Inflammation & Allergy-Drug Targets (Discontinued) - Volume 8, Issue 5, 2009

It is well known that passive smoking (PS) is a major threat to public health [1-4] as PS exposure is linked to an ever increasing frequency of diseases among children and adults, such as asthma, respiratory illness, vascular dysfunction, otitis media, sudden infant death syndrome, and predisposition towards cardiovascular disease and cancer [5-8] The majority of studies that have appeared on the unfavorable effects of PS have evaluated longitudinal epidemiological data, while exposure studies assessing the acute and short-term PS effects are limited [9]. However, as the latter is essential and of the utmost importance for elucidating the underlying physiological mechanisms involved in PS-induced system disruption [9, 10] research on the acute affects of PS has spread into different areas during the past 10 years and new scientific evidence continues to accumulate. The aim of the present Special Issue is to critically evaluate the existing biological evidence regarding the acute health effects of PS exposure. A variety of topics is included covering primarily the cardiovascular, the respiratory and the endocrine systems in human - both adults and children - and animal models. Acting as the introduction to the Special Issue, the review by Faught et al. [11]. surveys the epidemiological literature examining the association between PS and cardiovascular disease (CVD). The various screening methods available in assessing smoking behavior and quantifying nicotine absorption are summarized while taking into consideration the natural history of those exposed to PS and the associated risk of CVD. Based on the presented evidence, the risk of developing an acute cardiac syndrome or chronic lifetime coronary events is >30% in individuals frequently exposed to PS, while a reduction in the incidence of a myocardial infarction decreases by nearly 50% in the absence of PS exposures. The review concludes that epidemiological research provides ample evidence to support a causal inference between PS exposure and increased risks of CVD morbidity and mortality among both men and women. Continuing on the CVD topic, the review by Vardavas and Panagiotakos [12] focuses on the relationship between PS and inflammation on the development of CVD. Recent evidence has indicated that PS can lead to a 70-80% increase in the risk of coronary heart disease (CHD), nearly as much as light smoking. The authors describe the different mechanisms through which PS may induce an inflammatory response that may lead to the development of CVD, on a whole and through certain of its toxic constituents. Based on the presented evidence, the review concludes with effects suggesting a causal relationship between exposure to passive smoking and the development of cardiovascular disease. The mechanisms contributing to the PS-induced increased CHD risk are complex and include endothelial dysfunction, lipoprotein modification, increased inflammation and platelet activation. Although the vascular effects of PS are well known, its effects on the heart have not been reviewed despite that recently several studies have shown that PS exposure can result in cardiac remodeling and compromised cardiac function. These issues are the primary focus of the review by Minicucci et al. [13]. which evaluates the recent findings as to the effects of PS in acute and chronic phases of vascular and cardiac remodeling. Changing the theme from cardiovascular to respiratory, the review by Bergren [14] examines the link between PS exposure and airway hyperresponsiveness. Recent evidence suggested that PS is associated with changes in lung development and morphology, airway hyperresponsiveness and obstruction and development of asthma and its increased severity. However these PS-induced effects are not universally supported while we lack a complete understanding of PS effects on pulmonary function as well as its mechanism of action. The author addresses the respiratory effects of PS in human and animal models, particularly those with existing airway hyperresponsiveness, as well as the PS role as an adjuvant to airway hyperresponsiveness and its contribution to development of antigenic tolerance. Several physiological systems, with the respiratory being the primary, are disrupted by PS and progressively deteriorate through chronic exposures. This is of particular importance in children, given that respiratory complications during childhood can be transferred to adulthood and leading to significantly inferior health profiles. In this light, the reviews by Metsios et al. [15] and Bakirtas [16] evaluate current evidence linking PS with asthma and allergy in children, particularly with regards to brief PS exposures. Data thus far suggest that the chemical and carcinogenic constituents of PS have profound effects on children's health as they may disrupt normal biological development. Children that are exposed to PS either in-utero or following birth demonstrate increased prevalence for allergies and asthma. Moreover, PS appears to have pronounced effects on respiratory parameters that promote asthma development and persistent wheezing rather than other allergies. Regarding asthma, PS seems to affect different aspects of disease control not only diurnal and nocturnal symptoms and exacerbations but also rescue medication use and lung functions as well as bronchial hyperreactivity, school absenteeism and quality of life. Acute PS effects in all these asthma parameters seem to be additive to those of chronic exposure. Moving on to the endocrine system, growing evidence suggests that PS interferes with normal thyroid function, a topic that is reviewed in the paper by Carrillo et al. [17]. Toxic elements contained in PS such as thiocyanate may be partially responsible for impaired thyroid hormonogenesis. Moreover, a recently-discovered PS-induced inflammatory stress may impair thyroid hormonogenesis and iodine uptake initiating interleukin 6 production from thyroid epithelial cells which, in turn, stimulates the expression of molecules that exacerbate thyroid autoimmunity. Elevated inflammatory stress and thyroid hormone secretion in response to PS exposure initiates catabolic processes that alter body composition via lean body mass breakdown; translating to an elevation in resting energy expenditure of ∼10%. The combination of certain biological factors, such as sex and/or existing thyroid disease that may stimulate differential PS-induced effects on thyroid function is also reviewed. The final review by Onozaki [18] evaluates etiological and biological aspects of PS in rheumatoid arthritis. Polycyclic aromatic hydrocarbons, constituents of cigarette smoke, and cigarette smoke extracts are able to induce proinflammatory cytokines from rheumatoid arthritis patient-derived fibroblast-like synoviocytes. Recent studies also suggest an important role of T helper 17 cells in rheumatoid arthritis and contribution of aryl hydrocarbon receptor to the induction and development of T helper 17 cells and rheumatoid arthritis. These new findings may lead to uncovering the basis for the etiological role of PS in rheumatoid arthritis.

The objective of this paper was to review the epidemiological literature examining the association between secondhand smoke (SHS) and cardiovascular disease (CVD). Specifically, we examined the various screening methods available in assessing smoking behaviour and quantifying nicotine absorption. Further, we considered the natural history of those exposed to SHS and the associated risk of CVD. We reviewed routine methods used to assess exposure to SHS; evaluated the utility of subjective screening questions regarding smoking behaviour and examined the efficacy of nicotine and cotinine biomarkers used to quantify SHS exposure in epidemiological and clinical-based research. Self-reporting is practical and cost-effective in identifying smoking behaviour patterns, but is subject to recall bias and underestimation of exposure, especially in the presence of children. Nicotine and cotinine biomarkers have proven valuable in quantifying tobacco smoke absorption and establishing biological plausibility. A combination of SHS self-reported and biomarker evaluation provide the most stringent method of establishing exposure. Sufficient evidence is reported in epidemiological research to support a causal association between SHS exposure and increased risks of CVD morbidity and mortality among both men and women. The risk of developing an acute cardiac syndrome or chronic lifetime coronary events is at least 30%. Similarly, reduction in the incidence of a myocardial infarction decreases by nearly 50% in the absence of SHS. Considering the biological plausibility and dose-response relationship between SHS and CVD, effective interventions that incorporate a comprehensive screening method of behavioral and biological measures of exposure coupled with efficacious treatment should elicit favorable change for at-risk populations.

During the past years several factors have been established as risk markers for the development of heart disease, including both active and passive smoking. Current evidence has indicated that exposure to passive smoking can lead to a 70-80% increase in the risk of coronary heart disease, nearly as much as light smoking. This disproportionate effect could possibly be explained by a number of different interactions between human physiology of the cardiovascular system and passive smoke exposure. In this review we present the different mechanisms through which passive smoking may induce an inflammatory response that may lead to the development of cardiovascular disease, on a whole and through certain of its toxic constituents. Passive smoke itself, is a volatile mixture of numerous toxins, chemicals and carcinogens, that interact with in vivo mechanisms and induce vascular damage, including endothelium inflammation, atherosclerosis development, lipid peroxidisation, alterations in cytokines and acute phase proteins (such as CRP), as well as platelet aggravation. Acting alone or in synergy, the above mentioned effects suggest a causal relationship between exposure to passive smoking and the development of cardiovascular disease.

Coronary heart disease (CHD) is the most common cause of death in many developed countries. The major risk factors for CHD are smoking, high blood pressure, diabetes, high cholesterol levels, and lack of physical activity. Importantly, passive smoke also increases the risk for CHD. The mechanisms involved in the effects of passive smoke in CHD are complex and include endothelial dysfunction, lipoprotein modification, increased inflammation and platelet activation. Recently, several studies have shown that exposure to tobacco smoke can result in cardiac remodeling and compromised cardiac function. Potential mechanisms for these alterations are neurohumoral activation, oxidative stress, and MAPK activation. Although the vascular effects of cigarette smoke exposure are well known, the effects of tobacco smoking on the heart have received less attention. Therefore, this review will focus on the recent findings as to the effects of passive smoking in acute and chronic phases of vascular and cardiac remodeling.

Environmental tobacco smoke (ETS) exposure is a common health concern despite legislation to limit its presence, especially in public environments. ETS exposure is associated with changes in lung development and morphology, airway hyperresponsiveness and obstruction and development of asthma and its increased severity. However these effects of ETS exposure are not universally supported. Clinical data as well as studies in laboratory animals report ETS exposure may even attenuate airway hyperresponsiveness (AHR). Therefore, we lack complete understanding of ETS effects on pulmonary function as well as its mechanism of action. Disparate clinical and laboratory reports likely result from variables of ETS exposure, degrees of atopy and mechanisms of sensitization. The present review addresses the effects of ETS on AHR reported in humans and animal models. ETS role as an adjuvant to AHR as well as it contribution to development of antigenic tolerance is also reviewed. Possible neurogenic, cellular and intracellular mechanisms of ETS-induced ARH are proposed based on the existing literature. Enhanced understanding of the effects and mechanism of ETS will enhance therapy strategies in treatment of ARH and related disease such as COPD as well as enhancing public presentation of convincing evidence to avoid ETS.

Despite the recent campaigns to eliminate smoking and hinder the detrimental effects of passive smoking (PS), actual smoking rates still increase worldwide. Several physiological systems, with the respiratory being the primary, are disrupted by PS and progressively deteriorate through chronic exposures. This is of particular importance in children, given that respiratory complications during childhood can be transferred to adulthood, lead to significantly inferior health profiles. Hence, it is no surprise that children that are exposed to PS either in utero or during their adulthood may have an increased prevalence of allergies and asthma. However, investigating the acute effects of PS in children is inherently limited by complexities pertaining mainly to ethical constrains. Knowledge of the acute effects could be very important as it is the dose-dependant acute effects of passive smoking that lead to the long-term adaptations linked with the development of allergy and asthma. Current available data show that the chemical and carcinogenic constituents of tobacco have profound effects on children's health as they may disrupt normal biological development. PS appears to have pronounced effects on respiratory parameters that promote asthma development and persistent wheezing rather than other allergies. As such, PS exposure has to be eliminated and researchers have to develop interventions for supporting smoking cessation as well as minimised PS exposure either this is in utero or during childhood.

Although evidence-based asthma guidelines report passive smoke exposure as one of the triggers of asthma symptoms and exacerbations, its prevelance is still high among children with asthma especially in those coming from low income families. Passive smoke exposure affects different aspects of asthma control not only diurnal and nocturnal symptoms and exacerbations but also rescue medication use and lung functions as well as bronchial hyperreactivity, school absenteeism and quality of life. Immediate effects of passive smoke exposure in all these asthma parameters seem to be additive to those of chronic exposure. Smoking cessation interventions therefore play a pivotal role for a better asthma control.

Growing evidence suggests that the effects of second hand smoke (SHS) exposure contribute to disruptions in thyroid function. Toxic elements contained in cigarette smoke, such as thiocyanate, may be partially responsible for impaired thyroid hormonogenesis. SHS-induced inflammatory stress, namely interleukin 1β (IL-1β), impairs thyroid hormonogenesis and iodine uptake; initiates interleukin 6 (IL-6) production from thyroid epithelial cells and stimulates the expression of molecules that exacerbate thyroid autoimmunity. The link between SHS exposure and thyroid autoimmune disease is not well documented and thus, remains to be fully understood. Elevated inflammatory stress and thyroid hormone secretion in response to SHS exposure initiates catabolic processes that alter body composition via lean body mass breakdown; translating to an elevation in resting energy expenditure of ∼10%. The combination of certain biological factors, such as sex and/or existing thyroid disease may stimulate differential SHS-induced effects on thyroid function. Nevertheless, exposure to SHS disturbs vital human processes via thyroid disruption.

Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by the chronic inflammation of the synovium, which develops to joint destruction. Quite interestingly RA has not been present in the old world until 17 century. Tobacco has come from the new world, and epidemiological studies revealed cigarette smoking as a major risk factor for the disease. However, the mechanism how cigarette smoking contributes to RA has been largely unknown. It has been demonstrated that polycyclic aromatic hydrocarbons, constituents of cigarette smoke, and cigarette smoke extracts are able to induce proinflammatory cytokines from RA patient-derived fibroblast-like synoviocytes. Recent studies also suggest an important role of Th17 in RA and contribution of aryl hydrocarbon receptor to the induction and development of Th17 and RA. These new findings lead to uncovering the basis for the etiological role of cigarette smoking in the disease.

Morbidity and mortality are markedly elevated in chronic kidney disease (CKD) patients as consequence of cardiovascular risk factors clustering. Non-traditional risk factors such as inflammation are far more prevalent in this population and contribute significantly to atherosclerosis and cardiovascular disease (CVD). CKD results in a chronic, low-grade inflammatory process that becomes evident even in the early stages of the disease. C-reactive protein (CRP) and interleukin-6 (IL-6) are the most extensively studied inflammatory biomarkers in CVD. Circulating levels of both of these factors are elevated in CKD patients and increase with renal function deterioration. In end-stage renal disease (ESRD), elevated CRP levels are a strong predictor of all-cause and cardiovascular mortality. Recent studies showed IL-6 to predict more reliably CVD and mortality in ESRD patients. However, the issue of the ideal inflammatory marker remains open. Several factors are involved in triggering the inflammatory process including patient-related factors, such as underlying disease, comorbidity, oxidative stress, infectious, genetic or immunologic factors and uremia per se, as well as those arising from dialysis treatment itself, mainly membrane and dialysate biocompatibility. This inflammatory state is associated with adverse outcomes, such as malnutrition, anemia and erythropoietin hyporesponsiveness, high rate of CVD, decreased quality of life, as well as increased mortality and hospitalization in CKD patients. There is currently no consensus on how to manage the inflammatory syndrome in this population. However, adequate knowledge of its causes and their potential prevention or treatment may improve poor clinical outcome in CKD patients.

A new family of cytokines, the interleukin (IL)-17 family, has recently been defined, which reveals unique functions and distinct ligand-receptor signaling systems. This family contains six members, IL-17 (also called IL-17A), IL17B, IL-17C, IL-17D, IL-17E (IL-25) and IL-17F. The IL-17F gene was discovered in 2001, and is located on chromosome 6p12. Notably, among this family, IL-17F has been well characterized both in vitro and in vivo, and has been shown to have a pro-inflammatory role in asthma. IL-17F is clearly expressed in the airway of asthmatics and its expression level is correlated with disease severity. Moreover, a coding region variant (H161R) of the IL-17F gene is inversely associated with asthma and encodes an antagonist for the wild-type IL-17F. IL-17F is able to induce several cytokines, chemokines and adhesion molecules in bronchial epithelial cells, vein endothelial cells, fibroblasts and eosinophils. IL-17F utilizes IL-17RA and IL-17RC as its receptors, and activates the MAP kinase related pathway. IL-17F is derived from several cell types such as Th17 cells, mast cells and basophils, and shows a wide tissue expression pattern including lung. Overexpression of IL-17F gene in the airway of mice is associated with airway neutrophilia, the induction of many cytokines, an increase in airway hyperreactivity, and mucus hypersecretion. Hence, IL-17F may have a crucial role in allergic airway inflammation, and have important therapeutic implications in asthma.

Introduction: Myocardial inflammation often coexists with different types of autoimmune diseases. Our aim was to investigate the presence of myocarditis in these patients by Cardiovascular Magnetic Resonance (CMR) and endomyocardial biopsy. Patients-Methods: Twenty patients, aged 20-55 yrs with autoimmune diseases and cardiac symptoms (3 with Takayasu's arteritis, 3 with systemic lupus erythematosus, 5 with rheumatoid arthritis, 7 with autoimmune thyroid disease and 2 with systemic sclerosis) and 20 patients with the same autoimmune diseases but without cardiac symptoms (controls) were studied. The presence of myocarditis and LV function were evaluated by CMR. Myocarditis was documented using T2- weighted (T2-W), T1-weighted (T1-W) before and after contrast media injection and late enhanced images. In 10 patients (positive for myocarditis by CMR with either low LVEF or recent increase in troponin), endomyocardial biopsy was also performed. Myocardial specimens were evaluated by histology and polymerase chain reaction techniques (PCR). Results: Myocarditis was identified in 18/20 patients by CMR. In the T2-W images the signal ratio of myocardium to skeletal muscle was 1.89±0.25 (control values 1.57±0.13, p<0.05). From the T1-W images the relative myocardial enhancement was 11.31±11.18 (control values 3.09±0.05, p<0.05). Epicardial late gadolinium enhanced areas were identified in 18/20. In myocardial specimens, histology revealed inflammation in 5/10 (50%) and PCR documented viral or microbial genomes in 8/10 (80%). Positive histology and PCR were in agreement with 50% and 80% of positive CMR examinations, respectively. Herpes virus was identified in 3/10, Adeno in 1/10, Coxsackie B6 in 1/10, echo in 1/10, Parvo-B19 in 3/10, CMV in 1/10 and Chlamydia trachomatis in 8/10. Conclusions: Myocardial inflammation is a common finding in patients with autoimmune diseases and cardiac symptoms. The diagnosis can be confirmed by CMR, which is a noninvasive and reliable tool for the investigation of these patients.

Though atopic dermatitis (AD) is relatively uncommon in the elderly, elderly patients with AD are gradually increasing in industrialized countries associated with an aging society. Therefore, the clinical features of senile AD are becoming more apparent in some aspects. Three patterns of onset-senile onset, recurrence of AD with a history of classic childhood AD, and recurrence or continuation of adult AD-are associated with AD in the elderly. A male predominance in elderly AD may be a characteristic feature that differs from adult AD. Localized lichenifications in the folds of elbows and knees that are typical of classic AD are uncommon. Similar to AD in the other age groups, both extrinsic and intrinsic forms of AD exist in the elderly, and the major environmental allergens in the extrinsic form are house dust mite, followed by pollens and foods. In addition to the clinical features, this review focuses on the pathogenesis, diagnosis, management and future directions of this new subgroup of AD.