Current
Respiratory Medicine Reviews
ISSN: 1573-398X
Current Respiratory Medicine
Reviews
Volume 4, Number 2, May 2008
Contents
Obesity and the Lung
Guest Editors: Neil S. Cherniack and E. Paul
Cherniack
Editorial:
Pp. 77-78
Respiration and Energy Homeostasis Pp.79-84
Musa A. Haxhiu, Prabha Kc and Neil S. Cherniack
[Abstract]
Orexins: Relation Between Sleeping, Eating, and
Breathing Pp. 85-89
Prabha Kc, Musa A. Haxhiu and Kannan V. Balan
[Abstract]
Obesity: Its Consequences Upon Respiratory System
Function Pp. 90-94
Marc H. Lavietes
[Abstract]
Obstructive Sleep Apnea and Obesity
Pp. 95-99
Shyam Subramanian and Kingman Strohl
[Abstract]
The Obesity Hypoventilation Syndrome
Pp. 100-104
Neil S. Cherniack
[Abstract]
Obesity in the Patient with Lung Disease
Pp.105-109
Zaza I. Cohen
[Abstract]
Critical Illness in the Obese Patient
Pp. 110-115
Steven Y. Chang, John P. Kress and Jesse B. Hall
[Abstract]
Obesity and the Aging Respiratory System
Pp. 116-121
E. Paul Cherniack
[Abstract]
Management of Obesity Pp. 122-130
Marvin A. Kirschner
[Abstract]
Bariatric Surgery and it Effects on the Respiratory
System Pp. 131-136
E. Paul Cherniack and Neil S. Cherniack
[Abstract]
Smoking and Weight Pp. 137-149
Norman Hymowitz
[Abstract]
Cardiovascular Complications of Obesity
Pp. 150-155
Gerard Oghlakian and Marc Klapholz
[Abstract]
Abstracts
[Back to top]
Editorial: Seeing the BIG Picture:
A Weighty Matter for Pulmonary Physicians
Seeing the BIG Picture: A Weighty Matter for Pulmonary Physicians
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.
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[2] Pi-Sunyer FX. The obesity epidemic: pathophysiology and
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[3] Klesges RC, Ward KD, Ray JW, Cutter G, Jacobs, Wagenknecht
LE. The prospective relationship between smoking and weight
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[4] O’Hara P, Connett JE, Lee WW, Nides M, Murray R,
Wise R. Early and late weight gain following smoking cessation
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[5] Bjorntorp P. The associations between obesity, adipose
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[6] Pi-Sunyer X. The metabolic syndrome: how to approach differing
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effects of fatness and fat distribution on respiratory functions
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[8] Parameswaran K, Todd DC, Soth M. Altered respiratory physiology
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Hyperleptinemia, respiratory drive and hypercapnic response
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[12] Shahar E, Whitney C, Redline S, et al. Sleep
disordered breathing and cardiovascular disease: cross sectional
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[13] Nahmias J, Kirschner M, Karetzky MS. Weight loss and
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[14] Spiegel K, Tasali E, Penev P, van Cauter E. Brief communication:
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decreased leptin levels, elevated ghrelin levels, and increased
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[15] Olson AL, Zwillich C. The obesity hypoventilation syndrome.
Am J Med 2005; 118: 948-56.
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The obesity - hypoventilation syndrome revisited. Chest 2001;
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[17] Matarasso A, Roslin MS, Kurian M. Bariatric Surgery:
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[18] Marik PE, Doyle H, Varon J. Is Obesity Protective During
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[19] Tremblay A, Bandi V. Impact of body mass index on outcomes
following critical care. Chest 2003; 123: 1202-7.
[20] Agusti AG, Sauleda J, Miralles C, et al. Skeletal
muscle apoptosis and weight loss in chronic obstructive pulmonary
disease. Am J Respir Crit Care Med 2002; 166(4): 485-9.
[21] Bolton CE, Ionescu AA, Shiels KM, et al. Associated
loss of fat-free mass and bone mineral density in chronic
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170: 1286-93.
[22] Marquis K, Debigare R, Lacasse Y, et al. Midthigh
muscle cross-sectional area is a better predictor of mortality
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809-13.
[23] Visscher TL, Seidell JC, Molarius A, van der Kuip D,
Hofman A, Witteman JC. A comparison of body mass index, waist
hip ratio and waist circumference as predictors of all-cause
mortality among the elderly: the Rotterdam study. Int J Obes
Relat Metab Disord 2001; 25: 1730-1735.
[24] Horner RL, Mohiaddin RH, Lowell DG, et al. Sites
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Neil S. Cherniack
New Jersey Medical School
UMDNJ, Newark
NJ 07950
USA
E-mail: cherniac@umdnj.edu
E. Paul Cherniack
Miami VA Hospital
University of Miami
Miami, FL 33136
USA
E-mail: evan.cherniack@va.gov
[Back to top]
Respiration and Energy Homeostasis
Musa A. Haxhiu, Prabha Kc and Neil S. Cherniack
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.
[Back to top]
Orexins: Relation Between Sleeping, Eating, and Breathing
Prabha Kc, Musa A. Haxhiu and Kannan V. Balan
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.
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Obesity: Its Consequences Upon Respiratory System Function
Marc H. Lavietes
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.
[Back to top]
Obstructive Sleep Apnea and Obesity
Shyam Subramanian and Kingman Strohl
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%.
[Back to top]
The Obesity Hypoventilation Syndrome
Neil S. Cherniack
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.
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Obesity in the Patient with Lung Disease
Zaza I. Cohen
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).
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Critical Illness in the Obese Patient
Steven Y. Chang, John P. Kress and Jesse B. Hall
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.
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Obesity and the Aging Respiratory System
E. Paul Cherniack
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.
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Management of Obesity
Marvin A. Kirschner
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. Meta-analyses
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.
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Bariatric Surgery and it Effects on the Respiratory System
E. Paul Cherniack and Neil S. Cherniack
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.
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Smoking and Weight
Norman Hymowitz
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.
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Cardiovascular Complications of Obesity
Gerard Oghlakian and Marc Klapholz
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.
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