Luiz Eduardo Nery

Reference values for lung function tests: I. Static volumes

Static lung volume (LV) measurements have a number of clinical and research applications; however, no previous studies have provided reference values for such tests using a healthy sample of the adult Brazilian population. With this as our main purpose, we prospectively evaluated 100 non-smoking subjects (50 males and 50 females), 20 to 80 years old, randomly selected from more than 8,000 individuals. Gender-specific linear prediction equations were developed by multiple regression analysis with total lung capacity (TLC), functional residual capacity (FRC), residual volume (RV), RV/TLC ratio and inspiratory capacity (IC) as dependent variables, and with age, height, weight, lean body mass and indexes of physical fitness as independent ones. Simpler demographic and anthropometric variables were as useful as more complex measurements in predicting LV values, independent of gender and age (R2 values ranging from 0.49 to 0.78, P < 0.001). Interestingly, prediction equations from North American and European studies overestimated the LV at low volumes and underestimated them at high volumes (P < 0.05). Our results, therefore, provide a more appropriate frame of reference to evaluate the normalcy of static lung volume values in Brazilian males and females aged 20 to 80 years.

Reference values for lung function tests: III. Carbon monoxide diffusing capacity (transfer factor)

Carbon monoxide diffusing capacity (DLCO) or transfer factor (TLCO) is a particularly useful test of the appropriateness of gas exchange across the lung alveolocapillary membrane. With the purpose of establishing predictive equations for DLCO using a non-smoking sample of the adult Brazilian population, we prospectively evaluated 100 subjects (50 males and 50 females aged 20 to 80 years), randomly selected from more than 8,000 individuals. Gender-specific linear prediction equations were developed by multiple regression analysis with single breath (SB) absolute and volume-corrected (VA) DLCO values as dependent variables. In the prediction equations, age (years) and height (cm) had opposite effects on DLCOSB (ml min-1 mmHg-1), independent of gender (-0.13 (age) + 0.32 (height) - 13.07 in males and -0.075 (age) + 0.18 (height) + 0.20 in females). On the other hand, height had a positive effect on DLCOSB but a negative one on DLCOSB/ VA (P < 0.01). We found that the predictive values from the most cited studies using predominantly Caucasian samples were significantly different from the actually measured values (P < 0.05). Furthermore, oxygen uptake at maximal exercise (VO2max) correlated highly to DLCOSB (R = 0.71, P < 0.001); this variable, however, did not maintain an independent role to explain the VO2max variability in the multiple regression analysis (P > 0.05). Our results therefore provide an original frame of reference for either DLCOSB or DLCOSB/VA in Brazilian males and females aged 20 to 80 years, obtained from the standardized single-breath technique.

The variability of the apnoea–hypopnoea index

This study was designed to evaluate the variability of the apnoea–hypopnoea index (AHI) in 20 patients with obstructive sleep apnoea–hypopnoea syndrome (OSAHS) and to determine possible relationships of this variability with other polysomnographic parameters. The subjects were recorded on four consecutive nights. The mean AHI values were not significantly altered throughout the four recording nights (P=0.67). The intraclass correlation coefficient of the AHI on the four nights was 0.92. However, the Bland and Altman plot showed that, individually, the AHI presented an important variability, which was not related to its initial value. In regard to the OSAHS severity, 50% of the patients changed the classification from the first to the subsequent nights. Thirteen of the 20 patients (65%) presented a variation in the AHI value equal or higher than 10 events h–1. When we evaluated the AHI mean values for a specific body position and sleep stage, no difference was observed among the nights. In both supine and lateral–ventral decubitus, higher AHI was observed during Stages 1 and 2 than the other stages. Additionally, the AHI during Stages 1 and 2 and REM sleep was higher on the supine than on the lateral–ventral decubitus. The AHI in OSAHS patients presented a good correlation among the four recording nights; however, a significant individual variability should be considered, especially when AHI is applied in OSAHS classification or as a criterion of therapeutic success.

A step test to assess exercise-related oxygen desaturation in interstitial lung disease

A 6-min step test (6MST) may constitute a practical method for routinely assessing effort tolerance and exercise-related oxyhaemoglobin desaturation (ERD) in the primary care of patients with interstitial lung disease. In total, 31 patients (19 males) with idiopathic pulmonary fibrosis (n = 25) and chronic hypersensitivity pneumonia were submitted, on different days, to two 6MSTs. Physiological responses were compared with those found on maximal and submaximal cycle ergometer tests at the same oxygen uptake (V′O2). Chronic breathlessness was also determined, as measured by the baseline dyspnoea index (BDI). Responses to 6MST were highly reproducible: 1.3±2.0 steps·min-1, ±5 beats·min-1 (cardiac frequency), ±50 mL·min-1 (V′O2), ±7 L·min-1 (minute ventilation) and ±2% (arterial oxygen saturation measured by pulse oximetry (Sp,O2)). The number of steps climbed in 6 min was correlated to peak V′O2 and the BDI. There were significant associations among the tests in relation to presence (change in Sp,O2 between rest and exercise ≥4%) and severity (Sp,O2 <88%) of ERD. Four patients, however, presented ERD only in response to 6MST. Resting diffusing capacity of the lung for carbon monoxide and alveolar–arterial oxygen tension difference were the independent predictors of the number of steps climbed. A single-stage, self-paced 6-min step test provided reliable and reproducible estimates of exercise capacity and exercise-related oxyhaemoglobin desaturation in interstitial lung disease patients.

Inspiratory fraction and exercise impairment in COPD patients GOLD stages II-III

The inspiratory-to-total lung capacity ratio or “inspiratory fraction” (inspiratory capacity(IC)/total lung capacity (TLC)) may be functionally more representative than traditional indices of resting airflow limitation and lung hyperinflation in patients with chronic obstructive pulmonary disease (COPD). In the present retrospective study, a comparison was made of the individual performance of post-bronchodilator IC, IC/TLC and forced expiratory volume in one second (FEV1) in predicting a severely reduced peak oxygen uptake (V′O2; <60% predicted) in 44 COPD patients Global Initiative for Chronic Obstructive Lung Disease stages II-III (post-bronchodilator FEV1 ranging from 31–79% pred). Patients with lower IC/TLC values (≤0.28) showed increased lung volumes and reduced exercise capacity as compared with other subjects. Following a multiple linear regression analysis, only IC/TLC and FEV1 remained as independent predictors of V′O2 (r2 = 0.33). A receiver operating characteristic (ROC) curve analysis revealed that an IC/TLC ≤0.28 had the highest specificity (89.6%), positive predictive value (80%) and overall accuracy (86.3%) in identifying patients with V′O2 <60% pred. In addition, the area under the ROC curve tended to be higher for IC/TLC than IC. In conclusion, post-bronchodilator total lung capacity-corrected inspiratory fraction provides useful information in addition to forced expiratory volume in one second and inspiratory capacity, to estimate the likelihood of chronic obstructive pulmonary disease patients to present with severely reduced maximal exercise capacity.

Effects of respiratory muscle unloading on leg muscle oxygenation and blood volume during high-intensity exercise in chronic heart failure

Blood flow requirements of the respiratory muscles (RM) increase markedly during exercise in chronic heart failure (CHF). We reasoned that if the RM could subtract a fraction of the limited cardiac output (QT) from the peripheral muscles, RM unloading would improve locomotor muscle perfusion. Nine patients with CHF (left ventricle ejection fraction = 26 +/- 7%) undertook constant-work rate tests (70-80% peak) receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (Delta%) in deoxy-hemoglobyn, oxi-Hb ([O2Hb]), tissue oxygenation index, and total Hb ([HbTOT], an index of local blood volume) in the vastus lateralis were measured by near infrared spectroscopy. In addition, QT was monitored by impedance cardiography and arterial O2 saturation by pulse oximetry (SpO2). There were significant improvements in exercise tolerance (Tlim) with PAV. Blood lactate, leg effort/Tlim and dyspnea/Tlim were lower with PAV compared with sham ventilation (P < 0.05). There were no significant effects of RM unloading on systemic O2 delivery as QT and SpO2 at submaximal exercise and at Tlim did not differ between PAV and sham ventilation (P > 0.05). Unloaded breathing, however, was related to enhanced leg muscle oxygenation and local blood volume compared with sham, i.e., higher Delta[O2Hb]% and Delta[HbTOT]%, respectively (P < 0.05). We conclude that RM unloading had beneficial effects on the oxygenation status and blood volume of the exercising muscles at similar systemic O2 delivery in patients with advanced CHF. These data suggest that blood flow was redistributed from respiratory to locomotor muscles during unloaded breathing.

Clinical, Anthropometric and Upper Airway Anatomic Characteristics of Obese Patients with Obstructive Sleep Apnea Syndrome

Background: Obese subjects are at increased risk of developing obstructive sleep apnea syndrome (OSAS). However, the individual role of local (i.e., upper airway-related) and general (clinical and whole-body anthropometric) characteristics in determining OSAS in obese patients is still controversial. Objectives: To contrast the clinical, anthropometric and upper airway anatomical features of obese subjects presenting or not presenting with OSAS. Methods: Thirty-seven obese (BMI ≧30 kg/m2) males with OSAS and 14 age- and gender-matched obese controls underwent clinical and anthropometric (BMI, waist-to-hip ratio and neck circumference) evaluation. In a subgroup of subjects (18 and 11 subjects, respectively), magnetic resonance imaging (MRI) during wakefulness was used to study the upper airway anatomy. Results: OSAS patients showed significantly higher BMI, waist-to-hip ratio and neck circumference as compared to controls (p < 0.05). They also referred to nonrepairing sleep, impaired attention, and previous car accidents more frequently (p < 0.05). The transversal diameter of the airways (TDAW) at the retroglossal level by MRI was found to be an independent predictor of the presence and severity of OSAS (p < 0.05). Parapharyngeal fat increase, however, was not related to OSAS. A TDAW >12 mm was especially useful to rule out severe OSAS (apnea-hypopnea index >30, negative predictive value = 88.9%, likelihood ratio for a negative test result = 0.19). Conclusions: MRI of the upper airway can be used in association with clinical and anthropometric data to identify obese males at increased risk of OSAS.

The effect of age on the power/duration relationship and the intensity-domain limits in sedentary men.

Abstract The time to fatigue (t) in response to high-intensity constant-load exercise decreases hyperbolically with increasing power (W˙), at least in active and younger individuals [i.e. (W˙−θF)t=W′, where θF is the critical power asymptote and W′ is the curvature constant]. Little is known, however, about the combined effects of age and sedetarity on these parameters. We therefore evaluated 17 non-trained males (9 aged 60–75 years and 8 aged below 30 years) who underwent ramp-incremental cycle ergometry and, on different days, 4 high-intensity constant-load tests to t. Compared to their younger counterparts, the older subjects presented significantly lower maximum oxygen uptake (i.e. the maximum value of oxygen uptake attained at the end of a progressive exercise with the subject exerting a presumably maximal effort, μV˙O2), estimated lactate threshold (V˙O2θL), V˙O2θF, and W′ (P < 0.05). Interestingly, however, both V˙O2θL and V˙O2θF, when expressed as a percentage of μV˙O2, were higher in older than in younger men [61.8 (6.2)% versus 45.4 (4.6)% and 87.8 (7.3)% versus 79.0 (8.2)%, P < 0.05, respectively]. Therefore, age was associated with an increase in the relative magnitude of the “moderate”, sub-θL exercise-intensity domain (+30.4%), mainly at the expense of the “very-heavy”, supra-θF domain (−56%). Our results demonstrate that age and sedentarity are associated with: (1) marked reductions in both the aerobic (θF) and anaerobic (W′) determinants of the W˙/t relationship, and (2) changes in either the absolute or relative magnitudes of the exercise-intensity domains. These findings are consistent with the notion that endurance-related parameters are less diminished with ageing than the maximal capacity, thereby mitigating the deleterious effects of senescence in the functional capacity.

The pattern and timing of breathing during incremental exercise: a normative study.

Clinical evaluation of the pattern and timing of breathing during submaximal exercise can be valuable for the identification of the mechanical ventilatory consequences of different disease processes and for assessing the efficacy of certain interventions. Sedentary individuals (60 male/60 female, aged 20–80 yrs) were randomly selected from >8,000 subjects and submitted to ramp incremental cycle ergometry. Tidal volume (VT)/ resting inspiratory capacity, respiratory frequency, total respiratory time (Ttot), inspiratory time (TI), expiratory time (TE), duty cycle (TI/Ttot) and mean inspiratory flow (VT/TI) were analysed at selected submaximal ventilatory intensities. Senescence and female sex were associated with a more tachypnoeic breathing pattern during isoventilation. The decline in Ttot was proportional to the TI and TE reductions, i.e. TI/Ttot was remarkably constant across age strata, independent of sex. The pattern, but not timing, of breathing was also influenced by weight and height; a set of demographically and anthropometrically based prediction equations are therefore presented. These data provide a frame of reference for assessing the normality of some clinically useful indices of the pattern and timing of breathing during incremental cycle ergometry in sedentary males and females aged 20–80 yrs.

Maximal aerobic power and leg muscle mass and strength related to age in non-athletic males and females

Abstract To investigate the relationships between the age-associated decline in peak oxygen uptake (peak V˙O2), leg muscle mass (LMM) and leg strength (LS) under the modulating effect of gender and level of physical activity (LPA, as assessed by questionnaire), we evaluated 71 sedentary subjects [males(M):females(F), 34:37], aged 20–80 years. Peak V˙O2 at maximum cycle ergometry was related to LMM (dual energy X-ray absorptiometry) and LS (isokinetic dynamometry) using both standard (y · x−1) and power function ratios (allometry). Absolute values of all variables were higher in males and declined with age (P < 0.01). Differences between the genders disappeared after peak V˙O2·LS−1.46 (M) or −1.62 (F) adjustment but remained significant between peak V˙O2·LMM-−0.51 (M) or −0.45 (F) and LS·LMM-−0.91 (M) or −1.10 (F) corrected values. Allometric correction of peak V˙O2 and LS by LMM slowed their age-related declines; the flattening effect however, was more evident in the females. Interestingly, while no age-related decrement in peak V˙O2·LS−1 was found, power function ratio values also declined with age, and at a slower rate in females. These findings are consistent with those obtained following a multiple regression analysis using LPA as an independent covariate (P < 0.01). We conclude that using adequate scaling methods and controlling by LPA: (1) no gender differences are observed in peak V˙O2 adjusted for LS, (2) loss of LS and LMM are important determinants of the age-associated reduction in physical fitness in both genders but (3) age per se has an LS- and LMM-independent influence on the functional decline, although this intrinsic effect of senescence is less pronounced in females.