| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
* From the School of Clinical Medical Sciences, University of Newcastle upon Tyne, and Departments of Cardio-respiratory Medicine and Radiology, University Hospital of North Tees, Stockton on Tees, Cleveland, UK.
Correspondence to: P D. Snashall, MD, Department of Medicine, University Hospital of North Tees, Stockton on Tees, Cleveland, TS19 8PE, UK; e-mail: snashall{at}ukgateway.net
 |
Abstract |
|---|
 TOP Abstract IntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
Interventions: Lung function testing and limited HRCT scanning.
Design: Lung function measurements and scans were analyzed independently of each other. We used analysis of covariance to compare FEV1 and maximum expiratory flow at 50% of vital capacity (MEF50) values after suitable corrections, between subjects with and without parenchymal damage (emphysema and/or reduced carbon monoxide transfer coefficient [KCO]), and to compare indexes of parenchymal damage between subjects with and without airflow obstruction.
Setting: Radiology and lung function departments of a district general hospital.
Participants: Eighty current cigarette smokers and 20 lifetime nonsmoking control subjects (aged 35 to 65 years) who volunteered following publicity in local media. In all subjects, FEV1 was > 1.5 L; no subjects were known to have lung disease.
Measurements and results: FEV1 and MEF50 were measured spirometrically; static lung volumes were measured by helium dilution and body plethysmography; KCO was measured by a single-breath technique. HRCT scans were analyzed for emphysema by two radiologists. Of smokers, 25% had HRCT emphysema, generally mild; 16.3% and 25% had reduced FEV1 and MEF50, respectively; 12.5% had reduced KCO. Smokers with airflow obstruction were not more likely to have parenchymal damage. Smokers with parenchymal damage did not have reduced airway function. Nonsmokers generally had normal airways and parenchyma.
Conclusions: "Normal" smokers with lung damage had either airflow obstruction or parenchymal damage, but not generally both.
Key Words: airflow obstruction • COPD • emphysema • smoking
|
Introduction |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
High-resolution CT (HRCT) is a highly sensitive method for demonstrating and quantifying emphysema2 4 9 10 and has demonstrated mild degrees of emphysema in symptomless smokers,11 in whom COPD might therefore be thought to be developing. Radiographic and pathologic correlations demonstrate the sensitivity of the CT technique.12 The present study addresses the question of whether mild emphysema demonstrated by HRCT in symptomless smokers is associated with airflow obstruction. We have analyzed lung function and radiographic data from a cross-sectional study13 of current cigarette smoking and never-smoking volunteers, none of whom were known to have COPD or other obstructive lung diseases.
|
Materials and Methods |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
The study was approved by the North Tees Local Research Ethics Committee. Subjects consented in writing after reading a description of the study and possible risks. At the end of the study, all subjects were informed of their results via their general practitioner. Smokers were offered information and help on smoking abstinence. Subjects also completed a Medical Research Council Respiratory Health Questionnaire.
HRCT scanning was performed (IGE Sytec 3000i CT scanner; GEC;
Milwaukee, WI). Three 1-mm cuts from the upper, middle, and lower zones
of the right lung were obtained at total lung capacity (TLC). The
images were examined by two radiologists who worked independently and
were unaware of the subjects’ smoking status. They primarily examined
for areas of emphysema, characterized as areas of abnormally low
radiographic density, lacking a well-defined wall, and where marked,
associated with a disruption of the normal vascular markings. When they
disagreed, they viewed the images together and came to an agreed
decision. Emphysema was graded using criteria of Remy-Jardin et
al,11
, ie, grade 1, 
25% of lung fields
affected by emphysema; grade 2, > 25%, 50%; grade 3, > 50%,
75%; and grade 4, > 75%.
Lung Function
Forced spirometry, lung volumes (helium dilution), and carbon
monoxide transfer were measured using automated apparatus (model TTUSA;
P.K. Morgan; Chatham, Kent, UK). Lung volumes were also measured using
a constant volume body plethysmograph (model 1190; P.K. Morgan). All
measurements were adjusted to body temperature and pressure,
saturated. Measurements of residual volume (RV), functional
residual capacity (FRC), and TLC were repeated until duplicate
measurements of TLC were within 7%. In subjects in whom satisfactorily
reproducible volume measurements were made by both helium dilution and
body plethysmographic methods, the quoted value is the mean of the two
methods. Where only one method yielded adequately reproducible results,
the quoted value is for that method alone. Calibration checks on all
instruments were carried out daily.
Expiratory flow-volume curves were recorded from a computerized dry rolling-seal spirometer. Forced expiratory maneuvers were repeated until duplicate estimates of FVC and FEV1 were within 5% of each other. Maximum expiratory flow at 50% of vital capacity (MEF50) was derived automatically from the expiratory flow volume curve. Carbon monoxide transfer was measured by the single-breath method14 using a 9-s breath-hold time. Duplicate measurements were accepted where estimates of carbon monoxide transfer factor (TLCO) and effective alveolar volume (VA) were within 5%; carbon monoxide transfer coefficient (KCO) was derived (KCO = TLCO/VA). Four smokers achieved unacceptable KCO reproducibility. Hemoglobin was measured and in all cases was within the normal range.
Statistics
Data were analyzed using a statistical package (SPSS Inc.;
Chicago, IL). We assumed that lung function measures were
normally distributed. We used analysis of covariance (ANCOVA) to
compare FEV1 and MEF50
(corrected for pack-years, age, height, and sex) between grades of HRCT
emphysema, and in subjects with and without significantly low
KCO. We similarly compared KCO (corrected for
pack-years) between subjects with and without a significantly low
FEV1, and we compared emphysema grade (corrected
for age, sex, smoking status, and height) in subjects with and without
significantly low KCO and subjects with and without
significantly low FEV1. A p value of < 0.05 was
accepted as significant. Predicted lung function values used were
derived from a nonsmoking, white, urban British
population,15
and we adopted (mean - 1.645 SD) as the
lower limit of normal for FEV1 and
KCO. Values below this will occur by chance on 5% of
occasions in a normal population.15
We used the
2 statistic to compare the actual frequency of
coexistence of parenchymal and airway abnormalities with frequencies
expected by chance.
|
Results |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
|
Of 20 smokers with radiographic emphysema, 5 subjects had airflow obstruction (low FEV1 and/or low MEF50), as would be expected by chance. Six smokers had a significantly low KCO; two or three smokers would have had a significantly low KCO expected by chance (p < 0.025).
Relationships Between Lung Function and Emphysema
ANCOVA demonstrated several significant relationships among lung
function and radiographic variables (Table 2
). A low FEV1 was associated with high RV and FRC,
but with no significant changes in carbon monoxide transfer or with
HRCT emphysema score. A low KCO was associated with high
TLC and FRC and with an increased emphysema score, but with no
significant change in FEV1 or
MEF50. The presence of HRCT emphysema was
associated with reduced KCO and TLCO, but with
no significant changes in FEV1,
MEF50, or lung volumes. In emphysema grades 0 to
3, FEV1 averaged 2.89 L, 3.19 L, 3.07 L, and 2.91
L, respectively (p = 0.20).
|
Twenty-one smokers were breathless when hurrying on a flat surface or walking up a slight hill, and 16 smokers had a productive cough for > 3 mo/yr. FEV1 was reduced in breathless smokers compared with nonbreathless smokers (p < 0.01) and in those with productive cough compared with those without cough (p < 0.01). There was no significant relationship between breathlessness and emphysema or a reduced KCO. Seventeen smokers (21%) recollected nonasthmatic childhood chest trouble; 4 of these smokers had emphysema and 3 smokers had a reduced FEV1.
|
Discussion |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
This lack of relationship, which has also been shown by others,1 2 argues against a causal relationship between parenchymal destruction and airflow obstruction as measured by FEV1 and MEF50. Early in its genesis, smokers’ airflow obstruction is due either to intrinsic airway disease or to loss of lung elastic recoil pressure, independent of detectable emphysema.3 In established COPD, however, there is a significant correlation between extent of emphysema and severity of airflow obstruction4 and it is probable that emphysema aggravates airway narrowing.6 7
A previously published analysis13 of these data, taken with indexes of smoke inhalation, suggested that different patterns of smoke inhalation may result in different patterns of lung damage. We found indirect evidence that deep or prolonged smoke inhalation predisposes to emphysema.
Looking at the lung function of the groups as a whole, we see that the effect of smoking is to cause airway obstruction, a loss of carbon monoxide transfer capacity, and an increase in the lower divisions of lung volume, RV, and FRC. There was no significant effect on TLC for reasons that are not clear.
We found a clear association between HRCT emphysema and reduced carbon monoxide transfer, as have others.2 4 KCO was lower in subjects with HRCT emphysema, and emphysema grade was higher in subjects with a low KCO. Thus, although emphysema was generally minor and focal and was not associated with an increase in lung volume, it was associated with a general defect in parenchymal function. In subjects with a significantly reduced KCO, lung volume, particularly at TLC, was elevated, suggesting a loss of lung elastic recoil pressure. A low KCO therefore indicated more severe or generalized parenchymal damage than HRCT emphysema alone. Because maximal expiratory flow depends on elastic recoil pressure, one might expect to have found reduced expiratory flows in those with low KCO, but there was no hint of this. We assume that hyperinflation maintained recoil pressure at near normal values.
Subjects with a significantly low FEV1 had a raised RV, suggesting air trapping at low lung volumes, presumably due to intrinsic small airway disease. The HRCT emphysema score was not increased, nor was there any hint of a reduction of KCO.
The study population showed a surprisingly high incidence of abnormalities, particularly emphysema. In total, of 80 "normal" smokers, 39 subjects (49%) had a lung function or HRCT abnormality or both. Admittedly, most of the HRCT emphysema was minor (grade 1), as were most of the airway abnormalities. By contrast, only two nonsmoking subjects (10%) had minor abnormalities of lung function, and no emphysema was detected. Some smoking subjects volunteered because of concerns about their health, and the group may therefore have an excess of subjects with developing lung disease. Conversely, we may have underestimated the prevalence of emphysema by restricting HRCT scanning to three slices, which was done to limit radiographic exposure. Our findings are in line with an earlier study11 of younger smokers, 21% of whom had mild HRCT emphysema.
|
Conclusion |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
|
Footnotes |
|---|
Funded by grants from the Northern and Yorkshire Regional Health Authority and North Tees Health (NHS) Trust.
Received for publication January 18, 2000. Accepted for publication April 10, 2001.
|
References |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  G.-C. Funk, D. Doberer, V. Petkov, L. H. Block, R. Walter, R. Givelber, G. O'Connor, and D. Gottlieb Hyperglycemia, Bronchial Artery Sclerosis, and Lung Function Am. J. Respir. Crit. Care Med., February 1, 2004; 169(3): 427 - 427. [Full Text] [PDF]
|
|
|
|
 |
|
 N Minematsu, H Nakamura, M Iwata, H Tateno, T Nakajima, S Takahashi, S Fujishima, and K Yamaguchi Association of CYP2A6 deletion polymorphism with smoking habit and development of pulmonary emphysema Thorax, July 1, 2003; 58(7): 623 - 628. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
