Exhaled particles and small airways Bake, B; Larsson, P; Ljungkvist, G ...
Respiratory research,
01/2019, Volume:
20, Issue:
1
Journal Article
Peer reviewed
Open access
Originally, studies on exhaled droplets explored properties of airborne transmission of infectious diseases. More recently, the interest focuses on properties of exhaled droplets as biomarkers, ...enabled by the development of technical equipment and methods for chemical analysis. Because exhaled droplets contain nonvolatile substances, particles is the physical designation. This review aims to outline the development in the area of exhaled particles, particularly regarding biomarkers and the connection with small airways, i e airways with an internal diameter < 2 mm.
Generation mechanisms, sites of origin, number concentrations of exhaled particles and the content of nonvolatile substances are studied. Exhaled particles range in diameter from 0.01 and 1000 μm depending on generation mechanism and site of origin. Airway reopening is one scientifically substantiated particle generation mechanism. During deep expirations, small airways close and the reopening process produces minute particles. When exhaled, these particles have a diameter of < 4 μm. A size discriminating sampling of particles < 4 μm and determination of the size distribution, allows exhaled particle mass to be estimated. The median mass is represented by particles in the size range of 0.7 to 1.0 μm. Half an hour of repeated deep expirations result in samples in the order of nanogram to microgram. The source of these samples is the respiratory tract ling fluid of small airways and consists of lipids and proteins, similarly to surfactant. Early clinical studies of e g chronic obstructive pulmonary disease and asthma, reported altered particle formation and particle composition.
The physical properties and content of exhaled particles generated by the airway reopening mechanism offers an exciting noninvasive way to obtain samples from the respiratory tract lining fluid of small airways. The biomarker potential is only at the beginning to be explored.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Nitrogen multiple breath washout (N2 MBW) is a sensitive method to identify peripheral airway involvement in asthma, but is a time‐consuming test. The N2 vital capacity single breath (VC SBW) ...test offers greater time efficiency, but concordance with N2 MBW is poorly understood. The prevalence of peripheral airway abnormality was determined by N2 MBW and N2 SBW tests in 194 asthmatic subjects aged 18–1 years. N2 MBW data were related to findings in 400 healthy controls, aged 17–71 years, while N2 SBW data were compared to findings in 224 healthy controls, aged 15–65 years, to derive equipment‐specific reference values. Amongst asthmatic subjects, relationships between N2 SBW and N2 MBW outcomes were studied. N2 SBW relationship with clinical history, spirometry, blood eosinophils and fraction exhaled nitric oxide (FENO) data was also explored. The prevalence of peripheral airway involvement (i.e. abnormal ventilation distribution) determined by N2 SBW‐derived phase III slope (N2 SIII) was 24·7%, compared to 44% determined by N2 MBW‐derived lung clearance index (LCI) (P<0·001). Predictors of abnormal N2 SIII were older age, smoking history and lower FEV1. N2 SBW offers lower sensitivity than N2 MBW to detect small airway dysfunction in adult asthma, but may be a marker of more severe disease.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Measures of trophic position (TP) are critical for understanding food web interactions and human‐mediated ecosystem disturbance. Nitrogen stable isotopes (δ15N) provide a powerful tool to estimate TP ...but are limited by a pragmatic assumption that isotope discrimination is constant (change in δ15N between predator and prey, Δ15N = 3.4‰), resulting in an additive framework that omits known Δ15N variation. Through meta‐analysis, we determine narrowing discrimination from an empirical linear relationship between experimental Δ15N and δ15N values of prey consumed. The resulting scaled Δ15N framework estimated reliable TPs of zooplanktivores to tertiary piscivores congruent with known feeding relationships that radically alters the conventional structure of marine food webs. Apex predator TP estimates were markedly higher than currently assumed by whole‐ecosystem models, indicating perceived food webs have been truncated and species‐interactions over simplified. The scaled Δ15N framework will greatly improve the accuracy of trophic estimates widely used in ecosystem‐based management.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Stable‐isotope analysis (SIA) can act as a powerful ecological tracer with which to examine diet, trophic position and movement, as well as more complex questions pertaining to community dynamics and ...feeding strategies or behaviour among aquatic organisms. With major advances in the understanding of the methodological approaches and assumptions of SIA through dedicated experimental work in the broader literature coupled with the inherent difficulty of studying typically large, highly mobile marine predators, SIA is increasingly being used to investigate the ecology of elasmobranchs (sharks, skates and rays). Here, the current state of SIA in elasmobranchs is reviewed, focusing on available tissues for analysis, methodological issues relating to the effects of lipid extraction and urea, the experimental dynamics of isotopic incorporation, diet‐tissue discrimination factors, estimating trophic position, diet and mixing models and individual specialization and niche‐width analyses. These areas are discussed in terms of assumptions made when applying SIA to the study of elasmobranch ecology and the requirement that investigators standardize analytical approaches. Recommendations are made for future SIA experimental work that would improve understanding of stable‐isotope dynamics and advance their application in the study of sharks, skates and rays.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Particles in exhaled air (PEx) may reflect the composition of respiratory tract lining fluid (RTLF); thus, there is a need to assess their potential as sources of biomarkers for respiratory diseases. ...In the present study, we compared PEx from patients with asthma and controls using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and multivariate analysis. Particles were collected using an instrument developed in-house. 15 nonsmoking subjects with physician-diagnosed asthma and 11 nonsmoking healthy controls performed 10 consecutive forced exhalations into the instrument. Particle concentrations were recorded and samples of particles collected on silicon plates were analysed by TOF-SIMS. Subjects with asthma exhaled significantly lower numbers of particles than controls (p=0.03) and the ratio of unsaturated to saturated phospholipids was significantly lower in samples from subjects with asthma (0.25 versus 0.35; p=0.036). Orthogonal partial least squares-discriminant analysis models showed good separation between both positive and negative spectra. Molecular ions from phosphatidylcholine and phosphatidylglycerol, and protein fragments were found to discriminate the groups. We conclude that analysis of PEx is a promising method to examine the composition of RTLF. In the present explorative study, we could discriminate between subjects with asthma and healthy controls based on TOF-SIMS spectra from PEx.
Summary
Background
Conflicting data have been presented as to whether nitric oxide (NO) in exhaled air is merely reflecting atopy rather than airway inflammation.
Objective
To investigate the ...relationship between exhaled NO (eNO) and nasal NO (nNO), respiratory symptoms, and atopy, in the context of a cross‐sectional study of the respiratory health of bleachery workers.
Methods
Two hundred and forty‐six non‐smoking bleachery and paper‐mill workers answered a questionnaire and were examined by measurements of eNO and nNO and spirometry, outside the pollen season. Blood samples were collected and analysed for specific IgE against common aeroallergens (birch, timothy, cat and house dust mite). Atopy was defined as a positive Phadiatop™ test.
Results
The atopic and the non‐atopic subjects without asthma or rhinitis had similar levels of eNO. Subjects reporting asthma or rhinitis who were also sensitized to perennial allergens had higher levels of eNO, whereas those sensitized to only seasonal allergens had similar eNO levels as non‐atopic subjects with asthma or rhinitis. In multiple linear regression models adjusted for nNO, eNO was associated with asthma and sensitization to perennial allergens.
Conclusion
The results indicate that only atopic subjects who have recently been exposed to the relevant allergen have elevated levels of eNO. Atopic subjects who are not being exposed to a relevant allergen or have never experienced symptoms of asthma or rhinitis show normal eNO. These data indicate that eNO relates to airway inflammation in atopic subjects.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Aim: Exhaled ethane, pentane and isoprene have been proposed as biomarkers of oxidative stress. The objectives were to explore whether ethane, pentane and isoprene are produced within the airways ...and to explore the effect of different sampling parameters on analyte concentrations.
Methods: The flow dependency of the analyte concentrations, the concentrations in dead‐space and alveolar air after breath‐holding and the influence of inhaling purified air on analyte concentrations were investigated. The analytical method involved thermal desorption from sorbent tubes and gas chromatography. The studied group comprised 13 subjects with clinically stable asthma and 14 healthy controls.
Results: Ethane concentrations decreased slightly, but significantly, at higher flow rates in subjects with asthma (P = 0.0063) but not in healthy controls. Pentane levels were increased at higher flow rates both in healthy and asthmatic subjects (P = 0.022 and 0.0063 respectively). Isoprene levels were increased at higher flow rates, but only significantly in healthy subjects (P = 0.0034). After breath‐holding, no significant changes in ethane levels were observed. Pentane and isoprene levels increased significantly after 20 s of breath‐holding. Inhalation of purified air before exhalation resulted in a substantial decrease in ethane levels, a moderate decrease in pentane levels and an increase in isoprene levels.
Conclusion: The major fractions of exhaled ethane, pentane and isoprene seem to be of systemic origin. There was, however, a tendency for ethane to be flow rate dependent in asthmatic subjects, although to a very limited extent, suggesting that small amounts of ethane may be formed in the airways.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background:Particulate air pollution affects cardiovascular and pulmonary disease and mortality. A main hypothesis about the mechanisms involved is that particles induce inflammation in lower ...airways, systemic inflammation and oxidative stress.Objectives:To examine whether short-term exposure to wood smoke in healthy subjects affects markers of pulmonary inflammation and oxidative stress.Methods:13 subjects were exposed first to clean air and then to wood smoke in a chamber during 4-hour sessions, 1 week apart. The mass concentrations of fine particles at wood smoke exposure were 240–280 μg/m3, and number concentrations were 95 000–180 000/cm3, about half of the particles being ultrafine (<100 nm). Blood and breath samples were taken before and at various intervals after exposure to wood smoke and clean air and examined for exhaled nitric oxide and Clara cell protein in serum and urine, and malondialdehyde in exhaled breath condensate.Results:Exposure to wood smoke increased alveolar nitric oxide 3 hours post-exposure while malondialdehyde levels in breath condensate were higher both immediately after and 20 hours after exposure. Serum Clara cell protein was increased 20 hours after exposure.Conclusions:Wood smoke at levels that can be found in smoky indoor environments caused an inflammatory response and signs of increased oxidative stress in the respiratory tract, especially in the lower airways.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Objective: To investigate nutritional status and its relationship to cognition, well-being, functional ability and energy intake in frail elderly service flat residents. Design: Cross-sectional and ...prospective study. Setting: Two municipal service flat complexes. Subjects: A total of 80 residents (median age 85.5 (79-90) y) with regular home care assistance participated. A subgroup of 35 residents took part in a re-examination 1 y later. Methods: Mini Nutritional Assessment (MNA), Short Portable Mental Status Questionnaire, Barthel Index and Health Index were used for the evaluation of nutritional, cognitive and ADL function and well-being, respectively. Results: In all, 30% of the frail and chronically ill service flat residents were assessed as malnourished and 59% were at risk of malnutrition. The malnourished residents had worse cognitive conditions (P<0.001) and well-being (P<0.05), lower functional ability (P<0.01) and they had a greater need for daily assistance (P<0.05) than the other residents. The median night fast period was 14.0 (12.5-15.0) h. Five subjects classified as malnourished at baseline had lost a median of -9.6 kg (range -11.0 to +7.3 kg) (P<0.05) in body weight at the 1-y follow-up, which contrasted significantly from the weight stability in residents classified as at risk for malnutrition or well-nourished. Conclusion: Out of 10 residents, nine were assessed to have impending nutritional problems that related to impaired well-being, cognition, and functional ability. Malnourished residents had a significant weight loss over one year. Studies are needed to determine whether weight loss and nutrition-related dysfunction in service flat residents are preventable or treatable.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Introduction
The fractional exhaled nitric oxide (FENO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FENO as a reliable biomarker, it is important ...to investigate factors that influence FENO in healthy individuals. Men have higher levels of FENO than women, but it is unclear whether determinants of FENO differ by sex.
Objective
To identify determinants of FENO in men and women without lung diseases.
Method
Fractional exhaled nitric oxide was validly measured in 3881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease.
Results
Exhaled NO levels were 21.3% higher in men compared with women P < 0.001. Being in the upper age quartile (60.3‐67.6 years), men had 19.2 ppb (95% CI: 18.3, 20.2) higher FENO than subjects in the lowest age quartile (39.7‐48.3 years) P = 0.02. Women in the two highest age quartiles (54.6‐60.2 and 60.3‐67.6 years) had 15.4 ppb (14.7, 16.2), P = 0.03 and 16.4 ppb (15.6, 17.1), P = <0.001 higher FENO, compared with the lowest age quartile.
Height was related to 8% higher FENO level in men (P < 0.001) and 5% higher FENO levels in women (P = 0.008). Men who smoked had 37% lower FENO levels and women had 30% lower levels compared with never‐smokers (P < 0.001 for both). Men and women sensitized to both grass and perennial allergens had higher FENO levels compared with non‐sensitized subjects 26% and 29%, P < 0.001 for both.
Conclusion and Clinical Relevance
Fractional exhaled nitric oxide levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. FENO started increasing at lower age in women than in men, suggesting that interpretation of FENO levels in adults aged over 50 years should take into account age and sex.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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