Bronchiectasis refers to irreversible dilation of the bronchi or bronchioles. The airway enlargement is a result of weakening of the bronchial walls in response to chronic inflammation. Impairment of the mucus transport mechanism contributes to the formation of exudative filling of the dilated bronchus. Bacterial colonization of the abnormal bronchus leads to progressive damage.

Three forms of bronchiectasis are recognized. The cylindrical type consists of diffuse dilation of the involved bronchus (Figure 4-1). With the varicose form, the dilated bronchus has a beaded configuration. Bronchiectasis is saccular if there are bronchial cysts that are at least 1 cm in diameter.

Radiographs and CT show bronchiectasis as airfilled dilated tubular structures, usually with thickened irregular walls. When viewed on end, the dilated bronchus appears as a ring that is larger than the accompanying pulmonary artery, producing the “signet ring sign” (Figure 4-2). When filled with fluid or mucous, the dilated bronchi may appear as linear soft-tissue density structures that are branching or finger-like. When viewed on end, they appear nodular.

Cystic fibrosis is the most common cause of bronchiectasis. Other etiologies include dysmotile cilia syndrome, allergic bronchopulmonary aspergillosis in asthma patients, chronic infection, and immunodeficiency (Table 4-1).¹

Bronchiolitis obliterans (obliterative bronchiolitis) refers to fibrous obliteration of the small airways. The fibrosis is caused by the repair process that occurs following inflammation and damage to the bronchiolar epithelium. Potential causes of bronchiolitis obliterans include lung infection (particularly adenovirus pneumonia), chronic graft-versus-host disease in transplantation patients, Stevens-Johnson syndrome, drug reactions, connective tissue disease, and toxic gas inhalation. The most common cause of bronchiolitis in children who have not undergone transplantation is adenovirus pneumonia. Unilateral bronchiolitis obliterans caused by bronchiolitis in infancy is termed Swyer-James syndrome.^2,3

Standard chest radiographs of patients with bronchiolitis obliterans may show hyperinflation, attenuated peripheral pulmonary vascular markings, and nodular or reticulonodular opacities. However, chest radiographs are sometimes normal despite symptomatic disease. High-resolution CT typically demonstrates centrilobular branching structures and centrilobular nodules caused by thickening of the bronchial walls. Indirect signs that are sometimes present on CT include central bronchial dilation, air trapping, and mosaic attenuation (geographic hyperlucency; Figure 4-3).^4,5

Bronchiolitis obliterans organizing pneumonia (BOOP), also termed cryptogenic organizing pneumonia or proliferative bronchiolitis, is characterized by the deposition of granulation tissue within small airways and the presence of areas of organizing pneumonia. The granulation tissue is predominantly located in the bronchioles, alveolar ducts, and alveoli. BOOP is a nonspecific response to various types of lung injury. The most common iatrogenic cause is bone marrow transplantation; the onset is typically 2 to 3 months after transplantation. Other causative conditions include pneumonia, drug reactions, vascular disease, and radiation therapy. In many patients, however, the process is idiopathic. The clinical features include dry cough, dyspnea, and low-grade fever.

Standard radiographs and CT of patients with BOOP show patchy areas of airspace consolidation and/or nodules (Figures 4-4 and 4-5). Pathologically, the nodules and the consolidation represent different degrees of inflammation in bronchioles, alveolar ducts, and alveoli. A predominantly subpleural distribution of the airspace consolidation occurs in some patients. High-resolution CT shows ground-glass opacities. Mild bronchial and bronchiolar dilation sometimes occurs. Occasionally, there are small pleural effusions. An additional potential CT pattern consists of crescentic and ring-shaped opacities (granulomatous tissue) surrounding areas of ground-glass attenuation (alveolar septal inflammation).⁶ Differentiation from idiopathic pulmonary fibrosis is achieved by noting the absence of parenchymal distortion and fibrosis.^4,7

Follicular bronchiolitis, or follicular hyperplasia of bronchial-associated lymphoid tissue, is a rare idiopathic chronic bronchiolitis. Hyperplastic aggregates of lymphoid tissue are present in the subepithelial tissues at the bronchial bifurcations and along distal bronchi and bronchioles. The most common associated conditions are collagen vascular diseases and immunodeficiency syndromes. The usual clinical presentations are exertional dyspnea or recurrent pneumonia. High-resolution CT often demonstrates peripheral small centrilobular nodules. Other potential CT findings include ground-glass opacities, bronchiectasis, bronchiolectasis, and branching opacities. A normal CT does not exclude the diagnosis, however. Biopsy is required for a definitive diagnosis.^8–11

Nonasthmatic allergic lung disease represents an allergic response of the lung to an antigenic substance. A variety of environmental substances and medications can result in a non–immunoglobulin (Ig) E-mediated allergic pneumonitis. Categorization of the resultant allergic pulmonary diseases is based on the physiological features, mechanism of tissue damage, and/or nature of the etiological agent. An important goal in the clinical and diagnostic imaging evaluations of these children is to differentiate nonasthmatic allergic pulmonary disease from asthma.

An allergic response of the lung to an antigenic substance can occur at any age. In infants, the clinical and radiographic manifestations are typically similar to those of bronchiolitis. In the older child, the findings often mimic asthma or pneumonia. Hyperinflation is the predominant radiographic finding in patients with allergic lung disease. The diaphragm is flattened and the anteroposterior diameter of the chest is prominent. Subsegmental atelectasis is common. Manifestations of an interstitial pneumonia may accompany acute allergic episodes, with bilateral interstitial parenchymal opacities.

Milk allergy is a potential cause of recurrent or chronic allergic pneumonitis in the young infant. Serial radiographs show chronic lung abnormalities that change in character and distribution with time. Removing milk from the diet may result in clinical and radiographic improvement.

Löffler syndrome (pulmonary infiltrates with eosinophilia) is a manifestation of allergy that consists of transient and migratory radiographic pulmonary opacities, eosinophilia, and mild systemic manifestations. Löffler syndrome is uncommon in children, and extremely rare in infants. The most common cause in the pediatric age group is a reaction produced by the migratory phase of parasitic nematodes such as Toxocara canis. A variety of medications, including aspirin, penicillin, and nitrofurantoin, can also result in Löffler syndrome. Radiographic evaluation of patients with Löffler syndrome demonstrates fleeting pulmonary infiltrates that are predominantly alveolar. Pulmonary overaeration is an inconsistent feature. Adenopathy and pleural effusion are rare.¹²

Asthma (reactive airway disease) is characterized by excessive resistance to airflow in the small airways. Airway narrowing in these patients is a result of smooth muscle contraction in the bronchial walls, bronchospasm, bronchial inflammation, and mucus plugging. The tracheobronchial tree of the asthma patient has an abnormally elevated responsiveness to various stimuli. The clinical manifestations of asthma include wheezing, coughing, and dyspnea, with an acute onset. A preceding or concurrent upper respiratory infection is common. There is rapid relief of symptoms in response to bronchodilator therapy.

Asthma is the most common chronic disease in the pediatric age group, affecting 5% to 10% of all children. In young children, asthma is more common in boys. This gender predilection largely disappears in teenagers. Asthma is a potentially fatal condition, with most deaths occurring because of an acute event outside of the hospital setting. Asthma-related morbidity and mortality are increased in populations of urban black and Hispanic children.¹³

The pathophysiology of childhood asthma is complex and multifactorial. There is likely an interaction between genetic susceptibility and environmental factors, such as allergens and infections. The pathological findings in asthma include mucus plugging, mucosal edema, and denudation of the bronchial and bronchiolar epithelium. There is eosinophilia in the submucosa. The airways contain a multicellular inflammatory infiltrate. Manifestations of chronic airway involvement include thickening of the basement membrane, airway smooth muscle hypertrophy, and mucous gland hypertrophy. A clinical asthma attack is characterized by a combination of bronchospasm and acute airway inflammation. Mucus plugging, airway edema, and intraluminal cellular infiltration lead to additional airway obstruction. Ball-valve obstruction causes segmental hyperinflation.^14,15

The initiating event in allergen-induced asthma is binding of the allergen to preformed IgG on the surface of mucosal mast cells. Cross-linking of these IgG molecules triggers degranulation of the mast cell and the release of mediators that include histamine, leukotrienes, prostaglandin D₂, platelet-activating factor, and various cytokines. The released mediators trigger airway smooth muscle constriction (bronchospasm), increased vascular permeability (mucosal edema), and mucous secretion. This “early asthmatic response” lasts for a few hours after exposure to the antigen. This is followed by the “late asthmatic response” that is characterized by the recruitment of neutrophils, eosinophils, basophils, and lymphocytes. A second wave of mediator release occurs, causing additional bronchospasm, edema, and mucous secretion. This process may lead to epithelial damage and impaired mucociliary function, which further aggravates bronchoconstriction and mucous secretion.

With chronic asthma, the long-term presence of inflammatory cells may lead to goblet cell hyperplasia and airway wall remodeling. The pathological features of this airway remodeling include subepithelial fibrosis, smooth muscle hypertrophy, and increase in mucus gland mass.^16,17 These alterations cause chronic wall thickening, predominantly in the small airways. The identification of bronchial wall thickening with high-resolution CT in asthmatic children suggests significant inflammation and greater risk for the development of permanent airway remodeling.¹⁸

Many children with asthma have normal chest radiographs. The most common radiographic findings are air trapping and atelectasis, with retrosternal airspace enlargement, flattening of the diaphragm, and peripheral arterial attenuation (Figures 4-6 and 4-7). Central peribronchial markings are often prominent because of bronchial wall thickening (Figures 4-8 and 4-9). Potential complications include pneumothorax, pneumomediastinum, lung infection, allergic bronchopulmonary aspergillosis, and pulmonary arterial hypertension.⁴

High-resolution CT can provide supplemental information about the severity of asthma, and may help identify patients at particular risk for the development of irreversible airway remodeling. High-resolution CT of children with difficult to treat asthma frequently demonstrates bronchial wall thickening. Other potential findings include bronchiectasis, atelectasis, centrilobular opacities, mucous plugging, hyperinflation, and fibrosis. A combination of air trapping and regions of decreased lung perfusion can lead to a mosaic pattern on CT. There is often focal peripheral air trapping on images obtained during expiration. Pulmonary function testing can be normal despite CT evidence of bronchial wall thickening.^19–21

Cystic fibrosis is an autosomal recessive hereditary disease that involves the mucous-secreting glands throughout the body. The major sites of exocrine gland dysfunction are the tracheobronchial tree, pancreas, colon, salivary glands, and sweat glands. Approximately 30,000 Americans have cystic fibrosis. Cystic fibrosis is the most common lethal hereditary disease among whites, with an estimated prevalence in this population of 1 per 2500 livebirths. Approximately 4% of individuals of European descent are heterozygous carriers for the cystic fibrosis gene. The prevalence of cystic fibrosis in individuals of African descent is approximately 1 in 17,000. The prevalence in Hispanics is approximately 1 in 9000. This disease is rare in Asians (1 in 31,000). Ireland has the highest prevalence of cystic fibrosis in the world; approximately 1 in 19 individuals in Ireland carry the gene.^22–24

Ninety-five percent of patients with cystic fibrosis die of respiratory complications. Without treatment, most individuals with cystic fibrosis die early in childhood. Treatment regimens are increasingly effective, however. Based on 2010 data from its registry, the Cystic Fibrosis Foundation reports a median predicted age of survival of 38.3 years for cystic fibrosis patients in the United States.²⁵ The Canadian Cystic Fibrosis Foundation reports a median survival age of 48.1 years (2010 data).²⁶

The gene for cystic fibrosis is located on the long arm of chromosome 7. This gene encodes the cystic fibrosis transmembrane conductance regulator (CFTR), which regulates fluid balance across epithelial cell membranes in the airways, bile ducts, pancreas, sweat ducts, and vas deferens. More than 1500 mutations of the cystic fibrosis gene have been identified, not all of which result in overt cystic fibrosis. The ΔF508 mutation is present in 90% of Americans with cystic fibrosis, and approximately 70% are homozygous for this mutation.^27,28

The lungs of an infant born with cystic fibrosis are initially normal. However, deficient function of cystic fibrosis transmembrane conductance regulator leads to abnormally increased viscosity of fluid within the tracheobronchial tree. This is predominantly a result of secretion of abnormal mucous, but also is related to cellular degradation products from white blood cells. There is deficient mucociliary clearance, and airways become plugged. The chronic inflammation and repeated infections that occur because of impaired mucociliary clearance lead to an influx of neutrophils into the airways. The activity of the released neutrophil serine proteinases (particularly elastase) exceeds the antiproteinase capacity of the endogenous serine proteinase inhibitors in the airways, thereby facilitating airway damage. As more damage occurs, the susceptibility to additional infections increases. The small bronchi and bronchioles become narrowed by irregular collections of mucous and inflammatory exudates in the lumen and/or by inflammatory thickening and fibrosis of the bronchial wall. Damage to the supporting structure of the airways and elevated pressure from airway obstruction lead to bronchiectasis.²⁹

Approximately 70% of children with cystic fibrosis are diagnosed during the first year of life, usually by neonatal screening (level of blood immunoreactive trypsinogen) or GI symptomatology (meconium ileus). The diagnosis is made in 90% of patients by 12 years of age.³⁰ Respiratory symptoms usually increase in severity with increasing patient age. Early in life, the clinical and radiographic manifestations of pulmonary involvement may be subtle. Potential manifestations of pulmonary involvement include recurrent pneumonias, dyspnea, chronic cough, and hemoptysis. Pulmonary function tests become abnormal during early childhood in most patients. The typical method for confirmation of the diagnosis is the sweat chloride test. Genotyping is an alternative method of diagnosis, but is not foolproof since there are myriad uncommon mutations. Individuals with CFTR gene mutations experience a spectrum of sequelae that ranges from recurrent sinusitis in adulthood to severe lung, pancreatic, or liver disease in infancy.²⁴

In addition to bronchiectasis and recurrent pneumonias, various additional pulmonary complications can occur in patients with cystic fibrosis. Chronic Pseudomonas colonization of the lung is present in at least 80% of cystic fibrosis patients, and this may incite an accelerated decline in pulmonary function. Other complications in cystic fibrosis patients include lung abscess, hemoptysis, sudden death from asphyxia, and cor pulmonale with intractable right-heart failure as a consequence of pulmonary hypertension. Pleural effusion and empyema are rare. Pneumothorax is relatively common in these patients, and can be recurrent or refractory.

The prevalence of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis is approximately 6% to 10%. There is considerable overlap in the clinical manifestations of cystic fibrosis and allergic bronchopulmonary aspergillosis. The major clinical manifestation is episodic bronchial obstruction. Laboratory evaluation may show elevation of total IgE and Aspergillus fumigatus-specific IgE.³¹

Improving therapy for cystic fibrosis is increasing the life expectancy of these patients. Exacerbations are treated with parenteral antibiotics and pulmonary physiotherapy. Also useful are inhaled medications, such as bronchodilators, hypertonic saline, recombinant human deoxyribonuclease, antibiotics, and ibuprofen. Lung transplantation is an option for some patients with end-stage pulmonary disease. Various innovative therapies are currently under investigation, and continued improvement in the quality of life of individuals with cystic fibrosis is to be expected. The increasing armamentarium of treatment options for cystic fibrosis influences the indications for diagnostic imaging evaluations, particularly in young children for whom the pulmonary manifestations are first occurring and the potential to mitigate irreversible lung damage is greatest.

The major radiographic manifestations of lung involvement with cystic fibrosis are hyperinflation and bronchiectasis. Chest radiographs of infants with cystic fibrosis are typically normal. The earliest findings are hyperinflation and slight prominence of central peribronchial markings. This is a nonspecific pattern that occurs with a variety of lung abnormalities, including common viral bronchiolitis. Eventually, the lungs fail to contract normally, and fixed pulmonary overaeration develops. Early in the course of the disease, peripheral round or poorly defined linear opacities up to 5 mm in diameter are sometimes visible on chest radiographs. Initially, there is bronchial wall thickening without dilation (Figure 4-10). As the pulmonary manifestations of the disease progress, there are increases in bronchial diameter, bronchial wall thickness, hyperinflation, and the number and size of peripheral opacities.

Bronchiectasis is a hallmark feature of cystic fibrosis in older children. This appears radiographically as air-filled dilated tubular structures, usually with thickened irregular walls. When viewed on end, the dilated air-filled bronchus appears as a ring that is larger than the accompanying pulmonary artery. When filled with fluid or mucous, the abnormal bronchi may appear as linear opacities that are branching or finger-like; when viewed on end, they appear nodular. In some patients, the earliest and most prominent manifestations of bronchiectasis occur in the upper lobes. The cylindrical form predominates, particularly in children. Older patients usually have areas of cystic and varicose bronchiectasis as well. Air-filled cysts are frequently present in cystic fibrosis patients with advanced disease; these cysts represent cystic bronchiectasis, bullae, or pneumatoceles.

Patients with cystic fibrosis are prone to develop lobar or segmental atelectasis, most commonly in the upper lobes and right middle lobe (Figure 4-11). In older patients, hilar lymphadenopathy may occur. Hilar fullness can also result from central pulmonary artery dilation because of pulmonary hypertension. Generalized tracheal dilation is common in older patients.

There are various proposed scoring systems based on the chest radiographic findings to assess the severity of cystic fibrosis. The Brasfield, Chrispin-Norman, National Institutes of Health (NIH), Wisconsin, and Northern methods are the most commonly utilized. The Brasfield system assigns scores from 0 (absent) to 5 (severe) for air trapping, linear markings, nodular cystic lesions, large lesions, and general severity. These various scoring techniques are of limited effectiveness in young children, particularly those with mild disease.^32–35

As compared to standard radiographs, high-resolution CT provides more precise characterization of the pathological anatomy in children with cystic fibrosis. CT can detect pulmonary abnormalities earlier than pulmonary function testing, particularly when only a small portion of the lung is affected. The most common CT finding in older patients with cystic fibrosis is diffuse thickening of the bronchial walls, because of chronic inflammation. Nearly all cystic fibrosis patients have evidence of bronchiectasis as well (Figure 4-12). Other common CT findings include pleural thickening, hilar adenopathy, and bronchoceles. A minority of patients have subpleural bullous dystrophic emphysema and atelectasis. Early in the course of the disease in children, mosaic perfusion may be the only high-resolution CT abnormality. As the disease progresses, bronchial thickening, bronchiectasis and mucoid impaction develop. Mucoid impaction typically produces an appearance of large nodules in the central aspect of the lung and centrilobular or tree-in-bud patterns in the peripheral aspect of the lung (Figure 4-13).³⁶

Cystic fibrosis scoring systems based on high-resolution CT provide some advantages over those based on standard radiographs.^37–39 The CT features that are utilized in the scoring systems include bronchiectasis, bronchial wall thickening, mucus plugging, air trapping or hyperinflation, bullae, sacculations, atelectasis, consolidation, mosaic perfusion, ground-glass opacities, acinar nodules, alveolar consolidation, and thickening of interlobular and intralobular septa.⁴⁰ The most frequently used CT scoring system was proposed by Bhalla et al in 1991.³⁷ It is based on the severity of bronchiectasis and peribronchial thickening, and the distribution of bronchiectasis, mucous plugging, sacculations or abscesses, bullae, emphysema, collapse, and consolidation. Nathanson et al proposed a cystic fibrosis scoring system specifically designed for pediatric patients.⁴¹ Scoring based on high-resolution CT findings correlates with clinical measures of disease severity, temporary progression of disease during exacerbations, and response to treatment; however, the practical usefulness of this information for the care of children with cystic fibrosis is a matter of some debate.

MRI is not routinely used in the evaluation of the lungs in patients with cystic fibrosis. Motion artifact, limited resolution, and limited signal from the lung parenchyma limit the usefulness of this technique. However, the avoidance of exposure to ionizing radiation is an advantage to MR.^42,43 Assessment of lung ventilation patterns with MRI utilizing inhaled hyperpolarized helium-3 is currently under investigation. This technique provides higher-resolution than scintigraphic ventilation imaging.^44,45

The most common causes of hemoptysis in children are cystic fibrosis and congenital heart disease. Hemoptysis caused by intraalveolar hemorrhage can occur because of toxins, medication, coagulopathy, pneumonia, collagen vascular disease, vasculitis, and idiopathic pulmonary hemosiderosis. The most common causes of massive hemoptysis are bronchiectasis, tuberculosis, aspergillosis, actinomycosis, a vascular lesion, or a tumor. The radiographic appearance of acute pulmonary hemorrhage is that of diffuse airspace consolidation. CT findings that help localize a bleeding site in patients with massive hemoptysis include localized parenchymal opacification (usually with a ground-glass pattern) or an underlying mass.^46–48

Allergic bronchopulmonary fungal disease most often occurs as a complication of chronic asthma or cystic fibrosis. The pathophysiology involves an altered immune response to inhaled spores, rather than an invasive fungal infection. The most commonly involved organism is Aspergillus; in which case, the term allergic bronchopulmonary aspergillosis is appropriate. The clinical manifestations of allergic aspergillosis include anorexia, malaise, fever, episodic wheezing, and a cough that produces sputum plugs. The serum level of IgE is elevated (total IgE, as well as A. fumigatus-specific IgE), and there is eosinophilia in the blood and sputum. Other fungi that can cause allergic bronchopulmonary fungal disease include Candida albicans, Curvularia species, Helminthosporium species, Torulopsis glabrata, Bipolaris species, Cladosporium species, Saccharomyces cerevisiae, Schizophyllum commune, and Trichosporon beigelii.⁴⁹

The radiographic manifestations of allergic bronchopulmonary fungal disease predominate in the upper lobes. In the acute phase, variably sized areas of consolidation are intermixed with patches of atelectasis. Consolidation or atelectasis only rarely involves an entire lobe. Mucoid impaction within dilated bronchi may result in nodular branching structures that radiate from the hilum. If a rim of air surrounds the mucoid impaction, a “tramline” pattern may be present. Mucoid impactions are frequently associated with large areas of atelectasis. The typical CT findings in allergic bronchopulmonary fungal disease consist of mucoid impaction and bronchiectasis (Figure 4-14). There is a predilection for involvement of the segmental and subsegmental bronchi of the upper lobes. In the chronic phase, the major radiographic findings are bronchiectasis and pulmonary fibrosis. The radiographic diagnosis of aspergillosis in patients with cystic fibrosis is difficult because the findings overlap those of the underlying lung disease. The identification of central bronchiectasis in an asthma patient is essentially pathognomonic of allergic bronchopulmonary aspergillosis.^50,51

Primary ciliary dyskinesia (also termed dysmotile cilia syndrome, immotile cilia syndrome, and dyskinetic cilia syndrome) is an autosomal recessive disorder of deficient ciliary function. The prevalence is 1 in 15,000 to 30,000. Dysmotility or complete immotility of cilia results in a multisystem disease of variable severity, characterized by respiratory tract infections (leading to bronchiectasis), hearing impairment, and male subfertility. Ultrastructural defects are present in ciliated mucosa and spermatozoa. Situs inversus or heterotaxy is present in approximately half of these patients. The Kartagener syndrome refers to the combination of dysmotile cilia, situs inversus, bronchiectasis, and sinusitis. There is also an association with pectus excavatum (approximately 10% of patients). Gene mapping studies of patients with primary ciliary dyskinesia have shown extensive locus heterogeneity.^52,53

Various clinical presentations occur with primary ciliary dyskinesia. Most often, there is a history of chronic or recurrent respiratory infections. Chronic rhinosinusitis, chronic productive cough, and episodes of otitis media are common. In patients with these symptoms and situs inversus, the diagnosis is straightforward. Otherwise, a variety of other conditions should be considered in the differential diagnosis, including cystic fibrosis, allergy, immunological disorders and α₁-antitrypsin deficiency. Some neonates with dysmotile cilia syndrome present with respiratory distress; the correct diagnosis is suggested by the presence of situs inversus or a family history, as well as exclusion of other neonatal respiratory disorders such as hyaline membrane disease, aspiration syndromes, neonatal pneumonia, pneumothorax, cardiovascular abnormalities, and metabolic diseases. The definitive diagnosis of dysmotile cilia syndrome is by ultrastructural analysis of cilia obtained by lung biopsy.^54–56

The typical radiographic pattern of primary ciliary dyskinesia is that of chronic airway disease, with progression from bronchial wall thickening to bronchiectasis. About half of patients have findings of situs inversus or heterotaxy (Figure 4-15). The bronchiectasis can be central or diffuse, but isolated peripheral involvement is lacking. There is a predilection for right middle-lobe bronchiectasis; the lower lobes are the next most common sites (Figure 4-16). The early upper-lobe involvement that is common in cystic fibrosis is not a feature of primary ciliary dyskinesia. Other potential radiographic findings include atelectasis, mucous plugging, and peribronchial consolidation. High-resolution CT is the most sensitive technique for the early detection of these alterations. An additional potential finding on CT is mosaic perfusion.^57,58

Sickle cell disease encompasses a group of disorders that are characterized by the presence of at least 50% sickle hemoglobin in the erythrocytes and hemolytic anemia that varies in severity between patients. Sickle hemoglobin, or hemoglobin S (HbS), results from a mutation in the β-globin gene on chromosome 11. Polymerization of deoxygenated HbS forms fibers that make erythrocytes rigid and distorted in shape. Red blood cells that contain high proportions of HbS undergo cycles of sickling and desickling as oxygenation and deoxygenation occur. Hemolysis and vascular occlusion are the 2 major pathophysiological consequences of intravascular sickling. The mean erythrocyte life span in patients with HbSS disease is only 10 to 20 days, which is 10 times shorter than normal. Sickled cells in the circulation tend to adhere to the vascular endothelium, which can lead to blockage and resultant ischemia or infarction.⁵⁹

Hemolysis and shortened erythrocyte life span in children with sickle cell disease result in chronic anemia. With time, this leads to mild cardiomegaly that can be detected on chest radiographs. The cardiac silhouette typically has a globular configuration. There is also pulmonary vascular plethora caused by an elevated cardiac output in response to anemia. Frequently, a splenic silhouette is lacking on radiographs (Figure 4-17). Osseous manifestations of sickle cell disease, when present, are confirmatory; these include sclerosis and irregularity of the humeral heads and vertebral end plate notching (see Chapter 61).

The 2 major pulmonary complications in children with sickle cell disease are pneumonia and pulmonary vasoocclusive disease (acute chest syndrome). The risk for the development of pneumonia is 5 to 6 times greater in children with sickle cell disease than in children in the general population. This increased risk may be related to a deficiency of phagocytosis, as well as functional hyposplenism. The most common organisms responsible for pneumonia in patients with sickle cell disease are Streptococcus pneumoniae, Mycoplasma, and Salmonella. Bacterial pneumonias in children with sickle cell disease tend to resolve more slowly than those in normal children.^60,61

Pulmonary vascular abnormalities in children sickle cell disease predominately result from two pathophysiological mechanisms. Intravascular sickling because of subnormal oxygenation in the pulmonary vascular bed is the major mechanism. This creates a cascade in which increased blood viscosity and thrombolysis lead to further interference with oxygenation and additional intravascular sickling. The second potential mechanism is pulmonary embolization with marrow fat caused by the bone marrow necrosis that occurs during an aplastic crisis.

Acute chest syndrome is a major source of morbidity and mortality in individuals with sickle cell disease. Acute chest syndrome is a descriptive term applied to a specific constellation of clinical and radiographic findings that occurs in children with sickle cell disease. This consists of chest pain, fever, leukocytosis, and respiratory symptoms, in conjunction with an acute consolidative process on chest radiographs. To meet the criteria of acute chest syndrome, the radiographic lung opacity must occupy at least one complete bronchopulmonary segment, without evidence of substantial volume loss (Figure 4-18).^62,63

The radiographic differentiation between pneumonia and pulmonary vasoocclusive disease in sickle cell patients is unreliable, and frequently impossible. Both processes usually result in dense consolidation on chest radiographs. Pleural effusion can occur with both processes. Acute chest syndrome is the most likely diagnosis when radiographs are clear at the time of the clinical onset of symptoms, followed by rapid development of consolidation, sometimes over the course of hours. A lack of prompt resolution of consolidation on serial radiographs is more often associated with an infectious etiology, and may predict a longer clinical course.⁶⁴

CT imaging can be useful in selected patients for confirming the diagnosis of acute chest syndrome. The predominant pulmonary manifestations of acute chest syndrome are capillary obstruction by sickled cells and associated local thrombosis. CT may show areas of decreased attenuation that contain fewer small pulmonary vessels than normal, presumably due to diminished perfusion. Areas of ground-glass opacity can also occur; these represent regions of hemorrhagic edema caused by ischemia, or areas of relative overperfusion. Areas of denser consolidation represent true tissue infarction or infective consolidation. Multifocal interstitial lung opacities on CT are present in many patients with sickle cell disease as a long-term result of prior episodes of infarction and infection.^65–67

α₁-Antitrypsin deficiency is a potentially lethal autosomal recessive disorder that causes pathological changes within the liver and lung. Symptomatic abnormalities in other organ systems are rare. Manifestations of liver pathology dominate the clinical picture during infancy and childhood, with hepatosplenomegaly as well as signs and symptoms of obstructive jaundice and cirrhosis (e.g., esophageal or gastric varices). Symptomatic lung involvement does not usually occur until the teenage years or early adulthood. Potential symptoms related to pulmonary pathology in patients with this disorder include wheezing, dyspnea, respiratory failure, and cor pulmonale.^68–70

α₁-Antitrypsin is the major protease inhibitor in plasma; it serves to prevent enzymes from degrading normal host tissue. The pulmonary involvement in patients with this syndrome is due to accelerated destruction of elastin in the alveolar walls, which leads to panacinar emphysema. Because of the reduced levels of circulating α₁-antitrypsin, there is insufficient protection of the lower respiratory tract from neutrophil elastase, thereby permitting progressive destruction of the alveoli.^29,71 The process is potentiated by other pulmonary insults, such as pneumonia, cigarette smoking, and inhalation of toxins.⁷²

Children with α₁-antitrypsin deficiency and no pulmonary symptoms sometimes have hyperinflation on chest radiographs. Imaging of adolescents and adults with this disorder typically demonstrates more severe hyperinflation. Other findings eventually develop in most patients, including bronchiectasis, emphysema, and bullae (Figure 4-19). The lung bases are oligemic, and increased pulmonary blood flow occurs in the upper lobes. Manifestations of cor pulmonale may be present, including cardiomegaly and enlarged pulmonary arteries.⁷³

Williams-Campbell syndrome is a rare developmental lung disease in which bronchial cartilage deficiency leads to severe bronchiectasis in infancy. Most affected patients present with cough and wheezing during the first 2 years of life. CT demonstrates cystic bronchiectasis of fourth-generation through sixth-generation bronchi (Figure 4-20). The bronchi distend on inspiration and collapse on expiration. There is distal air trapping on expiration images.^74,75

The immune deficiencies are a variable group of disorders in which there are one or more abnormalities in the normal defense mechanisms against infection. These defenses involve B cells, T cells, natural killer cells, phagocytes, complement proteins, and physical barriers. The clinical manifestations of the immunodeficiency disorders are determined in large part by the interplay of abnormalities in these defenses. The lungs are continuously exposed to infectious pathogens, and lung involvement occurs to varying degrees in nearly all patients with an immune deficiency. Pulmonary symptomatology is sometimes the first clinical indicator of the presence of the underlying disorder. Likewise, radiographic examinations sometimes provide the initial clues to the possibility of an underlying immunodeficiency, by demonstrating recurrent lung infections or a suspicious pattern of lung involvement.

T cells are leukocytes that provide “cell-mediated” immunity. The primary site of production of T cells is the thymus. B lymphocytes, or B cells, are responsible for “humoral” immunity. B lymphocyte production is in the bone marrow, lymph nodes, and spleen. On exposure to an antigen, B lymphocytes mature into plasma cells that synthesize a specific immunoglobulin to that antigen. There are 5 classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM. An additional factor in immunity is the complement system, which serves to neutralize viruses and to opsonize and destroy bacteria. Phagocytic cells engulf and destroy bacteria, and aid in antigen processing.

Primary immunodeficiency diseases comprise a heterogeneous group of disorders that are caused by genetic defects that affect the function of neutrophils, macrophages, dendritic cells, complement proteins, natural killer cells, T lymphocytes, or B lymphocytes. The International Union of Immunological Societies has designated 8 classes of primary immunodeficiencies, with more than 150 individual conditions (Table 4-2). Symptomatic primary immune deficiency syndromes are rare. Mild forms are often asymptomatic. The prevalence of selective IgA deficiency in the general population is approximately 1:600. Other examples of primary immunodeficiency include chronic granulomatous disease, DiGeorge syndrome, and α₁-antitrypsin deficiency. Differentiation among these immunodeficiency disorders requires specific clinical and laboratory investigations, correlation with diagnostic imaging information, and investigation of family histories.^76–79