The Code of Practice (Control and prevention of tuberculosis in the United Kingdom)[1] provides us with evidence based gold
standards for best practice in this field. The exception is of promoting
routine immigrant screening and the context within which it is
recommended.
I welcome a general health check for immigrants on arrival, but does
routine screening for tuberculosis needs to be part of it?...
The Code of Practice (Control and prevention of tuberculosis in the United Kingdom)[1] provides us with evidence based gold
standards for best practice in this field. The exception is of promoting
routine immigrant screening and the context within which it is
recommended.
I welcome a general health check for immigrants on arrival, but does
routine screening for tuberculosis needs to be part of it? Emphasis on
such screening implies convincing evidence. The Code’s reference to
Ormerod contradicts that assumption.[2][3]
Ormerod states that most tuberculosis is not evident on arrival.
Birmingham stopped adult screening some years back. Birmingham is
arguably the largest receiver of immigrants from the Indian subcontinent
to the UK. It was rare for even a single case to be recorded annually
when screening was practised in the city.
We must also take into account the cumulative radiological hazards of
screening; comparative cost benefits and effectiveness of diagnosing an
active case and its subsequent management as against relying on a disease
management policy alone. Human rights issue of equating immigration with
tuberculosis cannot be ignored.[4] [5]
The context in which immigrant screening is recommended is also worth
noting. Increased number of tuberculosis cases in the country does not
necessarily mean increased incidence. We have very poor measures of the
population base against which rates could be determined.
The natural immigrant population increase (some communities have an
above average birth rate) added to the number of new arrivals is an
unknown quantity since the last census a decade ago. The immigrant
population has also aged and could account for a higher age-specific
number of tuberculosis cases. Race and age specific rates may indeed be
falling while overall prevalence shows an increase. Much higher prevalence
of age-related diabetes in the immigrant population is an additional risk
factor for tuberculosis.[6]
It may well be that the increase in numbers is accompanied by
decrease in age and race specific rates due to improved living conditions
and better treatment facilities. The Code does add to the confusion,
referring to geographical preponderance when in reality the increase is
due to the presence of inhabitants from different parts of the world.
Areas such as Liverpool, though densely populated but with fewer immigrants
of Indian subcontinent origin, have a much lower overall prevalence of
tuberculosis.[7]
Tuberculosis is a slow evolving disease. It will be decades before
those who have migrated in the second half of the last century come into
equilibrium with rest of the indigenous population. There is the urgent
need to show whether this population is progressing towards that end or
that there is reversal in the secular trend of decrease of tuberculosis.
The latter would indeed be most worrying and call for the most detailed of
measures including screening.
We do not yet know of the impact of any control strategy on the trend
of tuberculosis. A disease management policy in affluent countries will at
least reduce the burden of disease and suffering. Diverting resource to a
screening programme will be counter productive.[8]
References
(1) BTS guidelines. Control and prevention of tuberculosis in the
United Kingdom: Code of Practice 2000. Thorax 2000;55:887-901.
(2) Ormerod LP. Tuberculosis screening and prevention in new
immigrants 1983-88. Respir Med 1990;84:269-71.
(3) Ormerod LP. Is immigrant screening for tuberculosis still
worthwhile? J Infect 1998;37:39-40.
(4) Bakhshi SS. screening immigrants at risk of tuberculosis. BMJ 1994;308:416.
(5) Bakhshi S. Detecting tuberculosis in new arrivals to UK. BMJ 2000;321:569.
(6) Stead WW, Dutt AK. Tuberculosis in the elderly. Semin Respir Infect 1989;4:189-97.
(7) Jeremy IH, Bakhshi SS, Ali S, Farrington CP. Ecological analysis
of ethnic differences in relation between tuberculosis and poverty. BMJ 1999;319:1031-4.
(8) Bwire R, et al. Tuberculosis screening among immigrants in The Netherlands: what is its contribution to public health? The Netherlands J Med 2000;56:63-71.
If the abstract indicates correctly that children of totally non-smoking parents were not included in the study, I see that as a significant weakness.
The study found, as might be expected by many, an increase in contacts for asthma episodes among children most heavily exposed to environmental tobacco smoke (ETS).
However, it also found a non-significant but noteworthy decrease in asthma epi...
If the abstract indicates correctly that children of totally non-smoking parents were not included in the study, I see that as a significant weakness.
The study found, as might be expected by many, an increase in contacts for asthma episodes among children most heavily exposed to environmental tobacco smoke (ETS).
However, it also found a non-significant but noteworthy decrease in asthma episode contacts among those with "moderate" exposure as opposed to "low" exposure. If non-smoking parents (which would presumably usually
have children with *extremely* low exposure) had been included as a study group as well, we might have seen a continuation of the U-shaped curve indicating support for the idea that moderate levels of tobacco smoke in
the air might act in some way as a suppressor to asthma or asthma episodes
among children regularly exposed to such. Such a finding would also be in
line with the observed increase in asthma among American children over the
last few decades that seems to form a strikingly inverse relationship with
the exposure of American children to secondary smoke in the home and such
venues as fast-food restaurants and child care facilities.
Such a theory is of course anathema to the standard view that *any* exposure is "bad" for children and others, but it's possible that it could prove correct if properly studied.
Simler et al. raise an interesting possibility of the prognostic
value of plasma VEGF in interstitial lung disease. Meyer et al. in a
previous study [1] did not find any difference
in serum VEGF165 levels in patients with diffuse parenchymal lung disease.
It would have been interesting to know the BALF VEGF levels of these
patients as Meyer et al.and Koyama et al. [2] have shown reduced BAL fluid VEGF...
Simler et al. raise an interesting possibility of the prognostic
value of plasma VEGF in interstitial lung disease. Meyer et al. in a
previous study [1] did not find any difference
in serum VEGF165 levels in patients with diffuse parenchymal lung disease.
It would have been interesting to know the BALF VEGF levels of these
patients as Meyer et al.and Koyama et al. [2] have shown reduced BAL fluid VEGF levels in interstitial
lung disease. This might simply reflect damage to the alveolar epithelium
(a known major source) in this disease or indeed VEGF may have an
important role in the pathogenesis of interstitial disease. Interestingly,
VEGF receptor blockade has been shown to lead to an induction of apoptosis
and an emphysema-like histological appearance in rats but with no evidence
of fibrosis or inflammatory cells [3].
In addition, it is interesting to speculate the cellular source of
the elevated plasma VEGF in the more fibrotic patients? Could this
represent alveolar-capillary membrane damage with leakage of intra-
alveolar VEGF which is known to be compartmentalised [4] and hence lower BALF levels as described in the previous
studies? Or does it represent an inflammatory cell source of systemic VEGF
correlating with an inflammatory response that is here associated with a
poorer outcome? Or is there some other mechanism.
Finally, Koyama et al. have shown smokers also have reduced BAL VEGF
levels and this may be of relevance (if intrapulmonary VEGF is postuated
as having a role in this disease) given the DIP group had all smoked
compared to 50% of the NSIP, and only 20% of the controls.
References
(1) J Lab Clin Med 2000;135:332-8.
(2) Am J Resp Crit Care Med 2002;166: 382-5.
(3) Kasahara et al. J Clin Invest. 2000
Dec;106(11):1311-9.
We read with interest the recent article from Simler et al in Thorax
investigating angiogenic cytokines in patients with idiopathic
interstitial pneumonia [1]. We were surprised by their reported high
levels of plasma VEGF in the normal control group. Previously, several
other groups, including the manufacturers of the ELISA (R&D systems)
quote normal plasma VEGF levels in the range of 36-76 pg/...
We read with interest the recent article from Simler et al in Thorax
investigating angiogenic cytokines in patients with idiopathic
interstitial pneumonia [1]. We were surprised by their reported high
levels of plasma VEGF in the normal control group. Previously, several
other groups, including the manufacturers of the ELISA (R&D systems)
quote normal plasma VEGF levels in the range of 36-76 pg/ml[2, 3]. Indeed
one of the authors of the paper previously quoted normal VEGF levels as 76
pg/ml using a matched pair ELISA [4]. It is clear, therefore that the
levels quoted of 648 pg/ml for normal controls are nearly 10 fold higher
than reported previously.
One possible explanation for this finding is the low centrifugal
force used for preparation of plasma (300g for 12 minutes). The
manufacturer of the ELISA recommends 1000 g for 15 minutes as a way to
reduce platelet contamination of plasma. Platelet secretion of VEGF is the
reason for elevated serum levels of VEGF when compared to plasma and might
therefore explain the extraordinarily high levels of VEGF found in these
normal subjects [4]. Interestingly 14/49 (28.5%) of patients included were
on immunosuppressant drugs that potentially reduce platelet count. This
offers an alternative explanation as to why there was no difference
between normal patients and those with pulmonary fibrosis in contrast to
earlier reports in connective tissue disease related pulmonary fibrosis
from 1998 [5].
Although the plasma levels of VEGF correlated with fibrosis based
upon CT score it is difficult to fully appreciate the relevance of this
finding, without knowing the concentration of VEGF actually within the
lung compartment. This is because in the normal individual, epithelial
lining fluid levels of VEGF at 9-11 ng/ml are several orders of magnitude
greater than that found in the circulation [6, 7]. Furthermore, previous
investigators have reported reduced levels of alveolar VEGF in patients
with IPF [8]. Low BALF VEGF levels are also seen in patients with acute
lung injury, sarcoidosis, emphysema and the transplanted lung. Thus it
would appear that a reduced alveolar level of VEGF is a common feature of
diseases associated with alveolar epithelial damage. Indeed, in ARDS,
alveolar levels of VEGF are lowest in those with the worst lung injury.
This is probably a result of reduced epithelial cell secretion of VEGF and
increased expression of its soluble receptor sVEGFR-1, which acts as a
natural inhibitor to the bioactivity of VEGF. The trophic role of VEGF
within the lung is supported by the fact that VEGF acts as a proliferative
factor for fetal pulmonary epithelial cells (9) and because lung-targeted
VEGF inactivation leads to an emphysema phenotype in mice[10]. These
studies suggest that reduced alveolar levels of VEGF may inhibit
epithelial repair in a wide variety of lung diseases.
To summarize, we have some concerns about the
validity/reproducibility of the VEGF levels reported in this study.
Furthermore, based upon the available evidence, we believe it is
inappropriate to suggest that antagonizing VEGF would be a successful
potential therapy for patients with pulmonary fibrosis. To the contrary we
believe this would hasten epithelial cell apoptosis and promote alveolar
septal cell loss with resultant honeycombing and functional deterioration.
References
(1) Simler, N. R., P. E. Brenchley, A. W. Horrocks, S. M. Greaves, P.
S. Hasleton, and J. J. Egan. 2004. Angiogenic cytokines in patients with
idiopathic interstitial pneumonia. Thorax 59(7):581-585.
(2) Thickett, D. R., L. Armstrong, S. J. Christie, and A. B. Millar. 2001.
Vascular endothelial growth factor may contribute to increased vascular
permeability in acute respiratory distress syndrome. Am J Respir Crit Care
Med 164(9):1601-5.
(3) Himeno, W. 2001. Angiogenic growth factors in patients with cyanotic
congenital heart disease and in normal children. Kurume Med J 48(2):111-6.
(4) Webb, N. J., M. J. Bottomley, C. J. Watson, and P. E. Brenchley. 1998.
Vascular endothelial growth factor (VEGF) is released from platelets
during blood clotting: implications for measurement of circulating VEGF
levels in clinical disease. Clin Sci (Lond) 94(4):395-404.
(5) Kikuchi, K., M. Kubo, T. Kadono, N. Yazawa, H. Ihn, and K. Tamaki.
1998. Serum concentrations of vascular endothelial growth factor in
collagen diseases. Br J Dermatol 139(6):1049-51.
(6) Kaner, R. J., and R. G. Crystal. 2001. Compartmentalization of vascular
endothelial growth factor to the epithelial surface of the human lung. Mol
Med 7(4):240-6.
(7) Thickett, D. R., L. Armstrong, and A. B. Millar. 2002. A role for
vascular endothelial growth factor in acute and resolving lung injury. Am
J Respir Crit Care Med 166(10):1332-7.
(8) Koyama, S., E. Sato, M. Haniuda, H. Numanami, S. Nagai, and T. Izumi.
2002. Decreased level of vascular endothelial growth factor in
bronchoalveolar lavage fluid of normal smokers and patients with pulmonary
fibrosis. Am J Respir Crit Care Med 166(3):382-5.
(9) Brown, K. R., K. M. England, K. L. Goss, J. M. Snyder, and M. J.
Acarregui. 2001. VEGF induces airway epithelial cell proliferation in
human fetal lung in vitro. Am J Physiol Lung Cell Mol Physiol 281(4):L1001
-10.
(10) Tang, K., H. B. Rossiter, P. D. Wagner, and E. C. Breen. 2004. Lung-
targeted VEGF inactivation leads to an emphysema phenotype in mice. J Appl
Physiol.
I read the article by Janssen-Heijnen et al with interest [1]. There are
large differences in the reported survival of patients presenting with
lung cancer. Those presenting in the United states and Spain are reported
to have up to twice the chance of surviving five years when compared to
those presenting in the United Kingdom [2-4]. This may be due to differences
in disease, differences in performanc...
I read the article by Janssen-Heijnen et al with interest [1]. There are
large differences in the reported survival of patients presenting with
lung cancer. Those presenting in the United states and Spain are reported
to have up to twice the chance of surviving five years when compared to
those presenting in the United Kingdom [2-4]. This may be due to differences
in disease, differences in performance status or co-morbidity, differences
in treatment, or differences in recording, but it demands a critical
analysis of current practice. This study informs the discussion suggesting
that age and co-morbidity do not significantly alter prognosis but it
includes only those with a histologically confirmed non small cell lung
cancer. It seems likely that age and significant co-morbidity might reduce
the chances of getting histology. Do the authors know the rate of
histological confirmation in the population described and, if so, is it
influenced by age or co-morbidity? It is hard to base any conclusion on
the role of these factors in outcomes for the whole population on those
with confirmed histology without first quantifying age and co-morbidity in
those without histological confirmation.
References
(1) Janssen-Heijnen MLG. Effect of comorbidity on the treatment and prognosis of elderly patients with non-small cell lung cancer. Thorax 2004; 59: 602-607
(2) Berrino F, Capocaccia R, Estève T, et al. Survival of cancer
patients in Europe- the EUROCARE 2 Study. (IARC Scientific Publications
No. 151) International Agency for Research on Cancer (Lyon: 1999)
(3) Sikora K. Cancer survival in Britain. BMJ 1999; 319: 461-2
(4) American Cancer Society, Inc. Cancer Facts and Figures 2002.
Surveillance Research (2002)
The paper by Fitzgerald et al [1] raises important questions as to
what patients should be advised to do during periods of less well
controlled asthma. In other words, the commonly advised practice of
doubling the inhaled corticosteroid dose is not backed up by a wealth of
evidence, in turn resulting in an embarassing paucity of clear guidance
for patients.
The paper by Fitzgerald et al [1] raises important questions as to
what patients should be advised to do during periods of less well
controlled asthma. In other words, the commonly advised practice of
doubling the inhaled corticosteroid dose is not backed up by a wealth of
evidence, in turn resulting in an embarassing paucity of clear guidance
for patients.
It has become apparent in the management of chronic asthma, that
additional 2nd line controller therapy is generally more advantageous than
doubling the dose of inhaled corticosteroid. [2] In the treatment and
prevention of asthma exacerbations, a similar pharmacotherapeutic
rationale may also become the norm and be incorporated into individualised
asthma action plans. In other words, adding further 2nd line therapy for a
short period of time during deteriorating asthma control - while
maintaining the same inhaled corticosteroid dose - may be appropriate.
For example, the hybrid actions of leukotriene antagonism would
attenuate airway hyperresponsiveness and further dilate the airways, while
add on long acting ß2-agonist would maximally bronchodilate the airways
with the provision of an “airway stabilising effect”.[3] Indeed, Aalbers
et al demonstrated that the use of budesonide and eformoterol in
combination, with dose adjustment according to patients symptoms,
conferred benefit in terms of exacerbations, lung function and reliever
use. Perhaps in asthmatics already using an inhaled corticosteroid plus
long acting ß2-agonist, the addition of montelukast may be worthwhile, as
“triple therapy” has been shown to confer further benefit in terms of
surrogate inflammatory biomarkers and attenuating airway
hyperresponsiveness.[5]
In conclusion, studies evaluating the effects of “short bursts” of
leukotriene receptor antagonists or add-on long acting ß2-agonists
compared to doubling the inhaled corticosteroid dose during deteriorating
asthma control are urgently required.
Graeme P Currie
Daniel K C Lee †
Department of Respiratory Medicine, Aberdeen Royal Infirmary,
Foresterhill, Aberdeen AB25 2ZN, Scotland, United Kingdom
† Department of Respiratory Medicine, Ipswich Hospital, Heath Road,
Ipswich IP4 5PD, Suffolk, England, United Kingdom
References
1. FitzGerald JM, Becker A, Sears MR, et al. Doubling the dose of
budesonide versus maintenance treatment in asthma exacerbations. Thorax
2004;59:550–6
2. British Guideline on the Management of Asthma. Thorax 2003; 58
(Suppl 1):1-83.
3. Currie GP, Jackson CM, Ogston SA, Lipworth BJ. Airway-stabilising
effect of long-acting ß2-agonists as add-on therapy to inhaled
corticosteroids. QJM 2003;96: 435-40.
4. Aalbers R, Backer V, Kava TTK, et al. Adjustable maintenance
dosing with budesonide/formoterol compared with fixed-dose
salmeterol/fluticasone in moderate to severe asthma. Curr Med Research and
Opinion 2004; 20: 225-40.
5. Currie GP, Lee DKC, Haggart K, et al. Effects of montelukast on
surrogate inflammatory markers in corticosteroid treated patients with
asthma. Am J Respir Crit Care Med 2003; 167:1232-8.
Dr McFadden is putting forward an interpretation of the small non-
significant decrease in asthma episode contacts seen amongst those with
moderate exposure to passive smoking. In our view this is unwise. The
effect could well be due simply to the play of chance. Further we have
shown that non-clinical factors have a dominant influence on visit
frequency and that the frequency of contacts is a poor measu...
Dr McFadden is putting forward an interpretation of the small non-
significant decrease in asthma episode contacts seen amongst those with
moderate exposure to passive smoking. In our view this is unwise. The
effect could well be due simply to the play of chance. Further we have
shown that non-clinical factors have a dominant influence on visit
frequency and that the frequency of contacts is a poor measure of asthma
morbidity. In consequence our study gives no support at all to the idea
that moderate levels of tobacco smoke suppress asthma. We agree that
further research is needed both into the consequences of passive smoking
and also into the determinants of health care utilisation among children
with asthma.
Iain K Crombie, Professor
Linda Irvine, Research Fellow
Department of Epidemiology and Public Health University of Dundee, Dundee DD1 9SY, UK
We agree with Anderson that age and significant co-morbidity might
reduce the chances of getting histology. In the population of our study
the proportion of patients with a clinical diagnosis was 7%. This
proportion varied from almost 3% for patients younger than 65 to 8% for
those aged 65-79 and 22% for those aged 80 or older. In patients younger
than 65 or in those aged 80 or older this proportio...
We agree with Anderson that age and significant co-morbidity might
reduce the chances of getting histology. In the population of our study
the proportion of patients with a clinical diagnosis was 7%. This
proportion varied from almost 3% for patients younger than 65 to 8% for
those aged 65-79 and 22% for those aged 80 or older. In patients younger
than 65 or in those aged 80 or older this proportion did not decrease with
significant co-morbidity. In patients aged 65-79, however, the proportion
of patients with a clinical diagnosis increased from 5% for patients
without co-morbidity to 7% for those with one co-morbid condition, and to
10% for those with at least two co-morbid conditions.
In our study we only included patients with non-small cell lung
cancer. In those with localized disease 3-year survival significantly
decreased with age.
However, the differences in lung cancer survival within Europe cannot
entirely be explained by differences in age distribution. In the EUROCARE
study [1,2] survival rates were standardised to a common age structure.
Furthermore, the rates were adjusted for the age-specific background
mortality to keep to a minimum the effect of age and competing causes of
death on the overall comparisons. In the United Kingdom the proportion of
microscopically verified lung cancer cases was rather low (about 60%) [3].
Therefore, differences in access to diagnostic care might be responsible
for variation in lung cancer survival, rather than differences in age
distribution or the prevalence of co-morbidity. Registration procedures
might also play a role, because we do not dispose on notifications from
death certificates. This problem becomes larger when access to care is
less optimal. The number of chest physicians in the Netherlands was 2 to 3
times as high as in the UK.
References
(1) Janssen-Heijnen ML, Gatta G, Forman D, et al. Variation in survival
of patients with lung cancer in Europe, 1985-1989. EUROCARE Working Group.
Eur J Cancer 1998;34:2191-6.
(2) Sant M, Aareleid T, Berrino F, et al. EUROCARE-3: survival of
cancer patients diagnosed 1990-94-results and commentary. Ann Oncol
2003;14 Suppl 5:V61-V118.
(3) Capocaccia R, Gatta G, Roazzi P, et al. The EUROCARE-3 database:
methodology of data collection, standardisation, quality control and
statistical analysis. Ann Oncol 2003;14 Suppl 5:V14-V27.
We read with interest the recent article by Niimi et al reporting low
levels of exhaled breath condensate (EBC) pH in patients with chronic
cough [1]. We and others have described low EBC pH in association with
airway inflammation in allergic asthma, cystic fibrosis and
COPD [2][3][4]. In these studies there is a relatively close association
between inflammation and low pH which is shown by the furth...
We read with interest the recent article by Niimi et al reporting low
levels of exhaled breath condensate (EBC) pH in patients with chronic
cough [1]. We and others have described low EBC pH in association with
airway inflammation in allergic asthma, cystic fibrosis and
COPD [2][3][4]. In these studies there is a relatively close association
between inflammation and low pH which is shown by the further fall in pH
during exacerbations [2]. However in non-asthmatic chronic cough whilst
there is a low grade inflammation present in some subjects this is much
less than would be required to invoke inflammation as the major cause of
airway acidification.
It is unclear from the description of the assessment protocol how
patients were allotted their individual diagnostic categories. A positive
methacholine challenge test is not infrequently found in patients with
reflux [5] and, even in classical asthma, reflux is a common phenomenon [6].
We would suggest that there has been a significant under diagnosis of
reflux disease in this cohort because of the lack of a structured history,
the non uniform application of investigations and the failure to perform
full oesophageal assessment, particularly manometry. We have shown that
when oesophageal manometry is not performed a significant number of
patients with reflux cough will be missed [7]. Proton pump inhibitors at
conventional doses only temporarily increase the pH of gastric reflux and
do not prevent reflux per se and, unsurprisingly, only improve symptoms in
a proportion of patients with reflux cough. A failure of cough to improve
with proton pump inhibitors does not therefore adequately rule out reflux
cough.
The simplest explanation for the low airway pH observed by Niimi et
al would be that a large proportion of the subjects have laryngopharyngeal
reflux. This would also explain the otherwise surprising finding of
similar EBC pH across the authors’ diagnostic categories.
References
(1) Niimi A, Nguyen LT, Usmani O, Mann B, Chung KF. Reduced pH and
chloride levels in exhaled breath condensate of patients with chronic
cough. Thorax 2004; 59: 608-612.
(2) Ojoo JC, Mulrennan S, Kastelik JA, Morice AH, Redington AE.
Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma
and in cystic fibrosis. Thorax 2004; (In Press)
(3) Kostikas K, Papatheodorou G, Ganas K, Psathakis K, Panagou P,
Loukides S. pH in expired breath condensate of patients with inflammatory
airway diseases. Am J Respir Crit Care Med. 2002; 165: 1364-1370.
(4) Tate S, MacGregor G, Davis M, Innes JA, Greening AP. Airways in
cystic fibrosis are acidified: detection by exhaled breath condensate.
Thorax 2002; 57: 926-929.
(5) Bagnato GF, Gulli S, Giacobbe O, De Pasquale R, Purello DF.
Bronchial hyperresponsiveness in subjects with gastroesophageal reflux.
Respiration 2000; 67: 507-509.
(6) Vincent D, A.M., Leport J, et al. Gastro-oesophageal reflux
prevalence and relationship with bronchial reactivity in asthma. Eur
Respir J 1997; 10: 2255-2259.
(7) Kastelik JA, Redington AE, Aziz I, et al. Abnormal oesophageal
motility in patients with chronic cough. Thorax 2003; 58: 699-702.
in a recent issue of the Journal, Gan WQ et al. published a systematic review
and meta-analysis of 14 reports which confirmed the strong association between
COPD and biological markers of systemic inflammation [1]. In 6 reports, COPD was
diagnosed according to the presence of a FEV1/FVC ratio lower than 0.7. However,
in the remaining 8 studies this measure was not available, and authors assumed
as affecte...
in a recent issue of the Journal, Gan WQ et al. published a systematic review
and meta-analysis of 14 reports which confirmed the strong association between
COPD and biological markers of systemic inflammation [1]. In 6 reports, COPD was
diagnosed according to the presence of a FEV1/FVC ratio lower than 0.7. However,
in the remaining 8 studies this measure was not available, and authors assumed
as affected by COPD all participants in the lowest quartile of FEV1% and, for
one study [2], of FVC%. In these cases, the corresponding highest quartile group
served as control. Since a COPD diagnosis based on the decreased FEV1/FVC ratio
was lacking in 8 reports, the possibility cannot be excluded that a certain
number of patients included in the meta-analysis did not have COPD, but a
restrictive ventilatory defect. This could be particularly true for participants
to the study by Engstrom [2], who were characterized only by a low FVC.
According to the current GOLD guidelines [3], only a FEV1/FVC ratio lower
than 0.7 indicates airflow obstruction, thus allowing a COPD diagnosis. Indeed,
in the absence of particular pulmonary diseases, many subjects show an
homogenous decrease of all dynamic lung volumes (FEV1, FVC, PEF), without any
alteration of FEV1/FVC ratio, and are thus considered as having “impaired lung
function”. The occurrence of respiratory symptoms [4], the systemic inflammation
[2] and the increased risk of cardiovascular disease [5] are the only features
that restrictive subjects share with COPD. In fact, whereas COPD is
characterized by a decrease in BMI and blood lipids, restrictive subjects often
have abdominal obesity, insulin-resistance and other metabolic risk factors [6].
Although we believe that most of the included patients were really affected
by COPD, the possible inclusion of restrictive patients may have altered the
statistical conclusions of the meta-analysis. In addition, the choice of
selecting patients in the lowest quartile of FEV1 or FVC hindered the authors
from confirming the absence of inflammation in mild COPD (GOLD stage I and II),
a finding previously reported by the same group in a study not included in this
meta-analysis [7].
Because the two groups of restrictive and COPD patients have different
features, the generic term ”impaired lung function” should not be used. Future
studies about the role of inflammation and other cardiovascular risk conditions
in respiratory patients, as well as those investigating the outcome of these
subjects, should clearly distinguish restrictive from COPD patients.
References
(1) Gan WQ, Man SFP, Senthilselvan A, Sin DD. Association between chronic
obstructive pulmonary disease and systemic inflammation: a systematic review and
a meta-analysis. Thorax 2004; 59: 574-580
(2) Engstrom G, Lind P, Hedblad B et
al. Lung function and cardiovascular risk. Relationship with
inflammatory-sensitive plasma protein. Circulation 2002; 106: 2555-2560
(3)
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Publication no.
2701. Bethesda, National Institute for Health, 2001 (2004 update).
(4) Mannino
DM, Ford ES, Redd SC. Obstructive and restrictive lung disease and functional
limitation: data from the Third national Health and Nutrition Examination.
Journal of Internal Medicine 2003; 254: 540-547
(5) Hole DJ, Watt GC, Davey-Smith
G et al. Impaired lung function and mortality risk in men and women: findings
from the Renfrew and Paisley prospective population study. BMJ 1996; 313:
711-715
(6) Lawlor DA, Ebrahim S, Davey-Smith G. Associations of measures of lung
function with insulin resistance and type 2 diabetes: findings from the British
Women’s heart and health Study. Diabetologia 2004; 47: 195-203
(7) Sin DD, Man SFP. Why are patients with obstructive pulmonary disease at increased risk of
cardiovascular diseases? The potential role of systemic inflammation in Chronic
Obstructive Pulmonary Disease. Circulation 2003; 107: 1514-1519
The Code of Practice (Control and prevention of tuberculosis in the United Kingdom)[1] provides us with evidence based gold standards for best practice in this field. The exception is of promoting routine immigrant screening and the context within which it is recommended.
I welcome a general health check for immigrants on arrival, but does routine screening for tuberculosis needs to be part of it?...
If the abstract indicates correctly that children of totally non-smoking parents were not included in the study, I see that as a significant weakness.
The study found, as might be expected by many, an increase in contacts for asthma episodes among children most heavily exposed to environmental tobacco smoke (ETS).
However, it also found a non-significant but noteworthy decrease in asthma epi...
Dear Editor
Simler et al. raise an interesting possibility of the prognostic value of plasma VEGF in interstitial lung disease. Meyer et al. in a previous study [1] did not find any difference in serum VEGF165 levels in patients with diffuse parenchymal lung disease. It would have been interesting to know the BALF VEGF levels of these patients as Meyer et al.and Koyama et al. [2] have shown reduced BAL fluid VEGF...
Dear Editor
We read with interest the recent article from Simler et al in Thorax investigating angiogenic cytokines in patients with idiopathic interstitial pneumonia [1]. We were surprised by their reported high levels of plasma VEGF in the normal control group. Previously, several other groups, including the manufacturers of the ELISA (R&D systems) quote normal plasma VEGF levels in the range of 36-76 pg/...
Dear Editor
I read the article by Janssen-Heijnen et al with interest [1]. There are large differences in the reported survival of patients presenting with lung cancer. Those presenting in the United states and Spain are reported to have up to twice the chance of surviving five years when compared to those presenting in the United Kingdom [2-4]. This may be due to differences in disease, differences in performanc...
Dear Editor,
The paper by Fitzgerald et al [1] raises important questions as to what patients should be advised to do during periods of less well controlled asthma. In other words, the commonly advised practice of doubling the inhaled corticosteroid dose is not backed up by a wealth of evidence, in turn resulting in an embarassing paucity of clear guidance for patients.
It has become apparent in the...
Dr McFadden is putting forward an interpretation of the small non- significant decrease in asthma episode contacts seen amongst those with moderate exposure to passive smoking. In our view this is unwise. The effect could well be due simply to the play of chance. Further we have shown that non-clinical factors have a dominant influence on visit frequency and that the frequency of contacts is a poor measu...
Dear Editor
We agree with Anderson that age and significant co-morbidity might reduce the chances of getting histology. In the population of our study the proportion of patients with a clinical diagnosis was 7%. This proportion varied from almost 3% for patients younger than 65 to 8% for those aged 65-79 and 22% for those aged 80 or older. In patients younger than 65 or in those aged 80 or older this proportio...
Dear Editor
We read with interest the recent article by Niimi et al reporting low levels of exhaled breath condensate (EBC) pH in patients with chronic cough [1]. We and others have described low EBC pH in association with airway inflammation in allergic asthma, cystic fibrosis and COPD [2][3][4]. In these studies there is a relatively close association between inflammation and low pH which is shown by the furth...
Dear Editor
in a recent issue of the Journal, Gan WQ et al. published a systematic review and meta-analysis of 14 reports which confirmed the strong association between COPD and biological markers of systemic inflammation [1]. In 6 reports, COPD was diagnosed according to the presence of a FEV1/FVC ratio lower than 0.7. However, in the remaining 8 studies this measure was not available, and authors assumed as affecte...
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