Age-associated phenotypic imbalance in TCD4 and TCD8 cell subsets: comparison between healthy aged, smokers, COPD patients and young adults.

BACKGROUND: COPD is associated with an abnormal lung immune response that leads to tissue damage and remodeling of the lung, but also to systemic effects that compromise immune responses. Cigarette smoking also impacts on innate and adaptative immune responses, exerting dual, pro- and anti-inflammatory effects. Previously, we showed that COPD patients presented accelerated telomere shortening and decreased telomerase activity, while, paradoxically, cigarette-smokers exhibited preserved telomerase activity and slower rate of telomere shortening. RESULTS: Here, we evaluated the naive, CM, EM and TEMRA subsets of TCD4 and TCD8 cells according to the expression of CCR7/CD45RA. We compared age-matched COPD patients, cigarette-smokers without clinical-laboratory evidence of pulmonary compromise, and healthy individuals. They were additionally compared with a group of young adults. For each subset we analysed the expression of markers associated with late differentiation, senescence and exhaustion (CD27/CD28/CD57/KLRG1/PD1). We show that COPD patients presented a drastically reduced naive cells pool, and, paradoxically, increased fractions of naive cells expressing late differentiation, senescence or exhaustion markers, likely impacting on their immunocompetence. Pronounced phenotypic alterations were also evidenced in their three memory T-cell subsets compared with the other aged and young groups, suggesting an also dysfunctional memory pool. Surprisingly, our smokers showed a profile closer to the Healthy aged than COPD patients. They exhibited the usual age-associated shift of naive to EM TCD4 and TCD8 cells, but not to CM or TEMRA T-cells. Nonetheless, their naive T-cells phenotypes were in general similar to those of the Youngs and Healthy aged, suggesting a rather phenotypically preserved subset, while the memory T-cells exhibited increased proportions of cells with the late-differentiation or senescence/exhaustion markers as in the Healthy aged. CONCLUSION: Our study extends previous findings by showing that COPD patients have cells expressing a full range of late differentiated, senescent or exhausted phenotypes encompassing all TCD4 and TCD8 subsets, consistent with a premature immunosenescence phenotype. Surprisingly, the smokers group's results suggest that moderate to heavy chronic cigarette smoking did not accelerate the pace of immunosenescence as compared with the Healthy aged.

Identification of asthma phenotypes based on extrapulmonary treatable traits.

Asthma is a heterogeneous and complex disease, and a description of asthma phenotypes based on extrapulmonary treatable traits has not been previously reported.The objective of this study was to identify and characterise clusters based on clinical, functional, anthropometrical and psychological characteristics in participants with moderate-to-severe asthma.This was a cross-sectional multicentre study involving centres from Brazil and Australia. Participants (n=296) with moderate-to-severe asthma were consecutively recruited. Physical activity and sedentary time, clinical asthma control, anthropometric data, pulmonary function and psychological and health status were evaluated. Participants were classified by hierarchical cluster analysis and the clusters compared using ANOVA, Kruskal--Wallis and Chi-squared tests. Multiple logistic and linear regression models were performed to evaluate the association between variables.We identified four clusters: 1) participants with controlled asthma who were physically active; 2) participants with uncontrolled asthma who were physically inactive and more sedentary; 3) participants with uncontrolled asthma and low physical activity, who were also obese and experienced anxiety and/or depression symptoms; and 4) participants with very uncontrolled asthma who were physically inactive, more sedentary, obese and experienced anxiety and/or depression symptoms. Higher levels of sedentary time, female sex and anxiety symptoms were associated with increased odds of exacerbation risk, while being more active showed a protective factor for hospitalisation. Asthma control was associated with sex, the occurrence of exacerbation, physical activity and health status.Physical inactivity, obesity and symptoms of anxiety and/or depression were associated with worse asthma outcomes, and closely and inextricably associated with asthma control. This cluster analysis highlights the importance of assessing extrapulmonary traits to improve personalised management and outcomes for people with moderate and severe asthma.

Failure of Noninvasive Ventilation in Acute Respiratory Failure is Associated with Higher Mortality in Patients with Solid Tumors: A Retrospective Cohort Study.

BACKGROUND: Noninvasive Ventilation (NIV) is a well-established treatment for Acute Respiratory Failure (ARF) in hematological cancer. However, the NIV impact on mortality in patients with solid tumors is unclear. OBJECTIVE: To define the factors associated with NIV failure and mortality and to describe the mortality risk of patients with solid tumors requiring NIV for ARF treatment in the intensive care unit (ICU). METHODS: A retrospective cohort study of patients with solid tumors admitted into an ICU between Jan 2016 and Dec 2017, for cancer treatment, with ARF diagnosis that had used the NIV as first-line treatment. Our primary outcome was ICU and in-hospital mortality. The secondary outcome was NIV failure. A Cox proportional hazards regression was used to identify variables associated with mortality and NIV failure. Kaplan-Meier analyses were performed to demonstrate cumulative survival. RESULTS: A total of 226 patients with solid tumors were included. The ICU and hospital mortality rates were 57.5% and 69.5%, respectively. NIV failed in 52.2% of the patients. The use of vasopressors (HR 2.48 [95% CI: 1.43-4.30] p = 0.001), baseline lactate (HR 1.20 [95% CI: 1.07-1.35] p = 0.003), baseline PaO2/FiO2 ratio (HR1.33 [1.11-1.55] p = 0.002), and NIV success (HR0.17 [95% CI: 0.10-0.27] p = 0.005) was independently associated with hospital mortality. The use of vasopressors (HR 2.58 [95% CI: 1.41-4.73] p = 0.02), NIV duration (HR 0.93 [95% CI: 0.89-0.97] p = 0.003), and baseline lactate (HR 1.13 [95% CI: 1.06-1.20] p = 0.001) was associated with NIV failure. CONCLUSIONS: NIV failure was independently associated with an increase in both ICU and hospital mortality rates. In patients with NIV therapy indication, the duration of this intervention was associated with NIV failure.

Effect of an Exercise Program on Lymphocyte Proliferative Responses of COPD Patients.

Exercise training has been shown to reduce symptoms and exacerbations in COPD patients; however, the exercise effect on patients' immune response is poorly known. We thus verified if an exercise program (EP) impacted on proliferative T cell response of COPD patients. Fourteen non-O2 dependent COPD patients on standard treatment were studied. EP consisted in 24 sessions of aerobic and muscular training. Peripheral blood mononuclear cells were stimulated with the mitogen phytohemagglutinin and antigens from Haemophilus influenzae and cytomegalovirus, and the lymphocyte proliferative response (LPR) was assessed through the expression of Ki67 before and after the EP. The Quality of life [COPD assessment test (CAT)], dyspnea [(modified Medical Research Council scale (mMRC)], and 6-min walk distance were also assessed. The EP program increased significantly the LPR of TCD4+ lymphocytes to phytohemagglutinin and cytomegalovirus and H. influenzae antigens, but with TCD8+ lymphocytes the increase was less marked. Consistent with this, a higher proportion of TCD8+ than TCD4+ cells did not express the costimulatory molecule CD28. The EP also resulted in improvement of the quality of life, dyspnea, and physical capacity. The improvement in TCD4+ cell function may represent an additional mechanism through which the EP results in less exacerbations and hospitalizations.

Immune and Inflammatory Response in Atopic Elite Endurance Athletes.

The present study aimed to compare the immune and inflammatory responses between atopic (n=20) and non-atopic (n=39) elite endurance athletes. Fifty-nine elite runners and triathletes were assessed for the following measurements: Th1, Th2 and lymphocyte phenotyping and plasma levels of cortisol, chemokines, inflammatory cytokines and specific immunoglobulin E (IgE). Levels of salivary IgA, allergic symptoms and training data were also evaluated. No difference was observed in baseline lymphocyte levels. However, the Th1 lymphocytes of atopic athletes presented a lower response after activation. In contrast to this result, levels of salivary IgA and CXCL9 chemokine were higher in the atopic athletes. It was observed that the volume of training per week was linearly associated with Th1 levels, allergic symptoms and IgE levels. In addition, linear multiple regression analysis demonstrated that the volume of training was the only factor associated with allergic symptoms in atopic athletes (r=0.53; p=0.04). These results suggest that compared to non-atopic athletes, atopic athletes present a reduced Th1 response and higher levels of salivary IgA. Training volume is associated with the immune response and allergic symptoms, which suggests that they may play a role in the atopy in elite endurance athletes.

Elastic tape reduces dyspnea and improves health status in the short term in nonobese COPD males: A randomized controlled trial.

INTRODUCTION AND OBJECTIVES: The elastic tape (ET) is a novel intervention that acutely improves exercise capacity in laboratory tests; however, its effect on a patient's daily life remains unknown. This randomized controlled trial evaluated the effects of ET on daily life physical activity (DLPA), dyspnea symptoms, health status, and health-related quality of life (HRQoL) in individuals with COPD. METHODS: Fifty males with moderate to very severe COPD were randomly assigned to an intervention group (ETG, n = 25), receiving ET on the chest wall and abdomen, or a control group (CG, n = 25). The intervention was for 14 days. DLPA (accelerometry; steps per day, and sedentary time), dyspnea symptoms (transition dyspnea index, TDI; and modified Medical Research Council, mMRC), health status (COPD assessment test, CAT), and health-related quality of life (HRQoL, CRQ) were evaluated at baseline and on Day 21 after the intervention. RESULTS: No change in the DLPA was observed in between-group comparison. CG presented a reduction in step counts after 21days (-707,p <0.05) while ETG. maintained (-114,p > 0.94). However, ET reduced dyspnea symptoms in all TDI domains (functional, task, and effort) and on the mMRC scale after 14 days compared with CG (p < 0.01). Also, the ETG improved CAT score compared to the CG, reaching minimal clinical important difference (MCID) (-4.4 score, p <0.01). The ETG also improved in most CRQ domains reaching MCID after 21 days. CONCLUSIONS: ET does not modify DLPA but reduces dyspnea and improves health status and HRQoL in nonobese males with moderate to very severe COPD in the short term. This novel and low-cost intervention improves COPD symptoms.

Physical training in adults with asthma: An integrative approach on strategies, mechanisms, and benefits.

Asthma is a chronic airway disease characterized by airflow limitation and respiratory symptoms associated with chronic airway and systemic inflammation, bronchial hyperreactivity (BHR), and exercise-induced bronchoconstriction (EIB). Asthma is a heterogeneous disease classified according to distinct airway and systemic inflammation. Patients commonly present with several comorbidities, including anxiety, depression, poor sleep quality, and reduced physical activity levels. Individuals with moderate to severe asthma often have more symptoms and difficulty achieving adequate clinical control, which is associated with poor quality of life, despite proper pharmacological treatment. Physical training has been proposed as an adjunctive therapy for asthma. Initially, it was suggested that the effect of physical training might be attributed to the improved oxidative capacity and reduced production of exercise metabolites. However, in the last decade, there has been evidence that aerobic physical training promotes anti-inflammatory effects in asthma patients. Physical training improves BHR and EIB, asthma symptoms, clinical control, anxiety, and depression levels, sleep quality, lung function, exercise capacity, and dyspnea perception. Furthermore, physical training reduces medication consumption. The most commonly used exercise strategies are moderate aerobic and breathing exercises; however, other techniques, such as high-intensity interval training, have shown promising effects. In the present study, we reviewed the strategies and beneficial effects of exercise on clinical and pathophysiological asthma outcomes.

Functional impact on adults and older people after hospitalization by Covid-19.

BACKGROUND AND OBJECTIVES: Hospitalization by Covid-19 can cause persistent functional consequences after hospital discharge due to direct and indirect effects of SARS-COV-2 in several organs and systems of the body added to post-intensive care syndrome and prolonged bed rest. These impacts can lead to dependency in activities of daily living, mainly in older people due to aging process and functional decline. This study aimed to compare the effects of hospitalization by Covid-19 on functional capacity of adults and older people and to identify its associated factors. METHODS: Cross-sectional observational study of 159 survivors of hospitalization by Covid-19 after 1 month from discharge at Hospital das Clínicas of the University of São Paulo, divided into groups: adults (aged < 60 years) and older people (aged ≥ 60 years). Those who did not accept to participate, without availability or without ability to understand the questionnaires were excluded. Functional capacity was assessed by the Barthel Index and patients were classified according to their scores. Data analysis was performed in JASP Statistics program and the sample was compared between the age groups. Wilcoxon test was applied to compare before and after periods, Mann-Whitney test was used for between groups comparison. We adopted alpha = 0.05. RESULTS: The total Barthel Index median score was lower 1 month after hospital discharge than in the pre-Covid-19 period. Older people had worse functional status than adults before and also showed greater impairment after hospital discharge. Both groups showed lower Barthel Index classification than before, and older people presented more functional dependence than adults in both periods. Age, sarcopenia and frailty were associated factors. DISCUSSION: Hospitalization by Covid-19 impacts functional capacity after 1 month from discharge, especially in older people. Age, sarcopenia and frailty are associated factors. These results suggest need for care and rehabilitation of Covid-19 survivors.

Physical activity in daily life in Brazilian COPD patients during and after exacerbation.

BACKGROUND: Although hospitalization is recognized as an important cause of reduction in physical activity in daily life (PADL) in COPD, there is only one study evaluating this effect, and it was performed in European COPD patients who have a lower PADL than that of South American COPD patients. OBJECTIVES: To investigate the effect of hospitalization due to acute exacerbation of PADL in Brazilian COPD patients and to evaluate the factors that determines the physical activity levels during hospitalization and after discharge. METHODS: PADL was quantified using a 3-axis accelerometer on the 3rd day of hospitalization and 1 month after discharge in Brazilian COPD patients who were hospitalized due to disease exacerbation. Six-minute walking distance (6MWD), lower limb strength and pulmonary function were also evaluated. RESULTS: A total of 20 patients completed the study. During hospitalization, patients spent most of the time (87%) lying down or sitting; however, 1 month after they were walking >40 min/day. In addition, patients with prior hospitalization had a lower level of physical activity compared to those without a previous history of hospitalization. The time spent walking during hospitalization was significantly explained by the quadriceps strength (r(2) = 0.29; p < 0.05), while 1 month after, the time spent walking was only significantly explained by the 6MWD (r(2) = 0.51; p = 0.02). CONCLUSIONS: Brazilian COPD patients are inactive during hospitalization but become active 1 month after discharge. Previously hospitalized are more inactive both during and after exacerbation. The quadriceps strength and 6MWD explain the physical activity levels during hospitalization and at home, respectively.

Constant-Load Exercise Versus High-Intensity Interval Training on Aerobic Fitness in Moderate-to-Severe Asthma: A Randomized Controlled Trial.

BACKGROUND: The effects of high-intensity interval training (HIIT) on dyspnea and aerobic fitness in adults with asthma are poorly understood. OBJECTIVE: To compare constant-load exercise (CLE) versus HIIT for improvements in dyspnea symptoms and clinical control in adults with moderate-to-severe asthma. METHODS: Participants were randomized into 2 groups: CLE (n = 27; started with 70% of maximal watts [Wmax] obtained during cardiopulmonary exercise testing [CPET]) and HIIT (n = 28; started with 80% and increased until 140% Wmax). Exercise training lasted 12 weeks (twice/week, 40 minutes/session on a cycle ergometer), and the intensity was based on CPET. Clinical asthma control (Asthma Control Questionnaire), aerobic fitness (the peak of oxygen uptake), health-related quality of life (Asthma Quality of Life Questionnaire), physical activity levels (PAL; accelerometer), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale questionnaire), and dyspnea were evaluated before and after the intervention. Systemic and airway inflammation were also assessed. Two-way analysis of variance and χ2 tests were used for comparisons. Sixteen participants dropped out during the interventions and returned for the final evaluations. RESULTS: The CLE and HIIT groups showed similar improvements in aerobic fitness. The HIIT group had lower dyspnea and fatigue perception scores and higher PAL than the CLE group (P < .05) and clinical improvements in the psychosocial distress. In addition, only the HIIT group achieved a minimal clinically important difference in asthma symptoms. There was no change in the systemic and airway inflammation (P > .05). CONCLUSION: Both interventions promoted similar improvements in aerobic fitness; however, HIIT induced a greater reduction in dyspnea and fatigue perception. Similar responses were observed for other variables.

Ambulation capacity, age, immunosuppression, and mechanical ventilation are risk factors of in-hospital death in severe COVID-19: a cohort study.

IMPORTANCE: Despite ambulation capacity being associated with a decreased level of physical activity and survival may be influenced by the functional capacity, studies have not addressed the association between ambulation capacity and death in patients hospitalized by COVID-19. OBJECTIVE: To verify the functional, clinical, and sociodemographic risk factors associated with in-hospital death in individuals with severe COVID-19. METHODS: It is a cohort retrospective study performed at a large tertiary hospital. Patients 18 years of age or more, of both sexes, hospitalized due to severe COVID-19 were included. Cases with dubious medical records and/or missing essential data were excluded. Patients were classified according to their ambulation capacity before the COVID-19 infection. Information regarding sociodemographic characteristics, in-hospital death, total hospital stays, Intensive Care Unit (ICU) stays, and the necessity of Mechanical Ventilation (MV) were collected from medical records and registered in a RedCap database. Multiple logistic regression analysis was used to identify possible factors associated with the in-hospital death rate. RESULTS: Data from 1110 participants were included in the statistical analysis. The median age of the patients was 57 (46‒66) years, 58.42% (n = 590) were male, and 61.73% (n = 602) were brown or black. The case fatality rate during hospitalization was 36.0% (n = 363). In-hospital death was associated with ambulation capacity; dependent ambulators (OR = 2.3; CI 95% = 1.2-4.4) and non-functional ambulation (OR = 1.9; CI 95% = 1.1-3.3), age [older adults (OR = 3.0; CI 95% = 1.9‒4.), ICU stays (OR = 1.4; CI 95% = 1.2‒1.4), immunosuppression (OR = 5.5 CI 95% = 2.3‒13.5) and mechanical ventilation (OR = 27.5; CI 95% = 12.0-62.9). CONCLUSION AND RELEVANCE: Decreased ambulation capacity, age, length of ICU stay, immunosuppression, and mechanical ventilation was associated with a high risk of in-hospital death due to COVID-19.

Fat mass to fat-free mass ratio and its associations with clinical characteristics in asthma.

BACKGROUND: Fat mass to fat-free mass ratio (FM/FFM) assesses the combined effect of the balance between fat mass and fat-free mass. AIMS: to evaluate the associations beetween FM/FFM and clinical outcomes in asthma and to compare clinical characteristics between individuals with higher and lower FM/FFM. METHODS: 128 participants with asthma underwent anthropometric, spirometry and bioelectrical impedance assessments. Physical activity in daily life (PADL) was assessed by the Actigraph for 7 days. Daily dose of inhaled medication, steps of pharmacological treatment, Asthma Control Questionnaire, Asthma Quality of Life Questionnaire and Hospital Anxiety and Depression Scale were also assessed. Participants were classified into two groups according to the 50th percentile of reference values for FM/FFM. RESULTS: Individuals with higher FM/FFM (n=75) used higher daily doses of inhaled corticosteroids, had worse lung function and fewer steps/day when compared to those with lower FM/FFM (n=53) (P≤0.021). Associations were found between absolute values of FM/FFM with lung function (FEV1 and FVC [liters]): R2=0.207 and 0.364;P<0.0001), and between the categories of lower or higher FM/FFM with steps of medication treatment (Cramer's V=0.218;P=0.016) and level of PADL (Cramer's V=0.236;P=0.009). The highest FM/FFM was a determining factor of physical inactivity (OR: 3.21;95%CI:1.17-8.78) and highest steps of pharmacological treatment (OR: 8.89;95%CI:1.23-64.08). CONCLUSION: Higher FM/FFM is significantly associated with worse clinical characteristics in individuals with asthma, such as higher doses of inhaled corticosteroids, worse lung function and fewer steps/day. Moreover, higher FM/FFM is a determining factor of physical inactivity and the highest steps of pharmacological treatment for asthma.

Musculoskeletal dysfunction and pain in adults with asthma.

BACKGROUND: The mechanical alterations related to the overload of respiratory muscles observed in adults with persistent asthma might lead to the development of chronic alterations in posture, musculoskeletal dysfunction and pain; however, these changes remain poorly understood. OBJECTIVE: This study aimed to assess postural alignment, muscle shortening and chronic pain in adults with persistent asthma. METHODS: This cross-sectional and controlled study enrolled 30 patients with mild (n = 17) and severe (n = 13) persistent asthma. Fifteen non-asthmatic volunteers were also assessed. Asthma was classified by the Global Initiative for Asthma (GINA) guidelines. Postural alignment and muscle shortening were evaluated by head and shoulder positions, chest wall mobility, and posterior (trunk and lower limb) muscle flexibility. In addition, the measures used were previously tested for their reproducibility. Pain complaints were also assessed. RESULTS: In comparison with non-asthmatic subjects, patients with mild or severe persistent asthma held their head and shoulders more forward and had lower chest wall expansion, decreased shoulder internal rotation, and decreased thoracic spine flexibility. Chronic lower thoracic, cervical, and shoulder pain was significantly increased in patients with mild or severe asthma compared with non-asthmatic subjects (p < 0.05). CONCLUSION: Adults with persistent asthma have musculoskeletal dysfunction and chronic pain that is independent of the severity of their disease but that might be related to their age at the onset of disease symptoms.

Walking Training Improves Ambulatory Blood Pressure Variability in Claudication. / Treinamento de Caminhada Melhora a Variabilidade da Pressão Arterial Ambulatorial em Claudicantes.

BACKGROUND: Walking training (WT) improves walking capacity and reduces clinic blood pressure (BP) in patients with peripheral artery disease (PAD), but its effects on ambulatory BP remains unknown. OBJECTIVE: To investigate the effect of 12 weeks of WT on ambulatory BP and its variability in patients with PAD. METHODS: Thirty-five male patients with PAD and claudication symptoms were randomly allocated into two groups: control (n = 16, 30 min of stretching) and WT (n = 19, 15 bouts of 2 min of walking at the heart rate of leg pain threshold interspersed by 2 min of upright rest). Before and after 12 weeks, 24-hour ambulatory BP was assessed. Ambulatory BP variability indices assessed at both time points included the 24-hour standard deviation (SD24), the awake and asleep weighted standard deviation (SDdn), and the 24-hour average real variability (ARV24). Data were analyzed by mixed two-way ANOVAs, considering P<0.05 as significant. RESULTS: After 12 weeks, neither group had significant changes in 24-hour, awake and sleep BPs. The WT decreased systolic and mean BP variabilities (Systolic BP - 13.3±2.8 vs 11.8±2.3, 12.1±2.84 vs 10.7±2.5 and 9.4±2.3 vs 8.8±2.2 mmHg); Mean BP - 11.0±1.7 vs 10.4±1.9, 10.1±1.6 vs 9.1±1.7 and 8.0.±1.7 vs 7.2±1.5 mmHg) for SD24, SDdn and ARV24, respectively). Neither group had significant changes in diastolic BP variabilities after 12 weeks. CONCLUSIONS: The WT does not change ambulatory BP levels but decreases ambulatory BP variability in patients with PAD. This improvement may have a favorable impact on the cardiovascular risk of patients with symptomatic PAD. (Arq Bras Cardiol. 2021; 116(5):898-905).

FUNDAMENTO: O treinamento de caminhada (TC) melhora a capacidade de caminhar e reduz a pressão arterial (PA) clínica em pacientes com doença arterial periférica (DAP), mas seus efeitos na PA ambulatorial permanecem desconhecidos. OBJETIVO: Investigar o efeito de 12 semanas de TC na PA ambulatorial e sua variabilidade em pacientes com DAP. MÉTODOS: Trinta e cinco pacientes do sexo masculino com DAP e sintomas de claudicação foram alocados aleatoriamente em dois grupos: controle (n = 16, 30 min de alongamento) e TC (n = 19, 15 séries de 2 minutos de caminhada na frequência cardíaca em que ocorreu limiar de dor intercalados por 2 minutos de repouso em pé). Antes e depois de 12 semanas, a PA ambulatorial de 24 horas foi avaliada. Os índices de variabilidade da PA ambulatorial avaliados em ambos os momentos incluíram o desvio-padrão de 24 horas (DP24), o desvio-padrão ponderado de vigília e sono (DPvs) e a variabilidade real média de 24 horas (VRM24). Os dados foram analisados por ANOVAs mistas de dois fatores, considerando significativo P<0,05. RESULTADOS: Após 12 semanas, nenhum dos grupos apresentou alterações na PA de 24 horas, vigília e sono. O TC diminuiu as variabilidades da PA sistólica e média (PA sistólica ­ 13,3 ± 2,8 vs 11,8 ± 2,3; 12,1 ± 2,84 vs 10,7 ± 2,5; e 9,4 ± 2,3 vs 8,8 ± 2,2 mmHg; PA média ­ 11,0 ± 1,7 vs 10,4 ± 1,9; 10,1 ± 1,6 vs 9,1 ± 1,7; e 8,0 ± 1,7 vs 7,2 ± 1,5 mmHg para DP24, DPvs e VRM24, respectivamente). Nenhum dos grupos apresentou mudanças significantesnos índices de variabilidade da PA diastólica após 12 semanas. CONCLUSÕES: O TC não altera os níveis ambulatoriais da PA, mas diminui a sua variabilidade em pacientes com DAP. Essa melhora pode ter um impacto favorável no risco cardiovascular de pacientes com DAP sintomática. (Arq Bras Cardiol. 2021; 116(5):898-905).

Strength training increases walking tolerance in intermittent claudication patients: randomized trial.

OBJECTIVE: To analyze the effects of strength training (ST) in walking capacity in patients with intermittent claudication (IC) compared with walking training (WT) effects. METHODS: Thirty patients with IC were randomized into ST and WT. Both groups trained twice a week for 12 weeks at the same rate of perceived exertion. ST consisted of three sets of 10 repetitions of whole body exercises. WT consisted of 15 bouts of 2-minute walking. Before and after the training program walking capacity, peak VO(2), VO(2) at the first stage of treadmill test, ankle brachial index, ischemic window, and knee extension strength were measured. RESULTS: ST improved initial claudication distance (358 +/- 224 vs 504 +/- 276 meters; P < .01), total walking distance (618 +/- 282 to 775 +/- 334 meters; P < .01), VO(2) at the first stage of treadmill test (9.7 +/- 2.6 vs 8.1 +/- 1.7 mL.kg(-1).minute; P < .01), ischemic window (0.81 +/- 1.16 vs 0.43 +/- 0.47 mm Hg minute meters(-1); P = .04), and knee extension strength (19 +/- 9 vs 21 +/- 8 kg and 21 +/- 9 vs 23 +/- 9; P < .01). Strength increases correlated with the increase in initial claudication distance (r = 0.64; P = .01) and with the decrease in VO(2) measured at the first stage of the treadmill test (r = -0.52; P = .04 and r = -0.55; P = .03). Adaptations following ST were similar to the ones observed after WT; however, patients reported lower pain during ST than WT (P < .01). CONCLUSION: ST improves functional limitation similarly to WT but it produces lower pain, suggesting that this type of exercise could be useful and should be considered in patients with IC.

Role of nitric oxide in hyperpnea-induced bronchoconstriction and airway microvascular permeability in guinea pigs.

The present study aimed to evaluate the role of nitric oxide (NO) on hyperpnea-induced bronchoconstriction (HIB) and airway microvascular hyperpermeability (AMP). Sixty-four guinea pigs were anesthetized, tracheotomized, cannulated, and connected to animal ventilator to obtain pulmonary baseline respiratory system resistance (Rrs). Animals were then submitted to 5 minutes hyperpnea and Rrs was evaluated during 15 minutes after hyperpnea. AMP was evaluated by Evans blue dye (25 mg/kg) extravasation in airway tissues. Constitutive and inductible NO was evaluated by pretreating animals with N(G)-nitro-L-arginine methyl ester (L-NAME) (50 mg/kg), aminoguadinine (AG) (50 mg/kg), and L-arginine (100 mg/kg) and exhaled NO (NOex) was evaluated before and after drug administration and hyperpnea. The results show that L-NAME potentiated (57%) HIB and this effect was totally reversed by L-arginine pretreatment, whereas AG did not have effect on HIB. L-NAME decreased basal AMP (48%), but neither L-NAME nor AG had any effect on hyperpnea-induced AMP. NOex levels were decreased by 50% with L-NAME, effect that was reversed by L-arginine treatment. These results suggest that constitutive but not inducible NO could have a bronchoprotective effect on HIB in guinea pigs. The authors also observed that neither constitutive nor inducible NO seems to have any effect on hyperpnea-induced AMP.

Dysfunctional breathing: what do we know?

Dysfunctional breathing (DB) is a respiratory condition characterized by irregular breathing patterns that occur either in the absence of concurrent diseases or secondary to cardiopulmonary diseases. Although the primary symptom is often dyspnea or "air hunger", DB is also associated with nonrespiratory symptoms such as dizziness and palpitations. DB has been identified across all ages. Its prevalence among adults in primary care in the United Kingdom is approximately 9.5%. In addition, among individuals with asthma, a positive diagnosis of DB is found in a third of women and a fifth of men. Although DB has been investigated for decades, it remains poorly understood because of a paucity of high-quality clinical trials and validated outcome measures specific to this population. Accordingly, DB is often underdiagnosed or misdiagnosed, given the similarity of its associated symptoms (dyspnea, tachycardia, and dizziness) to those of other common cardiopulmonary diseases such as COPD and asthma. The high rates of misdiagnosis of DB suggest that health care professionals do not fully understand this condition and may therefore fail to provide patients with an appropriate treatment. Given the multifarious, psychophysiological nature of DB, a holistic, multidimensional assessment would seem the most appropriate way to enhance understanding and diagnostic accuracy. The present narrative review was developed as a means of summarizing the available evidence about DB, as well as improving understanding of the condition by researchers and practitioners.

Dose-dependent hepatic response to subchronic administration of nandrolone decanoate.

BACKGROUND: Androgenic anabolic steroids (AAS) are synthetic hormone derivatives of testosterone and are mainly used to enhance athletic performance and muscle mass, but medical applications also have been described. Short- and long-term side effects have been demonstrated in many organs, but the liver adverse effects are the most common and serious ones associated with AAS use. However, these effects have been supported by few clinical and experimental studies. OBJECTIVE: To evaluate the hepatic function and structure after 5 wk of nandrolone decanoate administration at three different doses. METHODS: Twenty-seven adult male Wistar rats were randomly assigned to the following groups: control, clinical, intermediate, and suprapharmacological doses of nandrolone decanoate during 5 wk. RESULTS: The biochemical studies showed that nandrolone decanoate administration leads to a dose-dependent increase in serum levels of the aspartate aminotransferase (AST) (P < 0.05), alanine aminotransferase (ALT) (P < 0.01), and alkaline phosphatase (ALP) (P < 0.001), as well as a significant decrease in total proteins (P < 0.01), bilirubin (P < 0.05), total cholesterol and fractions (P < 0.05), and triglycerides (P < 0.05). Although a significant statistical difference was found for AST, ALT, and ALP when compared with the control group, their values remained within the normal range. The number of Kupffer cells was increased in the liver parenchyma (P < 0.05), and the content of collagen was increased in the central lobular vein wall, in the hepatic parenchyma, and in the portal space (P < 0.05). CONCLUSIONS: These results suggest that subchronic treatment with nandrolone decanoate, mainly administered at higher-than-clinical doses, are potentially deleterious to the liver, leading to incipient fibrosis.

Air trapping: The major factor limiting diaphragm mobility in chronic obstructive pulmonary disease patients.

BACKGROUND AND OBJECTIVE: Patients with COPD can have impaired diaphragm mechanics. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. This study evaluated the relationship between pulmonary function and diaphragm mobility, as well as that between respiratory muscle strength and diaphragm mobility, in COPD patients. METHODS: COPD patients with pulmonary hyperinflation (n = 54) and healthy subjects (n = 20) were studied. Patients were tested for pulmonary function, maximal respiratory pressures and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein. RESULTS: COPD patients had less diaphragm mobility than did healthy individuals (36.5 +/- 10.9 mm vs 46.3 +/- 9.5 mm, P = 0.001). In COPD patients, diaphragm mobility correlated strongly with pulmonary function parameters that quantify air trapping (RV: r = -0.60, P < 0.001; RV/TLC: r = -0.76, P < 0.001), moderately with airway obstruction (FEV(1): r = 0.55, P < 0.001; airway resistance: r = -0.32, P = 0.02) and weakly with pulmonary hyperinflation (TLC: r = -0.28, P = 0.04). No relationship was observed between diaphragm mobility and respiratory muscle strength (maximal inspiratory pressure: r = -0.11, P = 0.43; maximal expiratory pressure: r = 0.03, P = 0.80). CONCLUSION: The results of this study suggest that the reduction in diaphragm mobility in COPD patients is mainly due to air trapping and is not influenced by respiratory muscle strength or pulmonary hyperinflation.

Exercise training on disease control and quality of life in asthmatic children.

PURPOSE: Aerobic training has been shown to be effective in improving cardiopulmonary fitness in asthmatic children. However, the actual impact of physical training on clinical indicators of disease control remains controversial. METHODS: Thirty-eight children with moderate to severe persistent asthma were randomly assigned to control (N=17) and training (N=21) groups. Spirometry, exercise challenge, and maximum incremental cardiopulmonary exercise tests were performed 16 wk apart. Daily doses of inhaled steroids and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores were also recorded. RESULTS: Physical training was associated with significant improvements in physiological variables at peak and submaximal exercise (P<0.05); in contrast, no significant changes were found in controls. Severity of exercise-induced bronchoconstriction (EIB) and postexercise breathlessness were significantly lessened in trained patients; improvement in fitness and EIB, however, were not linearly related (P>0.05). In addition, PAQLQ scores improved only in trained children (P<0.01). Daily doses of inhaled steroids were reduced in trained patients (52%), but they remained unchanged or increased in controls (70.6%) (P=0.07). CONCLUSION: Supervised exercise training might be associated with beneficial effects on disease control and quality of life in asthmatic children. These data suggest an adjunct role of physical conditioning on clinical management of patients with more advanced disease.