Accreditation of medical education in Brazil: an evaluation of seventy-six medical schools.

BACKGROUND: We present the first results of the Accreditation System of Medical Schools (Sistema de Acreditação de Escolas Médicas - SAEME) in Brazil. METHODS: We evaluated the results of the accreditation of medical schools from 2015 to 2023. The self-evaluation form of the SAEME is specific for medical education programs and has eighty domains, which results in final decisions that are sufficient or insufficient for each domain. We evaluated the results of the first seventy-six medical schools evaluated by the SAEME. RESULTS: Fifty-five medical schools (72.4%) were accredited, and 21 (27.6%) were not. Seventy-two (94.7%) medical schools were considered sufficient in social accountability, 93.4% in integration with the family health program, 75.0% in faculty development programs and 78.9% in environmental sustainability. There was an emphasis on SAEME in student well-being, with seventeen domains in this area, and 71.7% of these domains were sufficient. The areas with the lowest levels of sufficiency were interprofessional education, mentoring programs, student assessment and weekly distribution of educational activities. CONCLUSION: Medical schools in Brazil are strongly committed to social accountability, integration with the national health system, environmental sustainability and student well-being programs. SAEME is moving from episodic evaluations of medical schools to continuous quality improvement policies.

Professional values at the beginning of medical school: a quasi-experimental study.

BACKGROUND: Teaching professionalism in medical schools is central to medical education and society. We evaluated how medical students view the values of the medical profession on their first day of medical school and the influence of a conference about the competences of this profession on these students' levels of reflection. METHODS: We studied two groups of medical students who wrote narratives about the values of the medical profession and the influence of the COVID-19 pandemic on these values. The first group wrote the narratives after a conference about the competences of the medical profession (intervention group), and the second group wrote the same narratives after a biochemistry conference (control group). We also compared the levels of reflection of these two groups of students. RESULTS: Among the 175 medical students entering in the 2022 academic year, 159 agreed to participate in the study (response rate = 90.8%). There were more references to positive than negative models of doctor‒patient relationships experienced by the students (58.5% and 41.5% of responses, respectively). The intervention group referred to a more significant number of values than the control group did. The most cited values were empathy, humility, and ethics; the main competences were technical competence, communication/active listening, and resilience. The students' perspectives of the values of their future profession were strongly and positively influenced by the pandemic experience. The students realized the need for constant updating, basing medical practice on scientific evidence, and employing skills/attitudes such as resilience, flexibility, and collaboration for teamwork. Analysis of the levels of reflection in the narratives showed a predominance of reflections with a higher level in the intervention group and of those with a lower level in the control group. CONCLUSIONS: Our study showed that medical students, upon entering medical school, already have a view of medical professionalism, although they still need to present a deeper level of self-reflection. A single, planned intervention in medical professionalism can promote self-reflection. The vision of medical professional identity was strongly influenced by the COVID-19 pandemic, positively impacting the formation of a professional identity among the students who decided to enter medical school.

Is there an association among spirituality, resilience and empathy in medical students?

BACKGROUND: Spirituality has religious and nonreligious dimensions and is often linked to well-being, positive emotions, connection and meaning in life. Both empathy and resilience are important in medical training and future professional practice since they are considered core skills related to professionalism and patient care. Our study aimed to understand the relationships among spirituality, resilience, and empathy in medical students. We also aimed to determine whether there are differences by gender and between medical students in different years of a medical program. METHODS: Medical students (n = 1370) of the first to fourth years of a six-year medical program, from six medical schools, completed questionnaires to assess empathy (Jefferson Empathy Scale and Davis Multidimensional Interpersonal Reactivity Scale) and resilience (Wagnild & Young Scale) and to rate their spirituality. RESULTS: Medical students with high spirituality showed higher scores for both resilience and empathy (p < 0.001). In addition, we observed higher levels of both spirituality and empathy, but not resilience, in female medical students than in male medical students. In contrast, we did not detect significant differences in spirituality, empathy, or resilience between students in different years of medical school. CONCLUSION: Medical students with high levels of spirituality have also higher scores for both empathy and resilience. Spirituality, empathy and resilience have similar values for students in different years of a medical program.

Medical students' participation in the Volunteering Program during the COVID-19 pandemic: a qualitative study about motivation and the development of new competencies.

BACKGROUND: Considering evidence on competency-based curricula and the benefits of volunteering, this study highlights innovative ideas to improve medical education during the COVID-19 pandemic. We investigated the motivations and perceptions of competencies developed as leadership and management skills in medical students who joined the COVID-19 Volunteering Program in a Brazilian medical school. METHODS: We performed a cross-sectional, qualitative study involving medical students from the University of São Paulo, Brazil. They were invited to participate in an institutional Volunteering Program during the pandemic and filled out online application forms, including sociodemographic fields and two open-ended questions about their motivation to volunteer and perceptions of their own competencies. At the end of the program, students who were involved in management-related activities were also invited to participate in focus group interviews to track their perceptions about volunteering in this area. Data were submitted to descriptive and content analysis methods. All participants provided informed consent with electronic signatures. RESULTS: A total of 286 medical students subscribed to the Volunteering Program: 171 (60%) were men, 152 (53%) were enrolled in their 5th year of medical school, and 158 (55%) were 23-25 years old. One hundred and twelve (44%) students reported that they were motivated by altruistic reasons, 95 (37%) reported duty and 47 (19%) prioritized academic interests. Concerning CanMEDS competencies, 91 (36%) students' responses matched the Scholar component, followed by 51 (20%) with Collaborator, 49 (20%) with Professional, 32 (13%) with Communicator, 17 (7%) with Leader and 11 (4%) with Health Advocate. In focus groups, students reported the importance of management and leadership skills as a curricular component, motivations to volunteer, and acquired skills from volunteering in management and leadership-related activities, thereby indicating the development of resilient attitudes. CONCLUSIONS: Students who participated in the School of Medicine of University of Sao Paulo (FMUSP) Volunteering Program reported being motivated to help others (altruistic reasons) and to serve society as future health professionals (duty). Knowledge and work-related competencies prevailed over leadership or soft skills, emphasizing the importance of including such activities in the curriculum. Participating in management-related activities could help develop a more resilient attitude toward medical training. Volunteering programs offer students opportunities to develop competencies essential for their roles as future health professionals. Thus, we should think about including such activities in the curricular structure.

Sleepiness, sleep deprivation, quality of life, mental symptoms and perception of academic environment in medical students.

BACKGROUND: It has been previously shown that a high percentage of medical students have sleep problems that interfere with academic performance and mental health. METHODS: To study the impact of sleep quality, daytime somnolence, and sleep deprivation on medical students, we analyzed data from a multicenter study with medical students in Brazil (22 medical schools, 1350 randomized medical students). We applied questionnaires of daytime sleepiness, quality of sleep, quality of life, anxiety and depression symptoms and perception of educational environment. RESULTS: 37.8% of medical students presented mild values of daytime sleepiness (Epworth Sleepiness Scale - ESS) and 8.7% presented moderate/severe values. The percentage of female medical students that presented ESS values high or very high was significantly greater than male medical students (p <  0.05). Students with lower ESS scores presented significantly greater scores of quality of life and perception of educational environment and lower scores of depression and anxiety symptoms, and these relationships showed a dose-effect pattern. Medical students reporting more sleep deprivation showed significantly greater odds ratios of presenting anxiety and depression symptoms and lower odds of good quality of life or perception of educational environment. CONCLUSIONS: There is a significant association between sleep deprivation and daytime sleepiness with the perception of quality of life and educational environment in medical students.

The relationship between heart rate and VO2 in moderate-to-severe asthmatics.

Objective: The main purpose of this study was to evaluate whether the %HRR-%VO2R relationship and %HRR-VO2peak relationship are affected in patients with moderate or severe asthma and whether airway obstruction and aerobic capacity influence these relationships.Methods: A linear regression was calculated using the paired %VO2R-%HRR and %VO2peak-%HRR for 93 subjects with asthma. The mean slope and y-intercept were calculated and compared with the line of identity (y-intercept = 0, slope = 1) for all patients and subgroups for the following conditions: low and normal VO2peak and low and normal FEV1.Results: The slope and intercepts of %VO2R-%HRR were similar to the line of identity for all groups (p > 0.05), and the regressions between %HRR and %VO2peak did not coincide with the line of identity for all groups (p < 0.05). There were no associations between the intercepts of the %HRR-VO2peak and the %HRR-%VO2R relationship with the VO2peak (p > 0.05) or FEV1 (p > 0.05).Conclusions: This is the first study to confirm a constant equivalence between %HRR and %VO2R in outpatients with moderate or severe asthma. Our data also suggest that the relationship between %HRR and %VO2peak is unreliable. These results support the use of %HRR in relation to %VO2R to estimate exercise intensity in this population, independently of the pulmonary function and fitness level.

Seasonal changes influence the improvement in asthma symptoms by exercise training in subjects with asthma*.

OBJECTIVE: To investigate whether patients with moderate-to-severe asthma who commence an exercise training program in winter or summer show differences in exercise capacity, health-related quality of life (HRQoL) and asthma symptoms. METHODS: Forty-two consecutive subjects visiting the outpatient clinic were enrolled in the 17-week rehabilitation program. One group of patients received the intervention from summer to winter (SWG, n = 21), and the other group participated from winter to summer (WSG, n = 21). Before and after the exercise training program, all patients were evaluated by cardiopulmonary exercise test, pulmonary function test, quality of life questionnaire and a daily diary that evaluated clinical asthma symptoms. RESULTS: After the training period, both groups improved similarly in health-related quality of life (HRQoL) and aerobic capacity. The WSG patients had a greater increase that those in the SWG in asthma symptom-free days (p < 0.05). CONCLUSIONS: Our results indicate that seasonal variations affect the improvement in asthma symptoms after an exercise training program but have no effect on health-related quality of life, exercise capacity or pulmonary function.

Vesicular acetylcholine transport deficiency potentiates some inflammatory responses induced by diesel exhaust particles.

Endogenous acetylcholine (ACh), which depends of the levels of vesicular ACh transport (VAChT) to be released, is the central mediator of the cholinergic anti-inflammatory system. ACh controls the release of cytokine in different models of inflammation. Diesel exhaust particles (DEP) are one of the major environmental pollutants produced in large quantity by automotive engines in urban center. DEP bind the lung parenchyma and induce inflammation. We evaluated whether cholinergic dysfunction worsens DEP-induced lung inflammation. Male mice with decreased ACh release due to reduced expression of VAChT (VAChT-KD mice) were submitted to DEP exposure for 30 days (3 mg/mL of DEP, once a day, five days a week) or saline. Pulmonary function and inflammation as well as extracellular matrix fiber deposition were evaluated. Additionally, airway and nasal epithelial mucus production were quantified. We found that DEP instillation worsened lung function and increased lung inflammation. Higher levels of mononuclear cells were observed in the peripheral blood of both wild-type (WT) and VAChT-KD mice. Also, both wild-type (WT) and VAChT-KD mice showed an increase in macrophages in bronchoalveolar lavage fluid (BALF) as well as increased expression of IL-4, IL-6, IL-13, TNF-α, and NF-κB in lung cells. The collagen fiber content in alveolar septa was also increased in both genotypes. On the other hand, we observed that granulocytes were increased only in VAChT-KD peripheral blood. Likewise, increased BALF lymphocytes and neutrophils as well as increased elastic fibers in alveolar septa, airway neutral mucus, and nasal epithelia acid mucus were observed only in VAChT-KD mice. The cytokines IL-4 and TNF-α were also higher in VAChT-KD mice compared with WT mice. In conclusion, decreased ability to release ACh exacerbates some of the lung alterations induced by DEP in mice, suggesting that VAChT-KD animals are more vulnerable to the effects of DEP in the lung.

Acute lung injury is reduced by the α7nAChR agonist PNU-282987 through changes in the macrophage profile.

Nicotinic α-7 acetylcholine receptor (nAChRα7) is a critical regulator of cholinergic anti-inflammatory actions in several diseases, including acute respiratory distress syndrome (ARDS). Given the potential importance of α7nAChR as a therapeutic target, we evaluated whether PNU-282987, an α7nAChR agonist, is effective in protecting the lung against inflammation. We performed intratracheal instillation of LPS to generate acute lung injury (ALI) in C57BL/6 mice. PNU-282987 treatment, either before or after ALI induction, reduced neutrophil recruitment and IL-1ß, TNF-α, IL-6, keratinocyte chemoattractant (KC), and IL-10 cytokine levels in the bronchoalveolar lavage fluid (P < 0.05). In addition, lung NF-κB phosphorylation decreased, along with collagen fiber deposition and the number of matrix metalloproteinase-9+ and -2+ cells, whereas the number of tissue inhibitor of metalloproteinase-1+ cells increased (P < 0.05). PNU-282987 treatment also reduced lung mRNA levels and the frequency of M1 macrophages, whereas cells expressing the M2-related markers CD206 and IL-10 increased, suggesting changes in the macrophage profile. Finally, PNU-282987 improved lung function in LPS-treated animals. The collective results suggest that PNU-282987, an agonist of α7nAChR, reduces LPS-induced experimental ALI, thus supporting the notion that drugs that act on α7nAChRs should be explored for ARDS treatment in humans.-Pinheiro, N. M., Santana, F. P. R., Almeida, R. R., Guerreiro, M., Martins, M. A., Caperuto, L. C., Câmara, N. O. S., Wensing, L. A., Prado, V. F., Tibério, I. F. L. C., Prado, M. A. M., Prado, C. M. Acute lung injury is reduced by the α7nAChR agonist PNU-282987 through changes in the macrophage profile.

The Role of Exercise in a Weight-Loss Program on Clinical Control in Obese Adults with Asthma. A Randomized Controlled Trial.

RATIONALE: Clinical control is difficult to achieve in obese patients with asthma. Bariatric surgery has been recommended for weight loss and to improve asthma control; however, the benefits of nonsurgical interventions have been poorly investigated. OBJECTIVES: To examine the effect of exercise training in a weight-loss program on asthma control, quality of life, inflammatory biomarkers, and lung function. METHODS: Fifty-five obese patients with asthma were randomly assigned to either a weight-loss program plus exercise (WL + E group, n = 28) or a weight-loss program plus sham (WL + S group, n = 27), where the weight-loss program included nutrition (caloric restriction) and psychological therapies. The WL + E group incorporated aerobic and resistance muscle training, whereas the WL + S group incorporated breathing and stretching exercises. MEASUREMENTS AND MAIN RESULTS: The primary outcome was clinical improvement in asthma control over 3 months. Secondary outcomes included quality of life, lung function, body composition, aerobic capacity, muscle strength, and inflammatory/antiinflammatory biomarkers. After 3 months, 51 patients were analyzed. Compared with the WL + S group, the WL + E group demonstrated improved clinical control scores (median [25th to 75th percentile], -0.7 [-1.3 to -0.3] vs. -0.3 [-0.9 to 0.4]; P = 0.01) and greater weight loss (mean ± SD, -6.8% ± 3.5 vs. -3.1% ± 2.6; P < 0.001) and aerobic capacity (median [25th to 75th percentile], 3.0 [2.4 to 4.0] vs. 0.9 [-0.3 to 1.3] ml O2 × kg-1 × min-1; P < 0.001). These improvements in the WL + E group were also accompanied by improvements in lung function, antiinflammatory biomarkers, and vitamin D levels, as well as reductions in airway and systemic inflammation. CONCLUSIONS: Adding exercise to a short-term weight-loss program should be considered as a useful strategy for achieving clinical control of asthma in obese patients. Clinical trial registered with www.clinicaltrials.gov (NCT 02188940).

Prophylactic and therapeutic treatment with the flavonone sakuranetin ameliorates LPS-induced acute lung injury.

Sakuranetin is the main isolate flavonoid from Baccharis retusa (Asteraceae) leaves and exhibits anti-inflammatory and antioxidative activities. Acute respiratory distress syndrome is an acute failure of the respiratory system for which effective treatment is urgently necessary. This study investigated the preventive and therapeutic effects of sakuranetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Animals were treated with intranasal sakuranetin 30 min before or 6 h after instillation of LPS. Twenty-four hours after ALI was induced, lung function, inflammation, macrophages population markers, collagen fiber deposition, the extent of oxidative stress, and the expression of matrix metalloprotease-9 (MMP-9), tissue inhibitor of MMP-9 (TIMP-1) and NF-κB were evaluated. The animals began to show lung alterations 6 h after LPS instillation, and these changes persisted until 24 h after LPS administration. Preventive and therapeutic treatment with sakuranetin reduced the neutrophils in the peripheral blood and in the bronchial alveolar lavage. Sakuranetin treatment also reduced macrophage populations, particularly that of M1-like macrophages. In addition, sakurnaetin treatment reduced keratinocyte-derived chemokines (IL-8 homolog) and NF-κB levels, collagen fiber formation, MMM-9 and TIMP-1-positive cells, and oxidative stress in lung tissues compared with LPS animals treated with vehicle. Finally, sakuranetin treatment also reduced total protein, and the levels of TNF-α and IL-1ß in the lung. This study shows that sakuranetin prevented and reduced pulmonary inflammation induced by LPS. Because sakuranetin modulates oxidative stress, the NF-κB pathway, and lung function, it may constitute a novel therapeutic candidate to prevent and treat ALI.

Regulatory T-Cell Distribution within Lung Compartments in COPD.

The importance of the adaptive immune response, specifically the role of regulatory T (Treg) cells in controlling the obstruction progression in smokers, has been highlighted. To quantify the adaptive immune cells in different lung compartments, we used lung tissues from 21 never-smokers without lung disease, 22 current and/or ex-smokers without lung disease (NOS) and 13 current and/or ex-smokers with chronic obstructive pulmonary disease (COPD) for histological analysis. We observed increased T, B, IL-17 and BAFF+ cells in small and large airways of COPD individuals; however, in the NOS, we only observed increase in T and IL-17+ cells only in small airways. A decrease in the density of Treg+, TGF-ß+ and IL-10+ in small and large airways was observed only in COPD individuals. In the lymphoid tissues, Treg, T,B-cells and BAFF+ cells were also increased in COPD; however, changes in Treg inhibitory associated cytokines were not observed in this compartment. Therefore, our results suggest that difference in Treg+ cell distributions in lung compartments and the decrease in TGF-ß+ and IL-10+ cells in the airways may lead to the obstruction in smokers.

Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases.

Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effects in vitro and in vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action.

Structurally Related Monoterpenes p-Cymene, Carvacrol and Thymol Isolated from Essential Oil from Leaves of Lippia sidoides Cham. (Verbenaceae) Protect Mice against Elastase-Induced Emphysema.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes (p-cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae). METHODS: Mices received porcine pancreatic elastase (PPE) and were treated with p-cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated. RESULTS: In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1ß, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-κB-positive cells in lung parenchyma (p < 0.05). All treatments attenuated levels of 8-iso-PGF2α but only thymol was able to reduced exhaled nitric oxide (p < 0.05). CONCLUSION: Monoterpenes p-cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.

Aerobic training decreases bronchial hyperresponsiveness and systemic inflammation in patients with moderate or severe asthma: a randomised controlled trial.

BACKGROUND: The benefits of aerobic training for the main features of asthma, such as bronchial hyperresponsiveness (BHR) and inflammation, are poorly understood. We investigated the effects of aerobic training on BHR (primary outcome), serum inflammatory cytokines (secondary outcome), clinical control and asthma quality of life (Asthma Quality of Life Questionnaire (AQLQ)) (tertiary outcomes). METHODS: Fifty-eight patients were randomly assigned to either the control group (CG) or the aerobic training group (TG). Patients in the CG (educational programme+breathing exercises (sham)) and the TG (same as the CG+aerobic training) were followed for 3 months. BHR, serum cytokine, clinical control, AQLQ, induced sputum and fractional exhaled nitric oxide (FeNO) were evaluated before and after the intervention. RESULTS: After 12 weeks, 43 patients (21 CG/22 TG) completed the study and were analysed. The TG improved in BHR by 1 doubling dose (dd) (95% CI 0.3 to 1.7 dd), and they experienced reduced interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) and improved AQLQ and asthma exacerbation (p<0.05). No effects were seen for IL-5, IL-8, IL-10, sputum cellularity, FeNO or Asthma Control Questionnaire 7 (ACQ-7; p>0.05). A within-group difference was found in the ACQ-6 for patients with non-well-controlled asthma and in sputum eosinophil and FeNO in patients in the TG who had worse airway inflammation. CONCLUSIONS: Aerobic training reduced BHR and serum proinflammatory cytokines and improved quality of life and asthma exacerbation in patients with moderate or severe asthma. These results suggest that adding exercise as an adjunct therapy to pharmacological treatment could improve the main features of asthma. TRIAL REGISTRATION NUMBER: NCT02033122.

A flavanone from Baccharis retusa (Asteraceae) prevents elastase-induced emphysema in mice by regulating NF-κB, oxidative stress and metalloproteinases.

BACKGROUND: Pulmonary emphysema is characterized by irreversible airflow obstruction, inflammation, oxidative stress imbalance and lung remodeling, resulting in reduced lung function and a lower quality of life. Flavonoids are plant compounds with potential anti-inflammatory and antioxidant effects that have been used in folk medicine. Our aim was to determine whether treatment with sakuranetin, a flavonoid extracted from the aerial parts of Baccharis retusa, interferes with the development of lung emphysema. METHODS: Intranasal saline or elastase was administered to mice; the animals were then treated with sakuranetin or vehicle 2 h later and again on days 7, 14 and 28. We evaluated lung function and the inflammatory profile in bronchoalveolar lavage fluid (BALF). The lungs were removed to evaluate alveolar enlargement, extracellular matrix fibers and the expression of MMP-9, MMP-12, TIMP-1, 8-iso-PGF-2α and p65-NF-κB in the fixed tissues as well as to evaluate cytokine levels and p65-NF-κB protein expression. RESULTS: In the elastase-treated animals, sakuranetin treatment reduced the alveolar enlargement, collagen and elastic fiber deposition and the number of MMP-9- and MMP-12-positive cells but increased TIMP-1 expression. In addition, sakuranetin treatment decreased the inflammation and the levels of TNF-α, IL-1ß and M-CSF in the BALF as well as the levels of NF-κB and 8-iso-PGF-2α in the lungs of the elastase-treated animals. However, this treatment did not affect the changes in lung function. CONCLUSION: These data emphasize the importance of oxidative stress and metalloproteinase imbalance in the development of emphysema and suggest that sakuranetin is a potent candidate that should be further investigated as an emphysema treatment. This compound may be useful for counteracting lung remodeling and oxidative stress and thus attenuating the development of emphysema.

Chronic exposure of diesel exhaust particles induces alveolar enlargement in mice.

BACKGROUND: Diesel exhaust particles (DEPs) are deposited into the respiratory tract and are thought to be a risk factor for the development of diseases of the respiratory system. In healthy individuals, the timing and mechanisms of respiratory tract injuries caused by chronic exposure to air pollution remain to be clarified. METHODS: We evaluated the effects of chronic exposure to DEP at doses below those found in a typical bus corridor in Sao Paulo (150 µg/m3). Male BALB/c mice were divided into mice receiving a nasal instillation: saline (saline; n = 30) and 30 µg/10 µL of DEP (DEP; n = 30). Nasal instillations were performed five days a week, over a period of 90 days. Bronchoalveolar lavage (BAL) was performed, and the concentrations of interleukin (IL)-4, IL-10, IL-13 and interferon-gamma (INF-γ) were determined by ELISA-immunoassay. Assessment of respiratory mechanics was performed. The gene expression of Muc5ac in lung was evaluated by RT-PCR. The presence of IL-13, MAC2+ macrophages, CD3+, CD4+, CD8+ T cells and CD20+ B cells in tissues was analysed by immunohistochemistry. Bronchial thickness and the collagen/elastic fibers density were evaluated by morphometry. We measured the mean linear intercept (Lm), a measure of alveolar distension, and the mean airspace diameter (D0) and statistical distribution (D2). RESULTS: DEP decreased IFN-γ levels in BAL (p = 0.03), but did not significantly alter IL-4, IL-10 and IL-13 levels. MAC2+ macrophage, CD4+ T cell and CD20+ B cell numbers were not altered; however, numbers of CD3+ T cells (p ≤ 0.001) and CD8+ T cells (p ≤ 0.001) increased in the parenchyma. Although IL-13 (p = 0.008) expression decreased in the bronchiolar epithelium, Muc5ac gene expression was not altered in the lung of DEP-exposed animals. Although respiratory mechanics, elastic and collagen density were not modified, the mean linear intercept (Lm) was increased in the DEP-exposed animals (p ≤ 0.001), and the index D2 was statistically different (p = 0.038) from the control animals. CONCLUSION: Our data suggest that nasal instillation of low doses of DEP over a period of 90 days results in alveolar enlargement in the pulmonary parenchyma of healthy mice.

Organic and inorganic fractions of diesel exhaust particles produce changes in mucin profile of mouse trachea explants.

Diesel exhaust particles (DEP) contain organic and inorganic elements that produce damage to the respiratory epithelium. The aim of this study was to determine the mucus profile of tracheal explants exposed to either crude diesel exhaust particles (DEP) or DEP treated with nitric acid (DEP/NA), with hexane (DEP/HEX), or with methanol (DEP/MET) at concentrations of 50 and 100 µg/ml for 30 and 60 min. Tracheal explants were subjected to morphometric analyses to study acidic (AB+), neutral (PAS+), and mixed (AB+/PAS+) mucus production and vacuolization (V). Incubation with 50 µg/ml crude DEP resulted in a rise in acid mucus production, an increase in vacuolization at 30 min, and reduction in neutral mucus at 30 and 60 min. Tracheas exposed to DEP/MET at 50 µg/ml for 30 or 60 min resulted in a significant decrease in neutral mucus production and an elevation in acid mucus production. DEP/HEX increased vacuolization at both 50 and 100 µg/ml at 30 and 60 min of exposure. Treatment with 50 µg/ml for 30 or 60 min significantly elevated mixed mucus levels. These results suggest that DEP appear to be more toxic when administered in combination with HEX or MET. DEP/MET modified the mucus profile of the epithelium, while DEP/HEX altered mucus extrusion, and these responses might be due to bioavailability of individual elements in DEP fractions.

The effects of exercise training in a weight loss lifestyle intervention on asthma control, quality of life and psychosocial symptoms in adult obese asthmatics: protocol of a randomized controlled trial.

BACKGROUND: Asthma and obesity are public health problems with increasing prevalence worldwide. Clinical and epidemiologic studies have demonstrated that obese asthmatics have worse clinical control and health related quality of life (HRQL) despite an optimized medical treatment. Bariatric surgery is successful to weight-loss and improves asthma control; however, the benefits of nonsurgical interventions remain unknown. METHODS/DESIGN: This is a randomized controlled trial with 2-arms parallel. Fifty-five moderate or severe asthmatics with grade II obesity (BMI ≥ 35 kg/m(2)) under optimized medication will be randomly assigned into either weight-loss program + sham (WL + S group) or weight-loss program + exercise (WL + E group). The weight loss program will be the same for both groups including nutrition and psychological therapies (every 15 days, total of 6 sessions, 60 min each). Exercise program will include aerobic and resistance muscle training while sham treatment will include a breathing and stretching program (both programs twice a week, 3 months, 60 min each session). The primary outcome variable will be asthma clinical control. Secondary outcomes include HRQL, levels of depression and anxiety, lung function, daily life physical activity, body composition, maximal aerobic capacity, strength muscle and sleep disorders. Potential mechanism (changes in lung mechanical and airway/systemic inflammation) will also be examined to explain the benefits in both groups. DISCUSSION: This study will bring a significant contribution to the literature evaluating the effects of exercise conditioning in a weight loss intervention in obese asthmatics as well as will evaluate possible involved mechanisms. TRIAL REGISTRATION: NCT02188940.

Comparison between breathing and aerobic exercise on clinical control in patients with moderate-to-severe asthma: protocol of a randomized trial.

BACKGROUND: Asthma is a chronic inflammatory airway disease characterized by reversible obstruction, inflammation and hyperresponsiveness to different stimulus. Aerobic and breathing exercises have been demonstrated to benefit asthmatic patients; however, there is no evidence comparing the effectiveness of these treatments. METHODS/DESIGN: This is a prospective, comparative, blinded, and randomized clinical trial with 2 groups that will receive distinct interventions. Forty-eight asthmatic adults with optimized medical treatment will be randomly divided into either aerobic (AG) or breathing exercises (BG). Patients will perform breathing or aerobic exercise twice a week for 3 months, totalizing 24 sessions of 40 minutes each. Before intervention, both groups will complete an educational program consisting of 2 educational classes. Before and after interventions, the following parameters will be quantified: clinical control (main outcome), health related quality of life, levels of anxiety and depression, daily living physical activity and maximal exercise capacity (secondary outcome). Hyperventilation syndrome symptoms, autonomic nervous imbalance, thoracoabdominal kinematics, inflammatory cells in the sputum, fraction of exhaled nitric oxide (FENO) and systemic inflammatory cytokines will also be evaluated as possible mechanisms to explain the benefits of both interventions. DISCUSSION: Although the benefits of breathing and aerobic exercises have been extensively studied, the comparison between both has never been investigated. Furthermore, the findings of our results will allow us to understand its application and suitability to patients that will have more benefits for every intervention optimizing its effect. TRIAL REGISTRATION: Clinicaltrials.gov; Identifier: NCT02065258.