Effect of Autologous Blood Patch Injection Versus BioSentry Hydrogel Tract Plug in the Reduction of Pneumothorax Risk Following Lung Biopsy Procedures
Phase: PHASE3
Conditions: Lung Biopsy
Sponsor: Memorial Sloan Kettering Cancer Center

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
 
 
 
 
 
 
MSK PROTOCOL COVER SHEET 
 
Effect Of Autologous Blood Patch Injection Versus Biosentry Hydrogel Tract Plug In The 
Reduction Of Pneumothorax Risk Following Lung Biopsy Procedures 
 
 
 
Amgad Moussa, MD/Radiology 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 23 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
Page 2 of 23 
 
 
 
 
 
Table of Contents 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA ...................................................................... 3 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS ............................................................................... 5 
3.0 
BACKGROUND AND RATIONALE ..................................................................................... 5 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION ................................................................... 7 
4.1 
Design ................................................................................................................................ 7 
4.2 
Intervention ............................................................................................................................. 7 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS ............................................................................. 9 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY ................................................................................ 9 
6.1 
Subject Inclusion Criteria .................................................................................................... 9 
6.2 
Subject Exclusion Criteria ................................................................................................ 10 
7.0 
RECRUITMENT PLAN ...................................................................................................................................... 10 
8.0 
PRETREATMENT EVALUATION ...................................................................................... 11 
9.0 
TREATMENT/INTERVENTION PLAN ............................................................................... 11 
10.0 
EVALUATION DURING TREATMENT/INTERVENTION .................................................... 11 
11.0 
TOXICITIES/SIDE EFFECTS .................................................................................................... 12 
12.0 
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT ........................ 12 
13.0 
CRITERIA FOR REMOVAL FROM STUDY ....................................................................... 13 
14.0 
BIOSTATISTICS ............................................................................................................... 13 
15.0 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES14 
15.1 Research Participant Registration ......................................................................................... 14 
15.2 
Randomization ................................................................................................................... 14 
16.0 
DAT A M ANAGEMENT ISSUES ........................................................................................ 14 
16.1 
Quality Assurance ............................................................................................................ 14 
16.2 
Data and Safety Monitoring .................................................................................................. 15 
17.0 
PROTECTION OF HUMAN SUBJECTS ............................................................................ 15 
17.1 
Privacy ............................................................................................................................. 16 
17.2 
Serious Adverse Event (SAE) Reporting ............................................................................. 16 
17.2.1.........................................................................................................................................18 
18.0 
INFORMED CONSENT PROCEDURES .................................................................................. 18 
19.0 
REFERENCES ...................................................................................................................... 18 
20.0 
APPENDICES ................................................................................................................... 20 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
Page 3 of 23 
 
 
 
 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
 
This study will compare the effectiveness of autologous blood patch injection (ABPI) versus 
the BioSentry (formerly known as Bio-Seal) hydrogel Tract Plug (developed by Angiotech, 
Vancouver British Columbia)  in reducing the rate of iatrogenic pneumothoraces when used 
in routine image guided lung biopsy procedures involving passage through aerated lungs. 
Both techniques are within the current standard of care in our institution. This involves the 
very last step of a lung biopsy which is removal of introducer needle. Patients who fulfill 
inclusion criteria will be randomized to one of two arms of the introducer needle removal 
technique. The patients will then be monitored in the post operative period for at least two 
hours with chest radiographs and any complications will be treated all as per standard of 
care practice. The vast majority of iatrogenic pneumothoraces from image guided lung 
biopsies occur within the first two hours post biopsy as determined by our own clinical 
experience [2] and confirmed by similar studies in the literature [3–5] . A follow up phone call 
(Appendix 20.4) to patients  within two weeks after the lung biopsy is made to assess 
possible delayed pneumothoraces which are very rare and involve less than 1% of patients 
[2,3,5]. The phone call is not within standard of care. However any consequent treatments are 
within standard of care practice. We expect that less than 5 percent of all biopsies may end 
up being excluded during the procedure from intraprocedural complications precluding the 
use of a tract sealant. 
The main objective is to determine non-inferiority of ABPI in the reduction of pneumothorax 
rate which is much cheaper to perform as opposed to BioSentry. 
Potential candidates for this study will be recruited from patients referred to our Interventional 
Radiology service for lung biopsy. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
Page 4 of 23 
 
 
 
 
 
 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
Page 5 of 23 
 
 
 
 
2.1 
OBJECTIVES AND SCIENTIFIC AIMS 
 
Primary objective: 
 
• 
To determine non-inferiority of ABPI when compared to BioSentry in reducing the rate 
of iatrogenic pneumothorax during the routine observation stay within 2 hours 
following image guided lung biopsy. 
Secondary objective: 
 
• 
To evaluate ABPI and BioSentry in reducing the rate of iatrogenic pneumothorax 
during the routine observation stay within 2 hours following image guided biopsy in a 
per-protocol analysis. 
• 
To evaluate ABPI and BioSentry in reducing the rate of chest tube placement for 
pneumothorax up to  two weeks following lung biopsy. 
• 
To evaluate ABPI and BioSentry in reducing the rate of delayed pneumothorax up to 
two weeks following lung biopsy. 
3.0 
BACKGROUND AND RATIONALE 
 
Percutaneous needle biopsy of lung is a well accepted and accurate method of diagnosis of 
pulmonary nodules and masses (90 % sensitive; almost 100% specific for malignancy) [6–8]. 
The demand for percutaneous lung needle biopsies is on the rise given the rising incidence  
of lung cancer, increased detection of asymptomatic lung nodules on imaging and the need 
for tissue for new molecular diagnostics [9]. In 2012 IR service performed 1128 lung biopsies 
which resulted in 86 chest tube placements and consequent admissions (%7.2). The total 
number of lung biopsies has constantly increased over time at our institution. IR service 
currently performs around 100 lung biopsies each month. The most common complication of 
a percutaneous lung biopsy is pneumothorax [10] or lung collapse and is caused by air  
leaking out of the lung through needle puncture site on the visceral pleura once the needle is 
removed. This is determined clinically and is observed either on the final post procedure CT 
images or on the follow up chest radiographs performed within 2 hours of the procedure  
while the patient is still in the recovery room. The majority of iatrogenic pneumothoraces is 
small and managed conservatively but they may require intervention by either aspiration or 
placement of a chest tube which usually implies a hospital admission. Most large series 
report an incidence of 15-25% for iatrogenic pneumothorax, but in some studies, the rate can 
reach as high as 40% [10]. In our institution, the rate of post biopsy pneumothorax is 
estimated at 23% based on a study performed in 2004 which is close to the literature findings 
[1]. The risk of pneumothorax requiring intervention, chest tube placement and admission is 
smaller but nonetheless appreciable and reported risks range between 4% and 6% [10]  
similar to the rate we reported from our institution which is 6.8% [1]. There is no accurate 
method of predicting which patient will develop a pneumothorax or require chest tube 
placement although multiple factors such as chronic lung disease, small nodule size, 
increased depth from skin and needle gauge size have been shown to be contributing 
elements [1,11]. However, when these complications do occur, the psychological and 
economic burden can be significant. A study in 1998 by Gurley et al evaluated the cost of 
inpatient management of patients with chest tubes and found that the average total 
management costs amounted to $3,950 which was $2,261 more than that for outpatients 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
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($1,689). The significant cost difference was found to be related primarily to the room charge, 
pharmacy charges, and the number of follow-up chest radiographs obtained during the 
inpatient hospital stay[12]. In our institution where the semi-private rate for inpatient hospital 
stay per day of stay is 4,180$, we expect these charges to be even higher reaching up to 
$10,342 of added cost when compared to biopsy patients who did not require a chest tube or 
admission. Given the rising need for biopsies, the relatively high incidence of iatrogenic 
pneumothoraces which can be potentially life-threatening and the high cost this particular 
complication incurs on healthcare resources when requiring treatment, there is great interest 
in techniques that reduce the occurrence of iatrogenic pneumothoraces. One such technique 
is the injection of certain materials into the biopsy path to close the puncture site, thus 
physically preventing air from leaking out into the pleural cavity. These materials have ranged 
from saline, to autologous blood, to manufactured plugs with varying results. The              
most popular of these have been the autologous blood patch and more recently a 
manufactured hydrogel plug called BioSentry [13] 
An autologous blood patch consists of using the patient’s coagulated blood to seal the 
puncture site at the end of a lung biopsy. The earliest report of its potential role in decreasing 
the incidence of pneumothorax was in 1988 where it was used in a limited number of  
patients, and though the results were not statistically significant, it did show a decrease in 
pneumothorax rate from 34.1% to 28% and a decrease in chest tube insertion rate from 9%  
to 7.7% [14]. Since then multiple other studies have evaluated the usefulness of the blood 
patch technique. Lang et al. showed a significant reduction in pneumothorax rate from 47%  
to 9% (p<0.05) in a study in 2000, and most recently in 2013, a randomized clinical trial was 
published in American Journal of Roentgenology (AJR) supporting the use of ABPI, mainly in 
reducing the rate of chest tube placement and admission from 18% to 9% (p<0.05) and 
similarly showing a trend in the reduction of pneumothorax rate from 35% to 26% 
(p>0.05)[15,16]. Following that same rationale, manufactured plugs have also been developed 
in recent years toward the same purpose. One such material is the BioSentry hydrogel plug 
developed by Angiotech and approved by FDA. BioSentry is deployed at the visceral pleural 
puncture site through the introducer needle using a deploying device (Figure 1). It swells 
upon contact with moisture and seals the pleural puncture site. It is absorbed by the patient’s 
body over time. A supportive study of BioSentry by Zaetta et al. demonstrated a significant 
reduction of pneumothorax rate from 31% to 18%, and also a reduction –albeit non- 
significant- in the chest tube insertion rate from 11% to 4% compared to an untreated control 
group [13]. In an observation at our institution between 2007 and 2009, 181 consecutive 
patients undergoing lung biopsy by the author received blood patch. The rates of 
pneumothorax and chest tube placement, 6.6% (12/181) and 1.1% (2/181) respectively, were 
significantly lower than our group historical averages. Both of these techniques -either ABPI 
or BioSentry - along with “no plugging” are routinely used during lung biopsy procedures 
performed in our institution. Although both ABPI and BioSentry techniques have been 
independently validated in reducing the rate of pneumothorax and chest tube placement 
compared to controls, no head-to-head comparison has been made as to the effectiveness of 
these two techniques to justify the use of one over the other. There is no measurable added 
cost related to use of ABPI since the nursing personnel used in acquiring and handling the 
blood specimens are also involved in the patients’ procedural sedation and thus perform 
these services within the scope of the procedure. Up to two standard stock syringes and 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
Page 7 of 23 
 
 
 
 
needles are used, the costs of which are negligible and lumped into the procedural costs. In 
comparison, the cost of a BioSentry device ranges around 200$ per device.  Given the 
economic advantage of using ABPI in that it is almost free, it is of interest for us to prove that 
ABPI is at least as effective as manufactured plug in reducing pneumothorax and chest tube 
rates as they occur in our institution in order to justify its exclusive use. 
4.1 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
 
4.2 
Design 
 
This study will determine the rate of all pneumothoraces and those pneumothoraces requiring 
treatment following percutaneous lung biopsy in patients who have received ABPI                
or BioSentry at the end of the biopsy procedure. The data collected will be used to determine 
if there is equal effectiveness in the reduction of pneumothorax rates from both interventions. 
4.3 
Intervention 
 
Patients with a focal lung lesion amenable to needle biopsy who meet initial inclusion criteria 
will be randomized and will report for their scheduled appointments as per standard practice. 
Once the patient arrives into the procedure room, the appropriate sealant technique will be 
prepared based on the assigned randomization arm. If the patient was randomized to the 
manufactured plug arm, the device will be made available at the start of the procedure. If the 
patient was randomized to the blood patch arm, then before the start of the procedure, 
phlebotomy will be performed, drawing  2-3 mL of the patient’s blood into a labeled 
anticoagulant-free syringe which will be capped and left to clot in a cap-down position. 
The specific anatomical site of the biopsy will be selected by the interventional radiologist. 
All standard protocol for lung biopsy will be followed routinely including NPO status, 
monitored sedation, and withholding of anticoagulation medications along with aspirin and 
clopidogrel bisulfate as per guidelines of MSKCC IR service. All biopsies will be performed 
using coaxial technique under CT guidance. 
A limited CT scan of the lesion and adjacent lung parenchyma is acquired for biopsy 
planning. A biopsy path will be chosen to avoid pulmonary blebs, fissures, and pulmonary 
and superficial vessels, while the patient is positioned accordingly. 
A biopsy path traversing at least 1.5 cm of aerated lung will be preferred so that an effective 
ABPI or BioSentry might be applied. Biopsies will be performed by any of the attending 
interventional radiologists or by an interventional radiology fellow under the direct supervision 
of an attending. A small sterile field is set. Local anesthesia will be used. An Angiotech 19- 
gauge introducer needle will be advanced into the corresponding lung with the needle tip at 
the near edge of the lesion. A 20-gauge automatic spring-loaded core biopsy gun (for 
example Temno, ACT) or a 20-22 Gauge FNA needle (for example Westcott) will be used to 
obtain core tissue and/or FNA samples.  A cytotechnologist will be present on-site for all 
biopsies to assess adequacy of tissue samples as per standard of care. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
Page 8 of 23 
 
 
 
 
Once the sample has been deemed adequate, and prior to removal of the guiding needle,  
the appropriate sealant technique will be delivered based on the patient’s randomization arm. 
If the patient was assigned to the ABPI group, a blood patch will be administered using the 
clotted blood in the syringe obtained at the beginning of the procedure. The guiding needle 
will be retracted up to 1.5-2 cm from the pleural surface, and the blood will be injected 
steadily and gently as the needle is pulled back out of the pleura. Injection will stop when the 
operator feels the needle is in subcutaneous tissues. 
If the patient is assigned to BioSentry group, using the manufacturer’s deployment device 
(Figure 1) the introducer needle is positioned so that the tip is at least 1.5 cm deep to the 
visceral pleura.  The coaxial introducer needle hub will be prehydrated with a drop of saline, 
the BioSentry plug housing will be mated and locked to the hub and the plug will be 
deployed. 
If during the biopsy procedure, there was onset of a pneumothorax before deployment of 
autologous or manufactured plug, or there was more than one pleural puncture, or passage 
through a fissure, a bleb, non aerated lung, the sealant may be administered if still 
technically feasible, and the decision will be at the discretion of the operator. If a coaxial 
system was not used, the sealant cannot be administered. These cases will be included in 
the primary intent-to-treat analysis, but excluded in a secondary per-protocol analysis: 
o More than 1 needle pass through visceral pleura 
o Passage of needle through  pleural fissure, bleb, or bulla 
o Passage of needle through consolidated or non-aerated lung 
o Co-axial biopsy system not used 
o Development of pneumothorax before deployment of BioSentry or ABPI 
o Use of introducer needle larger than 19 gauge 
o Needle length more than 15 cm 
We expect that less than 5 percent of all biopsies may end up being excluded during the 
procedure from intraprocedural complications precluding the use of a tract sealant. 
After the procedure, all patients will be transferred to the recovery unit where at least two 
chest radiographs will be obtained immediately and 2 hours after the procedure according to 
standard of care.  Additional radiographs may be obtained if indicated according to standard 
of care. 
The post procedure chest radiographs will be evaluated by the biopsy operator for the 
presence of pneumothorax which will appear as free air collection overlying the lung 
parenchyma inside the chest wall. A Pneumothorax is generated from air leaking from the 
needle puncture site into the visceral pleura. Patients with no or small stable asymptomatic 
pneumothoraces will be discharged. 
A chest tube will be placed for patients with a large pneumothorax, patients with a 
pneumothorax that is increasing in size, or symptomatic patients with potentially any size 
pneumothorax on post procedure chest radiographs. Most patients who undergo chest tube 
placement will be admitted for overnight observation. Chest tubes will be removed when 
there is no longer an air leak and the radiographic appearance remains stable for 2 hours 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
Page 9 of 23 
 
 
 
 
with the chest tube clamped. This happens the next day of the biopsy for the majority of 
cases. Patients will be discharged home once the chest tube is removed. At the time of 
discharge all patients will be given contact information and will be asked to call back with any 
symptoms that might be related to delayed pneumothorax. In addition, patients who do not 
have a chest tube placed will be also followed up with a phone call by a member of IR 
service at one week checking for delayed pneumothorax (appendix 20.4). In case any of the 
study patients present with symptomatic or incidental delayed pneumothorax after being 
discharged, these patients’ data will be captured for analysis. This phone call is the only part 
of this study which is not a part of standard of care however any consequent interventions 
based on the phone call are within standard of care practice. 
All biopsy chest radiographs and CT images will be analyzed by the radiologist performing 
the procedure to identify emphysema (appendix 20.2.2) if present. .The prescan images, as 
well as any recent chest CT studies, if available, will be examined in lung windows on the 
PACS workstation. The lung parenchyma surrounding the lesion and in the region of the 
biopsy needle course will be analyzed for emphysema, blebs and transfissural approach. 
Pneumothorax (appendix 20.2.1) will be mainly defined based on post procedure chest x- 
rays. Any discernible pneumothorax on chest x-rays is considered a positive finding. 
Miniscule pneumothorax (a tiny film of air) which is sometimes seen on the last set of CT 
images of a biopsy procedure after the introducer needle is removed is not considered a 
positive finding. This is due to high sensitivity of CT imaging. Any pneumothorax larger than 
miniscule on CT images is considered a positive finding. 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS 
 
The BioSentry Biopsy Tract Plug (Angiotech Pharmaceuticals, Inc. Vancouver, Canada; 
Figure 1, Appendix 20.1), is a hydrogel based tract sealant which has been FDA approved to 
be used through standard Angiotech 19 gauge coaxial needles. It can be made currently 
available in stock for routine use during lung biopsy procedures. 
An autologous blood patch injection (ABPI) consists of drawing 2-3 mL of the patient’s blood 
prior to the procedure and leaving it in a sterile syringe to clot, then using the patient’s 
coagulated blood to seal the puncture site at the end of a lung biopsy. This technique can be 
used through 19 gauge needles. 
6.1 
CRITERIA FOR SUBJECT ELIGIBILITY 
 
6.2 
Subject Inclusion Criteria 
 
• 
≥18 years of age 
• 
Referred for CT guided biopsy of lung lesion 
• 
Target lesion of any size 
• 
Target lesion located 1.5 cm or more away from visceral pleura based on the needle 
path 
• 
Skin thickness ≤7 cm (from skin to pleura) 
• 
Needle path without transgression of pleural fissure, bleb, or bulla is possible 
• 
Coaxial biopsy technique using  Angiotech 19-Gauge introducer needle 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
Page 10 of 23 
 
 
 
 
 
• 
Needle length ≤15 cm 
 
 
6.3 
Subject Exclusion Criteria 
 
• 
Preprocedural exclusion criteria 
o Passage through non-aerated lung or tissue 
o More than 1 biopsy on the same side requiring more than 1 pleural puncture 
o History of prior ipsilateral lung interventions including: 
▪ 
Chest tube placement 
▪ 
Surgery 
▪ 
Pleurodesis 
▪ 
Radiation treatment 
 
7.0 
RECRUITMENT PLAN 
 
The subjects of this study will be identified and recruited by members of the Interventional 
Radiology service through referrals for lung biopsy. There will be no selection preferences 
based on age, gender, race, indication or target lesion characteristics. The patients will be 
selected initially based on the inclusion criteria outlined above and also based on appropriate 
clinical history as outlined in the exclusion criteria. This process will be conducted during the 
patient’s visit to the interventional radiology clinic or in the inpatient unit prior to the patient’s 
biopsy. The interventional radiologist performing the clinic evaluation or procedure consent 
will determine eligibility of the patient and discuss potential enrollment in the study. Subjects 
recruited as inpatients will be consented to the protocol and biopsy on the inpatient floor 
about an hour prior to the procedure. As these biopsies are not planned in advance, the time 
between ordering and performing the biopsy is minimal. The consenting professional will give 
ample time for discussion and questions. 
All parameters related to the study are collected by treating IR physicians in Physicians Data 
Form for each patient (Appendix 20.3). 
 
 
During the initial conversation between the investigator/research staff and the patient, the 
patient may be asked to provide certain health information that is necessary to the 
recruitment and enrollment process.The investigator/research staff may also review portions 
of their medical records at MSKCC in order to further assess eligibility. They will use the 
information provided by the patient and/or medical record to confirm that the patient is  
eligible and to contact the patient regarding study enrollment. If the patient turns out to be 
ineligible for the research study, the research staff will destroy all information collected on the 
patient during the initial conversation and medical records review, except for any information 
that must be maintained for screening log purposes. 
 
In most cases, the initial contact with the prospective subject will be conducted either by the 
treatment team, investigator or the research staff working in consultation with the treatment 
team. The recruitment process outlined presents no more than minimal risk to the privacy of 
the patients who are screened and minimal PHI will be maintained as part of a screening log. 
For these reasons, we seek a (partial) limited waiver of authorization for the purposes of (1) 
reviewing medical records to identify potential research subjects and obtain information 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
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relevant to the enrollment process; (2) conversing with patients regarding possible 
enrollment; (3) handling of PHI contained within those records and provided by the potential 
subjects; and (4) maintaining information in a screening log of patients approached (if 
applicable). 
 
During a biopsy procedure, less than ideal conditions may occur such as outlined above that 
may affect clinical outcome. In this case deployment of blood patch or plug may still proceed 
at the performing physician’s discretion, and the patient will be included in the intent-to-treat 
analysis. 
The recruitment process outlined presents no more than minimal risk to the privacy of the 
patients who are screened and minimal PHI will be maintained in a secure database as part 
of a screening log.  The screening log will be maintained in order to ensure that patients who 
do not wish to participate are not approached again. 
8.0 
PRETREATMENT EVALUATION 
 
No additional pretreatment evaluation will be necessary other than those required for the 
lung biopsy procedure as per standard of care. These include pre-procedure imaging and 
routine blood tests such as Prothrombin Time, INR, Platelet counts, WBC and pre-surgical 
testing if deemed necessary by the treating physician. Depending on the type of medications, 
non-steroidal anti inflammatory drugs, anti platelet agents and anticoagulants are held from 
1-5 days from the date of biopsy. 
 
9.0 
TREATMENT/INTERVENTION PLAN 
 
Both ABPI and the BioSentry are being used during routine lung biopsy procedures in 
MSKCC IR service although inconsistently, with preferences and usages varying among 
practitioners. Candidates enrolled in the study will selectively receive one or the other 
intervention as part of standard treatment protocol during lung biopsy procedures. Either one 
of these interventions is considered as an equivalent standard of care, and no additional fees 
should be incurred for the sole purpose of research. 
Randomization will be done electronically after patient registration. Either the blood patch will 
be drawn or the BioSentry device will be made available at the start of the procedure in the  
IR room based on the randomization arm. If the patient was assigned to the ABPI group, a 
blood patch will be administered using the clotted blood in the labeled syringe obtained at the 
beginning of the procedure. The guiding needle will be retracted up to 2 cm from the pleural 
surface, and the blood will be injected slowly and steadily as the needle is pulled back out of 
the pleura. 
If the patient is assigned to the BioSentry group, using the manufacturer’s deployment 
system the introducer needle is positioned so that the tip is at least 1.5 cm deep to the 
visceral pleura.  The coaxial introducer needle hub will be prehydrated with a drop of saline, 
and the tract plug housing will be mated and locked to the hub. The plug will be deployed. 
10.0  EVALUATION DURING TREATMENT/INTERVENTION 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
Page 12 of 23 
 
 
 
 
After the biopsy, the patient will be transferred to the recovery unit. Two chest radiographs 
will be obtained immediately and 2 hours after the procedure as per standard of care. 
Additional radiographs may be obtained when indicated as per standard of care. 
 
Patients with no or with a small stable asymptomatic pneumothorax on the post procedure 
chest radiographs will be discharged. 
A chest tube will be placed for patients with a large pneumothorax, patients with a 
pneumothorax that is increasing in size rapidly, or symptomatic patients with any 
pneumothorax. Patients who undergo chest tube placement will generally be admitted for 
overnight observation. Chest tubes will be removed when there is no longer an air leak and 
the radiographic appearance remains stable for 2 hours with the chest tube clamped. This 
happens the next day of the biopsy for the majority of cases. Patients will be discharged 
home once the chest tube is removed. At the time of discharge all patients will be given 
contact information and will be asked to call back with any symptoms that might be related to 
delayed pneumothorax. In addition, patients who did not have a chest tube placed will be 
followed up with a phone call  within two weeks for assessment of delayed pneumothorax, a 
rare occurrence. The only step in the peri, intra and post procedural management of these 
patients which is not a part of standard of care is the one-week post procedure phone call. All 
other steps are within standard of care. Any treatment as a consequence to the follow-up 
phone call is also a part of standard of care. 
In case any of the study patients present with symptomatic or incidental delayed 
pneumothorax after being discharged, these patients will be captured for analysis. 
To help keep impartiality, in addition to the standard of care review of post biopsy chest x- 
rays, at a later time, all chest radiographs will be reviewed by an interventional radiologist 
who was not involved with the biopsy procedure and is unaware of the randomization arm. 
All disagreements will be solved based on consensus after a third impartial interventional 
radiologist reviews the images. 
11.0 
TOXICITIES/SIDE EFFECTS 
 
There are no anticipated additional side effects to the intervention other than those expected 
during regular lung biopsy procedures. 
12.0 
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT 
 
Lack of any detectable pneumothorax as visualized on post procedure chest radiographs at 2 
hours following the procedure is considered success. The rate of any pneumothorax that did 
not require treatment as well as those which require chest tube placement will be captured  
for analysis in each group. 
Lack of prospective follow up chest x-ray at one week after biopsy will lower the accuracy of 
the study due to suboptimal capturing of delayed pneumothoraces by a phone call although 
this number is expected to be very low. For patients that are unable to be reached or unable 
to complete the follow up phone call, the incidence of a delayed pneumothorax and/or chest 
tube placement will be determined by a review of the patient’s chart by the PI in the 2 weeks 
following the lung biopsy. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 14-141 A(10) 
Approval date: 18-Jan-2022 
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13.0 
CRITERIAFOR REMOVAL FROM STUDY 
 
Patient exclusion will be performed after chart review and interview. Patients will be excluded 
from the study in the event the patient was found to have a history of prior ipsilateral lung 
intervention as outlined above. Once randomized, patients will be included in the intent to 
treat analysis whether they received a blood patch/BioSentry plug or not. 
 
 
14.0 
BIOSTATISTICS 
 
This is a randomized trial comparing autologous blood patch injection with BioSentry on the 
rate of pneumothorax after percutaneous lung biopsy.  The primary endpoint is the rate of 
pneumothorax within 2 hours following biopsy.  Pneumothorax is observed on post 
procedure CT scan or on follow-up chest radiographs while the patient is in the recovery 
room, according to standard of care. 
 
This study will have a non-inferiority design to evaluate whether ABPI is associated with less 
than a 10% increase in pneumothorax rate compared to BioSentry.  We will test the null 
hypothesis that ABPI is inferior, with a 10% or more increase in pneumothorax rate 
compared to BioSentry.  The non-inferiority margin of 10% is considered clinically 
acceptable.  Allowing for 1 interim assessment, the study will require 276 patients in each 
arm (552 patients total) to have 90% power to test this hypothesis.  This sample size 
estimate assumes the pneumothorax rate with tract plug is approximately 20% based on a 
randomized study by Zaetta et al.  An interim assessment will be performed after 
approximately half the patients (roughly 276 patients) have been enrolled onto the study. 
Using the Lan-DeMets spending function, the trial will terminate early for non-inferiority if with 
half the patients, a one-sided nominal Z-score of -2.538 (p-value ≤ 0.0056) is observed. This 
nominal z-score will be recalculated based on the available exact information fraction at the 
time of the Data Safety Monitoring Board review. If the trial continues, the final assessment 
will use a Z-score of -1.662 with an associated p-value of 0.0482.  This preserves a 5% 
overall probability (1-sided type I error) of falsely concluding that ABPI is non-inferior to tract 
plug when it is truly worse.  In 2012 IR service performed 1128 lung biopsies. IR service 
currently performs around 100 lung biopsies each month. With an anticipated eligibility rate  
of 50%, this study will take up to 24 months. 
 
All randomized patients who undergo a biopsy will be analyzed for the primary outcome on a 
modified intent-to-treat basis according to the randomized treatment assignment regardless 
of the actual intervention received.   The difference between pneumothorax rates for ABPI 
and BioSentry will be estimated and assessed using a Z-test.  The same analysis method will 
be used to perform a secondary analysis on only patients who have a sealant placed after 
their biopsy. 
 
Secondary outcomes will include comparisons of ABPI with BioSentry on 1) delayed 
pneumothorax occurring after outpatient observation stay and within  2 weeks following lung 
biopsy, and 2) pneumothorax requiring chest tube placement up to 2 weeks following lung 

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biopsy.  These outcomes will be assessed in a similar manner to the primary outcome. For 
patients that are unable to be reached or unable to complete the follow up phone call, the 
incidence of a delayed pneumothorax and/or chest tube placement will be determined by a 
review of the patient’s chart by the PI in the 2 weeks following the lung biopsy. 
 
15.1 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES 
 
15.2 
Research Participant Registration 
 
Confirm eligibility as defined in the section entitled Criteria for Patient/Subject Eligibility. 
 
Obtain informed consent, by following procedures defined in section entitled Informed 
Consent Procedures. 
During the registration process registering individuals will be required to complete a protocol 
specific Eligibility Checklist. 
All participants must be registered through the Protocol Participant Registration (PPR) Office 
at Memorial Sloan-Kettering Cancer Center. PPR is available Monday through Friday from 
8:30am – 5:30pm at 646-735-8000. Registrations must be submitted via the PPR Electronic 
Registration System (http://ppr/).  The completed signature page of the written consent/RA or 
verbal script/RA, a completed Eligibility Checklist and other relevant documents must be 
uploaded via the PPR Electronic Registration System. 
15.3 
Randomization 
 
Patients will be randomized to receive either ABPI or BioSentry.  Randomization will be done 
electronically using the Clinical Research Database (CRDB) after patient registration. Either 
the blood patch will be drawn or the BioSentry device will be made available at the start of 
the procedure in the IR room based on the randomization arm. Randomization will be 
accomplished by the method of random permuted block. 
 
 
16.1 
DATA MANAGEMENT ISSUES 
 
A Research Study Assistant/RSA will be assigned to the study. The responsibilities of the 
RSA include project compliance, data collection, abstraction and entry, data reporting, 
regulatory monitoring, problem resolution and prioritization, and coordinate the activities of 
the protocol study team. 
The data collected for this study will be entered into a secure database. Source 
documentation will be available to support the computerized patient record. 
16.2 
Quality Assurance 
 
Weekly registration reports will be generated to monitor patient accruals and completeness 
of registration data.  Routine data quality reports will be generated to assess missing data 
and inconsistencies.  Accrual rates and extent and accuracy of evaluations and follow-up will 

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be monitored periodically throughout the study period and potential problems will be brought 
to the attention of the study team for discussion and action. 
16.3 
Data and Safety Monitoring 
 
The Data and Safety Monitoring (DSM) Plans at Memorial Sloan-Kettering Cancer Center 
were approved by the National Cancer Institute in September 2001.  The plans address the 
new policies set forth by the NCI in the document entitled “Policy of the National Cancer 
Institute for Data and Safety Monitoring of Clinical Trials” which can be found at:  
http://www.cancer.gov/clinicaltrials/conducting/dsm -guidelines /page1.  The DSM Plans at 
MSKCC were established and are monitored by the Office of Clinical Research.  The 
MSKCC Data and Safety Monitoring Plans can be found on the MSKCC Intranet at:  
http://smskpsps9/dept/ocr/OCR%20Website%20Documents/Clinical%20Research%20Qualit  
y%20Assurance%20(CRQA)/MSKCC%20Data%20and%20Safety%20Monitoring%20Plan.p  
df 
 
There are several different mechanisms by which clinical trials are monitored for data, safety 
and quality.  There are institutional processes in place for quality assurance (e.g., protocol 
monitoring, compliance and data verification audits, therapeutic response, and staff  
education on clinical research QA) and departmental procedures for quality control, plus  
there are two institutional committees that are responsible for monitoring the activities of our 
clinical trials programs.  The committees: Data and Safety Monitoring Committee (DSMC) for 
Phase I and II clinical trials, and the Data and Safety Monitoring Board (DSMB) for Phase III 
clinical trials, report to the Center’s Research Council and Institutional Review Board. 
 
During the protocol development and review process, each protocol will be assessed for it’s 
level of risk and degree of monitoring required.  Every type of protocol (e.g., NIH sponsored, 
in-house sponsored, industrial sponsored, NCI cooperative group, etc.) will be addressed 
and the monitoring procedures will be established at the time of protocol activation. 
17.1 
PROTECTION OF HUMAN SUBJECTS 
Risks to Subjects 
Human Subjects Involvement and Characteristics: All patients at MSKCC who meet the 
inclusion criteria will be eligible. Patients will be 18 years of age or older.  Both men and 
women and members of all ethnic groups are eligible for this trial. Pregnant and breast- 
feeding women are excluded from this study. This protocol does not include children  
because the number of children is expected to be limited for the patient population expected 
to be accrued onto this study. Also, the majority of children are already accessed by a 
nationwide pediatric cancer research network. This statement is based on exclusion 4b of the 
NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving 
Human Subjects. 
Adequacy of protection against risks 
 
Participation in the trial is voluntary. 
 
Possible Toxicities/Side-Effects: The risks of biopsy are described in the informed consent 
and in Section 8.0. There is no known additional toxicities/side effects related to any of the 
two techniques. 

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Costs:  The cost of the study does not exceed standard treatment costs. 
 
Alternatives: The alternative to this trial would be use of either sealant technique versus no 
use of sealant at the discretion of the treating physician. 
Confidentiality: Every effort will be made to maintain patient confidentiality. Research and 
hospital records are confidential. Patients’ names and any other identifying information will 
not be used in reports or publications resulting from this study. Other appropriate personnel 
(e.g. qualified monitors from MSKCC) may review patient records as required. 
Patient safety: Patients are monitored by physicians and nurses who are very familiar with 
lung biopsy procedures. In the case of an adverse reaction, immediate medical attention is 
available. In the evenings and weekends, we have a 24-hour urgent care facility for 
outpatients. The PI or co-PI will also be available at all times to organize any necessary 
intervention. 
Monitoring of data to ensure safety: This study is to be monitored by the institutional IRB. 
This incorporates an independent data and safety monitoring board established by 
arrangement with the National Cancer Institute. The analysis of safety will include all 
patients. Adverse events, including all toxic effects of treatment, will be tabulated individually, 
and summarized by severity and causality. 
17.2 
Privacy 
 
MSKCC’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form. The use and disclosure of 
protected health information will be limited to the individuals described in the Research 
Authorization form. A Research Authorization form must be completed by the Principal 
Investigator and approved by the IRB and Privacy Board (IRB/PB). 
17.3 
Serious Adverse Event (SAE) Reporting 
 
 
 
An adverse event is considered serious if it results in ANY of the following outcomes: 
• 
Death 
• 
A life-threatening adverse event 
• 
An adverse event that results in inpatient hospitalization or prolongation of existing 
hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect 
• 
Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition 
Note: Hospital admission for a planned procedure/disease treatment is not considered an 
SAE. 

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SAE reporting is required as soon as the participant signs consent. We realize that patients 
may be hospitalized for reasons related to their cancer. As such, we will only report Grades 4 
and 5 adverse events such as infection, bleeding, etc. that are thought to be possibly, 
probably, or definitely related to either sealant technique. SAE reporting is required for 30- 
days after the participant’s last investigational treatment or intervention. Any events that  
occur after the 30-day period and that are at least possibly related to protocol treatment must 
be reported. 
 
If an SAE requires submission to the IRB office per IRB SOP RR-408 ‘Reporting of Serious 
Adverse Events’, the SAE report must be sent to the IRB within 5 calendar days of the event. 
The IRB requires a Clinical Research Database (CRDB) SAE report be submitted 
electronically to the SAE Office as follows: 
Reports that include a Grade 5 SAE should be sent to saegrade5@mskcc.org. All other 
reports should be sent to sae@mskcc.org. 
 
The report should contain the following information: 
Fields populated from CRDB: 
• 
Subject’s initials 
• 
Medical record number 
• 
Disease/histology (if applicable) 
• 
Protocol number and title 
Data needing to be entered: 
• 
The date the adverse event occurred 
• 
The adverse event 
• 
The grade of the event 
• 
Relationship of the adverse event to the treatment (drug, device, or intervention) 
• 
If the AE was expected 
• 
The severity of the AE 
• 
The intervention 
• 
Detailed text that includes the following 
o A explanation of how the AE was handled 
o A description of the subject’s condition 
o Indication if the subject remains on the study 
• 
If an amendment will need to be made to the protocol and/or consent form 
• 
If the SAE is an Unanticipated Problem 
The PI’s signature and the date it was signed are required on the completed report. 
For IND/IDE protocols: 
The CRDB SAE report should be completed as per above instructions.  If appropriate, the 
report will be forwarded to the FDA by the SAE staff through the IND Office. 

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Page 18 of 23 
 
 
 
 
17.2.1 
 
18.1 
INFORMED CONSENT PROCEDURES 
 
Before protocol-specified procedures are carried out, consenting professionals will explain  
full details of the protocol and study procedures as well as the risks involved to participants 
prior to their inclusion in the study. Participants will also be informed that they are free to 
withdraw from the study at any time. Consent for lung biopsy is separate than the consent for 
this protocol. All participants must sign an IRB/PB-approved consent form indicating their 
consent to participate. This consent form meets the requirements of the Code of Federal 
Regulations and the Institutional Review Board/Privacy Board of this Center. The consent 
form will include the following: 
1. The nature and objectives, potential risks and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of supportive 
care for therapeutic studies.) 
4. The name of the investigator(s) responsible for the protocol. 
5. The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time. 
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information.  In 
addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
 
19.0 
REFERENCES 
 
1. 
Covey AM, Gandhi R, Brody LA, Getrajdman GI, Thaler HT, Brown KT. Factors associated 
with pneumothorax and pneumothorax requiring treatment after percutaneous lung biopsy in 
443 consecutive patients. J Vasc Interv Radiol. 2004;15(5):479–83. 
doi:10.1097/01.RVI.0000124951.24134.50. 
 
2. 
Brown KT, Brody LA, Getrajdman GI, Napp TE. Outpatient treatment of iatrogenic 
pneumothorax after needle biopsy. Radiology. 1997;205(1):249–52. 
doi:10.1148/radiology.205.1.9314993. 
 
3. 
Perlmutt LM, Braun SD, Newman GE, Oke EJ, Dunnick NR. Timing of chest film follow-up 
after transthoracic needle aspiration. AJR Am J Roentgenol. 1986;146(5):1049–50. 
doi:10.2214/ajr.146.5.1049. 
 
4. 
Dennie CJ, Matzinger FR, Marriner JR, Maziak DE. Transthoracic needle biopsy of the lung: 
results of early discharge in 506 outpatients. Radiology. 2001;219(1):247–51. 
doi:10.1148/radiology.219.1.r01ap11247. 

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5. 
Choi C-M, Um S-W, Yoo C-G, et al. Incidence and risk factors of delayed pneumothorax after 
transthoracic needle biopsy of the lung. Chest. 2004;126(5):1516–21. 
doi:10.1378/chest.126.5.1516. 
 
6. 
Swischuk JL, Castaneda F, Patel JC, et al. Percutaneous transthoracic needle biopsy of the 
lung: review of 612 lesions. J Vasc Interv Radiol. 1998;9(2):347–52. 
 
7. 
Westcott JL, Rao N, Colley DP. Transthoracic needle biopsy of small pulmonary nodules. 
Radiology. 1997;202(1):97–103.   doi:10.1148/radiology.202.1.8988197. 
 
8. 
Shaham D. Semi-invasive and invasive procedures for the diagnosis and staging of lung 
cancer. I. Percutaneous transthoracic needle biopsy. Radiol Clin North Am. 2000;38(3):525– 
34. 
 
9. 
Marshall D, Laberge JM, Firetag B, Miller T, Kerlan RK. The changing face of percutaneous 
image-guided biopsy: molecular profiling and genomic analysis in current practice. J Vasc 
Interv Radiol. 2013;24(8):1094–103.  doi:10.1016/j.jvir.2013.04.027. 
 
10. 
Wiener RS, Wiener DC, Gould MK. Risks of Transthoracic Needle Biopsy: How High? Clin 
Pulm Med. 2013;20(1):29–35.  doi:10.1097/CPM.0b013e31827a30c1. 
 
11. 
Geraghty PR, Kee ST, McFarlane G, Razavi MK, Sze DY, Dake MD. CT-guided transthoracic 
needle aspiration biopsy of pulmonary nodules: needle size and pneumothorax rate. 
Radiology. 2003;229(2):475–81.  doi:10.1148/radiol.2291020499. 
 
12. 
Gurley MB, Richli WR, Waugh KA. Outpatient management of pneumothorax after fine-needle 
aspiration: economic advantages for the hospital and patient. Radiology. 1998;209(3):717–22. 
doi:10.1148/radiology.209.3.9844664. 
 
13. 
Zaetta JM, Licht MO, Fisher JS, Avelar RL. A lung biopsy tract plug for reduction of 
postbiopsy pneumothorax and other complications: results of a prospective, multicenter, 
randomized, controlled clinical study. J Vasc Interv Radiol. 2010;21(8):1235–43.e1–3. 
doi:10.1016/j.jvir.2010.04.021. 
 
14. 
Bourgouin PM, Shepard J-AO, McLoud TC, Spizarny DL, Dedrick CG. Transthoracic needle 
aspiration biopsy: evaluation of the blood patch technique. Radiology. 1988;166(1 Pt 1):93–5. 
doi:10.1148/radiology.166.1.3336708. 
 
15. 
Lang EK, Ghavami R, Schreiner VC, Archibald S, Ramirez J. Autologous blood clot seal to 
prevent pneumothorax at CT-guided lung biopsy. Radiology. 2000;216(1):93–6. 
 
16. 
Malone LJ, Stanfill RM, Wang H, Fahey KM, Bertino RE. Effect of intraparenchymal blood 
patch on rates of pneumothorax and pneumothorax requiring chest tube placement after 
percutaneous lung biopsy. AJR Am J Roentgenol. 2013;200(6):1238–43. 
doi:10.2214/AJR.12.8980. 

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20.1 
APPENDICES 
 
20.2 
FIGURES 
 
Figure 1: The BioSentry Lung Biopsy Tract Plug 
 
 
 
20.3 
DEFINITIONS 
 
Adapted from: 
 
Grainger RG, Allison D, Adam A et al. Grainger's and Allison's Diagnostic Radiology, A 
Textbook of Medical Imaging. Philadelphia : Churchill Livingstone Elsevier, 2008.; 2008. 
Dähnert W. Radiology Review Manual. Lippincott Williams & Wilkins; 2011. 
 
20.3.1 PNEUMOTHORAX 
 
Pneumothorax is defined as the accumulation of air in the pleural space causing lung 
collapse. The degree of pneumothorax and subsequent lung collapse can range from mild 
requiring no intervention to severe requiring evacuation of the air in the pleural space by 
placement of a chest tube. Pneumothorax can be associated with back, shoulder pain or 
shortness of breath. The diagnosis of pneumothorax in our study will be made with the chest 

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radiograph, which also detects complications and predisposing conditions and helps in 
management. These are seen on an erect or semi-erect radiographs in which the pleural air 
rises to the lung apex, in more severe cases it might become circumferential. Under these 
conditions the visceral pleural line becomes separated from the chest wall by a transradiant 
zone devoid of vessels. 
Other signs that suggest a pneumothorax on a chest radiograph are: 
 
• 
ipsilateral transradiancy, either generalized or hypochondrial 
 
• 
a deep, finger-like costophrenic sulcus laterally 
 
• 
a visible anterior costophrenic recess seen as an oblique line or interface in the 
hypochondrium; when the recess is manifest as an interface it mimics the adjacent 
diaphragm (‘double diaphragm sign’) 
• 
a transradiant band parallel to the diaphragm and/or mediastinum with undue clarity of 
the mediastinal border 
• 
visualization of the undersurface of the heart, and of the cardiac fat pads as rounded 
opacities suggesting masses 
• 
diaphragm depression. 
 
A large pneumothorax can potentially lead to tension pneumothorax. When intrapleural 
pressure becomes positive relative to atmospheric pressure for a significant part of the 
respiratory cycle it can impair gas exchange and cardiovascular function and eventually lead 
to life threatening  respiratory distress. Ideally, evacuation of the air in the pleural space by 
placement of a chest tube is performed before onset of a tension pneumothorax. A 
pneumothorax is targeted for treatment when it is considered to be occupying more than 20- 
30% of the pleural space. At this stage, pneumothoraces may still be asymptomatic yet are 
large enough to accommodate placement of a chest tube. A smaller pneumothorax may be 
treated if it is associated with one or all of the symptoms described above. The chest tube is 
usually connected to a water-seal device to allow escape but prevent reflux of air into the 
pleural space. 
20.3.2 EMPHYSEMA 
 
Emphysema is defined as a condition of the lung characterized by permanent, abnormal 
enlargement of airspaces distal to the terminal bronchioles, accompanied by the destruction 
of their walls without obvious fibrosis. The most important aetiological factor by far is  
cigarette smoking. Emphysema is thought to result from the destruction of elastic fibres 
caused by an imbalance between proteases and protease inhibitors in the lung and from the 
mechanical stresses of ventilation and coughing. Proteases are normally released in low 
concentration by phagocytes in the lung. Tobacco smoke increases the number of pulmonary 
macrophages and neutrophils, reduces antiprotease activity, and may impair the synthesis of 
elastin. As emphysema develops lung destruction progresses, airspaces enlarge and elastic 
recoil declines. This, in turn, renders the lungs more vulnerable to injury from needle biopsies 
due to increased friability, and more prone to air leaks due to the larger airspaces. 

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Radiographic findings 
 
The main radiographic manifestations of emphysema are overinflation  and alterations in the 
lung vessels. Signs of overinflation are the best predictors of the presence and severity of 
emphysema. Signs of overinflation include the height of the right lung being greater than 29.9 
cm, location of the right hemidiaphragm at or below the anterior aspect of the seventh rib, 
flattening of the hemidiaphragm, enlargement of the retrosternal space, widening of the 
sternodiaphragmatic angle and narrowing of the transverse cardiac diameter). Alterations in 
lung vessels include arterial depletion, whereas vessels of normal, or occasionally increased, 
calibre are present in unaffected areas of the lung, absence or displacement of vessels 
caused by bullae, widened branching angles with loss of side branches and vascular 
redistribution. Bullae are much more common in the upper zones, but  the distribution can be 
much more even. 

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20.4 
PHYSICIAN DATA FORM