Guidance for a personal target value of F(E)NO in allergic asthma: case report and theoretical example.

In clinically stable asthma the exhaled NO values (F(E)NO) are generally higher than in control subjects. Therefore, reference values are of limited importance in clinical practice. This is demonstrated in this case report, but it is also shown that NO parameters from non-linear modelling do have a clinical value. A subject with asthma was treated with inhaled corticosteroids for 1 week. The non-linear NO model was used to measure the response to treatment. The NO parameters from subjects with atopic rhinitis and asthma were fed into a computer program to generate theoretical F(E)NO0.05 values, i.e. target values. There was a dramatic decrease in F(E)NO0.05 due to treatment, from 82 to 34 ppb, but it remained higher than in healthy controls. This is due to the elevated diffusion rate of NO, unchanged by treatment. When the NO parameters are known, a personal best value of F(E)NO0.05 (fractional concentration of exhaled NO in the gas phase, 0.05 L/s) can be calculated, which can be the target value when only F(E)NO0.05 can be monitored. In conclusion, reference values for NO parameters are shown to be clinically useful. It is essential that every patient receives his/her target value of F(E)NO0.05, when only a single NO measurement is available. In our opinion, this is the reason why there are few successful studies of trying to target the NO value with inhaled corticosteroids.

Correlation of visual-evoked hemodynamic responses and potentials in human brain.

The interaction of brain hemodynamics and neuronal activity has been intensively studied in recent years to yield better understanding of brain function. We investigated the relationship between visual-evoked hemodynamic responses (HDRs), measured with near-infrared spectroscopy (NIRS), and neuronal activity in humans, approximated with the stimulus train duration or with visual-evoked potentials (VEPs). Concentration changes of oxyhemoglobin (HbO(2)) and deoxyhemoglobin (HbR) in tissue and VEPs were recorded simultaneously over the occipital lobe of ten healthy subjects to 3, 6, and 12 s pattern-reversing checkerboard stimulus trains having a reversal frequency of 2 Hz. We found that the area-under-the-curves (Sigma) of HbO(2) and HbR were linearly correlated with the stimulus train duration and with the SigmaVEP summed over the 3, 6, and 12 s stimulus train durations. The correlation was stronger between the SigmaHbO(2) or the SigmaHbR and the SigmaVEP than between the SigmaHbO(2) or the SigmaHbR and the stimulus train duration. The SigmaVEPs explained 55% of the SigmaHbO(2) and 74% of the SigmaHbR variance, whereas the stimulus train duration explained only 45% of the SigmaHbO(2) and 51% of the SigmaHbR variance. We used Sigma of the NIRS responses and VEPs because we wanted to incorporate all possible processes (e.g., attention, habituation, etc.) affecting the responses. The results indicate that the relationship between brain HDRs and VEPs is approximately linear for 3-12 s long stimulus trains consisting of checkerboard patterns reversing at 2 Hz. To interpret hemodynamic responses, the measurement of evoked potentials is beneficial compared to the use of indirect parameters such as the stimulus duration. In addition, interindividual differences in the HbO(2) and HbR responses may be partly explained with differences in the VEPs.

Hemodynamic responses to speech and music in newborn infants.

We used near-infrared spectroscopy (NIRS) to study responses to speech and music on the auditory cortices of 13 healthy full-term newborn infants during natural sleep. The purpose of the study was to investigate the lateralization of speech and music responses at this stage of development. NIRS data was recorded from eight positions on both hemispheres simultaneously with electroencephalography, electrooculography, electrocardiography, pulse oximetry, and inclinometry. In 11 subjects, statistically significant (P < 0.02) oxygenated (HbO2) and total hemoglobin (HbT) responses were recorded. Both stimulus types elicited significant HbO2 and HbT responses on both hemispheres in five subjects. Six of the 11 subjects had positive HbO2 and HbT responses to both stimulus types, whereas one subject had negative responses. Mixed positive and negative responses were observed in four neonates. On both hemispheres, speech and music responses were significantly correlated (r = 0.64; P = 0.018 on the left hemisphere (LH) and r = 0.60; P = 0.029 on the right hemisphere (RH)). On the group level, the average response to the speech stimuli was statistically significantly greater than zero in the LH, whereas responses on the RH or to the music stimuli did not differ significantly from zero. This suggests a more coherent response to speech on the LH. However, significant differences in lateralization of the responses or mean response amplitudes of the two stimulus types were not observed on the group level.

Comparison of principal and independent component analysis in removing extracerebral interference from near-infrared spectroscopy signals.

Near-infrared spectroscopy (NIRS) is a method for noninvasive estimation of cerebral hemodynamic changes. Principal component analysis (PCA) and independent component analysis (ICA) can be used for decomposing a set of signals to underlying components. Our objective is to determine whether PCA or ICA is more efficient in identifying and removing scalp blood flow interference from multichannel NIRS signals. Concentration changes of oxygenated (HbO(2)) and deoxygenated (HbR) hemoglobin are measured on the forehead with multichannel NIRS during hyper- and hypocapnia. PCA and ICA are used separately to identify and remove signal contribution from extracerebral tissue, and the resulting estimates of cerebral responses are compared to the expected cerebral responses. Both methods were able to reduce extracerebral contribution to the signals, but PCA typically performs equal to or better than ICA. The improvement in 3-cm signal quality achieved with both methods is comparable to increasing the source-detector separation from 3 to 5 cm. Especially PCA appears to be well suited for use in NIRS applications where the cerebral activation is diffuse, such as monitoring of global cerebral oxygenation and hemodynamics. Performance differences between PCA and ICA could be attributed primarily to different criteria for identifying the surface effect.

Extended NO analysis in a healthy subgroup of a random sample from a Swedish population.

INTRODUCTION: There is an interest in modelling exhaled nitric oxide (NO). Studies have shown that flow-independent NO parameters i.e. NO of the alveolar region (C(A)NO), airway wall (C(aw)NO), diffusing capacity (D(aw)NO) and flux (J(aw)NO), are altered in several disease states such as asthma, cystic fibrosis, alveolitis and chronic obsmuctive pulmonary disease (COPD). However, values from a healthy population are missing. OBJECTIVES: To calculate NO parameters in a healthy population by collecting NO values at different exhalation flow rates. METHODS: A random sample from the ECRHS II study was investigated. Among the 281 subjects that had performed a bronchial hyperreactivity (BHR)-test, FEV(1.0), IgE and NO-analyses 89 were found to be healthy. RESULTS: There were no differences in F(E)NO(0.05) or NO parameters between men and women. There were weak correlations between height and both F(E)NO(0.05) (r = 0.23, P = 0.03) and C(aw)NO (r = 0.22, P = 0.04). There was also a correlation between age and C(A)NO (r = 0.28, P = 0.007). When controlled for gender, this correlation was more powerful in women (r = 0.51, P = 0.001) but did not remain for male subjects. CONCLUSION: Extended NO analysis is a simple non-invasive tool that gives by far more information than F(E)NO(0.05). Based on our results, we suggest that the values for healthy subjects should be considered to fall between the following ranges: F(E)NO(0.05), 10-30 ppb; C(aw)NO, 50-250 ppb; D(aw)NO, 5-15 ml s(-1); J(aw)NO, 0.8-1.6 nl s(-1); and C(A)NO, 0-4 ppb. Values outside these intervals indicate the need for further investigation to exclude a state of disease.

An assessment of the validity of spectral entropy as a measure of sedation state in mechanically ventilated critically ill patients.

OBJECTIVE: To assess whether the Entropy Module (GE Healthcare, Helsinki, Finland), a device to measure hypnosis in anesthesia, is a valid measure of sedation state in critically ill patients by comparing clinically assessed sedation state with Spectral Entropy DESIGN: Prospective observational study. SETTING: Teaching hospital general ICU. PATIENTS AND PARTICIPANTS: 30 intubated, mechanically ventilated patients without primary neurological diagnoses or drug overdose receiving continuous sedation. INTERVENTIONS: Monitoring of EEG and fEMG activity via forehead electrodes for up to 72h and assessments of conscious level using a modified Ramsay Sedation Scale. MEASUREMENTS AND RESULTS: 475 trained observer assessments were made and compared with concurrent Entropy numbers. Median State (SE) and Response (RE) Entropy values decreased as Ramsay score increased, but wide variation occurred, especially in Ramsay 4-6 categories. Discrimination between different sedation scores [mean (SEM) P(K) value: RE 0.713 (0.019); SE 0.710 (0.019)] and between lighter (Ramsay 1-3) vs.deeper (Ramsay 4-6) sedation ranges was inadequate [P(K): RE 0.750 (0.025); SE 0.748 (0.025)]. fEMG power decreased with increasing Ramsay score but was often significant even at Ramsay 4-6 states. Frequent "on-off" effects occurred for both RE and SE, which were associated with fEMG activity. Values switched from low to high values even in deeply sedated patients. High Entropy values during deeper sedation were strongly associated with simultaneous high relative fEMG powers. CONCLUSIONS: Entropy of the frontal EEG does not discriminate sedation state adequately for clinical use in ICU patients. Facial EMG is a major confounder in clinical sedation ranges.

IgE sensitisation in relation to flow-independent nitric oxide exchange parameters.

BACKGROUND: A positive association between IgE sensitisation and exhaled NO levels has been found in several studies, but there are no reports on the compartment of the lung that is responsible for the increase in exhaled NO levels seen in IgE-sensitised subjects. METHODS: The present study comprised 288 adult subjects from the European Community Respiratory Health Survey II who were investigated in terms of lung function, IgE sensitisation (sum of specific IgE), smoking history and presence of rhinitis and asthma. Mean airway tissue concentration of NO (CawNO), airway transfer factor for NO (DawNO), mean alveolar concentration of NO (CalvNO) and fractional exhaled concentration of NO at a flow rate of 50 mL s(-1) (FENO 0.05) were determined using the extended NO analysis. RESULTS: IgE-sensitised subjects had higher levels (geometric mean) of FENO 0.05 (24.9 vs. 17.3 ppb) (p < 0.001), DawNO (10.5 vs. 8 mL s(-1)) (p = 0.02) and CawNO (124 vs. 107 ppb) (p < 0.001) and positive correlations were found between the sum of specific IgE and FENO 0.05, CawNO and DawNO levels (p < 0.001 for all correlations). Sensitisation to cat allergen was the major determinant of exhaled NO when adjusting for type of sensitisation. Rhinitis and asthma were not associated with the increase in exhaled NO variables after adjusting for the degree of IgE sensitisation. CONCLUSION: The presence of IgE sensitisation and the degree of allergic sensitisation were related to the increase in airway NO transfer factor and the increase in NO concentration in the airway wall. Sensitisation to cat allergen was related to the highest increases in exhaled NO parameters. Our data suggest that exhaled NO is more a specific marker of allergic inflammation than a marker of asthma or rhinitis.

Nitric oxide airway diffusing capacity and mucosal concentration in asthmatic schoolchildren.

Asthmatic patients show increased concentrations of nitric oxide (NO) in exhaled air (Feno). The diffusing capacity of NO in the airways (Dawno), the NO concentrations in the alveoli and the airway wall, and the maximal airway NO diffusion rate have previously been estimated noninvasively by measuring Feno at different exhalation flow rates in adults. We investigated these variables in 15 asthmatic schoolchildren (8-18 y) and 15 age-matched control subjects, with focus on their relation to exhaled NO at the recommended exhalation flow rate of 0.05 L/s (Feno0.05), age, and volume of the respiratory anatomic dead space. NO was measured on-line by chemiluminescence according to the European Respiratory Society's guidelines, and the NO plateau values at three different exhalation flow rates (11, 99, and 382 mL/s) were incorporated in a two-compartment model for NO diffusion. The NO concentration in the airway wall (p < 0.001), Dawno (p < 0.01), and the maximal airway NO diffusion rate (p < 0.001) were all higher in the asthmatic children than in control children. In contrast, there was no difference in the NO concentration in the alveoli (p = 0.13) between the groups. A positive correlation was seen between the volume of the respiratory anatomic dead space and Feno0.05 (r = 0.68, p < 0.01), the maximal airway NO diffusion rate (r = 0.71, p < 0.01), and Dawno (r = 0.56, p < 0.01) in control children, but not in asthmatic children. Feno0.05 correlated better with Dawno in asthmatic children (r = 0.65, p < 0.01) and with the NO concentration in the airway wall in control subjects (r < 0.77, p < 0.001) than vice versa. We conclude that Feno0.05 increases with increasing volume of the respiratory anatomic dead space in healthy children, suggesting that normal values for Feno0.05 should be related to age or body weight in this age group. Furthermore, the elevated Feno0.05 seen in asthmatic children is related to an increase in both Dawno and NO concentration in the airway wall. Because Dawno correlates with the volume of the respiratory anatomic dead space in control subjects and Feno0.05 correlates with Dawno in asthmatic children, we suggest that Dawno partly reflects the total NO-producing surface area and that a larger part of the bronchial tree produces NO in asthmatic children than in control children.

Indirect calorimetry in patients with active respiratory infection--prevention of cross-infection.

BACKGROUND: Measurement of resting energy expenditure in patients with active respiratory infection is hampered by the risk of contamination of indirect calorimeters and connecting tubes that cannot be sterilized. This validation study tested whether the use of disposable standard-bore air tubes and an antibacterial filter, by reducing air flow, introduces an error due to recirculation of expired air in the canopy. METHODS: Eleven healthy volunteers underwent indirect calorimetry twice in random order, using a Deltatrac calorimeter either with standard wide-bore tubing or with a disposable standard-bore air tube and filter. Methods were compared by Bland-Altman plots and by calculating trends over time. RESULTS: The new tube and filter reduced air flow by 40%. Measured resting energy expenditure did not differ significantly between methods, with limits of agreement -135 to +188 kcal/d. Carbon dioxide flow (VCO(2)) and respiratory quotient (RQ), but not oxygen flow decreased slowly over time with both methods. CONCLUSIONS: The use of an air filter and standard-bore tubes do not introduce a systematic error into indirect calorimetry. Although trends in VCO(2) and RQ are consistent with minor recirculation of exhaled air, this modified Deltatrac system can be safely and reliably used to measure resting energy expenditures in patients with active tuberculosis and other airborne infection.

Characterization of micromachined spiked biopotential electrodes.

We present the characterization of dry spiked biopotential electrodes and test their suitability to be used in anesthesia monitoring systems based on the measurement of electroencephalographic signals. The spiked electrode consists of an array of microneedles penetrating the outer skin layers. We found a significant dependency of the electrode-skin-electrode impedance (ESEI) on the electrode size (i.e., the number of spikes) and the coating material of the spikes. Electrodes larger than 3 x 3 mm2 coated with Ag-AgCl have sufficiently low ESEI to be well suited for electroencephalograph (EEG) recordings. The maximum measured ESEI was 4.24 k(omega) and 87 k(omega), at 1 kHz and 0.6 Hz, respectively. The minimum ESEI was 0.65 k(omega) an 16 k(omega), at the same frequencies. The ESEI of spiked electrodes is stable over an extended period of time. The arithmetic mean of the generated dc offset voltage is 11.8 mV immediately after application on the skin and 9.8 mV after 20-30 min. A spectral study of the generated potential difference revealed that the ac part was unstable at frequencies below approximately 0.8 Hz. Thus, the signal does not interfere with a number of clinical applications using real-time EEG. Comparing raw EEG recordings of the spiked electrode with commercial Zipprep electrodes showed that both signals were similar. Due to the mechanical strength of the silicon microneedles and the fact that neither skin preparation nor electrolytic gel is required, use of the spiked electrode is convenient. The spiked electrode is very comfortable for the patient.

Pulsed delivery of nitric oxide counteracts hypoxaemia in the anaesthetized horse.

OBJECTIVE: To study the effect of the pulsed delivery of nitric oxide (NO) on pulmonary gas exchange in the anaesthetized horses. Design Prospective, controlled randomized. ANIMALS: Five healthy Standardbred trotters, three geldings and two mares. METHODS: The horses were anaesthetized with thiopentone and isoflurane and positioned in dorsal recumbency. Nitric oxide was added as a pulse to the inspired gas during the first half of each inspiration. In three horses the effect of NO on the ventilation-perfusion distribution was also investigated using the multiple inert gas elimination technique. Data were analysed with repeated measures ANOVA. RESULTS: During spontaneous breathing, arterial oxygen tension (PaO2) increased with NO inhalation, from 14 ± 2 to 29 ± 3 kPa (105 ± 15 to 218 ± 23 mm Hg) (p < 0.001). Arterial oxygen tension also increased, from 17 ± 3 to 31 ± 5 kPa (128 ± 23 to 233 ± 38 mm Hg) (p < 0.05) during intermittent positive pressure ventilation. The increase in PaO2 was mainly due to a reduced right to left vascular shunt, but ventilation and perfusion matching also improved. The beneficial effect of NO inhalation was lost within 5 minutes of its discontinuation. CONCLUSION: Delivery of NO as a pulse during inspiration is an effective method for counteracting impaired gas exchange caused by anaesthesia in horses. Pulsation has to be continuous because of the transience of NO's therapeutic effect. CLINICAL RELEVANCE: Horses with impaired pulmonary gas exchange during anaesthesia can be treated with pulsed NO inhalation.