Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human ...lung, and underlying details of this apparent synergy are poorly understood.
To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects.
18 blinded atopic volunteers were exposed to filtered air or 300 µg PM(2.5)/m(3) of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points.
Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells.
Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust.
NCT01792232.
Mudway and Sandstrom discuss the study by Maestre-Batlle and colleagues on the potential acute impacts of one common indoor air pollutant, dibutyl phthalate (DBP), on allergic airway responses. ...Phthalates (classified as plasticizers) are typically solvents found in plastic-based products that have aroused concern historically as endocrine-disrupting chemicals, but there is observational data also linking indoor concentrations, often in household dust, with increased risk of asthma, allergy, and wheeze. They comment that the study elegantly bridges indications from population-based studies, with placebo-controlled human exposures in allergen-sensitized individuals, to demonstrate evidence of enhanced allergic responses after inhalation of phthalate fumes.
The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past ...statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies.This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution.
We evaluated the effect of dual, longacting inhaled bronchodilator treatment on exacerbations in patients with severe and very severe chronic obstructive pulmonary disease (COPD).
In this ...parallel-group study, 2224 patients (aged ≥40 years, Global Initiative for Chronic Obstructive Lung Disease stages III-IV, and one or more moderate COPD exacerbation in the past year) were randomly assigned (1:1:1; via interactive voice response or web system; stratified for smoking status) to once-daily QVA149 (fixed-dose combination of indacaterol 110 μg and glycopyrronium 50 μg), glycopyrronium 50 μg, or tiotropium 18 μg for 64 weeks. Assignment to QVA149 and glycopyrronium was double-blind; tiotropium was open-label. Efficacy was assessed in all patients randomly assigned to treatment groups who received at least one dose of study drug; safety was assessed in all patients who received at least one dose whether or not they were assigned to a group. The primary objective was to show superiority of QVA149 versus glycopyrronium for rate of moderate to severe COPD exacerbations (defined by worsening symptoms and categorised by treatment requirements) during treatment. This completed trial is registered at ClinicalTrials.gov, NCT01120691.
Between April 27, 2010, and July 11, 2012, 741 patients were randomly assigned to receive QVA149, 741 to receive glycopyrronium, and 742 to receive tiotropium (729, 739, and 737 patients, respectively, analysed for efficacy). QVA149 significantly reduced the rate of moderate to severe exacerbations versus glycopyrronium by 12% (annualised rate of exacerbations 0·84 95% CI 0·75-0·94 vs 0·95 0·85-1·06; rate ratio 0·88, 95% CI 0·77-0·99, p=0·038). Adverse events (including exacerbations) were reported for 678 (93%) of 729 patients on QVA149, 694 (94%) of 740 on glycopyrronium, and 686 (93%) of 737 on tiotropium. Incidence of serious adverse events was similar between groups (167 23% patients on QVA149, 179 24% on glycopyrronium, and 165 22% on tiotropium); COPD worsening was the most frequent serious adverse event (107 15% patients on QVA149, 116 16% on glycopyrronium, 87 12% on tiotropium).
The dual bronchodilator QVA149 was superior in preventing moderate to severe COPD exacerbations compared with the single longacting antimuscarinic bronchodilator glycopyrronium, with concomitant improvements in lung function and health status. These results indicate the potential of dual bronchodilation as a treatment option for patients with severe and very severe COPD.
Novartis Pharma AG.
In this issue of the Journal, Wooding and colleagues (pp. 565–574), a Vancouver-based group of scientists, have studied the role of traffic-related air pollution on respiratory function and allergen ...responsiveness by means of controlled chamber exposure experiments in allergen-sensitized individuals (9). Contrary to their hypothesis, removing particles using a high-efficiency particulate air filter and electrostatic precipitation to mimic catalytic particle traps used on diesel vehicles did not protect against the allergen-induced effects, despite 93% effectiveness in filtering particles. Associations of long-term exposure to ultrafine particles and nitrogen dioxide with increased incidence of congestive heart failure and acute myocardial infarction.
Severe asthma—A population study perspective Backman, Helena; Jansson, Sven‐Arne; Stridsman, Caroline ...
Clinical and experimental allergy,
June 2019, Volume:
49, Issue:
6
Journal Article
Peer reviewed
Summary
Background
Severe asthma is a considerable challenge for patients, health‐care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern ...definitions of which none based on a population study.
Objective
To describe characteristics and estimate the prevalence of severe asthma in a large adult population‐based asthma cohort followed for 10‐28 years.
Methods
N = 1006 subjects with asthma participated in a follow‐up during 2012‐14, when 830 (mean age 59 years, 56% women) still had current asthma. Severe asthma was defined according to three internationally well‐known criteria: the ATS workshop definition from 2000 used in the US Severe Asthma Research Programme (SARP), the 2014 ATS/ERS Task force definition and the GINA 2017. All subjects with severe asthma according to any of these criteria were undergoing respiratory specialist care and were also contacted by telephone to verify treatment adherence.
Results
The prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS Taskforce), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >90% did not have controlled asthma according to the asthma control test. Severe asthma was related to age >50 years, nasal polyposis, impaired lung function, sensitization to aspergillus, and tended to be more common in women. Further, neutrophils in blood significantly discriminated severe asthma from other asthma.
Conclusions and Clinical Relevance
Severe asthma differed significantly from other asthma in terms of demographic, clinical and inflammatory characteristics, results suggesting possibilities for improved treatment regimens of severe asthma. The prevalence of severe asthma in this asthma cohort was 4%‐6%, corresponding to approximately 0.5% of the general population.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
7.
Adverse cardiovascular effects of air pollution Mills, Nicholas L; Donaldson, Ken; Hadoke, Paddy W ...
Nature clinical practice cardiovascular medicine,
01/2009, Volume:
6, Issue:
1
Journal Article
Peer reviewed
Air pollution is increasingly recognized as an important and modifiable determinant of cardiovascular disease in urban communities. Acute exposure has been linked to a range of adverse cardiovascular ...events including hospital admissions with angina, myocardial infarction, and heart failure. Long-term exposure increases an individual's lifetime risk of death from coronary heart disease. The main arbiter of these adverse health effects seems to be combustion-derived nanoparticles that incorporate reactive organic and transition metal components. Inhalation of this particulate matter leads to pulmonary inflammation with secondary systemic effects or, after translocation from the lung into the circulation, to direct toxic cardiovascular effects. Through the induction of cellular oxidative stress and proinflammatory pathways, particulate matter augments the development and progression of atherosclerosis via detrimental effects on platelets, vascular tissue, and the myocardium. These effects seem to underpin the atherothrombotic consequences of acute and chronic exposure to air pollution. An increased understanding of the mediators and mechanisms of these processes is necessary if we are to develop strategies to protect individuals at risk and reduce the effect of air pollution on cardiovascular disease.
Diesel emissions are a major contributor to combustion-generated airborne ambient particles. To understand the role of diesel particulate emissions on health effects, it is important to predict the ...actual particulate dose deposited in the human respiratory tract, with respect to number, surface area and mass. This is complicated by the agglomerate nature of some of these particles. In this study the respiratory tract deposition fraction in the size range 10–500nm, was determined for 10 healthy volunteers during both idling and transient engine running conditions of a heavy duty diesel engine. The aerosol was characterized with respect to both chemical and physical properties including size resolved particle effective density. The dominating part of the emitted particles had an agglomerate structure. For those formed during transient running conditions, the relationship between particle mass and mobility diameter could be described by a power law function. This was not the case during idling, most likely because of volatile compounds condensing on the agglomerates. The respiratory tract particle deposition revealed large intra-subject variability with some subjects receiving a dose that was twice as high as that of others, when exposed to the same particle concentration. Associations were found between total deposited fractions (TDF), and breathing pattern. There was a difference between the idling and transient cycle with TDF being higher with respect to number during idling. The measured size-dependent deposition fraction of the agglomerated exhaust particles from both running conditions was nearly identical and closely resembled that of spherical hydrophobic particles, if plotted as a function of mobility diameter. Thus, for the size range covered, the mobility diameter could well describe the diameter-dependent particle respiratory tract deposition probability, regardless of the agglomeration state of the particles. Whilst mobility diameter well describes the deposition fraction, more information about particle characteristics is needed to convert this to volume equivalent diameter or estimate dose with respect to surface area or mass. A methodology is presented and applied to calculate deposited dose by surface area and mass of agglomerated particles. The methodology may be useful in similar studies estimating dose to the lung, deposition onto cell cultures and in animal studies.
► Respiratory tract deposition was measured for two types of agglomerated diesel soot particles. ► Deposition resembled that of spherical particles if regarded as a function of mobility diameter. ► Large inter-subject variability on lung deposition fractions were found. ► Associations found between total deposited fractions, tidal volume and breathing frequency. ► Particle effective density was measured and a methodology is presented assessing surface area.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
After exposure to dilute diesel exhaust, men with coronary disease had increased exercise-induced myocardial ischemia, along with depressed fibrinolytic function. The data reported suggest possible ...mechanisms for the detrimental effect of air pollution from traffic in patients with coronary disease.
After exposure to dilute diesel exhaust, men with coronary disease had increased exercise-induced myocardial ischemia, along with depressed fibrinolytic function.
The World Health Organization (WHO) estimates that air pollution is responsible for 800,000 premature deaths worldwide each year.
1
Short-term exposure to air pollution has been associated with increases in cardiovascular morbidity and mortality, with deaths due to ischemia, arrhythmia, and heart failure.
2
In a large cohort study from the United States, Miller et al. recently reported that long-term exposure to air pollution increases the risk of death from cardiovascular disease by 76%.
3
These associations are strongest for fine particulate air pollutants (particulate matter of less than 2.5 μm in aerodynamic diameter PM
2.5
), of which the combustion-derived nanoparticulate in . . .
Studies have emphasised the importance of combustion-derived particles in eliciting adverse health effects, especially those produced by diesel vehicles. In contrast, few investigations have explored ...the potential toxicity of particles derived from tyre and brake wear, despite their significant contributions to total roadside particulate mass. The objective of this study was to compare the relative toxicity of compositionally distinct brake abrasion dust (BAD) and diesel exhaust particles (DEP) in a cellular model that is relevant to human airways. Although BAD contained considerably more metals/metalloids than DEP (as determined by inductively coupled plasma mass spectrometry) similar toxicological profiles were observed in U937 monocyte-derived macrophages following 24 h exposures to 4-25 μg ml-1 doses of either particle type. Responses to the particles were characterised by dose-dependent decreases in mitochondrial depolarisation (p ≤ 0.001), increased secretion of IL-8, IL-10 and TNF-α (p ≤ 0.05 to p ≤ 0.001) and decreased phagocytosis of S. aureus (p ≤ 0.001). This phagocytic deficit recovered, and the inflammatory response resolved when challenged cells were incubated for a further 24 h in particle-free media. These responses were abrogated by metal chelation using desferroxamine. At minimally cytotoxic doses both DEP and BAD perturbed bacterial clearance and promoted inflammatory responses in U937 cells with similar potency. These data emphasise the requirement to consider contributions of abrasion particles to traffic-related clinical health effects.
PDF
