Japanese Dental Science Review (2010) 46, 102111

a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m

journal homepage: www.elsevier.com/locate/jdsr

Review article

Aspiration pneumonia: With special reference to

pathological and epidemiological aspects,
a review of the literature
Kayo Kuyama *, Yan Sun, Hirotsugu Yamamoto

Department of Oral Pathology, Nihon University School of Dentistry at Matsudo, 2-870-1, Sakaecho-Nishi,
Matsudo City, Chiba 271-8587, Japan

Received 27 July 2009; received in revised form 2 November 2009; accepted 5 November 2009

KEYWORDS Summary Silent aspiration plays an important role in the pathogenesis of bacterial pneumonia in
Aspiration pneumonia; the elderly. Defense of the airway is impaired in the elderly by alteration in respiratory mechanics;
Silent aspiration; decreased mucociliary clearance and immunosenescence. And, the number of microorganisms in
Oral hygiene; the oral cavity of the elderly is usually larger than that of young adults because of gradual reduction
Aging; in production of saliva. A relationship between poor oral health and respiratory disease has been
Etiology suggested by a number of recent microbiologic and epidemiologic studies, especially in elder
subjects; who requiring help with feeding, wearing denture/edentate, with periodontal disease,
and so on. Several researchers have reported that using professional oral health care (POHC) can
prevent pneumonia. Oral/respiratory mucosal tissues produced cytokine that stimulated by oral
microorganisms and were altered expression of various cell adhesion molecules on their surface in
response to cytokine stimulation. Then, aspiration pneumonia histopathologically characterized
with inflammatory response including macrophage infiltration was caused by aspiration of oral
microorganisms, acid and food particle. In conclusion, silent aspiration may be a key risk factor for
the pathogenesis of pneumonia in the elderly patients with poor oral hygiene.
# 2009 Japanese Association for Dental Science. Published by Elsevier Ireland. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
2. Silent aspiration and oral hygiene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
2.1. Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
2.2. Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
2.3. Candida spp.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
2.4. Professional oral health care (POHC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

* Corresponding author. Tel.: +81 47 360 9334; fax: +81 47 360 9335.
E-mail address: kuyama.kayo@nihon-u.ac.jp (K. Kuyama).

1882-7616/$ see front matter # 2009 Japanese Association for Dental Science. Published by Elsevier Ireland. All rights reserved.
doi:10.1016/j.jdsr.2009.11.002
Aspiration pneumonia: With special reference to pathological and epidemiological aspects, a review of the literature 103

3. Etiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
3.1. Pathological approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
3.2. Animal experimental approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
4. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109

1. Introduction silent aspiration in some dysphagic patients with neurological

Pneumonia is the fourth leading cause of death in Japan,
resulting in 110,000 deaths in 2007, which represents a
mortality rate of 87.4 per 100,000 individuals [1]. The mor-
tality rate due to pneumonia increases with age. Pneumonia
is an inflammation of the lungs by viruses, fungi, parasites or
bacterial infections, and the last one is usually classified as
community-acquired pneumonia (CAP) or nosocomial (hospi-
tal-acquired) pneumonia. The differential diagnosis is impor-
tant because the pathogens implicated and the preventive
measures taken are different for the 2 types. The causative
microorganisms of these 2 types differ. CAP is usually asso-
ciated with infection by Streptococcus pneumoniae and Hae-
mophilus influenzae and with other species such as
Mycoplasma pneumoniae, Chlamydia pneumoniae and Legio-
nella pneumophila; a variety of anaerobic species can also be
involved [2]. The spectrum of microorganisms responsible for
nosocomial pneumonia is quite different, with Gram-nega-
tive bacteria and Staphylococcus aureus being the most
prevalent [3].
Aspiration pneumonia (AP) is defined as lower respira-
tory tract infections mostly in elderly people who have
aspirated oropharyngeal or gastric contents, and this con-
dition is most often associated with dysphasia [4]. Though
researchers have indicated that 515% of CAP is AP [5,6],
AP likely occurs more frequently than reported, because
the disease is not recognized in many cases. The reason the
disease is not always recognized is that the causative
microorganism of AP is common to CAP and nosocomial
pneumonia and the spectrum of AP is even broader [3].
Bartlett et al. reported that anaerobic bacteria were
detected in 93% of AP, and the mixed infection of anaerobic
bacteria and aerobically growing bacteria were often
observed [7]. Namely, the causative bacteria involved
are indigenous oral flora or they are acquired in the
hospital. But the frequency of infection with anaerobic
microorganisms is uncertain because of the technical dif-
ficulty associated with anaerobic culture and the possibi-
lity of contamination by anaerobic oral flora during
sampling. Anaerobic bacteria are not routinely cultured
from bronchial secretions due to these difficulties [8], and
this might be one of the reasons why little research exists
concerning oral flora and aspiration pneumonia.
The term aspiration was mainly used as apparent
aspiration for the pediatric accident of swallowing foreign
bodies until around 1995 [9,10]. As for silent aspiration, it is
defined as the inhalation of oropharyngeal or gastric contents
into the larynx and lower respiratory tract and may cause
infections such as AP or aspiration pneumonitis. The right
lung of incident rate of AP is high. The foreign body drops
easily to right bronchia because right bronchium is sharper
bifurcated angle from the trachea than a left one [11].
Contraction of AP or aspiration pneumonitis was caused by
disorders [12]; Parkinsons disease or alcoholism was sus-
pected [8]. And children with neurologically based dyphagia
were also thought to be at high risk [13]. Generally, abnormal
oropharyngeal colonization as a result of medical complica-
tions is shown in dysphagic patients who have decreased
immunity and/or impaired pulmonary clearance. Those sub-
sequently develop pneumonia when potential respiratory
pathogens are aspirated together with food and/or liquid
[14].
Further, nondysphagic persons may occasionally experi-
ence microaspiration of pharyngeal secretions during sleep
or at times of depressed consciousness [1517]. Also,
approximately half of all healthy adults also aspirate small
amounts of oropharyngeal secretions during sleep [16,17]. In
1994, Kikuchi et al. examined the occurrence of silent
aspiration during sleep in elderly patients with CAP by using
indium-111. Silent aspiration in patients with CAP was more
frequent than in age-matched control subjects (71% vs 10%)
[18]. Therefore, it seems reasonable to conclude that silent
aspiration has an important role in pneumonia that occurs in
the elderly.
2. Silent aspiration and oral hygiene
2.1. Aging
Silent aspiration appears to play an important role in the
pathogenesis of bacterial pneumonia and chronic pulmonary
disease [1922]. Elderly people frequently aspirate during
sleep [16,17], and pneumonia develops when the defense
mechanism of the healthy lung organization is overwhelmed
[23] and/or weaken by aging. Defense of the airway is
impaired in the elderly by alteration in respiratory
mechanics, decreased mucociliary clearance, immunosenes-
cence and, in some cases, concomitant illnesses that predis-
pose to aspiration [24,25].
It is suggested that swallowing function and the cough
reflex are important defenses to the aspiration [26]. Seki-
zawa et al. described that marked depression of the cough
reflex was shown in elderly patients with pneumonia [27].
Petroianni et al. also reported that the increased incidence of
AP with aging might be a consequence of impairment of
swallowing and the cough reflex [28].
In contrast, the occurrence of aspiration in healthy elderly
people is not different from that in younger persons in
previous studies, though older people swallow more slowly
[29]. The cough reflex also did not decrease with aging [30].
Therefore, it may be considered that aging alone is not
causes of elderly AP. However, oropharyngeal deglutition is
impaired with aging, because of increased neural processing
time and diminished oral control [23]. Further, the incidence
of cerebrovascular and degenerative neurologic disease
increase with aging, and these impediments are strongly
104
associated with impaired swallow and cough reflex and
increased risk of aspiration [30]. The number of microorgan-
isms in the oral cavity of the elderly is usually larger than that
of young adults because of a gradual reduction in basic oral
function [31,32], such as diminished production of saliva as a
result of medications and oral/dental disease [14]. It is
thought that these oral environments of elder person become
risks of AP.
Adaptive immune responses are required to defend the
lung against pathogens. Microbes initiate both innate
immune responses and specific adaptive immune response
[33]. The aging of lungs is a diversified decline in pulmonary
immune function, on the contrary. Alveolar defenses are
divided into resident defense mechanisms, inflammatory
responses, and specific immune responses. Aged T-lympho-
cytes are markedly impaired in their ability to activation and
proliferation in response to an antigen [25,34]. In addition,
the ability of the T-lymphocytes with secreting interleukin-2
declines with age, and the macrophages by senescent T cells
were diminished [34].
These many interacting and compounding impairments
may explain the increased susceptibility of the elderly to
pulmonary infection.
2.2. Epidemiology
It was at the 1990s that the epidemiologic studies of the
environment in the oral cavity, quality of life and pneumonia
were started [3539]. The history of the epidemiologic study
concerning elderly AP is comparatively shallow. Because the
mortality rate of pneumonia rises remarkably with aging [40],
the elder generation is a logical target of this research. And
elder person often has complex factors; poor nutritional
status and medication could confound the relationship
between oral conditions and pneumonia. In the most recent
studies [8,14,41], oral conditions emerged as potentially
important risk factors of AP after adjustment for established
medical risk factors. A relationship between poor oral health
and respiratory disease has been suggested by a number of
recent microbiologic and epidemiologic studies, especially in
high-risk subjects.
Terpenning et al. [39] reported that requiring help with
feeding was one of the most significant risk factor of AP in
dentate patients. As for requiring help with feeding, it means
serious oral health problems; including poor oral hygiene,
high level of dental needs and low rates of dental care
utilization [42,43]. For instance, Scannapieco et al.
described a plaque index (OHI) was associated with chronic
respiratory disease [44]. Significant positive correlation was
found between salivary bacteria and visual evaluation of
plaque index in dentate patients [45]. And, the number of
patients developing pneumonia is larger in dentate patients
with tongue plaque index (TPI)-based poor scores than those
with good scores [45]. In addition, it is known that anaerobic
lung infectious disease develops after saliva aspiration, espe-
cially in patients with periodontal disease [46]. Scannapieco
et al. reviewed the association between periodontal disease
and pneumonia, and mentioned that poor oral hygiene and
periodontal diseases appeared to be related with pneumonia
[47,48]. In conclusion, the periodontal disease and dental
plaque may act as a reservoir of respiratory pathogens in
dentate patients.
K. Kuyama et al.
As for denture-wearing patients, denture hygiene is sug-
gested to be a significant factor in pharyngeal bacterial
colonization [49]. Eighteen species of microorganisms were
detected in denture plaque. A variety of pathogens colonized
on dentures of dependent elderly [50]. In addition, agree-
ment rate of the race of the bacillus of the denture and the
pharynx is reported to be 68.5% [49]. It is necessary to think
about the denture as an important reservoir of microorga-
nization. Tongue-coating is a risk indicator of AP also in
edentate subjects [45]. It is not overemphasized even if it
is describe that denture plaque controlling is necessary for
the prevention of aspiration pneumonia. [51,52].
Plaque is a complex system that associates microorgan-
isms embedded in an extracellular matrix. Bacteria consti-
tute approximately 7080% of the solid material, and 1 mm3
of plaque contains more than 106 bacteria with 300 different
aerobic and anaerobic species [53]. From the above-men-
tioned reports, plaque may serve as a reservoir for respira-
tory pathogens, especially in high-risk elder patients with
poor oral hygiene, periodontal disease, dentate and edentate
by epidemiology [4452,54,55].
2.3. Candida spp.
Pneumonia is an inflammation of the lungs by microorganism
infection. One study reported a patient suspected of Candi-
dal pneumonia, though the majority of AP is a bacterium [56].
Pulmonary fungal infection of community-acquired origins is
becoming a serious problem. Candidal pneumonia has 2
forms. The most common form is a hematogenously disse-
minated pulmonary infection along with various other
organs, often resulting in fungal emboli in the lungs. The
other form is rare and occurs after aspiration of oral/oro-
pharyngeal material, causing primary pneumonia [57].
For latter form, Candida infection usually occurs in at-risk
patients. It is described that aspiration is important as the
route of entry of intrabronchial and intraalveolar fungi that is
not vascular invasion [58]. Then, Yamamoto et al. performed
amplified polymorphic DNA analysis and DNA sequence exam-
ination of Candida strains isolated from the oral cavity and
autopsied lung. It was revealed the identity of both strains as
Candida albicans. The DNA analyses therefore suggest that
oral Candida was aspirated and multiplied in the lungs, and
this result suggests the importance of oral hygiene for AP
[59].
C. albicans is the most common Candida pathogen not only
in systemic but also in Candidal pneumonia [6063]. Candida
glabrata accounts for up to 20% of Candidal pneumonia [63]
occurs almost exclusively in immunocompromised patients
[64]. However, some epidemiologic studies have described
that C. glabrata is a pathogen of lower respiratory infections
[6163].
Report of C. albicans infection of denture plaque was
published [65]. As for the etiology of the Candida growth
environment, adherence of C. albicans to denture-based
acrylic resin, in vitro, is related to the hydrophobicity of
the organism [66]. That is, denture-based acrylic resin is
easily colonized by oral endogenous bacteria and Candida
spp., and eventually by extra-oral species such as Staphylo-
coccus spp., Pseudomonadaceae or members of Enterobac-
teriaceae. This microbial reservoir may be responsible for AP,
especially in geriatric patients [51]. Abe et al. reported that
Aspiration pneumonia: With special reference to pathological and epidemiological aspects, a review of the literature 105

Table 1 The review papers concerning about oral health and pneumonia.

Author Ref. no. Year Main purpose to know for review Reference Total
no. reference no.
Mojon P. [8] 2002 1 Direct evidence of an association between 12 38
pulmonary infection and oral diseases
Scannapieco [48] 2003 1 The relationship between epidemiological/ 11
et al. micrological studies on oral health and
nosocomical pneumonia
2 Intervention studies of oral cleaning and pneumonia 8 40
Garcia [53] 2005 1 Evidence of asscociation between oropharyngeal 19 180
colonization and pulmonary infection
2 Evidence of effective intervention plans 12
Kikawada et al. [14] 2005 1 Risk factors for aspiration pneumonia 37
2 The assessment of oral care and pneumonia 2 112
Azarpazhooh [82] 2006 1 Evidence of relationship between oral health and 5 46
and Leake incidence of pneumonia
2 Evidence of relationship between intervention of 10
oral health and respiratory infection
Scannapieco [83] 2006 1 Oral interventions and pneumonia in nonambulatory 16 28
patients
Paju and [81] 2007 1 The role of improved oral cleaning in reducing 17 45
Scannapieco pneumonia
Sarin et al. [68] 2008 1 Comparison of microorganisms of the oral cavity and 6 64
known respiratory pathogens
2 The relationship between aspiration pneumonia 16
and oral health

POHC in elderly people decreased the cell numbers of
Candida in the oral cavity [67].
2.4. Professional oral health care (POHC)
Dentists have the role of maintaining oral health to prevent
AP. Sarin et al. [68] reviewed microorganisms that caused AP
and provided oral health care guidelines. The common micro-
organisms of the oral cavity and respiratory system are S.
aureus, H. influenzae, Actinomyces species and Peptostrep-
tococcus. Previous epidemiological studies reported that
elderly people who received POHC showed a lower preva-
lence for respiratory pathogens [69,70] such as Staphylococ-
cus species [71,72], Streptococci [71], Pseudomonas
aeruginosa [72] and C. albicans [72] than those who did not.
The relationship between potential respiratory pathogens
that cause pneumonia and colonize the oral cavity of high-
risk elderly people, for example, those in intensive care units
[22,73,41], and nursing home residents [41,74,75] were
reported. Significantly, results from 3 preliminary interven-
tion trials demonstrate that attention to oral hygiene, either
by the use of mechanical cleaning and/or oral antiseptic
rinses, significantly reduces the rate of lower respiratory
infection in institutionalized subjects [7678]. Further, the
ratio of fatal AP [72] and dying from pneumonia [79] in POHC
patients was significantly lower than that in patients without
POHC. In another report, cough reflex sensitivities in the
intervention group were significantly higher than those of the
control group ( p < 0.05) [80]. Like the above-mentioned
study, many review papers with positive results concerning
the relationship between POHC and AP [8,14,48,8183] have
been reported (Table 1).
However, some researchers have reported that there is no
relationship between oral health and AP. Multivariate analy-
sis identified tube feeding, presence of a hyperextended
neck, contractions, malnutrition, and the use of benzodia-
zepines and anticholinergics as risk factors for AP for long-
term care patients, but the results were not sufficient for
dental characteristics [84]. There is a report that mechani-
cally ventilated intensive care is mainly a risk factor for
bacterial pneumonia [85]. Although medical ICU patients
tended to have more dental plaque than preventative den-
tistrys outpatient, there was no significant difference noted
between the presence of dental plaque and respiratory
pathogen colonization [73].
Most data showed a high level of dental needs; untreated
coronal and/or root decay among the majority of nursing
home residents, accompanied by significantly reduced oral
health-related quality of life [86]. Interventional epidemio-
logical studies indicate that oral microorganisms might cause
lung infection.
3. Etiology
3.1. Pathological approach
Though interventional epidemiologic research had been a
main method in the research of AP, it is shifting to experi-
106
Figure 1 Flow until approving aspiration pneumonia.
mental pathology research. For instance, it was reported
that DNA of microorganism in the bronchial tube and oral
cavity of pneumonia patients were consisted [87]. Therefore,
pathological approach of the process the aspiration of the
microorganism in the oral cavity to bronchial tube, prolif-
eration, and progressing to AP is necessary.
An illustration of aspiration pneumonia is shown in Fig. 1.
Aspiration of indigenous oral flora and colonization into the
lung are the course of lung infection by the oral microorgan-
ism. In short, the oral flora are released into the saliva and
aspirated into the lower airway.
The pathogenesis of pneumonia begins with the coloniza-
tion of the oropharyngeal surfaces by potential respiratory
pathogens. The adhesion of bacteria to these surfaces is
usually mediated by specialized bacterial surface structures,
which bind to specific receptors on the host surface. Oral
bacteria are potent stimulators of cytokine production from
oral epithelial cells [88], and those may also modulate the
adhesion of respiratory pathogens to respiratory epithelial
cells. Oral bacterial products or cytokines in oral/pharyngeal
aspirates have 2 kinds of function; one is stimulating cytokine
production from oral/respiratory epithelial cells [88,89], and
the other is modulating the adhesion of respiratory epithelial
cells [89]. Then, epithelial cells also alter expression of
various cell adhesion molecules on their surface in response
to cytokine stimulation [90]. Variation in expression of such
adhesion molecules may alter the interaction of bacterial
pathogens on the mucosal surface [91]. Once aspirated into
the lower airway, the bacteria adhere to the bronchial or
alveolar epithelium, again via specific adhesionreceptor
interactions, which include lectin as well as protein-protein
interactions for glycoproteins and glucolipids [89]. Epithelial
cell destruction by adhered bacteria may be due to the direct
effect of bacterial products on membrane permeability.
Wilson R et al. have demonstrated that bronchial secretions
may also contain bacterial toxins, which can cause epithelial
necrosis and disrupt ciliary ultrastructure [92]. One of the
K. Kuyama et al.
main functions of the airway epithelium is to inactivate and
remove infectious particles from inhaled air and thereby
prevent infection of the distal lung. Necrosis in airway
epithelium might decrease removal capacity.
Studies of pulmonary infections have demonstrated that
there is also a close relationship between bacterial load and
neutrophil recruitment [93]. In acid aspiration-induced sys-
temic organ injury, cytokines have been shown to increase
neutrophilendothelial adhesion [94]. Therefore, the neu-
trophils engulf and degenerate necrotic cells. Neutrophils
may play important roles in the phagocytosis and pathogen-
esis of infective lung diseases, due to their ability to release a
variety of oxidants and proteolytic enzymes capable of caus-
ing acute and chronic lung injury. As grounds for this hypoth-
esis, neutrophils with a left shift were a common finding in
dogs with AP [95].
AP is characterized histopathologically as granulomatous
bronchopneumonia with prominent formation of macro-
phages/multi-nucleated giant cells. Migration of macro-
phages is caused by repeatable chronic aspiration of
particulate food matter [96] and response of acid-induced
lung injury [97]. However, phagocytic exposure of the macro-
phages was inhibited by in vitro exposure of the macrophages
to acid [98]. In addition, a robust tumor necrosis factor-alpha
(TNFalpha) response is seen following aspiration of food
particles, while there is only a modest response to acid.
TNFalpha might play a role in the pathogenesis of AP induced
by food matter [99]. In conclusion, this accumulation of
harmful bacteria and local inflammatory agents at the
moment of aspiration may be the key risk factor in the
pathogenesis of pneumonia associated with poor oral
hygiene.
However, further research is necessary, because only
recently research has focused on the mechanisms responsible
for acid and base secretion into the airway surface liquid
[100], and reports of the AP animal model with silent aspira-
tion of food matter at the present stage are scarce.
 Aspiration pneumonia: With special reference to pathological and epidemiological aspects, a review of the literature
Table 2 Animal experimental papers of aspiration pneumonia.

Author Ref. Year Animal Method Control group Experimenal group Instillation Analytical item Main result
condition
Kudoh et al. [106] 2001 Wister rat Trans-oral PBS (pH 7.4) 1 HCL (pH 1.0, 0.1 ml) 0.1 ml Cultured alveolar 1 ++ TNF-a nitric oxide
endotracheal macrophage
instillation
1
Mitsushima [103] 2002 Mouse Intratracheal NS 1 HCL 10 to 10 4N 50 ml Histophatological 3 ++ Numerous neutrophils
et al. instillation analysis infiltrated in the lung
tissue in HCL 10 1N
with bacteria
2 Bacteria SEM study 3 ++ Numerous bacteria
were found on
exfoliated epithelium
3 HCL 10 1 to 10 4
N
+ bacteria
Raghavendran [108] 2005 WT and MCP-1 Intratracheal Normal saline 1 NS* + HCL (pH 1.25) 3.6 ml/kg Histopathological 1,2,3 WT Granuloma formation
et al. ( / ) mice instillation (pH 5.3) analysis
2 NS* + gastric particle 1,2,3 MCP-1 Severe diffuse
(pH 5.3) ( / ) pneumonia
3 NS* + gastric particle BAL analysis MCP-1 Several inflammatory
+ HCL (pH 1.25) ( / ) mediators
>WT
Rotta et al. [107] 2004 Long Evans Aspiration NS* (pH 5.3) 1 Gastric aspirate 1.2 ml/kg Mortality rate 1,2,NS 0.0%
rat introduced in (pH 1.25) + NS * 3 31.8%
the trachea by
direct puncture
2 NS* + bacteria BAL analysis 3 >12 Neutrophil counts
3 Gastric aspirate Cytokine analysis 1,3 ++ MCP-1
(pH 1.25) + bacteria
Allen et al. [101] 2007 C57BL/6 Instilled from PBS (pH 7.4) 1 HCL (pH 1.8) 75 ml Histopathological 1 ++ Fibrinogen and fibrin
mice deep oropharynx analysis accumulation
BALF analysis 1 ++ Total cells Neutrophils
Total lung fibrin levels
Appel et al. [105] 2007 F344 rat Aspirathion NS * 1 Gastric fluid Cytokine analysis 1 ++ Macrophage Tcell
through
ventilator
placed
1 ++ Fibrosis score
*
Nader et al. [98] 2007 Long Evans Intratracheal NS 1 Low pH saline Cytokine analysis 2,3 >1 Mononuclear cells
rat instillation

107
108 K. Kuyama et al.

3.2. Animal experimental approach

No significance in BAL
Chronic inflammation
with multi-nucleated
Table 2 shows details of the research on aspiration pneumonia

among groups
in animal models. Some research that used animal models of
Main result

AP used artificial suction of acid. Acid aspiration in mice leads

giant cells
to substantial deterioration in lung function. Bronchoalveolar
lavage fluid demonstrated a significant rise in total cells by
4 h and a significant increase in neutrophils relative to saline
controls by 24 h, and both remained elevated to 48 h. Total
fibrin lung levels increased progressively compared to the
control group and showed significantly greater levels of fibrin
and fibrinogen from 4 to 48 h by immunohistochemistry [101].
Histopathological 1,2,5

Cytokine analysis 15

It was shown that suction of acid caused migration of inflam-

matory cells; mainly neutrophils and beginning of tissue
restoration. Likewise, lung-lining fluid is a primary constitu-
Instillation Analytical item

ent of the pulmonary host defense system. The pathogenicity

of microorganism in airways and alveoli might be increased
when microorganism clearance in both regions were sup-
analysis

pressed by low pH [102]. As a result, it is suggested that

bacterial adheremce to epithelium of the lungs would be
enhanced [103].
0.5 ml/kg

The lung tissue of rats was histopathologically demon-

condition

strated to have bronchopneumonia with formation of multi-

nucleated giant cells, on the contrary [104]. As for the
relation between aspiration and macrophage infiltration,
an inflammatory reaction that consists of T cells and macro-
2 Neutralized gastric
Experimenal group

phages was caused by repetitive aspiration [105,106].

3 Acidified particles

4 Bile solution from

1 Gastric fluid from

5 Food suspension

Chronic inflammatory infiltrates including multi-nucleated

2 Small non-acid

fluid from rats

3 HCL (pH 2.2)

rats (pH 2.2)

rats (pH 7.4)

giant cells were observed when treated with gastric fluid,

neutralized gastric fluid, bile and food suspension [96]. In
particles

(pH 7.0)

(pH 6.8)

addition, bronchoalveolar lavage of rats that were firstly

aspirated with rat gastric fluid adjusted to pH 1.2, and
secondly aspirated with bacteria, had remarkably increased
MCP-1 concentration [107]. WT mice had prominent granu-
Control group

loma formation in lung tissue after aspiration, though MCP-

1( / ) mice had little or no evidence of granuloma forma-
tion [108]. From this, acid aspiration-induced airway epithe-
lial injury and enhanced bacteria adherence to the
NS *

epithelium. And, macrophages/multi-nucleated giant cells

play a key role in repeated aspiration. That is, these cells
tube instillation

migrate to encapsulate aspirated foreign body and to stop the

Endotracheal

inflammation.
Method

4. Conclusion

The research of AP has been advanced based on epidemiol-

ogy analysis. Especially, several researchers have reported
2008 Wister rat

that intervention with POHC can help prevent pneumonia.

Animal

Silent aspiration of oropharynx bacterial pathogen to the

lower respiratory tract is an important risk factor for noso-
comial pneumonia [109]. Knowledge within the profession
Year

will improve the environment in the oral cavity of elderly

people who need intensive care. For instance, Chiba et al.
described that around 90% of caregiver managers recognized
Ref.

[96]
Table 2 (Continued )

NS*: Normal saline.

the importance of oral care and were interested in oral care

[110]. Caregiver oral care knowledge is important for pre-
venting AP. Dentist should initiate POHC though a lot of
professions of the nurse, the care person, and the helper,
Downing
et al.
Author

etc. are involved. Therefore, dentists should study AP more,

and instruct other care providers. In addition, more research
on AP is needed.
Aspiration pneumonia: With special reference to pathological and epidemiological aspects, a review of the literature
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