Marieann Högman

Influence of gas composition on recurrence of atelectasis after a reexpansion maneuver during general anesthesia

Background Atelectasis, an important cause of impaired gas exchange during general anesthesia, may be eliminated by a vital capacity maneuver. However, it is not clear whether such a maneuver will have a sustained effect. The aim of this study was to determine the impact of gas composition on reappearance of atelectasis and impairment of gas exchange after a vital capacity maneuver. Methods A consecutive sample of 12 adults with healthy lungs who were scheduled for elective surgery were studied. Thirty minutes after induction of anesthesia with fentanyl and propofol, the lungs were hyperinflated manually up to an airway pressure of 40 cmH2 O. FI sub O2 was either kept at 0.4 (group 1, n = 6) or changed to 1.0 (group 2, n = 6) during the recruitment maneuver. Atelectasis was assessed by computed tomography. The amount of dense areas was measured at end-expiration in a transverse plane at the base of the lungs. The ventilation-perfusion distributions (V with dot A/Q with dot) were estimated with the multiple inert gas elimination technique. The static compliance of the total respiratory system (Crs) was measured with the flow interruption technique. Results In group 1 (FIO2 = 0.4), the recruitment maneuver virtually eliminated atelectasis for at least 40 min, reduced shunt (V with dot A/Q with dot < 0.005), and increased at the same time the relative perfusion to poorly ventilated lung units (0.005 < V with dot A/Q with dot < 0.1; mean values are given). The arterial oxygen tension (PaO2) increased from 137 mmHg (18.3 kPa) to 163 mmHg (21.7 kPa; before and 40 min after recruitment, respectively; P = 0.028). In contrast to these findings, atelectasis recurred within 5 min after recruitment in group 2 (FIO2 = 1.0). Comparing the values before and 40 min after recruitment, all parameters of V with dot A/Q with dot were unchanged. In both groups, Crs increased from 57.1/55.0 ml *symbol* cmH2 O sup -1 (group 1/group 2) before to 70.1/67.4 ml *symbol* cmH2 O sup -1 after the recruitment maneuver. Crs showed as low decrease thereafter (40 min after recruitment: 61.4/60.0 ml *symbol* cmH2 O sup -1), with no difference between the two groups. Conclusions The composition of inspiratory gas plays an important role in the recurrence of collapse of previously reexpanded atelectatic lung tissue during general anesthesia in patients with healthy lungs. The reason for the instability of these lung units remains to be established. The change in the amount of atelectasis and shunt appears to be independent of the change in the compliance of the respiratory system.

Exhaled nitric oxide and its relationship to airway responsiveness and atopy in asthma

Abstract Exhaled nitric oxide (NO) has attracted increasing interest as a non-invasive marker of airway inflammation. The purpose of this study was to determine whether exhaled nitric oxide in subjects with asthma varied according to their atopic status and to examine its correlation with airway hyperresponsiveness and lung function measurements. Forty patients with asthma and 13 controls participated in the study. Nitric oxide was measured on three occasions with intervals of at least 3 days, using a chemiluminescence method. Airway responsiveness was assessed with methacholine challenge and lung function measurements were made. All subjects recorded peak expiratory flow and kept a symptom diary during a 17-day period. There was no significant difference in lung function measurements, peak expiratory flow or symptom score between the two asthma groups. Atopic patients with asthma had a significantly higher mean amount of exhaled NO than non-atopic subjects with asthma (162 ± 68 vs. 113 ± 55 nl min −1 ; P = 0·03) and the control group (88 ± 52 nl min −1 ; P = 0·004). No significant difference was found in the amount of exhaled NO between non-atopic patients with asthma and the controls. In atopic subjects with asthma the mean exhaled NO was significantly correlated to the dose-response slope for methacholine ( r = −0·52; P = 0·02), while no such correlation was found in the non-atopic group. In conclusion; in this study, atopic subjects with asthma had higher levels of exhaled NO than non-atopic subjects. Atopic status should be taken into account when measuring levels of exhaled NO in subjects with asthma.

Population-based study of multiplexed IgE sensitization in relation to asthma, exhaled nitric oxide, and bronchial responsiveness

BACKGROUND IgE sensitization is an important risk factor for the development of asthma. OBJECTIVE The aim of this study was to investigate the IgE antibody profile for a broad spectrum of allergen molecules in asthmatic patients. METHODS Participants from the European Community Respiratory Health Survey II (n=467) were tested with ImmunoCAP ISAC against 103 allergen molecules. The presence of bronchial hyperresponsiveness was measured with a methacholine challenge test and bronchial inflammation with fraction of exhaled nitric oxide (Feno). RESULTS A total of 38% of the controls and 72% of the asthmatic patients were sensitized against at least 1 of the allergen components (P<.0001). Asthma was independently related to having IgE antibodies against pollen (odds ratio=2.2) and perennial airway allergens (odds ratio=5.6), increased Feno was independently related to having IgE antibodies against food allergens and perennial allergens, while bronchial responsiveness was independently associated with having IgE antibodies against only perennial allergens. Sensitization to food allergens was related to asthma and increased Feno if IgE antibody against pollen allergens was present. Simultaneous sensitization to perennial, pollen, and food allergens involves the highest risk of asthma (odds ratio=18.3), bronchial inflammation, and responsiveness. CONCLUSIONS Feno, bronchial responsiveness, and the risk of asthma increase with multiple sensitizations to different allergen groups. We show for the first time that the presence of IgE antibodies against food allergens is independently associated with increased Feno and increases the risk of asthma in subjects with simultaneous sensitization to pollen allergens.

A European Respiratory Society technical standard: exhaled biomarkers in lung disease

Breath tests cover the fraction of nitric oxide in expired gas (FENO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FENO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FENO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management. Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members. Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised. Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice. ERS technical standard: exhaled biomarkers in lung disease http://ow.ly/mAjr309DBOP

Exhaled nitric oxide monitoring by quantum cascade laser: comparison with chemiluminescent and electrochemical sensors.

Fractional exhaled nitric oxide (F(E)NO) is considered an indicator in the diagnostics and management of asthma. In this study we present a laser-based sensor for measuring F(E)NO. It consists of a quantum cascade laser (QCL) combined with a multi-pass cell and wavelength modulation spectroscopy for the detection of NO at the sub-part-per-billion by volume (ppbv, 110(-9)) level. The characteristics and diagnostic performance of the sensor were assessed. A detection limit of 0.5 ppbv was demonstrated with a relatively simple design. The QCL-based sensor was compared with two market sensors, a chemiluminescent analyzer (NOA 280, Sievers) and a portable hand-held electrochemical analyzer (MINO, Aerocrine AB, Sweden). F(E)NO from 20 children diagnosed with asthma and treated with inhaled corticosteroids were measured. Data were found to be clinically acceptable within 1.1 ppbv between the QCL-based sensor and chemiluminescent sensor and within 1.7 ppbv when compared to the electrochemical sensor. The QCL-based sensor was tested on healthy subjects at various expiratory flow rates for both online and offline sampling procedures. The extended NO parameters, i.e. the alveolar region, airway wall, diffusing capacity, and flux were calculated and showed a good agreement with the previously reported values.

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

BackgroundA 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.MethodsThe 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.ResultsIgE-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.ConclusionThe 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 Societys 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.

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.

The Safety of One, or Repeated, Vital Capacity Maneuvers During General Anesthesia

A vital capacity maneuver (VCM) (inflating the lungs to 40 cm H2O for 15 s) is effective in relieving atelectasis during general anesthesia or after cardiopulmonary bypass (CPB). The study was undertaken to investigate the safety of one or repeated VCM. Five groups of six pigs were studied. Two groups had general anesthesia for 6 h and one group received a VCM every hour. Three other groups received CPB. VCM was performed after CPB in two of these groups. VCM was then repeated every hour in one of the groups. Lung damage was evaluated by extravascular lung water (EVLW) measurement, light microscopy, and the half-time (T1/2) of disappearance from the lung of a nebulized aerosol containing 99mTc-DTPA. No changes were noted in extravascular lung water. The pigs subjected to VCM decreased their T1/2. In the groups exposed to repeated VCM, T1/2 remained lowered (CPB pigs) or decreased over time (non-CPB pigs). No lung damage could be seen on the morphology study. These results suggest that one VCM is a safe procedure. The increase in lung clearance of 99mTc-DTPA not associated with an increase in lung water when VCM is repeated may have been caused by an increase in lung volume. Therefore, repeated VCM also appears to be safe. Implications This study demonstrates in an animal model that inflating the lung once or repeatedly to the vital capacity is a safe procedure. This maneuver, also called the vital capacity maneuver, can be used to relieve lung collapse which occurs in all patients during general anesthesia.

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 (CANO), airway wall (CawNO), diffusing capacity (DawNO) and flux (JawNO), 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.