26   AJTCCM  VOL. 24  NO. 1  2018
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Background. It is a common, yet unproven, belief that patients with post-inflammatory lung disease have a better functional reserve than 
patients with lung cancer when compared with their respective functional parameters of operability – forced expiratory volume in one 
second (FEV1), maximum oxygen uptake in litres per minute (VO2max) and the diffusion capacity for carbon monoxide (DLCO).
Objectives. The aim of this study was to compare a group of patients with lung cancer with a group with post-inflammatory lung disease 
according to their respective functional parameters of operability. We also aimed to investigate any associations of FEV1 and/or DLCO with 
VO2max within the two groups.
Methods. We retrospectively included 100 adult patients considered for lung resection. All patients were worked up using a validated 
algorithm and were then sub-analysed according to their parameters of functional operability.
Results. Two-thirds of patients had post-inflammatory lung diseases whilst the rest had lung cancer. The majority of the patients in the lung 
cancer group had coexistent chronic obstructive pulmonary disease (COPD) (n=18). Most (n=47) of the patients in the post-inflammatory 
group were diagnosed with a form of pulmonary TB (active or previous). Among the two groups, the lung cancer group had a higher median 
%FEV1 value (62.0%; interquartile range (IQR) 51.0 - 76.0) compared with the post-inflammatory group (52%; IQR 42.0 - 63.0; p=0.01). 
There was no difference for the %DLCO and %VO2max values. The lung cancer group also had higher predicted postoperative (ppo) 
values for %FEV1 (41.0%; IQR 31.0 - 58.0 v. 34.0%; IQR 23.0 - 46.0; p=0.03, respectively) and %VO2max (58.0%; IQR 44.0 - 68.0 v. 46.0%;  
IQR 35.0 - 60.0; p=0.02). There was no difference in the %DLCO ppo values between the groups.
Conclusion. Patients with lung cancer had higher percentage values for FEV1 and ppo parameters for %FEV1 and %VO2max compared with 
those who had post-inflammatory lung disease. Our findings suggest that lung cancer patients have a better functional reserve.
Afr J Thoracic Crit Care Med 2018;24(1):26-29. DOI:10.7196/AJTCCM2018.v24i1.158 
Cancer is one of the leading causes of mortality worldwide. Lung 
cancer is the leading cause of cancer-related mortality globally, 
causing 1.6 million deaths in 2012.[1] However, in southern Africa, the 
relationship between lung cancer and its mortality rate remains low in 
comparison with other cancers and respiratory diseases.[2-5] 
According to the World Health Organization (WHO), an estimated 
7.7 million cases of pulmonary tuberculosis (PTB) occurred worldwide 
in 2007[6] and South Africa (SA) had the third highest tuberculosis 
(TB) burden.[7,8] Treated PTB can lead to complications, including 
progressive loss of lung function, persistent pulmonary symptoms[9] 
and chronic pulmonary aspergillosis.[10-12] These complications 
frequently necessitate surgery. A study by Rizzi et al.[13] reported that 
patients with post tuberculous chronic haemoptysis (10.0%), lung 
destruction (8.1%), chest wall involvement (1.9%), suspected cancer 
(24.2%), cavitatory lung disease (21.9%) and bronchiectasis (16.1%) 
required elective surgery, whereas those with massive bleeding (5.4%) 
or a bronchopleural fistula (3.1%) required emergency surgery. 
Lung resection can be a high-risk procedure, especially in patients 
with underlying cardiopulmonary disease. Predictors of mortality 
include the extent of resection, comorbidities and cardiopulmonary 
reserve.[14,15] 
Ninety percent of lung cancer patients are current or past smokers, 
which is frequently associated with varying degrees of concomitant 
chronic obstructive pulmonary disease and/or ischaemic heart 
disease. Furthermore, many of these patients are of advanced age and 
this places them at an increased risk of post-operative complications 
and mortality.[16,17] A number of prospective studies have validated 
a percentage-predicted forced expiratory volume in one second 
predicted postoperative value (%FEV1 ppo) of <40% as a prohibitive 
threshold for pulmonary resection, with mortality rates as high as 
50% in such patients. Ferguson et al.[18] demonstrated that a diffusion 
capacity for carbon monoxide (DLCO) of <60% of the predicted value 
was a cut-off value for major pulmonary resection. The maximum 
oxygen uptake in litres per minute predicted postoperative (VO2 
max ppo) value of <10 ml/kg/min, obtained from either formal 
cardiopulmonary exercise testing (CPET) or low-technology 
(minimal achievement) exercise tests, is associated with a high risk 
of post-operative complications and death. Regarding the cardiac 
A comparison of the functional parameters of operability in 
patients with post-inflammatory lung disease and those with lung 
cancer requiring lung resection
M H Amirali, MD, MMed (Int), FCP (SA); E M Irusen, MB ChB, FCP (SA), FCCP, PhD;  
C F N Koegelenberg, MB ChB, MMed (Int), FCP (SA), FRCP (UK), Cert Pulm (SA), PhD
Division of Pulmonology, Department of Medicine, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa
Corresponding author: M H Amirali (mazheramirali@gmail.com)
AJTCCM  VOL. 24  NO. 1  2018   27
RESEARCH
risk assessment, the Revised Cardiac Risk Index (RCRI)[19] is used by 
many authorities. The criteria contain six independent variables that 
correlate with post-operative cardiac complications - these include 
a high-risk type of surgery, a history of ischaemic heart disease, 
cardiac failure, cerebrovascular disease, diabetes requiring treatment 
with insulin and pre-operative serum creatinine of >177 µmol/L. 
Patients with more than two variables have a postoperative cardiac 
complication rate >10% and are considered to be at high risk.[17]
The validated algorithms used to assess candidates for lung 
resection are based on spirometry, the DLCO and the VO2 max.[14] 
One such algorithm proposed by Bolliger and Perruchoud[15] has been 
used widely as a tool for evaluating cardiorespiratory reserves of lung 
resection candidates. The algorithm proposes that patients undergo 
successive steps of functional testing, the results of which qualify them 
for varying extents of resection or alternatively preclude them from 
any surgery.[15]
Apart from the underlying cardiopulmonary disease and other 
comorbidities, the calculated predicted postoperative (ppo) values for 
FEV1, VO2max and DLCO are directly proportional to postoperative 
functional state and mortality.[21] 
It is a commonly held belief by various experts in the field of 
pulmonology that patients with post-inflammatory lung disease 
have a better functional reserve postoperatively than patients with 
lung cancer, when comparing their respective FEV1, VO2max and 
DLCO values; however, there is limited evidence to support the 
belief.[16]
The aim of the present study was to compare two groups of patients 
(i.e. patients with lung cancer v. patients with post-inflammatory 
lung disease), and to investigate the association of functional 
parameters of operability within these two groups of patients.
Methods
Study design and population
We retrospectively enrolled adult patients who had been considered 
for lung resection and were referred to the Division of Pulmonology at 
Tygerberg Academic Hospital, Cape Town, with either lung cancer or 
post-inflammatory lung disease. Ethical approval for this retrospective 
analysis was obtained from the Stellenbosch University Research 
Ethics Committee (ref. no. S15/04/074). The application included a 
waiver of consent due to the retrospective nature and anonymity of 
the study design. 
Cases were identified from existing medical records; they were 
stratified into two groups, namely ‘A’ and ‘B’, where ‘A’ comprised 
patients with non-small-cell lung cancer while ‘B’ comprised 
patients with post-inflammatory lung disease (bronchiectasis, 
active/post tuberculous haemoptysis, and aspergilloma). After 
obtaining permission from the chief medical superintendent, the 
original medical records of all cases identified were requested and 
data were collected anonymously. The data collected included the 
demographics (age, gender), comorbidities of patients, indications for 
lung resection, extent of lung resection, and their pulmonary function 
test values (i.e. FEV1, FVC, DLCO and VO2max). The ppo value for 
these parameters can be calculated by the equation in Fig. 2, where 
the pulmonary function test (PFT) can either be %FEV1, %VO2max 
or %DLCO. We used three validated ways of estimating the relative 
functional contribution or split function, i.e. anatomical calculation, 
split radionucleotide perfusion scanning and quantitative computer 
tomography scanning and dynamic perfusion magnetic resonance 
imaging (MRI).  
Anatomical calculations of ppo values were performed on all 
patients who required pre-operative estimation of post-operative lung 
function. Patients who required further evaluation underwent either 
radionucleotide perfusion scanning or quantitative CT scanning. 
All patients were worked up for lung resection using the algorithm 
for the assessment of their cardiorespiratory reserves (functional  
operability).[17] Patients were generally followed up as outpatients 
and CPET was only performed once the risk of haemoptysis was 
Diagnosis
• Stress ECG
• Echo
• Perfusion scan
• Angiogram
Treatment
• Medical
• Surgical
High risk
Resection up to 
calculated extent
Split function
VO2max, ppo
Split function
• FEV1, ppo
• DLCO, ppo
Exercise testing
VO2max
Lungs
• FEV1
• DLCO
Heart
• History
• ECH
Pneumonectomy
Positive
Negative
Negative
Positive
Yes
No
<40% or 
<10 mL.kg–1.min–1
Both <40%
<35% or 
<10 mL.kg–1.min–1
>35% and
>10 mL.kg–1.min–1
Either one >40%
40 - 75% and
10 - 20 mL.kg–1.min–1
Either one <80%
>75% or
>20 mL.kg–1.min–1
Both >80%
Fig. 1. Algorithm proposed by Bolliger et al.,[15] adapted by Koegelenberg 
et al.[17] (ECG = electrocardiogram ; FEV1 = forced expiratory 
volume in one second ; DLCO = diffusion capacity for carbon 
monoxide; VO2max = maximum oxygen uptake in litres per minute;  
mL = millilitres; kg = kilograms; )
%PFT ppo = [%PFT – ((a/n) × %PFT)] × 100
where
PFT = pulmonary function test
a = number of segments to be resected
n = total number of segments
Fig. 2. Equation used to calculate %PFT ppo value. (ppo = predicted 
postoperative, PFT = pulmonary function test.)
28   AJTCCM  VOL. 24  NO. 1  2018
RESEARCH
evaluated (i. e. no haemoptysis for 2 weeks). Patients included in the 
study were then evaluated for their respective functional operability 
parameters.
Statistical analysis
χ2 comparisons and Pearson product-moment correlation coefficient 
(Pearson’s r or ‘r-squared’) of proportional data were performed. 
We did not make any assumptions for normality; hence, these non-
parametric inferences were used for statistical analysis. A p-value <0.05 
in a two-tailed test of proportions (χ2) was considered statistically 
significant. Unless stated otherwise, data are displayed as median with 
interquartile range (IQR) values. 
Results
We included 100 patients in our study. The demographic data, 
primary diagnoses and comorbidities of the patients are summarised 
in Table 1.The majority of our patients were male (n=66/100);  
51 were diagnosed with a post-inflammatory lung disease, while the 
rest had lung cancer.
The most common diagnosis in the post-inflammatory group was 
that of haemoptysis (n=47). Bronchiectasis and aspergilloma were the 
second most common diagnoses, followed by post-TB bronchiectasis 
and destroyed lung. 
The majority of the patients in the lung cancer group had COPD 
(n=18), 11 of them were either active or previous smokers. Two of 
the patients had ischaemic heart disease. Most (n=47) of the patients 
in the post inflammatory group were diagnosed with some form of 
pulmonary TB (active or previous). COPD and smoking had the 
second and third highest prevalence, and 17 patients had no associated 
comorbidities.
When comparing the various functional parameters of operability 
between the two groups, the lung cancer group had higher %FEV1 
values (62.0%; IQR 51.0 - 76.0; p=0.01), there were no differences 
between the %DLCO (56.0%; IQR 44.0 - 75.0; p=0.509), and 
%VO2max values (80.0%; IQR 66.0 - 89.0; p=0.105). The lung 
cancer group also had higher ppo values for %FEV1 (41.0%; IQR 
31.0 - 58.0; p=0.03), and %VO2max (58.0%; IQR 44.0 - 68.0; p=0.02); 
there was ,however, no difference for %DLCO ppo values 40.0%  
(IQR 23.0 - 51.0; p=0.849). The values for the post-inflammatory 
group were: %FEV1 52.0% (IQR 42.0 - 63.0); %DLCO 63.0%  
(IQR 51.0 - 75.0); and %VO2max 72.0% (IQR 59.0 - 82.0). The ppo 
values were: %FEV1 34.0% (IQR 23.0 - 46.0); %VO2max 46.0% (IQR 
35.0 - 60.0); and %DLCO 39.0% (IQR 26.0 - 55.0). Correlation 
analysis did not show any correlation between the two groups. 
Table 1. Demographic and clinical data of study population 
(N=100)
n (%)*
Male
66 (66.0)
Female
34 (34.0)
Age (years), mean (range)
46.7 (17 - 72)
Medical condition
Lung cancer
Male
15 (62.5)
Female
9 (37.5)
Comorbidities
Hypertension
8 (19.0)
HIV
0 (0.0)
Pulmonary TB
1 (2.4)
COPD
18 (42.9)
Smoking
11 (26.2)
CAD
2 (4.8)
None
2 (4.8)
Post-inflammatory
Male
51 (67.1)
Female
25 (32.9)
Diagnoses
    Post-TB bronchiectasis
14 (19.7)
Bronchiectasis
18 (25.3)
Aspergillomata
18 (25.3)
Destroyed lung
14 (19.7)
Echinococcal cysts
3 (4.2)
Empyema
1 (1.4)
Adenomatoid malformation
1 (1.4)
Post-TB upper-lobe changes
1 (1.4)
MDR-TB
1 (1.4)
Comorbidities
Hypertension
6 (4.30)
HIV
12 (8.70)
Pulmonary TB (active and previous)
47 (34.0)
COPD
30 (21.7)
Smoking
23 (16.7)
    CAD
2 (1.4)
Bronchiectasis
1 (0.7)
None
17 (12.3)
TB = tuberculosis; COPD = chronic obstructive pulmonary disease; CAD = coronary artery 
disease; MDR-TB = multidrug-resistant tuberculosis.
*Unless otherwise specified.
Table 2. Comparison of functional parameters of operability among the two groups
 
All, median (IQR)
A,* median (IQR)
B,† median (IQR)
p-value
%FEV1
55 (43 - 65)
62 (51 - 76)
52 (42 - 63)
0.01
%FEV1 ppo
35 (26 - 48)
41 (31 - 58)
34 (23 - 46)
0.03
%VO2max
73 (60 - 84)
80 (66 - 89)
72 (59 - 82)
0.105
%VO2max ppo
49 (38 - 63)
58 (44 - 68)
46 (35 - 60)
0.02
%DLCO
62 (50 - 75)
56 (44 - 75)
63 (51 - 75)
0.509
%DLCO ppo
40 (26 - 54)
40 (23 - 51)
39 (26 - 55)
0.849
IQR = interquartile range; %FEV1 = percentage predicted for forced expiratory volume in one second; %FEV1 ppo =  percentage predicted for forced expiratory volume in one second predicted postoperative; 
%VO2max = percentage predicted for maximum oxygen uptake in litres per minute; %VO2max ppo = percentage predicted for maximum oxygen uptake in litres per minute predicted postoperative; 
%DLCO =  percentage predicted for diffusion capacity for carbon monoxide; %DLCO ppo = percentage predicted for diffusion capacity for carbon monoxide predicted postoperative.
*Non-small-cell lung cancer group.
†Post-inflammatory group (bronchiectasis, post tuberculous haemoptysis, aspergilloma).
AJTCCM  VOL. 24  NO. 1  2018   29
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Discussion
We found statistically significant differences between the two groups 
when comparing the %FEV1, %FEV1 ppo, and %VO2max ppo; the lung 
cancer group had a higher %FEV1 (p=0.01), and higher ppo values for 
%FEV1 and %VO2max (p=0.03 and p=0.02, respectively). We found 
no statistically significant differences between the two groups when 
we compared the %DLCO, %DLCO ppo and %VO2max. No gender-
based differences were observed. There was no correlation between 
the variables in either group. Therefore, both FEV1 and DLCO did not 
predict VO2max in either group.
It is well-known that the pre-operative assessment predicts 
postoperative functional reserve, morbidity and mortality. Usually, 
a FEV1 ppo, DLCO ppo, and VO2max ppo <40% of normal values 
have all been found to indicate increased mortality.[22] We have shown 
that patients with lung cancer have a better functional reserve when 
compared with those who have post-inflammatory lung disease, and 
that neither FEV1 nor DLCO predicted VO2max in either group. 
There was also no predilection of the functional reserve towards the 
sex or age of our patients. We believe that these findings will have 
implications for the surgical management of patients with lung cancer, 
in that they may now be more readily considered for lung resection. 
Depending on the extent and the time elapsed from the operation, 
lung resections determine a variable reduction in functional reserve. 
A study by Brunelli et al.[23] showed that at one month after lobectomy, 
the FEV1, DLCO, and VO2max values were 79.5%, 81.5%, and 96% 
of preoperative values, respectively. These recovered to 84%, 88.5% 
and 97%, respectively, after 3 months. Regarding pneumonectomy, the 
%FEV1, %DLCO, and VO2max values were 65%, 75%, and 87% of pre-
operative values at 1 month, respectively; at 3 months postoperatively, 
the values were 66%, 80%, and 89%, respectively. Other studies have 
shown similar results.[24-26]
Inferring from these data, the lung cancer group in our study would 
most likely have a better overall functional reserve postoperatively. 
Therefore, the assumption that lung cancer patients have a worse 
functional reserve postoperatively when compared with patients who 
have post-inflammatory lung disease is untrue.
Study strengths and limitations
This was a single-centre study, which benefits from strict adherence 
to a validated algorithm. The retrospective nature of the study, as well 
as the potential selection bias, could be limiting as only patients who 
were deemed clinically fit were recruited as study participants. We did 
not collect data on postoperative complications and mortality. 
Conclusion
We found that patients with lung cancer had higher percentage-
predicted values for FEV1 and predicted postoperative values for 
%FEV1 and %VO2 compared with those who had post-inflammatory 
lung disease. Future prospective studies should preferably include 
the postoperative outcomes among the two groups to provide a 
comprehensive analysis.
Acknowledgements. We would like to thank all members of the pulmonary 
function laboratory team of Tygerberg Academic Hospital for their 
assistance and Mr Maxwell Chirehwa and Ms Tonya Esterhuizen for help 
with the statistical analysis.
Author contributions. MHA was the principal investigator, who collected 
the data and wrote the manuscript. CFNK assisted with data analysis and 
reviewed the manuscript. EMI reviewed the final manuscript. 
Funding. None.
Conflicts of interest. None.
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Accepted 10 October 2017.

A comparison of the functional parameters of operability in patients with post-inflammatory lung disease and those with lung cancer requiring lung resection.
Amirali, M H,Irusen, E M,Koegelenberg, C F N