S. F. van Eeden

Wood smoke exposure induces a pulmonary and systemic inflammatory response in firefighters

Epidemiological studies report an association between exposure to biomass smoke and cardiopulmonary morbidity. The mechanisms for this association are unclear. The aim of the present study was to characterise the acute pulmonary and systemic inflammatory effects of exposure to forest fire smoke. Seasonal forest firefighters (n = 52) were recruited before and/or after a day of fire-fighting. Exposure was assessed by questionnaires and measurement of carbon monoxide levels (used to estimate respirable particulate matter exposure). The pulmonary response was assessed by questionnaires, spirometry and sputum induction. Peripheral blood cell counts and inflammatory cytokines were measured to define the systemic response. Estimated respirable particulate matter exposure was high (peak levels >2 mg·m−3) during fire-fighting activities. Respiratory symptoms were reported by 65% of the firefighters. The percentage sputum granulocytes increased significantly from 6.5 to 10.9% following fire-fighting shifts, with concurrent increases in circulating white blood cells (5.55×109 to 7.06×109 cells·L−1) and band cells (0.11×109 to 0.16×109 cells·L−1). Serum interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 levels significantly increased following fire-fighting. There were no changes in band cells, IL-6, and IL-8 following strenuous physical exertion without fire-fighting. There was a significant association between changes in sputum macrophages containing phagocytosed particles and circulating band cells. In conclusion, acute exposure to air pollution from forest fire smoke elicits inflammation within the lungs, as well as a systemic inflammatory response.

The expression of adhesion molecules in cigarette smoke-induced airways obstruction.

Cigarette smoking produces peripheral airway inflammation in all smokers, and chronic airways obstruction in approximately 20% of heavy smokers. The present study was designed to test the hypothesis that airways obstruction is related to changes in the expression of adhesion molecules involved in the recruitment of cells to sites of inflammation in the lung. Freshly resected lungs from heavy smokers with airways obstruction (n = 10) and from heavy smokers with normal lung function (n = 10) were collected in the operating room, inflated with optimal cutting temperature (OCT) medium and frozen over liquid nitrogen. Six micrometres thick cryostat sections cut from random samples of this tissue were stained, using immunohistochemistry, with monoclonal antibodies to the adhesion molecules on leucocytes: L-selectin, very late activation antigen-4 (VLA-4), CD11a/CD18, CD11b/CD18, CD11c/CD18; and on endothelial and epithelial surfaces: E-selectin, P-selectin, vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM)-1 and ICAM-2 using the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. The slides were coded and the expression of each molecule scored by three observers using a semiquantitative grading system. Two inducible adhesion molecules, E-selectin on endothelium and CD11b on leucocytes, were also evaluated using quantitative morphometric analysis. The results showed a distribution of adhesion molecules that was consistent with the inflammatory response in the airways and parenchyma of all subjects but failed to show any differences between those with or without airways obstruction. We conclude that development of airways obstruction in heavy smokers cannot be explained by differences in the expression of adhesion molecules known to be involved in the control of cell traffic in the lung.

Bone marrow progenitors in inflammation and repair: new vistas in respiratory biology and pathophysiology

### Bone marrow-derived stem cells Respiratory and allergic/immune diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, cystic fibrosis, and acute and chronic lung infections are leading causes of morbidity and mortality in Canada as well as globally. Inflammatory pathology is central to all of these diseases, recently recognised to include systemic processes involving the active recruitment and differentiation of bone marrow-derived haemopoietic and nonhaemopoietic “progenitors” (termed BMSC). These cells have the potential to differentiate into a diversity of cell types found in normal tissue 1–4, as well as to contribute to repair and remodelling following lung injury. Recently, it has been proposed that circulating BMSC can “sense” injured tissue, and undergo migration and recruitment to sites of tissue damage. Here they can differentiate into inflammatory effector cells (such as neutrophils, eosinophils, basophils, mast cells and monocytes), or nonhaemopoietic cells that can promote structural and functional tissue repair, revealing the plasticity of these pluripotent cell populations 5 and their participation in regenerative and/or inflammatory processes. Within tissues, the fate of haemopoietic progenitors is determined by locally elaborated growth factors that permit a process termed “ in situ haemopoiesis” 6–9. This leads to the accumulation of inflammatory effector cells, immunocompetent cells and tissue structural cells ( e.g. dendritic and endothelial cells). ### Markers of BMSC A critically important marker of haemopoietic progenitors in the marrow, circulatory and tissue compartments 10–13 is the CD34 antigen. This is an integral membrane differentiation stage-specific glycoprotein that is expressed on the majority of immature haemopoietic cells 14, 15. It is also expressed on tissue structural cells, including fibroblasts and vascular endothelial cells 15, 16, functioning to regulate adhesion of these cells to haemopoietic inductive microenvironmental stroma and, presumably, to other elements in blood vessels and peripheral tissues 17. The CD34-knock …

The reliability of short-term measurement of heart rate variability during spontaneous breathing in people with chronic obstructive pulmonary disease

BACKGROUND Reduced heart rate variability (HRV), a marker of autonomic system dysfunction, has been reported in patients with chronic obstructive pulmonary disease (COPD). Yet, limited data exists on the reliability of HRV measurement in this population. Here we investigated the reliability of short-term HRV measurement performed during spontaneous breathing in patients with COPD. METHODS Thirteen individuals (8 males) with moderate-to-severe COPD (FEV1 46±16% predicted; FEV1/FVC 49±13) underwent standard time and frequency domain HRV measurements derived from 5-minute electrocardiograms collected on two separate days using a SphygmoCor device. Absolute and relative reliability was assessed by a number of coefficients including within-subject random variation, systematic change in the mean, and retest correlations. RESULTS Within-subject coefficients of variation (CV) ranged from 4.3% to 193.4%. The intraclass correlation coefficients (ICCs) ranged from 0.72 to 0.93 for parameters related to overall HRV, and from 0.57 to 0.59 for those related to parasympathetic tone in both time and frequency domains. Mean heart rate was the only parameter that showed excellent absolute and relative reliability (CV=4.3%, ICC=0.93). CONCLUSION The HRV measurements showed overall moderate-to-substantial reliability during spontaneous breathing in COPD population. Our findings support the use of HRV parameters for diagnosis and cardiac risk assessment, but only mean heart rate can be used reliably for monitoring changes in autonomic status following rehabilitation intervention in this population.

Slaying the CVD dragon with steroids

Cardiovascular diseases (CVD) are a big problem worldwide, accounting for 29% of all deaths and over 16 million deaths annually 1. Ischaemic heart disease (IHD) and stroke are by far the most important contributors to total CVD mortality, responsible for 43% (7.2 million) and 33% (5.5 million) of all CVD deaths, respectively. At the heart of IHD and stroke is atherosclerosis, characterised by foamy macrophages, cholesterol crystals, smooth muscle proliferation and endothelial dysfunction 2. The three leading modifiable risk factors for atherosclerosis are hyperlipidaemia, hypertension and tobacco smoking, accounting for 50–75% of total population attributable risk for CVD mortality 3. By targeting and treating these risk factors, tremendous improvements in health outcomes from IHD and stroke have been achieved over the past 30 yrs, largely owing to population-based reductions in blood pressure, cholesterol, saturated fat intake and cigarette smoking. However, recent disappointing results of torcetrapib (which dramatically raised high-density lipoprotein cholesterol) 4, combination therapy with fenofibrate and simvastatin (which reduced low-density lipoprotein cholesterol) 5 and renin–angiotensin system blockers (which reduced blood pressure) 6, 7 for the attenuation of cardiovascular events beyond standard therapy have been sobering; these findings have suggested that we may have reached the limits of risk reduction with these interventions, and raise an urgent call to find novel pathways and targets to further fight the large burden of IHD and stroke worldwide. Unfortunately, there is a dearth of promising compounds in the pipeline and many large pharmaceutical companies, including Pfizer, have abandoned CVD drug development altogether, after a decade of repeated failures 8. The report in this issue of European Respiratory Journal by Otsuki et al. 9, showing that inhaled corticosteroids (ICS) are associated with reduced atherosclerosis in patients with asthma, is welcome news for patients with CVD. In this …