Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry.

Rationale: Postbronchodilator spirometry is used for the diagnosis of chronic obstructive pulmonary disease. However, prebronchodilator reference values are used for spirometry interpretation. Objectives: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or postbronchodilator reference values generated within SCAPIS (Swedish CArdioPulmonary bioImage Study) when interpreting postbronchodilator spirometry in a general population. Methods: SCAPIS reference values for postbronchodilator and prebronchodilator spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or postbronchodilator reference values, with respiratory burden in the SCAPIS general population (28,851 individuals). Measurements and Main Results: Bronchodilation resulted in higher predicted medians and lower limits of normal (LLNs) for FEV1/FVC ratios. The prevalence of postbronchodilator FEV1/FVC ratio lower than the prebronchodilator LLN was 4.8%, and that of postbronchodilator FEV1/FVC lower than the postbronchodilator LLN was 9.9%, for the general population. An additional 5.1% were identified as having an abnormal postbronchodilator FEV1/FVC ratio, and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%; P < 0.001), and self-reported physician-diagnosed chronic obstructive pulmonary disease (2.8% vs. 0.5%, P < 0.001) than subjects with a postbronchodilator FEV1/FVC ratio greater than the LLN for both pre- and postbronchodilation. Conclusions: Pre- and postbronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of postbronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using postbronchodilator reference values when interpreting postbronchodilator spirometry might enable the identification of individuals with mild disease and be clinically relevant.

Assessment of Global Lung Function Initiative (GLI) reference equations for diffusing capacity in relation to respiratory burden in the Swedish CArdioPulmonary bioImage Study (SCAPIS).

The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (D LCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired D LCO We examined if the GLI LLN for D LCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, D LCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50-64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for D LCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of D LCO GLI LLN but GLI LLN but GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.The GLI LLN for D LCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with D LCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.

Restrictive spirometric pattern and true pulmonary restriction in a general population sample aged 50 - 64 years.

BACKGROUND: There is low diagnostic accuracy of the proxy restrictive spirometric pattern (RSP) to identify true pulmonary restriction. This knowledge is based on patients referred for spirometry and total lung volume determination by plethysmograpy, single breath nitrogen washout technique or gas dilution and selected controls. There is, however, a lack of data from general populations analyzing whether RSP is a valid proxy for true pulmonary restriction. We have validated RSP in relation to true pulmonary restriction in a general population where we have access to measurements of total lung capacity (TLC) and spirometry. METHODS: The data was from the Swedish CArdioPulmonary bioImage Study (SCAPIS Pilot), a general population-based study, comprising 983 adults aged 50-64. All subjects answered a respiratory questionnaire. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained before and after bronchodilation. TLC and residual volume (RV) was recorded using a body plethysmograph. All lung function values are generally expressed as percent predicted (% predicted) or in relation to lower limits of normal (LLN). True pulmonary restriction was defined as TLC < LLN5 defined as a Z score < - 1.645, i e the fifth percentile. RSP was defined as FEV1/FVC ≥ LLN and FVC < LLN after bronchodilation. Specificity, sensitivity, positive and negative likelihood ratios were calculated, and 95% confidence intervals (CIs) were calculated. RESULTS: The prevalence of true pulmonary restriction was 5.4%, and the prevalence of RSP was 3.4%. The sensitivity of RSP to identify true pulmonary restriction was 0.34 (0.20-0.46), the corresponding specificity was 0.98 (0.97-0.99), and the positive likelihood ratio was 21.1 (11.3-39.4) and the negative likelihood ratio was 0.67 (0.55-0.81). CONCLUSIONS: RSP has low accuracy for identifying true pulmonary restriction. The results support previous observations that RSP is useful for ruling out true pulmonary restriction.

Prediction of COPD and Related Events Improves by Combining Spirometry and the Single Breath Nitrogen Test.

Chronic obstructive pulmonary disease (COPD) develops in small airways. Severity of small airway pathology relates to progression and mortality. The present study evaluated the prediction of COPD of a validated test for small airway disease, i.e. a slope of the alveolar plateau of the single breath nitrogen test (N2-slope). The N2-slope, spirometry, age, smoking habits, and anthropometric variables at baseline were obtained in a population-based sample (n = 592). The cohort was followed for first COPD events (first hospital admission of COPD or related conditions or death from COPD) during 38 years. During follow-up, 52 subjects (8.8%) had a first COPD event, of which 18 (3.0%) died with a first COPD diagnosis. In the proportional hazard regression analysis adjusted for age and smoking habits, the cumulative COPD event incidence increased from 5% among those with high forced expired volume in one second (FEV1) to 25% among those with low FEV1, while increasing from 4% among those with the lowest N2-slope to 26% among those with the highest. However, combining the N2-slope and FEV1 resulted in considerable synergy in the prediction of first COPD event and even more so when taking account of smoking habits. The cumulative COPD event incidence rate was 75% among heavy smokers with the highest N2-slope and lowest FEV1, and less than 1% among never smokers with the lowest N2-slope and highest FEV1. Thus, combining the results of the single breath N2-slope and FEV1 considerably improved the prediction of COPD events as compared to either test alone.

Reference values of fractional excretion of exhaled nitric oxide among non-smokers and current smokers.

BACKGROUND: Fractional exhaled nitric oxide (FENO) is used to assess of airway inflammation; diagnose asthma and monitor adherence to advised therapy. Reliable and accurate reference values for FENO are needed for both non-smoking and current smoking adults in the clinical setting. The present study was performed to establish reference adult FENO values among never-smokers, former smokers and current smokers. METHODS: FENO was measured in 5265 subjects aged 25-75 years in a general-population study, using a chemiluminescence (Niox ™) analyser according to the guidelines of the American Thoracic Society and the European Respiratory Society. Atopy was based on the presence of immunoglobulin E (IgE) antibodies to common inhalant allergens (measured using Phadiatop® test). Spirometry without bronchodilation was performed and forced vital capacity (FVC), forced expired volume in 1 s (FEV1) and the ratio of FEV1 to FVC values were obtained. After excluding subjects with asthma, chronic bronchitis, spirometric airway obstruction and current cold, 3378 subjects remained. Equations for predictions of FENO values were modelled using nonparametric regression models. RESULTS: FENO levels were similar in never-smokers and former smokers, and these two groups were therefore merged into a group termed "non-smokers". Reference equations, including the 5th and 95th percentiles, were generated for female and male non-smokers, based on age, height and atopy. Regression models for current smokers were unstable. Hence, the proposed reference values for current smokers are based on the univariate distribution of FENO and fixed cut-off limits. CONCLUSIONS: Reference values for FENO among respiratory healthy non-smokers should be outlined stratified for gender using individual reference values. For current smokers separate cut-off limits are proposed.

[Exhaled droplets and Covid-19]. / Mängden utandade partiklar varierar stort mellan individer.

Exhaled droplets are composed of water, salts and organic material and the physical designation is particles. These particles vary in size from 0.01 µm to very large, e g produced during coughing. The respiratory tract lining fluid (RTLF) is the main source of the particles. Large and small exhaled particles are produced in central airways, vocal cords and mouth whereas small particles (< about 5 µm) are produced also in small airways, generated during inspiration by the airway closure/opening mechanism. These particles are composed mainly of surfactant. Exhaled small particles may carry virus and cause airborne transmission and infection, which may be an important transmission route indoors. Ventilation, concentration of people, activities and face mask occurrence influence the risk of infection. Outdoor transmission is in addition influenced by outdoor pollution and wind speed.

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.

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 (N2-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 N2-slope was determined. Proportional hazard regression (Cox regression) analysis was used for the prediction model. The N2-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<0.005), a prediction applicable to subjects without (p=0.001) and with (p<0.05) airway obstruction. Dyspnoea and wheezing were the most predictive symptoms. The combination of the N2-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 ∼70% and ∼90% for a very steep N2-slope combined with many respiratory symptoms in subject without and with airway obstruction, respectively. The alveolar N2-slope should be considered in the critical need for further research on early diagnosis of COPD.

Current smoking alters phospholipid- and surfactant protein A levels in small airway lining fluid: An explorative study on exhaled breath.

Small airways are difficult to access. Exhaled droplets, also referred to as particles, provide a sample of small airway lining fluid and may reflect inflammatory responses. We aimed to explore the effect of smoking on the composition and number of exhaled particles in a smoker-enriched study population. We collected and chemically analyzed exhaled particles from 102 subjects (29 never smokers, 36 former smokers and 37 current smokers) aged 39 to 83 years (median 63). A breathing maneuver maximized the number exhaled particles, which were quantified with a particle counter. The contents of surfactant protein A and albumin in exhaled particles was quantified with immunoassays and the contents of the phospholipids dipalmitoyl- and palmitoyl-oleoyl- phosphatidylcholine with mass spectrometry. Subjects also performed spirometry and nitrogen single breath washout. Associations between smoking status and the distribution of contents in exhaled particles and particle number concentration were tested with quantile regression, after adjusting for potential confounders. Current smokers, compared to never smokers, had higher number exhaled particles and more surfactant protein A in the particles. The magnitude of the effects of current smoking varied along the distribution of each PEx-variable. Among subjects with normal lung function, phospholipid levels were elevated in current smokers, in comparison to no effect of smoking on these lipids at abnormal lung function. Smoking increased exhaled number of particles and the contents of lipids and surfactant protein A in the particles. These findings might reflect early inflammatory responses to smoking in small airway lining fluid, also when lung function is within normal limits.

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.

Airway monitoring by collection and mass spectrometric analysis of exhaled particles.

We describe a new method for simultaneously collecting particles in exhaled air for subsequent chemical analysis and measuring their size distribution. After forced exhalation, particles were counted and collected in spots on silicon wafers with a cascade impactor. Several phospholipids were identified by time-of-flight secondary ion mass spectrometric analysis of the collected spots, suggesting that the particles originated from the lower airways. The amount of particles collected in ten exhalations was sufficient for characterizing the phospholipid composition. The feasibility of the technique in respiratory research is demonstrated by analysis of the phospholipid composition of exhaled particles from healthy controls, patients with asthma, and patients with cystic fibrosis. We believe this technology will be useful for monitoring patients with respiratory disease and has a high potential to detect new biomarkers in exhaled air.

Absolute lung size and the sex difference in breathlessness in the general population.

BACKGROUND: Breathlessness is associated with major adverse health outcomes and is twice as common in women as men in the general population. We evaluated whether this is related to their lower absolute lung volumes. METHODS: Cross-sectional analysis of the population-based Swedish CardioPulmonarybioImage Study (SCAPIS) Pilot, including static spirometry and diffusing capacity (n = 1,013; 49% women). Breathlessness was measured using the modified Medical Research Council (mMRC) scale and analyzed using ordinal logistic regression adjusting for age, pack-years of smoking, body mass index, chronic airway limitation, asthma, chronic bronchitis, depression and anxiety in all models. RESULTS: Breathlessness was twice as common in women as in men; adjusted odds ratio (OR) 2.20 (95% confidence interval, 1.32-3.66). Lower absolute lung volumes were associated with increased breathlessness prevalence in both men and women. The sex difference in breathlessness was unchanged when adjusting for lung function in %predicted, but disappeared when controlling for absolute values of total lung capacity (OR 1.12; 0.59-2.15), inspiratory capacity (OR 1.26; 0.68-2.35), forced vital capacity (OR 0.84; 0.42-1.66), forced expiratory volume in one second (OR 0.70; 0.36-1.35) or lung diffusing capacity (OR 1.07; 0.58-1.97). CONCLUSION: In the general population, the markedly higher prevalence of breathlessness in women is related to their smaller absolute lung volumes.

Fraction of exhaled nitric oxide at 50 mL/s: reference values for adult lifelong never-smokers.

BACKGROUND: The measurement of fractional exhaled nitric oxide (FENO) is used as a marker of airway inflammation. The aim of this study was to establish reference values of FENO for adults. METHODS: FENO at a flow rate of 50 mL/s was analyzed in 3,376 adults using a chemiluminescence analyzer according to American Thoracic Society/European Respiratory Society guidelines. Blood samples were analyzed, and atopy was defined as the presence of specific IgE. All subjects responded to a respiratory questionnaire. Those who had never smoked (n = 1,803) were selected for this study. After the exclusion of subjects with physician-diagnosed asthma, asthma symptoms, ever wheezing, dry cough, or use of inhaled steroids, 1,131 healthy never-smokers remained, including 845 nonatopic and 286 atopic subjects. RESULTS: Based on multiple regression modeling, we propose the following reference equation for healthy never-smoking adults: Ln(FENO) = 0.057 + 0.013 x height (in centimeters) + 0.0088 x age (in years). The residual SD was 0.51, and the explanatory value was 9%. In a model, based on nonatopic subjects alone, the reference equation obtained was slightly different, as follows: Ln(FENO) = -0.0026 + 0.013 x height (in centimeters) + 0.010 x age (in years). The residual SD for this equation was 0.48, and the explanatory value was 11%. CONCLUSIONS: Normal values of FENO for adults may be predicted on the basis of age and height. However, as the reference equations only account for about 9 to 11% of the variation, the most important information that could be extracted from the study is that the upper limits of FENO range from 24.0 to 54.0 parts per billion, depending on age and height.

Myeloperoxidase as a marker of increasing systemic inflammation in smokers without severe airway symptoms.

BACKGROUND: There is increasing evidence of systemic inflammation in patients with chronic obstructive pulmonary disease (COPD), but there is very little information on the development of systemic inflammation in smokers without severe airway symptoms. In this longitudinal study, we examined whether smokers with mild or no airway symptoms develop signs of systemic inflammation by assessing inflammatory markers in blood over a 6-year period. METHODS: Forty smokers and 28 male never-smokers were investigated in 1995 (year 0) and 6 years later (year 6). At year 6, 11 smokers had stopped smoking (quitters); these subjects were analysed as a separate group. At year 0 and 6, we measured serum levels of myeloperoxidase (MPO), lysozyme and human neutrophil lipocalin (HNL), regarded as markers of activity in neutrophils plus monocyte-lineage cells, monocyte-lineage cells only and neutrophils only. RESULTS: All systemic markers of inflammation (MPO, HNL and lysozyme) were significantly higher in smokers than in never smokers at year 6. For MPO alone, smokers only displayed a unique pattern compared with the other groups; the concentration of MPO in blood increased among smokers during the 6-year period, and this increase was statistically significant compared with that observed in never-smokers. Even though quitters did not display any clear change in MPO, we observed a statistically significant negative correlation between the change in blood MPO and the duration of smoking cessation in this group. For HNL and lysozyme, the changes over time were similar in smokers and never-smokers, with no statistically significant difference compared with quitters. CONCLUSION: This study provides evidence that male smokers without severe airway symptoms develop an increasing systemic inflammation during a 6-year period. The study forwards both direct and indirect evidence that MPO may be an early marker of this systemic inflammation. However, our study also forwards indirect evidence that ongoing tobacco smoking may "drive" the level of systemic HNL and lysozyme. The origin of the increased MPO and its value as an easily measured predictor for future COPD deserves to be further evaluated.

Evaluation of reconstruction techniques for lung single photon emission tomography: a Monte Carlo study.

BACKGROUND: In studies of the distribution of lung function, the image quality of lung single photon emission computed tomography (SPECT) is important and one factor influencing it is the reconstruction algorithm. AIM: To systematically evaluate ordered subsets expectation maximization (OSEM) and compare it with filtered back-projection (FBP) for lung SPECT with Tc. METHODS: The evaluation of the number of iterations used in OSEM was based on the image quality parameter contrast. The comparison between OSEM and FBP was based on trade-off plots between statistical noise and spatial resolution for different filter parameters, collimators and count-levels. A Monte Carlo technique was used to simulate SPECT studies of a digital thorax phantom containing two sets of activity: one with a homogeneous activity distribution within the lungs and the other with superposed high- and low-activity objects. Statistical noise in the reconstructed images was calculated as the coefficient of variation (CV) and spatial resolution as full width at half-maximum (FWHM). RESULTS: For the configuration studied, the OSEM reconstruction in combination with post-filtering should be used in lung SPECT studies with at least 60 MLEM equivalent iterations. Compared to FBP the spatial resolution was improved by about 1 mm. For a constant level of CV, a four-fold increase in count level resulted in an increased resolution of about 2 mm. Spatial resolution and cut-off frequency depends on what value of noise in the image is acceptable also increased by using a low-energy, high-resolution collimator for CV values above 3%. The choice of noise-reducing filter and cut-off frequency depends on what value of noise in the image is acceptable.

High tidal end expiratory flow--an index of dynamic hyperinflation?

Dynamic hyperinflation is considered an important mechanism behind shortness of breath and reduced exercise capacity in chronic obstructive pulmonary disease (COPD) patients. Prevailing methods to assess dynamic hyperinflation are crude because of the large normal variation of both functional residual capacity and inspiratory capacity (IC). In the present study, we hypothesized that expiratory flow on a relatively high level near the end of tidal expiration is an indication of dynamic hyperinflation. A method to measure tidal end expiratory flow (TEEF), i.e. the flow between 0.6 s and 0.04 s before start of inspiration is presented and evaluated in 15 healthy subjects and 16 COPD patients. The COPD patients had more than twice as high TEEF values compared with the healthy subjects (45.4 +/- 23.8 and 20.4 +/- 7.3 ml s(-1) respectively; mean +/- SD; P = 0.0002, for TEEF at 0.4 s before start of inspiration). TEEF values correlated to IC, e.g. TEEF at 0.4 s before start of inspiration expressed as a fraction of mean expiratory flow, correlated to IC (% pred.) (r = 0.74; P<0.0001). These results justifies further testing of the relationship between TEEF and dynamic hyperinflation.

Spirometric reference equations for Swedish adults.

New spirometric reference equations for Swedish adults are required. Three different older sets of reference equations clinically used in Sweden have various drawbacks and the recently published 'The Global Lung Function 2012 (GLI) equations' have been shown not to be adequate for Swedish normal, healthy non-smokers. We have recently concluded that a piecewise linear model presented by Lubinski and Gólczewski accurately describes the distribution of spirometric variables in a large Swedish random population sample. This piecewise linear model also offers the important advantage of implementing easily physiologically interpretable coefficients. The present study aimed at presenting piecewise linear reference equations for Swedish adults based on a random population sample of 6685 individuals aged 25-75 years. Predicted normal values by the piecewise linear reference equations and lower limit normal (LLN) were compared with the three reference equations frequently used clinically in Sweden and the GLI equations. We found predicted normal values according to the present piecewise linear reference equations close to 100% predicted normal as expected, whereas the other equations either overestimated or underestimated normal subjects. Concerning LLN, the present equations, i.e. 1·645 × RSD, showed the least deviation from the expected 5% and, e.g., the GLI equations systematically identified too few subjects below LLN. We conclude that the present piecewise linear reference equations, based on a relatively large general population sample, ought to be considered for clinical use in Sweden. Application of 1·645 × RSD below predicted value gave an acceptably accurate LLN.

Exhaled Particles After a Standardized Breathing Maneuver.

BACKGROUND: Particles in exhaled air (PEx) provide samples of respiratory tract lining fluid from small airways and offer a new opportunity to monitor pathological changes. The exhaled particles are produced by reopening of closed small airways and contain surfactant. The amount of PEx varies by orders of magnitude among subjects. A standardized breathing pattern reduces the variation, but it remains large and the reasons are unknown. The aim of the present study was to assess to what extent sex, age, body size, and spirometry results explain the interindividual variation of PEx among healthy middle-aged subjects. METHODS: The PExA® instrument was used to measure PEx in 126 healthy middle-aged nonsmoking subjects participating in the European Respiratory Community Health Survey (ERCS-III). The subjects performed a standardized breathing maneuver involving expiration to residual volume, a breath-hold of 3 seconds, a full inspiration, and then a full expiration into the PExA instrument. PEx number concentrations were expressed per exhalation and per exhaled liter. Age and anthropometric and spirometric variables were analyzed as potential predictors. RESULTS: PEx/L was consistently and negatively associated to lung size-related variables and accordingly lower in men than in women. PEx/Exhalation was similar in women and men. Increasing age was associated with increasing PEx. Reference equations are presented based on age, weight, and spirometry variables and independent of sex. These predictors explained 28%-29% of the interindividual variation. CONCLUSIONS: The interindividual variation of PEx after a standardized breathing maneuver is large and the considered predictors explain a minor part only.

Exhaled particles as markers of small airway inflammation in subjects with asthma.

Exhaled breath contains suspended particles of respiratory tract lining fluid from the small airways. The particles are formed when closed airways open during inhalation. We have developed a method called Particles in Exhaled air (PExA® ) to measure and sample these particles in the exhaled aerosol. Here, we use the PExA® method to study the effects of birch pollen exposure on the small airways of individuals with asthma and birch pollen allergy. We hypothesized that birch pollen-induced inflammation could change the concentrations of surfactant protein A and albumin in the respiratory tract lining fluid of the small airways and influence the amount of exhaled particles. The amount of exhaled particles was reduced after birch pollen exposure in subjects with asthma and birch pollen allergy, but no significant effect on the concentrations of surfactant protein A and albumin in exhaled particles was found. The reduction in the number of exhaled particles may be due to inflammation in the small airways, which would reduce their diameter and potentially reduce the number of small airways that open and close during inhalation and exhalation.

The effect of exhalation flow on endogenous particle emission and phospholipid composition.

Exhaled particles constitute a micro-sample of respiratory tract lining fluid. Inhalations from low lung volumes generate particles in small airways by the airway re-opening mechanism. Forced exhalations are assumed to generate particles in central airways by mechanisms associated with high air velocities. To increase knowledge on how and where particles are formed, different breathing manoeuvres were compared in 11 healthy volunteers. Particles in the 0.41-4.55µm diameter range were characterised and sampled. The surfactant lipid dipalmitoylphosphatidylcholine (DPPC) was quantified by mass spectrometry. The mass of exhaled particles increased by 150% (95% CI 10-470) for the forced exhalation and by 470% (95% CI 150-1190) for the airway re-opening manoeuvre, compared to slow exhalations. DPPC weight percent concentration (wt%) in particles was 2.8wt% (95%CI 1.4-4.2) and 9.4wt% (95%CI 8.0-10.8) for the forced and the airway re-opening manoeuvres, respectively. In conclusion, forced exhalation and airway re-opening manoeuvres generate particles from different airway regions having different DPPC concentration.