Exhaled nitric oxide collected with two different mouthpieces: a study in asthmatic patients

Techniques for collecting exhaled nitric oxide (ENO) recommend the use of antibacterial filters of 0.3 µm. The aim of the present study was to compare the measurements of ENO obtained with two different filtering devices. Air samples from 17 asthmatic and 17 non-asthmatic subjects were collected by a recommended off-line technique using two different mouthpieces: 1) the Sievers disposable tool (A) under a breathing pressure of 18 cmH2O, and 2) a mouthpiece containing a HEPA filter (B) under a breathing pressure of 12 cmH2O. The nitric oxide samples were collected into an impermeable reservoir bag. Values for ENO were compared using two-way repeated measures ANOVA followed by the Tukey test. Agreement was assessed by Bland-Altman analysis. ENO values obtained with mouthpieces A and B were comparable for asthmatic (mean ± SEM, 42.9 ± 6.9 vs 43.3 ± 6.6 ppb) and non-asthmatic (13.3 ± 1.3 vs 13.7 ± 1.1 ppb) subjects. There was a significant difference in ENO between asthmatics and non-asthmatics using either mouthpiece A (P<0.001) or B (P<0.001). There was a positive correlation between mouthpiece A and mouthpiece B for both groups. The Bland-Altman limits of agreement were considered to be acceptable. Mouthpiece B was less expensive than A, and these data show that it can be used without compromising the result. Our data confirm reports of higher ENO values in the presence of airway inflammation.

Effects of age and physical activity on the autonomic control of heart rate in healthy men

The effects of the aging process and an active life-style on the autonomic control of heart rate (HR) were investigated in nine young sedentary (YS, 23 ± 2.4 years), 16 young active (YA, 22 ± 2.1 years), 8 older sedentary (OS, 63 ± 2.4 years) and 8 older active (OA, 61 ± 1.1 years) healthy men. Electrocardiogram was continuously recorded for 15 min at rest and for 4 min in the deep breathing test, with a breath rate of 5 to 6 cycles/min in the supine position. Resting HR and RR intervals were analyzed by time (RMSSD index) and frequency domain methods. The power spectral components are reported in normalized units (nu) at low (LF) and high (HF) frequency, and as the LF/HF ratio. The deep breathing test was analyzed by the respiratory sinus arrhythmia indices: expiration/inspiration ratio (E/I) and inspiration-expiration difference (deltaIE). The active groups had lower HR and higher RMSSD index than the sedentary groups (life-style condition: sedentary vs active, P < 0.05). The older groups showed lower HFnu, higher LFnu and higher LF/HF ratio than the young groups (aging effect: young vs older, P < 0.05). The OS group had a lower E/I ratio (1.16) and deltaIE (9.7 bpm) than the other groups studied (YS: 1.38, 22.4 bpm; YA: 1.40, 21.3 bpm; OA: 1.38, 18.5 bpm). The interaction between aging and life-style effects had a P < 0.05. These results suggest that aging reduces HR variability. However, regular physical activity positively affects vagal activity on the heart and consequently attenuates the effects of aging in the autonomic control of HR.

Repercussions of a sleep medicine outreach program

Despite the high prevalence of sleep disorders, many healthcare professionals and lay people have little knowledge of Sleep Medicine. Mindful of such a reality, in 2001 the Sleep Institute of the Associação Fundo de Incentivo à Psicofarmacologia launched a campaign to increase Sleep Medicine awareness. Media features, exhibitions, inserts, and classes were used to reach 2,000,000 people and 55,000 healthcare professionals during the period from 2001 to 2004. To evaluate this program, we compared data for polysomnography referrals to the Institute in 2000 and in 2004. A total of 8805 referrals were evaluated (2000: 2164; 2004: 6641). Over the 4 years of the program, the number of beds increased by 43%; more women were referred (31 vs 37%; P < 0.001), mainly with a diagnostic hypothesis of sleep-disorder breathing (SDB). SDB was the most frequent diagnostic hypothesis in 2000 and 2004. In 2004 there were fewer referrals without a diagnostic hypothesis (27 vs 21%; P < 0.001) and for controlling surgically treated SDB (2.3 vs 1.6%; P < 0.05), and an increase in the following diagnostic hypotheses: non-invasive treatment of SDB (8.3 vs 12.3%; P < 0.001) and insomnia (3.5 vs 6.5%; P < 0.001). Insomnia diagnostic hypothesis was better correlated with SDB on referral documents in 2004 and less with a diagnostic hypothesis of limb movement disturbance. The program helped increase polysomnography referrals, particularly among women. Healthcare professionals appear to have a more developed understanding of sleep disorders.

Ambient particulate air pollution from vehicles promotes lipid peroxidation and inflammatory responses in rat lung

Oxidative stress plays a major role in the pathogenesis of particle-dependent lung injury. Ambient particle levels from vehicles have not been previously shown to cause oxidative stress to the lungs. The present study was conducted to a) determine whether short-term exposure to ambient levels of particulate air pollution from vehicles elicits inflammatory responses and lipid peroxidation in rat lungs, and b) determine if intermittent short-term exposures (every 4 days) induce some degree of tolerance. Three-month-old male Wistar rats were exposed to ambient particulate matter (PM) from vehicles (N = 30) for 6 or 20 continuous hours, or for intermittent (5 h) periods during 20 h for 4 consecutive days or to filtered air (PM <10 µm; N = 30). Rats continuously breathing polluted air for 20 h (P-20) showed a significant increase in the total number of leukocytes in bronchoalveolar lavage compared to control (C-20: 2.61 x 105 ± 0.51;P-20: 5.01 x 105 ± 0.81; P < 0.05) and in lipid peroxidation ([MDA] nmol/mg protein: C-20: 0.148 ± 0.01; P-20: 0.226 ± 0.02; P < 0.05). Shorter exposure (6 h) and intermittent 5-h exposures over a period of 4 days did not cause significant changes in leukocytes. Lipid damage resulting from 20-h exposure to particulate air pollution did not cause a significant increase in lung water content. These data suggest oxidative stress as one of the mechanisms responsible for the acute adverse respiratory effects of particles, and suggest that short-term inhalation of ambient particulate air pollution from street with high automobile traffic represents a biological hazard.

Effect of smoking habits on sleep

To evaluate the effect of smoking habits on sleep, data from 1492 adults referred to the Sleep Institute were accessed and divided into 3 categories of smoking status: current, former and non-smokers. Categories of pack-years (<15 and ≥15) defined smoking severity. The association of smoking status and smoking severity with sleep was analyzed for sleep parameters, especially apnea and hypopnea index (AHI) ≥5, more than 5% of total sleep time (TST) spent with oxyhemoglobin saturation (SaO2) <90%, and arousal index. The arousal index was higher among current (21 ± 17) and former smokers (20 ± 17) than non-smokers (17 ± 15; P < 0.04). Former smokers had a higher percent of TST at SaO2 <90% than non-smokers (9 ± 18 vs 6 ± 13; P < 0.04). Former smokers with pack-years ≥15 compared to <15 exhibited higher AHI (22 ± 24 vs 16 ± 21; P < 0.05) and arousal index (22 ± 19 vs 18 ± 15; P < 0.05). Current smokers with pack-years ≥15 compared to <15 exhibited higher arousal index (23 ± 18 vs 18 ± 16; P < 0.05) and percent of TST at SaO2 <90% (11 ± 17 vs 6 ± 13; P < 0.05). Smoking status and pack-years were not associated with AHI ≥5 on logistic regression analysis, but current smokers with pack-years ≥15 were 1.9 times more likely to spend more than 5% of TST at SaO2 <90% than non-smokers (95%CI = 1.21-2.97; P = 0.005). The variability of arousal index was influenced by gender, AHI and current smokers with pack-years ≥15 (all P < 0.01). Smoking habits seem to be associated with arousal and oxyhemoglobin desaturation during sleep, but not with AHI. The effect was more pronounced in current than former smokers.

Control of respiration in fish, amphibians and reptiles

Fish and amphibians utilise a suction/force pump to ventilate gills or lungs, with the respiratory muscles innervated by cranial nerves, while reptiles have a thoracic, aspiratory pump innervated by spinal nerves. However, fish can recruit a hypobranchial pump for active jaw occlusion during hypoxia, using feeding muscles innervated by anterior spinal nerves. This same pump is used to ventilate the air-breathing organ in air-breathing fishes. Some reptiles retain a buccal force pump for use during hypoxia or exercise. All vertebrates have respiratory rhythm generators (RRG) located in the brainstem. In cyclostomes and possibly jawed fishes, this may comprise elements of the trigeminal nucleus, though in the latter group RRG neurons have been located in the reticular formation. In air-breathing fishes and amphibians, there may be separate RRG for gill and lung ventilation. There is some evidence for multiple RRG in reptiles. Both amphibians and reptiles show episodic breathing patterns that may be centrally generated, though they do respond to changes in oxygen supply. Fish and larval amphibians have chemoreceptors sensitive to oxygen partial pressure located on the gills. Hypoxia induces increased ventilation and a reflex bradycardia and may trigger aquatic surface respiration or air-breathing, though these latter activities also respond to behavioural cues. Adult amphibians and reptiles have peripheral chemoreceptors located on the carotid arteries and central chemoreceptors sensitive to blood carbon dioxide levels. Lung perfusion may be regulated by cardiac shunting and lung ventilation stimulates lung stretch receptors.

Autonomic control of cardiorespiratory interactions in fish, amphibians and reptiles

Control of the heart rate and cardiorespiratory interactions (CRI) is predominantly parasympathetic in all jawed vertebrates, with the sympathetic nervous system having some influence in tetrapods. Respiratory sinus arrhythmia (RSA) has been described as a solely mammalian phenomenon but respiration-related beat-to-beat control of the heart has been described in fish and reptiles. Though they are both important, the relative roles of feed-forward central control and peripheral reflexes in generating CRI vary between groups of fishes and probably between other vertebrates. CRI may relate to two locations for the vagal preganglionic neurons (VPN) and in particular cardiac VPN in the brainstem. This has been described in representatives from all vertebrate groups, though the proportion in each location is variable. Air-breathing fishes, amphibians and reptiles breathe discontinuously and the onset of a bout of breathing is characteristically accompanied by an immediate increase in heart rate plus, in the latter two groups, a left-right shunting of blood through the pulmonary circuit. Both the increase in heart rate and opening of a sphincter on the pulmonary artery are due to withdrawal of vagal tone. An increase in heart rate following a meal in snakes is related to withdrawal of vagal tone plus a non-adrenergic-non-cholinergic effect that may be due to humoral factors released by the gut. Histamine is one candidate for this role.

Central chemoreceptors and neural mechanisms of cardiorespiratory control

The arterial partial pressure (P CO2) of carbon dioxide is virtually constant because of the close match between the metabolic production of this gas and its excretion via breathing. Blood gas homeostasis does not rely solely on changes in lung ventilation, but also to a considerable extent on circulatory adjustments that regulate the transport of CO2 from its sites of production to the lungs. The neural mechanisms that coordinate circulatory and ventilatory changes to achieve blood gas homeostasis are the subject of this review. Emphasis will be placed on the control of sympathetic outflow by central chemoreceptors. High levels of CO2 exert an excitatory effect on sympathetic outflow that is mediated by specialized chemoreceptors such as the neurons located in the retrotrapezoid region. In addition, high CO2 causes an aversive awareness in conscious animals, activating wake-promoting pathways such as the noradrenergic neurons. These neuronal groups, which may also be directly activated by brain acidification, have projections that contribute to the CO2-induced rise in breathing and sympathetic outflow. However, since the level of activity of the retrotrapezoid nucleus is regulated by converging inputs from wake-promoting systems, behavior-specific inputs from higher centers and by chemical drive, the main focus of the present manuscript is to review the contribution of central chemoreceptors to the control of autonomic and respiratory mechanisms.

Cardiopulmonary exercise testing variables as predictors of long-term outcome in thoracic sarcoidosis

Cardiopulmonary exercise testing (CPET) plays an important role in the assessment of functional capacity in patients with interstitial lung disease. The aim of this study was to identify CPET measures that might be helpful in predicting the vital capacity and diffusion capacity outcomes of patients with thoracic sarcoidosis. A longitudinal study was conducted on 42 nonsmoking patients with thoracic sarcoidosis (median age = 46.5 years, 22 females). At the first evaluation, spirometry, the measurement of single-breath carbon monoxide diffusing capacity (D LCOsb) and CPET were performed. Five years later, the patients underwent a second evaluation consisting of spirometry and D LCOsb measurement. After 5 years, forced vital capacity (FVC)% and D LCOsb% had decreased significantly [95.5 (82-105) vs 87.5 (58-103) and 93.5 (79-103) vs 84.5 (44-102), respectively; P < 0.0001 for both]. In CPET, the peak oxygen uptake, maximum respiratory rate, breathing reserve, alveolar-arterial oxygen pressure gradient at peak exercise (P(A-a)O2), and Δ SpO2 values showed a strong correlation with the relative differences for FVC% and D LCOsb% (P < 0.0001 for all). P(A-a)O2 ≥22 mmHg and breathing reserve ≤40% were identified as significant independent variables for the decline in pulmonary function. Patients with thoracic sarcoidosis showed a significant reduction in FVC% and D LCOsb% after 5 years of follow-up. These data show that the outcome measures of CPET are predictors of the decline of pulmonary function.

Intercostal and forearm muscle deoxygenation during respiratory fatigue in patients with heart failure: potential role of a respiratory muscle metaboreflex

The purpose of this study was to determine the effect of respiratory muscle fatigue on intercostal and forearm muscle perfusion and oxygenation in patients with heart failure. Five clinically stable heart failure patients with respiratory muscle weakness (age, 66±12 years; left ventricle ejection fraction, 34±3%) and nine matched healthy controls underwent a respiratory muscle fatigue protocol, breathing against a fixed resistance at 60% of their maximal inspiratory pressure for as long as they could sustain the predetermined inspiratory pressure. Intercostal and forearm muscle blood volume and oxygenation were continuously monitored by near-infrared spectroscopy with transducers placed on the seventh left intercostal space and the left forearm. Data were compared by two-way ANOVA and Bonferroni correction. Respiratory fatigue occurred at 5.1±1.3 min in heart failure patients and at 9.3±1.4 min in controls (P<0.05), but perceived effort, changes in heart rate, and in systolic blood pressure were similar between groups (P>0.05). Respiratory fatigue in heart failure reduced intercostal and forearm muscle blood volume (P<0.05) along with decreased tissue oxygenation both in intercostal (heart failure, -2.6±1.6%; controls, +1.6±0.5%; P<0.05) and in forearm muscles (heart failure, -4.5±0.5%; controls, +0.5±0.8%; P<0.05). These results suggest that respiratory fatigue in patients with heart failure causes an oxygen demand/delivery mismatch in respiratory muscles, probably leading to a reflex reduction in peripheral limb muscle perfusion, featuring a respiratory metaboreflex.

Rheological characterization of polysaccharide gels

In this Master’s Thesis work the rheological properties of different polysaccharide gels have been studied. The results of this study are used as a starting point for further investigations of potential applications. In order to understand rheological behavior of studied materials, the commercial hydrocolloids such as sodium carboxymethyl cellulose, xanthan gum and guar gum were used as reference and comparison material for rheological studies. As a part the rheological research the development and implementation of proper measurement methods for studied materials were carried out. In the literature review, short introductions of studied materials and application areas of rheological modifiers are summarized. In addition, basic rheological concepts and key fundamentals are explained. In the experimental part the focus was on the rheological characterization of aqueous suspensions of studied materials. Especially, gel strength and solution stability were investigated. The rheological measurements included both rotational and oscillatory measurements in different conditions, where several chemical and physical properties were measured with Anton Paar MCR302 dynamic rotational rheometer. Studied polysaccharide gels can be clearly defined to be shear thinning and thixotropic materials. They have strong gel forming properties even at low concentrations, which explains the superior thickening behavior for some of the samples. Along with rheological characterization of selected materials the factors behind different phenomena were investigated. To reveal value and potential use of polysaccharide gels the influence of various factors such as concentration, temperature and ionic strength were determined. The measurements showed a clear difference between studied materials under investigated external parameters.

Stability of fruit bases and chocolate fillings

Syrups with high sugar content and dehydrated fruits in its composition can be added to chocolate fillings to reduce the need of artificial flavor and dyes attributing a natural appeal to the product. Fruit bases were produced with lyophilized strawberry, passion fruit, and sliced orange peel. Rheological dynamic oscillatory tests were applied to determine the products stability and tendency of shelf life. Values of G´< G´´ were observed for strawberry and passion fruit flavor, whereas values of G´ > G´´ were found for orange flavor during the 90 days of storage. It was observed that shear stress values did not vary significantly suggesting product stability during the studied period. For all fillings, it was found a behavior similar to the fruit base indicating that it has great influence on the filling behavior and its stability. The use of a sugar matrix in fillings provided good shelf life for the fruit base, which could be kept under room temperature conditions for a period as long as one year. The good stability and storage conditions allow the use of fruit base for handmade products as well as for industrialized products.

An Electrophysiological Investigation into the Role of Cognitive Control in the Attentional Blink

Accuracy at reporting a second-target (T2) is reduced if it is presented within approximately 500 ms of the first target (T1) – an attentional blink (AB). Early models explained the AB in terms of attentional limitations creating a processing bottleneck such that T2 processing would be impaired while T1 processing was ongoing. Theoretical models of the AB have more recently been expanded to include the role of cognitive control. In this dissertation I propose that cognitive control, defined as the optimization of information processing in order to achieve goals, is maladapted to the dual-task conditions of the AB task in that cognitive control optimizes the T1 goal, due to its temporal proximity, at the cost of T2. I start with the concept that the role of cognitive control is to serve goals, and that how goals are conceived of and the degree of motivation associated with those goals will determine whether cognitive control will create the condition that cause the AB. This leads to the hypothesis that electrophysiological measures of cognitive control and the degree of attentional investment resulting from cognitive control modulate the AB and explain individual differences in the AB. In a series of four studies feedback-related N2 amplitude, (reflecting individual differences in the strength of cognitive control), and event-related and resting alpha frequency oscillatory activity (reflecting degree of attentional investment), are used to explain both intra- and inter-individual variability in performance on the AB task. Results supported the hypothesis that stronger cognitive control and greater attentional investment are associated with larger AB magnitudes. Attentional investment, as measured by alpha frequency oscillations, and cognitive control, as measured by the feedback-related N2, did not relate to each other as hypothesized. It is proposed that instead of a measure of attentional investment alone, alpha frequency oscillatory activity actually reflects control over information processing over time, in other words the timing of attention. With this conceptualization, various aspects of cognitive control, either related to the management of goals (feedback-related N2) or the management of attention over time to meet goals, explain variability in the AB.

Evaporative respiratory cooling augments pit organ thermal detection in rattlesnakes

Rattlesnakes use their facial pit organs to sense external thermal fluctuations. A temperature decrease in the heat-sensing membrane of the pit organ has the potential to enhance heat flux between their endothermic prey and the thermal sensors, affect the optimal functioning of thermal sensors in the pit membrane and reduce the formation of thermal ‘‘afterimages’’, improving thermal detection. We examined the potential for respiratory cooling to improve strike behaviour, capture, and consumption of endothermic prey in the South American rattlesnake, as behavioural indicators of thermal detection. Snakes with a higher degree of rostral cooling were more accurate during the strike, attacking warmer regions of their prey, and relocated and consumed their prey faster. These findings reveal that by cooling their pit organs, rattlesnakes increase their ability to detect endothermic prey; disabling the pit organs caused these differences to disappear. Rattlesnakes also modify the degree of rostral cooling by altering their breathing pattern in response to biologically relevant stimuli, such as a mouse odour. Our findings reveal that low humidity increases their ability to detect endothermic prey, suggesting that habitat and ambush sites election in the wild may be influenced by external humidity levels as well as temperature.

A domain-general perspective on medial frontal brain activity during performance monitoring

Activity of the medial frontal cortex (MFC) has been implicated in attention regulation and performance monitoring. The MFC is thought to generate several event-related potential (ERPs) components, known as medial frontal negativities (MFNs), that are elicited when a behavioural response becomes difficult to control (e.g., following an error or shifting from a frequently executed response). The functional significance of MFNs has traditionally been interpreted in the context of the paradigm used to elicit a specific response, such as errors. In a series of studies, we consider the functional similarity of multiple MFC brain responses by designing novel performance monitoring tasks and exploiting advanced methods for electroencephalography (EEG) signal processing and robust estimation statistics for hypothesis testing. In study 1, we designed a response cueing task and used Independent Component Analysis (ICA) to show that the latent factors describing a MFN to stimuli that cued the potential need to inhibit a response on upcoming trials also accounted for medial frontal brain responses that occurred when individuals made a mistake or inhibited an incorrect response. It was also found that increases in theta occurred to each of these task events, and that the effects were evident at the group level and in single cases. In study 2, we replicated our method of classifying MFC activity to cues in our response task and showed again, using additional tasks, that error commission, response inhibition, and, to a lesser extent, the processing of performance feedback all elicited similar changes across MFNs and theta power. In the final study, we converted our response cueing paradigm into a saccade cueing task in order to examine the oscillatory dynamics of response preparation. We found that, compared to easy pro-saccades, successfully preparing a difficult anti-saccadic response was characterized by an increase in MFC theta and the suppression of posterior alpha power prior to executing the eye movement. These findings align with a large body of literature on performance monitoring and ERPs, and indicate that MFNs, along with their signature in theta power, reflects the general process of controlling attention and adapting behaviour without the need to induce error commission, the inhibition of responses, or the presentation of negative feedback.