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1.
Clin Lab ; 69(12)2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38084690

ABSTRACT

BACKGROUND: Aspiration pneumonia in patients in immunocompetent populations is rare, and secondary pyothorax due to puncture operations during treatment has been reported rarely. METHODS: We report a confirmed case of aspiration pneumonia caused by Prevotella. The pathogen was detected and confirmed using percutaneous lung puncture and high-throughput next-generation sequencing (NGS). RESULTS: The patient developed secondary pyothorax, severe rash, and exacerbation of symptoms following the lung puncture. Finally, after adjusting the antibiotic regimen and performing chest drainage and washout, the patient's lesions were absorbed, symptoms improved, and the rash disappeared. CONCLUSIONS: Prevotella aspiration pneumonia can occur in immunocompetent individuals, and invasive bronchoscopic alveolar lavage may be considered as an option to reduce the risk of infectious organism translocation.


Subject(s)
Empyema, Pleural , Exanthema , Pneumonia, Aspiration , Humans , Lung/pathology , Pneumonia, Aspiration/etiology , Pneumonia, Aspiration/pathology , Punctures , Empyema, Pleural/diagnosis , Empyema, Pleural/etiology , Exanthema/pathology
2.
Int J Clin Oncol ; 28(12): 1607-1615, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37798414

ABSTRACT

BACKGROUND: This study aimed to reveal the long-term outcomes and late toxicities (> 5 years) after definitive intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). METHODS: Data from 43 patients (median age, 55 years; range, 17-72 years) with NPC who underwent definitive IMRT between 2001 and 2018 were analyzed. All patients were alive and disease-free 5 years after IMRT. A total dose of 70 (range, 66-70) Gy was delivered in 35 (33-35) fractions with concurrent cisplatin chemotherapy. RESULTS: The median follow-up duration was 119 (range, 61.5-242.1) months. Three patients developed locoregional failure at 79, 92, and 149 months after IMRT, respectively. Of these, 2 patients died of disease progression at 136 and 153 months after IMRT. One patient died of aspiration pneumonia 141 months after IMRT, despite salvage of the recurrent tumor by re-irradiation. In addition, one patient died of aspiration pneumonia 62 months after the IMRT. Thus, the 10-year overall survival, progression-free survival, and locoregional control rates were 98%, 92%, and 94%, respectively. Grade ≥ 2 and ≥ 3 late toxicities were observed in 28 (65%) and 9 (21%) patients, respectively. Nine second primary cancers, including five tongue cancers and two external auditory canal carcinomas, were observed in seven (16%) patients. CONCLUSION: Late recurrences, severe late toxicities, and second primary cancers were observed > 5 years after IMRT. A long-term follow-up of > 5 years is needed in patients with NPC.


Subject(s)
Nasopharyngeal Neoplasms , Neoplasms, Second Primary , Pneumonia, Aspiration , Radiotherapy, Intensity-Modulated , Humans , Middle Aged , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/pathology , Neoplasms, Second Primary/pathology , Neoplasm Staging , Neoplasm Recurrence, Local/pathology , Radiotherapy, Intensity-Modulated/adverse effects , Disease Progression , Pneumonia, Aspiration/etiology , Pneumonia, Aspiration/pathology
3.
Hum Genet ; 139(5): 623-646, 2020 May.
Article in English | MEDLINE | ID: mdl-32206879

ABSTRACT

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.


Subject(s)
ATP-Binding Cassette Transporters/genetics , Ethnicity/genetics , Evolution, Molecular , Multigene Family , Pneumonia, Aspiration/etiology , Polymorphism, Genetic , Geography , Humans , Pneumonia, Aspiration/pathology
4.
Curr Opin Infect Dis ; 32(2): 152-157, 2019 04.
Article in English | MEDLINE | ID: mdl-30676341

ABSTRACT

PURPOSE OF REVIEW: Our purpose is to describe aspiration pneumonia/pneumonitis as a spectrum of infectious/noninfectious diseases affecting the lung. We summarize diagnosis, risk factors, treatment, and strategies for prevention of aspiration. RECENT FINDINGS: Aspiration is present in normal individuals, and disease manifestation depends on the chemical characteristics, frequency, and volume of inoculum. Anaerobes, though present, are no longer the predominant microbes isolated in aspiration pneumonia. Targets for preventing aspiration including improved oral hygiene and positional feeding have had mixed results. Patients diagnosed by clinicians with aspiration pneumonia experience greater morbidity and mortality than patients with community-acquired pneumonia. SUMMARY: Aspiration pneumonia and pneumonitis are part of the pneumonia continuum and share similarities in pathophysiology, microbiology, and treatment. Modern microbiology demonstrates that the lung is not sterile, and isolates in aspiration pneumonia frequently include aerobes or mixed cultures. Treatment for aspiration pneumonia should include antibiotic coverage for oral anaerobes, aerobes associated with community-acquired pneumonia, and resistant organisms depending on appropriate clinical context. Additional studies targeting prevention of aspiration and investigating the increased morbidity and mortality associated with aspiration pneumonia are warranted.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Diagnostic Tests, Routine/methods , Disease Management , Pneumonia, Aspiration/diagnosis , Pneumonia, Aspiration/drug therapy , Pneumonia/diagnosis , Pneumonia/drug therapy , Humans , Pneumonia/pathology , Pneumonia/prevention & control , Pneumonia, Aspiration/pathology , Pneumonia, Aspiration/prevention & control
5.
Am J Physiol Lung Cell Mol Physiol ; 315(3): L390-L403, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29745252

ABSTRACT

Recurrent aspiration of gastric contents has been associated with several interstitial lung diseases. Despite this association, the pathogenic role of aspiration in these diseases has been poorly studied and little is known about extracellular matrix (ECM) changes in animal models of repetitive events of aspiration. Our aim was to study the repair phase of lung injury induced by each of several instillations of gastric fluid in Sprague-Dawley rats to evaluate changes in ECM and their reversibility. Anesthetized animals received weekly orotracheal instillations of gastric fluid for 1, 2, 3, and 4 wk and were euthanized at day 7 after last instillation. For reversibility studies, another group received 7 weekly instillations and was euthanized at day 7 or 60 after last instillation. Biochemical and histological measurements were used to evaluate ECM changes. Lung hydroxyproline content increased progressively and hematoxylin and eosin, Masson's trichrome, and alpha-SMA stains showed that after a single instillation, intra-alveolar fibrosis predominated, whereas with repetitive instillations this fibrosis pattern became less prominent and interstitial fibrosis progressively became evident. Both type I and III collagen increased in intra-alveolar and interstitial fibrosis. Imbalance between matrix metalloproteinase-2 (MMP-2) activity and tissue inhibitor of metalloproteinase-2 (TIMP-2) expression was observed, favoring either collagen degradation or accumulation depending on the number of instillations. Caspase-3 activation was also dose dependent. ECM changes were partially reversible at long-term evaluation, since Masson bodies, granulomas, and foreign body giant cells disappeared, whereas interstitial collagen accumulated. In conclusion, repetitive lung instillations of gastric fluid induce progressive fibrotic changes in rat lung ECM that persist at long-term evaluation.


Subject(s)
Acute Lung Injury/metabolism , Extracellular Matrix/metabolism , Gastric Juice , Pneumonia, Aspiration/metabolism , Pulmonary Fibrosis/metabolism , Acute Lung Injury/pathology , Animals , Extracellular Matrix/pathology , Male , Matrix Metalloproteinase 2/biosynthesis , Pneumonia, Aspiration/pathology , Pulmonary Fibrosis/pathology , Rats , Rats, Sprague-Dawley , Tissue Inhibitor of Metalloproteinase-2/biosynthesis
6.
Respir Res ; 19(1): 165, 2018 Aug 31.
Article in English | MEDLINE | ID: mdl-30170599

ABSTRACT

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.


Subject(s)
Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Elastin/metabolism , Gastric Juice/metabolism , Pneumonia, Aspiration/metabolism , Pneumonia, Aspiration/pathology , Acute Lung Injury/etiology , Animals , Male , Rats , Rats, Sprague-Dawley
7.
Dis Aquat Organ ; 131(1): 1-11, 2018 10 16.
Article in English | MEDLINE | ID: mdl-30324910

ABSTRACT

The Amazon river dolphin Inia geoffrensis and tucuxi Sotalia fluviatilis are classified as Data Deficient species. Despite very limited knowledge on health and disease aspects of these species, the main threats to their conservation include incidental mortality in fishing gear, population fragmentation, habitat loss and environmental pollution. It is also suggested that underlying diseases may contribute to their mortality rates. Herein, we retrospectively describe gross and microscopic pulmonary lesions in free-ranging I. geoffrensis (n = 24) and S. fluviatilis (n = 28) found dead. Nearly 85% of the examined animals presented some kind of primary lung disease, wherein the main etiological diagnoses were verminous pneumonia by Halocercus brasiliensis (25%), bacterial pneumonia (25%) and a single case of meconium aspiration syndrome (1.9%). An etiology was not determined in 36.5% (19/52) of animals. These results indicate a high incidence of pulmonary pathology in these species, raising concerns about population impacts and potential zoonotic implications in some instances. These data may provide a scientific basis for future medical and conservation efforts focused on Amazonian dolphins.


Subject(s)
Dolphins , Lung Diseases, Parasitic/veterinary , Pneumonia, Aspiration/veterinary , Pneumonia, Bacterial/veterinary , Animals , Brazil , Female , Lung/pathology , Lung Diseases, Parasitic/epidemiology , Lung Diseases, Parasitic/pathology , Male , Pneumonia, Aspiration/epidemiology , Pneumonia, Aspiration/pathology , Pneumonia, Bacterial/epidemiology , Pneumonia, Bacterial/pathology , Retrospective Studies
8.
Am J Respir Cell Mol Biol ; 64(5): 641-643, 2021 05.
Article in English | MEDLINE | ID: mdl-33929292
9.
J Cell Mol Med ; 20(9): 1706-17, 2016 09.
Article in English | MEDLINE | ID: mdl-27061967

ABSTRACT

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.


Subject(s)
Inflammation/therapy , Lung Injury/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Pneumonia, Aspiration/therapy , Animals , Cell Movement/drug effects , Inflammation/complications , Inflammation/pathology , Lung/drug effects , Lung/pathology , Lung Injury/complications , Lung Injury/pathology , Male , Pneumonia, Aspiration/complications , Pneumonia, Aspiration/pathology , Prostaglandin D2/administration & dosage , Prostaglandin D2/analogs & derivatives , Prostaglandin D2/metabolism , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/pharmacology
10.
Am J Physiol Lung Cell Mol Physiol ; 309(7): L639-52, 2015 Oct 01.
Article in English | MEDLINE | ID: mdl-26254421

ABSTRACT

The lung has a unique structure consisting of three functionally different compartments (alveolar, interstitial, and vascular) situated in an extreme proximity. Current methods to localize lung leukocytes using bronchoalveolar lavage and/or lung perfusion have significant limitations for determination of location and phenotype of leukocytes. Here we present a novel method using in vivo antibody labeling to enable accurate compartmental localization/quantification and phenotyping of mouse lung leukocytes. Anesthetized C57BL/6 mice received combined in vivo intravenous and intratracheal labeling with fluorophore-conjugated anti-CD45 antibodies, and lung single-cell suspensions were analyzed by flow cytometry. The combined in vivo intravenous and intratracheal CD45 labeling enabled robust separation of the alveolar, interstitial, and vascular compartments of the lung. In naive mice, the alveolar compartment consisted predominantly of resident alveolar macrophages. The interstitial compartment, gated by events negative for both intratracheal and intravenous CD45 staining, showed two conventional dendritic cell populations, as well as a Ly6C(lo) monocyte population. Expression levels of MHCII on these interstitial monocytes were much higher than on the vascular Ly6C(lo) monocyte populations. In mice exposed to acid aspiration-induced lung injury, this protocol also clearly distinguished the three lung compartments showing the dynamic trafficking of neutrophils and exudative monocytes across the lung compartments during inflammation and resolution. This simple in vivo dual-labeling technique substantially increases the accuracy and depth of lung flow cytometric analysis, facilitates a more comprehensive examination of lung leukocyte pools, and enables the investigation of previously poorly defined "interstitial" leukocyte populations during models of inflammatory lung diseases.


Subject(s)
Leukocytes , Lung , Neutrophil Infiltration , Pneumonia, Aspiration , Staining and Labeling/methods , Animals , Antibodies/pharmacology , Flow Cytometry/methods , Leukocyte Common Antigens/metabolism , Leukocytes/metabolism , Leukocytes/pathology , Lung/metabolism , Lung/pathology , Mice , Pneumonia, Aspiration/metabolism , Pneumonia, Aspiration/pathology
11.
J Surg Res ; 193(2): 909-19, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25260956

ABSTRACT

BACKGROUND: The study aimed to examine whether methylene blue (MB) prevents different pulmonary aspiration materials-induced lung injury in rats. METHODS: The experiments were designed in 60 Sprague-Dawley rats, ranging in weight from 250-300 g, randomly allotted into one of six groups (n = 10): saline control, Biosorb Energy Plus (BIO), hydrochloric acid (HCl), saline + MB treated, BIO + MB treated, and HCl + MB treated. Saline, BIO, and HCl were injected into the lungs in a volume of 2 mL/kg. After surgical procedure, MB was administered intraperitoneally for 7 days at a daily dose of 2 mg/kg per day. Seven days later, rats were killed, and both lungs in all groups were examined biochemically and histopathologically. RESULTS: Our findings show that MB inhibits the inflammatory response reducing significantly (P < 0.05) peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, interstitial fibrosis, granuloma, and necrosis formation in different pulmonary aspiration models. Pulmonary aspiration significantly increased the tissue hydroxyproline content, malondialdehyde levels, and decreased (P < 0.05) the antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities. MB treatment significantly (P < 0.05) decreased the elevated tissue hydroxyproline content and malondialdehyde levels and prevented the inhibition of superoxide dismutase and glutathione peroxidase (P < 0.05) enzymes in the tissues. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase (iNOS), terminal deoxynucleotidyl transferase dUTP nick end labeling, and arise in the expression of surfactant protein D in lung tissue of different pulmonary aspiration models with MB therapy. CONCLUSIONS: MB treatment might be beneficial in lung injury and therefore shows potential for clinical use.


Subject(s)
Acute Lung Injury/prevention & control , Enzyme Inhibitors/therapeutic use , Methylene Blue/therapeutic use , Pneumonia, Aspiration/complications , Acute Lung Injury/etiology , Acute Lung Injury/pathology , Animals , Drug Evaluation, Preclinical , Immunohistochemistry , In Situ Nick-End Labeling , Lung/pathology , Pneumonia, Aspiration/drug therapy , Pneumonia, Aspiration/pathology , Random Allocation , Rats, Sprague-Dawley
12.
Regul Toxicol Pharmacol ; 73(3): 930-7, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26408152

ABSTRACT

Miglyol 812(®), a mixture of medium-chain triglycerides, has been identified as an oral vehicle that could improve the solubility and possibly the bioavailability of orally administered drugs during the non-clinical safety assessment. The toxicity of Miglyol was assessed in Göttingen(®) minipigs upon daily oral administration (gavage) for six weeks, at dosing-volumes of 0.5 and 2 mL/kg/day, compared to controls receiving 0.5% CarboxyMethylCellulose/0.1% Tween(®) 80 in water at 2 mL/kg/day. The control vehicle did not induce any findings. Miglyol at 0.5 and 2 mL/kg/day induced transient tremors, abnormal color of feces and increase in triglycerides. Miglyol at 2 ml/kg/day also induced reduced motor activity, decreased food intake, respiratory signs (2/6 animals) and increased total and LDL-cholesterol. At necropsy, the lung of 3/6 animals treated at 2 mL/kg/day presented abnormal color and/or irregular surface correlated with a chronic bronchiolo-alveolar inflammation. This finding is probably due to aspiration pneumonia in relation to the administration method and the high viscosity of Miglyol. Overall, the oral administration of pure Miglyol 812(®) for six weeks up to 2 mL/kg was less tolerated than that of the control vehicle. Miglyol as vehicle for sub-chronic oral toxicity studies in minipigs should be used with a limited dosing-volume.


Subject(s)
Pharmaceutical Vehicles/toxicity , Triglycerides/toxicity , Administration, Oral , Animals , Behavior, Animal/drug effects , Drug Administration Schedule , Eating/drug effects , Female , Lung/drug effects , Lung/pathology , Lung/physiopathology , Male , Motor Activity/drug effects , Pharmaceutical Vehicles/administration & dosage , Pneumonia, Aspiration/chemically induced , Pneumonia, Aspiration/pathology , Pneumonia, Aspiration/physiopathology , Respiration , Risk Assessment , Swine , Swine, Miniature , Time Factors , Triglycerides/administration & dosage
13.
J Infect Chemother ; 20(7): 436-42, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24834866

ABSTRACT

Pneumonia is a leading cause of death among elderly patients. Although aspiration pneumonia (AP) commonly occurs with aging, its clinical features and outcomes are still uncertain. The aims of this study were to describe the clinical features and outcomes of AP and to assess whether presence of AP affects clinical outcomes in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). We retrospectively analyzed patients with CAP and HCAP hospitalized in our institution in Japan from October 2010 to March 2012. We compared clinical features and outcomes between AP and non-AP, and investigated risk factors for recurrence of pneumonia and death. Of 214 consecutive patients, 100 (46.7%) were diagnosed as having aspiration pneumonia. These patients were older and had lower body mass index, more comorbidities, and poorer Eastern Cooperative Oncology Group performance status (ECOG PS) than the patients with non-AP. Patients with AP had more severe disease, required longer hospital stays, and had a frequent recurrence rate of pneumonia and higher mortality. In multivariate analyses, AP, age, and ECOG PS were related to recurrence of pneumonia, and the prognostic factors were CURB-65 score and ECOG PS. AP was not a significant indicator for prognosis but was the strongest risk factor for recurrence of pneumonia. Clinical background and outcomes including recurrence and mortality of AP were obviously different from those of non-AP; therefore AP should be considered as a distinct subtype of pneumonia, and it is important to prevent the recurrence of pneumonia in the patients with AP.


Subject(s)
Community-Acquired Infections/pathology , Cross Infection/pathology , Pneumonia, Aspiration/pathology , Pneumonia/pathology , Age Factors , Aged , Aged, 80 and over , Community-Acquired Infections/mortality , Comorbidity , Cross Infection/mortality , Female , Hospital Mortality , Humans , Japan/epidemiology , Male , Pneumonia/mortality , Pneumonia, Aspiration/mortality , Prognosis , Recurrence , Retrospective Studies , Risk Factors , Severity of Illness Index
15.
Int J Mol Sci ; 15(11): 19650-61, 2014 Oct 28.
Article in English | MEDLINE | ID: mdl-25353180

ABSTRACT

Inflammation is involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have shown that Semaphorin 7A (SEMA7A) promotes inflammation, there are limited reports regarding immunological function of SEMA7A in seawater aspiration-induced ALI. Therefore, we investigated the role of SEMA7A during seawater aspiration-induced ALI. Male Sprague-Dawley rats were underwent seawater instillation. Then, lung samples were collected at an indicated time for analysis. In addition, rat pulmonary microvascular endothelial cells (RPMVECs) were cultured and then stimulated with 25% seawater for indicated time point. After these treatments, cells samples were collected for analysis. In vivo, seawater instillation induced lung histopathologic changes, pro-inflammation cytokines release and increased expression of SEMA7A. In vitro, seawater stimulation led to pro-inflammation cytokine release, cytoskeleton remodeling and increased monolayer permeability in pulmonary microvascular endothelial cells. In addition, knockdown of hypoxia-inducible factor (HIF)-1α inhibited the seawater induced increase expression of SEMA7A. Meanwhile, knockdown of SEMA7A by specific siRNA inhibited the seawater induced aberrant inflammation, endothelial cytoskeleton remodeling and endothelial permeability. These results suggest that SEMA7A is critical in the development of lung inflammation and pulmonary edema in seawater aspiration-induced ALI, and may be a therapeutic target for this disease.


Subject(s)
Acute Lung Injury/etiology , Acute Lung Injury/metabolism , Antigens, CD/metabolism , Endothelial Cells/metabolism , Pneumonia, Aspiration/etiology , Pneumonia, Aspiration/metabolism , Seawater/adverse effects , Semaphorins/metabolism , Acute Lung Injury/pathology , Animals , Antigens, CD/genetics , Capillary Permeability/genetics , Cytokines/metabolism , Cytoskeleton/metabolism , Disease Models, Animal , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Inflammation Mediators/metabolism , Male , Phenotype , Pneumonia, Aspiration/pathology , RNA, Small Interfering/genetics , Rats , Semaphorins/genetics
16.
Zhonghua Jie He He Hu Xi Za Zhi ; 37(8): 592-6, 2014 Aug.
Article in Zh | MEDLINE | ID: mdl-25351266

ABSTRACT

OBJECTIVE: To explore the clinicopathological characteristics of aspiration pneumonia in the elderly. METHODS: The clinical data of 30 cases of autopsy-proven aspiration pneumonia in Beijing Hospital from 1973 to 2002 were reviewed. The patients consisted of 28 males and 2 females, aged from 63 to 103 [mean (83 ± 9)] years. RESULTS: Only 15 cases were clinically diagnosed as aspiration pneumonia before death. Concomitant diseases were severe and complex, mostly coronary disease, cerebrovascular disease, hypertension, COPD, and diabetes mellitus. All the patients suffered from at least 3 concomitant diseases. Long-term bedridden and nasogastric feeding was seen in 11 and 17 patients respectively. The clinical presentation and chest X-ray of aspiration pneumonia in the elderly were nonspecific and variable. Mixed infections were common . The main bacteria isolated were Gram-negative bacilli, in particular Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Escherichia coli and Candida albicans. By pathology, macrophages with foreign bodies were found in all the 30 cases and multiple small abscesses were found in 14 cases. The lesions were adjacent to the bronchioles and in the lung tissue around the bronchioles, mostly multi-lobar and bilateral. Unilateral or bilateral pleural effusion developed in 20 patients. The accordance between radiological and pathological diagnosis of aspiration pneumonia was very poor. The foci of infection detected by X-ray were proven by autopsy in 13 patients, while pleural effusions in X-ray were proven by autopsy in 15 patients. CONCLUSIONS: Multi-concomitant diseases, mixed infection and extra-pulmonary presentations were common in elderly patients with aspiration pneumonia. Multiple small abscesses were the pathological characteristics of aspiration pneumonia in the aged. A definite clinical diagnosis of aspiration pneumonia was difficult. Recurrent silent microaspiration was a feature of aspiration in the elderly. The assessment of risk factor of aspiration played an important role in the clinical diagnosis of aspiration pneumonia.


Subject(s)
Gram-Negative Bacteria/isolation & purification , Pneumonia, Aspiration/pathology , Aged , Aged, 80 and over , Cerebrovascular Disorders/complications , Female , Foreign Bodies/complications , Humans , Male , Middle Aged , Pleural Effusion/complications , Pneumonia, Aspiration/diagnosis , Pneumonia, Aspiration/etiology , Retrospective Studies , Risk Factors
17.
J Small Anim Pract ; 64(4): 280-287, 2023 04.
Article in English | MEDLINE | ID: mdl-36428285

ABSTRACT

OBJECTIVES: To describe computed tomographic (CT) findings in dogs diagnosed with aspiration pneumonia and to assess for any correlation with patient outcome. MATERIALS AND METHODS: Retrospective analysis of 38 cases with a presumptive diagnosis of aspiration pneumonia at two UK referral centres. Medical records were reviewed for signalment, history, physical examination and clinicopathologic data. CT examinations of the thorax were reviewed by the European College of Veterinary Diagnostic Imaging board-certified radiologist for all dogs to describe the characteristics and distribution of the pulmonary lesions. RESULTS: The most common CT findings were lung lobe consolidation associated with air bronchograms (100%) followed by ground-glass attenuation (89.4%), bronchial wall thickening (36.8%), bronchiolectasis (31.5%) and bronchiectasis (15.7%). Large-breed dogs were overrepresented. Duration of hospitalisation ranged between 0 and 8 days (mean 3 days). Overall, 89.4% of dogs survived the aspiration event and were discharged from the hospital. The four dogs that did not survive to discharge had five or more lobes affected on CT. CLINICAL SIGNIFICANCE: CT findings in dogs with aspiration pneumonia are described. CT is a useful imaging modality to diagnose aspiration pneumonia.


Subject(s)
Dog Diseases , Pneumonia, Aspiration , Dogs , Animals , Retrospective Studies , Pneumonia, Aspiration/diagnostic imaging , Pneumonia, Aspiration/veterinary , Pneumonia, Aspiration/pathology , Lung , Tomography, X-Ray Computed/veterinary , Dog Diseases/diagnostic imaging , Dog Diseases/pathology
19.
Exp Lung Res ; 38(1): 9-18, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22149928

ABSTRACT

Adjunctive corticosteroid treatment to reduce excessive local inflammatory response in pneumonia is controversial. To study the effects of an early local adjunct dexamethasone treatment on the course of pneumonia and inflammatory/cytokine response, mice were intratracheally inoculated with live Porphyromonas gingivalis and treated with either clindamycin (C), dexamethasone (D), C+D combination, or were not treated (Pg). Six mice from each group were euthanized at 6, 24, 72, and 168 hours after inoculation. Levels of tumor necrosis factor (TNF)-α, soluble TNF-α receptors (sTNFR1 and sTNFR2), interleukin (IL)-1ß, and IL-6 in the serum and lung-homogenate supernatant were determined. Lung samples were histopathologically assessed and all findings compared to those found in 24 sham-inoculated mice (phosphate-buffered saline [PBS]). Severe P. gingivalis-induced bronchopneumonia progressed from 24 hours, peaked at 72 hours, and resolved after 168 hours with changes in local and systemic cytokine levels. Clindamycin-treated mice developed only mild bronchopneumonia that resolved fast (72 hours) with an early (6-24 hours) normalization of local and systemic cytokine levels. Similar course of pneumonia and cytokine level changes were observed in mice treated with C+D, but later. Early (6-24 hours) local elevation of sTNFRs was observed in C and C+D groups of mice, whereas nontreated (Pg) mice had increased systemic sTNFRs. Severe bronchopneumonia with delayed resolution was observed in D-group mice, with an early local and systemic decrease in sTNFR1 and persistent elevation of local TNF-α. Clindamycin or a clindamycin-dexamethasone combination treatment significantly improves the course of P. gingivalis-aspiration pneumonia, but more so if clindamycin alone is used. A favorable course of pneumonia seems to be associated with an early elevation of sTNFRs and normalization of TNF-α.


Subject(s)
Bacteroidaceae Infections/drug therapy , Bronchopneumonia/drug therapy , Clindamycin/administration & dosage , Dexamethasone/administration & dosage , Pneumonia, Aspiration/drug therapy , Porphyromonas gingivalis/isolation & purification , Administration, Inhalation , Animals , Anti-Bacterial Agents/administration & dosage , Bacteroidaceae Infections/metabolism , Bacteroidaceae Infections/microbiology , Bacteroidaceae Infections/pathology , Bronchopneumonia/metabolism , Bronchopneumonia/microbiology , Bronchopneumonia/pathology , Chemotherapy, Adjuvant/methods , Disease Models, Animal , Interleukin-1beta/blood , Interleukin-1beta/metabolism , Interleukin-6/blood , Interleukin-6/metabolism , Lung/drug effects , Lung/immunology , Lung/metabolism , Lung/pathology , Male , Mice , Mice, Inbred BALB C , Nasal Sprays , Pneumonia, Aspiration/metabolism , Pneumonia, Aspiration/microbiology , Pneumonia, Aspiration/pathology , Receptors, Tumor Necrosis Factor, Type I/blood , Receptors, Tumor Necrosis Factor, Type I/metabolism , Receptors, Tumor Necrosis Factor, Type II/blood , Receptors, Tumor Necrosis Factor, Type II/metabolism , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/metabolism
20.
J Postgrad Med ; 58(4): 290-3, 2012.
Article in English | MEDLINE | ID: mdl-23298925

ABSTRACT

Patients with upper aerodigestive epithelial cancers frequently develop second primary cancers due to common risk factors or develop distant metastases depending on the locoregional status of the primary tumor. In most instances, the organ affected is the lung. Pulmonary spread usually occurs due to hematogenous or lymphatic dissemination. The following is a report of two patients with upper aerodigestive tract squamous cell carcinomas who developed lung metastases due to aspiration, a route not well documented in recent literature.


Subject(s)
Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/secondary , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Mouth Neoplasms/pathology , Otorhinolaryngologic Neoplasms/secondary , Autopsy , Deglutition Disorders/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Neoplasms, Multiple Primary/pathology , Neoplasms, Second Primary/pathology , Otorhinolaryngologic Neoplasms/pathology , Pneumonia, Aspiration/pathology
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