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1.
Artigo em Inglês | MEDLINE | ID: mdl-33525689

RESUMO

Recent technical developments brought negative side effects such as air pollution and large-scale fires, increasingly exposing people to diesel engine exhaust particles (DEP). Testing how DEP inhalation triggers pathophysiology in animal models could be useful in determining how it affects humans. To this end, the aim of this study was to investigate the effects of pulmonary exposure to DEP for seven consecutive days in experimental male C5BL6/N mice. Twenty-four C5BL6/N mice were treated with one of the three test materials: distilled water for control, a low DEP exposure (5 mg/kg), or a high DEP exposure (15 mg/kg). Exposure to DEP induced decreased body weight; however, it gradually increased pulmonary weight in a DEP-dose-dependent manner. DEP exposure significantly elevated soot accumulation in the lungs, with the alteration of pulmonary homeostasis. It also elevated infiltrated immune cells, thus significantly increasing inflammatory cytokine mRNA and protein production in the lungs and broncho-alveolar lavage fluid, respectively. Pulmonary DEP exposure also altered behavioral responses in the open field test (OFT). Low exposure elevated moving distance and speed, while significantly decreasing the number of trials to enter the central zone. Different concentrations of DEP resulted in different behavioral changes; however, while anxiety levels increased, their degree was independent of DEP concentrations. Results suggest that DEP exposure may possess pro-inflammatory responses in the lungs and trigger anxiety.


Assuntos
Pneumonia , Emissões de Veículos , Animais , Ansiedade/induzido quimicamente , Líquido da Lavagem Broncoalveolar , Citocinas , Masculino , Camundongos , Material Particulado/toxicidade , Pneumonia/induzido quimicamente , Emissões de Veículos/toxicidade
2.
Sci Total Environ ; 772: 145509, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33571778

RESUMO

BACKGROUND: Smaller sizes of ambient particulate matter (PM) can be more toxic and can be breathed into lower lobes of a lung. Children are particularly vulnerable to PM air pollution because of their adverse effects on both lung functions and lung development. However, it remains unknown whether a smaller PM has a greater short-term impact on childhood pneumonia. AIMS: We compared the short-term effects on childhood pneumonia from PM with aerodynamic diameters ≤1 µm (PM1), ≤2.5 µm (PM2.5), and ≤10 µm (PM10), respectively. METHODS: Daily time-series data (2016-2018) on pneumonia hospitalizations in children aged 0-17 years, records of air pollution (PM1, PM2.5, PM10, and gaseous pollutants), and weather conditions were obtained for Hefei, China. Effects of different PM were quantified using a quasi-Poisson generalized additive model after controlling for day of the week, holiday, seasonality and long-term time trend, and weather variables. Stratified analyses (gender, age, and season) were also performed. RESULTS: For each 10 µg/m3 increase in PM1, PM2.5, and PM10 concentrations over the past three days (lag 0-2), the risk of pneumonia hospitalizations increased by 10.28% (95%CI: 5.88%-14.87%), 1.21% (95%CI: 0.34%-2.09%), and 1.10% (95%CI: 0.44%-1.76%), respectively. Additionally, both boys and girls were at risk of PM1 effects, while PM2.5 and PM10 effects were only seen in boys. Children aged ≤12 months and 1-4 years were affected by PM1, but PM2.5 and PM10 were only associated with children aged 1-4 years. Furthermore, PM1 effects were greater in autumn and winter, while greater PM2.5 and PM10 effects were evident only in autumn. CONCLUSION: This study suggests a greater short-term impact on childhood pneumonia from PM1 in comparison to PM2.5 and PM10. Given the serious PM pollution in China and other rapid developing countries due to various combustions and emissions, more investigations are needed to determine the impact of different PM on childhood respiratory health.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Pneumonia , Adolescente , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Criança , Pré-Escolar , China/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Tamanho da Partícula , Material Particulado/efeitos adversos , Material Particulado/análise , Pneumonia/induzido quimicamente , Pneumonia/epidemiologia
3.
J Med Case Rep ; 15(1): 41, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522942

RESUMO

BACKGROUND: Pneumonitis belongs to the fatal toxicities of anti-PD-1/PD-L1 treatments. Its diagnosis is based on immunotherapeutic histories, clinical symptoms, and the computed tomography (CT) imaging. The radiological features were typically ground-glass opacities, similar to CT presentation of 2019 Novel Coronavirus (COVID-19) pneumonia. Thus, clinicians are cautious in differential diagnosis especially in COVID-19 epidemic areas. CASE PRESENTATION: Herein, we report a 67-year-old Han Chinese male patient presenting with dyspnea and normal body temperature on the 15th day of close contact with his son, who returned from Wuhan. He was diagnosed as advanced non-small cell lung cancer and developed pneumonitis post Sintilimab injection during COIVD-19 pandemic period. The chest CT indicated peripherally subpleural lattice opacities at the inferior right lung lobe and bilateral thoracic effusion. The swab samples were taken twice within 72 hours and real-time reverse-transcription polymerase-chain-reaction (RT-PCR) results were COVID-19 negative. The patient was thereafter treated with prednisolone and antibiotics for over 2 weeks. The suspicious lesion has almost absorbed according to CT imaging, consistent with prominently falling CRP level. The anti-PD-1 related pneumonitis mixed with bacterial infection was clinically diagnosed based on the laboratory and radiological evidences and good response to the prednisolone and antibiotics. CONCLUSION: The anti-PD-1 related pneumonitis and COVID-19 pneumonia possess similar clinical presentations and CT imaging features. Therefore, differential diagnosis depends on the epidemiological and immunotherapy histories, RT-PCR tests. The response to glucocorticoid is still controversial but helpful for the diagnosis.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Diagnóstico Diferencial , Humanos , Masculino , Anamnese , Pneumonia/induzido quimicamente , Pneumonia/diagnóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tomografia Computadorizada por Raios X
4.
Cell Death Dis ; 12(1): 53, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414457

RESUMO

Interleukin-38 has recently been shown to have anti-inflammatory properties in lung inflammatory diseases. However, the effects of IL-38 in viral pneumonia remains unknown. In the present study, we demonstrate that circulating IL-38 concentrations together with IL-36α increased significantly in influenza and COVID-19 patients, and the level of IL-38 and IL-36α correlated negatively and positively with disease severity and inflammation, respectively. In the co-cultured human respiratory epithelial cells with macrophages to mimic lung microenvironment in vitro, IL-38 was able to alleviate inflammatory responses by inhibiting poly(I:C)-induced overproduction of pro-inflammatory cytokines and chemokines through intracellular STAT1, STAT3, p38 MAPK, ERK1/2, MEK, and NF-κB signaling pathways. Intriguingly, transcriptomic profiling revealed that IL-38 targeted genes were associated with the host innate immune response to virus. We also found that IL-38 counteracts the biological processes induced by IL-36α in the co-culture. Furthermore, the administration of recombinant IL-38 could mitigate poly I:C-induced lung injury, with reduced early accumulation of neutrophils and macrophages in bronchoalveolar lavage fluid, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines and permeability of the alveolar-epithelial barrier. Taken together, our study indicates that IL-38 plays a crucial role in protection from exaggerated pulmonary inflammation during poly(I:C)-induced pneumonia, thereby providing the basis of a novel therapeutic target for respiratory viral infections.


Assuntos
/metabolismo , Imunidade Inata/efeitos dos fármacos , Influenza Humana/metabolismo , Interleucinas/farmacologia , Pneumonia/prevenção & controle , Poli I-C/toxicidade , Sistema Respiratório/imunologia , Animais , /virologia , Citocinas/metabolismo , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Vírus da Influenza A/isolamento & purificação , Influenza Humana/imunologia , Influenza Humana/virologia , Interleucina-1/sangue , Interleucinas/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Pneumonia/patologia , Sistema Respiratório/metabolismo , Sistema Respiratório/patologia , /isolamento & purificação
5.
Int J Mol Sci ; 22(1)2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33401552

RESUMO

Gender differences in pulmonary inflammation have been well documented. Although low molecular mass hyaluronan (LMMHA) is known to trigger pulmonary lung inflammation, sex differences in susceptibility to LMMHA are still unknown. In this study, we test the hypothesis that mice may display sex-specific differences after LMMHA administration. After LMMHA administration, male mice have higher neutrophil, cytokine, and chemokine counts compared to that of their female counterparts. Additionally, Ovariectomized (OVX) mice show greater LMMHA-induced inflammation compared to that of mice with intact ovaries. Injections of OVX mice with 17ß-estradiol can decrease inflammatory responses in the OVX mice. These results show that ovarian hormones regulate LMMHA induced lung inflammation.


Assuntos
Ácido Hialurônico/toxicidade , Pneumonia/patologia , Viscossuplementos/toxicidade , Doença Aguda , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peso Molecular , Pneumonia/induzido quimicamente , Fatores Sexuais
6.
Sci Total Environ ; 758: 143696, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33333306

RESUMO

Subpollen particles (SPPs) with diameter less than 1 mm released from allergenic pollen grains contain allergens could trigger asthma and lung inflammation after being inhaled. In the meaning time, ambient fine particles attached on the pollen grains could have further effects on the inflammation. However, the mechanisms underlying these phenomena have not been fully elucidated. In this study, the effects of autophagy triggered by PM2.5 and Platanus SPPs were evaluated by using the A549 cell lines and a pollen sensitized rat model. First, autophagy in A549 cells was analyzed after exposure to PM2.5 using acridine orange staining, real-time quantitative PCR (qRT-PCR), and western blot (WB) assays. The increased levels of ROS, superoxide dismutase, and malonaldehyde in the lung homogenates of rats exposed to SPPs indicated that inflammatory response was triggered in the lungs. Treatment with autophagy-inhibiting drugs showed that autophagy suppressed ROS formation and decreased the production of thymic stromal lymphopoietin (TSLP), a critical pathway altering the inflammatory response. Although the effect was indirect, autophagy appeared to negatively regulate TSLP levels, resulting in a compromised immune response. These results suggested that SPPs promote ROS generation and increase TSLP levels, triggering downstream inflammation reactions. However, ambient PM2.5 could aggravate autophagy, which in turn effectively suppressed ROS and TSLP levels, leading to the alleviation of the immune response and pulmonary inflammation.


Assuntos
Material Particulado , Pneumonia , Animais , Autofagia , Citocinas , Pulmão , Material Particulado/toxicidade , Pneumonia/induzido quimicamente , Pólen , Ratos
7.
Nanotoxicology ; 15(2): 238-256, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33332178

RESUMO

Inhalation of multi-walled carbon nanotubes (MWCNTs) induces lung inflammation. Depending on industrial applications, CNTs with different physicochemical characteristics are produced and workers can potentially be exposed. This raises concerns about the long-term health effects of these nanomaterials. Because of the wide variety of MWCNTs, it is essential to study the toxicological effects of CNTs of various shapes and to better understand the impact physical and chemical properties have on their toxicity. In this study, rats were exposed by nose-only to two pristine MWCNTs with different morphologies: the long and thick NM-401 or the short and thin NM-403. After four weeks of inhalation, animals were euthanized at four different times during the recovery period: three days (short-term), 30 and 90 days (intermediate-term) and 180 days (long-term). Analyses of the transcriptome in the whole lung and the proteome in the bronchoalveolar lavage fluid of exposed animals were performed to understand the MWCNT underlying mechanisms of toxicity. Following inhalation of NM-401, we observed a dose-dependent increase in the number of differentially expressed genes and proteins, whereas there is no clear difference between the two concentrations of NM-403. After NM-403 inhalation, the number of differentially expressed genes and proteins varied less between the four post-exposure times compared to NM-401, which supports the postulation of a persistent effect of this type of CNT. Our toxicogenomics approaches give insights into the different toxicological profile following MWCNT exposure.


Assuntos
Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Pneumonia/induzido quimicamente , Proteoma/metabolismo , Transcriptoma/efeitos dos fármacos , Administração por Inalação , Animais , Líquido da Lavagem Broncoalveolar/química , Feminino , Nanotubos de Carbono/química , Pneumonia/metabolismo , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície , Toxicogenética
8.
Molecules ; 25(24)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33371364

RESUMO

Diesel exhaust particulates (DEP) have adverse effects on the respiratory system. Endoplasmic reticulum (ER) abnormalities contribute to lung inflammation. However, the relationship between DEP exposure and ER stress in the respiratory immune system and especially the alveolar macrophages (AM) is poorly understood. Here, we examined ER stress and inflammatory responses using both in vivo and in vitro study. For in vivo study, mice were intratracheally instilled with 25, 50, and 100 µg DEP and in vitro AM were stimulated with DEP at 1, 2, and 3 mg/mL. DEP increased lung weight and the number of inflammatory cells, especially neutrophils, and inflammatory cytokines in bronchoalveolar lavage fluid of mice. DEP also increased the number of DEP-pigmented AM and ER stress markers including bound immunoglobulin protein (BiP) and CCAAT/enhancer binding protein-homologous protein (CHOP) were upregulated in the lungs of DEP-treated mice. In an in vitro study, DEP caused cell damage, increased intracellular reactive oxygen species, and upregulated inflammatory genes and ER stress-related BiP, CHOP, splicing X-box binding protein 1, and activating transcription factor 4 expressions in AM. Furthermore, DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. In conclusion, DEP may contribute to neutrophilic lung inflammation pathogenesis by modulating ER stress-mediated CXCL1/KC expression in AM.


Assuntos
Quimiocina CXCL1/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Material Particulado/efeitos adversos , Pneumonia/induzido quimicamente , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Feminino , Pulmão/metabolismo , Macrófagos Alveolares/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/metabolismo , Pneumonia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Fator de Transcrição CHOP/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/ética , Emissões de Veículos
9.
Gan To Kagaku Ryoho ; 47(9): 1363-1365, 2020 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-33130701

RESUMO

We present an unusual case of late-onset acute pneumonitis developing 21 months after pembrolizumab monotherapy. An 80-year-old male with primary, pulmonary, squamous cell carcinoma underwent right lower lobectomy and lymph node dissection(ND2a-2); the postoperative pathological stage was ⅢA(pT2bN2M0)and the PD-L1 tumor proportion score 70%. Six months after surgery, he developed mediastinal lymph node(#2R), bilateral pulmonary, and hepatic metastases; pembrolizumab was administered every 3 weeks as a first-line treatment. A partial response was evident after 3 courses; we thus continued the monotherapy. However, after 28 courses(21 months)of pembrolizumab, we discontinued the regimen because acute pneumonitis(Grade 3)developed; we prescribed prednisolone at 50 mg/day. The acute pneumonitis shadow improved and prednisolone was tapered over 2 months. The patient exhibited no new lesion and no progressive disease 6 months after pembrolizumab was discontinued.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Pneumonia , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Masculino , Recidiva Local de Neoplasia , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico
10.
J Pharmacol Sci ; 144(4): 189-196, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33070837

RESUMO

Pneumonia is a common illness that continues to be the major killer of remaining to be a significant source of morbidity and mortality in the patient population. Many microorganisms cause pneumonia, and now concern is turning to the importance of the cause the new therapies for viral pneumonia. In the current study, we report the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on poly I: C-induced pneumonia. Andrographolide sulfonate was administrated through intraperitoneal injection to mice with poly I: C-induced pneumonia. Recruitment of airway inflammatory cells, alteration of lung histological induced by Poly I: C were significantly ameliorated by andrographolide sulfonate. The protein levels of pro-inflammatory cytokines in bronchoalveolar fluid (BALF) and serum were reduced by andrographolide sulfonate treatment. The levels of MUC5AC and MUC5B in lung tissue were also suppressed. These results reveal that andrographolide sulfate remarkably alleviated pneumonia induced by poly I:C in mice. Moreover, andrographolide sulfonate markedly inhibited the activation of nuclear factor-κB (NF-κB). Taken together, we demonstrated that andrographolide sulfonate ameliorated poly I: C-induced pneumonia in mice, suggesting the possible use of andrographolide sulfonate for virus-induced pneumonia in clinical.


Assuntos
Diterpenos/administração & dosagem , Diterpenos/farmacologia , NF-kappa B/metabolismo , Fitoterapia , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Poli I-C/efeitos adversos , Animais , Citocinas/sangue , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Injeções Intraperitoneais , Masculino , Camundongos Endogâmicos C57BL , Mucina-5AC/metabolismo , Mucina-5B/metabolismo , Pneumonia/induzido quimicamente , Pneumonia/patologia , Pneumonia Viral/tratamento farmacológico
11.
Medicine (Baltimore) ; 99(41): e22567, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031304

RESUMO

BACKGROUND: We put the meta-analysis into practice to reveal the relationship between the incidence risk of immune-related pneumonitis and the use of programmed cell death-1 (PD-1) and ligand 1 (PD-L1) inhibitors related pneumonitis in cancer patients. METHOD: The meta-analysis was put into practice according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Odds ratio (OR) was evaluated by random effect model. RESULTS: After screening and eligibility assessment, 33 clinical trials involving 19,854 patients were selected and used for the final meta-analysis after selection criteria checked. Compared with chemotherapy, the use of PD-1/PD-L1 inhibitors alone increased the incidence risk of all-grade (OR = 4.29, 95% confidence interval: [2.97, 6.19], P < .00001) and grade 3 to 5 immune-related pneumonitis (OR = 3.53, 95% confidence interval: [2.04, 6.11], P < .00001). Similar trend could also be found when PD-1/PD-L1 inhibitors were prescribed alone or in combination with other anti-tumor therapies. CONCLUSION: Whether PD-1/PD-L1 inhibitors were used alone or combined with other antitumor drugs, the incidence risk of immune-related pneumonitis would be increased.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Pneumonia/induzido quimicamente , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Humanos , Pneumonia/imunologia
12.
Oncology (Williston Park) ; 34(9): 370-376, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32965669

RESUMO

In an asymptomatic 77-yearold woman, former 55 packyears smoker, a routine X-ray showed a 45-mm superior left lobe lesion. A chest CT scan confirmed a 36-mm superior left lobe lesion and an aortic-pulmonary lymph node enlargement measuring 42 mm, suspicious for neoplasia. A PET-CT scan showed an elevated uptake in the primary lesion, in the aortic-pulmonary lymph node, and in the left hilar lymph node with a standardized uptake value - 40 and 4.3, respectively. CT-guided lung biopsy showed a lung squamous cell carcinoma. An endobronchial ultrasound-guided transbronchial needle aspiration for lymph-node staging was negative for lymph node spread. Brain MRI was negative. Final staging was determined to be a IIIA (T2bN2) squamous cell carcinoma of the lung.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Escamosas/terapia , Infecções por Coronavirus/diagnóstico , Neoplasias Pulmonares/terapia , Pneumonia Viral/diagnóstico , Pneumonia/diagnóstico , Idoso , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Betacoronavirus , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Quimiorradioterapia , Quimioterapia de Consolidação , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Paclitaxel/administração & dosagem , Pandemias , Pneumonia/induzido quimicamente
14.
J Am Heart Assoc ; 9(18): e017368, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32896206

RESUMO

E-cigarette or vaping product use-associated lung injury was recognized in the United States in the summer of 2019 and is typified by acute respiratory distress, shortness of breath, chest pain, cough, and fever, associated with vaping. It can mimic many of the manifestations of coronavirus disease 2019 (COVID-19). Some investigators have suggested that E-cigarette or vaping product use-associated lung injury was due to tetrahydrocannabinol or vitamin E acetate oil mixed with the electronic cigarette liquid. In experimental rodent studies initially designed to study the effect of electronic cigarette use on the cardiovascular system, we observed an E-cigarette or vaping product use-associated lung injury-like condition that occurred acutely after use of a nichrome heating element at high power, without the use of tetrahydrocannabinol, vitamin E, or nicotine. Lung lesions included thickening of the alveolar wall with foci of inflammation, red blood cell congestion, obliteration of alveolar spaces, and pneumonitis in some cases; bronchi showed accumulation of fibrin, inflammatory cells, and mucus plugs. Electronic cigarette users should be cautioned about the potential danger of operating electronic cigarette units at high settings; the possibility that certain heating elements may be deleterious; and that E-cigarette or vaping product use-associated lung injury may not be dependent upon tetrahydrocannabinol, vitamin E, or nicotine.


Assuntos
Dronabinol/toxicidade , Vapor do Cigarro Eletrônico/toxicidade , Sistemas Eletrônicos de Liberação de Nicotina , Lesão Pulmonar/induzido quimicamente , Pulmão/efeitos dos fármacos , Pneumonia/induzido quimicamente , Vaping/efeitos adversos , Vitamina E/toxicidade , Animais , Exposição por Inalação , Pulmão/patologia , Lesão Pulmonar/patologia , Modelos Animais , Óleos , Pneumonia/patologia , Ratos , Medição de Risco
15.
Artigo em Inglês | MEDLINE | ID: mdl-32872121

RESUMO

Anticholinergic drugs may increase the risk of serious respiratory infection, especially in the elderly. The study aims to investigate the prevalence of anticholinergic drugs and the correlation of incident pneumonia associated with the use of anticholinergic drugs among the elderly in Taiwan. The study population was 275,005 elderly patients aged ≥65 years old, selected from the longitudinal health insurance database (LHID) in 2016. Among all the elderly patients, about 60% had received anticholinergic medication at least once. Furthermore, the study selected elderly patients who had not been diagnosed with pneumonia and had not received any anticholinergic drugs in the past year in order to evaluate the correlation between pneumonia and anticholinergic drugs. The study excluded elderly patients who died or had received related drugs of incident pneumonia during the study period and selected elderly patients receiving anticholinergic drugs as the case group. Propensity score matching (PSM) on a 1:1 scale was used to match elderly patients that were not receiving any anticholinergic drugs as the control group, resulting in a final sample of 32,215 patients receiving anticholinergic drugs and 32,215 patients not receiving any anticholinergic drugs. Conditional logistic regression was used to estimate the association between anticholinergic drugs and pneumonia after controlling for potential confounders. Compared with patients not receiving anticholinergic drugs, the adjusted odds ratio of patients receiving anticholinergic drugs was 1.33 (95% confidence interval: 1.18 to 1.49). Anticholinergic medication is common among elderly patients in Taiwan. Elderly patients receiving anticholinergic drugs may increase their risk of incident pneumonia. The safety of anticholinergic drugs in the elderly should be of concern in Taiwan.


Assuntos
Antagonistas Colinérgicos/efeitos adversos , Demência/tratamento farmacológico , Pneumonia/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Prescrição Inadequada , Masculino , Farmacoepidemiologia , Pneumonia/epidemiologia , Vigilância da População , Lista de Medicamentos Potencialmente Inapropriados , Prevalência , Taiwan/epidemiologia
16.
Br J Radiol ; 93(1115): 20200409, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32783627

RESUMO

OBJECTIVE: To investigate the clinical and radiological features of immune checkpoint inhibitor-related pneumonitis (ICI-P), a rare but serious pulmonary complication of cancer immunotherapy and to evaluate key differences between lung cancer (LC) and non-LC patients. METHODS: 247 patients (LC, n = 151) treated with ICI for malignancies were retrospectively screened in a single institute. The number of patients, history of other immune-related adverse events (irAE), the onset, serum KL-6 levels, and chest CT features (types of pneumonitis, symmetry, laterality, location) were recorded for the ICI-P population and compared for LC and non-LC groups. RESULTS: ICI-P was identified in 26 patients in total (LC, n = 19; non-LC, n = 7). The incidence of other irAE was significantly higher in ICI-P group (63%) compared with patients without ICI-P (34%) (p = 0.0056). An earlier onset of ICI-P was recorded in LC (78 days) compared to non-LC patients (186 days) (p = 0.0034). Serum KL-6 was significantly elevated only in the non-LC group when ICI-P was noticed (p = 0.029). Major CT findings of ICI-P, irrespective of primary disease, were organizing pneumonia pattern and ground glass opacities. LC patients commonly exhibited consolidation and traction bronchiectasis and were prone to asymmetrical shadows (p < 0.001). Non-LC patients were more likely to exhibit symmetrical infiltrations. A small fraction of both groups experienced relapse or moving patterns of ICI-P. CONCLUSION: ICI-P patients more often experienced other irAE prior to the development of ICI-P. The characteristics of ICI-P can differ in terms of the onset, KL-6 reliability, and chest CT findings between LC and non-LC patients. ADVANCES IN KNOWLEDGE: In ICI-P patients, a history of other irAE can be more frequently observed. Differences in disease onset and radiological patterns between LC and non-LC patients might be helpful to make a diagnosis of ICI-P; however, longitudinal observation of chest CT scans is advised to observe the pneumonitis activity irrespective of cancer types.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias/terapia , Pneumonia/induzido quimicamente , Pneumonia/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Bronquiectasia/diagnóstico por imagem , Antígeno CTLA-4/antagonistas & inibidores , Pneumonia em Organização Criptogênica/induzido quimicamente , Pneumonia em Organização Criptogênica/diagnóstico por imagem , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Polissacarídeos Bacterianos/sangue , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Pneumonite por Radiação/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
19.
Nanotoxicology ; 14(8): 1058-1081, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32813574

RESUMO

Nickel nanoparticles (NiNPs) are increasingly used in nanotechnology applications, yet information on sex differences in NiNP-induced lung disease is lacking. The goal of this study was to explore mechanisms of susceptibility between male and female mice after acute or subchronic pulmonary exposure to NiNPs. For acute exposure, male and female mice received a single dose of NiNPs with or without LPS by oropharyngeal aspiration and were necropsied 24 h later. For subchronic exposure, mice received NiNPs with or without LPS six times over 3 weeks prior to necropsy. After acute exposure to NiNPs and LPS, male mice had elevated cytokines (CXCL1 and IL-6) and more neutrophils in bronchoalveolar lavage fluid (BALF), along with greater STAT3 phosphorylation in lung tissue. After subchronic exposure to NiNPs and LPS, male mice exhibited increased monocytes in BALF. Moreover, subchronic exposure of male mice to NiNP only induced higher CXCL1 and CCL2 in BALF along with increased alveolar infiltrates and CCL2 in lung tissue. STAT1 in lung tissue was induced by subchronic exposure to NiNPs in females but not males. Males had a greater induction of IL-6 mRNA in liver after acute exposure to NiNPs and LPS, and greater CCL2 mRNA in liver after subchronic NiNP exposure. These data indicate that susceptibility of males to acute lung inflammation involves enhanced neutrophilia with increased CXCL1 and IL-6/STAT3 signaling, whereas susceptibility to subchronic lung inflammation involves enhanced monocytic infiltration with increased CXCL1 and CCL2. STAT transcription factors appear to play a role in these sex differences. This study demonstrates sex differences in the lung inflammatory response of mice to NiNPs that has implications for human disease.


Assuntos
Pulmão/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Níquel/toxicidade , Pneumonia/induzido quimicamente , Caracteres Sexuais , Animais , Líquido da Lavagem Broncoalveolar/citologia , Quimiocina CXCL1/metabolismo , Feminino , Humanos , Exposição por Inalação , Interleucina-6/metabolismo , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Pneumonia/patologia , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica
20.
Am J Case Rep ; 21: e927586, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32840240

RESUMO

BACKGROUND Rifampicin-induced pneumonitis is an infrequent occurrence, with only a few cases reported in the literature. Furthermore, this condition constitutes a diagnostic challenge, particularly in the era of COVID-19 infection. Here, we report a case of rifampicin-induced pneumonitis with clinical, imaging, and histological features of acute respiratory distress syndrome (ARDS), which required severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to exclude a diagnosis of coronavirus disease 2019 (COVID-19) pneumonia. CASE REPORT A 43-year-old man on anti-TB treatment for TB meningitis developed new-onset fever, fatigue, hypoxemic respiratory failure, and bilateral pulmonary opacities. His clinical, chest X-ray, and CT thorax findings of ARDS were similar to both rifampicin-induced pneumonitis and severe COVID-19 pneumonia. However, reverse transcription polymerase chain reaction (RT-PCR) testing from a nasopharyngeal swab and bronchoalveolar lavage (BAL) via the GeneXpert system was negative for SARS-CoV-2. A detailed workup, including lung biopsy, revealed drug-induced pneumonitis as the cause of his presentation. His pneumonitis improved after discontinuation of rifampicin and recurred following the rifampicin challenge. CONCLUSIONS This case highlights the importance of early, rapid, and accurate testing for SARS-CoV-2 during the COVID-19 pandemic for patients presenting with acute respiratory symptoms, so that accurate diagnosis and early patient management are not delayed for patients with treatable causes of acute and severe lung diseases. Timely identification of rifampicin-induced pneumonitis via a high clinical suspicion, detailed workup, and histopathological analysis is required to avoid permanent damage to the lungs.


Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Pneumonia/induzido quimicamente , Rifampina/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Tuberculose Meníngea/tratamento farmacológico , Adulto , Antibióticos Antituberculose/efeitos adversos , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Humanos , Masculino , Pandemias , Pneumonia/diagnóstico , Pneumonia Viral/epidemiologia , Tuberculose Meníngea/complicações
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