Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. Both peptides controlled the experimental IPF, maintaining the tissue characteristics and standard function properties and regulating fibrotic-associated cytokine production. Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF.

Long-Term Effects of a Kinematic Bikefitting Method on Pain, Comfort, and Fatigue: A Prospective Cohort Study.

The purpose of this study is to analyze the long-term riders' subjective responses to a standardized bikefitting method on their bicycles. Eighty-six amateur mountain bikers had their riding posture and bicycle components ergonomically adjusted through a 3D kinematic bikefitting method. Validated subjective scales (Feeling, OMNI, and Numerical Rating Pain Scale) were used to assess their overall riding comfort and fatigue along with localized pain for six body parts. Data were collected just before intervention (baseline or pre), immediately after (or post), and 30, 60, 90, and 120 days after the bikefit session. A Student's t-test comparing before bikefit and after 120 days showed significant (p < 0.05) reduction in localized pain for all six body parts and riding comfort along with a large effect size effect (d = 1.18) for riding comfort. Although initially reduced, fatigue scores gradually increased over the months, showing a high correlation (r = 0.946) with increased monthly training volume. In conclusion, overall riding discomfort and pain were significantly decreased after a standardized kinematic bikefit session even after 120 days post intervention. However, fatigue scores began to rise after 30 days, showing a high correlation with increasing monthly training volume.

Fish Oil Nanoemulsion Supplementation Attenuates Bleomycin-Induced Pulmonary Fibrosis BALB/c Mice.

Diets rich in omega-3 or -6 fatty acids will produce different profiles for cell membranes phospholipid constitutions. Omegas 3 and 6 are part of the diet and can modulate the inflammatory profile. We evaluated the effects of the oral absorption of fish oil, when associated with a lipid nanoemulsion in an experimental pulmonary inflammatory model. Pulmonary fibrosis is a disease associated with excessive extracellular matrix deposition. We determined to investigate the morphophysiological mechanisms in mice that were pretreated after induction with bleomycin (BLM). The pretreatment was for 21 days with saline solution, sunflower oil (SO), fish oil (FO), and fish oil nanoemulsion (NEW3). The animals received a daily dose of 50 mg/Kg of docosahexaenoic acid DHA and 10 mg/Kg eicosapentaenoic (EPA) (100 mg/Kg), represented by a daily dose of 40 µL of NEW3. The blank group was treated with the same amount daily (40 µL) during the 21 days of pretreatment. The animals were treated with SO and FO, 100 mg/Kg (containing 58 mg/Kg of polyunsaturated fats/higher% linoleic acid) and 100 mg/Kg (50 mg/Kg of DHA and 10 mg/Kg EPA), respectively. A single dose of 5 mg/mL (50 µL) bleomycin sulfate, by the intratracheal surgical method in BALB/cAnNTac (BALB/c). NEW3 significantly reduced fibrotic progression, which can be evidenced by the protection from loss of body mass, increase in respiratory incursions per minute, decreased spacing of alveolar septa, decreased severity of fibrosis, and changes in the respiratory system. NEW3 attenuated the inflammatory changes developed in the experimental model of pulmonary fibrosis, while group SO showed a significant increase in inflammatory changes. This concluded that the presented results demonstrated that is possible to positively modulate the immune and inflamamtory response to an external agressor, by changing the nutitional intake of specific fatty acids, such as omega-3 placed in fish oil. Moreover, these benefits can be improved by the nanoencapsulation of fish oil in lipid nanoemulsions.

Local envenomation caused by a bioactive peptide fraction of Bothrops jararaca snake venom induces leukocyte influx in the lung and changes in pulmonary mechanics.

The crude venom of the Bothrops jararaca snake (Bj-CV) is a complex mixture of biologically active proteins that includes a variety of peptides in the low molecular weight fraction (Bj-PF). We investigated how an intramuscular injection of Bj-CV (1.2 mg kg-1) and Bj-PF (0.24 mg kg-1) influenced lung mechanics and lung and muscle inflammation in male Swiss mice 15 min, 1, 6, and 24 h after inoculation. Pressure dissipation against lung resistive components (ΔP1) rose significantly from 1 to 24 h after Bj-CV and 6-24 h after Bj-PF inoculation. Both Bj-CV and Bj-PF increased the total pressure variation of the lung (ΔPtot) 24 h after injection. Lung static elastance increased significantly after injection in all time periods investigated by Bj-CV and from 6 to 24 h by Bj-PF. Lung static elastance increased significantly after injection in all time periods investigated by Bj-CV and from 6 to 24 h by Bj-PF. Furthermore, intramuscular inoculation of Bj-CV and Bj-PF resulted in an increase in muscle and pulmonary inflammation, as evidenced by an increase in leukocyte influx when compared to the control group. Finally, both Bj-CV and Bj-PF cause acute lung injury, as shown by pulmonary inflammation and decreased lung mechanics. Furthermore, the fact that Bj-PF produces mechanical alterations in the lungs and muscular inflammation implies that non-enzymatic compounds can cause inflammation.

Combined exercise training improved exercise capacity and lung inflammation in rats with hepatopulmonary syndrome.

AIM: Physical exercise training attenuates pulmonary inflammation, but its effects on impaired respiratory function caused by hepatopulmonary syndrome (HPS) have not been evaluated. We determined if the combination of moderate intensity aerobic and resistance training during HPS development modifies exercise capacity, respiratory system mechanics, and lung inflammation responses. MAIN METHODS: Wistar rats were randomly divided into sham, HPS, and HPS + combined exercise training groups. Fifteen days after HPS induction, a moderate intensity aerobic plus resistance exercise training protocol was performed five times a week for 5 weeks on alternate days. Exercise capacity, respiratory system mechanics, lung inflammation, pulmonary morphology, and immunohistochemistry were evaluated. KEY FINDINGS: Overall, our findings indicated that combined exercise training efficiently increased the maximal running and resistance capacity of HPS animals. The training regimen reduced the expression of P2X7 in parenchymal leukocytes (P < 0.01), partially restored the expression of interleukin-10 in airway epithelium (P < 0.01), and increased the expression of TFPI in the airway epithelium (P < 0.01) as well as reduced its expression in parenchymal leukocytes (P < 0.01). However, exercise training did not attenuate HPS-induced respiratory mechanical derangements or lung tissue remodeling. SIGNIFICANCE: Combined exercise training can elicit adaptation with regard to both maximal running capacity and maximum strength and modify the expression of P2X7 and TFPI in parenchymal leukocytes and that of IL-10 in airway epithelium.

Right ventricular contractility decreases during exercise in patients with non-advanced idiopathic pulmonary fibrosis.

ABSTRACT: Early right ventricular dysfunction in patients with non-advanced idiopathic pulmonary fibrosis (IPF) has not been fully elucidated. Thus, we aimed to assess right ventricular functions in IPF patients and controls by speckle-tracking strain echocardiography at rest and peak exercise.We screened 116 IPF patients from February to August 2019 to include 20 patients with no history of oxygen therapy, peripheral saturation levels ≥92% at rest, Gender-Age-Physiology Index score ≤5, and modified Medical Research Council score ≤3. Additionally, we enrolled 10 matched controls. Transthoracic echocardiography images were acquired at rest and during a cardiopulmonary exercise test. We analyzed 2-dimensional echocardiographic parameters and right ventricular function using the global longitudinal strain assessed by the 2-dimensional speckle-tracking technique.In the control group, we found normal values of right ventricle longitudinal strain (RVLS) at rest and at peak exercise, the latter being much more negative (-23.6 ±â€Š2.2% and -26.8 ±â€Š3.1%, respectively; P < .001). By contrast, RVLS values in the IPF group increased from -21.1 ±â€Š3.8% at rest to -17.0 ±â€Š4.5% at peak exercise (P < .001). The exercise revealed a difference between the 2 groups as the mean RVLS values moved during peak exercise in opposite directions. Patients with IPF got worse, whereas control patients presented improved right ventricular contractility.Right ventricular dysfunction was unveiled by speckle-tracking echocardiography during exercise in non-advanced IPF patients. We suggest that this reflects an inadequate right ventricular-arterial coupling decreasing the right ventricular longitudinal contraction during exercise in these patients. This parameter may be useful as an early index of suspected pulmonary hypertension.

Right ventricular dysfunction in patients with non-severe idiopathic pulmonary fibrosis: a cross-sectional prospective single-center study.

BACKGROUND: Little is known about right ventricular dysfunction in non-advanced idiopathic pulmonary fibrosis (IPF) patients without hypoxemia at rest. We evaluated it at rest and during exercise. RESEARCH DESIGN AND METHODS: 123 IPF patients were evaluated, and 27 met all the following criteria: Gender-Age-Physiology Index score ≤5, modified Medical Research Council dyspnea score ≤3, peripheral oxygen saturation ≥92% at rest, and no history of oxygen therapy. They were submitted to two-dimensional speckle-tracking echocardiography at rest and during cardiopulmonary exercise to analyze right ventricular global longitudinal strain. RESULTS: Abnormal speckle-tracking echocardiography findings were identified in 10/27 patients (37%), indicating right ventricular (RV) dysfunction. No patients had abnormalities observed in conventional echocardiographic parameters. Significant differences in mPAP were observed between patients with RV dysfunction and those without dysfunction (at rest: 26.0 ± 4.8 vs. 19.1 ± 4.2 mmHg, p = 0.001; during exercise: 51.3 ± 6.4 vs. 36.9 ± 14.7 mmHg, p = 0.002). CONCLUSIONS: RV dysfunction was detected in 37% of non-advanced IPF patients and early recognition was only possible using speckle-tracking echocardiography. Special attention should be given to these patients as RV dysfunction is suggestive of worse prognosis. These patients could benefit from new specific drugs or even oxygen therapy for transitory hypoxia.

Lung MRI to predict response or lack of response to treatment in interstitial lung disease: initial observations on SSFSE/PROPELLER T2 match/mismatch.

BACKGROUND: Ground-glass opacities (GGO) are frequently found in interstitial lung diseases (ILD) and may represent either active inflammation or subresolution interstitial fibrosis. We sought to investigate the ability of lung MRI to predict treatment response in individuals with ILD presenting with predominant GGO. Methods: prospective cohort, 15 participants presenting with ILD manifested as predominant GGO and referred for a new treatment regimen with a systemic glucocorticoid and/or an immunosuppressive agent, underwent 1.5 T lung MRI. SSFSE/PROPELLER T2 mismatch sign, relative signal intensity on T2-weighted images and relative enhancement of lung lesions were compared to functional response, defined as a greater than 10% increase in forced vital capacity in 10 weeks (primary endpoint). RESULTS: SSFSE/PROPELLER T2 match/mismatch was able to discriminate responders from nonresponders for the primary endpoint in 12 of 15 participants (80% accuracy, p = 0.026) for readers 1 and 2, and in 13 of 15 participants (87% accuracy, p = 0.011) for reader 3, with interrater agreement of 87% between readers 1 and 2 (Cohen's kappa coefficient of 0.732) and 93% between readers 1/2 and 3 (Cohen's kappa coefficient of 0.865). CONCLUSIONS: SSFSE-PROPELLER T2 match/mismatch was predictive of treatment response status in this group of ILD patients. Abbreviations FVC: forced vital capacityGGO; ground-glass opacities; HRCT: High-Resolution Computed Tomography; ILD: interstitial lung disease; LAVA: Liver Acquisition with Volume Acceleration; mMRC: modified Medical Research Council dyspnea score; MRI: Magnetic Resonance Image; PROPELLER: Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction; SI: signal intensity; SSFSE: Single-Shot Fast Spin Echo.

Concentric and eccentric isokinetic hamstring injury risk among 582 professional elite soccer players: a 10-years retrospective cohort study.

BACKGROUND/AIM: Different authors have tried to correlate the peak isokinetic torque values with the incidence of soccer match injuries. However, due to the wide variety of assessment testing protocols, such an inference becomes difficult. This study aimed to verify the capacity of an isokinetic test to establish injury risk reference values for hamstring strain injuries. METHODS: A retrospective cohort study based on isokinetic data and clinical records from the last 10 years was conducted in 582 Brazilian elite-professional soccer players, who were subjected to the same isokinetic test protocol, machine, and tester. A Multivariate Logistic Regression Analysis for Complex Data Sampling was used to generate injury risk statistical indexes. RESULTS: Multivariate regression analysis of both legs provided important data to identify the cut-off values of Concentric Peak Torque (181.82 Newton/*metres), Concentric Work (236.23 watts) and Concentric Power (130.11 joules). CONCLUSIONS: The injury risk indexes indicate that an increase of just one Newton unit in CPT (Concentric Peak Torque) and CJ (Concentric Power) above those cut-off values, can reduce the risk of future injuries by 2% and 2.7%, respectively.

Noninvasive assessment of peripheral skeletal muscle weakness in idiopathic pulmonary fibrosis: a pilot study with multiparametric MRI of the rectus femoris muscle.

BACKGROUND: To investigate differences in magnetic resonance imaging (MRI) features of rectus femoris muscle between idiopathic pulmonary fibrosis (IPF) patients and healthy volunteers. METHODS: Thirteen IPF patients with GAP Index stage II disease were subjected to pulmonary function tests, 6-minute walk test (6MWT), quadriceps femoris muscle strength measurement and MRI of the thigh at rest. At MRI, muscle cross-sectional areas, T2 and T2* relaxometry, and 3-point Dixon fat fraction were measured. The results were compared to those of eight healthy sedentary volunteers. RESULTS: IPF patients had significantly lower %predicted FVC, FEV1 and DLCO (p<0.001 for the three variables) and walked significantly less in the 6MWT (p=0.008). Mean quadriceps femoris muscle strength also was significantly lower in IPF patients (p=0.041). Rectus femoris muscle T2* measurements were significantly shorter in IPF patients (p=0.027). No significant intergroup difference was found regarding average muscle cross-sectional areas (p=0.790 for quadriceps and p=0.816 for rectus femoris) or rectus femoris fat fraction (p=0.901). Rectus femoris T2 values showed a non-significant trend to be shorter in IPF patients (p=0.055). CONCLUSIONS: Our preliminary findings suggest that, besides disuse atrophy, other factors such as hypoxia (but not inflammation) may play a role in the peripheral skeletal muscle dysfunction observed in IPF patients. This might impact the rehabilitation strategies for IPF patients and warrants further investigation.

Diretrizes Brasileiras de Mobilização Precoce em Unidade de Terapia Intensiva / Brazilian Guidelines for Early Mobilization in Intensive Care Unit

RESUMO A imobilidade pode causar várias complicações que influenciam na recuperação de doentes críticos, incluindo atrofia e fraqueza muscular esquelética. Esse efeito pode ser amenizado com a realização de mobilização precoce. Seis questões primordiais nortearam essa pesquisa: É segura? Quem é o candidato à mobilização precoce? Quais são as contraindicações? Qual a dose adequada e como defini-la? Quais os resultados obtidos? Quais os indicadores prognósticos em sua utilização? O objetivo desta diretriz foi elaborar um documento que reunisse recomendações e sugestões baseadas em níveis de evidência sobre a mobilização precoce do paciente crítico adulto, visando melhorar o entendimento sobre o tema, com impacto positivo no atendimento aos pacientes. Esta diretriz foi desenvolvida com base em uma revisão sistemática de artigos, utilizando a estratégia de busca no modelo PICO, conforme recomendado pelo Projeto de Diretrizes da Associação Médica Brasileira. Foram selecionados ensaios clínicos randomizados, estudos de coortes prognósticos, revisões sistemáticas com ou sem metanálise, sendo as evidências classificadas segundo Oxford Centre for Evidence-based Medicine - Levels of Evidence. Em todas as questões abordadas, foram encontradas evidências suficientes para a realização da mobilização precoce de forma segura e bem definida, com indicadores prognósticos que evidenciam e recomendam a técnica. A mobilização precoce está associada a melhores resultados funcionais, devendo ser realizada sempre que indicada. É segura e deve ser meta de toda equipe multidisciplinar.

ABSTRACT Immobility can cause several complications, including skeletal muscle atrophy and weakness, that influence the recovery of critically ill patients. This effect can be mitigated by early mobilization. Six key questions guided this research: Is early mobilization safe? Which patients are candidates for early mobilization? What are the contraindications? What is the appropriate dose, and how should it be defined? What results are obtained? What are the prognostic indicators for the use of early mobilization? The objective of this guideline was to produce a document that would provide evidence-based recommendations and suggestions regarding the early mobilization of critically ill adult patients, with the aim of improving understanding of the topic and making a positive impact on patient care. This guideline was based on a systematic review of articles conducted using the PICO search strategy, as recommended by the Guidelines Project of the Associação Médica Brasileira. Randomized clinical trials, prognostic cohort studies, and systematic reviews with or without meta-analysis were selected, and the evidence was classified according to the Oxford Center for Evidence-based Medicine Levels of Evidence. For all the questions addressed, enough evidence was found to support safe and well-defined early mobilization, with prognostic indicators that support and recommend the technique. Early mobilization is associated with better functional outcomes and should be performed whenever indicated. Early mobilization is safe and should be the goal of the entire multidisciplinary team.

Accuracy of chest auscultation in detecting abnormal respiratory mechanics in the immediate postoperative period after cardiac surgery.

OBJECTIVE: To investigate the accuracy of chest auscultation in detecting abnormal respiratory mechanics. METHODS: We evaluated 200 mechanically ventilated patients in the immediate postoperative period after cardiac surgery. We assessed respiratory system mechanics - static compliance of the respiratory system (Cst,rs) and respiratory system resistance (R,rs) - after which two independent examiners, blinded to the respiratory system mechanics data, performed chest auscultation. RESULTS: Neither decreased/abolished breath sounds nor crackles were associated with decreased Cst,rs (≤ 60 mL/cmH2O), regardless of the examiner. The overall accuracy of chest auscultation was 34.0% and 42.0% for examiners A and B, respectively. The sensitivity and specificity of chest auscultation for detecting decreased/abolished breath sounds or crackles were 25.1% and 68.3%, respectively, for examiner A, versus 36.4% and 63.4%, respectively, for examiner B. Based on the judgments made by examiner A, there was a weak association between increased R,rs (≥ 15 cmH2O/L/s) and rhonchi or wheezing (ϕ = 0.31, p < 0.01). The overall accuracy for detecting rhonchi or wheezing was 89.5% and 85.0% for examiners A and B, respectively. The sensitivity and specificity for detecting rhonchi or wheezing were 30.0% and 96.1%, respectively, for examiner A, versus 10.0% and 93.3%, respectively, for examiner B. CONCLUSIONS: Chest auscultation does not appear to be an accurate diagnostic method for detecting abnormal respiratory mechanics in mechanically ventilated patients in the immediate postoperative period after cardiac surgery.

Brazilian Guidelines for Early Mobilization in Intensive Care Unit. / Diretrizes Brasileiras de Mobilização Precoce em Unidade de Terapia Intensiva.

Immobility can cause several complications, including skeletal muscle atrophy and weakness, that influence the recovery of critically ill patients. This effect can be mitigated by early mobilization. Six key questions guided this research: Is early mobilization safe? Which patients are candidates for early mobilization? What are the contraindications? What is the appropriate dose, and how should it be defined? What results are obtained? What are the prognostic indicators for the use of early mobilization? The objective of this guideline was to produce a document that would provide evidence-based recommendations and suggestions regarding the early mobilization of critically ill adult patients, with the aim of improving understanding of the topic and making a positive impact on patient care. This guideline was based on a systematic review of articles conducted using the PICO search strategy, as recommended by the Guidelines Project of the Associação Médica Brasileira. Randomized clinical trials, prognostic cohort studies, and systematic reviews with or without meta-analysis were selected, and the evidence was classified according to the Oxford Center for Evidence-based Medicine Levels of Evidence. For all the questions addressed, enough evidence was found to support safe and well-defined early mobilization, with prognostic indicators that support and recommend the technique. Early mobilization is associated with better functional outcomes and should be performed whenever indicated. Early mobilization is safe and should be the goal of the entire multidisciplinary team.

A imobilidade pode causar várias complicações que influenciam na recuperação de doentes críticos, incluindo atrofia e fraqueza muscular esquelética. Esse efeito pode ser amenizado com a realização de mobilização precoce. Seis questões primordiais nortearam essa pesquisa: É segura? Quem é o candidato à mobilização precoce? Quais são as contraindicações? Qual a dose adequada e como defini-la? Quais os resultados obtidos? Quais os indicadores prognósticos em sua utilização? O objetivo desta diretriz foi elaborar um documento que reunisse recomendações e sugestões baseadas em níveis de evidência sobre a mobilização precoce do paciente crítico adulto, visando melhorar o entendimento sobre o tema, com impacto positivo no atendimento aos pacientes. Esta diretriz foi desenvolvida com base em uma revisão sistemática de artigos, utilizando a estratégia de busca no modelo PICO, conforme recomendado pelo Projeto de Diretrizes da Associação Médica Brasileira. Foram selecionados ensaios clínicos randomizados, estudos de coortes prognósticos, revisões sistemáticas com ou sem metanálise, sendo as evidências classificadas segundo Oxford Centre for Evidence-based Medicine - Levels of Evidence. Em todas as questões abordadas, foram encontradas evidências suficientes para a realização da mobilização precoce de forma segura e bem definida, com indicadores prognósticos que evidenciam e recomendam a técnica. A mobilização precoce está associada a melhores resultados funcionais, devendo ser realizada sempre que indicada. É segura e deve ser meta de toda equipe multidisciplinar.

Accuracy of chest auscultation in detecting abnormal respiratory mechanics in the immediate postoperative period after cardiac surgery / Acurácia da ausculta torácica na detecção de mecânica respiratória anormal no pós-operatório imediato de cirurgia cardíaca

ABSTRACT Objective: To investigate the accuracy of chest auscultation in detecting abnormal respiratory mechanics. Methods: We evaluated 200 mechanically ventilated patients in the immediate postoperative period after cardiac surgery. We assessed respiratory system mechanics - static compliance of the respiratory system (Cst,rs) and respiratory system resistance (R,rs) - after which two independent examiners, blinded to the respiratory system mechanics data, performed chest auscultation. Results: Neither decreased/abolished breath sounds nor crackles were associated with decreased Cst,rs (≤ 60 mL/cmH2O), regardless of the examiner. The overall accuracy of chest auscultation was 34.0% and 42.0% for examiners A and B, respectively. The sensitivity and specificity of chest auscultation for detecting decreased/abolished breath sounds or crackles were 25.1% and 68.3%, respectively, for examiner A, versus 36.4% and 63.4%, respectively, for examiner B. Based on the judgments made by examiner A, there was a weak association between increased R,rs (≥ 15 cmH2O/L/s) and rhonchi or wheezing (ϕ = 0.31, p < 0.01). The overall accuracy for detecting rhonchi or wheezing was 89.5% and 85.0% for examiners A and B, respectively. The sensitivity and specificity for detecting rhonchi or wheezing were 30.0% and 96.1%, respectively, for examiner A, versus 10.0% and 93.3%, respectively, for examiner B. Conclusions: Chest auscultation does not appear to be an accurate diagnostic method for detecting abnormal respiratory mechanics in mechanically ventilated patients in the immediate postoperative period after cardiac surgery.

RESUMO Objetivo: Investigar a acurácia da ausculta torácica na detecção de mecânica respiratória anormal. Métodos: Foram avaliados 200 pacientes sob ventilação mecânica no pós-operatório imediato de cirurgia cardíaca. Foi avaliada a mecânica do sistema respiratório - complacência estática do sistema respiratório (Cest,sr) e resistência do sistema respiratório (R,sr) - e, em seguida, dois examinadores independentes, que desconheciam os dados referentes à mecânica do sistema respiratório, realizaram a ausculta torácica. Resultados: Nem murmúrio vesicular diminuído/abolido nem crepitações foram associados à Cest,sr reduzida (≤ 60 ml/cmH2O), independentemente do examinador. A acurácia global da ausculta torácica foi de 34,0% e 42,0% para os examinadores A e B, respectivamente. A sensibilidade e a especificidade da ausculta torácica para a detecção de murmúrio vesicular diminuído/abolido e/ou crepitações foi de 25,1% e 68,3%, respectivamente, para o examinador A, versus 36,4% e 63,4%, respectivamente, para o examinador B. Com base nos julgamentos feitos pelo examinador A, houve uma fraca associação entre R,sr aumentada (≥ 15 cmH2O/l/s) e roncos e/ou sibilos (ϕ = 0,31, p < 0,01). A acurácia global para a detecção de roncos e/ou sibilos foi de 89,5% e 85,0% para os examinadores A e B, respectivamente. A sensibilidade e a especificidade para a detecção de roncos e/ou sibilos foi de 30,0% e 96,1%, respectivamente, para o examinador A, versus 10,0% e 93,3%, respectivamente, para o examinador B. Conclusões: A ausculta torácica não parece ser um método diagnóstico acurado para a detecção de mecânica respiratória anormal em pacientes sob ventilação mecânica no pós-operatório imediato de cirurgia cardíaca.

Effects of repetitive transcranial magnetic stimulation of upper airway muscles during sleep in obstructive sleep apnea patients.

We tested the hypothesis that stimulating the genioglossus by repetitive transcranial magnetic stimulation (rTMS) during the ascendant portion of the inspiratory flow of airflow-limited breaths would sustain the recruitment of upper airway dilator muscles over time and improve airway dynamics without arousing obstructive sleep apnea (OSA) patients. In a cross-sectional design, nine OSA patients underwent a rTMS trial during stable non-rapid eye movement (NREM) sleep. Submental muscle motor threshold (SUB) and motor-evoked potential were evaluated during wakefulness and sleep. During NREM sleep, maximal inspiratory flow, inspiratory volume, inspiratory time, shifts of electroencephalogram frequency, and pulse rate variability were assessed under three different stimulation paradigms completed at 1.2 sleep SUB stimulation output: 1) 5Hz-08 (stimulation frequency: 5 Hz; duration of train stimulation: 0.8 s); 2) 25Hz-02 (stimulation frequency: 25 Hz; duration of train stimulation: 0.2 s); and 3) 25Hz-04 (stimulation frequency: 25 Hz; duration of train stimulation: 0.4 s). SUB increased during NREM sleep (wakefulness: 23.8 ± 6.1%; NREM: 26.8 ± 5.2%; = 0.001). Two distinct airflow patterns were observed in response to rTMS: with and without initial airflow drops, without other airflow variables change regardless the stimulation paradigm applied. Finally, rTMS-induced cortical and/or autonomic arousal were observed in 36, 26, and 35% of all delivered rTMS trains during 5Hz-08, 25Hz-02, and 25Hz-04 stimulation paradigms, respectively. In conclusion, rTMS does not provide any airflow improvement of flow-limited breaths as seen with nonrepetitive TMS of upper airway dilator muscles. However, rTMS trains were free of arousals in the majority of cases.

Prevalence of lung structure abnormalities in patients with acromegaly and their relationship with gas exchange: cross-sectional analytical study with a control group.

CONTEXT AND OBJECTIVE: Different functional respiratory alterations have been described in acromegaly, but their relationship with pulmonary tissue abnormalities is unknown. The objective of this study was to observe possible changes in lung structure and explain their relationship with gas exchange abnormalities. DESIGN AND SETTING: Cross-sectional analytical study with a control group, conducted at a university hospital. METHODS: The study included 36 patients with acromegaly and 24 controls who were all assessed through high-resolution computed tomography of the thorax (CT). Arterial blood gas, effort oximetry and serum growth hormone (GH) and insulin-like growth factor I (IGF-1) were also assessed in the patients with acromegaly. RESULTS: The abnormalities found in the CT scan were not statistically different between the acromegaly and control groups: mild cylindrical bronchiectasis (P = 0.59), linear opacity (P = 0.29), nodular opacity (P = 0.28), increased attenuation (frosted glass; P = 0.48) and decreased attenuation (emphysema; P = 0.32). Radiographic abnormalities were not associated with serum GH and IGF-1. Hypoxemia was present in seven patients; however, in six of them, the hypoxemia could be explained by underlying clinical conditions other than acromegaly: chronic obstructive pulmonary disease in two, obesity in two, bronchial infection in one and asthma in one. CONCLUSION: No changes in lung structure were detected through thorax tomography in comparison with the control subjects. The functional respiratory alterations found were largely explained by alternative diagnoses or had subclinical manifestations, without any plausible relationship with lung structural factors.

Prevalence of lung structure abnormalities in patients with acromegaly and their relationship with gas exchange: cross-sectional analytical study with a control group / Prevalência de alterações na estrutura pulmonar em pacientes com acromegalia e sua relação com a troca gasosa: estudo transversal analítico com grupo controle

CONTEXT AND OBJECTIVE: Different functional respiratory alterations have been described in acromegaly, but their relationship with pulmonary tissue abnormalities is unknown. The objective of this study was to observe possible changes in lung structure and explain their relationship with gas exchange abnormalities. DESIGN AND SETTING: Cross-sectional analytical study with a control group, conducted at a university hospital. METHODS: The study included 36 patients with acromegaly and 24 controls who were all assessed through high-resolution computed tomography of the thorax (CT). Arterial blood gas, effort oximetry and serum growth hormone (GH) and insulin-like growth factor I (IGF-1) were also assessed in the patients with acromegaly. RESULTS: The abnormalities found in the CT scan were not statistically different between the acromegaly and control groups: mild cylindrical bronchiectasis (P = 0.59), linear opacity (P = 0.29), nodular opacity (P = 0.28), increased attenuation (frosted glass; P = 0.48) and decreased attenuation (emphysema; P = 0.32). Radiographic abnormalities were not associated with serum GH and IGF-1. Hypoxemia was present in seven patients; however, in six of them, the hypoxemia could be explained by underlying clinical conditions other than acromegaly: chronic obstructive pulmonary disease in two, obesity in two, bronchial infection in one and asthma in one. CONCLUSION: No changes in lung structure were detected through thorax tomography in comparison with the control subjects. The functional respiratory alterations found were largely explained by alternative diagnoses or had subclinical manifestations, without any plausible relationship with lung structural factors.

CONTEXTO E OBJETIVO: Diferentes alterações funcionais respiratórias são descritas na acromegalia. Sua relação com anormalidades do tecido pulmonar é desconhecida. O objetivo foi observar possíveis alterações da estrutura pulmonar e explicar sua relação com anormalidades da troca gasosa. TIPO DE ESTUDO E LOCAL: Estudo transversal, analítico, com grupo de controle, realizado em um hospital universitário. MÉTODOS: Incluíram-se 36 pacientes com acromegalia e 24 controles que foram avaliados com tomografia computadorizada de alta resolução de tórax (TC); os acromegálicos também foram avaliados com gasometria arterial, oximetria de esforço e dosagens de hormônio de crescimento (GH) e fator de crescimento semelhante à insulina (IGF-1). RESULTADOS: As alterações encontradas na TC não foram estatisticamente diferentes entre os grupos acromegálico e de controle: bronquiectasia cilíndrica leve (P = 0,59), opacidades lineares (P = 0,29), opacidades nodulares (P = 0,28), aumento da atenuação (vidro fosco) (P = 0,48) e redução da atenuação (enfisema; P = 0,32). As alterações radiológicas não se relacionaram com as dosagens de GH e IGF-1. Hipoxemia estava presente em sete pacientes; contudo, em seis deles a hipoxemia poderia ser explicada por condição clínica subjacente diversa da acromegalia: doença pulmonar obstrutiva crônica em dois, obesidade em dois, infecção brônquica em um e asma em um. CONCLUSÕES: Não foram observadas alterações da estrutura pulmonar por tomografia de tórax, quando comparadas ao grupo de controle; as alterações funcionais respiratórias encontradas são explicáveis em grande parte por diagnósticos alternativos, ou se manifestam de forma subclínica, não apresentando relação plausível com o aspecto da estrutura pulmonar.

Mechanical effects of repetitive transcranial magnetic stimulation of upper airway muscles in awake obstructive sleep apnoea subjects.

NEW FINDINGS: What is the central question of this study? Can repetitive transcranial magnetic stimulation (rTMS) of the genioglossus enhance the beneficial effects observed with transcranial magnetic stimulation single twitches on upper airway mechanical properties? What is the main finding and its importance? We found that both inspiratory and expiratory rTMS protocols induce a different activation pattern of upper airway muscles, with evidence for an increase in genioglossus corticomotor excitability in response to rTMS. This is of major importance because it might open the door for rTMS protocols with the goal of increasing corticomotor excitability and, thus, possibly increasing the tonic genioglossus activity, which is known to be diminished during sleep in subjects with sleep apnoea. ABSTRACT: Stimulation of upper airway (UA) muscles during sleep by isolated transcranial magnetic stimulation (TMS) twitch can improve airflow dynamics without arousal, but the effect of repetitive TMS (rTMS) on UA dynamics is unknown. Phrenic nerve magnetic stimulation (PNMS) can be used to produce painless experimental twitch-induced flow limitation during wakefulness. The aim of this study was to quantify the effects of rTMS applied during wakefulness on UA mechanical properties using PNMS in subjects with obstructive sleep apnoea (OSA). Phrenic nerve magnetic stimulation was applied to 10 subjects, with and without simultaneous rTMS, during inspiration and expiration. Flow-limitation characteristics and UA obstruction level were determined [maximal (V̇I,max)and minimal inspiratory airflow (V̇I,min),V̇I,max-V̇I,min flow drop (ΔV̇I),oropharyngeal (POro,peak ) and velopharyngeal peak pressures, oropharyngeal k1 /k2 ratios with k1 and k2 determined by the polynomial regression model between instantaneous flow and pharyngeal pressure and UA resistance]. Both genioglossus and diaphragm root mean squares and motor-evoked potential amplitudes (geniolossus, GGAmp ) and latencies were computed. A flow-limitation pattern always occurred after PNMS. A decrease in V̇I,max and an increase in ΔV̇I occurred following rTMS applied during inspiration, and POro,peak values were more negative with both inspiratory and expiratory rTMS. The GGAmp also increased significantly from the second to the last rTMS expiratory train twitch. All other parameters remained unchanged. These results suggest the following conclusions: (i) rTMS does not improve UA mechanical properties in awake subjects with OSA; (ii) the activation pattern of UA muscles differs following isolated twitch and repetitive cortical stimulation of the genioglossus; and (iii) rTMS applied during expiration induces corticomotor facilitation.

Accuracy of pulmonary auscultation to detect abnormal respiratory mechanics: a cross-sectional diagnostic study.

Pulmonary auscultation is a method used in clinical practice for the evaluation and detection of abnormalities relating to the respiratory system. This method has limitations, as it depends on the experience and hearing acuity of the examiner to determine adventitious sounds. In this context, it's important to analyze whether there is a correlation between auscultation of lung sounds and the behavior of the respiratory mechanical properties of the respiratory system in patients with immediate postoperative cardiac surgery.

Pulmonary arterial hypertension and sepsis: prothrombotic profile and inflammation can changes pulmonary mechanics?

Pulmonary arterial hypertension (PAH) is associated to cellular and structural alterations of lung vasculature. Endothelial dysfunction promotes vasoconstriction, smooth muscle hypertrophy, intimal proliferation, angioproliferative plexiform lesions, and in situ thrombosis increasing pulmonary vascular resistance and arterial stiffness. Indeed, an inflammatory component has been defined in PAH on the last years. Sepsis is a systemic complex syndrome, of infectious origin. The presence of inflammation is well established in this condition and it is also considered a risk factor for acute lung injury. Thrombotic events play important role in sepsis pathophysiology. The association between PAH and sepsis potentiate the metabolic oxygen consumption/offer imbalance, with very high mortality risk. Furthermore, it is possible that the association of these two conditions should intensify thrombotic events on pulmonary microcirculation, reducing area of pulmonary vascular bed available for blood flow. For the other side, an inflammation synergism observed on these two conditions should increase the respiratory system impedance.