16.

IMPACT OF PERIODONTAL INFECTION ON SYSTEMIC HEALTH

For a comprehensive reading on this topic, please refer to CHAPTER 15 - IMPACT OF
PERIODONTAL INFECTION ON SYSTEMIC HEALTH in Carranza’s Clinical
Periodontology, 13th ed., 2018.

1. Pathobiology of Periodontitis
The modern opinion over periodontal disease’s patho-biological processes view the
bacterial subgingival biofilm as their fundamental cause. Despite the fact that the variety of
periodontal bacterial pathogens from patient to patient is rather limited, and in some cases of
periodontal disease the characteristics of the biofilm are similar, the periodontal pathology can
be extremely different from patient to patient, in terms of its onset, evolution and treatment
response. This high clinical diversity is caused by the important role that the host immune-
response plays in regulating the way the disease manifests itself, its evolution pace and therapy
reactivity. The host immune-response is mainly genetically determined, but it can be largely
influenced by a vast variety of endogenous and exogenous factors, ranging from the patient’s
age and hormonal balance to their dietary habits and stress level. Therefore, all factors which
can impact a patient’s immune-response, in a negative or positive manner, have a direct impact
on the clinical manifestations, evolution rate and treatment response of the periodontal disease.
Many systemic diseases that influence the immune response, in a lesser or greater manner, are
associated with the periodontal pathology. Conversely, the periodontal pathology can also
impact the development and characteristics of certain systemic conditions. These mutual
interactions have been reunited under the concept of “periodontal medicine”.
This concept encompasses more than 50 various general diseases that have been proven
to have certain connections, some of which, of mutual nature, with periodontal pathologies.
These systemic conditions include coronary/vascular disease and diabetes mellitus, that have
a solid scientific basis for their bi-directional connection with the periodontal pathology (90,
110, 132). Other, less profoundly studied connections, are those between periodontitis and
conditions such as chronic kidney disease (20, 43, 44, 84, 85, 153), cancers of the liver or
pancreas (2, 45, 118, 119, 160), rheumatoid arthritis (29, 30) and neurological diseases like
dementia or Alzheimer’s (75, 76, 90, 157, 159, 178).

2. Focal Infection Theory Revisited

One of the first pioneers to connect periodontal disease to various systemic conditions
was William Hunter, a British medic, who during the early 1900s performed hundreds of tooth
extractions in order to ameliorate the manifestations of certain illnesses. Hunter believed that the
removal of carious or infected teeth would improve the status of systemic conditions which, at
that time, did not have a clear, proven cause. His method had little or no scientific background
and fell into disapproval during the 1940s, when medical advances showed that the diseases he
targeted had no etiological connections with dental issues (123, 173). Nevertheless, the “focal
infection theory”, as it has been called, probably intuited the mutual influences that periodontal
disease could have with certain systemic disease, but since it had not been able to scientifically
prove this, fell into neglect. Ironically, the modern periodontal advances confirmed some of the
theory’s ideas, and, based on a strong scientifically basis, promotes the concept of “periodontal
medicine”, aimed at raising awareness among patients and physicians that the consequences of
untreated periodontal disease may be far more reaching than the oral cavity.
 3. Evidence-Based Clinical Practice
Modern clinical practice is increasingly based on scientific evidence that has proven its
significance and applicability. The process of scientific research is layered, following various
types of studies, each with its advantages and disadvantages and with different scientific impact.
Beginning with scientific case reports, continuing with cross-sectional and longitudinal studies
or interventional trials and ending with systematic reviews with meta-analysis, scientific
researchers are working constantly in order to provide significant and impact-full results that
will change the way that diseases are diagnosed and treated. This is also the case for periodontal
diseases and their associations with other systemic conditions. These associations need to be
thoroughly tested, in terms of the available scientific evidence, the absent or needed scientific
evidence for their proof and finally, the validation of their mechanisms.
4. Subgingival Environment as a Reservoir for Bacteria
In the absence of a professional, regular cleaning procedure of the teeth, the subgingival
biofilm can develop undisturbed for an unlimited period of time. As it grows, the biofilm will
host increasingly more pathogenic bacteria species, capable of inflicting important damage to
the periodontal tissues. Gradually, these microorganisms and their toxins will penetrate the
sulcular gingival epithelium, which lacks the protective keratin layer or may be discontinued by
various lesions, such as ulcers, entering the inner space of the body. Here the bacteria will
trigger an inflammatory reaction, aimed at resolving the infectious challenge. If the subgingival
biofilm is not thoroughly removed, the bacterial challenge will continue, leading to a chronic
inflammatory reaction. This reaction can interfere with other similar, local or systemic immune
responses, causing a misbalance of other conditions (35, 59, 92, 109).
5. Periodontal Disease and Mortality
Certain studies have reported a higher mortality rate in patients suffering from various
forms of periodontal diseases (2, 20, 37, 46, 71, 89, 142). Periodontal parameters, such as
alveolar bone resorption, have been considered as significant indicators for mortality risk
assessment, independently from other well-known risk factors such as smoking or body mass.
Patients with important alveolar bone loss had an increased risk of mortality by 52%. However,
this finding is not a causative one, and it may only suggest that periodontal patients also have
other mortality risk factors, such as smoking, that are common for periodontal and systemic
health problems.
The systemic risk factors that favor the onset of periodontal disease, such as smoking,
stress, metabolic and hormonal disorders, are also involved in the pathogenic processes of
multiple general conditions. Therefore, it is important that during research studies, these factors
are as isolated as possible, so as to objectively determine their implication in the periodontal and
general pathological processes, as individual elements, and not as collective ones.

6. Periodontal Disease, Coronary Heart Disease, and Atherosclerosis

The connections between periodontal disease and coronary heart disease have been the center of
attention for both the American Academy of Periodontology and the European Federation of
Periodontology, who have released in 2013, a common guidebook on the subject (32, 38, 136, 147).
The association between periodontal disease and coronary heart disease needs to be assessed in
a bi-directional manner. On the one hand, patients who suffered coronal vascular events, such as
myocardial infarction, had a significantly more negative dental status, in terms of odontal, pulpar and
periodontal diseases, than the control group (70, 103, 104). On the other hand, the risk of cardio-
vascular events in patients with generalized periodontal disease was higher than that in patients with
localized forms of periodontitis. Despite this association between the two types of diseases, showed by
cross-sectional studies, their results could not prove a causative connection among them. However,
more complex, longitudinal studies showed that the incidence of coronal vascular events was higher
amongst patients who had been previously diagnosed with periodontal disease, than amongst those
periodontally healthy, the risk for the former category of patients being higher by 25% (36, 106).
It is important to clarify the exact moment in time of the onset of certain diseases, in
order to determine the causative nature of the relation between them. Periodontal disease and
coronary heart disease share some common risk factors, such as smoking, which may influence
the development and progression of both them, by making smokers more prone to become ill. It
can be argued that it is not possible to completely isolate the favoring risk factor, when assessing
its implication in the pathogenic processes of one illness or another, given the integrated nature
of the human body, that can allow a harmful action of an element on numerous and different
organs and systems.
The systematic reviews, the so-called “studies of studies”, with the highest point of scientific
significance, have shown that the risk for cardio-vascular events in periodontal patients, can be
increased by 14% to 222% (9).
As concluded by the 2013 guidebook of the two periodontal professional associations, the
data regarding the connections between cardiovascular events and periodontal disease is strong
from a epidemiologic standpoint, but required additional results from interventional trials, that
should clarify if this relationship is not only associative, but causative as well (169).
Effects of Periodontal Infection
The pathogenic mechanisms of periodontal and cardio-vascular diseases share some
similarities, in terms of etiology that involves genetic and environmental elements. Moreover,
the two types of disease also share common risk factors for their onset and evolution, such as
smoking (77, 136, 147).
Ischemic Heart Disease
During ischemic heart disease, the blood vessels can become clogged-up with
atheromatous plaque or thrombi, blocking normal blood flow to the tissues. The inflammatory
reaction that controls the atheromatous plaque formation and the increased blood viscosity could
eventually lead to cardio-vascular events, including myocardial infarction or stroke (Fig.15.1,
15.2) (98, 169).
Systemic Infections
During systemic infections, the viscosity of blood can increase, due to the elevated
fibrinogen and leukocyte levels caused by the inflammatory reactions. This can lead to an
increased risk of cardio-vascular events in patients who are at risk for these. Such inflammatory
reactions include chronic periodontal disease, a condition that sometimes implies elevated blood
coagulation factor levels in affected patients, which increased the risk for blood cloths
formation (Fig.15.3). Therefore, periodontal disease may act as a risk factor for the onset and
decompensation of cardio-vascular diseases (22, 88).
Daily Activity
The subgingival space contains important quantities of bacteria, including high
periodontal pathogens of Gram-negative species. When the gingival tissues are inflamed,
bleeding can frequently occur, either spontaneously or during regular, daily activities, such as
eating or teeth brushing. When gingival bleeding occurs, the bacteria of the subgingival space
can enter the blood stream and cause a systemic bacteremia. When entering the systemic
circulatory network, the periodontal bacteria and their endotoxins can inflict damage to the
blood vessels’ walls (47).
Thrombogenesis
The endothelial lesions caused by circulating bacteria and their endo-toxins will act as
high-risk areas of atheromatous plaque formation, as they will be covered by blood platelets and
cholesterol crystals. Consequently, the risk of atheromatous plaque formation is higher in
patients with periodontal disease, due to the increased bacterial charge that they have.
Porphyromonas gingivalis has been shown to be frequently found in the circulatory system of
periodontal patients. Blood platelets are believed to be able to attach to the surface of some
strains of this bacterium, increasing the risk of thrombogenesis and thrombo-embolic events (60,
61).
Atherosclerosis
Periodontal disease can influence the development of cardio-vascular diseases not only
by increasing the risk of thrombogenesis by direct action of periodontal bacterial pathogens, but
also by indirect means. These include the activity of pro-inflammatory cytokines (such as IL-1,
TNF-α and PGE2), which have elevated levels during periodontal inflammation. These cytokines
can cause an increase of the thickness of the arterial walls, mostly of the intima and media.
These processes characterize atherosclerosis, in which the thickening of the arterial walls can
impair normal blood flow and lead to cardiovascular events (Fig.15.4).
Role of Periodontal Disease in Atherosclerotic Myocardial or Cerebral Ischemia
The periodontal bacteria can enter the systemic circulation and reach the internal
arterial walls, inflicting damage and causing lesions that may eventually lead to the formation of
atheromas. The inflammatory reaction, that periodontal disease involves, also contributes to a
thickening of the vascular walls, increasing the risk of cardio-vascular events (Fig.15.5). The
combined action of modified coagulability patterns, injured endothelial walls and blood platelet
activity, that can be found in periodontal patients acts as a predisposing factor for the onset of
cardio-vascular diseases in such patients (21, 57, 180, 180).
The periodontal inflammatory reaction tends to be extremely varied, from patient to
patient, as it is mainly genetically determined. Given the unique character of one’s genetic
background, it has been observed that patients with a hyper-inflammatory phenotype (MØ+)
will develop more intense inflammatory reactions, when dealing with a bacterial challenge. This
translates to an increased production of pro-inflammatory cytokines (such as IL-1, TNF-α and
PGE2) by monocyte and macrophage cells in these patients that drive and accelerate the
inflammatory reaction (Fig. 15.6). Such patients often develop aggressive or refractory forms of
periodontal disease and often have other systemic diseases, such as type 1 diabetes. The MØ+
phenotype can also act as risk factor for cardio-vascular disease, therefore connecting the two
types of diseases (13).
Cardiovascular diseases comprise an important inflammatory element, similar to the
inflammatory periodontal reaction. By means of common pro-inflammatory cytokines, the two
reactions could have a compatible activity. Important risk factors for cardiovascular disease, such as
the elevated serum levels of C-reactive protein (CRP) and fibrinogen are also found in increased
levels in periodontal patients, as compared to control subjects (138, 139, 27, 94, 175). Therefore,
more pathogenic connections could exist between the cardio-vascular and periodontal pathologies.
The influence of periodontal disease on the cardio-vascular pathology has also been
demonstrated by the assessment of the consequences of periodontal treatment. It has been shown
that after periodontal procedures, such as scaling and root planing, the serum levels of
inflammatory markers (IL-6, CRP) will decrease and that an improvement of vascular health
markers will occur in treated patients, even leading to a complete normalization (33, 34).
Therefore, periodontal treatment seems to have beneficial effects on the cardio-vascular status
of patients, decreasing the risk of pathologic events and reducing the level of normal blood flow
impairment. In addition, the effects of periodontal treatment also enhance the viability of the
associations between periodontal and cardio-vascular diseases (148, 168).
7. Periodontal Disease and Stroke
Cerebro-vascular accidents (stroke) are pathologic events in which normal blood flow to
the brain tissues in impaired, either in ischemic or hemorrhagic manner. These events can
occur after systemic infections, which as important risk factors for their onset, along with
elevated blood pressure, smoking, diabetes and conorary-heart disease.
The current research shows that periodontal disease is mainly linked to the ischemic
forms of stroke, caused by the blockage of brain blood vessels by trombi and a subsequent
blood deprivation of a cerebral area. In numerous studies, the risk of stoke has been
significantly higher in periodontal patients, as compared to control subjects. The risk can be as
three times higher mainly in male patients, who are younger than 65 years and suffer from
severe forms of periodontal disease (69, 176).
The patterns of periodontal influence on stroke risk are similar to those of cardio-
vascular diseases, acting directly through the bacterial challenge on the blood vessels, or
indirectly, by increasing the inflammatory status, by means of systemic elevated levels of pro-
inflammatory cytokines, CRP and fibrinogen.

8. Periodontal Disease and Diabetes Mellitus

Diabetic patients often exhibit more severe and extended forms of periodontal disease than
non-diabetic ones, this aspect being highlighted by numerous epidemiologic studies, which
eventually lead to an official recognition of periodontal disease as the 6 th complication of diabetes,
by the American Diabetes Association. Due to this fact, diabetic patients need to be referred to
dental practitioners for extensive and complete periodontal assessment (112, 99, 5).
Diabetes can have important influences on the periodontal tissues, which predisposes the
onset of periodontal disease, as well as the disease’s evolution pattern (112). The incidence of type
2 diabetes was higher in periodontal patients than in those without periodontal disease and that
when occurring in diabetic patients, periodontal disease can have a deleterious effect on
glycemic level control (15, 161). For example, the glycemic control is worse in diabetic patients
who also suffer from periodontal disease, as opposed to diabetic patients without periodontal
damage. Moreover, the presence of periodontal disease in diabetic patients can also influence
the onset of other diabetes-related complications, by making their prevalence higher in this
category of patients than in diabetic patients with no periodontal conditions (167).
The negative effect that periodontal disease has on optimal glycemic control is also
highlighted by the positive effect that periodontal disease treatment has on this diabetic critical
parameter. Many studies have shown than comprehensive periodontal treatment in diabetic
patients with periodontal disease can improve glycemic control, by lowering the HbA1c levels
(41, 112, 151, 1540. In contrast, diabetic patients with periodontal disease who received no
periodontal treatment, showed no signs of improvement in glycemic control.
The cause of elevated glycemia in type 1 and type 2 diabetes is different and it has been
shown through extensive studies that the effects of periodontal therapy on glycemic control are
more obvious for type 2 diabetes patients (16). Some positive effects of periodontal treatment of
glycemic control can also be found in type 1 diabetes patients, being more significant if the
baseline glycemia levels are very elevated.
Systemic use of antibiotics, as part of comprehensive periodontal therapy, can be used in
periodontal patients with diabetes, particularly in patients with elevated levels of glycemia and
severe forms of periodontitis.
 Periodontal Infection Associated with Glycemic Control in Diabetes
Systemic infections can have great influence on glycemic control, by being able to change
the cellular response to insulin action. Thus, when pro-inflammatory markers, such as cytokines
(interleukins, prostaglandins etc) are released into the blood stream by monocytes or
macrophages as a result of bacterial challenge, different cells become insensitive to the action of
insulin, which enables the cellular intake of glucose. Consequently, glucose cannot be metabolized
and increases its serum levels, leading to hyperglycemia, the clinical expression of diabetes
mellitus. One such bacterial challenge that may lead to severe inflammation is found in periodontal
disease (33, 94, 162).
In periodontal disease, the chronic bacterial challenge by periodontal pathogens causes an
increase in the expression of pro-inflammatory markers such as IL-1β, TNF-α and IL-6 (Fig. 15.7).
These cytokines have been associated with increased cellular insulin resistance. Hence, in
periodontal patients glycemic control could be more difficult to reach. The bacterial challenge in
periodontal disease is a chronic, prolonged one, leading to an increased pro-inflammatory marker
secretion for a long period of time, which causes an increased insulin resistance that has deleterious
effects on the diabetic status of affected patients. The effects of periodontal treatment in diabetic
patients decrease the bacterial challenge and reduce the intensity of the inflammatory reaction. As
a result of the periodontal treatment, the levels of circulating pro-inflammatory cytokines may
decrease, leading to a reduction of insulin resistance and an improvement of glycemic control,
mainly in type 2 diabetes patients (16).
9. Periodontal Disease and Pregnancy Outcome
Low-birth-weight (LBW) infants (i.e., those weighing <2500 g at birth) are 40 times
more likely to die during the neonatal period than normal-birth-weight (NBW) infants (107).
The social and financial costs of LBW infants are enormous, and an emphasis on the prevention
of low birth weight is preferred to the high-cost intensive care often required to allow for the
survival of LBW infants.
The primary cause of LBW deliveries is preterm labor or premature rupture of
membranes (PROM). Factors such as smoking, alcohol, or drug use during pregnancy;
inadequate prenatal care; race; low socioeconomic status; hypertension; old or young maternal
age; diabetes; and genitourinary tract infections increase the risk of preterm LBW delivery.
However, these risk factors are not present in approximately one-fourth of preterm LBW cases,
which results in a continued search for other causes (48, 127).
Research has examined the relationship between maternal infection and preterm labor,
PROM, and LBW delivery. The true extent of this relationship is difficult to determine, because
the majority of maternal infections may be subclinical. Genitourinary tract infections have been
associated with adverse pregnancy outcomes.

Bacterial Vaginosis

Bacterial vaginosis is the most common vaginal disorder in women of reproductive age.
It is caused by changes in the vaginal microflora in which normally predominant facultative
lactobacilli are replaced by Gardnerella vaginalis; anaerobic organisms, including species of
Prevotella, Bacteroides, Peptostreptococcus, Porphyromonas, and Mobiluncus; and other
organisms (62). Bacterial vaginosis is a known risk factor for preterm labor, PROM, and LBW
delivery (54, 172). The incidence of preterm birth is approximately three times greater among
women with bacterial vaginosis as compared with those without.
 The exact mechanism by which vaginal colonization or genitourinary tract infection may
cause PROM and preterm labor is not known (100, 172). The primary mechanism has
traditionally been thought to be ascending infection from the vagina and the endocervix.
Endotoxins (LPSs) and bioactive enzymes produced by many organisms associated with
vaginosis may directly injure tissues and induce the release of proinflammatory cytokines and
prostaglandins. Throughout normal gestation, amniotic prostaglandin levels rise steadily until a
sufficient threshold is reached that induces labor and delivery. Maternal infection may cause
increased amniotic prostaglandin production, and it may also result in labor-inducing levels
being reached before full gestation. In addition to prostaglandins, various proinflammatory
cytokines (e.g., IL-1, IL-6, TNF-α) have been found in the amniotic fluid of women with
preterm labor. Women with preterm labor often have culture-positive amniotic fluid, even in the
absence of clinical infection. Among culture-positive patients, the species that is most often
isolated is Fusobacterium nucleatum (63).
Many of the other species isolated from amniotic fluid in women with preterm labor are
those often found with bacterial vaginosis, which supports an ascending route of infection.
However, the frequency of F. nucleatum detection suggests other possible routes of infection.
Some investigators have suggested infection by a hematogenous route from a location in which
the organism is often detected, like the mouth (63). F. nucleatum is a common oral species that
is highly prevalent in patients with periodontitis, and it could reach the amniotic fluid via
hematogenous spread from the oral cavity. This route is also suggested by the occasional
isolation of Capnocytophaga species in the amniotic fluid of women with preterm labor; this is
an organism that is rarely isolated from the vagina but is common in the oral cavity. The species
and subspecies of F. nucleatum isolated from amniotic fluid cultures of women with preterm
labor more closely match those found in subgingival plaque than strains identified from the
lower genital tract. In addition to hematogenous spread, another possible route of infection is by
oral–genital contact involving the transfer of oral organisms to the vagina (63).
Bacterial infection of the chorioamnion, or extraplacental membrane, may lead to
chorioamnionitis, a condition that is strongly associated with PROM and preterm delivery.
Maternal infection may lead to the presence of amniotic bacterial products, such as LPSs from
gram-negative organisms, which stimulate the production of host-derived cytokines in the
amnion and the decidua (eFig. 15.1). These cytokines, including IL-1, TNF-α, and IL-6,
stimulate increased prostaglandin production from the amnion and the decidua, which leads to
the onset of preterm labor.
The question then arises as to what stimulates the increased cytokine levels and the
resultant increased prostaglandin levels seen during preterm delivery in patients with no
evidence of genitourinary infection. Many cases of preterm LBW could result from infections of
unknown origin, such as those that originate in areas other than the genitourinary tract.

Role of Periodontitis in PROM

Periodontitis is a remote Gram-negative infection that may play a role in LBW

infants.100 As discussed previously, periodontopathic organisms and their products may have
wide-ranging effects that are most likely mediated through the stimulation of host cytokine
production in target tissues. Animal studies suggest that remote reservoirs of gram-negative
organisms and their products may have a negative impact on pregnancy outcome. Remote
nondisseminated infection with P. gingivalis may result in abnormal pregnancy outcomes.
P. gingivalis–induced experimental periodontitis in animal models resulted in decreased
fetal birth weight and increased amniotic fluid levels of TNF-α and PGE2 (eFig. 15.2) (127).
This provides direct evidence that periodontal infection can affect the fetal environment and
pregnancy outcomes. Animal studies have led to an examination of the potential effects of
periodontitis on pregnancy outcomes in humans (68). Women with periodontitis that resulted in
more than 3 mm of attachment loss in at least 60% of sites had a 7.5-fold increased risk of
having an LBW infant. Pregnant women with generalized periodontitis had a fivefold increased
risk of preterm birth before 35 weeks’ gestation and a sevenfold increased risk of delivery before
32 weeks’ gestation as compared with women without periodontitis (73). These studies indicate
a strong association between periodontal infection and adverse pregnancy outcomes.
Studies consistently demonstrated a significant association between periodontitis and
adverse pregnancy outcomes.
There are two major pathways by which periodontal diseases may be associated with
increased adverse pregnancy outcomes: (1) a direct pathway in which oral microorganisms
disseminate to the fetal-placental unit either through a hematogenous route from the oral cavity
or by an ascending route via the genitourinary tract, or (2) an indirect pathway in which elevated
inflammatory mediators from the periodontal tissues reach the fetal-placental unit directly
through the systemic vasculature or reach the liver and stimulate hepatic production of even
more proinflammatory cytokines, which subsequently affects the fetal-placental unit.
Women who had LBW infants had significantly higher levels of Aggregatibacter
(formerly Actinobacillus) actinomycetemcomitans, Tannerella forsythia, P. gingivalis, and
Treponema denticola in their subgingival plaque than did the control women who had NBW
infants (127).
The immune system of preterm infants is often challenged by organisms from the
mother’s oral cavity. The increased bacterial challenge may have broader systemic effects,
thereby resulting in an elevated challenge to the fetal immune system.
Periodontal disease may also increase the risk for preeclampsia (68). This hypertensive
disorder affects about 5% to 10% of pregnancies, and it is a major cause of perinatal and
maternal morbidity and mortality. Preeclampsia has multiple potential etiologies, several of
which involve vascular changes in the placenta that are similar to those seen with
atherosclerosis. The presence of periodontitis during pregnancy or a worsening of periodontal
disease during pregnancy is associated with a twofold to 2.5-fold increased risk for preeclampsia
(14). Periodontal disease was associated with a significant 60% to 76% overall increase in the
risk of preeclampsia (26, 68).
Numerous trials have examined the effects of treating periodontal disease during
gestation rather than waiting until after parturition to provide needed care. Women who received
scaling and root planing before 28 weeks’ gestation, followed by prophylaxis every 2 weeks
until parturition, had an LBW rate of 1.8% (96). Conversely, women who did not receive
periodontal therapy during gestation but instead were treated after parturition had an LBW rate
of 10.1%. Periodontal treatment during gestation may be most appropriate for women at greater
risk for adverse pregnancy outcomes.
Given the conflicting evidence, it is currently unclear whether periodontal therapy
provided during gestation has a beneficial effect on pregnancy outcome. What is clear is that
scaling and root planing provided during the second and third trimesters of gestation are safe
procedures. Every intervention trial published to date has shown that scaling and root planing
during pregnancy are associated with either a decrease or no change in adverse pregnancy
outcome rates. Not a single study has shown an increase in adverse outcome rates. Thus, the
clinician should feel comfortable providing scaling and root planing during the second and
third trimesters of pregnancy. Use of local anesthetics is acceptable during such treatment,
because research has demonstrated no increase in birth weight, gestational age at delivery, or
miscarriage rate in pregnant women receiving dental local anesthetics compared with pregnant
women not receiving anesthetics (56).
 10. Periodontal Disease and Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction

that results from chronic bronchitis or emphysema. Bronchial mucous glands enlarge, and an
inflammatory process occurs during which neutrophils and mononuclear inflammatory cells
accumulate within the lung tissue (58, 165).
COPD shares similar pathogenic mechanisms with periodontal disease. With both
diseases, a host inflammatory response is mounted in response to chronic challenge by bacteria
in periodontal disease and by factors such as cigarette smoking in COPD. The resulting
neutrophil influx leads to the release of oxidative and hydrolytic enzymes that cause tissue
destruction directly. The recruitment of monocytes and macrophages leads to further release of
proinflammatory mediators.
Less is known about the clinical relationship between periodontal disease and COPD.
There is a significant twofold increased risk of COPD in those with periodontal disease as
compared with those without (181). However, more evidence is needed to establish a strong
relationship between the two diseases (144).
In COPD patients with periodontitis, periodontal therapy may impact respiratory health.
COPD exacerbation is an acute event in which respiratory symptoms are worsened, usually to
the point where a change in medication is needed. Most COPD exacerbations are caused by
infections. In controlled clinical trials, scaling and root planing was associated with a decrease in
the frequency of COPD exacerbations compared with nontreatment (86, 182).

11. Periodontal Disease and Acute Respiratory Infections

The upper respiratory passages are often contaminated with organisms derived from the
oral, nasal, and pharyngeal regions. Conversely, the lower airways, in which gas exchange
occurs, are generally maintained free of microorganisms by a combination of host immune
factors and mechanical clearance through the cough reflex, the ciliary transport of aspirated
contaminants, and the movement of secretions from the lower airways into the trachea (165).
Pneumonia is an infection of the lungs that is caused by bacteria, viruses, fungi, or mycoplasma
and is broadly categorized as either community-acquired or hospital-acquired. A wide variety of
bacteria can cause pneumonia, and the spectrum of offending organisms differs greatly between
community-acquired and hospital-acquired infections.
Community-acquired bacterial pneumonia is caused primarily by the inhalation of
infectious aerosols or the aspiration of oropharyngeal organisms. Streptococcus pneumoniae and
Haemophilus influenzae are the most common, although numerous other species may be found,
including anaerobic bacteria (130). Antibiotic therapy is highly successful for the resolution of
most cases of community-acquired bacterial pneumonia. To date, no associations have been
found between oral hygiene or periodontal disease and the risk for acute respiratory conditions
such as pneumonia in community-dwelling individuals (145).
Potentially Respiratory Pathogens (PRPs) may also originate in the oral cavity, with
dental plaque serving as a reservoir of these organisms (8). Poor oral hygiene is common in
hospital and nursing home settings, especially among severely ill patients (146). PRPs are more
often isolated from the supragingival plaque and buccal mucosa of patients in intensive care
units than from those in outpatient settings. Organisms that are not routinely found in dental
plaque become plaque colonizers after prolonged hospitalization. Subgingival plaque may also
harbor PRPs, and putative periodontal pathogens have been associated with nosocomial
pneumonia. Furthermore, anaerobic organisms from periodontal pockets may serve as the
primary inoculum for suppurative respiratory diseases (e.g., pulmonary abscesses) that involve
significant morbidity and mortality.
Few studies have examined the potential impact of periodontitis on the risk for
nosocomial pneumonia. Interventions used to improve oral hygiene, such as mechanical
toothbrushing and chemical antimicrobial rinses, have the potential to decrease the risk of
nosocomial pneumonia in high-risk patients, such as those in intensive care units or those on
ventilators (8, 144). Improved oral hygiene by the patient in combination with frequent
professional oral health care reduces both the incidence and progression of respiratory diseases
in older patients living in nursing homes, and these practices have a major impact on individuals
in intensive care units, for whom the risk for nosocomial pneumonia is markedly elevated.

12. Periodontal Disease and Asthma

There is little scientific evidence on the association between periodontal disease and
asthma, the few studies on the subject highlighting by increased risk of asthma onset in severe
periodontal disease patients, by up to more 4.8 times, compared to non-periodontal patients
(50).
13. Periodontal Medicine in Clinical Practice
The effects of periodontal disease are far more reaching than the oral cavity, extending to
other areas of the body and influencing the development of other conditions. Some patients,
with particular genetic background or medical history, may exhibit certain conditions that are
connected to the periodontal pathology and whose evolution and prognosis is influenced by the
complementary periodontal treatment. Therefore, the concepts of periodontal medicine need to
be taken into serious consideration by dental practitioners when dealing with periodontal
patients, and a holistic approach of these patients needs to be put into practice.