Interstitial lung disease (ILD) is a group of diseases with

Diagnostic Surgical Lung Biopsies for Suspected Interstitial Lung Diseases: A Retrospective Study Martin I. Sigurdsson, MD, Helgi J. Isaksson, MD, Gunnar Gudmundsson, MD, PhD, and Tomas Gudbjartsson, MD, PhD Departments of Cardiothoracic Surgery, Pathology, and Respiratory Medicine, Landspitali University Hospital, and Faculty of Medicine, University of Iceland, Reykjavik, Iceland Background. Current guidelines for interstitial lung disease support a surgical biopsy for optimal diagnosis and treatment, yet only a minority of patients undergo such biopsy. Our objectives were to address the properties of a surgical lung biopsy for suspected interstitial lung disease, the diagnostic yield of the procedure, and whether it resulted in changes in diagnosis and treatment. Methods. A retrospective nationwide study including 73 patients (mean age, 57.3 years; 58% males) who underwent a surgical lung biopsy for suspected interstitial disease in Iceland between 1986 and 2007 was conducted. Patient records and histologic specimens were reviewed. Before the surgical biopsy a transbronchial or computed tomography guided biopsy had been performed in two thirds of the patients. Results. The complication rate for surgical lung biopsy was 16%, and 30-day operative mortality was 2.7%, both significantly higher in patients with preoperative respiratory failure. After the procedure, a definite histopathologic diagnosis was obtained in 81% of the patients. Usual interstitial pneumonia was the most common diagnosis (31%). The clinical diagnosis was changed for 73% of the patients, and in 53% of the patients the biopsy resulted in changes in treatment. Conclusions. Surgical lung biopsy is a powerful tool for diagnosis of suspected interstitial lung disease. It results in a specific diagnosis for the majority of patients and changes in treatment for more than half. Operative morbidity and mortality are low but still significant, so patients should be carefully selected for the procedure, especially those with respiratory failure. (Ann Thorac Surg 2009;88:227 32) 2009 by The Society of Thoracic Surgeons Interstitial lung disease (ILD) is a group of diseases with great diversity regarding treatment options and prognosis. The current classification of ILD and guidelines support a surgical lung biopsy (SLB) for definite diagnosis of ILD but encourage physicians to balance the benefit carefully against the risks of performing the surgery [1, 2]. Increased quality of both high-resolution computerized tomography and transbronchial biopsies obtained through bronchoscopy has raised the question of necessity for SLBs [3]. Together with clinical information, specificity and sensitivity of these diagnostic measures are in the 60% to 80% range [4, 5]. Recently accurate diagnosis of idiopathic pulmonary fibrosis using only radiologic and clinical data has been demonstrated [6]; however, this approach is highly dependent on physician expertise [7]. Also, transbronchial biopsies are less accurate for diseases when a substantial amount of tissue is required for histologic diagnosis (such as idiopathic pulmonary fibrosis) [8]. According to recent studies postoperative mortality after SLB is 4.3% to 4.8% [9, 10]. However, some subgroups of patients, ie, immunocompromised patients or patients with severe respiratory failure, have substantially higher operative mortality [9, 10]. The shift from conventional thoracotomy toward video-assisted thoracoscopic surgery (VATS) Accepted for publication April 1, 2009. Address correspondence to Prof Gudbjartsson, Landspitali University Hospital, Hringbraut, Reykjavik, 101, Iceland; e-mail: tomasgud@landspitali.is. favors the new technique in regards to mortality [11] and hospital stay [12]. However, many physicians are still reluctant to refer their patients for SLB for suspected ILD. For instance a recent study from Iceland revealed that the percentage of patients diagnosed with organizing pneumonia using SLB was only 22% [13]. The contribution of SLB to the final diagnosis and treatment selection has not been previously documented. In the study of Lettieri and colleagues [10] on patients with suspected idiopathic pulmonary fibrosis, the final diagnosis was changed for 40% of the patients after an SLB. This study, however, neither addressed the initiated treatment changes nor did it include patients suspected of having other ILDs. We therefore designed a study to address these issues in a population-based cohort of patients with suspected ILD. For the study we used our nationwide database that includes all SLBs performed in Iceland for 22 years from 1986. The main objectives of this study were to address the diagnostic yield of SLB for suspected ILD, the risks of the procedure, and whether the results of the biopsy led to changes in treatment. Patients and Methods Patient Identification All patients undergoing SLB for suspected ILD during a 22-year period between January 1, 1986, and December 2009 by The Society of Thoracic Surgeons 0003-4975/09/$36.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2009.04.002

228 SIGURDSSON ET AL Ann Thorac Surg SURGICAL LUNG BIOPSIES 2009;88:227 32 30, 2007, were identified through two registries separately. During the study period, the average number of people living in Iceland was 273,052 (minimum of 242,203 in 1986, maximum of 315,459 in 2007; Icelandic National Registry). A computerized diagnosis and operation registry was used to identify patients undergoing open or thoracoscopic lung biopsy at Landspitali University Hospital (the single institution performing pulmonary surgery in Iceland). Furthermore a centralized pathology registry from the Department of Pathology implementing the Systematized Nomenclature of Medicine codes was used to identify patients who had a part of lung biopsied. All patients undergoing a surgical lung biopsy through thoracoscopy or an open surgery were evaluated for the study. Patients with a solitary pulmonary nodule or patients in whom the surgery was used to remove foreign bodies or for treatment of recurrent pulmonary infections were excluded. As a quality control, the list of patients was compared with an ILD patient registry, confirming a 100% match with the subset diagnosed with SLB. Patients were assigned a date and a cause of death or identified as living on December 31, 2007, using data from the Icelandic National Registry. Mean follow-up time was 72.5 months (range, 0 to 259 months), and no patients were lost to follow-up. The study was approved by the Icelandic National Bioethics Committee and the Icelandic Data Protection Commission. As individual patients were not identified, individual consent for the study was waived. Clinical Data Clinical data were collected retrospectively from clinical records from hospitals and private offices using a standardized data sheet and reviewed by two of the authors (M.I.S., G.G.). The following information was collected when available: age, sex, date and cause of death, clinical symptoms, smoking history, clinical examination, spirometry and diffusion capacity for carbon monoxide results, laboratory results, chest radiographs and chest computed tomography results, information on bronchoscopy results, indication and relative contraindications for the surgical biopsy, clinical diagnosis before and after the biopsy, treatment before and after the biopsy, and information regarding the clinical condition of the patient for the first year after the biopsy. Respiratory failure was defined as arterial partial pressure of oxygen less than 60 mm Hg needing either supplementary oxygen by nasal cannula or mask (n 6) or needing mechanical ventilation before the surgery (n 2). Patients undergoing chemotherapy or radiation for active malignant disease, patients using immunomodulating drugs or steroids as a result of organ transplantation or autoimmune diseases, patients with acquired immunodeficiency syndrome, and patients with chronic renal failure were defined as immunocompromised. The diagnosis being treated before the operation or the primary differential diagnosis mentioned was registered as the preoperative diagnosis. Pathologic Diagnosis All pathologic specimens were evaluated at the Department of Pathology at Landspitali University Hospital in Reykjavik using the Systematized Nomenclature of Medicine coding system. All lung specimens were read by one of the attending pathologists and frequently reviewed by one or more additional pathologists before codes were assigned. For the present study, all specimens were reviewed by one pathologist (H.J.I.), an experienced thoracic histopathologist. Information on the size and quality of the pathologic specimen as well as the pathologic diagnosis was obtained from pathologic reports and registered in a standardized sheet and reviewed by two of the authors (M.I.S., H.J.I.). Handling of the lung tissue has not changed during the years with the exception of the use of the tissue bank for preserving frozen tissue samples for special research purposes in rare cases. Hematoxylin and eosin staining was sufficient for making the diagnosis in most cases. In general, special stains did make much of a difference in arriving at a diagnosis. Surgical Technique and Postoperative Care Six thoracic surgeons performed the surgeries. Two techniques were used, open thoracotomies and minimally invasive technique using VATS, the latter technique being increasingly used after 1991. With a few exceptions, patients were extubated in the operating room. One chest tube (with suction of 20 cm H 2 O) was placed in the chest after the operation for the majority of patients (n 63). The tube was removed the next day if the lungs were fully expanded, no air leakage was present, and pleural drainage was less than 100 ml/24 h. Hospital morbidity was assessed by means of intraoperative and postoperative complications, reoperations, and length of stay. Extended air leakage was defined as continuous air leakage more than 96 hours postoperatively. Extended mechanical ventilation was defined as mechanical ventilation for more than 72 hours. Operative mortality was defined as the number of patients who died within 30 days of surgery. Information regarding operation type, skin to skin operation time, sample location, duration of hospital stay, duration of thoracic drainage, and operation mortality and morbidity were obtained from patient charts and surgical reports, registered in a standardized data sheet and reviewed by two of the authors (M.I.S., T.G.). Statistical Analysis Statistical analysis on categorical variables was performed using the 2 test or Fisher s exact test on 2 2 tables. Overall survival rate for the study group was estimated using the Kaplan-Meier method [14]. A probability value of less than 0.05 was considered statistically significant. Microsoft Excel (Microsoft Corp, Redmond, WA) was used for descriptive statistics; all other analysis was done using the R statistical package, version 2.5.1 (R Foundation for Statistical Computing, Vienna, Austria).

Ann Thorac Surg SIGURDSSON ET AL 2009;88:227 32 SURGICAL LUNG BIOPSIES 229 Table 1. Lung Function Tests and Radiologic Evaluation a Variable Number Percentage A-a gradient Normal 11 (15) Increased 36 (49) Information not available 26 (36) Chest radiograph Normal 2 (3) Bilateral basilar interstitial change 27 (37) Patchy bilateral airspace opacities 28 (38) Unilateral diffuse airspace opacities 4 (5) Focal opacity 10 (14) Other 12 (16) Chest CT Ground glass 19 (26) Honeycombing 13 (18) Multiple nodules 23 (32) Peripheral consolidations 11 (15) Fibrosis 6 (8) Pulmonary embolism 1 (1) Pulmonary cysts 1 (1) Pleural effusion 1 (1) Not done 14 (19) a Results from lung function tests and radiologic evaluation before a surgical lung biopsy for 73 patients. A-a gradient alveolar to arterial gradient for oxygen; CT computed tomography. Results During the 22-year study period a total of 73 patients underwent an SLB for suspected ILD in Iceland, on average 3.3 patients per year with a range of 0 to 10 per year. The average age at diagnosis was 57.3 years (range, 20 to 88 years) and the number of men (58%) and women (42%) did not differ statistically (p 0.20). A vast majority of the population had a history of smoking (75%), with 53% of the patients being heavy smokers ( 20 pack-years). Table 2. Postoperative Complications and Operative Mortality a Variable Number b Percentage Postoperative complications 12 (16) Prolonged air leakage 9 (12) Need for mechanical ventilation 3 (4) Pneumonia 3 (4) Acute exacerbation of respiratory 2 (3) failure Other 1 (1) Operative mortality 30 days 2 (3) 90 days 3 (4) Hospital mortality 3 (4) a Postoperative complications and operative mortality for 73 patients undergoing surgical lung biopsy for suspected interstitial lung disease in Iceland 1986 2007. b Some patients had more than one complication. Table 3. Pathologic Diagnosis a Variable Number Percentage Interstitial diagnosis Usual interstitial pneumonia 23 (32) Organizing pneumonia 17 (23) Nonspecific interstitial pneumonia 6 (8) Desquamative interstitial pneumonia 4 (5) Sarcoidosis 3 (4) Lymphocytic interstitial pneumonia 1 (1) Respiratory bronchiolitis-associated 1 (1) interstitial lung disease Alveolar lipoproteinosis 1 (1) Wegener s granulomatosis 1 (1) Nonspecific fibrosis 12 (16) Noninterstitial diagnosis Pneumonia 2 (3) Benign tumor 1 (1) Rheumatoid nodule 1 (1) Emphysema 1 (1) Vascular intimal fibrosis 1 (1) Nonspecific inflammation 2 (3) a Histopathologic properties of 73 patients undergoing surgical lung biopsy for suspected interstitial lung disease in Iceland 1986 2007. The dominant presenting symptoms were dyspnea in 50 patients (68%) and cough in 43 patients (59%). The duration of symptoms was less than 3 months in 37% of patients, but 36% of patients had symptoms for more than 12 months before surgery. Blood gases were evaluated in 47 patients (64%), indicating an increased alveolar to arterial gradient for oxygen ( 10 mm Hg) for the vast majority (n 36) of patients. Preoperatively, a chest radiograph was obtained for all patients and a computed tomography scan in 59 patients (81%). The imaging studies usually revealed either multiple opacities in both lungs or interstitial changes (Table 1). Before the SLB, a transbronchial lung biopsy by means of bronchoscopy had already been obtained for 51 patients (70%) with no specific change in the rate of transbronchial biopsy frequency during the study period. Also, 2 patients had computed tomography directed biopsy. These biopsies all revealed either normal lung tissue or nonspecific inflammation. Open minithoracotomy was the most common surgical procedure (n 45; 62%), including 3 cases of VATS that were converted to thoracotomy. A total of 28 patients underwent VATS, with the majority of these operations being performed during the end of the study period (85% of operations after 2005). Operation mortality and morbidity did not differ statistically between the two procedures. Mean operation time was 46 minutes (range, 15 to 110 minutes), median chest tube drainage time was 2 days (range, 1 to 83 days), and median hospital stay was 4 days (range, 0 to 89 days). The only registered intraoperative complication was a patient with a pulmonary bleeding who required a transfusion. Postoperative complications were registered in 12

230 SIGURDSSON ET AL Ann Thorac Surg SURGICAL LUNG BIOPSIES 2009;88:227 32 Table 4. Comparison Between Preoperative and Postoperative Diagnosis a Postoperative Diagnosis Preoperative Diagnosis AL DIP Nonspecific Fibrosis LIP NSIP OP RBILD Sarcoidosis UIP WG Noninterstitial Disease Interstitial disease LIP 1 NSIP 1 OP 2 1 Sarcoidosis 1 1 1 1 1 Undetermined 1 2 5 5 1 12 3 UIP 1 1 6 WG 1 Noninterstitial disease No diagnosis 1 1 4 1 2 Farmers lung 1 Infection 2 4 1 Neoplasm 1 1 3 2 Pulmonary eosinophilia 1 a A contingency table showing postoperative diagnosis compared with the preoperative diagnosis for 73 patients undergoing surgical lung biopsy for suspected interstitial lung disease in Iceland 1986 2007. AL alveolar lipoproteinosis; DIP desquamative interstitial pneumonia; LIP lymphocytic interstitial pneumonia; NSIP nonspecific interstitial pneumonia; OP organizing pneumonia; RBILD respiratory bronchiolitis-associated interstitial lung disease; UIP usual interstitial pneumonia; WG Wegener s granulomatosis. patients (16%) and are listed in Table 2. Three of these complications were major, including a bronchopleural fistula, stroke, and empyema that needed a reoperation. The most common complication, however, was prolonged air leakage in 9 patients. Three patients died in the hospital after the procedure (hospital mortality, 4.1%), all of severe respiratory failure, including 2 who died within 30 days of the procedure (operative mortality, 2.7%; Table 2). Complications were significantly more common in patients with preoperative respiratory failure (n 8) than those without (63% versus 11%; p 0.002). Hospital mortality was also higher in this subgroup of patients (25% versus 2%; p 0.03). In 51 patients (70%) a single biopsy with a maximum diameter of greater than 2 cm was obtained, and biopsies from two different lobes were performed in 17 patients (20%). Biopsies were more often from the right lung than the left (66% versus 34%; p 0.01). After the procedure, 65 patients (83%) received a definitive histopathologic diagnosis. A diagnosis of a single interstitial disease was made in 65 patients (89%), and a single diagnosis of noninterstitial disease was diagnosed in 4 patients (5%). In 4 patients (5%), both an interstitial and a noninterstitial diagnosis was obtained. Interestingly, pneumonia was diagnosed in 2 patients. In both patients, sputum cultures and cultures from bronchial washings had been performed with inadequate results. After the SLB, Pneumocystis jiroveci pneumonia and Legionella pneumonia was diagnosed by use of special stains for these patients. Both of these organisms were not suspected previously and were therefore unlikely to be detected as they both require special cultures. Detailed information on the histopathologic diagnosis of the biopsies is shown in Table 3, the most common diagnosis being usual interstitial pneumonia (32%). In a total of 14 patients (19%) there was a nonspecific histopathologic diagnosis (nonspecific interstitial fibrosis or nonspecific inflammation). In patients in whom a solitary biopsy from the lingula was performed (n 22), a nonspecific histopathologic diagnosis was not more common compared with patients with biopsies from other parts of the lungs (23% versus 18%; p 0.52). Biopsies taken from two different lobes did not increase the diagnostic efficacy of the procedure compared with a single biopsy (72% versus 73%; p 1.0). Table 4 compares preoperative and postoperative diagnosis. The diagnosis was changed for 53 (73%) patients after the SLB. When an interstitial disease of any kind was the suggested diagnosis before the operation, an interstitial disease was diagnosed in 94% of the patients. However, when a noninterstitial disease was suggested as a diagnosis before the operation, a noninterstitial disease was diagnosed in only 4% of the patients. After the biopsy, a change in treatment strategy (initiation of a new treatment, cessation of previous treatment, or a change in treatment strategy) was documented for 42 patients (53%). At 1 year of follow-up, clinical improvement was registered in 35 patients, no change in 22 patients, and 13 patients were feeling worse. Overall 2- and 5-year survival was 86% and 67%, respectively. Comment In this nationwide retrospective study we found that SLB is diagnostic for specific disease in 81% of our patients and that treatment strategy was changed for every other patient. We have addressed several unreported but important issues related to SLB in suspected ILD, such the

Ann Thorac Surg SIGURDSSON ET AL 2009;88:227 32 SURGICAL LUNG BIOPSIES 231 diagnostic yield of the biopsy, how often it changes the diagnosis, and how often treatment is changed. Our 73% ratio of changed diagnosis is higher than the 49% reported by Lettieri and associates [10] in their series of 83 patients with suspected Idiopathic pulmonary fibrosis. This could be attributable to several factors, such as different inclusion criteria for surgical referral. The high diagnostic yield of the surgical biopsies is of special interest, keeping in mind that two thirds of these patients already underwent a range of less invasive diagnostic studies that did not lead to a definite diagnosis. The preferred workup of suspected ILD in Iceland includes both a high-resolution computed tomography and a transbronchial biopsy unless contraindicated. In a recent study on the Icelandic population, it was found that 78% of patients with cryptogenic organizing pneumonia were diagnosed by means of a transbronchial biopsy [13]. Therefore, it is likely that a transbronchial biopsy will remain the primary diagnostic procedure for ILD. Our study, however, indicates that when transbronchial biopsies fail to reach a definite diagnosis, an SLB can be of further diagnostic benefit. The SLB is a safe procedure with a 30- and 90-day operative mortality of 2.7% and 4.1%, respectively. Our mortality rates are similar to other studies, most of them ranging from 4% to 5% and 6%, respectively [9 11]. Complications were usually minor and most often prolonged air leakage (12% of patients). This complication requires chest tube drainage and prolongs hospital stay and increases costs. Major complications were only detected in 3 patients (4%), and one of them, a stroke, was not directly related to the procedure. Patients with preoperative respiratory failure had increased mortality and morbidity, and the 3 patients who died after the procedures all died because of respiratory failure. Our findings are similar to many other studies [9, 10]. Based on our results, we cannot determine a critical point of respiratory failure at which an SLB is not safe and the patient should be treated empirically. This would, however, be an interesting and important study subject for future research. We did not find any differences in outcome after thoracotomy or VATS. This study, with its retrospective nonrandomized design, was not designed to compare these two techniques. Other studies have shown VATS to have lower mortality [11] and shorter hospital stay. From 2005 this technique has been our method of choice in Iceland. It is usually recommended to refer patients for biopsy at earlier stages, both for early treatment optimization and also because end-stage pathologic appearance of most ILDs is indistinguishable. On the other hand, suggestions about the absolute number, size, and location of the surgical biopsies vary substantially. Some surgeons favor the readily accessible lingula of the upper left lobe for the biopsy [15], whereas others find the diagnostic success from lingula biopsies unacceptable [16]. We did not find a trend for a higher rate of diagnostic failure when a solitary lingula biopsy was performed. Some earlier studies have recommended to biopsy at least two different lobes [17]. In our study multiple biopsies did not increase the diagnostic rate, and the diagnostic yield was 78% despite a single lobe biopsy for 80% of the patients. This indicates that a solitary biopsy is possibly sufficient. Our results are in line with a prior study in which multiple biopsies in 28 patients did not increase the diagnostic yield [18]. We found that the most common pathologic diagnoses obtained were usual interstitial pneumonia (32%) and organizing pneumonia (23%). Epidemiologic studies of ILD usually report that usual interstitial pneumonia is approximately 31% to 38% of ILD [19, 20], but the ratio of organizing pneumonia is around 5% [20]. Our higher ratio of organizing pneumonia could be related to a selection bias as patients with atypical presentation of ILD are more likely to be referred to an SLB. A strength of this study is its nationwide design, minimizing the risk for selection bias. Patients were identified through two different registries separately and operated on in a single cardiothoracic center by 6 surgeons. This reduces variability owing to different centers and surgeons and the likelihood that patients are missing. Furthermore, all 73 patients were treated before and after surgery by respiratory physicians, increasing the likelihood of optimal treatment. Main weaknesses are the limited number of patients and the retrospective design. Although histopathologic processing and reading remained the same, significant improvements in computed tomography imaging and surgical techniques occurred during the relatively long study period. Also, indications for referring patients for surgical biopsy were not standardized during the whole study period. In summary, we conclude that an SLB is a powerful tool for obtaining an exact diagnosis of suspected ILD, and it results in changes in the clinical diagnosis and a new treatment strategy for the majority of patients. The operative morbidity and mortality is low but significant, so patients should be carefully selected for the procedure. This is important for patients with severe respiratory failure. References 1. 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. 2. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 2000;161: 646 64. 3. Halkos M, Gal A, Kerendi F, et al. Role of thoracic surgeons in the diagnosis of idiopathic interstitial lung disease. Ann Thorac Surg 2005;2172 9. 4. 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 6.

232 SIGURDSSON ET AL Ann Thorac Surg SURGICAL LUNG BIOPSIES 2009;88:227 32 5. Raghu G, Mageto YN, Lockhart D, et al. The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung disease: a prospective study. Chest 1999;116:1168 74. 6. Flaherty KR, King TE Jr, Raghu G, et al. Idiopathic interstitial pneumonia: what is the effect of a multidisciplinary approach to diagnosis? Am J Respir Crit Care Med 2004;170: 904 10. 7. Flaherty KR, Andrei AC, King TE Jr, et al. Idiopathic interstitial pneumonia: do community and academic physicians agree on diagnosis? Am J Respir Crit Care Med 2007;175: 1054 60. 8. Gal AA. Use and abuse of lung biopsy. Adv Anat Pathol 2005;12:195 202. 9. Park J, Kim D, Kim D, et al. Mortality and risk factors for surgical lung biopsy in patients with idiopathic interstitial pneumonia. Eur J Cardiothorac Surg 2007;1115 9. 10. Lettieri CJ, Veerappan GR, Helman DL, et al. Outcomes and safety of surgical lung biopsy for interstitial lung disease. Chest 2005;127:1600 5. 11. Tiitto L, Heiskanen U, Bloigu R, Pääkkö P, Kinnula V, Kaarteenaho-Wiik R. Thoracoscopic lung biopsy is a safe procedure in diagnosing usual interstitial pneumonia. Chest 2005;128:2375 80. 12. Ravini M, Ferraro G, Barbieri B, Colombo P, Rizzato G. Changing strategies of lung biopsies in diffuse lung diseases: the impact of video-assisted thoracoscopy. Eur Respir J 1998;11:99 103. 13. Sveinsson OA, Isaksson HJ, Sigvaldason A, et al. Clinical features in secondary and cryptogenic organising pneumonia. Int J Tuberc Lung Dis 2007;11:689 4. 14. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457 81. 15. Ayed AK. Video-assisted thoracoscopic lung biopsy in the diagnosis of diffuse interstitial lung disease. A prospective study. J Cardiovasc Surg (Torino) 2003;44:115 8. 16. Monaghan H, Wells AU, Colby TV, et al. Prognostic implications of histologic patterns in multiple surgical lung biopsies from patients with idiopathic interstitial pneumonias. Chest 2004;125:522 6. 17. Klassen KP, Andrews NC. Biopsy of diffuse pulmonary lesions: A seventeen-year experience. Ann Thorac Surg 1967;4:117 24. 18. Flint A, Martinez FJ, Young ML, et al. Influence of sample number and biopsy site on the histologic diagnosis of diffuse lung disease. Ann Thorac Surg 1995;60:1605 8. 19. Demedts M, Wells AU, Anto JM, et al. Interstitial lung diseases: an epidemiological overview. Eur Respir J Suppl 2001;32:2s 16. 20. Lopez-Campos JL, Rodriguez-Becerra E. Incidence of interstitial lung diseases in the south of Spain 1998 2000: the RENIA study. Eur J Epidemiol 2004;19:155 61. INVITED COMMENTARY This article [1] is particularly useful because it addresses a specific subset of patients who are potential candidates for surgical lung biopsy. It includes only patients with interstitial lung disease (ILD). What it does not include is patients with acute respiratory distress syndrome (ARDS) or patients with pulmonary masses who are candidates for a wedge resection for either diagnosis or treatment. Focusing solely on this particular subset of patients allows conclusions that are not confounded by the inclusion of these other types of patients. Therefore, the observations and conclusions for patients with ILD are credible and useful. Their findings are that the clinical diagnosis was changed in 73% of their patients and the revised diagnosis resulted in treatment changes in 53% of patients. The cost for this was a modest morbidity and an in-hospital mortality rate of 4.1%. Consistent with previous reports, these results document a significant positive impact on clinical care as a result of these biopsy findings. However, another perspective is that the procedure did not affect the clinical care of half the patients, and while the mortality and morbidity rates seem low, they are not absent. In this context, I agree with the author s suggested algorithm for the approach to patients with ILD. The initial diagnostic evaluation, in addition to the patient s history, should begin with a high resolution computed tomographic scan of the chest and a transbronchial biopsy. According to the authors experience, this will be diagnostic in 78% of patients. This leaves a small number of patients to be considered for surgical biopsy, which should be performed when patients are not responding appropriately to the ongoing management based on their clinical diagnosis. For the biopsy procedure, either a limited thoracotomy or a video-assisted thoracic surgical (VATS) procedure is a reasonable option. Although not shown in this study, video-assisted thoracic surgery is probably superior (both in terms of pain control and access to multiple lung areas) for biopsy. However, there is sufficient morbidity and mortality that even a VATS procedure should not be performed simply out of curiosity, but only if patient management might be affected. Alex G. Little, MD Department of Surgery Wright State University Boonshoft School of Medicine One Wyoming St 7801 WCHE Dayton, OH 45409 e-mail: alex.little@wright.edu Reference 1. Sigurdsson MI, Isaksson HJ, Gudmundsson G, Gudbjartsson T. Diagnostic surgical lung biopsies for suspected interstitial lung diseases: a retrospective study. Ann Thorac Surg 2009;88:227 32. 2009 by The Society of Thoracic Surgeons 0003-4975/09/$36.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2009.04.052