neumonitis

1. Review
Update on the pathogenesis and management of
pneumonia in the elderly-roles of aspiration
pneumonia
Shinji Teramoto, M.D., Ph.D.a,n
, Kazufumi Yoshida, M.D.b
,
Nobuyuki Hizawa, M.D., Ph.D.c
a
Department of Pulmonary Medicine, Hitachinaka Medical Education and Research Center, University of Tsukuba,
20-1 Hitachinaka-shi, Ibaraki 329-8575, Japan
b
Department of Pulmonary Medicine, Hitachinaka General Hospital, Hitachi Ltd., Ibaraki, Japan
c
Department of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki,
Japan
a r t i c l e i n f o
Article history:
Received 17 December 2014
Received in revised form
20 January 2015
Accepted 21 January 2015
Keywords:
Aspiration pneumonia
Dysphagia
Swallowing rehabilitation
Oral health care
Pneumococcal vaccination
a b s t r a c t
Pneumonia in the elderly results in the highest mortality among cases of community-
acquired pneumonia (CAP). The pathophysiology of pneumonia in the elderly is primarily
due to aspiration pneumonia (ASP). ASP comprises two pathological conditions: airspace
infiltration with bacterial pathogens and dysphagia-associated miss-swallowing. The first-
line therapy for the treatment of bacterial pneumonia in the elderly is a narrow spectrum
of antibiotics, including sulbactam/ampicillin, which are effective against major lower
respiratory infection pathogens and anaerobes. The bacterial pathogens of ASP cases of
pneumonia in the elderly are similar to those associated with adult CAP. In addition to an
appropriate course of antibiotics, pharmacologic and non-pharmacologic approaches for
dysphagia and upper airway management are necessary for the treatment and prevention
of pneumonia. Swallowing rehabilitation, oral health care, pneumococcal vaccination,
gastroesophageal reflux management, and a head-up position during the night are
necessary for the treatment and prevention of repeated episodes of pneumonia in elderly
patients. In addition, tuberculosis should always be considered for the differential
diagnosis of pneumonia in this patient population.
& 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Contents
1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2. Pathogenesis of pneumonia in the elderly: the role of aspiration pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Contents lists available at ScienceDirect
journal homepage: www.elsevier.com/locate/resinv
Respiratory Investigation
http://dx.doi.org/10.1016/j.resinv.2015.01.003
2212-5345/& 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
n
Corresponding author. Tel.: þ81 29 354 5111; fax: þ81 29 354 5926.
E-mail address: shinjit-tky@umin.ac.jp (S. Teramoto).
r e s p i r a t o r y i n v e s t i g a t i o n ] ( ] ] ] ] ) ] ] ] – ] ] ]
Please cite this article as: Teramoto Shinji, et al. Update on the pathogenesis and management of pneumonia in the elderly-
roles of aspiration pneumonia. Respiratory Investigation (2015), http://dx.doi.org/10.1016/j.resinv.2015.01.003

2. 3. Clinical symptoms and diagnostic difficulty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
4. Causative pathogens of pneumonia in the elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
5. Pneumonia management strategies for the elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
5.1. Principles of selection and administration of antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
5.2. Non-pharmacologic approaches for dysphagia and upper airway management . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
5.3. Pharmacologic approaches for dysphagia and upper airway management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
6. Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1. Introduction
Community-acquired pneumonia (CAP) is one of the most
frequent infections requiring hospitalization and is a leading
cause of mortality in the majority of developed countries
[1–3]. Furthermore, the hospitalized CAP mortality rate
increases dramatically with age [1–3]. Since pneumonia-
related hospitalization and mortality are predominantly
associated with older patients, the development of manage-
ment strategies for pneumonia in the elderly is a priority in
clinical infectious medicine and geriatric medicine. Although
there are numerous established therapeutic guidelines for
CAP, these may not apply to elderly patients [4,5]. However,
the Japanese Respiratory Society has published new thera-
peutic guidelines for pneumonia in the elderly, including
nursing- and healthcare-associated pneumonia (NHCAP) [6].
This review summarizes recent advancements in the man-
agement of pneumonia in the elderly.
2. Pathogenesis of pneumonia in the elderly:
the role of aspiration pneumonia
The dominance of aspiration pneumonia (ASP) in hospita-
lized CAP and hospital-acquired pneumonia (HAP) among the
elderly has been previously reported [7]. Approximately 70%
of hospitalized pneumonia cases can be diagnosed as ASP
based on the definition determined by Japanese NHCAP and
HAP guidelines [6,8]. The ratio of ASP to the incidence of
pneumonia increases with age (Fig. 1). ASP comprises two
pathological conditions: airspace infiltration with bacterial
pathogens and dysphagia-associated miss-swallowing
(Fig. 2). Microaspiration of oropharyngeal contents is extre-
mely common in frail elderly patients, including those post-
stroke, and can cause small infiltrations of the lung, which
then develop into ASP [9–11]. Pneumonia occurring among
outpatients in contact with the healthcare system is termed
healthcare-associated pneumonia. The incidence of ASP is
high in older frail patients and those with healthcare-
associated pneumonia [12]. Swallowing function assessment
is very important for the diagnosis and management of
pneumonia in the elderly. Dysphagia diagnostic methods
range from bedside assessments to swallowing videofluoro-
scopic examinations (Table 1). When performed in elderly
patients who require a high level of nursing care, bedside
swallowing function assessments and simple swallowing
provocation tests may be preferable [13–15].
3. Clinical symptoms and diagnostic difficulty
The signs and symptoms of pneumonia in the elderly differ
from the general population. Elderly patients complain of
significantly fewer symptoms than younger patients. In some
cases, appetite loss, lethargy, conscious disturbances, and
delirium are the major symptoms of pneumonia in the
elderly [16,17]. Since the majority of elderly patients with
pneumonia have two or more co-morbidities, including
stroke, ischemic heart disease, and chronic obstructive pul-
monary disease, their clinical signs and symptoms may not
be specific for pneumonia [17]. The diagnosis of pneumonia
in these patients can therefore be difficult in some cases.
Furthermore, the prevalence of tuberculosis increases with
age and the symptoms of tuberculosis in the elderly often
mimic those of pneumonia [18]. Consequently, tuberculosis
should always be taken into consideration for the differential
diagnosis of elderly pneumonia.
4. Causative pathogens of pneumonia in the
elderly
The bacterial pathogens of ASP cases of pneumonia in the
elderly are similar to those associated with adult CAP.
Streptococcus pneumoniae is the most common cause of pneu-
monia among the elderly, with or without healthcare and
nursing (Table 2) [19–28]. Staphylococcus aureus, Pseudomonas
aeruginosa, and enteric gram-negative rods are also important
Fig. 1 – Incidence of aspiration pneumonia (ASP) and non-
ASP in total pneumonia as a function of age. ASP, aspiration
pneumonia; non-ASP, pneumonia without aspiration nor
dysphagia [7].
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Please cite this article as: Teramoto Shinji, et al. Update on the pathogenesis and management of pneumonia in the elderly-
roles of aspiration pneumonia. Respiratory Investigation (2015), http://dx.doi.org/10.1016/j.resinv.2015.01.003

3. pathogens in elderly patients. Lorber and Swenson isolated
anaerobic bacteria from 21 out of 24 ASP cases of CAP and
found that these were the only isolates in 13 cases [19].
Anaerobes were recorded in eight out of 23 cases and were
the only isolates in two ASP cases of HAP [19]. Recent data
suggest that anaerobes and oral bacteria are detected
in patients with CAP more frequently than previously
thought [29]. These bacteria may play important roles in
ASP cases of pneumonia in the elderly. Gram negative rods
and methicillin-resistant S. aureus are frequently isolated in
elderly patients with pneumonia. The potential multiple drug
resistant pathogen P. aeruginosa has been shown to be highly
prevalent among isolated pathogens in elderly patients with
pneumonia. However, recent data suggest that P. aeruginosa
has only a slightly, and non-significant, higher prevalence
among cases of pneumonia with Gram-negative bacilli in
the elderly, with or without healthcare [26–28]. Atypical
pneumonia-causing organisms such as Mycoplasma and
Chlamydophila rarely cause pneumonia in the elderly. Further-
more, viral pneumonia is usually less severe; however, bacter-
ial pneumonia can cause complications.
5. Pneumonia management strategies for the
elderly
5.1. Principles of selection and administration of
antibiotics
The empirical antibiotic therapy recommended for adult CAP
is also considered to be appropriate for the majority of elderly
patients with pneumonia [27,28]. A narrow spectrum of
antibiotics, including sulbactam/ampicillin, which are effec-
tive against major lower respiratory infection pathogens and
anaerobes, may be selected as a first-line therapy [30–33].
Antibiotics that are effective against indigenous oral and
Airspace infiltration
with bacterial pathogens
Aging
Frailty
comorbidities
Proper antibiotics
administration
(e.g. SBT/ABPC,
etc.)
Management strategy
Swallowing
rehabilitation
Oral care
Physical therapy
Anti-aspiration
agents
Vaccines
Head-up position Nutrition
GER Tx
Elderly pneumonia
Dysphagia-associated
miss-swallowing
Fig. 2 – The management strategy for the treatment of pneumonia in relation to its mechanisms. Pneumonia in the elderly is
characterized by airspace infiltration with bacterial pathogens and dysphagia-associated miss-swallowing. SBT/ABPC,
sulbactam/ampicillin; GER Tx, treatment for gastroesophageal reflex.
Table 1 – Clinical assessments of swallowing function in elderly patients predisposed to aspiration pneumonia (ASP).
Screening method Swallowing function evaluation
Clinical features to assess risk of aspiration, such as abnormal gag,
volitional cough, and voice
Water swallowing test
Bedside swallowing assessment Combination of water swallow and pulse oximetry
Changes in arterial oxygen saturation when swallowing at bedside Swallowing provocation test
Repeated saliva swallowing test Two-step simple swallowing provocation test
Water swallowing test Laryngoscopic evaluation of swallowing
Simple swallowing provocation test, etc. Swallowing pressure measurement
Videofluorographic swallowing study
Fiberoptic endoscopic evaluation of swallowing
Confirmation of radioisotope uptake into lungs applied to teeth
the previous night, etc.
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Please cite this article as: Teramoto Shinji, et al. Update on the pathogenesis and management of pneumonia in the elderly-
roles of aspiration pneumonia. Respiratory Investigation (2015), http://dx.doi.org/10.1016/j.resinv.2015.01.003

4. anaerobic bacteria are administered as a priority when treat-
ing elderly patients with an aspiration risk. Additional ther-
apy options include carbapenem antibiotics, in combina-
tion with macrolides [34,35]. Although it is very difficult to
identify causative bacteria in sputum specimens from elderly
patients, maximum effort should be applied to identify the
causative agents, and drugs with the highest activity against
these agents should be selected. Since pneumonia often
reoccurs within 90 days in frail elderly patients with nursing
care, this narrow spectrum of antibiotics should be preferen-
tially administered. De-escalation procedures should be con-
ducted when the causative agents have been identified and
the clinical manifestations have improved.
5.2. Non-pharmacologic approaches for dysphagia and
upper airway management
Since antimicrobial agents cannot improve swallowing dys-
function, dysphagia therapy is a secondary approach for the
treatment of pneumonia. Episodes of aspiration may worsen
during pneumonia treatment due to bedridden-induced
immobility and inflammation. Both swallowing rehabilitation
and oral health care management should be initiated and
continued in parallel with antibiotic treatment [36–40]. Oral
care reduces fever and pneumonia incidence among elderly
patients [41,42]. It has been reported that a dependence for
feeding and oral care, the number of decayed teeth, and tube
feeding are significant predictors for the development of ASP
[43]. Oral hygiene management intervention may be an
efficient mortality risk factor modifier in nursing home-
associated pneumonia. Furthermore, recent data suggest that
early rehabilitation by physical therapists may reduce 30-day
in-hospital mortality rates in geriatric patients with severe
ASP [44].
Percutaneous Endoscopic Gastrostomy (PEG) is often per-
formed as a means of preventing ASP; however, there is little
evidence to indicate that it prevents pneumonia. The inci-
dence of ASP in PEG patients is similar to that in patients fed
through a nasogastric tube [45]. Route changes, in addition to
swallowing rehabilitation, may be necessary to reduce silent
aspiration in these patients [43]. A slightly head-up position,
by approximately 301, during the day and night, may be
effective in reducing gastroesophageal regurgitation (GER)-
associated aspiration [46,47]. Mosapride, a gastroprokinetic
agent, may prevent GER and reduce the incidence of pneu-
monia in patients with PEG [48,49].
5.3. Pharmacologic approaches for dysphagia and upper
airway management
Unique pharmacologic approaches relating to the treatment
of dysphagia have been introduced for the prevention of
ASP. Several anti-aspiration agents, which improve swal-
lowing dysfunction, are clinically available. Angiotensin
converting enzyme (ACE) inhibitors and cilostazol have
reported efficacy in the prevention of pneumonia among
elderly patients who have a history of cerebral infarction
[50–53]. Aspiration is related to the dysfunction of dopami-
nergic neurons by cerebrovascular disease, resulting in both
swallowing- and cough-reflex impairments. ACE inhibitors
Table2–Potentialcausativemicrobiologicalpathogensinelderlypatientswithvarioustypesofpneumonia.
InvestigatorsLorberBartlettMicekCarratalàMaruyamaIshidaMiyashitaPolverinoChalmersYamasaki
Citationno.[19][20][21][22][23][24][25][26][28][29]
TypeofpneumoniaASPASPHCAPHCAPNHAPNHCAPNHCAPHCAPHCAPCAP
Numberofpatients47704311262117359923813364
FacilitiesSingleSingleSingleSingleSingleSingleMulti-centerMulti-centerSingleSingle
Meanage(years)23–73–59.869.591.78280.178.87663.2
GPCS.pneumoniae21.2%15.7%10.4%27.8%35.2%31.8%13.9%62.7%49.4%18.8%
GPCS.aureus8.5%15.7%13.9%2.4%3.7%11.0%6.1%2.4%10.1%3.1%
GPCMRSA––30.6%0.8%–8.1%7.7%0%2.2%–
GNRP.aeruginosa17%10%25.5%1.6%0%13.3%5.0%5%2.2%–
GNRE.coli10.6%8.6%4.2%2.4%–7.5%3.3%––3.1%
GNRH.influenza––4.2%11.9%0%9.2%8.1%1.2%14.6%18.8%
GNRK.pneumoniae2.1%11.4%6.5%0%–11.6%9.0%––17.2%
GNREnterobacter–5.7%9.0%–3.7%–––6.7%–
Anaerobicbacteria61.7%61%––0%2.9%–––15.7%
ASP,aspirationpneumonia;HCAP,HealthCare-AssociatedPneumonia;NHAP,nursinghome-associatedpneumonia;NHCAP,NursingandHealthCare-AssociatedPneumonia;CAP,community-
acquiredpneumonia;GPC,Grampositivecocci;GNR,Gramnegativerods;S.pneumonia,Streptococcuspneumonia;S.aureus,Staphylococcusaureus;MRSA,methicillin-resistantStaphylococcusaureus;
P.aeruginosa,Pseudomonasaeruginosa;E.coli,Escherichiacoli;H.influenza,Haemophilusinfluenzae;K.pneumonia,Klebsiellapneumonia.
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Please cite this article as: Teramoto Shinji, et al. Update on the pathogenesis and management of pneumonia in the elderly-
roles of aspiration pneumonia. Respiratory Investigation (2015), http://dx.doi.org/10.1016/j.resinv.2015.01.003

5. and cilostazol are thought to increase substance P levels in
the airways and plasma, improving both swallowing and
cough reflexes in the elderly [54,55]. In a 2-year follow-up
study of stroke patients, pneumonia-associated mortality
was significantly lower in older hypertensive patients admi-
nistered with ACE inhibitors than in those treated with other
antihypertensive drugs [50]. Unless the patient is bedridden
with a very low level of activities of daily living (ADL), these
drugs may be effective in preventing pneumonia in the
elderly with nursing care. However, while the efficacy of
these drugs has been observed in elderly Asian patients,
they have not been found to prevent aspiration pneumonia
in Caucasian elderly patients [56]. Furthermore, the preven-
tion of pneumonia in the elderly may not be achieved by all
of the available ACE inhibitors [57].
Several swallowing disturbance agents are known to exist;
medications, which cause dry mouth (xerostomia), may
interfere with swallowing by impairing the elderly person's
ability to move food. Anticholinergic agents, tricyclic anti-
depressants, diuretics, and selective serotonin reuptake inhi-
bitors should therefore be administered with caution. Since
the depressed conscious level impairs the swallowing reflex,
antipsychotic/neuroleptic medications should not be admi-
nistered in elderly patients with a high risk of pneumonia. In
addition, anesthetics also impair the swallowing reflex in
both old animals and humans [58].
Vaccination is one of the most important preventive
approaches for pneumonia in the elderly. There are two types
of vaccines administered to prevent pneumonia in the elderly:
pneumococcal and influenza vaccines. The CAPAMIS study
indicated a protective effect of a recent (within the previous 5
years) pneumococcal polysaccharide vaccine (PPV) 23 vaccina-
tion, against both pneumococcal and all-cause CAP, among the
general population aged Z60 years [59]. Another study also
reported that PPV23 protects elderly patients from hospitaliza-
tion due to S. pneumonia CAP; however, this was found in
women rather than men [60]. The Centers for Disease Control
and Prevention recently recommended one dose of pneumo-
coccal conjugate vaccine (PCV13) for the inoculation of adults
aged Z19 years with a weakened immune system. Preliminary
data from Nicaragua indicated that the introduction of a
combined pediatric and adult pneumococcal immunization
program using PCV13 reduces pneumonia-related mortality in
older adults [61]. Other data have also highlighted the favorable
effect of PCV13 on the reduction of severe lower respiratory
tract infections in elderly patients with chronic conditions [62].
The effectiveness of the pneumococcal conjugate vaccination
for patients with a high risk of ASP should be further examined
using several other vaccines.
Influenza vaccine has also been recommended for the treat-
ment of pneumonia in the elderly. The incidence of pneumo-
coccal pneumonia has been shown to increase following
influenza virus infection in the elderly [63]. Although the effec-
tiveness, in relation to hospitalization and mortality rates, of the
influenza vaccine alone in elderly patients has not been assessed
by meta-analysis in the previous studies [64,65], a combined
vaccination of the influenza vaccine and PPV is thought to be
effective in these patients [66]. Inoculation with both these
vaccines may have an additive effect in reducing pneumonia
hospitalization in elderly patients with a risk of ASP [67].
6. Conclusion
The incidence of pneumonia, predominately ASP cases, in
the elderly increases with age and with the occurrence of
co-morbidities. Since the major pathogenesis is oropharyn-
geal dysphagia with bacterial lung inflammation, a variety of
preventive approaches such as oral healthcare management,
swallowing rehabilitation, and physical therapy are impor-
tant for the treatment of pneumonia in the elderly.
Conflict of interest
The authors have no conflicts of interest.
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roles of aspiration pneumonia. Respiratory Investigation (2015), http://dx.doi.org/10.1016/j.resinv.2015.01.003