External validity of type 2 diabetes clinical trials on cardiovascular outcomes for a multimorbid population.

AIM: To investigate the external validity of recent antihyperglycaemic trials evaluating cardiovascular outcomes in a multimorbid population. MATERIALS AND METHODS: Selection criteria of 15 randomized controlled trials from the 2020 American Diabetes Association Standard of Care statement were applied in a stepwise manner to tertiary care patients with type 2 diabetes. Primary outcomes were the number of patients eligible per individual trial and for the aggregate of trials. Secondary outcomes included patient predictors of trial eligibility. RESULTS: Of 1059 patients, the mean (SD) age was 66 (10.74) years, the median (IQR) Charlson index was 2 (2, 3) and 458 (43%) had documented cardiovascular disease. The median (IQR) number of patients included in individual trials was 263 (174.25-308.75) and 795 (75.1%) of them were eligible for at least one trial. Among those 264 ineligible, 127 (48.1%) had an HbA1c level of 7% or less and no cardiovascular disease; 53.5% and 34.4% of the patients were eligible for two and three different classes of drugs, respectively. The strongest predictor of trial eligibility was cardiovascular disease (risk ratio 2.17, 95% CI 2.01-2.35). CONCLUSIONS: A considerable proportion of multimorbid patients would be eligible for recent antihyperglycaemic trials. This positive finding can be attributed to development guidance in diabetes trials and the different approach we took, in which we evaluated inclusion by trials as an aggregate.

Barriers to daily life physical activities for Brazilian children with asthma: a cross-sectional study.

BackgroundObjective: To identify barriers to daily life physical activities (DLPA) and to evaluate physical activity levels for children with asthma and without asthma.Method: This is a cross-sectional study that enrolled 130 children with asthma and 54 non-asthma, from 7 to 12 years old. All of the children in both groups used an accelerometer for 6 consecutive days to assess DLPA and completed a questionnaire to evaluate barriers to physical activity. Accelerometer was used to measure each child's total number of steps, as well as the number of steps and the time spent in moderate-to-vigorous physical activity (MVPA). The barrier questionnaire to DLPA included 11 questions, divided into three domains: personal, social and environmental.Results: The most commonly described barrier to DLPA in the asthma and non-asthma groups was an unsafe environment (23.6% vs 28.5%, respectively). The asthma group reported having asthma (19%) and lack of parental encouragement (17.3%) as being other important barriers to DLPA. It was also observed that the asthma and non-asthma groups presented similar values for the total number of steps (13,379 ± 3,837 vs 14,055 ± 3,914, respectively, p > 0.05), number of steps in MVPA (5,654 ± 1,988 vs. 6,025 ± 2,058, p > 0.05), and time spent in MVPA (46 ± 16 min vs. 50.8 ± 14.7 min, p > 0.05).Conclusions: An unsafe environment is the main barrier to physical activity for Brazilian children. Moreover, a lack of parental encouragement and having asthma were considered to be barriers to physical activity. And lastly, children have similar levels of physical activity whether they have asthma or do not have asthma.

Differences in clerkship development between public and private Brazilian medical schools: an overview.

BACKGROUND: Around the world, it is very expensive to become a physician. Although public medical schools are less expensive than private medical schools, tuition fees are charged at public medical schools in the majority of countries. In Brazil, public medical schools, with the exception of municipal schools, are free. There has been little investigation of any differences in conditions offered by paid or free medical schools or what occurs in public and private clerkships in Brazil. We investigated the clerkship conditions offered to the students in both public and private Brazilian medical schools by gathering the opinions of clerkship coordinators and others responsible for clerkships. METHODS: A cross-sectional, descriptive, analytical study using an electronic questionnaire was answered by clerkship coordinators to compare the clerkships of 30 public and 38 private Brazilian medical schools from all regions of the country. The questionnaires covered various aspects of the clinical environments, student supervision, faculty development, student assessments, rotation evaluations and extracurricular activities developed by students. RESULTS: We observed significant differences between public and private medical schools in several aspects investigated. Based on the opinions of the clerkship coordinators, with the exception of access to university hospitals, which was predominantly offered by public medical schools, private medical schools offer better clerkship conditions. The main differences were related to the number of positions, infrastructure, clinical learning environments, faculty development, student assessments, rotation evaluations and students' extracurricular activities. CONCLUSION: This is the first study comparing Brazilian medical clerkships in private and public medical schools and provides a general vision of these programmes. It is necessary to further investigate clerkship development in the Brazilian medical school system and to study the differences between private and public medical schools globally.

Gender differences in the perception of quality of life during internal medicine training: a qualitative and quantitative analysis.

BACKGROUND: The higher level of participation by women in medicine may impact this profession's evolution due to gender differences perceived during medical school, after graduation and during residency. Gender differences regarding quality of life are associated with higher states of anxiety and depression among female physicians. We aimed to assess gender differences in the perception of quality of life with quantitative methods and to understand further, from the female residents´ point of view, the reasons that may influence the perception of quality of life using qualitative method. Resilience, empathy and daytime sleepiness were also scored. METHODS: We performed a cross-sectional study with first-year internal medicine residents to evaluate self-reported quality of life factors specific to medical residents (VERAS-Q), including empathy (Jefferson Scale of Empathy), resilience (Wagnild and Young Brief Resilience Scale) and daytime sleepiness (Epworth Scale). We explored, from the female residents´ view which factors may influence the perception of quality of life using a focus group method. RESULTS: In our study, one hundred and nine residents completed the survey: 31 (28.4%) were female and 78 (71.6%) were male. Female residents exhibited significantly lower scores than those of male residents for quality of life in the domains of time management (30.3, females vs 41.1, males; p < 0.001), psychology (48.1, females vs 56.7, males; p < 0.01) and physical health (42.8, females vs 53.6, males; p < 0.05). Female residents also scored higher for daytime sleepiness (13.0, females vs 9.0, males; p < 0.001), with pathological scores for daytime sleepiness. No significant gender differences were found in the resilience or empathy scores. The focus group assessment revealed difficulty in concentration and knowledge acquisition, insecurity, feelings of loss, greater critical perception, self-doubt and difficulty in creating effective bonds to support the training period as the main factors involved in the lower perception of quality of life among the women. CONCLUSIONS: In conclusion, female residents had lower scores for quality of life and higher scores for daytime sleepiness. Measures to improve quality of life among female residents during this critical period of medical training might include investing in mentoring to help them better manage their time and encouraging activities that facilitate relationship development.

Diesel exhaust particulates affect cell signaling, mucin profiles, and apoptosis in trachea explants of Balb/C mice.

Particulate matter from diesel exhaust (DEP) has toxic properties and can activate intracellular signaling pathways and induce metabolic changes. This study was conducted to evaluate the activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) and to analyze the mucin profile (acid (AB(+) ), neutral (PAS(+) ), or mixed (AB/PAS(+) ) mucus) and vacuolization (V) of tracheal explants after treatment with 50 or 100 µg/mL DEP for 30 or 60 min. Western blot analyses showed small increases in ERK1/2 and JNK phosphorylation after 30 min of 100 µg/mL DEP treatment compared with the control. An increase in JNK phosphorylation was observed after 60 min of treatment with 50 µg/mL DEP compared with the control. We did not observe any change in the level of ERK1/2 phosphorylation after treatment with 50 µg/mL DEP. Other groups of tracheas were subjected to histological sectioning and stained with periodic acid-Schiff (PAS) reagent and Alcian Blue (AB). The stained tissue sections were then subjected to morphometric analysis. The results obtained were compared using ANOVA. Treatment with 50 µg/mL DEP for 30 min or 60 min showed a significant increase (p < 0.001) in the amount of acid mucus, a reduction in neutral mucus, a significant reduction in mixed mucus, and greater vacuolization. Our results suggest that compounds found in DEPs are able to activate acid mucus production and enhance vacuolization and cell signaling pathways, which can lead to airway diseases.

Daily physical activity in asthmatic children with distinct severities.

OBJECTIVE: The objective of this study was to evaluate daily physical activity (DPA) in asthmatic children with different levels of disease severity, but with good asthma control, relative to a control group. METHODS: This was a cross-sectional study in which a total of 121 children between the ages of 7 and 12 years old were evaluated; 72 were asthmatic children (32 mild, 24 moderate and 23 severe), and 42 children were not asthmatics. The asthmatic children studied had been in medical treatment for at least 6 months and experienced no change in symptoms during the 4 weeks prior to the study. The DPA was monitored over 6 days (4 weekdays and 2 weekend days). Motor activity was recorded with an accelerometer that measured the total number of steps (TNS), the number of steps in moderate physical activity (NS-MPA) and the duration, in minutes, of physical activity performed at moderate intensity. RESULTS: There were no differences among the TNS performed by children with mild, moderate or severe persistent asthma and the control group (14 410 ± 4379, 14 710 ± 4892, 13 838 ± 3341 and 12 968 ± 3682 steps, respectively). The NS-MPA was also similar among all of the groups (6589 ± 2065, 6605 ± 2324, 6223 ± 1689 and 5990 ± 1840 steps, respectively). Sedentary asthmatic children were overweight more often than asthmatic children who were physically active, although lung function was not different between these groups. CONCLUSION: Children with good asthma control, independent of disease severity, had DPA levels similar to children without asthma. However, more asthmatic children were overweight if sedentary as compared to physically active asthmatic children.

The effects of academic unprofessional behaviour on disciplinary action by medical boards: Systematic review and meta-analysis.

OBJECTIVE: The objective of this study is to evaluate the association of disciplinary actions by regulatory councils and unprofessional behaviour during medical graduation. METHODS: A search strategy was developed using the terms: 'physicians', 'disciplinary action', 'education', 'medical', 'undergraduate' and their synonyms, subsequently applied to the electronic databases MEDLINE, Embase, Cochrane Library, LILACs and grey literature, with searches up to November 2023. The risk of bias was assessed using the Newcastle-Ottawa scale and statistical analysis was performed using the RevMan software. RESULTS: A total of 400 studies were found in the databases, and 15 studies were selected for full-texting reading. Four studies met the inclusion criteria and were included, bringing together a total of 3341 evaluated physicians. Three studies were included in the meta-analysis, showing a greater chance of disciplinary actions among physicians who exhibited unprofessional behaviour during medical graduation (OR: 2.54; 95%CI: 1.87-3.44; I2: 0%; P < 0.0001; 3077 participants; physicians with disciplinary action: 107/323; control physicians: 222/2754). CONCLUSIONS: There is a statistically significant association between unprofessional behaviour during medical undergraduate study and subsequent disciplinary actions by Medical Councils. The tools for periodic assessments of student behaviour during undergraduate studies can be a perspective for future studies aimed at reducing disciplinary actions among physicians.

Effect of VAChT reduction on lung alterations induced by exposure to iron particles in an asthma model.

INTRODUCTION: Pollution harms the health of people with asthma. The effect of the anti-inflammatory cholinergic pathway in chronic allergic inflammation associated to pollution is poorly understood. METHODS: One hundred eight animals were divided into 18 groups (6 animals). Groups included: wild type mice (WT), genetically modified with reduced VAChT (VAChTKD), and those sensitized with ovalbumin (VAChTKDA), exposed to metal powder due to iron pelletizing in mining company (Local1) or 3.21 miles away from a mining company (Local2) in their locations for 2 weeks during summer and winter seasons. It was analyzed for hyperresponsivity, inflammation, remodeling, oxidative stress responses and the cholinergic system. RESULTS: During summer, animals without changes in the cholinergic system revealed that Local1 exposure increased the hyperresponsiveness (%Rrs, %Raw), and inflammation (IL-17) relative to vivarium animals, while animals exposed to Local2 also exhibited elevated IL-17. During winter, animals without changes in the cholinergic system revealed that Local2 exposure increased the hyperresponsiveness (%Rrs) relative to vivarium animals. Comparing the exposure local of these animals during summer, animals exposed to Local1 showed elevated %Rrs, Raw, and IL-5 compared to Local 2, while in winter, Local2 exposure led to more IL-17 than Local1. Animals with VAChT attenuation displayed increased %Rrs, NFkappaB, IL-5, and IL-13 but reduced alpha-7 compared to animals without changes in the cholinergic system WT. Animals with VAChT attenuation and asthma showed increased the hyperresponsiveness, all inflammatory markers, remodeling and oxidative stress compared to animals without chronic lung inflammation. Exposure to Local1 exacerbated the hyperresponsiveness, oxidative stressand inflammation in animals with VAChT attenuation associated asthma, while Local2 exposure led to increased inflammation, remodeling and oxidative stress. CONCLUSIONS: Reduced cholinergic signaling amplifies lung inflammation in a model of chronic allergic lung inflammation. Furthermore, when associated with pollution, it can aggravate specific responses related to inflammation, oxidative stress, and remodeling.

Lung Mechanics Over the Century: From Bench to Bedside and Back to Bench.

Lung physiology research advanced significantly over the last 100 years. Respiratory mechanics applied to animal models of lung disease extended the knowledge of the workings of respiratory system. In human research, a better understanding of respiratory mechanics has contributed to development of mechanical ventilators. In this review, we explore the use of respiratory mechanics in basic science to investigate asthma and chronic obstructive pulmonary disease (COPD). We also discuss the use of lung mechanics in clinical care and its role on the development of modern mechanical ventilators. Additionally, we analyse some bench-developed technologies that are not in widespread use in the present but can become part of the clinical arsenal in the future. Finally, we explore some of the difficult questions that intensive care doctors still face when managing respiratory failure. Bringing back these questions to bench can help to solve them. Interaction between basic and translational science and human subject investigation can be very rewarding, as in the conceptualization of "Lung Protective Ventilation" principles. We expect this interaction to expand further generating new treatments and managing strategies for patients with respiratory disease.

Exposure to Sodium Hypochlorite or Cigarette Smoke Induces Lung Injury and Mechanical Impairment in Wistar Rats.

Pulmonary irritants, such as cigarette smoke (CS) and sodium hypochlorite (NaClO), are associated to pulmonary diseases in cleaning workers. We examined whether their association affects lung mechanics and inflammation in Wistar rats. Exposure to these irritants alone induced alterations in the lung mechanics, inflammation, and remodeling. The CS increased airway cell infiltration, acid mucus production, MMP-12 expression, and alveolar enlargement. NaClO increased the number of eosinophils and macrophages in the bronchoalveolar lavage fluid, with cells expressing IL-13, MMP-12, MMP-9, TIMP-1, and iNOS in addition to increased IL-1ß and TNF-α levels. Co-exposure to both irritants increased epithelial and smooth muscle cell area, acid mucus production, and IL-13 expression in the airways, while it reduced the lung inflammation. In conclusion, the co-exposure of CS with NaClO reduced the pulmonary inflammation, but increased the acidity of mucus, which may protect lungs from more injury. A cross-resistance in people exposed to multiple lung irritants should also be considered.

Physical fitness and quality of life in adolescents with asthma and fixed airflow obstruction.

Asthma is a disease characterized by reversible bronchoconstriction, but some subjects develop fixed airflow obstruction (FAO). Subjects with FAO present more asthma symptoms and may have increased sedentary behavior; however, the effect of FAO on aerobic fitness and physical activity levels (PAL) remains poorly understood. AIM: To compare adolescents with asthma and FAO and adolescents with asthma without FAO in terms of aerobic fitness, PAL, muscle strength, and health-related quality of life (HRQoL). METHODS: This cross-sectional study included adolescents with asthma, both sexes, and aged 12-18 years. They were divided into two groups: FAO and non-FAO groups. The adolescents were diagnosed with asthma according to the Global Initiative for Asthma guidelines and underwent optimal pharmacological treatment for at least 12 months. FAO was diagnosed when the forced expiratory volume in the first second/forced vital capacity ratio was below the lower limit of the normal range after optimal treatment. Aerobic fitness, PAL, peripheral and respiratory muscle strength, and HRQoL were evaluated. RESULTS: No significant differences were observed between FAO and non-FAO groups regarding the peak oxygen uptake (34.6 ± 8.5 vs. 36.0 ± 8.4 mLO2 /min/kg), sedentary time (578 ± 126 vs. 563 ± 90 min/day), upper limb muscle strength (29.1 ± 5.9 vs. 28.1 ± 5.7 kilograms of force [kgf]), lower limb muscle strength (42.8 ± 8.6 vs. 47.6 ± 9.6 kgf), or HRQoL (5.1 ± 1.3 vs. 4.7 ± 1.4 score; p > .05). However, the FAO group exhibited a higher maximal expiratory pressure than the non-FAO group (111.5 ± 15.5 vs. 101.5 ± 15.0 cmH2 O, respectively). CONCLUSION: Our results suggest that FAO does not impair aerobic fitness, PAL, peripheral muscle strength, or HRQoL in adolescents with asthma. Furthermore, adolescents with asthma were physically deconditioned.

Low-dose chlorine exposure impairs lung function, inflammation and oxidative stress in mice.

AIM: To explore the different consequences of acute and chronic exposure to chlorine gas (Cl2) on the functional and histological parameters of health mice. MAIN METHODS: Firstly, male BALB/c mice were acute exposed to 3.3 or 33.3 or 70.5 mg/m3 Cl2. We analyzed the lung function, the inflammatory cells in the bronchoalveolar lavage, cell influx in the peribrochoalveolar space and mucus production. In a second phase, mice were chronic exposed to 70.5 mg/m3 Cl2. Besides the first phase analyses, we also evaluated the epithelial cells thickness, collagen deposition in the airways, immunohistochemistry stain for IL-1ß, iNOS, IL-17 and ROCK-2 and the levels of IL-5, IL-13, IL-17, IL-1ß and TNF-α in lung homogenate. KEY FINDINGS: Acute exposure to chlorine impaired the lung function, increased the number of inflammatory cells in the BALF and in the airways, also increased the mucus production. Furthermore, when chlorine was exposed chronically, increased the airway remodeling with collagen deposition and epithelial cells thickness, positive cells for IL-1ß, iNOS, IL-17 in the airways and in the alveolar walls and ROCK-2 in the alveolar walls, lung inflammation with increased levels of IL-5, IL-13, IL-1ß and TNF-α in the lung homogenate, and also, induced the acid mucus production by the nasal epithelium. SIGNIFICANCE: Acute and chronic exposure to low dose of chlorine gas worsens lung function, induces oxidative stress activation and mucus production and contributes to augmenting inflammation in health mice.

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.

Author Correction: Low dose of chlorine exposure exacerbates nasal and pulmonary allergic inflammation in mice.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Low dose of chlorine exposure exacerbates nasal and pulmonary allergic inflammation in mice.

Work-exacerbated asthma (WEA) is defined as preexisting asthma that worsens with exposure to irritants [e.g., chlorine (Cl2) derivatives] in the workplace. The maximum allowable concentration in the workplace of Cl2 exposure is 3 mg/ m3 (described in OSHA). We investigated in an experimental asthma model in mice the effects of a single exposure to a sodium hypochlorite dose with this allowed chlorine concentration and a tenfold higher dose. Acute chlorine exposure at 3.3 mg/m3 in the OVA-sensitized group increased eosinophils in the peribronquial infiltrate, cytokine production, nasal mucus production and the number of iNOS positive cells in the distal lung compared to only sensitized mice. The exposure to a higher dose of 33.3 mg/m3 in the OVA-sensitized group resulted in an increase in respiratory system elastance, in the total and differential numbers of inflammatory cells in bronchoalveolar lavage fluid, IL-4, IL-5, and IL-17 in the lungs, eosinophils in peribronquial infiltrate and mucus content in nasal compared to non-exposed and sensitized animals. In this asthma model, chorine exposures at an allowable dose, contributed to the potentiation of Th2 responses. The functional alterations were associated with increased iNOS and ROCK-2 activation in the distal lung.

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.

Effects of overinflation on procollagen type III expression in experimental acute lung injury.

INTRODUCTION: In acute lung injury (ALI), elevation of procollagen type III (PC III) occurs early and has an adverse impact on outcome. We examined whether different high-inflation strategies of mechanical ventilation (MV) in oleic acid (OA) ALI alter regional expression of PC III. METHODS: We designed an experimental, randomized, and controlled protocol in which rats were allocated to two control groups (no injury, recruited [alveolar recruitment maneuver after tracheotomy without MV; n = 4 rats] and control [n = 5 rats]) or four injured groups (one exposed to OA only [n = 10 rats] and three OA-injured and ventilated). The three OA-injured groups were ventilated for 1 hour according to the following strategies: LVHP-S (low volume-high positive end-expiratory pressure [PEEP], supine; n = 10 rats, tidal volume [VT] = 8 ml/kg, PEEP = 12 cm H2O), HVLP-S (high volume-low PEEP, supine; n = 10 rats, VT = 20 ml/kg, PEEP = 5 cm H2O), and HVLP-P (high volume-low PEEP, prone; n = 10 rats). Northern blot analysis for PC III and interleukin-1-beta (IL-1beta) and polymorphonuclear infiltration index (PMI) counting were performed in nondependent and dependent regions. Regional differences between groups were assessed by two-way analysis of variance after logarithmic transformation and post hoc tests. RESULTS: A significant interaction for group and region effects was observed for PC III (p = 0.012) with higher expression in the nondependent region for HVLP-S and LVHP-S, intermediate for OA and HVLP-P, and lower for control (group effect, p < 0.00001, partial eta2 = 0.767; region effect, p = 0.0007, partial eta2 = 0.091). We found high expression of IL-1beta (group effect, p < 0.00001, partial eta2 = 0.944) in the OA, HVLP-S, and HVLP-P groups without regional differences (p = 0.16). PMI behaved similarly (group effect, p < 0.00001, partial eta2 = 0.832). CONCLUSION: PC III expression is higher in nondependent regions and in ventilatory strategies that caused overdistension. This response was partially attenuated by prone positioning.

Dynamic hyperinflation and exercise limitations in obese asthmatic women.

Obese individuals and patients with asthma can develop dynamic hyperinflation (DH) during exercise; however, no previous study has investigated DH as a factor associated with reduced exercise capacity in obese asthmatic women. The aim of the present study was to examine the occurrence of DH and exercise limitations in obese asthmatics. Obese grade II [obese group (Ob-G); BMI 35-39.9 kg/m2; n=36] and nonobese [nonobese group (NOb-G); BMI 18.5-29.9 kg/m2; n=18] asthmatic patients performed a cardiopulmonary test to quantify peak V̇o2 and a submaximal exercise test to assess DH. Anthropometric measurements, quadriceps endurance, and lung function were also evaluated. A forward stepwise regression was used to evaluate the association between exercise tolerance (wattage) and limiting exercise factors. Fifty-four patients completed the protocol. The Ob-G (n = 36) presented higher peak V̇o2 values but lower power-to-weight ratio values than the NOb-G (P <0 .05). DH was more common in the Ob-G (72.2%) than in the NOb-G (38.9%, P < 0.05). The Ob-G had a greater reduction in the inspiratory capacity (-18 vs. -4.6%, P < 0.05). Exercise tolerance was associated with quadriceps endurance (r = 0.65; p<0.001), oxygen pulse (r = 0.52; p=0.001), and DH (r = -0.46, P = 0.005). The multiple regression analysis showed that the exercise tolerance could be predicted from a linear association only for muscular endurance (r = 0.82 and r2 = 0.67). This study shows that dynamic hyperinflation is a common condition in obese asthmatics; they have reduced fitness for activities of daily living compared to nonobese asthmatics. However, peripheral limitation was the main factor associated with reduced capacity of exercise in these patients.NEW & NOTEWORTHY This is the first study to investigate the occurrence of dynamic hyperinflation (DH) in obese asthmatics. Our results demonstrate that obese asthmatics present a higher frequency and intensity of DH than nonobese asthmatics. We also show that physical deconditioning in this population is linearly associated with cardiac (O2 pulse), respiratory (DH), and peripheral muscle (resistance) limitation. However, multiple linear regression demonstrated that peripheral muscle limitation may explain the exercise limitation in this population.

Compensatory lung growth after bilobectomy in emphysematous rats.

Lung volume reduction surgery (LVRS) is an option for emphysematous patients who are awaiting lung transplantation. LVRS reduces nonfunctional portions of lung tissues and favors the compensatory lung growth (CLG) of the remaining lobes. This phenomenon diminishes dyspnea and improves both the respiratory mechanics and quality of life for the patients. An animal model of elastase-induced pulmonary emphysema was used to investigate the structural and functional lung response after LVRS. Bilobectomy was performed six weeks after elastase instillation. Two weeks after bilobectomy, CLG effects were evaluated by lung mechanics and histomorphometric analysis. After bilobectomy, the emphysematous animals presented decreased mean linear intercepts, increased elastic fiber proportion, and increased alveolar surface density, total volumes of airspace, tissue and respiratory region and absolute surface area. We conclude that bilobectomy promoted CLG in emphysematous animals, resulting in alveolar architecture repair.

Time-course effects of aerobic physical training in the prevention of cigarette smoke-induced COPD.

A previous study by our group showed that regular exercise training (ET) attenuated pulmonary injury in an experimental model of chronic exposure to cigarette smoke (CS) in mice, but the time-course effects of the mechanisms involved in this protection remain poorly understood. We evaluated the temporal effects of regular ET in an experimental model of chronic CS exposure. Male C57BL/6 mice were divided into four groups: Control (sedentary + air), Exercise (aerobic training + air), Smoke (sedentary + smoke), and Smoke + Exercise (aerobic training + smoke). Mice were exposed to CS and ET for 4, 8, or 12 wk. Exercise protected mice exposed to CS from emphysema and reductions in tissue damping and tissue elastance after 12 wk (P < 0.01). The total number of inflammatory cells in the bronchoalveolar lavage increased in the Smoke group, mainly due to the recruitment of macrophages after 4 wk, neutrophils and lymphocytes after 8 wk, and lymphocytes and macrophages after 12 wk (P < 0.01). Exercise attenuated this increase in mice exposed to CS. The protection conferred by exercise was mainly observed after exercise adaptation. Exercise increased IL-6 and IL-10 in the quadriceps and lungs (P < 0.05) after 12 wk. Total antioxidant capacity and SOD was increased and TNF-α and oxidants decreased in lungs of mice exposed to CS after 12 wk (P < 0.05). The protective effects of exercise against lung injury induced by cigarette smoke exposure suggests that anti-inflammatory mediators and antioxidant enzymes play important roles in chronic obstructive pulmonary disease development mainly after the exercise adaptation.NEW & NOTEWORTHY These experiments investigated for the first time the temporal effects of regular moderate exercise training in cigarette smoke-induced chronic obstructive pulmonary disease. We demonstrate that aerobic conditioning had a protective effect in emphysema development induced by cigarette smoke exposure. This effect was most likely secondary to an effect of exercise on oxidant-antioxidant balance and anti-inflammatory mediators.