Obesity Has Implications for Lung Disease, Sleep Disorders, and Critical Care

Key Point

The obesity epidemic is affecting the practice of medicine in patients with pulmonary and sleep disorders, and in patients in the ICU.

CHICAGO—A panel discussion during the American College of Chest Physicians’ 2007 Annual International Scientific Assembly focused on the current clinical information about the relationship between obesity and pulmonary disease, sleep disorders, and critical care.

OBESITY OFTEN ANTEDATES ASTHMA

Session Chair Paula J. Anderson, MD, from the University of Arkansas for Medical Sciences in Little Rock, presented a review of the literature as it relates to obesity and lung disease, primarily asthma. In a landmark study, researchers followed 86,000 women in the Nurses’ Health Study over a four-year period and determined that being overweight at baseline increased asthma risk, Dr. Anderson remarked. In a Norwegian study—during which 135,000 men and women were followed for an average of 21 years—asthma risk increased as BMI rose. In men with a BMI of 25 to 30, asthma risk increased 10% for every BMI-unit increase; for women, risk increased 7% for every BMI-unit increase. Investigators in this and several other trials confirmed a connection between asthma and obesity; the incidence of asthma is related to preexisting obesity, independent of diet, exercise, and smoking, Dr. Anderson said. It is not clear, however, if increased BMI is related to increases in asthma severity, she added.

What causes this association between obesity and asthma? A statistical analysis of twin data from the University of Washington database showed that common genes may code for both obesity and asthma. According to Dr. Anderson, changes in immune or inflammatory responses in obese persons and increases in inflammatory markers may be predisposing factors.

Although the effect of BMI on asthma is not mediated by leptin alone, leptin is a mediator that has been much studied, said Dr. Anderson. She pointed out that leptin levels are high in obese patients and higher in asthma patients. In a study of 102 children with asthma and 33 healthy children, high leptin levels were predictive of asthma in boys (BMIs were similar in the study groups). In a smaller study, researchers looked at 23 newly diagnosed asthmatic children prior to treatment with inhaled corticosteroids and 20 controls. Leptin levels, after treatment with corticosteroids, fell significantly and were comparable with those in the control group. Again, BMI was similar in both groups.

Dr. Anderson noted that only a few studies have addressed the issue of whether obese people with asthma respond differently to treatment than do other asthma patients, but there is evidence to suggest that overweight and obese asthma patients are more likely to have poorly controlled asthma, that theophylline works less well than montelukast in this patient population, and that beclomethasone may be less effective than montelukast.

Weight loss (whether through caloric restriction or bariatric surgery) appears to be effective in improving asthma in obese patients, but the studies on this topic are “not great,” said Dr. Anderson. She remarked that the 2007 revision of the National Asthma Guidelines includes a recommendation that “‘clinicians consider advising asthma patients who are overweight or obese that weight loss, in addition to improving overall health, might also improve their asthma control,’ and that was evidence level B because of limited studies.”

Research shows that obesity may be protective in patients with COPD (ie, a lower BMI increases the risk of death), Dr. Anderson noted. Obesity seems to be related to increased risk of gastrointestinal reflux disease—which can worsen asthma or predispose to aspiration, among other lung problems—and venous thromboembolism. Future treatments may require different strategies for obese patients with asthma, including weight loss, the use of agents that work on inflammation, systemic agents, drugs that are now used in patients with type 2 diabetes mellitus, and immune therapies.

OBESITY AND SLEEP DIFFICULTIES

Babak Mokhlesi, MD, Assistant Professor of Medicine and Director of the Clinical Sleep Disorders Center at the University of Chicago, discussed the parallel rises in the number of obese patients and the number of patients who have sleep disorders, and the relationship between the two conditions. He reviewed National Health and Nutrition Examination Survey data demonstrating that the overweight adult population has remained relatively steady over the last three decades, while the number of obese persons has doubled. Dr. Mokhlesi also remarked that the prevalence of severe obesity (BMI > 40) has increased fourfold to fivefold in the past 15 years.

The incidence of sleep-disordered breathing (SDB) also has increased over the years. In 1993, the Wisconsin Sleep Cohort Study showed a prevalence of moderate to severe sleep apnea of 9% among middle-aged men and 4% among middle-aged women. In the years since these results were reported, the obesity trends in the United States have continued to rise. Therefore, it is plausible that SDB prevalence in middle-aged adults may be even higher.

Results of a multinational study showed that the prevalence of obesity hypoventilation syndrome among patients with obstructive sleep apnea (OSA) rises as BMI increases, Dr. Mokhlesi pointed out. In the US, 15% to 20% of patients with OSA also have obesity hypoventilation syndrome. These patients have higher morbidity and mortality compared to OSA patients with similar degrees of obesity but without hypoventilation, Dr. Mokhlesi added.

In a study by researchers from the University of Colorado, approximately 6,000 medical patients admitted to the hospital were screened; 150 of 277 patients identified as having BMIs greater than 35 were enrolled. Forty-seven had obesity-related hypoventilation; none died during their hospital stay, though compared with the control patients with similar degrees of obesity but without hypoventilation, more of these patients were admitted to ICUs, had invasive mechanical ventilation, and/or were discharged to long-term care facilities. Most patients with obesity hypoventilation were discharged from the hospital without any therapy for it. After 18 months of follow-up, 23% of patients with obesity hypoventilation had died versus 9% of patients with similar degrees of obesity but without hypoventilation, with the survival curve beginning to diverge as early as two to three months.

Traditional thinking posits that obesity causes abnormal sleep, largely through SDB. However, according to Dr. Mokhlesi, the reverse also may be true: Abnormal sleep may contribute to obesity. He noted that most adults report needing seven to nine hours sleep per night to feel well. However, in 2004, about 33% of men and women said that they regularly have less than six hours’ sleep.

Insufficient sleep, noted Dr. Mokhlesi, also is epidemic in children and adolescents. The 2006 National Sleep Foundation poll reported that most adolescents surveyed said they sleep seven to eight hours per night instead of the recommended nine hours per night, leading to a chronic sleep deficit.Are obesity and sleep deprivation interacting epidemics? “That remains to be elucidated,” Dr. Mokhlesi said.

Investigators from the University of Chicago studied men in their 20s who had no sleep problems and who were lean and healthy. For each of three nights, the men slept for about eight hours per night, followed by six nights of “sleep restriction” (four hours per night, from 1:00 to 5:00 am). Their glucose tolerance was tested. Then, they were allowed to sleep for as long as they wanted (“sleep extension”), initially for an average of 12 hours per night; this tapered to 9.5 hours. More glucose tolerance testing was done. The investigators found that after sleep restriction, the glucose area-under-the-curve in patients was significantly higher than in patients after sleep extension. For the sleep-restricted, otherwise healthy subjects, their insulin resistance approached prediabetes status.

Another University of Chicago study looked at the effects of sleep deprivation on appetite regulation in 12 lean, healthy subjects in their 20s and 30s in a randomized cross-over fashion. Subjects were assigned to either four or 10 hours of sleep, followed by complex blood sampling to measure glucose tolerance and to assess levels of leptin (an anorexigenic hormone that suppresses appetite) and ghrelin (an orexigenic peptide that stimulates appetite). In addition, hunger and appetite were assessed with validated questionnaires. The investigators found that with only two days of sleep deprivation subjects had an 18% drop in leptin, a 28% increase in ghrelin, and a 32% increase in appetite.

Does obesity alone worsen sleep? A study of 73 subjects who had no sleep problems at baseline and BMIs in the 40s showed that they experienced worse sleep, more wakening after sleep onset, and worse sleep latency, compared with 45 age-matched, nonobese controls.
In a follow-up study, 25 nonobese healthy volunteers were awakened after six hours of sleep every night for a week. At the end of the week, blood measurements showed significantly higher levels of interleukin 6, demonstrating that even modest sleep loss can be associated with a proinflammatory state.

Dr. Mokhlesi suggested that sleep loss can lead to weight gain and an increased risk of type 2 diabetes mellitus through the mechanisms of increased inflammation, decreased glucose tolerance, increased appetite, and decreased energy expenditure. Dr. Mokhlesi concluded that considerable data from epidemiologic and laboratory-based studies establish a strong association between sleep deprivation and obesity. However, this association does not establish cause and effect, he added. Further study is needed to establish the direction of causality.

OBESITY IN THE ICU IS SUBJECT TO PERCEPTION

James M. O’Brien, Jr, MD, MSc, from Ohio State University in Columbus, reviewed the relationship between excess weight and ICU outcomes, as well as the provision of care for obese patients in the ICU.

Epidemiologic studies look at BMI as a risk factor in obese patients. However, the distribution of fat could be a major consideration, Dr. O’Brien pointed out, as abdominal fat likely is a bigger issue in managing the patient’s ventilation than is the amount of fat in the thighs.

By the same token, medical staff make changes to patients’ BMIs within two hours of their arrival in the ICU, either by ridding patients of their fluid overload with diuretics or by giving them liters of fluid (each liter equaling 2.2 lb) to treat shock. Therefore, what is being measured—patients’ excess weight or the results of therapeutic treatment?

Determining a patient’s “native” BMI on entry to the ICU is a limiting factor in analyzing existing studies and may result in disparate outcomes. Dr. O’Brien suggested that a number of variables, including patient factors, provider beliefs and biases about the patient, and system factors can affect ICU care and, ultimately, prognoses. Epidemiologic studies, he concluded, rarely evaluate disparities in care provided.

One area in which obese patients might be prone to adverse events is during the establishment of artificial airways. Dr. O’Brien urged the use of protocols in assessing and placing endotracheal tubes for mechanical ventilation. Many studies demonstrate that use of protocols result in better care and better outcomes. Such protocols include assessment of airway difficulty, use of adjunctive and rescue techniques, and use of rapid sequence intubation when appropriate.

Upon patients’ admission to the ICU, physicians should perform and document the results of an airway examination of patients who are not intubated, Dr. O’Brien stressed.

One useful tool to assess the difficult airway is the “LEMONS” law:
Look for apparent characteristics that may predict a potentially difficult airway
Evaluate the “3-3-2” rule
Mallampati score
Obstruction
Neck mobility
Saturation (oxygen).

Of these components, the 3-3-2 rule and the Mallampati score are particularly important for the obese patient, Dr. O’Brien contended. He explained that he and his colleagues have an airway cart positioned at the bedside of patients who are obese and hypoxemic, as they are more than likely to have a difficult airway. Dr. O’Brien suggested that physicians become proficient in a few “favorite” rescue devices in the airway cart—he uses a glide scope for all his obese ICU patients—and recommended rapid access to a cricothyroidotomy tray.

To determine whether physician perception affects the provision of care to obese ICU patients, Dr. O’Brien and his colleagues conducted a survey of intensivists. The survey presented various clinical vignettes in which the only differences were age (50 or 70), medical history, and BMI. The respondents indicated that obese patients had a 4.2% higher predicted mortality than did nonobese patients. In turn, this perception was associated with higher odds of prescribing antibiotics, using low volume tidal ventilation, and suggesting a limitation of care.

Respondents also surmised that these hypothetical patients would have a 5.3% higher probability of difficulties with activities of daily life at six months. In other words, physicians expected obese patients to do worse.

There are very few studies that have assessed medication dosages in obese ICU patients, said Dr. O’Brien. Nor has much been published about nutritional needs of obese ICU patients. According to one study, obese patients under stress metabolize their protein; as a result, they may be more protein-deficient than are nonobese patients. From many points of view, therefore, “we are poorly equipped to deal with [the epidemic of obesity in the ICU],” concluded Dr. O’Brien.            

—Mary Brady Service

Suggested Reading
American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Practice guidelines for management of the difficult airway: an updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology. 2003;98(5):1269-1277.
Mokhlesi B, Tulaimat A. Recent advances in obesity hypoventilation syndrome. Chest. 2007;132(4): 1322-1336.
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007. www
.nhlbi.nih.gov/guidelines/asthma. Accessed January 3, 2007.
Young T, Peppard PE, Taheri S. Excess weight and sleep-disordered breathing. J Appl Physiol. 2005; 99(4):1592-1599.

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