The first important determinant in creating a differential diagnosis is establishing if the disease process has involved the same location or different areas of the lung (Table 35–2). In actual practice, this division depends on both a cogent historian and the availability of radiographic data.
Pathology affecting a single region can be related to obstruction of the airway lumen that subtends the area by intraluminal obstruction or compression, intrinsic narrowing of the airway, or an abnormality of the involved parenchyma. Causes of intraluminal obstruction include such entities as foreign body, tumor, or mucous plug. Compression of the airway is seen with lymphadenopathy from various causes, including infection—such as tuberculosis, histoplasmosis, and other mycotic infections—and from noninfectious causes, including sarcoidosis and neoplasms. Additionally, external compression can arise from an abnormality of the vasculature, such as a vascular ring, or from mediastinal tumors or duplication cysts.
Structural airway abnormalities that cause retention of secretions can result in chronic or recurrent infection.10 These include anomalies of airway configuration, such as a tracheal bronchus, which is a right upper lobe bronchus that emanates from the trachea, rather than from the right main bronchus. When its orifice is smaller than normal or the airway takes off from the trachea at an acute angle, the airway is prone to obstruction from secretions. Similarly, a “bridging bronchus,” a right lower lobe bronchus that arises from the left bronchial tree, can impair proper drainage. Localized bronchial stricture or stenosis occurs most commonly in a main or middle lobe bronchus,11 but these lesions can also occur in the distal trachea; especially when acquired as a result of airway intubation and suctioning.12–14 Bronchial atresia may be asymptomatic, or can result in lobar degeneration distal to the obstruction, leaving a mucus-filled or fluid-filled cystic structure in its place, which can then become infected. Bronchomalacia, or excessive collapsibility of the airway wall, predisposes to retained secretions. Localized bronchiectasis may be congenital, which is rare, or be a result of chronic localized infection or a prior viral illness.15
Right middle lobe syndrome is an entity described in both the pediatric and adult literature in which a recurrent radiographic density associated with respiratory symptoms occurs in the right middle lobe region (Figure 35–1). It requires special mention, because of the unique nature of the anatomy of the right middle lobe. The normal anatomy of the right middle lobe—the airway's acute angular take off from the bronchus intermedius, narrower caliber, and longer distance without branching, as well as the lack of collateral ventilation to the lobe itself—predisposes to difficulties with airway clearance and retained secretions. Asthma is the most common underlying disorder associated with the right middle lobe syndrome. Bronchoscopic findings in 52 of 55 children with middle lobe syndrome included airway mucosal edema, retained secretions, and mucus plugging, rather than complete obstruction. Additionally, more than half of these patients had elevated eosinophils in lavage fluid.16,17
(A) Posterior–anterior and (B) lateral radiographs of a 7-year-old girl with asthma and right middle lobe syndrome. There is a density in the right middle lobe that improved following aggressive management of asthma. Subsequent bronchoscopy demonstrated normal anatomy, and bronchoalveolar lavage yielded elevated numbers of eosinophils.
Congenital lung malformations become infected as a result of either abnormalities in the airways leading to them, or compromised blood flow to them. Bronchogenic cysts, which result from aberrant budding of the tracheobronchial tree during development, are often located centrally and on the right. These unilocular structures do not communicate with the airway, although they may carry their own blood supply. They can become infected, or they may cause symptoms by compressing adjacent airways and impeding airway clearance. Bronchogenic cysts will appear radiodense initially, but become lucent when infected.18 Congenital cystic adenomatoid malformations (CCAM) are lesions in which varying degrees of cystic and glandular structures replace normal alveolar tissue. A CCAM usually involves a single lobe, unlike bronchogenic cysts, CCAMs communicate with the tracheobronchial tree. On radiographs, CCAMs appear as uni- or multiloculated lucent or dense structures. Pulmonary sequestrations are masses of lung parenchyma usually without connection to the tracheobronchial tree, but with a defined systemic blood supply, usually arising from the aorta. Sequestrations can be intralobar (invested in the pleura of normal lung) or, less commonly, extralobar (covered with their own pleura). Intralobar sequestrations are found most commonly in the left lower lobe and most often present as recurrent pneumonia. Radiographic appearance is initially radiodense, but, with infection, the degree of lucency can increase.
Recurrent pneumonia involving different locations often is associated with a systemic disease process. Aspiration has been described in several case studies as the most common cause of recurrent pneumonia.5,6 Recurrent pneumonia from aspiration itself can also be associated with several other conditions. Impaired swallowing with inadequate airway protection can result from a variety of neuromuscular disorders, including cranial nerve injury, cerebral palsy, and muscular dystrophy. Anatomic abnormalities of the larynx including vocal cord paralysis or laryngeal cleft compromise airway protection. Esophageal obstruction, from foreign body, foregut malformation, or vascular ring may impair the normal swallow and worsen reflux of gastric contents. Similarly, esophageal dysmotility, from achalasia or tracheoesophageal fistula, also predisposes to aspiration19 (Figure 35–2).
Anterior–posterior chest radiographs of a child with repaired tracheoesophageal fistula, and history of recurrent aspiration. (A) Right middle lobe density at 17 months; (B) right middle and left lower lobe densities at 30 months. Interval radiographs demonstrated clearing of the lesions.
Asthma is one of the most common causes of recurrent pneumonia. Undertreated asthma is associated with airway inflammation, increased mucus production, and luminal narrowing from airway wall edema. Whether radiographic densities seen during acute exacerbations represent true areas of infection or atelectasis is often uncertain. Recent data using sensitive detection techniques, however, suggest that acute viral infections account for as much as 85% of asthma exacerbations in school-aged children.20
Malfunction or deficiency in any component of the immune system, adaptive or innate, often leads to recurrent pulmonary infections. It is extremely unlikely, however, for a child to have recurrent pneumonia from an immunodeficiency without also having a history of recurrent otitis or sinusitis, and chronic purulent rhinitis. A clear way to classify these defects is into disorders of phagocyte function, B cell function, and T cell function. The most common example of phagocyte dysfunction in children with recurrent pulmonary disease is chronic granulomatous disease (CGD). Children with CGD, with an incidence of 1 in 20,000, experience severe pneumonia and abscesses. Most often, infections are caused by catalase positive organisms like Staphylococcus aureus, Aspergillus spp., Burkholderia cepacia, Nocardia spp., and Serratia spp. These infections occur as a result of a loss of NADPH oxidative function. Hyper IgE, or Job, syndrome is associated with severe pneumonia, often resulting in pneumatocele formation, eczema, and coarse facial features. The immune defect in hyper IgE syndrome is unclear, but has been hypothesized to relate to neutrophil dysfunction.21
Defects in B cells result in problems with formation of antibodies, which are essential for opsonization and clearance of encapsulated organisms, such as Streptococcus pneumoniae and Haemophilus influenzae. These defects often present in late infancy, after maternal IgG is cleared. X-linked, or Bruton's, agammaglobulinemia, presents with recurrent pneumonias as well as Pneumocystis carinii (now P. jirovecii) infection. Common variable immune deficiency (CVID), in which there are varying low levels of immune globulins, especially gamma globulin, does not present with opportunistic pathogens, but with recurrent bacterial infections of the sinuses or lungs. If not diagnosed in childhood, individuals with CVID often develop bronchiectasis as adults.22 IgG subclass deficiencies also can present with recurrent pneumonia. Most is known about IgG2 deficiency, which often presents as asthma. The most common immune globulin defect is IgA deficiency, with an incidence of 1/400–3000. IgA deficiency often coexists with an IgG subclass deficiency. A recent study, however, found that although 50% of a population of IgA-deficient patients presenting to an immunology clinic for evaluation had recurrent respiratory infections, they were not more likely to have an associated IgG2 subclass deficiency or poor responses to the pneumococcal vaccine.23
T cells have populations of antigen-presenting or helper cells as well as killer cells. T cells are responsible for the orchestration of the adaptive immune system, as well as direct elimination of viruses and fungi. Severe combined immune deficiency, in which both T cell and B cell function is severely reduced or absent, presents early in infancy. 67% of patients with severe combined immune deficiency have pulmonary disease at diagnosis and are susceptible throughout life to opportunistic pathogens. Other T cell deficiencies can present more subtly. Children with DiGeorge syndrome, associated with 22q11 microdeletion, absent 3rd and 4th pharyngeal pouches, thymic aplasia to hypoplasia, and hypoparathyroidism have a range of immune defects, most commonly pneumonia caused by Gram-negative bacteria and severe respiratory syncytial virus infection. Those with absence of the thymus have more severe defects and are at risk for pneumocystis infections. Several conditions present with subtle and combined immune problems, relating to interaction between T and B lymphocytes. Wiskott Aldrich syndrome is an X-linked recessive condition with thrombocytopenia, eczema, and recurrent bacterial infection. Immune defects include lymphopenia and a decreased response to polysaccharide antigens.24 Ataxia-telangiectasia is a progressive neurologic disorder associated with varying degrees of immune deficiency and recurrent pulmonary involvement.25
A local defense mechanism that is critical for clearing the airways of inhaled debris and infecting organisms is the mucociliary escalator. Dysfunction of the mucociliary clearance system occurs in both cystic fibrosis and primary ciliary dyskinesia. In cystic fibrosis, the airway surface liquid is depleted, resulting in increased mucous viscosity and an inability of the cilia to clear airway secretions effectively. Because of the increased mucus viscosity, cough becomes ineffective at clearing secretions. In contrast, primary ciliary dyskinesia affects only the beating action of the cilia, and the mucus itself is normal; cough is effective in this case. In both conditions, however, mucus stasis results in recurrent infections and ultimately leads to bronchiectasis.
Diffuse processes such as hypersensitivity pneumonitis, allergic bronchopulmonary aspergillosis, or eosinophilic pneumonia represent abnormal immunological responses. While these entities do not cause pneumonia per se, recurrent radiographic densities are prominent features in each. Similarly, children with recurrent pulmonary hemorrhage or sickle cell disease can develop diffuse densities and respiratory symptoms with varying degrees of clearing. It is occasionally difficult to distinguish pneumonia in children with sickle cell disease from acute infarction.