RESUMEN
BACKGROUND: Use of electronic cigarettes (e-cigarettes) is prevalent among adolescents and young adults, but there has been limited knowledge about health consequences in human populations. We conduct a systematic review and meta-analysis of results on respiratory disorders from studies of general-population samples and consider the mapping of these results to findings about biological processes linked to e-cigarettes in controlled laboratory studies. METHOD: We conducted a literature search and meta-analysis of epidemiological studies on the association of e-cigarette use with asthma and with COPD. We discuss findings from laboratory studies about effects of e-cigarettes on four biological processes: cytotoxicity, oxidative stress/inflammation, susceptibility to infection and genetic expression. RESULTS: Epidemiological studies, both cross-sectional and longitudinal, show a significant association of e-cigarette use with asthma and COPD, controlling for cigarette smoking and other covariates. For asthma (n=15 studies), the pooled adjusted odds ratio (aOR) was 1.39 (95% CI 1.28-1.51); for COPD (n=9 studies) the aOR was 1.49 (95% CI 1.36-1.65). Laboratory studies consistently show an effect of e-cigarettes on biological processes related to respiratory harm and susceptibility to illness, with e-cigarette conditions differing significantly from clean-air controls, although sometimes less than for cigarettes. CONCLUSIONS: The evidence from epidemiological studies meets established criteria for consistency, strength of effect, temporality, and in some cases a dose-response gradient. Biological plausibility is indicated by evidence from multiple laboratory studies. We conclude that e-cigarette use has consequences for asthma and COPD, which is of concern for respirology and public health.
Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Vapeo , Adolescente , Estudios Transversales , Humanos , Laboratorios , Vapeo/efectos adversos , Adulto JovenAsunto(s)
Hipertensión/epidemiología , Síndrome Metabólico/epidemiología , Esmog/efectos adversos , Contaminación del Aire/efectos adversos , Hawaii/epidemiología , Humanos , Hipertensión/etiología , Síndrome Metabólico/etiología , Dióxido de Azufre/efectos adversos , Ácidos Sulfúricos/efectos adversos , Ácidos Sulfúricos/química , Erupciones Volcánicas/efectos adversosRESUMEN
OBJECTIVES: Little evidence is available on the association of e-cigarettes with health indices. We investigated the association of e-cigarette use with diagnosed respiratory disorder among adults in data from the Behavioral Risk Factor Surveillance Survey (BRFSS). METHODS: The 2016 Hawaii BRFSS, a cross-sectional random-dial telephone survey, had 8087 participants; mean age was 55 years. Items asked about e-cigarette use, cigarette smoking, and being diagnosed by a health professional with (a) asthma or (b) chronic obstructive pulmonary disease. Multivariable analyses tested associations of e-cigarette use with the respiratory variables controlling for smoking and for demographic, physical, and psychosocial variables. RESULTS: Controlling for the covariates and smoking there was a significant association of e-cigarette use with chronic pulmonary disorder in the total sample (AOR = 2.58, CI 1.36-4.89, p < 0.01) and a significant association with asthma among nonsmokers (AOR = 1.33, CI 1.00-1.77, p < 0.05). The associations were stronger among nonsmokers than among smokers. Results were similar for analyses based on relative risk and absolute risk. There was also a greater likelihood of respiratory disorder for smokers, females, and persons with overweight, financial stress, and secondhand smoke exposure. CONCLUSIONS: This is the first study to show a significant independent association of e-cigarette use with chronic respiratory disorder. Several aspects of the data are inconsistent with the possibility that e-cigarettes were being used for smoking cessation by persons with existing respiratory disorder. Theoretical mechanisms that might link e-cigarettes use and respiratory symptoms are discussed.
Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Trastornos Respiratorios/epidemiología , Vapeo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Hawaii , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Cese del Hábito de Fumar , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Acute rheumatic fever (ARF) is an autoimmune disorder associated with Streptococcus pyogenes infection. A prevailing hypothesis to account for this disease is that epitopes of self-antigens, such as cardiac myosin react to antibodies against S. pyogenes. The goal of our study was to confirm disease epitopes of cardiac myosin, identify immunodominant epitopes and to monitor the epitope response pattern in acute and convalescent rheumatic fever. METHODS: Enzyme-linked immunosorbant assays were used to determine epitopes immunodominant in acute disease and to track the immune response longitudinally to document any changes in the epitope pattern in convalescent sera. Multiplex fluorescence immunoassay was used to correlate anti-streptolysin O (ASO) and anti-human cardiac myosin antibodies. RESULTS: Disease-specific epitopes in rheumatic fever were identified as S2-1, 4 and 8. Epitopes S2-1, 4, 8 and 9 were found to be immunodominant in acute sera and S2-1, 8, 9, 29 and 30 in the convalescent sera. Frequency analysis showed that 50% of the ARF subjects responded to S2-8. S2-8 responders tended to maintain their epitope pattern throughout the convalescent period, whereas the S2-8 nonresponders tended to spread their responses to other epitopes later in the immune response. There was a significant correlation between anti-cardiac myosin and ASO titers. In addition, S2-8 responders showed elevated ASO titers compared with S2-8 non responders. CONCLUSION: Our studies confirm the existence of S2-1, 4 and 8 as disease-specific epitopes. We provide evidence that cardiac myosin S2-8 responders remain epitope stable in convalescence, whereas S2-8 nonresponders shift to neoepitopes. Multiplex data indicated a correlation between elevated ASO and anti-human cardiac myosin antibody titers. Mapping of cardiac myosin epitopes recognized in rheumatic fever sera may identify immunophenotypes of rheumatic fever.
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Autoanticuerpos/inmunología , Miosinas Cardíacas/inmunología , Fiebre Reumática/inmunología , Autoanticuerpos/sangre , Miosinas Cardíacas/química , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Epítopos/inmunología , Hawaii , Humanos , Fiebre Reumática/sangre , Fiebre Reumática/fisiopatología , Streptococcus pyogenesRESUMEN
OBJECTIVES: To determine the autonomic cardiovascular control among residents of Hawaii who are exposed to varying levels of volcanic air pollution (vog), which consists largely of sulfur dioxide (SO(2)) and acid aerosols. METHODS: In a cross-sectional study between April 2006 and June 2008, the authors measured cardiovagal autonomic function by heart-rate variability (HRV) in 72 healthy individuals who lived in four exposure zones on Hawaii Island: vog-free (n=18); episodic exposure to SO(2) >200 ppb and acid aerosol (n=19); chronic exposure to SO(2) ≥30 ppb and acid aerosol (n=15); and chronic exposure to acid aerosols (n=20). Individuals with diabetes or heart disease, or who had smoked in the preceding month were excluded. HRV was measured in all subjects during rest, paced breathing and active standing (Ewing manoeuvre). HRV was analysed in time and frequency domains and compared between the four exposure zones. RESULTS: There were no significant differences between exposure zones in HRV, in either time or frequency domains, even after adjustment for age, gender, ethnicity and body mass index. There was no significant HRV change in three individuals in whom HRV was measured before and during an exposure to combined SO(2) 100-250 ppb and concentration of respirable particles of diameter ≥2.5 µ (PM(2.5)) >500 µg/m(3). Age was significantly correlated with time-domain parameters during paced breathing and the Ewing manoeuvre. CONCLUSIONS: This study of healthy individuals found no appreciable effects of vog on the autonomic nervous system.
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Asthma can progress to subepithelial airway fibrosis, mediated in large part by transforming growth factor-beta (TGF-beta). The scaffolding protein caveolin-1 (cav1) can inhibit the activity of TGF-beta, perhaps by forming membrane invaginations that enfold TGF-beta receptors. The study goals were 1) to evaluate how allergen challenge affects lung expression of cav1 and the density of caveolae in vivo 2) to determine whether reduced cav1 expression is mediated by interleukin (IL)-4 and 3) to measure the effects of decreased expression of cav1 on TGF-beta signaling. C57BL/6J, IL-4-deficient mice, and cav1-deficient mice, sensitized by intraperitoneal injections of phosphate-buffered saline or ovalbumin (OVA) at days 0 and 12, received intranasal phosphate-buffered saline or OVA challenges at days 24, 26, and 28. Additionally, another group of C57BL/6J mice received IL-4 by intratracheal instillation for 7 days. We confirmed that the OVA-allergen challenge increased eosinophilia and T-helper type 2-related cytokine levels (IL-4, IL-5, and IL-13) in bronchoalveolar lavage. Allergen challenge reduced lung cav1 mRNA abundance by 40%, cav1 protein by 30%, and the number of lung fibroblast caveolae by 50%. Administration of IL-4 in vivo also substantially decreased cav1 expression. In contrast, the allergen challenge did not decrease cav1 expression in IL-4-deficient mice. The reduced expression of cav1 was associated with activation of TGF-beta signaling that was further enhanced in OVA-sensitized and challenged cav1-deficient mice. This study demonstrates a previously unknown modulation of TGF-beta signaling by IL-4, via cav1, suggesting novel therapeutic targets for controlling the effects of TGF-beta and thereby ameliorating pathological airway remodeling.
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Alérgenos/farmacología , Asma/metabolismo , Caveolina 1/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Células Th2/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Alérgenos/inmunología , Animales , Asma/complicaciones , Asma/genética , Asma/inmunología , Asma/patología , Lavado Broncoalveolar , Caveolina 1/genética , Caveolina 1/inmunología , Regulación hacia Abajo/inmunología , Interleucinas/inmunología , Interleucinas/farmacología , Ratones , Ratones Noqueados , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/terapia , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Células Th2/inmunología , Células Th2/patología , Factores de Tiempo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/inmunologíaRESUMEN
A mouse model for allergic airway inflammation involving ovalbumin (OVA) sensitization and challenge has been developed that reproduces hallmark features of human asthma and has provided valuable insight into the mechanisms by which this disease occurs. Cellular infiltrate in lungs of mice used in this model have conventionally been evaluated using histological examination of tissue sections and light microscopic analysis of lung lavage samples. As an alternative or complementary approach for characterizing cellular infiltrate, we developed a multicolor fluorescence-activated cell sorter (FACS) method involving the simultaneous detection of seven different markers on lung cell suspensions: CD4, CD8, B220, CD11b, Gr-1, CD49b, and FcepsilonRI. Only some of these cell types increased in OVA-challenged mice compared to PBS controls, including the CD4(+), B220(+), CD11b(+), and FcepsilonRI(+) groups. We also examined subpopulations of cells for coexpression of these markers and dissected heterogeneous populations as further evaluation procedures to characterize the cellular infiltrate resulting from OVA challenge. Finally, we combined FACS with real-time PCR to analyze certain cell types in terms of mRNA levels for factors involved in asthma, including GATA-3 and IL-1beta. Overall, these FACS-based techniques provide a powerful approach for analyzing cellular profiles in lung tissue from mice used in the mouse model of asthma and may also prove valuable in evaluating cellular infiltrates for other models of inflammation and immune responses.
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Citometría de Flujo/métodos , Subgrupos Linfocitarios/citología , Hipersensibilidad Respiratoria/inmunología , Alérgenos/inmunología , Animales , Líquido del Lavado Bronquioalveolar/citología , Masculino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Asthma is driven by allergic airway inflammation and involves increased levels of oxidative stress. This has led to speculation that antioxidants like selenium (Se) may play important roles in preventing or treating asthma. We fed diets containing low (0.08 parts per million), medium (0.25 parts per million), or high (2.7 parts per million) Se to female C57BL/6 mice and used an established OVA challenge protocol to determine the relationship between Se intake and the development of allergic airway inflammation. Results demonstrated that mice fed medium levels of Se had robust responses to OVA challenge in the lung as measured by lung cytokine levels, airway cellular infiltrate, eosinophilia, serum anti-OVA IgE, airway hyperreactivity, goblet cell hyperplasia, and phosphorylated STAT-6 levels in the lung. In contrast, responses to OVA challenge were less robust in mice fed low or high levels of Se. In particular, mice fed low Se chow showed significantly lower responses compared with mice fed medium Se chow for nearly all readouts. We also found that within the medium Se group the expression of lung glutathione peroxidase-1 and liver selenoprotein P were increased in OVA-challenged mice compared with PBS controls. These data suggest that Se intake and allergic airway inflammation are not related in a simple dose-response manner, which may explain the inconsistent results obtained from previous descriptive studies in humans. Also, our results suggest that certain selenoproteins may be induced in response to Ag challenges within the lung.