2nd Canadian Respiratory Conference: A Breath of Fresh Air Overdiagnosis of asthma in obese and nonobese Canadian adults 2nd CAnAdiAn RespiRAtORy COnFeRenCe

T he molecular mechanisms underlying the development of inten- sive care unit (ICU)-acquired muscle dysfunction are being delineated through studies on rodent models of disease and humans. This presentation highlights three key phenomena now recognized to underpin the development of acute and persistent muscle dysfunction in the ICU survivor. Skeletal muscle atrophy is a well-recognized phenomenon that occurs in multiple disease states including ICU-acquired muscle dysfunction. Loss of skeletal muscle mass results from an imbalance between protein synthesis and degradation, with increased muscle proteolysis relative to protein synthesis. Degradation of muscle protein is mediated via several intracellular signalling networks, but ubiquitin-dependent proteolysis is the predominant mechanism responsible for the development of muscle atrophy. Protein ubiquitination is a process whereby proteins to be degraded are tagged with chains of ubiquitin moieties, which serve as recognition markers, targeting proteins for cleavage by the 26S proteasome. Ubiquitin ligases are the critical enzymes that both link ubiquitin moieties to the target protein and confer specificity to the system by interacting directly with the target protein through well-defined protein-protein interaction domains. The ubiquitin ligases atro-gin-1 and MuRF1 are key regulators of muscle atrophy. O bstructive sleep apnea (OSA) is common and has significant morbid- ity. OSA is caused by repetitive collapse of the upper airway (UA) during sleep, but the cause of UA collapse is not completely understood. neck circumference consistently gaps knowledge translation (KTA) key on review and models. implementers. will operationalize the KTA process using a smoking cessation intervention as an example. T he classical model of patient care has used a pyramidal structure, with instructions emanating from the doctor to nursing and allied health. Furthermore, the patient is viewed as an individual, out of context to their social situation. In reality, the patient lives in a complex social network involving spouses, parents, siblings, dependents and others, including work or education responsibilities. This network will impact the patient’s ability to cope with illness and manage symptoms and treatments. It is also important to differentiate disability or physiological impairment from handicap, or the consequences of this disability. Limited respiratory ability may result in a patient’s curtail-ment of pleasant or important social interactions or being unable to comfortably perform activities of daily living. A is with the at the the team members circled around them connected by the radial spokes, and the dynein arms helping the other team members. The cystic fibrosis (CF) gene defect leads to an absent or malfunc-tioning CF transmembrane regulator (CFTR) protein, which results in abnormal chloride conductance on the apical membrane of epithelial cells. More than 1500 different mutations have been described, but the majority of these mutations are rare: less than 10 mutations occur in a frequency of more than 1% (1). CFTR mutations are grouped into different classes based on their functional consequences on CFTR within the cell. Until recently, the prognostic knowledge of the genetic mutation has been of limited clinical value, but new treatment approaches that address specific CFTR mutations are currently being tested. For instance, the most common mutation worldwide (DF508 CFTR) leads to a misfolded protein that is degraded intracellulary before reaching the plasma membrane. However, DF508 CFTR has functional activity and drugs that potentially correct the intracellular trafficking defect of DF508 CFTR are currently in development. CFTR acts as a chloride channel in apical membranes, but pos-sesses other important functions (2). CFTR has been described as a regulator of other membrane channels, to transport or regulate bicar-bonate transport and to act as a channel for other proteins such as glutathione. In addition, interactions with many other intracellular proteins have been described. This may potentially be important for therapeutic interventions, because drugs that induce chloride secretion, but do not affect other CFTR functions may not address all relevant aspects of CF pathophysiology. Lack CFTR and, ion gradient, water into the epithelial surface layer. results in airway surface liquid (ASL) deple-tion, and, because ASL essential et A controlled trial of for obstructive L ongitudinal studies of childhood asthma reveal considerable heterogeneity, but most cases of persistent asthma have their first symptoms in early life. Domestic animal exposure reduces risk of allergy (1), but breastfeeding may increase later childhood risks (2). Viral infections may be major pathogenetic factors (3). Patterns of asthma track from childhood into adult life, and loss of lung function may be established early. In the Dunedin Multidisciplinary Child Development Study, independent risk factors for persistence of childhood asthma included female sex, methacholine airway responsiveness, house dust mite allergy and personal smoking (4). Longitudinal assessment of lung function in those with persistent asthma indicated that lung function had tracked substantially lower than normal from age 9, suggesting the damage occurred in early childhood. Many questions remain unanswered. What influences lung growth and development in infancy and early childhood? Is the development of asthma related primarily to nature or nurture? What role does environment play in the development of allergy and asthma? Do early childhood infections decrease or increase the risk of allergy and asthma? How do gene-environment interactions impact allergy and asthma? To address these questions, a new longitudinal birth cohort study has been developed in conjunction with several interested groups, the Canadian Healthy Infant Longitudinal Development (CHILD) study. Researchers at McMaster University and the University of Toronto questioned whether children with persistent asthma are born with small airways, or whether the early environment (pollutants, infections, allergens) damages the airway. The Allergy, Genes and Environment (AllerGen) Network of Centres of Excellence (NCE) is seeking to determine the underlying causes of the major increase in allergic diseases, including asthma. The Canadian Institutes of Health Research (CIHR) expressed strong interest in the impact of the built environment on the health of the growing child,