American Journal of Respiratory and Critical Care Medicine

Rationale: Surgical lung biopsy can help to determine a specific diagnosis in interstitial lung disease but has associated risks. Most currently available mortality data are derived from case series and may not be generalizable to broader populations.

Objectives: To assess in-hospital mortality after surgical lung biopsy for interstitial lung disease in a national secondary care dataset from the United States.

Methods: Data were obtained from the 2000–2011 Nationwide Inpatient Sample. Cases were identified using International Classification of Diseases codes for interstitial lung disease and surgical lung biopsies. Lung resections and cases of lung cancer were excluded. Weighted data were used to estimate numbers of biopsies nationwide and in-hospital mortality, and multivariable logistic regression was used to adjust for sex, age, geographic region, comorbidity, type of operation, and provisional diagnosis.

Measurements and Main Results: We estimated there to be around 12,000 surgical lung biopsies performed annually for interstitial lung disease in the United States, two-thirds of which were performed electively. In-hospital mortality was 1.7% for elective procedures but significantly higher for nonelective procedures (16.0%). Male sex, increasing age, increasing comorbidity, open surgery, and a provisional diagnosis of idiopathic pulmonary fibrosis or connective tissue disease–related interstitial lung disease were risk factors for increased mortality.

Conclusions: In-hospital mortality after elective surgical lung biopsy for interstitial lung disease is just under 2% but significantly higher for nonelective procedures. Identified risk factors for death should be taken into account when counseling patients on whether to pursue a histologic diagnosis.

Scientific Knowledge on the Subject

Surgical lung biopsy for interstitial lung disease can help clarify the diagnosis but mortality has been reported to be high in some case series.

What This Study Adds to the Field

In a large national dataset, in-hospital mortality after elective lung biopsy was 1.7% but significantly higher in nonelective procedures. Male sex, increasing age, and comorbidity were associated with increased risk.

In a patient with characteristic clinical features, a confident diagnosis of idiopathic pulmonary fibrosis (IPF) can be made after excluding alternative causes of interstitial lung disease (ILD) and demonstrating typical features on high-resolution computed tomography of the lungs (1). In patients with atypical features on imaging or other cause for diagnostic uncertainty, a surgical lung biopsy may be required to confirm diagnosis. This may be important for management, because treatment options and prognosis differ greatly between the various types of ILD.

Because patients with ILD often have impaired pulmonary function, the risks of thoracic surgery are an important consideration when contemplating surgical lung biopsy. Several case series have explored morbidity and mortality after the procedure, with 30-day mortality varying from 0 to 24% (2, 3).

This study assesses the risks of surgical lung biopsy for ILD in the United States using a national secondary care dataset.

We used the Nationwide Inpatient Sample (NIS), an anonymized stratified yearly sample of U.S. community hospitals (4). Individual records represent discharges from hospital, and details are provided on diagnoses and procedures using coding based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). To preserve confidentiality, unique patient identifiers are unavailable. Further information on the NIS is available in the online supplement.

We used data from 2000 to 2011 and selected all records with the following ICD-9-CM codes for ILD: 515 (postinflammatory pulmonary fibrosis), 516.3 (idiopathic fibrosing alveolitis), 517.2 (lung involvement in systemic sclerosis), 714.81 (rheumatoid lung), 517.8 (lung involvement in diseases classified elsewhere), 495 (extrinsic allergic alveolitis), 500–505 (pneumoconiosis, including asbestosis), and 135 (sarcoidosis). Codes 517.2, 714.81, and 517.8 were grouped together as connective tissue disease–related ILD (CTD-ILD). Code 516.3 was labeled “idiopathic pulmonary fibrosis clinical-syndrome” (IPF-CS) to reflect the fact that most of these cases would be IPF, but some would be other idiopathic interstitial pneumonias (5). We then selected those hospital stays involving a surgical lung biopsy using the following ICD-9-CM procedure codes: 33.28 (open biopsy of lung), 32.29 (other local excision or destruction of lesion or tissue of lung), 33.20 (thoracoscopic lung biopsy), and 32.20 (thoracoscopic excision of lesion or tissue of lung), the latter two codes being introduced in October 2007. We considered the “biopsy” codes (33.28 and 33.20) to be potentially more accurate than the “excision” codes (32.29 and 32.20) and therefore also performed a sensitivity analysis using these alone.

We excluded records with additional codes for segmental resection, lobectomy, or pneumonectomy that implied a therapeutic rather than diagnostic procedure. We also excluded records with a diagnostic code for lung cancer to ensure that diagnostic procedures for malignancy were not included. We focused on procedures coded as “elective” or “scheduled” (as opposed to “nonelective,” “urgent” or “emergency”), because these would be most relevant to the clinician planning a biopsy in the office setting.

We used weighted data to estimate the frequency of biopsy procedures nationwide. Our primary outcome measure was in-hospital mortality. We assessed risk factors for mortality using multiple logistic regression, adjusting for age, sex, census region, type of operation (thoracoscopic vs. open), and comorbidity. Comorbidity was assessed using the updated Charlson index (6, 7): Scores were derived from additional diagnostic codes and matched according to published guidance (see the online supplement for further details) (8). Because the specific diagnosis in the discharge record may not have been the final pathologic diagnosis, we presumed this to be the working or provisional diagnosis, and assessed its effect on mortality in our multivariable model, excluding records with multiple ILD diagnoses for clarity.

We also assessed length of stay and presence of complications. Complications were derived from additional diagnostic codes and therefore only assessed for elective procedures to exclude problems occurring before unplanned inpatient surgery. We limited our assessment to conditions we were confident were acute postoperative complications (see the online supplement).

Statistical analysis was performed using Stata version 13.1 (StataCorp, College Station, TX). To account for the complex stratified sample design, estimates were calculated using the specialized survey commands, taking account of year and strata, and using weights to create national estimates (9).

After exclusions, there were 32,022 records with a surgical lung biopsy for ILD in the NIS between 2000 and 2011 (Figure 1). Using weighted data, 66.3% of admissions were for elective procedures, 32.2% were for nonelective procedures, and for 1.5% the urgency of the operation was not clear. A total of 48% of total records were male, with 61% younger than age 65 (Table 1, unweighted raw data; see Table E1A in the online supplement, weighted data). Total numbers of records by year are presented online (see Table E1B), alongside demographics for “biopsy” and “excision” codes (see Tables E2 and E3).

Table 1. Demographics of Biopsy Cohort (Unweighted Data)

 Total Admissions (n = 32,022) [Number (%)]Elective Admissions (n = 21,227) [Number (%)]Nonelective Admissions (n = 10,310) [Number (%)]
 Male15,351 (47.94)9,942 (46.84)5,163 (50.08)
 Female16,671 (52.06)11,285 (53.16)5,147 (49.92)
Age group, yr
 <455,192 (16.21)3,153 (14.85)1,958 (18.99)
 45–546,264 (19.56)4,229 (19.92)1,944 (18.86)
 55–648,093 (25.27)5,643 (26.58)2,331 (22.61)
 65–748,147 (25.44)5,623 (26.58)2,406 (23.34)
 75–844,037 (12.61)2,431 (11.45)1,535 (14.89)
 >84289 (0.90)148 (0.70)136 (1.32)
Level of comorbidity (updated Charlson score)
 013,908 (43.43)10,627 (50.06)3,030 (29.39)
 110,844 (33.86)7,158 (33.72)3,558 (34.51)
 23,304 (10.32)1,728 (8.14)1,523 (14.77)
 ≥33,966 (12.39)1,714 (8.07)2,199 (21.33)

Higher updated Charlson score = greater comorbidity.

After applying weightings to adjust for sampling, we estimated there to be about 12,000 surgical lung biopsies performed for ILD each year in the United States (see Table E4). Numbers were relatively stable over time (Figure 2), although use of “biopsy” codes decreased, and “excision” codes became more prevalent (see Tables E5 and E6).

Biopsies were less commonly performed in the West census region (see Tables E7–E9). The most commonly coded provisional diagnosis (excluding cases with more than one type of ILD coded) was postinflammatory fibrosis (ICD-9-CM 515, 80% of the cohort), followed by IPF-CS (9.3%) and sarcoidosis (5.4%). A total of 8.3% of records had codes for more than one type of ILD (excluded from the multivariable analysis). The estimated number of biopsies for a suspected diagnosis of IPF-CS dropped noticeably around 2003 (Figure 3).

There were 2,051 deaths recorded before hospital discharge in our biopsy cohort. Nationally there were estimated to be 9,700 deaths (95% confidence interval [CI], 9,209–10,192) after surgical lung biopsy for ILD (before hospital discharge) between 2000 and 2011, giving an overall in-hospital mortality of 6.4% (95% CI, 6.1–6.7%). This comprised 1,695 deaths after elective operations (95% CI, 1,506–1,883), giving an in-hospital mortality of 1.7% (95% CI, 1.5–1.9%), and 7,796 deaths after nonelective operations (95% CI, 7,361–8,230), giving an in-hospital mortality of 16.0% (95% CI, 15.2–18.8%). In-hospital mortality reduced over time (Table 2, Figure 4).

Table 2. In-Hospital Mortality after Surgical Lung Biopsy for Interstitial Lung Disease, by Year

Year of BiopsyTotal Admissions [Deaths (% Mortality)]Elective Admissions [Deaths (% Mortality)]Nonelective Admissions [Deaths (% Mortality)]
2000822 (7.6)120 (1.2)591 (16.6)
2001962 (7.5)173 (2.2)690 (17.6)
2002923 (6.9)196 (2.1)727 (17.5)
2003934 (7.3)173 (2.1)761 (17.6)
2004875 (7.0)131 (1.6)745 (18.8)
2005876 (6.6)148 (1.7)727 (16.6)
2006876 (6.6)139 (1.6)736 (16.5)
2007696 (5.4)116 (1.3)580 (14.1)
2008715 (5.8)135 (1.6)580 (15.0)
2009709 (5.5)123 (1.5)586 (13.2)
2010696 (5.7)139 (1.7)557 (14.3)
2011617 (4.9)101 (1.2)516 (13.5)
Total9,700 (6.4)1,695 (1.7)7,796 (16.0)

Death estimates rounded to nearest integer. Totals calculated using raw data rather than sum of rounded values.

Increasing mortality was associated with male sex, increasing age, higher comorbidity scores, undergoing open rather than thoracoscopic surgery, and having a provisional diagnosis of IPF-CS or CTD-ILD (Table 3, elective patients; see Tables E10 and E11, overall and nonelective patients; all weighted data). After adjusting for sex, age, comorbidity, census region, type of operation, and provisional diagnosis, the associations remained significant. There were some differences between regions but no clear trends for elective and nonelective procedures. Repeating the analyses for records with “biopsy” codes only made a small difference to the overall results: mortality increased to 2.6% in elective patients (9.4% overall, 20.0% nonelective patients), and most of the associations were strengthened slightly (see Tables E12–E14).

Table 3. Multivariable Analysis (Associations with In-Hospital Death after Surgical Lung Biopsy) Elective Procedures

VariablesCasesDeaths (%)Unadjusted OR (95% CI)P ValueAdjusted OR (95% CI)P Value
 Female53,552733 (1.4)1.00 1.00 
 Male47,147962 (2.0)1.50 (1.22–1.85)<0.0011.41 (1.14–1.76)0.002
Age, yr
 <4514,98595 (0.6)1.00<0.001 (P for trend)1.00<0.001 (P for trend)
 45–5420,073148 (0.7)1.16 (0.67–2.01)1.20 (0.68–2.12)
 55–6426,680393 (1.5)2.33 (1.42–3.83)2.00 (1.19–3.38)
 65–7426,702611 (2.3)3.66 (2.28–5.88)3.09 (1.87–5.09)
 75–8411,547418 (3.6)5.86 (3.63–9.47)4.46 (2.69–7.40)
 >8471129 (4.0)6.56 (2.58–16.65)5.25 (2.16–12.74)
Updated Charlson score
 050,389410 (0.8)1.00<0.001 (P for trend)1.00<0.001 (P for trend)
 133,949509 (1.5)1.86 (1.41–2.45)1.83 (1.38–2.43)
 28,222359 (4.4)5.56 (4.09–7.56)5.17 (3.75–7.14)
 ≥38,139417 (5.1)6.58 (4.83–8.96)5.95 (4.32–8.20)
Geographic region
 South35,345716 (2.0)1.00 1.00 
 Northeast22,108234 (1.1)0.52 (0.37–0.73)<0.0010.53 (0.37–0.76)0.001
 Midwest26,824492 (1.8)0.91 (0.69–1.19)0.4770.94 (0.71–1.25)0.668
 West16,421252 (1.5)0.75 (0.55–1.03)0.0760.75 (0.54–1.04)0.083
Year group      
 2000–200223,311490 (2.1)1.000.009 (P for trend)1.000.028 (P for trend)
 2003–200525,719452 (1.8)0.83 (0.62–1.12)0.83 (0.61–1.14)
 2006–200826,163391 (1.5)0.71 (0.53–0.95)0.76 (0.56–1.05)
 2009–201125,505362 (1.4)0.67 (0.49–0.93)0.67 (0.47–0.95)
Type of operation (post-October 2007 patients only)
 VATS26,647314 (1.2)1.00 
 Open9,511218 (2.3)1.96 (1.36–2.83)<0.001
Provisional diagnosis (patients with single ILD diagnostic code only)
 PIF79,8531,143 (1.4)1.00 1.00 
 IPF-CS7,303374 (5.1)3.71 (2.83–4.88)<0.0013.17 (2.36–4.26)<0.001
 CTD-ILD1,11167 (6.0)4.39 (2.52–7.64)<0.0012.93 (1.65–5.22)<0.001
 Sarcoid5,27015 (0.3)0.19 (0.06–0.59)0.0040.28 (0.09–0.89)0.031
 Other3,14814 (0.5)0.32 (0.10–1.00)0.0500.19 (0.06–0.61)0.005

Definition of abbreviations: CI = confidence interval; CTD-ILD = connective tissue disease–related interstitial lung disease; IPF-CS = idiopathic pulmonary fibrosis clinical syndrome; OR = odds ratio; PIF = postinflammatory fibrosis; VATS = video-assisted thoracoscopic surgery.

Multivariable analysis excludes type of operation because of lower numbers; type of operation remained significant if included.

Higher Updated Charlson score reflects greater degree of comorbidity.

Estimated numbers of cases and deaths rounded to nearest integer.

“Other” refers to hypersensitivity pneumonitis and pneumoconioses (including asbestosis), grouped because of smaller numbers.

Table 4 shows the risk of in-hospital mortality after elective surgical lung biopsy for ILD using the key demographic determinants of sex, age, and comorbidity level (6). Comorbidity was classified into two categories: an Updated Charlson score of 0–1 (consistent with either no comorbidity, or a single lower scoring condition, such as chronic pulmonary disease, diabetes, or renal disease), or an updated Charlson score 2 or greater (consistent with multiple comorbidities, or a single higher-scoring condition, such as liver disease, dementia, heart failure, or malignancy) (further details are available online). Table 4 demonstrates the significant increase in mortality with male sex, increasing age, and increasing comorbidity.

Table 4. Risk of In-Hospital Mortality after Elective Surgical Lung Biopsy for Interstitial Lung Disease, by Age and Comorbidity

 Age <55 yr [% (95% CI)]Age 55–74 yr [% (95% CI)]Age >74 yr [% (95% CI)]
 Updated Charlson score, 0–10.4 (0.19–0.67)1.5 (1.20–1.92)2.7 (1.82–3.86)
 Updated Charlson score, ≥23.7 (2.29–6.06)5.4 (4.02–7.12)10.1 (7.33–13.87)
 Updated Charlson score, 0–10.4 (0.25–0.70)1.1 (0.87–1.48)1.9 (1.21–2.94)
 Updated Charlson score, ≥21.9 (1.00–3.46)4.0 (2.95–5.48)5.7 (3.36–9.51)

Definition of abbreviation: CI = confidence interval.

Updated Charlson score from Quan and colleagues (6).

For information on how to calculate the updated Charlson score, see Figure E1.

The median length of stay in our cohort of patients was 5 days, with a range of 0–308 days. A total of 96% of records were for stays of 30 days or less. Excluding those remaining in-hospital more than 30 days, in-hospital 30-day mortality was 5.4% (1.5% for elective patients, 14.2% for nonelective patients). Median length of stay was less for elective operations (3 vs. 12 d).

Possible complications were estimated to occur in 30% of elective records. The most common were postoperative pneumothorax (8.7%), pulmonary collapse (6.4%), pneumonia (5.8%), pleural effusion (3.2%), respiratory failure (3.1%), other respiratory complications (encompassing ventilator-associated pneumonia, chemical pneumonitis, and transfusion-related acute lung injury) (2.0%), ventilator dependence (1.8%), acute kidney injury (1.7%), bleeding complications (accidental puncture, laceration, bleeding, hemorrhage, or hematoma complicating the procedure) (1.7%), and surgical emphysema (1.1%).

Our cohort of surgical lung biopsies for ILD from hospitals across the United States has shown in-hospital mortality of just under 2% for elective operations, but a significantly increased mortality (16%) for nonelective (urgent and emergency) procedures. There was a strong but unsurprising link of mortality risk with increasing age and comorbidity, and also associations with male sex, open rather than thoracoscopic surgery, and a suspected diagnosis of IPF-CS or CTD-ILD.

The size of our cohort, at more than 30,000 procedures, is the largest reported series of surgical lung biopsies for ILD, and encompasses multiple centers from a large country. The NIS is the largest all-payer inpatient care database that is publically available in the United States, including patients covered by Medicare, Medicaid, private insurance, and the uninsured, and therefore is likely to be representative of the wider patient population. We focused on later years of the dataset (year 2000 onward) that were likely to have higher data completeness, with weightings used to adjust for sampling techniques. Although there is no universally agreed standard for assessing comorbidity using large datasets, our use of a contemporaneous score and published coding guidance helped ensure that our measures of comorbidity were reliable. We identified some differences between regions of the United States, although it is unclear whether this reflects variation in clinical practice or disease incidence.

The main limitation with using the NIS was the lack of unique patient identifiers, which limited our ability to assess readmissions, and raised the concern that a patient could be included more than once. However, it would be unusual for a patient to undergo a surgical lung biopsy on multiple occasions. A further limitation was the different diagnostic codes used for surgical lung biopsies, which in turn are dependent on clinical coders’ interpretations of operation notes; however, we used both broader and narrower terms to assess this impact. The large difference between elective and nonelective procedures could be affected by incorrect coding; however, it would be expected that more urgent cases might have higher mortality because of the severity of their illness.

Our exclusion of records with a code for lung cancer may have excluded some biopsy patients (who are likely to have been higher risk) but we believed this was necessary to prevent inclusion of those undergoing biopsies for their cancer. It is possible that some patients with suspected malignancy but no confirmed diagnostic code were included in the cohort inappropriately, but it is hoped these would be a small group. One disadvantage of using discharge records compared with a case series was the lack of a definitive histologic diagnosis, and the popularity of the nonspecific ICD-9-CM code for postinflammatory fibrosis, a condition not widely recognized in updated guidelines, limited our ability to assess the impact of the type of ILD.

We were unable to assess 30- or 90-day mortality, measures commonly used in other case series, and because most of our patients were discharged within 30 days it is likely that 30-day mortality would be slightly higher than our estimate, to account for deaths at home and after readmissions. Our analysis of comorbidity codes was only able to include those mentioned on the admission record, and it is possible that having a longer baseline period would have captured further conditions, thereby putting patients into higher risk comorbidity categories, and potentially lowering the mortality risk associated with higher comorbidity; however, it would be hoped that the more significant comorbidities coded with the updated Charlson score would be highlighted on an inpatient admission.

Finally, we lacked reliable data on medications, such as corticosteroids, immunosuppression, anticoagulation, and preoperative oxygen requirements, all of which have been associated with adverse outcomes in surgical lung biopsy case series (1012), and these should clearly be taken into account when counseling patients on risk. Nevertheless, our risk table (Table 4) gives a reasonable estimate of surgical risk that may be useful in the preoperative consultation. The possibility that this may underestimate the true risks (because of exclusion of some higher risk patients and those dying after hospital discharge, and misclassification of some patients as “nonelective”) should be kept in mind.

We systematically reviewed the literature for studies reporting mortality after surgical lung biopsy for ILD, and identified more than 50 reports from at least 20 countries. Differences in research aims, case selection (IPF vs. any ILD), type of surgery (open vs. thoracoscopic), and reporting outcomes (30-d mortality vs. “postoperative” or other) limited comparison between studies, but mortality estimates ranged from 0–34%. Studies reporting higher mortality tended to highlight the presence of acute symptoms, older age, preoperative respiratory failure or mechanical ventilation, and immunosuppression as associated with poor outcomes (3, 1317), suggesting more careful case selection could improve outcomes. Supporting this, one U.S. study specifically of patients undergoing biopsy during an acute exacerbation showed survival in only one of seven patients (18). Few studies distinguished between elective and nonelective surgery, although many included patients who were acutely unwell and likely to have undergone an urgent procedure.

Our estimate of 1.7% for in-hospital mortality after elective surgery is comparable with other estimates. Nguyen and Meyer (19) quoted “overall mortality” of 3.5% in their recent comprehensive review of studies (2.1% mortality for thoracoscopic surgery, 4.3% for open), although it was unclear how many of these were elective procedures. Kreider and colleagues (10) reviewed previous studies in 2007, and derived a composite postoperative mortality of 4.5%, noting a significantly increased mortality of 47% in those requiring preoperative ventilation compared with 2.2% in those free from ventilation. Overall, our data support the far higher risk of surgery in unplanned procedures. The fact that one in three patients in our dataset underwent a nonelective procedure suggests that these higher risk procedures are still being performed regularly. Although it is impossible to state the contribution of the surgery itself toward postoperative death, in a cohort who are clearly unwell because of underlying lung disease, patients should be aware of the mortality of those undergoing surgery in these circumstances. The decrease in procedures for suspected IPF-CS after 2003 likely reflects the publication of American Thoracic Society guidelines clarifying the diagnostic criteria for IPF and suggesting biopsy is not needed in those with typical radiologic appearances (20).

The overall incidence of ILD in the United States is not clear, but studies of such conditions as rheumatoid arthritis–associated ILD and sarcoidosis suggest it is increasing (21, 22). Most data surround IPF, which seems to be increasing worldwide (23), although perhaps less so recently in the United States (24, 25), which may reflect fewer patients meeting strict American Thoracic Society criteria, and an increasing number with “unclassified” ILD. It is possible that the stable absolute number of surgical lung biopsies performed over time reflects decreasing use of the procedure in an increasing number of patients with ILD, who are being diagnosed more commonly using radiology and multidisciplinary meetings.

In conclusion, our data suggest that surgical lung biopsy for ILD is associated with in-hospital mortality of 1.7% in elective patients, but a significantly increased mortality of greater than 15% in unplanned procedures. Increasing age and comorbidity were the main risk factors for mortality, but male sex, open surgery, and a provisional diagnosis of IPF-CS or CTD-ILD were also associated. Clinicians should make patients aware of the high-risk nature of nonelective surgical biopsy for ILD, and tailor their advice to individual clinical risk profiles.

The authors thank the Nationwide Inpatient Sample 2000–2011, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality for data.

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Correspondence and requests for reprints should be addressed to John P. Hutchinson, B.M. B.S., B.Med.Sci., C100 Clinical Sciences Building, City Hospital Campus, Hucknall Road, Nottingham NG5 1PB, UK. E-mail:

Author Contributions: J.P.H., A.W.F., T.M.M., and R.B.H. conceived and designed the study. J.P.H. obtained, prepared, and analyzed the data with assistance from T.M.M. J.P.H. wrote the first draft. All authors were involved in reviewing and shaping the manuscript, and all approved the final version before submission.

This article has an online supplement, which is accessible from this issue's table of contents at

Originally Published in Press as DOI: 10.1164/rccm.201508-1632OC on December 8, 2015

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American Journal of Respiratory and Critical Care Medicine

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