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Aspiration pneumonia is thought to be associated with a poor outcome in patients with community acquired pneumonia (CAP). However, there has been no systematic review regarding the impact of aspiration pneumonia on the outcomes in patients with CAP. This review was conducted using the MOOSE guidelines: Patients: patients defined CAP. Exposure: aspiration pneumonia defined as pneumonia in patients who have aspiration risk. Comparison: confirmed pneumonia in patients who were not considered to be at high risk for oral aspiration. Outcomes: mortality, hospital readmission or recurrent pneumonia. Three investigators independently identified published cohort studies from PubMed, CENTRAL database, and EMBASE. Nineteen studies were included for this systematic review. Aspiration pneumonia increased in-hospital mortality (relative risk, 3.62; 95% CI, 2.65–4.96; P < 0.001, seven studies) and 30-day mortality (3.57; 2.18–5.86; P < 0.001, five studies). In contrast, aspiration pneumonia was associated with decreased ICU mortality (relative risk, 0.40; 95% CI, 0.26–0.60; P < 0.00001, four studies). Although there are insufficient data to perform a meta-analysis on long-term mortality, recurrent pneumonia, and hospital readmission, the few reported studies suggest that aspiration pneumonia is also associated with these poor outcomes. In conclusion, aspiration pneumonia was associated with both higher in-hospital and 30-day mortality in patients with CAP outside ICU settings.

Respiratory failure appears to be the ultimate mechanism of death in most patients with severe coronavirus disease 2019 (COVID-19) infection. Studies of postmortem COVID-19 lungs largely report diffuse alveolar damage and capillary fibrin thrombi, but we have also observed other patterns. To report demographic and radiographic features along with macroscopic, microscopic, and microbiologic postmortem lung findings in patients with COVID-19 infections. Patients with confirmed COVID-19 infection and postmortem examination (March 2020-May 2020) were included. Clinical findings were abstracted from medical records. Lungs were microscopically reviewed independently by 4 thoracic pathologists. Imaging studies were reviewed by a thoracic radiologist. Eight patients (7 men, 87.5%; median age, 79 years; range, 69-96 years) died within a median of 17 days (range, 6-100 days) from onset of symptoms. The median lung weight was 1220 g (range, 960-1760 g); consolidations were found in 5 patients (62.5%) and gross thromboemboli were noted in 1 patient (12.5%). Histologically, all patients had acute bronchopneumonia; 6 patients (75%) also had diffuse alveolar damage. Two patients (25%) had aspiration pneumonia in addition. Thromboemboli, usually scattered and rare, were identified in 5 patients (62.5%) in small vessels and in 2 of these patients also in pulmonary arteries. Four patients (50%) had perivascular chronic inflammation. Postmortem bacterial lung cultures were positive in 4 patients (50%). Imaging studies (available in 4 patients) were typical (n = 2, 50%), indeterminate (n = 1, 25%), or negative (n = 1, 25%) for COVID-19 infection. Our study shows that patients infected with COVID-19 not only have diffuse alveolar damage but also commonly have acute bronchopneumonia and aspiration pneumonia. These findings are important for management of these patients.

Aspiration pneumonia exacerbates swallowing and respiratory muscle atrophy. It induces respiratory muscle atrophy through three steps: proinflammatory cytokine production, caspase-3 and calpain, and then ubiquitin–proteasome activations. In addition, autophagy induces swallowing muscle atrophy. Nrf2 is the central detoxifying and antioxidant gene whose function in aspiration pneumonia is unclear. We explored the role of Nrf2 in aspiration pneumonia by examining swallowing and respiratory muscle mass and function using wild-type and Nrf2-knockout mice. Pepsin and lipopolysaccharide aspiration challenges caused aspiration pneumonia. The swallowing (digastric muscles) and respiratory (diaphragm) muscles were isolated. Quantitative RT-PCR and Western blotting were used to assess their proteolysis cascade. Pathological and videofluoroscopic examinations evaluated atrophy and swallowing function, respectively. Nrf2-knockouts showed exacerbated aspiration pneumonia compared with wild-types. Nrf2-knockouts exhibited more persistent and intense proinflammatory cytokine elevation than wild-types. In both mice, the challenge activated calpains and caspase-3 in the diaphragm but not in the digastric muscles. The digastric muscles showed extended autophagy activation in Nrf2-knockouts compared to wild-types. The diaphragms exhibited autophagy activation only in Nrf2-knockouts. Nrf2-knockouts showed worsened muscle atrophies and swallowing function compared with wild-types. Thus, activation of Nrf2 may alleviate inflammation, muscle atrophy, and function in aspiration pneumonia, a major health problem for the aging population, and may become a therapeutic target.

ATP-binding cassette (ABC) transporters constitute a superfamily of 48 structurally similar membrane transporters that mediate the ATP-dependent cellular export of a plethora of endogenous and xenobiotic substances. Importantly, genetic variants in ABC genes that affect gene function have clinically important effects on drug disposition and can be predictors of the risk of adverse drug reactions and efficacy of chemotherapeutics, calcium channel blockers, and protease inhibitors. Furthermore, loss-of-function of ABC transporters is associated with a variety of congenital disorders. Despite their clinical importance, information about the frequencies and global distribution of functionally relevant ABC variants is limited and little is known about the overall genetic complexity of this important gene family. Here, we systematically mapped the genetic landscape of the entire human ABC superfamily using Next-Generation Sequencing data from 138,632 individuals across seven major populations. Overall, we identified 62,793 exonic variants, 98.5% of which were rare. By integrating five computational prediction algorithms with structural mapping approaches using experimentally determined crystal structures, we found that the functional ABC variability is extensive and highly population-specific. Every individual harbored between 9.3 and 13.9 deleterious ABC variants, 76% of which were found only in a single population. Carrier rates of pathogenic variants in ABC transporter genes associated with autosomal recessive congenital diseases, such as cystic fibrosis or pseudoxanthoma elasticum, closely mirrored the corresponding population-specific disease prevalence, thus providing a novel resource for rare disease epidemiology. Combined, we provide the most comprehensive, systematic, and consolidated overview of ethnogeographic ABC transporter variability with important implications for personalized medicine, clinical genetics, and precision public health.

Background Aspiration pneumonia is a severe health concern, particularly for ICU patients with impaired airway defenses. Current animal models fail to fully replicate the condition, focusing solely on chemical lung injury from gastric acid while neglecting pathogen‐induced inflammation. This gap hinders research on pathogenesis and treatment, creating an urgent need for a clinically relevant model. This study aimed to develop an improved rat model of aspiration pneumonia by combining hydrochloric acid (HCl) and lipopolysaccharide (LPS) administration. Methods Specific pathogen‐free Sprague Dawley rats underwent intratracheal instillation of HCl and LPS. Techniques included rat weight measurement, tracheal intubation, pulmonary function monitoring, lung tissue sampling with HE staining and scoring, bronchoalveolar lavage fluid (BALF) sampling, protein and inflammatory cytokine analysis via BCA and ELISA, BALF pH determination, Evans Blue dye assessment, blood gas analysis, FITC‐dextran leakage, Western blotting, electron microscopy, survival analysis, and transcriptome sequencing with bioinformatics. Statistical analysis was performed using GraphPad Prism. Results The optimal model involved instillation of 1.5 μL/g.wt HCl (pH = 1) followed by 20 μg/g.wt LPS after 1 h. This model reproduced acute lung injury, including tissue damage, pulmonary microvascular dysfunction, inflammatory responses, hypoxemia, and impaired pulmonary ventilation, with recovery observed at 72 h. PANoptosis was confirmed, characterized by increased markers. Concentration‐dependent effects of HCl and LPS on lung damage were identified, alongside cytokine elevation and microvascular dysfunction. Conclusions This optimized model closely mimics clinical aspiration pneumonia, providing a valuable tool for studying pathophysiology and therapeutic strategies. Aspiration pneumonia was induced in Sprague Dawley rats by intratracheal instillation of hydrochloric acid (HCl, 1.5 μL/g.wt, pH = 1) followed by lipopolysaccharide (LPS, 20 μg/g.wt) after 1 h. The model reproduced hallmark features of acute lung injury, including histological lung damage, microvascular dysfunction, inflammation, hypoxemia, and impaired ventilation. Comprehensive analyses were performed, including lung histology (HE staining), bronchoalveolar lavage fluid (BALF) analysis, cytokine quantification (BCA and ELISA), pH measurement, vascular permeability (Evans Blue dye, FITC‐dextran), and blood gas analysis. Transcriptome sequencing and Western blotting revealed evidence of PANoptosis, with markers of pyroptosis, apoptosis, and necroptosis identified. Recovery from lung injury was observed at 72 h post‐induction. This model serves as a clinically relevant tool for studying aspiration pneumonia pathophysiology and therapeutic interventions.

Gastric aspiration lung injury is one of the most common clinical events. This study investigated the effects of bone‐marrow‐derived mesenchymal stem cells (BMSCs) on combined acid plus small non‐acidified particle (CASP)‐induced aspiration lung injury. Enhanced green fluorescent protein (EGFP+) or EGFP− BMSCs or 15d‐PGJ2 were injected via the tail vein into rats immediately after CASP‐induced aspiration lung injury. Pathological changes in lung tissues, blood gas analysis, the wet/dry weight ratio (W/D) of the lung, levels of total proteins and number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) were determined. The cytokine levels were measured using ELISA. Protein expression was determined by Western blot. Bone‐marrow‐derived mesenchymal stem cells treatment significantly reduced alveolar oedema, exudation and lung inflammation; increased the arterial partial pressure of oxygen; and decreased the W/D of the lung, the levels of total proteins and the number of total cells and neutrophils in BALF in the rats with CASP‐induced lung injury. Bone‐marrow‐derived mesenchymal stem cells treatment decreased the levels of tumour necrosis factor‐α and Cytokine‐induced neutrophil chemoattractant (CINC)‐1 and the expression of p‐p65 and increased the levels of interleukin‐10 and 15d‐PGJ2 and the expression of peroxisome proliferator‐activated receptor (PPAR)‐γ in the lung tissue in CASP‐induced rats. Tumour necrosis factor‐α stimulated BMSCs to secrete 15d‐PGJ2. A tracking experiment showed that EGFP+ BMSCs were able to migrate to local lung tissues. Treatment with 15d‐PGJ2 also significantly inhibited CASP‐induced lung inflammation and the production of pro‐inflammatory cytokines. Our results show that BMSCs can protect lung tissues from gastric aspiration injury and inhibit lung inflammation in rats. A beneficial effect might be achieved through BMSC‐derived 15d‐PGJ2 activation of the PPAR‐γ receptor, reducing the production of proinflammatory cytokines.

The morphological appearance of the crystals appeared identical to crystals seen in the gastrointestinal tract in patients treated with the drug Sevelamer. 1 A diagnosis of chronic aspiration of Sevelamer resulting in bronchial crystal deposition was made.

Background There are limited data from low‐ to middle‐income countries (LMIC) on the incidence, risk factors, treatment outcomes, and antibiotic susceptibility spectrum of aspiration pneumonia (AsP). Methods We conducted a post hoc analysis of a randomized control trial in which adult patients with locally advanced head and neck cancers had received 66–70 Gy of radiation combined with cisplatin 30 mg/m2 weekly for 6–7 weeks or cisplatin at the same dose with nimotuzumab 200 mg once weekly till the completion of radiation. The following data were extracted and analyzed—the incidence of AsP, time to the onset of AsP, risk factors, treatment outcomes of AsP, and its impact on progression‐free survival (PFS), locoregional control (LRC) rates, and overall survival (OS). Results Out of 536 patients enrolled in the study, 151 (28.3%, 95% confidence interval [CI] 24.5–2.1) patients developed AsP. The median time to develop AsP was 39 days (95% CI 34–44). Only baseline dysphagia (odds ratio = 3.76, 95% CI 1.05–13.51, p = 0.042) was associated with a significant risk of development of AsP. Among the patients in which pathogenic organism was isolated (69 patients), gram‐negative species was isolated in 63 patients (89%). Cisplatin at 200 mg/m2 or more was delivered in 312 (81%) patients in the non‐AsP cohort versus 107 (70.9%) patients in AsP cohort (p = 0.014). There was no statistical difference in LRC (hazard ratio [HR] = 1.057; 95% CI 0.771–1.448), PFS (HR = 1.176; 95% CI 0.89–1.553), and OS (HR = 1.233; 95% CI 0.939–1.618) between the two cohorts. Conclusion Aspiration pneumonia is a common complication in head and neck malignancies and patients with baseline dysphagia are at high risk. Gram‐negative bacteria are the predominant causative agents. The use of broad‐spectrum antibiotics results in resolution of symptoms. Aspiration pneumonia is a common complication in head and neck malignancies and patients with baseline dysphagia are at high risk. Gram‐negative bacteria are the predominant causative agents. The use of broad‐spectrum antibiotics results in resolution of symptoms.

Background Gastric contents aspiration is a high-risk condition for acute lung injury (ALI). Consequences range from subclinical pneumonitis to respiratory failure, depending on the volume of aspirate. A large increment in inflammatory cells, an important source of elastase, potentially capable of damaging lung tissue, has been described in experimental models of aspiration. We hypothesized that in early stages of aspiration-induced ALI, there is proteolytic degradation of elastin, preceding collagen deposition. Our aim was to evaluate whether after a single orotracheal instillation of gastric fluid, there is evidence of elastin degradation. Methods Anesthesized Sprague-Dawley rats received a single orotracheal instillation of gastric fluid and were euthanized 4, 12 and 24 h and at day 4 after instillation ( n  = 6/group). We used immunodetection of soluble elastin in lung tissue and BALF and correlated BALF levels of elastin degradation products with markers of ALI. We investigated possible factors involved in elastin degradation and evaluated whether a similar pattern of elastin degradation can be found in BALF samples of patients with interstitial lung diseases known to have aspirated. Non-parametric ANOVA (Kruskall-Wallis) and linear regression analysis were used. Results We found evidence of early proteolytic degradation of lung elastin. Elastin degradation products are detected both in lung tissue and BALF in the first 24 h and are significantly reduced at day 4. They correlate significantly with ALI markers, particularly PMN cell count, are independent of acidity and have a similar molecular weight as those obtained using pancreatic elastase. Evaluation of BALF from patients revealed the presence of elastin degradation products not present in controls that are similar to those found in BALF of rats treated with gastric fluid. Conclusions A single instillation of gastric fluid into the lungs induces early proteolytic degradation of elastin, in relation to the magnitude of alveolar-capillary barrier derangement. PMN-derived proteases released during ALI are mostly responsible for this damage. BALF from patients showed elastin degradation products similar to those found in rats treated with gastric fluid. Long-lasting effects on lung elastic properties could be expected under conditions of repeated instillations of gastric fluid in experimental animals or repeated aspiration events in humans.