneumonia as a potential sequela of antidepressant medication treatment, and to discuss possible pathogenetic mechanisms linking antidepressants to eosinophilic pneumonia. Methods and Data Selection: A literature search was performed in PubMed and Scopus databases from 1963 to October 2024. The search strategy used the terms “eosinophilic pneumonia AND antidepressants”. Sources included in this review were screened for relevance, focusing on references discussing eosinophilic pneumonia associated with any class of antidepressants. Case reports meeting the diagnostic criteria for acute eosinophilic pneumonia (AEP) or chronic eosinophilic pneumonia (CEP) were included in the review. Clinical, epidemiological, laboratory, radiology and bronchoscopy data, implicated antidepressant and dosage, and therapeutic interventions were reported. Results: This study found that various types of antidepressants are associated with AEP and CEP. The clinical presentation ranges from mild symptoms to respiratory failure and intubation. Outcomes were favorable in most cases, with complete remission achieved after discontinuation of the causative drug and, in severe cases, a short course of corticosteroids. Conclusions: Although a rare cause, antidepressants may lead to eosinophilic pneumonia, and should be considered in the differential diagnosis of unexplained pulmonary infiltrates. Clinical suspicion must be aroused, as early recognition would prevent unnecessary work-up and navigation of the diagnosis. Full article

Background/Objectives: The interpretation of evidence on the de-escalation of triple therapy with the withdrawal of inhaled corticosteroids (ICSs) to dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstructive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discontinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: We searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov, and CENTRAL for RCTs and observational studies from inception to 22 March 2024, investigating the effect of triple therapy de-escalation with the withdrawal of ICSs to dual therapy on the risk of COPD exacerbation, pneumonia, and lung function. This study was registered with PROSPERO, CRD42024527942. Results: A total of 3335 studies was screened; 3 RCTs and 3 real-world non-interventional studies were identified as eligible. The analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80–1.15; I² = 77%) for ICS withdrawal compared to triple therapy continuation. The analysis according eosinophil levels showed that COPD subjects with ≥300 eosinophils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated to LABA/LAMA (pooled HR: 1.35, 95% CI: 1.00–1.82; I²: 56%). ICS withdrawal did not significantly affect the risk of mortality and pneumonia. Conclusions: The de-escalation of triple therapy with ICS withdrawal does not affect the main outcomes evaluated (moderate or severe exacerbations, change in trough FEV₁). COPD patients with high blood eosinophils (≥2% or ≥300 cells/µL) are most likely to benefit from continuing triple therapy. Full article

USA300, a dominant clone of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), is circulating globally and can cause necrotizing pneumonia with high morbidity and mortality. To further reveal the host anti-MRSA infection immune response, we established a mouse model of acute primary MRSA pneumonia challenged with aerosols of the USA300 clone. A time-course transcriptome analysis of the lungs collected at 0, 12, 24, 48 and 96 h post-infection (hpi) was conducted using RNA sequencing (RNA-seq) and multiple bioinformatic analysis methods. The change trend of histopathology and five innate immune cell (neutrophils, mononuclear cells, eosinophils, macrophages, DC cells) proportions in the lungs after infection was also examined. We observed a distinct acute pulmonary recovery process. A rapid initiation period of inflammation was present at 12 hpi, during which the IL-17 pathway dominantly mediated inflammation and immune defense. The main stages of host inflammatory response occurred at 24 and 48 hpi, and the regulation of interferon activation and macrophage polarization played an important role in the control of inflammatory balance at this stage. At 96 hpi, cellular proliferation processes associated with host repair were observed, as well as adaptive immunity and complement system responses involving C1q molecules. More importantly, the data provide new insight into and identify potential functional genes involved in the checks and balances occurring between host anti-inflammatory and proinflammatory responses. To the best of our knowledge, this is the first study to investigate transcriptional responses throughout the inflammatory recovery process in the lungs after MRSA infection. Our study uncovers valuable research targets for key regulatory mechanisms underlying the pathogenesis of MRSA lung infections, which may help to develop novel treatment strategies for MRSA pneumonia. Full article

Acute exacerbations of COPD (AECOPD) are clinically significant events having therapeutic and prognostic consequences. However, there is a lot of variation in its clinical manifestations described by phenotypes. The phenotypes of AECOPD were categorized in this study based on pathology and exposure. In our cross-sectional study, conducted between 1 January 2016 to 31 December 2020, the patients were categorized into six groups based on pathology: non-bacterial and non-eosinophilic; bacterial; eosinophilic; bacterial infection with eosinophilia; pneumonia; and bronchiectasis. Further, four groups were classified based on exposure to tobacco smoke (TS), biomass smoke (BMS), both, or no exposure. Cox proportional-hazards regression analyses were performed to assess hazard ratios, and Kaplan–Meier analysis was performed to assess survival, which was then compared using the log-rank test. The odds ratio (OR) and independent predictors of ward admission type and length of hospital stay were assessed using binomial logistic regression analyses. Of the 2236 subjects, 2194 were selected. The median age of the cohort was 67.0 (60.0 to 74.0) and 75.2% were males. Mortality rates were higher in females than in males (6.2% vs. 2.3%). AECOPD-B (bacterial infection) subjects [HR 95% CI 6.42 (3.06–13.46)], followed by AECOPD-P (pneumonia) subjects [HR (95% CI: 4.33 (2.01–9.30)], were at higher mortality risk and had a more extended hospital stay (6.0 (4.0 to 9.5) days; 6.0 (4.0 to 10.0). Subjects with TS and BMS-AECOPD [HR 95% CI 7.24 (1.53–34.29)], followed by BMS-AECOPD [HR 95% CI 5.28 (2.46–11.35)], had higher mortality risk. Different phenotypes have different impacts on AECOPD clinical outcomes. A better understanding of AECOPD phenotypes could contribute to developing an algorithm for the precise management of different phenotypes. Full article

Background: Acute eosinophilic pneumonia (AEP) is a rare acute respiratory disease accompanied by fever, shortness of breath, and cough. Although the pathogenesis of the disease is not yet established, the patient’s condition improves with a rapid therapeutic response to systemic corticosteroids. Conventional cigarettes or heat-not-burn cigarettes are the most common cause of AEP among young people. Case Presentation: A 22-year-old woman with dyspnea, cough, and fever did not improve after visiting the local medical center and was admitted to the emergency room. The patient denied having any recent travel history or insect bites. She was treated with appropriate antibiotics according to the community acquired pneumonia, but there was no improvement. Chest radiography showed bilateral patches of pulmonary infiltration, and chest computed tomography revealed bilateral multifocal patchy consolidations with multiple small nodular ground-glass opacities and interlobular septal thickening. The bronchoalveolar lavage result was dominantly eosinophilic. The patient’s condition improved rapidly after the use of intravenous methylprednisolone and then a change to oral methylprednisolone. Finally, the patient was hospitalized for 9 days, and the duration of use of methylprednisolone including outpatient visits was 14 days. Results: The early treatment of AEP yields a good prognosis, but since the symptoms of AEP are similar to those of infectious diseases such as community-acquired pneumonia, physicians should be meticulous in differentiating AEP from other diseases. Conclusions: Since AEP shows a good response to steroids, early detection using an appropriate diagnostic method is recommended. In addition, there should be strong education against smoking in any form. Full article

Acute Eosinophilic Pneumonia (AEP) is a rare idiopathic disease caused by an accumulation of eosinophils in the pulmonary alveoli and interstitial tissue of the lungs. The onset of symptoms is acute; some patients develop respiratory failure. The diagnosis is based on clinical symptoms, diffuse interstitial infiltrates in the lungs on imaging studies, and eosinophilia exceeding 25% on bronchoalveolar lavage or pleural fluid smear. Smokers are primarily at increased risk for the disease. We present a case of venous thromboembolic disease (VTE) that developed in the course of AEP in a previously healthy male smoker. Complete remission of the disease was achieved with anticoagulation therapy combined with a low dose of steroids. Surprisingly, further diagnostics revealed the presence of thrombophilia: antithrombin (AT) deficiency and increased homocysteine level. According to our knowledge, this is the first case of VTE diagnosed in the course of AEP combined with thrombophilia. Full article

Background: The study developed accurate explainable machine learning (ML) models for predicting first-time acute exacerbation of chronic obstructive pulmonary disease (COPD, AECOPD) at an individual level. Methods: We conducted a retrospective case–control study. A total of 606 patients with COPD were screened for eligibility using registry data from the COPD Pay-for-Performance Program (COPD P4P program) database at Changhua Christian Hospital between January 2017 and December 2019. Recursive feature elimination technology was used to select the optimal subset of features for predicting the occurrence of AECOPD. We developed four ML models to predict first-time AECOPD, and the highest-performing model was applied. Finally, an explainable approach based on ML and the SHapley Additive exPlanations (SHAP) and a local explanation method were used to evaluate the risk of AECOPD and to generate individual explanations of the model’s decisions. Results: The gradient boosting machine (GBM) and support vector machine (SVM) models exhibited superior discrimination ability (area under curve [AUC] = 0.833 [95% confidence interval (CI) 0.745–0.921] and AUC = 0.836 [95% CI 0.757–0.915], respectively). The decision curve analysis indicated that the GBM model exhibited a higher net benefit in distinguishing patients at high risk for AECOPD when the threshold probability was <0.55. The COPD Assessment Test (CAT) and the symptom of wheezing were the two most important features and exhibited the highest SHAP values, followed by monocyte count and white blood cell (WBC) count, coughing, red blood cell (RBC) count, breathing rate, oral long-acting bronchodilator use, chronic pulmonary disease (CPD), systolic blood pressure (SBP), and others. Higher CAT score; monocyte, WBC, and RBC counts; BMI; diastolic blood pressure (DBP); neutrophil-to-lymphocyte ratio; and eosinophil and lymphocyte counts were associated with AECOPD. The presence of symptoms (wheezing, dyspnea, coughing), chronic disease (CPD, congestive heart failure [CHF], sleep disorders, and pneumonia), and use of COPD medications (triple-therapy long-acting bronchodilators, short-acting bronchodilators, oral long-acting bronchodilators, and antibiotics) were also positively associated with AECOPD. A high breathing rate, heart rate, or systolic blood pressure and methylxanthine use were negatively correlated with AECOPD. Conclusions: The ML model was able to accurately assess the risk of AECOPD. The ML model combined with SHAP and the local explanation method were able to provide interpretable and visual explanations of individualized risk predictions, which may assist clinical physicians in understanding the effects of key features in the model and the model’s decision-making process. Full article

A recently reported parallel preclinical study between a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine and an inactivated SARS-CoV-2 vaccine adjuvanted with alum showed pulmonary immunopathology typical of eosinophil accumulation in a mouse pneumonia model for the latter, which implied a potential role of cellular immunity in the difference in the protection rate between these two forms of vaccines. For those who have been vaccinated with alum-adjuvanted subunit or inactivated SARS-CoV-2 vaccines, whether the Th2 responses that have been established and the absence of induced cellular immunity could be changed is an open question. Using two heterologous boosts with Th1-oriented CpG ODN-adjuvanted S1-based SARS-CoV-2 subunit vaccines for mice that were primed with two doses of Th2-oriented alum-adjuvanted S1-based SARS-CoV-2 subunit vaccines, we demonstrated that established Th2 orientation could not be reversed to Th1 orientation and that no cellular immunity was induced, which should have been induced if the boosting vaccines were used as the prime vaccines. These results remind us that if widely administered alum-adjuvanted SARS-CoV-2 vaccines cannot overcome the challenge of coronavirus disease 2019 (COVID-19) and that if cellular immunity is important for the efficacy of SARS-CoV-2 vaccines in the future, the choice of more powerful heterologous boosting vaccine forms that can induce cellular immunity should be considered very carefully before application. Full article

Background and objectives: Bronchoalveolar lavage (BAL) is commonly performed to evaluate diffuse lung disease and occasionally to identify alveolar hemorrhage. However, the clinical impact of alveolar hemorrhage and its risk factors in patients with diffuse lung disease have not been clarified. Materials and Methods: We retrospectively analyzed the medical records of all patients who underwent BAL to evaluate diffuse lung disease from January 2017 to December 2020. Alveolar hemorrhage was defined as progressive hemorrhagic BAL fluid or the presence of ≥20% hemosiderin-laden macrophages in the BAL fluid. Logistic regression analysis was performed to assess the association between alveolar hemorrhage and other factors. Results: Sixty subjects were enrolled in this study. Alveolar hemorrhage was observed in 19 subjects (31.7%) with idiopathic interstitial pneumonia, acute respiratory distress syndrome, interstitial pneumonia with autoimmune features, drug-induced lung injury, eosinophilic pneumonia, adenocarcinoma, and systemic lupus erythematosus. The use of anticoagulants was a significant risk factor for alveolar hemorrhage (odds ratio 7.57, p = 0.049). Patients with alveolar hemorrhage required intubated mechanical ventilation more frequently (63.2% vs. 24.4%, p = 0.005) and had higher in-hospital mortality rates (26.3% vs. 4.9%, p = 0.028) than those without alveolar hemorrhage. Conclusions: Alveolar hemorrhage was observed in various etiologies. The use of anticoagulants was a significant risk factor for alveolar hemorrhage. Patients with alveolar hemorrhage showed more severe respiratory failure and had higher in-hospital mortality than those without alveolar hemorrhage. Full article

Infection with SARS-CoV-2, the virus responsible for the global COVID-19 pandemic, causes a respiratory illness that can severely impact other organ systems and is possibly precipitated by cytokine storm, septic shock, thrombosis, and oxidative stress. SARS-CoV-2 infected individuals may be asymptomatic or may experience mild, moderate, or severe symptoms with or without pneumonia. The mechanisms by which SARS-CoV-2 infects humans are largely unknown. Mouse hepatitis virus 1 (MHV-1)-induced infection was used as a highly relevant surrogate animal model for this study. We further characterized this animal model and compared it with SARS-CoV-2 infection in humans. MHV-1 inoculated mice displayed death as well as weight loss, as reported earlier. We showed that MHV-1-infected mice at days 7–8 exhibit severe lung inflammation, peribronchiolar interstitial infiltration, bronchiolar epithelial cell necrosis and intra-alveolar necrotic debris, alveolar exudation (surrounding alveolar walls have capillaries that are dilated and filled with red blood cells), mononuclear cell infiltration, hyaline membrane formation, the presence of hemosiderin-laden macrophages, and interstitial edema. When compared to uninfected mice, the infected mice showed severe liver vascular congestion, luminal thrombosis of portal and sinusoidal vessels, hepatocyte degeneration, cell necrosis, and hemorrhagic changes. Proximal and distal tubular necrosis, hemorrhage in interstitial tissue, and the vacuolation of renal tubules were observed. The heart showed severe interstitial edema, vascular congestion, and dilation, as well as red blood cell extravasation into the interstitium. Upon examination of the MHV-1 infected mice brain, we observed congested blood vessels, perivascular cavitation, cortical pericellular halos, vacuolation of neuropils, darkly stained nuclei, pyknotic nuclei, and associated vacuolation of the neuropil in the cortex, as well as acute eosinophilic necrosis and necrotic neurons with fragmented nuclei and vacuolation in the hippocampus. Our findings suggest that the widespread thrombotic events observed in the surrogate animal model for SARS-CoV-2 mimic the reported findings in SARS-CoV-2 infected humans, representing a highly relevant and safe animal model for the study of the pathophysiologic mechanisms of SARS-CoV-2 for potential therapeutic interventions. Full article

The Kaliningrad region is known for its specific climate, which can negatively affect the adaptive potential of the body. This manifests in an increased incidence of respiratory diseases and skin conditions. To prevent high morbidity, a plant protein product was included in the diet of first-year university students. This study aimed to assess the effectiveness of this food intervention in preventing the most common diseases among Kaliningrad students. Two groups of university students took part in the food trial. In the control group, catabolic processes prevailed in nutrient metabolism. Disadaptation manifested itself in the metabolism of proteins, vitamins, minerals, hematopoiesis and humoral immunity. Inflammation was indicated by α1- and α2-globulins, a weak immune response, and IgM and IgG. High oxidative stress and low antioxidative ability of blood serum were observed. The plant-based protein product (FP) helped preserve testosterone level and prevent an increase in catabolic reactions. Moreover, it had a positive effect on both red blood cell hematopoiesis (a smaller increase in the average volume of erythrocytes, the same average concentration and content of hemoglobin, an increased relative red cell distribution width (RDW) and white blood cell hematopoiesis (a beneficial effect for the immune system: lymphocytes, the relative content of neutrophils, monocytes, basophils and eosinophils). The stimulation of humoral immunity was evidenced by beta- and gamma-globulins, an active immune response, the level of IgM and IgG, antioxidant protection, reduction of peroxides and an increase in antioxidant activity of blood serum. The 34-week observation showed a 1.7-fold decrease in the incidence of respiratory illnesses and a 5.7-fold decrease in skin and subcutaneous tissue diseases. Acute respiratory infections were reduced 1.8-fold. There were no cases of community-acquired pneumonia in the treatment group, compared with 55.1‰ in the control group. The incidence of respiratory diseases was 3.3–10.6 times lower in the treatment group than in the control group in weeks 6–19. The findings testify to the prophylactic effect of functional food during social adaptation and acclimatization of students. Full article