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1.
Thromb Haemost ; 123(4): 393-401, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36535657

RESUMO

BACKGROUND: Previous studies have reported inconsistent findings regarding the association between obstructive sleep apnea (OSA) and incident venous thromboembolism (VTE). More specifically, the association between OSA and unprovoked VTE was barely evaluated. We aimed to evaluate whether apnea hypopnea index (AHI) and nocturnal hypoxemia markers were associated with unprovoked VTE incidence in patients investigated for OSA. MATERIAL AND METHODS: Data from the Pays de la Loire Sleep Cohort were linked to the French health administrative data to identify incident unprovoked VTE in patients suspected for OSA and no previous VTE disease. Cox proportional hazards models were used to evaluate the association of unprovoked VTE incidence with AHI and nocturnal hypoxemia markers including the time spent under 90% of saturation (T90), oxygen desaturation index, and hypoxic burden (HB), a more specific marker of respiratory events related to hypoxia. The impact of continuous positive airway pressure (CPAP) was evaluated in the subgroup of patients who were proposed the treatment. RESULTS: After a median [interquartile range] follow-up of 6.3 [4.3-9.0] years, 104 of 7,355 patients developed unprovoked VTE, for an incidence rate of 10.8 per 1,000 patient-years. In a univariate analysis, T90 and HB predicted incident VTE. In the fully adjusted model, T90 was the only independent predictor (hazard ratio: 1.06; 95% confidence interval: [1.01-1.02]; p = 0.02). The CPAP treatment has no significant impact on VTE incidence. CONCLUSION: Patients with more severe nocturnal hypoxia are more likely to have incident unprovoked VTE.


Assuntos
Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/complicações , Síndromes da Apneia do Sono/complicações , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Hipóxia/complicações , Sono
2.
Am J Respir Crit Care Med ; 206(11): 1393-1404, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35816570

RESUMO

Rationale: Randomized controlled trials showed no effect of positive airway pressure (PAP) therapy for obstructive sleep apnea (OSA) on cardiovascular (CV) risk. However, patient selection and low PAP adherence preclude the generalization of their data to clinical samples. Objectives: To evaluate the association between hours of PAP use, mortality, and CV morbidity in real-life conditions. Methods: Data from the Pays de la Loire Cohort were linked to health administrative data to identify incident major adverse cardiovascular events (MACEs; a composite outcome of mortality, stroke, and cardiac diseases) in patients with OSA who were prescribed PAP. Cox proportional hazards analyses were conducted to evaluate the association between MACEs and quartiles of average daily PAP use over the study period. Measurements and Main Results: After a median follow-up of 6.6 years, 961 of 5,138 patients experienced MACEs. Considering nonadherent patients (0-4 h/night) as the reference group, adjusted hazard ratios (95% confidence intervals) for MACEs were 0.87 (0.73-1.04) for the 4-6 h/night group, 0.75 (0.62-0.92) for the 6-7 h/night group, and 0.78 (0.65-0.93) for the ⩾7 h/night group (P = 0.0130). Sensitivity analyses using causal inference approaches confirmed the association of PAP use with MACEs. The association was stronger in male patients (P value for interaction = 0.0004), patients without overt CV disease at diagnosis (P < 0.0001), and those belonging to the excessively sleepy symptom subtype (P = 0.060). Conclusions: These real-life clinical data demonstrate a dose-response relationship between PAP adherence and incident MACEs in OSA. Patient support programs may help improve PAP adherence and CV outcomes in patients with OSA.


Assuntos
Doenças Cardiovasculares , Síndromes da Apneia do Sono , Humanos , Masculino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/complicações , Pressão Positiva Contínua nas Vias Aéreas , Cooperação do Paciente , Síndromes da Apneia do Sono/complicações , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapia , Resultado do Tratamento
4.
Am J Respir Crit Care Med ; 205(1): 108-117, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648724

RESUMO

Rationale: Data from population-based cohorts suggest that symptom subtypes and obstructive sleep apnea (OSA)-specific hypoxic burden (HB) could help to better identify patients with OSA at high cardiovascular (CV) risk. Objectives: We aimed to evaluate whether those new markers are associated with the risk of major adverse CV events (MACE) in clinical setting. Methods: Data from the Pays de la Loire cohort were linked to health administrative data to identify the occurrence of MACE (a composite outcome including all-cause mortality, acute myocardial infarction, stroke, and unplanned coronary revascularization) in patients with newly diagnosed OSA and no overt CV disease. Latent class analysis was used to identify subtypes based on eight clinically relevant variables. HB was defined as the total area under the respiratory event-related desaturation curve. Cox proportional hazards models were used to evaluate the association of symptom subtypes and HB with MACE. Measurements and Main Results: Four symptom subtypes were identified (minimally symptomatic [22.0%], disturbed sleep [17.5%], excessively sleepy [49.8%], and moderately sleepy [10.6%]). After a median follow-up of 78 months (interquartile range, 52-109), 592 (11.05%) of 5,358 patients experienced MACE. In a fully adjusted model, HB and overall nocturnal hypoxemia assessed by sleep time with oxygen saturation <90% were the only predictors of MACE (hazard ratio, 1.21; 95% confidence interval, 1.07-1.38; and hazard ratio, 1.34; 95% confidence interval, 1.16-1.55, respectively). The association appeared stronger toward younger patients and women. Conclusion: In clinical setting, patients with OSA who demonstrate elevated OSA-specific HB are at higher risk of a CV event and all-cause mortality. Symptom subtypes were not associated with MACE after adjustment for confounders.


Assuntos
Doenças Cardiovasculares/etiologia , Fatores de Risco de Doenças Cardíacas , Hipóxia/fisiopatologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Idoso , Doenças Cardiovasculares/mortalidade , Análise por Conglomerados , Bases de Dados Factuais , Feminino , Seguimentos , França/epidemiologia , Humanos , Hipóxia/complicações , Hipóxia/diagnóstico , Hipóxia/mortalidade , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Modelos de Riscos Proporcionais , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/mortalidade
5.
Eur Respir J ; 59(4)2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34475228

RESUMO

BACKGROUND: Increasing evidence suggests that obstructive sleep apnoea (OSA) contributes to cancer risk; however, limited data are available on the impact of continuous positive airway pressure (CPAP) therapy on cancer incidence. We aimed to determine whether adherence to CPAP therapy is associated with a reduction in all-cancer incidence compared with nonadherent patients with OSA. METHODS: The study relied on data collected by the multicentre Pays de la Loire Sleep Cohort study, linked to health administrative data, so as to identify new-onset cancer. We included patients who were prescribed CPAP for OSA, with no history of cancer before the diagnostic sleep study or during the first year of CPAP. Patients with documented CPAP use for ≥4 h per night were defined as adherent. Those who discontinued or used CPAP <4 h per night constituted the nonadherent group. A propensity score inverse probability of treatment weighting analysis was performed to assess the effect of CPAP adherence on cancer risk. RESULTS: After a median (interquartile range) follow-up of 5.4 (3.1-8.0) years, 437 (9.7%) out of 4499 patients developed cancer: 194 (10.7%) in the nonadherent group (n=1817) and 243 (9.1%) in adherent patients (n=2682). The final weighted model showed no significant impact of CPAP adherence on all-cause cancer risk (subdistribution hazard ratio 0.94, 95% CI 0.78-1.14). CONCLUSIONS: Adherence to CPAP therapy in OSA patients was not associated with a reduction in all-cancer incidence. Whether adherent CPAP therapy of OSA might reduce the risk of specific cancer sites should be further evaluated.


Assuntos
Neoplasias , Apneia Obstrutiva do Sono , Estudos de Coortes , Pressão Positiva Contínua nas Vias Aéreas , Humanos , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/terapia , Cooperação do Paciente , Polissonografia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapia
6.
Physiol Meas ; 42(10)2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34571502

RESUMO

Objective. Cardiovascular disease (CVD) is one of the leading causes of death worldwide. There are many CVD risk estimators but very few take into account sleep features. Moreover, they are rarely tested on patients investigated for obstructive sleep apnea (OSA). However, numerous studies have demonstrated that OSA index or sleep features are associated with CVD and mortality. The aim of this study is to propose a new simple CVD and mortality risk estimator for use in routine sleep testing.Approach. Data from a large multicenter cohort of CVD-free patients investigated for OSA were linked to the French Health System to identify new-onset CVD. Clinical features were collected and sleep features were extracted from sleep recordings. A machine-learning model based on trees, AdaBoost, was applied to estimate the CVD and mortality risk score.Main results. After a median [inter-quartile range] follow-up of 6.0 [3.5-8.5] years, 685 of 5234 patients had received a diagnosis of CVD or had died. Following a selection of features, from the original 30 features, 9 were selected, including five clinical and four sleep oximetry features. The final model included age, gender, hypertension, diabetes, systolic blood pressure, oxygen saturation and pulse rate variability (PRV) features. An area under the receiver operating characteristic curve (AUC) of 0.78 was reached.Significance. AdaBoost, an interpretable machine-learning model, was applied to predict 6 year CVD and mortality in patients investigated for clinical suspicion of OSA. A mixed set of simple clinical features, nocturnal hypoxemia and PRV features derived from single channel pulse oximetry were used.


Assuntos
Doenças Cardiovasculares , Apneia Obstrutiva do Sono , Inteligência Artificial , Doenças Cardiovasculares/diagnóstico , Fatores de Risco de Doenças Cardíacas , Humanos , Oximetria , Polissonografia , Fatores de Risco , Apneia Obstrutiva do Sono/diagnóstico
7.
Ann Am Thorac Soc ; 18(6): 1043-1051, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33433302

RESUMO

Rationale: Nocturnal hypoxemia and sympathetic/parasympathetic imbalance might contribute to the occurrence or atrial fibrillation (AF) in patients with obstructive sleep apnea (OSA). During sleep recordings, pulse rate variability (PRV) derived from oximetry might provide an accurate estimation of heart rate variability, which reflects the autonomic cardiovascular control. Objectives: We aimed to evaluate whether indices of oxygen desaturation and PRV derived from nocturnal oximetry were associated with AF incidence in patients investigated for OSA. Methods: Data from a large multicenter cohort of AF-free patients investigated for OSA between May 15, 2007, and December 31, 2017, were linked to health administrative data to identify hospitalized and nonhospitalized patients with new-onset AF. Cox proportional hazards models were used to evaluate the association between AF incidence and oximetry-derived indices automatically generated from sleep recordings. Results: After a median (interquartile range) follow-up of 5.34 (3.3-8.0) years, 181 of 7,205 patients developed AF (130 were hospitalized for AF). After adjusting for confounders, including anthropomorphic data, alcohol intake, cardiac, metabolic and respiratory diseases, ß blocker/calcium channel blocker medications, type of sleep study, study site, and positive airway pressure adherence, AF risk was associated with increasing nocturnal hypoxemia (P trend = 0.004 for quartiles of percentage of recording time with oxygen saturation <90%) and PRV (P trend < 0.0001 for quartiles of root mean square of the successive normal-normal beat interval differences), and decreasing sympathetic/parasympathetic tone (P trend = 0.0006 for quartiles of low-frequency power/high-frequency power ratio). The highest risk of AF was observed in patients with the highest quartiles of both the percentage of recording time with oxygen saturation <90% and the root mean square of the successive normal-normal beat interval differences compared with those with neither of these conditions (adjusted hazard ratio, 3.61; 95% confidence interval, 2.10-6.22). Similar associations were observed when the analyses were restricted to hospitalized AF. Conclusions: In patients investigated for OSA, nocturnal hypoxemia and PRV indices derived from single-channel pulse oximetry were independent predictors of AF incidence. Patients with both marked nocturnal hypoxemia and high PRV were at higher risk of AF. Oximetry may be used to identify patients with OSA at greatest risk of developing AF.


Assuntos
Fibrilação Atrial , Apneia Obstrutiva do Sono , Fibrilação Atrial/epidemiologia , Frequência Cardíaca , Humanos , Hipóxia/epidemiologia , Oximetria , Polissonografia , Apneia Obstrutiva do Sono/epidemiologia
8.
Am J Pathol ; 177(2): 974-83, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20566740

RESUMO

Endothelial dysfunction is involved in vascular complications of obstructive sleep apnea (OSA). In this study, circulating microparticles (MPs) from patients with OSA-induced nocturnal desaturations were characterized and their effects on endothelial function were evaluated. Two age-matched groups of patients undergoing polysomnography for OSA were compared: 35 desaturators with a 3% oxyhemoglobin desaturation index (ODI) > or = 10 events per hour of sleep and 27 nondesaturators with ODI <10 events per hour. MPs were characterized by flow cytometry and then either used to treat in vitro human endothelial cells or to study endothelial function in mice. Circulating MPs did not differ between groups, but MPs from granulocytes and activated leukocytes (CD62L(+)) were found at higher levels in desaturators. In vitro, MPs from desaturators reduced endothelial nitric oxide (NO) production by enhancing phosphorylation of endothelial NO synthase at the site of inhibition and expression of caveolin-1. CD62L(+) MPs positively correlated with ODI. Endothelial NO production negatively correlated with both CD62L(+) MPs and ODI. MPs from desaturators increased expression of endothelial adhesion molecules including E-selectin, ICAM-1 and ITGA5, and cyclooxygenase 2. Moreover, injection of MPs from desaturators into mice impaired endothelium-dependent relaxation in aorta and flow-induced dilation in small mesenteric arteries. This study demonstrates an association between endothelial dysfunction and increased circulating levels of CD62L(+) MPs. This may initiate atherogenic processes in patients with OSA and severe nighttime hypoxia.


Assuntos
Micropartículas Derivadas de Células/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/fisiopatologia , Apneia Obstrutiva do Sono , Adolescente , Adulto , Idoso , Indutores da Angiogênese/metabolismo , Animais , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Células Endoteliais/citologia , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/fisiopatologia , Adulto Jovem
9.
Chest ; 138(1): 84-90, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20348200

RESUMO

BACKGROUND: Few data are available on the long-term outcome of noninvasive positive pressure ventilation (NPPV) for obesity hypoventilation syndrome (OHS). This study was designed to determine long-term survival, treatment adherence, and prognostic factors in patients with OHS in whom NPPV was initiated in an acute setting vs under stable clinical conditions. METHODS: One hundred thirty consecutive patients with OHS (56 women) who started NPPV between January 1995 and December 2006 either under stable conditions (stable group, n = 92) or during ICU management of acute hypercapnic exacerbation (acute group, n = 38) were retrospectively analyzed. RESULTS: Arterial blood gases and the Epworth sleepiness scale were both significantly improved after 6 months of NPPV. With a mean follow-up of 4.1 +/- 2.9 years, 24 (18.5%) patients died and 24 (18.5%) discontinued NPPV. On Kaplan-Meier analysis, 1-, 2-, 3-, and 5-year survival probabilities were 97.5%, 93%, 88.3%, and 77.3%, respectively. Mortality was lower than that described in a previous series of patients with untreated OHS. Supplemental oxygen therapy was the only independent predictor of mortality. The probability of continuing NPPV was 80% at 3 years with a high rate of daily use ( > 7 h). Female sex was predictive of lower long-term adherence to NPPV. The acute and stable groups did not differ in terms of arterial blood gases and Epworth sleepiness scale at 6 months, long-term survival, and treatment adherence. CONCLUSIONS: The results of this study support long-term NPPV as an effective and well-tolerated treatment of OHS whether initiated in the acute or chronic setting.


Assuntos
Síndrome de Hipoventilação por Obesidade/terapia , Respiração com Pressão Positiva/métodos , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Hipoventilação por Obesidade/fisiopatologia , Oximetria , Consumo de Oxigênio , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
10.
Diabetes Care ; 33(5): 1044-9, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20185739

RESUMO

OBJECTIVE: Obstructive sleep apnea is common in patients with type 2 diabetes, and its association with insulin and insulin resistance has been examined in cross-sectional studies. We evaluate risk factors for incident observed sleep apnea in a general population not selected for sleep disturbances. RESEARCH DESIGN AND METHODS: A total of 1,780 men and 1,785 women, aged 33 to 68 years, from the cohort Data from an Epidemiologic Study on the Insulin Resistance Syndrome (D.E.S.I.R.) responded to the question, "Has someone said to you that you stop breathing during your sleep?" at baseline and 6 years. Anthropometric, clinical, and biological factors were recorded at both time points. RESULTS: At baseline, 14% of men and 7% of women reported having observed sleep apnea (positive response to question); 6-year incidences were 14 and 6%, respectively. Age, anthropometric parameters, blood pressure, and sleep characteristics were all associated with prevalent, observed apnea episodes, in both sexes. Baseline waist circumference was the strongest predictor of incident apnea: standardized odds ratio (OR), adjusted for age and sex, 1.34 (95% CI 1.19-1.52). After adjustment for age, sex, and waist circumference, the standardized ORs for incident observed apnea were identical for fasting insulin and the homeostasis model assessment of insulin resistance: 1.31 (1.13-1.51) and 1.24 (1.09-1.41) for triglycerides and 1.52 (1.12-2.05) for smoking. Observed apnea at baseline was not associated with changes in anthropometric or biological parameters over the 6-year follow-up. CONCLUSIONS: The most important baseline risk factor for incident apnea was adiposity. After accounting for adiposity, other risk factors were high insulin, insulin resistance, high triglycerides, and smoking, factors amenable to lifestyle intervention.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Resistência à Insulina , Insulina/sangue , Síndromes da Apneia do Sono/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Síndromes da Apneia do Sono/sangue , Fumar/epidemiologia , Triglicerídeos/sangue , Circunferência da Cintura
11.
Eur J Pharm Biopharm ; 73(2): 239-46, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19560538

RESUMO

Aerosol drug delivery permits the development of dose-intensification strategies in severe, malignant lung diseases. The aim of the study was to demonstrate that the encapsulation of paclitaxel in lipid nanocapsules (LNCs), a novel drug nanocarrier for lipophilic components, allows one to provide pulmonary drug delivery of paclitaxel by nebulisation, thereby allowing preclinical and clinical studies. LNC dispersions are made into aerosols with commercial nebulisers. The structure, drug payload and cytotoxicity of nebulised LNCs were compared to fresh LNCs. The results demonstrated that LNC dispersions could be made into aerosols by using mesh nebulisers without altering the LNC structure. Only eFlow rapid-produced aerosols are compatible with human use: the mean duration to nebulise 3 ml of LNC dispersion is less than 9 min, with an aerosol mass median aerodynamic diameter equal to 2.7+/-0.1 microm and a fine-particle fraction (between 1.0 and 5.0 microm) of 81.5+/-3.1%. No modifications of drug payload or cytotoxicity effects of paclitaxel-loaded LNC (PTX-LNC) were observed. In order to carry out preclinical studies, a scaled-up LNC formulation protocol was used. Chemical parameters, such as acidity and osmolarity, were optimised, and a storage procedure for PTX-LNC batches was set-up. Animal studies are now needed to determine the tolerance and therapeutic potential of LNC dispersion aerosols.


Assuntos
Antineoplásicos Fitogênicos/química , Portadores de Fármacos , Lipídeos/química , Nanocápsulas , Paclitaxel/química , Administração por Inalação , Aerossóis , Antineoplásicos Fitogênicos/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Relação Dose-Resposta a Droga , Composição de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Estudos de Viabilidade , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Neoplasias Pulmonares/patologia , Nebulizadores e Vaporizadores , Concentração Osmolar , Paclitaxel/administração & dosagem , Tamanho da Partícula , Solubilidade
12.
Sleep Med ; 10(7): 746-52, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19147401

RESUMO

OBJECTIVES: Endothelial dysfunction has been proposed as a potential mechanism implicated in the pathogenesis of cardiovascular complications of obstructive sleep apnea syndrome (OSAS). This study aimed to evaluate the microvascular endothelial function (MVEV) in OSAS and the impact on MVEF of 2 months of treatment with continuous positive airway pressure (CPAP) and mandibular advancement device (MAD). METHODS: Microvascular reactivity was assessed using laser Doppler flowmetry combined with acetylcholine (Ach) and sodium nitroprusside (SNP) iontophoresis in 24 OSAS patients and 9 control patients. In 12 of the 24 OSAS patients, microvascular reactivity was reassessed after 2 months of CPAP and MAD using a randomized cross-over design. RESULTS: Ach-induced vasodilation was significantly lower in OSAS patients than in matched controls and correlated negatively with apnea hypopnea index (r=-0.49, p<0.025) and nocturnal oxygen desaturations (r=-0.63, p<0.002). Ach-induced vasodilation increased significantly with both CPAP and MAD. The increase in Ach-induced vasodilation under OSAS treatment correlated with the decrease in nocturnal oxygen desaturations (r=0.48, p=0.016). CONCLUSION: Our study shows an impairment of MVEF in OSAS related to OSAS severity. Both CPAP and MAD treatments were associated with an improvement in MVEF that could contribute to improve cardiovascular outcome in OSAS patients.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Endotélio Vascular/fisiopatologia , Avanço Mandibular/métodos , Microvasos/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Adolescente , Adulto , Idoso , Estudos Cross-Over , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Reologia , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/diagnóstico , Vasodilatação , Adulto Jovem
13.
Respiration ; 76(4): 386-92, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18797161

RESUMO

BACKGROUND: Previous studies have documented an effect of mandibular advancement (MA) on pharyngeal airway size and collapsibility. OBJECTIVES: We aimed to describe the course of the apnea-hypopnea index (AHI) and the snoring index (SI) during progressive MA and to evaluate the long-term efficacy, tolerance and usage of MA therapy after progressive MA titration in sleep apnea patients. METHODS: Sixty-six patients with obstructive sleep apnea syndrome underwent sequential sleep recordings during progressive MA titration. Long-term effectiveness, compliance and side effects of oral appliance (OA) in the titrated position were evaluated by questionnaires. RESULTS: OA therapy was started at 80% of the maximum MA. Seventy percent of the patients had only one increment in MA with a marked decrease in mean AHI from 36 to 10. In the remaining cases, further increments in MA were associated with a progressive reduction in AHI and an increase in the number of patients responding to treatment. OA in the titrated position resulted in a 70% decrease in AHI, with 54% of patients showing complete responses, 29% partial responses and 17% no response. Daytime sleepiness and quality of life improved, too. Seventeen months after the start of treatment, 82% of the patients declared that they were still using OA almost all nights. Reported side effects including subjective occlusal changes were frequent but mild. CONCLUSIONS: Improvement in AHI during OA is dependent on the amount of MA. Sequential sleep recordings facilitate MA titration. Long-term MA therapy in the titrated position is effective and well tolerated. Reported side effects are frequent but mild.


Assuntos
Avanço Mandibular , Apneia Obstrutiva do Sono/terapia , Ronco/terapia , Aparelhos Ativadores , Adulto , Feminino , Humanos , Masculino , Avanço Mandibular/efeitos adversos , Pessoa de Meia-Idade , Cooperação do Paciente , Satisfação do Paciente , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
14.
Lung Cancer ; 58(1): 139-43, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17614157
15.
Cancer Chemother Pharmacol ; 58(2): 237-44, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16328414

RESUMO

AIM: To characterize gemcitabine aerosol, its in vitro activity against lung cancer cells, its deposition, and tolerance in a non-human primate model. METHODS: In vitro cytotoxicity of nebulized gemcitabine against NCI-H460 and A549 lung cancer cells was tested using a growth inhibition assay and compared with non-nebulized gemcitabine. The (99m)Tc-DTPA-radiolabeled gemcitabine aerosol was characterized by cascade impaction and the gemcitabine mass/(99m)Tc activity relationship was established for further quantitative nuclear imaging. Nine weekly inhalations at a target dose of 1 mg/kg body weight of gemcitabine were performed in three baboons using dynamic scintigraphic acquisitions for continuous monitoring of gemcitabine delivery during inhalation. Gemcitabine plasma concentrations were measured during the first inhalation. RESULTS: Growth inhibition assays for both NCI-H460 and A549 cells did not differ between nebulized and non-nebulized gemcitabine. Aerosol characterization showed a particle mass median aerodynamic diameter of 3.7+/-0.8 microm and a linear relationship between gemcitabine mass (y) and (99m)Tc activity (x) (y=0.82x - 10(-5), R (2)=0.88). No toxicity was observed after nine weekly inhalations of a mean dose of gemcitabine of 11.1 mg (88% of the target dose) as assessed from scintigraphic data. A dose-dependent peak plasma concentration of gemcitabine (20-74 ng/ml) was observed by the tenth minute of inhalation. CONCLUSIONS: We have characterized a gemcitabine aerosol suitable for intrathoracic airway deposition and demonstrated that jet nebulization does not alter the cytotoxic properties of the drug. In a primate model, we have developed a scintigraphic procedure for the monitoring of aerosol deposition, and we have demonstrated the safety of nine weekly aerosol administrations of gemcitabine.


Assuntos
Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Experimentais/tratamento farmacológico , Aerossóis , Animais , Desoxicitidina/administração & dosagem , Desoxicitidina/sangue , Desoxicitidina/uso terapêutico , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Modelos Animais , Neoplasias Experimentais/diagnóstico por imagem , Papio , Cintilografia , Gencitabina
16.
J Aerosol Med ; 18(2): 198-206, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15966774

RESUMO

The purpose of this research was to evaluate the safety of pulmonary administration of gemcitabine and to determine the maximum tolerated dose by weekly pulmonary administrations in an animal model. Five groups of eight Wistar rats received gemcitabine at doses of 2, 4, 6, or 8 mg/kg or the vehicle solution by endotracheal spray with scintigraphic imaging of lung deposition. In order to document the safety of digestive exposure, five groups of eight rats received gemcitabine at the same dosages or the vehicle solution by gavage. Nine weekly sessions were planned, and blood cell counts and histological examinations were performed in live animals at day 64. Scintigraphic imaging confirmed pulmonary deposition in 310 of 316 spray administrations (98%) with homogeneous pattern of deposition. The maximum tolerated dose of gemcitabine by pulmonary administration was 4 mg/kg. At this dosage, administered once a week for 9 consecutive weeks, there were no chemotherapy-related deaths and no clinical, histological, or hematological signs of toxicity except for a decrease in platelet and red blood cell counts, with no clinical significance. The toxicity of gemcitabine was higher via oral than lung delivery in terms of weight loss and white blood cell toxicity at dosages of 2, 4, and 6 mg/kg. Pulmonary administration of gemcitabine is safe in rats at a maximum tolerated dose of 4 mg/kg once a week for 9 weeks. At an equivalent dosage, the toxicity of gemcitabine is lower by lung than oral administration.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Sistemas de Liberação de Medicamentos , Pulmão/metabolismo , Administração por Inalação , Administração Oral , Animais , Estudos de Viabilidade , Feminino , Pulmão/diagnóstico por imagem , Dose Máxima Tolerável , Cintilografia , Ratos , Ratos Wistar , Gencitabina
17.
Rev Prat ; 54(13): 1425-31, 2004 Sep 15.
Artigo em Francês | MEDLINE | ID: mdl-15497796

RESUMO

The term chronic obstructive pulmonary disease (COPD) is mainly characterised by an irreversible obstructive airway obstruction, that in most cases, is secondary to tobacco exposure. Management of the disease includes an assessment of severity, and measures to decrease FEV decline, to treat bronchial obstruction, to improve exercise tolerance and to correct abnormal gas exchange. Treatment not only requires drug therapy, but also respiratory rehabilitation, surgery of emphysema, and psychosocial support. In this way, a global strategy, adapted to the severity of COPD, can be proposed.


Assuntos
Doença Pulmonar Obstrutiva Crônica/reabilitação , Doença Pulmonar Obstrutiva Crônica/terapia , Tolerância ao Exercício , Volume Expiratório Forçado , Humanos , Prognóstico , Índice de Gravidade de Doença
18.
Respiration ; 70(1): 54-9, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12584392

RESUMO

BACKGROUND: There is currently disagreement on the way of expressing the reversibility of airflow obstruction, with some evaluations based on the initial FEV(1) while others use predicted FEV(1) (according to age, gender and height). OBJECTIVES: To test the relevance of expressing bronchodilator response as a percentage of predicted FEV(1), we evaluated the influence of morphological data on the response to bronchodilators in a population with a large range of predicted values. METHODS: We measured the change in FEV(1) after inhalation of 200 microg of salbutamol in 30 asthmatic subjects (15 adults and 15 children) in whom predicted FEV(1) ranged between 1.13 and 4.10 liters and analyzed the respective influence of initial and predicted FEV(1 )on bronchodilator response. RESULTS: We have shown a significant relationship between the absolute variation in FEV(1), in liters, and predicted FEV(1) (p = 0.0019). There was also a significant relationship between the absolute variation in FEV(1) and initial FEV(1), in liters (p = 0.02). This relationship was no longer significant (p = 0.8) when the variation and initial FEV(1) were both expressed as percentages of predicted FEV(1). In addition, multiple regression analysis showed that predicted FEV(1) was the only independent variable correlating with the response to bronchodilators. CONCLUSION: This study showed the influence of predicted FEV(1) on bronchodilator response. This result provides an additional argument for expressing bronchodilator response as a percentage of predicted FEV(1).


Assuntos
Albuterol/farmacologia , Asma/tratamento farmacológico , Broncodilatadores/farmacologia , Adolescente , Adulto , Idoso , Asma/fisiopatologia , Testes de Provocação Brônquica , Criança , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de Regressão
19.
Sleep ; 25(7): 753-7, 2002 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-12405611

RESUMO

STUDY OBJECTIVES: To validate a new method of evaluation of respiratory efforts during polysomnographic recordings. SETTING: NA PARTICIPANTS: 26 patients with sleep apnea syndrome, either during diagnostic assessment (n=16) or under nasal continuous positive airway pressure (n=10). METHODS: This method consists of measuring suprastemal pressure by a pressure transducer placed over the trachea above the sternal notch (Pst). It was compared to the reference method (ie, esophageal pressure) during the same polysomnogram. RESULTS: The analysis was based on 3,261 episodes of apnea, classified as obstructive in 2,556 cases, mixed in 347 cases, and central in 358 cases according to the esophageal pressure monitor. The concordance between the two methods was very good, with a sensitivity of Pst of 99.4% for the detection of apneas with respiratory efforts and a specificity of 93.6%. Twenty-three (6.4%) of the 358 central apneas were classified by Pst as apneas with respiratory efforts and 18 of the 353 central apneas classified by Pst were actually apneas with respiratory efforts on the esophageal pressure monitor. CONCLUSION: The suprasternal pressure transducer, which presents a good sensitivity and a good specificity for identification of respiratory efforts, can be used to classify apneas during polysomnographic recordings in clinical practice.


Assuntos
Síndromes da Apneia do Sono/classificação , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/instrumentação , Respiração com Pressão Positiva , Pressão , Síndromes da Apneia do Sono/terapia , Esterno , Transdutores
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