Respiratory System Defense Mechanisms Against Infection

Pneumonias, sometimes recurrent, occur with increased frequency in children who have defective immune or pulmonary defense mechanisms. Conditions that are associated with an increased risk of pneumonia include abnormalities of antibody production (e.g., agammaglobulinemia), deficient mucociliary function (e.g., cystic fibrosis and dysmotile cilia syndrome), and abnormalities of polymorphonuclear leukocytes (e.g., chronic granulomatous disease). Infants with congenital heart disease also have a propensity for developing recurrent pneumonias.

Mechanical Defense Mechanism

The mechanical defense mechanism of the lung provides filtration and clearance functions. In the nasopharynx, filtration occurs by trapping of material in the nasal hairs and mucous and by turbulence created as air passes through the irregular, tortuous channels of the nasal cavity. The nasopharyngeal filtering system predominantly traps particles that are greater than 5 μm in diameter. With mouth breathing, minimal filtration effect is provided by the angular course that incoming air follows in the posterior aspect of the oropharynx. Particles that gain access to the tracheobronchial tree are predominantly deposited on the walls of the airway, usually at sites of bifurcation where airflow is turbulent. In the peripheral aspects of the lungs, particle deposition occurs predominantly by sedimentation and diffusion.

Various clearance mechanisms are present in the respiratory system to remove particles from the airways. Sneezing clears nasopharyngeal material, and coughing removes particles in the trachea and large bronchi. Mucociliary activity is an additional important clearance mechanism that functions in the nasopharynx and tracheobronchial tree. The 3 components of the mucociliary clearance mechanism are mucous, cilia, and a coupling mechanism. The mucus that lines the tracheobronchial tree serves to trap particles, humidify inspired air, lubricate the airways, dilute toxic substances, and support neutrophils and macrophages. Secretion of mucus is by goblet cells that are interspersed among the ciliated epithelial cells of the airways. The cilia are the second major component of the mucociliary clearance mechanism. A corrugated beating motion of the cilia propels the overlying mucus in a cephalad direction within the airways. Effective propulsion relies on a viscous-chemical coupling mechanism that links the overlying mucus to the beating action of the cilia.

A variety of factors can result in compromise of the mechanical pulmonary defense mechanisms. The nasal filtration mechanism is bypassed when patients with an upper respiratory viral infection resort to mouth breathing because of nasopharyngeal secretions and mucosal edema. The pharyngeal and upper tracheal mechanical barriers are bypassed in patients with endotracheal or tracheostomy tubes. Patients with a depressed cough reflex have diminished clearance of secretions and the infectious agents trapped in those secretions. Viral and Mycoplasma infections can be toxic to the respiratory cilia, thereby compromising the mucociliary transport mechanism and increasing susceptibility to bacterial infections. Intrinsic abnormalities of the cilia result in compromised mechanical pulmonary defense in patients with cystic fibrosis and dysmotile cilia syndrome.

Phagocytic Defense Mechanism

Inhaled organisms and other particles that are not captured and removed by the mechanical defense system of the respiratory tract are ingested, inactivated, and removed by the phagocytic defense mechanism. The 2 types of cells in the lung that provide this phagocytic activity are polymorphonuclear leukocytes and macrophages. Pulmonary macrophages are normally present in the alveoli, lung parenchyma, and conducting airways. The majority of polymorphonuclear leukocytes in the lung reside in the pulmonary vascular bed.

In response to deposition of particles on airway surfaces, migration of polymorphonuclear leukocytes occurs through the interstitium to the airway. The actions of various chemotactic factors induce this phagocytic cell migration. Stimulation of phagocytic cell migration in the nonimmune host is by components of bacterial cell walls that have chemotactic activity, generation of chemotaxin C5a as a result of activation of the alternate complement pathway by organisms, and release of chemotactic factors by pulmonary macrophages after ingestion of particles. In the immune host, an organism-specific antibody forms antigen–antibody complexes that activate the classic complement pathway, leading to the production of chemotactic factors. Leukocytes that migrate to the particles also release chemotactic factors.

Polymorphonuclear leukocytes phagocytize, devitalize, and remove particles from the walls of the airways. Phagocytosis requires opsonization of the particle, which is provided by the complement fragment C3b (produced by the alternate pathway of complement activation) in the nonimmune host, and by specific antibodies as well as C3b (produced by the classic pathway of complement activation) in the immune host. After phagocytosis, the ingested particle is encased in a phagosome, which then fuses with lysosomes to form a phagolysosomal vacuole that kills and digests the particle. The phagocytized organism is killed by both oxidative and nonoxidative mechanisms. The polymorphonuclear leukocytes subsequently die and macrophages remove the cellular debris.

Pulmonary macrophages derive from monocytes that originate in the bone marrow and migrate to the pulmonary parenchyma. Chemotactic factors influence the migration of monocytes into the lung and the movement of macrophages in the lung. Macrophages phagocytize particles in a similar manner to polymorphonuclear leukocytes. Organisms phagocytized by macrophages are exposed to oxygen free radicals and hydrolytic enzymes. Mycobacterium tuberculosis is resistant to these microbicidal mechanisms.

Neutropenia is the most common mechanism by which the phagocytic defense mechanism of the lung is compromised. There is a substantial increase in the risk for severe pulmonary infection when the absolute granulocyte count falls below 500 cells per mm³. There are also conditions that result in intrinsic defects in pulmonary phagocytosis. Intracellular microbicidal activity is defective in both macrophages and polymorphonuclear leukocytes in patients with chronic granulomatous disease, thereby resulting in increased frequency and severity of infections with Staphylococcus aureus, Gram-negative organisms, Candida, and Aspergillus. Patients with Chediak-Higashi syndrome have abnormal phagolysosomal function (because of a deficiency of the opsin C3b), leading to frequent infections with S. aureus.

Immune Defense Mechanism

The major components of the immune defense mechanism of the lung are immunoglobulins (antibodies) produced by B lymphocytes and cellular immune responses carried out by the action of T lymphocytes. The immune system response is organism specific, as it occurs in response to the presence of a specific antigen. Macrophages ingest and process the antigen, and then display the antigen on their surface membranes. Antigen-reactive B and T lymphocytes then interact with this macrophage. After exposure of a T lymphocyte to an antigen to which is sensitive, it undergoes proliferation and differentiation into an effector cell. These activated T lymphocytes serve to mediate delayed hypersensitivity and to regulate the various components of the immune system. When B lymphocytes are exposed to an antigen to which they are sensitive, they differentiate into plasma cells and memory B lymphocytes. The plasma cells secrete an immunoglobulin that is specific for the antigen. The memory B lymphocytes elicit secondary anamnestic responses when they are subsequently exposed to the same antigen.

Individuals who have a deficiency of B lymphocyte function are prone to infections with pyogenic organisms such as Streptococcus pneumoniae, S. aureus, Streptococcus pyogenes, Neisseria species, and Haemophilus influenzae. Primary immunodeficiencies that predominantly involve deficient numbers or function of B lymphocytes include X-linked agammaglobulinemia, combined variable immunodeficiency, and selective (isolated) immunoglobulin A deficiency. Secondary immune deficiencies can occur as a result of immunosuppressive medications, infections, nutritional deficiencies, chronic renal disease, and chronic liver disease.

A deficiency of T lymphocyte function is associated with an increased susceptibility to infections with M. tuberculosis, Listeria monocytogenes, Toxoplasma gondii, Pneumocystis jiroveci, viruses, and fungi. Primary disorders of T lymphocyte function include DiGeorge syndrome, ataxia telangiectasia, cartilage hair hypoplasia, and Wiskott-Aldrich syndrome. Immune suppressive drugs in organ transplantation patients suppress T-cell activity. AIDS results in severe impairment of T-lymphocyte function.

There are characteristic types and causes of pneumonia in the immunocompromised host. The most frequent infecting organisms in these patients are cytomegalo-virus, P. jiroveci, varicella zoster virus, Candida species, and Aspergillus species. Lymphoid interstitial pneumonia can occur in children with AIDS. Less frequent causes of pneumonitis in immunocompromised children include T. gondii, Cryptosporidium, herpes simplex, adenovirus, Gram-negative bacillary infections (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Legionella pneumophila), Nocardia species, Zygomycetes, and Cryptococcus neoformans. With the exception of varicella-zoster pneumonitis, biopsy is often required to establish a definitive diagnosis.¹

Clinical Presentations of Pneumonia

The lower respiratory tract consists of the lungs, the bronchi, and the trachea; that is, the structures distal to the glottis. The clinical manifestations of lower respiratory tract infection include variable combinations of cough, fever, stridor, and chest pain. Other potential findings include alterations in the breathing pattern, retractions, cyanosis, and hemoptysis. Chest auscultation may demonstrate wheezing, rales, and diminished or absent breath sounds. The most common responsible pathogens vary with the age of the patient (Table 3-1).

The estimated worldwide incidence of pneumonia in children younger than 5 years of age is 150 million cases per year.² Viral infection is the most common cause of pneumonia in children, particularly in young children. Viruses account for approximately 90% of pneumonias in children younger than 3 years of age. Various viruses are associated with pneumonia, including respiratory syncytial virus, influenza, parainfluenza, and adenovirus. Cytomegalovirus is an important pulmonary pathogen in immunocompromised individuals. There is a seasonal pattern of most viral lower respiratory tract infections. Respiratory syncytial virus and influenza virus are most prevalent during the winter months. Parainfluenza virus infection tends to occur during the spring. There is no significant seasonal variation with adenovirus infections.³

Viral lung infection causes alterations in the defense mechanisms of the respiratory tract, which can predispose to the development of bacterial pneumonia as a secondary process. Viral infection alters the properties of pulmonary secretions, inhibits phagocytosis, modifies the bacterial flora, and can cause epithelial cell damage. The signs and symptoms of viral pneumonia are frequently nonspecific, and manifestations of upper respiratory tract involvement may predominate. Most viral pneumonias are preceded by several days of nonspecific respiratory symptoms, such as cough and rhinitis. The only clinical clues to lung infection in these children may be increasing severity of cough and fever. Infants and young children sometimes have dyspnea and tachypnea.

Mycoplasma pneumoniae is the single most common organism responsible for pneumonia in children. This agent causes 40% to 60% of pneumonias in school-age children. However, Mycoplasma pneumonia is uncommon in children younger than 3 years of age. M. pneumoniae infection most often occurs in the summer and autumn. In older children, Chlamydia pneumoniae and Chlamydia psittaci produce respiratory infections that are clinically indistinguishable from those caused by Mycoplasma. Mycoplasma and Chlamydia infections in older children are grouped under the term atypical pneumonia.

Bacteria cause approximately 5% to 10% of pneumonias in children. Community-acquired bacterial pneumonias are frequently preceded by an upper respiratory infection. Bacterial pneumonias are somewhat more prevalent in the winter months. The most common organisms are S. pneumoniae and S. aureus. Neonates can have bacterial lung infections caused by group B Streptococcus and various Gram-negative bacilli.

The clinical presentation of bacterial pneumonia typically consists of the abrupt onset of fever, chills, tachypnea, and tachycardia (Table 3-2). In older children, chest pain, headache, and malaise may be present. Some patients have abdominal manifestations, such as vomiting, pain, distention, and diarrhea. Lower-lobe pneumonia is an important mimic of acute appendicitis, as fever and abdominal pain can dominate the clinical picture early in the infection.

M. tuberculosis is an important cause of pulmonary infection worldwide. Primary infection of the lung is often asymptomatic. Some patients have nonspecific constitutional symptoms, such as weight loss, cough, fever, and failure to thrive.

Symptomatic pulmonary infections with fungal organisms are uncommon in immune-competent children. Asymptomatic infections with Histoplasma capsulatum are common in endemic areas. Symptomatic lung infection with Blastomyces dermatitis can occur in children after inhalation of spores from contaminated soil, most often with relatively mild nonspecific clinical manifestations. Fungal pneumonias and infections with P. jiroveci are common in immunocompromised children.

Worldwide, there are approximately 4 million fatal pediatric acute respiratory infections each year, with most of the deaths occurring in developing countries. Pneumococcal pneumonia is the most common pathogen in these fatal pneumonias.⁴ Fatal bacterial pneumonias in children often occur as complications of other infections, such as measles or pertussis, and can occur in association with severe malnutrition. Mortality from acute respiratory infections in children is highest in the neonatal period and decreases with age.^5,6

Pathophysiology and Terminology of Lung Infections

The terminology of lower respiratory tract infection is based on the predominant site of involvement. The broad categories of clinical syndromes describing lower respiratory tract infection include tracheobronchitis, bronchiolitis, and pneumonia. Bronchiolitis and pneumonia are infections that occur in the lung proper, with involvement of bronchioles, alveoli, and/or interstitium. Additional involvement of the bronchi (bronchitis), trachea (tracheitis), and pleura (effusion, empyema) may contribute to the clinical and radiographic features of the infection. The pathophysiological manifestations of lower respiratory tract infection are determined by the interplay of several factors, including the infecting organism(s), the patient’s immune status, the patient age, the mechanism of inoculation, and coexistent lung pathology.

Bronchiolitis

Bronchiolitis is the most common lower respiratory infection in children. This consists of acute inflammation of the bronchioles, which are the small peripheral airways that lack cartilage. Bronchiolitis is nearly always caused by an acute viral infection. Respiratory syncytial virus is the most commonly isolated virus, followed by adenovirus, parainfluenza virus, influenza virus, and human metapneumovirus. S. pneumoniae is the most frequently isolated bacterium in patients with bronchiolitis, followed by Bordetella pertussis and H. influenzae type b.^7–10

The lung infection in bronchiolitis causes necrosis of the bronchiolar epithelium and destruction of ciliated epithelial cells. Lymphocytes accumulate around the bronchioles, and cell-mediated hypersensitivity to viral antigens causes release of lymphokines that produce inflammation and activate eosinophils, neutrophils, and monocytes. The submucosal layer of the bronchioles becomes edematous. Mucus, fibrin, and cellular debris within the bronchiolar lumen and edema in the wall combine to produce varying degrees of peripheral airway narrowing or complete occlusion. Air trapping commonly occurs beyond narrowed airways, while atelectasis results from greater degrees of obstruction.

Because of elevated airway resistance and diminished lung compliance in patients with bronchiolitis, there is substantial increase in the work of breathing. Gas exchange alterations occur because of atelectasis and the bronchiolar obstruction. Hypoxemia may occur as a result of ventilation–perfusion mismatch. With severe lung infection, hypercapnia may develop.

Chest radiographs of patients with bronchiolitis show diffuse hyperinflation, sometimes with superimposed subsegmental atelectasis. The walls of larger central bronchi usually appear thickened, because of bronchial wall inflammation and fluid in the interstitial tissues. Although not required for most patients with bronchiolitis, high-resolution CT more clearly documents the bronchial wall thickening. CT also shows patchy areas of diminished lung attenuation (mosaic perfusion) because of heterogeneous perfusion produced by hypoxic vasoconstriction in areas of air trapping. Centrilobular nodules and tree-in-bud opacities are often visible on high-resolution images.^11,12

Pneumonia

Pneumonia refers to infection in the alveoli, terminal airways, and peripheral interstitium. The predominant pathological characteristics of pneumonia are inflammation and infection in the terminal airways and alveoli. Pneumonia can be caused by viral, bacterial, mycoplasmal, fungal, and parasitic infections. Bacterial pneumonia most often results from inhalation of microorganisms, dispersed either in ambient air or in secretion droplets, or by aspiration of nasopharyngeal bacteria. If the infecting microorganisms survive the host defense mechanisms and reach the alveoli, neutrophils are recruited and initiate an intense cytokine-mediated inflammation. This leads to edema, hyperemia, and a fibrinopurulent exudate. The fluid-filled alveoli in the infected portion of the lung no longer have functional gas exchange. Bacterial lung infections occasionally occur because of hematogenous seeding from a nonpulmonary source (e.g., septic thromboembolism or miliary tuberculosis) or direct extension from an adjacent mediastinal, osseous, or chest wall infection.^13,14

With viral pneumonia, there is initial destruction of ciliated epithelium within the distal airway. Cellular material sloughs into the lumen. Initially, the inflammatory response is located in the interstitium, and is predominantly mononuclear. Inflammation may subsequently involve the alveoli as well.

Mycoplasma microorganisms attach to ciliated respiratory epithelial cells. The resulting infection causes local sloughing of cells. A peribronchial lymphocytic inflammatory response occurs and there is neutrophil recruitment to the airway lumen. Mycoplasma infection typically occurs as a bronchitis or bronchopneumonia.

Radiographic Patterns of Pneumonia

The diagnostic imaging features of lung infection reflect the patterns of tissue damage and host response. The 3 basic patterns of increased lung density (i.e., radiographic opacification) caused by infection are consolidation (airspace disease), interstitial densities, and mixed densities with both alveolar and interstitial involvement. Additional radiographic manifestations of acute infection include atelectasis, overaeration, and pleural effusion. The presence of alveolar consolidation, particularly with lobar involvement, is an indicator of bacterial pneumonia in children with community-acquired infections. However, interstitial opacities can occur with both viral and bacterial pneumonias. Pneumonias can be radiographically categorized as bronchiolitis, interstitial pneumonia, lobar pneumonia, and bronchopneumonia (Table 3-3).^15–17

Bronchiolitis

The dominant radiographic features of bronchiolitis are hyperinflation and prominence of interstitial markings (Figure 3-1). High-resolution CT shows small centrilobular nodules and branching lines caused by inflammation of the bronchiolar walls and exudates within the bronchiolar lumens. This is sometimes referred to as the tree-in-bud pattern. Some patients with bronchiolitis have normal chest radiographs or mild overaeration with clear lungs.

Interstitial Pneumonia

When edema and inflammatory cellular infiltrate are predominantly located in the interstitial tissue of the alveolar septa and the surrounding small airways, the infection is termed an interstitial pneumonia. Interstitial pneumonia is most frequently caused by viral or Mycoplasma infections. Chest radiographs show reticular or reticulonodular pulmonary opacities, sometimes with septal (Kerley B) lines (Figure 3-2). High-resolution CT shows areas of ground-glass attenuation. CT may also demonstrate reticular opacities, small nodules, and interlobular septal thickening. Interstitial pneumonia is frequently accompanied by bronchiolitis and bronchitis, which may alter the radiographic appearance.

Lobar Pneumonia

Lobar pneumonia (nonsegmental pneumonia) refers to nonsegmental homogeneous consolidation within a single lobe or, less commonly, multiple lobes. This type of pneumonia is characterized pathologically by the rapid accumulation of fluid in the peripheral airspaces, with only mild cellular reaction. The fluid spreads directly to adjacent alveoli, acini, and bronchopulmonary segments via the pores of Kohn and other small peripheral collateral channels.

Segmental boundaries do not impede the spread of fluid; therefore, radiographic consolidation with lobar pneumonia is nonsegmental and homogeneous (Figure 3-3). The airways often remain patent; therefore, air bronchograms are typically visible. Occasionally, the inflammatory exudate results in expansion of a lobe, resulting in a “bulging fissure” sign (Figure 3-4). The most common causative organism of lobar pneumonia is S. pneumoniae.

Bronchopneumonia

Bronchopneumonia (lobular pneumonia) is characterized radiographically by a patchy, mixed pattern of consolidation (Figure 3-5). The location of the infection is within small membranous and respiratory bronchioles; peribronchial thickening is a common radiographic finding at this stage. The infection then spreads to adjacent alveoli and there is rapid exudation of polymorphonuclear leukocytes in addition to the local accumulation of transudative fluid. Fluid accumulates in the walls and lumina of the terminal and respiratory bronchioles and adjacent alveoli, resulting in centrilobular nodular opacities on radiographs. These air space nodules are between a few and several millimeters in size. A pattern of lobular consolidation occurs when the process extends to involve an entire secondary pulmonary lobule. The consolidation tends to follow a segmental distribution, and sometimes progresses to involve an entire lobe. Airway involvement frequently leads to areas of volume loss, which can be subsegmental, segmental, or lobar. Extensive, confluent bronchopneumonia results in a radiographic appearance that overlaps that of lobar pneumonia. Bronchopneumonia can occur with various infecting microorganisms; the most common include M. pneumoniae, S. aureus, group A streptococci, and Gram-negative bacteria.

Miliary Pneumonia

A miliary pneumonia consists of multiple small discrete pulmonary lesions. The typical mechanism is hematogenous seeding of the lungs. This pattern can occur with tuberculosis, varicella, fungal infections such as histoplasmosis, and metastatic disease (e.g., thyroid carcinoma). Neonatal bacterial pneumonias sometimes have a miliary pattern.¹⁸

Sonography of Pneumonia

Pneumonic consolidation results in a solid, echogenic appearance with ultrasound. Air-filled bronchi can often be identified within the consolidated lung as echogenic foci (Figure 3-6). Occasionally, these appear as linear branching structures that converge toward the hilum. This pattern is termed the sonographic air bronchogram. Fluid-filled bronchi are demonstrated as hypoechoic tubular branching structures; this pattern is termed the sonographic fluid bronchogram. Air-filled alveoli may result in echogenic foci within consolidated lung, most often occurring during the resolution phase of pneumonia; this pattern is termed the sonographic air alveologram. A sonographic sign of volume loss in atelectatic lung is crowding of pulmonary vessels and air-filled bronchi.^19,20

High-Resolution CT

High-resolution CT provides important diagnostic information concerning suspected infections and various other lung abnormalities in children. The findings with this technique can be analyzed with a pattern approach. These patterns include consolidation; ground-glass opacity; centrilobular nodules; randomly distributed nodules; bronchiolar disease; air trapping; septal thickening; mosaic perfusion; honeycombing; parenchymal bands; architectural distortion; air-filled cysts; emphysema; the signet ring sign; the halo sign; and the crazy-paving pattern. The 3 general radiographic patterns of increased lung density are demonstrated to greater advantage by this technique than with standard radiographs: consolidation, interstitial opacification, and mixed opacification (combined airspace and interstitial disease). Interstitial lung disease is associated with five patterns on high-resolution CT: reticular, septal, nodular, reticulonodular, and ground-glass.

Consolidation

Consolidation, or airspace disease, indicates filling of the pulmonary airspaces by liquid, cells, or both. Consolidation is demonstrated on high-resolution CT as relatively homogeneous increase in pulmonary parenchymal attenuation, with obscuration of vessel margins and airway walls. Air bronchograms are common. The increased attenuation is due to alveolar filling by fluid, pus, tissue, or other material. The most common causes of consolidation in children are pneumonia, lung contusion, pulmonary edema, and pulmonary hemorrhage. Bronchopneumonia (lobular pneumonia) typically results in consolidative opacification of multiple secondary lobules, with adjacent normal parenchyma.

Ground-Glass Opacity

The ground-glass opacity pattern on high-resolution CT refers to hazy homogeneous increased attenuation of the lung, with preservation of the vascular and bronchial markings. Alveolar filling, interstitial thickening, partial alveolar collapse, or increased capillary blood volume can produce this pattern. It is important to recognize that the ground-glass opacity pattern is present in normal lung during expiration. Consequently, diffuse ground-glass opacity should only be considered abnormal if the images were obtained during full inspiration. A patchy or mosaic pattern of ground-glass opacity is usually a result of air trapping distal to abnormal small airways, with the ground-glass opacity representing normal lung.

Pathological ground-glass opacity is most often caused by infectious pneumonia. The extensive differential diagnosis includes pulmonary edema; pulmonary hemorrhage; lung contusion; acute lung transplant rejection; adult respiratory distress syndrome; leukemic infiltration; collagen vascular disease; alveolar proteinosis; extrinsic allergic alveolitis; drug toxicity (e.g., cyclophosphamide, bleomycin); sarcoidosis; idiopathic pulmonary fibrosis; and cryptogenic organizing pneumonia. The most common lung infections (usually in an immunocompromised host) associated with isolated ground-glass opacity are P. jiroveci pneumonia, Cytomegalovirus pneumonia, and various additional viral pathogens.²¹

Mosaic Pattern

The mosaic pattern refers to alternating regions of hypoattenuation and ground-glass opacity (Figure 3-7). There are 3 main pathophysiological mechanisms of the mosaic pattern. (a) Probably the most common mechanism in children is small airway disease, with the low attenuation areas on CT because of air trapping and local hypoxic vasoconstriction. Most often, the ground-glass opacities represent normal lung that empties appropriately during expiration. This is the predominant mechanism for the mosaic pattern in children with asthma, bronchiolitis obliterans, cystic fibrosis, and bronchopulmonary dysplasia. In these patients, the mosaic pattern is accentuated on (or is only visible on) images obtained during expiration (Figure 3-8). (b) The mosaic pattern can also result from infiltrative lung disease. (c) The third mechanism for the mosaic pattern is reduced vascularity in the low-attenuation regions as a result of primary vascular disease, such as pulmonary hypertension or thromboembolism.

Halo Sign

The halo sign refers to a ring of ground-glass opacity surrounding a nodule or mass. This is usually associated with hemorrhagic nodules. The halo sign may be present on high-resolution CT imaging of patients with invasive pulmonary aspergillosis, metastatic osteosarcoma, pulmonary hemorrhage, tuberculosis, lymphoproliferative disorders, and Wegener granulomatosis. In the appropriate clinical setting, the halo sign is considered early evidence of pulmonary aspergillosis even before serological tests become positive.²²

Pulmonary Nodules

Pulmonary nodules are focal, rounded opacities that represent focal expansion of the parenchymal interstitium by fibrous tissue, cellular infiltrate, or both. Important imaging characteristics of nodules are size, uniformity, distribution, and sharpness. The subclassification of small (<5 mm) nodules is based on the relationship to secondary lobular structures. Centrilobular nodules are located adjacent to, surround, or obscure the centrilobular arteries. They are usually located between 5 and 10 mm from the periphery of a pleural surface or interlobar septum. They can range from a few millimeters up to a centimeter in size. Occasionally, an air-filled centrilobular bronchiole appears as a round hypoattenuating focus within the nodule (Figure 3-9). The differential diagnosis of the centrilobular nodule pattern in children includes cystic fibrosis, bronchiectasis, infectious bronchitis, tuberculosis, dysmotile cilia syndrome, hypersensitivity pneumonitis, asthma, Langerhans cell histiocytosis, lymphocytic interstitial pneumonitis, congenital pulmonary lymphangiectasia, bronchiolitis obliterans, and pulmonary hemosiderosis.^23–25 Randomly distributed nodules may be located anywhere within the secondary pulmonary lobules, including immediately adjacent to interlobular septa and pleural surfaces (Figure 3-10). The differential diagnosis of randomly distributed small nodules includes miliary tuberculosis, fungal infection, Langerhans cell histiocytosis, and metastatic disease. There is a broad differential diagnosis of multiple large nodules (>5 mm): metastatic disease, septic emboli, histoplasmosis, tuberculosis, mycotic infections, lymphoproliferative disorders, vasculitis, Langerhans cell histiocytosis, and bronchiolitis obliterans organizing pneumonia (Figure 3-11).

The most common solid malignant tumors in children to cause nodular pulmonary metastases are Hodgkin disease, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, Wilms tumor, and neuroblastoma. The CT imaging characteristics of a pulmonary nodule can help classify the lesion as benign versus malignant. Cohen et al reported that one-third of pulmonary nodules identified on conventional radiographs in children with cancer were benign.²⁶ The differential diagnosis of 1 or more nodules in a child with a known extrapulmonary solid tumor includes metastatic disease, granuloma, infection, manifestation of chemotherapy, pseudotumor, round atelectasis, and primary benign tumor. The presence of multiple, newly developing, or enlarging pulmonary nodules has a strong correlation with malignancy. Nodules that diminish in size without antineoplastic therapy or remain stable over several months are most likely benign. A nodule that is smaller than 5 mm in diameter and has irregular margins is more likely to be benign. Nodules over 5 mm in diameter with sharp margins tend to be malignant. The presence or absence of calcification, the relation of the nodule to the bronchovascular bundle, and the location within the lung do not appear to be useful factors in the differentiation between benign and malignant nodules.^27,28

Tree-in-Bud Pattern

The tree-in-bud pattern is caused by luminal impaction of small airways (bronchioles). These are small, well-defined branching opacities. When viewed in cross-section, bronchiolar impaction may produce opacities that resemble toy jacks. The differential diagnosis of the tree-in-bud pattern on high-resolution CT includes infectious bronchiolitis, cystic fibrosis, allergic bronchopulmonary aspergillosis, immotile cilia syndrome, bronchiolitis obliterans, asthma, and tuberculosis.

Septal Thickening

The septal-thickening pattern on high-resolution CT refers to abnormal widening of 1 or more interlobular septa (the tissue between secondary pulmonary lobules). In the peripheral aspect of the lung, this appears as fine, linear, pleural-based opacities perpendicular to the pleural surface. In the central aspect of the lung, septal thickening produces a polygonal pattern of linear opacities. The most common cause of interlobular septal thickening is interstitial edema. Other entities in the differential diagnosis include pulmonary lymphangiectasia, bronchopulmonary dysplasia, pneumonia, collagen vascular disease, neoplasm, alveolar proteinosis, and pulmonary fibrosis.

Crazy-Paving Pattern

The crazy-paving pattern refers to thickened interlobular septa in a background of ground-glass opacification (Figure 3-12). This is the classic appearance of alveolar proteinosis. This pattern can also occur with acute respiratory distress syndrome, acute interstitial pneumonia, and lipoid pneumonia.^29,30

Air Trapping

Air trapping refers to abnormal retention of air in all or part of the lung during expiration. Air trapping can involve both lungs, 1 lung, or any subdivision of the lung. CT imaging during expiration may be required to demonstrate its presence. When only portions of the lung are involved, air trapping produces a mosaic pattern on expiration imaging. Air trapping is most often caused by partial airway obstruction, but can also be caused by abnormalities of pulmonary compliance. The most common pediatric lung abnormalities associated with air trapping are bronchiolitis, cystic fibrosis, asthma, bronchiectasis, and bronchiolitis obliterans. Unilateral or lobar air trapping is an important imaging feature of an airway foreign body.

Honeycomb Pattern

The honeycomb pattern on CT refers to multiple clustered cystic airspaces with walls that measure 1 to 3 mm in thickness. The cysts are predominantly located in the peripheral aspect of the lungs, and may occupy contiguous layers. The air-filled cysts do not empty during expiration. Honeycombing indicates destroyed, fibrotic, and cystic lung. The honeycomb pattern can occur with desquamative interstitial pneumonitis, nonspecific interstitial pneumonitis, end-stage pulmonary fibrosis, lupus, Langerhans cell histiocytosis, and scleroderma.^31–34

Air-Filled Cystic Lung Lesions

Air-filled cystic lung lesions include pneumatoceles, bullae, and lung cysts. Pneumatoceles occur as a result of pneumonia, trauma, or hydrocarbon ingestion. Other air-filled cystic lung lesions include congenital cysts, Langerhans cell histiocytosis, septic emboli, papillomatosis, Wegener granulomatosis, barotrauma-related pseudocyst, and Williams-Campbell syndrome.

Signet Ring Sign

The signet ring sign indicates an air-filled ring-shaped opacity (an enlarged, thick-walled bronchus) abutting a round soft-tissue attenuation opacity (an adjacent pulmonary artery) (Figure 3-13). This finding indicates the presence of bronchiectasis, and occurs when the CT image is perpendicular to the abnormal bronchus.

Bronchiectasis

The features of bronchiectasis on high-resolution CT include the internal diameter of a bronchus being larger than the diameter of the adjacent pulmonary artery branch, a lack of normal tapering of the bronchus, and a thickened bronchial wall. Abnormal visualization of a bronchus in the lung periphery (within 1 to 2 cm of the pleura) is an additional sign of bronchiectasis. There are 3 types of bronchiectasis. Cylindrical bronchiectasis refers to a lack of normal bronchial tapering. The severity of bronchial dilation is usually mild with this form of bronchiectasis. The bronchial walls are smooth or only mildly irregular (Figure 3-14). Abrupt termination is often present distally. With varicose bronchiectasis, dilated bronchi that are parallel to the imaging plane have a beaded appearance (Figures 3-15 and 3-16). There are often bulbous terminations of the involved bronchi. Cystic bronchiectasis has a cystic or saccular configuration (Figure 3-17).³⁵

Retained secretions within bronchiectatic airways sometimes cause air–fluid levels or nodular opacities. A secretion-filled bronchus may appear as a linear or branching structure when it courses parallel to the imaging plane. In small peripheral bronchi, retained secretions may produce the centrilobular nodule or tree-in-bud pattern. The most common etiology of widespread bronchiectasis in pediatric patients is cystic fibrosis. Other associated conditions include immotile cilia syndrome, pneumonia, tuberculosis, and hypogammaglobulinemia. Imaging of patients with pulmonary fibrosis (usually postinfectious) may demonstrate traction bronchiectasis; that is, enlargement of an airway because of mechanical traction from adjacent parenchymal disease.

Streptococcus pneumoniae

Lung infection with S. pneumoniae is termed pneumococcal pneumonia (Figure 3-18). This organism is the most common cause of bacterial pneumonia in children. The peak seasonal incidence of pneumococcal pneumonia is in late winter and early spring. Although this infection can occur in individuals of any age, the greatest prevalence in pediatric patients is during the first 4 years of life. Asymptomatic carriers of pathogenic types of S. pneumoniae may play an important role in dissemination of this organism. The incidence of invasive pneumococcal disease in children in the developing world is several times higher than in industrialized countries. Developing countries account for most of the greater than 1 million children worldwide who die of invasive pneumococcal disease (pneumonia, meningitis, and febrile bacteremia) every year. The emergence of drug-resistant pneumococcal strains among infants and young children has complicated the management of pneumococcal pneumonia.^36–40

The clinical manifestations of pneumococcal pneumonia vary somewhat with age. In infants, there is frequently a prodromal illness of several days duration, with the clinical characteristics of a mild upper respiratory tract infection. This ends with the abrupt onset of high fever and respiratory distress. Cough is usually not a prominent feature of this illness, but may develop later in the course. Tachypnea, tachycardia, and sternal retractions occur in some children. Approximately 30% of infants with pneumococcal pneumonia are bacteremic.

In older children and teenagers, the clinical onset of pneumococcal pneumonia often follows a brief illness that has the characteristics of a mild upper respiratory tract infection. High fever, shaking chills, and tachypnea herald the onset of the more severe illness. The cough that occurs in patients with pneumococcal pneumonia is typically nonproductive. Laboratory evaluation demonstrates leukocytosis.

Most individuals who contract pneumococcal pneumonia are otherwise healthy. However, there is an increased occurrence of this infection in children with various underlying medical conditions. The incidence of pneumococcal pneumonia is at least 50 times greater in children with sickle cell disease than in hematologically normal black children; this is a result of functional hyposplenism and a deficiency of properdin. Other predisposing conditions to pneumococcal pneumonia include severe chronic liver disease, renal failure, insulin-dependent diabetes, immunosuppressive disorders, and hyposplenism. The elevated risk in patients with known predisposing conditions is partially mitigated by penicillin prophylaxis and the use of pneumococcal vaccines.^41–43

S. pneumoniae is a Gram-positive diplococcus. The presence of a polysaccharide capsule provides this organism with resistance to phagocytosis and thereby facilitates infection of the lung. Approximately 90 capsular types have been identified, some of which are frequently associated with clinical disease and others only rarely. The precipitating event is inhalation of an inoculum, which usually lodges in the periphery of the lung. The initial infection elicits an inflammatory exudate that fills the alveolus and then extends peripherally through the interalveolar communications (the pores of Kohn and the canals of Lambert). This centrifugal spread results in a spherical character of the enlarging area of consolidation on chest radiographs. Segmental boundaries do not confine the spreading infection. The exudate is predominantly located within the alveoli. Most adjacent bronchi remain aerated; therefore, air bronchograms are usually present on radiographs.

Because the inoculum frequently lodges in the peripheral aspect of the lung, the resultant consolidation often abuts a pleural surface. If the infection is located more centrally, the consolidation is spherical; this is termed a round pneumonia (Figure 3-19). Pneumococcal pneumonia is the most common cause of the radiographic round pneumonia pattern. When a spherical consolidation caused by pneumococcal pneumonia has sharp margins and lacks air bronchograms, the possibility of a mass such as a bronchogenic cyst or lung abscess needs to be considered (Figure 3-20). Most often, followup radiographs are adequate to confirm clearing of the lesion; alternatively, CT can be used for further characterization.⁴⁴

Parenchymal lung consolidation in patients with pneumococcal pneumonia can progress to involve the entire lobe; this is more common in older children than in infants. Because the primary pathological process consists of filling of alveoli with inflammatory exudate, there are usually no radiographic signs of substantial volume loss. In some patients, displacement of an adjacent fissure indicates expansion of the consolidated lobe. Atelectasis sometimes occurs during the resolution phase, likely related to extension of exudate into the airways. With proper medical treatment, uncomplicated pneumococcal pneumonia typically undergoes substantial radiographic improvement within several days.

Potential complications of pneumococcal pneumonia include parapneumonic pleural effusion, empyema, pneumatocele (usually developing early during the resolution phase), and lung abscess. Pneumococcal pneumonia is the most common cause of parapneumonic effusion in children, in part because this is such a common infection.⁴⁵

Staphylococcus aureus

Pneumonia caused by S. aureus is often a serious and aggressive infection. Complications such as pneumatoceles, pneumothorax, and parapneumonic effusion are common. Staphylococcal pneumonia is more common in infants than in older children, with approximately 70% of these infections occurring in children younger than 1 year of age. Staphylococcal pneumonia in older children often occurs as a superinfection in a debilitated patient. The prevalence of staphylococcal pneumonia is increased during the winter months.

As with many bacterial pneumonias, symptoms of a mild respiratory tract infection often precede the clinical onset of staphylococcal pneumonia. These mild symptoms abruptly give way to respiratory distress, cough, and high fever. A rapid progression of clinical symptoms is a characteristic of staphylococcal pneumonia. Marked dyspnea and shock can occur in severely affected patients.

Staphylococcal pneumonia is most often caused by inhalation or aspiration of bacteria. Hematogenous inoculation of the lung is also common with this organism, particularly in older children. Staphylococcus is among the more common bacteria to be associated with pulmonary septic emboli. When imaging studies show multiple focal areas of consolidation, with or without cavitation, consideration should be given to a possible distant source of infection. Septic emboli frequently have a fluffy character on radiographs, and may increase rapidly in number and size.

Staphylococcal pneumonia typically begins in the airways, rather than in the alveoli. Initially, consolidation of peribronchiolar acinar units occurs in a segmental distribution, resulting in a radiographic bronchopneumonia pattern. The consolidative process may be rapidly progressive, and cause extensive areas of hemorrhagic necrosis and irregular areas of cavitation. Septic thrombosis of pulmonary veins can occur within areas of consolidation.

A parapneumonic effusion accompanies approximately 90% of staphylococcal pneumonias. This can rapidly expand to a size that requires tube thoracostomy drainage (Figure 3-21). A frank empyema can also occur with this infection. Rarely, spread of infection into the chest wall (empyema necessitatis) produces a soft-tissue abscess or osteomyelitis.

Potential intrapulmonary complications of S. aureus pneumonia include pneumatocele and lung abscess. A lung abscess appears on imaging studies as a round mass or thick-walled cavity. It contains fluid and debris. Gas is often present. An upright or decubitus view may show an air–fluid level. An abscess is best detected and characterized with contrast-enhanced CT. Rupture of a subpleural abscess can produce a pyopneumothorax. Erosion into a bronchus can lead to an expanding air-filled abscess cavity or a bronchopleural fistula.⁴⁶

Forty percent to 60% of patients with staphylococcal pneumonia develop pneumatoceles (Figure 3-22). They most often appear during the first week of the infection, and disappear spontaneously over the subsequent weeks or months (Figure 3-23). A pneumatocele is an area of overexpanded lung that is a consequence of partial obstruction a small airway by intraluminal exudate or a peribronchial abscess. A pneumatocele can also result from necrosis of the wall of a peripheral airway, allowing air to dissect into the interstitium. Most often, multiple pneumatoceles of varying size are present. A pneumatocele is differentiated radiographically from a primary lung abscess by its thin wall and predominantly air-filled lumen (Figure 3-24). Fluid levels can be present in pneumatoceles, however. A pneumatocele with a persistent air–fluid level on serial radiographs is likely infected and is therefore functionally an abscess. Rupture of a pneumatocele can produce a pneumothorax or bronchopleural fistula.

Streptococcal Pneumonia

In addition to S. pneumoniae (see “Streptococcus pneumoniae” above), other streptococcal species can also cause pneumonia. These infections most frequently occur as a complication of an antecedent viral or chronic illness. Group B β-hemolytic Streptococcus is the most common infectious agent in neonatal bacterial pneumonias.

S. pyogenes (group A Streptococcus) most often causes infections of the upper respiratory tract; that is, pharyngitis and tonsillitis. Infection of the lung with this organism occasionally occurs in healthy children, but more often is a superinfection that complicates a viral infection such as rubeola or influenza. If a viral illness precedes the pneumonia, an increasing severity of the clinical symptoms heralds the onset of the bacterial infection. The radiographic evaluation of these children sometimes demonstrates a more severe infection than the clinical features suggest. The imaging appearance is often similar to that of staphylococcal pneumonia (Figure 3-25).

S. pyogenes infections of the lower respiratory tract can occur as a tracheitis, bronchitis, bronchopneumonia, interstitial pneumonia, or any combination of these patterns. Lobar pneumonia is uncommon. Most often, the infection progresses from the trachea distally in the bronchial tree. Consequently, radiographs typically show a bronchopneumonia pattern in a segmental distribution. The consolidation may be either homogeneous or patchy. Atelectasis is common. Extension into the interalveolar septi can lead to lymphatic involvement. Subsequent dissemination through the lymphatics can result in mediastinal and hilar lymphadenopathy, as well as pleural effusions. Lymphatic distention and interstitial edema can produce interstitial densities on radiographs. Approximately 20% of children with pneumonia caused by S. pyogenes develop a parapneumonic effusion. Pneumatoceles or lung abscesses can occur. Bronchiectasis is a potential late complication.

Group B β-hemolytic Streptococcus can cause a fulminant pulmonary infection in neonates. The clinical onset is often during the first few days of life, with progressive respiratory failure and circulatory collapse. The clinical and radiographic findings are sometimes nearly indistinguishable from those of severe respiratory distress syndrome. However, group B streptococcal septicemia is typically associated with more severe systemic symptoms and a more rapid clinical progression.

Chest radiographs of the neonate with group B streptococcal pneumonia typically show rapidly progressive extensive consolidation. The most common pattern consists of widespread fluffy nodular opacities and air bronchograms.

Term infants may have lobar or segmental consolidation, rather than the diffuse pattern that is typical of streptococcal pneumonia in premature neonates. The consolidation is sometimes unilateral. The typical findings of hyperinflation and pleural effusion in group B streptococcal pneumonia help to radiographically differentiate this condition from respiratory distress syndrome.

Haemophilus influenzae Pneumonia

H. influenzae type B is a virulent pathogen that can cause bronchopneumonia, bronchitis, epiglottitis, pharyngitis, otitis media, and meningitis in infants and children. There are also nonencapsulated forms of H. influenzae that are commonly associated with upper respiratory tract infections, but only rarely cause pneumonia. The widespread use of a vaccine against H. influenzae type B has markedly decreased the incidence of infections caused by this agent. Pneumonia caused by H. influenzae type B most often occurs in children younger than 5 years of age. There is an increased risk of this infection in children with sickle cell disease, immunocompromise, or malignancy. Most pneumonias caused by H. influenzae occur during the winter and spring.

The symptoms of H. influenzae pneumonia tend to have an insidious onset. The associated cough is nonproductive. Pyrexia, tachypnea, and retractions may be noted. Infants with this form of pneumonia are particularly susceptible to complications such as bacteremia, pericarditis, pleuritis, empyema, septic arthritis, and meningitis. Meningitis occurs in approximately 15% of young children and infants with H. influenzae pneumonia.

H. influenzae infection typically produces a bronchopneumonia pattern on radiographs (Figure 3-26). The patchy mixed airspace consolidation is usually lobar or segmental in distribution. Initial interstitial opacification progresses to airspace consolidation. A round pneumonia pattern is rare with this infection. Pleural effusion occurs in approximately 90% of patients with H. influenzae pneumonia, but it is often small. Enlargement of the cardiac silhouette on chest radiographs indicates the possibility of superimposed pericarditis.

Klebsiella pneumoniae

K. pneumoniae is an encapsulated Gram-negative rod that is a member of the Enterobacteriaceae family. Lung infection caused by K. pneumoniae is unusual in otherwise healthy patients; most pneumonias caused by this organism occur in individuals with chronic bronchopulmonary disease, diabetes mellitus, debilitation, or immunosuppression. It can be a secondary invading organism in patients with tuberculosis or influenza. K. pneumoniae is a relatively common isolate in hospital-acquired (nosocomial) pneumonias in children, usually occurring in association with an underlying chronic illness or serious acute event (e.g., intubation, burn, surgery). Primary Klebsiella pneumonia can occur in epidemics in nurseries, although most of the culture-positive infants in these situations are asymptomatic. K. pneumoniae resides in the respiratory and gastrointestinal tracts of approximately 5% of normal individuals.^47–50

The clinical presentation of Klebsiella pneumonia is usually nonspecific. As with other bacterial pneumonias, there is often an abrupt onset of symptoms. Pyrexia is usually of moderate severity. Cough is nearly always productive with this infection. The sputum may be purulent, greenish, and blood streaked. “Currant jelly sputum” has been described in these patients, with a dark-red gelatinous appearance. The presentation of Klebsiella pneumonia sometimes mimics that of pulmonary reactivation tuberculosis: hemoptysis in combination with cavitating lesions on radiographs. Neonates with primary Klebsiella infection often present with diarrhea and vomiting that progresses to an abrupt onset of respiratory difficulty.^51,52

Lung infection with K. pneumoniae produces an acute airspace pneumonia. Radiographs show homogeneous lobar consolidation and air bronchograms. A characteristic feature of Klebsiella pneumonia is lobar expansion as a result of the voluminous inflammatory exudates, with bulging of the interlobar fissures. Similar findings, however, occur in many patients with pneumococcal pneumonia. Although lobar pneumonia is the most common pattern with Klebsiella infection, some patients have a bronchopneumonia pattern, with patchy bilateral or unilateral nonsegmental airspace consolidation. Cavitation, lung abscess, parapneumonic effusion, and empyema are also common with this aggressive infection. CT of these patients may show manifestations of a necrotizing pneumonia, with enhancing homogeneous areas of inflamed lung occurring in conjunction with poorly marginated low-attenuation areas of deficient enhancement that contain multiple small cavities.^53–56

Pertussis Pneumonia

Pertussis, or whooping cough, is a clinical syndrome caused by pulmonary infection with B. pertussis. Pertussis is one of the most contagious diseases known, with attack rates of nearly 100% in susceptible populations. Pertussis is a serious illness that can be fatal. Life-threatening pertussis pneumonia most often occurs in premature infants or unvaccinated infants. Many patients with pertussis have serological evidence of concurrent infection with respiratory viruses or M. pneumoniae. Widespread immunization has markedly reduced the prevalence and severity of pertussis, but immunity is neither complete nor permanent. Worldwide, pertussis occurs in tens of millions of people each year and results in hundreds of thousands of deaths.^57–59

Children with B. pertussis pneumonia usually have a prolonged course of moderate to severe coughing spasms. Infants may have pronounced feeding difficulties. The most specific clinical indicator of B. pertussis pneumonia is a cough of at least a few weeks duration that has a whooping character. Vomiting may also occur. Most patients experience an initial catarrhal stage of 1 to 2 weeks’ duration, during which the symptoms mimic those of a minor upper respiratory viral illness. The paroxysmal stage lasts for 2 to 4 weeks, and is characterized by an increase in the frequency and severity of the cough. The characteristic whoop at the end of a coughing paroxysm is caused by the sudden inrush of inspired air through the edematous narrowed glottis.^60,61

The radiographic appearance of pertussis pneumonia most often consists of moderate to severe hyperinflation and bilateral parahilar interstitial densities. Segmental or subsegmental patches of atelectasis or consolidation are common. These factors combine to produce a “shaggy heart” pattern that is characteristic of pertussis pneumonia (Figure 3-27). However, not all children with pertussis pneumonia have this radiographic pattern, and infections with other pathogens, such as Chlamydia and adenovirus, can produce an identical appearance. Hilar lymphadenopathy is radiographically visible in approximately one-third of children with pertussis pneumonia. Although atelectasis is common with uncomplicated pertussis, the presence of lobar consolidation suggests a secondary bacterial infection.

Considerable radiographic improvement should occur within 2 weeks of the beginning of the convalescent stage of pertussis. Stringy central lung opacities may persist for 1 month or longer, although the patient is usually asymptomatic at this time. Bronchiectasis is a potential long-term complication of pertussis pneumonia, usually occurring in association with severe or inadequately treated acute phases on the illness. B. pertussis pneumonia during childhood can lead to reduced ventilatory function as an adult.⁴

Chlamydia

Chlamydia infection can produce pneumonia in infants and young children. In older children and teenagers, infection with this organism is associated with either bronchitis or pneumonia. Chlamydia is an obligate intracellular bacterium that is unable to independently generate adenosine triphosphate. Chlamydia trachomatis is an important cause of transnatally acquired infections of neonates, resulting in conjunctivitis and/or pneumonia. Chlamydophila pneumoniae (previously termed Chlamydia pneumoniae) is an obligate intracellular bacterial pathogen that is distinct from the other species of Chlamydia. This organism is a common cause of atypical pneumonia. Approximately 90% of infections with C. pneumoniae are mild or asymptomatic. In children, teenagers are most commonly affected. Transmission occurs via respiratory droplets. Chlamydia respiratory infection can occur in association with acute chest syndrome in sickle cell disease patients, serve as an infectious trigger for asthma, or cause pulmonary exacerbations in cystic fibrosis patients. Approximately 20% of older children with Chlamydia respiratory infections have concomitant M. pneumoniae infections.^62,63

Pneumonia caused by C. pneumoniae is usually associated with clinical manifestations of mild severity, including fever, headache, cough, and manifestations of pharyngitis. There are nonspecific findings on physical examination, such as rales and wheezing. Chest radiographs often show one or more focal areas of patchy mixed airspace consolidation. Some patients have an interstitial pattern. Hilar lymphadenopathy is common. The radiographic findings often are more pronounced than the clinical manifestations would suggest. A specific diagnosis of C. pneumoniae infection can be achieved with serological studies or isolation of the organism in tissue culture.