WHO world no tobacco day 2014
31st May is the World Health Organization (WHO) world no tobacco day. Tobacco kills millions of people each year through smoking or exposure to second hand smoke.
Associate Professor Ling-Pei Ho is a HEFCE Clinical Senior Lecturer at the MRC Human Immunology Unit and a Consultant in Respiratory Medicine. To mark no tobacco day, NDM asked her about the link between respiratory diseases and smoking, and her own research on idiopathic pulmonary fibrosis (IPF). She is part of NDM's Experimental Medicine unit and has research groups based at the MRC Human Immunology Unit as well as the Translational Lung Immunology Group in the NDMRB building.
Q: In your experience as a clinician, what lung conditions do you commonly see in patients who are smokers?
Ling-Pei Ho: Tobacco smoking is most highly linked with lung cancer. Sir Richard Doll was the first to show this in 1954. Since then, smoking has been shown to have strong causal relationships with chronic obstructive pulmonary disease (COPD) and emphysema, and worsens nearly every lung disease including: asthma, lung fibrosis, asbestosis, and allergic lung diseases (e.g. bird fancier’s lungs). Smoking also predisposes an individual to lung infections and hinders the recovery from an exacerbation of COPD, asthma, and lung infections.
Q: Is there a link between inflammation of the lungs caused by smoking and lung disease other than cancer?
LPH: Yes, many researchers have shown that at every level of airway biology – from expression of inflammatory genes, modification of gene behaviour, to changes in function of structural cells (e.g. over production of mucus and reduction in motility of cilia) to proliferation of certain immune cells (e.g. increase and changes in function of alveolar macrophages) - tobacco smoke enhances harmful inflammatory responses and worsens on-going disease processes such as asthma, COPD and lung fibrosis.
My research group has a particular interest in interstitial lung disease, specifically, sarcoidosis and idiopathic pulmonary fibrosis (IPF). IPF is a progressive disease characterised by a dysregulated wound healing response that leads to accumulation of fibroblasts and extracellular matrix in the lung. Injury to a subset of the alveolar epithelial cells is thought to be one of the key initiating events for the disease. Both genetic factors, (such as mutations in telomerase gene) as well as environmental factors (like cigarette smoking and viral infections) have been implicated as potential initiating triggers in the development of IPF. After this trigger, immune cells, (e.g. T cells and macrophages) and activated structural cells (e.g. myofibroblasts) perpetuate this cascade of epithelial cell repair. Foci of over-repairing areas appear in lungs. The mechanism for this perpetuation of repair is not clear but cigarette smoking could be one factor. IPF is also often complicated by smoking-induced emphysema which deprives the lungs of more functioning unit and accelerates the loss of lung function.
Q: How many people does IPF affect?
LPH: The estimated prevalence of IPF in Europe (depending on case definition) is 2-23 cases per 100,000 people; with an estimated incidence of about 5 cases per 100,000 people per year obtained from several studies in the UK [1]. In addition to metal and wood dust exposure, smoking, has been found to be significantly associated with IPF [2,3]. Among these risk factors, cigarette smoking seems to be the most strongly associated risk factor in both sporadic IPF and familial pulmonary fibrosis. Recent work suggests that smoking may also have a detrimental effect on survival of patients with IPF [4].
Q: How is your research aiming to improve the prognosis of people with idiopathic pulmonary fibrosis?
LPH: From diagnosis, IPF patients have a median survival of 3 years, and lose lung function progressively. A typical IPF patient admitted to our respiratory ward has an 80% mortality rate. We would like to understand the dominant immune cellular processes involved in driving the progression and acute deterioration of the disease. We are conducting detailed mapping of the immune landscape in the blood and lungs of patients, comparing fast and slowly progressing IPF, and during stable and acute decline periods of their disease. We are particularly interested in the role of subsets of monocytes (precursors of macrophages) which have recently been shown to have both reparative and pro-fibrotic capacity during different points of the disease. In parallel we are in the process of generating a miniature representation of the fibrotic lung interface in petri dishes, so that we can test some of the hypothesis generated from our human studies in a human organotypic model. If we are able to drill down to prove that these cells have a significant role in influencing outcome of the condition, we will be in a good position to harness immune tools to modulate their function and programme their eventual differentiation to different types of macrophages in the lungs.
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