Effects of Aging on the Respiratory System

Introduction

I. Upper Airway Changes

• Impaired protective reflexes: Cough and swallowing reflexes are blunted with age. The sensory arc (controlled by cortical and subcortical structures, not merely brainstem) is more vulnerable to aging than the motor arc.
• Increased aspiration risk: Aspiration of oropharyngeal contents becomes increasingly common and may be silent (without symptoms) due to blunted sensory function.
• Gastroesophageal reflux: Reflux esophagitis severity increases with age while heartburn severity paradoxically decreases, due to sensory impairment. Esophageal motor abnormalities worsen reflux. Recurrent aspiration leads to airway inflammation, bronchiectasis, and pneumonia.

II. Structural Changes in the Lung

• Shape: Increased anteroposterior diameter causes "rounding" of the lung, secondary to thoracic cage changes (kyphosis from vertebral fractures - 25% have severe kyphosis >50 degrees after age 75).
• Conducting airways: Slight increase in size of larger airways with age (modest increase in anatomic dead space); calcification of cartilaginous walls; hypertrophy of bronchial mucus glands - these have little physiologic significance.
• Ciliary motility: Significantly reduced in both upper and lower airways with aging, impairing mucociliary clearance.
• Lung parenchyma / Alveoli (Senile Emphysema):
  • The most important structural change: enlargement of terminal airspaces - previously called "senile emphysema."
  • Unlike centrilobular emphysema of smokers, this is a uniform process involving all lung zones, without destruction of alveolar walls.
  • There is reduction in alveolar surface area: from ~70 m² at age 30 to ~60 m² at age 70.
  • This results from widening of alveolar ducts rather than alveolar wall destruction.
  • The result: ventilation/perfusion (V/Q) mismatch and impaired gas exchange.

III. Changes in the Bellows Apparatus (Chest Wall and Respiratory Muscles)

• Chest wall stiffness increases due to: calcification of costal cartilages, progressive kyphoscoliosis from vertebral changes, and increased rib-to-vertebral joint rigidity.
• Respiratory muscle strength decreases: maximum static inspiratory and expiratory pressures decline with age. There is loss of diaphragm muscle mass and strength.
• Net effect: the work of breathing increases even at rest.

IV. Changes in Lung Mechanics and Pulmonary Function Tests

• Loss of elastic recoil is the dominant mechanical change. The lung becomes more compliant (floppy), and the chest wall becomes less compliant (stiffer).
• The closing volume rises with age and may exceed FRC in the supine position, causing airway closure during normal tidal breathing. This is a major cause of V/Q mismatch and hypoxemia.
• In interpreting PFTs in the elderly: the GLI (Global Lung Initiative) reference equations should be used as standard reference values. The elderly are under-represented in most reference datasets.

V. Gas Exchange

• PaO2 decreases with age. A useful estimate: PaO2 (mmHg) = 100 - 0.32 x age (years), or approximately 104.2 - (0.27 x age).
• PaCO2 remains unchanged in healthy aging.
• The alveolar-arterial (A-a) gradient widens with age (normal A-a gradient = 2.5 + 0.21 x age in years).
• Mechanism: predominantly V/Q mismatch from early airway closure and loss of alveolar surface. True shunt plays a minor role.
• Diffusing capacity (DLCO) decreases with age due to reduced alveolar surface area and reduced pulmonary capillary blood volume.

VI. Ventilatory Control

• Blunted ventilatory responses to both hypercapnia and hypoxia - one of the most important and clinically dangerous changes.
• Classic studies (Kronenberg & Drage, 1973): Elderly men (64-73 yr) showed markedly diminished ventilatory responses to hypoxia compared to young controls (22-30 yr) during isocapnic progressive hypoxia.
• The deficit is specifically in tidal volume response (not respiratory rate), indicating reduced respiratory drive/neural output from the respiratory center.
• Occlusion pressure (P100) responses to both hypoxia and hypercapnia are significantly reduced in the elderly, even when corrected for reduced respiratory muscle strength - confirming this reflects diminished central respiratory drive.
• It is uncertain whether this reflects altered chemoreceptor (peripheral) function or altered respiratory center (central) function.
• Clinical significance: Elderly patients may develop severe hypoxemia or hypercapnia with less warning (dyspnea), and are at greater risk of respiratory failure during intercurrent illness.

VII. Sleep and Breathing

• Sleep quality decreases with age: increased nocturnal awakenings, decreased total sleep time, reduced sleep efficiency.
• Stage 3 and 4 (slow-wave / delta) sleep decreases markedly with aging; changes begin as early as age 20.
• Prevalence of sleep-disordered breathing increases dramatically:
  • Community-based studies in individuals aged 71-87 show 55% prevalence of sleep-disordered breathing by polysomnography (38% obstructive sleep apnea, 17% central sleep apnea).
  • In nursing home residents: 42% had apnea index >5/hr.
• Sleep apnea in the elderly is complicated by the use of sedatives/hypnotics (common in elderly women) which can worsen apnea.
• Altered circadian rhythms (temperature, cortisol, TSH) also contribute to sleep disruption.

VIII. Cardiovascular Interactions

• Age-related cardiac changes compound the respiratory effects:
  • Decreased maximum heart rate (220 - age = estimated maximal HR)
  • Decreased maximal cardiac output
  • Decreased responsiveness to hypoxemia at the cardiac level
• The combined effect is reduced maximal exercise capacity and oxygen delivery.

IX. Biology of Lung Aging (Molecular/Cellular)

• Cellular senescence in lung cells (type II pneumocytes, endothelial cells, fibroblasts) with age.
• Telomere shortening: a marker of cumulative cell division and biological aging; reduced telomere length is linked to accelerated lung function decline and increased susceptibility to fibrosis.
• Oxidative stress accumulates with age, damaging lipids, proteins, and DNA.
• Altered protease-antiprotease balance: reduced alpha-1-antitrypsin activity and altered matrix metalloprotease regulation contribute to connective tissue changes.
• Extracellular matrix (ECM) remodeling: loss of cross-linked elastin results in increased lung compliance; increased collagen cross-linking contributes to chest wall stiffness.
• Impaired immune and inflammatory responses: reduced mucociliary clearance, impaired macrophage function, blunted innate and adaptive immune responses - increasing susceptibility to pneumonia, influenza, and atypical infections.

X. Interpreting PFTs in the Elderly

• The elderly are under-represented in reference value studies; values after age 80 are essentially extrapolations.
• GOLD spirometry thresholds (FEV1/FVC <0.70) may over-diagnose COPD in elderly as a fixed ratio does not account for physiologic age-related decline.
• LLN (Lower Limit of Normal) approach using age-specific predictions is preferred.
• Effort-dependence of spirometry is greater in elderly subjects; technical quality must be carefully assessed.

Summary Table (Fishman's Table 18-1)

Key Points for 10-Mark Answer

1. Upper airway: Impaired cough/swallowing reflexes → aspiration risk; reduced ciliary clearance.
2. Structure: Senile emphysema (uniform airspace enlargement, no wall destruction); reduced surface area (70 → 60 m²); kyphosis.
3. Mechanics: Increased lung compliance (lost elasticity) + decreased chest wall compliance (stiffer) = increased work of breathing; rising closing volume.
4. PFTs: FEV1 declines ~30 mL/year; RV increases; VC decreases; DLCO decreases; FRC increases.
5. Gas exchange: PaO2 falls with age; A-a gradient widens; V/Q mismatch (main mechanism); PaCO2 unchanged.
6. Ventilatory control: Blunted hypoxic and hypercapnic ventilatory drive; reduced tidal volume response; reduced P100 - major clinical danger.
7. Sleep: Increased sleep apnea (obstructive and central); reduced slow-wave sleep.
8. Respiratory muscles: Reduced inspiratory and expiratory muscle strength; diaphragmatic weakness.
9. Immunologic: Impaired innate immunity, reduced macrophage function, decreased mucociliary clearance → increased infection susceptibility.
10. Molecular: Telomere shortening, oxidative stress, cellular senescence, ECM remodeling underlie all structural changes.