Objective: To determine whether a restrictive pattern on spirometry is associated with the level of physical activity in daily life (PADL), as well as with cardiovascular disease (CVD) risk factors, in asymptomatic adults. Methods: A total of 374 participants (mean age, 41 ± 14 years) underwent spirometry, which included the determination of FVC and FEV1. A restrictive pattern on spirometry was defined as an FEV1/FVC ratio > 0.7 and an FVC < 80% of the predicted value. After conducting demographic, anthropometric, and CVD risk assessments, we evaluated body composition, muscle function, and postural balance, as well as performing cardiopulmonary exercise testing and administering the six-minute walk test. The PADL was quantified with a triaxial accelerometer. Results: A restrictive pattern on spirometry was found in 10% of the subjects. After multivariate logistic regression, adjusted for confounders (PADL and cardiorespiratory fitness), the following variables retained significance (OR; 95% CI) as predictors of a restrictive pattern: systemic arterial hypertension (17.5; 1.65-184.8), smoking (11.6; 1.56-87.5), physical inactivity (8.1; 1.43-46.4), larger center-of-pressure area while standing on a force platform (1.34; 1.05-1.71); and dyslipidemia (1.89; 1.12-1.98). Conclusions: A restrictive pattern on spirometry appears to be common in asymptomatic adults. We found that CVD risk factors, especially systemic arterial hypertension, smoking, and physical inactivity, were directly associated with a restrictive pattern, even when the analysis was adjusted for PADL and cardiorespiratory fitness. Longitudinal studies are needed in order to improve understanding of the etiology of a restrictive pattern as well as to aid in the design of preventive strategies.

Keywords: Spirometry; Hypertension; Motor activity; Sedentary lifestyle; Smoking.

Objective: Many patients with proportional reductions in FVC and FEV1 on spirometry show no reduction in TLC. The aim of this study was to evaluate the role that measuring lung volumes and airway resistance plays in the correct classification of patients with a possible restrictive pattern on spirometry. Methods: This was a prospective study involving adults with reduced FVC and FEV1, as well as an FEV1/FV(C) ratio within the predicted range. Restrictive lung disease (RLD) was characterized by TLC below the 5th percentile, as determined by plethysmography. Obstructive lung disease (OLD) was characterized by high specific airway resistance, significant changes in post-bronchodilator FEV1, or an FEF25-75% < 50% of predicted, together with a high RV/TLC ratio. Nonspecific lung disease (NLD) was characterized by TLC within the predicted range and no obstruction. Combined lung disease (CLD) was characterized by reduced TLC and findings indicative of airflow obstruction. Clinical diagnoses were based on clinical suspicion, a respiratory questionnaire, and the review of tests of interest. Results: We included 300 patients in the study, of whom 108 (36%) were diagnosed with RLD. In addition, 120 (40%) and 72 (24%) were diagnosed with OLD/CLD and NLD, respectively. Among the latter, 24 (33%) were clinically diagnosed with OLD. In this sample, 151 patients (50.3%) were obese, and obesity was associated with all patterns of lung disease. Conclusions: Measuring lung volumes and airway resistance is often necessary in order to provide an appropriate characterization of the pattern of lung disease in patients presenting with a spirometry pattern suggestive of restriction. Airflow obstruction is common in such cases.

Keywords: Spirometry; Airway resistance; Lung volume measurements.

Objective: To evaluate characteristics of physical activities in daily life in COPD patients in Brazil, correlating those characteristics with physiological variables. Methods: Physical activities in daily life were evaluated in 40 COPD patients (18 males; 66 ± 8 years of age; FEV1 = 46 ± 16 % of predicted; body mass index = 27 ± 6 kg/m2) and 30 healthy age- and gender-matched subjects, using a multiaxial accelerometer-based sensor for 12 h/day on two consecutive days. We also assessed maximal and functional exercise capacity, using the incremental exercise test and the six-minute walk test (6MWT), respectively; MIP and MEP; peripheral muscle force, using the one-repetition maximum test and the handgrip test; quality of life, using the Saint George's Respiratory Questionnaire (SGRQ); functional status, using the London Chest Activity of Daily Living questionnaire; and dyspnea sensation, using the Medical Research Council (MRC) scale. Results: Mean walking time/day was shorter for COPD patients than for the controls (55 ± 33 vs. 80 ± 28 min/day; p = 0.001), as movement intensity was lower (1.9 ± 0.4 vs. 2.3 ± 0.6 m/s2; p = 0.004). The COPD patients also tended to spend more time seated (294 ± 114 vs. 246 ± 122 min/day, p = 0.08). Walking time/day correlated with the 6MWT (r = 0.42; p = 0.007) and maximal workload (r = 0.41; p = 0.009), as well as with age, MRC scale score and SGRQ activity domain score (−0.31 ≤ r ≤ −0.43; p ≤ 0.05 for all). Conclusions: This sample of Brazilian patients with COPD, although more active than those evaluated in studies conducted in Europe, were less active than were the controls. Walking time/day correlated only moderately with maximal and functional exercise capacity.

Keywords: Pulmonary disease, chronic obstructive; Motor activity; Exercise tolerance.

Objective: To determine whether the level of physical activity in daily life (PADL) is associated with pulmonary function in adult smokers. Methods: We selected 62 adult smokers from among the participants of an epidemiological study conducted in the city of Santos, Brazil. The subjects underwent forced spirometry for pulmonary function assessment. The level of PADL was assessed by the International Physical Activity Questionnaire and triaxial accelerometry, the device being used for seven days. The minimum level of PADL, in terms of quantity and intensity, was defined as 150 min/week of moderate to vigorous physical activity. Correlations between the studied variables were tested with Pearson's or Spearman's correlation coefficient, depending on the distribution of the variables. We used linear multiple regression in order to analyze the influence of PADL on the spirometric variables. The level of significance was set at 5%. Results: Evaluating all predictors, corrected for confounding factors, and using pulmonary function data as outcome variables, we found no significant associations between physical inactivity, as determined by accelerometry, and spirometric indices. The values for FVC were lower among the participants with arterial hypertension, and FEV1/FVC ratios were lower among those with diabetes mellitus. Obese participants and those with dyslipidemia presented with lower values for FVC and FEV1. Conclusions: Our results suggest that there is no consistent association between physical inactivity and pulmonary function in adult smokers. Smoking history should be given special attention in COPD prevention strategies, as should cardiovascular and metabolic comorbidities.

Keywords: Smoking; Respiratory function tests; Motor activity; Accelerometry.

Objective: To compare the Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index scores and its individual components between COPD patients with and without severe physical inactivity, as well as to correlate the number of steps/day with scores of physical activity questionnaires, age, and the BODE index (including its components). Methods: We included 30 patients, who were evaluated for body composition, pulmonary function (FEV1), perception of dyspnea (modified Medical Research Council scale), and exercise capacity (six-minute walk distance [6MWD]). The patients also completed the International Physical Activity Questionnaire (IPAQ), short version, and the modified Baecke questionnaire (mBQ). The level of physical activity was assessed by the number of steps/day (as determined by pedometer), using the cut-off of 4,580 steps/day to form two groups: no severe physical inactivity (SPI−) and severe physical inactivity (SPI+). We used the Mann-Whitney test or t-test, as well as Pearson's or Spearman's correlation tests, in the statistical analysis. Results: In comparison with the SPI− group, the SPI+ group showed more advanced age, higher mBQ scores (leisure domain), lower 6MWD (in m and % of predicted), and lower IPAQ scores (metabolic equivalent-walk/week domain and total). The IPAQ scores showed weak correlations with steps/day (r = 0.399), age (r = −0.459), and 6MWD-in m (r = 0.446) and in % of predicted (r = 0.422). Conclusions: In our sample, the cut-off of 4,580 steps/day was not sensitive enough to identify differences between the groups when compared with the predictors of mortality. The IPAQ, short version score correlated with steps/day.

Keywords: Pulmonary disease, chronic obstructive/mortality; Pulmonary disease, chronic obstructive/ prevention and control; Motor activity.

Objective: Barriers to physical activity can affect the functional capacity and quality of life of patients with pulmonary hypertension (PH). This study aimed to identify the main barriers to physical activity in patients with PH and to examine whether those barriers are related to functional capacity, echocardiographic variables, or quality of life. Methods: This was a cross-sectional observational study involving 70 patients. Participants scored seven potential barriers to their activities, with a score = 5 indicating a significant barrier. Participants completed the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and Manchester Respiratory Activity of Daily Living questionnaire, as well as the six-minute walk test. Correlation analysis, univariate analysis and multiple logistic regression were performed. Results: As a perceived barrier to physical activity, 'lack of will' or 'lack of energy' was cited by 67% of the patients. The 'lack of will' barrier was found to correlate with all SF-36 domains except bodily pain. We also identified a correlation between the SF-36 vitality domain and the barriers 'lack of energy', 'lack of will' and 'lack of structure'. The logistic regression analysis indicated that the vitality domain correlated significantly with the barriers 'social influence', 'lack of energy', 'lack of will', and 'lack of structure'. For each unit decrease in the vitality score, there was a 10% increase in the probability of citing the barrier 'lack of will'. No significant correlations were identified between any of the perceived barriers and echocardiographic parameters. Conclusions: The perceived barrier most commonly reported was 'lack of will/energy', which correlated with almost all SF-36 domains, especially vitality. The 'lack of will' barrier also correlated with functional capacity.

Keywords: Pulmonary arterial hypertension; Exercise; Motivation; Quality of life; Surveys and questionnaires; Walk test.

Objective: Obstructive sleep apnea (OSA) is associated with an increased risk of mortality and cardiometabolic diseases. The STOP-Bang questionnaire is a tool to screen populations at risk of OSA and prioritize complementary studies. Our objective was to evaluate the clinical utility of this questionnaire in identifying patients at an increased risk of mortality after discharge in a cohort of hospitalized patients. Methods: This was a prospective cohort study involving consecutive patients admitted to an internal medicine unit between May and June of 2017 who were reevaluated three years after discharge. At baseline, we collected data on comorbidities (hypertension, obesity, diabetes, and fasting lipid profile) and calculated STOP-Bang scores, defining the risk of OSA (0-2 score, no risk; = 3 score, risk of OSA; and = 5 score, risk of moderate-to-severe OSA), which determined the study groups. We also recorded data regarding all-cause and cardiovascular mortality at the end of the follow-up period. Results: The sample comprised 435 patients. Of those, 352 (80.9%) and 182 (41.8%) had STOP-Bang scores = 3 and = 5, respectively. When compared with the group with STOP-Bang scores of 0-2, the two groups showed higher prevalences of obesity, hypertension, diabetes, and dyslipidemia. Multivariate analysis showed an independent association between cardiovascular mortality and STOP-Bang score = 5 (adjusted hazard ratio = 3.12 [95% CI, 1.39-7.03]; p = 0.01). Additionally, previous coronary heart disease was also associated with cardiovascular mortality. Conclusions: In this cohort of hospitalized patients, STOP-Bang scores = 5 were able to identify patients at an increased risk of cardiovascular mortality three years after discharge.

Keywords: Sleep Apnea, Obstructive; Risk assessment; Surveys and questionnaires; Cardiovascular diseases/mortality.

Objective: To evaluate the ability of COPD patients to perform activities of daily living (ADL); to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT), and an ADL limitation score. Methods: In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days. A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL) scale were used in order to identify the factors that prevent the performance of ADL. The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT. Results: We evaluated 40 COPD patients and 40 controls. In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5  25.8 min/day vs. 105.2  49.4 min/day; p < 0.001), as was the distance walked (3.9  1.9 km/day vs. 6.4  3.2 km/day; p < 0.001). The COPD patients also walked fewer steps/day. The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower. The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results. Conclusions: Patients with COPD are less active than are healthy adults of a comparable age. Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures.

Keywords: Pulmonary disease, chronic obstructive; Activities of daily living; Exercise tolerance.

Objective: To adapt the PROactive Physical Activity in COPD-clinical visit (C-PPAC) instrument to the cultural setting in Brazil and to determine the criterion validity, test-retest reliability agreement, and internal consistency of this version. Methods: A protocol for cultural adaptation and validation was provided by the authors of the original instrument and, together with another guideline, was applied in a Portuguese-language version developed by a partner research group from Portugal. The adapted Brazilian Portuguese version was then cross-sectionally administered twice within a seven-day interval to 30 individuals with COPD (57% were men; mean age was 69 ± 6 years; and mean FEV1 was 53 ± 18% of predicted) to evaluate internal consistency and test-retest reliability. Participants also completed the International Physical Activity Questionnaire (IPAQ), the modified Medical Research Council scale, the COPD Assessment Test, and Saint George's Respiratory Questionnaire to evaluate criterion validity. Results: The C-PPAC instrument showed good internal consistency and excellent test-retest reliability: "amount" domain = 0.87 (95% CI, 0.73-0.94) and "difficulty" domain = 0.90 (95% CI, 0.76-0.96). Bland & Altman plots, together with high Lin's concordance correlation coefficients, reinforced that agreement. Criterion validity showed moderate-to-strong correlations of the C-PPAC with all of the other instruments evaluated, especially with the IPAQ (rho = -0.63). Conclusions: The Brazilian Portuguese version of the C-PPAC is a reliable and valid instrument for evaluating the experience of Brazilian individuals with COPD with their physical activity in daily life.

Keywords: Pulmonary disease, chronic obstructive; Validation study; Activities of daily living; Psychometrics.

Objective: To evaluate diaphragmatic mobility in relation to lung function, respiratory muscle strength, dyspnea, and physical activity in daily life (PADL) in patients with COPD. Methods: We included 25 patients with COPD, classified according to the Global Initiative for Chronic Obstructive Lung Disease criteria, and 25 healthy individuals. For all of the participants, the following were evaluated: anthropometric variables, spirometric parameters, respiratory muscle strength, diaphragmatic mobility (by X-ray), PADL, and the perception of dyspnea. Results: In the COPD group, diaphragmatic mobility was found to correlate with lung function variables, inspiratory muscle strength, and the perception of dyspnea, whereas it did not correlate with expiratory muscle strength or PADL. Conclusions: In patients with COPD, diaphragmatic mobility seems to be associated with airway obstruction and lung hyperinflation, as well as with ventilatory capacity and the perception of dyspnea, although not with PADL.

Keywords: Pulmonary disease, chronic obstructive; Diaphragm; Spirometry; Dyspnea; Maximal respiratory pressures.

Objective: To determine the efficacy of chest compression accompanied by a 10-cmH2O increase in baseline inspiratory pressure on pressure support ventilation, in comparison with that of aspiration alone, in removing secretions, normalizing hemodynamics, and improving respiratory mechanics in patients on mechanical ventilation. Methods: This was a randomized crossover clinical trial involving patients on mechanical ventilation for more than 48 h in the ICU of the Porto Alegre Hospital de Clínicas, in the city of Porto Alegre, Brazil. Patients were randomized to receive aspiration alone (control group) or compression accompanied by a 10-cmH2O increase in baseline inspiratory pressure on pressure support ventilation (intervention group). We measured hemodynamic parameters, respiratory mechanics parameters, and the amount of secretions collected. Results: We included 34 patients. The mean age was 64.2  14.6 years. In comparison with the control group, the intervention group showed a higher median amount of secretions collected (1.9 g vs. 2.3 g; p = 0.004), a greater increase in mean expiratory tidal volume (16  69 mL vs. 56  69 mL; p = 0.018), and a greater increase in mean dynamic compliance (0.1  4.9 cmH2O vs. 2.8  4.5 cmH2O; p = 0.005). Conclusions: In this sample, chest compression accompanied by an increase in pressure support significantly increased the amount of secretions removed, the expiratory tidal volume, and dynamic compliance. (ClinicalTrials.gov Identifier:NCT01155648 [http://www.clinicaltrials.gov/])

Keywords: Physical therapy modalities; Respiration, Artificial; Intensive care units; Respiratory therapy.

Objective: To clarify whether, in healthy individuals, practicing yoga can modify maximal inspiratory pressure and spirometric indices when compared with the practice of aerobic exercise. Methods: A controlled clinical trial. A total of 31 healthy volunteers were allocated to practice aerobic exercise (n = 15) or to practice yoga (n = 16). Those in the first group served as controls and engaged in aerobic exercise for 45-60 minutes, twice a week for three months. Those in the second group practiced selected yogic techniques, also in sessions of 45-60 minutes, twice a week for three months. Forced vital capacity, forced expiratory volume in one second and maximal inspiratory pressure were measured before and after the three months of training. Results: No significant alterations were seen in the spirometric indices. A slight, although not significant, improvement in maximal inspiratory pressure was seen in both groups. However, there was a significant difference, seen in both genders, between the absolute delta (final value minus baseline value) of maximal inspiratory pressure for the group practicing yoga and that obtained for the group engaging in aerobic exercise (males: 19.5 cm H2O versus 2.8 cm H2O, p = 0.05; females: 20 cm H2O versus 3.9 cm H2O, p = 0.01). Conclusion: Neither yoga nor aerobic exercise provided a statistically significant improvement in maximal inspiratory pressure after three months. However, the absolute variation in maximal inspiratory pressure was greater among those practicing yoga.

Keywords: Yoga; Exercise; Respiratory muscles; Respiratory function tests; Maximal voluntary ventilation; Spirometry; Inspiratory capacity/physiology

Chylothorax occurs when there is rupture, laceration or obstruction of the thoracic duct, resulting in the release of chyle into the pleural space. Chylothorax can occur in cases of congenital lymphatic malformation, lymphoma, mediastinal tumor and infectious disease, as well as during surgical procedures and after traffic accident-related trauma. It can also be idiopathic. The condition presents clinical signs of dyspnea, hypotension, generalized edema and cyanosis. The diagnosis is usually made through thoracocentesis, and the treatment is conservative. Spontaneous chylothorax is an uncommon form of pleural effusion, and its diagnosis should be hypothesized only after all other causes have been ruled out. Herein, we describe a case of spontaneous chylothorax associated with light physical activity at a fitness center.

Keywords: Chylothorax; Pleural effusion; Motor; Case reports [Publication type]

Objective: The identification of persistent airway obstruction is key to making a diagnosis of COPD. The GOLD guidelines suggest a fixed criterion-a post-bronchodilator FEV1/FVC ratio < 70%-to define obstruction, although other guidelines suggest that a post-bronchodilator FEV1/FVC ratio < the lower limit of normal (LLN) is the most accurate criterion. Methods: This was an observational study of individuals = 40 years of age with risk factors for COPD who were referred to our pulmonary function laboratory for spirometry. Respiratory symptoms were also recorded. We calculated the prevalence of airway obstruction and of no airway obstruction, according to the GOLD criterion (GOLD+ and GOLD-, respectively) and according to the LLN criterion (LLN+ and LLN-, respectively). We also evaluated the level of agreement between the two criteria. Results: A total of 241 individuals were included. Airway obstruction was identified according to the GOLD criterion in 42 individuals (17.4%) and according to the LLN criterion in 23 (9.5%). The overall level of agreement between the two criteria was good (? = 0.67; 95% CI: 0.52-0.81), although it was lower among the individuals = 70 years of age (? = 0.42; 95% CI: 0.12-0.72). The proportion of obese individuals was lower in the GOLD+/LLN+ category than in the GOLD+/LLN- category (p = 0.03), as was the median DLCO (p = 0.04). Conclusions: The use of the GOLD criterion appears to be associated with a higher prevalence of COPD. The agreement between the GOLD and LLN criteria also appears to be good, albeit weaker in older individuals. The use of different criteria to define airway obstruction seems to identify individuals with different characteristics. It is essential to understand the clinical meaning of discordance between such criteria. Until more data are available, we recommend a holistic, individualized approach to, as well as close follow-up of, patients with discordant results for airway obstruction.

Keywords: Pulmonary disease, chronic obstructive; Airway obstruction; Spirometry.

Objective: To determine whether serum selenium levels are associated with the conversion of bacteriological tests in patients diagnosed with active pulmonary tuberculosis after eight weeks of standard treatment. Methods: We evaluated 35 healthy male controls and 35 male patients with pulmonary tuberculosis, the latter being evaluated at baseline, as well as at 30 and 60 days of antituberculosis treatment. For all participants, we measured anthropometric indices, as well as determining serum levels of albumin, C-reactive protein (CRP) and selenium. Because there are no reference values for the Brazilian population, we used the median of the serum selenium level of the controls as the cut-off point. At 30 and 60 days of antituberculosis treatment, we repeated the biochemical tests, as well as collecting sputum for smear microscopy and culture from the patients. Results: The mean age of the patients was 38.4  11.4 years. Of the 35 patients, 25 (71%) described themselves as alcoholic; 20 (57.0%) were smokers; and 21 (60.0%) and 32 (91.4%) presented with muscle mass depletion as determined by measuring the triceps skinfold thickness and arm muscle area, respectively. Of 24 patients, 12 (39.2%) were classified as moderately or severely emaciated, and 15 (62.5%) had lost > 10% of their body weight by six months before diagnosis. At baseline, the tuberculosis group had lower serum selenium levels than did the control group. The conversion of bacteriological tests was associated with the CRP/albumin ratio and serum selenium levels 60 days after treatment initiation. Conclusions: Higher serum selenium levels after 60 days of treatment were associated with the conversion of bacteriological tests in pulmonary tuberculosis patients.

Keywords: Selenium; Nutritional status; Tuberculosis; Immunity.

Objective: To evaluate the effects that early and late systemic administration of methylprednisolone have on lungs in a rat model of brain death. Methods: Twenty-four male Wistar rats were anesthetized and randomly divided into four groups (n = 6 per group): sham-operated (sham); brain death only (BD); brain death plus methylprednisolone (30 mg/kg i.v.) after 5 min (MP5); and brain death plus methylprednisolone (30 mg/kg i.v.) after 60 min (MP60). In the BD, MP5, and MP60 group rats, we induced brain death by inflating a balloon catheter in the extradural space. All of the animals were observed and ventilated for 120 min. We determined hemodynamic and arterial blood gas variables; wet/dry weight ratio; histological score; levels of thiobarbituric acid reactive substances (TBARS); superoxide dismutase (SOD) activity; and catalase activity. In BAL fluid, we determined differential white cell counts, total protein, and lactate dehydrogenase levels. Myeloperoxidase activity, lipid peroxidation, and TNF-α levels were assessed in lung tissue. Results: No significant differences were found among the groups in terms of hemodynamics, arterial blood gases, wet/dry weight ratio, BAL fluid analysis, or histological score-nor in terms of SOD, myeloperoxidase, and catalase activity. The levels of TBARS were significantly higher in the MP5 and MP60 groups than in the sham and BD groups (p < 0.001). The levels of TNF-α were significantly lower in the MP5 and MP60 groups than in the BD group (p < 0.001). Conclusions:áIn this model of brain death, the early and late administration of methylprednisolone had similar effects on inflammatory activity and lipid peroxidation in lung tissue.

Objective: To compare somatic growth, lung function, and level of physical activity in schoolchildren who had been very-low-birth-weight preterm infants (VLBWPIs) or normal-birth-weight full-term infants. Methods: We recruited two groups of schoolchildren between 8 and 11 years of age residing in the study catchment area: those who had been VLBWPIs (birth weight < 1,500 g); and those who had been normal-birth-weight full-term infants (controls, birth weight ≥ 2,500 g). Anthropometric and spirometric data were collected from the schoolchildren, who also completed a questionnaire regarding their physical activity. In addition, data regarding the perinatal and neonatal period were collected from the medical records of the VLBWPIs. Results: Of the 93 schoolchildren screened, 48 and 45 were in the VLBWPI and control groups, respectively. No significant differences were found between the groups regarding anthropometric characteristics, nutritional status, or pulmonary function. No associations were found between perinatal/neonatal variables and lung function parameters in the VLBWPI group. Although the difference was not significant, the level of physical activity was slightly higher in the VLBWPI group than in the control group. Conclusions: Among the schoolchildren evaluated here, neither growth nor lung function appear to have been affected by prematurity birth weight, or level of physical activity.

Keywords: Premature birth; Birth weight; Respiratory function tests; Motor activity; Pediatrics.