Infections of the Lower Respiratory System



Infections of the Lower Respiratory System



Objectives



1. Define the trachea, bronchi, bronchioles, and alveoli, and explain the anatomic structure of the lower respiratory system.


2. List the most common etiologic agents responsible for lower respiratory disease and pneumonia in patients of various ages and categories: children <5 years of age, school-age children, young adults, older adults, and immunocompromised patients.


3. Describe the virulence factors found in bacteria and viruses associated with infection of the lower respiratory tract.


4. List the four possible routes of transmission or dissemination within the body that allow organisms to cause an infection in the lungs.


5. Name the most important decision for physicians regarding the treatment of pneumonia in older individuals, and list the three-step process used to guide them in this decision.


6. List the most prevalent cause of community-acquired pneumonia in adults.


7. Differentiate between community-acquired and hospital-acquired pneumonia.


8. State the factors anaerobic bacteria possess that enhance their ability to produce disease; explain how these anaerobes gain entrance to the lungs.


9. Define Lukens trap, and explain the type of patient or specimen associated with the method.


10. Describe the difference between early-onset or late-onset hospital- or ventilator-associated pneumonia.


11. List the etiologic agent of lung infections identified in cystic fibrosis patients.


12. Name the organisms most often associated with pneumo-opportunistic infection in HIV-positive individuals.


13. Explain the mechanisms that, because of the bacterial production of toxins, enable microorganisms to produce respiratory-associated disease.


14. Explain how the host immune system can contribute to microorganism growth in the respiratory disease process.


15. Explain why Mycobacterium tuberculosis is a classic representative of an intracellular pathogen.


16. Describe specimens collected for respiratory infections including determination of specimen quality and rejection criteria for the following: sputum, induced sputum, endotracheal suction, pleural fluid, bronchoalveolar lavage, bronchial washing, and bronchial brush sample.


17. Explain how the microbiologist would test for the less common causes of respiratory infection, including Pneumocystis jiroveci, Legionella spp., Chlamydophila pneumonia, Bordetella pertussis, Mycoplasma pneumonia, and Norcardia.



General Considerations


Anatomy


The respiratory tract can be divided into two major areas: the upper respiratory tract consists of all structures above the larynx, whereas the lower respiratory tract follows airflow below the larynx through the trachea to the bronchi and bronchioles and then into the alveolar spaces where gas exchange occurs (Figure 69-1). The respiratory and gastrointestinal tracts are the two major connections between the interior of the body and the outside environment. The respiratory tract is the pathway through which the body acquires fresh oxygen and removes unneeded carbon dioxide. It begins with the nasal and oral passages, which humidify inspired air, and extends past the nasopharynx and oropharynx to the trachea and then into the lungs. The trachea divides into bronchi, which subdivide into bronchioles, the smallest branches that terminate in the alveoli. Some 300 million alveoli are estimated to be present in the lungs; these are the primary microscopic gas exchange structures of the respiratory tract.


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Figure 69-1 Anatomy of the respiratory tract, including upper and lower respiratory tract regions.

Familiarization with the anatomic structure of the thoracic cavity ensures proper specimen collection from various sites in the lower respiratory tract for processing by the laboratory. The thoracic cavity, which contains the heart and lungs, has three partitions separated from one another by pleura (see Figure 69-1). The lungs occupy the right and left pleural cavities, whereas the mediastinum (space between the lungs) is occupied mainly by the esophagus, trachea, large blood vessels, and heart.



Pathogenesis of the Respiratory Tract: Basic Concepts


Microorganisms primarily cause disease by a limited number of pathogenic mechanisms (see Chapter 3). Because these mechanisms relate to respiratory tract infections, they are discussed briefly. Encounters between the human body and microorganisms occur many times each day. However, establishment of infection after such contact tends to be the exception rather than the rule. Whether an organism is successful in establishing an infection depends not only on the organism’s ability to cause disease (pathogenicity) but also on the human host’s ability to prevent the infection.



Host Factors


The human host has several mechanisms that nonspecifically protect the respiratory tract from infection: the nasal hairs, convoluted passages, and the mucous lining of the nasal turbinates; secretory IgA and nonspecific antibacterial substances (lysozyme) in respiratory secretions; the cilia and mucous lining of the trachea; and reflexes such as coughing, sneezing, and swallowing. These mechanisms prevent foreign objects or organisms from entering the bronchi and gaining access to the lungs, which remain sterile in the healthy host. Aspiration of minor amounts of oropharyngeal material, as occurs often during sleep, plays an important role in the pathogenesis of many types of pneumonia. Once particles escape the mucociliary sweeping activity and enter the alveoli, alveolar macrophages ingest them and carry them to the lymphatics.


In addition to these nonspecific host defenses, normal flora of the nasopharynx and oropharynx help prevent colonization by pathogenic organisms of the upper respiratory tract. Normal bacterial flora prevent the colonization by pathogens by competing for the same space and nutrients as well as production of bacteriocins and metabolic products that are toxic to invading organisms. Some of the bacteria that can be isolated as part of the indigenous flora of healthy hosts, as well as many species that may cause disease under certain circumstances and are often isolated from the respiratory tracts of healthy persons, are listed in Box 69-1. Under certain circumstances and for unknown reasons, these colonizing organisms can cause disease—perhaps because of previous damage by a viral infection, loss of some host immunity, or physical damage to the respiratory epithelium (e.g., from smoking). Differentiation of normal flora of the respiratory tract is important for determining the importance of an isolate in the clinical laboratory. Colonization does not always represent an infection. It is important to differentiate colonization from infection based on the specimen source, number of organisms present, and presence or quantity of white blood cells. (Organisms isolated from normally sterile sites in the respiratory tract by sterile methods that avoid contamination with normal flora should be definitively identified and reported to the clinician.)



Box 69-1   Organisms Present in the Nasopharynx and Oropharynx of Healthy Humans





Microorganism Factors


Organisms possess traits or produce products that promote colonization and subsequent infection in the host. The virulence, or disease-producing capability of an organism, depends on several factors including adherence, production of toxins, amount of growth or proliferation, tissue damage, avoiding the host immune response, and ability to disseminate.



Adherence.

For any organism to cause disease, it must first gain a foothold within the respiratory tract to grow to sufficient numbers to produce symptoms. Therefore, most etiologic agents of respiratory tract disease must first adhere to the mucosa of the respiratory tract. The presence of normal flora and the overall state of the host affect the ability of microorganisms to adhere. Surviving or growing on host tissue without causing overt harmful effects is termed colonization. Except for those microorganisms inhaled directly into the lungs, all etiologic agents of disease must first colonize the respiratory tract before they can cause harm.


Streptococcus pyogenes possess specific adherence factors such as fimbriae comprised of molecules such as lipoteichoic acids and M proteins. These molecules appear as a thin layer of fuzz surrounding the bacteria. Staphylococcus aureus and certain viridans streptococci are other bacteria that posses these lipoteichoic acid adherence complexes. Many gram-negative bacteria (which do not have lipoteichoic acids), including Enterobacteriaceae, Legionella spp., Pseudomonas spp., Bordetella pertussis, and Haemophilus spp., also adhere by means of proteinaceous finger-like surface fimbriae. Viruses possess either a hemagglutinin (influenza and parainfluenza viruses) or other proteins that mediate their epithelial attachment.



Toxins.

Certain microorganisms are almost always considered to be etiologic agents of disease if they are present in any numbers in the respiratory tract because they possess virulence factors that are expressed in every host. These organisms are listed in Box 69-2. The production of extracellular toxin was one of the first pathogenic mechanisms discovered among bacteria. Corynebacterium diphtheriae is a classic example of a bacterium that produces disease through the action of an extracellular toxin. Once the organism colonizes the upper respiratory epithelium, it produces a toxin that is disseminated systemically, adhering preferentially to central nervous system cells and muscle cells of the heart. Systemic disease is characterized by myocarditis, peripheral neuritis, and local disease that can lead to respiratory distress. Growth of C. diphtheriae causes necrosis and sloughing of the epithelial mucosa, producing a “diphtheritic (pseudo) membrane,” which may extend from the anterior nasal mucosa to the bronchi or may be limited to any area between—most often the tonsillar and peritonsillar areas. The membrane may cause sore throat and interfere with respiration and swallowing. Although nontoxic strains of C. diphtheriae can cause local disease, it is much milder than disease associated with toxigenic strains.



Box 69-2   Respiratory Tract Pathogens




Some strains of Pseudomonas aeruginosa produce a toxin similar to diphtheria toxin. Whether this toxin actually contributes to the pathogenesis of respiratory tract infection with P. aeruginosa has not been established. Bordetella pertussis, the agent of whooping cough, also produces toxins. The role of these toxins in production of disease is not clear. They may act to inhibit the activity of phagocytic cells or to damage cells of the respiratory tract. Staphylococcus aureus and beta-hemolytic streptococci produce extracellular enzymes capable of damaging host cells or tissues. Extracellular products of staphylococci aid in the production of tissue necrosis and the destruction of phagocytic cells and contribute to the abscess formation associated with infection caused by this organism. Although S. aureus can be recovered from throat specimens, it has not been proved to cause pharyngitis. Enzymes of streptococci, including hyaluronidase, allow rapid dissemination of the bacteria. Many other etiologic agents of respiratory tract infection also produce extracellular enzymes and toxins.



Microorganism Growth.

In addition to adherence and toxin production, pathogens cause disease by merely growing in host tissue, interfering with normal tissue function, and attracting host immune effectors, such as neutrophils and macrophages. Once these cells begin to attack the invading pathogens and repair the damaged host tissue, an expanding reaction ensues with more nonspecific and immunologic factors being attracted to the area, increasing the amount of host tissue damage. Respiratory viral infections usually progress in this manner, as do many types of pneumonias, such as those caused by Streptococcus pneumoniae, S. pyogenes, Staphylococcus aureus, Haemophilus influenzae, Neisseria meningitidis, Moraxella catarrhalis, Mycoplasma pneumoniae, Mycobacterium tuberculosis, and most gram-negative bacilli.



Avoiding the Host Response.

Another virulence mechanism present in various respiratory tract pathogens is the ability to evade host defense mechanisms. S. pneumoniae, N. meningitidis, H. influenzae, Klebsiella pneumoniae, mucoid P. aeruginosa, Cryptococcus neoformans, and others possess polysaccharide capsules that serve both to prevent engulfment by phagocytic host cells and to protect somatic antigens from being exposed to host immunoglobulins. The capsular material is produced in such abundance by certain bacteria, such as pneumococci, that soluble polysaccharide antigen particles can bind host antibodies, blocking them from serving as opsonins. Vaccine consisting of capsular antigens provides host protection to infection, indicating that the capsular polysaccharide is a major virulence mechanism of H. influenzae, S. pneumoniae, and N. meningitidis.


Some respiratory pathogens evade the host immune system by multiplying within host cells. Chlamydia trachomatis, Chlamydia psittaci, Chlamydia pneumoniae, and all viruses replicate within host cells. They have evolved methods for being taken in by the “nonprofessional” phagocytic cells of the host to where they thrive within the intracellular environment. Once within these cells, the organism is protected from host humoral immune factors and other phagocytic cells. This protection lasts until the host cell becomes sufficiently damaged that the organism is then recognized as foreign by the host and is attacked. A second group of organisms that cause respiratory tract disease comprises organisms capable of survival within phagocytic host cells (usually macrophages). Once inside the phagocytic cell, these respiratory tract pathogens are able to multiply. Legionella, Pneumocystis jiroveci (Pneumocystis carinii), and Histoplasma capsulatum are some of the more common intracellular pathogens.


Mycobacterium tuberculosis is the classic representative of an intracellular pathogen. In primary tuberculosis, the organism is carried to an alveolus in a droplet nucleus, a tiny aerosol particle containing tubercle bacilli. Once phagocytized by alveolar macrophages, organisms are carried to the nearest lymph node, usually in the hilar or other mediastinal chains. In the lymph node, the organisms slowly multiply within macrophages. Ultimately, M. tuberculosis destroys the macrophage and is subsequently taken up by other phagocytic cells. Tubercle bacilli multiply to a critical mass within the protected environment of the macrophages, which are prevented from accomplishing phagosome-lysosome fusion capable of destroying the bacteria. Having reached a critical mass, the organisms spill out of the destroyed macrophages, through the lymphatics, and into the bloodstream, producing mycobacteremia and carrying tubercle bacilli to many parts of the body. In most cases, the host immune system reacts sufficiently at this point to kill the bacilli; however, a small reservoir of live bacteria may be left in areas of normally high oxygen concentration, such as the apical (top) portion of the lung. These bacilli are walled off, and years later, an insult to the host, either immunologic or physical, may cause breakdown of the focus of latent tubercle bacilli, allowing active multiplication and disease (secondary tuberculosis). In certain patients with primary immune defects, the initial bacteremia seeds bacteria throughout a compromised host, leading to disseminated or miliary tuberculosis. Growth of the bacteria within host macrophages and histiocytes in the lung causes an influx of more effector cells, including lymphocytes, neutrophils, and histiocytes, eventually resulting in granuloma formation, then tissue destruction and cavity formation. The lesion consists of a semisolid, amorphous tissue mass resembling semisoft cheese, from which it received the name caseating necrosis (death of cells or tissues). The infection can extend into bronchioles and bronchi from which bacteria are disseminated via respiratory secretions and coughing. Aerosolized droplets are produced by coughing and contain organisms that are inhaled by the next susceptible host. Other portions of the patient’s lungs may become infected as well through aspiration (inhalation of a fluid or solid).



Diseases of the Lower Respiratory Tract


Bronchitis


Acute


Acute bronchitis is characterized by acute inflammation of the tracheobronchial tree. This condition may be part of, or preceded by, an upper respiratory tract infection such as influenza (the “flu”) or the common cold. Most infections occur during the winter when acute respiratory tract infections are common.


The pathogenesis of acute bronchitis has no specific documented etiology but appears to be a mixture of viral cytopathic events and a response by the host immune system. Regardless of the cause, the protective functions of the bronchial epithelium are disturbed and excessive fluid accumulates in the bronchi. Depending on the etiology, destruction of the bronchial epithelium may be either extensive (e.g., influenza virus) or minimal (e.g., rhinovirus colds).


Clinically, bronchitis is characterized by cough, variable fever, and sputum production. Sputum (pus from the lungs) is often clear at the onset but may become purulent as the illness persists. Bronchitis may manifest as croup (a clinical condition marked by a barking cough or hoarseness).


The value of microbiologic studies to determine the cause of acute bronchitis in otherwise healthy individuals has not been established. Acute bronchitis is caused by viral agents, such as influenza and respiratory syncytial virus (RSV). The bacterium Bordetella pertussis is often associated with bronchitis in infants and preschool children (Table 69-1). The best specimen for diagnosis of pertussis is a deep nasopharyngeal specimen collected with a calcium alginate swab (see Chapter 37).




Chronic versus Acute


Chronic bronchitis is a common condition affecting about 10% to 25% of adults. This disease is defined by clinical symptoms in which excessive mucus production leads to coughing up sputum on most days during at least 3 consecutive months for more than 2 successive years. Cigarette smoking, infection, and inhalation of dust or fumes are important contributing factors. Acute bronchitis is not related to long-term etiologies causing damage to the lungs, but is typically a result of an infectious process.


Patients with chronic bronchitis can suffer from acute flare-ups of infection, but determination of the cause of the infection is difficult. Potentially pathogenic bacteria, such as nonencapsulated strains of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, are frequently cultured from the bronchi of these patients. Because of chronic colonization, it is difficult to incriminate one of these organisms as the specific cause of an acute infection in patients with chronic bronchitis. Although the role of bacteria in acute infections in these patients is questionable, viruses are frequent causes.



Bronchiolitis


Bronchiolitis, the inflammation of the smaller diameter bronchiolar epithelial surfaces, is an acute viral lower respiratory tract infection that primarily occurs during the first 2 years of life. Characteristic clinical manifestations include an acute onset of wheezing and hyperinflation as well as cough, rhinorrhea (runny nose), tachypnea (rapid breathing), and respiratory distress. The disease is primarily caused by viruses including a recently discovered virus, human metapneumovirus. RSV accounts for 40% to 80% of cases of bronchiolitis and demonstrates a marked seasonality; the etiologic agents of bronchiolitis are listed in Box 69-3. Like other viral infections, bronchiolitis shows a marked seasonality in temperate climates with a yearly increase in cases during winter to early spring.



Box 69-3   Viral Agents That Cause Bronchiolitis




Initially, the virus replicates in the epithelium of the upper respiratory tract, but in the infant it rapidly spreads to the lower tract airways. Early inflammation of the bronchial epithelium progresses to necrosis. Symptoms such as wheezing may be related to the type of inflammatory response to the virus as well as other host factors. For the most part, patients are managed based on clinical parameters, with the laboratory having a role in cases that require hospitalization; a specific viral etiology can be identified in a large number of infants by viral isolation from respiratory secretions, preferably from a nasal wash (see Chapter 65).



Pneumonia


Pneumonia (inflammation of the lower respiratory tract involving the lung’s airways and supporting structures) is a major cause of illness and death. There are two major categories of pneumonias: those considered community-acquired pneumonia (patients are believed to have acquired their infection outside the hospital setting) and those including hospital- or ventilator-associated (patients are believed to have acquired their infection within the hospital setting, usually at least 2 days following admission) or health care–associated pneumonia (affects only patients hospitalized in an acute care hospital for 2 or more days within 90 days of infection from a long-term care facility, or patients who have received recent intravenous antibiotic therapy, chemotherapy, or wound care within 30 days of the current infection, or who have attended a hospital or hemolysis clinic). Nevertheless, once a microorganism has successfully invaded the lung, disease can follow affecting the alveolar spaces and their supporting structure, the interstitium, and the terminal bronchioles.



Pathogenesis


Organisms can cause infection of the lung by four possible routes: by upper airway colonization or infection that subsequently extends into the lung, by aspiration of organisms (thereby avoiding the upper airway defenses), by inhalation of airborne droplets containing the organism, or by seeding of the lung via the blood from a distant site of infection. Viruses cause primary infections of the respiratory tract, as well as inhibit host defenses that, in turn, can lead to a secondary bacterial infection. For example, viruses may destroy respiratory epithelium and disrupt normal ciliary activity. Presumably, the growth of viruses in host cells disrupts the function of the latter and encourages the influx of nonspecific immune effector cells exacerbating the damage. Damage to host epithelial tissue by virus infection is known to predispose patients to secondary bacterial infection.


Aspiration of oropharyngeal contents is important in the pathogenesis of many types of pneumonia. Aspiration may occur during a loss of consciousness such as during anesthesia or a seizure, or after alcohol or drug abuse, but other individuals, particularly geriatric patients, may also develop aspiration pneumonia. Neurologic disease or esophageal pathology and periodontal disease or gingivitis are other important risk factors. Aided by gravity and often by loss of some host nonspecific protective mechanisms, organisms reach lung tissue, where they multiply and attract host inflammatory cells. Other mechanisms include inhalation of aerosolized material and hematogenous seeding. The buildup of cell debris and fluid contributes to the loss of lung function and thus to the pathology.


Furthermore, regarding the pathogenesis of hospital-associated, health care–associated, and ventilator-associated pneumonias, health care devices, the environment, and the transfer between the patient and staff or other patients can serve as sources of pathogens causing pneumonia. The primary routes for bacterial entry into the lower respiratory tract are by aspiration of oropharyngeal organisms or leakage of secretions containing bacteria around an endotracheal tube. For these reasons, intubation and mechanical ventilation significantly increase the risk of pneumonia (6- to 21-fold). In addition, bacterial and viral biofilm in the endotracheal tube with subsequent spread to distal airways may be important in the pathogenesis of ventilator-associated pneumonia.



Clinical Manifestations


The symptoms suggestive of pneumonia include fever, chills, chest pain, and cough. In the past, pneumonias were classified into two major groups: (1) typical or acute pneumonias (e.g., Streptococcus pneumoniae) and (2) atypical pneumonias, based on whether the cough was productive or nonproductive of mucoid sputum. However, analysis of symptoms of pneumonia caused by the atypical pneumonia pathogens (Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydophila pneumoniae) has revealed no significant differences from those symptoms of patients with typical bacterial pneumonias. Because of this overlap in symptoms, it is important to consider all possible etiologies associated with the patient’s clinical presentation.


Some patients with pneumonia exhibit no signs or symptoms related to their respiratory tract (i.e., some only have fever). Therefore, physical examination of the patient, chest radiograph findings, patient history, and clinical laboratory findings are important. In addition to respiratory symptoms, 10% to 30% of patients with pneumonia complain of headache, nausea, vomiting, abdominal pain, diarrhea, and myalgias.



Epidemiology/Etiologic Agents


As previously mentioned, there are two major categories of pneumonias: those considered community-acquired pneumonias and hospital-, ventilator-, or health care–associated pneumonias. Because the epidemiology and etiologies can differ, these two categories are discussed separately. Pneumonia in the immunocompromised patient is addressed separately in this chapter. Emerging viral infections associated with severe acute respiratory syndrome (SARS) and influenza outbreaks (H1N1) are typically associated with upper respiratory infections but may lead to serious lower respiratory infections in the young, elderly, or immunocompromised patient. See Chapter 66 for detailed information related to these emerging viral infectious diseases and diagnostic recommendations.



Community-Acquired Pneumonia.

In the United States, pneumonia is the sixth leading cause of death and the number one cause of death from infectious diseases. It is estimated that as many as 2 million to 3 million cases of community-acquired pneumonia occur annually, and roughly one fifth of these require hospitalization; 45,000 pneumonia-related deaths occur in the United States each year. The etiology of acute pneumonias is strongly dependent on age. More than 80% of pneumonias in infants and children are caused by viruses, compared to less than 10% to 20% of pneumonias in adults.



Children.

Community-acquired pneumonia in children is a common and potentially serious infection. The annual incidence of pneumonia in children younger than 5 years of age is 34 to 40 cases per 1000 in Europe and North America. Determining the cause of pneumonia is challenging because the lungs are rarely sampled directly and sputum is difficult to obtain from children. Among previously healthy patients 2 months to 5 years old, RSV, human metapneumovirus, parainfluenza, influenza, and adenoviruses are the most common etiologic agents of lower respiratory tract disease. Children suffer less commonly from bacterial pneumonia, usually caused by H. influenzae, S. pneumoniae, or S. aureus. Neonates may acquire lower respiratory tract infections with C. trachomatis or P. jiroveci (which likely indicates an immature immune system or an underlying immune defect).


M. pneumoniae and C. pneumoniae are the most common causes of bacterial pneumonia in school-age children (5-14 years of age). The four most common causes of community-acquired viral pneumonia in children include influenza, RSV, parainfluenza, and adenovirus. The agents associated with nosocomial outbreaks in children include the influenza virus, RSV, and adenovirus. Mixed viral and bacterial infections have been documented in 35% of patients, with the majority of these (81%) being mixed viral-bacterial infections. In addition, the time of onset of hospital- or ventilator-associated pneumonia is an important epidemiologic variable and risk factor: early-onset pneumonia (defined as occurring within the first 4 days of hospitalization), usually carries a better prognosis, being more likely to be caused by antibiotic-sensitive bacteria, whereas late-onset pneumonia (5 days or more) is more likely to be caused by multidrug-resistant organisms and is associated with increased patient morbidity and mortality.

Related posts:

  1. Acinetobacter, Stenotrophomonas, and Similar Organisms
  2. Haemophilus
  3. Vibrio, Aeromonas, Chromobacterium, and Related Organisms
  4. Gastrointestinal Tract Infections

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Aug 25, 2016 | Posted by in MICROBIOLOGY | Comments Off on Infections of the Lower Respiratory System

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