Idiopathic Interstitial Pneumonias
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The idiopathic interstitial pneumonias are a distinct group of clinicopathologic entities. High-resolution computed tomography (HRCT) plays a critical role in the evaluation and management of patients. In the appropriate clinical setting, characteristic HRCT findings may be diagnostic, obviating the need for open lung biopsy. In more challenging or complicated cases, consensus among the clinician, radiologist, and pathologist may be required. This chapter describes and depicts the characteristic HRCT features of usual interstitial pneumonia, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, respiratory bronchiolitis, respiratory bronchiolitis associated interstitial lung disease, desquamative interstitial pneumonia, and lymphoid interstitial pneumonia.
KeywordsInterstitial lung disease (ILD) High-resolution computed tomography (HRCT) Usual interstitial pneumonia (UIP) Nonspecific interstitial pneumonia (NSIP) Cryptogenic organizing pneumonia (COP) Respiratory bronchiolitis (RB) Respiratory bronchiolitis–interstitial lung disease (RB-ILD) Desquamative interstitial pneumonia (DIP) Lymphoid interstitial pneumonia (LIP)
Over 200 causes of interstitial lung disease have been described. Environmental and occupational exposures, systemic diseases, and genetic causes can all result in a variety of interstitial lung diseases. The idiopathic interstitial pneumonias (IIP) refer to a group of distinct clinicopathologic entities without known causes . Classification of IIP has undergone several iterations as understanding of these entities evolves [2, 3, 4]. The most common IIP is idiopathic pulmonary fibrosis (IPF), which accounts for approximately 40% of all idiopathic interstitial lung disease . While idiopathic forms do exist, the other IIPs more commonly result from exposures, such as tobacco smoke or connective tissue disease.
High-resolution computed tomography (HRCT) plays a key role in assessing the patient with known or suspected interstitial lung disease. While the primary function of HRCT is to distinguish patients with usual interstitial pneumonia (UIP), which is associated with IPF, from those without UIP, HRCT findings can often suggest other causes of diffuse lung disease. Although surgical biopsy is advocated in patients with suspected IIP who do not have a definite UIP pattern on HRCT, consensus between clinicians and radiologists with expertise in interstitial lung disease may suffice to establish a diagnosis.
Usual Interstitial Pneumonia
IPF is uncommon with an incidence of 6.8–16.3 per 100,000 persons in the USA . Men are affected twice as often as women, and the incidence increases with increasing age. While the exact cause of IPF remains unknown, environmental factors such as occupational dusts and fumes , cigarette smoke , and Epstein-Barr virus infection  may be contributory. Prognosis remains poor with fewer than 50% of patients surviving 5 years following diagnosis .
Studies have shown that the positive predictive value of a confident CT diagnosis of UIP by expert pulmonary radiologists ranges from 90 to 100%. However, these studies also show that a confidant diagnosis is not made in 25–50% of histologically proven cases of UIP [21, 22, 23, 24, 25, 26, 27]. Silva et al. demonstrated that the findings of basal honeycombing, the absence of subpleural sparing, and the absence of centrilobular nodules best distinguish UIP from chronic hypersensitivity pneumonitis and nonspecific interstitial pneumonia (NSIP) . CT findings that should suggest alternative etiologies include micronodules; air trapping; non-honeycomb cysts; consolidation; a peribronchovascular distribution of fibrosis, and significant pleural calcifications, plaques, or effusion .
Nonspecific Interstitial Pneumonia
Nonspecific interstitial pneumonia (NSIP) was first used to classify patients with interstitial lung disease and surgical biopsies not fitting into any well-defined histologic pattern . Currently, idiopathic NSIP is recognized as a distinct clinicopathologic entity associated with a better prognosis than IPF. Patients with idiopathic NSIP tend to be lifetime non-smoking females of Asian ethnicity . However, NSIP is most commonly associated with connective tissue disease such as systemic sclerosis or may be the sequela of a drug reaction.
While the HRCT findings of NSIP have proven to be more variable than was initially suggested [43, 44, 45, 46], the majority of cases have ground-glass opacities and findings of fibrosis including fine reticulation, traction bronchiectasis, and volume loss in a symmetric mid to lower lung distribution (Figs. 12.7, 12.8) [47, 48]. The severity and distribution of these parenchymal abnormalities are more uniform than in UIP. Distribution along the axial plane may be peripheral, peribronchovascular, or diffuse. When present and in the appropriate setting, a thin rim of subpleural sparing is a rather specific finding for NSIP and should heighten diagnostic confidence (Fig. 12.9) . As with IPF, mild mediastinal lymphadenopathy is common, particularly at the right paratracheal and subcarinal stations, and correlates with the degree of parenchymal involvement. Given the high association of NSIP with underlying collagen vascular diseases and other disorders, associated abnormalities may be sought on available imaging studies.
Although NSIP is characterized by two histologic subtypes, cellular and fibrotic, there are generally no imaging features to reliably distinguish between the two. As would be expected, reticulation is more commonly seen with fibrotic subtype, although the cellular subtype may also demonstrate fine reticulation. In our experience, a posterior basilar and anterior apical distribution of reticulation, when present in the appropriate setting, is relatively specific for the fibrotic subtype. However, with regard to the extent of ground-glass opacity, consolidation, or traction bronchiectasis, there is no reliable separation in CT findings between the two subtypes [10, 49, 50, 51].
Cryptogenic Organizing Pneumonia
Organizing pneumonia (OP) refers to the histologic pattern described as polypoid plugs of loose organizing connective tissue within the alveoli. This pattern may be idiopathic but is more commonly associated with one of numerous underlying etiologies, including connective tissue disease and drug reaction. Formerly termed bronchiolitis obliterans organizing pneumonia (BOOP), cryptogenic OP (COP) refers to an idiopathic clinical syndrome characterized by organizing pneumonia. The newer terminology reflects the primary histologic features while avoiding confusion with small airways disease (bronchiolitis). Patients with COP are often initially diagnosed with community acquired pneumonia, and further workup is often pursued after failure of antibiotic treatment.
Respiratory Bronchiolitis, Respiratory Bronchiolitis–Interstitial Lung Disease, and Desquamative Interstitial Pneumonia
Respiratory bronchiolitis (RB), RB-associated interstitial lung disease (RB-ILD), and desquamative interstitial pneumonia (DIP) are included in the most recent IIP classification despite being almost invariably associated with cigarette smoking. RB, RB-ILD, and DIP represent a spectrum of smoking-related interstitial lung disease characterized by the accumulation of pigmented macrophages in the respiratory bronchioles and alveoli . With RB, pigmented macrophages are limited primarily to the respiratory bronchioles whereas macrophage accumulation is more extensive with RB-ILD and diffuse in DIP. By definition, patients with RB are asymptomatic while those with RB-ILD and DIP may present with dyspnea, cough, and abnormal pulmonary function tests .
Acute Interstitial Pneumonia
If a patient with AIP recovers, consolidation and ground-glass opacities typically clear in a progressive fashion, while residual areas of reticulation and hypoattenuation remain, particularly in the nondependent lung .
Lymphoid Interstitial Pneumonia
Lymphoid interstitial pneumonia (LIP) is a rare diagnosis most commonly seen in patients with Sjögren syndrome. Additional associations include other connective tissue and autoimmune diseases as well as AIDS, the latter particularly in children. Despite being a lymphoproliferative disorder, LIP is included in the most recent classification system as an interstitial lung disease, given its inclusion in associated differential diagnoses of diffuse lung disease and its histologic pattern, which is characterized by a polyclonal lymphocytic and plasma cell infiltration of the alveolar septum .
In summary, HRCT is critical to evaluating patients with known or suspected diffuse lung disease. In patients with the appropriate clinical presentation, a highly confident diagnosis of UIP on HRCT is sufficient to establish a diagnosis of IPF. HRCT may also suggest the presence of other interstitial or diffuse lung diseases. Finally, consensus among the clinician, radiologist, and pathologist may be required to establish a diagnosis when the pieces of the diagnostic puzzle are not straightforward.
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