DIAGNOSIS OF LOWER RESPIRATORY TRACT INFECTIONS.

General Goal: To know how to diagnose pneumonia.

Specific Educational Objectives: The student should be able to:

1. describe how one determines a person has pneumonia.  Know the common causes pneumonia based on a person's age, where or how they acquire the pneumonia, and based on when signs and symptoms of pneumonia begin (acute, subacute, chronic).

2. describe the differences between typical and atypical pneumonia.

3. know why on examination of a smear of sputum the laboratory will reject some samples as saliva and not sputum.

4. if necessary know how to get a definitive diagnosis.

5. describe how some pneumonias can be prevented.

Lecture: Dr. Neal R. Chamberlain

References: 

• of the large number of organisms capable of causing pneumonia,
• clinical findings associated with many of these agents are very similar,
• less invasive procedures (sputum samples, blood cultures) for definitive diagnosis are commonly contaminated with normal flora or negative for growth of the etiological agent, and
• the invasive procedures (translaryngeal aspirate, lung biopsy, etc.) used for definitive diagnosis are rarely performed.

• There are a number of ways to classify pneumonias. In this particular disease the clinical and epidemiological data are quite useful in narrowing down the number of possible etiological agents.
• Is the pneumonia acute, subacute, or chronic in onset? Acute usually means 24 to 48 hours between onset of generalized symptoms and development of pneumonia. A subacute pneumonia usually requires 1 to 2 weeks to develop into pneumonia. In a chronic onset the disease process is much slower and may require 4 to 6 weeks to develop into pneumonia.
• If the pneumonia was acquired in the hospital (a nosocomial infection) a different set of organisms will be suspect than when the pneumonia is community-acquired.
• The age of the patient will also help to narrow down the number of possible agents since certain organisms are more common at certain ages.

Person to person transmission
• S. pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, S. aureus, S. pyogenes, K. pneumoniae, N. meningitidis, B. catarrhalis, influenza virus
Animal or environmental exposure
• Legionella pneumophila, Francisella tularensis, Coxiella burnetii, C. psittaci, Yersinia pestis (plague), Bacillus anthracis (anthrax), Pseudomonas pseudomallei (melioidosis), Pasteurella multocida (pasteurellosis)
Pneumonia in the infant & young child
• Chlamydia trachomatis, Respiratory Syncytial virus & other respiratory viruses, S. aureus, Group B Streptococcus, Cytomegalovirus, S. pneumoniae, H. influenza type b

Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter calcoaceticus, Staphylococcus aureus

• Mycobacterium tuberculosis

• Histoplasma capsulatum, Blastomyces dermatitides, Coccidioides immitis, Cryptococcus neoformans

• Mixed anaerobic & aerobic bacterial organisms

• Pneumocystis jirovecii, Cytomegalovirus, atypical mycobacterium such as M. avium etc., Nocardia, Aspergillus, Phycomycetes mucor, Candida

Pneumonia Resulting from Unusual Exposure:

3. What information do we need to make a diagnosis?

• A complete history: (age of the patient, onset of symptoms, occupation, prior or continuing illnesses, travel to other countries, hobbies, pets, recent contact with other people having an infectious disease)
• A thorough physical examination: Listening for lung sounds (wheezing, rales, dullness to percussion, normal lung sound), heart sounds, skin lesions, pulse rate, blood pressure, temperature, etc.
• Results of chest X-rays: Consolidation in the lungs. Whether the consolidation is unilateral, bilateral, localized, uniform, etc.
• Gram stain of sputum: (If obtainable) Look for hemoptysis and purulent vs. mucoid sputum. Usually only done on patients you must admit to the hospital.

• Does the person have pneumonia? Evidence for involvement of the lung parenchyma.
• Are there physical findings such as rales, dullness to percussion, pleural pain, cough, dyspnea, fever, chills, sputum production?
• Does the chest X-ray reveal any new abnormal lung consolidation(s) (fig. 1 and 2 ) not explained by other disease processes? Note: Lung consolidations in early pneumococcal pneumonia, metastatic pneumonia in bacteremic patients, and pneumonia in neutropenic patients may not be present. Other signs such as tachypnea and an otherwise unexplained depression of the blood oxygen tension are clues to the presence of pneumonia.
• Other diseases can mimic pneumonia and require differentiation. (examples: Lung cancers, immunologic disorders, pulmonary emboli, drug reactions, etc.)

• Define whether the pneumonia is acute or chronic and whether the patient is normal or immunosuppressed.

• Determine whether the pneumonia is typical ("bacterial") or atypical ("nonbacterial").

• Nonbacterial pneumonia is often used in two different ways. In one way it refers to a pneumonia that does not result in a productive cough (expectoration of sputum). In the second way it refers to whether the pneumonia is caused by a bacteria or not. The term "nonbacterial"pneumonia can be quite confusing so instead I will use the terms typical and atypical pneumonia.
• Typical pneumonia: A pneumonia which results in sputum production, is caused by a bacteria, and is usually acute in onset.
• Atypical pneumonia: A pneumonia which results in little to no sputum production, and is usually more chronic in onset.

• The Chest Roentgenograph or chest X-ray is very helpful in assisting the physician in their presumptive diagnosis, as well as determining whether the treatment used for the pneumonia is effective. Often times the atypical pneumonias present on chest X-ray as a patchy non-defined infiltrate. This is often described as a cobweb appearance. Typical pneumonias on the other hand often present on chest X-ray as consolidated, well defined densities. Certain organisms will form abscesses in the lung (S. aureus and anaerobic organisms). The chest X-ray is useful in demonstrating abscess formation. If proper treatment for a pneumonia is given the infiltrates seen upon admission to the hospital will clear. This is a good sign that appropriate treatment has been provided.

• Gram staining of the sputum is another very important test that can sometimes aid the physician in developing a presumptive diagnosis. However, for this sample to be of any use requires proper collection. The patient should be instructed on how to obtain the specimen. Three general criteria can help the physician in determining a presumptive diagnosis of the etiologic agent from gram staining the sputum. They are:
1. evaluation of the adequacy of the specimen. If the sputum contains too many squamous epithelial cells [>10 cells per high powered field (100X magnification)] the sample is not useful since it is overly contaminated with oropharyngeal organisms
2. evaluation of the quantity of polymorphonuclear cells (PMN's) and organisms. The presence of many PMN's implies an inflammatory process. The presence of many bacteria implies a bacterial infection.
3. evaluation of the kind and number of organisms present; particularly the predominant type of organism. The predominant type of bacterial cell indicates the likely cause of the pneumonia. Here one is looking at the gram stain reaction (whether the bug is gram negative or gram positive) and the shape of the organism (bacilli, cocci, diplococci, coccobacilli).
4. Steps to obtain a proper sputum specimen
• Assemble equipment: wide-mouthed container with ID label, gloves, tissues, water, and mouthwash.
• direct the patient to blow their nose to expell excess nasopharyngeal secretions. The patient should then brush their teeth and rinse with mouthwash to reduce the numbers of bacteria in the oral flora.
• direct the patient to breath deeply and cough deeply to bring up sputum. If possible, have the patient hold and expectorate directly into the container.
• If this fails an aerosol nebulizer, intermittent positive-pressure breathing with an aerosol or chest physiotherapy may help loosen thickened secretions.
• While wearing gloves cap the container.
• Label the container "sputum specimen" with the patient's name, time of collection, and if antibiotics have been given to the patient.  IMMEDIATELY transport to the laboratory.

• Summary of approach to obtaining a presumptive diagnosis
1. Determine whether or not the patient has pneumonia.
2. Stratify those with pneumonia into those with and without sputum production. Sputum production = typical bacterial pneumonia. No or little sputum production = atypical pneumonia.
3. Examine the sputum and X-ray results. Sputum containing many PMNs and many bacteria are the likely findings in those producing sputum. If sputum is obtainable from those with atypical pneumonia then usually many PMNs and few bacteria are seen. The X-ray results can also be helpful in that consolidations or abscesses usually indicate typical bacterial pneumonia whereas nondefined infiltrates indicate an atypical pneumonia.

• Culture of the sputum sample for bacteria, or fungi.
• Blood samples that are cultured for bacteria, fungi or viruses, the white blood cell count is performed, and the differential is obtained (A sedimentation rate can also be performed).
• Serology to detect antibodies produced against the pathogen or as a result of infection with the pathogen (cold agglutinins for Mycoplasma pneumoniae, detection of antibodies to the capsule of S. pneumoniae).
• Antigen tests to detect certain antigens produced by the pathogen (polysaccharide testing for S. pneumoniae and H. influenzae).
• Skin tests to detect delayed type hypersensitivity reactions to certain pathogens (M. tuberculosis, some of the fungi).
• In certain cases sputum and blood collection is not able to determine the etiologic agent. Other techniques have been developed to avoid the contamination of the sample with normal flora. These techniques include translaryngeal aspiration, bronchoscopy, needle biopsy of the lung, and open lung biopsy. These techniques are often required when an anaerobic bacterial, a fungal, a gram negative bacillary, or a parasitic infection, is suspected.
• Obtain pleural fluids or fluids from other affected areas for gram stains and culture.

7. Prevention:
Influenza vaccine (MMWR; April 14, 2000 / 49(RR03);1-38)should be given to all high-risk patients (persons 50 years old and older, patients with chronic diseases, immunocompromised patients, etc.). This vaccine may not prevent influenza (efficacy 50-60% in the elderly) but it appears to lower the number of secondary bacterial pneumonias and hospitalizations of elderly patients.

Vaccination schedule: give the vaccine every year starting in mid-October to mid-November.

Two Streptococcus pneumoniae vaccines are available for use in high risk groups.

This polysaccharide vaccine may not prevent pneumonia but it has been shown to lower the chances of invasive pneumococcal infections (bacteremia, meningitis). Pneumococcal infection causes an estimated 40,000 deaths annually in the United States, accounting for more deaths than any other vaccine-preventable bacterial disease. Approximately half of these deaths potentially could be prevented through the use of vaccine. Case-fatality rates are highest for meningitis and bacteremia, and the highest mortality occurs among the elderly and patients who have underlying medical conditions.

Merck and Company, Inc. (Pneumovax 23) and Lederle Laboratories (Pnu-Immune 23), include 23 purified capsular polysaccharide antigens of S. pneumoniae (serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F). These vaccines were licensed in the United States in 1983 and replaced an earlier 14-valent formulation that was licensed in 1977. One dose (0.5 mL) of the 23-valent vaccine contains 25 ug of each capsular polysaccharide antigen dissolved in isotonic saline solution with phenol (0.25%) or thimerosal (0.01%) added as preservative and no adjuvant. The 23 capsular types in the vaccine represent at least 85%-90% of the serotypes that cause invasive pneumococcal infections among children and adults in the United States. The six serotypes (6B, 9V, 14, 19A, 19F, and 23F) that most frequently cause invasive drug-resistant pneumococcal infection in the United States are represented in the 23-valent vaccine. Advisory Committee on Immunization Practices (ACIP) concerning pneumococcal polysaccharide vaccine (MMWR April 04, 1997 / 46(RR-08);1-24). ACIP recommends that the vaccine be used more extensively and administered to all persons in the following groups:

1. persons aged greater than or equal to 65 years
2. immunocompetent persons aged greater than or equal to 2 years who are at increased risk for illness and death associated with pneumococcal disease because of chronic illness (cardiovascular disease (e.g., congestive heart failure {CHF} or cardiomyopathies), chronic pulmonary disease (e.g., COPD or emphysema, but not asthma), diabetes mellitus, alcoholism, chronic liver disease (cirrhosis), or CSF leaks)
3. persons aged greater than or equal to 2 years with functional or anatomic asplenia
4. persons aged greater than or equal to 2 years living in environments in which the risk for disease is high
5. immunocompromised persons aged greater than or equal to 2 years who are at high risk for infection

Vaccination schedule: This vaccine is usually only given once. In certain high-risk groups patients can be revaccinated every 5 years. However, its long term efficacy has not been studied.

The other pneumoncoccal vaccine was approved by the FDA in February 2000 (MMWR; October 06, 2000 / 49(RR09);1-38). It is a 7-valent pneumococcal polysaccharide-protein conjugate vaccine (Prevnar,™ marketed by Wyeth Lederle Vaccines). By attaching the 7 most common polysaccharides in this age group (86% of bacteremia, 83%
of meningitis, and 65% of acute otitis media (AOM) among children aged <6 years occurring in the United States) from S. pneumoniae to a protein (a nontoxic variant of diphtheria toxin) they can elicite a good T-cell dependent antibody response.

This vaccine was licensed for use among infants and young children. CDC's Advisory Committee on Immunization Practices (ACIP) recommends that the vaccine be used for all children aged 2--23 months and for children aged 24--59 months who are at increased risk for pneumococcal disease (e.g., children with sickle cell disease, human immunodeficiency virus infection, and other immunocompromising or chronic medical conditions).

ACIP also recommends that the vaccine be considered for all other children aged 24--59 months, with priority given to a) children aged 24--35 months, b) children who are of Alaska Native, American Indian, and African-American descent, and c) children who attend group day care centers.

Vaccination Schedule. For children aged 24--59 months with underlying medical conditions, ACIP recommends two doses of PCV7, administered 2 months apart, followed by one dose of Pneumovax 23 or Pnu-Immune 23 administered >2 months after the second dose of PCV7.

This conjugate vaccine decreases colonization, and PCV7 prevents pneumococcal disease among children aged <2 years. Data from a prospective double-blind study (really CDC's description of the study) among patients of a health maintenance organization in northern California (37,830 healthy children) using PCV7 provide evidence of the vaccine's efficacy against invasive pneumococcal disease, as well as its effectiveness against clinical pneumonia and AOM among healthy children aged <2 years.