Different Relationships between FENO and COPD Characteristics in Smokers and Ex-Smokers.

Exhaled nitric oxide (FENO) is a marker of type-2 inflammation in asthma and is used in its management. However, smokers and ex-smokers have lower FENO values, and the clinical use of FENO values in COPD patients is unclear. Therefore, we investigated if FENO had a relationship to different COPD characteristics in smoking and ex-smoking subjects. Patients with COPD (n = 533, 58% females) were investigated while in stable condition. Measurements of FENO50, blood cell counts, IgE sensitisation and lung function were performed. Medication reconciliation was used to establish medication usage. Smokers (n = 150) had lower FENO50 9 (8, 10) ppb (geometric mean, 95% confidence interval) than ex-smokers did (n = 383) 15 (14, 16) ppb, p < 0.001. FENO50 was not associated with blood eosinophil or neutrophil levels in smokers, but in ex-smokers significant associations were found (r = 0.23, p < 0.001) and (r = -0.18, p = 0.001), respectively. Lower FENO values were associated with lower FEV1% predicted in both smokers (r = 0.17, p = 0.040) and ex-smokers (r = 0.20, p < 0.001). Neither the smokers nor ex-smokers with reported asthma or IgE sensitisation were linked to an increase in FENO50. Ex-smokers treated with inhaled corticosteroids (ICS) had lower FENO50 14 (13, 15) ppb than non-treated ex-smokers 17 (15, 19) ppb, p = 0.024. This was not found in smokers (p = 0.325). FENO is associated with eosinophil inflammation and the use of ICS in ex-smoking COPD subjects, but not in smoking subjects suggesting that the value of FENO as an inflammatory marker is more limited in smoking subjects. The association found between low FENO values and low lung function requires further investigation.

Effects of growth and aging on the reference values of pulmonary nitric oxide dynamics in healthy subjects.

The lung just like all other organs is affected by age. The lung matures by the age of 20 and age-related changes start around middle age, at 40-50 years. Exhaled nitric oxide (FENO) has been shown to be age, height and gender dependent. We hypothesize that the nitric oxide (NO) parameters alveolar NO (CANO), airway flux (JawNO), airway diffusing capacity (DawNO) and airway wall content (CawNO) will also demonstrate this dependence. Data from healthy subjects were gathered by the current authors from their earlier publications in which healthy individuals were included as control subjects. Healthy subjects (n = 433) ranged in age from 7 to 78 years. Age-stratified reference values of the NO parameters were significantly different. Gender differences were only observed in the 20-49 age group. The results from the multiple regression models in subjects older than 20 years revealed that age, height and gender interaction together explained 6% of variation in FENO at 50 ml s-1 (FENO50), 4% in JawNO, 16% in CawNO, 8% in DawNO and 12% in CANO. In conclusion, in this study we have generated reference values for NO parameters from an extended NO analysis of healthy subjects. This is important in order to be able to use these parameters in clinical practice.

Allergen extract vs. component sensitization and airway inflammation, responsiveness and new-onset respiratory disease.

BACKGROUND: The absence of IgE sensitization to allergen components in the presence of sensitization to the corresponding extract has been reported, but its clinical importance has not been studied. OBJECTIVE: To evaluate the clinical significance of IgE sensitization to three aeroallergen extracts and the corresponding components in relation to the development of respiratory disease. METHODS: A total of 467 adults participated in the European Community Respiratory Health Survey (ECRHS) II and 302 in ECRHS III, 12 years later. IgE sensitization to allergen extract and components, exhaled nitric oxide (FeNO) and bronchial responsiveness to methacholine were measured in ECRHS II. Rhinitis and asthma symptoms were questionnaire-assessed in both ECRHS II and III. RESULTS: A good overall correlation was found between IgE sensitization to extract and components for cat (r = 0.83), timothy (r = 0.96) and birch (r = 0.95). However, a substantial proportion of subjects tested IgE positive for cat and timothy allergen extracts but negative for the corresponding components (48% and 21%, respectively). Subjects sensitized to both cat extract and components had higher FeNO (P = 0.008) and more bronchial responsiveness (P = 0.002) than subjects sensitized only to the extract. Further, subjects sensitized to cat components were more likely to develop asthma (P = 0.005) and rhinitis (P = 0.007) than subjects sensitized only to cat extract. CONCLUSION: Measurement of IgE sensitization to cat allergen components would seem to have a higher clinical value than extract-based measurement, as it related better to airway inflammation and responsiveness and had a higher prognostic value for the development of asthma and rhinitis over a 12-year period.

Extended nitric oxide analysis may improve personalized anti-inflammatory treatment in asthmatic children with intermediate F(E)NO50.

Exhaled nitric oxide (F(E)NO) is elevated in asthma, and a clinical practice guideline has been published with recommendations for anti-inflammatory treatment. It summarizes that a F(E)NO at an expiratory flow rate of 50 ml s(-1) (F(E)NO50) above 35 ppb in children indicates eosinophilic inflammation, and the most likely response is to use inhaled corticosteroids. Intermediate F(E)NO50 between 20-35 ppb should be interpreted cautiously. The aim of the study was to investigate this guideline in a small group of asthmatic children. Thirty-seven asthmatic children; 23 boys and 14 girls, visited the outpatient clinic, and provided exhaled breath samples for offline NO measurement. These samples were analysed with chemiluminescence techniques. Three flow rates, namely 16, 90 and 230 ml s(-1) were used for the extended NO analysis (Högman-Meriläinen algorithm, HMA) to estimate the alveolar concentration (C(A)NO), diffusion rate of the airway wall (D(aw)NO) and airway wall content (C(aw)NO). For accuracy of the HMA, the estimated value of F(E)NO at 50 ml s(-1) (F(E)NO50) was compared with measured F(E)NO50. In nine children the difference was more than 5 ppb and the data were therefore excluded. Five children with F(E)NO50 <20 ppb had no known allergy and their F(E)NO50 geometrical mean (25th; 75th percentile) was 11 (10;14) and CawNO was 32 (20;43) ppb. Ten children with F(E)NO50 > 35 ppb had an allergy and had F(E)NO50 of 56 (47;60) ppb and C(aw)NO of 140 (121;172) ppb. Thirteen children with allergies, with intermediate F(E)NO50, had F(E)NO50 of 27 (25;30) ppb with a wide range of C(aw)NO. In five of these children, values were comparable to healthy children, 44 (43;50) ppb while eight children had elevated C(aw)NO values of 108 (95;129) ppb. Our data indicate the clinical potential use of extended NO analysis to determine the personal target value of F(E)NO50 for monitoring the treatment outcome. Furthermore, for children with intermediate F(E)NO50 more than half of them could possibly benefit from an adjustment of inhaled corticosteroids if the C(aw)NO value was considered.

A practical approach to the theoretical models to calculate NO parameters of the respiratory system.

Expired nitric oxide (NO) is used as a biomarker in different respiratory diseases. The recommended flow rate of 50 mL s⁻¹ (F(E)NO0.05) does not reveal from where in the lung NO production originated. Theoretical models of NO transfer from the respiratory system, linear or nonlinear approaches, have therefore been developed and applied. These models can estimate NO from distal lung (alveolar NO) and airways (bronchial flux). The aim of this study was to show the limitation in exhaled flow rate for the theoretical models of NO production in the respiratory system, linear and nonlinear models. Subjects (n = 32) exhaled at eight different flow rates between 10-350 mL s⁻¹ for the theoretical protocols. Additional subjects (n = 32) exhaled at tree flow rates (20, 100 and 350 mL s⁻¹) for the clinical protocol. When alveolar NO is calculated using high flow rates with the linear model, correction for axial back diffusion becomes negligible, -0.04 ppb and bronchial flux enhanced by 1.27. With Högman and Meriläinen algorithm (nonlinear model) the corrections factors can be understood to be embedded, and the flow rates to be used are ≤20, 100 and ≥350 mL s⁻¹. Applying these flow rates in a clinical setting any F(E)NO can be calculated necessitating fewer exhalations. Hence, measured F(E)NO0.05 12.9 (7.2-18.7) ppb and calculated 12.9 (6.8-18.7) ppb. In conclusion, the only possibility to avoid inconsistencies between research groups is to use the measured NO values as such in modelling, and apply tight quality control to accuracies in both NO concentration and exhaled flow measurements.

Methods of NO detection in exhaled breath.

There is still an unexplored potential for exhaled nitric oxide (NO) in many clinical applications. This study presents an overview of the currently available methods for monitoring NO in exhaled breath and the use of the modelling of NO production and transport in the lung in clinical practice. Three technologies are described, namely chemiluminescence, electrochemical sensing and laser-based detection with their advantages and limitations. Comparisons are made in terms of sensitivity, time response, size, costs and suitability for clinical purposes. The importance of the flow rate for NO sampling is discussed from the perspective of the recent recommendations for standardized procedures for online and offline NO measurement. The measurement of NO at one flow rate, such as 50 ml s(-1), can neither determine the alveolar site/peripheral contribution nor quantify the difference in NO diffusion from the airways walls. The use of NO modelling (linear or non-linear approach) can solve this problem and provide useful information about the source of NO. This is of great value in diagnostic procedures of respiratory diseases and in treatment with anti-inflammatory drugs.

Suffering from meticillin-resistant Staphylococcus aureus: experiences and understandings of colonisation.

The objective was to explore individuals' experiences and understandings of meticillin-resistant Staphylococcus aureus (MRSA) colonisation. Thirteen interviews were performed and processed using content analysis, resulting in the theme 'Invaded, insecure and alone'. The participants experienced fears and limitations in everyday life and expressed a need to protect others from contagion. Moreover, they experienced encounters with, and information from, healthcare workers differently: some were content, whereas others were discontent. The described fears, limitations and inadequate professional-patient relationship generated unacceptable distress for MRSA-colonised persons. Thus, the healthcare sector should assume responsibility for managing MRSA, and healthcare workers must improve their professionalism and information skills, so as to better meet MRSA-colonised persons' needs.

Both allergic and nonallergic asthma are associated with increased FE(NO) levels, but only in never-smokers.

BACKGROUND: Allergic asthma is consistently associated with increased FE(NO) levels whereas divergence exists regarding the use of exhaled nitric oxide (NO) as marker of inflammation in nonallergic asthma and in asthmatic smokers. The aim of this study is to analyze the effect of having allergic or nonallergic asthma on exhaled nitric oxide levels, with special regard to smoking history. METHODS: Exhaled NO measurements were performed in 695 subjects from Turin (Italy), Gothenburg and Uppsala (both Sweden). Current asthma was defined as self-reported physician-diagnosed asthma with at least one asthma symptom or attack recorded during the last year. Allergic status was defined by using measurements of specific immunoglobulin E (IgE). Smoking history was questionnaire-assessed. RESULTS: Allergic asthma was associated with 91 (60, 128) % [mean (95% CI)] increase of FE(NO) while no significant association was found for nonallergic asthma [6 (-17, 35) %] in univariate analysis, when compared to nonatopic healthy subjects. In a multivariate analysis for never-smokers, subjects with allergic asthma had 77 (27, 145) % higher FE(NO) levels than atopic healthy subjects while subjects with nonallergic asthma had 97 (46, 166) % higher FE(NO) levels than nonatopic healthy subjects. No significant asthma-related FE(NO) increases were noted for ex- and current smokers in multivariate analysis. CONCLUSIONS: Both allergic and nonallergic asthma are related to increased FE(NO) levels, but only in never-smoking subjects. The limited value of FE(NO) to detect subjects with asthma among ex- and current smokers suggests the predominance of a noneosinophilic inflammatory phenotype of asthma among ever-smokers.

Extended NO analysis in asthma.

The discovery of the flow dependence of exhaled NO made it possible to model NO production in the lung. The linear model provides information about the maximal flux of NO from the airways and the alveolar concentrations of NO. Nonlinear models give additional flow-independent parameters such as airway diffusing capacity and airway wall concentrations of NO. When these models are applied to patients with asthma, a clear-cut increase in NO flux is found, and this is caused by an increase in both airway diffusing capacity and airway wall concentrations of NO. There is no difference in alveolar concentrations of NO compared to healthy subjects, except in severe asthma where an increase has been found. Inhaled corticosteroids are able to reduce the airway wall concentrations but not diffusing capacity or alveolar concentrations. Oral prednisone affects the alveolar concentration, suggesting that in severe asthma there is a systemic component. Steroids distributed by any route do not affect the airway diffusing capacity. Therefore, the airway diffusing capacity should be in focus in testing new drugs or in combination treatment for asthma. Exhaled NO analysis is a promising tool in characterizing asthma in both adults and children. However, there is a strong need to agree on the models and to standardize the flow rates to be used for the modelling in order to perform a systematic and robust analysis of NO production in the lung.

Effect of smoking on exhaled nitric oxide and flow-independent nitric oxide exchange parameters.

It is a well-known fact that smoking is associated with a reduction in exhaled nitric oxide (NO) levels. There is, however, limited knowledge relating to the smoking-induced changes in production or exchange of NO in different compartments of the airways. This study comprised 221 adult subjects from the European Community Respiratory Health Survey II, who were investigated in terms of their exhaled NO, lung function, immunoglobulin E sensitisation and smoking habits. The following parameters were determined using extended NO analysis: airway tissue nitric oxide concentration (Caw,NO), airway transfer factor (or diffusing capacity) for nitric oxide (Daw,NO), alveolar nitric oxide concentration (CA,NO) and fractional exhaled nitric oxide concentration at a flow rate of 50 mL x s(-1) (FeNO,0.05). Maximum total airway nitric oxide flux (J'aw,NO) was calculated from Daw,NO(Caw,NO-CA,NO). Current smokers (n = 35) exhibited lower (geometric mean) FeNO,0.05 (14.0 versus 22.8 ppb), Caw,NO (79.0 ;versus 126 ppb) and J'aw,NO (688 versus 1,153 pL x s(-1)) than never-smokers (n = 111). Ex-smokers (n = 75) were characterised by lower FeNO,0.05 (17.7 versus 22.8 ppb) and Jaw,NO (858 versus 1,153 pL x s(-1)) than never-smokers. These relationships were maintained after adjusting for potential confounders (sex, age, height, immunoglobulin E sensitisation and forced expiratory volume in one second), and, in this analysis, a negative association was found between current smoking and CA,NO. Snus (oral moist snuff) consumption (n = 21) in ex-smokers was associated with an increase in Daw,NO and a reduction in Caw,NO, after adjusting for potential confounders. Passive smoking was associated with a higher CA,NO. Using extended nitric oxide analysis, it was possible to attribute the reduction in exhaled nitric oxide levels seen in ex- and current smokers to a lower total airway nitric oxide flux in ex-smokers and reduced airway and alveolar nitric oxide concentrations in current smokers. The association between snus (oral tobacco) use and reduced nitric oxide concentrations in the airways and increased nitric oxide transfer from the airways warrants further studies.

Gut mucosal granulocyte activation precedes nitric oxide production: studies in coeliac patients challenged with gluten and corn.

BACKGROUND AND AIMS: To elucidate the dynamics of nitric oxide (NO) production induced by rectal gluten challenge and the relation between NO production and mucosal granulocyte activation. SUBJECTS AND METHODS: Release of rectal NO was measured in 13 patients with coeliac disease and in 18 controls before and after rectal wheat gluten challenge. Rectal gas was collected with a rectal balloon using a newly developed instrument/technique, the "mucosal patch technique". The instrument allows simultaneous measurements of concentrations of granulocyte mediators in the rectal mucosa. We measured myeloperoxidase (MPO), eosinophil cationic protein (ECP), and histamine. For comparison, we made similar measurements after corn (maize) gluten challenge. RESULTS: In all coeliac patients rectal NO concentration increased after gluten challenge and reached a peak after 15 hours (mean 9464 (SEM 2393) parts per billion (ppb); range 250-24982). The maximum MPO and ECP increase occurred five hours after challenge. A correlation was found between mucosal MPO and NO production at 15 hours. Six of the patients showed an increase in NO production 15 hours after rectal corn gluten challenge but this was much smaller than after gluten challenge. No increases were seen in the control group after either challenge. CONCLUSION: Mucosal activation of neutrophils and eosinophils precedes pronounced enhancement of mucosal NO production after rectal wheat gluten challenge in patients with coeliac disease. Some of our coeliac patients displayed signs of an inflammatory reaction, as measured by NO and granulocyte markers, after rectal corn gluten challenge.

Oleic acid lung injury: a morphometric analysis using computed tomography.

BACKGROUND: The oleic acid-induced lung injury (OAI) model is considered to represent the early phase of acute respiratory distress syndrome (ARDS). Its inherent properties are important for the design and the interpretation of interventional studies. The aim of this study was to describe the evolution of morphometric lung changes during OAI using computed tomography (CT) analysis. Furthermore, the effect of a temporary change in positive end-expiratory pressure (PEEP) was evaluated. METHODS: Fifteen anaesthetized pigs were ventilated in volume-controlled mode with a baseline PEEP of 5 cm H(2)O. Helical CT scans were taken at baseline and 1 h after oleic acid injection. The PEEP was then either increased to 10 cm H(2)O (n = 5), decreased to 0 cm H(2)O (n = 5) or kept constant (n = 5) for 30 min. For the next 30 min, the baseline PEEP level was applied in all animals before the final CT scans 2 h after the induction of OAI. Dimensional and volumetric changes were determined from radiographical attenuation values. RESULTS: There was a major decrease in gas volume and an increase in tissue volume within the first hour. A net increase in total lung volume, with a larger transverse area but no displacement of the diaphragm, was manifest after 2 h. A minor increase in volume of non-aerated lung, located to the caudal region, was observed during the second hour. The tidal volume was redistributed to the middle and apical regions. The temporary change in PEEP did not influence the morphological progress of OAI. CONCLUSION: Decreased gas volume and increased tissue volume are the dominating morphometric characteristics of oleic acid lung injury, occurring mainly within the first hour. With these changes manifest, the course of injury is not affected by a limited period of moderately changed PEEP during the second hour. The net increase of total lung volume suggests a predominance of oedema formation over airway and alveolar collapse.

Post-suction recruitment manoeuvre restores lung function in healthy, anaesthetized pigs.

Endotracheal suction can cause partial lung collapse and hypoxia and alter lung mechanics. We investigated the effects of adding a recruitment manoeuvre directly after endotracheal suction to restore lung volume in volume-controlled ventilation and pressure-controlled ventilation modes. Five anaesthetized pigs were investigated. The effects of endotracheal suction with or without a recruitment manoeuvre were compared in random order. In volume-controlled ventilation, compliance decreased after suction from 33 +/- 5 to 26 +/- 6 ml x cmH2O(-1) (P<0.05), and 30 minutes later it remained decreased at 25 +/- 6 ml x cmH2O(-1). Venous admixture increased after suction from 5 +/- 2 to 8 +/- 4% (P<0.05), but had recovered at 30 minutes. In pressure-controlled ventilation, compliance decreased after suction from 34 +/- 3 to 25 +/- 7 ml x cmH2O(-1) (P<0.05), and 30 minutes later it remained decreased at 25 +/- 7 ml x cmH2O(-1). Venous admixture increased after suction from 5 +/- 2 to 13 +/- 7% (P<0.05), and had not recovered after 30 minutes, 10 +/- 4%. When a recruitment manoeuvre was applied directly after suction, no negative side-effects were registered in volume-controlled ventilation or pressure-controlled ventilation. We conclude that the impairment of lung mechanics and gas exchange induced by endotracheal suction can be prevented by a simple post-suction recruitment manoeuvre. Further studies are needed to identify a suitable suction recruitment manoeuvre in patients with diseased lungs.

Hyperosmolarity decreases the relaxing potency of sodium nitroprusside on guinea-pig trachea by the release of superoxide anions.

UNLABELLED: Increased osmolarity of the airway surface has been shown to abolish the airway relaxant effects of inhaled nitric oxide in rabbits in vivo and in guinea-pig trachea in vitro. AIM: In this study, we used a guinea-pig tracheal perfusion method to investigate whether superoxide anions, which rapidly react with nitric oxide, could be responsible for the reduced effect of nitric oxide in hyperosmolar airways. METHODS: Guinea-pig tracheas were constricted with carbachol (CCh) and then subjected to the nitric oxide donor sodium nitroprusside (SNP) under isoosmolar or hyperosmolar conditions. Hyperosmolarity was created by increasing the NaCl concentration of the buffer on the epithelial side of the airway. RESULTS: The relaxation produced by SNP was significantly less following hyperosmolar challenge, with a relaxation by 31 +/- 7% in hyperosmolar conditions as compared to 53 +/- 6% under normal isoosmolar conditions (P<0.05). The experiment was then performed in the presence of superoxide dismutase (SOD) that reduces levels of superoxide anions. SOD restored the relaxing potency of SNP in hyperosmolar conditions back to normal, to 46 +/- 5%. CONCLUSION: This study shows that superoxide anions are responsible for the reduced relaxing potency of the nitric oxide donor SNP following an intraluminal hyperosmolar challenge in guinea-pig trachea in vitro. The finding may form the basis for new treatment of patients not responding to treatment with inhaled nitric oxide.

Administration of nitric oxide into open lung regions: delivery and monitoring.

BACKGROUND: Pulsed administration of nitric oxide has proven effective in relieving pulmonary hypertension and in improving oxygenation. With this delivery method the nitric oxide administration to low ventilated lung regions is avoided with subsequent enhancement in oxygenation. This study presents (i) pulsed administration technique for nitric oxide during artificial ventilation, (ii) evaluation of the delivery in an animal model, and (iii) validation of the delivery device in a laboratory setting. METHODS: Nitric oxide was delivered in four different pulse volumes synchronously with inspiration. The delivery was monitored with a fast responding high sensitivity nitric oxide monitor and nitric oxide uptake was calculated. Pulse delivery dose range, accuracy of the delivered dose, and stability of successive doses were analysed in a laboratory setting. RESULTS: Uptake of the delivered nitric oxide was 87-92%. Measured nitric oxide pulse concentration was 1.6-fold the delivery concentration, calculated as the ratio of nitric oxide flow to inspiration flow. Dose accuracy and stability were both 5% or 3 nmol in the validated range of 3-1000 nmol. CONCLUSION: With pulsed administration nitric oxide therapy can be directed to well-ventilated lung regions. Avoiding administration to the anatomic dead space eliminates nitric oxide exhalation effectively, which makes the method optimal for nitric oxide therapy in a rebreathing circuit. The required dose range from paediatric to adult is covered by the delivery device with a single nitric oxide gas supply.

Hypertonic saline increases tight junction permeability in airway epithelium.

Asthmatics are known to react to inhaled hyperosmolar solution. Therefore, the effect of hyperosmolar salt solutions on tight junctions of the airway epithelium was investigated by electron microscopy. Rat trachea was perfused with different concentrations of sodium chloride (NaCl) and then fixed from the luminal side with glutaraldehyde to which the electron dense tracer lanthanum chloride had been added. Lanthanum penetrated 3+/-1% of the tight junctions in trachea perfused with 295 mOsm Krebs-Ringer's buffer (KRB). Adding NaCl to the KRB (KRB-NaCl) increased osmolarity of the solution. After perfusion with 589 or 876 mOsm KRB-NaCl, lanthanum was observed in the lateral intercellular spaces in 50+/-11 and 57+/-6%, respectively. The effect of hyperosmolarity was reversible and only 6+/-1% of the tight junctions were penetrated after perfusion with 295 mOsm KRB solution following 589 mOsm KRB-NaCl perfusion. Adding mannitol to the KRB to an osmolarity of 589 mOsm only caused 5+/-1% of the tight junctions to open, even though osmotic effects were observed. Opening the tight junctions with hyperosmolar salt solutions may play a role in exercise-induced asthma. It may also open the prospect for increased penetration of inhaled drugs into the interstitium and the circulation.

Increased nitric oxide elimination from the airways after smoking cessation.

Smokers have been found to have low exhaled nitric oxide (NO) levels. The aim of the present study was to investigate where in the respiratory system the decrease in NO occurs, and whether this decrease was affected by smoking cessation. Measurements of exhaled NO were carried out in smokers (n=20) and non-smoking control subjects (n=30). In nine of the smokers, exhaled NO was analysed 1, 2 and 4 weeks after smoking cessation. The level of exhaled NO at a flow rate of 0.1 litre/s was significantly lower in smokers (4+/-2 p.p.b.) than in non-smokers (7+/-5 p.p.b.; P=0.007). A calculation of the contributions from different areas of the lung showed that the NO flux from the airways was significantly lower (14+/-10 compared with 36+/-26 nl/min; P=0.0001) and the alveolar fraction was significantly higher (2.1+/-0.8 compared with 1.5+/-0.9 p.p.b.; P=0.006) in smokers than in non-smokers. Nine smoking subjects refrained from smoking for 4 weeks, and this resulted in increased NO flux from the airways of 28+/-17 nl/min, which was no longer significantly different from controls. In conclusion, endogenous production of NO in the airways is decreased in smokers, but can be restored to normal values by 4 weeks after cessation of smoking. Smokers have an increased alveolar fraction of NO, and this might be a diagnostic sign of lung damage. Thus NO monitoring can be used to indicate improvements when a smoker decides to stop smoking.

Effect of different pulses of nitric oxide on venous admixture in the anaesthetized horse.

BACKGROUND: Dependent atelectatic lung areas open towards the end of inspiration when the lung opening pressure increases, and recollapse during expiration. We hypothesized that inhaled nitric oxide (NO) counteracts hypoxic vasoconstriction in these collapsing lung areas, resulting in increased pulmonary shunt perfusion. METHODS: We administered NO as a pulse and varied the pulse timing during inspiration in equine anaesthesia, where atelectasis develops regularly. Six spontaneously breathing standard breed trotters were studied under isoflurane anaesthesia in lateral recumbency. NO pulsed into the first 30% of inspiration (group NOp1) was assumed to affect open lung areas. To cover more open lung areas NO was then pulsed into the first 60% of inspiration (group NOp2). In a third group, administration between 50 and 80% of inspiration was aimed at the intermittently opening lung areas (group NOp3). RESULTS: With NOp1, venous admixture decreased by 8 (2)% (mean (SEM), P=0.045) and with NOp2 by 10 (1)% (P=0.01). With NOp3, venous admixture reduction was insignificant. CONCLUSIONS: Pulsed administration of NO in early inspiration is optimal in reducing right to left vascular shunt in atelectatic equine lung. This reduction is positively correlated with the magnitude of the initial shunt. With administration in early inspiration, NO is mostly taken up by the lung. This prevents NO accumulation and NO2 formation in rebreathing circuits. These findings may be important in humans when atelectasis occurs increasingly with overweight and age during anaesthesia, but also in postoperative intensive care and in ARDS.

Extended NO analysis applied to patients with COPD, allergic asthma and allergic rhinitis.

The recommended method to measure exhaled nitric oxide (NO) cannot reveal the source of NO production. We applied a model based on the classical Fick's first law of diffusion to partition NO in the lungs. The aim was to develop a simple and robust solution algorithm with a data quality control feature, and apply it to patients with known alterations in exhaled NO. Subjects with allergic rhinitis, allergic asthma, chronic obstructive pulmonary disease (COPD) smokers and controls were investigated. NO was measured at three expiratory flow rates. An iteration method was developed to partition NO. The airway tissue content of NO was increased in asthma, 144 +/- 80 ppb (P = 0.04) and decreased in smokers, 56 +/- 36 ppb (P = 0.02). There was no difference between subjects with rhinitis, 98 +/- 40 ppb and controls, 98 +/- 44 ppb. The airway transfer rate was increased in allergic asthma and allergic rhinitis, 12 +/- 4 vs. 12 +/- 5 ml sec(-1), compared to controls, 8 +/- 2 ml sec(-1) (P < 0.001). The alveolar levels were no different from controls, 2 +/- 1 ppb. In COPD the alveolar levels were increased, 4 +/- 2 ppb (P < 0.001). Extended NO analysis reveals from where in the respiratory system NO is generated. Hence, this new test can be added to the tools the physician has for the diagnosis and treatment of patients with respiratory disorders.

Assessment of respiratory system mechanics by artificial neural networks: an exploratory study.

We evaluated 1) the performance of an artificial neural network (ANN)-based technology in assessing the respiratory system resistance (Rrs) and compliance (Crs) in a porcine model of acute lung injury and 2) the possibility of using, for ANN training, signals coming from an electrical analog (EA) of the lung. Two differently experienced ANNs were compared. One ANN (ANN(BIO)) was trained on tracings recorded at different time points after the administration of oleic acid in 10 anesthetized and paralyzed pigs during constant-flow mechanical ventilation. A second ANN (ANN(MOD)) was trained on EA simulations. Both ANNs were evaluated prospectively on data coming from four different pigs. Linear regression between ANN output and manually computed mechanics showed a regression coefficient (R) of 0.98 for both ANNs in assessing Crs. On Rrs, ANN(BIO) showed a performance expressed by R = 0.40 and ANN(MOD) by R = 0.61. These results suggest that ANNs can learn to assess the respiratory system mechanics during mechanical ventilation but that the assessment of resistance and compliance by ANNs may require different approaches.