Objective: To evaluate autonomic modulation in individuals with COPD, compared with healthy controls, via recurrence plots (RPs) and linear heart rate variability (HRV) indices. Methods: We analyzed data on 74 volunteers, who were divided into two groups: COPD (n = 43) and control (n = 31). For calculation of HRV indices, heart rate was measured beat-by-beat during 30 min of supine rest using a heart-rate meter. We analyzed linear indices in the time and frequency domains, as well as indices derived from the RPs. Results: In comparison with the control group, the COPD group showed significant increases in the indices derived from the RPs, as well as significant reductions in the linear indices in the time and frequency domains. No significant differences were observed in the linear indices in the frequency domains expressed in normalized units or in the low frequency/high frequency ratio. Conclusions: Individuals with COPD show a reduction in both sympathetic and parasympathetic activity, associated with decreased complexity of autonomic nervous system function, as identified by RPs, which provide important complementary information in the detection of autonomic changes in this population.

Keywords: Pulmonary disease, chronic obstructive; Autonomic nervous system; Nonlinear dynamics; Recurrence; Heart rate; Sympathetic nervous system.

Objective: To determine the role of the IL8 rs4073 polymorphism in predicting the risk of central nervous system (CNS) toxicity in patients receiving standard pharmacological treatment for multidrug-resistant tuberculosis (MDR-TB). Methods: A cohort of 85 consenting MDR-TB patients receiving treatment with second-line antituberculosis drugs had their blood samples amplified for the IL8 (rs4073) gene and genotyped. All patients were clinically screened for evidence of treatment toxicity and categorized accordingly. Crude and adjusted associations were assessed. Results: The chief complaints fell into the following categories: CNS toxicity; gastrointestinal toxicity; skin toxicity; and eye and ear toxicities. Symptoms of gastrointestinal toxicity were reported by 59% of the patients, and symptoms of CNS toxicity were reported by 42.7%. With regard to the genotypes of IL8 (rs4073), the following were identified: AA, in 64 of the study participants; AT, in 7; and TT, in 11. A significant association was found between the dominant model of inheritance and CNS toxicity for the crude model (p = 0.024; OR = 3.57; 95% CI, 1.18-10.76) and the adjusted model (p = 0.031; OR = 3.92; 95% CI, 1.13-13.58). The AT+TT genotype of IL8 (rs4073) showed a 3.92 times increased risk of CNS toxicity when compared with the AA genotype. Conclusions: The AT+TT genotype has a tendency to be associated with an increased risk of adverse clinical features during MDR-TB treatment.

Keywords: Tuberculosis, multidrug-resistant; Immunity; Pharmacogenetics; Polymerase chain reaction; Risk.

Objective: To evaluate lung function and inspiratory muscle strength, correlating them with exercise tolerance, in obese individuals with obstructive sleep apnea syndrome (OSAS). Methods: The sample comprised 31 adult subjects with moderate-to-severe OSAS diagnosed by polysomnography. We used spirometry to measure FVC, FEV1, and FVC/FEV1 ratio, using pressure manometry to measure MIP and MEP. The incremental shuttle walk test (ISWT) and the six-minute walk test (6MWT) were used in order to determine functional exercise capacity. Results: In this sample, the mean values for FVC (% of predicted), FEV1 (% of predicted): MIP, and MEP were 76.4 ± 12.3%, 80.1 ± 6.3%, 60.0 ± 21.9 cmH2O, and 81.3 ± 22.2 cmH2O, respectively. The mean distances covered on the ISWT and 6MWT were 221 ± 97 m and 480.8 ± 67.3 m, respectively. The ISWT distance showed moderate positive correlations with FVC (r = 0.658; p = 0.001) and FEV1 (r = 0.522; p = 0.003). Conclusions: In this sample of obese subjects with untreated OSAS, lung function, inspiratory muscle strength, and exercise tolerance were all below normal. In addition, we found that a decline in lung function, but not in respiratory muscle strength, was associated with exercise tolerance in these patients.

Keywords: Sleep apnea syndromes; Exercise tolerance; Respiratory function tests; Respiratory muscles.

Objective: To investigate the validity of an eight-contact electrode bioelectrical impedance analysis (BIA) system within a household scale for assessing whole body composition in COPD patients. Methods: Seventeen patients with COPD (mean age = 67 ± 8 years; mean FEV1 = 38.6 ± 16.1% of predicted; and mean body mass index = 24.7 ± 5.4 kg/m2) underwent dual-energy X-ray absorptiometry (DEXA) and an eight-contact electrode BIA system for body composition assessment. Results: There was a strong inter-method correlation for fat mass (r = 0.95), fat-free mass (r = 0.93), and lean mass (r = 0.93), but the correlation was moderate for bone mineral content (r = 0.73; p < 0.01 for all). In the agreement analysis, the values between DEXA and the BIA system differed by only 0.15 kg (−6.39 to 6.70 kg), 0.26 kg (−5.96 to 6.49 kg), −0.13 kg (−0.76 to 0.50 kg), and −0.55 kg (−6.71 to 5.61 kg) for fat-free mass, lean mass, bone mineral content, and fat mass, respectively. Conclusions: The eight-contact electrode BIA system showed to be a valid tool in the assessment of whole body composition in our sample of patients with COPD.

Keywords: Pulmonary disease, chronic obstructive; Body composition; Electric impedance.

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 the magnitude of diurnal changes in the parameters of pulmonary function and respiratory muscle strength/endurance in a sample of patients with COPD. Methods: A group of 7 patients underwent spirometry, together with determination of MIP and MEP, at two distinct times (between 8:00 and 8:30 a.m. and between 4:30 and 5:00 p.m.) on a single day. Between assessments, the patients remained at rest in the laboratory. Results: In accordance with the Global Initiative for Chronic Obstructive Pulmonary Disease staging system, COPD was classified as moderate, severe, and very severe in 1, 3, and 3 of the patients, respectively. From the first to the second assessment, there were significant decreases in FVC, FEV1, and MEP (of 13%, 15%, and 10%, respectively), as well as (less than significant) decreases in PEF, MIP, and maximal voluntary ventilation (of 9%, 3%, and 11%, respectively). Conclusions: In this sample of COPD patients, there were diurnal variations in the parameters of pulmonary function and respiratory muscle strength. The values of FEV1, FVC, and MEP were significantly lower in the afternoon than in the morning.

Keywords: Pulmonary disease, chronic obstructive; Respiratory function tests; Respiratory muscles.

Objective: To evaluate the anthropometric data obtained for residents of the city of São Paulo, Brazil, in a study of Latin America conducted in two phases (baseline, in 2003, and follow-up, in 2012). Methods: This was an analysis of data obtained for São Paulo residents in a two-phase population-based study evaluating the prevalence of COPD and its relationship with certain risk factors among individuals ≥ 40 years of age. The anthropometric data included values for weight, height, body mass index (BMI), and waist circumference. In the follow-up phase of that study, the same variables were evaluated in the same population sample as that of the baseline phase. Results: Of the 1,000 São Paulo residents enrolled in the baseline phase of that study, 587 participated in the follow-up phase, and 80 (13.6%) of those 587 subjects had COPD. Comparing the baseline and follow-up phases, we found increases in all anthropometric measures in both groups (COPD and non-COPD), although the differences were significant only in the non-COPD group. The subjects with mild COPD showed increases in weight and BMI (Δweight = 1.6 ± 5.7 and ΔBMI = 0.7 ± 2.2), whereas those with moderate or severe COPD showed reductions (Δweight = −1.7 ± 8.1 and ΔBMI = −0.4 ± 3.0), as did those with severe or very severe COPD (Δweight = −0.5 ± 5.4 and ΔBMI = −0.8 ± 3.3). Conclusions: Between the two phases of the study, the subjects with mild COPD showed increases in weight and BMI, whereas those with a more severe form of the disease showed reductions.

Keywords: Pulmonary disease, chronic obstructive; Body mass index; Obesity; Waist circumference.

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.

To describe the intra-rater and inter-rater reliability of the Brazilian Portuguese version of the fatigue severity scale (FSS) in patients with COPD and to identify the presence of its association with parameters of pulmonary function, dyspnea, and functional capacity. Methods: This was an observational cross-sectional study involving 50 patients with COPD, who completed the FSS in interviews with two researchers in two visits. The FSS scores were correlated with those of the Medical Research Council (MRC) scale, as well as with FEV1, FVC, and six-minute walk distance (6MWD). Results: The mean age of the patients was 69.4 ± 8.23 years, whereas the mean FEV1 was 46.5 ± 20.4% of the predicted value. The scale was reliable, with an intraclass correlation coefficient of 0.90 (95% CI, 0.81-0.94; p < 0.01). The FSS scores showed significant correlations with those of MRC scale (r = 0.70; p < 0.01), as well as with 6MWD (r = −0.77; p < 0.01), FEV1 (r = −0.38; p < 0.01), FVC (r = −0.35; p < 0.01), and stage of the disease in accordance with the Global Initiative for Chronic Obstructive Lung Disease criteria (r = 0.37; p < 0.01). Conclusions: The Brazilian Portuguese version of the FSS proved reliable for use in COPD patients in Brazil and showed significant correlations with sensation of dyspnea, functional capacity, pulmonary function, and stage of the disease.

Keywords: Fatigue; Pulmonary disease, chronic obstructive; Reproducibility of results; Validation studies.

Objective: To evaluate peripheral respiratory system resistance and reactance (Rrs and Xrs, respectively) in obese individuals. Methods: We recruited 99 individuals, dividing them into four groups by body mass index (BMI): < 30.0 kg/m2 (control, n = 31); 30.0-39.9 kg/m2 (obesity, n = 13); 40.0-49.9 kg/m2 (severe obesity, n = 28); and ≥ 50.0 kg/m2 (morbid obesity, n = 13). Using impulse oscillometry, we measured total Rrs, central Rrs, and Xrs. Peripheral Rrs was calculated as the difference between total Rrs and central Rrs. All subjects also underwent spirometry. Results: Of the 99 individuals recruited, 14 were excluded because they failed to perform forced expiratory maneuvers correctly during spirometry. The individuals in the severe obesity and morbid obesity groups showed higher peripheral Rrs and lower Xrs in comparison with those in the two other groups. Conclusions: Having a BMI ≥ 40 kg/m2 was associated with a significant increase in peripheral Rrs and with a decrease in Xrs.

Keywords: Obesity; Airway obstruction; Oscillometry; Respiratory function tests.

Objective: Impaired respiratory mechanics and gas exchange may contribute to sleep disturbance in patients with COPD. We aimed to assess putative associations of different domains of lung function (airflow limitation, lung volumes, and gas exchange efficiency) with polysomnography (PSG)-derived parameters of sleep quality and architecture in COPD. Methods: We retrospectively assessed data from COPD 181 patients = 40 years of age who underwent spirometry, plethysmography, and overnight PSG. Univariate and multivariate linear regression models predicted sleep efficiency (total sleep time/total recording time) and other PSG-derived parameters that reflect sleep quality. Results: The severity of COPD was widely distributed in the sample (post-bronchodilator FEV1 ranging from 25% to 128% of predicted): mild COPD (40.3%), moderate COPD (43.1%), and severe-very severe COPD (16.6%). PSG unveiled a high proportion of obstructive sleep apnea (64.1%) and significant nocturnal desaturation (mean pulse oximetry nadir = 82.2% ± 6.9%). After controlling for age, sex, BMI, apnea-hypopnea index, nocturnal desaturation, comorbidities, and psychotropic drug prescription, FEV1/FVC was associated with sleep efficiency (ß = 25.366; R2 = 14%; p < 0.001), whereas DLCO predicted sleep onset latency (ß = -0.314; R2 = 13%; p < 0.001) and rapid eye movement sleep time/total sleep time in % (ß = 0.085; R2 = 15%; p = 0.001). Conclusions: Pulmonary function variables reflecting severity of airflow and gas exchange impairment, adjusted for some potential confounders, were weakly related to PSG outcomes in COPD patients. The direct contribution of the pathophysiological hallmarks of COPD to objectively measured parameters of sleep quality seems to be less important than it was previously assumed.

Keywords: Pulmonary disease, chronic obstructive; Respiratory function tests; Sleep; Sleep apnea, obstructive; Comorbidity.

Objective: To evaluate oral health-related quality of life (OHRQoL) among individuals with severe asthma, comparing it with that observed among individuals with mild-to-moderate asthma and individuals without asthma. Methods: We conducted a cross-sectional study of 125 individuals: 40 with severe asthma; 35 with mild-to-moderate asthma; and 50 without asthma. We calculated the decayed, missing, and filled teeth (DMFT) index, as well as the Periodontal Screening and Recording index, and determined the stimulated salivary flow rate. We applied three structured questionnaires: the 14-item Oral Health Impact Profile (OHIP-14); the Medical Outcomes Study 36-Item Short-Form Health Survey, version 2 (SF-36v2); and the Work Ability Index (WAI). Results: Periodontitis and reduced salivary flow were both more common in the severe asthma group than in the mild-to-moderate asthma and no-asthma groups. In addition, the WAI scores were lower in the severe asthma group than in the mild-to-moderate asthma and no-asthma groups, as were the scores for all SF-36v2 domains. The individuals with severe asthma also scored lower for the OHIP-14 domains than did those without asthma. Although the mean DMFT index did not differ significantly among the groups, the mean number of missing teeth was highest in the severe asthma group. Strong correlations between the SF-36v2 Component Summaries and poorer OHRQoL were only observed in the severe asthma group. Conclusions: Severe asthma appears to be associated with poorer oral health, poorer OHRQoL, a lower WAI, and lower scores for SF-36v2 domains.

Keywords: Oral health; Periodontal diseases; Asthma.

Objective: The clinical, functional, radiological and genotypic descriptions of patients with an alpha-1 antitrypsin (A1AT) gene mutation in a referral center for COPD in Brazil. Methods: A cross-sectional study of patients with an A1AT gene mutation compatible with deficiency. We evaluated the A1AT dosage and genotypic, demographic, clinical, tomographic, and functional characteristics of these patients. Results: Among the 43 patients suspected of A1AT deficiency (A1ATD), the disease was confirmed by genotyping in 27 of them. The A1AT median dosage was 45 mg/dL, and 4 patients (15%) had a normal dosage. Median age was 54, 63% of the patients were male, and the respiratory symptoms started at the age of 40. The median FEV1 was 1.37L (43% predicted). Tomographic emphysema was found in 77.8% of the individuals. The emphysema was panlobular in 76% of them and 48% had lower lobe predominance. The frequency of bronchiectasis was 52% and the frequency of bronchial thickening was 81.5%. The most common genotype was Pi*ZZ in 40.7% of participants. The other genotypes found were: Pi*SZ (18.5%), PiM1Z (14.8%), Pi*M1S (7.4%), Pi*M2Z (3.7%), Pi*M1I (3.7%), Pi*ZMnichinan (3.7%), Pi*M3Plowell (3.7%), and Pi*SF (3.7%). We did not find any significant difference in age, smoking load, FEV1, or the presence of bronchiectasis between the groups with a normal and a reduced A1AT dosage, neither for 1 nor 2-allele mutation for A1ATD. Conclusions: Our patients presented a high frequency of emphysema, bronchiectasis and bronchial thickening, and early-beginning respiratory symptoms. The most frequent genotype was Pi*ZZ. Heterozygous genotypes and normal levels of A1AT also manifested significant lung disease.

Keywords: Alpha-1 antitrypsin; Emphysema; Alleles.

Objective: Current debates on the bronchodilator response in COPD patients and whether the variation in FEV1 can be considered as an indicator of complete reversibility in such patients motivated us to conduct this study. The objective of the study was to determine the effect of albuterol on the resistive and reactive properties of the respiratory system in COPD patients. Methods: We evaluated 70 patients with COPD, divided into two groups based on spirometry findings: bronchodilator (BD)-negative (n = 39); and BD-positive (n = 31). We used the forced oscillation technique (FOT) to evaluate the following parameters: resistance at the intercept (R0), associated with the total resistance of the respiratory system; mean resistance (Rm), associated with central airway resistance; dynamic compliance (Cdyn); and the slope of resistance (S) and mean reactance (Xm), both of which are associated with the homogeneity of the respiratory system. Results: The use of albuterol resulted in significant reductions in R0 (p < 0.00002) and Rm (p < 0.0002). There were also significant increases in S (p < 0.0001), Cdyn (p < 0.0001) and Xm (p < 0.00004). These modifications occurred in both groups, the changes in FOT parameters being greater than those observed for spirometric parameters. Conclusions: The use of albuterol improved the resistive and reactive properties of the respiratory system of the COPD patients under study. These changes occurred regardless of the FEV1-based classification, thereby indicating that the use of this parameter in isolation might not suffice to identify the physiological effects involved.

Keywords: Pulmonary disease, chronic obstructive; Bronchodilator agents; Spirometry; Albuterol.