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Airway distensibility and lung inflation effects on the maximal expiratory flow volume curve in elderly adults

Award Number: R21AG083488
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Airway distensibility and lung inflation effects on the maximal expiratory flow volume curve in elderly adults - PROJECT SUMMARY Both the total number of elderly persons and the incidence of lung disease will increase in the coming decades. It is vital that we define the normal physiological changes that take place in the aging respiratory system. Peak lung function occurs in early adulthood and progressively declines with age. The decreased lung function is readily apparent in the maximal expiratory flow volume curve (MEFV), depicting decreases in maximal expiratory airflow (MEF) at all lung volumes in elderly adults. Clinically, the reduced MEF is attributed to a concomitant, progressive loss of lung elastic recoil. However, in young-to-middle aged adults, the inhalation to total lung capacity that precedes a maximal forced expiration causes a transient airway dilation. The deep inflation-induced airway dilation results in higher MEF than can be achieved in the absence of the deep inflation (DI). The effects of normal aging on the dynamic interaction between a DI and MEF is not known. This is problematic, since the MEFV curve is interpreted assuming that the airway response to a DI is equal across the aging spectrum. We hypothesize that one cause of the decreased MEF with aging is a blunted airway dilatory effect of a DI. If this hypothesis is true, it would indicate that the MEFV curve exaggerates the reduced MEF in elderly adults. Three specific aims will test our hypothesis. Aim 1 will compare the effect of a DI on the MEFV curve in young and elderly adults. We hypothesize that a DI will increase MEF in young adults whereas it will decrease MEF in elderly adults. The effect of a DI on airway caliber will be quantified by comparing MEF after a DI with MEF during a forced expiration begun at normal end-inspiratory lung volume (maximal:partial [M:P]). All M:P measurements will be analyzed at 40% of vital capacity. Aim 2 will determine the effect of aging on the bronchodilatory effect of a DI. In young adults, a DI exerts a bronchodilatory effect on airways that have been constricted by inhaled methacholine (airway smooth muscle agonist). We hypothesize that the bronchodilatory effect of a DI will be reduced in elderly adults. Inhaled methacholine will be used to cause bronchoconstriction. M:P measurements will be used to determine the magnitude of DI-induced bronchodilation (as in SA1). If findings support our hypothesis, they will provide evidence that aging is associated with the loss of an essential mechanism for preserving airway function. Aim 3 will compare airway distensibility in young and elderly adults. We hypothesize that airway distensibility will be lower in elderly adults than young adults. Using impulse oscillometry, airway distensibility will be quantified as the change in airway conductance relative to the change in lung volume (∆Grs/∆VL), [l·cmH2O-1·s-1·l-1]). These experiments will generate insight into the effects of aging on the strength of coupling between the airways and the surrounding elastic tissues. This proposal will generate novel data that addresses the question: Is interpretation of the MEFV curve inaccurate in elderly patients? The findings will lend insight into the mechanisms for the maladaptive changes to lung function with aging and might significantly impact clinical interpretation of spirometry in elderly adults.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $191,471 )
2025	2025	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Aging Research	000	2	7/31/2025	NON-COMPETING CONTINUATION	$191,471
														Subtotal = $191,471

Issue Date FY: 2024 ( Subtotal = $235,026 )
2024	2024	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Aging Research	000	1	8/21/2024	NEW	$235,026
														Subtotal = $235,026

Grand Total All Awards = $426,497

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Airway distensibility and lung inflation effects on the maximal expiratory flow volume curve in elderly adults

Award Number: R21AG083488

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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