Table 3 Lung capacities are sum of two or more static lung volumes Inspiratory capacity (IC) TV + IRV Functional residual capacity (FRC) RV + ERV Vital capacity (VC) TV + IRV + ERV Total lung capacity (TLC) TV + IRV + ERV + RV Abbreviations: ERV, expiratory reserve volume; IRV, inspiratory reserve volume; RV, residual volume;TV, tidal volume. lung volume (TLC) and alveolar ventilation. Diffusion across the alveolar–capillary interface is directly proportional to the alveolar surface and inversely proportional to the alveolar–capillary membrane thickness. Stam et al (1994) studied effect of age on diffusion capacity in 55 healthy subjects (age ≥70 yrs, n=3) and showed a decline in DLCO with age corrected for alveolar volume. This suggests alteration in the alveolar–capillary membrane as the potential mechanism, though not proven. Dyspnea and response to hypoxia and hypercapnia Minute ventilation, a product of volume inhaled per breath and respiratory rate over one minute, is identical in younger and older individuals. There is no change in tidal volume with age, and older individuals maintain the required minute ventilation by increasing the respiratory rate. The ventilatory response to lower oxygen tension or raised carbon dioxide tension is markedly impaired in older adults. Kronenberg and Drage (1973) studied 8 healthy young and 8 older subjects and noted a 50% reduction in response to hypoxia and 40% reduction in response to hypercarbia. These results were confirmed by Peterson et al (1981) in a study of older healthy adults. Aging is associated with loss of potentially protective mechanisms and this patient population is more likely to be exposed to these states, making them more vulnerable. The likely explanation of reduced response is age-related decline in efferent neural output to respiratory Aging and respiratory system muscles during hypoxic or hypercarbic states, supported by the fact that older adults generate lower occlusion pressure compared with younger individuals during these states (Peterson et al 1981). Bronchial hyper-responsiveness and age-related pulmonary receptor changes Age had a significant effect on airway reactivity and response to bronchodilator therapy. Airway reactivity is studied using methacholine challenge in the pulmonary function laboratory. Most individuals will experience bronchospasm to inhaled methacholine, and the dose required to cause significant reduction in FEV1 (ie, 20% reduction from the baseline) determines the bronchial reactivity. Lower doses signify increased bronchial reactivity and higher likelihood of asthma. Hopp et al (1985) retrospectively studied the cumulative methacholine dose required to produce a 20% decline in FEV1 in 148 healthy subjects (age ≥70, n=7) and showed a hyperbolic curve, suggesting that younger and older individuals required lesser methacholine doses to cause significant bronchoconstriction compared with middle-aged individuals. Not only do older individuals require a lower cumulative dose to cause bronchoconstriction, they take longer to recover post β- adrenergic agonist therapy (Connolly et al 1995). The exact mechanisms of these findings are unclear. It is speculated that this is likely due to age-related β-adrenergic receptor dysfunction. β-adrenoreceptor β-adrenoreceptor stimulation by agonist or antagonist is mediated through cyclic adenosine monophosphate (AMP) production. Adenosine triphosphate (ATP) is converted to cyclic AMP by catalytic unit of adenylate cyclase in the presence of a ligand. The β-adrenoreceptor can exist in two Table 4 Lung function studies Study Time Morris et al Crapo et al Knudson et al Dockery et al Burrows et al Ware et al Enright et al 1969–70 1979–80 1972–75 1974–76 1972–84 1974–83 1989–90 Cross-sectional (C)/ Longitudinal (L) C C C C L L C Age range 20–84 18–91 6–88 25–74 20–72 25–74 65–85 N 988 251 421 2454 466 2454 777 Note: Adapted from Kerstjens HAM, Rijcken B, Schouten JP, et al. 1997. Decline of FEV by age and smoking status: facts, figures, and fallacies. Thorax, 52:820-7. Copyright © 1997. Reproduced with permission from BMJ. Clinical Interventions in Aging 2006:1(3) Age ≥65 years Decline 79 68 - 430 - 430 777 Linear Linear Linear Nonlinear Nonlinear Nonlinear Linear 257