The Influence of Radiographic Phenotype and Smoking Status on Peripheral Blood Biomarker Patterns in Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is characterized by both airway remodeling and parenchymal destruction. The identification of unique biomarker patterns associated with airway dominant versus parenchymal dominant patterns would support the existence of unique phenotypes representing independent biologic processes. A cross-sectional study was performed to examine the association of serum biomarkers with radiographic airway and parenchymal phenotypes of COPD. Methodology/Principal Findings: Serum from 234 subjects enrolled in a CT screening cohort was analyzed for 33 cytokines and growth factors using a multiplex protein array. The association of serum markers with forced expiratory volume in one second percent predicted (FEV1%) and quantitative CT measurements of airway thickening and emphysema was assessed with and without stratification for current smoking status. Significant associations were found with several serum inflammatory proteins and measurements of FEV1%, airway thickening, and parenchymal emphysema independent of smoking status. The association of select analytes with airway thickening and emphysema was independent of FEV1%. Furthermore, the relationship between other inflammatory markers and measurements of physiologic obstruction or airway thickening was dependent on current smoking status. Conclusions/Significance: Airway and parenchymal phenotypes of COPD are associated with unique systemic serum biomarker profiles. Serum biomarker patterns may provide a more precise classification of the COPD syndrome, provide insights into disease pathogenesis and identify targets for novel patient-specific biological therapies. © 2009 Bon et al

Mechanical Work as an Indirect Measure of Subjective Costs Influencing Human Movement

To descend a flight of stairs, would you rather walk or fall? Falling seems to have some obvious disadvantages such as the risk of pain or injury. But the preferred strategy of walking also entails a cost for the use of active muscles to perform negative work. The amount and distribution of work a person chooses to perform may, therefore, reflect a subjective valuation of the trade-offs between active muscle effort and other costs, such as pain. Here we use a simple jump landing experiment to quantify the work humans prefer to perform to dissipate the energy of landing. We found that healthy normal subjects (N = 8) preferred a strategy that involved performing 37% more negative work than minimally necessary (P<0.001) across a range of landing heights. This then required additional positive work to return to standing rest posture, highlighting the cost of this preference. Subjects were also able to modulate the amount of landing work, and its distribution between active and passive tissues. When instructed to land softly, they performed 76% more work than necessary (P<0.001), with a higher proportion from active muscles (89% vs. 84%, P<0.001). Stiff-legged landings, performed by one subject for demonstration, exhibited close to the minimum of work, with more of it performed passively through soft tissue deformations (at least 30% in stiff landings vs. 16% preferred). During jump landings, humans appear not to minimize muscle work, but instead choose to perform a consistent amount of extra work, presumably to avoid other subjective costs. The degree to which work is not minimized may indirectly quantify the relative valuation of costs that are otherwise difficult to measure

Biomechanical approaches to understanding the potentially injurious demands of gymnastic-style impact landings

<p>Abstract</p> <p>Gymnasts are exposed to a high incidence of impact landings due to the execution of repeated dismount performances. Biomechanical research can help inform recent discussions surrounding a proposed rule change in potentially injurious gymnastic dismounting. The review examines existing understanding of the mechanisms influencing the impact loads incurred in gymnastic-style landings achieved using biomechanical approaches. Laboratory-based and theoretical modelling research of inherent and regulatory mechanisms is appraised. The integration of the existing insights into injury prevention interventions studies is further considered in the appraisals. While laboratory-based studies have traditionally been favoured, the difficulty in controlling and isolating mechanisms of interest has partially restricted the understanding gained. An increase in the use of theoretical approaches has been evident over the past two decades, which has successfully enhanced insight into less readily modified mechanisms. For example, the important contribution of mass compositions and 'tuned' mass coupling responses to impact loading has been evidenced. While theoretical studies have advanced knowledge in impact landing mechanics, restrictions in the availability of laboratory-based input data have suppressed the benefits gained. The advantages of integrating laboratory-based and theoretical approaches in furthering scientific understanding of loading mechanisms have been recognised in the literature. Since a multi-mechanism contribution to impact loading has been evident, a deviation away from studies examining isolated mechanisms may be supported for the future. A further scientific understanding of the use of regulatory mechanisms in alleviating a performer's inherent injury predisposition may subsequently be gained and used to inform potential rule changes in gymnastics. While the use of controlled studies for providing scientific evidence for the effectiveness of gymnastics injury counter measures has been advocated over the past decade, a lack of information based on randomised controlled studies or actual evaluation of counter measures in the field setting has been highlighted. The subsequent integration of insight into biomechanical risk factors of landing with clinical practice interventions has been recently advocated.</p