RESUMEN
Regulatory T (Treg) cell responses and apoptotic cell clearance (efferocytosis) represent critical arms of the inflammation resolution response. We sought to determine whether these processes might be linked through Treg-cell-mediated enhancement of efferocytosis. In zymosan-induced peritonitis and lipopolysaccharide-induced lung injury, Treg cells increased early in resolution, and Treg cell depletion decreased efferocytosis. In advanced atherosclerosis, where defective efferocytosis drives disease progression, Treg cell expansion improved efferocytosis. Mechanistic studies revealed the following sequence: (1) Treg cells secreted interleukin-13 (IL-13), which stimulated IL-10 production in macrophages; (2) autocrine-paracrine signaling by IL-10 induced Vav1 in macrophages; and (3) Vav1 activated Rac1 to promote apoptotic cell engulfment. In summary, Treg cells promote macrophage efferocytosis during inflammation resolution via a transcellular signaling pathway that enhances apoptotic cell internalization. These findings suggest an expanded role of Treg cells in inflammation resolution and provide a mechanistic basis for Treg-cell-enhancement strategies for non-resolving inflammatory diseases.
Asunto(s)
Apoptosis/inmunología , Inflamación/inmunología , Macrófagos/inmunología , Fagocitosis/inmunología , Linfocitos T Reguladores/inmunología , Animales , Línea Celular , Células Cultivadas , Humanos , Inflamación/metabolismo , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-10/metabolismo , Interleucina-13/genética , Interleucina-13/inmunología , Interleucina-13/metabolismo , Células Jurkat , Lipopolisacáridos , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/inmunología , Enfermedades Pulmonares/metabolismo , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Peritonitis/inducido químicamente , Peritonitis/inmunología , Peritonitis/metabolismo , Linfocitos T Reguladores/metabolismo , ZimosanRESUMEN
Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin-containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population-based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age- and sex-matched comparators from the background population. Median follow-up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30-3.68]), with a 10-year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35-26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43-2.76]), with a 10-year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43-1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B-symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work-up of pulmonary symptoms.
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Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedad de Hodgkin , Enfermedades Pulmonares , Humanos , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/tratamiento farmacológico , Femenino , Masculino , Adulto , Dinamarca/epidemiología , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/etiología , Anciano , Bleomicina/efectos adversos , Bleomicina/administración & dosificación , Adulto Joven , Incidencia , Procarbazina/efectos adversos , Procarbazina/administración & dosificación , Vincristina/efectos adversos , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Estudios de Cohortes , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Adolescente , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificaciónRESUMEN
Electronic cigarette (e-cigarette) use continues to rise globally. E-cigarettes have been presented as safer alternatives to combustion cigarettes that can mitigate the harm associated with tobacco products; however, the degree to which e-cigarette use itself can lead to morbidity and mortality is not fully defined. Herein we describe how e-cigarettes function; discuss the current knowledge of the effects of e-cigarette aerosol on lung cell cytotoxicity, inflammation, antipathogen immune response, mucociliary clearance, oxidative stress, DNA damage, carcinogenesis, matrix remodelling and airway hyperresponsiveness; and summarise the impact on lung diseases, including COPD, respiratory infection, lung cancer and asthma. We highlight how the inclusion of nicotine or flavouring compounds in e-liquids can impact lung toxicity. Finally, we consider the paradox of the safer cigarette: the toxicities of e-cigarettes that can mitigate their potential to serve as a harm reduction tool in the fight against traditional cigarettes, and we summarise the research needed in this underinvestigated area.
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Sistemas Electrónicos de Liberación de Nicotina , Pulmón , Humanos , Pulmón/efectos de los fármacos , Enfermedades Pulmonares/inducido químicamente , Nicotina/efectos adversos , Reducción del Daño , Estrés Oxidativo , Vapeo/efectos adversos , Daño del ADN , Productos de Tabaco/efectos adversosRESUMEN
BACKGROUND AND OBJECTIVE: Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are rare but well-known diseases that manifest during or after methotrexate (MTX) administration. Limited information is available on the clinical characteristics of OIIA-LPD of the lung because only a few cases have been reported. Thus, we aimed to assess the incidence and prognosis of patients with OIIA-LPD of the lung. METHODS: Patients with OIIA-LPD of the lung treated at our institution between January 2008 and July 2020 were retrospectively analysed. RESULTS: Among the 51 patients with OIIA-LPD, 16 (31.3%, 7 men, 9 women) had OIIA-LPD of the lung (median age, 69 [range, 63-82] years). Peripheral lesions were observed in 10 (62.5%), central lesions in two (12.5%), and both lesions in four (25.0%) patients. Nine of the 16 patients underwent bronchoscopic biopsy, seven were diagnosed (diagnostic yield, 77.8%) and, re-biopsy was performed in 2 patients. Eight (50.0%) patients had LPD and six (37.5%) had diffuse large B-cell lymphoma. In the 14 patients with confirmed treatment efficacy, the overall response rate to MTX withdrawal was 71.4%. However, chemotherapy was required in case of larger lesions (three patients). Death related to OIIA-LPD occurred in only one patient, and 11 of the 14 patients were alive during the study period (median follow-up time, 53.7 [range, 4.3-84.2] months). CONCLUSION: The incidence of OIIA-LPD of the lung is 31.3% and higher than that reported previously. The treatment effect of MTX withdrawal seems to be sufficient; however, in some cases, chemotherapy may be required from the beginning.
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Enfermedad Iatrogénica , Trastornos Linfoproliferativos , Metotrexato , Humanos , Metotrexato/efectos adversos , Metotrexato/administración & dosificación , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Anciano , Trastornos Linfoproliferativos/inducido químicamente , Trastornos Linfoproliferativos/epidemiología , Incidencia , Pronóstico , Anciano de 80 o más Años , Enfermedad Iatrogénica/epidemiología , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/epidemiología , Síndromes de Inmunodeficiencia/inducido químicamente , Síndromes de Inmunodeficiencia/epidemiología , Pulmón/patología , Pulmón/efectos de los fármacosRESUMEN
Many inhalation exposures induce pulmonary inflammation contributing to disease progression. Inflammatory processes are actively regulated via mediators including bioactive lipids. Bioactive lipids are potent signaling molecules involved in both pro-inflammatory and resolution processes through receptor interactions. The formation and clearance of lipid signaling mediators are controlled by multiple metabolic enzymes. An imbalance of these lipids can result in exacerbated and sustained inflammatory processes which may result in pulmonary damage and disease. Dysregulation of pulmonary bioactive lipids contribute to inflammation and pulmonary toxicity following exposures. For example, inhalation of cigarette smoke induces activation of pro-inflammatory bioactive lipids such as sphingolipids, and ceramides contributing to chronic obstructive pulmonary disease. Additionally, exposure to silver nanoparticles causes dysregulation of inflammatory resolution lipids. As inflammation is a common consequence resulting from inhaled exposures and a component of numerous diseases it represents a broadly applicable target for therapeutic intervention. With new appreciation for bioactive lipids, technological advances to reliably identify and quantify lipids have occurred. In this review, we will summarize, integrate, and discuss findings from recent studies investigating the impact of inhaled exposures on pro-inflammatory and resolution lipids within the lung and their contribution to disease. Throughout the review current knowledge gaps in our understanding of bioactive lipids and their contribution to pulmonary effects of inhaled exposures will be presented. New methods being employed to detect and quantify disruption of pulmonary lipid levels following inhalation exposures will be highlighted. Lastly, we will describe how lipid dysregulation could potentially be addressed by therapeutic strategies to address inflammation.
Asunto(s)
Enfermedades Pulmonares , Nanopartículas del Metal , Humanos , Exposición por Inhalación/efectos adversos , Plata , Inflamación/inducido químicamente , Enfermedades Pulmonares/inducido químicamente , Ceramidas , Mediadores de Inflamación/metabolismoRESUMEN
BACKGROUND: Iopamidol is a non-ionic, water-soluble iodine contrast agent that is considered safe for intravenous or intra-arterial administration and is widely used both in the general population and in patients undergoing oncological treatment. While adverse reactions to iopamidol have been documented, to date, no pulmonary and gastric hemorrhages induced by iopamidol have been reported in oncology patients. We report the first case of this complication. CASE PRESENTATION: We report the case of a 60-year-old woman with marginal zone lymphoma who was receiving antineoplastic therapy. As part of the investigation for the condition, she underwent chest enhancement CT with iopamidol. Shortly thereafter(within five minutes), she experienced hemoptysis and hematemesis. She was intubated and admitted to the intensive care unit. Pre- and post-contrast images demonstrated the course of the hemorrhage. Flexible bronchoscopy and gastroscopy on the following day showed no active bleeding, and the patient recovered completely after antiallergy treatment. We speculate that contrast-induced hypersensitivity was the most likely cause of the transient pulmonary and gastric bleeding. CONCLUSION: Although rare, the complications of iopamidol, which may cause allergic reactions in the lungs and stomach, should be considered.
Asunto(s)
Medios de Contraste , Hemoptisis , Yopamidol , Linfoma de Células B de la Zona Marginal , Tomografía Computarizada por Rayos X , Humanos , Femenino , Persona de Mediana Edad , Medios de Contraste/efectos adversos , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/complicaciones , Yopamidol/efectos adversos , Yopamidol/administración & dosificación , Hemoptisis/inducido químicamente , Hemorragia Gastrointestinal/inducido químicamente , Enfermedades Pulmonares/inducido químicamente , Broncoscopía , Hematemesis/inducido químicamenteRESUMEN
The epidemiological evidences for the association between cooking fuel exposure and respiratory health were inconsistent, and repeated-measures prospective evaluation of cooking fuel exposure was still lacking. We assessed the longitudinal association of chronic lung disease (CLD) and lung function with cooking fuel types among Chinese adults aged ≥ 40 years. In this prospective, nationwide representative cohort of the China Health and Retirement Longitudinal Study from 2011 to 2018, 9004 participants from 28 provinces in China were included. CLD was identified based on self-reported physician diagnosis in 2018. Lung function was assessed by peak expiratory flow (PEF) in 2011, 2013 and 2015. Multivariable logistic and linear mixed-effects repeated-measures models were conducted to measure the associations of CLD and PEF with cooking fuel types. Three-level mixed-effects model was performed as sensitivity analysis. Among the participants, 3508 and 3548 participants used persistent solid and clean cooking fuels throughout the survey, and 1948 participants who used solid cooking fuels at baseline switched to clean cooking fuels. Use of persistent clean cooking fuels (adjusted odds ratio [aOR] = 0.73, 95 % confidence interval [CI]: 0.61, 0.88) and switch of solid fuels to clean fuels (aOR = 0.81, 95 % CI: 0.67, 0.98) were associated with lower risk of CLD. The use of clean cooking fuels throughout the survey and switch of solid fuels to clean fuels in 2013 were also significantly associated with higher PEF level. Similar results were observed in stratified analyses and different statistical models. The evidence from CHARLS cohort suggested that reducing solid cooking fuel exposure was associated with lower risk of CLD and better lung function. Given the recent evidence, improving household air quality will reduce the burden of chronic lung diseases.
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Contaminación del Aire Interior , Enfermedades Pulmonares , Adulto , Humanos , Estudios Longitudinales , Jubilación , Estudios Prospectivos , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/epidemiología , Culinaria/métodos , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/análisis , China/epidemiologíaRESUMEN
Long-term exposure to ambient PM2.5 is known associated with cardiovascular and respiratory health effects. However, the heterogeneous concentrationresponse function (CRF) between PM2.5 exposure across different concentration range and cardiopulmonary disease and diabetes mellitus (DM) incidence, and their implications on attributable years lived with disability (YLD) and regulation policy has not been well-studied. In this retrospective longitudinal cohort study, disease-free participants (approximately 170,000 individuals, aged ≥ 30 years) from the MJ Health Database were followed up (2007-2017) regarding incidents of coronary heart disease (CHD), ischemic stroke, chronic obstructive pulmonary disease (COPD), lower respiratory tract infections (LRIs), and DM. We used a time-dependent nonlinear weight-transformation Cox regression model for the CRF with an address-matched 3-year mean PM2.5 exposure estimate. Town/district-specific PM2.5-attributable YLD were calculated by multiplying the disease incidence rate, population attributable fraction, disability weight, and sex-age group specific subpopulation for each disease separately. The estimated CRFs for cardiopulmonary diseases were heterogeneously with the hazard ratios (HRs) increased rapidly for CHD and ischemic stroke at PM2.5 concentration lower than 10 µg/m3, whereas the HRs for DM (LRIs) increased with PM2.5 higher than 15 (20) µg/m3. Women had higher HRs for ischemic stroke and DM but not CHD. Relative to the lowest observed PM2.5 concentration of 6 µg/m3 of the study population, the PM2.5 level with an extra risk of 0.1 % (comparable to the disease incidence) for CHD, ischemic stroke, DM, and LRIs were 8.59, 11.85, 22.09, and 24.23 µg/m3, respectively. The associated attributable YLD decreased by 51.4 % with LRIs reduced most (83.6 %), followed by DM (63.7 %) as a result of PM2.5 concentration reduction from 26.10 to 16.82 µg/m3 during 2011-2019 in Taiwan. The proportion of YLD due to CHD and ischemic stroke remained dominant (56.4 %-69.9 %). The cost-benefit analysis for the tradeoff between avoidable YLD and mitigation cost suggested an optimal PM2.5 exposure level at 12 µg/m3. CRFs for cardiopulmonary diseases, attributable YLD, and regulation level, may vary depending on the national/regional background and spatial distribution of PM2.5 concentrations, as well as demographic characteristics.
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Contaminantes Atmosféricos , Diabetes Mellitus , Exposición a Riesgos Ambientales , Material Particulado , Humanos , Material Particulado/análisis , Incidencia , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Adulto , Contaminantes Atmosféricos/análisis , Diabetes Mellitus/epidemiología , Anciano , Estudios Longitudinales , Taiwán/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/inducido químicamente , Contaminación del Aire/estadística & datos numéricos , Contaminación del Aire/efectos adversosRESUMEN
The lungs, in addition to participating in gas exchange, represent the first line of defense against inhaled pathogens and respiratory toxicants. Cells lining the airways and alveoli include epithelial cells and alveolar macrophages, the latter being resident innate immune cells important in surfactant recycling, protection against bacterial invasion and modulation of lung immune homeostasis. Environmental exposure to toxicants found in cigarette smoke, air pollution and cannabis can alter the number and function of immune cells in the lungs. Cannabis (marijuana) is a plant-derived product that is typically inhaled in the form of smoke from a joint. However, alternative delivery methods such as vaping, which heats the plant without combustion, are becoming more common. Cannabis use has increased in recent years, coinciding with more countries legalizing cannabis for both recreational and medicinal purposes. Cannabis may have numerous health benefits owing to the presence of cannabinoids that dampen immune function and therefore tame inflammation that is associated with chronic diseases such as arthritis. The health effects that could come with cannabis use remain poorly understood, particularly inhaled cannabis products that may directly impact the pulmonary immune system. Herein, we first describe the bioactive phytochemicals present in cannabis, with an emphasis on cannabinoids and their ability to interact with the endocannabinoid system. We also review the current state-of-knowledge as to how inhaled cannabis/cannabinoids can shape immune response in the lungs and discuss the potential consequences of altered pulmonary immunity. Overall, more research is needed to understand how cannabis inhalation shapes the pulmonary immune response to balance physiological and beneficial responses with potential deleterious consequences on the lungs.
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Cannabinoides , Cannabis , Enfermedades Pulmonares , Humanos , Cannabis/efectos adversos , Pulmón , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/tratamiento farmacológico , Cannabinoides/farmacología , InmunidadRESUMEN
As the public health burden of air pollution continues to increase, new strategies to mitigate harmful health effects are needed. Dietary antioxidants have previously been explored to protect against air pollution-induced lung injury producing inconclusive results. Inhaled (pulmonary or nasal) administration of antioxidants presents a more promising approach as it could directly increase antioxidant levels in the airway surface liquid (ASL), providing protection against oxidative damage from air pollution. Several antioxidants have been shown to exhibit antioxidant, anti-inflammatory, and anti-microbial properties in in vitro and in vivo models of air pollution exposure; however, little work has been done to translate these basic research findings into practice. This narrative review summarizes these findings and data from human studies using inhaled antioxidants in response to air pollution, which have produced positive results, indicating further investigation is warranted. In addition to human studies, cell and murine studies should be conducted using more relevant models of exposure such as air-liquid interface (ALI) cultures of primary cells and non-aqueous apical delivery of antioxidants and pollutants. Inhalation of antioxidants shows promise as a protective intervention to prevent air pollution-induced lung injury and exacerbation of existing lung disease.
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Contaminantes Atmosféricos , Contaminación del Aire , Enfermedades Pulmonares , Lesión Pulmonar , Humanos , Ratones , Animales , Antioxidantes/farmacología , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/prevención & control , Pulmón , Contaminantes Atmosféricos/efectos adversosRESUMEN
Lactoferrin (LTF), an iron binding protein, is known to exhibit immune modulatory effects on pulmonary pathology during insult-induced models of primary Mycobacterium tuberculosis (Mtb) infection. The effects of LTF correlate with modulation of the immune related development of the pathology, and altering of the histological nature of the physically compact and dense lung granuloma in mice. Specifically, a recombinant human version of LTF limits immediate progression of granulomatous severity following administration of the Mtb cell wall mycolic acid, trehalose 6,6'-dimycolate (TDM), in part through reduced pro-inflammatory responses known to control these events. This current study investigates a limited course of LTF to modulate not only initiation, but also maintenance and resolution of pathology post development of the granulomatous response in mice. Comparison is made to a fusion of LTF with the Fc domain of IgG2 (FcLTF), which is known to extend LTF half-life in circulation. TDM induced granulomas were examined at extended times post insult (day 7 and 14). Both LTF and the novel FcLTF exerted sustained effects on lung granuloma pathology. Reduction of pulmonary pro-inflammatory cytokines TNF-α and IL-1ß occurred, correlating with reduced pathology. Increase in IL-6, known to regulate granuloma maintenance, was also seen with the LTFs. The FcLTF demonstrated greater impact than the recombinant LTF, and was superior in limiting damage to pulmonary tissues while limiting residual inflammatory cytokine production.
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Factores Cordón , Granuloma del Sistema Respiratorio , Lactoferrina , Enfermedades Pulmonares , Animales , Humanos , Ratones , Factores Cordón/metabolismo , Factores Cordón/toxicidad , Lactoferrina/uso terapéutico , Mycobacterium tuberculosis/metabolismo , Granuloma del Sistema Respiratorio/inducido químicamente , Granuloma del Sistema Respiratorio/tratamiento farmacológico , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/tratamiento farmacológicoRESUMEN
OBJECTIVE: To evaluate the effectiveness and safety of linezolid-containing regimens for treatment of M. abscessus pulmonary disease. METHODS: The records of 336 patients with M. abscessus pulmonary disease who were admitted to Shanghai Pulmonary Hospital from January 2018 to December 2020 were retrospectively analyzed. A total of 164 patients received a linezolid-containing regimen and 172 controls did not. The effectiveness, safety, antibiotic susceptibility profiles, outcomes, culture conversion, cavity closure, and adverse reactions were compared in these two groups. RESULTS: The two groups had similar treatment success (56.1% vs. 48.8%; P > 0.05), but treatment duration was shorter in the linezolid group (16.0 months [inter-quartile ranges, IQR: 15.0-17.0] vs. 18.0 months [IQR: 16.0-18.0]; P < 0.01). The rates of sputum culture conversion were similar (53.7% vs. 46.5%, P > 0.05), but time to conversion was shorter in the linezolid group (3.5 months [IQR: 2.5-4.4] vs. 5.5 months [IQR: 4.0-6.8]; P < 0.01). The linezolid group had a higher rate of cavity closure (55.2% vs. 28.6%, P < 0.05) and a shorter time to cavity closure (3.5 months [IQR: 2.5-4.4] vs. 5.5 months [IQR: 4.0-6.8]; P < 0.01). Anemia and peripheral neuropathy were more common in the linezolid group (17.7% vs. 1.7%, P < 0.01; 12.8% vs. 0.6%, P < 0.01). CONCLUSIONS: The linezolid and control groups had similar treatment success rates. The linezolid group had a shorter treatment duration, shorter time to sputum culture conversion, and higher rate and shorter time to lung cavity closure. More patients receiving linezolid developed anemia and peripheral neuropathy.
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Anemia , Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Enfermedades del Sistema Nervioso Periférico , Humanos , Linezolid/efectos adversos , Estudios Retrospectivos , China , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/microbiología , Resultado del Tratamiento , Anemia/inducido químicamente , Anemia/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Antibacterianos/efectos adversosRESUMEN
A 68-year-old male, who was undergoing XELOX plus trastuzumab therapy for gastric cancer, developed proteinuria, hematuria, and progressive increase in creatinine after 3 months. Subsequently, the patient also experienced hemoptysis, nasal bleeding. Chest CT examination shown pulmonary hemorrhage. The MRI of the nasopharynx ruled out nasopharyngeal cancer recurrence. The MPO and PR3 were elevated, and renal biopsy confirmed ANCA-related vasculitis, which affected the lungs, kidneys, and nasopharynx. Based on the review of the patient''s medical history and medication, it is believed that ANCA-related vasculitis was caused by XELOX plus trastuzumab chemotherapy, but it is difficult to confirm which specific drug caused it. After stopping XELOX plus trastuzumab chemotherapy, glucocorticoids and cyclophosphamide was given, the patient''s pulmonary hemorrhage and nasal bleeding stopped, and the lung lesions were absorbed. The renal function also improved. The patient later experienced pulmonary infection again, and tNGS indicated Legionella pneumophila and pulmonary tuberculosis infection. Despite anti-infection treatment, steroid dose was rapidly reduced. Ultimately, the patient gave up on treatment and eventually died.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Enfermedades Renales , Enfermedades Pulmonares , Neoplasias Nasofaríngeas , Masculino , Humanos , Anciano , Oxaliplatino , Anticuerpos Anticitoplasma de Neutrófilos , Trastuzumab/efectos adversos , Capecitabina , Epistaxis/complicaciones , Neoplasias Nasofaríngeas/complicaciones , Recurrencia Local de Neoplasia/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inducido químicamente , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Enfermedades Pulmonares/inducido químicamente , Enfermedades Renales/complicaciones , PeroxidasaRESUMEN
Methotrexate (MTX) is an anticancer agent widely used in clinical practice for various oncological, rheumatological, autoimmune, and inflammatory diseases. However, the side effects of MTX limit its usage for treatment. In addition, diffuse alveolar damage, interstitial pneumonia, fibrosis, and pleural reactions may be encountered in MTX-induced pulmonary toxicity. Ramelteon (RML), a melatonin receptor agonist, has antioxidant, anti-inflammatory, and protective effects are shown by several studies. This study aimed to show the antioxidant, anti-inflammatory, and antiapoptotic effects of RML and its effect on the airway surface liquid volume homeostasis via aquaporins (AQP) in MTX-induced lung injury. Thirty-two female Wistar Albino rats were grouped into four groups as control, MTX (20 mg/kg, intraperitoneally, a single dose), MTX + RML, and RML (10 mg/kg, via oral gavage, for seven days) groups. Once the experiment ended, the rats' lung tissues were taken for biochemical, genetic, histopathological, and immunohistochemical examinations. MTX significantly increased oxidative stress index and total oxidative status, and decreased total antioxidant status levels by 202.0%, 141.4%, 20.2%, respectively, relative to the control (p Ë 0.001 for all). AQP-1/5, which is an indicator of lung damage, was also found to decrease significantly (p Ë 0.001). In addition, a significant increase was observed in interleukin-1ß, interferon-beta, and caspase-8 expressions and histopathological changes as a result of immunohistochemical and histochemical examinations (p Ë 0.001). RML treatment ameliorated all these changes and significantly regressed lung damage. Our results suggest that RML might be used as a lung-protective agent in various models of lung and tissue injury.
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Antioxidantes , Enfermedades Pulmonares , Animales , Ratas , Femenino , Antioxidantes/metabolismo , Ratas Wistar , Metotrexato/toxicidad , Estrés Oxidativo , Enfermedades Pulmonares/inducido químicamente , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacologíaRESUMEN
Nickel compounds are environmental toxicants, prevalent in the atmosphere due to their widespread use in several industrial processes, extensive consumption of nickel containing products, as well as burning of fossil fuels. Exposure to nickel is associated with a multitude of chronic inflammatory lung diseases including asthma, chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. In addition, nickel exposure is implicated in the development of nasal and lung cancers. Interestingly, a common pathogenic mechanism underlying the development of diseases associated with nickel exposure is epithelial-mesenchymal transition (EMT). EMT is a process by which the epithelial cells lose their junctions and polarity and acquire mesenchymal traits, including increased ability to migrate and invade. EMT is a normal and essential physiological process involved in differentiation, development and wound healing. However, EMT also contributes to a number of pathological conditions, including fibrosis, cancer and metastasis. Growing evidence suggest that EMT induction could be an important outcome of nickel exposure. In this review, we discuss the role of EMT in nickel-induced lung diseases and the mechanisms associated with EMT induction by nickel exposure.
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Transición Epitelial-Mesenquimal/efectos de los fármacos , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/patología , Níquel/efectos adversos , Animales , HumanosRESUMEN
Inflammation and resolution are dynamic processes comprised of inflammatory activation and neutrophil influx, followed by mediator catabolism and efferocytosis. These critical pathways ensure a return to homeostasis and promote repair. Over the past decade research has shown that diverse mediators play a role in the active process of resolution. Specialized pro-resolving mediators (SPMs), biosynthesized from fatty acids, are released during inflammation to facilitate resolution and are deficient in a variety of lung disorders. Failed resolution results in remodeling and cellular deposition through pro-fibrotic myofibroblast expansion that irreversibly narrows the airways and worsens lung function. Recent studies indicate environmental exposures may perturb and deregulate critical resolution pathways. Environmental xenobiotics induce lung inflammation and generate reactive metabolites that promote oxidative stress, injuring the respiratory mucosa and impairing gas-exchange. This warrants recognition of xenobiotic associated molecular patterns (XAMPs) as new signals in the field of inflammation biology, as many environmental chemicals generate free radicals capable of initiating the inflammatory response. Recent studies suggest that unresolved, persistent inflammation impacts both resolution pathways and endogenous regulatory mediators, compromising lung function, which over time can progress to chronic lung disease. Chronic ozone (O3) exposure overwhelms successful resolution, and in susceptible individuals promotes asthma onset. The industrial contaminant cadmium (Cd) bioaccumulates in the lung to impair resolution, and recurrent inflammation can result in chronic obstructive pulmonary disease (COPD). Persistent particulate matter (PM) exposure increases systemic cardiopulmonary inflammation, which reduces lung function and can exacerbate asthma, COPD, and idiopathic pulmonary fibrosis (IPF). While recurrent inflammation underlies environmentally induced pulmonary morbidity and may drive the disease process, our understanding of inflammation resolution in this context is limited. This review aims to explore inflammation resolution biology and its role in chronic environmental lung disease(s).
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Asma , Enfermedades Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Pulmón/metabolismo , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/metabolismo , MorbilidadRESUMEN
The gut microbiota contributes to shaping efficient and safe immune defenses in the gut. However, little is known about the role of the gut and/or lung microbiota in the education of pulmonary innate immune responses. Here, we tested whether the endogenous microbiota in general can modulate the reactivity of pulmonary tissue to pathogen stimuli by comparing the response of specific-pathogen-free (SPF) and germ-free (GF) mice. Thus, we observed earlier and greater inflammation in the pulmonary compartment of GF mice than that of SPF mice after intranasal instillation to lipopolysaccharide (LPS), a component of Gram-negative bacteria. Toll-like receptor 4 (TLR4) was more abundantly expressed in the lungs of GF mice than those of SPF mice at steady state, which could predispose the innate immunity of GF mice to strongly react to the environmental stimuli. Lung explants were stimulated with different TLR agonists or infected with the human airways pathogen, respiratory syncytial virus (RSV), resulting in greater inflammation under almost all conditions for the GF explants. Finally, alveolar macrophages (AM) from GF mice presented a higher innate immune response upon RSV infection than those of SPF mice. Overall, these data suggest that the presence of microbiota in SPF mice induced a process of innate immune tolerance in the lungs by a mechanism which remains to be elucidated. Our study represents a step forward to establishing the link between the microbiota and the immune reactivity of the lungs.
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Microbioma Gastrointestinal/fisiología , Vida Libre de Gérmenes , Lipopolisacáridos/toxicidad , Pulmón/inmunología , Pulmón/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Citocinas/genética , Citocinas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/metabolismo , Enfermedades Pulmonares/inducido químicamente , Masculino , Ratones , Organismos Libres de Patógenos Específicos , Técnicas de Cultivo de Tejidos , Receptor Toll-Like 4/genéticaRESUMEN
BACKGROUND: American Indians have a higher burden of chronic lung disease compared to the US average. Several metals are known to induce chronic lung disease at high exposure levels; however, less is known about the role of environmental-level metal exposure. We investigated respiratory effects of exposure to single metals and metal-mixtures in American Indians who participated in the Strong Heart Study. METHODS: We included 2077 participants with data on 6 metals (As, Cd, Mo, Se, W, Zn) measured from baseline urine samples (1989-1991) and who underwent spirometry testing at follow-up (1993-1995). We used generalized linear regression to assess associations of single metals with spirometry-defined measures of airflow limitation and restrictive ventilatory pattern, and continuous spirometry. We used Bayesian Kernel Machine Regression to investigate the joint effects of the metal-mixture. Sensitivity analyses included stratifying by smoking status and diabetes. RESULTS: Participants were 40% male, with median age 55 years. 21% had spirometry-defined airflow limitation, and 14% had a restrictive ventilatory pattern. In individual metal analyses, Cd was associated with higher odds of airflow limitation and lower FEV1 and FEV1/FVC. Mo was associated with higher odds of restrictive ventilatory pattern and lower FVC. Metal-mixtures analyses confirmed these models. In smoking stratified analyses, the overall metal-mixture was linearly and positively associated with airflow limitation among non-smokers; Cd was the strongest contributor. For restrictive ventilatory pattern, the association with the overall metal-mixture was strong and linear among participants with diabetes and markedly attenuated among participants without diabetes. Among those with diabetes, Mo and Zn were the major contributors. CONCLUSIONS: Environmental-level exposure to several metals was associated with higher odds of spirometry-defined lung disease in an American Indian population. Exposure to multiple metals, including Cd and Mo, may have an under-recognized adverse role on the respiratory system.
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Exposición a Riesgos Ambientales , Enfermedades Pulmonares , Adulto , Teorema de Bayes , Exposición a Riesgos Ambientales/análisis , Femenino , Volumen Espiratorio Forzado , Humanos , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Espirometría , Indio Americano o Nativo de AlaskaRESUMEN
Humans will set foot on the Moon again soon. The lunar dust (LD) is potentially reactive and could pose an inhalation hazard to lunar explorers. We elucidated LD toxicity and investigated the toxicological impact of particle surface reactivity (SR) using three LDs, quartz, and TiO2. We first isolated the respirable-size-fraction of an Apollo-14 regolith and ground two coarser samples to produce fine LDs with increased SR. SR measurements of these five respirable-sized dusts, determined by their in-vitro ability to generate hydroxyl radicals (â¢OH), showed that ground LDs > unground LD ≥ TiO2 ≥ quartz. Rats were each intratracheally instilled with 0, 1, 2.5, or 7.5 mg of a test dust. Toxicity biomarkers and histopathology were assessed up to 13 weeks after the bolus instillation. All dusts caused dose-dependent-increases in pulmonary lesions and toxicity biomarkers. The three LDs, which possessed mineral compositions/properties similar to Arizona volcanic ash, were moderately toxic. Despite a 14-fold â¢OH difference among these three LDs, their toxicities were indistinguishable. Quartz produced the lowest â¢OH amount but showed the greatest toxicity. Our results showed no correlation between the toxicity of mineral dusts and their ability to generate free radicals. We also showed that the amounts of oxidants per neutrophil increased with doses, time and the cytotoxicity of the dusts in the lung, which supports our postulation that dust-elicited neutrophilia is the major persistent source of oxidative stress. These results and the discussion of the crucial roles of the short-lived, continuously replenished neutrophils in dust-induced pathogenesis are presented.
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Polvo , Enfermedades Pulmonares , Animales , Biomarcadores , Polvo/análisis , Enfermedades Pulmonares/inducido químicamente , Luna , Oxidantes/toxicidad , Cuarzo/toxicidad , Ratas , Dióxido de Silicio/toxicidad , TitanioRESUMEN
BACKGROUND: There is limited evidence regarding factors associated with mortality in septic patients receiving etomidate. This study aimed to determine independent pre-intubation factors predicting 28-day mortality in septic patients receiving single-dose etomidate as an induction agent during rapid sequence intubation (RSI). METHODS: This single-center retrospective cohort study included intubated septic patients receiving etomidate as an induction agent during RSI in the emergency department of Siriraj hospital, Bangkok, Thailand, between January 1st, 2016 and June 30th, 2020. Pre-intubation characteristics were compared between survivors and non-survivors. Independent risk factors associated with 28-day mortality were identified using the Cox proportional hazards regression model. Association between etomidate dosage and mortality was also determined. RESULTS: A total of 344 patients, 238 (69%) survivors and 106 (31%) non-survivors, were included in the analyses. The initial Cox hazards model identified a pre-intubation lactate level ≥ 4 mmol/L as an independent factor associated with mortality (adjusted Hazards ratio [aHR] 2.66, 95% confidence interval [CI] 1.55-4.56). After removing lactate level from the model due to limited lactate values in the data, cancer was also predictive of 28-day mortality (aHR 1.83, 95%CI 1.10-3.04), while patients with respiratory infections and underlying chronic lung disease were associated with lower mortality (aHR 0.54, 95%CI 0.37-0.80 and aHR 0.57, 0.33-0.96, respectively). Etomidate dosage was not associated with mortality in our study. CONCLUSION: In septic patients who received a single dose of etomidate, a pre-intubation lactate level ≥ 4 mmol/L and cancer were associated with increased 28-day mortality, while respiratory infection and underlying chronic lung disease were associated with lower mortality. Physicians may take these factors into consideration when selecting induction agents for septic patients.