Tuesday Case Conference

History:

54 yr old man with progressive dyspnea over the last few years. Now only able to walk 100 feet or climb one flight of stairs. Also complains of an occasional wheeze.

Patient denies chest pain, cough, fevers, orthopnea, PND. ROS otherwise negative.

PMHx:HTNGERD

SHx:50 pk yr, ¼ ppdNo EtOH/IVDUNo recent travel

FHx:Father died of emphysema

at 65 yrs old, otherwise negative

NKDA

MedicationsHCTZ

Zantac prn

Labs:

14.5 normal diff

7.2 311

45.8

141 99 11

4.0 32 1.0

Physical Exam:

BP 146/95 HR 90

sat 90% wt 160 lbs

NAD A+O

HEENT-normal

CV-RRR no MRG

Lungs-decreased BS, prolonged expiration

Abd-benign

Ext-no CCE

115

Pulmonary Function:

Pre-BD Post-BD

FVC 1.77 (37%) 2.44 (Δ 37%)

FEV1 0.82 (23%) 0.83 (Δ 1%)

FEV1/FVC 46%

TLC 7.79 (110%)

RV 5.62 (247%)

DLCO 8.31 (30%)

DL/VA 2.68 (68%)

ABG = 7.4 / 52 / 58 on RA

History (continued):

Patient is started on albuterol, atrovent, serevent and azmacort. He is also started on oxygen and undergoes pulmonary rehabilitation with only slight improvement in symptoms and stable PFT’s.

Patient also quits smoking and is interested in other potential therapeutic options.

Exercise Test:

A non-invasive exercise study is performed

• Patient achieves 40 watts (22%)

• VO2 max is 0.62 liters/min (24%)

• Maximum HR is 117 (67%)

History continued:

After extensive evaluation, the patient is electively admitted and undergoes left bullectomy and bilateral lung volume reduction surgery.

The patients is able to come off oxygen and notes a dramatic improvement in symptoms which has been sustained over the last four years.

Pre-Op POD #500

Change in Pulmonary Function:Lung Volumes

0

2

4

6

8

10

0 10 20 30 40

Months

Lite

rs

TLC

RV

FVC

FEV1

LVRS

Change in Pulmonary Function:Diffusion Capacity

810121416182022

0 10 20 30 40

Months

mL/

min

/mm

HG

LVRS

0

20

40

60

80

100

0 5 10 15 20

MonthsW

atts

0

0.5

1

1.5

2

0 5 10 15 20

Months

Lite

rs/M

in

Maximum Work Load

Maximum VO2

LVRS

Lung Volume Reduction Surgery

A Surgical Approach to Emphysema:

• LVRS described by Brantigan in the 1950’s. Post-operative mortality was 18%. Problems with persistent air leaks.

• Better surgical techniques and use of material to reinforce the staple line lead to renewed interest in the 1990’s.

Brantigan et al, ARRD 1959, 80:194-202

Cooper et al, J Th and CV Surg 1995, 109:106-119

Physiologic Rationale

By removing areas of emphysematous lung, elastic recoil will improve leading to open airways and increased flow .

Brantigan et al, ARRD 1959, 80:194-202

LVRS Improves Elastic Recoil

Sciurba et al, NEJM 1996, 334:1095-1099

The pressure-volume relationship was measured for 10 patients before and 3 months after LVRS.

Small randomized trial of 48 patients shows improvement in FEV1 and FVC in the LVRS group.

LVRS vs Medical Therapy

Geddes et al, NEJM 2000, 343:239-245

LVRS vs Medical Therapy

This study also showed improvement in exercise and quality of life score.

Geddes et al, NEJM 2000, 343:239-245

High Risk Patients Do Poorly with LVRSEarly Results from NETT

High Risk:

• FEV1 <20%

• DLCO <20%

• Homogeneous

NETT, NEJM 2001, 345:1075-1083

Patient Selection Criteria for LVRS

Upper (n=106)

Non-Upper (n=32)

p Value

Δ FEV1

(Liters)0.43 0.22 0.0013

Δ Dyspnea (Score 0-4)

1.63 1.88 0.34

McKenna et al, J Th and CV Surg 1997, 114:957-967

Questions about LVRS:

• Does LVRS improve survival?

• Is there a subset of patients that benefits more from LVRS?

• Is there a subset of patients that should not undergo LVRS?

NETT Study Design

Multi-center, randomized trial

1218 patients enrolled from 1/1998 to 7/2002• FEV1 ≤45%, TLC ≥100%, RV≥150%• PaCO2 ≤60 mmHg, PaO2 ≥45 mmHg on room air• 6 minute walk ≥140 meteres• Emphysema on HRCT• Disease stable on ≤20 mg prednisone

All received pulmonary rehab for 6 to 10 weeks then randomized to receive medical therapy or LVRS

NETT, J Th and CV Surg 1999, 118:518-528

NETT ResultsOverall Survival

NETT, NEJM 2003, 348:2059-2073

NETT ResultsSurvival: High Risk vs Non-high Risk

NETT, NEJM 2003, 348:2059-2073

NETT Study Design

The non-high risk patients were further characterized for subgroup analysis based on:

• Distribution (upper vs non-upper lobe)

• Exercise Capacity (Sex-specific 40th percentile)

Yielding four subgroups:(1) Upper lobe, low exercise

(2) Upper lobe, high exercise

(3) Non-upper lobe, low exercise

(4) Non-upper lobe, high exercise

NETT, NEJM 2003, 348:2059-2073

NETT ResultsSurvival: Upper Lobe

NETT, NEJM 2003, 348:2059-2073

NETT ResultsSurvival: Non-Upper Lobe

NETT, NEJM 2003, 348:2059-2073

Change in Maximal Workload, FEV1 and Quality of Life at 24 Months

NETT, NEJM 2003, 348:2059-2073

Change in Maximal Workload Upper lobe and Low Exercise Subgroup

NETT, NEJM 2003, 348:2059-2073

Is LVRS Cost-Effective?Dollars per Quality-Adjusted Life Year Gained

NETT, NEJM 2003, 348:2092-2102

OverallUpper Lobe

Low Exercise

3 Years $190,000 $98,000

10 Years $53,000 $21,000

Conclusions from the NETT:

• Overall, LVRS does not improve survival, but does improve exercise capacity and quality of life.

• LVRS does improve survival in patients with upper lobe disease and low exercise capacity.

• LVRS is cost-effective.

• High risk patients and patients with non-upper lobe disease and high exercise capacity are poor candidates for LVRS

NETT, NEJM 2003, 348:2059-2073

LVRS versus Lung Transplant:

Retrospective, single-center analysis

• LVRS: 33 patients• Single Lung TXP: 39 patients• Double Lung TXP: 25 patients

Compared changes in physiologic parameters and survival.

Gaissert et al, J Th CV Surg 1996, 111:296-307

LVRS versus Lung Transplant:Change in FEV1 and FVC

BLT

SLT

BLT

SLT

LVRS LVRS

Gaissert et al, J Th CV Surg 1996, 111:296-307

LVRS versus Lung Transplant:Change in PaO2 and PaCO2

BLT

SLT

LVRS

BLT

LVRS

SLT

Gaissert et al, J Th CV Surg 1996, 111:296-307

LVRS versus Lung Transplant:Change in Six Minute Walk

BLT

SLT

LVRS

Gaissert et al, J Th CV Surg 1996, 111:296-307

LVRS versus Lung Transplant:Oxygen Requirement

Gaissert et al, J Th CV Surg 1996, 111:296-307

0

20

40

60

80

100

1 2 3

LVRS

Single TXP

Double TXP

Pre-Op 3 Mo 6 Mo

LVRS versus Lung Transplant:Mortality

Gaissert et al, J Th CV Surg 1996, 111:296-307

LVRS Single TXP Double TXP

Early Deaths 0 - 30 days

0% 2.5% 8.0%

Late Deaths 30 d - 1 yr

3.0% 7.7% 8.0%

Total 3.0% 10.2% 16.0%

LVRS versus Lung Transplant:12 LVRS Patients Who Were TXP

Candidates

0

20

40

60

80

0 3 6

Months

% C

ha

ng

e FEV1

6min walk

PaO2

Gaissert et al, J Th CV Surg 1996, 111:296-307

LVRS versus Lung Transplant:Authors Conclusions

“Although single and bilateral lung transplantation results in superior lung function, volume reduction achieves satisfactory improvement in disabling symptoms early after operation while avoiding immunosuppression and transplant-specific complications.”

Gaissert et al, J Th CV Surg 1996, 111:296-307

LVRS as a Bridge to Transplant?

Retrospective study of 27 patients who underwent LVRS followed by transplant (22.9 months later).

A subgroup of patients had physiologic improvement and improvement in nutritional status.

Senbaklaviaci et al, Eur J CT Surg 2002, 22:363-367

LVRS as a Bridge to Transplant?

Retrospective study of 15 patients who underwent LVRS followed by transplant (28.1 months later).

No difference in survival in this group compared to matched transplant alone group.

Burns et al, Ann Th Surg 2002, 73:1587-1593

Conclusions:

• LVRS improves physiologic parameters, exercise capacity and quality of life in some patients with emphysema.

• LVRS improves survival in patients with upper lobe disease and low exercise capacity

• The role of LVRS and lung transplant in patients with emphysema is not well studied.

References:

Brantigan et al, ARRD 1959, 80:194-202Cooper et al, J Th and CV Surg 1995, 109:106-119Sciurba et al, NEJM 1996, 334:1095-1099Geddes et al, NEJM 2000, 343:239-245NETT, NEJM 2001, 345:1075-1083NETT, J Th and CV Surg 1999, 118:518-528NETT, NEJM 2003, 348:2059-2073NETT, NEJM 2003, 348:2092-2102Gaissert et al, J Th CV Surg 1996, 111:296-307Senbaklaviaci et al, Eur J CT Surg 2002, 22:363-367Burns et al, Ann Th Surg 2002, 73:1587-1593