Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minn., USA
Summary
Aging results in a progressive fall in vital capacity and maxi-mal expiratory flows, at a rate which may accelerate in the more advanced years of life. In addition, there is an apparent reduction in pulmonary capillary blood volume, a gradual rise in pulmonary vascular pressures, and an altered ventilation distri-bution as aging progresses. These changes result in a reduction in ventilatory reserve and in theory would make the older adult more susceptible to gas exchange abnormalities during exer-cise. Nevertheless, the healthy older adult is generally able to maintain an appropriate alveolar ventilation to maintain arterial oxygenation and reduce arterial carbon dioxide levels, even during heavy exercise. The primary limitation resulting from the age-related changes in the pulmonary system may be relat-ed to the large work and cost of breathing which could limit exercise performance by competing for blood flow with the locomotory muscles.
The large capacities of the respiratory system allow for significant erosion in function between maturity and senescence with minimal impact on normal breathing.
Only during moderate to heavy exercise does it appear that the aged-induced changes significantly impact nor-mal breathing, and then primarily through an effect on breathing strategy, work and cost of breathing rather than on alveolar to arterial gas exchange [1–4]. The focus of this review will be the impact of age-related changes in the respiratory system on the response to exercise. For a
for-mal review of baseline changes in the pulmonary system with aging, the reader is referred to several previous papers [5–9].
Table 1 summarizes the changes in lung and chest wall function, gas exchange and ventilatory control with aging and the impact of these age-related changes on the response to exercise in the healthy, active, older adult.
Pulmonary Mechanics
With the decline in pulmonary function (due primarily to a loss of lung elastic recoil), older subjects have a reduced ability to increase tidal volume (VT) and to increase flow rates during exercise. In the average 70-year-old subject, the reduction amounts to a 30% loss in vital capacity (VC) and forced expiratory volume in 1 s (FEV1) relative to the 20-year-old adult [4, 9, 10]. The relative reduction in flow rates is particularly great over the lower lung volumes (functional residual capacity, FRC, and below) and thus limits the ability to increase flow in the older adult over this lung volume range [1]. Interestingly, ventilatory (VE) demand tends to fall with aging commen-surate with the fall in metabolic demand so that it may be theorized that the relative demand/capacity balance may be similar to the average fit young adult. It is this relation-ship of demand to capacity that in part determines the adequacy of the ventilatory compensation to exercise in the older adult. Interestingly, recent studies have suggest-ed that the decline in pulmonary function with aging may accelerate beyond age 50–60 years and that this decline in
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Table 1. Influence of age-related changes in the respiratory system on the response to heavy exercise
Baseline change (or proposed change) Result Response to exercise in the older adult
Pulmonary Mechanics
↓Elastic recoil
↑Chest wall stiffness
↓Respiratory muscle strength
↓Intervertebral space
↓Lung volumes (TLC, VC)
↓Flow rates
↓Pressure generation capacity
↑Expiratory flow limitation
Altered regulation of end-expiratory lung volume
↓Expiratory and inspiratory pressure reserve
↑VT/VC
↑Work and oxygen cost of breathing
↑Competition for blood flow between locomotor and respiratory muscles
Gas Exchange/Hemodynamics
↓Elastic recoil (nonuniform)
↑Alveolar duct diameter
↓Alveolar septa
↑Stiffness of pulmonary arteries and capillaries
Diastolic dysfunction
↓Pulmonary capillary blood volume
↓Surface area
↑VA/Qc inhomogeneity
↑Pulmonary pressures
↑Dead space ventilation
↑VE to maintain alveolar PO2
Arterial PO2 maintained within 5 mm Hg resting values Alveolar to arterial PO2 difference ↑threefold
Ventilatory Control
↓Integration of sensory inputs in CNS
↓Perceptual sensitivity to inspiratory and expiratory loads
↓Inspiratory neuromuscular output
↓Response to chemical and mechanical stimuli
VE response generally adequate to maintain PaO2 near resting values and to ↓PaCO2 below resting values
function is not modified by habitual physical activity nor high aerobic capacity [4, 7]. Thus in advanced age, the loss in capacity may begin to play a role in limiting human performance, especially in the elderly that maintain rela-tively high levels of activity [2–4].
Ventilatory Demand
Ventilatory demand is dependent foremost on meta-bolic demand (quantified by measurements of oxygen consumption, VO2, or carbon dioxide production, VCO2), but also on the dead space ventilation (VD) and regula-tion of arterial CO2 levels (PaCO2). This relationship is summarized in the following equation: VE = (KWVCO2)/
[PaCO2 W(1 – VD/VT)] (K = the constant 0.863 and repre-sents the factor needed to transform fractional gas con-centration to partial pressure and to express gas volumes at body temperature and pressure saturated with water vapor). Many studies have evaluated changes in maximal oxygen consumption with aging and most demonstrate a decline of approximately 0.4–0.6%/year beyond the age of 30–35 and attribute the decline primarily to a reduced cardiac output as a result of a decline in heart rate, although a loss of muscle mass and altered mitochondrial function may play a role [11–14]. Thus the average 25- to
30-year-old may have a peak exercise VO2 of 45 ml/kg/
min and the average 70-year-old, 25 ml/kg/min. This results in a comparable decline in VCO2 and thus it can be predicted (from the above equation) that the peak ventila-tion necessary for maintaining normal alveolar oxygen levels during peak exercise (assumes a similar dead space to tidal volume ratio, VD/VT) will fall by approximately 30–40% or a decrease from 120 l/min for the normally active 30-year-old to 70 l/min for the average fit 70-year-old adult. However, given the increase in dead space ven-tilation with aging (↑ 0.1–0.6%/year beyond age 25–30), it is expected the decline in ventilatory demand for the aver-age 70-year-old will only be 25–30% [9, 15]. With in-creased fitness it can subsequently be predicted that for every 500 ml increase in metabolic demand (F50 W on a cycle ergometer), the ventilatory requirements will in-crease by F15 l/min. The ventilatory demands would fur-ther increase as pH falls with heavy exercise and arterial CO2 is reduced in an attempt to compensate for the acido-sis.
Breathing Pattern
The typical response to exercise is to increase both the frequency of breathing and the tidal volume. Most studies
Pulmonary Consequences of Aging 91 Fig. 1. Ventilatory response to exercise in young untrained adults (A) and older active adults (B) matched for exercise capacity. Tidal breathing exercise flow-volume loops at increasing work intensities are plotted according to a mea-sured end-expiratory lung volume within the maximal volitional flow-volume envelope (MFVL). Additional mean gas exchange parameters are given for both groups. Dotted or dashed segments of the MFVL represent the expiratory flow obtained immediately post-exercise. From Johnson BD, Badr MS, Dempsey JA: Impact of the aging pulmonary system on the response to exercise; in Weisman IM, Zeballos RJ (eds): Clinics in Chest Medicine. Philadelphia, Saunders, 1994, vol 15, pp 229–246, with permission.
have demonstrated a primary increase in tidal volume early in exercise in healthy adults followed by a primary frequency response, especially in heavy and maximal exercise [16]. The aged tend to achieve a tidal volume that reaches a greater percent of their VC than their younger counterparts [1, 9].
Several factors likely determine the peak VT chosen during exercise. Previous work by McParland et al. [17].
added dead space during exercise and found that most subjects will attempt to preserve gas exchange (eliminate CO2 and maintain alveolar O2) by increasing the tidal breath, suggesting a given tidal breath may be optimal for preserving gas exchange. On the other hand, lung inflation (stretch receptors in the lung) and the inspiratory elastic load (chest wall receptors) may act to limit the tidal breath so that the work and oxygen cost of breathing are not excessive. Of course this is dependent a great deal on where the subject breathes on the pressure-volume rela-tionship of the lung and chest wall, i.e., regulation of end-expiratory lung volume (EELV). Thus in the aged adult,
the increased lung compliance facilitates achieving a high-er lung volume during exhigh-ercise (end inspiratory lung vol-ume, EILV) while the reduced compliance of the chest wall inhibits large tidal breaths (especially at a high per-centage of total lung capacity (TLC), ↑ EELV).
Regulation of End Expiratory Lung Volume
Figure 1 demonstrates an example of the flow and vol-ume response to progressive exercise in young adults rela-tive to older ‘fit’ subjects (similar exercise capacity as the young average fit adults (VO2max = 43 ml/kg/min) [1, 18–
20]. Shown is the resting tidal breathing flow volume loop in the young and older adult and tidal breathing loops associated with progressive exercise relative to the voli-tional maximal flow-volume envelope (MFVL). In the young adult, tidal volume increases during exercise by encroachment on the inspiratory and expiratory reserve volumes. The encroachment on the expiratory reserve volume is accomplished by a reduction in EELV below the resting relaxation volume (i.e., FRC). The reduction
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Fig. 2. Corresponding (to the flow-volume data shown in figure 1) tidal pressure-volume responses to progressive exercise in young untrained adults (A) and older fit adults (B). Pmaxe = Maximal effective pressure generation;
Pcapi = capacity for inspiratory pressure generation (determined at the flow and volume where peak inspiratory pressure occurred). From Johnson BD: Age-associated changes in pulmonary reserve; in Evans JG, Williams TF, Beattie LB, et al. (eds): Oxford Textbook of Geriatric Medicine, ed 2. Oxford, Oxford University Press, 2000, pp 483–497, with permission.
in EELV is thought to increase inspiratory muscle length thereby optimizing the length-tension relationship of the inspiratory muscles so that for a given neural input, great-er force production occurs [21]. The drop in EELV also allows the tidal breath during exercise to stay on the linear portion of the pressure-volume relationship of the lung and chest wall, thus minimizing the elastic work and oxy-gen cost of breathing. The fall in EELV tends to progress with exercise intensity and averages 0.5–1.0 l in an aver-age fit, young adult at peak exercise [19, 22].
In the older subjects (age 70 years), EELV typically decreases in a similar fashion with the onset of exercise as in the young adult. However, due to expiratory flow limi-tation (i.e., tidal flow volume breath that meets the expira-tory boundary of the MFVL) particularly near the end of each tidal breath, the majority of older subjects subse-quently fail to decrease EELV further or actually increase EELV to avoid further expiratory flow limitation [1, 2, 4].
On average, significant expiratory flow limitation begins to occur at a ventilation of F40 l/min, 40–50% of VO2max. Thus in the older adult, EILV encroaches to a greater extent on TLC than in the younger adult and the
potential benefits from an increased inspiratory muscle length through a decrease in EELV are compromised [1–4].
Expiratory Flow and Pressure Development
As noted, expiratory flow reaches the maximal avail-able flows over a significant portion of the tidal breath in the aged subjects beginning at a ventilation of F40 l/min.
This is in contrast with young adults who do not achieve this level of expiratory flow constraint until a ventilation of 100–120 l/min or near-peak exercise.
Figure 2 gives the corresponding tidal pleural-pres-sure-volume response in the young and older adults (rela-tive to the flow-volume loops shown in figure 1). As shown, the expiratory pleural pressures become positive early in exercise in the older adults suggesting significant expiratory muscle recruitment and reach the maximal effective pressures (expiratory pressures that produce maximal flow, Pmaxe) over a significant portion of the tidal breath near peak exercise. This is in contrast to the young adult where expiratory pleural pressures do not become positive until near-maximal exercise and then
Pulmonary Consequences of Aging 93
only near EELV. The increase in expiratory pleural pres-sure development in the aged is out of proportion to the rise in expiratory flow so that resistance during expiration increases relative to the young adult at a similar level of ventilation [2]. Interestingly, despite the large positive pleural pressure produced on expiration and the degree of expiratory flow limitation, the older subject typically does not produce wasted effort (i.e., pressures in excess of effective pressures) suggesting a precise degree of expira-tory muscle regulation during heavy exercise [2].
Inspiratory Flow and Pressure Development
Both inspiratory flow (muscle shortening velocity) and lung volume (muscle length, expressed as a percent of TLC) increase during exercise causing the capacity for pleural pressure generation (Pcapi,) to decline [2]. Despite an increase in peak inspiratory flow to 4 l/s (fig. 1) and peak inspiratory pressures that reach 75% of TLC (fig. 2), at peak exercise the average fit young adult only ap-proaches 50% of the capacity of the inspiratory muscles to produce pressure [23]. Thus substantial reserve remains to increase ventilation through greater inspiratory pres-sure generation. In contrast the older adult, at a similar level of ventilation, approaches 80–90% of their dynamic capacity for pleural pressure generation (Pcapi) [2]. The cause of the reduced pressure generating capacity in the older adult is primarily due to the rise in EELV causing peak inspiratory pressure and EILV to reach much higher lung volumes (95% TLC). Thus, the strategy used to limit expiratory flow limitation, by increasing EELV, results in encroachment on TLC and the inspiratory capacity for pressure generation. Indirectly this is the result of the loss of elastic recoil.
Work and Cost of Breathing during Exercise
With low levels of exercise (ventilation !40 l/min) lit-tle difference is noted in breathing pattern and strategy between the young and older adult and therefore, the work and cost associated with breathing are small. As expiratory flow limitation occurs and breathing strategy is modified by increasing EELV and producing large expira-tory pressures, the work and cost of breathing accelerates.
Figure 3 demonstrates the work and O2 cost of breathing in our average fit, young adults and young athletes relative to older fit subjects [2, 19]. As shown, the work and cost associated with breathing accelerate in the older adults and by peak exercise these values are 50–60% higher than the young adult (at a similar ventilation). The increased metabolic demands of the younger athlete however result in a work and cost that exceeds the fit older adults, but at a
Fig. 3. Ventilatory work and the oxygen cost of breathing during pro-gressive exercise in 30-year-old untrained adults (dotted line), 26-year-old endurance athletes (dashed line), and 70-26-year-old moderate-ly fit older adults (solid line).
ventilation that is 50 l/min greater than our older subjects.
The cost of breathing was estimated at 13% of the total body VO2 in the older subjects (range 7–23%), 6% in the young average fit subjects (range 5–8%) at a similar venti-lation and 13% (range 10–16%) in the young athletes at peak exercise [2, 19, 24]. This represents a significant demand for blood flow to the respiratory muscles during exercise, which could theoretically compromise blood flow to the working locomotor muscles. Previous work by Saltin [25] has suggested that leg blood flow measure-ments at a given work intensity are reduced in the older subject, while extraction across the vascular bed is in-creased. Recent work by Proctor et al. [13] has confirmed that leg blood flow is reduced with aging for a given work intensity in older subjects (age = 63, n = 6) matched with young adults (age = 27, n = 6) for muscle mass, fitness and hemoglobin levels. Although speculative, it is likely that at least part of the reduction in leg blood flow with aging may be related to the increased work and cost of breathing in the older subjects. Work by Harms and colleagues [26–
28] has suggested that the respiratory muscles may prefer-entially recruit blood flow at the expense of the locomotor muscles. Figure 4 shows leg blood flow relative to whole body VO2 in older relative to younger subjects (fig. 4a) along with an estimate of the overall blood flow distribu-tion if the majority of the decline in leg blood flow with aging is due to the enhanced work and cost of breathing (fig. 4b) [13].
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Fig. 4. A Leg blood flow during cycle ergometry in young and older adults matched for muscle mass, fitness and hemoglobin. For a given oxygen consumption, leg blood flow is reduced in the older adults. It is hypothesized that some of the blood flow may be going to support the demands of the respiratory muscles in the older adults due to the high work and cost of breathing [13]. B Do the respiratory muscles preferentially ‘steal’ blood flow from the locomotor muscles? Esti-mated demands of the respiratory muscles (RM) relative to total car-diac output with age [estimated from 13, 26–28].
Fig. 5. Diffusing capacity of the lungs for carbon monoxide (DLCO) obtained by rebreathing at rest and during exercise relative to cardiac output in young, highly trained (triangles, n = 8) adults relative to older, average fit (squares, n = 7) healthy adults. DLCO is reduced at rest in the older adults, but increases in a linear fashion with progres-sive exercise similar to the young adults. From Johnson BD: Age-associated changes in pulmonary reserve; in Evans JG, Williams TF, Beattie LB, et al. (eds): Oxford Textbook of Geriatric Medicine, ed 2.
Oxford, Oxford University Press, 2000, pp 483–497, with permis-sion.
Pulmonary Gas Exchange
The changes in ventilation-perfusion relationships, re-duced surface area for diffusion, a stiffening of the pulmo-nary vasculature and increased dead space ventilation would theoretically limit the adaptations available to maintain gas exchange homeostasis in the elderly [9].
However, as will be demonstrated, despite these age-relat-ed changes, the reserve available to the respiratory system
to meet the demands of heavy exercise generally remain sufficient.
Dead Space and Alveolar Ventilation
In the limited studies that have measured this directly (with arterial blood gases), VD/VT drops with exercise similar to the decrease observed in the young adult [9, 29].
However, because baseline values are elevated, the values at peak exercise remain significantly elevated. The effect of the increased VD/VT on total ventilation becomes sig-nificant, especially as breathing frequency begins to in-crease during heavy and maximal exercise. In the young adult, at an average breathing frequency of 35 breaths per minute (bpm), VD approaches 7% of the total VE, and 13% in young athletes at a breathing frequency of 60 bpm.
In the aged adults, it approaches 30% of the VE by peak exercise [9].
Lung Diffusion (Effective Alveolar-Capillary Surface Area)
We have measured the diffusing capacity of the lungs for carbon monoxide (DLCO) using the rebreathe tech-nique in young endurance athletes and in a limited num-ber of healthy older subjects (age = 62, n = 9) of average
Pulmonary Consequences of Aging 95 Fig. 6. Alveolar (PAO2) and arterial oxygen (PaO2) tensions during
progressive exercise in young untrained adults (diamonds, maximum shown only), young endurance trained adults (open circles), and moderately fit older adults (solid circles) [9, 29]. From Johnson BD, Badr MS, Dempsey JA: Impact of the aging pulmonary system on the response to exercise; in Weisman IM, Zeballos RJ (eds): Clinics in Chest Medicine. Philadelphia, Saunders, 1994, vol 15, pp 229–246, with permission.
fitness (VO2max = 24 ml/kg/min). The relationship of DLCO to cardiac output is shown in figure 5 for the old (squares) and younger (triangles) subjects. Similar to what has been described using the single breath technique, DLCO is reduced at rest in the older subjects using the rebreathe technique. With increasing work intensities during exercise, DLCO increases in a linear fashion with the rise in cardiac output in both the young and older
fitness (VO2max = 24 ml/kg/min). The relationship of DLCO to cardiac output is shown in figure 5 for the old (squares) and younger (triangles) subjects. Similar to what has been described using the single breath technique, DLCO is reduced at rest in the older subjects using the rebreathe technique. With increasing work intensities during exercise, DLCO increases in a linear fashion with the rise in cardiac output in both the young and older