Effect of Impaired Lung Function on the Development and Progression of Endobronchial Premalignant Lesions

doi:10.4236/jct.2012.324048

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Journal of Cancer Therapy, 2012, 3, 364-371

http://dx.doi.org/10.4236/jct.2012.324048 Published Online September 2012 (http://www.SciRP.org/journal/jct)

Effect of Impaired Lung Function on the Development and

Progression of Endobronchial Premalignant Lesions

Vijayvel Jayaprakash1,2,3, Gregory M. Loewen4, Martin C. Mahoney3,5, Samjot Dhillon5,

Sai Yendamuri6, D. Kyle Hogarth7, Enrique Machare-Delgado8, Ravi J. Menezes9,

Sandra M. Jacob5, Mary E. Reid1,3,5*

1Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, USA; 2Department of Dentistry, Roswell Park

Cancer Institute, Buffalo, USA; 3Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo,

USA; 4Pulmonary Oncology, Sacred Heart Medical Center, Spokane, USA; 5Department of Medicine, Roswell Park Cancer Institute,

Buffalo, USA; 6Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, USA; 7Section of Pulmonary and Critical

Care Medicine, University of Chicago, Chicago, USA; 8School of Medicine, State University of New York at Buffalo, Buffalo, USA;

9Department of Medical Imaging, University Health Network, Toronto, Canada.

Email: *[email protected]

Received July 27th, 2012; revised August 29th, 2012; accepted September 11th, 2012

ABSTRACT

Background: Chronic obstructive pulmonary disease (COPD) and the presence of endobronchial premalignant lesions

(EPL) are individual risk factors for lung cancer (LC). However, effect of impaired lung function (ILF) on the natural

history of EPL has not been explored. Patients and Methods: This study included 217 high-risk participants from a

hospital-based LC surveillance cohort who underwent pulmonary function testing followed by bronchoscopy with en-

dobronchial biopsies. Baseline histopathology diagnoses included 91 cases (41.9%) with squamous metaplasia (SM), 25

(11.5%) with squamous dysplasia (SD), 1 (0.5%) with in-situ carcinoma and 5 (2.3%) with invasive LC. Follow-up

biopsies were obtained for 69 patients, and 16 (23.2%) patients demonstrated progression to a higher grade lesion. Re-

gression models were used to evaluate the relationship between ILF and EPL. All the models were adjusted for age,

gender and tobacco smoking. Results: Patients with FEV1% of <50% had 4.5 times greater risk of being diagnosed with

an EPL [95% confidence interval: 1.93 - 10.80] and 8-fold greater risk of SD, compared to patients with FEV1% ≥ 80.

COPD was associated with 2.7 and 4.8 times greater risk of SM and SD, respectively. The mean time to progression to

a higher-grade lesion was shorter in COPD patients compared to patients without COPD (27 versus 50 months, p =

0.02). Conclusion: Our results indicate that ILF may be a predictor of prevalence and progression of EPLs among pa-

tients at high risk of LC. Therefore, spirometry can be a complementary pre-screening tool for identifying patients with

EPL who need more intense LC surveillance.

Keywords: COPD; Lung Cancer; Premalignant Lesions; Dysplasia; Pulmonary Function Test; Spirometry

1. Introduction

Although the mortality rate due to lung cancer (LC) has

been steadily declining over the last decade, the overall

5-year survival rate has remained a dismal 15% [1]. This

poor survival rate can be attributed to the fact that most

patients have an advanced disease stage at diagnosis,

often limiting the management strategy to palliative op-

tions. While it is considered that early detection and

treatment can improve the long term survival rate of LC

patients [2], the efficacy and cost effectiveness of LC

screening in average or low risk populations is question-

able [3-5]. Therefore, selective targeted surveillance in

high risk patients is currently a more feasible way to de-

tect and treat the disease at the earliest stage.

Intra-epithelial lesions, like squamous metaplasia (SM),

squamous dysplasia (SD) and carcinoma-in-situ (CIS)

have been classified as precursors to invasive squamous

cell carcinoma of lung (SCC) [6-9]. Patients with these

endobronchial premalignant lesions (EPL) have been

shown to be at a much greater risk of developing a squa-

mous cell carcinoma of the lung. Targeted surveillance in

such high-risk subgroup will be a more efficient strategy

for early detection and chemoprevention. However, the

natural history of these EPLs and factors predicting the

progression of these lesions are not yet clear.

Chronic obstructive pulmonary disease (COPD) and

LC are both respiratory diseases that share similar risk

factors and disease mechanisms [10-12]. The “Global

*Corresponding author.

Effect of Impaired Lung Function on the Development and Progression of Endobronchial Premalignant Lesions 365

Initiative for Chronic Obstructive Lung Disease” (GOLD)

defines COPD as a disease with progressive airflow

limitation, which is not completely reversible [13]. Spi-

rometry is a widely available and inexpensive test for

evaluating the airflow limitation and lung function (LF).

It has been shown that patients with moderate to severe

COPD are at more than 4 fold increased risk of LC, with

a significant linear increase in risk with a greater degree

of airway obstruction [14-19]. However, the relationship

between impaired LF (ILF) and the risk of development

and progression of EPLs is less clear. Clarifying any

such association will be useful for defining a high risk

cohort in need of intense LC surveillance. This study was

conducted to examine the association between spiromet-

ric LF measurements and EPLs identified via broncho-

scopy aided biopsy.

2. Materials and Methods

2.1. Study Population

The LC Risk Assessment Center at Roswell Park Cancer

Institute (RPCI), Buffalo, NY, assesses and manages pa-

tients considered to be high risk by virtue of at least two

of the following risk factors: >20 pack-year history of

tobacco use, asbestos-related lung disease, diagnosed

chronic obstructive pulmonary disease with a forced ex-

piratory volume in per second (FEV1) < 70% of pre-

dicted, and/or prior aerodigestive or respiratory cancer

treated with curative intent with no evidence of disease

for at least 6 months prior to enrollment. As a component

of the evaluation, the patients undergo spirometry and a

computerized tomography (CT) of the chest, followed by

combined white light and autofluorescence bronchoscopy

with biopsies. Detailed demographic, histologic and cli-

nical history was collected on these patients. This study

was approved by the Institutional Review Board at RPCI.

The current analysis includes only high risk patients

who had at least one complete spirometric evaluation

within the 6 months preceding their baseline broncho-

scopic evaluation. Patients who had a history of previous

LC treated with a bi-lobectomy or pneumonectomy were

excluded. Patients with a previously diagnosed and un-

treated EPL (either SM, SD or CIS) were also excluded

from this analysis. The current analysis includes 217 pa-

tients who satisfied all the inclusion criteria. Among

these 217 persons, 69 completed a follow-up broncho-

scopy with biopsies and were evaluated for changes in

the lesions detected at the baseline bronchoscopy.

2.2. Clinical Exam and Data Collection

The patients underwent lung function tests using hand-

held spirometry based on American Thoracic Society

(ATS) guidelines [20]. The spirometric measurements

included FEV1 and forced vital capacity (FVC). FEV1/

FVC ratio was calculated using these values. The per-

centage of predicted value of FEV1 (FEV1%) and FVC

(FVC%) were calculated based on predicted equation of

Crapo et al. [21]. For patients who had more than one

spirometry performed within 6 months prior to baseline

examination, the spirometry performed closest to the date

of diagnosis was considered for this study. Broncho-

scopic examination was conducted using the light in-

duced fluorescence endoscopy (LIFE) device (Xillix

LIFE-Lung Fluorescence Endoscopy System, Xillix tech-

nologies Corp, Richmond, BC, Canada). Lesions identi-

fied under white light and/or fluorescent light were biop-

sied and were histopathologically graded as benign, SM,

SD (mild, moderate or severe), CIS and invasive LC

(SCC or adenocarcinoma of the lung). The follow-up

bronchoscopy was performed on a pre-specified schedule:

6 months to 1 year for patients with SD and 2 to 3 years

for patients with SM, unless there was any exacerbation

of symptoms warranting intermediary evaluation based

on clinical judgment.

3. Analysis

For analysis purposes, FEV1% was stratified into 3

groups: ≥80% (normal), 50% to <80% (mild/moderate

impairment) and <50% (severe impairment) and FEV1/

FVC was stratified as: ≥70% (normal), 50% to <70%

(mildly reduced) and <50% (moderately/severely re-

duced). The GOLD criterion was used to stratify patients

as mild, moderate and severe COPD [13]. According to

the GOLD criteria, a patient is diagnosed with mild

COPD if FEV1/FVC < 70% and FEV1 ≥ 80%, moderate

COPD if FEV1/FVC < 70% and 50% ≤ FEV1 ≥ 80% and

severe COPD if FEV1/FVC < 70% and FEV1 < 50%. The

association between ILF and the odds of detecting EPLs

was examined by calculating adjusted odds ratio (OR)

and 95% confidence intervals (CI) using unconditional

logistic regression. The risk estimates reported here were

adjusted for other significant risk factors like age at time

of spirometry, gender and pack-years of cigarettes

smoked. The highest histopathologic grade lesion for

each person determined the final diagnosis for analytic

purpose. For example, if a patient had both SM and

moderate SD, the final diagnosis for analytic purposes

was moderate SD. Due to the limited number of SDs

detected, all grades of SD (mild, moderate and severe)

were grouped together for this analysis. Similarly, CIS

and LC were also grouped together for analysis purposes.

For the follow-up analysis, any change to a higher grade

lesion on follow-up biopsy was considered as progress-

sion. The risk of progression for baseline EPLs was

evaluated using hazard ratios (HR) based upon Cox re-

gression models. Risk estimates were adjusted for other

Effect of Impaired Lung Function on the Development and Progression of Endobronchial Premalignant Lesions

366

risk factors like age at time of spirometry, gender and

pack-years of cigarettes smoked. The statistical package

SPSS version 15.0 (SPSS Inc., Chicago, Ill) was used to

conduct these analyses.

4. Results

The descriptive characteristics of the 353 patients in the

overall screening cohort and the 217 participants in-

cluded in this analysis are presented in Table 1. More

than two-thirds of the 217 patients were males and most

self-identified as Caucasian. About 93.1% of the study

participants were either former or current smokers and

41.9% reported a history of asbestos exposure. Based on

baseline biopsy, 91 patients (41.9%) were diagnosed with

SM, 12 (5.5%) with mild SD, 10 (4.6%) with moderate

SD, 3 (1.4%) with severe SD and 1 (0.5%) with CIS, 4

(1.8%) with SCC and 1 (0.5%) with adenocarcinoma.

Table 2 presents the risk estimates for the identifica-

tion of EPLs based on categorical measures of FEV1%,

FEV1/FVC values and COPD. The category of most se-

vere FEV1% impairment (<50% of predicted) was asso-

ciated with more than 4.5 times greater risk of detecting

EPLs, compared to FEV1% of ≥80%. Results were simi-

lar for categories of FEV1/FVC and when SM and SD

were individually examined. Significant trends in the risk

of EPLs were noted with increasing severity of COPD

overall and within categories of lesions. Similar analysis

was also performed for linear estimates of FEV1% and

FEV1/FVC (Figure 1). The results showed a trend for

increased risk of detection of EPLs associated with the

decreased LF measured by every liter decrease in FEV1

volume and every 10% decrease in the FEV1/FVC ratio.

The risk of detecting EPLs was also analyzed separately

for males and females (Table 3). A statistically signifi-

cant increase in risk associated with the highest category

of airflow limitation was observed in both genders. The

risk of detecting EPLs in patients with FEV1% < 50 was

3.8 times greater in males and 6.5 times greater in fe-

males, compared to patients with FEV1% > 80.

We analyzed the risk of progression from baseline

EPLs based on COPD status at baseline (Figure 2). A

total of 69 patients who completed both baseline and

follow-up bronchoscopy were included; follow-up bron-

choscopy was completed at a median follow-up interval

of 13 months (range: 5 to 73 months). The baseline de-

mographic characteristics of the 69 patients were com-

parable to the overall population of 217 patients (Table

1). In 16 of the 69 patients (23%) the baseline lesion

progressed to a higher grade, including 11 of 44 (25%)

patients with COPD and 5 of 25 (20%) patients without

COPD at baseline. The range of time to progression of

lesions on these patients was 7 to 73 months. Among

these 16 patients, 10 patients had their baseline SM pro-

gress (6 to mild SD and 4 to moderate SD), 2 patients

1.1

1.2

1.3

1.4

1.5

1.6

BenignMetaplasia Dysplasia

Lesion Type

Odds ratio

1.00

1.19 (1.01-1.35)

1.39 (1.13-1.58)

1.39 (1.12-1.59)

1.53 (1.08-1.76)

Legend:

Measured FEV1—every one litre decrease

FEV1/FVC—every 10% decrease

Figure 1. Trend in the odds of detecting premalignant le-

sions based on linear measures of lung function.

Subjects with COPD

Subjects without COPD

+ Censored

Figure 2. Kaplan-Meier curve to evaluate the difference in

progression of baseline premalignant lesions based on

COPD status (GOLD criteria).

had their mild SD progress to moderate SD and one pa-

tient who had a moderate SD at baseline progressed to

severe SD. In 3 other patients who did not have any

baseline EPL, 2 were diagnosed with mild SD and 1 pa-

tient had moderate SD on follow bronchoscopy. The

hazard ratio for the risk of progression was calculated

based on a Cox regression model, adjusting for age,

gender and pack-years of smoking. The results show that

the patients with COPD had a non-statistically significant

2.5 times greater risk of their baseline lesion progressing

Effect of Impaired Lung Function on the Development and Progression of Endobronchial Premalignant Lesions

367

Table 1. Baseline demographic characteristics of all patients who were evaluated for the lung cancer surveillance study.

Characteristics

All screening patients

(353 patients)

Patients evaluated with

spirometry followed by

baseline bronchoscopy

(217 patients)

Patients evaluated with

follow-up bronchoscopy

(69 patients)

Gender

Female 120 (34.0) 67 (30.9) 22 (31.9)

Male 233 (66.0) 150 (69.1) 46 (68.1)

Race

Caucasian 336 (95.2) 206 (94.9) 66 (95.7)

Black 15 (4.2) 9 (4.1) 2 (2.8)

Other 2 (0.6) 2 (1.0) 1 (1.4)

Age

<60 years 132 (37.4) 80 (36.9) 30 (43.5)

60 - 69 years 125 (35.4) 84 (38.7) 25 (36.2)

≥70 years 96 (27.2) 53 (24.4) 14 (20.3)

Smoking Status

Never 25 (7.1) 15 (6.9) 4 (5.8)

Former 221 (62.6) 129 (59.4) 41 (59.4)

Current 106 (30.0) 73 (33.7) 24 (34.8)

Pack-years1 Mean (SD)† 50.8 (29.5) 50.5 (27.4) 50.5 (23.5)

Asbestos exposure (yes) 140 (39.7) 91 (41.9) 29 (42.1)

Lung cancer history (yes) 130 (36.8) 59 (27.2) 18 (26.1)

Reason for screening

Risk factors only* 161 (45.6) 100 (46.1) 33 (47.8)

Risk factors and symptoms** 192 (54.4) 117 (53.9) 36 (52.2)

†Among patients with a history of smoking; *History of heavy smoking, asbestos exposure, previous aero-digestive cancer and clinical diagnosis of COPD;

**Symptoms include hemoptysis, persistent cough or progressive dyspnea.

Table 2. Adjusted risk estimates for detection of premalignant bronchial lesions or lung cancers based on the pulmonary

function test results in 217 high risk patients.

Normal All EPLs/Cancers1 Squamous MetaplasiaSquamous Dysplasia

(any grade) CIS/Invasive Cancer

Pulmonary

Function

Parameter N = 95

n (%) N = 122

n (%)

Adjusted OR2

(95% CI)

N = 91

n (%)

Adjusted OR2

(95% CI)

N = 25

n (%)

Adjusted OR2

(95% CI) N = 6

n (%)

Adjusted OR2

(95% CI)

FEV1% PREDICTED

≥80% 32 (33.7) 22 (18.0) Referent 18 (19.8)Referent 3 (12.0)Referent 2 (33.3) Referent

≥50% - <80% 48 (50.5) 58 (47.5) 1.58

(0.79 - 3.18) 43 (47.3)1.42

(0.67 - 3.00) 11 (44.0)2.17

(0.54 - 8.65) 3 (50.0) 2.09

(0.22 - 19.76)

<50% 15 (15.8) 42 (34.4) 4.56

(1.93 - 10.80) 30 (33.0)4.06

(1.62 - 10.15)11 (44.0)7.95

(1.77 - 35.67) 1 (16.7) 2.92

(0.12 - 68.10)

Ptrend3 0.001 0.003 0.005 0.47

Effect of Impaired Lung Function on the Development and Progression of Endobronchial Premalignant Lesions

368

Continued

FEV1/FVC %

≥70% 44 (50.6) 38 (33.3) Referent 33 (37.9)Referent 4 (19.0)Referent 1 (16.7) Referent

≥50% - <70% 32 (36.8) 47 (41.2) 1.83

(0.94 - 3.57) 31 (35.6)1.36

(0.66 - 2.79) 11 (52.4)3.35

(0.92 - 12.15) 4 (66.7) 9.81

(0.75 - 128.50)

<50% 11 (12.6) 29 (25.4) 3.29

(1.36 - 7.97) 23 (26.4)3.11

(1.25 - 7.72) 6 (28.6)5.08

(1.03 - 25.01) 1 (16.7) 8.77

(0.35 - 217.53)

Ptrend3 0.006 0.02 0.04 0.11

COPD - GOLD CRITERIA4, 5

No/ Mild

COPD 50 (57.5) 41 (36.0) Referent 34 (39.1)Referent 5 (23.8)Referent 2 (33.3) Referent

Moderate

COPD 23 (29.4) 37 (32.5) 2.03

(1.00 - 4.15) 25 (28.7)1.64

(0.76 - 3.52) 9 (42.9)3.27

(0.91 - 11.83) 3 (50.0) 4.89

(0.57 - 42.22)

Severe COPD 14 (16.1) 36 (31.6) 3.79

(1.67 - 8.64) 28 (32.2)3.70

(1.57 - 8.70) 7 (33.3)4.84

(1.15 - 20.43) 1 (16.7) 2.19

(0.13 - 37.94)

Ptrend 3 0.001 0.003 0.03 0.40

CI, confidence interval; OR, odds ratio; EPL, Endobronchial premalignant lesion; CIS, In-situ carcinoma. 1Includes pathological diagnoses—squamous meta-

plasia, dysplasia, carcinoma in-situ and invasive bronchial carcinoma; 2For overall analysis—adjusted for age at pulmonary function test, gender and pack-years

of smoking; 3p for trend; 4Mild COPD: (FEV1/FVC < 70% and FEV1 ≥ 80%); Moderate COPD: (FEV1/FVC < 70% and 50% ≤ FEV1 ≥ 80%); Severe COPD:

(FEV1/FVC < 70% and FEV1 < 50%); 5Patients who were missing either FEV1 or FVC information were not included in this analysis.

Table 3. Adjusted risk estimates for detection of premalignant bronchial lesions or lung cancers based on the pulmonary

function test results, stratified by gender.

MALES FEMALES

Pulmonary Function

parameter

Normal

(N = 64)3

n (%)

EPLs/Cancers1

(N = 86)3

n (%)

Adjusted OR2

(95% CI)

Normal

（N = 31)3

n (%)

EPLs/Cancers1

(N = 36)3

n (%)

Adjusted OR2

(95% CI)

FEV1% PREDICTED

≥80% 22 (34.4) 17 (19.8) Referent 10 (32.3) 6 (16.7) Referent

≥50% - <80% 34 (53.1) 43 (50.0) 1.43 (0.63 - 3.25)14 (45.2) 14 (38.9) 1.52 (0.40 - 5.75)

<50% 8 (12.5) 26 (30.2) 3.85 (1.34 - 11.10)7 (22.6) 16 (44.4) 6.54 (1.42 - 30.16)

Ptrend4 0.01 0.02

FEV1/FVC %

≥70% 32 (54.2) 28 (35.4) Referent 12 (42.9) 10 (28.6) Referent

≥50% - <70% 20 (33.9) 31 (39.2) 1.76 (0.79 - 3.93)12 (42.9) 16 (45.7) 1.93 (0.56 - 6.56)

<50% 7 (11.9) 20 (25.3) 3.59 (1.25 - 10.33)4 (14.3) 9 (25.7) 3.76 (0.74 - 19.04)

Ptrend4 0.02 0.10

COPD—GOLD CRITERIA5

No/Mild COPD 36 (61.0) 30 (38.0) Referent 14 (50.0) 11 (31.4) Referent

Moderate COPD 15 (25.4) 25 (31.6) 3.01 (0.85 - 4.76)8 (28.6) 12 (34.3) 1.98 (0.53 - 7.31)

Severe COPD 8 (13.6) 24 (30.4) 3.78 (1.40 - 10.19)6 (21.4) 12 (34.3) 4.54 (1.00 - 20.72)

Ptrend4 0.007 0.05

CI, confidence interval; OR, odds ratio; EPL, Endobronchial premalignant lesion; CIS, In-situ carcinoma. 1Includes pathological diagnoses—squamous meta-

plasia, dysplasia, carcinoma in-situ and and invasive bronchial carcinoma; 2For overall analysis—adjusted for pack-years of smoking and age at pulmonary

function test; 3Patients who were missing FEV1 or FVC information were excluded for certain analysis; 4p for trend; 5Mild COPD: (FEV1/FVC < 70% and

FEV1 ≥ 80%); Moderate COPD: (FEV1/FVC < 70% and 50% ≤ FEV1 ≥ 80%); Severe COPD: (FEV1/FVC < 70% and FEV1 < 50%).

Effect of Impaired Lung Function on the Development and Progression of Endobronchial Premalignant Lesions

369

to a higher grade [Hazard Ratio 2.48 (95% CI 0.65 -

9.41), p-value = 0.18)]. The mean time to progression

from a lower grade lesion to a higher grade was 27 months

for patients with COPD and 50 months for patients with-

out COPD (p = 0.02). The limited sample size precluded

more detailed analyses of histologic progresssion.

5. Discussion

Several previous studies have reported that ILF and

COPD are consistently associated with an increased risk

of incident LC [14-19]. ILF has also been shown to be

related to LC mortality [14,22,23]. Several mechanisms

are proposed to explain the relationship between im-

paired LF and incident LC. Chronic inflammation of the

airway and lung tissue is suggested to be the common

pathway in the development of COPD and/or LC [24,25].

Transactivation of genes involved in inflammation and

nuclear factor NF-κB activation can play an important

role in development of both LC and COPD [26]. Im-

paired mucociliary clearance associated with COPD re-

sults in decreased clearing of inhaled particulate matter

resulting in greater amount of carcinogens getting depos-

ited in the airway [25]. This prolonged contact of car-

cinogens to lung tissue may be a determinant in the de-

velopment of LC. This theory might have more credence

if the association between ILF and development and pro-

gression of EPLs can be demonstrated.

Few studies have examined the relationship between

ILF and EPLs. Prindiville et al. failed to identify any

increased risk of squamous atypia with greater degree of

airflow obstruction [27]. On the other hand, Kennedy et

al. reported a high prevalence of SD in patients with

COPD who reported at least 40 pack-years of smoking

[28]. Both of these studies used sputum cytology to de-

fine atypia/SD rather than histopathologic review of bi-

opsy specimens, as was done in our current study. Two

other studies have evaluated the prevalence of EPLs us-

ing autofluorescence bronchoscopy guided biopsies [7,

29]. While Breuer et al. noted no significant relation be-

tween COPD and the prevalence of EPLs (p = 0.40),

Lam et al. used linear predictors of LF measures and

reported that the risk of high-grade EPLs was greater in

patients with lower FEV1 volume and FEV1/FVC ratio

[29]. Consistent with Lam et al., our study results also

show that the patients with lower measures of LF were at

a greater risk of EPLs. In addition, the current study also

examines the risk of detecting EPLs using categorical

measures of LF and demonstrates a “dose-response” re-

lationship with greater level of LF impairment. While

Lam et al., noted statistically significant risk estimates

for EPLs in men and not in women, our results showed a

significant increase in risk among both genders. However,

considerable overlap in odds ratios prevents us from

evaluating the difference between the two genders.

The relationship between ILF and LC development has

previously been shown to be more pronounced with the

squamous cell subtype. In a study on patients undergoing

lung resection for non-small cell lung cancer (NSCLC),

impaired FEV1% was associated with significant in-

crease in risk for SCC subtype [17]. In another study,

Malhotra et al. also reported that impaired FEV1 was

associated with greater chance of SCC [30]. We observed

that ILF was associated with a 3 to 7 fold increased risk

of identifying SM and SD, precursors of SCC.

In addition to demonstrating a greater risk of EPL de-

tection with COPD, our results show that the mean time

to progression of the baseline lesions in COPD patients

was lesser than the non-COPD patients. Experimental

and modeling studies demonstrate total lung deposition

of inhaled particulate matter is much greater in patients

with obstructive disease compared to healthy individuals,

and the deposition enhancement is generally confined to

central airways [31,32]. This may explain the greater

prevalence and risk of progression for EPLs in the setting

of airflow obstruction. These patients could be a sub-

group that would require a more intense surveillance for

LC. However, it should be noted that in our study not all

patients had a follow-up biopsy limiting our ability to

perform detailed stratified analysis. Also, our study was

not powered to assess the risk of detecting invasive LC

or to evaluate the risk of progression in detail. In spite of

these limitations, our study provides preliminary evi-

dence that impaired lung function may increase the risk

of progression of EPLs.

6. Conclusion

The current study provides compelling evidence that im-

paired lung function is associated with a substantially

increased risk of developing EPLs. However, larger stud-

ies are needed to confirm and expand on these results,

and to evaluate progression rates among patients with air-

flow limitation. Overall, office spirometry can be a non-

invasive and inexpensive pre-screening tool to identify

patients with EPLs who need active surveillance for LC.

7. Acknowledgements

The authors would like to thank Wayne P. Slowik,

RRT/RPFT; Sandra J. Michel, RN BSN; and the Stacey

Scott Lung Cancer Registry team for their valuable con-

tribution in collecting, cleaning and maintaining clinical

information and PFT data.

This study was supported in part by the funding from

the Stacey Scott Lung Cancer Registry, Roswell Park

Cancer Institute

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