2002 - the aging lung - the implications for diagnosis & therapy)

7/25/2019 2002 - The Aging Lung - The Implications for Diagnosis & Therapy)

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The Ag ing Lung: Im pl ica t ions ForD iag nosis and Trea t m ent o f Resp i ra t oryI l ln e sse s in t he Eld e r ly

I n t r o d u c t i o nRespiratory conditions are among theleading causes of morbidity and mortal-ity worldwide. Although they are cur-rently listed as the fifth leading cause ofdeath in Canada, respiratory diseases arepredicted to be the third leading cause ofmortality by the year 2020, followingischemic heart disease and stroke.1 Fur-thermore, since the prevalence of theseconditions increases with age, theadverse impact of respiratory illnesses onthe Canadian health care system willgrow enormously over the next fewdecades as the overall population ages2

and treatments for other common condi-

tions, such as ischemic heart disease,stroke and diabetes, improve. A goodunderstanding of the aging process of therespiratory system is clearly needed toformulate better strategies to prevent,diagnose and manage respiratory condi-tions in Canada.

Wh y a r e R e s pi r a tor y D ise a s e sso Pr e v a le nt in t he E lde r ly ?

The lungs of elderly persons are subjectto a lifetime of exposure to known and

unknown harmful agents. Decades maypass before the physical manifestationsof cigarette smoke, pollution and othernoxious environmental agents becomeclinically apparent. Furthermore, the res-piratory system of an elderly person mayhave battle scars from repeated boutsof upper and lower respiratory tractinfections, aspiration pneumonia, hyper-sensitivity reactions and other acuteinsults. The accumulated left-over

damages from these acute episodes maybuild up over the years to produce func-tional impairments. Elderly individualsalso may have many more comorbid ill-nesses than their younger counterparts.Comorbidities that affect oxygen deliv-erysuch as congestive heart failure,anemia or cardiac ischemiafrequentlyexacerbate dyspnea associated withunderlying respiratory conditions, andmake it more refractory to standard ther-apy. Finally, as we will discuss further, thepulmonary system ages physiologically,making elderly individuals susceptible tofrequent respiratory illnesses.

Phy s io log ic A ge - r e la te dC ha nge s o f the LungLung Parenchymal Changes

With the aging process, the elastin com-ponent of the lung matrix decreaseswhile the amount of type III collagenincreases,3 making the pulmonary sys-tem more compliant. Because of this, dur-ing respiratory cycles alveolar units canbecome destabilized, leading tofluid/mucous retention and atelectasis.Alveolar basement membrane also thick-

ens with aging,4 which reduces diffusioncapacity and may result in poor gasexchange (i.e., increased alveolar-arterialoxygen gradient). Indeed, the arterialoxygen tension (Pa02) decreases withaging independent of any superimposeddisease processes such as chronicobstructive pulmonary disease (COPD),pulmonary hypertension or heart failure.Even among elderly individuals withoutany associated lung disease, the alveolar-

arterial oxygen gradient is larger thanthat observed in the young, healthy pop-ulation, making it imperative that pre-diction equations for oxygen tension takeinto account age-related changes to Pa02.Carbon dioxide tension, on the otherhand, is not materially influenced by age.

A i r w a y s

Even in the absence of any material insultor injury to the airways, bronchiolardiameter diminishes significantly afterage 40, largely in response to decreasedelastin fiber deposition in the supportingconnective tissues.4 Physiologically, thisleads to a marked reduction in the teth-ering forces of the surrounding matrixto keep the adjacent airways patent. Thiscan increase airway resistance and pro-mote premature airway closure (Figure1), and as such, elderly individuals candemonstrate mild airflow obstruction atlow lung volumes even in the absence of

any disease. Since airway inflammationis not a prominent feature of age-relatedchanges in the airways, corticosteroidsand bronchodilators are largely ineffec-tive in reversing mild airflow obstructionassociated with aging.

Chest Wal l

There are two important components ofthe chest wall that become adverselyaffected with the aging process: thebony structures and the respiratory

muscles. With bone demineralizationand osteoporosis, kyphoscolioticchanges may become apparent in someelderly individuals, which may dimin-ish chest wall expansion and producelung restriction. Moreover, some maydevelop significant calcification andfusion of rib-vertebrae joints, which canproduce similar physiologic impair-ments. Although muscle fiber atrophyhas not been consistently demonstrated

Benjamin Chiam,MD, Department of Medicine, Pulmonary Division, University

of Alberta, Edmonton,AB.

Don D.Sin, MD, FRCP(C),Department of Medicine,Pulmonary Division,University

of Alberta, and The Insti tute of Health Economics,Edmonton,AB.

Biology of Aging


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The Aging Lung

with aging,5 there is a progressive lossin muscle fibers after the fifth decade,which probably explains the reducedrespiratory muscle strength associatedwith aging. Because the diaphragm isalso involved, additional ventilatoryloading (during acute illnesses) can

quickly lead to respiratory musclefatigue and respiratory failure in someelderly individuals.6

Vent i la to ry Responsiveness toHype rcapn ia and Hypox ia

Ventilatory responsiveness as well asneural output from central and peripher-al chemoreceptors are diminished withaging.7 The changes are most promi-nently observed with hypercapnia.8

Compared to healthy young individuals,elderly persons have a blunted ventilato-ry response to increases in carbon diox-ide. They also have a reduced perceptionof dyspnea associated with hypercapnia,hypoxia and/or airflow obstruction,which can delay their presentations to

health care providers for treatment of res-piratory infections.9 Such delays canmarkedly increase their risk for arrhyth-mias, respiratory failure and even sud-den deaths.

Paradoxically, during exertion theelderly have a more vigorous ventilatoryresponse to exercise compared toyounger individuals, which allows themto reach their ventilatory ceiling atlower workloads, thus limiting their

overall exercise capacity.10 Peak oxygenconsumption falls because of other age-related physiologic changes, includingloss of muscle mass, airflow obstructionand reduced stroke volume.

Pu lmona ry Vascu la tu re

Although the effects of aging on the pul-monary vasculature are not well under-stood, pulmonary vessels become lessdistensible and more constricted withaging, principally due to vascular wallremodeling. This may limit the individ-uals ability to increase cardiac outputduring exertion.11 However, age-relatedchanges in the pulmonary circulationusually have minimal impact on cardiacoutput at rest.11

Physiolog ic Effe cts of Aging on the Lung

Pulmonary artery

Lung Parenchyma

Alveoli

Int ima

Adventi t ia

Thickenedin t ima

Increasedcollagen

M edia(collagenstained pink)

basementmembrane

Reduced numberof folds Thickened

basementmembrane

elastin

collagen

reduced elastin

increased collagen

wi t h ag e

wi t h ag ewi t h ag e


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A g e - r e l a t e d Ch a n g e s i nPulmona r y Func t ionThere are two directly opposing forcesthat govern lung expansion and contrac-tion: elastic recoil pressure and expansiveforce of the chest wall. At end-expiration

(or functional residual capacity [FRC]),

the recoil pressure of the lung generatedby elastic fibers is balanced perfectly byan equal but opposite (expansive) forcegenerated by the chest wall. Because thelung recoil pressure decreases with agedue to a reduction in elastic tissues, FRC

increases. The residual volume (RV) is the

principal component of FRC that isincreased. Vital capacity (VC), on theother hand, remains the same or decreas-es slightly with aging12 (Figure 2). If FRCexceeds the closing volume (i.e., the lungvolume at which airways begin to close),

premature airway closure can occur dur-ing normal expiration, leading to flow-limitation.

Owing to age-related physiologicchanges to the airways, forced expirato-ry volume in one second (FEV1), forcedvital capacity (FVC) and FEV1 to FVCratio also decrease with age. FEV1 isreduced by approximately 1530cc/yearamong non-smoking men and 1020cc/year among non-smoking women.13

The decline in FEV1 accelerates after age65 and is further exacerbated by smok-ing. Inspiratory and expiratory pressuresalso decrease with age, reflecting thedecline in respiratory muscle strength.The reduced surface area and increasedthickness of alveolar walls cause a declinein diffusing capacity from midlife at arate of 2.03mL/min/mmHg per decadein men and 1.47mL/min/mmHg perdecade in women.14

I m p a ct o f A g e o n D i a g n o si s o fR e spi r a t or y D is or de r s

Obst ruc t i ve A i rw ay D iseasesMost of the deaths in asthma and COPDare among elderly patients. There is ageneral under-recognition and under-treatment of these disorders in the elder-ly, which may, in part, be related todecreased patient perception and report-ing of symptoms and to the frequentoccurrence of comorbidities that mayconfound the diagnosis and lead to anunder-appreciation of disease severity.15

Decreased perception of airflow obstruc-

tion, hypoxia and hypercapnia may alsolead to a significant delay in elderlypatients seeking medical care. Even whencare is sought, the patients may trivializethe significance of their symptoms, lead-ing to inappropriate management.15

Whenever possible, clinicians shouldsupplement patients history with objec-tive measurements of lung functionthrough spirometric testing in order toestablish disease severity.

Young Older

Young Older

A.

B.

Figure 1

(A) The schematic represents a cross-sectional view of a small airway. Note thatreduction of tethering effect reduces the airway diameter. (B) The practical implicationof reduced tethering is demonstrated when expiration increases transpulmonarypressure (arrows). Smaller diameter airways are at higher risk of obstructing.


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Despite the usefulness of lung func-tion data in the evaluation of elderly indi-viduals with dyspnea or cough,spirometric testing is an underutilizedresource in the community. Therefore, thediagnosis of obstructive airway disease is

frequently overlooked or missed entire-ly.16 In the setting of symptoms (i.e., dys-pnea and/or cough), an FEV1 to FVCratio of less than 0.70 indicates airflowobstruction. Complete reversal of airflowobstruction with bronchodilators is high-ly suggestive of asthma. Incompletereversal, on the other hand, is suggestiveof COPD. Aclear distinction betweenasthma and COPD is often difficult in theelderly patient because their symptomsare very similar and, even with pureasthma, airflow obstruction is rarely com-pletely reversed. Moreover, unlikeyounger individuals with asthma, theprevalence of allergy and atopy is low inthe elderly population and very few reactpositively to immediate skin testing orhave detectable circulating IgE levels.15

Bronchoprovocation with methacholineor histamine may be used in cases wherethe diagnosis of hyper reactive airwaydisease is ambiguous. Despite importantphysiologic changes in the airway,bronchial responsiveness remains stable

with age.17

Pneumon ia

The elderly individual is at increased riskof developing pneumonias. The patho-physiology of pneumonia among the eld-erly is complex. However, it is wellknown that with aging, immunitywanes.15 Not only do neutrophils andlymphocytes decrease in number, theyalso become less functional. Tonically andwith antigenic challenge, the production

(and release) of cytokines andchemokines diminishes with age, mak-ing it difficult for elderly individuals tomount a serious immune response to vir-ulent pathogenic organisms.18 Immunityis further compromised by a negativenitrogen balance, resulting from poorappetite and cachexia, commonlyobserved in the frail elderly population.19

Gag reflex and swallowing mechanismmay also be suboptimal in some elderly

individuals, making them susceptible toaspiration pneumonias.19 Those in nurs-ing homes and other long-term care cen-tres have an increased risk of nosocomialpneumonias, which are associated withvery poor clinical responses and out-comes.20

I m p a ct o f A g e o n Tr e a t m e n t o fR e spi r a t or y D is or de r sObst ruc t i ve A i rw ay D iseases

Management of elderly patients withobstructive airway disease should be

similar to that of younger patients. Prop-er education and follow-up are of para-mount importance in the elderly. There isa higher rate of adverse reactions in theelderly compared to the non-elderly pop-ulation due to a variety of factors, includ-ing altered drug metabolism, potentialfor multiple drug interactions and pres-ence of comorbidities. Elderly patientsmust be followed carefully to monitor forany significant toxic effects related totheir pulmonary medications. As well,

they should be instructed regularly onthe proper use of the inhaler devices.Some elderly patients have poor eyesightor have poor hand to eye coordination;they may also have trouble holding theirbreath for the required period of time,resulting in suboptimal inhaler use andinadequate delivery of medications to thesites of active disease.15

As a general rule, systemic adminis-tration of bronchodilators is best avoided

in the elderly, as many have co-existingcardiovascular conditions that increasetheir risk for life-threatening arrhythmiasand ischemic events.21 When theo-phyllines are used, their levels should bechecked regularly. Co-administration oftheophyllines with cimetidine,ciprofloxacin, allopurinol and other med-ications can unintentionally elevate theo-phylline levels beyond the toxicthreshold, leading to nausea, vomitingand in serious cases, seizures and life-threatening arrhythmias.22

In many cases, prolonged use of sys-temic corticosteroids also should beavoided. Many elderly patients haveunderlying risk factors for diabetes,hypertension, peptic ulcer disease, osteo-porosis, cataracts, glaucoma and psychi-atric illnesses, all of which can beexacerbated by systemic corticosteroidtherapy. If steroids must be used, the low-est possible dose should be employed.Concomitant therapy with a bone-spar-ing medication such as calcium supple-

ments and/or bisphosphonates shouldbe instituted for at least the duration oftheir systemic steroid therapy. Inhaledcorticosteroids should be used for elder-ly patients with asthma. They appear toexert a beneficial effect in moderate tosevere COPD. Although inhaled corti-costeroids have a safer toxicity profilethan the systemic formulations, they, nev-ertheless, can decrease bone mass andincrease the risk for cataracts and glau-

IRV

TV

ERV

RV

IRV'

TV '

ERV'

RV'

Young

FRC

VCVC'

FRC'

Older

Figure 2

Ag e - r e l a t e d Ch a n g e s i n Lu n g V o l um e s

IRV: Inspiratory reserve volume; TV: Tidal volume; ERV: Expiratory reserve volume;RV: Residual volume; VC: Vital capacity; FRC: Functional residual capacity.


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coma.23 It is also important to note thatcertain commonly used medications,such as topical beta-blocking agents andnon-steroidal anti-inflammatories, canexacerbate underlying obstructive airwaydisease.

Pneumon ia

Because pneumonia is a common prob-lem among the elderly, vaccinationshould be considered. Although elderlyindividuals have diminished humoralimmune responses to vaccines in gener-al, influenza vaccination is still very effec-tive in preventing clinically relevant andsevere influenza infections. Accordingly,all individuals 65 years of age and oldershould receive yearly influenza vaccina-tion, regardless of their clinical status.24

The clinical efficacy of pneumococcalvaccination is modest. However, it hasbeen demonstrated to be effective in pre-venting pneumococcal sepsis and possi-bly reducing lung infections. Elderlypatients, and especially those with sig-nificant comorbid illnesses, shouldreceive pneumococcal vaccination.

S u m m a r y

In summary, because of the physiologiceffects of aging on the respiratory system

and accumulated exposures to harmfulinfectious and non-infectious respiratoryagents, obstructive airway disease andother respiratory conditions are commonin the elderly population. In the presenceof dyspnea and/or cough, spirometryshould be used to confirm the diagnosisof obstructive airway disease and thera-py should be instituted, when necessary.If medications are implemented, the low-est possible dose should be used andtheir effects need to be carefully followed

and monitored.

No competing financial interests declared.

R e fe r e nc e s

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