Objective: To determine the cut-off points for FEV1, FEV0.75, FEV0.5, and FEF25-75% bronchodilator responses in healthy preschool children and to generate reference values for FEV0.75. Methods: This was a cross-sectional community-based study involving children 3-5 years of age. Healthy preschool children were selected by a standardized questionnaire. Spirometry was performed before and after bronchodilator use. The cut-off point of the response was defined as the 95th percentile of the change in each parameter. Results: We recruited 266 children, 160 (60%) of whom were able to perform acceptable, reproducible expiratory maneuvers before and after bronchodilator use. The mean age and height were 57.78 ± 7.86 months and 106.56 ± 6.43 cm, respectively. The success rate for FEV0.5 was 35%, 68%, and 70% in the 3-, 4-, and 5-year-olds, respectively. The 95th percentile of the change in the percentage of the predicted value in response to bronchodilator use was 11.6%, 16.0%, 8.5%, and 35.5% for FEV1, FEV0.75, FEV0.5, and FEF25-75%, respectively. Conclusions: Our results provide cut-off points for bronchodilator responsiveness for FEV1, FEV0.75, FEV0.5, and FEF25-75% in healthy preschool children. In addition, we proposed gender-specific reference equations for FEV0.75. Our findings could improve the physiological assessment of respiratory function in preschool children.

Keywords: Spirometry; Bronchodilator agents; Reference values; Child, preschool.

Objective: To generate reference values for spirometry in Brazilian children 3-12 years of age and to compare those values with the values employed in the equations currently in use in Brazil. Methods: This study involved healthy children, 3-12 years of age, recruited from 14 centers (primary data) and spirometry results from children with the same characteristics in six databases (secondary data). Reference equations by quantile regressions were generated after log transformation of the spirometric and anthropometric data. Skin color was classified as self-reported by the participants. To determine the suitability of the results obtained, they were compared with those predicted by the equations currently in use in Brazil. Results: We included 1,990 individuals from a total of 21 primary and secondary data sources. Of those, 1,059 (53%) were female. Equations for FEV1, FVC, the FEV1/FVC ratio, FEF between 25% and 75% of the FVC (FEF25-75%) and the FEF25-75%/FVC ratio were generated for white-, black-, and brown-skinned children. The logarithms for height and age, together with skin color, were the best predictors of FEV1 and FVC. The reference values obtained were significantly higher than those employed in the equations currently in use in Brazil, for predicted values, as well as for the lower limit of normality, particularly in children with self-reported black or brown skin. Conclusions: New spirometric equations were generated for Brazilian children 3-12 years of age, in the three skin-color categories defined. The equations currently in use in Brazil seem to underestimate the lung function of Brazilian children 3-12 years of age and should be replaced by the equations proposed in this study.

Keywords: Spirometry; Reference values; Child; Child, preschool; Respiratory function tests.

Objective: To derive reference equations for spirometry in healthy Black adult never smokers in Brazil, comparing them with those published in 2007 for White adults in the country. Methods: The examinations followed the standards recommended by the Brazilian Thoracic Association, and the spirometers employed met the technical requirements set forth in the guidelines of the American Thoracic Society/European Respiratory Society. The lower limits were defined as the 5th percentile of the residuals. Results: Reference equations and limits were derived from a sample of 120 men and 124 women, inhabitants of eight Brazilian cities, all of whom were evaluated with a flow spirometer. The predicted values for FVC, FEV1 , FEV1 /FVC ratio, and PEF were better described by linear equations, whereas the flows were better described by logarithmic equations. The FEV1 and FVC reference values derived for Black adults were significantly lower than were those previously derived for White adults, regardless of gender. Conclusions: The fact that the predicted spirometry values derived for the population of Black adults in Brazil were lower than those previously derived for White adults in the country justifies the use of an equation specific to the former population.

Keywords: Spirometry; Reference values; African continental ancestry group.

Objective: To compare the most recent (2006) predicted values of forced vital capacity and forced expiratory volume in one second for spirometry in Brazilians with those obtained using other reference equations and to validate the findings through comparisons with a new sample of normal Brazilians. Methods: Forced spirometry was performed, in accordance with the Brazilian Thoracic Society guidelines, in 643 nonsmoking adult Caucasians. The predicted values obtained by Brazilian researchers in 1992 and those obtained by four groups of foreign researchers were compared with the new Brazilian predicted values obtained in 2006. In the second phase, the mean values obtained in 65 adult females and 79 adult males were compared with the predicted values obtained using the various reference equations. Results: A t-test for paired samples revealed significant differences between the predicted values obtained using the six equations and those obtained using the 2006 Brazilian equation. In the second phase, the mean predicted values obtained by Crapo et al., as well as those obtained by Hankinson et al. for Mexican-Americans, were similar to those found in the new sample. However, when the predicted values obtained in the new sample were compared with those obtained by those authors, discrepancies were found, with high and low predicted values. The mean values obtained using the 2006 Brazilian equation presented the smallest differences in comparison with the mean values obtained in the new sample. Conclusions: These results underscore the importance of using prediction equations for spirometry that are appropriate for our population.

Keywords: Spirometry; Reference values; Respiratory function tests.

Objective: To describe spirometric reference equations for healthy Brazilian adults who have never smoked and to compare the predicted values with those derived in 1992. Methods: Reference equations for spirometry were derived in 270 men and 373 women living in eight cities in Brazil. Ages ranged from 20 to 85 years in women and from 26 to 86 years in men. Spirometry examinations followed the recommendations of the Brazilian Thoracic Society. Lower limits were derived by the analysis of the fifth percentiles of the residuals. Results: Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC and FEV1/forced expiratory volume in six seconds (FEV6) were best fitted by linear regression. Flows were best fitted using log equations. For both genders, greater height resulted in lower values for FEV1/FVC, FEV1/FEV6 and flow/FVC ratios. The reference values for FEV1 and FVC in the present study were higher than those derived for Brazilian adults in 1992. Conclusion: New predicted values for forced spirometry were obtained in a sample of white Brazilians. The values are greater than those obtained in 1992, probably due to technical factors.

Keywords: Spirometry; Reference Values; Respiratory Function Tests.

Objective: Given that ß2 agonists constitute the primary treatment for asthma and that treatment response varies as a result of polymorphisms in the ADRB2 gene, we sought to investigate the associations between ADRB2 gene variants and bronchodilator response (BDR) in asthma patients. Methods: A genetic database comprising 813 individuals was analyzed for variants in the ADRB2 gene. A longitudinal analysis of severe asthma patients was performed to evaluate changes in BDR over time. Results: The rs1042713, rs1042714, and rs1042717 variants were associated with age-related changes in BDR in patients with severe asthma. The G allele (rs1042714) and the A allele (rs1042717) were associated with uncontrolled asthma, with carriers of the G46/G79/A252 alleles showing a higher risk of difficult-to-control asthma. Notably, no association was found between these variants and ADRB2 expression levels. Conclusions: Our findings suggest that a genetic panel including ADRB2 variants, as well as age-related differences in BDR, is a useful complementary tool in asthma management.

Keywords: Bronchodilator agents; Beta-2 adrenergic receptor; Genetic variation;; Asthma; Ethnic groups

Objective: To use the forced oscillation technique to evaluate asthma patients presenting positive bronchodilator responses (confirmed through spirometry) and compare the results with those obtained in healthy individuals. Methods: The study sample consisted of 53 non-smoking volunteers: 24 healthy subjects with no history of pulmonary disease and 29 asthmatics presenting positive bronchodilator response, as determined through analysis of spirometry findings. All of the subjects were submitted to forced oscillation technique and spirometry immediately before and 20 minutes after the administration of salbutamol spray (300 g). The parameters derived from the forced oscillation technique were total respiratory resistance, total respiratory reactance, resistance extrapolated to the y axis, the slope of resistance, and dynamic compliance. The parameters measured in the spirometry evaluation tests were forced expiratory volume in one second and forced vital capacity. Results: In the control group, bronchodilator use produced a significant alteration in the resistance extrapolated to the y axis (p < 0.001), although no significant differences were observed in the slope of resistance or in dynamic compliance. Analysis of the asthma patients revealed significant differences between the prebronchodilator and postbronchodilator values for all spirometry and forced oscillation technique parameters. Values of p < 0.001 were obtained for all comparisons between the two groups. Conclusion: The modifications provoked by use of the forced oscillation technique were in direct concordance with the pathophysiology of the bronchodilator response in asthma patients, indicating that the forced oscillation technique could be useful as a complement to spirometry in these patients.

Keywords: Asthma; Bronchial hyperreactivity; Spirometry/methods; Bronchial provocation tests; Forced expiratory volume/physiology; Oscillometry

Objective: To compare the reference values for PEF suggested by other authors in 1963, 1989 and 2001 (for populations in the USA, England and Cuba, respectively) with those obtained from a population sample in the city of São Carlos, Brazil, and to determine whether there is concordance among them. Methods: A total of 243 volunteers (123 females and 120 males; 20-70 years of age) participated in the study. The PEF measurements were performed with the volunteer standing, using a nose clip, by means of a portable peak flow meter. These measurements were compared with the reference values using the Friedman test and Dunn's post-hoc test (p < 0.05). Results: Significant differences were found in all age groups from both genders regarding the values predicted in 1989; the same occurred in the 20-30 and 31-40 age groups (both genders), as well as in the 61-70 age group (females only), regarding those predicted in 2001, as well as in the 20-30 age group (males only) regarding those predicted in 1963. Conclusions: The values predicted in 1963 are appropriate for a population of individuals with the same characteristics as the study sample, except for males in the 20-30 age group. Our study is relevant due to the fact that our sample was larger than that evaluated in the 1963 study. The majority of the values predicted in 1989 and 2001 overestimated the PEF values obtained in our study, proving to be inappropriate for the population studied.

Keywords: Reference values; Respiratory function tests; Airway obstruction; Peak expiratory flow rate.

Objective: To determine reference values for the six-minute pegboard and ring test (6PBRT) in healthy adults in Brazil, correlating the results with arm length, circumference of the upper arm/forearm of the dominant arm, and the level of physical activity. Methods: The participants (all volunteers) performed two 6PBRTs, 30 min apart. They were instructed to move as many rings as possible in six minutes. The best test result was selected for data analysis. Results: The sample comprised 104 individuals, all over 30 years of age. Reference values were reported by age bracket. We found that age correlated with 6PBRT results. The number of rings moved was higher in the 30- to 39-year age group than in the > 80-year age group (430.25 ± 77.00 vs. 265.00 ± 65.75), and the difference was significant (p < 0.05). The 6PBRT results showed a weak, positive correlation with the level of physical activity (r = 0.358; p < 0.05) but did not correlate significantly with any other variable studied. Conclusions: In this study, we were able to determine reference values for the 6PBRT in healthy adults in Brazil. There was a correlation between 6PBRT results and age.

Keywords: Upper extremity; Physical endurance; Exercise tolerance; Exercise test.

In lung function laboratories, statistical responses after bronchodilators (Bd) administration are widely used in patients with airflow limitation. However, their clinical relevance is debatable. Objective: To determine which spirometric parameters best reflect improvement in both exercise tolerance and exertional dyspnea in response to bronchodilators in obstructive lung diseases. Methods: Fifty patients with persistent asthma and/or COPD (FEV1/FVC = 41 ± 11%) were submitted to slow and forced vital capacity testing, MVV and a six-minute walking test (6 MW) following practice, before and after a 400 mg dose of salbutamol was given by MDI. Responses to Bd were expressed in absolute values and considered as increments to the initial values and predicted values. Responses to Bd were considered clinically significant if distance was longer than 30 m in the 6 MW test and/or if there was a 2-point decrease in the Borg scale in the walking distance. Results: 32 patients were responsive (R) to Bd and 18 were non-responsive (NR). As DMW correlated with age, (rs = -0.38 - p < 0.01) an analysis on spirometric data, including age as covariant, was performed and expressed as x ± SE. No difference in FEV1 was observed between the groups (R = 255 ± 57 ml; NR = 256 ± 43 ml). The same occurred regarding MVV (R = 11± 2 L/min; NR = 10 ± 2 L/min.). The best separation (p < 0.01) was given by changes in inspiration capacity (IC) followed by changes in slow vital capacity (SVC): IC% of initial R = 23 ± 3% and NR = 3 ± 4%; absolute IC = 411 ± 58 ml and NR = 163 ± 77 ml; predicted IC%: R = 19 ± 3% and NR = 3 ± 4%. For SVC, the values were: % initial - R = 18 ± 2% and NR = 9 ± 3%; absolute changes - R = 448 ± 52 ml and NR = 256 ± 70 ml. Increases in IC > 15% of the initial values and 0.3 L and increases in SVS > 15% of the initial values and 0.4 L determined responsive patients with positive predicted values as approximately 90%. Conclusion: Variations in FEV1, FVC and MVV do not predict improvement in exercise capacity after Bd. This is best reflected by 15% of increases in IC and/or in the SVC initial values.

Keywords: Obstructive lung diseases. Spirometry. Predictive value of tests. Bronchodilator agents. Exercise tolerance. Dyspnea.

Objective: To evaluate whether the use of inhaled albuterol via a metered-dose inhaler with a large-volume spacer with antistatic treatment modifies the bronchodilator test results when compared with the usual technique (no spacer). Methods: A prospective study involving 24 patients, 18-45 years of age, clinically suspected of having asthma, and under treatment at the Outpatient Pulmonary Clinic of the Federal University of Minas Gerais Hospital das Clínicas, located in the city of Belo Horizonte, Brazil. All of the patients underwent two bronchodilator tests: one with and one without the use of a large-volume spacer. Results: There was no significant difference in the variation of FEV1 prior to and after bronchodilator use between the two techniques (mean FEV1 = 0.01 L; 95% CI: −0.05 to 0.06; p = 0.824). No statistically significant difference was found between the two techniques regarding the qualitative results on the bronchodilator test (p = 1.00). There was concordance between the techniques in terms of the bronchodilator test results (kappa coefficient = 0.909; p < 0.005). Conclusions: According to the results of this study, the use of large-volume spacers does not significantly modify bronchodilator test results.

Keywords: Asthma; Spirometry; Inhalation spacers.

Objective: To develop regression equations for six-minute walk distance (6MWD) in healthy adults (20-80 years of age) in Brazil. Methods: We included 132 volunteers (66 males) without respiratory disease, cardiac disease, or comorbidities that affect ambulation. The volunteers completed three six-minute walk tests. Prior to and at the end of each test, we obtained SpO2 and maximal HR, as well as the Borg scale scores for sensation of dyspnea and lower limb fatigue. The data included in the final analysis were derived from the test with the greatest 6MWD. Results: The mean 6MWD values were 566 ± 87 m and 538 ± 95 m in males and females, respectively (p = 0.08). The 6MWD was greater in taller individuals and decreased in parallel with increases in age or body index mass (BMI). The best adjusted model was the quadratic model. We derived the following equation (valid for both genders): 6MWD = 511 + stature2 (cm) × 0.0066 − age2 × 0.030 − BMI2 × 0.068. This equation explained 55% of the variance in 6MWD. Conclusions: Reference values explaining a high proportion of the variance were derived by a quadratic regression model in healthy adults (of a wide range of ages) in Brazil. Keywords: Reference values; Exercise test; Walking.

Keywords: Reference values; Exercise test; Walking.

Objective: To compare FEV1 and FVC, calculated using three sets of reference equations (devised by Polgar & Promadhat, Hsu et al. and Mallozi in 1971, 1979 and 1995, respectively), and to determine whether the three are similar in predicting lung function in children and adolescents with distinct body mass indices (BMIs). Methods: The individuals were separated into four groups in accordance with the reference standards of the National Center for Health Statistics: underweight (UW), normal weight (NW), overweight (OW), and obese (OB). All were then submitted to spirometry. Results: We evaluated 122 healthy children and adolescents, aged 7-14 years. The FVC values predicted for NW females and UW males through the use of the Hsu et al. equation were significantly higher than the measured values, as were the FEV1 values for UW females and males predicted via the Polgar & Promadhat and Hsu et al. equations. In NW females, the FEV1 values predicted via the Polgar & Promadhat equation were significantly higher than were the measured values. Conclusions: In individuals with distinct BMIs, the measured FVC and FEV1 values were not equivalent to those predicted via the Polgar & Promadhat and Hsu et al. equations. The same was not true for the Mallozi equations. The BMI was not a relevant factor for the predictive index of these equations; therefore, the Mallozi equations can be used without alteration for children and adolescents with distinct BMIs.

Keywords: Spirometry; Reference values; Body mass index; Child; Adolescent.

Objective: To evaluate, using pulmonary function tests, the effectiveness of formoterol as a bronchodilator at 30 min after its administration in patients with poorly reversible COPD. Methods: A prospective study including 40 COPD patients not responding to the short-acting bronchodilator used in the spirometric test-variation of less than 200 mL and less than 7% of predicted in forced expiratory volume in one second (FEV1). All patients were classified as having stage II, III, or IV COPD (Brazilian Thoracic Society/Global Initiative for Chronic Obstructive Lung Disease) and presented FEV1 ≤ 70% of predicted value. The patients were randomized into two groups of 20, with similar clinical characteristics, receiving, via a dry powder inhaler, either formoterol or a placebo. The pulmonary function testing (plethysmography) was repeated at 30 min after formoterol or placebo administration. Results: In the formoterol group, the mean values obtained for FEV1, inspiratory capacity, and forced vital capacity were significantly greater than those obtained in the placebo group (p = 0.00065, p = 0.05, and p = 0.017, respectively), whereas that obtained for airway resistance was significantly lower (p = 0.010). Less pronounced differences were observed for residual volume, vital capacity and specific airway conductance, which were lower, higher and higher, respectively, in the formoterol group. Conclusions: In COPD patients not responding to the short-acting bronchodilator used in the spirometric test, formoterol promoted significant improvement in lung function at 30 min after of administration. Further studies are required to confirm whether formoterol can also be used as a medication for immediate relief of symptoms in COPD.

Keywords: Chronic obstructive pulmonary disease; Respiratory function tests; Bronchodilator agents.

Objective: To evaluate the spirometry values predicted by the 2012 Global Lung Function Initia-tive (GLI) equations, which are recommended for international use, in comparison with those obtained for a sample of White adults used for the establishment of reference equations for spirometry in Brazil. Methods: The sample comprised 270 and 373 healthy males and females, respectively. The mean differences between the values found in this sample and the predicted values calculated from the GLI equations for FVC, FEV1, and VEF1/FVC, as well as their lower lim-its, were compared by paired t-test. The predicted values by each pair of equations were com-pared in various combinations of age and height. Results: For the males in our study sample, the values obtained for all of the variables studied were significantly higher than those predicted by the GLI equations (p < 0.01 for all). These differences become more evident in subjects who were shorter in stature and older. For the females in our study sample, only the lower limit of the FEV1/FVC ratio was significantly higher than that predicted by the GLI equation. Conclusions: The predicted values suggested by the GLI equations for White adults were significantly lower than those used as reference values for males in Brazil. For both genders, the lower limit of the FEV1/FVC ratio is significantly lower than that predicted by the GLI equations.

Keywords: Respiratory function tests/statistics and numerical data; Respiratory function tests/diagnosis; Reference values.

Objective: To identify reference values for handgrip strength through a literature search and compare the agreement of reference values from Brazil with others for handgrip strength in a sample of COPD patients in Brazil, as well as to determine which set of reference values is more discriminative regarding differences in clinical characteristics between individuals with low handgrip strength and normal handgrip strength. Methods: To identify reference values for handgrip strength, a literature search was performed; a retrospective cross-sectional analysis of baseline-only data from two unrelated studies was then performed. Individuals were evaluated for handgrip strength, peripheral muscle strength, respiratory muscle strength, pulmonary function, body composition, exercise capacity, dyspnea, and functional status. Results: Of the 45 studies that were initially selected, 9 met the criteria for inclusion in the analysis, which included 99 COPD patients in Brazil (52% of whom were male with GOLD stage II-IV COPD). The prevalence of low handgrip strength varied across studies (from 9% to 55%), the set of reference values for handgrip strength in a sample of individuals in Brazil having classified 9% of the study sample as having low handgrip strength. The level of agreement between the reference values for a sample of individuals in Brazil and the other sets of reference values varied from weak to excellent. The reference values for a sample of individuals in Brazil showed the highest number of significantly different characteristics between individuals with low and normal handgrip strength. Conclusions: The level of agreement between national and international sets of reference values for handgrip strength varied from weak to excellent in COPD patients in Brazil. Reference values for handgrip strength with higher discriminative capacity are not necessarily those that identify more individuals as having low handgrip strength.

Keywords: Pulmonary disease, chronic obstructive; Hand strength; Muscle weakness; Muscle strength; Reference values.

Objective: Post-infectious bronchiolitis obliterans (PIBO) is a clinical entity that has been classified as constrictive, fixed obstruction of the lumen by fibrotic tissue. However, recent studies using impulse oscillometry have reported bronchodilator responses in PIBO patients. The objective of this study was to evaluate bronchodilator responses in pediatric PIBO patients, comparing different criteria to define the response. Methods: We evaluated pediatric patients diagnosed with PIBO and treated at one of two pediatric pulmonology outpatient clinics in the city of Porto Alegre, Brazil. Spirometric parameters were measured in accordance with international recommendations. Results: We included a total of 72 pediatric PIBO patients. The mean pre- and post-bronchodilator values were clearly lower than the reference values for all parameters, especially FEF25‑75%. There were post-bronchodilator improvements. When measured as mean percent increases, FEV1 and FEF25-75%, improved by 11% and 20%, respectively. However, when the absolute values were calculated, the mean FEV1 and FEF25-75% both increased by only 0.1 L. We found that age at viral aggression, a family history of asthma, and allergy had no significant effects on bronchodilator responses. Conclusions: Pediatric patients with PIBO have peripheral airway obstruction that is responsive to treatment but is not completely reversible with a bronchodilator. The concept of PIBO as fixed, irreversible obstruction does not seem to apply to this population. Our data suggest that airway obstruction is variable in PIBO patients, a finding that could have major clinical implications.

Keywords: Bronchiolitis obliterans; Infection/complications; Airway obstruction; Bronchodilator agents.