Swallowing and Swallowing Disorders 10 March 2005 Pneumonia: Factors Beyond Aspiration entry of foreign materials into the lower airway and to readily expel John R. Ashford any foreign materials that may gain VA Tennessee Valley Health Care System entry to the lower airway. Impair- Nashville, TN ment of laryngeal innervation from stroke or impairment of cartilagi- Introduction ing infected exudate into the alveoli. nous and muscular structures of the Efficient exchange of oxygen and larynx from treatments for cancer Aspiration and its potential carbon dioxide is compromised, af- reduces laryngeal efficiency and danger to the respiratory system fecting cell functions throughout the impairs the timing of opening and were described by Hippocrates in body (Cole & MacKay, 1990; Scanna- closing. This increases the potential 400 B.C. Later, Hunter in 1781, pieco & Mylotte, 1996; Skerrett, for aspiration. The relationship be- Simpson in 1898, and Mendelson in 1994; Skerrett, Niederman, & Fein, tween laryngeal aspiration and 1946 described more clearly the 1989). pneumonia has been well recog- clinical and pathological conditions nized (Langmore et al., 1998). How- associated with aspiration, includ- Nosocomial Pneumonia ever, observational evidence of la- ing the potential for death (Chokshi, ryngeal inefficiency and aspiration The diagnosis of nosocomial Asper, & Khandheria, 1986). Clini- provides but one piece to the com- pneumonia, a subclass of pneumo- cally, speech-language pathologists plex puzzle of pulmonary infection. are asked to determine the efficiency nia, is restricted to people develop- and safety of the oropharyngeal ing the disease while in hospital or Marik (2001) defined aspira- swallow mechanism and to assist nursing facilities (Dasaraju & Liu, tion pneumonia as an infection that in determining the potential for 1996; Wilson, 2003b). Nosocomial develops after inhaling oropharyn- pneumonia development. A per- pneumonia usually has a bacterial geal pathogens into the lungs that plexing question, however, is, “Why origin. Among the more common have first colonized in the orophar- do some patients with dysphagia microorganisms identified as caus- ynx. It represents 8% to 33% of all who aspirate develop pneumonia ing nosocomial pneumonia are en- nosocomial infections (Tobin & and others do not?” The purpose of teric gram-negative bacteria, or Sta- Grenvik, 1984). However, the use of this paper is to examine factors, phylococcus aureus, and gram-nega- the term aspiration pneumonia is other than laryngeal aspiration, that tive aerobic bacteria, or Pseudomo- not without controversy. Jurado and contribute to pneumonia develop- nas aeruginosa, Klebsiella pneumoniae, Franco-Paredes (2001) stated that ment in some patients. and Escherichia coli (Wilson). Viral- the use of this term should be dis- based nosocomial infections are couraged because, “aspiration is a Pneumonia relatively rare, usually seasonal, pathogenic mechanism for several and caused by exposure to infected inflammatory diseases of the lung, Pneumonia is an acute infec- persons (Thompson, 1994). Tobin both infectious and noninfectious” tion and inflammation of the alveoli and Grenvik (1984) cited Sanford (p. 1612). Inhaling large quantities pulmoni, or pits, at the cellular level and Pierce’s observations that noso- of pathogens into the lower reaches of the lungs or its parenchyma comial pneumonia is usually not of the respiratory tract is generally (Dasaraju & Liu, 1996). Infection, or present or incubating at the time of recognized as the probable cause of the presence of living pathogens admission, but symptoms begin to aspiration pneumonia (Jurado & within the tissue, develops when the appear after the first 48 to 72 hours Franco-Paredes, 2001; Skerrett et al., resident immune defenses are insuf- of admission. At higher risk are 1989; Tobin & Grenvik). Whether ficient to meet the challenge of bac- those patients who are intubated or pneumonia develops from one or terial or viral pathogens entering in the critical care unit. Thompson more episodes of aspiration de- and colonizing the lower respira- reported that hospital stays increase pends on the volume of aspirated tory system (Wilson, 2003a). Inflam- 4 to 13 days in patients developing material, the characteristics of the mation is a bodily response that in- nosocomial pneumonia. In addition, aspirate (e.g., bacterial load, liquid volves the delivery of fluid and im- patients who develop nosocomial versus particulate matter, pH level), mune properties through the blood pneumonia are at high risk for the frequency of aspiration events, system to the area of injury or ne- death. and the integrity of the immune sys- crosis to counter these invading tem (Johnson & Hirsch, 2003; pathogens. With pneumonia, infec- Aspiration Pneumonia Langmore et al., 1998; Shockley, tion and inflammation begin in the 1995). Patients may develop aspi- The larynx is the gatekeeper to respiratory bronchioles and spread ration pneumonia as a response to the lower respiratory system. In this through extracellular fluid spaces one episode of aspiration of mate- respect, its function is to prevent over large areas of lung tissue pour- rial. Others may experience epi- Swallowing and Swallowing Disorders 11 March 2005

sodes of aspiration pneumonia af- present for 3 months or longer (Na- more severe and adverse challenges, ter aspirating small amounts of tional Center for Health Statistics, the stress mechanism response is material over a longer period of 2004). prolonged, and the body is unable time. They present to their physi- to regain complete equilibrium. The onset of a serious illness cians with symptoms including fe- initiates a highly complex and sig- If stress responses are sus- ver, malaise, weight loss, and cough- nificant physiological stress re- tained for lengthy periods of time, a ing for one or 2 weeks. Blood sponse. Stress is defined as the host of inflammatory diseases, in- screens indicate an elevated im- body’s reaction to physical, chemi- cluding cardiovascular disease, can mune response, and chest radio- cal, or emotional forces that cause develop. Autoimmune diseases may graphs show lung infiltrates bodily or mental tension disrupting also develop, including asthma, (Johnson & Hirsch; Kannel, Ander- normal physiologic equilibrium, or rashes, rheumatoid arthritis, and son, & Wilson, 1992). homeostasis. The stress response multiple sclerosis. Secondary effects may also be a factor in causing dis- of these diseases may lead to heart Pneumonia and Illness ease (McEwen & Lasley, 2002; Mish, attacks, stroke, headaches, peptic Aspiration pneumonia does et al., 1986; Spraycar et al., 1995). ulcers, and hypertension (Carlson, not develop as a singular and inde- Homeostasis is constantly chal- 1994; Chrousos & Gold, 1992; pendent disease entity. It is an op- lenged by intrinsic or extrinsic ad- Kannel, et al., 1992; McEwen & portunistic, secondary disease reli- verse forces attempting to disrupt Lasley, 2004). Dysphagia is a com- ant upon the established presence the balance of the body’s internal mon symptom of many of these dis- of a serious illness from another dis- environment (Chrousos, 1998; eases, with pneumonia as a com- ease or medical condition (Bartlett Sheridan, Dobbs, Brown, & mon secondary illness. If, within the & Gorbach, 1975; Shafazand & Zwilling, 1994). context of the protracted stress re- Weinacker, 2002). Skerrett and col- sponse, the abrupt onset of an even The concept of harmony and leagues (1989) reported, “The more serious challenge occurs, such disharmony in nature dates back greater the degree of serious illness as a stroke, the stress mechanism over two thousand years. Hippo- in a given patient, the more likely increases its response and drives crates described good health as the he or she is to have gram-negative the body further into disequilib- harmonious balance of the elements colonization of the oropharynx . . .” rium. and qualities of life. Disharmony of (p. 470). The increasing severity of these elements and qualities was Serious illness, such as stroke the underlying illness or physical blamed as the cause of disease or surgery, challenges the survival disability provides significantly (Chrousos & Gold, 1992). In the early of the patient. The physiological re- more opportunities for gram-nega- 1900s, Cannon described the poten- sponses of stress resulting from a tive bacteria colonization and for tial effect of stress on the body and serious illness are mediated prima- pneumonia to develop (Ramphal, introduced the phrase “fight-or- rily through neurological, endo- 1994). Underlying serious illnesses flight response.” This phrase re- crine, and autonomic nervous sys- often associated with aspiration ferred to physiological reactions tem interconnections and integrate pneumonia include chronic lung necessary to prepare the body to to maintain homeostasis. Regula- disease, cystic fibrosis, chronic car- defend itself or to flee. Cannon hy- tion is carried out through two diac disease, diabetes, malignancy, pothesized that critical stress lev- mechanisms: the hypothalamic-pi- neurological disorders, azotemia, els could alter the body’s homeosta- tuitary-adrenal (HPA) axis and the and renal failure (Salata & Ellner, sis affecting blood sugar and oxy- autonomic nervous system (ANS) 1988). gen levels (Carlson, 1994; Chrousos (Carlson, 1994; McEwen & Lasley, & Gold; McEwen & Lasley, 2002). 2002; Sheridan et al., 1994). The hy- Mechanism of Stress In the 1930s, Selye described the pothalamus is a small structure lo- Serious illnesses are classified “General Adaptation Syndrome.” cated at the base of the brain below as either acute or chronic. An acute This hypothesis suggested that the the thalamus and situated on both condition is an illness or injury that body has a sophisticated physiologi- sides of the inferior aspect of the lasts for less than 3 months, was cal mechanism capable of coping third ventricle. Attached to its base first noticed less than 3 months be- with a variety of challenges is the pituitary stalk leading down fore initial examination, and is se- (McEwen & Lasley). For brief or to the anterior pituitary gland, rious enough to have an impact on milder challenges, the stress mecha- which is encased in cranial bone behavior. A chronic condition is an nism responds but subsides quickly (Hardy & Chronister, 1997; Nolte, illness that has not been cured once as the body regains equilibrium. In 1999). The adrenal glands are small acquired, such as diabetes, heart some cases, these challenges are endocrine glands located atop each disease, birth defects, or amputa- perceived as pleasant and become of the kidneys. The autonomic ner- tion. A chronic illness must be positive learning experiences. With vous system is a branch of the pe- Swallowing and Swallowing Disorders 12 March 2005 ripheral nervous system and com- mediate changes to heart rate, oxy- cortisol levels in normal subjects. prises two subsystems: the sympa- gen intake, glandular output, and The hypercortisolemia that was thetic and the parasympathetic ner- peripheral blood vessels (McEwen found to be common among CVA vous systems. These two sub- & Lasley, 2002). Oxygen and glu- patients correlated positively with systems have opposite duties. The cose reserves are shifted away from acute confusion and extensive mo- sympathetic system acts to expend maintenance functions of the body tor impairment. Furthermore, high energy from body reserves in times such as digestion, growth, and re- levels of cortisol were associated of crisis, while the parasympathetic production. These energy sources with poorer functional outcomes system acts to restore energy after are sent to muscles and organs criti- and higher mortality. Similar find- the crisis has passed (Carlson, cal to immediate survival (Chrou- ings were reported by Fassbender, 1994). These two systems directly sos, 1995). Reduction in salivary Schmidt, Mossner, Daffertshofer, influence salivation and mucous gland secretions and restriction of and Hennerici (1994). Slowik and production required for deglutition capillaries result in significant colleagues (2002) compared cortisol and immune protection in the changes to the environments of the and other blood products levels of oropharyngeal cavities and along oropharyngeal cavities and the 70 CVA patients and 24 matched the tracheobronchial tree. lower respiratory tract inviting controls. Patients were followed for gram-negative bacteria coloniza- 90 days. Results indicated that In mildly acute illnesses, cells tion. hypercortisolemia was associated affected at the localized disease site with old age, greater neurological release molecules known as stres- Later, as the illness is con- deficits, larger ischemic lesion on sors. These stressors enter the blood tained by the immune system, the CT, and worse prognoses. Pro- stream and recruit circulating im- HPA axis responds to the elevated longed hypercortisolemia has also mune cells called phagocytes. These levels of adrenaline by producing been associated with chronic under- phagocytes rush to the site of the additional hormones that will re- lying diseases such as diabetes, car- diseased cells and mount a local- store homeostasis. The primary diovascular and cerebrovascular ized inflammatory response (Sheri- stress hormone is cortisol which is diseases, and hypertension dan et al., 1994). The illness is iso- released from the adrenal glands. (McEwen & Lasley, 2002). lated and managed locally in a rela- Cortisol activates the parasympa- tively short period of time. Many thetic nervous system to begin re- It is now apparent that the on- acutely ill patients may have nor- ducing the stress response. Much set of illness, whether acute or mal swallowing functions and sel- like a thermostat, cortisol acts to chronic, initiates a dramatic dom develop pneumonia. slow down the stress response, counter-response by the body to which in turn reduces the immune protect and repair itself. Following In seriously acute illnesses, response. Consequently, inflamma- the initial response to pathogenic such as stroke or surgery, the local- tion and swelling from tissue dam- processes, a counter-response can ized inflammatory response is un- age are reduced. In addition, heart alter normal immune, glandular, able to contain the spread of disease rate reduces, blood vessels dilate, and muscular functions. These or injury, and the stressors activate glandular functions increase, and changes may jeopardize the safety the next higher level of defense—the energy stores are replenished and efficiency of deglutition and HPA axis (Carlson, 1994; Chrousos (McEwen & Lasley, 2002). safety of the lower respiratory sys- & Gold, 1992; McEwen & Lasley, tem. 2002; Rosmond & Bjorntorp, 2000). As mentioned earlier, certain The HPA axis is the central physi- diseases may result from the sus- Immune Functions ological mechanism responsible for tained stress response. In some se- producing the general adaptation vere acute and chronic illnesses, the The immune system responds stress response. Using hormones, HPA axis does not regulate prop- to illness by sending increased num- the HPA axis influences the func- erly. Overproduction of cortisol bers of phagocytes into the blood- tions of glands, muscles, hemato- leads to hypercortisolemia. Of sig- stream and to the site of inflamma- logical properties, and the immune nificance to developing pneumonia, tion. Phagocytes, or white blood response. As a result, functions re- this condition causes the immune cells, make up about 1% of the lated to deglutition and airway pro- system to become immunosuppres- blood’s composition and specialize tection may be altered. With the on- sive, or “turning on itself.” Immu- to serve a number of immune func- set of a stroke, for example, the HPA nosuppression allows pathogens to tions. Among these specialized axis releases adrenaline into the greatly increase and infections to cells, neutrophils are predominant. blood stream. Adrenaline triggers a continue unabated (Schteingart, Their function is to specifically seek stronger immune response and ac- 2003). Olsson, Marklund, Gustaf- out and destroy bacteria (Janeway, tivates the sympathetic nervous sys- son, and Näsman (1992) compared Travers, Walport, & Shlomchik, tem. Adrenaline also stimulates im- cortisol levels in CVA patients to 2001; Miyaski, 1991). Neutrophils Swallowing and Swallowing Disorders 13 March 2005

are part of the initial immune re- oropharyngeal cavity and the tra- ing home residents. Among the pre- sponse and take one to 3 hours to cheobronchial tree to maintain en- dictors were the number of decayed arrive at the site of the inflamma- vironmental homeostasis. The vis- teeth, the number of medications tion (Cole & MacKay, 1990). Jane- cosity of the mucous and saliva en- taken, multiple medical diagnoses, way and colleagues state that this traps bacteria. The proteins in these and smoking. These factors alter the initial immune response requires 4 secretions destroy the bacteria or environmental integrity of the to 7 days before producing a signifi- inhibit them from adhering to the oropharyngeal cavity and the lower cant effect at the inflammation site. mucosa or cavity surfaces and colo- respiratory tract. Terpenning and This coincides with Skerrett’s (1994) nizing (Bartlett & Gorbach, 1975; colleagues (2001) reported a signifi- observations that the primary re- Gibson & Barrett, 1992; Scanna- cant prevalence of decayed teeth sponse by the immune system to pieco & Mylotte, 1996; Stockley, and visible dental plaque among a pneumonia requires 5 to 7 days. 1995). In healthy persons, one cu- group of patients with aspiration These findings support Sanford and bic centimeter of saliva contains pneumonia. Many medications de- Pierce’s observations, as cited by approximately 108, or 100,000,000, hydrate the mucosa reducing epi- Tobin and Grenvik (1984), that bacterial pathogens that populate thelium protection. Smoking im- symptoms of nosocomial pneumo- the oropharyngeal cavities at any pairs the ciliary action of the nia are usually not present at the given time (Langmore et al., 1998; mucociliary escalator reducing its time of admission, but begin to ap- Skerrett, 1994). Aspiration of 0.01 ml ability to remove debris and patho- pear after the first 48 to 72 hours of of oral contents (secretions, water, gens from the airway. These find- admission. or food) can introduce 106 to 108 ings support the need for good oral pathogens into the lower respiratory care of hospital patients and nurs- The high risk of developing system (Tobin & Grenvik, 1984). ing home residents to help reduce pneumonia within the first week Johanson, Pierce, and Sanford, as growth and colonization of bacte- following the onset of a serious ill- cited by Salata and Ellner (1988), ria in the airway tracts (Watando et ness is a significant clinical factor reported that bacterial colonization al.). when assessing for dysphagia and of the oropharynx was found in 6% potential aspiration. Decisions to of normal individuals, 35% of mod- Muscle Functions feed or not to feed should be influ- erately ill patients, and 73% of se- enced by the current status of the With activation of the stress re- verely ill patients. A strong relation- immune system. In acute care set- sponse, increases in adrenaline re- ship has been shown between tings, current blood test results are sult in extraction of fatty acids, oropharyngeal bacteria and devel- available in the patient’s medical amino acids, and glucose from skel- opment of pneumonia (Mojon, 2002; record. Abnormally high white etal muscles and from adipose tis- Russell, Boylan, Kaslick, Scanna- blood cell and, more specifically, sue. These fuels are sent to visceral pieco, & Katz, 1999; Scannapieco, neutrophil counts should alert the organs to ensure their vital func- 1999; Watando et al., 2004). With examining clinician that an infec- tions and to repair tissue injury severe illness and activation of the tion exists and is not controlled. An (Wilmore, 2000). The result is a re- HPA axis, the blood supply may be elevated neutrophil count in concert duction in available energy for the restricted, reducing levels of sali- with demonstrated laryngeal aspi- mechanisms of digestion, including vary and mucous enzymes manu- ration provides ample evidence that the muscles of deglutition. Seri- factured by these glands. This de- conditions are optimal for pneumo- ously acute illness also reduces lev- creases epithelium protection and nia to develop. Pneumonia will not els of oxygen and iron in the blood allows increased bacterial coloni- occur unless both of these key fac- stream resulting in weakness of the zation during illness (Scannapieco). tors are present. slow and fast twitch muscle fibers Colonization occurs when bacteria necessary for efficient swallowing Oropharyngeal and penetrate the oral epithelium and (Chi-Fishman & Pfalzer, 2003; Tracheobronchial adhere to the surfaces of the teeth. Hudson, Daubert, & Mills, 2000). Here bacteria feed off of extracellu- Environments With prolonged illnesses, this lar fluids and multiply (Peterson, marked catabolic response may re- Stress response activation re- 1996). Reduced volume and avail- sult in protein wasting and loss of duces saliva and mucous produc- ability of these protective secretions lean body mass, which in turn, leads tion in the upper and lower respira- permit rapid colonization. Within to impaired immunity, poor wound tory systems. Saliva glands and 12 hours, without adequate immune healing, and muscle weakness mucous glands have rich blood control, these bacteria can increase (Hadley & Hinds, 2002). Weakness supplies and are regulated by the nearly 2.5 times (Stockley). of the oral and pharyngeal muscles ANS. These glands manufacture Langmore and colleagues reported may result in delayed swallow on- and transport saliva and mucous predictors of aspiration pneumonia set, reduced oral and pharyngeal and their protein enzymes to the among hospital patients and nurs- peristalsis, and inefficient laryn- Swallowing and Swallowing Disorders 14 March 2005 geal opening and closing, which in- Vanderbilt University School of Medi- Gibson, G., & Barrett, E. (1992). The role creases the risk of aspiration. cine and an adjunct professorship at of salivary function on oropha- Coupled with low red blood cell Tennessee State University. He chairs ryngeal colonization. Special Care count, low hemoglobin and hemat- the VA Best Practices in Dysphagia in Dentistry, 12, 153-156. ocrit values, an imbalance of elec- Treatment Taskforce and is consultant Hadley, J. S., & Hinds, C. J. (2002). trolytes, and an elevated immune to the Tennessee State Board of Health. Anabolic strategies in critical ill- response, seriously ill patients be- ness. Current Opinions in Pharma- come systemically debilitated. This References cology, 2, 700-707. condition is characterized by weak- Bartlett, J. G., & Gorbach, S. L. (1975). Hardy, S. G. P., & Chronister, R. B. ness, lethargy, and lack of energy, The triple threat of aspiration (1997). The hypothalamus. In D. each with the potential of affecting pneumonia. Chest, 68, 560-566. E. Haines (Ed.), Fundamental neu- swallowing and respiratory safety. roscience (pp. 432-442). New York: Low counts among the red blood cell Carlson, N. R. (1994). Physiology of be- Churchill Livingstone. havior. 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The phagocyte in the immune to an underlying stroke, and direct system that specifically locates Epidemiology of Stroke admission to a nursing home may and destroys bacteria is Stroke is one of the most common never be coded as an incident case of a. the white blood cell and devastating clinical disorders stroke. b. cortisol that can affect any person. A stroke is c. the neutrophil characterized by the sudden and While some of the additional fi- nancial impact of stroke is due to long- d. the hematocrit rapid development of clinical symp- toms and signs due to focal or global term care, most of the resultant in- 4. How does the stress response to loss of cerebral function that lasts creased costs are due to greater re- seriously acute illness affect the more than 24 hours or leading to quirement for acute care and rehabili- oropharyngeal and tracheobron- death within that period. In all clini- tation, rather than long-term care. It chial environments? cal cases there is no apparent cause is well documented that 74% of pa- a. It increases salivary and other than that of vascular origin tients still need some help with ac- mucous production which (Hatano, 1976). tivities of daily living such as wash- enhances the immune ing, dressing, and feeding themselves system’s protection of the In the United Kingdom (UK), even 3 months after stroke (Dewey et epithelium. more than 100,000 people each year al., 2002). suffer their first stroke. Worldwide, b. It reduces sensation to the after myocardial infarction and can- muscles and epithelial Pathophysiology of Stroke cer, stroke is the third most common surfaces due to restricted cause of death (Thorvaldsen, A stroke occurs when the blood blood supply. Asplund, Kuulasmaa, Rajakangas, & supply to part of the brain is inter- c. It reduces salivary and Schroll, 1995). The annual incidence rupted. The majority of strokes are mucous production which of first stroke without adjustment for due to the blockage of an artery by reduces the immune system’s age, gender or race is calculated to be either clot or plaque within the ves- protection of the epithelium. approximately 2.4/1,000 head of sel. A smaller but significant number d. It reduces salivary and population. This rises with increas- of strokes are due to hemorrhage from mucous production which ing age, such that the incidence for a ruptured vessel that results in a de- reduces lubrication of the oral those aged over 85 years is 10 per pendent area of brain tissue being cavity and impairs bolus 1,000 head of population (Wade & deprived of its supply of oxygen and formation and propulsion. Hewer, 1987). In the UK, stroke causes nutrients, thus becoming necrotic. Whatever the underlying patho- 5. Aspiration pneumonia can only an estimated 60,000 deaths per an- physiology, functions that were nor- develop num (ONS Mortality Statistics Cause, mally supplied by that area of brain a. when food carrying a 1997). In the UK, the cost of strokes to tissue are therefore lost. concentrated bacterial load the National Health Service (NHS) is passes through the larynx. estimated to be at least £2.3 billion per annum, with at least 25% of long Clinical Features b. when food passes through term and 20% of acute care beds be- the larynx and reaches the All clinical symptoms and signs ing occupied by patients following a trachea and bronchi. depend on the areas of the brain that stroke. c. when any contents carrying are affected by the stroke, irrespective a concentrated bacterial load While these statistics show that of whether an infarct or a hemorrhage from the oropharynx or from stroke is an ever increasing problem has occurred. These include paraly- the stomach pass through the worldwide, it may still be a gross un- sis of the limbs and trunk on one side larynx into an immune- derestimate, as some authors such as of the body, an inability to speak or compromised lower respira- Leibson and colleagues (1998) have understand speech and problems tory tract. found that as many as 45% of stroke with swallowing and/or vision. Im- mediately following a stroke there d. the red blood cell count is patients are never admitted to a hos- may be altered levels of conscious- high and the white blood cell pital and, thus, may not be identified ness with patients being very drowsy count is low. in statistical summaries. In addition, sudden death may not be attributed or even unconscious.