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BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) and hyperlipidaemia are independent risk factors for cardiovascular disease. This study investigates the association between OSA and prevalence of hyperlipidaemia in patients of the European Sleep Apnea Database (ESADA) cohort. METHODS: The cross-sectional analysis included 11 892 patients (age 51.9 ± 12.5 years, 70% male, body mass index (BMI) 31.3 ± 6.6 kg/m2 , mean oxygen desaturation index (ODI) 23.7 ± 25.5 events/h) investigated for OSA. The independent odds ratio (OR) for hyperlipidaemia in relation to measures of OSA (ODI, apnoea-hypopnoea index, mean and lowest oxygen saturation) was determined by means of general linear model analysis with adjustment for important confounders such as age, BMI, comorbidities and study site. RESULTS: Hyperlipidaemia prevalence increased from 15.1% in subjects without OSA to 26.1% in those with severe OSA, P < 0.001. Corresponding numbers in patients with diabetes were 8.5% and 41.5%, P < 0.001. Compared with ODI quartile I, patients in ODI quartiles II-IV had an adjusted OR (95% CI) of 1.33 (1.15-1.55), 1.37 (1.17-1.61) and 1.33 (1.12-1.58) (P < 0.001), respectively, for hyperlipidaemia. Obesity was defined as a significant risk factor for hyperlipidaemia. Subgroups of OSA patients with cardio-metabolic comorbidities demonstrated higher prevalence of HL. In addition, differences in hyperlipidaemia prevalence were reported in European geographical regions with the highest prevalence in Central Europe. CONCLUSION: Obstructive sleep apnoea, in particular intermittent hypoxia, was independently associated with the prevalence of hyperlipidaemia diagnosis.
Assuntos
Doenças Cardiovasculares/epidemiologia , Hiperlipidemias/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Polissonografia , Prevalência , Fatores de RiscoRESUMO
Gas exchange abnormalities occur firstly during sleep in restrictive and obstructive chronic respiratory failure. Nocturnal hypoxemia is often a revealing feature of a sleep-related hypoventilation/hypoxemia syndrome in patients who will have later a diurnal hypoxemia. On the other hand, sleep may induce breathing abnormalities in individuals without lung diseases, like in obstructive sleep apnea syndrome (OSAS). In OSAS, repeated closure and/or narrowing of the pharynx during sleep increases the inspiratory effort and induces sleep fragmentation. Intermittent hypoxemia is another consequence of the obstructive events in OSAS. Besides its direct consequences on sleep, OSAS is also associated with an increased risk of cardiovascular morbi-mortality. Reduced daytime alertness and cognitive functions are usually present in patients with sleep-disordered breathing. These features are believed to be related to both sleep fragmentation and nocturnal hypoxia/hypercapnia. Sleep-related hypoventilation/hypoxemia and pharyngeal obstructive events may occur together in patients with respiratory insufficiency, especially in obese and/or chronic obstructive pulmonary disease (COPD) subjects. A correct qualitative and quantitative assessment of sleep-disordered breathing may only be performed by recording specific physiological signals during sleep.
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Síndromes da Apneia do Sono/diagnóstico , Humanos , Oximetria , PolissonografiaRESUMO
We studied the perception of bronchoconstriction in asthmatic subjects who were randomly treated with inhaled beta 2 agonist given either alone (n = 9) or associated with inhaled corticosteroids (n = 9). Methacholine and bradykinin challenges, bronchoalveolar lavage, and bronchial biopsies were performed in all subjects. After each dose of agonist, breathlessness was assessed using a visual analog scale (VAS) and the forced expiratory volume in 1 s (FEV1) was measured. The relationship between VAS scores and FEV1 and the slope of the regression line of VAS scores on the corresponding FEV1 (VAS/FEV1 slope) were analyzed for each agonist. Subjects without corticosteroids had good perception of methacholine but poor perception of bradykinin-induced bronchoconstriction. In subjects with corticosteroids, bronchoconstriction was well perceived whatever the agonist. VAS/FEV1 slopes for bradykinin but not for methacholine correlated negatively with the magnitude of eosinophilic inflammation in airway mucosa. VAS/FEV1 slopes for each agonist correlated positively with the percentage of basement membrane covered by airway epithelium. We conclude that in asthmatic patients perception of bronchoconstriction is related to eosinophilic inflammation and to epithelial damage in airways and that corticosteroid treatment is associated with improved perception of bronchoconstriction induced by bradykinin, a mediator endogenously produced in asthma.
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Corticosteroides/uso terapêutico , Asma/fisiopatologia , Brônquios/patologia , Broncoconstrição/efeitos dos fármacos , Eosinófilos/patologia , Inflamação/fisiopatologia , Adulto , Idoso , Asma/tratamento farmacológico , Bradicinina/farmacologia , Epitélio/patologia , Feminino , Humanos , Inflamação/patologia , Masculino , Cloreto de Metacolina/farmacologia , Pessoa de Meia-Idade , PercepçãoRESUMO
INTRODUCTION: Recent recommendations advise against the use of portable home respiratory polygraphy systems for the diagnosis of the obstructive sleep apnoea syndrome (OSAS). Nevertheless such systems are widely used, particularly in France. Our aim was to assess the diagnostic value of one of these systems in the diagnosis of OSAS. METHODS: 65 consecutive patients were assessed prospectively, on account of suspicion of OSAS, by home respiratory polygraphy (HRP, Medcare Embletta). HRP confirmed severe OSAS [apnoea/hypopnoea index (AHI)>30/hr] in 8 patients. Those having AHI<30 hr or a failure of HRP (5 patients) were studied by full polysomnography in the sleep laboratory (PSG). RESULTS: In 52 patients the AHI obtained by HRP and analysed manually correlated weakly with that obtained by PSG (n=52; p<0.001; r=0.36). The AHI-PSG was 27.1+/-2.8/hr and the AHI-HRP was 12+/-0.9/hr. The mean difference (HRP-PSG) was 15.1+/-37.5/hr with poor concordance. A better cut off value in terms of efficacy of HRP was an AHI of 10/hr, with sensitivity of 61.4% and a specificity of 100%. CONCLUSION: A negative result by HRP does not exclude OSAS and full PSG is required in patients suspected of having this condition.
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Polissonografia/métodos , Apneia Obstrutiva do Sono/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Estudos ProspectivosRESUMO
Oxidants have been implicated in the pathogenesis of many inflammatory airway diseases. Neutral endopeptidase (also called enkephalinase, EC 3.4.24.11) is a peptidase that is involved in the degradation of several proinflammatory peptides, such as tachykinins and kinins. Indirect evidence suggests that airway neutral endopeptidase is inactivated by oxidants. To determine whether hydrogen peroxide inactivates neutral endopeptidase, we studied the activity of this peptidase in washed crude preparations of membranes from guinea pig lungs. Washed crude membrane preparations were exposed to increasing concentrations of hydrogen peroxide (1.25-25 mM) in the presence or absence of two different concentrations of catalase (300 and 700 U/mL). Neutral endopeptidase activity was inhibited by hydrogen peroxide in a concentration-dependent fashion (p = .0001). Addition of catalase prevented, in a concentration-dependent fashion, the inhibition of neutral endopeptidase induced by hydrogen peroxide (p = .0001). Mannitol (40 mM) and L-methionine (20 mM) did not prevent inhibition of neutral endopeptidase induced by hydrogen peroxide (2.5 mM). It can be concluded that neutral endopeptidase is inactivated by hydrogen peroxide, an effect that is prevented by catalase. Hydrogen peroxide-induced inactivation of neutral endopeptidase is not mediated by spontaneous generation of either hydroxyl radical or hypochlorous acid in the membrane preparation. Our results suggest that neutral endopeptidase inactivation may occur in airway diseases associated with exposure to or production of oxidants.
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Peróxido de Hidrogênio/farmacologia , Pulmão/enzimologia , Neprilisina/antagonistas & inibidores , Animais , Catalase/farmacologia , Indução Enzimática , Cobaias , Radical Hidroxila/metabolismo , Ácido Hipocloroso/metabolismo , Masculino , Neprilisina/metabolismoRESUMO
We studied the role of neutral endopeptidase (NEP) and kininase II (angiotensin-converting enzyme; ACE) in the modulation of exogenous substance P (SP)-induced nasal response in normal subjects and in patients with allergic rhinitis. We measured the nasal conductance in response to increasing doses of SP 2 h after oral administration of either placebo or the ACE inhibitor, cilazapril (5 mg), or the NEP inhibitor, acetorphan (300 mg), given in a randomized, double-blind, cross-over manner. We performed three separate studies: acetorphan versus placebo and cilazapril versus placebo, in normal subjects (n = 6 and n = 8, respectively), and acetorphan versus cilazapril versus placebo in patients with allergic rhinitis (n = 6). In normal as well as in rhinitic subjects, SP decreased nasal conductance in a dose-dependent fashion (p < 0.001). With placebo, the decrease in nasal conductance in normal subjects was similar to that in patients with allergic rhinitis (p > 0.5). In normal subjects, acetorphan potentiated the decrease in nasal conductance (p < 0.001), whereas cilazapril did not (p = 0.12). In patients with allergic rhinitis, the decrease in nasal conductance was potentiated by acetorphan (p < 0.001) and by cilazapril (p < 0.001). With acetorphan, the decrease in nasal conductance was not different in patients with allergic rhinitis and in normal subjects (p > 0.9). Conversely, with cilazapril, the nasal response to SP was greater in patients with allergic rhinitis than in normal subjects (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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Cilazapril/uso terapêutico , Obstrução Nasal/tratamento farmacológico , Obstrução Nasal/fisiopatologia , Neprilisina/antagonistas & inibidores , Neprilisina/fisiologia , Peptidil Dipeptidase A/fisiologia , Rinite Alérgica Perene/complicações , Tiorfano/análogos & derivados , Administração Intranasal , Administração Oral , Adulto , Resistência das Vias Respiratórias/efeitos dos fármacos , Análise de Variância , Cilazapril/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Sinergismo Farmacológico , Humanos , Masculino , Obstrução Nasal/induzido quimicamente , Obstrução Nasal/diagnóstico , Testes de Provocação Nasal , Substância P , Tiorfano/farmacologia , Tiorfano/uso terapêuticoRESUMO
Acute exposure to cigarette smoke provokes airway hyperresponsiveness to substance P and inactivates neutral endopeptidase (NEP). To determine whether nedocromil sodium can prevent cigarette smoke-induced hyperresponsiveness to substance P, we studied two groups of anaesthetized guinea-pigs. One group of guinea-pigs was pretreated with aerosolized 0.9% NaCl solution (90 breaths), the other group was pretreated with aerosolized nedocromil sodium (10(-4) M, 90 breaths). In each animal, pretreatment was followed by either exposure to the smoke of one cigarette or exposure to air. After acute exposure to cigarette smoke or to air, we measured the change in total pulmonary resistance (RL) induced by increasing concentrations of aerosolized substance P. In the absence of nedocromil sodium, the bronchoconstrictor responses to substance P were greater in cigarette smoke-exposed guinea-pigs than in air-exposed animals. Aerosolized nedocromil sodium had no effect on the response to substance P in air-exposed animals, but it reduced cigarette smoke-induced hyperresponsiveness to substance P. The preventive effect on cigarette smoke-induced hyperresponsiveness to substance P was observed at concentrations of aerosolized nedocromil sodium of 3 x 10(-5), 10(-4), and 3 x 10(-4) M. In vitro, cigarette smoke solution inhibited NEP activity from lung membrane preparations, but this inhibitory effect was not modified by nedocromil sodium (10(-4) M). We conclude that aerosolized nedocromil sodium reduces cigarette smoke-induced airway hyperresponsiveness to substance P in vivo. This action of nedocromil sodium is not due to a protective effect on cigarette smoke-induced inactivation of NEP in vitro.
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Broncoconstrição/efeitos dos fármacos , Nedocromil/farmacologia , Substância P/farmacologia , Poluição por Fumaça de Tabaco , Aerossóis , Animais , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/fisiopatologia , Broncoconstrição/fisiologia , Relação Dose-Resposta a Droga , Cobaias , Técnicas In Vitro , Pulmão/enzimologia , Masculino , Neprilisina/metabolismoRESUMO
Heat shock proteins (HSPs), which are important targets for gammadelta T-lymphocytes, are thought to play a role in inflammatory and immune diseases. The purpose of this study was to characterize, in asthma, the presence and distribution of alphabeta and gammadelta T-lymphocytes and of hsp60, hsp70 and hsp90 in bronchial biopsies, and to seek for a co-localization of gammadelta T-cells and HSPs. Ten subjects with mild atopic asthma and nine control subjects underwent fibreoptic bronchoscopy and bronchial biopsies, to which specific monoclonal antibodies and immunohistochemical techniques were applied. T-lymphocytes present in bronchi both of asthmatic and control subjects were predominantly of the alphabeta T-cell receptor phenotype (median 642 cells x mm(-2) (range 85-1,510 cells x mm(-2)), and 855 cells x mm(-2) (286-2,424 cells x mm(-2)), respectively), whereas, gammadelta T-lymphocytes were always rare (median 26 cells x mm(-2) (range 0-114 cells x mm(-2)), and 0 cells x mm(-2 (0-57 cells x mm(-2), respectively). Both in asthmatic and control subjects, bronchial epithelium was positive for hsp60, hsp70 and hsp90. There was no significant difference in the percentages of positive epithelial cells between asthmatic and control subjects. No co-localization of HSPs and gammadelta T-cells was observed. Our findings do not support the hypothesis that heat shock proteins and gammadelta T-cells play an important role in inflammatory and immune responses in mild asthma.
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Asma/imunologia , Brônquios/metabolismo , Proteínas de Choque Térmico/biossíntese , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/imunologia , Adulto , Asma/metabolismo , Asma/patologia , Biópsia , Brônquios/patologia , Broncoscopia , Estudos de Casos e Controles , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Linfócitos T/metabolismoRESUMO
Attachment theory suggests, first, that patterns of dyadic behavior cohere across salient relationships and, second, that such linkages are mediated by working models, defined as cognitive/emotional representations of relationships abstracted from dyadic experience. In this longitudinal study, adolescents' (age 19) Adult Attachment Interview (AAI) coherence ratings and classifications (e.g. working model proxies) were related prospectively to their observed dyadic behaviors with romantic partners in young adulthood (age 20-21). Results demonstrated significant associations between adolescents' representations of their relationships with parents and the later quality of their interactions with romantic partners. Next, a model was tested whereby participants' working models, as inferred from the AAI, mediate the across-time correlation between a subset of observationallv assessed parent-child dyadic behaviors (age 13) and the romantic relationship behaviors of these participants eight years later in young adulthood (age 20-21). Results of mediational analyses were consistent with the fundamental tenet of the organizational-developmental model that salient parent-child experiences are internalized and carried forward into adult relationships.
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Corte , Controle Interno-Externo , Apego ao Objeto , Relações Pais-Filho , Desenvolvimento da Personalidade , Adolescente , Adulto , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Determinação da Personalidade , Pobreza/psicologia , Carência Psicossocial , Fatores de RiscoRESUMO
BACKGROUND: Angiotensin-converting enzyme (ACE) is a peptidase involved in the metabolism of several bioactive peptides. It may be involved in the airway inflammation and hyperresponsiveness that occur in asthma. OBJECTIVE: We studied the expression of ACE in the airway mucosa of normal and asthmatic subjects and assessed the relationship between ACE expression and airway inflammation and bronchial hyperresponsiveness in asthma. METHODS: We used immunohistochemistry to study the ACE expression and airway inflammation in bronchial biopsy samples obtained by fiberoptic bronchoscopy from 20 asthmatic subjects randomly assigned to groups treated with (n = 10) or without inhaled corticosteroids (n = 10) and from normal subjects (n = 10). Airway response to methacholine and bradykinin was also determined for all subjects. RESULTS: In normal subjects ACE was present in the surface epithelium, the endothelial cells of the lamina propria, and the submucosal glands, in which ACE was found in seromucous cells and in secreted mucus. ACE was not detected in smooth muscle cells and in most of the endothelial cells of the vascular network surrounding the glands. ACE was absent or present at lower levels in the surface epithelium of asthmatic subjects not treated with corticosteroids compared with those treated with corticosteroids and the control group. In asthmatic subjects low levels of ACE in the epithelium were associated with larger numbers of eosinophils in the epithelium and lamina propria. There was no relationship between ACE levels in the airway mucosa and airway responsiveness to methacholine and bradykinin. CONCLUSION: ACE expression is decreased in the epithelium of asthmatic patients and is associated with increased eosinophil inflammation.
Assuntos
Asma/enzimologia , Eosinófilos , Inflamação/enzimologia , Peptidil Dipeptidase A/biossíntese , Sistema Respiratório/enzimologia , Asma/fisiopatologia , Biópsia , Brônquios/patologia , Hiper-Reatividade Brônquica/enzimologia , Líquido da Lavagem Broncoalveolar/citologia , Epitélio/enzimologia , Volume Expiratório Forçado , Humanos , Imuno-HistoquímicaRESUMO
We investigated the relationship between airway inflammation and airway responsiveness, as assessed by PD15, to methacholine and to bradykinin in asthmatic patients. Bronchoalveolar lavage (BAL), bronchial biopsies, and methacholine and bradykinin challenges were performed in 18 nonsmoking subjects with mild or moderate perennial asthma. Bradykinin PD15 correlated negatively with eosinophil count in BAL (p < 0.05), in the epithelium (p < 0.05), in the lamina propria (p = 0.02) and in the total submucosa (p < 0.01). Conversely, no significant correlation existed between airway responsiveness to methacholine and eosinophil count in BAL or in airway mucosa. Airway responsiveness to either agonist did not correlate with the thickness of the basement membrane, the shedding of the airway epithelium, the count of lymphocytes in the airway mucosa, or the percentage of neutrophils, lymphocytes, and macrophage in BAL. The presence of degranulated eosinophils was associated with an increased number of eosinophils in the airway epithelium (p = 0.04), in the lamina propria (p = 0.03), in the total submucosa (p = 0.02), and with increased airway responsiveness to bradykinin (p < 0.02). We conclude that in asthmatic patients, airway responsiveness to bradykinin but not to methacholine is related to the magnitude of eosinophilic inflammation in the airway mucosa.