Lung biopsies are often required for diagnosing pulmonary diseases. These can be obtained either surgically or bronchoscopically. Currently, transbronchial forceps biopsies (TBFB) are the most common bronchoscopic modality for obtaining tissue specimens in diffuse parenchymal lung diseases (DPLD). However, TBFB are often limited by their small sample size and crush artifacts1 which adversely impact the diagnostic yield. The diagnostic yield for TBFB in DPLD has been reported to be 20% to 30%.2,3 Even though TBFB are relatively safe, due to their low diagnostic yield many patients end up requiring surgical lung biopsies (SLB) to obtain adequate tissue samples.
It is well-known that larger biopsy specimens increase the diagnostic yield.4 SLB allows for the retrieval of significantly larger samples with fewer artifacts and is considered the standard of reference. However, they carry a significant risk of morbidity and mortality. The in-hospital mortality with SLB is around 2%. However, it can be as high as 16% in certain patient populations.5 Therefore, there has been a growing need for novel techniques to improve diagnostic yield with an acceptable safety profile. In the past jumbo forceps were studied, they retrieved larger specimens with fewer crush artifacts but were limited by the need for deep sedation and rigid bronchoscopy.6
Recently, transbronchial cryobiopsies (TBCB) have been used to increase the yield of bronchoscopy for the diagnosis of DPLD. Cryotechnology has been utilized for both therapeutic and diagnostic purposes since the 1970s.7 Cryoprobes utilize the Joules Thomson effect.8 They work by applying cooling agents (eg, carbon dioxide or nitric oxide) under high pressure. As these gases expand due to sudden release to atmospheric pressure, there is a rapid drop in temperature (−80 to −90°C) at the probe tip. Pulmonary tissue firmly adheres to the cold probe tip and is easily extracted when the cryoprobe is withdrawn from the lung.
A number of meta-analyses have previously evaluated the performance of TBCB for diagnosing DPLD.9–14 Unfortunately, these analyses have been limited by the small number of studies included. Moreover, most of these analyses only included published studies and excluded conference abstracts, while failing to report any formal assessment for publication bias. It is a well-established fact that published studies tend to show a greater treatment impact as compared with unpublished studies.15,16 This is probably because authors and reviewers are less likely to publish studies with less significant or negative results.17 Moreover, studies from larger academic centers with greater expertise and more favorable outcomes are more likely to be published. Therefore, only including published studies in a meta-analysis will induce publication bias and potentially lead to an exaggerated assessment of the treatment impact. Many experts have previously warned against this practice.18,19
We have therefore, performed a comprehensive meta-analysis of both published and unpublished studies assessing the performance of TBCB. Our goal is to minimize the risk of publication bias and ensure that the results are generalizable across a large spectrum of clinical settings.
MATERIALS AND METHODS
A comprehensive and systematic search of MEDLINE (PubMed and OVID), EMBASE (Scopus), and Google Scholar was done in August 2017. We used “cryobiopsy” OR “cryoprobe” OR “cryotechnology” AND “diffuse parenchymal lung disease” OR “interstitial lung disease” as search terms to identify relevant studies. Additional studies were identified by reviewing reference lists of the considered articles. Conference abstract books were searched for additional studies that had been presented but not published as manuscripts.
Study selection was independently performed by 2 authors (J.S. and M.S.A.). Studies were initially screened by titles and abstracts. Where possible, full-text review was done for the screened studies to identify studies meeting the following selection criteria: (a) study employed TBCB in patients with DPLD; (b) diagnosis was confirmed either based on characteristic histopathologic findings or after a multidisciplinary team discussion; (c) study described the procedure-related complications or provided adequate data for the calculation of the diagnostic yield. Our exclusion criteria were: (a) case reports or series with <10 patients; (b) studies where TBCB was performed for pulmonary nodules or posttransplant surveillance bronchoscopies; (c) review papers. Non-English studies were also considered if they met the inclusion criteria.
Quality Assessment and Risk of Bias
Quality Assessment, Data Abstraction and Synthesis-2 (QUADAS-2) tool was used to assess the quality of eligible studies for risk of bias and applicability.20 It comprises of 4 main components: patient selection, index test, reference standard and, flow and timing. Signaling questions are used to assess each of these components for risk of bias as low, high or uncertain. Similarly, the first 3 domains are also assessed for concerns about lack of applicability. Two authors (M.A. and D.M.) separately assessed the quality of included studies. Inter-rater agreement between the 2 authors was assessed using the Kappa statistic.
Two authors (M.S.A. and J.S.) independently reviewed titles and identified studies from the previously identified sources. They independently reviewed abstracts and manuscripts (for published studies) to select studies meeting the inclusion criteria. Disagreements were settled by consensus, after having a third author weigh in. Following data was collected: study design, type of publication, mean/median age of participants, procedural protocols, final diagnoses, frequency of crush artifacts, mean size of biopsied specimens, type and frequency of complications and mortality data. The primary outcome was the diagnostic yield, which was calculated by dividing the number of successfully diagnosed cases (either based on characteristic histopathologic findings or multidisciplinary team discussion) by the total number of cases. Bleeding severity was classified as mild (resolved with simple suctioning), moderate (required wedging the bronchoscope into the effected segment to create a tamponade), and severe (required additional interventions such as bronchial blockers, topical fibrin sealant, blood transfusions or ICU admission).21 Moderate and severe bleeding episodes were considered significant. Any pneumothorax seen on the postprocedure x-ray was considered significant, whether or not it needed chest tube drainage.
MedCalc (version 17.2) was used to conduct the meta-analysis. A P-value of <0.05 was considered statistically significant. Inverse variance weighting was used to aggregate diagnostic yield proportions across studies. I2 index was used to assess study heterogeneity and I2 index of >40% was considered to be indicative of significant heterogeneity. If significant heterogeneity was identified, random effects model was utilized for data analysis. Publication bias was assessed using a funnel plot. Begg and Mazumdar, Duval and Tweedie’s trim and fill, and Egger tests were also performed for further assessment of publication bias. These additional tests for publication bias were performed using Comprehensive Meta-analysis software (version 3).
Search and Study Selection
Our search returned 457 titles on initial search across MEDLINE, EMBASE, and other sources. After removing duplicates total 252 titles and abstracts were screened. After initial screening 44 studies (28 published studies, 16 abstracts) were considered for inclusion and full-text review (where applicable). Amongst these 13 studies (10 published studies, 3 abstracts) were excluded. Four studies had overlapping study populations and were excluded to prevent duplication of patients.22–25 Three studies were excluded since they were not deemed to have enough diagnostic or safety data.26–28 Three studies were excluded because they evaluated cryobiopsies for endobronchial lesions, 2 were excluded because they used TBCB for posttransplant surveillance and 1 study was excluded because it used TBCB for diagnosing suspected lung cancer.29–34 A total of 31 studies (18 published, 13 abstracts) were included in the analysis.13,35–64 Included studies were published between February 2009 and August 2017. Four of these studies only provided safety-related data, therefore they were only used while analyzing safety profile.36,51,53,54 Only 1 non-English study was included. It was published by Fournier and colleagues in French. Figure 1 shows the Prisma flow diagram for the meta-analysis. Basic characteristics of the included studies are outlined in Table 1.
Application of QUADAS-2 tool showed low risks of bias and lack of applicability in the patient selection and index test domains. Most of the studies did not refer the patients for SLB, therefore these studies had undetermined risks of bias and lack of applicability in the reference standard domain. Details of application of QUADAS-2 tool are summarized in Table 2. Inter-rater agreement between the authors was good, with a Kappa statistic of 0.9 [95% confidence interval (CI), 0.7-1.0]. The funnel plot (Supplementary Fig. 1, Supplemental Digital Content 1, http://links.lww.com/LBR/A163) was not asymmetric which reflected the absence of publication bias. Similarly, Begg and Mazumdar, Duval and Tweedie’s trim and fill, and Egger tests also did not suggest publication bias.
Data were pooled from 27 studies, with 1443 patients with DPLD, for the calculation of the diagnostic yield. Between studies the diagnostic yield ranged from 40% to 95.1%. The inverse variance–weighted diagnostic yield for TBCB for the diagnosis of DPLD was 72.9% (95% CI, 67.9%-77.7%). I2 index of 75.4% (95% CI, 64.3-83.0) indicated significant heterogeneity. Figure 2 shows the forest plot for the meta-analysis.
In order to explore the causes of heterogeneity we performed subgroup analyses. Analyses were separately performed for retrospective and prospective studies, abstracts and full manuscripts. We also analyzed subgroups of prospective studies published as full manuscripts, studies which used only 1.9 mm probes and high-quality studies. High-quality studies were defined as the studies which had a low risk of bias in all 4 domains, that is patient selection, index test, reference standard, and flow and timing. All of these subgroups continued to have high heterogeneity, reflecting that the high over all heterogeneity was unlikely to be related to the differences in study design (retrospective vs. prospective), type of publication (abstract vs. manuscript), the differences in the cryoprobe sizes and the disparity in the study quality as assessed by QUADAS-2 tool. The results of our subgroup analyses are summarized in Table 3.
Specimen area was reported by 9 studies. Two of these studies had previously been excluded to prevent duplication of cases.23,24 Pooled mean specimen size of TBCB specimens was 23.4 mm2 (95% CI, 9.6-37.3 mm2). Significant heterogeneity was observed with I2 index was 87.61%. Forest plot for this meta-analysis is shown in Supplementary Figure 2 (Supplemental Digital Content 2, http://links.lww.com/LBR/A164).
Five studies commented on the crush artifacts. Kronborg-White et al44 reported crush artifact in just one sample. Pajares and colleagues reported crush artifacts as the proportion of samples with >75% artifact-free area. In all, 66.6% of the TBCB specimens had a >75% artifact-free area as compared with 31.6% of TBFB specimens (P=0.012).59 Jabbardarjani et al61 reported that the proportion of TBCB specimens with crush artifacts was significantly lower than TBFB specimens; however, it was not mentioned as to how the crush artifacts were quantified. Hernández-González et al55 and Babiak et al64 reported that they did not observe crush artifacts on any of the cryobiopsy specimens.
The overall complication rate was 23.1%. Most commonly reported complications were bleeding and pneumothoraces. A total of 30 studies reported data regarding the incidence of pneumothorax. The pooled incidence of pneumothoraces was 9.4% (95% CI, 6.7%-12.5%). Supplementary Figure 3 (Supplemental Digital Content 3, http://links.lww.com/LBR/A165), shows the forest plot for this analysis. In contrast, the pooled incidence of significant (moderate and severe) bleeding was 14.2% (95% CI, 7.9%-21.9%). This analysis was based on 27 studies and Supplementary Figure 4 (Supplemental Digital Content 4, http://links.lww.com/LBR/A166), shows the forest plot. A total of 33 studies reported mortality. There was a total of 6 deaths within 30 days of the procedure. Procedural mortality was 0.3%. The details of complications for each of the study are presented in supplementary Table 1 (Supplemental Digital Content 5, http://links.lww.com/LBR/A167).
Supplementary Table 2 (Supplemental Digital Content 5, http://links.lww.com/LBR/A167), summarizes the final diagnoses in different studies. There were marked differences in the prevalence of different DPLDs in different studies. This may have contributed to the high overall heterogeneity.
To our knowledge, this is the largest meta-analysis evaluating diagnostic performance and safety of TBCB for the diagnosis of DPLD. The overall, inverse variance–weighted diagnostic yield of 72.9% is higher than TBFB’s previously reported diagnostic yield.2,3 TBFB are often limited by small specimen size and crush artifacts. In our analysis TBCB yielded larger sample sizes [mean area 23.4 mm2 (95% CI, 9.6-37.3 mm2)] when compared with previous reports for TBFB. In addition, less crush artifact and more alveolar tissue was reported with TBCB specimens.
The 72.9% diagnostic yield in our meta-analysis appears to be in line with the diagnostic yields previously reported in other TBCB meta-analyses. Table 4 lists the pooled diagnostic yields from recent TBCB meta-analyses. The pooled complication rates in our meta-analyses are also similar to those reported previously. Table 5 lists the rates of significant bleeding and pneumothoraces from recent meta-analyses. According to American Thoracic Society(ATS)/European Respiratory Society (ERS) guidelines, SLB remains the reference standard.65 However, they are not without risks and are often associated with significant morbidity and mortality. Most recent studies show a 30-day mortality of between 3% and 10.6%, with a greater risk in patients undergoing open lung biopsy.66–68 Because of these risks pursuing bronchoscopic biopsies which are much safer, before SLB is a lucrative option. TBFB are limited in terms of their diagnostic yield (20% to 30%) but have a low rate of complications. The rate of pneumothorax is 0.7% to 2%, while the rate of significant bleeding is 1% to 4%.12,69
On the basis of the results of our meta-analysis TBCB when compared with TBFB, increased the diagnostic yield from 20%-30% to 74.6%. However, there is a significant concomitant increase in the risks of pneumothorax (from 0.7%-2% to 9.4%) and significant bleeding (1-4% to 14.2%). Some of the benefit in terms of the improved diagnostic yield appears to be off set by the marked increase in the risk of complications. Also, there is a concern about the reporting of mortality data. Most of the studies only reported those 30-day deaths which the authors deemed to be related to TBCB. Therefore, the true 30-day postprocedure mortality is likely higher than 0.3% reported in our meta-analysis.
For the above reasons, it is apparent that more research is needed before the TBCB can be more widely adopted in a broad range of clinical settings. We found marked variations in the procedural protocols between studies. Flexible versus rigid bronchoscopy, laryngeal mask airway versus endotracheal tube, use of prophylactic bronchial blockers, the size of the cryoprobes, number of samples taken, contact time of cryoprobe, use of fluoroscopy, etc., are some of the areas where there was significant variation between the studies. Supplementary Table 3 (Supplemental Digital Content 5, http://links.lww.com/LBR/A167), highlights the different procedure protocols followed by different investigators. Perhaps standardizing the procedure will help further increase the diagnostic yield and reduce the complication rates for TBCB. For example, Ravaglia and colleagues prophylactically used Fogarty balloons after each TBCB and no significant bleeding episodes were seen in their study. In contrast, most of the other investigators did not use prophylactic bronchial blockers, which may have led to higher bleeding rates. Other experts have also called on the community of interventional pulmonologists and interstitial lung disease experts, to shoulder the responsibility of formulating a consensus statement, guiding the implementation of TBCB.70
Randomized controlled trials can allow for head to head comparison between SLB, TBFB, and TBCB. Such trials will allow for standardization of the procedure and will also allow to better study the factors that might be associated with higher complications rates. An understanding of these factors can lead to a more informed patient selection which in turn will improve TBCB’s safety profile. Experts have also called for mandatory procedure-specific training for interventional pulmonologists before implementation of TBCB programs and creation of an international registry.70
There are several limitations of our meta-analysis. Firstly, several studies utilized a retrospective study design, which has an inherent potential for bias. Secondly, there was marked heterogeneity amongst the studies. We were unable to definitively find the reasons behind this heterogeneity; however, it may be related to the differences in the procedure protocols, disparities in the expertise of operators and the differences in the prevalence of various DPLDs in different studies. Thirdly, most of the patients who were diagnosed with TBCB did not undergo SLB, which is currently the standard of reference. It is therefore hard to assess if TBCB led to misclassification of some of the DPLD cases. Fourthly, studies did not report the TBCB diagnostic yield for specific DPLDs. It was not possible to assess if TBCB might have a higher yield for certain DPLDs as compared with others. Fifthly, in some circumstances the complication rates reported in our study might be higher than what is considered clinically significant. For example, an episode of bleeding that was controlled by wedging the bronchoscope is considered moderate (and hence significant) in our analysis; however, for some clinicians it may not be of much clinical consequence. Similarly, pneumothoraces which did not require chest tube insertion are considered significant in the current analysis however others may debate their clinical significance. Unfortunately, some studies just reported the significant bleeds without specifying the precise number of moderate and severe bleeds, therefore it is hard to calculate the true incidence of only severe bleeds. Never the less our definition of significant complications which includes both moderate and severe bleeds, and all pneumothoraces regardless of chest tube insertion and duration of air-leak, is in line with most of the available TBCB literature including prior meta-analyses. Sixthly, there is a difference in the definition of significant complications between the bronchoscopy and surgical literature. Therefore, it is hard to directly compare the complication rates of TBCB with SLB. As a result, we have relied on the mortality outcomes to compare the two. Lastly, 13 studies in our meta-analysis were conference abstracts. For some these studies assessing the study quality was hard, based on the limited information available in the published abstract.
Our meta-analysis shows that TBCB has a good diagnostic yield but at the cost of a significant risk of complications. These results are in line with the prior meta-analyses on this topic even though we included a higher number of studies. Our meta-analysis yet again highlights the marked heterogeneity in the procedural techniques at different centers. Randomized controlled trials comparing SLB, TBFB and TBCB are needed before more definitive recommendations can be made regarding TBCB’s place in DPLD’s diagnostic algorithm. Convening experts, offering procedure-specific training and forming an international registry are some of the other ways to standardize the procedure and improve its safety profile. Until then it is important that patients are carefully selected and the procedure is performed at centers with considerable experience.
1. Griff S, Ammenwerth W, Schönfeld N, et al. Morphometrical analysis of transbronchial cryobiopsies. Diagn Pathol. 2011;6:53.
2. Berbescu EA, Katzenstein A-LA, Snow JL, et al. Transbronchial biopsy in usual interstitial pneumonia. Chest. 2006;129:1126–1131.
3. Sheth JS, Belperio JA, Fishbein MC, et al. Utility of transbronchial vs surgical lung biopsy in the diagnosis of suspected fibrotic interstitial lung disease. Chest. 2017;151:389–399.
4. Curley FJ, Johal JS, Burke ME, et al. Transbronchial lung biopsy: can specimen quality be predicted at the time of biopsy? Chest. 1998;113:1037–1041.
5. Hutchinson JP, Fogarty AW, McKeever TM, et al. In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States. 2000 to 2011. Am J Respir Crit Care Med. 2015;193:1161–1167.
6. Casoni GL, Gurioli C, Chhajed PN, et al. The value of transbronchial lung biopsy using jumbo forceps via rigid bronchoscope in diffuse lung disease. Monaldi Arch Chest Dis. 2008;69:59–64.
7. Rodgers BM, Rosenfeld M, Talbert JL. Endobronchial cryotherapy in treatment of tracheal strictures. J Pediatr Surg. 1977;12:443–449.
8. Poletti V, Casoni GL, Gurioli C, et al. Lung cryobiopsies: a paradigm shift in diagnostic bronchoscopy
? Respirology. 2014;19:645–654.
9. Iftikhar IH, Alghothani L, Sardi A, et al. Transbronchial lung cryobiopsy
and video-assisted thoracoscopic lung biopsy in the diagnosis of diffuse parenchymal lung disease. A meta-analysis
of diagnostic test accuracy. Ann Am Thorac Soc. 2017;14:1197–1211.
10. Ganganah O, Guo S, Chiniah M, et al. Efficacy and safety of cryobiopsy
versus forceps biopsy for interstitial lung diseases and lung tumours: a systematic review and meta-analysis
. Respirology. 2016;21:834–841.
11. Johannson KA, Marcoux VS, Ronksley PE, et al. Diagnostic yield and complications of transbronchial lung cryobiopsy
for interstitial lung disease. A systematic review and metaanalysis. Ann Am Thorac Soc. 2016;13:1828–1838.
12. Sharp C, McCabe M, Adamali H, et al. Use of transbronchial cryobiopsy
in the diagnosis of interstitial lung disease-a systematic review and cost analysis. QJM. 2017;110:207–214.
13. Ravaglia C, Bonifazi M, Wells AU, et al. Safety and diagnostic yield of transbronchial lung cryobiopsy
in diffuse parenchymal lung diseases
: a comparative study versus video-assisted thoracoscopic lung biopsy and a systematic review of the literature. Respiration. 2016;91:215–227.
14. Dhooria S, Sehgal IS, Aggarwal AN, et al. Diagnostic yield and safety of cryoprobe transbronchial lung biopsy in diffuse parenchymal lung diseases
: systematic review and meta-analysis
. Respir Care. 2016;61:700–712.
15. McAuley L, Pham B, Tugwell P, et al. Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses? Lancet (London, England). 2000;356:1228–1231.
16. Eyding D, Lelgemann M, Grouven U, et al. Reboxetine for acute treatment of major depression: systematic review and meta-analysis
of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials. BMJ. 2010;341:c4737.
17. Turner EH, Matthews AM, Linardatos E, et al. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008;358:252–260.
18. Hopewell S, McDonald S, Clarke M, et al. Grey literature in meta-analyses of randomized trials of health care interventions. Cochrane Database Syst Rev. 2007:MR000010.
19. Driessen E, Hollon SD, Bockting CLH, et al. Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis
of US National Institutes of Health-Funded Trials. PLoS ONE. 2015;10:e0137864.
20. Whiting PF, Rutjes AWS, Westwood ME, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–536.
21. Ernst A, Eberhardt R, Wahidi M, et al. Effect of routine clopidogrel use on bleeding complications after transbronchial biopsy in humans. Chest. 2006;129:734–737.
22. Tomassetti S, Wells AU, Costabel U, et al. Bronchoscopic lung cryobiopsy
increases diagnostic confidence in the multidisciplinary diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2016;193:745–752.
23. Casoni GL, Tomassetti S, Cavazza A, et al. Transbronchial lung cryobiopsy
in the diagnosis of fibrotic interstitial lung diseases. PLoS ONE. 2014;9:1–7.
24. Kropski JA, Pritchett JM, Mason WR, et al. Bronchoscopic cryobiopsy
for the diagnosis of diffuse parenchymal lung disease. PLoS ONE. 2013;8:6–11.
25. Ravaglia C, Wells AU, Tomassetti S, et al. Transbronchial lung cryobiopsy
in diffuse parenchymal lung disease: comparison between biopsy from 1 segment and biopsy from 2 segments—diagnostic yield and complications. Respiration. 2017;93:285–292.
26. Fernandez AMM, Pajares V, Lucena C, et al. Safety of transbronchial lung criobiopsy in mechanically ventilated patients in critical care. Multicenter study. Eur Respir J. 2016;48:OA3019.
27. Hetzel J, Eberhardt R, Petermann C, et al. Bleeding severity after transbronchial cryobiopsies is influenced by body height and age (Abstract ID-A7408). Am J Respir Crit Care Med. 2017;195:A7408.
28. Steele MP, Benzaquen S, Myers JL, et al. Cohort comparison between transbronchial cryobiopsy
and surgical lung biopsy (SLB) in patients undergoing a workup for interstitial lung disease (ILD) from a multi-center, prospective trial (abstract ID-A3464). Am J Respir Crit Care Med. 2017;195:A3464.
29. Aktas Z, Gunay E, Hoca NT, et al. Endobronchial cryobiopsy
or forceps biopsy for lung cancer diagnosis. Ann Thorac Med. 2010;5:242–246.
30. Schumann C, Hetzel J, Babiak AJ, et al. Cryoprobe biopsy increases the diagnostic yield in endobronchial tumor lesions. J Thorac Cardiovasc Surg. 2010;140:417–421.
31. Hetzel J, Eberhardt R, Herth FJF, et al. Cryobiopsy
increases the diagnostic yield of endobronchial biopsy: a multicentre trial. Eur Respir J. 2012;39:685–690.
32. Yarmus L, Akulian J, Gilbert C, et al. Cryoprobe transbronchial lung biopsy in patients after lung transplantation a pilot safety study. Chest. 2013;143:621–626.
33. Fruchter O, Fridel L, Rosengarten D, et al. Transbronchial cryo-biopsy in lung transplantation patients: first report. Respirology. 2013;18:669–673.
34. Chou C-L, Wang C-W, Lin S-M, et al. Role of flexible bronchoscopic cryotechnology in diagnosing endobronchial masses. Ann Thorac Surg. 2013;95:982–986.
35. Roglic M, Sonja B, Ana H, et al. Transbronchial cryobiopsy
: do we really need fluoroscopic guidance (Abstract ID-OP-26). Belgrade, Serbia: European Association of Bronchology and Interventional Pulmonology (EABIP); 2017.
36. Schmutz A, Dürk T, Idzko M, et al. Feasibility of a supraglottic airway device for transbronchial lung cryobiopsy
—a retrospective analysis. J Cardiothorac Vasc Anesth. 2017;4:1343–1347.
37. Sriprasart T, Aragaki A, Baughman R, et al. A single US center experience of transbronchial lung cryobiopsy
for diagnosing interstitial lung disease with a 2-scope technique. J Bronchol Interv Pulmonol. 2017;24:131–135.
38. Bondue B, Pieters T, Alexander P, et al. Role of transbronchial lung cryobiopsies in diffuse parenchymal lung diseases
: interest of a sequential approach. Pulm Med. 2017;2017:e6794343.
39. Brueder A, Raj R, Kamp DW, et al. Transbronchial cryobiopsy
for the diagnosis of interstitial lung diseases: diagnostic yield, outcomes and risk factors for complications (abstract ID-A1119). Am J Respir Crit Care Med. 2017;195:A1119.
40. Cooley J, Balestra R, Aragaki A, et al. Transbronchial cryobiopsy
for diagnosing interstitial lung disease with a two-scope technique (abstract ID-A3451). Am J Respir Crit Care Med. 2017;195:A3451.
41. Bango-Álvarez A, Ariza-Prota M, Torres-Rivas H, et al. Transbronchial cryobiopsy
in interstitial lung disease: experience in 106 cases—how to do it. ERJ Open Res. 2017;3:pii: 00148–pii: 02016.
42. Owuor A, Kern I, Rozman A. Diagnostic yield and safety of transbronchial cryobiopsy
(abstract ID-OP-37). Belgrade, Serbia: European Association of Bronchology and Interventional Pulmonology (EABIP); 2017.
43. DiBardino DM, Haas AR, Lanfranco AR, et al. High complication rate after introduction of transbronchial cryobiopsy
into clinical practice at an Academic Medical Center. Ann Am Thorac Soc. 2017;6:851–857.
44. Kronborg-White S, Folkersen B, Rasmussen TR, et al. Introduction of cryobiopsies in the diagnostics of interstitial lung diseases—experiences in a referral center. Eur Clin Respir J. 2017;4:1274099.
45. Fournier C, Wemeau-Stervinou L, Copin MC, et al. Cryobiopsies transbronchiques dans le diagnostic des pneumopathies interstitielles diffuses: résultats préliminaires [Transbronchial cryobiopsy
for the diagnosis of diffuse interstitial pneumonias: preliminary results] (abstract ID-278). Rev Mal Respir. 2017;34 (suppl):A124–A125.
46. Ussavarungsi K, Kern RM, Roden AC, et al. Transbronchial cryobiopsy
in diffuse parenchymal lung disease: retrospective analysis of 74 cases. Chest. 2016;151:400–408.
47. Ramaswamy A, Homer R, Killam J, et al. Comparison of transbronchial and cryobiopsies in evaluation of diffuse parenchymal lung disease. J Bronchol Interv Pulmonol. 2016;23:14–21.
48. Hagmeyer L, Theegarten D, Wohlschläger J, et al. The role of transbronchial cryobiopsy
and surgical lung biopsy in the diagnostic algorithm of interstitial lung disease. Clin Respir J. 2016;10:589–595.
49. Palazon MAM, Cosío BG, Sala E, et al. Transbronchial cryobiopsy
in the diagnosis of the idiopathic interstitial pneumonias (abstract ID-PA4669). Eur Respir J. 2016;48:PA4669.
50. Cortadellas MC, Oezkan F, Boerner EB, et al. Diagnosing interstitial lung dieseases via cryobiopsy
in rigid bronchoscopy
: preliminary results (abstract ID-PA4668). Eur Respir J. 2016;48:PA4668.
51. Dalvi P, Kretz G, Clum S, et al. Transbronchial lung cryobiopsy
(TBLC) at a tertiary referral hospital: a two-year experience. Pulm Crit Care Med. 2016;2:1–4.
52. Lentz RJ, Taylor TM, Kropski JA, et al. Utility of flexible bronchoscopic cryobiopsy
for diagnosis of diffuse parenchymal lung diseases
. J Bronchol Interv Pulmonol. 2017;25:88–96.
53. Mikolasch TA, Borg E, Thakrar R, et al. Transbronchial cryobiopsies in the diagnosis of interstitial lung diseases—first UK experience (abstract ID-S42). Thorax. 2015;70:A27–A28.
54. Gershman E, Fruchter O, Benjamin F, et al. Safety of cryo-transbronchial biopsy in diffuse lung diseases: analysis of three hundred cases. Respiration. 2015;90:40–46.
55. Hernández-González F, Lucena CM, Ramírez J, et al. Cryobiopsy
in the diagnosis of diffuse interstitial lung disease : yield and cost-effectiveness analysis. Arch Bronconeumol. 2015;51:261–267.
56. López V, López X, Herrero S, et al. Complications of transbronchial cryobiopsy
in insterticial lung diseases (abstract ID-PA2194). Eur Respir J. 2015;46:PA2194.
57. Griff S, Schönfeld N, Ammenwerth W, et al. Diagnostic yield of transbronchial cryobiopsy
in non-neoplastic lung disease: a retrospective case series. BMC Pulm Med. 2014;14:171.
58. Fruchter O, Fridel L, El Raouf BA, et al. Histological diagnosis of interstitial lung diseases by cryo-transbronchial biopsy. Respirology. 2014;19:683–688.
59. Pajares V, Puzo C, Castillo D, et al. Diagnostic yield of transbronchial cryobiopsy
in interstitial lung disease: a randomized trial. Respirology. 2014;19:900–906.
60. Oberle AS, Hann Von Weyhern CW, Horger M, et al. The diagnostic work-up of interstitial lung disease is significantly improved by transbronchial cryobiopsies without notable clinical complications (abstract ID-A6640). Am J Respir Crit Care Med. 2014;189:A6640.
61. Jabbardarjani H, Kiani A, Karimi M, et al. Cryobiopsy
shows better safety profile and diagnostic yield as compared to conventional forceps for interstitial lung disease (abstract ID-P2301). Eur Respir J. 2013;42:P2301.
62. Pritchett JM, Kropski JA, Mason WR, et al. Bronchoscopic cryobiopsy
for the diagnosis of diffuse parenchymal lung disease (abstract ID-A5978). Am J Respir Crit Care Med. 2013;187:A5978.
63. Böing S, Hagmeyer L, Stieglitz S, et al. Retrospective study of transbronchial cryobiopsy
(TCB) data in a case series of 20 patients with interstitial lung disease (abstract ID-P3604). Eur Respir J. 2012;40:P3604.
64. Babiak A, Hetzel J, Krishna G, et al. Transbronchial cryobiopsy
: a new tool for lung biopsies. Respiration. 2009;78:203–208.
65. Raghu G, Collard HR, Egan JJ, et al. An Official ATS/ERS/JRS/ALAT Statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788–824.
66. Fibla JJ, Brunelli A, Cassivi SD, et al. Aggregate risk score for predicting mortality after surgical biopsy for interstitial lung disease. Interact Cardiovasc Thorac Surg. 2012;15:276–279.
67. Lettieri CJ, Veerappan GR, Helman DL, et al. Outcomes and safety of surgical lung biopsy for interstitial lung disease. Chest. 2005;127:1600–1605.
68. Kaarteenaho R. The current position of surgical lung biopsy in the diagnosis of idiopathic pulmonary fibrosis. Respir Res. 2013;14:43.
69. Bradley B, Branley HM, Egan JJ, et al. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax. 2008;63(suppl 5):v1–v58.
70. Lentz RJ, Argento AC, Rickman OB, et al. Transbronchial cryobiopsy
: a cautionary tale and opportunities for improvement. Ann Am Thorac Soc. 2017;14:1230–1231.