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Abstract

Background Chronic obstructive pulmonary disease (COPD) and periodontitis are severe debilitating disorders of inflammatory origin. COPD manifests as inflammation of the lung connective tissue caused by irritants such as smoking and dust particles, resulting in narrowing of the airway. Periodontitis follows the same inflammatory course with the resultant destruction of the local connective tissue, and several irritants are well-documented risk factors for this disease. Highlights Neutrophilic dominance is well established in both of these conditions, and some evidence suggests that periodontopathogens play a role in causing respiratory infections. Given the similarities in the etiopathogenesis and the risk factor profiles of these diseases, a common foundation exists to suggest an inter relationship between the two diseases. Conclusion The present article briefly reviews the interlinking mechanisms between the two diseases, starting with the role of periodontal pathogens, innate immunity, and, ultimately, imbalances in oxidative stress and the protease-antiprotease system. Although epidemiological evidence provides no clear association between these two diseases, the striking commonalities should not be overlooked. Hence, future research should be targeted to this area in order to obtain constructive information. © 2015 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.
Review
Chronic obstructive pulmonary disease and periodontitis unwinding
their linking mechanisms
Asha Ramesh
n
, Sheeja S. Varghese
1
, N.D. Jayakumar
2
, Sankari Malaiappan
3
Department of Periodontics, Saveetha Dental College and Hospital, No. 162, Poonamallee High Road, Velappanchavadi 600077, Chennai, India
article info
Article history:
Received 25 August 2015
Received in revised form
11 September 2015
Accepted 15 September 2015
Available online 3 October 2015
Keywords:
Periodontitis
COPD
Neutrophil
Oxidative stress
Association
abstract
Background: Chronic obstructive pulmonary disease (COPD) and periodontitis are severe debilitating
disorders of inammatory origin. COPD manifests as inammation of the lung connective tissue caused
by irritants such as smoking and dust particles, resulting in narrowing of the airway. Periodontitis follows
the same inammatory course with the resultant destruction of the local connective tissue, and several
irritants are well-documented risk factors for this disease.
Highlights: Neutrophilic dominance is well established in both of these conditions, and some evidence
suggests that periodontopathogens play a role in causing respiratory infections. Given the similarities in
the etiopathogenesis and the risk factor proles of these diseases, a common foundation exists to suggest
an inter relationship between the two diseases.
Conclusion: The present article briey reviews the interlinking mechanisms between the two diseases,
starting with the role of periodontal pathogens, innate immunity, and, ultimately, imbalances in oxi-
dative stress and the proteaseantiprotease system. Although epidemiological evidence provides no clear
association between these two diseases, the striking commonalities should not be overlooked. Hence,
future research should be targeted to this area in order to obtain constructive information.
&2015 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2. Role of periodontal pathogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.1. Neutrophilic predominance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.2. Neutrophil extracellular traps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.3. Protease/anti-protease imbalance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
2.4. Oxidative stress in the midst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Ethical approval. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Conict of interest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
References.............................................................................................................. 26
1. Introduction
Periodontitis is a chronic inammatory disease that results in the
destruction of the supporting structures of the teeth. The etiology is
multifactorial, with periodontopathogens being the major crux in the
initiation and progression of the disease. Plaque build-up allows the
growth of anaerobic bacteria [1], which eventually leads to the
recruitment and activation of neutrophils. This results in the up-
regulation of pro-inammatory cytokines, leading to the release of
neutrophilic enzymes to combat the invaders. Prolonged exposure of
Contents lists available at ScienceDirect
journal homepage: www.elsevier.com/locate/job
Journal of Oral Biosciences
http://dx.doi.org/10.1016/j.job.2015.09.001
1349-0079/&2015 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.
Abbreviations: COPD, Chronic obstructive pulmonary disease; Fmlp, N-formyl-
Met-Leu-Phe; NET, Neutrophil extracellular traps; GCF, Gingival crevicular uid;
MMP, Matrix metalloproteinase
n
Corresponding author. Tel.: þ91 9841722113.
E-mail addresses: ash.periopg@gmail.com (A. Ramesh),
drsheeja@rediffmail.com (S.S. Varghese),
principaldental@saveetha.com (N.D. Jayakumar),
msankari@gmail.com (S. Malaiappan).
1
Tel.: 9884042252.
2
Tel.: 9444071930.
3
Tel.: 9840285905.
Journal of Oral Biosciences 58 (2016) 2326
the connective tissue to these insults results in its degradation and the
subsequent loss of ligamentous support and alveolar bone, eventually
leading to tooth loss [2].
The focal infection theory proposed by William Hunter in the
1800s suggested that the oral cavity was the root cause of all sys-
temic diseases; however, this theory was widely disregarded in the
1930s. This theory has been revisited in the modern era because of
the multitude of systemic inuences exerted by periodontal infec-
tions, which are a current focus of research [3]. Recent evidence has
established that periodontitis could be a probable risk factor for
cardiovascular diseases such as atherosclerosis, stroke, myocardial
infarction, diabetes, adverse pregnancy outcome, and respiratory
disorders. This paradoxical shift has been studied extensively and is
now termed periodontal medicine.
Respiratory disorders rank high in the leading causes of mor-
tality and morbidity globally, with upper respiratory infections
affecting over 2 billion people and chronic respiratory infections
causing an increase in years lived with disability (YLD) [4]. Chronic
obstructive pulmonary disease (COPD) is a generic term that is
dened by the chronic obstruction of airow. The pathological
subtypes include emphysema, chronic bronchitis, and small airways
disease; although these are distinct entities, they can occur together
in a single patient. This is also a predominantly neutrophil-
mediated inammatory disease, and an increased number of neu-
trophils has been reported in the airways of patients with COPD [5].
Periodontitis and COPD share a common risk factor prole,
with both diseases showing increased susceptibility of the host to
environmental and genetic factors. Both of these diseases are
bacterial in origin, with a neutrophilic predominance, and they
manifest as chronic inammation with underlying connective
tissue destruction of the respective areas. Further, an imbalance is
present in the redox system and in proteaseantiprotease activity,
which are prime targets in the pathogenesis of the two diseases.
Several epidemiological studies have attempted to nd an asso-
ciation between the two diseases [6,7]. A randomized clinical trial
showed that non-surgical periodontal therapy improved lung
function in COPD patients with chronic periodontitis [8]. In addi-
tion, a recent meta-analysis by Zeng et al. of 14 observational
studies showed that populations with periodontal disease had an
overall increased risk of developing COPD (odds ratio, 2.40); these
authors concluded that periodontal disease signicantly increased
the risk of COPD, but the mechanisms remain unclear [9]. Since the
oral cavity physically continues into the respiratory tract, and
because these two diseases share innumerable contributory
mechanisms, elucidating the connecting links is necessary in order
to deduce the association between these two chronic diseases.
This review will focus on the role of periodontal pathogens and
various other mechanisms through which these conditions are
inter-connected.
2. Role of periodontal pathogens
Scannapieco elucidated various mechanisms by which oral
bacteria can contribute to the pathogenesis of respiratory infec-
tions [10]:
1. The aspiration of oral pathogens, such as Porphyromonas gingi-
valis (P. gingivalis), Aggregatibacter actinomycetemcomitans (A.
actinomycetemcomitans), etc., into the lung can cause infection.
2. Periodontal disease-associated enzymes in saliva may modify
the mucosal surfaces to promote adhesion and colonization by
respiratory pathogens, which are then aspirated into the lung.
3. Periodontal disease-associated enzymes may destroy salivary
pellicles on pathogenic bacteria to hinder their clearance from
the mucosal surface.
4. Cytokines originating from the periodontal tissues may alter the
respiratory epithelium to promote infection by respiratory
pathogens.
Laboratory studies have suggested that oral anaerobes such as
P. gingivalis can cause marked inammation when instilled into
the lungs of laboratory animals [11]. Further, the colonization of
the Prevotella species (a periodontopathogen) in patients may be
associated with an infectious process leading to ventilator-
associated pneumonia and a systemic humoral response [12].
As previously mentioned, oral bacteria can modulate the adhe-
sion of respiratory pathogens on epithelial cell lines. Oral bacterial
products or cytokines in the oral/pharyngeal aspirate may stimulate
cytokine production from respiratory epithelial cells, resulting in
the recruitment of inammatory cells. The resulting inamed epi-
thelium may be more prone to respiratory infection. A study by
Scannapieco et al showed that A. actinomycetemcomitans was the
stronger stimulant in the production of pro-inammatory cytokines
from epithelial cells when compared with P. gingivalis [13].A. acti-
nomycetemcomitans has been established as the most prominent
pathogen in human periodontal disease [14].
2.1. Neutrophilic predominance
Although many immune cells like macrophages and dendritic
cells have been proposed to play a role in the pathogenesis of
periodontitis and COPD, neutrophils are considered the most
important because of their high preponderance in both diseases.
Neutrophil counts are high in COPD, and this does not correlate
with effective elimination of the microbes. This results in collateral
lung tissue damage due to the release of enzymes and reactive
oxygen species (ROS). The amount of neutrophil elastase present
in the lung tissue has been correlated with the severity of
emphysema [15]. Further, neutrophilic function is impaired in
COPD patients. A previous study reported that neutrophils isolated
from the blood of individuals with moderate-to-severe COPD
showed decreased chemotaxis in response to classical chemoat-
tractants such as bacterial protein N-formyl-Met-Leu-Phe (fMLP)
and the pro-inammatory cytokine interleukin (IL)-8, with a cor-
relation between the reduced chemotaxis of neutrophils to fMLP
and the degree of airow limitation [16]. Moreover, neutrophils
from individuals with COPD migrate faster than those from heal-
thy subjects, but the accuracy of migration toward known che-
moattractants, such as fMLP and IL-8, is markedly reduced [17].
Cigarette smoke, which is an exogenous source of oxidants, free
radicals, and neutrophils have been shown to induce oxidative
stress in the lung tissue of COPD patients.
The role of neutrophils in periodontitis has not been clearly
elucidated since both qualitative and quantitative differences
have been observed. Neutrophil function shows both hyper and
hypo activity in response to bacterial stimuli in various forms of
periodontitis. Evidence suggests that neutrophil defects generally
lead to a predisposition for aggressive forms of periodontitis and
hyperactivity or that elevated function is associated with an
increased respiratory burst of the neutrophils [18]. Thus, under-
standing the role of neutrophils in periodontitis and COPD is
necessary to ascertain the common pathophysiological pathway
between these two diseases.
2.2. Neutrophil extracellular traps
Neutrophil extracellular traps (NETs) are web-like extracellular
structures of decondensed chromatin associated with histones and
enzymes such as neutrophil elastase (NE) and myeloperoxidase
(MPO), which are both antimicrobial and cytotoxic. They are
released by activated neutrophils, mainly during a distinct process
A. Ramesh et al. / Journal of Oral Biosciences 58 (2016) 232624
of cell death termed NETosis [19]. The triggers of NETosis are the
bacterial cell wall components that activate complement recep-
tors, Fc receptors, or toll-like receptors on neutrophil surfaces [20].
Once in the extracellular space, these components have the ability
to trap micro-organisms and to expose them to high local con-
centrations of degradative enzymes [21]. This is a type of adaptive
mechanism, wherein the bacterial elimination occurs even after
the death of the neutrophil. These mechanisms form an important
part of innate immunity and they are associated with the release
of ROS and degradative enzymes that play a crucial role in bacteria
elimination and the concomitant tissue damage in chronic dis-
eases like periodontitis and COPD.
A study performed by using the sputa of patients with both the
stable and exacerbated forms of COPD showed that this is char-
acterized by the presence of large amounts of NETs and NET-
forming neutrophils [22]. In addition, studies have shown that an
abundance of NETs contain trapped bacteria in the periodontal
pocket (pocket surface, gingival crevicular uid [GCF], and pus)
[2325]. The knowledge that NETs are involved in both diseases
invokes the possibility of developing new therapeutic strategies
that target the host immune defense mechanisms.
2.3. Protease/anti-protease imbalance
Neutrophils are the prime source of proteolytic enzymes such as
matrix metalloproteinase (MMP) and elastase. The neutrophil elastase
present in the azurophilic granules has been shown to play a pivotal
role in the pathogenesis of COPD. This hypothesis was proposed in the
1960s, when patients with deciency of
α
1
-antitrypsin (AAT) were
noted to be specically susceptible to the development of early onset
emphysema, disproportionate to smoking history [26].AATwaslater
foundtohaveaninhibitoryactiononneutrophilelastase.Insupportof
this mechanism, a relationship between the elastase and anti-elastase
imbalance and the extent of emphysema was evident in the broncho
alveolar lavage uid from patients with COPD [27]. This tilt in the
balance in favor of proteases is associated with connective tissue
destruction, in which components like collagen, laminin, and elastin
are targeted by neutrophil elastase.
MMPs are endogenous enzymes with proteolytic activity
against all components of the extracellular matrix and basement
membrane, leading to subsequent periodontal destruction.
Pathogens in microbial dental plaque are capable of stimulating
host cells to increase MMP release, which is considered one of the
indirect mechanisms of tissue destruction observed in period-
ontitis [28]. Vernooy et al. reported increased MMP-8 and MMP-9
activity in the airway compartment of patients with mild-to-
moderate COPD and suggested that an impaired proteinase-
antiprotease balance exists in COPD [29].
Since all of these enzymes comprise the host response compo-
nent in the pathogenesis of these diseases, therapeutic strategies
such as host modulation have been implemented. For periodontitis,
the FDA has approved the use of the host modulatory agent Periostat
(a sub antimicrobial dose of doxycycline) in conjunction with non-
surgical periodontal therapy. In a landmark study by Canton et al, the
usage of a sub antimicrobial dose of doxycycline in conjunction with
scaling and root planing resulted in a signicant improvement in
clinical parameters like probing depth and the clinical attachment
level in adult periodontitis patients [30].Thelong-termuseofmac-
rolides such as azithromycin was shown to reduce the risk of acute
exacerbations in patients with COPD. This was highlighted in a study
where 1142 patients at an increased risk of COPD exacerbation were
randomly assigned at a 1:1 ratio to receive azithromycin (n¼570) at
a dose of 250 mg daily or placebo (n¼572) for 1 year in addition to
their usual care [31]. The median time to acute COPD exacerbation
was 266 days in the azithromycin group compared with 174 days in
the placebo group.
2.4. Oxidative stress in the midst
Excessive production of free radicals and ROS occurs when oxida-
tive stress increases. The lungs are the site of the majority of redox
reactions with exposure to free radicals derived from tobacco smoke
and air pollution [32]. Immune cells such as macrophages and neu-
trophils are endogenous producers of free radicals, which are released
because of bacterial stimulation or environmental insults [33].ROS
may damage the tissues of the body, depending on the amount and
duration of exposure, and may further act as triggers for enzymatically
generated ROS released from respiratory, immune, and inammatory
cells. The body is equipped with antioxidant defense mechanisms
with enzymes such as superoxide dismutase, glutathione peroxidase,
catalase, and peroxiredoxins. These antioxidants function by degrading
the free radicals and ROS and nullifying their harmful effects.
A positive relationship exists between sputum neutrophils and
hydrogen peroxide levels in patients with severe COPD, suggesting
that these cells are the major source of oxidants [34]. Further,
neutrophils from COPD patients were shown to have greater oxi-
dant production than those of smokers with normal lung function
and non-smoking control individuals [35]. The levels of protective
antioxidants are signicantly depleted in the alveolar macro-
phages of COPD patients, and recent studies indicate that anti-
oxidative mechanisms are not sufciently adapted in inamma-
tory respiratory diseases such as COPD; therefore, the oxidants
may subsequently take on the leading role under these conditions.
Polymorphonuclear neutrophils (PMNs) have an established role in
periodontitis, but whether their hyperactivity is responsible for period-
ontal destruction remains a controversial topic. This is because neu-
trophil defects have been associated with localized aggressive period-
ontitis, which is a more rampant and severe form of the disease;
therefore, the pathogenic mechanism remains to be elucidated. Never-
theless, oxidative stress markers have been routinely studied in period-
ontal research. In chronic periodontitis, even unstimulated neutrophils
had greater spontaneous ROS production, as detected by chemilumi-
nescence, than cells from control individuals [36].Anotherstudyshowed
that antioxidant enzymes like superoxide dismutase, catalase, and glu-
tathione reductase are signicantly lower in chronic periodontitis sub-
jects when compared to healthy controls [37]. Thus, cumulative evidence
suggests that oxidative stress plays a major role in both diseases.
3. Conclusion
Since these two diseases have many features in common, i.e., they
follow the same inammatory course with the resultant destruction
of the local connective tissue, it is reasonable to suppose that a
holistic treatment approach is required to combat these two condi-
tions. Neutrophils, with their oxidants and proteases, play a pre-
dominant role in the pathogenesis of both disorders. The future
scope of research should be targeted towards nding the triggers
that cause the imbalance within neutrophils and initiate the disease
process. Although current epidemiologic studies have provided little
evidence to support an association between these two diseases, the
striking similarities in the disease processes suggest that such a
relationship exists. Clinical trials analyzing the causality and patho-
logical basis of these diseases are a necessity.
Ethical approval
Ethical approval was not obtained since this is a review article.
Conict of interest
None.
A. Ramesh et al. / Journal of Oral Biosciences 58 (2016) 2326 25
Acknowledgments
The authors wish to thank the staff and students of the
Department of Periodontics, Saveetha Dental College, for their
assistance with this manuscript.
References
[1] Listgarten MA. Pathogenesis of periodontitis. J Clin Periodontol 1986;13:41830.
[2] Laine ML, Crielaard W, Loos BG. Genetic susceptibility to periodontitis. Periodontol
2000 2012;58:3768.
[3] Hunter W. The coming of age of oral sepsis. Br Med J 1921;1:859.
[4] Global Burden of Disease Study 2013 Collaborators. Global, regional, and
national incidence, prevalence, and years lived with disability for 301 acute
and chronic diseases and injuries in 188 countries, 1990-2013: a systematic
analysis for the Global Burden of Disease Study 2013. Lancet 2015;386:743
800.
[5] Confalonieri M, Mainardi E, Della PR, Bernorio S, Gandola L, Beghe B, Spane-
vello A. Inhaled corticosteroids reduce neutrophil bronchial inammation in
patients with chronic obstructive pulmonary disease. Thorax 1998;53:5835.
[6] Wang Z, Zhou X, Zhang J, Zhang L, Song Y, Hu FB, Wang C. Periodontal health,
oral health behaviours, and chronic obstructive pulmonary disease. J Clin Per-
iodontol 2009;36:7505.
[7] Liu Z, Zhang W, Zhang J, Zhou X, Zhang L, Song Y, Wang Z. Oral hygiene, per-
iodontal health and chronic obstructive pulmonary disease exacerbations. J Clin
Periodontol 2012;39:4552.
[8] Zhou X, Han J, Liu Z, Song Y, Wang Z, Sun Z. Effects of periodontal treatment on
lung function and exacerbation frequency in patients with chronic obstructive
pulmonary disease and chronic periodontitis: a 2-year pilot randomized
controlled trial. J Clin Periodontol 2014;41:56472.
[9] Zeng XT, Tu ML, Liu DY, Zheng D, Zhang J, Leng W. Periodontal disease and risk of
chronic obstructive pulmonary disease: a meta-analysis of observational studies.
PLoS One 2012;7:e46508.
[10] Scannapieco FA, Mylotte JM. Relationships between periodontal disease and
bacterial pneumonia. J Periodontol 1996;67:S111422.
[11] Nelson S, Laughon BE, Summer WR, Eckhaus MA, Bartlett JG, Jakab GJ. Char-
acterization of the pulmonary inammatory response to an anaerobic bac-
terial challenge. Am Rev Respir Dis 1986;133:2127.
[12] Grollier G, Doré P, Robert R, Ingrand P, Gréjon C, Fauchere JL. Antibody
response to Prevotella spp. in patients with ventilator-associated pneumonia.
Clin Diagn Lab Immunol 1996;3:615.
[13] Scannapieco FA, Wang B, Shiau HJ. Oral bacteria and respiratory infection:
effects on respiratory pathogen adhesion and epithelial cell proinammatory
cytokine production. Ann Periodontol 2001;6:7886.
[14] Slots J, Zambon JJ, Rosling BG, Reynolds HS, Christersson LA, Genco RJ. Acti-
nobacillus actinomycetemcomitans in human periodontal disease. Associa-
tion, serology, leukotoxicity, and treatment. J Periodontal Res 1982;17:4478.
[15] Damiano VV, Tsang A, Kucich U, Abrams WR, Rosenbloom J, Kimbel P, Fal-
lahnejad M, Weinbaum G. Immunolocalization of elastase in human emphy-
sematous lungs. J Clin Investig 1986;78:48293.
[16] Yoshikawa T, Dent G, Ward J, Angco G, Nong G, Nomura N, Hirata K, Djuka-
novic R. Impaired neutrophil chemotaxis in chronic obstructive pulmonary
disease. Am J Respir Crit Care Med 2007;175:4739.
[17] Sapey E, Stockley JA, Greenwood H, Ahmad A, Bayley D, Lord JM, Insall RH,
Stockley RA. Behavioral and structural differences in migrating peripheral
neutrophils from patients with chronic obstructive pulmonary disease. Am J
Respir Crit Care Med 2011;183:117686.
[18] Ryder MI. Comparison of neutrophil functions in aggressive and chronic per-
iodontitis. Periodontol 2000 2010;53:12437.
[19] Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y,
Brinkmann V, Zychlinsky A. Novel cell death program leads to neutrophil
extracellular traps. J Cell Biol 2007;176:23141.
[20] Kaplan MJ, Radic M. Neutrophil extracellular traps: double-edged swords of
innate immunity. J Immunol 2012;189:268995.
[21] Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS,
Weinrauch Y, Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science
2004;303:15325.
[22] Grabcanovic-Musija F, Obermayer A, Stoiber W, Krautgartner W, Steinbacher
P, Winterberg N, Bathke AC, Klappacher M, Studnicka M. Neutrophil extra-
cellular trap (NET) formation characterises stable and exacerbated COPD and
correlates with airow limitation. Respir Res 2015;16:59.
[23] Krautgartner WD, Klappacher M, Hannig M, Obermayer A, Hartl D, Marcos V,
Vitkov L. Fibrin mimics neutrophil extracellular traps in SEM. Ultrastruct
Pathol 2010;34:22631.
[24] Vitkov L, Klappacher M, Hannig M, Krautgartner WD. Neutrophil fate in gin-
gival crevicular uid. Ultrastruct Pathol 2010;34:2530.
[25] Vitkov L, Klappacher M, Hannig M, Krautgartner WD. Extracellular neutrophil
traps in periodontitis. J Periodontal Res 2009;44:66472.
[26] Eriksson S. Pulmonary emphysema and alpha-1 antitrypsin deciency. Acta
Med Scand 1964;175:197205.
[27] Fujita J, Nelson NL, Daughton DM, Dobry CA, Spurzem JR, Irino S, Rennard SI.
Evaluation of elastase and antielastase balance in patients with chronic
bronchitis and pulmonary emphysema. Am Rev Respir Dis 1990;142:5762.
[28] Overall CM, Sodek J. Initial characterization of a neutral metalloproteinase,
active on native 3/4-collagen fragments, synthesized by ROS 17/2.8 osteo-
blastic cells, periodontal broblasts, and identied in gingival crevicular uid.
J Dent Res 1987;66:127182.
[29] Vernooy JH, Lindeman JH, Jacobs JA, Hainemaaijer R, Wouters EF. Increased
activity of matrix metalloproteinase-8 and matrix metalloproteinase-9 in
induced sputum from patients with COPD. Chest 200 4;126:180210.
[30] Caton JG, Ciancio SG, Blieden TM, Bradshaw M, Crout RJ, Hefti AF, Massaro JM,
Polson AM, Thomas J, Walker C. Treatment with subantimicrobial dose dox-
ycycline improves the efcacy of scaling and root planing in patients with
adult periodontitis. J Periodontol 2000;71:52132.
[31] Albert RK, Connett J, Bailey WC, Casaburi R, Cooper Jr JA, Criner GJ, Curtis JL,
Dranseld MT, Han MK, Lazarus SC, MakeB, Marchetti N, Martinez FJ, Madinger
NE, McEvoy C, Niewoehner DE, Porsasz J, Price CS, Reilly J, Scanion PD, Sciurba
FC, Scharf SM, Washko GR, Woodruff PG, Anthonisen NR, COPD Clinical
Research Network. Azithromycin for prevention of exacerbations of COPD. N
Engl J Med 2011;365:68998.
[32] Loukides S, Bakakos P, Kostikas K. Oxidative stress in patients with COPD. Curr
Drug Targets 2011;12:46977.
[33] Weiss SJ. Tissue destruction by neutrophils. N Engl J Med 1989;320:36576.
[34] Kostikas K, Papatheodorou G, Psathakis K, Panagou P, Loukides S. Oxidative stress
in expired breath condensate of patients with COPD. Chest 2003;124:137380.
[35] Noguera A, Batle S, Miralles C, Iglesias J, Busquets X, MacNee W, Agusti AG.
Enhanced neutrophil response in chronic obstructive pulmonary disease.
Thorax 2001;56:4327.
[36] Matthews JB, Wright HJ, Roberts A, Cooper PR, Chapple IL. Hyperactivity and
reactivity of peripheral blood neutrophils in chronic periodontitis. Clin Exp
Immunol 2007;147:25564.
[37] Trivedi S, Lal N, Mahdi AA, Singh B, Pandey S. Association of salivary lipid
peroxidation levels, antioxidant enzymes, and chronic periodontitis. Int J
Periodontics Restorative Dent 2015;35:e149.
A. Ramesh et al. / Journal of Oral Biosciences 58 (2016) 232626
... Chronic periodontitis triggers the development of (OSCC) oral squamous cell carcinoma [13]. Recently, there is improving enthusiasm in the development of various types of cancer and their contribution to inflammation as also the underlying pathophysiological factors that lead to malignant transformation [34,14]. ...
... Despite utmost significance of tooth brushing, about half of the population brush twice a day. There are various types of toothbrushes in reducing dental plaque [34]. ...
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The occurrence of periodontal diseases in humans has been a global problem. Certain risk factors affect the initiation, progression and severity of periodontitis. The present study has been designed to assess the periodontal status in patients with oral leukoplakia. The study was carried out among 27 subjects with oral leukoplakia. The required data were collected and imported to SPSS analysis software for analysis. A total of 44.4% were reported to have generalized chronic gingivitis and 55.6% were having generalized chronic periodontitis. It was observed that elderly patients between 50 to 80 years (55.6%) are more prone to generalised chronic periodontitis. The p value obtained is 0.503 which is not significant (p>0.05). We also observed that males (96.3%) were more commonly reported with oral leukoplakia and diagnosed with periodontal diseases than females (3.7%).The results of this study provide the prevalence of periodontal diseases in oral leukoplakia. The association of periodontitis with premalignant lesions may influence the risk of disease progression and thus preventive therapeutic measures for periodontal diseases can be planned for oral leukoplakia patients.
... The relationship between oral and systemic diseases has been discussed frequently in recent years. In many studies, this relationship was focused mainly on periodontal diseases [39,14,38,27,28]. Cardiovascular diseases rank first among the causes of death in developed countries. ...
... Within the limitations of the present study, periodontitis was more prevalent in patients with cardiac disorders and there was no significant association between gender and periodontal disease. matory process displays individual variations [13,21,27,30,29]. ...
... Periodontitis can cause pathological loss of the tooth and various other systemic complications such as heart attack, stroke or even infective endocarditis. It is also aggravated and seen in association with various systemic complications like diabetes mellitus [45,49,50] etc. In light of various recent breakthroughs in treatment planning and execution, for extensive and comprehensive treatment for periodontitis there are various approaches [21,39,49,50,52,53,62]. ...
... It is also aggravated and seen in association with various systemic complications like diabetes mellitus [45,49,50] etc. In light of various recent breakthroughs in treatment planning and execution, for extensive and comprehensive treatment for periodontitis there are various approaches [21,39,49,50,52,53,62]. Periodontal therapy is aimed at arresting the progression of disease by controlling the infection, and regenerating the lost attachment apparatus of the tooth. ...
... However it should be remembered that the choice of therapy again is dictated by the severity of furcation lesion and the pattern of bone destruction. Apart from all these oral hygiene maintenance during follow up, genetic factors, environmental factors may also have played a role in survival of the teeth with furcation involvement [24][25][26][27][28][29], which were not assessed in our study [30][31][32][33][34][35][36]. Also, inconsistencies between our results with previous reports may be due to differences in the severity of furcation involvement at baseline [28,[37][38][39][40], duration of recall intervals, levels of plaque control and presence of risk factors such as smoking [41][42][43][44][45] and genetic susceptibility. ...
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The management of furcation involvement is found to be one of the greatest challenges in periodontal therapy as they respond less favourably to the conventional periodontal therapy, and the molars are lost more often than any other tooth type. This may be due to the complexity and difficulty in treating the furcation involved areas during periodontal therapy. The necessity for better survival rate strives for better standards of treatment. The objective of this study is to find the survival rate of Grade II furcation-involved teeth following periodontal therapy. The data analysis of 86,000 patient data records were done and required data regarding periodontal parameter, demographic details preoperative and findings of tooth survival 6 month after periodontal therapy was extracted and descriptive statistics were performed on the data in IBM SPSS Statistical Analyzer (23.0 version) after the data were tabulated. The survival rate of Grade II furcation involved teeth was found to be 66.35%. The survival of Grade II furcation involved mandibular molars was found to have a better survival rate when compared to maxillary molars and (Chi square value, p value =0.003(<0.05)). Also the survival of teeth was found to decrease with increase in mobility (Chi square value, p value =0.000(<0.05)) and with increased bone loss (Chi square value, p value =0.002(<0.05)). Within the limitations of the study, the survival of Grade II furcation involved teeth was found to be moderate post periodontal treatment.
... gummy smile [40] and isolated gingival recession with coronally advanced flap [41]. association of pulmonary disease [42]and dental implants in chronic periodontitis [43] and variation in course of Inferior alveolar nerve [44]. ...
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Gingival recession is the displacement of soft tissue apically which eventually leads to root surface exposure. There are various factors causing gingival recession predominantly tooth malposition, occlusal trauma and high muscle attachment.When the gingiva recede away from their natural level they move downwards and start to expose the root portion of the tooth.To cover the exposed roots, root coverage can be considered. Root coverage can be done either with white bonding or filling material or with tissue grafting. The aim of the study is to evaluate the occurrence of gingival recession among Class II division 2 malocclusion patients. Records of patient records with Class II div 2 malocclusion were reviewed and analysed for presence or absence of gingival recession. 101 records were included in the study based on inclusion criteria. The presence or absence of gingival recession in these patients were recorded. Cross verification was done with the help of photographic evaluation. The tabulated data was imported into SPSS and analysed. The results showed that 18.8% of the study population presented with gingival recession.
... Previously numerous clinical trials [14][15][16][17][18][19], and literature reviews [20][21][22][23][24][25][26][27][28] over the past 5 years have been done on mechanism, treatment of gingival recession and other related fields of study. Gingival recession is a well researched field of Periodontics. ...
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Gingival recession is a term for apical displacement of gingival margin below the cemento enamel junction. It is a common and undesirable condition which is usually common with increase in age. Gingival recession is a common finding in most general practice. It may be indicative of poor oral hygiene. The present study aims to evaluate the prevalence of gingival recession in patients with good oral hygiene. A retrospective study was done based on data analysed from 86000 patient records collected in a dental outpatient department, out of which 2843 patient records who had presented with good oral hygiene were reviewed. Presence or absence of gingival recession was recorded. Excel tabulation was done and then imported the data to SPSS version 20 for statistical analysis. Out of the 2843, people in the age group of 36-55 years had higher gingival recession and good oral hygiene compared to other age groups that is about 33%. 64% of sample size in the age group of 56 - 80 years showed gingival recession despite having good oral hygiene status. Within the limits of the study, good oral hygiene may not be linked with gingival recession, however habits such as improper tooth brushing technique may cause recession. 18.4% of the total study group showed good oral hygiene and gingival recession.
... Furthermore, any disturbance in the integrity of the respiratory epithelium can allow translocation of bacteria to enter the systemic circulation. The presence of chronic periodontitis is associated with increase in exacerbations of COPD, likely due to a combination of factors including micro-aspiration, translocation of pathogenic oral bacteria to the respiratory tract [81][82][83]. This is potentially an important under-recognised causal or at least an associated factor in recurrent AECOPD. ...
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Background Unfortunately, many COPD patients continue to exacerbate despite good adherence to GOLD Class D recommended therapy. Acute exacerbations lead to an increase in symptoms, decline in lung function and increased mortality rate. The purpose of this review is to do a literature search for any prophylactic anti-microbial treatment trials in GOLD class D patients who ‘failed’ recommended therapy and discuss the role of COPD phenotypes, lung and gut microbiota and co-morbidities in developing a tailored approach to anti-microbial therapies for high frequency exacerbators. Main text There is a paucity of large, well-conducted studies in the published literature to date. Factors such as single-centre, study design, lack of well-defined controls, insufficient patient numbers enrolled and short follow-up periods were significant limiting factors in numerous studies. One placebo-controlled study involving more than 1000 patients, who had 2 or more moderate exacerbations in the previous year, demonstrated a non-significant reduction in exacerbations of 19% with 5 day course of moxifloxacillin repeated at 8 week intervals. In Pseudomonas aeruginosa ( Pa ) colonised COPD patients, inhaled antimicrobial therapy using tobramycin, colistin and gentamicin resulted in significant reductions in exacerbation frequency. Viruses were found to frequently cause acute exacerbations in COPD (AECOPD), either as the primary infecting agent or as a co-factor. However, other, than the influenza vaccination, there were no trials of anti-viral therapies that resulted in a positive effect on reducing AECOPD. Identifying clinical phenotypes and co-existing conditions that impact on exacerbation frequency and severity is essential to provide individualised treatment with targeted therapies. The role of the lung and gut microbiome is increasingly recognised and identification of pathogenic bacteria will likely play an important role in personalised antimicrobial therapies. Conclusion Antimicrobial therapeutic options in patients who continue to exacerbate despite adherence to guidelines-directed therapy are limited. Phenotyping patients, identification of co-existing conditions and assessment of the microbiome is key to individualising antimicrobial therapy. Given the impact of viruses on AECOPD, anti-viral therapeutic agents and targeted anti-viral vaccinations should be the focus of future research studies.
... The Candida species are opportunistic pathogens that can cause disease in hosts who are compromised by underlying local or systemic pathological processes [1][2][3]. Candida albicans is the species most often associated with oral lesions but other candida species including C. glabrata, C. tropicalis, C. parapsilosis, C. krusei have also been isolated in the saliva [4][5][6]. Fungal organisms commonly colonise the tongue, palate and buccal mucosa but may also occur in subgingival plaque of adults with periodontitis [7][8][9]. ...
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Aim : The aim of the present study was to assess the prevalence of flap surgery among patients with diabetes mellitus and hypertension.The purpose of the study was to determine the prevalence of flap surgery among patients with diabetes mellitus and hypertension. Materials : A hospital based cross-sectional study was conducted for 48 patients with diabetes and/ or hypertension attending Saveetha Dental College and Hospital from June 2019 to March 2020 were included in the study. The data were gathered through semi-closed ended questionnaires and clinical examinations. Prevalence rate of flap surgery among patients with diabetes and hypertension was assessed by student's independent t-test or one way analysis of variance. Results : Results showed that the prevalence of diabetes and hypertension among patients undergoing flap surgery were majorly males with a history of diabetes mellitus. Data analysis was done using a chi square analysis between gender and prevalence of diabetes (chi-square-6.750;df-1;p-0.009) we found the results were statistically significant (P<0.05). Discussion : Prevalence of diabetes mellitus and hypertension among patients undergoing flap surgery were found to be higher in patients with diabetes. Conclusion : Therefore, additional care should be taken into consideration when it comes to dealing with patients with underlying systemic conditions like diabetes and hypertension.
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COPD is a progressive disease of the airways that is characterized by neutrophilic inflammation, a condition known to promote the excessive formation of neutrophil extracellular traps (NETs). The presence of large amounts of NETs has recently been demonstrated for a variety of inflammatory lung diseases including cystic fibrosis, asthma and exacerbated COPD. We test whether excessive NET generation is restricted to exacerbation of COPD or whether it also occurs during stable periods of the disease, and whether NET presence and amount correlates with the severity of airflow limitation. Patients, materials and methods Sputum samples from four study groups were examined: COPD patients during acute exacerbation, patients with stable disease, and smoking and non-smoking controls without airflow limitation. Sputum induction followed the ECLIPSE protocol. Confocal laser microscopy (CLSM) and electron microscopy were used to analyse samples. Immunolabelling and fluorescent DNA staining were applied to trace NETs and related marker proteins. CLSM specimens served for quantitative evaluation. Sputum of COPD patients is clearly characterised by NETs and NET-forming neutrophils. The presence of large amounts of NET is associated with disease severity (p < 0.001): over 90 % in exacerbated COPD, 45 % in stable COPD, and 25 % in smoking controls, but less than 5 % in non-smokers. Quantification of NET-covered areas in sputum preparations confirms these results. NET formation is not confined to exacerbation but also present in stable COPD and correlates with the severity of airflow limitation. We infer that NETs are a major contributor to chronic inflammatory and lung tissue damage in COPD.
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Many epidemiological studies have found a positive association between periodontal disease (PD) and risk of chronic obstructive pulmonary disease (COPD), but this association is varied and even contradictory among studies. We performed a meta-analysis to ascertain the relationship between PD and COPD. PubMed and Embase database were searched up to January 10, 2012, for relevant observational studies on the association between PD and risk of COPD. Data from the studies selected were extracted and analyzed independently by two authors. The meta-analysis was performed using the Comprehensive Meta-Analysis software. Fourteen observational studies (one nested case-control, eight case-control, and five cross-sectional) involving 3,988 COPD patients were yielded. Based on random-effects meta-analysis, a significant association between PD and COPD was identified (odds ratio = 2.08, 95% confidence interval = 1.48-2.91; P<0.001), with sensitivity analysis showing that the result was robust. Subgroups analyses according to study design, ethnicity, assessment of PD/COPD, and adjusted/unadjusted odds ratios also revealed a significant association. Publication bias was detected. Based on current evidence, PD is a significant and independent risk factor of COPD. However, whether a causal relationships exists remains unclear. Morever, we suggest performing randomized controlled trails to explore whether periodontal interventions are beneficial in regulating COPD pathogenesis and progression.
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Spectacular images of neutrophils ejecting nuclear chromatin and bactericidal proteins, in response to microbes, were first reported in 2004. As externalized chromatin could entangle bacteria, these structures were named neutrophil extracellular traps (NETs). Subsequent studies identified microorganisms and sterile conditions that stimulate NETs, as well as additional cell types that release extracellular chromatin. The release of NETs is the most dramatic stage in a cell death process called NETosis. Experimental evidence suggests that NETs participate in pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. Exaggerated NETosis or diminished NET clearance likely increases risk of autoreactivity to NET components. The biological significance of NETs is just beginning to be explored. A more complete integration of NETosis within immunology and pathophysiology will require better understanding of NET properties associated with specific disease states and microbial infections. This may lead to the identification of important therapeutic targets.
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To the Editor: In the excellent article by Weiss on tissue destruction by neutrophils (Feb. 9 issue),¹ there is an implicit assumption that neutrophils lack endogenous reducing substances that could quench intracellular or extracellular oxidants. We would therefore like to emphasize that ascorbic acid is present in human neutrophils, in concentrations 20 to 30 times higher than in plasma.² Although the function of ascorbic acid in neutrophils is unknown, it has been proposed that it quenches free radicals,³ either within or perhaps outside neutrophils. However, before this or other functions of neutrophil ascorbic acid can be addressed, it is of…
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This study assessed the activities of antioxidant enzymes superoxide dismutase (SOD), glutathione reductase (GR), and catalase (CAT) and free radical damage marker malondialdehyde (MDA) levels in saliva of 30 patients with chronic periodontitis (CP) compared to 30 healthy controls by spectrophotometry. MDA levels were significantly elevated in the CP group, whereas the SOD, CAT, and GR activities were significantly reduced compared to healthy controls. MDA levels demonstrated a significant direct correlation with all periodontal parameters, whereas all antioxidant enzymes studied (SOD, CAT, and GR) showed an inverse correlation. These findings support the idea that oxidative stress has a role in periodontal disease pathogenesis.
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AimTo evaluate the direct effects of periodontal therapy in Chronic Obstructive Pulmonary Disease (COPD) patients with chronic periodontitis (CP). Materials and Methods In a pilot randomized controlled trial, 60 COPD patients with CP were randomly assigned to receive scaling and root planing (SRP) treatment, supragingival scaling treatment, or oral hygiene instructions only with no periodontal treatment. We evaluated their periodontal indexes, respiratory function and COPD exacerbations at baseline, 6 months, 1 year, and 2 years. ResultsCompared with the control group, measurements of periodontal indexes were significantly improved in patients in two treatment groups at 6-month, 1-year, and 2-year follow-up (all p<0.05). Overall, the means of forced expiratory volume in the first second / forced vital capacity (FEV1/FVC) and FEV1 were significantly higher in the two therapy groups compared with the control group during the follow-up (p<0.05). Additionally, the frequencies of COPD exacerbation were significantly lower in the two therapy groups than in the control group at 2-year follow-up (p<0.05). Conclusions Our preliminary results from this pilot trial suggest that periodontal therapy in COPD patients with CP may improve lung function and decrease the frequency of COPD exacerbation.This article is protected by copyright. All rights reserved.
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In this systematic review, we explore and summarize the peer-reviewed literature on putative genetic risk factors for susceptibility to aggressive and chronic periodontitis. A comprehensive literature search on the PubMed database was performed using the keywords 'periodontitis' or 'periodontal disease' in combination with the words 'genes', 'mutation', 'SNP' or 'polymorphism'. The studies selected were written in English, had a case-control design, and reported genotype distribution. Only studies with at least 100 individuals in either the case or control group were included. Research on genetic polymorphisms has only had limited success in identifying significant and reproducible genetic factors for susceptibility to aggressive periodontitis and chronic periodontitis. Taking together the data published on gene polymorphisms in aggressive and chronic periodontitis, we conclude that there are differences among the various studies for the rare allele carriage rates. Nevertheless, there is some evidence that polymorphisms in the IL1B, IL1RN, FcγRIIIb, VDR and TLR4 genes may be associated with aggressive periodontitis susceptibility, and polymorphisms in the IL1B, IL1RN, IL6, IL10, VDR, CD14, TLR4 and MMP1 genes may be associated with chronic periodontitis susceptibility as a single genetic factor in certain populations. Future studies should apply stricter disease classifications, use larger study cohorts, adjust for relevant risk factors in aggressive and chronic periodontiti,s and include analysis of multiple genes and polymorphisms. Establishing consortia and performing collaborative studies may help to conquer the limitations of small sample size and limited statistical power.