Uneven distribution of ventilation in acute respiratory distress syndrome

INTRODUCTION: The aim of this study was to assess the volume of gas being poorly ventilated or non-ventilated within the lungs of patients treated with mechanical ventilation and suffering from acute respiratory distress syndrome (ARDS). METHODS: A prospective, descriptive study was performed of 25 sedated and paralysed ARDS patients, mechanically ventilated with a positive end-expiratory pressure (PEEP) of 5 cmH(2)O in a multidisciplinary intensive care unit of a tertiary university hospital. The volume of poorly ventilated or non-ventilated gas was assumed to correspond to a difference between the ventilated gas volume, determined as the end-expiratory lung volume by rebreathing of sulphur hexafluoride (EELV(SF6)), and the total gas volume, calculated from computed tomography images in the end-expiratory position (EELV(CT)). The methods used were validated by similar measurements in 20 healthy subjects in whom no poorly ventilated or non-ventilated gas is expected to be found. RESULTS: EELV(SF6 )was 66% of EELV(CT), corresponding to a mean difference of 0.71 litre. EELV(SF6 )and EELV(CT )were significantly correlated (r(2 )= 0.72; P < 0.001). In the healthy subjects, the two methods yielded almost identical results. CONCLUSION: About one-third of the total pulmonary gas volume seems poorly ventilated or non-ventilated in sedated and paralysed ARDS patients when mechanically ventilated with a PEEP of 5 cmH(2)O. Uneven distribution of ventilation due to airway closure and/or obstruction is likely to be involved

Single breath N2-test and exhaled nitric oxide in men

SummaryThe N2 slope is an index of inhomogeneous distribution of ventilation and has been suggested to be suited for early testing of chronic obstructive pulmonary disease (COPD) in smokers. The aim of the present study was to examine the association between the fraction of exhaled nitric oxide (FENO) and the N2 slope in a random population of smoking and non-smoking men. Altogether 57 subjects were included in the study, 24 never-smokers, seven ex-smokers and 26 current smokers. Subjects were examined twice, in 1995 when they regarded themselves as healthy, and in a follow-up in 2001. Spirometry, N2 slope and high-resolution computed tomography (HRCT) were performed in 1995 while the follow-up examination included also measurement of FENO.The FENO value was significantly lower and the N2 slope higher in current smokers. In smokers but not in never- or ex-smokers FENO was correlated to the difference in N2 slope between 1995 and 2001 (rs=0.49, P=0.01). We analysed the data by multiple linear regression adjusted for smoking, mild respiratory symptoms and inhaled steroids. There were significant associations between FENO and the N2 slope both in 1995 and in 2001. The strongest association was found to exist with the change in N2 slope during these years.Sixteen of the subjects could be classified as having COPD, six with mild and ten with moderate COPD. There was a trend for an increase in N2 slope with increased severity of COPD; among subjects with no COPD the N2 slope in 2001 was 2.3% N2/L, and those with mild and moderate COPD had 2.5% N2/L and 3.9% N2/L, respectively (P=0.0004). No such trend was seen for FENO (17.8, 15.5 and 20.3 parts per billion (ppb), respectively, P=0.8).The results show that FENO is associated with the N2 slope, indicating that FENO reflects inflammatory changes in the peripheral airways of both non-smoking and smoking subjects

Prediction of BOS by the single-breath nitrogen test in double lung transplant recipients

Abstract Background The present study analyses the ability of the alveolar slope of the single-breath nitrogen washout test (N2-slope) to diagnose and predict the development of the bronchiolitis obliterans syndrome (BOS). Methods We present a retrospective analysis of 61 consecutive bilateral lung or heart-lung transplant recipients who were followed at regular control visits during a three year follow-up. The operating characteristics of the N2-slope to diagnose BOS and potential BOS (BOS 0-p) and to predict BOS were determined based on cut off values of 95% specificity. Results The sensitivity of the N2-slope to identify BOS was 96%, and BOS 0-p 100%. The predictive ability to predict BOS with a N2-slope > 478% of the predicted normal was 56%, and if combined with a coincident FEV1 Conclusions The predictive ability of either the N2-slope or of FEV1 to diagnose BOS is limited but the combination of the two appears useful. Follow-up protocols of bilateral lung and heart-lung transplant recipients should consider including tests sensitive to obstruction of the peripheral airways.</p

Relation Between Humidity and Size of Exhaled Particles

Background: Aerosol particles are generated in human airways, and leave the body with exhaled air. These particles may carry indicators of various lung conditions. To fully utilize the information provided by endo- genously produced exhaled particles, it is important to understand their formation mechanism and physical properties. The scope of this work was to measure number size distributions of exhaled aerosol particles at various surrounding relative humidities (RH) in order to gain some knowledge of the size distribution at the point of particle generation. <p> </p> Methods: Number size distributions of exhaled particles were measured at various RHs, using an optical particle counter. Breathing with airway closure was employed. <p> </p> Results: A relation between particle volume and RH was fitted to experimental data and used to predict how exhaled droplets behave at RHs not easily accessible by experiments. The diameter of an exhaled particle is reduced by a factor of 0.42 when the RH is changed from 99.5 to 75% at 309 K. Calculations also show that the droplets are concentrated solutions near saturation at 75% RH. <p> </p> Conclusions: It is concluded that the particles are supersaturated liquid particles, rather than crystalline solids, in ambient air with RH below 75%. A size distribution related to the aerosol at the moment of formation is given. A successful detailed formation mechanismshould be able to accommodate the size distribution predicted at 99.5%RH

Size Distribution of Exhaled Particles in the Range from 0.01 to 2.0 µm

This study investigates the number size distribution of endogenously produced exhaled particles during tidal breathing and breathing with airway closure. This is the first time that the region below 0.4 µm has been investigated. The particle concentration was generally lower for tidal breathing than for airway closure, although the inter-individual variation was large. During tidal breathing, the size distribution peaks at around 0.07 µm. This peak is still present during the airway closure manoeuvre, but an additional broad and strong peak is found between 0.2 and 0.5 µm. This suggests that different mechanisms govern the generation of particles in the two cases. The particles produced from airway closure may be attributed to formation of film droplets in the distal bronchioles during inhalation. It is speculated that the very small particles are film droplets originating from the alveolar region

Prediction of COPD by the single-breath nitrogen test and various respiratory symptoms

Early identification of subjects running an increased risk of contracting COPD enables focus on individual preventive measures. The slope of the alveolar plateau of the single-breath nitrogen washout test (N-2-slope) is a sensitive measure of small-airway dysfunction. However, its role remains unexplored in predicting hospital admission or death related to COPD, i.e. incident COPD events, in relation to the presence of various respiratory symptoms. A random population sample of 625 men, aged 50 (n=218) or 60 years (n=407), was followed for 38 years for incident COPD events. At baseline, a questionnaire on respiratory symptoms and smoking habits was collected, spirometry and the single-breath nitrogen test were performed, and the N-2-slope was determined. Proportional hazard regression (Cox regression) analysis was used for the prediction model. The N-2-slope improved the prediction of COPD events significantly beyond that of respiratory symptoms weighted all together and other covariates (hazard ratio 1.63, 95% CI 1.20-2.22; p&lt;0.005), a prediction applicable to subjects without (p=0.001) and with (p&lt;0.05) airway obstruction. Dyspnoea and wheezing were the most predictive symptoms. The combination of the N-2-slope and number of respiratory symptoms notably resulted in an effective prediction of incident COPD events even in nonobstructive subjects, as evidenced by a predicted incidence of similar to 70% and similar to 90% for a very steep N-2-slope combined with many respiratory symptoms in subject without and with airway obstruction, respectively. The alveolar N-2-slope should be considered in the critical need for further research on early diagnosis of COPD

Airway effects of salmeterol in healthy individuals

The long-acting beta 2-agonist salmeterol has been shown in several in vitro studies to produce non-beta-mediated relaxant effects. The aim of the present study was to investigate whether these effects have any relevance in humans in vivo. Thirteen healthy individuals were studied in a randomized, double-blind, cross-over study on five separate days. The subjects were pre-treated orally with either propranolol 400 mg in order to block beta-adrenoceptor mediated effects or placebo. Two hours after drug intake, three increasing doses of salmeterol (25 + 50 + 100 micrograms), salbutamol (100 + 200 + 400 micrograms) or placebo were given from matched meter dose inhalers at 1-h intervals between doses. Specific airway conductance (sGAW) was measured in a body plethysmograph at the beginning of the experiment and 30 and 60 min after each inhaled dose of the beta-agonists. Salmeterol and salbutamol produced the same maximal increase in sGAW and had the same area under the dose-response curves. Pre-treatment with propranolol totally inhibited the effect of both drugs. In conclusion, salmeterol at clinically used doses did not produce any non-beta-mediated bronchodilating effect in normal individuals, measured as sGAW. Salmeterol and salbutamol showed the same efficacy but salmeterol was four times more potent than salbutamol

Intra-individual variation of particles in exhaled air and of the contents of Surfactant protein A and albumin.

INTRODUCTION:Particles in exhaled air (PEx) provide samples of respiratory tract lining fluid from small airways containing, for example, Surfactant protein A (SP-A) and albumin, potential biomarkers of small airway disease. We hypothesized that there are differences between morning, noon, and afternoon measurements and that the variability of repeated measurements is larger between days than within days. METHODS:PEx was obtained in sixteen healthy non-smoking adults on 11 occasions, within one day and between days. SP-A and albumin were quantified by ELISA. The coefficient of repeatability (CR), intraclass correlation coefficient (ICC), and coefficient of variation (CV) were used to assess the variation of repeated measurements. RESULTS:SP-A and albumin increased significantly from morning towards the noon and afternoon by 13% and 25% on average, respectively, whereas PEx number concentration and particle mean mass did not differ significantly between the morning, noon and afternoon. Between-day CRs were not larger than within-day CRs. CONCLUSIONS:Time of the day influences the contents of SP-A and albumin in exhaled particles. The variation of repeated measurements was rather high but was not influenced by the time intervals between measurements

Novel non-invasive particles in exhaled air method to explore the lining fluid of small airways-a European population-based cohort study

INTRODUCTION: Respiratory tract lining fluid of small airways mainly consists of surfactant that can be investigated by collection of the particles of exhaled aerosol (PExA) method. This offers an exciting prospect to monitor small airway pathology, including subjects with asthma and smokers. AIM: To explore the influence of anthropometric factors and gender on phospholipids, surfactant protein A (SP-A) and albumin of the lining fluid of small airwaysand to examine the association with asthma and smoking. Furthermore, to examine if the surfactant components can predict lung function in terms of spirometry variables. METHOD: This study employs the population-based cohort of the European Community Respiratory Health Survey III, including participants from Gothenburg city, Sweden (n=200). The PExA method enabled quantitative description and analytical analysis of phospholipids, SP-A and albumin of the lining fluid of small airways. RESULTS: Age was a significant predictor of the phospholipids. The components PC14:0/16:0, PC16:0/18:2 (PC, phosphatidylcholine) and SP-A were higher among subjects with asthma, whereas albumin was lower. Among smokers, there were higher levels particularly of di-palmitoyl-di-phosphatidyl-choline compared with non-smokers. Most phospholipids significantly predicted the spirometry variables. CONCLUSION: This non-invasive PExA method appears to have great potential to explore the role of lipids and proteins of surfactant in respiratory disease