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Oxidative stress, known to increase the risk of multiple metabolic and chronic disorders or cancer development, is defined as an imbalance between the production of reactive oxygen species (ROS) and the capacity of antioxidants to counteract the deleterious effects of oxidants [...].
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The effects of repetitive magnetic stimulation (rMS) have predominantly been studied in excitable cells, with limited research in non-excitable cells. This study aimed to investigate the impact of rMS on macrophages, which are crucial cells in the innate immune defense. THP-1-derived macrophages subjected to a 5 min session of 10 Hz rMS exhibited increased Nrf2 activation and decreased Keap1 expression. We found that activation of the Nrf2 signaling pathway relied on rMS-induced phosphorylation of p62. Notably, rMS reduced the intracellular survival of Staphylococcus aureus in macrophages. Silencing Nrf2 using siRNA in THP-1-derived macrophages or utilizing Nrf2 knockout in alveolar macrophages abolished this effect. Additionally, rMS attenuated the expression of IL-1ß and TNF-α inflammatory genes by S. aureus and inhibited p38 MAPK activation. These findings highlight the capacity of rMS to activate the non-canonical Nrf2 pathway, modulate macrophage function, and enhance the host's defense against bacterial infection.
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Peripheral nerve injuries induce long-lasting physiological and severe functional impairment due to motor, sensory, and autonomic denervation. Preclinical models allow us to study the process of nerve damage, evaluate the capacity of the peripheral nervous system for spontaneous recovery, and test diagnostic tools to assess the damage and subsequent recovery. Methods: In this study on Sprague-Dawley rats, we: (1) compared the use of two different anesthetics (isoflurane and urethane) for the evaluation of motor evoked potentials (MEPs) induced by trans-spinal magnetic stimulation (TSMS) in gastrocnemius and brachioradialis muscles; (2) monitored the evolution of gastrocnemius MEPs by applying paired-pulse stimulation to evaluate the neuromuscular junction activity; and (3) evaluated the MEP amplitude before and after left tibialis nerve crush (up to 7 days post-injury under isoflurane anesthesia). The results showed that muscle MEPs had higher amplitudes under isoflurane anesthesia, as compared with urethane anesthesia in the rats, demonstrating higher motoneuronal excitability under isoflurane anesthesia evaluated by TSMS. Following tibial nerve crush, a significant reduction in gastrocnemius MEP amplitude was observed on the injured side, mainly due to axonal damage from the initial crush. No spontaneous recovery of MEP amplitude in gastrocnemius muscles was observed up to 7 days post-crush; even a nerve section did not induce any variation in residual MEP amplitude, suggesting that the initial crush effectively severed the axonal fibers. These observations were confirmed histologically by a drastic reduction in the remaining myelinated fibers in the crushed tibial nerve. These data demonstrate that TSMS can be reliably used to noninvasively evaluate peripheral nerve function in rats. This method could therefore readily be applied to evaluate nerve conductance in the clinical environment.
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High spinal cord injuries (SCI) induce the deafferentation of phrenic motoneurons, leading to permanent diaphragm paralysis. This involves secondary injury associated with pathologic and inflammatory processes at the site of injury, and at the level of phrenic motoneurons. In the present study, we evaluated the antioxidant response in phrenic motoneurons involving the AMPK-Nrf2 signaling pathway following C2 spinal cord lateral hemi-section in rats. We showed that there is an abrupt reduction in the expression of phosphorylated AMPK and Nrf2 at one hour post-injury in phrenic motoneurons. A rebound is then observed at one day post-injury, reflecting a return to homeostasis condition. In the total spinal cord around phrenic motoneurons, the increase in phosphorylated AMPK and Nrf2 occurred at three days post-injury, showing the differential antioxidant response between phrenic motoneurons and other cell types. Taken together, our results display the implication of the AMPK-Nrf2 signaling pathway in phrenic motoneurons' response to oxidative stress following high SCI. Harnessing this AMPK-Nrf2 signaling pathway could improve the antioxidant response and help in spinal rewiring to these deafferented phrenic motoneurons to improve diaphragm activity in patients suffering high SCI.
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High spinal cord injuries (SCIs) lead to permanent diaphragmatic paralysis. The search for therapeutics to induce functional motor recovery is essential. One promising noninvasive therapeutic tool that could harness plasticity in a spared descending respiratory circuit is repetitive transcranial magnetic stimulation (rTMS). Here, we tested the effect of chronic high-frequency (10 Hz) rTMS above the cortical areas in C2 hemisected rats when applied for 7 days, 1 month, or 2 months. An increase in intact hemidiaphragm electromyogram (EMG) activity and excitability (diaphragm motor evoked potentials) was observed after 1 month of rTMS application. Interestingly, despite no real functional effects of rTMS treatment on the injured hemidiaphragm activity during eupnea, 2 months of rTMS treatment strengthened the existing crossed phrenic pathways, allowing the injured hemidiaphragm to increase its activity during the respiratory challenge (i.e., asphyxia). This effect could be explained by a strengthening of respiratory descending fibers in the ventrolateral funiculi (an increase in GAP-43 positive fibers), sustained by a reduction in inflammation in the C1-C3 spinal cord (reduction in CD68 and Iba1 labeling), and acceleration of intracellular plasticity processes in phrenic motoneurons after chronic rTMS treatment. These results suggest that chronic high-frequency rTMS can ameliorate respiratory dysfunction and elicit neuronal plasticity with a reduction in deleterious post-traumatic inflammatory processes in the cervical spinal cord post-SCI. Thus, this therapeutic tool could be adopted and/or combined with other therapeutic interventions in order to further enhance beneficial outcomes.
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Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration. Two important deleterious features are a Ca2+ dysregulation linked to Ca2+ influxes associated with ryanodine receptor hyperactivation, and a muscular nicotinamide adenine dinucleotide (NAD+ ) deficit. Here, we identified that deletion in mdx mice of CD38, a NAD+ glycohydrolase-producing modulators of Ca2+ signaling, led to a fully restored heart function and structure, with skeletal muscle performance improvements, associated with a reduction in inflammation and senescence markers. Muscle NAD+ levels were also fully restored, while the levels of the two main products of CD38, nicotinamide and ADP-ribose, were reduced, in heart, diaphragm, and limb. In cardiomyocytes from mdx/CD38-/- mice, the pathological spontaneous Ca2+ activity was reduced, as well as in myotubes from DMD patients treated with isatuximab (SARCLISA® ) a monoclonal anti-CD38 antibody. Finally, treatment of mdx and utrophin-dystrophin-deficient (mdx/utr-/- ) mice with CD38 inhibitors resulted in improved skeletal muscle performances. Thus, we demonstrate that CD38 actively contributes to DMD physiopathology. We propose that a selective anti-CD38 therapeutic intervention could be highly relevant to develop for DMD patients.
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Distrofia Muscular de Duchenne , ADP-Ribosil Ciclase 1 , Animais , Humanos , Camundongos , Camundongos Endogâmicos mdx , Músculo Esquelético , Distrofia Muscular de Duchenne/genética , Miócitos Cardíacos/patologia , NAD/genética , NAD/uso terapêutico , NAD+ Nucleosidase/genética , FenótipoRESUMO
BACKGROUND: The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD. METHODS: We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities. RESULTS: 62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity. CONCLUSIONS: The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD.
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Saúde da Criança , Doença Pulmonar Obstrutiva Crônica , Criança , Saúde Global , Humanos , Pobreza , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Projetos de PesquisaRESUMO
Repetitive transcranial magnetic stimulation (rTMS) is a promising, innovative, and non-invasive therapy used clinically. Efficacy of rTMS has been demonstrated to ameliorate psychiatric disorders and neuropathic pain through neuromodulation of affected neural circuits. However, little is known about the mechanisms and the specific neural circuits via which rTMS facilitates these functional effects. The aim of this study was to begin revealing the mechanisms by which rTMS may tap into existing neural circuits, by using a well characterized spinal motor circuit - the phrenic circuit. Here we hypothesized that rTMS can be used to enhance phrenic motoneuron excitability in anesthetized Sprague Dawley rats. Multiple acute rTMS protocols were used revealing 10 Hz rTMS protocol induced a robust, long-lasting increase in phrenic motoneuron excitability, functionally evaluated by diaphragm motor evoked potentials (59.1 ± 21.1 % of increase compared to baseline 60 min after 10 Hz protocol against 6.0 ± 5.8 % (p = 0.007) for Time Control, -5.8 ± 7.4 % (p < 0.001) for 3 Hz, and 5.2 ± 12.5 % (p = 0.008) for 30 Hz protocols). A deeper analyze allowed to discriminate "responder" and "non-responder" subgroups among 10 Hz rTMS treated animals. Intravenous injections of GABAA and GABAB receptor agonists prior to 10 Hz rTMS treatment, abolished the enhanced phrenic motoneuron excitability, suggesting GABAergic input plays a mechanistic role in rTMS-induced phrenic excitability. These data demonstrate that a single high frequency rTMS protocol at 10 Hz increases phrenic motoneuron excitability, mediated by a local GABAergic "disinhibition". By understanding how rTMS can be used to affect neural circuits non-invasively we can begin to harness the therapeutic potential of this neuromodulatory strategy to promote recovery after disease or injury to the central nervous system.
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Potencial Evocado Motor/fisiologia , Agonistas de Receptores de GABA-A/farmacologia , Agonistas dos Receptores de GABA-B/farmacologia , Neurônios Motores/fisiologia , Rede Nervosa/fisiologia , Nervo Frênico/fisiologia , Estimulação Magnética Transcraniana , Animais , Diafragma/efeitos dos fármacos , Diafragma/fisiologia , Potencial Evocado Motor/efeitos dos fármacos , Feminino , Neurônios Motores/efeitos dos fármacos , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/metabolismo , Nervo Frênico/efeitos dos fármacos , Nervo Frênico/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Cervical spinal cord injury (SCI) results in permanent life-altering motor and respiratory deficits. Other than mechanical ventilation for respiratory insufficiency secondary to cervical SCI, effective treatments are lacking and the development of animal models to explore new therapeutic strategies are needed. The aim of this work was to demonstrate the feasibility of using a mouse model of partial cervical spinal hemisection at the second cervical metameric segment (C2) to investigate the impact of 6 weeks training on forced exercise wheel system on locomotor/respiratory plasticity muscles. To measure run capacity locomotor and respiratory functions, incremental exercise tests and diaphragmatic electromyography were done. In addition, muscle fiber type composition and capillary distribution were assessed at 51 days following chronic C2 injury in diaphragm, extensor digitorum communis (EDC), tibialis anterior (TA) and soleus (SOL) muscles. Six-week exercise training increased the running capacity of trained SCI mice. Fiber type composition in EDC, TA and SOL muscles was not modified by our protocol of exercise. The vascularization was increased in all muscle limbs in SCI trained group. No increase in diaphragmatic electromyography amplitude of the diaphragm muscle on the side of SCI was observed, while the contraction duration was significantly decreased in sedentary group compared to trained group. Cross-sectional area of type IIa myofiber in the contralateral diaphragm side of SCI was smaller in trained group. Fiber type distribution between contralateral and ipsilateral diaphragm in SCI sedentary group was affected, while no difference was observed in trained group. In addition, the vascularization of the diaphragm side contralateral to SCI was increased in trained group. All these results suggest an increase in fatigue resistance and a contribution to the running capacity in SCI trained group. Our exercise protocol could be a promising non-invasive strategy to sustain locomotor and respiratory muscle plasticity following SCI.
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Medula Cervical/lesões , Exercício Físico , Músculos/fisiopatologia , Traumatismos da Medula Espinal/terapia , Animais , Medula Cervical/fisiopatologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/fisiopatologiaAssuntos
COVID-19 , Doenças Cardiovasculares/terapia , Sistema Cardiovascular/fisiopatologia , Diabetes Mellitus Tipo 2/terapia , Metabolismo Energético , Exercício Físico , Estilo de Vida Saudável , Sistema Imunitário/imunologia , Prognóstico , Comportamento de Redução do Risco , Animais , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Terapia por Exercício , Fatores de Risco de Doenças Cardíacas , Humanos , Medição de RiscoRESUMO
High spinal cord injuries (SCI) lead to permanent respiratory insufficiency, and the search for new therapeutics to restore this function is essential. To date, the most documented preclinical model for high SCI is the rat cervical C2 hemisection. However, molecular studies with this SCI model are limited due to the poor availability of genetically modified specimens. The aim of this work was to evaluate the pathophysiology of respiratory activity following a cervical C2 injury at different times post-injury in a C57BL/6 mouse model. No significant spontaneous recovery of diaphragmatic activity was observed up to 30 days post-injury in eupneic condition. However, during a respiratory challenge, i.e. mild asphyxia, a partial restoration of the injured diaphragm was observed at 7 days post-injury, corresponding to the crossed phrenic phenomenon. Interestingly, the diaphragmatic recording between 2 respiratory bursts on the injured side showed an amplitude increase between 1-7 days post-injury, reflecting a change in phrenic motoneuronal excitability. This increase in inter-burst excitability returned to pre-injured values when the crossed phrenic phenomenon started to be effective at 7 days post-injury. Taken together, these results demonstrate the ability of the mouse respiratory system to express long-lasting plasticity following a C2 cervical hemisection and genetically modified animals can be used to study the pathophysiological effects on these plasticity phenomena.
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Medula Cervical/lesões , Diafragma/fisiopatologia , Neurônios Motores/fisiologia , Nervo Frênico/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Modelos Animais de Doenças , Eletromiografia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Inflammation plays a crucial role in the defense response of the innate immune system against pathogen infection. In this study, we selected 4 compounds for their potential or proven anti-inflammatory and/or anti-microbial properties to test on our in vitro model of bacteria-infected THP-1-derived macrophages. We first compared the capacity of sulforaphane (SFN), wogonin (WG), oltipraz (OTZ), and dimethyl fumarate (DMF) to induce the nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of the antioxidant, anti-inflammatory response pathways. Next, we performed a comparative evaluation of the antioxidant and anti-inflammatory efficacies of the 4 selected compounds. THP-1-derived macrophages and LPS-stimulated macrophages were treated with each compound and expression levels of genes coding for inflammatory cytokines IL-1ß, IL-6, and TNF-α were quantified by RT-qPCR. Moreover, expression levels of genes coding for M1 (IL-23, CCR7, IL-1ß, IL-6, and TNF-α) and M2 (PPARγ, MRC1, CCL22, and IL-10) markers were determined in classically-activated M1 macrophages treated with each compound. Finally, the effects of each compound on the intracellular bacterial survival of gram-negative E. coli and gram-positive S. aureus in THP-1-derived macrophages and PBMC-derived macrophages were examined. Our data confirmed the anti-inflammatory and antioxidant effects of SFN, WG, and DMF on LPS-stimulated THP-1-derived macrophages. In addition, SFN or WG treatment of classically-activated THP-1-derived macrophages reduced expression levels of M1 marker genes, while SFN or DMF treatment upregulated the M2 marker gene MRC1. This decrease in expression of M1 marker genes may be correlated with the decrease in intracellular S. aureus load in SFN- or DMF-treated macrophages. Interestingly, an increase in intracellular survival of E. coli in SFN-treated THP-1-derived macrophages that was not observed in PBMC-derived macrophages. Conversely, OTZ exhibited pro-oxidant and proinflammatory properties, and affected intracellular survival of E. coli in THP-1-derived macrophages. Altogether, we provide new potential therapeutic alternatives in treating inflammation and bacterial infection.
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Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Inflamação/tratamento farmacológico , Ativação de Macrófagos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/imunologia , Estresse Oxidativo/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Fumarato de Dimetilo/farmacologia , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/imunologia , Flavanonas/farmacologia , Humanos , Inflamação/imunologia , Isotiocianatos/farmacologia , Leucócitos Mononucleares , Ativação de Macrófagos/imunologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Estresse Oxidativo/imunologia , Pirazinas/farmacologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/efeitos dos fármacos , Sulfóxidos , Células THP-1 , Tionas , TiofenosRESUMO
Macrophages are active contributors to the innate immune defense system. As macrophage activation is clearly affected by the surrounding microenvironment, the present study investigated the effect of sulforaphane (SFN) on the bactericidal activity of macrophages and the underlying molecular mechanisms involved in this process. Human THP1derived macrophages, primary human peripheral blood mononuclear cellderived macrophages, and primary mouse bone marrow derivedmacrophages (BMDMs) pretreated with SFN or DMSO were utilized in a model of Staphylococcus aureus infection. The results suggested that SFN pretreatment of macrophages effectively repressed the intracellular survival of S. aureus through modulation of p38/JNK signaling and decreased S. aureusinduced caspases3/7dependent cell apoptosis, potentially through downregulation of microRNA (miR)1425p and miR146a5p. As SFN is a wellknown activator of nuclear factor erythroid 2related factor 2 (Nrf2), Nrf2/ BMDMs were used to demonstrate that the SFNmediated inhibitory effect was independent of Nrf2. Nevertheless, an increase in intracellular bacterial survival in Nrf2deficient macrophages was observed. In addition, SFN pretreatment suppressed S. aureusinduced transcriptional expression of genes coding for the proinflammatory cytokines interleukin (IL)1ß, IL6, and tumor necrosis factorα (TNFα), as well as for the M1 markers CC motif chemokine receptor 7, IL23 and inducible nitric oxide synthase (iNOS). Western blot analysis indicated that S. aureus challenge activated p38 mitogenactivated protein kinase (MAPK) (p38) and cJun Nterminal kinase (JNK) MAPK signaling pathways, while SFN pretreatment prevented p38 and JNK phosphorylation. Pretreatment with 2 specific inhibitors of p38 and JNK, SB203580 and SP600125, respectively, resulted in a decrease in S. aureusinduced proinflammatory gene expression levels compared with those observed in the SFNpretreated macrophages. Furthermore, THP1derived macrophages pretreated with SB203580 or SP600125 prior to bacterial infection exhibited a significant inhibition in intracellular S. aureus survival. In conclusion, we hypothesize that concomitant targeting of the p38/JNKinflammatory response and the S. aureusinduced apoptosis with SFN may be a promising therapeutic approach in S. aureus infection.
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Inflamação/tratamento farmacológico , Isotiocianatos/farmacologia , MAP Quinase Quinase 4/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Apoptose/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/metabolismo , MAP Quinase Quinase 4/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/metabolismo , Sulfóxidos , Células THP-1RESUMO
BACKGROUND: The severity of Hereditary Hemorrhagic Telangiectasia (HHT) disease is generally related to vascular visceral involvement represented by arteriovenous malformations (AVMs). Pulmonary function tests (PFTs) remain normal in HHT patients without Pulmonary AVMs (PAVMs) and respiratory comorbidity. The aim of our study was to compare the diffusing capacity of the lung for carbon monoxide (DLCO) and nitric oxide (DLNO) and its 2 components: the pulmonary capillary blood volume (Vc) and the alveolar-capillary membrane conductance (Dm), in HHT patients with PAVMs, PAVMs and liver AVMs (LAVMs), LAVMs without PAVM, no PAVM and LAVM, and controls. METHODS: Sixty one consecutive adult patients (HHT without PAVM and LAVM: n = 7; HHT with PAVMs: n = 8; HHT with PAVMs and LAVMs: n = 25; HHT with LAVMs: n = 21) and controls matched for age and sex ratio without respiratory, heart and liver pathology (n = 15) were non-invasively evaluated using PFTs, combined DLCO/DLNO, arterial blood gas at rest, contrast echocardiography and enhanced computed tomography scan of the liver and chest the day of pulmonary function testing. RESULTS: We found that patients with LAVMs but without PAVMs exhibited increased Vc/Dm ratio. Interestingly, HHT patients with hepatic artery enlargement showed higher Vc/Dm ratio than HHT patients with normal hepatic artery diameter. CONCLUSION: Vc/Dm ratio may have practical impact in HHT patients' management to detect precociously the occurrence of LVAMs. However, further studies are needed to assess the accuracy and potential prognostic value of pulmonary gas exchange measurements in HHT patients with LVAMs.
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Malformações Arteriovenosas/fisiopatologia , Volume Sanguíneo/fisiologia , Hepatopatias/fisiopatologia , Troca Gasosa Pulmonar/fisiologia , Telangiectasia Hemorrágica Hereditária/fisiopatologia , Adolescente , Adulto , Idoso , Malformações Arteriovenosas/diagnóstico , Malformações Arteriovenosas/epidemiologia , Feminino , Humanos , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The 6-min walk test (6MWT) encompasses potential and untapped information related to exercise capacity. However, this test does not yield any information about gait pattern. Recently, we used a ventilatory polygraph to reveal respiratory adaptation during the 6MWT with subjects having high or low body mass index (BMI). In this study, we aimed to determine gait parameters with the same device, which integrates an accelerometer. METHODS: Using a 30-m corridor, steps and U-turns were detected with a custom-made algorithm, compared to video recordings as a reference method, and analyzed offline. From the vertical acceleration signal, we were able to determine cadence and step length, and we could calculate the total distance covered in 6 min (6MWD). We then compared these variables between subjects with low BMI (n = 13 subjects) or high BMI (n = 29 subjects). RESULTS: Steps and U-turn detection correlated with video results (r = 0.99, P < .001 for both). The 6MWD calculation was also in line with classical measurements (r = 0.99, P < .001). High BMI subjects had a significantly lower 6MWD, cadence, and step length than controls (P < .001 for each). Walking speed was more closely correlated with step length (r = 0.92) than with cadence (r = 0.64) for both groups. CONCLUSION: Our results demonstrated that a ventilatory polygraph with an embedded accelerometer can be used to detect steps and U-turns, and to calculate 6MWD. This method is sufficiently sensitive to characterize significant BMI-dependent differences in gait pattern during a 6MWT and appears to be a promising tool for routine clinical use.
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Acelerometria/instrumentação , Análise da Marcha/métodos , Sobrepeso/fisiopatologia , Teste de Caminhada/métodos , Caminhada/estatística & dados numéricos , Acelerometria/métodos , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Noninvasive positive pressure ventilation is frequently prescribed to obese patients with obstructive sleep apnea syndrome and obesity hypoventilation syndrome. However, mechanical ventilation with a positive end-expiratory pressure can induce or worsen a right-to-left shunt through a patent foramen ovale associated with systemic hypoxemia. Thus, in obese patients treated with noninvasive positive pressure ventilation, a paradoxical worsening of hypoxemia may reveal the existence of a patent foramen ovale. CASE PRESENTATION: A 50-year-old African woman was referred to our sleep center for severe obstructive sleep apnea syndrome and obesity hypoventilation syndrome. Because she had alveolar hypoventilation and had failed previous obstructive sleep apnea syndrome therapy, noninvasive positive pressure ventilation was started. In May 2015, she had a normal residual apnea/hypopnea index calculated by the ventilator software with no hypoventilation. Six months later, severe hypoxemia without hypercapnia was noted. Contrast transthoracic echocardiography showed right-to-left shunt through a patent foramen ovale. This finding prompted a decrease in expiratory and inspiratory positive airway pressures, after which the ventilator software recorded a normal residual apnea/hypopnea index and the blood gas values improved. CONCLUSION: Noninvasive positive pressure ventilation therapy for combined obstructive sleep apnea syndrome and obesity hypoventilation syndrome must be monitored by arterial blood gas measurements, both to reassess the hypercapnia and to look for worsening hypoxemia due to a patent foramen ovale.
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Forame Oval Patente/diagnóstico por imagem , Hipóxia/terapia , Síndrome de Hipoventilação por Obesidade/terapia , Apneia Obstrutiva do Sono/terapia , Progressão da Doença , Feminino , Forame Oval Patente/complicações , Humanos , Hipóxia/etiologia , Pessoa de Meia-Idade , Ventilação não Invasiva/efeitos adversos , Síndrome de Hipoventilação por Obesidade/complicações , Respiração com Pressão Positiva/efeitos adversos , Apneia Obstrutiva do Sono/complicaçõesRESUMO
BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) are present in approximately 15-50% individuals with hereditary hemorrhagic telangiectasia (HHT). They may be isolated but more often are multiple. The goal of this study was to evaluate the influence of PAVMs on lung mechanical properties. METHODS: We reviewed the files of all adult patients (age ≥ 18 years) referred to our Center for evaluation of HHT between 2005 and 2013. The diagnosis of HHT was based on the Curacao criteria and/or the presence of a pathogenic mutation. Exclusion criteria included: chronic cardiac or lung disease (i.e. asthma or COPD), suspicion of pulmonary hypertension on echocardiography, current or past smoking (>10 pack-years), history of thoracic surgery, previous treatment of PAVMs by embolotherapy, lung infection or thromboembolic disease in the past 3 months, pregnancy and obesity (BMI > 30 kg/m2). Chest high resolution CT-scan and pulmonary function tests were performed the same day in all patients as part of our routine work-up. RESULTS: One hundred and fifty five patients with HHT were included (age: 44.4 ± 16.7 yrs - mean ± SD -; males: 39%). Eighty eight patients had no PAVM, 45 had 1-3 PAVMS and 22 had at least 4 PAVMs. Thirty eight patients had unilateral PAVMs and 29 bilateral PAVMs. We found no statistical relationship between the number, the size and the laterality of PAVMs and results of lung flows and volumes. CONCLUSION: We found no evidence that PAVMs have a significant influence on lung mechanical properties as measured using routine pulmonary function tests in adult patients with HHT, even in case of numerous, macroscopic or bilateral malformations.
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Fístula Arteriovenosa/fisiopatologia , Pulmão/fisiopatologia , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Telangiectasia Hemorrágica Hereditária/complicações , Adulto , Feminino , França , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Veias Pulmonares/fisiopatologia , Testes de Função Respiratória , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
We aim to evaluate thoracic respiratory inductive plethysmography (RIP) in high body mass index (BMI) subjects with a pneumotachometer (PT) as a reference. We simultaneously evaluated spontaneous breathing by RIP and PT in 10 low and 10 high BMI subjects at rest and in moderate exercise. We then recorded RIP amplitude with different excursions mimicking respiratory thoracic deformation, with different sizes of RIP belts surrounding cylinders of different perimeters with or without deformable foam simulating adipose tissue. RIP responses correlated with PT values in low and high BMI groups for inspiratory time (r=0.86 and r=0.91, respectively), expiratory time (r=0.96 and r=0.91, respectively) and amplitude (r=0.82 for both) but with a bias (-0.23±0.25L) for high BMI subjects. ANOVA revealed the effects of perimeter and simulated adiposity (p<0.001 for both). We concluded that thoracic perimeter and deformity of adipose tissue are responsible for biases in RIP response in high BMI subjects.
Assuntos
Índice de Massa Corporal , Pletismografia , Respiração , Tecido Adiposo/fisiopatologia , Adulto , Algoritmos , Análise de Variância , Elasticidade , Exercício Físico/fisiologia , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Obesidade/patologia , Obesidade/fisiopatologia , Tamanho do Órgão , Pletismografia/instrumentação , Descanso , Tórax/patologia , Tórax/fisiopatologia , Fatores de Tempo , ViscosidadeRESUMO
The pneumotachometer is currently the most accepted device to measure tidal breathing, however, it requires the use of a mouthpiece and thus alteration of spontaneous ventilation is implied. Respiratory inductive plethysmography (RIP), which includes two belts, one thoracic and one abdominal, is able to determine spontaneous tidal breathing without the use of a facemask or mouthpiece, however, there are a number of as yet unresolved issues. In this study we aimed to describe and validate a new RIP method, relying on a combination of thoracic RIP and nasal pressure signals taking into account that exercise-induced body movements can easily contaminate RIP thoracic signals by generating tissue motion artifacts. A custom-made time domain algorithm that relies on the elimination of low amplitude artifacts was applied to the raw thoracic RIP signal. Determining this tidal ventilation allowed comparisons between the RIP signal and simultaneously-recorded airflow signals from a calibrated pneumotachometer (PT). We assessed 206 comparisons from 30 volunteers who were asked to breathe spontaneously at rest and during walking on the spot. Comparisons between RIP signals processed by our algorithm and PT showed highly significant correlations for tidal volume (Vt), inspiratory (Ti) and expiratory times (Te). Moreover, bias calculated using the Bland and Altman method were reasonably low for Vt and Ti (0.04 L and 0.02 s, respectively), and acceptable for Te (<0.1 s) and the intercept from regression relationships (0.01 L, 0.06 s, 0.17 s respectively). The Ti/Ttot and Vt/Ti ratios obtained with the two methods were also statistically correlated. We conclude that our methodology (filtering by our algorithm and calibrating with our calibration procedure) for thoracic RIP renders this technique sufficiently accurate to evaluate tidal ventilation variation at rest and during mild to moderate physical activity.