Effect of Aging on Lung Mechanics in Healthy Nonsmokers

doi:10.1378/chest.68.4.538

Chest

Volume 68, Issue 4, October 1975, Pages 538-541

https://doi.org/10.1378/chest.68.4.538 Get rights and content

The purpose of the present investigation was to determine the effects of aging on air flow limitation. In 22 healthy nonsmoking subjects, we constructed maximum expiratory flow-static recoil pressure curves. Analysis indicates that with aging there was a progressive increase in the critical transmural pressure. The conductance of the S segment was not dependent on age, with the exception of a significant increase in the oldest group. This is probably due to a more peripheral location of the equal pressure point secondary to a loss of lung recoil or to increased resistance, or both.

Section snippets

METHODS

Pulmonary function studies were obtained in 53 healthy nonsmoking adult volunteers (24 women and 29 men) aged 26 to 74 years. All subjects were asymptomatic and had no history of pulmonary, cardiovascular, hepatic, or renal disease. Chest roentgenograms obtained on all subjects were normal.

Pulmonary function studies performed in the sitting position included vital capacity (VC) and its subdivisions, functional residual capacity⁵ and airway resistance.⁶ The forced expiratory volume in one second

RESULTS

There were ten subjects in each decade, except for 13 between the ages of 61 and 74 years of age. The mean height for the 53 subjects was 171 cm (5 ft 7 in) ± 10 cm (± 1 SD). The mean FVC was 3.7 ± 1.1 L (89 ± 14 percent predicted); for FEV₁, 3.05 ± 0.94 L (95.0 ± 15.2 percent predicted); for TLC, 5.9 ± 1.2 L (99.0 ± 11.4 percent predicted); and for Dsb, 34 ± 9 ml/min/mm Hg (116 ± 23 percent predicted). The mean airway resistance was 1.4 cm H₂O/L/sec, with a range of 0.8 to 2.4 cm H₂O/L/sec.

DISCUSSION

Mead et al³ proposed a model of flow limitation with the equation, Vmax = Pst(l)/Rus, where Pst(l) is the lung elastic recoil pressure, which is the effective driving pressure producing Vmax, and where Rus is the resistance of the upstream segment (us segment), ie, the airway segment between the alveoli and the points where the transmural pressure is zero (equal pressure points, EPP). It is only downstream from EPP that dynamic compression of airways occurs and, therefore, flow limitation

References (23)

DL Fry et al.
Pulmonary mechanics: A unified analysis of the relationship between pressure, volume, and gas flow in the lungs of normal and diseased human subjects
Am J Med
(1960)
RE Hyatt et al.
Relationship between maximum expiratory flow and degree of lung inflation
J Appl Physiol
(1958)
J Mead et al.
Significance of the relationship between lung recoil and maximum expiratory flow
J Appl Physiol
(1967)
NB Pride et al.
Determinants of maximal expiratory flow from the lungs
J Appl Physiol
(1967)
AB DuBois et al.
A rapid plethysmograph method for measuring thoracic gas volume: A comparison with a nitrogen washout method for measuring functional residual capacity in normal subjects
J Clin Invest
(1956)
AB DuBois et al.
A new method for measuring airway resistance in man using a body plethysmograph: Values in normal subjects and in patients with respiratory disease
J Clin Invest
(1956)
JF Morris et al.
Spirometric standards for healthy nonsmoking subjects
Am Rev Resp Dis
(1971)
CM Ogilvie et al.
A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide
J Clin Invest
(1957)
AF Gelb et al.
Physiologic diagnosis of subclinical emphysema
Am Rev Resp Dis
(1973)
G Grimby et al.
Frequency dependence of flow resistance in patients with obstructive lung disease
J Clin Invest
(1968)

J Mead

Volume displacement body plethysmograph for respiratory measurements in human subjects

J Appl Physiol

(1960)

Cited by (23)

Further Studies of Unsuspected Emphysema in Nonsmoking Patients With Asthma With Persistent Expiratory Airflow Obstruction
2018, Chest
Citation Excerpt :
We believe the epiphenomenon of asthma-related lung tissue breakdown leading to mild emphysema can be explained by a proinflammatory, proteolytic cascade.20,21 This is similar to small airways-lung parenchymal uncoupling in smokers with loss of lung elastic recoil in early emphysema as described by Saetta et al.42 In normal aging lungs compared with younger lungs, the loss of lung elastic recoil23 may be related to nearly homogeneous acinar hyperinflation and alveolar ductal ectasia without alveolar breakdown and/or fracture.26,27 Similar lung CT densitometry studies in an aging population by Bellia et al43 have also confirmed these findings, and the lower limit of normal was –901 HU.
Previously, we and other investigators have described reversible loss of lung elastic recoil in patients with acute and persistent, moderate-to-severe, chronic, treated asthma who never smoked, and its adverse effect on maximal expiratory airflow. In four consecutive autopsies, we reported the pathophysiologic mechanism(s) has been unsuspected mild, diffuse, middle and upper lobe centrilobular emphysema.
We performed prospective studies (5 to 22 years) in 25 patients (12 female) with chronic asthma, age 55 ± 15 years, who never smoked, with persistent moderate-to-severe expiratory obstruction. Studies included measuring blood eosinophils, IgE, total exhaled nitric oxide (NO), central airway NO flux, peripheral airway/alveolar NO concentration, impulse oscillometry, heliox curves, lung elastic recoil, and high-resolution thin-section (1 mm) lung CT imaging at full inspiration with voxel quantification.
In 25 patients with stable asthma with varying type 2 phenotype, after 270 μg of aerosolized albuterol sulfate had been administered with a metered dose inhaler with space chamber, FVC was 3.1 ± 1.0 L (83% ± 13% predicted) (mean ± SD), FEV₁ was 1.8 ± 0.6 L (59% ± 11%), the FEV₁/FVC ratio was 59% ± 10%, and the ratio of single-breath diffusing capacity of the lung for carbon monoxide to alveolar volume was 4.8 ± 1.1 mL/min/mm Hg/L (120% ± 26%). All 25 patients with asthma had loss of static lung elastic recoil pressure, which contributed equally to decreased intrinsic airway conductance in limiting expiratory airflow. Lung CT scanning detected none or mild emphysema. In all four autopsied asthmatic lungs previously reported and one unreported explanted lung, microscopy revealed unsuspected mild, diffuse centrilobular emphysema in the upper and middle lung fields, and asthma-related remodeling in airways. In eight cases, during asthma remission, there were increases in measured static lung elastic recoil pressure-calculated intrinsic airway conductance, and measured maximal expiratory airflow at effort-independent lung volumes.
As documented now in five cases, unsuspected microscopic mild centrilobular emphysema is the sentinel cause of loss of lung elastic recoil. This contributes significantly to expiratory airflow obstruction in never-smoking patients with asthma, with normal diffusing capacity and near-normal lung CT scan results.
Protocol No. 20070934 and Study No. 1090472, Western Institutional Review Board, Olympia, WA; ClinicalTrials.gov; No. NCT00576069; URL: www.clinicaltrials.gov.
Unraveling the pathophysiology of the asthma-COPD overlap syndrome: Unsuspected mild centrilobular emphysema is responsible for loss of lung elastic recoil in never smokers with asthma with persistent expiratory airflow limitation
2015, Chest
Investigators believe most patients with asthma have reversible airflow obstruction with treatment, despite airway remodeling and hyperresponsiveness. There are smokers with chronic expiratory airflow obstruction despite treatment who have features of both asthma and COPD. Some investigators refer to this conundrum as the asthma-COPD overlap syndrome (ACOS). Furthermore, a subset of treated nonsmokers with moderate to severe asthma have persistent expiratory airflow limitation, despite partial reversibility. This residuum has been assumed to be due to large and especially small airway remodeling. Alternatively, we and others have described reversible loss of lung elastic recoil in acute and persistent loss in patients with moderate to severe chronic asthma who never smoked and its adverse effect on maximal expiratory airflow. The mechanism(s) responsible for loss of lung elastic recoil and persistent expiratory airflow limitation in nonsmokers with chronic asthma consistent with ACOS remain unknown in the absence of structure-function studies. Recently we reported a new pathophysiologic observation in 10 treated never smokers with asthma with persistent expiratory airflow obstruction, despite partial reversibility: All 10 patients with asthma had a significant decrease in lung elastic recoil, and unsuspected, microscopic mild centrilobular emphysema was noted in all three autopsies obtained although it was not easily identified on lung CT scan. These sentinel pathophysiologic observations need to be confirmed to further unravel the epiphenomenon of ACOS. The proinflammatory and proteolytic mechanism(s) leading to lung tissue breakdown need to be further investigated.
Pulmonary Function Testing
2015, Murray and Nadel's Textbook of Respiratory Medicine: Volume 1,2, Sixth Edition
Increased nitric oxide concentrations in the small airway of older normal subjects
2011, Chest
Citation Excerpt :
Furthermore, we42 have shown previously that reduction in static lung elastic recoil at 80% to 50% of total lung capacity was insignificant in healthy nonsmokers aged 26 to 59 years, despite reduction in expiratory maximum flow, especially at 60% and 50% of total lung capacity. However, with increasing age (60-76 years) there was significant loss of both static lung elastic recoil and Dlco, reflecting the loss of alveolar-capillary surface area.42 We suspect that with aging, there is reduction in the available capillary Hgb sink to absorb NO, and that this is the predominant mechanism explaining the increase in Cano.
There is a paucity of normal-age stratified data for fraction of exhaled nitric oxide (Feno). Our goal was to obtain normal data for large-airway nitric oxide flux (J'awno) and small-airway and/or alveolar nitric oxide concentration (Cano) in nonsmoking, healthy, adult subjects of various ages.
In 106 normal volunteer subjects (60 women) aged 55 ± 20 years (mean ± SD), Feno (parts per billion [ppb]) was measured at 50, 100, 150, and 200 mL/s and J'awno (nL/s) and Cano (ppb) were calculated using a two-compartment model with correction for axial nitric oxide (NO) back diffusion. Fourteen older normal subjects were also treated with inhaled corticosteroid (540 μg budesonide bid) for 14 days.
We studied 34 younger normal subjects (17 women) aged 18 to 39 years (younger), 26 middle-aged normal subjects (22 women) aged 40 to 59 years (middle-aged), and 46 older normal subjects (21 women) aged 60 to 86 years (older). Feno at 50 mL/s in the younger group was 21 (14-28) ppb (median, 1-3 interquartile); in the middle-aged group it was 22 (18-30) ppb, and in the older group it was 27 (21-33) ppb, (analysis of variance [ANOVA]) P = .02. For Feno, the younger vs older groups was (Mann-Whitney) P = .03, and Feno in the combined younger and middle-aged groups was 21 (15-29) ppb vs 27 (21-33) ppb, P = .006 for the older group. Corrected J'awno in the younger group was 1.5 (1.0-2.1) nL/s; in the middle-aged group it was 1.4 (1.0-2.0) nL/s, and in the older group it was 1.8 (1.2-2.4) nL/s, (ANOVA) P = .3. Corrected Cano in the younger group was 1.9 (0.8-3.0) ppb; in the middle-aged group it was 2.8 (0.8-5.1) ppb, and in the older group it was 3.9 (1.4-6.6) ppb, (ANOVA) P = .02. Cano in the younger vs older groups was P = .003, and the combined younger and middle-aged group result was 2.0 (0.8-3.8) vs 3.9 (1.4-6.6), P = .01 in the older group. There was no change in NO gas exchange with inhaled corticosteroids.
In nonsmoking healthy subjects with normal spirometry, Feno at 50 mL/s and Cano increased significantly with age ≥ 60 years, whereas J'awno did not. We suspect the increase in Cano was due to a decrease in capillary blood volume with reduced NO diffusion, which is also reflected in increased Feno. Inhaled budesonide had no anti-NO-mediated inflammatory effect. Age-matched control subjects will be needed in NO comparative studies.
ClinicalTrials.gov; No.: NCT00576069 and NCT00568347; URL: www.clinicaltrials.gov
Chronic Obstructive Pulmonary Disease in the Older Patient
2007, Clinics in Chest Medicine
Citation Excerpt :
The criteria chosen to define airflow limitation on spirometry, and therefore to diagnose COPD, are especially important in older patients. The FEV1/FVC ratio decreases with age, and this relative degree of airflow limitation is attributed to increased airway collapsibility in the normal aging lung [37,38]. Using a fixed FEV1/FVC ratio to separate normal from “obstruction” creates a risk for over-diagnosis of COPD in older subjects [39–41].
Risk factors for near-fatal asthma
2004, Chest
Citation Excerpt :
This value represents the range for reproducibility in healthy subjects in our laboratory when three to five separate deflation static lung elastic recoil pressure curves were obtained. For a comparison of lung elastic recoil in asthmatic patients aged 30 to 49 years with normal control values, we used our previously published normal results.91012 And for asthmatic patients aged 16 to 26 years, we obtained normal values from 11 nonsmoking healthy volunteers, who had normal findings for spirometry, diffusing capacity, and lung volumes.
There is a paucity of lung function data in patients, both before and after episodes of near-fatal asthma (NFA), requiring transient endotracheal intubation and mechanical ventilation.
Lung function was initially measured in 43 asthmatic patients (age range, 16 to 49 years), who were observed and treated in a tertiary referral asthma clinic and were clinically stable at the time of study. Subsequently, clinical and physiologic follow-up studies were obtained over > 5 years. The primary outcomes were to determine (1) the integrity of lung elastic recoil and (2) the severity of expiratory airflow limitation, and (3) to correlate these outcomes with adverse clinical complications.
Fourteen of 26 asthmatic patients (54%) [age range, 30 to 49 years] had significantly reduced lung elastic recoil pressures at all lung volumes compared to 3 of 17 asthmatic patients (18%); p = 0.02 [χ² test and Fisher exact test] [age range, 16 to 26 years]. In asthmatic patients between the ages of 30 and 49 years, significant loss of lung elastic recoil was noted in 4 of 10 patients with mild reduction in FEV₁ (FEV₁, > 79% predicted), 6 of 12 patients with moderate reduction in FEV₁ (FEV₁, 61 to 79% predicted), and all 4 patients with severe reduction in FEV₁ (FEV₁, < 61% predicted). In asthmatic patients between the ages of 16 and 26 years, significant loss of lung elastic recoil was noted in 0 of 11 patients with mild reduction in FEV₁, 2 of 5 patients with moderate reduction in FEV₁, and 1 of 1 patient with severe reduction in FEV₁. A subgroup of 10 asthmatic patients (7 men) [mean (± SD) age, 37 ± 11 years] were studied when clinically stable, both before and after an episode of NFA in 8 cases and only after an episode of NFA in 2 additional cases. In 1 of 10 cases, the FEV₁ was mildly reduced, in 4 cases it was moderately reduced, and in 5 cases it was severely reduced, both before and after an episode of NFA. The sensitivity was 90%, the specificity was 61%, the positive predictive value was 41%, and the negative predictive value was 95% for NFA with an FEV₁ ≤ 79% predicted or FEV₁/FVC ratio of < 75%. Prior to an episode of NFA, all 8 asthmatic patients had significant loss of lung elastic recoil pressure, and afterward all 10 had significant loss of lung elastic recoil pressure (ie, less than the predicted normal mean minus 1.64 SD at a total lung capacity [TLC] of 100 to 70% predicted). The sensitivity was 100%, the specificity was 79%, the positive predictive value was 59%, and the negative predictive value was 100% for NFA with the loss of lung elastic recoil. The mean TLC measured with a plethysmograph in 10 patients with NFA was 7.2 ± 1.41 (124 ± 16% predicted). The sensitivity for TLC of > 115% predicted was 70%, the specificity was 70%, the positive predictive value was 88%, and the negative predictive value was 41% for NFA.
A persistent reduction in FEV₁ of ≤ 79% predicted or an FEV₁/FVC ratio of < 75%, and, especially, the loss of lung elastic recoil and hyperinflation at TLC are risk factors for NFA. The loss of lung elastic recoil in asthmatic patients was associated with increased age, duration of disease, and progressive expiratory airflow limitation.

View all citing articles on Scopus

: Manuscript October 5, 1974; revision accepted January 30.

View full text

Chest

Clinical InvestigationsEffect of Aging on Lung Mechanics in Healthy Nonsmokers

Section snippets

METHODS

RESULTS

DISCUSSION

Am J Med

Relationship between maximum expiratory flow and degree of lung inflation

J Appl Physiol

Significance of the relationship between lung recoil and maximum expiratory flow

J Appl Physiol

Determinants of maximal expiratory flow from the lungs

J Appl Physiol

A rapid plethysmograph method for measuring thoracic gas volume: A comparison with a nitrogen washout method for measuring functional residual capacity in normal subjects

J Clin Invest

A new method for measuring airway resistance in man using a body plethysmograph: Values in normal subjects and in patients with respiratory disease

J Clin Invest

Spirometric standards for healthy nonsmoking subjects

Am Rev Resp Dis

A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide

J Clin Invest

Physiologic diagnosis of subclinical emphysema

Am Rev Resp Dis

Frequency dependence of flow resistance in patients with obstructive lung disease

J Clin Invest

Volume displacement body plethysmograph for respiratory measurements in human subjects

J Appl Physiol

Clinical Investigations
Effect of Aging on Lung Mechanics in Healthy Nonsmokers