With the high prevalence of older horses and potential for increasing lifespan of elderly horses presented to veterinarians,[1, 2] a thorough understanding of normal aging-related changes is of paramount importance. Aging results in structural and functional modifications in all mammals. These changes must be recognized as normal features of aging rather than pathologic changes.
Aging-related changes in pulmonary function are well characterized in human medicine. Aging of the lungs is associated with decreased pulmonary elastic recoil, chest wall compliance, and respiratory muscle strength, as well as an increase in alveolar dead space.[3, 4] The basis for these functional changes includes loss of elastin content and resultant increase airspace dimensions. Functional consequences of the morphologic alterations in the lungs of older people include increased residual volume and functional residual capacity, decreased maximal expiratory flow rate and forced vital capacity, lower diffusion capacity, and higher ventilation/perfusion mismatch. Although no clinical signs are seen in healthy subjects as a result of these functional changes, there is a decrease in the reserve capacity of the lung in the presence of disease and these changes may impact exercise capacity. In conjunction with this decline in lung function, over 45% of elderly humans demonstrate an increase in airway responsiveness to nonspecific agonists such as histamine. Moreover, elderly humans have been shown to have increased airway inflammation.[7, 8]
In the horse, aging-related changes in pulmonary structure and function are poorly characterized. To our knowledge, only 2 studies have been performed that addressed aging-related changes to the respiratory system of horses. These studies indicate that older horses experience both functional and biochemical changes with age. One study showed that horses >20 years of age have lower arterial oxygen and carbon dioxide partial pressures and higher alveolar to arterial pressure gradient compared with horses 3–8 years of age. The other study included horses of 6–25 years of age and showed that surfactant phospholipid content decreased with age in horses. The age-related changes in lung function (ie, spirometry), airway reactivity, and BALF cytology in mature horses have not been investigated previously. The purpose of this study was to investigate the influence of aging on arterial blood gases, lung function, response to histamine bronchoprovocation, and cytology of BALF.
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- Material and Methods
To our knowledge, this is the first study to investigate changes in respiratory function and BALF cytology of horses that may be a function of the aging process. The diagnostic tests used in our study were selected based on their portability and usability in field conditions to better recruit healthy horses. Therefore, this study was aimed at providing information to the equine practitioner who is called to investigate clinical signs of respiratory disease in the geriatric horse. Although it is acknowledged that this is a small cross-sectional study, the findings suggest that differences between young and old horses are not likely to be biologically relevant for the endpoints examined. Thus, clinical changes in an aged horse with regard to its respiratory system should raise concern that these changes are more likely to be disease related rather than aging related.
In contrast to a previous report, our study showed no difference between the ABG results of young and aged horses. A possible explanation of this contradiction is the different age ranges of the horses included in each study. In the Aguilera-Tejero et al study, the age range was narrower in the young group (3–8 years versus 2–11 years in this study) and wider in the aged group (20–45 years versus 20–28 years in this study) when compared to our study. It would be interesting to evaluate horses >30 years of age to see if extreme age changed the ABG results. Also, the Aguilera-Tejero study corrected ABG results to rectal temperature, whereas ours did not. This could account in part for the different conclusions of these 2 studies. Temperature correction of ABG results is a controversial issue in human medicine[14, 15] and is likely unnecessary when the patient's temperature is measured within 1°C of 37°C which was the case of the horses in our study (mean ± SD, 37.3 ± 0.3°C; range, 36.6–38°C). Studies in geriatric dogs have not shown a significant difference in PaO2 or PaCo2 results compared to younger dogs.[16, 17] There is a well-characterized age-related decrease in the PaO2 of humans that reaches a plateau as humans reach their early-mid 70s.[18, 19]
The slightly greater Te observed in aged horses observed in this study is likely of no clinical relevance, because this value was within reference ranges previously reported for healthy horses[20, 21] and Te/Ti ratio was not different between groups. The higher Te may be a result of slightly lower respiratory rate (not statistically significant) observed in aged group after administration of sedation for RIP. The lower minute ventilation also may be explained in this manner. The absence of differences in the remainder of RIP-derived parameters is in agreement with reports in humans, where RIP showed no difference in the breathing pattern or ventilatory parameters between healthy young and healthy geriatric subjects.[22, 23]
There were no differences in the PC35 and PC50 values or the number of hyper-reactive horses in each of the groups. These findings are in contrast to the conclusion of a review article on the influence of age on airway reactivity in humans, which showed a positive association between age and airway hyper-reactivity. Several studies included in the review point to a bimodal distribution of airway reactivity, which appears to be highest in the early (children and adolescents) and late (elderly) phases of life. A trend for bimodal distribution of airway reactivity in the horse was not observed in the population studied as none of the 5 youngest horses (2–3 year old) or the 2 oldest horses (28 years old) from our study was hyper-reactive; however, no foals or horses >28 years of age were included in this study. In an earlier study, airway reactivity in foals (48–92 days old) was measured using more classical methods (resistance-compliance). Mean provocative dosage of histamine that induced a 35% decrease in dynamic compliance (comparable to PC50) was considerably lower for foals on average (5.4 ± 1.74 mg/mL) than adults in this study, which strongly resembles the patterns in humans. Interestingly, young cats (1–2 years) have much higher airway reactivity than geriatric cats (12–13 years). It was thought that age-related changes in airway reactivity in cats may explain the higher rate of spontaneous asthma-like conditions in younger cats. In the horse, inflammatory airway disease is more common in the young to middle-aged horse, but recurrent airway obstruction occurs more often in the older horse, implying that the functional and cytologic changes in these diseases are not directly related to aging.
The percentage of lymphocytes was higher and the percentage of macrophages was lower in the BALF of aged horses, with the mean percentages of lymphocytes being slightly higher than the reference values of 30–50% lymphocytes previously reported for the horse. Higher percentage of lymphocytes and a lower percentage of alveolar macrophages also have been reported in the geriatric human.[7, 28] The higher lymphocyte percentage in BALF of aged subjects may be caused by the cumulative antigenic stimulation over many years and the lower macrophage percentage is probably the reciprocal to the higher lymphocyte percentage and higher but not significant neutrophil percentage.
Asymptomatic airway hyper-reactivity has been documented in humans and seems to precede the occurrence of asthma usually by several years. The clinical relevance of the hyper-reactivity observed in several of the asymptomatic horses in our study is unknown, because no longitudinal studies with hyper-reactive horses have been performed to identify if they will develop inflammatory airway disease or recurrent airway obstruction. The lack of correlation between airway reactivity and BALF cytology previously has been reported in healthy humans. However, when asthmatic human subjects in remission were submitted to bronchoprovocation after exposure to an allergen, the increase in airway responsiveness was associated with an influx of eosinophils and lymphocytes in the bronchial lumen. In symptomatic horses, the only type of BALF cells that correlated with airway reactivity was mast cells as demonstrated in previous studies.[30, 31]
Environmental factors contribute to the development of lower airway inflammation in the horse. A limitation of our study is that environmental conditions that may have impacted pulmonary function or cytology were not standardized. To minimize the effect of possible environmental factors on the results of the tests, similar numbers of aged and young horses from each farm were included in the study. We also analyzed the amount of time spent in turnout and ambient conditions during the test period, both of which were similar for both groups. However, we cannot exclude the possibility that the data were biased by specific differences in the particulate matter inhaled by 1 group versus the other because there still could be differences in particulate exposure even between neighboring stalls.[32, 33] Future studies that carefully document particulate exposure at the personal breathing level would augment studies which attempt to examine the effects of age or other cohorts.
The results of this study suggest that the only aging-related changes in the horse detected with the diagnostic tests performed are a higher percentage of lymphocytes and a lower percentage of alveolar macrophages in the BALF. In conclusion, it is likely that any abnormalities detected on ABG values, RIP-derived variables, or bronchoprovocation results in a clinically affected aged horse are related to the disease process and not directly a result of aging, within the age categories studied here. Additional studies involving larger number of horses within a wider age range are warranted to validate these findings.
Conflict of Interest Declaration: Authors disclose no conflict of interest.