Abstract
Bacteria from the oral biofilms may be aspirated into the respiratory tract to influence the initiation and progression of systemic infectious conditions such as pneumonia. Oral bacteria, poor oral hygiene, and periodontitis seem to influence the incidence of pulmonary infections, especially nosocomial pneumonia episodes in high-risk subjects. Improved oral hygiene has been shown to reduce the occurrence of nosocomial pneumonia, both in mechanically-ventilated hospital patients and non-ventilated nursing home residents. It appears that oral colonization by potential respiratory pathogens, possibly fostered by periodontitis, and possibly by bacteria specific to the oral cavity or to periodontal diseases contribute to pulmonary infections. Thus, oral hygiene will assume an even more important role in the care of high-risk subjects – patients in the hospital intensive care and the elderly. The present paper critically reviews the recent literature on the effect of oral biofilms and periodontitis on pneumonia.
Keywords: infectious diseases, oral hygiene, pathogenesis, periodontitis, pneumonia
Pneumonia is an infection of the lungs caused by bacteria, mycoplasma, viruses, fungi, or parasites. Bacterial pneumonia is a common and significant cause of mortality and morbidity in human populations. Pneumonia together with influenza is a top ten cause of death in the world, and in elderly nursing home residents the leading cause of death. Pneumonia also results in morbidity and considerable decline in the individual quality of life as well as in increased medical care costs for the healthcare system. Bacterial pneumonia includes community-acquired pneumonia and hospital-acquired (nosocomial) pneumonia. Nosocomial pneumonia, occurring >48–72 h after admission to a hospital or nursing home, can be divided into two subtypes: ventilator-associated pneumonia (VAP) and non-VAP. Pneumonia accounts for 10% of infections in intensive care units (ICU) being the most common infection in this hospital setting (Vincent et al, 1995). The onset of pneumonia can easily double the length of the patient’s hospital stay, and the cost of VAP treatment has been estimated to average as high as $40 000 per patient (Rello et al, 2002). Pneumonia is also prevalent in nursing homes, comprising 13–48% of all infections (Crossley and Thurn, 1989). The mortality rate of nosocomial pneumonia can be as high as 25%.
The oral cavity may be an important source of bacteria that cause infections of the lungs. Dental plaque, a tooth-borne biofilm that initiates periodontal disease and dental caries may also influence the initiation and progression of pneumonia because of relocalization of the bacteria from the biofilm into the respiratory tract. Bacteria causing community-acquired pneumonia are typically species that normally colonize the oropharynx such as Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae. Nosocomial pneumonia is, in contrast, often caused by bacteria that are not common members of the oropharyngeal flora such as Pseudomonas aeruginosa, Staphylococcus aureus, and enteric Gram-negative bacteria. These organisms populate the oral cavity in certain settings, for example in institutionalized subjects and in people living in areas served by unsanitary water supplies (Scannapieco, 1999). Respiratory pathogens, such as S. aureus, P. aeruginosa, and Escherichia coli, have been found to be present in substantial numbers on the teeth in both institutionalized elders (Russell et al, 1999) and intensive care patients (Scannapieco et al, 1992). In this review we concentrate on the possible effect of oral biofilms and periodontitis on pneumonia.
Mechanisms behind the association between oral bacteria/periodontitis and pneumonia
One cubic millimeter of dental plaque contains about 100 million bacteria (Thoden van Velzen et al, 1984) and may serve as a persistent reservoir for potential pathogens, both oral and respiratory bacteria. It is likely that oral and respiratory bacteria in the dental plaque are shed into the saliva and are then aspirated into the lower respiratory tract and the lungs to cause infection (Scannapieco, 1999; Scannapieco et al, 2001). Cytokines and enzymes induced from the periodontally inflamed tissues by the oral biofilm may also be transferred into the lungs where they may stimulate local inflammatory processes preceding colonization of pathogens and the actual lung infection (Scannapieco, 1999; Scannapieco et al, 2001). Other possible mechanisms of pulmonary infection are inhalation of airborne pathogens or translocation of bacteria from local infections via bacteremia.
In a healthy subject, the respiratory tract is able to defend against aspirated bacteria. Patients with diminished salivary flow, decreased cough reflex, swallowing disorders, poor ability to perform good oral hygiene, or other physical disabilities have a high risk for pulmonary infections. Mechanically ventilated patients in ICUs with no ability to clear oral secretions by swallowing or by coughing, are at risk for VAP especially if the ventilation lasts for more than 48 h (Estes and Meduri, 1995). Oral bacterial load increases during intubation and higher dental plaque scores predict risk of pneumonia (Munro et al, 2006). Anaerobic bacteria are frequently found to colonize the lower respiratory tract in mechanically-ventilated patients (Estes and Meduri, 1995; Robert et al, 2003). Colonization of bacteria in the digestive tract has been suggested to be a source for nosocomial pneumonia, but recently oral and dental bacterial colonization has been proposed to be the major source of bacteria implicated in the etiology of VAP (Garcia, 2005).
In the institutionalized elderly the aspiration of saliva seems to be the main route of bacteria into the lungs causing aspiration pneumonia. Dysphagia seems to be an important risk factor, even a predictor, for aspiration pneumonia (Langmore et al, 1998). The major oral and dental risk factors for aspiration pneumonia in veteran residents of nursing homes were number of decayed teeth, periodontitis, oral S. aureus colonization, and requirement of help feeding (Terpenning et al, 2001). Inadequate oral care and swallowing diffculties were associated with pneumonia in 613 elderly nursing home patients (Quagliarello et al, 2005).
Studies on the relationship between the oral microflora /periodontitis and pneumonia
Very little data on the relationship of oral microflora to community-acquired pneumonia are available. Most of the studies have been conducted in populations with a high prevalence of pneumonia, such as hospitalized patients and the elderly in nursing homes. An epidemiologic study found no association between periodontal state or poor oral hygiene and acute respiratory disease in the community-dwelling population (Scannapieco et al, 1998), but ample evidence exists to support a role for oral bacteria and/or poor oral health in the pathogenesis of nosocomial pneumonia. Poor oral health, dental plaque, or oropharyngeal bacterial colonization have been associated with the occurrence of pneumonia in hospitalized or ICU patients (Scannapieco et al, 1992; Bonten et al, 1996; Garrouste-Orgeas et al, 1997; Fourrier et al, 1998; Preston et al, 1999; El-Solh et al, 2004), but a clear relationship between periodontitis and pneumonia has not always been found (Chabrand et al, 1986; Treloar and Stechmiller, 1995). Higher plaque scores, bacterial presence in saliva, or colonization in the oropharynx seem to be associated with pneumonia in elderly nursing home patients (Mojon et al, 1997; Langmore et al, 1998; Russell et al, 1999; Terpenning et al, 2001).
Recent systematic reviews of the literature substantiate the link between poor oral health and pneumonia (Scannapieco et al, 2003; Azarpazhooh and Leake, 2006), but more studies on the possible role of periodontitis are needed. Dentate status may be a risk for pneumonia and respiratory tract infections – patients with natural teeth developed aspiration pneumonia more often than edentulous subjects (Terpenning et al, 1993; Mojon et al, 1997). Cariogenic bacteria and periodontal pathogens in saliva or dental plaque are found to be risk factors for aspiration pneumonia in nursing home patients (Langmore et al, 1998; Terpenning et al, 2001). It is well known that the teeth and gingival margin are places that favour bacterial colonization, and periodontal pockets may serve as reservoirs for potential pathogens for pneumonia. Previous studies have shown that enteric bacteria colonize periodontal pockets (Slots et al, 1988; Rams et al, 1990). Periodontitis together with poor oral hygiene or by facilitating colonization of dental plaque may promote pneumonia.
Intervention studies on the role of improved oral cleaning in reducing pneumonia
Oral interventions to reduce pulmonary infections have been examined in both mechanically ventilated ICU patients and non-ventilated elderly patients. These studies included chemical intervention using topical antimicrobial agents and traditional oral mechanical hygiene performed by a professional.
Hospitalized ICU patients seem to benefit from daily oral cleansing. Studies have shown that the use of oral topical chlorhexidine (CHX) reduces pneumonia in mechanically ventilated patients and may even decrease the need of systemic IV antibiotics or shorten the duration of mechanical ventilation in the ICU (DeRiso et al, 1996; Fourrier et al, 2000; Genuit et al, 2001; Koeman et al, 2006). Moreover, oral application of CHX in the early post-intubation period lowers the numbers of cultivable oral bacteria and may delay the development of VAP (Grap et al, 2004). Studies validating the effectiveness of oral CHX on reducing pneumonia are not unanimous. For example, Fourrier et al found that gingival decontamination with CHX gel significantly decreased the oropharyngeal colonization by bacteria in ventilated patients, but was not sufficient to reduce the incidence of respiratory infections (Fourrier et al, 2005). Another study by Houston et al (2002) reported that a significant reduction in pneumonia using CHX rinse in ICU patients was achieved only after 24 h of intubation. However, the efficacy of oral CHX decontamination to reduce VAP needs further investigation as no clear reduction in mortality rate has been shown. In addition to CHX, other anti-plaque agents have been investigated. The use of antimicrobial gels including polymyxin B sulfate, neomycin sulfate, and vancomycin hydrochloride (Pugin et al, 1991) or gentamicin/colistin/vancomycin (Bergmans et al, 2001) have also been shown to reduce VAP. Recently, the first study showing that mechanical oral care in combination with povidone iodine significantly decreases pneumonia in ventilated ICU patients was published (Mori et al, 2006). This suggests that tooth brushing combined with a topical antimicrobial agent is a promising method for oral cleansing of mechanically ventilated patients.
Institutionalized but non-ventilated patients, mainly elders living in nursing homes, appear to benefit from improved oral care by showing lower levels of oral bacteria and fewer pneumonia episodes and febrile days. Daily tooth brushing and topical oral swabbing with povidone iodine significantly decreased pneumonia in residents in long-term care facilities (Yoneyama et al, 1999, 2002; Yoshida et al, 2001). However, in an earlier study by the same research group, oral care with both brushing and antimicrobial gargling had an effect only on febrile days but not on the incidence of pneumonia (Yoneyama et al, 1996). Interestingly, professional cleaning by a dental hygienist once a week significantly reduced the prevalence of fever and fatal pneumonia in 141 elderly patients in nursing homes (Adachi et al, 2002). Similar once-a-week professional oral cleaning significantly reduced influenza infections in an elderly population (Abe et al, 2006). Dental plaque is known to form clearly visible masses in the teeth in a few days, but these studies suggest that improved oral care even without chemical agents and even if not performed daily not only reduces the oral bacterial, viral, and fungal load, but may have an effect on reducing the risk of pneumonia. Therefore, more studies are needed to find the easiest oral decontamination methods to reduce pulmonary infections in elderly nursing home patients.
Our previously published systematic literature review revealed that interventions improving oral hygiene by mechanical and/or topical chemical disinfection or antibiotics reduce the incidence of hospital-acquired pneumonia by an average of 40% (Scannapieco et al, 2003). Oral cleansing reduces pneumonia in both edentulous and dentate subjects, suggesting that oral colonization of bacteria contributes to nosocomial pneumonia to a greater extent than periodontitis. However, intervention studies on the treatment of periodontitis on the incidence of pneumonia have not been performed due to the complexities required in investigating ICU or bed-bound nursing home patients. In edentulous people, dentures may easily serve as a similar reservoir as teeth for oral and respiratory bacteria if not cleaned properly and daily.
Conclusions and future visions
Poor oral health, dependence on help conducting daily oral hygiene, oral colonization of periodontal and respiratory pathogens, all possibly influenced by periodontitis, are associated with nosocomial pneumonia. A direct causal relationship between periodontitis and pneumonia has not been established, however. Based on the studies reviewed here it seems that oral colonization by potential respiratory pathogens contributes to pulmonary infections. The specific contribution of periodontitis per se to pneumonia risk is presently unknown. It will be difficult to determine whether periodontitis is related to pneumonia in ICU subjects, for example, due to the limited access to these patients’ oral cavity, and the rapid turnover of patients in the hospital that presents logistical challenges to such research. Thus, oral hygiene of both dentate and edentulous subjects will assume an even more important role in elder care.
Chronic periodontal infections are common – the prevalence of severe periodontitis in Western countries has been estimated to be 5–15%. Pneumonia and other respiratory infections are common in community-dwelling populations but especially in high-risk subjects such as mechanically-ventilated ICU patients and residents in long-term care facilities. With improved oral hygiene and preventative approaches to dental care, people are able to keep their natural teeth longer, even for life. Edentulousness will someday be a rare phenomenon; in the future there will be more elderly dentate people, having more teeth than ever, but who will also have impaired ability to perform oral hygiene, and hence more cases of periodontal diseases. To assure that improved knowledge and methods to save people’s natural teeth are not taking us from one problem to another, emphasis on the importance of good oral hygiene and periodontal treatment, especially in subjects who are in high risk for pulmonary infections, is crucial.
Acknowledgments
The authors are supported by grants 209152 and 211117 (SP) from the Academy of Finland and DE014685 (FAS) from the National Institutes of Health (USA).
References
- Abe S, Ishihara K, Adachi M, et al. Professional oral care reduces influenza infection in elderly. Arch Gerontol Geriatr. 2006;43:157–164. doi: 10.1016/j.archger.2005.10.004. [DOI] [PubMed] [Google Scholar]
- Adachi M, Ishihara K, Abe S, Okuda K, Ishikawa T. Effect of professional oral health care on the elderly living in nursing homes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;94:191–195. doi: 10.1067/moe.2002.123493. [DOI] [PubMed] [Google Scholar]
- Azarpazhooh A, Leake JL. Systematic review of the association between respiratory diseases and oral health. J Periodontol. 2006;77:1465–1482. doi: 10.1902/jop.2006.060010. [DOI] [PubMed] [Google Scholar]
- Bergmans DC, Bonten MJ, Gaillard CA, et al. Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 2001;164:382–388. doi: 10.1164/ajrccm.164.3.2005003. [DOI] [PubMed] [Google Scholar]
- Bonten MJ, Bergmans DC, Ambergen AW, et al. Risk factors for pneumonia, and colonization of respiratory tract and stomach in mechanically ventilated ICU patients. Am J Respir Crit Care Med. 1996;154:1339–1346. doi: 10.1164/ajrccm.154.5.8912745. [DOI] [PubMed] [Google Scholar]
- Chabrand F, Allamand JM, Duroux P, et al. Are orodental infectious foci responsible for bacterial pneumopathies? A statistical study. Rev Stomatol Chir Maxillofac. 1986;87:73–77. [PubMed] [Google Scholar]
- Crossley KB, Thurn JR. Nursing home-acquired pneumonia. Semin Respir Infect. 1989;4:64–72. [PubMed] [Google Scholar]
- DeRiso AJ, 2nd, Ladowski JS, Dillon TA, Justice JW, Peterson AC. Chlorhexidine gluconate 0.12% oral rinse reduces the incidence of total nosocomial respiratory infection and nonprophylactic systemic antibiotic use in patients undergoing heart surgery. Chest. 1996;109:1556–1561. doi: 10.1378/chest.109.6.1556. [DOI] [PubMed] [Google Scholar]
- El-Solh AA, Pietrantoni C, Bhat A, et al. Colonization of dental plaques: a reservoir of respiratory pathogens for hospital-acquired pneumonia in institutionalized elders. Chest. 2004;126:1575–1582. doi: 10.1378/chest.126.5.1575. [DOI] [PubMed] [Google Scholar]
- Estes RJ, Meduri GU. The pathogenesis of ventilator-associated pneumonia: I. Mechanisms of bacterial transcolonization and airway inoculation. Intensive Care Med. 1995;21:365–383. doi: 10.1007/BF01705418. [DOI] [PubMed] [Google Scholar]
- Fourrier F, Duvivier B, Boutigny H, Roussel-Delvallez M, Chopin C. Colonization of dental plaque: a source of nosocomial infections in intensive care unit patients. Crit Care Med. 1998;26:301–308. doi: 10.1097/00003246-199802000-00032. [DOI] [PubMed] [Google Scholar]
- Fourrier F, Cau-Pottier E, Boutigny H, et al. Effects of dental plaque antiseptic decontamination on bacterial colonization and nosocomial infections in critically ill patients. Intensive Care Med. 2000;26:1239–1247. doi: 10.1007/s001340000585. [DOI] [PubMed] [Google Scholar]
- Fourrier F, Dubois D, Pronnier P, et al. Effect of gingival and dental plaque antiseptic decontamination on nosocomial infections acquired in the intensive care unit: a double-blind placebo-controlled multicenter study. Crit Care Med. 2005;33:1728–1735. doi: 10.1097/01.ccm.0000171537.03493.b0. [DOI] [PubMed] [Google Scholar]
- Garcia R. A review of the possible role of oral and dental colonization on the occurrence of health care-associated pneumonia: underappreciated risk and a call for interventions. Am J Infect Control. 2005;33:527–541. doi: 10.1016/j.ajic.2005.02.005. [DOI] [PubMed] [Google Scholar]
- Garrouste-Orgeas M, Chevret S, Arlet G, et al. Oropharyngeal or gastric colonization and nosocomial pneumonia in adult intensive care unit patients. A prospective study based on genomic DNA analysis. Am J Respir Crit Care Med. 1997;156:1647–1655. doi: 10.1164/ajrccm.156.5.96-04076. [DOI] [PubMed] [Google Scholar]
- Genuit T, Bochicchio G, Napolitano LM, McCarter RJ, Roghman MC. Prophylactic chlorhexidine oral rinse decreases ventilator-associated pneumonia in surgical ICU patients. Surg Infect (Larchmt) 2001;2:5–18. doi: 10.1089/109629601750185316. [DOI] [PubMed] [Google Scholar]
- Grap MJ, Munro CL, Elswick RK, Jr, Sessler CN, Ward KR. Duration of action of a single, early oral application of chlorhexidine on oral microbial flora in mechanically ventilated patients: a pilot study. Heart Lung. 2004;33:83–91. doi: 10.1016/j.hrtlng.2003.12.004. [DOI] [PubMed] [Google Scholar]
- Houston S, Hougland P, Anderson JJ, et al. Effectiveness of 0.12% chlorhexidine gluconate oral rinse in reducing prevalence of nosocomial pneumonia in patients undergoing heart surgery. Am J Crit Care. 2002;11:567–570. [PubMed] [Google Scholar]
- Koeman M, van der Ven AJ, Hak E, et al. Oral decontamination with chlorhexidine reduces the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med. 2006;173:1348–1355. doi: 10.1164/rccm.200505-820OC. [DOI] [PubMed] [Google Scholar]
- Langmore SE, Terpenning MS, Schork A, et al. Predictors of aspiration pneumonia: how important is dysphagia? Dysphagia. 1998;13:69–81. doi: 10.1007/PL00009559. [DOI] [PubMed] [Google Scholar]
- Mojon P, Budtz-Jorgensen E, Michel JP, Limeback H. Oral health and history of respiratory tract infection in frail institutionalised elders. Gerodontology. 1997;14:9–16. doi: 10.1111/j.1741-2358.1997.00009.x. [DOI] [PubMed] [Google Scholar]
- Mori H, Hirasawa H, Oda S, et al. Oral care reduces incidence of ventilator-associated pneumonia in ICU populations. Intensive Care Med. 2006;32:230–236. doi: 10.1007/s00134-005-0014-4. [DOI] [PubMed] [Google Scholar]
- Munro CL, Grap MJ, Elswick RK, Jr, et al. Oral health status and development of ventilator-associated pneumonia: a descriptive study. Am J Crit Care. 2006;15:453–460. [PubMed] [Google Scholar]
- Preston AJ, Gosney MA, Noon S, Martin MV. Oral flora of elderly patients following acute medical admission. Gerontology. 1999;45:49–52. doi: 10.1159/000022055. [DOI] [PubMed] [Google Scholar]
- Pugin J, Auckenthaler R, Lew DP, Suter PM. Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. A randomized, placebo-controlled, double-blind clinical trial. JAMA. 1991;265:2704–2710. [PubMed] [Google Scholar]
- Quagliarello V, Ginter S, Han L, et al. Modifiable risk factors for nursing home-acquired pneumonia. Clin Infect Dis. 2005;40:1–6. doi: 10.1086/426023. [DOI] [PubMed] [Google Scholar]
- Rams TE, Babalola OO, Slots J. Subgingival occurrence of enteric rods, yeasts and staphylococci after systemic doxycycline therapy. Oral Microbiol Immunol. 1990;5:166–168. doi: 10.1111/j.1399-302x.1990.tb00416.x. [DOI] [PubMed] [Google Scholar]
- Rello J, Ollendorf DA, Oster G, et al. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest. 2002;122:2115–2121. doi: 10.1378/chest.122.6.2115. [DOI] [PubMed] [Google Scholar]
- Robert R, Grollier G, Frat JP, et al. Colonization of lower respiratory tract with anaerobic bacteria in mechanically ventilated patients. Intensive Care Med. 2003;29:1062–1068. doi: 10.1007/s00134-003-1729-8. [DOI] [PubMed] [Google Scholar]
- Russell SL, Boylan RJ, Kaslick RS, Scannapieco FA, Katz RV. Respiratory pathogen colonization of the dental plaque of institutionalized elders. Spec Care Dentist. 1999;19:128–134. doi: 10.1111/j.1754-4505.1999.tb01413.x. [DOI] [PubMed] [Google Scholar]
- Scannapieco FA. Role of oral bacteria in respiratory infection. J Periodontol. 1999;70:793–802. doi: 10.1902/jop.1999.70.7.793. [DOI] [PubMed] [Google Scholar]
- Scannapieco FA, Stewart EM, Mylotte JM. Colonization of dental plaque by respiratory pathogens in medical intensive care patients. Crit Care Med. 1992;20:740–745. doi: 10.1097/00003246-199206000-00007. [DOI] [PubMed] [Google Scholar]
- Scannapieco FA, Papandonatos GD, Dunford RG. Associations between oral conditions and respiratory disease in a national sample survey population. Ann Periodontol. 1998;3:251–256. doi: 10.1902/annals.1998.3.1.251. [DOI] [PubMed] [Google Scholar]
- Scannapieco FA, Wang B, Shiau HJ. Oral bacteria and respiratory infection: effects on respiratory pathogen adhesion and epithelial cell proinflammatory cytokine production. Ann Periodontol. 2001;6:78–86. doi: 10.1902/annals.2001.6.1.78. [DOI] [PubMed] [Google Scholar]
- Scannapieco FA, Bush RB, Paju S. Associations between periodontal disease and risk for nosocomial bacterial pneumonia and chronic obstructive pulmonary disease. A systematic review. Ann Periodontol. 2003;8:54–69. doi: 10.1902/annals.2003.8.1.54. [DOI] [PubMed] [Google Scholar]
- Slots J, Rams TE, Listgarten MA. Yeasts, enteric rods and pseudomonads in the subgingival flora of severe adult periodontitis. Oral Microbiol Immunol. 1988;3:47–52. doi: 10.1111/j.1399-302x.1988.tb00080.x. [DOI] [PubMed] [Google Scholar]
- Terpenning M, Bretz W, Lopatin D, et al. Bacterial colonization of saliva and plaque in the elderly. Clin Infect Dis. 1993;16(Suppl 4):S314–S316. doi: 10.1093/clinids/16.supplement_4.s314. [DOI] [PubMed] [Google Scholar]
- Terpenning MS, Taylor GW, Lopatin DE, et al. Aspiration pneumonia: dental and oral risk factors in an older veteran population. J Am Geriatr Soc. 2001;49:557–563. doi: 10.1046/j.1532-5415.2001.49113.x. [DOI] [PubMed] [Google Scholar]
- Thoden van Velzen SK, Abraham-Inpijn L, Moorer WR. Plaque and systemic disease: a reappraisal of the focal infection concept. J Clin Periodontol. 1984;11:209–220. doi: 10.1111/j.1600-051x.1984.tb02211.x. [DOI] [PubMed] [Google Scholar]
- Treloar DM, Stechmiller JK. Use of a clinical assessment tool for orally intubated patients. Am J Crit Care. 1995;4:355–360. [PubMed] [Google Scholar]
- Vincent JL, Bihari DJ, Suter PM, et al. The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA. 1995;274:639–644. [PubMed] [Google Scholar]
- Yoneyama T, Hashimoto K, Fukuda H, et al. Oral hygiene reduces respiratory infections in elderly bed-bound nursing home patients. Arch Gerontol Geriatr. 1996;22:11–19. doi: 10.1016/0167-4943(95)00672-9. [DOI] [PubMed] [Google Scholar]
- Yoneyama T, Yoshida M, Matsui T, Sasaki H. Oral care and pneumonia. Oral Care Working Group. Lancet. 1999;354:515. doi: 10.1016/s0140-6736(05)75550-1. [DOI] [PubMed] [Google Scholar]
- Yoneyama T, Yoshida M, Ohrui T, et al. Oral care reduces pneumonia in older patients in nursing homes. J Am Geriatr Soc. 2002;50:430–433. doi: 10.1046/j.1532-5415.2002.50106.x. [DOI] [PubMed] [Google Scholar]
- Yoshida M, Yoneyama T, Akagawa Y. Oral care reduces pneumonia of elderly patients in nursing homes, irrespective of dentate or edentate status. Nippon Ronen Igakkai Zasshi. 2001;38:481–483. doi: 10.3143/geriatrics.38.481. [DOI] [PubMed] [Google Scholar]