Diffuse Lung Disease
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Diffuse lung disease (DLD) comprises a diverse group of disorders characterized by widespread pulmonary parenchymal pathology and impaired gas exchange. While many of these disorders are categorized under the rubric of interstitial lung disease (ILD), some of these disorders involve the airspaces or peripheral airways in addition to, or rather than, the interstitium. Some of these disorders are present primarily in infancy or early childhood, while others that are prevalent in adulthood rarely occur in childhood. This chapter will review the classification of pediatric DLD and the characteristic imaging findings of specific disorders to facilitate accurate diagnosis and guide appropriate treatment of children with these disorders.
KeywordsBronchiolitis Obliterans Pulmonary Alveolar Proteinosis Cryptogenic Organize Pneumonia Lysinuric Protein Intolerance Diffuse Lung Disease
Diffuse lung disease (DLD) comprises a diverse group of disorders characterized by widespread pulmonary parenchymal pathology and impaired gas exchange. While many of these disorders in children are categorized under the rubric of interstitial lung disease (ILD), some of these disorders involve the airspaces or peripheral airways in addition to, or rather than, the interstitium, so that DLD is a less specific, but more inclusive term. The American Thoracic Society (ATS) /European Respiratory Society (ERS) international multidisciplinary classification of the idiopathic interstitial pneumonias (Travis et al. 2013) developed for the adult population is not well suited for children.
Many of the disorders that are most prevalent in adulthood rarely occur in childhood. Usual interstitial pneumonia (UIP), the pathologic correlate of idiopathic pulmonary fibrosis (IPF) and the predominant form of DLD in the adult ATS/ERS classification, is exceedingly rare in children and erroneous diagnoses likely account for reports of better outcomes of children with UIP compared to adults. Unrecognized mutations in surfactant-related genes likely account for many reported cases of desquamative interstitial pneumonia (DIP) in children diagnosed before the availability of tests for these mutations (Fan et al. 2004; Nogee 2006).
There are several types of DLD that present primarily or exclusively in infancy or early childhood, such as neuroendocrine cell hyperplasia of infancy (NEHI) and pulmonary interstitial glycogenosis (PIG). The stage of lung growth and development affects disease manifestations, and the injury and repair processes in immature lung differ from those in the mature adult lung (Clement and Eber 2008). In recognition of these differences with adult DLD, standardized approaches to the diagnosis and classification of pediatric DLD have been advocated, incorporating insights from diagnostic imaging, infant pulmonary function testing, molecular genetics, immunopathology, and electron microscopy (Deutsch et al. 2007). This chapter will review the classification, clinical features, and imaging findings of pediatric DLD.
2 Clinical Presentations and Classification
DLD is less prevalent in children than in adults and more common in infants than in older children. While rare, the true prevalence of pediatric DLD is likely understated in the medical literature as a consequence of more hesitant use of diagnostic lung biopsy in children compared to adults and the lack of familiarity with recently described disorders and appropriate classification.
Pediatric DLD usually presents either with rapid respiratory failure in the neonatal period or with an insidious course of respiratory signs and symptoms, failure to thrive, or exercise intolerance later in infancy, childhood, or adolescence. The signs and symptoms may be misattributed for many months or even years to common disorders, such as pulmonary infection, bronchopulmonary dysplasia (BPD), asthma, congenital heart disease, cystic fibrosis, or immunodeficiency. Once these common disorders have been eliminated as causal, criteria have been devised to assist clinicians in identifying children that warrant further investigation for possible DLD. A neonate or infant is proposed as having “childhood ILD syndrome” or “chILD syndrome” if at least three of the following criteria are present: (1) respiratory symptoms (cough, rapid, and/or difficult breathing, or exercise intolerance), (2) signs (tachypnea, adventitious sounds, retractions, digital clubbing, failure to thrive, or respiratory failure), (3) hypoxemia; and (4) diffuse pulmonary parenchymal abnormality on chest radiograph (CXR) or computed tomography (CT) (Kurland et al. 2013).
Classification scheme for pediatric diffuse lung disease
Disorders more prevalent in infants and young children
Diffuse developmental disorders
Congenital alveolar dysplasia
Alveolar capillary dysplasia with misalignment of the pulmonary veins
Chronic lung disease of infancy
Related to genetic disorders
Related to congenital heart disease
Specific disorders of unknown etiology
Pulmonary interstitial glycogenosis
Neuroendocrine cell hyperplasia of infancy
Surfactant dysfunction disorders
Related to a genetic defect
Related to autoimmune anti-GM-CSF antibody
Consistent histology without a recognized genetic defect
Disorders related to systemic disease processes
Autoimmune and autoinflammatory disorders
Connective tissue disease
Secondary (drug therapy, radiation therapy, bone marrow transplant)
Lymphoid hyperplasia and lymphoproliferative disorders
Lysosomal storage disorders
Langerhans cell histiocytosis
Disorders of the normal immunocompetent host
Infectious and post-infectious processes
Related to exposures
Acute interstitial pneumonia
Cryptogenic organizing pneumonia
Idiopathic nonspecific interstitial pneumonia
Idiopathic pulmonary hemosiderosis
Vascular disorders masquerading as diffuse lung disease
Pulmonary venous congestion or obstruction
Congestive heart failure
Congenital cardiovascular disease
Pulmonary veno-occlusive disease
The imaging technique and diagnostic efficacy of imaging for pediatric DLD have been addressed in previous review articles (Guillerman 2010; Guillerman and Brody 2011; Lee 2013). For some types of pediatric DLD, the imaging findings are highly specific, while for others the imaging findings are nonspecific and laboratory tests or lung biopsy are needed for definitive diagnosis (Kurland et al. 2013). In addition to suggesting or corroborating a specific diagnosis in some cases, imaging can be useful for refining the differential diagnosis, identifying biopsy sites, monitoring disease activity, and assessing response to therapy. The remainder of this chapter will provide an updated summary of the characteristic clinical and imaging features of the disorders categorized under a modified chILD classification scheme of pediatric DLD.
3 Categories of Disorders
3.1 Diffuse Developmental Disorders
Acinar dysplasia is characterized by lung developmental arrest in the pseudoglandular or early canalicular phase, resulting in essentially no alveolar spaces for gas exchange. Congenital alveolar dysplasia is characterized by arrest in the late canalicular/early saccular phase, resulting in incomplete alveolarization. Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is characterized by malpositioning of the pulmonary vein branches adjacent to the pulmonary artery branches rather than within the interlobular septa, medial hypertrophy of the pulmonary arterioles, reduced alveolar capillary density, and pulmonary lobular maldevelopment. Pulmonary lymphangiectasia is also present in about one-third of cases (Dishop 2011). The misaligned pulmonary veins in ACD/MPV may actually represent anastomotic bronchial veins associated with intrapulmonary right-to-left shunting. This shunting bypasses the alveolar capillary bed and exacerbates the hypoxemia from right-to-left extrapulmonary shunting associated with persistent pulmonary hypertension of the newborn (PPHN) (Galambos et al. 2014).
The diffuse developmental disorders of the lung are associated with markedly impaired alveolar gas exchange, resulting in respiratory failure and severe PPHN within hours or days of birth in the absence of the usual causative conditions of prematurity, meconium aspiration, congenital heart disease, perinatal asphyxia, or sepsis. Death usually ensues within a few days or weeks, unless the lung involvement is patchy rather than diffuse (Chow et al. 2013), or extracorporeal membrane oxygenation (ECMO) or paracorporeal lung assist devices are available as a bridge to lung transplantation (Sen et al. 2004; Michalsky et al. 2005; Hoganson et al. 2014). Approximately 80 % of cases of ACD/MPV are associated with extrapulmonary malformations, including hypoplastic left heart syndrome, aortic coarctation, alimentary tract atresia, annular pancreas, omphalocele, midgut malrotation, and urinary tract malformation. Sporadic or familial autosomal dominant FOXF1 gene mutations have been identified as a cause of some cases of ACD/MPV (Stankiewicz et al. 2009; Sen et al. 2013).
3.2 Growth Abnormalities
Growth abnormalities constitute the most common cause of chronic DLD in infancy. Lung growth abnormalities are characterized histologically by impaired alveolarization manifesting as lobular simplification with deficient alveolar vascularization and septation, reduced alveolar number, and increased alveolar size resembling emphysema (Dishop 2010). As a consequence, there is diminished total alveolar surface area and reduced pulmonary diffusing capacity relative to alveolar volume (Balinotti et al. 2010). Lung growth abnormalities are often accompanied by patchy PIG or by pulmonary arterial hypertensive changes related to increased vascular resistance from a deficient capillary bed (Dishop 2011).
Lung growth abnormalities can be related to prenatal or postnatal conditions (Deutsch et al. 2007). The most common prenatal form is pulmonary hypoplasia secondary to limited intrathoracic space in utero, such as from a congenital diaphragmatic hernia, oligohydramnios, thoracic mass lesion, or skeletal dysplasia. The most frequently encountered postnatal form is chronic lung disease of infancy (CLDI) related to prematurity. This includes “new” BPD, which is characterized by impaired alveolarization, but less fibrosis and airway obstruction compared to classic BPD (Bhandari and Bhandari 2009), and Wilson-Mikity syndrome, which is characterized by slowly progressive respiratory distress and cyst-like changes of the lungs developing within the first few weeks of life despite minimal respiratory support at birth (Hoepker et al. 2008; Philip 2009). Growth abnormalities can also be observed in near-term and term infants as an idiopathic disorder or in association with congenital heart disease or certain genetic disorders (Deutsch et al. 2007; Dishop 2010).
Patients with a lung growth abnormality typically present with respiratory difficulty as a neonate, and may either improve or worsen, depending on the extent of catch-up growth of the alveoli over time and whether or not pulmonary hypertension ensues. Most alveolarization occurs by two to three years postnatal age, but recent evidence from hyperpolarized gas magnetic resonance imaging suggests that neo-alveolarization continues to occur throughout childhood and adolescence in normal individuals (Narayanan et al. 2012). Gestational age at birth is an important determinant of subsequent alveolar development (Balinotti et al. 2010), but the capacity for catch-up neo-alveolarization in those with lung growth abnormalities is currently unknown.
3.3 Specific Disorders of Unknown Etiology
3.3.1 Pulmonary Interstitial Glycogenosis
PIG, previously known as infantile cellular interstitial pneumonitis, is characterized histologically by patchy or diffuse infiltration of the interstitium by vimentin-positive immature mesenchymal cells containing abundant cytoplasmic glycogen, without prominent inflammation or fibrosis (Smets et al. 2004). PIG has not been observed beyond infancy, suggesting a relationship of PIG to lung development and growth (Deterding 2010; Deutsch and Young 2010). Patchy PIG is often observed concomitantly with a lung growth abnormality (Deutsch et al. 2007), and may contribute to some exacerbations of CLDI (Dishop 2011) or persistent pulmonary hypertension in infants with congenital heart disease (Radman et al. 2013).
Most patients with PIG present in early infancy with tachypnea and a supplemental oxygen requirement. Pulmonary function testing reveals a restrictive lung disease with marked reduction of pulmonary diffusing capacity. The observations that resolution of PIG on histology and improvement in pulmonary diffusion capacity and forced vital capacity coincide with clinical improvement suggest that PIG impairs respiratory function via alveolar septal thickening (Ehsan et al. 2014), although the ultimate clinical outcome primarily depends upon the severity of any underlying lung growth abnormality (King et al. 2011), and no mortality is associated with cases of isolated PIG. Corticosteroid therapy may hasten the resolution of PIG, possibly due to acceleration of lung maturation rather than to suppression of inflammation (Deterding 2010; Deutsch and Young 2010; Canakis et al. 2002; Onland et al. 2005), but should be used judiciously in this self-limited disorder due to the risks of neuro-developmental impairment, immunosuppression, and poor wound healing associated with corticosteroids (Radman et al. 2013).
3.3.2 Neuroendocrine Cell Hyperplasia of Infancy
Neuroendocrine cell hyperplasia of infancy (NEHI), also known as persistent tachypnea of infancy, is characterized histologically by increased numbers of pulmonary neuroendocrine cells (PNECs) and innervated clusters of PNECs called neuroepithelial bodies in the epithelium of the peripheral airways (Deterding et al. 2005). Detection of PNECs on histology is facilitated by special staining for bombesin. PNECs are involved in oxygen sensing and fetal lung development, and rapidly decline in number in normal individuals after the neonatal period. The absence of other significant airway or interstitial disease is an important criterion for the diagnosis of NEHI, since increased numbers of PNECs can also be observed in dissimilar conditions, such as sudden infant death syndrome, BPD, pulmonary hypertension, cystic fibrosis, mechanical ventilation, and smoke exposure (Dishop 2011). NEHI may be associated with minor patchy inflammation or fibrosis in a small proportion of airways (Young et al. 2010). The existence of familial cases of NEHI suggests a genetic etiology for some cases (Popler et al. 2010). Heterozygous mutations in the NK2 homeobox 1 (NKX2-1) gene have been reported in a NEHI case, but are not suspected as the predominant cause of NEHI (Young et al. 2013).
NEHI usually presents by six months of age in full-term infants with persistent tachypnea, hypoxemia, and slow weight gain. There is a male predominance. Auscultation may reveal crackles, but wheezing is unusual. The anteroposterior diameter of the chest is often increased. Symptoms can be precipitated or exacerbated by viral respiratory infections or residence at high altitude (Gomes et al. 2013). Lung function tests show peripheral airway obstruction and profound air trapping with reduced forced expiratory flow (FEV) and markedly elevated functional residual capacity (FRC) and residual volume (RV) (Kerby et al. 2013; Lukkarinen et al. 2013). The severity of air trapping as measured by FRC and RV inversely correlates with room air oxygen saturation at short-term (6–12 months) followup, providing a possible prognostic marker. Compared to BPD patients, NEHI patients have similar degrees of airway obstruction, but greater air trapping (Kerby et al. 2013). The severity of airway obstruction correlates with the prominence of PNECs (Young et al. 2010). Treatment is largely supportive and focused on oxygen supplementation and nutritional support. Bronchodilators and corticosteroids have not been shown to be beneficial except for treatment of superimposed viral infections (Kerby et al. 2013; Lukkarinen et al. 2013). NEHI is not a life-threatening condition and most patients show clinical and radiographic improvement, especially after two years of age. However, some patients require supplemental oxygen for months to years, and air trapping and exercise intolerance may persist into adolescence (Deterding 2010; Gomes et al. 2013). The development of nonatopic asthma has also been reported in follow-up (Lukkarinen et al. 2013).
3.4 Surfactant Dysfunction Disorders
3.4.1 Genetic Disorders of Surfactant Metabolism
Pulmonary surfactant is composed primarily of phospholipids and surfactant proteins secreted by type II alveolar cells. The lowering of intra-alveolar surface tension by surfactant is required for normal respiratory function. Surfactant also plays a role in innate host defense. Surfactant is cleared by uptake into alveolar epithelial cells or alveolar macrophages under stimulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) (Suzuki et al. 2010).
Genetic disorders of surfactant metabolism are a primary cause of unexplained fatal respiratory distress syndrome (RDS) in term neonates, and are increasingly identified as a cause of chronic DLD in older infants, children, and adolescents. The most frequently identified disease-causing mutations involve the genes encoding ATP binding cassette A3 (ABCA3) (Hamvas 2010) and surfactant protein C (SP-C) (Nathan et al. 2012). Other disease-causing mutations may involve the genes encoding surfactant protein B (SP-B), colony-stimulating factor 2 receptor alpha (CSFRA), NK2 homeobox 1 (NKX2-1), and solute carrier family 7 amino acid transporter member 7 (SLC7A7) (Nogee 2010).
In young infants presenting with a genetic disorder of surfactant metabolism, histologic findings usually consist of PAP with diffuse alveolar epithelial hyperplasia and foamy macrophages without hyaline membrane formation. With aging, there tends to be a lesser degree of PAP, and histologic findings of lobular remodeling, cholesterol clefts, variable interstitial fibrosis, and interstitial inflammation develop in a CPI or DIP pattern later in infancy or childhood, or in a NSIP pattern later in childhood or adolescence. Endogenous lipoid pneumonia may also be observed. These overlapping histologic patterns limit genotypic-phenotypic correlation, although electron microscopy can be useful for identifying abnormal lamellar bodies that are characteristic of ABCA3 mutations (Dishop 2010).
Variable phenotypes ranging from acute severe RDS in term neonates to chronic DLD in children and adolescents are associated with spontaneous or inherited autosomal dominant SP-C gene mutations (Guillot et al. 2009; Thouvenin et al. 2010) or autosomal recessive ABCA3 gene mutations (Doan et al. 2008; Flamein et al. 2012). A common clinical presentation of DLD related to SP-C or ABCA3 gene mutations is cough, tachypnea, and hypoxemia beginning in infancy. Alternatively, affected individuals can remain asymptomatic for years despite progressive fibrosis before sudden life-threatening deterioration occurs. Heterozygosity for an ABCA3 mutation can modify the severity of DLD associated with an SP-C mutation (Bullard and Nogee 2007). Interestingly, monoallelic ABCA3 mutation carriers are overrepresented in infants of >34 weeks gestation age with RDS (Wambach et al. 2012). Treatment with corticosteroids, hydroxychloroquine, or azithromycin may be associated with clinical improvement of patients with genetic disorders of surfactant metabolism, but it is uncertain whether this is entirely due to the therapy or in part to the natural history of the disease, and there are no proven curative therapies except for lung transplantation in the terminal disease phase (Deterding 2010; Nogee 2010; Thouvenin et al. 2010).
Lysinuric protein intolerance (LPI) is a multisystem disease resulting from an inherited defect of cationic amino acid transport attributable to autosomal recessive SLC7A7 gene mutations. LPI is associated with dietary protein intolerance, failure to thrive, osteoporosis, hepatosplenomegaly, hemophagocytic lymphohistiocytosis, immune dysfunction, nephropathy, and lung involvement (Ogier de Baulny et al. 2012). The lung involvement can occur at any age, including childhood, and is characterized by endogenous lipoid pneumonia, PAP, or pulmonary hemorrhage. CT is a sensitive test for diagnosing early lung involvement that manifests as septal thickening, nodules, and subpleural cysts prior to the onset of respiratory symptoms or pulmonary function test abnormalities (Santamaria et al. 1996). Some patients rapidly progress to respiratory failure with widespread pulmonary airspace opacities on CXR and CT related to PAP from alveolar macrophage dysfunction (Parto et al. 1993; Ogier de Baulny et al. 2012). LPI is generally treated with dietary protein restriction and L-citrulline supplementation. The lung involvement can be treated with corticosteroids and whole-lung lavage (Ogier de Baulny et al. 2012).
Recognition of clinical and radiographic findings suggestive of a surfactant dysfunction disorder is important, since the diagnosis may then be confirmed by genetic testing for surfactant gene mutations, avoiding the risk of lung biopsy. Lung biopsy may still be appropriate if genetic testing is nondiagnostic or if awaiting genetic testing results would delay the diagnosis in patients with rapidly progressive disease requiring lung transplantation for continued survival (Doan et al. 2008; Mechri et al. 2010). Occasionally, cases are encountered with imaging and histologic findings suggestive of a surfactant dysfunction disorder, but genetic testing for known disease-causing mutations is negative. Some of these cases are likely related to as yet characterized genetic defects of surfactant metabolism, especially in those with a family history of unexplained childhood-onset DLD.
3.4.2 Autoimmune Pulmonary Alveolar Proteinosis
3.5 Disorders Related to Systemic Disease Processes
A large, diverse group of systemic disease processes is associated with pediatric DLD. These include vasculitis, connective tissue diseases, granulomatous disorders, lymphoid hyperplasia and lymphoproliferative disorders, primary and secondary immunodeficiencies, lysosomal storage disorders, and Langerhans cell histiocytosis. The clinical presentations and imaging appearances of these disease processes are covered in the chapter entitled Thoracic Manifestations of Systemic Diseases by Holland, Guillerman, and Brody in this book.
3.6 Disorders of the Normal Immunocompetent Host
3.6.1 Bronchiolitis Obliterans
The clinical syndrome of bronchiolitis obliterans (BO) is characterized histologically by constriction or obliteration of the lumens of small airways by a fibroblastic reparative response to injury. The inciting event is typically a respiratory infection (especially adenovirus, influenza virus, or Mycoplasma pneumoniae) with extensive airway mucosal necrosis. Other preceding conditions include Stevens-Johnson syndrome, toxic inhalational injury, graft-versus-host disease, and chronic airway rejection in the setting of lung transplantation (Dishop 2010). There is a predominance of male patients. The time interval between infection and symptoms and signs of obstructive lung disease, such as wheezing, tachypnea, and dyspnea is variable and can be as short as a few months, although the diagnosis after onset of symptoms is often delayed for many months (Lino et al. 2013).
Swyer-James-MacLeod syndrome is a variant of BO that typically presents with a hyperlucent hypovascular lung of small or normal volume on CXR several months or a few years after the inciting infection. In about a half of cases of Swyer-James-MacLeod syndrome, the findings of BO are actually found to be bilateral if CT is performed (Lucaya et al. 1998).
3.6.2 Eosinophilic Pneumonia
The eosinophilic lung diseases are a diverse group of disorders that are often, but not always, associated with peripheral eosinophilia. These disorders can be acute or chronic, idiopathic or secondary to parasitic infections or drug reactions, and isolated to the lungs or involve extrapulmonary tissues. In addition to suggesting the diagnosis of an eosinophilic lung disease, imaging can be useful in assessing the response to therapy (Oermann et al. 2000). The thoracic imaging findings vary with the type of disorder.
The findings of airspace opacities, septal thickening, and pleural effusions typical of idiopathic acute eosinophilic pneumonia (AEP) can be misconstrued as pulmonary edema. A presumptive diagnosis of AEP can be made without biopsy in children with these imaging findings, fever, acute respiratory failure requiring ventilatory support, and marked eosinophilia on BAL (Vece and Fan 2011). Some cases of AEP are thought to be precipitated by exposure to irritants such as smoke. Treatment with corticosteroids usually results in rapid clinical improvement and resolution of radiographic abnormalities.
Idiopathic chronic eosinophilic pneumonia (CEP) is characterized by peripherally-predominant consolidation or ground-glass opacities, marked eosinophilia in BAL fluid or peripheral blood, respiratory symptoms for greater than 4 weeks, and absence of other known causes of eosinophilic lung disease. The diagnosis can also be made with consistent lung biopsy findings in cases without clinical and radiographic improvement after first-line corticosteroid treatment. Many cases of idiopathic CEP are initially misdiagnosed as asthma, and a subset of persistent cases develop reticulonodular interstitial opacities and cysts (Giovannini-Chami et al. 2014).
3.6.3 Hypersensitivity Pneumonitis
3.6.4 Aspiration Pneumonia
3.6.5 Acute Interstitial Pneumonia
Diffuse alveolar damage (DAD) is a histopathologic pattern with an exudative phase characterized by edema, hyaline membranes, and interstitial acute inflammation, and an organizing phase characterized by loose organizing fibrosis, alveolar wall thickening, type II pneumocyte hyperplasia, and alveolar collapse. The term diffuse in DAD refers to involvement of all constituents of the alveolar wall, and there are often patchy areas of spared lung (Kligerman et al. 2013). DAD is a nonspecific reaction to variety of insults and can be associated with acute respiratory distress syndrome (ARDS), infection (especially CMV or Pneumocystis), toxic inhalation, drug reaction, bone marrow transplantation, primary graft dysfunction in lung transplant recipients, and idiopathic acute interstitial pneumonia (AIP).
3.6.6 Cryptogenic Organizing Pneumonia
3.6.7 Idiopathic Nonspecific Interstitial Pneumonia
3.6.8 Idiopathic Pulmonary Hemosiderosis
3.7 Vascular Disorders Masquerading as Diffuse Lung Disease
The chILD Research Cooperative classification (Deutsch et al. 2007) and expanded chILD classification (Rice et al. 2013) acknowledge the presence of certain vascular disorders with clinical and imaging features that can mimic childhood DLD. These includes disorders such as congestive heart failure, cor triatriatum, congenital mitral stenosis, anomalous pulmonary venous return, pulmonary vein stenosis, pulmonary vein atresia, and pulmonary veno-occlusive disease (PVOD) that are associated with transudative pulmonary edema from pulmonary venous congestion or obstruction. Also included are disorders such as lymphangiectasia and lymphangiomatosis that are associated with impaired clearance of interstitial lung fluid.
3.7.1 Pulmonary Veno-Occlusive Disease
PVOD is characterized by fibrous obstruction of the post-capillary pulmonary septal veins and pre-septal venules, resulting in pulmonary hypertension, transudative pulmonary edema, and capillary proliferation. PVOD can be idiopathic or associated with connective tissue disease, HIV infection, organ transplantation, chemotherapy, or toxic exposures. Patients with PVOD often present with progressive dyspnea with exertion, and delay in diagnosis is common (Woerner et al. 2014). Typical features of PVOD include normal pulmonary capillary wedge pressure, low pulmonary diffusing capacity, hypoxemia at rest, desaturation with exercise, and occult alveolar hemorrhage on BAL.
3.7.2 Pulmonary Lymphangiectasia
Pulmonary lymphangiectasia can be confused for lymphangiomatosis. In lymphangiomatosis, there is proliferation of complex anastomosing lymphatic channels with secondary dilation of the lymphatics. Septal thickening, ground-glass opacities and chylous effusions are observed in both lymphangiomatosis and lymphangiectasia. In contrast to lymphangiectasia, lymphangiomatosis tends to present later in childhood and involve extrapulmonary tissues, with lytic bone lesions and mediastinal soft tissue edema being particularly distinctive (Faul et al. 2000; Swenson et al. 1995; Shah et al. 2011). Lymphangiomatosis is further discussed in the chapter entitled Pulmonary and Extrathymic Mediastinal Tumors by Lyons, Guillerman, and McHugh in this book.
Pediatric DLD comprises a diverse group of disorders with widespread involvement of the pulmonary interstitium, distal airspaces, or peripheral airways resulting in impaired gas exchange and, in some cases, high morbidity and mortality. A novel classification scheme specific for pediatric DLD has been devised, acknowledging the effect of the stage of lung growth and development on disease manifestations, and incorporating recent insights into the etiology, pathophysiology, genetics, and clinical phenotypes of these disorders, some of which are unique to infants and young children. Familiarity with the classification, clinical presentation, and characteristic imaging features is required for appropriate diagnosis and management of pediatric DLD.
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