Sherriff and colleagues report an apparent association between
mothers’ self-reported frequency of use of assorted household ‘chemicals’
during pregnancy and ‘persistent wheeze’ in their offspring. Since their
paper suggests this may help explain recent rises in asthma, the
robustness of the data and other explanations for the observed statistical
association need careful consideration.
Sherriff and colleagues report an apparent association between
mothers’ self-reported frequency of use of assorted household ‘chemicals’
during pregnancy and ‘persistent wheeze’ in their offspring. Since their
paper suggests this may help explain recent rises in asthma, the
robustness of the data and other explanations for the observed statistical
association need careful consideration.
We see several concerns, including both exposure and outcome
measures, lack of a plausible biological mechanism for the suggested in
utero effect, and the possibility of both recall and selection bias.
The definition of persistent wheeze is weak, and far removed from
criteria currently considered to define asthma . Offspring are
categorised as having ‘persistent wheeze’ if mothers’ responses indicate
one instance of wheezing in three consecutive 12 month periods.
It is curious that the association appears using frequency of use
scores which treat 11 disparate product types as equal, irrespective of
composition, and remains when each in turn was removed from the analysis.
Some product types have nothing at all in common: we can see no
significant ingredient that is common even to the majority, nor any likely
shared toxic mode of action. Contrary to the authors’ suggestion
formaldehyde is little used in the products surveyed.
Self-reported frequency of use is a very poor measure of exposure:
variations in quantity of product used, duration of use and routes of
exposure (inhalation, dermal, ingestion etc) can yield scores which run
contrary to actual exposure.
We see little justification for aggregating disparate product
exposures as ‘Total Chemical Burden’ by analogy with particulate air
pollution: the action of particulates is plausibly associated more with
size, geometry and/or absorptive capacity than with chemical composition.
This concept cannot simply be extrapolated to vapours or non-particulates,
and the term itself unfortunately suggests some absorbed, retained load:
‘sum of reported product use frequencies’ would have been more
appropriate.
We are not aware of any substantiated toxicological effect that is
shared by all chemicals irrespective of composition, especially given that
the notion of a ‘chemical’ is essentially subjective. All matter,
natural or synthetic, is composed of atoms and molecules. How do the
products considered differ from the many household chemicals not
considered, and chemicals that make up the natural environment to which
people are continuously exposed?
It seems unlikely that the association is driven by one product type
since it remained when each in turn was removed from the analysis.
Further, previous analyses of these questionnaires for two specific types
(aerosols and air fresheners) found no association with wheeze . Per
capita consumption of cleaning products in different European countries
also shows no correlation with the patterns of asthma .
Other than chance, how else might the observed association have
arisen? Apart from confounding by other chemicals in the built or
natural environment, certain mothers may have over-reported both chemical
use and wheezing symptoms. While ‘chemicals’ are heterogeneous in terms
of composition and toxicology, the term perhaps has some homogeneous
psychological significance for certain people. We understand the question
about frequency of use was headed “Chemicals …… in your environment”.
The authors acknowledge some selection bias: “those excluded from the
analysis due to lack of chemical use data were more likely to have wheezed
at all ages than those included, and those excluded from the analysis due
to missing symptom data had, on average, higher TCB scores than those in
the analysis”. This is potentially significant since the numbers
excluded from the study for missing data (50%) are large.
Scrutinising household products for any possible role in the rise in
asthma is important but, to be meaningful, exposures must be properly
defined.
--------------------------------
References
1.Sherriff A, Farrow A, Golding A, the ALSPAC Study Team, Henderson
J. Frequent use of chemical household products is associated with
persistent wheezing in pre-school age children. Thorax 2005; 60: 45-49
2.Asher MI and Weiland SK on behalf of the ISAAC Steering Committee
(1998) The International Study of Asthma and Allergies in Childhood
(ISAAC). Clin Exp Allergy 28, Suppl 5, 52-66.
3. Farrow A, Taylor H, Northstone K, Golding J. Symptoms of Mothers
and Infants Related to Total Volatile Organic Compounds in Household
Products. Arch Environ Health. 2003 Oct;58(10):633-41.
4. Pickup J. Trends in home and consumer hygiene. In 'Are we too
clean? - a question of immunity balance'. RIPH Symposium Report. Published
as a supplement to Health & Hygiene. London: Royal Institute of Public
Health 2003: 6-7.
I would like to thank Dr M Ghrew for his interest in my letter. I
agree that a restrictive strategy of red-cell transfusion, in which
haemoglobin is maintained at 7–9 g per deciliter, is at least as
effective as and possibly superior to a liberal transfusion strategy, in
which haemoglobin is maintained at 10–12 g per deciliter. Hebert and his
colleagues in the Canadian Critical Care Trials Group reporte...
I would like to thank Dr M Ghrew for his interest in my letter. I
agree that a restrictive strategy of red-cell transfusion, in which
haemoglobin is maintained at 7–9 g per deciliter, is at least as
effective as and possibly superior to a liberal transfusion strategy, in
which haemoglobin is maintained at 10–12 g per deciliter. Hebert and his
colleagues in the Canadian Critical Care Trials Group reported that
mortality rate was significantly lower with the restrictive transfusion
strategy among patients with less severe illness (those with an APACHE
score <or = 20) and among patients who were <55 years of age, but
not among patients with clinically significant cardiac disease. The in-
hospital mortality rate was significantly lower in the restrictive
strategy group, although the 30-day mortality was similar.[1] Therefore,
further studies are required to decide if the restrictive strategy of red-
cell transfusion is still beneficial to the subgroups of patients with
cardiac disease [2], COPD [3], ARDS, more severe illness as well as older
patients. Unfortunately, O2 delivery (DO2) and O2 uptake (VO2) were not
calculated or measured in this trial, making it difficult to evaluate the
usefulness of the restrictive transfusion strategy in critically-ill
patients with hypoxemia and / or low cardiac output. A clinical setting in
which the arterial O2 content, O2 delivery and tissue oxygenation are all
reduced. I believe that many intensivists may be unwilling to use a
haemoglobin level of <7 g per deciliter as a threshold for transfusion
of red blood cells to critically-ill patients with ARDS or cardiogenic
shock, particularly if there is evidence of tissue hypoxia. Several
randomized controlled trials in which hemodynamic therapy (including
inotropic and vasopressor agents, volume expansion, packed RBCs and
vasodilators) aimed at achieving supranormal values of cardiac output (QT)
and O2 delivery failed to improve survival and may actually have been
detrimental [4, 5, 6]. On the contrary, I hypothesized that maintaining
adequate tissue oxygenation- by supranormal cardiac output – may enable
intensivists to use more protective ventilatory strategy (lower levels of
PEEP, FIO2 and I:E ratio) and to accept lower values of arterial O2
saturation (SaO2) aiming at minimizing the risks of pulmonary O2 toxicity,
barotrauma and lung injury that may be difficult to identify in the
clinical setting of ARDS. According to this hypothesis, SaO2 may be
allowed to decrease below 90 % (permissive hypoxemia) as long as no
evidence of tissue hypoxia (such as increased O2 extraction ratio and
elevated arterial blood lactate) is present.
DO2 = 1.34 x SaO2 x Hb x QT. According to this equation, I suggested that
O2 delivery could be maintained within normal or near-normal (not
supranormal) levels by augmenting cardiac output, if SaO2 is relatively
low. It should be noted that supranormal cardiac output is not a target in
itself, but is considered a compensatory mechanism to maintain adequate
tissue perfusion if 'permissive hypoxemia' has resulted in tissue hypoxia.
Finally, this tissue oxygenation-oriented approach remains hypothetical
waiting for further outcome studies to evaluate its impact on mortality of
patients with ARDS.
References
1. Hébert PC, Wells G, Blajchman MA, et al. A multicenter,
randomized, controlled clinical trial of transfusion requirements in
critical care. N Engl J Med 1999; 340:409-417.
2. Carson JL, Duff A, Poses RM, et al. Effect of anaemia and
cardiovascular disease on surgical mortality and morbidity. Lancet 1996;
348: 1055-1060.
3. Schönhofer B, Wenzel M, Geibel M, Köhler D. Blood transfusion and
lung function in chronically anemic patients with severe chronic
obstructive pulmonary disease. Crit Care Med 1998; 26:1824-1828.
4. Palazzo M, Hinds C, Watson D. Elevation of systemic oxygen
delivery in the treatment of critically ill patients. N Engl J Med 1994;
330:1717-1722.
5. Gattinoni L, Brazzi L, Pelosi P, et al. A trial of goal-oriented
hemodynamic therapy in critically ill patients. N Engl J Med 1995;
333:1025-1032.
6. Heyland DK, Cook DJ, King D, Kernerman P, Brun-Buisson C.
Maximizing oxygen delivery in critically ill patients: a methodologic
appraisal of the evidence. Crit Care Med 1996; 24:517-524
I was very interested to read of your research on the effect of
tomatoes, carrots, and leafy vegetables in reducing asthma.
A large-scale experiment to test these theories in practice, would be
to obtain the statistics for the population of Italy, where tomatoes
(especially) are an integral part of the national diet, and basil (a green
leafy vegetable) is nearly always included in tomato dis...
I was very interested to read of your research on the effect of
tomatoes, carrots, and leafy vegetables in reducing asthma.
A large-scale experiment to test these theories in practice, would be
to obtain the statistics for the population of Italy, where tomatoes
(especially) are an integral part of the national diet, and basil (a green
leafy vegetable) is nearly always included in tomato dishes.
This could then also be compared with other countries, such as
Switzerland & Austria (countries near to or neighbouring Italy), but
where tomatoes do not play such a prominent role in the diet.
And in case factors other than diet are influencing the outcome, then
several other countries could also be used for comparison eg, Finland,
Scotland, Kenya, South Africa, Paraguay, Fiji, and Australia.
The evidenced based-review by Gibson and Powell [1] highlights the
benefit of written action plans when incorporated into the care of
asthmatic patients. It is important to note that in most of their
randomised controlled trials, patients were instructed to at least double
the inhaled corticosteroid dose during deteriorating asthma control. A
study in the Lancet has however provided little evidence tha...
The evidenced based-review by Gibson and Powell [1] highlights the
benefit of written action plans when incorporated into the care of
asthmatic patients. It is important to note that in most of their
randomised controlled trials, patients were instructed to at least double
the inhaled corticosteroid dose during deteriorating asthma control. A
study in the Lancet has however provided little evidence that doubling the
inhaled corticosteroid dose per se confers direct benefit in terms of
reducing requirement of prednisolone.[2]
Recent data [3] 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. Indeed, this approach may well be best suited to asthmatics
with impaired lung function where the long acting ß2-agonist moiety would
maximally dilate the airways along with a concomitant “airway stabilising
effect” on exposure to a bronchoconstrictor stimulus.[4] Such patients are
likely to be on top of the dose-response curve for effects of inhaled
corticosteroids upon lung function,[5] suggesting that additional
bronchodilator therapy might be of greater value than doubling the
corticosteroid dose in less well controlled asthma.
Further studies are required to establish whether combined
corticosteroid/ long acting ß2-agonist inhalers - especially in patients
with impaired lung function - confer superiority compared to doubling the
inhaled corticosteroid dose in individualised asthma action plans.
References
1. Gibson PG, Powell H. Written action plans for asthma: an evidenced
-based review of the key components. Thorax 2004; 59: 94-9.
2. Harrison TW, Oborne J, Newton S, Tattersfield AE. Doubling the
dose of inhaled corticosteroid to prevent asthma exacerbations: randomised
controlled trial. Lancet 2004; 363: 271-5.
3. 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.
4. 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.
5. Holt S, Suder A, Weatherall M, et al. Dose-response relation of
inhaled fluticasone propionate in adolescents and adults with asthma: meta
-analysis. BMJ 2001; 323:253-6.
The editorial by Cullinan suggests that the relationship between
allergy, birth order and family size may not be completely explained by
the hygiene hypothesis.[1] A role for infection in protecting against
allergy has been under consideration for some years, although a credible
mechanism has not been identified. It has been suggested that reduced
exposure to infection in childhood shifted the balanc...
The editorial by Cullinan suggests that the relationship between
allergy, birth order and family size may not be completely explained by
the hygiene hypothesis.[1] A role for infection in protecting against
allergy has been under consideration for some years, although a credible
mechanism has not been identified. It has been suggested that reduced
exposure to infection in childhood shifted the balance between Th1 and Th2
cells in the adult immune system in favour of allergy associated Th2
cells.[2] This hypothesis failed to take account of the similarities in
epidemiology of Th1 type I diabetes and Th2 mediated allergic disease, and
while the role of infection was not challenged, the idea of Th2 dominated
adult immune system was rejected.3 Cullinan suggests that the effect of
birth order may be explained by differences in the intra uterine
environment or by some alternative, non-infective aetiology. If future
explanations are to have credibility, they require to take account of all
the available evidence. It is difficult to explain the higher prevalence
of Th1 and Th2 mediated disease in western societies and the more direct
evidence that exposure to a variety of infections is protective on the
basis of a non-infective cause.[2, 4-5]
The control of any immune response involves mechanisms which may
amplify or dampen the response. It seems likely that the presence of an
immune response to one infection may non-specifically down regulate other
immune responses, including allergic and autoimmune responses. The
mechanism of down regulation remains to be identified but a unifying
explanation which does not include infection seems implausible.
References
1. P Cullinan P. Childhood allergies, birth order and family size.
Thorax 2006; 61: 3-5.
2. Martinez F, Holt P. Role of microbial burdan in the aetiology of
allergy and asthma. Lancet 1999;354(Suppl 2):12-15.
3. Simpson C, Anderson W, Helms P, Taylor M, Watson L, Prescott G, et
al. Coincidence of immune-mediated diseases driven by Th1 and Th2 subsets
suggests a common aetiology. Clinical and experimental allergy
2002;2002:37-42.
4. Lynch N, Hagel I, Perez M, prisco MD, R RL, Alvarez N. Effect of
antihelminitic treatment on the allergic reactivity of children in a
tropical slum. Journal of Allergy and Clinical Immunology. 1993;92:404-
11.
5. Shirakawa T, Enomoto T, Shimazu S, JM. JH. The inverse association
between tuberculin responses and atopic disorder. Science 1997;275:77-9.
Imperatori et al. make a detailed comparison of lung cancer patients,
management and survival in two hospitals, one in England and one in Italy,
in an attempt to throw some light on the differences in published
survival between these nations[1]. In collecting similar data we have found
between 5 and 10% of the patients in our geographical catchment area have
not attended our hospital either as in-patie...
Imperatori et al. make a detailed comparison of lung cancer patients,
management and survival in two hospitals, one in England and one in Italy,
in an attempt to throw some light on the differences in published
survival between these nations[1]. In collecting similar data we have found
between 5 and 10% of the patients in our geographical catchment area have
not attended our hospital either as in-patients or as out-patients. These
patients were identified by our local cancer registry which uses
additional non-hospital sources to case find[2]. It is possible that
patients not referred or referred elsewhere are materially different from
those who are referred and that patterns of referral differ between the
two centres. Are the authors aware of any such patients in either centre
and could their inclusion alter the results?
References
1. Imperatori A, Harrison R, Leitch D, Rovera F, Lepore G, Dionigi G,
et al. Lung cancer in Teesside (UK) and Varese (Italy): a comparison of
management and survival. Thorax 2006(61):232-239.
2. Fitzpatrick D, Gavin A, Middleton R, Catney D. Cancer in Northern
Ireland 1993-2001. A Comprehensive report. Belfast: Northern Ireland
Cancer Registry.Queens University Belfast, 2004.
The correction by Zollner diverts the main issue we raised from
incorrectly citing our study as supporting the decrease/leveling off of
asthma and allergies in Germany when our study showed an increase, to a
reference order error [1]. Also, in Zollner's reply our data were again
misinterpreted, as we showed clearly for example that symptoms of asthma,
rhinitis, and rhino-conjunctivitis increased sig...
The correction by Zollner diverts the main issue we raised from
incorrectly citing our study as supporting the decrease/leveling off of
asthma and allergies in Germany when our study showed an increase, to a
reference order error [1]. Also, in Zollner's reply our data were again
misinterpreted, as we showed clearly for example that symptoms of asthma,
rhinitis, and rhino-conjunctivitis increased significantly among girls in
both age groups, while diagnosis of asthma and hey fever either did not
show the same trend or increased to a lesser extent (Tables 2,3) [2],
arguing against implicating a change in diagnostic behavior as a plausible
explanation for our findings [1,2]. We regret this continuing selective
approach to dealing with data unsupportive of the main claim of the
original article debated [3].
References
1- Maziak W, Keil U, Zollner I. Asthma and allergies in Germany.
Thorax 2006;61: 274.
2- Maziak W, Behrens T, Brasky TM, et al. Are asthma and allergies in
children and adolescents increasing? Results from ISAAC phase I and phase
III surveys in Münster, Germany. Allergy 2003;58:572–9.
3- Zollner IK, Weiland SK, Piechotowski I, et al. No increase in the
prevalence of asthma, allergies, and atopic sensitisation among children
in Germany: 1992–2001. Thorax 2005;60:545–8.
We read with great interest the article published in Thorax by
Dickinson et al (February 2006)(1) investigating the response of FEF50
following EVH (Eucapnic voluntary hyperventilation) or exercise challenges
in elite athletes as an adjunct to FEV1.0. We were however, slightly
confused as to the research design selected by the researchers. It appears
from the stated methods that the researchers used...
We read with great interest the article published in Thorax by
Dickinson et al (February 2006)(1) investigating the response of FEF50
following EVH (Eucapnic voluntary hyperventilation) or exercise challenges
in elite athletes as an adjunct to FEV1.0. We were however, slightly
confused as to the research design selected by the researchers. It appears
from the stated methods that the researchers used either an EVH challenge
or an exercise challenge for EIB diagnosis in their elite athletes. If
this is indeed the case then the underlying assumption is, that the
exercise challenge test selected by the authors is not different in its
impact upon pulmonary function than the EVH challenge test. As the authors
do not present this data in their paper then it is impossible for us to
know if the data from different challenge tests can be pooled to provide a
single sample. Indeed in a recent publication from the same authors (2)
their contention is that EVH and exercise tests do not give identical
results and that they should not be used synonymously.
In addition, we were concerned about the authors selection of the ATS
(3) guidelines as the basis for their use of 85% of maximal heart rate as
an exercise intensity for the exercise challenge test. The ATS guidelines
clearly indicate that cold dry air should be used during an exercise test
and that the test should “produce 4-6 minutes of exercise at near maximal
targets”(3). On the basis the subjects being tested were ‘current or
potential Olympic competitive standard’ we would have recommended using an
exercise challenge that stressed the elite athletes closer to their
maximal capabilities (4). It is well documented (5) that elite endurance
athletes can exhibit adaptations to their physiology that allow them to
exercise at higher intensities for longer durations and so it is possible
that these Olympic caliber athletes were not ventilating at a sufficient
level to exhibit symptoms of EIB during the exercise challenge(6). It has
been shown previously, in young asthmatic patients, that exercise load is
of paramount importance when exercise challenge testing for EIB (due to
the level of ventilation) (7). The difference between 85% and 95%
predicted maximal heart rate had a 60% difference in terms of EIB
diagnosis (7).
Therefore, as suggested in our communication to the editor of BJSM
and the authors of the current paper (8), the levels of ventilation
reached during each test would be extremely useful in comparing exercise
and EVH challenge tests. This would allow a further examination of the
data presented by the authors and the removal of the different tests as
extraneous variables when discussing the negative and positive diagnosis
of EIB based upon pulmonary function.
References
1 Dickinson, J.W., Whyte, G.P., McConnell, A.K., Nevill, A.M. and
Harries, M.G. Mid-expiratory flow versus FEV1 measurements in the
diagnosis of exercise induced asthma in elite athletes. Thorax 2006; 61: 111-114.
2 Dickinson, J.W., Whyte, G.P., McConnell, A.K., Harries, M.G. and
Rundell, K.W.
Screening elite winter athletes for exercise induced asthma: a comparison
of three challenge methods. Commentary. British Journal of Sports
Medicine., February 2006; 40: 179 - 182.
3 American Thoracic Society. Guidelines for Methacholine and
Exercise Challenge Testing – 1999.American Journal of Respiratory and
Critical Care Medicine 2000; 161: 309-329.
4 Mickleborough TD, Murray RL, Ionescu AA, Lindley MR. Fish oil
supplementation reduces severity of exercise-induced bronchoconstriction
in elite athletes. American Journal of Respiratory and Critical Care
Medicine 2003; 168: 1181-1189.
5 Jones, A.M. and Carter, H. The effect of endurance training on
parameters of aerobic fitness. Sports Medicine. 2000 June, Vol 29 Issue
(6) 373-386.
6 Anderson SD, Holzer K. Exercise-induced asthma: is it the right
diagnosis in elite athletes? J Allergy Clin Immunol 2000; 106: 419-428.
7 Carlsen, K.H., Engh, G. and Mork, M. Respiratory Medicine. 2000
Aug, Vol 94, Issue(8):pages750-5.
8 Lindley, M.R. and Mickleborough, T.D. Exercise challenge testing of
elite winter athletes for exercise-induced asthma. British Journal of
Sports Medicine. Published on 13 February 2006.
http://bjsm.bmjjournals.com/cgi/eletters/40/2/179.
Dear Editor,
Sherriff and colleagues report an apparent association between mothers’ self-reported frequency of use of assorted household ‘chemicals’ during pregnancy and ‘persistent wheeze’ in their offspring. Since their paper suggests this may help explain recent rises in asthma, the robustness of the data and other explanations for the observed statistical association need careful consideration.
We...
Dear Editor
I would like to thank Dr M Ghrew for his interest in my letter. I agree that a restrictive strategy of red-cell transfusion, in which haemoglobin is maintained at 7–9 g per deciliter, is at least as effective as and possibly superior to a liberal transfusion strategy, in which haemoglobin is maintained at 10–12 g per deciliter. Hebert and his colleagues in the Canadian Critical Care Trials Group reporte...
Dear Editor,
I was very interested to read of your research on the effect of tomatoes, carrots, and leafy vegetables in reducing asthma.
A large-scale experiment to test these theories in practice, would be to obtain the statistics for the population of Italy, where tomatoes (especially) are an integral part of the national diet, and basil (a green leafy vegetable) is nearly always included in tomato dis...
Dear Editor
The evidenced based-review by Gibson and Powell [1] highlights the benefit of written action plans when incorporated into the care of asthmatic patients. It is important to note that in most of their randomised controlled trials, patients were instructed to at least double the inhaled corticosteroid dose during deteriorating asthma control. A study in the Lancet has however provided little evidence tha...
Dear Editor,
The editorial by Cullinan suggests that the relationship between allergy, birth order and family size may not be completely explained by the hygiene hypothesis.[1] A role for infection in protecting against allergy has been under consideration for some years, although a credible mechanism has not been identified. It has been suggested that reduced exposure to infection in childhood shifted the balanc...
Dear Editor,
Imperatori et al. make a detailed comparison of lung cancer patients, management and survival in two hospitals, one in England and one in Italy, in an attempt to throw some light on the differences in published survival between these nations[1]. In collecting similar data we have found between 5 and 10% of the patients in our geographical catchment area have not attended our hospital either as in-patie...
Dear Editor,
The correction by Zollner diverts the main issue we raised from incorrectly citing our study as supporting the decrease/leveling off of asthma and allergies in Germany when our study showed an increase, to a reference order error [1]. Also, in Zollner's reply our data were again misinterpreted, as we showed clearly for example that symptoms of asthma, rhinitis, and rhino-conjunctivitis increased sig...
Dear Editor,
We read with great interest the article published in Thorax by Dickinson et al (February 2006)(1) investigating the response of FEF50 following EVH (Eucapnic voluntary hyperventilation) or exercise challenges in elite athletes as an adjunct to FEV1.0. We were however, slightly confused as to the research design selected by the researchers. It appears from the stated methods that the researchers used...
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