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(Chest. 2003;124:1199-1205.)
© 2003 American College of Chest Physicians

The Overlap Between Respiratory Bronchiolitis and Desquamative Interstitial Pneumonia in Pulmonary Langerhans Cell Histiocytosis*

High-Resolution CT, Histologic, and Functional Correlations

Robert Vassallo, MD; Eric A. Jensen, MD; Thomas V. Colby, MD, FCCP; Jay H. Ryu, MD, FCCP; William W. Douglas, MD; Thomas E. Hartman, MD and Andrew H. Limper, MD, FCCP

* From the Thoracic Diseases Research Unit, Division of Pulmonary, Critical Care and Internal Medicine (Drs. Vassallo, Ryu, and Douglas), the Department of Radiology (Drs. Jensen and Hartman), and the Department of Biochemistry and Molecular Biology (Dr. Limper), Mayo Clinic and Foundation, Rochester, MN; and the Division of Anatomic Pathology (Dr. Colby), Mayo Clinic, Scottsdale, AZ.

Correspondence to: Robert Vassallo, MD, Stabile Building 8-54, Mayo Clinic, Rochester, MN 55905; e-mail: vassallo.robert{at}mayo.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Objectives: To characterize the histologic, high-resolution CT (HRCT), and functional correlates of respiratory bronchiolitis (RB)/desquamative interstitial pneumonia (DIP)-like changes in biopsy specimens of adults with pulmonary Langerhans cell histiocytosis (PLCH).

Methods: We retrospectively identified 14 adult patients with histologically proven PLCH (all smokers) in whom both biopsy specimens and HRCT were available for review. The presence and extent of RB/DIP-like changes on lung biopsy specimens of patients with PLCH were correlated with total pack-years of smoking, lung function variables, and the presence of ground-glass attenuation on HRCT.

Results: Varying degrees of RB/DIP-like changes were identified in all biopsy specimens. The extent of involvement with RB/DIP-like changes correlated with the cumulative exposure to cigarettes smoked at the time of biopsy (r = 0.61, p = 0.03). Ground-glass attenuation was detected in three HRCTs, two of which had extensive RB/DIP-like changes (>= 70% involvement) on histology, suggesting that substantial smoking-induced RB/DIP-like changes may be the cause of ground-glass attenuation on the HRCT of patients with PLCH. No correlation was found between the extent of RB/DIP-like changes and total lung capacity, FEV1, or diffusion capacity of the lung for carbon monoxide.

Conclusions: RB/DIP-like changes are exceedingly common in PLCH, may be sufficiently severe to cause the appearance of ground-glass attenuation on HRCT, and correlate with the cumulative exposure to cigarettes smoked. This study provides additional evidence that PLCH, RB, and DIP form a spectrum of interstitial patterns of lung injury to cigarette smoke.

Key Words: cigarette smoking • desquamative interstitial pneumonia • interstitial lung disease • pulmonary Langerhans cell histiocytosis • respiratory bronchiolitis-associated interstitial lung disease


   Introduction
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 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon interstitial lung disorder that occurs almost exclusively in smokers.1 2 3 Cigarette smoking has also been implicated in the development of respiratory bronchiolitis (RB)-associated interstitial lung disease (ILD) [RB-ILD] and desquamative interstitial pneumonia (DIP), two uncommon ILDs with significant clinical and histopathologic overlap.4 5 6 7 These three ILDs are now often referred to as smoking-related ILDs, a term suggesting that PLCH, DIP, and RB-ILD may form a spectrum of patterns of interstitial lung injury that may occur in certain individuals who smoke.4 5 7 RB is a histologic lesion reported to occur in virtually all smokers.8 Since DIP is also etiologically linked to smoking, it is not unexpected that RB/DIP-like reactions frequently coexist in histologic specimens of PLCH, as reported in prior studies.1 9 However, very few studies describe the extent and clinical significance of RB/DIP-like changes on the lung biopsy and high-resolution CT (HRCT) of patients with PLCH. This descriptive retrospective study was prompted by the observation that in two individuals with histopathologically proven PLCH, chest HRCT demonstrated prominent ground-glass attenuation, accompanied with a marked RB/DIP-like reaction on the sampled lung tissue. This study was designed to identify the frequency and extent of RB/DIP-like changes in lung biopsy specimens of patients with PLCH, and correlate these findings with the HRCT and physiologic measures of lung function. We observed that RB/DIP-like changes were present in all PLCH biopsy specimens, and correlated with cumulative pack-years of cigarettes smoked, but did not correlate with measures of lung function. Of considerable interest is that in two patients, the extent of RB/DIP-like changes was very extensive, and was accompanied by ground-glass attenuation on HRCT.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
The medical record of two index patients with PLCH associated with marked RB/DIP-like changes on biopsy were reviewed and summarized. To further characterize the relationship between RB/DIP and PLCH, we searched the Mayo Clinic database and identified 10 additional cases for which both surgical lung biopsy specimens and HRCT scans were available for review. These 10 cases were part of a previously reported series.3 Patients with transbronchoscopic biopsy-proven PLCH were excluded from the study because the limited amount of tissue was believed to be inadequate for the purpose of the study. Two additional cases (with available lung biopsy and HRCT) were identified while conducting the study (during 1999). All lung biopsies were performed within 3 months of the CT scan. The diagnosis of PLCH was established by light microscopy in all cases. The use of immunostains in some cases was confirmatory but not considered necessary for the diagnosis. Immunostaining was utilized in four cases (all four positive for S-100 staining, and two were positive using both CD1a and S-100 immunostains). Electron microscopy was not utilized in any of the cases. A total of 14 patients were included in this study. The medical records were reviewed and data regarding smoking history, and results of pulmonary function testing (all performed in our laboratory using standard techniques) were recorded.10 All human studies were approved by the institutional review board.

All HRCT scans were reviewed in a blinded fashion by two radiologists (E.A.J. and T.E.H.), and scored to quantify various defined radiographic abnormalities including areas of ground-glass attenuation, cysts, and nodules. The severity of lesions were scored by a 0-to-3 point system (0 = absent, 1 = mild, 2 = moderate, 3 = severe involvement). When present, the distribution of the abnormalities such as adenopathy and emphysema was recorded. Surgical lung biopsy specimens were reviewed by a pathologist (T.V.C.) blinded to the findings on HRCT. Accumulation of pigmented macrophages in airspaces and around respiratory bronchioles was combined with more widespread airspace accumulation of macrophages (DIP-like change) as RB/DIP-like change. This score provided a rough quantification of the degree of airspace filling (both respiratory bronchiole and alveolar spaces) by macrophages. The extent of involvement of the biopsy by RB/DIP-like changes was classified by percentage (0 to 100%). A similar scoring system (0 to 100% involvement of biopsy) was used to quantify emphysema and alveolar septal fibrosis. The percentage estimates of RB/DIP-like changes and fibrosis were based on assessment of the total tissue area involved on all the tissue sections available for review. The fibrosis was considered to be related to PLCH when it was nodular or stellate in character, as is classic for PLCH. In many cases, Langerhans cells were present in these zones of fibrosis. Scarring was presumed to be related to RB/DIP when it was characterized by fine widening of alveolar septa with or without associated airspace enlargement The severity of cysts was scored by a 0-to-3 point system (0 = absent, 1 = mild, 2 = moderate, 3 = severe involvement).

To correlate findings between histology and HRCT, the extent of RB/DIP lesions observed on HRCT and histology were compared. Specifically, we wanted to define the frequency and extent of involvement of the biopsy specimens with RB/DIP, and correlate the extent and severity of RB/DIP-like changes with the presence of ground-glass attenuation on the HRCT. In addition, because RB/DIP are lesions associated with smoking, we correlated the extent of RB/DIP-like changes with total pack-years smoked at the time of biopsy. Correlations between the extent of RB/DIP-like changes (0 to 100% involvement of biopsy) and total pack-years smoked was performed using linear regression analysis and the Pearson correlation coefficient. Similarly, correlations between the extent of RB/DIP-like changes and pulmonary function variables total lung capacity [TLC], FEV1, and diffusion capacity of the lung for carbon monoxide [DLCO] was performed by linear regression and the Pearson correlation coefficient. Statistical analysis was performed using JMP software, version 4 (SAS Institute, Cary, NC) with p values < 0.05 considered statistically significant.


   Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Summary of the Two Index Cases
The first patient was a 52-year-old white woman (patient 1 in Tables 1 , 2 ) with a 70–pack-year smoking history referred for evaluation of dyspnea and cough. The pulmonary examination revealed bilateral end-inspiratory basal crackles. Pulmonary function testing revealed restriction, with a plethysmographically measured TLC of 70% predicted and a DLCO of 48% predicted (Table 1) . Chest HRCT demonstrated extensive areas of ground-glass attenuation bilaterally, most marked in the middle and upper lungs (Fig 1 , top). Tiny nodules were appreciated in the middle and upper lung zones. The provisional clinical diagnoses were of hypersensitivity pneumonitis, RB-ILD, or DIP. A videothoracoscopic biopsy of the right lower lobe demonstrated typical lesions of PLCH (detection of Langerhans cells confirmed by S-100 and CD1a immunostaining) associated with a marked DIP-like reaction in the surrounding lung parenchyma (Fig 1 , center and bottom). In spite of repeated attempts at smoking cessation, the patient was unable to quit, and did not appreciate any benefit from a trial of oral prednisone. In spite of continued smoking, her lung function stabilized and the patient declined any further specific therapy for her lung disease.


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  		Table 1. Summary of Smoking Histories, Histopathologic Findings, and Pulmonary Function Testing

 

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  		Table 2. HRCT Findings

 


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  		Figure 1. Top: HRCT of the first index patient showing bilateral areas of ground-glass attenuation with scattered nodules. Center: Scanning power microscopy shows diffuse moderate airspace filling by macrophages with patchy mild interstitial widening without definite nodules (hematoxylin-eosin). Bottom: Higher-power detail shows marked airspace filling by macrophages that have a faint tan pigmentation typical of smokers. The alveolar septa are widened with somewhat hyalinized eosinophilic-appearing fibrous tissue (hematoxylin-eosin).

 
The second patient (patient 2 in Tables 1 , 2 ) was a 48-year-old white man with a 30–pack-year smoking history referred for evaluation of progressive dyspnea. Although claiming to have quit smoking several months prior to evaluation, arterial blood gas analysis revealed a carbon monoxide concentration of 2%. The pulmonary examination revealed scattered bilateral basal crackles, and pulmonary function testing revealed a restrictive process with a plethysmographically measured TLC of 70% predicted and a DLCO of 55% predicted. HRCT of the chest demonstrated patchy areas of ground-glass attenuation in both lungs, believed to be most consistent with a diagnosis of hypersensitivity pneumonitis or RB-ILD. A videothoracoscopic biopsy of the right middle lobe demonstrated PLCH with prominent features of RB. The patient was treated with prednisone, 40 mg/d, but died of unrelated causes just weeks after the diagnosis was established.

Clinical and Radiographic Characteristics of the Study Population
The study population consisted of six men and eight women, with an average age of 49.3 years (Table 1) . All were either smokers at the time of diagnosis by lung biopsy or had quit smoking within the year preceding the lung biopsy (mean pack-years smoked at the time of diagnosis, 26.9; range, 1 to 70 pack-years). Results of pulmonary function testing (Table 1) were normal in three patients, revealed obstructive physiology in four patients (normal or increased TLC with an FEV1/FVC < 0.75), and restrictive physiology in seven patients (TLC < 80% of predicted). The DLCO was reduced (< 72% of predicted normal value) in seven patients (mean, 70.3%; range, 40 to 98%).

Lung nodules were the most frequent finding on HRCT (Table 2) , occurring in combination with cystic abnormalities in five cases, and in the absence of cystic change in six cases. Cystic change was identified as the sole HRCT abnormality in three cases. Ground-glass attenuation was detected on HRCT in three patients (Table 2) . Emphysema was detected in two cases on HRCT (14%). Mild subcarinal and pretracheal adenopathy (1 to 2 cm) was detected on the CT in three cases (21%).

Radiographic, Histologic, and Functional Correlates of RB/DIP in PLCH in the Study Population
All biopsy specimens showed diagnostic lesions of PLCH. Histopathologic evidence of RB/DIP-like changes were identified in all biopsy specimens (Table 1) , with the extent of involvement ranging from 10 to 80% of the biopsy specimen. Separate review of chest HRCTs identified three cases with ground-glass attenuation in a random distribution (Table 2) , two of which were found to have extensive RB/DIP-like changes (70 to 80%) on histologic examination, indicating that in these cases, the presence of extensive associated RB/DIP-like changes may have resulted in the radiographic appearance of ground-glass attenuation. The provisional diagnosis (and differential) based on the HRCT findings in these three cases associated with ground-glass attenuation did not include PLCH but favored hypersensitivity pneumonitis (Table 2) . Although several cases demonstrated moderate-to-extensive (> 60%) RB/DIP-like changes on biopsy (Table 1) , ground-glass attenuation was detected in only two of these cases and another case with mild (20%) histologic involvement.

Data regarding cumulative pack-years smoked at the time of lung biopsy were available from 13 patients. The cumulative amount of pack-years smoked at the time of diagnosis correlated with the extent of RB/DIP-like changes scored by the pathologist (Fig 2 ; r = 0.61, p = 0.027). A strong positive correlation was also found between the cumulative pack-years of cigarettes smoked and the extent of alveolar septal fibrosis detected on biopsy specimens (r = 0.86, p = 0.001). No correlation was found between the degree of RB/DIP-like changes and pulmonary function parameters, including TLC (r = - 0.22, p = 0.45), DLCO (r = - 0.42, p = 0.13), or FEV1 (r = 0.11, p = 0.71). Although both index patients had restrictive impairment on lung function testing, the extent of RB/DIP-like changes on biopsy did not correlate with the presence or absence of restrictive physiology in the whole group (Table 1) .



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  		Figure 2. Correlation of cumulative pack-years smoked at the time of lung biopsy with the extent of RB/DIP-like change.

 

   Discussion
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Although smoking is associated with COPD and lung cancer, the link between smoking and certain ILDs is less well recognized. Cigarette smoking causes a variety of nonneoplastic histologic and radiographic changes in the lung (Fig 3 ).7 11 12 13 In some smokers, combinations of these patterns of injury can be identified in the same individual, as demonstrated in this study (Fig 3) . Smoking-related ILD is a term used to describe the relationship between RB-ILD, DIP, and PLCH as interstitial disorders that are etiologically linked to cigarette smoking.5 Our study provides additional insight into the overlap between these diseases, demonstrating that in biopsy-proven PLCH, coexistent RB/DIP-like abnormalities are ubiquitous, and correlate with the amount of cigarettes consumed. In addition, we demonstrate that in some individuals, the extent of RB/DIP injury on lung biopsy may be very extensive, cause ground-glass attenuation on HRCT, and result in radiographic patterns that are suggestive of alternative diagnoses.



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  		Figure 3. Nonproportional Venn diagram illustrating the spectrum of airways and interstitial injury associated with cigarette smoking. The larger outer circle represents the virtually universal occurrence of RB in smokers. Emphysema will develop in approximately 20% of these smokers during their lifetime. ILD will develop in a small proportion of smokers due to DIP or PLCH. In a significant proportion of those in whom DIP or PLCH develops (or overlaps of both), there is accompanying emphysema (as in the current series). RB-ILD develops when a smoker has an exaggerated RB reaction associated with ILD.

 
Several descriptive histopathologic studies1 9 14 15 document the association of nonspecific DIP-like changes in biopsy specimens of patients with PLCH. It is generally accepted that a diagnosis of DIP is made following the systematic exclusion of other lung diseases that may be accompanied by such a DIP-like reaction.8 Similarly, the discovery of RB on lung biopsy is not equivalent to a diagnosis of RB-ILD. Whereas RB is an extremely common lesion that refers to the universal inflammatory reaction found in the respiratory bronchioles of cigarette smokers,8 16 17 RB-ILD is an uncommon ILD that occurs in a small proportion of smokers.8 17 In analogy to DIP, the diagnosis of RB-ILD can only be made following careful exclusion of other histologic entities that may explain the presence of ILD.8

What then is the clinical significance of determining RB/DIP-like changes on PLCH biopsy specimens? Although in the majority of patients with PLCH, the presence of associated RB/DIP-like changes is of little significance other than reflecting prior exposure to cigarette smoke, the current study suggests that occasionally, the extent of RB/DIP-like changes may be sufficiently severe to cause substantial interstitial thickening and partial alveolar filling to cause the appearance of ground-glass attenuation on the CT. Although uncommon, this observation has important diagnostic implications. As stated previously, in spite of the presence of RB- and DIP-like changes on lung biopsy specimens, one does not establish a diagnosis of DIP or RB-ILD in the presence of other distinct histopathologic lesions such as PLCH. Thus, traditionally, one would not consider these patients to have two diseases, ie, DIP or RB-ILD, and PLCH, but rather call this PLCH with prominent features of respiratory bronchiolitis or DIP-like changes. This is analogous to the demonstration that although a proportion of patients with usual interstitial pneumonia have areas of nonspecific interstitial pneumonia in different lobes, the lesion of usual interstitial pneumonia takes precedence as the principal diagnosis because it is this lesion that determines the outcome and prognosis.18 The relative role of RB/DIP-like changes and PLCH lesions to the physiologic and functional impairment seen in these patients is not clear. Our study suggests that in some individuals with PLCH, extensive RB/DIP-like changes may be the lesion responsible for the majority of physiologic and clinical abnormalities, rather than the lesions of PLCH. Irrespective of how one defines the final pathologic lesion, it is clear that the entire spectrum of smoking-related interstitial lung injury may be sometimes seen in the same patient, albeit to different degrees (Fig 3) .

Several studies have illustrated the utility of HRCT in the diagnostic workup of PLCH.19 20 This study and others5 21 illustrate the overlap between different radiologic patterns of smoking-induced interstitial patterns of injury, and the need for caution in establishing a diagnosis of these diseases without lung biopsy. We report the occurrence of ground-glass attenuation on HRCT, which may be indicative of significant associated RB/DIP. The only other study describing the presence of ground-glass attenuation in patients with PLCH is the one by Brauner et al,19 who reported the occurrence of ground-glass attenuation in 4 of 18 patients with PLCH. Although we identified 3 cases in the current series of 14, retrospective review of our database of PLCH cases indicates that ground-glass attenuation is an uncommon finding. In our database, we identified an additional 34 patients with PLCH who underwent CT in the diagnostic workup: 15 patients had HRCT alone for diagnosis, and 19 patients had HRCT and biopsy but radiographs and/or biopsy specimens were unavailable for review. Of this additional group of patients, only one patient was originally reported to have ground-glass attenuation (open-lung biopsy-confirmed PLCH). Thus, ground-glass attenuation is probably an uncommon radiographic manifestation in patients with PLCH.

In conclusion, the current study confirms that RB/DIP-like changes are exceedingly common in patients with PLCH, and are a reflection of lung injury associated with cigarette smoking. Some patients with PLCH have a marked component of RB/DIP-like changes, which may be associated with ground-glass attenuation on CT. Ground-glass attenuation and mild adenopathy are radiographic findings that may occur in PLCH and cause diagnostic difficulty. This study provides further evidence that smoking can cause the whole spectrum of RB, DIP, and PLCH in predisposed individuals.


   Footnotes
 
Abbreviations: DIP = desquamative interstitial pneumonia; DLCO = diffusion capacity of the lung for carbon monoxide; HRCT = high-resolution CT; ILD = interstitial lung disease; PLCH = pulmonary Langerhans cell histiocytosis; RB = respiratory bronchiolitis; RB-ILD = respiratory bronchiolitis-associated interstitial lung disease; TLC = total lung capacity

Funded by Mayo Clinic funds and the Robert N. Brewer Family Foundation funds.

Received for publication November 27, 2002. Accepted for publication March 28, 2003.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Travis, WD, Borok, Z, Roum, JH, et al (1993) Pulmonary Langerhans cell granulomatosis (histiocytosis X): a clinicopathologic study of 48 cases. Am J Surg Pathol 17,971-986[ISI][Medline]
  2. Vassallo, R, Ryu, JH, Colby, TV, et al Pulmonary Langerhans’-cell histiocytosis. N Engl J Med 2000;342,1969-1978[Free Full Text]
  3. Vassallo, R, Ryu, JH, Schroeder, DR, et al Clinical outcomes of pulmonary Langerhans’-cell histiocytosis in adults. N Engl J Med 2002;346,484-490[Abstract/Free Full Text]
  4. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 2002;165,277-304[Free Full Text]
  5. Moon, J, du Bois, RM, Colby, TV, et al Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease. Thorax 1999;54,1009-1014[Abstract/Free Full Text]
  6. Yousem, SA, Colby, TV, Gaensler, EA Respiratory bronchiolitis-associated interstitial lung disease and its relationship to desquamative interstitial pneumonia. Mayo Clin Proc 1989;64,1373-1380[ISI][Medline]
  7. Ryu, JH, Colby, TV, Hartman, TE, et al Smoking-related interstitial lung diseases: a concise review. Eur Respir J 2001;17,122-132[Abstract/Free Full Text]
  8. Fraig, M, Shreesha, U, Savici, D, et al Respiratory bronchiolitis: a clinicopathologic study in current smokers, ex-smokers, and never-smokers. Am J Surg Pathol 2002;26,647-653[CrossRef][ISI][Medline]
  9. Friedman, PJ, Liebow, AA, Sokoloff, J Eosinophilic granuloma of lung: clinical aspects of primary histiocytosis in the adult. Medicine (Baltimore) 1981;60,385-396[Medline]
  10. Lung function testing: selection of reference values and interpretative strategies. American Thoracic Society. Am Rev Respir Dis 1991;144,1202-1218[ISI][Medline]
  11. Aubry, MC, Wright, JL, Myers, JL The pathology of smoking-related lung diseases. Clin Chest Med 2000;21,11-35,vii[CrossRef][ISI][Medline]
  12. Mastora, I, Remy-Jardin, M, Sobaszek, A, et al Thin-section CT finding in 250 volunteers: assessment of the relationship of CT findings with smoking history and pulmonary function test results. Radiology 2001;218,695-702[Abstract/Free Full Text]
  13. Remy-Jardin, M, Edme, JL, Boulenguez, C, et al Longitudinal follow-up study of smoker’s lung with thin-section CT in correlation with pulmonary function tests. Radiology 2002;222,261-270[Abstract/Free Full Text]
  14. Colby, TV, Lombard, C Histiocytosis X in the lung. Hum Pathol 1983;14,847-856[ISI][Medline]
  15. Housini, I, Tomashefski, JF, Jr, Cohen, A, et al Transbronchial biopsy in patients with pulmonary eosinophilic granuloma: comparison with findings on open lung biopsy. Arch Pathol Lab Med 1994;118,523-530[ISI][Medline]
  16. Niewoehner, DE, Kleinerman, J, Rice, DB Pathologic changes in the peripheral airways of young cigarette smokers. N Engl J Med 1974;291,755-758[ISI][Medline]
  17. Myers, JL, Veal, CF, Jr, Shin, MS, et al Respiratory bronchiolitis causing interstitial lung disease: a clinicopathologic study of six cases. Am Rev Respir Dis 1987;135,880-884[ISI][Medline]
  18. Flaherty, KR, Travis, WD, Colby, TV, et al Histopathologic variability in usual and nonspecific interstitial pneumonias. Am J Respir Crit Care Med 2001;164,1722-1727[Abstract/Free Full Text]
  19. Brauner, MW, Grenier, P, Mouelhi, MM, et al Pulmonary histiocytosis X: evaluation with high-resolution CT. Radiology 1989;172,255-258[Abstract/Free Full Text]
  20. Bonelli, FS, Hartman, TE, Swensen, SJ, et al Accuracy of high-resolution CT in diagnosing lung diseases. AJR Am J Roentgenol 1998;170,1507-1512[Abstract/Free Full Text]
  21. Heyneman, LE, Ward, S, Lynch, DA, et al Respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, and desquamative interstitial pneumonia: different entities or part of the spectrum of the same disease process? AJR Am J Roentgenol 1999;173,1617-1622[Abstract]



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