Current Respiratory Medicine Reviews - Volume 4, Issue 2, 2008

Both smoking and overeating are very bad habits with serious adverse consequences for health [1, 2]. They are interrelated. Often, smoking is begun as a way to lose weight. On the other hand, smoking cessation is often accompanied by weight gain, which offsets some of the beneficial effects of not smoking [3, 4]. Both smoking and overeating can cause widespread damage to the body [5, 6] and interfere with breathing [7-9]. This hot topic issue of Current Respiratory Medicine Reviews considers obesity related lung disease within the broader context of energy homeostasis. It includes some of the final contributions of Musa A. Haxhiu, one of the pioneers in the neural control of energy homeostasis. This issue is unique in bringing together overviews of the effects of obesity on the respiratory system with summaries of the mechanisms of obesity and the systemic effects of adiposity. Particular attention is given to the medical and surgical treatment of obesity. In addition to its mass loading effects on the respiratory muscles and the upper airways, it is now appreciated that adipose tissue is metabolically active and the source of chemicals such as cytokines, leptin, and adioponectin that can exert systemic effects on the brain, immune regulation, the endocrine and other systems [10, 11]. Sleep apnea is an important example of how both the mechanical and systemic results of obesity play significant roles in causing and perpetuating the disease [12, 13]. Since sleeplessness is associated with overeating and weight gain, the sleep apnea patient may sometimes find himself trapped in a dangerous cycle [14]. Obesity and sleep apnea like hyperlipidemia, hypertension, and impaired glucose tolerance are features of the metabolic syndrome [6]. Although, obesity may lead to respiratory failure in patients with lung disease, the systemic and mechanical effects of obesity may produce respiratory failure even in patients with normal lungs [15, 16]. Moreover, obesity makes more likely the cardiovascular and metabolic complications that adversely affect the health of the lung patients and increase the difficulty in treatment [12]. The pulmonary physician's attempts to induce his patients to quit smoking may be thwarted by the patient's fear of becoming too fat [3]. Hence, it is important for the respiratory physician to appreciate the risks of obesity, understand the active role that the adipose tissue has on health, and to treat obesity-related lung disease as a manifestation of a systemic disease by becoming familiar with the available methods: diet, drugs, and surgery for weight loss [17]. The relationship of body weight and pulmonary disease can be quite complex. While obesity in general has a negative effect on long-term survival, being overweight may benefit patients acutely in the ICU [18, 19]. Moreover, in addition, some lung diseases themselves, such as, COPD and lung cancer are associated with under nutrition and loss of muscle tissue, which have a detrimental effect on survival [20-22]. Hence, the treatment of obesity in these patients must be carefully carried out so that excess adipose tissue is lost, but not muscle strength, or endurance. One of the important areas of research is the diagnosis of obesity. Although now commonly defined by the BMI (weight in kilograms/ height in meters squared), it is clear that there are health consequences to body fat distribution, and waist, hip, and neck circumference may also be important in determining the effects of obesity [23, 24]. In addition, because BMI reflects both fat and muscle mass, evaluation of weight changes and loss may require measurement of muscle mass as well as BMI [21]. As we learn more about obesity and its effects, it becomes increasingly clearer that obesity related lung diseases need a coordinated multi-disciplinary approach to diagnosis and treatment. REFERENCES [1] Hedley AA, Ogden CL, Johnson CL, et al. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA 2004; 291: 2847-2850. [2] Pi-Sunyer FX. The obesity epidemic: pathophysiology and consequences of obesity. Obes Res 2002; 10 Suppl 2: p. 97S-104S. [3] Klesges RC, Ward KD, Ray JW, Cutter G, Jacobs, Wagenknecht LE. The prospective relationship between smoking and weight in a young, biracial cohort: The Coronary Artery Risk Development in Young Adults Study. J Consult Clin Psychol 1998; 66: 487-93. [4] O'Hara P, Connett JE, Lee WW, Nides M, Murray R, Wise R. Early and late weight gain following smoking cessation in the Lung Health Study. Am J Epidemiol 1998; 148: 821-30. [5] Bjorntorp P. The associations between obesity, adipose tissue distribution and disease. Acta Med Scand Suppl 1998; 723: 121-34. [6] Pi-Sunyer X. The metabolic syndrome: how to approach differing definitions. Med Clin North Am 2007; 91: 1025-40. [7] Koziel S, Ulijaszek SJ, Szklarska A, et al. The effects of fatness and fat distribution on respiratory functions Annals of Human Biology 2007; 34(1): 123-131.

Respiration supplies the oxygen needed for energy usage and removes the carbon dioxide one of the waste products of energy consumption. Energy homeostasis is maintained through interacting networks that control food intake, energy usage and the sleep/wake cycle. Adipose tissue mass changes when energy gain s and losses are no longer in balance. But adipose tissue is not passive and through the release of chemical messages affects energy homeostasis. The chemical messages involved in energy homeostasis also can modify the performance of the respiratory system not just in sleep but in wakefulness as well.

Orexins (orexin-A and orexin-B) are produced in the lateral hypothalamic area, also known as the feeding center, have been implicated to play a critical role in central regulation and maintenance of sleep and wakefulness state, feeding and energy homeostasis by acing upon its receptors (orexin receptor 1 and orexin receptor 2) respectively. Orexin neurons are active during wakefulness period and exert an excitatory influence on monoaminergic-containing neurons, which are known to play an important role during arousal. Deficiency of orexin causes narcolepsy and fragmentation in sleep pattern. Orexinergic neurons senses body's external as well as internal environments and are also sensitive to metabolic cues indicating that theses neurons are involved in coordinating the feeding behavior and behavioral vigilance states for its survival. Orexin stimulates both feeding and metabolic rate and its deficiency leads to altered energy homeostasis, including decreased caloric intake with an increased body mass index as seen in narcoleptic patients. Experimental studies have shown that orexins have a role in regulating autonomic function; increase in blood pressure and heart rate following orexin administration suggests that orexins stimulates sympathetic outflow. It has also been shown that orexin decreases upper airway resistance during inspiration and maintains CO2 sensitivity during wake period suggesting its importance in state dependent control of the airways. Therefore, these findings suggest that orexinergic neurons provide a crucial link between arousal and energy balance, and modulate breathing in physiological state dependent manner.

Obesity affects pulmonary function profoundly. Lung pathology is rarely found in obese people. Thus the functional abnormalities often observed in obese people (e.g., reduced lung volumes, increased airway resistance, hypoxemia and hypercapnia) are a consequence of the added load presented by chest wall adiposity to the respiratory system. This paper describes the mechanisms whereby obesity brings about these functional abnormalities. It then describes the two major syndromes associated with obesity, one, the obesity - hypoventilation syndrome and two, the obstructive sleep apnea syndrome, and links these syndromes to the chest wall pathology and physiology which are their cause.

Obesity trends continue to rise in alarming proportions worldwide. Obstructive sleep apnea, an increasingly commonly recognized disorder, is characterized by recurrent episodes of upper airway closure during sleep, and obesity is proposed to be its strongest risk factor. Recognition strategies for OSA in obesity are overwhelmed by the sheer prevalence of obstructive sleep apnea, >80% in those with a BMI >40. Obesity has direct as well as indirect influences on upper airway mechanics and physiology. Obesity may also influence loop gain by exerting an influence on central chemosensory respiratory drive. Pattern of fat distribution rather than overall weight may have a modulatory effect on these influences. Obese patients also develop a syndrome of obesity-hypoventilation characterized by waketime hypercarbia, by mechanisms that are not entirely clear. Genetic mechanisms influencing obesity and OSA are bidirectional and likely exert mutually additive effects. Medical weight loss can be a treatment for OSA, but bariatric surgery has played an increasingly prominent role in the theraputic paradigm for OSA in the morbidly obese, with success rates of ∼85%.

The obesity hypoventilation syndrome (OHS) characterized by persistent hypercapnia with obesity has many causes. Probably the most common cause is the obstructive sleep apnea syndrome and related conditions, but some cases may occur along with depressed chemosensitivity and few apneas during sleep. The mechanisms that produce waking hypercapnia are still uncertain. Treatment of OHS consists of weight management and sometimes requires treatment with continuous applied pressure or non invasive positive pressure ventilation.

In the last few decades, obesity has captured the attention of the medical community, as well as the general public. Obesity has been shown to be a direct cause or a contributor to the development of various chronic diseases. In contrast, higher weight has been linked to better outcomes in patients with chronic obstructive pulmonary disease (COPD). It also has been recognized that “not all weight has been created equal” and it's not the absolute weight in kilograms or the body-mass index (BMI), but rather the fat-free mass index (FFMI) that is a better measure of the nutritional status and the overall prognosis in COPD patients. While the impact of the weight and the nutritional status on the lung cancer outcomes has been similar to that of COPD, the relationship between the obesity and asthma has been more complex and multi-faceted. The article will offer a concise, rather than a comprehensive review of such relationships between the nutritional status and the natural history of three chronic lung diseases. The effects of nutritional supplements, alternative medications, and other interventions will be discussed in the context of the individual diseases (COPD, asthma and lung cancer).

We review studies examining the impact of obesity on survival, morbidity, and respiratory failure in critical illness. Given the increasing rates of overweight and obesity, there is a surprising lack of well-conducted clinical trials addressing its interaction with critical illness. Unexpectedly, it seems that obesity may not negatively impact, or may even be protective with regards to mortality, though there are a few studies that support conventional wisdom, demonstrating worsened outcomes amongst the obese. Being obese does seem to predispose to respiratory failure, given altered lung and chest wall mechanics, and increased metabolic demands, though it is uncertain how it might impact survival in patients requiring ventilatory support.

The aging lung is characterized by changes that result in both loss of elasticity and muscle strength, causing alterations in lung volumes, such as decreased vital capacity. Obesity compounds these changes. Fat accumulates around the ribs and diaphragm, and there is increased inspiratory resistance and loss of chest wall compliance. This causes an increased work of breathing which, in the worst case, can lead to dyspnea. There is not a clear-cut relationship between parameters of body weight and mass and alterations in pulmonary function, but loss of expiratory reserve volume, functional residual capacity, forced expiratory volume and forced vital capacity have been described. Dieting can improve pulmonary function, but undernutrtion must be avoided.

Obesity is rapidly becoming a worldwide epidemic with serious consequences of life-shortening morbidity. This paper explores current modalities available for the control of overweight and obesity. Most overweight and obese persons setting out to lose weight envision achieving ideal body weight, a generally unrealistic goal. Studies collated in the National Heart & Lung Institute Monograph (1998) strongly suggest that a loss of 10% of body weight results in significant improvement of hypertension, dyslipidemia, diabetes, and cardiovascular risk factors, and is a far more achievable goal for weight control. Fad diets and commercial weight loss programs are widely used by the general population seeking weight loss. Metaanalyses show that these diets can result in 2-8% loss of weight after 1 year, although many of theses studies suffer from lack of adequate controls, and thus may over-estimate the weight losses. In the few studies comparing results from commercial programs to proper control groups, weight loss of 2-4% have been achieved. As for pharmacologic agents to aid in weight loss, the sympathomimetic drugs are FDA- approved for only 12 weeks of use. There are presently 2 drugs approved for long term weight loss; sibutramine (an SSRI and sympathomimetic reuptake inhibitor), and orlistat (an intestinal lipase inhibitor). Carefully controlled studies have shown that both drugs caused 3-5% weight loss after 1 year of continued use. With both drugs, the weight loss can be significantly enhanced (as much as 100%) with lifestyle changes involving exercise and behavior modification. A new highly anticipated drug which acts to inhibit endogenous cannabinod receptors, (Rimonabant) has shown 5-7% weight loss after 1 year, but its approval has been suspended by the FDA as of this writing. As for major weight loss programs, very low calorie diets (VLCD) were popular in the 1980-90s. This strenuous approach of consuming only protein-rich supplements resulted in 20-25% weight loss after 1 year, however on returning to normal food, there were high rates of weight regain. Surgical approaches to weight loss are reserved for patients with Type III Obesity and are becoming more widely used, yielding the greatest degree of weight loss and long-term maintenance.

Bariatric surgery for morbid obesity is an effective approach to weight loss in selected obese patients. The candidate for surgery must be massively obese and have failed to lose appreciable weight with diet, drugs, and exercise. He must also be committed to lifelong weight maintenance. Bariatric surgical procedures either limit the expansion of the stomach (restrictive surgery) or the effective mixing of gastric contents with bile and pancreatic enzymes (bypass surgery). Gastric bypass is the most commonly performed bariatric procedure in the United States. Bariatric surgery-induced weight loss is associated with improvements in cardiovascular respiratory, and metabolic function. Two recent studies have shown significant survival benefit for people who have bariatric surgery (most had restrictive surgery). However, bariatric surgery is risky with an appreciable perioperative mortality. Although bypass surgery usually produces more weight loss than restrictive surgery, it is associated with more complications caused by malabsorption of nutrients such as fat, protein, and fat soluble vitamins.

On average, adults who smoke cigarettes weigh less than nonsmokers. However, they have a greater tendency towards abdominal obesity, and, when they stop smoking, about 80% of them gain weight. Whereas original estimates of the amount of weight ex-smokers gain in one-year's time was about five pounds, long-term follow-up of sustained quitters suggests that the weight gain may be considerably greater. While the health benefits of quitting smoking outweigh the adverse health consequences of post-cessation weight gain, studies on the effects of smoking cessation on lung function show that the weight gained by quitters may significantly reduce the beneficial effects of smoking cessation on lung function. Prevention of post-cessation weight gain has proved to be an elusive target. However, studies show that life style changes, diet, exercise, and pharamacotherapy, alone and in combination, may reduce post-cessation weight gain, at least for the period of time that the treatments are in effect. Nicotine replacement therapy, bupropion SR, and, to a lesser extent, varenicline, are the most effective pharmacological deterrents to post-cessation weight gain, although the latter medication may yield the best quit smoking results. Research on pharmacogenetics and other medications may increase physicians' armamentarium in the future.

Obesity has become a worldwide epidemic and impacts cardiovascular health. It is closely associated with hypertension, diabetes and dyslipidemia which are known precursors of cardiovascular disease and have a significant impact on overall morbidity and mortality. Obesity has been identified as an independent risk factor in the development of dilated cardiomyopathy. This article will review the cardiovascular consequences of obesity and highlight some of the pathophysiologic derangements that have been identified to be associated with obesity.