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.     

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.     

Maximum respiratory pressures in morbidly obese subjects

Maximum inspiratory and expiratory pressures were measured at residual volume, total lung capacity, and functional residual capacity in 45 morbidly obese patients who on average weighed 183% of their predicted weights. The pressures were compared to determinations made in 25 subjects of similar age whose mean weight was 99% of predicted. For both men and women, pressures generated by control subjects tended to be higher than those produced by obese patients but the differences were not statistically significant. The mean vital capacity and total lung capacity were also similar in the 2 subject groups. The results indicate that despite working constantly against a less compliant chest wall, obese patients do not increase their capacity to generate maximal respiratory pressures.     

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.     

Effects of obesity on respiratory function

Obesity, because it alters the relationship between the lungs, chest wall, and diaphragm, has been expected to alter respiratory function. We studied 43 massively obese but otherwise normal, nonsmoking, young adults with spirometry, lung volume measurement by nitrogen washout, and single-breath diffusing capacity for carbon monoxide (DLCO). Changes in respiratory function were of two types, those that changed in proportion to degree of obesity--expiratory reserve volume (ERV) and DLCO--and those that changed only with extreme obesity--vital capacity, total lung capacity, and maximal voluntary ventilation. When compared with commonly used predicting equations, we found that mean values of subjects grouped by degree of obesity were very close to predicted values, except in those with extreme obesity in whom weight (kg)/height (cm) exceeded 1.0. In 29 subjects who lost a mean of 56 kg, significant increases in vital capacity, ERV, and maximal voluntary ventilation were found, along with a significant decrease in DLCO. Because most subjects fell within the generally accepted 95% confidence limits for the predicted values, we concluded that obesity does not usually preclude use of usual predictors. An abnormal pulmonary function test value should be considered as caused by intrinsic lung disease and not by obesity, except in those with extreme obesity.     

Role of ventilatory drive in asthma and chronic obstructive pulmonary disease

The ventilatory drive is affected by several factors such as chemosensitivity, basal arterial oxygen or carbon dioxide tension, mechanical impedance, and respiratory muscle dysfunction. Blunted ventilatory drive or a decrease in the perception of dyspnea in bronchial asthma and chronic obstructive pulmonary disease (COPD) could lead to a decrease in the alarm reaction to dangerous situations such as severe airway obstruction, severe hypoxemia, or severe hypercapnia. This could delay management and treatment, causing an increase in the morbidity and mortality of patients with bronchial asthma and COPD. The ventilatory drive to chemical stimuli can be altered by a beta-2-agonist, oxygen administration; and lung volume reduction, and an increased dyspnea sensation may be improved by corticosteroid, chest wall vibration, or lung volume reduction. The ventilatory drive has been found to play a key role in determining the severity of asthma and COPD.     

Airway-parenchyma uncoupling in nocturnal asthma

Airway flow resistance is well known to be dependent upon lung volume. The rise in lung volume that occurs in asthma is therefore thought to be an important mechanism that defends airway patency. The purpose of the current study was to investigate the interdependence or mechanical coupling between airways and lung parenchyma during the inflammatory processes that occur in the patient with nocturnal asthma. Five patients with documented nocturnal asthma were studied in both a vertical and a horizontal body plethysmograph. Lung volume was altered with continuous negative pressure as applied to the chest wall with a poncho cuirass in different postures and during sleep. We found during the awake phase that an increase in lung volume decreased lower pulmonary resistance (Rlp); however, within 30 min of sleep onset, functional residual capacity (FRC) fell and Rlp rose more than would be expected for the fall in FRC. Restoring FRC to presleep values either at an early (half-hour) or a late (3-h) time point did not cause Rlp to significantly fall. A second phase of the study showed that the loss of Rlp dependence on lung volume was not due to the assumption of the supine posture. Indirect measurements of lung compliance were consistent with a stiffening of the lung. We conclude that with sleep there is an immediate uncoupling of the parenchyma to the airway, resulting in a loss of interdependence that persists throughout sleep and may contribute to the morbidity and mortality associated with nocturnal asthma.     

Simulated obesity-related changes in lung volume increases airway responsiveness in lean, nonasthmatic subjects

STUDY OBJECTIVE: To determine if obesity-related changes in lung volume might contribute to airway reactivity, we investigated the effects of simulated mild obesity-related lung volume reductions on airway responsiveness in lean, nonasthmatic subjects. Participants and methods: We simulated the lung volume reductions of class 1 obesity in eight lean, nonasthmatic subjects by externally mass loading the chest wall and abdomen, and shifting blood volume into the lung with lower limb compression (LLC). Airway responsiveness was assessed by measuring FEV(1) before and after methacholine challenge tests (1, 2.5, 5, 10, and 25 mg/mL) with the following: (1) no intervention (control); (2) external chest loading (CL); (3) LLC; and (4) CL and LLC (COMB) on separate days. Lung function was measured before and after CL, LLC, and COMB were applied. RESULTS: The application of CL, LLC, and COMB decreased expiratory reserve volume, functional residual capacity, and total lung capacity compared with baseline. FVC and FEV(1) decreased significantly with CL and COMB, while FEV(1)/FVC did not change compared to baseline. The maximal response to the methacholine challenge increased with CL, LLC, and COMB, with a mean maximal fall of FEV(1) of 9%, 11%, and 18%, respectively, compared to a 6% fall with control. CONCLUSIONS: We conclude that decreases in lung volume increase airway responsiveness and may account for the increased propensity for increased airway responsiveness in the obese.     

Effect of ventilation by high-frequency oscillation on lung and chest wall mechanics in the dog

High-frequency oscillation (HFO) has been shown to be effective in maintaining gas exchange, but the effects of high-frequency, small-volume ventilation on the mechanical properties of the respiratory system are unknown. A volume displacement plethysmograph was used to study lung volumes and static pressure-volume (PV) curves during HFO in pentobarbital-anesthetized dogs. During long-term studies, adequate gas exchange was maintained with a stroke volume of 2.5 ml/kg and frequencies between 15 and 30 Hz. The effect of 5–7 hours of HFO on lung and chest wall mechanics was studied in 8 dogs. In another 8 dogs the relationship of volume history and respiratory muscle tone to occlusion airway pressure and lung volume during short-term HFO was investigated. With prolonged HFO, a small but significant decrease in total lung capacity occurred by 5 hours and the static respiratory system PV curve shifted slightly to the right. These changes were reversed by muscle paralysis and may be explained by a change in respiratory muscle tone. Static lung compliance and the hysteresis ratio (an index of tissue properties) remained unchanged. The relationship of occlusion airway pressure and lung volume during short-term HFO was dependent on the lung volume history and was influenced by respiratory muscle tone only at low airway pressures. These findings suggest that during prolonged HFO a small increase in chest wall stiffness may result. However, occlusion airway pressure and lung volume at the onset of HFO are mainly dependent on the volume history of the lung. Presented in part at the Fall Meeting of the American Physiological Society, Toronto, Canada, October 12–17, 1980     

Phasic respiratory pharyngeal mechanics by magnetic resonance imaging in lean and obese zucker rats

RATIONALE: Although obstructive sleep apnea is strongly associated with obesity, we have little understanding of how obesity may alter the mechanical properties of the pharynx and the role of obesity in the pathogenesis of sleep apnea. OBJECTIVES: The overall objective of this study was to determine the effect of obesity on pharyngeal airway size and pharyngeal wall tissue strain in lean and obese Zucker rats. METHODS: Respiratory-gated magnetic resonance imaging with noninvasive tissue tagging was performed in anesthetized, spontaneously breathing lean (n = 9) and obese (n = 9) Zucker rats. Images acquired during expiration and inspiration of the rostral, mid-, and caudal pharynx were analyzed for airway size and pharyngeal wall tissue strain, using planimetry, optical flow, and finite element analyses. Differences in cross-sectional airway area, lateral and anteroposterior airway diameters, and tissue strain (stretch, compression, and direction of stretch) in the lateral and ventral pharyngeal walls were compared by analysis of variance (significance at p < 0.05). MEASUREMENTS AND MAIN RESULTS: Compared with their lean littermates, obese rats had the following significant findings: reduced pharyngeal airway cross-sectional area during inspiration and expiration, smaller increases in airway area during inspiration, and decreased lateral airway dilation during inspiration. Tissue strain in the pharyngeal walls showed no significant differences between obese and lean rats. CONCLUSIONS: These findings suggest that obesity results in a mechanical abnormality that decreases pharyngeal airway size and prevents a normal airway response to a given change in pharyngeal wall tissue strain.     

Partitioning of respiratory mechanics in young adults. Effects of duration of anesthesia

General anesthesia increases total respiratory elastance and flow resistance within minutes after induction. We determined if respiratory mechanics changed progressively during anesthesia by measuring total respiratory elastance and resistance and their respective lung and chest wall components in 10 young adults free of cardiorespiratory disease at the start and end of premedicated anesthesia administered for orthopedic surgery (isoflurane, enflurane, or halothane, minimal alveolar concentration approximately 1.5 in 60% N2O-40% O2; interval between measurements was 0.42 to 5.0 h, mean +/- SD = 2.08 +/- 1.56 h). Static lung recoil pressure, static total respiratory and lung elastance, dynamic lung elastance, chest wall elastance, and total respiratory and lung and chest wall resistances were measured during steady-state breathing (greater than 10 min after induction). Resistance of the endotracheal tube, pneumotachygraph and connectors were subtracted from the total flow resistance to obtain total intrinsic resistance. Average values of static lung recoil pressure and all elastances and chest wall resistance did not change significantly from start to end of the study, regardless of the elapsed time. Total respiratory and lung resistance increased by 49% (p less than 0.05) and 45% (p less than 0.02), respectively, but were not time-dependent. We conclude that lung static recoil and total respiratory and lung elastances did not change beyond the first 10 min after induction, regardless of duration of anesthesia. The increases in total respiratory and lung resistance were small, independent of duration of anesthesia, and may have been due to accumulated airway secretions.     

Lung, chest wall, and total respiratory system resistances and elastances in the normal range of breathing.

We measured total respiratory system and lung and chest wall resistances (Rrs, Rl, and Rcw) and elastances (Ers, El, and Ecw) in awake, relaxed human subjects during sinusoidal volume forcing at the mouth from 0.2 to 0.6 Hz with tidal volumes (VT) of 6 to 18% VC at constant mean airway pressure. In addition, we repeated measurements with the lowest VT at a lower airway pressure and therefore at a lower mean lung volume (Vl). Rrs and Rcw decreased with increasing respiratory frequency (f) and VT, but Rl was independent of f and VT. All resistances were higher at the lower Vl. Ers and Ecw increased with increasing f and decreased with increasing VT. El increased slightly with increasing f but was not affected by VT. All elastances tended to increase at the lower Vl. We conclude that in the normal range of breathing amplitude and frequency, (1) lung properties are nearly constant if mean lung volume does not change, and (2) f and VT dependencies of total respiratory system properties are caused by the chest wall.     

Asthma and obesity: a known association but unknown mechanism

The obese asthma phenotype is an increasingly common encounter in our clinical practice. Epidemiological data indicate that obesity increases the prevalence and incidence of asthma, and evidence that obesity precedes the development of asthma raises the possibility of a causal association. Obese patients with asthma experience more symptoms and increased morbidity compared with non-obese asthma patients. Despite more than a decade of research into this association, the exact mechanisms that underlie the interaction of obesity with asthma remain unclear. It is unlikely that the asthma-obesity association is simply due to comorbidities such as obstructive sleep apnoea or gastroesophageal reflux disease. Although inflammatory pathways are purported to play a role, there is scant direct evidence in humans that systemic inflammation modulates the behaviour of the asthmatic airway or the expression of symptoms in the obese. The role of non-eosinophilic airway inflammation also requires further study. Obesity results in important changes to the mechanical properties of the respiratory system, and these obesity-related factors appear to exert an additive effect to the asthma-related changes seen in the airways. An understanding of the various physiological perturbations that might be contributing to symptoms in obese patients with asthma will allow for a more targeted and rational treatment approach for these patients.     

Physiological changes in respiratory function associated with ageing.

Physiological ageing of the lung is associated with dilatation of alveoli, enlargement of airspaces, decrease in exchange surface area and loss of supporting tissue for peripheral airways ("senile emphysema"), changes resulting in decreased static elastic recoil of the lung and increased residual volume and functional residual capacity. Compliance of the chest wall diminishes, thereby increasing work of breathing when compared with younger subjects. Respiratory muscle strength also decreases with ageing, and is strongly correlated with nutritional status and cardiac index. Expiratory flow rates decrease with a characteristic alteration in the flow-volume curve suggesting small airway disease. The ventilation-perfusion ratio (V'A/Q') heterogeneity increases, with low V'A/Q' zones appearing as a result of premature closing of dependent airways. Carbon monoxide transfer decreases with age, reflecting mainly a loss of surface area. In spite of these changes, the respiratory system remains capable of maintaining adequate gas exchange at rest and during exertion during the entire lifespan, with only a slight decrease in arterial oxygen tension, and no significant change in arterial carbon dioxide tension. Ageing tends to diminish the reserve of the respiratory system in cases of acute disease. Decreased sensitivity of respiratory centres to hypoxia or hypercapnia results in a diminished ventilatory response in cases of heart failure, infection or aggravated airway obstruction. Furthermore, decreased perception bronchoconstriction and diminished physical activity may result in lesser awareness of the disease and delayed diagnosis.     

The respiratory muscles in eucapnic obesity: Their role in dyspnea

Regular exercise appears to be one of the best predictors of successful weight maintenance. Although physical activity and exercise are important components in the prevention and treatment of obesity, many obese adults without coexisting disorders are unable to exercise due to dyspnea on exertion. As a result they may not participate in regular physical activity. Therefore exertional dyspnea in obese adults is also an obstacle to the prevention and treatment of obesity and coexisting comorbidities. The available data suggest that increased respiratory muscle force generation, and the concomitant increase in respiratory neural drive associated with increased ventilation are an important source of sensation of respiratory effort in obese subjects. Whether activity-related breathlessness is due to either abnormal respiratory mechanical factors (flow limitation and/or chest elastic loading) or the increased metabolic demand of locomotion in obesity, or both of these together, the available data indicate that intensity of dyspnea at any given ventilation and oxygen uptake does not increase in obese subjects as compared with normal weight control subjects. Does this mean that respiratory mechanical factors are unlikely to be contributory? Nonetheless, the component of metabolic cost of breathing may not be accounted for in the measured mechanical work of breathing because of the number of included complex variables. That a decrease in efficiency of the respiratory muscles during exercise contributes to dyspnea in hyperinflating obese subjects should not be disregarded.     

Obesity,expiratory flow limitation and asthma symptoms

Obesity is associated with poor asthma control, but the reason for this is unclear. Reduction in operating lung volume, as occurs in obesity, and bronchoconstriction, as occurs in asthma, can increase expiratory flow limitation during tidal breathing (EFLt), which may in turn increase respiratory symptoms. The aim of this study was to determine the effect of obesity on EFLt at baseline and after bronchoconstriction in non-asthmatic and asthmatic subjects, and to determine the association between EFLt, and respiratory symptoms. Data from previously published studies in non-asthmatic and asthmatic subjects were reanalyzed using an index of EFLt derived from respiratory system reactance measured by the forced oscillation technique. The analysis showed that during bronchoconstriction both non-asthmatic and asthmatic obese individuals were more likely to develop EFLt than non-obese subjects, despite similar changes in FEV1. Furthermore the index of EFLt was a significant determinant of the severity of breathlessness during challenge in non-asthmatic subjects, and of asthma symptom control in asthmatic subjects following anti-inflammatory treatment. These studies suggest that the combination of bronchoconstriction and low resting lung volume increase the risk of EFLt, and that this altered response to bronchoconstriction may increase the severity of symptoms and lead to worse asthma control.     

Obesity and asthma: implications for treatment

PURPOSE OF REVIEW: Epidemiological data as well as data from mouse models of asthma indicate a relationship between obesity and asthma. The purpose of this review is to evaluate recent data addressing this relationship and its biological basis, and to evaluate the implications of these data for treatment. RECENT FINDINGS: Obesity increases the prevalence, incidence, and possibly severity of asthma, while weight loss in the obese improves asthma outcomes. Obesity also influences asthma control and the response to standard asthma therapeutics. Moreover, obese mice exhibit innate airway hyperresponsiveness and increased responses to common asthma triggers. The biological basis for the relationship between obesity and asthma may be the result of common etiologies, comorbidities, effects of obesity on lung volume, or adipokines such as tumor necrosis factor alpha, leptin, and adiponectin. SUMMARY: Understanding the mechanistic basis for the relationship between obesity and asthma may lead to new therapeutic strategies for treatment of this susceptible population.     

Model of functional restriction in chronic obstructive pulmonary disease, transplantation, and lung reduction surgery.

Mechanical interactions between lung and chest wall are important determinants of respiratory function. When chest wall expansion during maximal inhalation generates insufficiently negative pleural pressures, the lungs remain functionally underinflated; this may be termed functional restriction. To explore mechanisms and effects of functional restriction in patients with emphysema, and to predict effects of single lung transplantation and lung volume reduction surgery (LVRS), we used a computational model based on standard physiology and measurements from individual patients. The model's lungs, separated by a compliant mediastinum, exhibit flow limitation according to the equal pressure point approach of Mead and coworkers. Pulmonary elastic recoil pressure is characterized by an exponential equation modified to reflect airway closure. Simulated respiratory maneuvers can be specified by variations in flow or pressure at the airway opening or in respiratory muscle activation. Model simulations successfully mimic recordings from individual patients. Input parameter values may then be altered to predict effects of surgical interventions in these same patients. The model simulations show the following. Single lung transplantation in emphysema can cause functional restriction of the normal transplanted lungs, and larger transplanted lungs may perform less well than smaller ones. LVRS improves lung and chest wall function in emphysema, but not in normal states. Surgical reduction of the native emphysematous lung after single lung transplantation can reduce functional restriction of the transplant and thereby improve its function.     

Respiratory mechanics of the horse during the first year of life

This study investigated the developmental changes in the mechanical properties of the respiratory system in growing horses. Pulmonary mechanics and lung volumes were serially measured in anesthetized foals during the first year of life. Quasi-static pressure-volume curves were generated, and functional residual capacity (FRC) was measured using a closed nitrogen equilibration technique. At birth, chest wall compliance normalized to body weight was substantially less than reported in other less precocious newborn species, while lung compliance normalized to body weight was similar to values reported for other species. Characteristics of the transition from the neonatal to adult respiratory system in the foal included a decrease in the ratios of chest wall to lung compliance (Cw/Cl) and the unstressed volume of the chest wall to TLC, and a constant FRC/TLC throughout most of the study period. The somatic growth of the foal and its respiratory system were uneven processes, with increases in lung volume lagging increases in overall body size.     

The effects of body mass index on lung volumes

BACKGROUND: Obesity is a major health issue in North America, and the trend is for obesity to be a more important medical issue in the future. Since obesity can cause respiratory symptoms, many obese people are referred for pulmonary function tests (PFTs). It is well known that obesity causes decreases in lung volumes, but there has never been a large study showing the correlation between body mass index (BMI) and the various lung volumes. DESIGN: We collected PFT results from 373 patients sent for lung function testing who had normal values for airway function but a wide range of BMIs. SETTING: The PFTs were done in two accredited outpatient laboratories. RESULTS: There were significant linear relationships between BMI and vital capacity and total lung capacity, but the group mean values remained within the normal ranges even for morbidly obese patients. However, functional residual capacity (FRC) and expiratory reserve volume (ERV) decreased exponentially with increasing BMI, such that morbid obesity resulted in patients breathing near their residual volume. An important finding was that the greatest rates of change in FRC and ERV occurred in the overweight condition and in mild obesity. At a BMI of 30 kg/m2, FRC and ERV were only 75% and 47%, respectively, of the values for a lean person with a BMI of 20 kg/m2. CONCLUSIONS: We showed that BMI has significant effects on all of the lung volumes, and the greatest effects were on FRC and ERV, which occurred at BMI values < 30 kg/m2. Our results will assist clinicians when interpreting PFT results in patients with normal airway function.