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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).

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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 3).

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.

(Table3): Major Causes of Acute Bronchitis:

Bacteria Viruses

Influenza virus, adenovirus, rhinovirus,

coronavirus (other less common

viruses: respiratory syncytial virus,

human metapneumovirus,

coxsackie A21 virus)

Bordetella pertussis,

B. parapertussis,

Mycoplasma pneumoniae,

Chlamydia pneumoniae

(Table 3): Viral Agents That Cause Bronchiolitis:

Respiratory syncytial virus

Parainfluenza viruses, types 1-3

Rhinoviruses

Adenoviruses

Influenza viruses

Enteroviruses

Human metapneumovirus

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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.

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.

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 (Table 4).

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.

Pneumonia:

Pneumonia (inflammation of the lower respiratory tract) is a major cause of illness and death. There are two

major categories of pneumonias: those considered communityacquired 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

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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.

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.

Chronic Lower Respiratory Tract Infections:

Mycobacterium tuberculosis is the most likely etiologic agent of chronic lower respiratory tract infection, but

fungal infection and anaerobic pleuropulmonary infection may also run a subacute or chronic course.

Mycobacteria other than M. tuberculosis may also cause such disease, particularly M. avium complex and M.

kansasii. Although possible causes of acute, community-acquired lower respiratory tract infections, fungi and

parasites are more commonly isolated from patients with chronic disease. Actinomyces and Nocardia may also

be associated with gradual onset of symptoms. Actinomyces is usually associated with an infection of the pleura

or chest wall, and Nocardia may be isolated along with an infection caused by M. tuberculosis.

The pathogenesis of many of the infections caused by agents of chronic lower respiratory tract disease is

characterized by the requirement for breakdown of cellmediated immunity in the host or the ability of these

agents to avoid being destroyed by host cell-mediated immune mechanisms. This may be caused by an effect

on macrophages, the ability to mask foreign antigens, sheer size, or some other factor, allowing microbes to

grow within host tissues without eliciting an overwhelming local immune reaction.

Cystic fibrosis (CF) is a genetic disorder that leads to persistent bacterial infection in the lung, causing airway

wall damage and chronic obstructive lung disease. Eventually, a combination of airway secretions and damage

leads to poor gas exchange in the lungs, cardiac malfunction, and subsequent death. Patients with CF may

present as young adults with chronic respiratory tract disease or, more commonly, as children with

gastrointestinal problems and stunted growth. Staphylococcus aureus is the most prevalent opportunistic

bacterial pathogen infecting 55% of children 0–9 years of age with CF, with Pseudomonas aeruginosa the most

prevalent (81%) in older children. A very mucoid Pseudomonas, characterized by production of copious

amounts of extracellular capsular polysaccharide, can be isolated from the sputum of almost all patients with

CF who are older than 18 years of age, becoming more prevalent with increasing age after 5 years. Even if CF

has not been diagnosed, isolation of a mucoid Pseudomonas aeruginosa from sputum should alert the clinician

to the possibility of underlying disease.

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Microbiologists should always report this unusual morphologic feature. In addition to mucoid Pseudomonas

and Staphylococcus aureus, important pathogens in patients with CF are likely to harbor Haemophilus

influenzae, Streptococcus pneumoniae, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Ralsotnia

spp. Cupriavidus spp.,

Pandoraea spp., Escherichia coli, strains of Burkholderia cepacia complex, fast growing mycobacteria, RSV,

influenza and fungi including Aspergillu, Scedosporium spp., and Exophiala dermatidis. In addition, due to the

viscous mucous plugs associated with CF, several anaerobic organisms have been detected in the lungs of CF

patients including Prevotella, Bifidobacterium, Veillonella, Peptostreptococcus and Fusobacterium.

Using advanced diagnostic molecular methods, additional organisms have also been identified in chronic

polymicrobial CF infections including viridans streptococci, Streptococcus constellatus, Streptococcus

intermedius and Streptococcus anginosus.

Lung abscess is usually a complication of acute or chronic pneumonia. In these circumstances, organisms

infecting the lung cause localized destruction of the lung parenchyma (functional elements of the lung).

Symptoms associated with lung abscess are similar to those of acute and chronic pneumonia, except symptoms

fail to resolve with treatment.

Immunocompromised Patients: Patients with Neoplasms. Patients with cancer are at high risk to become

infected because of either granulocytopenia or other defects in phagocytic defenses, cellular or humoral

immune dysfunction, damage to mucosal surfaces and the skin, and various medical procedures such as blood

product transfusion.

Transplant Recipients. For successful organ transplantation,the recipient’s immune system must be suppressed.

As a result, these patients are predisposed to infection. Regardless of the type of organ transplant

(heart, renal, bone marrow, heart/lung, liver, pancreas), most infections occur within 4 months following

transplantation. Major infections can occur within the first month but are usually associated with infections

carried over from the pretransplant period. Pulmonary infections are of great importance in this patient

population. Some of the most common causes of pneumonia include S. aureus Streptococcus pneumoniae,

Haemophilus influenzae, Pneumocystis jiroveci, and cytomegalovirus. In addition, other organisms such as

Cryptococcus neoformans, Aspergillus spp., Candida spp., Nocardia sp. and over, can cause life-threatening

pulmonary infection.

HIV-Infected Patients. Patients who are infected with human immunodeficiency virus (HIV) are at high risk

for developing pneumonia. opportunistic infections as a result of severe immunodeficiency are a major cause

of illness and death among these patients.

In the United States, the most common opportunistic infection among patients with acquired immunodeficiency

syndrome is Pneumocystis jiroveci pneumonia. Although P. jiroveci remains a major pulmonary pathogen,

other organisms must be considered in this patient population, including Mycobacterium tuberculosis and

Mycobacterium avium complex, as well as common bacterial pathogens such as Streptococcus pneumonia and

Haemophilus influenzae. In addition to these common pathogens, many other organisms can cause lower

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respiratory tract infections, including Nocardia spp., Rhodococcus equi (a gram-positive, aerobic, pleomorphic

organism), and Legionella spp.

Pleural infections

As a result of an organism infecting the lung and subsequently gaining access to the pleural space via an

abnormal passage (fistula), the patient may develop an empyema (pus in a body cavity such as the pleural

cavity).

(Table 5): Examples of Infectious Agents Frequently Associated with Certain Malignancies:

Malignancy (site and type of infections) Pathogen

Enterobacteriaceae

Pseudomonas

Staphylococci

Corynebacterium jeikeium

Candida

Aspergillus

Mucor

Hepatitis C and other non-A, non-B

Acute nonlymphocytic

leukemia (pneumonia,

oral lesions, cutaneous

lesions, urinary tract

infections, hepatitis,

most often sepsis

without obvious focus

Streptococci (all types)

Pneumocystis jiroveci (P. carinii)

Herpes simplex virus

Cytomegalovirus

Varicella zoster vi

Acute lymphocytic leukemia

(pneumonia, cutaneous

lesions, pharyngitis,

disseminated disease

Brucella

Candida (mucocutaneous)

Cryptococcus neoformans

Herpes simplex virus (cutaneous)

Varicella zoster virus

Cytomegalovirus

Pneumocystis jiroveci (P. carinii)

Toxoplasma gondii

Listeria monocytogenes

Mycobacteria

Nocardia

Salmonella

Staphylococci

Enterobacteriaceae

Pseudomonas

Strongyloides stercoralis

Lymphoma (disseminated

disease, pneumonia,

urinary tract infections,

sepsis, cutaneous

lesions)

Multiple myeloma Haemophilus influenza

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