Altered respiratory physiology in obesity

The major respiratory complications of obesity include a heightened demand for ventilation, elevated work of breathing, respiratory muscle inefficiency and diminished respiratory compliance. The decreased functional residual capacity and expiratory reserve volume, with a high closing volume to functional residual capacity ratio of obesity, are associated with the closure of peripheral lung units, ventilation to perfusion ratio abnormalities and hypoxemia, especially in the supine position. Conventional respiratory function tests are only mildly affected by obesity except in extreme cases. The major circulatory complications are increased total and pulmonary blood volume, high cardiac output and elevated left ventricular end-diastolic pressure. Patients with obesity commonly develop hypoventilation and sleep apnea syndromes with attenuated hypoxic and hypercapnic ventilatory responsiveness. The final result is hypoxemia, pulmonary hypertension and progressively worsening disability. Obese patients have increased dyspnea and decreased exercise capacity, which are vital to quality of life. Decreased muscle, increased joint pain and skin friction are important determinants of decreased exercise capacity, in addition to the cardiopulmonary effects of obesity. The effects of obesity on mortality in heart failure and chronic obstructive pulmonary disease have not been definitively resolved. Whether obesity contributes to asthma and airway hyper-responsiveness is uncertain. Weight reduction and physical activity are effective means of reversing the respiratory complications of obesity.     

Managing acute respiratory decompensation in the morbidly obese

Morbid obesity adversely affects respiratory physiology, leading to reduced lung volumes, decreased lung compliance, ventilation perfusion mismatch, sleep-disordered breathing and the impairment of ventilatory control, and neurohormonal and neuromodulators of breathing. Therefore, morbidly obese subjects are at increased risk of various pulmonary complications that can present either acutely or chronically. Respiratory failure is one of the most common pulmonary complications related to morbid obesity. Both acute hypoxaemic and hypercapnic respiratory failure are more common among obese patients. The management pathway of respiratory failure depends, to a large extent, on the underlying cause, primarily due to the diversity of the underlying triggering diseases, the pathophysiology and the prognosis associated with each disease. Morbidly obese patients with hypoventilation have an increased risk of acute hypercapnic respiratory failure. Early diagnosis of this disorder and the application of non-invasive ventilation in this group of patients have been shown to improve respiratory parameters, decrease the need for invasive mechanical ventilation and improve survival. Invasive ventilation remains the last life-saving procedure in patients with respiratory failure who do not respond to non-invasive measures. However, due to the abnormal respiratory physiology in obese patients, special precautions are required during intubation, mechanical ventilation and weaning.     

Physiologic responses to exercise in normal and obese women

The present study examines the possibility that the reduced activity commonly found in obese individuals could stem from a reduced physiological responsiveness to exercise. Responses to bicycle ergometer exercise (300 kpm/min) of four obese and four normal weight women were observed in a metabolic ward. This resulted in decreases in exercise heart rate and oxygen consumption, indicating an improvement in mechanical efficiency and suggesting an increase in physical working capacity. It also resulted in some decreases of resting oral temperature. The differences in the response to exercise between the obese and the normal weight groups were small and not statistically significant. The normal weight subjects showed a trend for greater decreases in heart rate and O2 consumption during exercise, while in the obese resting oral temperature tended to be more reduced. The results suggest that obesity in our subjects was not related to a deranged physiological response to physical activity.     

Exercise dyspnea in patients with COPD

Dyspnea, a symptom limiting exercise capacity in patients with COPD, is associated with central perception of an overall increase in central respiratory motor output directed preferentially to the rib cage muscles. On the other hand, disparity between respiratory motor output, mechanical and ventilatory response of the system is also thought to play an important role on the increased perception of exercise in these patients. Both inspiratory and expiratory muscles and operational lung volumes are important contributors to exercise dyspnea. However, the potential link between dyspnea, abnormal mechanics of breathing and impaired exercise performance via the circulation rather than a malfunctioning ventilatory pump per se should not be disregarded. Change in arterial blood gas content may affect dyspnea via direct or indirect effects. An increase in carbon dioxide arterial tension seems to be the most important stimulus overriding all other inputs from dyspnea in hypercapnic COPD patients. Hypoxia may act indirectly by increasing ventilation and indirectly independent of changes in ventilation. A greater treatment effect is often achieved after the addition of pulmonary rehabilitation with pharmacological treatment.     

Impact of obesity on exercise performance and pulmonary rehabilitation

While the impact of obesity on respiratory function has been extensively studied, and several definitive conclusions have emerged, its impact on exercise performance is complex, with the available data sometimes providing contradictory or inconclusive information. Based on the literature discussed, it appears that resting alterations in lung volumes and gas exchange become attenuated during exercise in the obese, while oxygen cost of breathing and dyspnoea are increased. Respiratory muscle function also seems to be impaired, such that inspiratory muscle strength is reduced and respiratory drive is increased. Furthermore, while there is no reduction in the absolute values of maximal oxygen uptake compared with normal-weight subjects, oxygen uptake at a given workload is increased and maximal workload is reduced in the obese, caused by increases in body mass and/or basal metabolic rate. To date, obesity has not been listed as an indication for pulmonary rehabilitation (PR), hence the reason why conclusive data on the impact of obesity per se on PR are lacking. The majority of evidence discussed is based on comparative data from obese versus normal-weight patients, with respiratory disorders currently established as indications for PR. The best evidence currently available regarding the impact of obesity on PR is for patients with chronic obstructive pulmonary disease (COPD); here, it appears that obesity per se has no negative impact on PR. Otherwise, there are no conclusive data on the impact of obesity on PR in respiratory disorders other than COPD, and this remains to be investigated in the future.     

Exercise in weight management of obesity

Obesity is a chronic metabolic disorder associated with CVD and increased morbidity and mortality. When the BMI is > or = 30 kg/m2, mortality rates from all causes, and especially CVD, are increased by 50% to 100%. There is strong evidence that weight loss in overweight and obese individuals improves risk factors for diabetes and CVD. Additional evidence indicates that weight loss and the associated diuresis reduce blood pressure in both overweight hypertensive and nonhypertensive individuals, reduce serum TG levels, increase high-density lipoprotein cholesterol levels, and may produce some reduction in low-density lipoprotein cholesterol concentrations. Of interest, even if weight loss is minimal, obese individuals showing a good level of cardiorespiratory fitness are at reduced risk for cardiovascular mortality than lean but poorly fit subjects. Insulin and catecholamines have pronounced metabolic effects on human adipose tissue metabolism. Insulin stimulates LPL and inhibits HSL; the opposite is true for catecholamines. There is regional variation in adipocyte TG turnover favoring lipid mobilization in the visceral fat depots and lipid storage in the peripheral subcutaneous sites. The hormonal regulation of adipocyte TG turnover is altered in obesity and is most marked in central obesity. There is resistance to insulin stimulation of LPL; however, LPL activity in fasted obese subjects is increased and remains so following weight reduction. Catecholamine-induced lipolysis is enhanced in visceral fat but decreased in subcutaneous fat. Numerous adaptive responses take place with physical training. These adaptations result in a more efficient system for oxygen transfer to muscle, which is now able to better utilize the unlimited lipid stores instead of the limited carbohydrate reserves available. In addition, the reduced adipose tissue mass represents an important mechanical advantage, allowing better long-term work. Gender differences have been reported in the adaptation of adipose tissue metabolism to aerobic exercise training. Physical training helps counteract the permissive and affluent environment that predisposes reduced-obese subjects to regain weight. An exercise program using weight resistance modalities may also be included safely, and it improved program retention in a multidisciplinary weight management program that was designed for obese children. Thirty to 45 minutes of physical activity of moderate intensity, performed 3 to 5 days a week, should be encouraged. All adults should set a long-term goal to accumulate at least 30 minutes or more of moderate-intensity physical activity on most, and preferably all days. Public health interventions promoting walking are likely to be the most successful. Indeed, walking is unique because of its safety, accessibility, and popularity. It is noteworthy that there is a clear dissociation between the adaptation of cardiorespiratory fitness and the improvements in the metabolic risk profile that can be induced by endurance training programs. It appears that as long as the increase in energy expenditure is sufficient, low-intensity endurance exercise is likely to generate beneficial metabolic effects that would be essentially similar to those produced by high-intensity exercise. The clinician should therefore focus on the improvement of the metabolic profile rather than on weight loss alone. Realistic goals should be set between the clinician and the patient, with a weight loss of approximately of 0.5 to 1 pound per week. It should be kept in mind that since it generally takes years to become overweight or obese, a weight loss pattern of 0.5 or 1 pound per week will require time and perseverance to reach the proposed target. However, the use of physical activity as a method to lose weight seems inversely related to patients' age and BMI and directly related to the level of education. Thus, public health interventions helping these groups to become physically active remain a challenge and further emphasize the importance of the one-on-one interaction between the clinician/health care professional with the obese individual "at risk" of CVD. This notion is critical, as it has been shown that less than half of obese adults have reported being advised to lose weight under the guidance of health care professionals.     

Work of breathing and respiratory drive in obesity

Obesity, particularly severe central obesity, affects respiratory physiology both at rest and during exercise. Reductions in expiratory reserve volume, functional residual capacity, respiratory system compliance and impaired respiratory system mechanics produce a restrictive ventilatory defect. Low functional residual capacity and reductions in expiratory reserve volume increase the risk of expiratory flow limitation and airway closure during quiet breathing. Consequently, obesity may cause expiratory flow limitation and the development of intrinsic positive end expiratory pressure, especially in the supine position. This increases the work of breathing by imposing a threshold load on the respiratory muscles leading to dyspnoea. Marked reductions in expiratory reserve volume may lead to ventilation distribution abnormalities, with closure of airways in the dependent zones of the lungs, inducing ventilation perfusion mismatch and gas exchange abnormalities. Obesity may also impair upper airway mechanical function and neuromuscular strength, and increase oxygen consumption, which in turn, increase the work of breathing and impair ventilatory drive. The combination of ventilatory impairment, excess CO(2) production and reduced ventilatory drive predisposes obese individuals to obesity hypoventilation syndrome.     

Efficacy of diaphragmatic breathing in patients with chronic obstructive pulmonary disease

This study investigated the effects of diaphragmatic breathing (DB) on ventilation and breathing pattern, seeking to identify predictors of its efficacy in patients with chronic obstructive pulmonary disease (COPD). Twenty-nine patients with moderate and severe COPD were monitored using respiratory inductance plethysmography and metabolic gas analysis. After 4 minutes of natural breathing, subjects completed 2 minutes of DB followed by 4 minutes of natural breathing. Dyspnea was measured using a visual analogue scale. Diaphragmatic mobility was assessed using chest radiography. DB was associated with a significant increase in tidal volume and reduction in breathing frequency, leading to higher ventilation and oxygen saturation, with a reduction in dead space ventilation and ventilatory equivalent for carbon dioxide. A total of 10 subjects with moderate (5) and severe (5) COPD performed DB with asynchronous thoracoabdominal motion, worsening the dyspnea, and decreasing the gain of tidal volume. Diaphragmatic mobility, inspiratory muscular strength, lower scores for dyspnea and hypoxemia as well as coordinated thoracoabdominal motion are associated with effective DB. In patients with COPD, DB can improve breathing pattern and ventilatory efficiency without causing dyspnea in patients whose respiratory muscular system is preserved.     

Exertional dyspnea and ventilation in hyperthyroidism.

Dyspnea is recognized to be an important feature in patients with hyperthyroidism at rest and during exercise. However, its etiology is not well-understood. Since dyspnea is thought to be related to the perception of excessive ventilatory effort, we explored the possibility that dyspnea in these patients might be related to an inappropriate ventilatory response to the increased metabolic rate. We studied 11 hyperthyroid patients and 11 age- and sex-matched controls, performing spirometry, lung volumes, mouth pressure measurements, and incremental exercise test. Central drive was estimated by measuring P0.1 and sensation of dyspnea by the Borg scale. We found that hyperthyroid patients (1) have higher ventilation than normal subjects during exercise even when corrected for VCO2 levels; (2) this increased ventilation is secondary to increased central drive which is correlated to the T3ria level (r = 0.85, p less than 0.01); (3) hyperthyroid patients are more dyspneic than controls; and (4) the increased drive can be normalized by beta-blockade. We conclude that the main ventilatory abnormality in hyperthyroid patients is an inappropriate increase in respiratory drive, possibly secondary to increased adrenergic stimulation.     

Ventilatory regulation in eucapnic morbid obesity

In morbid obesity, there is an increased hindrance to breathing caused by the effects of the increased mass on the chest wall and abdomen; subjects with morbid obesity can maintain eucapnia by increasing inspiratory neuromuscular drive and/or by altering central breath timing. We studied 23 eucapnic, obese subjects (greater than 190% predicted ideal weight), 7 males and 16 females with a mean age of 36.6 +/- 9.2 yr and 18 healthy, normal male subjects. Total lung capacity, functional residual capacity, and total thoracic compliance were significantly (p less than 0.05) reduced in the obese subjects. At rest, minute ventilation was significantly increased because of an increase in respiratory frequency, which in turn was due to a significant decrease in the expiratory time (TE) per breath; the ratio of inspiratory to expiratory time (TI/TE) was thus significantly altered, indicating an alteration in central breath timing. Resting inspiratory neuromuscular drive (as represented by mouth occlusion pressure) was significantly increased in the obese subjects, but tidal volume was not significantly altered. There was an increased ventilatory responsiveness to hypoxia and relatively decreased ventilatory responsiveness to hypercapnia in the obese subjects. These results indicate that morbidly obese subjects maintain eucapnia primarily by an alteration in central breath timing. Although these subjects have decreased responsiveness to CO2, putting them at some risk of developing respiratory failure under conditions of hypercapnic/hypoxic stress, it is possible that this is counteracted by the increased responsiveness to hypoxia.     

Obesity and asthma: evidence for and against a causal relation.

The evidence for an association between asthma and obesity in adults, and in children and adolescents, is reviewed. Few studies in adults measured height and weight, whereas the majority in children did. Evidence for the association is strong, but that for a gender interaction is weak. There is sufficient evidence to rule out asthma preceding obesity as an explanation, and that increased perception of symptoms in the obese, or a purely mechanical effect, is responsible. However, direct causality is unlikely, because in children the association is of recent origin, and trends in obesity do not explain the rising prevalence of asthma. Atopy was not associated with obesity in a large adult study. Potential explanations that require further investigation are that gastroesophageal reflux as a result of obesity causes asthma, that physical inactivity may promote both obesity and asthma, and that the diets of obese subjects may potentiate asthma.     

Clinical complications of obesity

The development of important respiratory disorders and significant hypertension in association with increasing body weight is not widely recognized. Altered respiratory function results from a combination of mechanical impedance to breathing exerted by thoracic and abdominal fat and a ventilation-perfusion mismatch. Sleep-disordered breathing with periods of hypoventilation, with or without apnoeic episodes, may commonly occur in patients with extreme obesity. Nocturnal hypercapnia and hypoxia in such patients may lead to a decrease in ventilatory drive, abnormal central respiratory control and possibly, in time, the development of the obese-hypoventilation syndrome. Respiratory abnormalities should be suspected in obese patients with a history of restlessness at night, loud snoring and daytime somnolence. Treatment is substantial weight reduction, but short-term measures include the use of compressed air via nasal cannulae for obstructive apnoea, and drugs which alter sleep pattern or stimulate respiration. The alterations in endocrine function, which accompany weight gain, may contribute to an increase in blood pressure and there appears to be a relationship between plasma insulin and catecholamine concentrations, fat cell size and the development of hypertension. The confirmation of a raised blood pressure requires that readings be taken with an adequately sized arm-cuff. In many instances endocrine function becomes normal with weight loss, and there is a corresponding decrease in blood pressure. The ideal management for an obese hypertensive patient is the combination of a suitable calorie-restricted diet with a programme of physical exercise.     

Mechanisms of exertion dyspnea in cardiac insufficiency

Effort dyspnea in cardiac failure corresponds to a subjective perception of difficulty in breathing which is itself secondary to a disproportion between the central bulbar respiratory regulation and the level of pulmonary ventilation attained. In cardiac failure, this situation is the result of dysfunction of both the respiratory apparatus and the skeletal striated muscle during exercise. During exercise a rise in left ventricular end diastolic pressure causes: a reduction in pulmonary compliance. The bronchial and alveolar capillaries drain into the pulmonary veins. The congestion of these capillaries and the resulting oedema makes the lung "stiffer"; an increase in the resistances of the small airways due to direct compression by congested bronchial vessels. The physiological dead space increases: the respiratory muscles ventilate pulmonary zones which are not perfused to no benefit. The reduction of pulmonary compliance, the increased resistances of the airways and of the physiological dead space all contribute to increase the work of the respiratory muscles. In addition to these mechanical phenomena, there is greater stimulation of the respiratory centre in the brain stem by the metabolic abnormalities of the skeletal striated muscles. During effort, they rapidly function under anaerobic conditions and the resulting hyperproduction of lactate and carbon dioxide stimulates the respiratory centres.     

Adipositaschirurgie

Every fifth German is obese, which means that 20% of male and 21.1% of female adults have a BMI of more than 30. In total 1.02 million adults in Germany are morbidly obese (BMI>40). This pandemic situation of obesity and morbid obesity is similar to the incidence of obesity in North America. In consideration of the increasing incidence of obesity the long-term success rate of conservative obesity treatment of 1?C2% does not ease this situation. Widespread prevention programs are not planned. The current only, as well long-term, effective therapy against morbid obesity is bariatric surgery. There is an arsenal of restrictive (e.g. gastric band, gastric sleeve) and combinations of restrictive and malabsorptive procedures (Roux-en-Y gastric bypass, biliopancreatic diversion) available to treat morbid obesity. Bariatric surgery can not only induce excess weight loss of 75?C80% but also a remission of co-morbidities, such as type 2 diabetes mellitus or metabolic syndrome. Even the tremendously reduced life expectancy of morbidly obese patients could be adapted to normal weight subjects by bariatric surgery.     

Metabolic studies in human obesity during overnutrition and undernutrition: thermogenic and hormonal responses to norepinephrine

Overfeeding increases the thermogenic response of norepinephrine (NE) in normal but not in certain genetically obese rodents. It has been suggested that human obesity may be associated with a similar thermogenic defect. To determine whether there are differences in the thermogenic sensitivity to NE in human obesity, energy expenditure in response to graded infusions of NE (0.05, 0.10, 0.15, 0.20 micrograms/min/kg fat-free mass) was measured in six lean and six obese subjects (9.5 +/- 1.8 v 36.3 +/- 3.8% body fat P less than 0.005). Resting metabolic rate (RMR), thermogenic response to NE, and thermogenic response to exercise were measured during weight maintenance and during the third week of feeding 1000 extra Kcal/d in the lean and obese subjects. These components of energy expenditure were also measured in the obese subjects during the third week of a 589 Kcal/d diet. Resting metabolic rate increased during overfeeding in lean (6.6%, P less than 0.05) but not in the obese subjects (2.7%, P = NS) and fell during underfeeding in the obese (-9.1%, P less than 0.02). There was a logarithmic increment above baseline in VO2 v plasma NE concentration during the NE infusions (r = 0.75, P less than 0.005) in lean subjects which was unaltered by overfeeding. The obese exhibited equivalent VO2 responses to NE to that measured in the lean. Supine plasma NE concentrations were lower but metabolic clearance rates (MCR) of NE were similar in the obese compared to lean subjects during both weight maintenance and overfeeding. Overfeeding minimally increased plasma concentration but not MCR of NE in both groups. The thermogenic response to exercise was similar in the lean and obese subjects and was unaltered by overfeeding or underfeeding. The increments in plasma glycerol and free fatty acid in response to the NE infusions were proportional to the total fat mass of each individual and were greater in the obese subjects. Overfeeding partially suppressed the lipolytic response to NE in both groups and underfeeding increased the lipolytic response in the obese. There are no differences in thermogenic responses to NE in human obesity to account for excessive fat deposition. Overfeeding does not increase the thermogenetic responses to NE in humans as has been reported in small mammals.     

Improvement in exercise capacity after nocturnal positive pressure ventilation and tracheostomy in a postpoliomyelitis patient.

Progressive neuromuscular symptoms years after recovery from acute paralytic poliomyelitis have been termed the PPS. We describe a 52-year-old man who contracted poliomyelitis at age 9 years who fully recovered and 33 years later developed progressive dyspnea. Neurologic evaluation revealed bilateral paralysis of the vocal cords, generalized weakness, and accentuated mouth occlusion pressure and ventilatory responses to hypercapnic, hyperoxic breathing. An EMG and muscle biopsy showed changes consistent with acute and chronic denervation. Cardiopulmonary exercise evaluation demonstrated a pulmonary mechanical limit with excessive ventilation relative to CO2 output. Tracheostomy and nocturnal positive pressure ventilation resulted in increased respiratory muscle strength, normalization of ventilatory drive and marked improvement in exercise capacity.     

Evaluation of respiratory disability in patients of respiratory diseases using relationships between ventilatory drive, ventilation and thoracic pump function during exercise

We studied the parameters of breathing control during exercise in patients with respiratory diseases for the evaluation of respiratory disability. The ventilatory drive during the same load exercise was increased in patients with respiratory diseases compared with that in normal subjects. In addition, the ratio of ventilation to ventilatory drive during exercise was decreased in patients with respiratory diseases. Impairment of rapid thoracic movement was suggested to be one of the mechanical limitations for ventilation in these patients, based on the findings of smaller esophageal pressure fluctuation during maximum ventilation of 40 respirations per minute than that in normal subjects. Flow at 0.1 sec after initiation of inspiration was designated V0.1. The increase of the ratio of V0.1 at rest to that at maximum voluntary inspiration (V0.0 (rest)/V0.1 (max)) indicate the grade of respiratory disability showing the impossibility of rapid movement of thorax as a parameter of thoracic pump function. It was recognized that the decrease of VE/P0.1 during incremental exercise indicated ventilatory insufficiency.     

The impact of morbid obesity on oxygen cost of breathing (VO(2RESP)) at rest.

Oxygen consumption dedicated to respiratory work (V O(2RESP)) during quiet breathing is small in normal patients. In the morbidly obese, at high minute ventilations, VO(2RESP) is greater than in normal patients, but VO(2RESP) during quiet breathing in these patients is not known. We postulated that such patients have increased VO(2RESP) at rest which may predispose them to respiratory failure when additional respiratory workloads are imposed. We measured baseline VO(2) in morbidly obese patients immediately prior to gastric bypass surgery and again after intubation, mechanical ventilation, and paralysis, and compared their change in VO(2) to nonobese patients scheduled for elective abdominal surgery. Baseline VO(2) was higher in the obese patients compared with control patients (354.6 versus 221.4 ml/min; p = 0.0001) and the change in VO(2) from spontaneous breathing to mechanical ventilation was significant in the obese patients (354.6 versus 297.2 ml/min; p = 0.0002) but not the control patients (221.4 versus 219.8 ml/min; p = 0.86). We conclude that morbidly obese patients dedicate a disproportionately high percentage of total VO(2) to conduct respiratory work, even during quiet breathing. This relative inefficiency suggests a decreased ventilatory reserve and a predisposition to respiratory failure in the setting of even mild pulmonary or systemic insults.