HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Michael E. Halkos Faraz Kerendi Daniel L. Miller Joseph I. Miller, Jr Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Halkos, M. E. Articles by Miller, J. I. Search for Related Content PubMed PubMed Citation Articles by Halkos, M. E. Articles by Miller, J. I., Jr Related Collections Lung - other

Ann Thorac Surg 2005;79:2172-2179
© 2005 The Society of Thoracic Surgeons

---

Review

Role of Thoracic Surgeons in the Diagnosis of Idiopathic Interstitial Lung Disease

^a Section of General Thoracic Surgery, Joseph B. Whitehead Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA
^b Department of Laboratory Medicine and Anatomic Pathology, Emory University School of Medicine, Atlanta, Georgia, USA

^_* Address reprint requests to Dr Miller, Division of Cardiothoracic Surgery, Emory Crawford Long Hospital, Medical Office Tower, 6th Floor, 550 Peachtree St, Atlanta, GA 30308 (E-mail: jmille6331{at}aol.com).

	Abstract

Top Abstract Introduction Material and Methods Idiopathic Interstitial... Indications for Surgical Biopsy Biopsy Methods Open Versus Thoracoscopic Biopsy Conclusions References

 
The interstitial lung disorders are a heterogenous group of pulmonary disorders in which the interstitium is the predominant tissue type involved in the disease process. The idiopathic interstitial pneumonias represent a subgroup of these disorders that can be distinguished by unique clinical, radiologic, and pathologic features. Recent changes have been made in the classification system, with important distinctions between idiopathic pulmonary fibrosis and the other idiopathic interstitial pneumonias. Surgical lung biopsy remains the gold standard for diagnosis. However, controversy exists regarding the methods and indications for biopsy. In this article, we review the salient clinical, radiologic, and pathologic features of these unique disorders as well as the updated classification scheme. We also discuss the current methods, approaches, and indications for biopsy.

	Introduction

Top Abstract Introduction Material and Methods Idiopathic Interstitial... Indications for Surgical Biopsy Biopsy Methods Open Versus Thoracoscopic Biopsy Conclusions References

 
Interstitial lung disease (ILD) represents a broad spectrum of pulmonary disorders that are characterized by varying degrees of inflammation and fibrosis. These nonneoplastic disorders primarily affect the interstitium, although the alveoli, bronchial airways, and pulmonary vasculature can be involved. Emphysema, chronic obstructive pulmonary disease, and pulmonary hypertension represent the more common lung diseases and are usually considered separately from interstitial lung disorders.

Pulmonary disorders associated with environmental exposures, drugs, or autoimmune diseases, those with unknown etiology including granulomatous disorders such as sarcoidosis, and certain rare parenchymal diseases such as Langerhans’ cell histiocytosis and lymphangioleiomyomatosis, each display unique clinicopathologic features and can often be diagnosed with minimally invasive approaches in lieu of videothoracoscopic or open biopsy. The idiopathic interstitial pneumonias (IIP), however, represent a subgroup of ILD in which the etiology is unknown, yet they can be separated from the other interstitial disorders by available clinical, radiologic, and pathologic methods.

Since the original classification of the idiopathic interstitial pneumonias by Liebow and Carrington [1], there has been much controversy over the histologic patterns and the clinicoradiologic features of these disorders. Recently, the American Thoracic Society and the European Respiratory Society [2] proposed an international consensus statement defining the clinical manifestations, radiologic features, and pathologic characteristics of the IIPs in an attempt to standardize the classification of these disorders into individual clinicopathologic entities (Fig 1): idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), acute interstitial pneumonia (AIP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated interstitial lung disease (RBILD), and lymphocytic interstitial pneumonia (LIP). Although this classification system standardizes the diagnostic and treatment approaches of the IIPs, achieving an accurate diagnosis requires a multidisciplinary approach on the part of the clinician, radiologist, and pathologist.

View larger version (21K): [in this window] [in a new window]   Fig 1. Diffuse parenchymal lung disease (DPLD) represents a spectrum of disorders including those associated with known and unknown etiology. The latter includes the idiopathic interstitial pneumonias (IIP), granulomatous disorders, and rare diffuse parenchymal diseases such as lymphangioleiomyomatosis (LAM), Langerhans’ cell histiocytosis, and eosinophilic pneumonia. The IIPs can be divided into the more common idiopathic pulmonary fibrosis (IPF) and the non-IPF interstitial pneumonias. (UIP = usual interstitial pneumonia.) (Adapted from Travis WD, et al, Am J Respir Crit Care Med; 2002;165;277–304 [2], with permission.)

Nonetheless, surgical biopsy remains the most sensitive and specific diagnostic approach for patients with interstitial lung diseases and should be performed whenever a confident diagnosis cannot be obtained from available clinical and radiologic information [2, 4, 8–13]. In this review, we will highlight the key clinical, radiologic, and pathologic features of the IIPs and evaluate the current surgical methods and indications for obtaining lung biopsies in patients afflicted with these conditions.

	Material and Methods

Top Abstract Introduction Material and Methods Idiopathic Interstitial... Indications for Surgical Biopsy Biopsy Methods Open Versus Thoracoscopic Biopsy Conclusions References

 
MEDLINE was used to conduct a literature search for articles on interstitial lung disease from 1965 to 2004. Keywords used included interstitial lung disease, interstitial lung disorders, idiopathic interstitial lung disorders, diffuse parenchymal lung diseases, and idiopathic interstitial pneumonias. A search on biopsy methods and indications for interstitial lung disease was also performed using the keywords lung biopsy, video-assisted thoracic surgery, minimally invasive thoracic surgery, and biopsy and interstitial lung disease. The idiopathic interstitial pneumonias are defined according to the latest classification scheme (2002) by the American Thoracic Society and the European Respiratory Society [2].

	Idiopathic Interstitial Pneumonias

Top Abstract Introduction Material and Methods Idiopathic Interstitial... Indications for Surgical Biopsy Biopsy Methods Open Versus Thoracoscopic Biopsy Conclusions References

 
Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is the most common IIP. Historically, the clinical diagnosis of IPF included different histologic patterns such as desquamative interstitial pneumonia (DIP), usual interstitial pneumonia (UIP), and nonspecific interstitial pneumonia (NSIP), but the current general consensus is that UIP is the histologic pattern that correlates with IPF [6]. When UIP is the only histopathologic pattern seen on multiple biopsy samples, it is termed concordant UIP. UIP can occur in conjunction with NSIP, referred to as discordant UIP, when multiple biopsies are taken, but these patients have long-term outcomes that mimic those with concordant UIP [14–16].

The clinical hallmarks of IPF include an insidious onset of nonproductive cough and progressive dyspnea, diffuse interstitial infiltrates on chest roentgenograms, restrictive physiology (reduced vital capacity with a normal or increased forced expiratory volume in 1 second/forced vital capacity [FEV₁/FVC] ratio), and impaired gas exchange (decreased diffusing capacity of the lung for carbon monoxide) on pulmonary function studies. For a diagnosis of IPF to be considered, the known causes of ILD need to be excluded, such as drug or occupational exposures, granulomatous diseases, or collagen vascular disorders.

Typically, the appearance of IPF on HRCT (Fig 2) is one of patchy, subpleural, peripheral, bibasilar, and reticular abnormalities with a predominant pattern of fibrosis rather than ground glass opacification [6, 17]. With more severe disease, subpleural honeycombing and traction bronchiectasis develop. Key histologic features include fibrosis with honeycombing, architectural distortion, and patchy peripheral distribution, with the most important feature being the presence of localized regions of fibroblastic proliferation, termed fibroblastic foci (Fig 3A and B). These can be identified adjacent to regions of established fibrosis, characterized by acellular dense collagen accumulation [7, 18, 19]. This pattern of temporal heterogeneity helps distinguish UIP from the other IIPs [2].

View larger version (120K): [in this window] [in a new window]   Fig 2. With idiopathic pulmonary fibrosis, high-resolution computed tomography shows bibasilar and peripheral predominant reticular abnormalities, with traction bronchiectasis and honeycombing associated with more advanced fibrosis.

View larger version (129K): [in this window] [in a new window]   Fig 3. (A) The typical histologic pattern of usual interstitial pneumonia/idiopathic pulmonary fibrosis is one of fibrosis with honeycombing, architectural distortion, and patchy peripheral distribution (5x magnification). (B) Key features of usual interstitial pneumonia (UIP) include the presence of fibroblastic foci (arrow) which represent areas of active inflammation adjacent to areas of established fibrosis characterized by acellular dense collagen accumulation. This pattern of temporal heterogeneity distinguishes UIP from the other idiopathic interstitial pneumonias (25x magnification).

Although immunosuppressive agents are used in the treatment of IPF, the clinical trials to date have failed to show a significant survival advantage with either corticosteroids, cyclophosphamide, colchicine, azathioprine, or a combination of these agents [24–26]. New therapeutic options such as interferon -1b have shown promise in patients with early stage disease [27], but larger clinical trials are needed before this therapy can be adopted for this subset of IPF patients [28].

Nonspecific Interstitial Pneumonia
In 1994 Katzenstein and Fiorelli [29] described a subset of patients diagnosed with IIP whose histologic patterns on surgical lung biopsy samples did not correlate with previously established pathologic criteria. Although NSIP was initially intended to indicate a histologic pattern with a variety of etiologies, it is now identified as a separate form of IIP, even though the clinical features may mimic the other IIPs [29]. Efforts to determine whether the histologic pattern of NSIP represents a true clinical entity rather than a broad spectrum of the IIPs are currently under debate [14]. However, several studies have documented that patients with NSIP respond better to treatment and survive longer than those with patterns of UIP [14–16, 20, 29, 30].

The clinical features of NSIP overlap with IPF with gradual onset of dyspnea and cough, but the physiologic abnormalities are usually milder and patients generally present a decade earlier [2, 29, 31]. The histologic exam may show a cellular or fibrotic pattern, with the fibrotic pattern being associated with a worse prognosis, although both forms are associated with better survival compared with UIP [2]. In contrast to UIP, the histologic pattern of NSIP is defined by a more uniform anatomic distribution of fibrosis and inflammation, with an absence of temporal heterogeneity or honeycombing (Fig 4). On HRCT, the diagnosis of NSIP may often be mistaken as IPF or other IIPs, although there may be more ground glass opacification than with UIP [17].

View larger version (149K): [in this window] [in a new window]   Fig 4. Nonspecific interstitial pneumonia can be distinguished by a temporally uniform organized pattern of fibrosis, with minimal honeycombing and absent fibroblastic foci (5x magnification).

Cryptogenic Organizing Pneumonia
In patients suspected of idiopathic interstitial lung disease, COP enters the differential diagnosis when other causes of organizing pneumonia can be excluded. Although initially referred to synonymously as idiopathic bronchiolitis obliterans-organizing pneumonia, COP is the preferred term because it lessens the likelihood of being mistakenly grouped in the same category as constrictive obliterative bronchiolitis [2], which is a common injury pattern of lung and bone marrow transplant patients.

COP has a different clinical picture than the other IIPs, because it is associated with a subacute onset of illness of relatively short duration that may mimic an infectious pneumonia, is responsive to steroid treatment, and is associated with an overall favorable prognosis, although disease recurrence is common after cessation of steroid therapy [2, 32, 33]. Histologically, COP is characterized by a patchy process of organizing pneumonia, with the involved alveoli and bronchioles being filled by intraluminal polyps of fibroblastic tissue and with most of the changes occurring in the small airways [32]. HRCT usually shows patchy areas of air space consolidation with a subpleural or peribronchial distribution, ground glass attenuation, and the presence of small nodules [2, 17, 33]. Achieving a diagnosis of COP requires the exclusion of other more common causes of organizing pneumonia, including hypersensitivity pneumonitis or infectious pneumonia.

Acute Interstitial Pneumonia
Formerly known as Hamman-Rich disease, AIP is characterized by a rapidly progressive and often fulminant form of interstitial pneumonia [2, 34]. Histologically, AIP takes the form of diffuse alveolar damage that is seen in patients with acute respiratory distress syndrome (ARDS) [34]. As such, most AIP patients usually meet the physiologic criteria for ARDS. It is distinguished by its lack of association from the known causes of ARDS; therefore, this term is reserved for cases that are idiopathic in nature.

Patients typically present with acute onset of respiratory failure and hypoxemia that requires mechanical ventilation. CT features include extensive ground glass opacification with random areas of focal consolidation [17]. Biopsy specimens show prominent hyaline membranes in the proliferative phase and type II pneumocyte hyperplasia and fibroblast proliferation in the organizing phase. Unfortunately, mortality rates exceed 50% and treatment is usually supportive [2].

Respiratory Bronchiolitis-Associated Interstitial Lung Disease
RBILD is a term given to those patients with clinical manifestations of interstitial lung disease that show respiratory bronchiolitis on biopsy [35, 36]. Exclusively a disease of heavy cigarette smokers, the pathologic changes of respiratory bronchiolitis are usually present in asymptomatic smokers [7, 37]. However, on the rare occasion that it presents as a form of interstitial lung disease, the disorder is defined as RBILD. Because other respiratory diseases are directly attributable to cigarette smoking, RBILD may be an incidental finding in the context of other forms of lung disease. Therefore, careful correlation of clinical, radiologic, and pathologic data is necessary to ensure an appropriate diagnosis.

The disease usually presents in current smokers in the fourth or fifth decade of life, with progressive dyspnea and a chronic cough [7, 38]. Histologically, RBILD can be distinguished from DIP, another smoking-related IIP, by centriacinar distribution of alveolar macrophages within the respiratory bronchioles instead of a diffuse intraalveolar distribution seen in DIP [32]. However, RBILD and DIP may display similar histopathologic patterns, and the pathologic diagnosis is somewhat arbitrary, making clinical and radiologic features important in the diagnosis [39]. CT findings include subtle ground glass attenuation, centrilobular nodules, and fine linear reticulations [17]. Upon smoking cessation, most patients either improve or remain stable [35, 36].

Desquamative Interstitial Pneumonia
DIP was originally believed to be caused by desquamation of epithelial cells within the alveolus [1]. This term remains controversial because it has been referred to as a precursor to UIP [7] and as a more severe form of RBILD [35, 36]. Similar to RBILD, DIP usually presents in heavy cigarette smokers during the fourth or fifth decade with similar albeit more severe symptoms. On histology, large numbers of macrophages with a diffuse distribution are present within the alveoli [32]. In contrast to RBILD, ground glass attenuation or consolidation and lower lobe involvement is more prominent on CT [2, 40]. Moreover, as RBILD is a disease almost exclusively of smokers, cases of DIP attributable to environmental or drug exposures have been reported in nonsmokers [41, 42]. The prognosis for patients with DIP is generally good, with most patients improving with corticosteroid therapy [42].

Lymphocytic Interstitial Pneumonia
Idiopathic LIP is a rare interstitial lung disorder characterized by diffuse interstitial pulmonary lymphoid hyperplasia. The interstitial lymphocytic infiltrate is usually more severe than that found with cellular NSIP, although this similarity can lead to misdiagnosis [32, 43]. Initially thought to represent a precursor to lymphoma, improvements in molecular analysis and immunohistochemistry have successfully differentiated this histologic pattern from the neoplastic lymphoproliferative disorders [32]. More often than not, LIP is associated with systemic or autoimmune disorders [2, 7, 32] that allow its exclusion from the IIPs; therefore, cases of LIP must be thoroughly investigated to rule out other known causes or associations. Clinical and radiologic presentations mimic those of the other more common IIPs, making histopathologic assessment a requirement.

	Indications for Surgical Biopsy

Top Abstract Introduction Material and Methods Idiopathic Interstitial... Indications for Surgical Biopsy Biopsy Methods Open Versus Thoracoscopic Biopsy Conclusions References

 
Before a patient with ILD undergoes surgical lung biopsy, a thorough clinical assessment should be performed to exclude disorders in which a diagnosis can be achieved with noninvasive methods. Patients with ILD usually present with exertional dyspnea, interstitial infiltrates on chest roentgenograms, and physiologic restrictive deficits on pulmonary function studies. A careful history may reveal recent environmental or drug exposure, a familial predisposition toward inherited interstitial lung disorders, immunodeficiency states with pulmonary manifestations, and extrapulmonary symptoms that may suggest systemic autoimmune disorders.

A transbronchial lung biopsy may be useful for excluding sarcoidosis, infection, or malignancy but provides inadequate tissue sampling for the IIPs [44]. Similarly, a transthoracic needle biopsy usually results in insufficient tissue sampling, with unacceptable diagnostic accuracy as a consequence [42].

In addition to providing a definitive diagnosis from histopathologic assessment, it is imperative to consider the impact that a surgical lung biopsy will have on treatment options and overall outcome. Patients with end-stage pulmonary fibrosis may derive little benefit from a biopsy, since the histologic changes seldom point to a specific underlying etiology. Furthermore, these debilitated patients may be at higher risk for complications from general anesthesia and surgery than those with better functional status [3, 4]. Therefore, patients who are referred for biopsy should be carefully evaluated for preoperative risk factors that may outweigh any potential benefit that can be derived from histopathologic diagnosis.

With the advent of HRCT, several reports have questioned the value of surgical lung biopsy in patients with typical clinical and radiologic features of IPF. Two recent reports highlight the value of surgical lung biopsy for patients in whom a confident clinical or radiologic diagnosis cannot be achieved.

Hunninghake and colleagues [11] analyzed the accuracy of clinical and radiologic diagnosis in patients with suspected IPF. A confident diagnosis of IPF could be made in only 58% of patients when available clinical and radiographic data were used. Of these patients, the radiologists and pulmonologists were accurate in 90% and 77% of cases, respectively. However, the overall accuracy, which included those without a confident clinical diagnosis, was only 75% for the radiologists and 77% for the pulmonologists. The authors concluded that a biopsy might not be necessary for patients in whom a confident clinical diagnosis for IPF can be made, but that a biopsy was indicated in those patents with non-IPF suspected ILD and in those in whom a confident clinical diagnosis could not be made.

Raghu and associates [12] reported that the accuracy of a clinical diagnosis of IPF was 62%, while the radiologic diagnosis was accurate in only 76% of patients. They concluded that a diagnosis of IPF would be missed in nearly one third of new-onset IPF cases despite careful clinical and radiologic evaluation.

Although these studies documented a high specificity of both clinical and radiologic diagnosis, the sensitivity was less than 80%. Clearly, the diagnosis of IPF can be made without a surgical biopsy specimen in some patients that present with classic clinical and radiologic features of IPF, but surgical lung biopsy remains an important tool for the accurate diagnosis of patients with ILD [13]. Furthermore, as new therapeutic agents become available for patients with IIP, an accurate pathologic diagnosis is necessary to determine the true efficacy of these novel agents in clinical trials.

	Biopsy Methods

Top Abstract Introduction Material and Methods Idiopathic Interstitial... Indications for Surgical Biopsy Biopsy Methods Open Versus Thoracoscopic Biopsy Conclusions References

 
Almost all patients referred for a surgical lung biopsy have been evaluated with preoperative HRCT. These images serve as a guide for the surgeon to sample active areas of disease while avoiding lung segments with end-stage nonspecific fibrosis that provide limited diagnostic value [8, 45]. A biopsy of localized fibrotic areas should be avoided since these changes can mimic UIP and mislead the pathologist to diagnose UIP instead of an isolated scar. In addition, the thoracic surgeon must be acutely aware of air leak control and use available methods, including sealants and bovine reinforcement strips, as may be deemed necessary. It is imperative that prolonged air leaks be prevented. To avoid macerating the tissue to be excised, it should be only minimally handled with either tissue forceps or small lung clamps.

The optimal size, site, and sample number to ensure adequate tissue sampling for diagnostic purposes remain controversial. Gaensler and Carrington [8], as well as Newman and colleagues [46], maintained that the lingula and middle lobe tip be avoided because it may over-represent the extent of fibrosis and vasculopathy. Others [3, 47–50] have found that specimens from lingular and middle lobe biopsies provide similar diagnostic yield compared with other lung segments. Nonetheless, the site of the biopsy should represent an area of active disease adjacent to grossly normal lung with care taken to avoid those areas of greatest involvement such as advanced honeycombing fibrosis. If the lingula is the preferred site for the biopsy, ILD should be diffuse so that this sample represents disease processes in other segments of the lung.

Other authors [44] remain cautious about the utility of lingular biopsy for interstitial lung disease because of the different pathologic processes that may occur in this portion of the lung. We believe that dialogue between the surgeon, radiologist, pulmonologist, and pathologist is crucial regarding the appropriate areas in which to perform the biopsy, especially in nonuniform disease.

Regarding the number of samples taken, Flint and associates [51] concluded that a single (> 2 cm diameter) specimen obtained from a region of the most radiographically involved lobe provided adequate tissue for diagnostic purposes. Qureshi and colleagues [3] reported no significant improvements in diagnostic accuracy when multiple biopsy samples were obtained, yet recommended more than one sample when feasible. However, several authors contend that multiple biopsy samples increase the odds that a specific diagnosis can be achieved [8, 44, 45, 52]. Both Qureshi [3] and Vidone [53] recommend two to three biopsy samples of approximately 3 x 2 x 1 cm³.

We believe that adequate samples from two different lobes (excluding the lingula or right middle lobe) from areas of visually and radiographically active disease, in addition to less involved or normal appearing areas adjacent to or remote from sites of active disease, enable the pathologist to achieve the highest diagnostic yield. If these criteria can be fulfilled from a single large biopsy specimen instead of multiple smaller samples, then an accurate pathologic diagnosis can probably be accomplished. The surgical exposure for a lung biopsy may play a role in the ability to obtain multiple biopsy samples from different lobes.

	Open Versus Thoracoscopic Biopsy

Top Abstract Introduction Material and Methods Idiopathic Interstitial... Indications for Surgical Biopsy Biopsy Methods Open Versus Thoracoscopic Biopsy Conclusions References

 
Patients referred for a surgical lung biopsy have traditionally required a thoracotomy for surgical exposure; however, the emergence of video-assisted thoracic surgery (VATS) has provided a valuable alternative to the standard open lung biopsy. In retrospective studies, VATS has been associated with lower postoperative analgesic requirements [54–59], shorter hospital stay [54, 56], less blood loss [56–58], and shorter duration of chest tube drainage [54]. Moreover, in these studies and others [60–62], diagnostic accuracy and specimen adequacy were comparable to open lung biopsy. These studies, however, are limited by their retrospective nature and lack of randomization. In a recent randomized controlled trial comparing thoracoscopy with limited thoracotomy, Miller and colleagues [63] reported no significant differences in postoperative analgesic requirements, operative time, duration of chest tube drainage, length of stay, or complications.

Although intrathoracic visualization may be enhanced with VATS, which may increase the number of biopsy samples taken [64], either approach is acceptable for adequate tissue sampling. Ultimately, the decision to use one method over another depends on the experience and preference of the surgeon. Nonetheless, pulmonologists may be more willing to refer patients for a surgical lung biopsy if they perceive the VATS approach to be less invasive than the standard thoracotomy. With this approach, biopsy sampling of sites other than the lingula may be more technically challenging [50]. Therefore, in these patients, ILD must truly be diffuse for the surgeon to rely on the lingula to be representative of the interstitial process.

The inability of critically ill, ventilator-dependent patients and those with severe lung disease to tolerate single-lung ventilation usually precludes the videothoracoscopic approach; thus, VATS offers no advantages over the standard minimal thoracotomy in these patients [59]. Many surgeons now prefer a limited 5-cm anterior targeted approach, usually through a submammary incision, and use the thoracoscopic instruments for the biopsy of generalized ILD. This obviates the need for double-lumen anesthesia in critically ill or ventilator-dependent patients.

The issue of cost remains controversial. In 1994, Molin and coworkers [65] reported increased hospital cost in patients undergoing VATS compared with open lung biopsy. These results were not confirmed in another study [58], which contended that these increased operative costs were offset by a shorter hospital stay. The lack of prospective randomized comparisons prohibits firm conclusions regarding the cost of thoracoscopy compared with open lung biopsy. Clearly, for VATS to be more cost-effective, patients must have shorter and less complicated hospital stays to offset the increased operative cost [66]. In conclusion, a surgical biopsy specimen can be successfully obtained with either a thoracoscopic or open approach.

	Conclusions

Top Abstract Introduction Material and Methods Idiopathic Interstitial... Indications for Surgical Biopsy Biopsy Methods Open Versus Thoracoscopic Biopsy Conclusions References

 
The spectrum of the idiopathic interstitial pneumonias continues to evolve as clinicians, radiologists, and pathologists refine their diagnostic skills. As these entities become better defined, new therapeutic strategies will likely be developed to specifically target the underlying mechanisms of these disorders. It is essential that thoracic surgeons be involved in the management of these patients, not only to serve as technicians in obtaining biopsy tissue, but also as part of a multidisciplinary approach to diagnose and treat patients with these obscure lung disorders.

	References

Top Abstract Introduction Material and Methods Idiopathic Interstitial... Indications for Surgical Biopsy Biopsy Methods Open Versus Thoracoscopic Biopsy Conclusions References

 

1. Liebow AA, Carrington CB. The interstitial pneumoniasIn: Simon M, Potchen EJ, Lemay E, editors. Frontiers in Pulmonary Radiology. New York: Grune and Stratton; 1969. pp. 102-141.
2. Travis WD, King Jr TE, Batenan F, et al. American Thoracic Society/European Respiratory Society Consensus classification of the idiopathic interstitial pneumonias Am J Respir Crit Care Med 2002;165:227-304.
3. Qureshi RA, Ahmed TA, Grayson AD, et al. Does lung biopsy help patients with interstitial lung disease? Eur J Cardiothorac Surg 2002;21:621-626.[Abstract/Free Full Text]
4. Kramer MR, Berkman N, Mintz B, et al. The role of open lung biopsy in the management and outcome of patients with diffuse lung disease Ann Thorac Surg 1998;65:198-202.[Abstract/Free Full Text]
5. Walker WA, Cole Jr FH, Khandekar A, Mahfood SS, Watson DC. Does lung biopsy affect treatment in patients with diffuse pulmonary infiltrates? J Thorac Cardiovasc Surg 1989;97:534-540.[Abstract]
6. King Jr TE, Costabel U, Cordier JF, et al. American Thoracic Society Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statementAmerican Thoracic Society (ATS), and the European Respiratory Society (ERS) Am J Respir Crit Care Med 2000;161:646-664.[Free Full Text]
7. Katzenstein AL, Myers JL. Idiopathic pulmonary fibrosisclinical relevance of pathologic classification. Am J Respir Crit Care Med 1998;157:1301-1315.[Free Full Text]
8. Gaensler EA, Carrington CB. Open biopsy for chronic diffuse infiltrative lung diseaseclinical roentgenographic and physiological correlations in 502 patients. Ann Thorac Surg 1980;30:411-426.[Abstract]
9. Chechani V, Landreneau RJ, Shaikh SS. Open lung biopsy for diffuse infiltrative lung disease Ann Thorac Surg 1992;54:296-300.[Abstract]
10. Hiatt JR, Gong H, Mulder DG, Ramming KP. The value of open lung biopsy in the immunosuppressed patient Surgery 1982;92:285-291.[Medline]
11. Hunninghake GW, Zimmerman MB, Schwartz DA, et al. Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis Am J Respir Crit Care Med 2001;164:193-196.[Abstract/Free Full Text]
12. Raghu G, Mageto YN, Lockhart D, Schmidt RA, Wood DE, Godwin JD. The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung diseasea prospective study. Chest 1999;116:1168-1174.[Abstract/Free Full Text]
13. Katzenstein AL, Myers JL. Idiopathic pulmonary fibrosis. To biopsy or not to biopsy Am J Respir Crit Care Med 2001;164:185-189.[Free Full Text]
14. Nicholson AG, Wells AU. Nonspecific interstitial pneumonia—nobody said it’s perfect Am J Respir Crit Care Med 2001;164:1553-1556.[Free Full Text]
15. 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]
16. Monaghan H, Wells AU, Colby TV, du Bois RM, Hansell DM, Nicholson AG. Prognostic implications of histologic patterns in multiple surgical lung biopsies from patients with idiopathic interstitial pneumonias Chest 2004;125:522-526.[Abstract/Free Full Text]
17. Strollo DC. Imaging of idiopathic interstitial lung diseases. Concepts and conundrums Am J Respir Cell Mol Biol 2003;29(3 Suppl):S10-S18.
18. Dacic S, Yousem SA. Idiopathic pulmonary fibrosishistologic classification of idiopathic chronic interstitial pneumonias. Am J Respir Cell Mol Biol 2003;29(3 Suppl):S5-S9.
19. Katzenstein AL, Zisman DA, Litzky LA, Nguyen BT, Kotloff RM. Usual interstitial pneumonia. Histologic study of biopsy and explant specimens Am J Surg Pathol 2002;26:1567-1577.[Medline]
20. Bjoraker JA, Ryu JH, Edwin MK, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis Am J Respir Crit Care Med 1998;157:199-203.
21. Nicholson AG, Fulford LG, Colby TV, du Bois RM, Hansell DM, Wells AU. The relationship between individual histologic features and disease progression in idiopathic pulmonary fibrosis Am J Respir Crit Care Med 2002;166:173-177.[Abstract/Free Full Text]
22. King Jr TE, Schwarz MI, Brown K, et al. Idiopathic pulmonary fibrosisrelationship between histopathologic features and mortality. Am J Respir Crit Care Med 2001;164:1025-1032.[Abstract/Free Full Text]
23. Latsi PI, du Bois RM, Nicholson AG, et al. Fibrotic idiopathic interstitial pneumoniathe prognostic value of longitudinal functional trends. Am J Respir Crit Care Med 2003;168:531-537.[Abstract/Free Full Text]
24. Johnson MA, Kwan S, Snell NJ. Randomised controlled trial comparing prednisolone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis Thorax 1989;44:280-288.[Abstract/Free Full Text]
25. Raghu G, Depaso WJ, Cain K. Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosisa prospective double-blind, randomized, placebo controlled clinical trial. Am Rev Respir Dis 1991;144:291-296.[Medline]
26. Douglas WW, Ryu JH, Swensen SJ. Colchicine versus prednisone in the treatment of idiopathic pulmonary fibrosisa randomized prospective study. Am J Respir Crit Care Med 1998;158:220-225.
27. Ziesche R, Hofbauer E, Wittmann K, Petkov V, Block LH. A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis New Engl J Med 1999;341:1264-1269.[Abstract/Free Full Text]
28. Meyer KC. Interferon gamma-1b therapy for idiopathic pulmonary fibrosisis the cart before the horse?. Mayo Clin Proc 2003;78:1073-1075.[Free Full Text]
29. Katzenstein AL, Fiorentino DF. Nonspecific interstitial pneumonia/fibrosis. Histologic features and clinical significance Am J Surg Pathol 1994;18:136-147.[Medline]
30. Travis WD, Matsui K, Moss J, Ferrans VJ. Idiopathic nonspecific interstitial pneumoniaprognostic significance of cellular and fibrosing patterns-survival comparison with usual interstitial pneumonia and desquamative interstitial pneumonia. Am J Surg Pathol 2000;24:19-33.[Medline]
31. Daniil ZD, Gilchrist FC, Nicholson AG, et al. A histologic pattern of nonspecific interstitial pneumonia is associated with a better prognosis than usual interstitial pneumonia in patients with cryptogenic fibrosing alveolitis Am J Respir Crit Care Med 1999;160:899-905.[Abstract/Free Full Text]
32. Nicholson AG. Classification of idiopathic interstitial pneumoniasmaking sense of the alphabet soup. Histopathology 2002;41:381-391.[Medline]
33. Cordier JF. Organising pneumonia Thorax 2000;55:318-328.[Free Full Text]
34. Katzenstein AL, Myers JL, Mazur MT. Acute interstitial pneumoniaa clinicopathologic, ultrastructural, and cell kinetic study. Am J Surg Pathol 1986;10:256-267.[Medline]
35. Myers JL, Veal Jr CF, Shin MS, Katzenstein AL. Respiratory bronchiolitis causing interstitial lung disease Am Rev Respir Dis 1987;135:880-884.[Medline]
36. 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.[Medline]
37. Niewoehner DE, Kleinerman J, Rice DB. Pathologic changes in the peripheral airways of young cigarette smokers New Engl J Med 1974;291:755-758.
38. Sadikot RT, Johnson J, Loyd JE, Christman JW. Respiratory bronchiolitis associated with severe dyspnea, exertional hypoxemia, and clubbing Chest 2000;117:282-285.[Abstract/Free Full Text]
39. Fraig M, Shreesha U, Savic D, Katzenstein AL. Respiratory bronchiolitisa clinic pathologic study on current smokers, ex-smokers, and never-smokers. Am J Surg Pathol 2002;26:647-653.[Medline]
40. Yamamoto S, Hara H, Sakatani M, Ueda E. Serial computed tomographic evaluation in desquamative interstitial pneumonia Thorax 1997;52:333-337.[Abstract]
41. Herbert A, Sterling G, Abraham J, Corrin B. Desquamative interstitial pneumonia in an aluminium welder Hum Pathol 1982;13:694-699.[Medline]
42. Carrington CB, Gaensler EA, Coutu RE, Fitzgerald MX, Gupta RG. Natural history and treated course of usual and desquamative interstitial pneumonia New Engl J Med 1978;298:801-809.[Abstract]
43. Travis WD, Colby TV, Koss MN, et al. Nonneoplastic disorders of the respiratory tract. Atlas of Nontumor Pathology, 1st series, fascicle 2. Washington, DC: Armed Forces Institute of Pathology and American Registry of Pathology; 2002. pp. 49-231.
44. Raghu G. Interstitial lung disease: A diagnostic approach. Are CT scan and lung biopsy indicated in every patient? Am J Respir Crit Care Med 1995;151:909-914.[Medline]
45. Orens JB, Kazerooni EA, Martinez FJ, et al. The sensitivity of high resolution CT in detecting idiopathic pulmonary fibrosis proved by open lung biopsya prospective study. Chest 1995;108:109-115.[Abstract/Free Full Text]
46. Newman SL, Michel RP, Wang NS. Lingular lung biopsyis it representative?. Am Rev Respir Dis 1985;132:1084-1086.[Medline]
47. Miller RR, Nelems B, Muller NL, Evans KG, Ostrow DN. Lingular and right middle lobe biopsy in the assessment of diffuse lung disease Ann Thorac Surg 1987;44:269-273.[Abstract]
48. Wetstein L. Sensitivity and specificity of lingular segmental biopsies of the lung Chest 1986;90:383-386.[Abstract/Free Full Text]
49. Ayed AK. Video-assisted thoracoscopic lung biopsy in the diagnosis of diffuse interstitial lung disease. A prospective study J Cardiac Surg 2003;41:115-118.
50. Blewett CJ, Bennett F, Miller JD, Urschel JD. Open lung biopsy as an outpatient procedure Ann Thorac Surg 2001;71:1113-1115.[Abstract/Free Full Text]
51. Flint A, Martinez FJ, Young ML, Whyte RI, Toews GB, Lynch 3rd JP. Influence of sample number and biopsy site on the histologic diagnosis of diffuse lung disease Ann Thorac Surg 1995;60:1605-1608.[Abstract/Free Full Text]
52. Chang AC, Yee J, Orringer MB, Iannettoni MD. Diagnostic thoracoscopic lung biopsyan outpatient experience. Ann Thorac Surg 2002;74:1942-1947.[Abstract/Free Full Text]
53. Vidone RA, Librtin CR. Laboratory investigation in the diagnosis of pulmonary diseaseIn: Shields TW, LoCicero J, Ponn RB, editors. General Thoracic Surgery. 5th ed.. Philadelphia: Lippicott Williams & Wilkins; 2000. pp. 225-244.
54. Mouroux J, Clary-Meinesz C, Padovani B, et al. Efficacy and safety of videothoracoscopic lung biopsy in the diagnosis of interstitial lung disease Eur J Cardiothoracic Surg 1997;11:22-26.[Abstract]
55. Ferson PF, Landreneau RJ, Dowling RD, et al. Comparison of open versus thoracoscopic lung biopsy for diffuse infiltrative pulmonary disease J Thorac Cardiovasc Surg 1993;106:194-199.[Abstract]
56. Ravini M, Ferraro G, Barbieri B, Colombo P, Rizzato G. Changing strategies of lung biopsies in diffuse lung diseasesthe impact of video-assisted thoracoscopy. Eur Respir J 1998;11:99-103.[Abstract/Free Full Text]
57. Bensard DD, McIntyre R, Waring B, Simon J. Comparison of video thoracoscopic lung biopsy to open lung biopsy in the diagnosis of interstitial lung disease Chest 1993;103:765-770.[Abstract/Free Full Text]
58. Carnochan FM, Walker WS, Cameron EW. Efficacy of video assisted thoracoscopic lung biopsyan historical comparison with open lung biopsy. Thorax 1994;49:361-363.[Abstract/Free Full Text]
59. Ferson PF, Landreneau RJ. Thoracoscopic lung biopsy or open lung biopsy for interstitial lung disease Chest Surg Clin N Am 1998;8:749-762.[Medline]
60. Reno O, Casadio C, Leo F, et al. Videothoracoscopic lung biopsy in the diagnosis of interstitial lung disease Eur J Cardiothorac Surg 1999;16:624-627.[Abstract/Free Full Text]
61. Rizzato G. The role of thoracic surgery in diagnosing interstitial lung disease Curr Opin Pulm Med 1999;5:284-286.[Medline]
62. Zegdi R, Azorin J, Tremblay B, Destable MD, Lajos PS, Valeyre D. Videothoracoscopic lung biopsy in diffused infiltrative lung diseasesa 5-year surgical experience. Ann Thorac Surg 1998;66:1170-1173.[Abstract/Free Full Text]
63. Miller JD, Urschel JD, Cox G, et al. A randomized, controlled trial comparing thoracoscopy and limited thoracotomy for lung biopsy in interstitial lung disease Ann Thorac Surg 2000;70:1647-1650.[Abstract/Free Full Text]
64. Krasna MJ, White CS, Aisner SC, Templeton PA, McLaughlin JS. The role of thoracoscopy in the diagnosis of interstitial lung disease Ann Thorac Surg 1995;59:348-351.[Abstract/Free Full Text]
65. Molin LJ, Steinberg JB, Lanza LA. VATS increases costs in patients undergoing lung biopsy for interstitial lung disease Ann Thorac Surg 1994;58:1595-1598.[Abstract]
66. Miller Jr JI. The present role and future considerations of video-assisted thoracoscopy in general thoracic surgery Ann Thorac Surg 1993;56:804-806.[Abstract]

This article has been cited by other articles:

				J. H. Ryu, C. E. Daniels, T. E. Hartman, and E. S. Yi Diagnosis of Interstitial Lung Diseases Mayo Clin. Proc., August 1, 2007; 82(8): 976 - 986. [Abstract] [Full Text] [PDF]

				H. Thomas, K. A. Risma, T. B. Graham, A. S. Brody, G. H. Deutsch, L. R. Young, and P. M. Joseph A Kindred of Children With Interstitial Lung Disease Chest, July 1, 2007; 132(1): 221 - 230. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Michael E. Halkos Faraz Kerendi Daniel L. Miller Joseph I. Miller, Jr Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Halkos, M. E. Articles by Miller, J. I. Search for Related Content PubMed PubMed Citation Articles by Halkos, M. E. Articles by Miller, J. I., Jr Related Collections Lung - other