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The Role of Woodstoves in the Etiology of Nasal Polyposis
Julie Kim, MD, FRCSC;
James A. Hanley, PhD
Arch Otolaryngol Head Neck Surg. 2002;128:682-686.
ABSTRACT
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Objective To determine the role of environmental pollutants in the etiology of
nasal polyposis.
Design Case-control study.
Setting A community-based hospital practice in the Gaspesian peninsula in rural
northeastern Quebec.
Patients Fifty-five case patients with nasal polyposis and 55 age-matched control
subjects without nasal polyposis who were seen at one physician's practice
(J.K.) from March 1, 1998, to December 19, 1998.
Interventions Exposure to woodstoves, indoor tobacco smoke, and pets and occupational
exposures to noxious inhalant compounds.
Results Forty-five (82%) of the cases, but only 14 (25%) of the controls, reported
using woodstoves, yielding a crude odds ratio (OR) of 13.1. The corresponding
risk associated with occupational exposure to noxious inhalant compounds was
also high (OR, 6.1). When adjusted in various ways for the presence of other
factors, these ORs remained high and statistically significant. For woodstove
use, the point estimates of the ORs were consistently above 10, with the lower
limits of 95% confidence intervals above 5. For occupational exposures to
noxious inhalant compounds, the various adjusted OR estimates were above 6,
with the lower limits above 1.5.
Conclusions There is a strong association between the use of woodstoves as a principal
source of heating and the development of nasal polyposis. Occupational exposures
to noxious inhalant compounds (other than tobacco smoke) also play an important
role in its etiology.
INTRODUCTION
NASAL POLYPOSIS is an inflammatory disorder of the nasal mucosa of unknown
etiopathogenesis. Several studies have investigated different pathogenic mechanisms.
First, there are atopic and nonatopic forms of nasal polyposis. But the atopic
form still remains controversial. Eosinophils are the hallmark of the disease.
Studies1 have demonstrated that the cytokine
RANTES (regulated on activation, normal T-cell expressed and secreted) is
a potent mediator of eosinophil chemotaxis in vitro and of leukocyte recruitment.
Other studies assessed the role of interleukins and interferon  ,2-3 intercellular adhesion molecule 1,4 and prostaglandins, leukotrienes, and u-plasminogen
activator.5-6 There have been
studies that examined the function of T cells infiltrating nasal polyps, the
CD8+ (suppressor cell) subpopulation being predominant.7 The most recent study8
investigated the relationship between the nitric oxide concentration in the
paranasal sinuses and the nasal polyp–derived superoxide anion.
Most studies in the literature have focused on the end point of the
inflammatory response. But what triggers this response? The role of infection
and inflammation as a cause of nasal polyposis has been widely debated.9 Ponikau et al10 studied
the role of fungus in the pathogenesis of chronic sinusitis with or without
nasal polyposis. They found that the response was non–IgE mediated,
with eosinophils as the common denominator. In the study by Morpeth et al,11 nasal polyps were found in 75% of cases of allergic
fungal sinusitis.
The use of woodstoves as a principal source of heating is more prevalent
in rural areas, where socioeconomic levels are lower. These stoves liberate
high concentrations of (1) suspended particulates of respirable size; (2)
gases such as aldehydes, nitrous oxides, carbon monoxide, and sulfur oxides;
and (3) polycyclic aromatic hydrocarbons.12
These noxious inhalant compounds have been known to cause irritation of the
mucosa of the upper and lower respiratory tracts, leading to an increased
risk of infections. Nitrogen dioxide and polycyclic hydrocarbons have been
shown to cause immunosuppression in animal studies.13
Formaldehyde is an important by-product of wood combustion.14
It will be discussed in more detail later because it is a ubiquitous substance
in industrialized nations. It is used in many industrial and consumer products,
in the textile, preservative, furniture, machinery, automotive, energy, construction,
cosmetic, and paper industries.15-16
There are conflicting data about the adverse effects of woodstoves on the
respiratory system.12-14,17-18
However, to our knowledge, there are no reports in the literature studying
the association between the use of woodstoves as a principal source of heating
and nasal polyposis. An epidemiological case-control study was conducted to
examine the role of environmental pollutants in the etiology of nasal polyposis.
PATIENTS AND METHODS
From March 1, 1998, to December 19, 1998, a case-control study was conducted
in the Gaspesian peninsula in northeastern Quebec. This is a rural community
with a population base of approximately 35 000. The population was homogeneous,
consisting of only white persons of predominantly Irish and French descent.
The prevalence of the acquired immunodeficiency syndrome in the community
was extremely low, near 0%. The socioeconomic status was predominantly low
and, therefore, an increasing percentage of homes were using woodstoves. One
source (Carl Sennett, oral communication, August 2001) estimates the rate
at approximately 30% to 40%. In fact, among those who owned a woodstove, most
used it as their principal source of heating. The hospital where the patients
were examined was in Gaspé (Centre Hospitalier l'Hotel Dieu de Gaspé).
There was only one otolaryngologist (J.K.) serving this community.
CASES
All patients who were referred to the ears, nose, and throat clinic
during this period for various ears, nose, and throat complaints were examined
by one of us (J.K.). Those who had nasal polyposis were selected for the study.
The diagnosis was made on endoscopic examination of the nasal cavity. All
cases had unilateral or bilateral disease. None had concurrent cystic fibrosis.
A total of 55 cases were identified.
CONTROLS
The 55 controls were randomly selected by one of us (J.K.) based on
time available for questioning among the patients who were referred to the
same ears, nose, and throat clinic during this period for nonrhinologic complaints.
Anyone who had a history of nasal polyposis or recurrent sinusitis or polyps
on endoscopic examination was excluded.
EXPOSURES AND OTHER INFORMATION
At the end of the patient visit, the patients were told that one of
us (J.K.) was conducting a study on nasal polyps. After obtaining verbal consent,
a standard written questionnaire was administered. The questionnaire inquired
about several items, in the following order: (1) telephone number; (2) age;
(3) ancestral origin; (4) occupation; (5) exposures to woodstoves, indoor
tobacco smoke, pets, and dust; (6) the presence of allergies (hay fever, food,
perfume, or aspirin); (7) the presence of associated respiratory illnesses,
such as asthma, bronchitis, sinusitis, or otitis; and (8) what season their
sinus problems were the most severe. The questions were asked in a standard,
orderly, and unbiased fashion. Both groups were unaware of the objective of
the study. Cases and controls were similarly distributed geographically and
socioeconomically. An additional telephone interview with each subject was
conducted by one of us (J.K.) in August 2001 to inquire about the duration
and intensity of exposure to woodstoves; these items were not covered in the
initial interview.
DATA ANALYSIS
All factors except age were represented as binary variables. The prevalences
of each factor in the case and the control ("denominator") series were calculated,
and crude odds ratios (ORs) were calculated. These ORs are used as estimates
of relative risk. The degree to which the use of a woodstove tended to co-occur
with other factors in the "base" population was assessed by (a) calculating the prevalence of woodstove use among persons in the
control series who had these other factors and (b)
comparing it with the overall 25% prevalence of woodstove use in all of the
controls. We also calculated and report the corresponding prevalences for
the case series. We did this so that the raw data showing the association
between woodstove use and nasal polyps may be reconstructed separately in
those with and without each factor.
As a first level of control for possible confounding of the woodstove–nasal
polyps association, we calculated, for each possible confounding factor, an
OR that was adjusted for just that factor. We did this by calculating separate
ORs for those who did and did not report having the factor. We then calculated
a summary OR using the Mantel-Haenszel summary estimator.
We also performed a multiple logistic regression, in which all of these
factors were included simultaneously along with the use of woodstoves. Although
the average ages of the cases and controls were nearly identical, we included
age in all models. We performed the regression analyses again, omitting variables
that were not independently associated with nasal polyps and whose exclusion
did not materially alter the association of interest. The 95% confidence intervals
used throughout indicate the level of precision of our estimates. Confidence
intervals that do not include unity indicate that the observed ORs would,
in a statistical test, be statistically different from unity at the 5% significance
level (2-sided).
RESULTS
The first 3 columns of Table 1
show the characteristics of the 55 cases and the 55 controls. By design, their
ages were quite similar (cases: range, 19-88 [median, 50] years; controls:
range, 18-80 [median, 48] years). As expected from existing knowledge, there
was a male preponderance in cases. Cases were significantly more likely than
controls to report a history of allergy, asthma, and aspirin intolerance.
We also expected a high prevalence of recurrent sinusitis in cases but a low
prevalence of recurrent otitis in both groups. For environmental exposures,
cases were more likely than controls to report the use of woodstoves. Cases
were also more likely than controls to report occupational exposures to noxious
inhalant compounds. There were no statistically significant differences for
exposures to indoor tobacco smoke and pets between cases and controls.
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Table 1. Prevalence of Studied Factors in Cases and Controls, Associated
Crude Odds Ratios, and Woodstove Use in Those With Each Factor*
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The last column of Table 1
allows us to assess whether this elevated OR of 13.1 relating woodstove use
to nasal polyposis could be an artifact. The controls (potential cases) who
had allergy, asthma, or aspirin intolerance were actually less likely than
average (25%) to use woodstoves. On the other hand, woodstove use was slightly
above average (ie, 3 of 7 controls) in those with occupational exposures.
Therefore, on balance, these factors should not materially alter the OR.
The second column of Table 2
shows the ORs when comparisons are restricted to those in whom the various
risk factors are absent. For example, in those without allergies, the OR associated
with woodstove use is 11.8; in those without asthma, it is 10.7; in those
without aspirin intolerance, it is 13.6; and in those without occupational
exposures to noxious inhalant compounds, it is 12.9. All of these ORs are
similar to the overall OR of 13.1. The numbers of persons with these factors
(third column) are smaller and, thus, less stable, but in these persons, the
ORs are also still statistically elevated. The last 2 columns of Table 2 give the summary (ie, adjusted)
OR estimates, obtained by aggregating the information from the like-with-like
comparisons in the first 2 columns. As expected, adjustment just for history
of allergy increases the OR from 11.8 to 18.3; for asthma, from 10.7 to 14.1;
and for aspirin intolerance, from 13.6 to 14.2. On the other hand, adjustment
for occupational exposures to noxious inhalant compounds reduces it slightly
from 12.9 to 11.2.
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Table 2. Odds Ratios Measuring the Association Between Nasal Polyps
and Woodstove Use
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Table 3 shows the raw data
and the ORs reflecting the association between nasal polyps and the use of
woodstoves in various homogeneous subgroups. Depending on the degree of restriction
(absence of factors), the ORs ranged from 10.5 to 15.5, and the lower limits
of the confidence intervals were in all instances statistically greater than
unity (P<.01 for all, 2-sided).
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Table 3. Raw Data and Odds Ratios Measuring the Association Between
Nasal Polyps and Woodstove Use in Various Increasingly Homogeneous Subgroups*
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The first row of Table 4
shows the association between nasal polyps and woodstove use before and after
adjustment via logistic regression for all of the other factors or for some
of the other factors. The remaining rows of Table 4 show the significant associations with allergy and with
occupational exposures to noxious inhalant compounds. As reflected by the
fact that the confidence intervals did not include unity, the ORs for woodstove
use, allergy, and occupational exposures to noxious inhalant compounds were
statistically significant (P<.01), no matter which
set of other factors we adjusted for. For aspirin intolerance, when adjusted
for all of the other factors or for some of the factors, the ORs were still
elevated but were not statistically significant at the conventional .05 level
because the lower limit of the confidence interval was below 1, reflecting
the low frequency of this recognized risk factor. Because of the small sample
sizes, and as reflected in the generally wide confidence intervals, the magnitudes
of the ORs cannot be quantified precisely.
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Table 4. Odds Ratio as a Measure of Association of Nasal Polyps With
Woodstove Use and Other Factors, Before and After Adjustment by Multiple Logistic
Regression
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Data on the duration of exposure to woodstoves are as follows: longer
than 10 years, 44 (98%) of 45 cases vs 13 (93%) of 14 controls; between 5
and 10 years, 1 (2%) of 45 cases vs 0 controls; and less than 5 years, 0 cases
vs 1 (7%) of 14 controls. Data on the intensity of exposure to woodstoves
are as follows: longer than 20 hours per day, 15 (33%) of 45 cases vs 0 controls;
longer than 14 hours per day, 22 (49%) of 45 cases vs 9 (64%) of 14 controls;
and between 6 and 8 hours per day, 8 (18%) of 45 cases vs 5 (36%) of 14 controls.
Subjects were exposed in the winter, from November to March. The woodstoves
were predominantly (90% [53/59]) located in the basement, where heat can diffuse
upward and warm the homes efficiently.
COMMENT
Findings in this study confirm the previously reported associations
between nasal polyposis, allergy, asthma, and aspirin intolerance.19-20 A male preponderance in cases was
also consistent with the literature.19 Two
findings are noteworthy. First, there was a remarkably high and statistically
significant association between the use of woodstoves as a principal source
of heating and nasal polyposis. To our knowledge, this is the first report
in the literature linking the 2 variables. Second, there was a strong association
between occupational exposures to noxious inhalant compounds (other than tobacco
smoke) and nasal polyposis. What is common between these 2 findings is that
they both involve exposure to noxious inhalant compounds.
The high ORs deserve comment. They can possibly be explained by the
high and prolonged exposure to woodstoves. Exposure was substantially higher
than in metropolitan areas for several reasons. The available work in this
rural community is mainly seasonal, leaving many people unemployed, and at
home, in the winter. Given their low socioeconomic level, and the abundance
of wood in the area, they tend to heat with wood rather than electricity or
oil.
There has been little in the literature regarding the role of noxious
environmental pollutants as a possible trigger in the inflammatory response.
Pimentel21 demonstrated in a clinicopathologic
study of 92 cases of nasal polyps that environmental pollutants may play a
role in their etiopathogenesis. Furthermore, there was a decrease in recurrence
when exposure to the offending agent was discontinued. Our study supports
Pimentel's findings of the role of noxious environmental pollutants in the
etiopathogenesis of nasal polyposis.
Urea-formaldehyde foam insulation is used extensively for the insulation
of buildings. Pross et al22 conducted a study
to measure hematological and immunologic variables in subjects with asthma
exposed to urea-formaldehyde foam insulation. The main findings were the following:
an increase in the eosinophil and basophil count, a slight increase in the
T8 (suppressor) cell subpopulation, and a decrease in the natural killer cell
response to a low concentration of interferon. Furthermore, the other variables
suggest that short-term exposure to formaldehyde may result in some degree
of immunosuppression. The acquired immunodeficiency syndrome is a good model
to study aberrations in the mean helper/suppressor cell ratio (T4/T8). In
patients with the acquired immunodeficiency syndrome, the T4/T8 ratio is severely
inverted. However, milder aberrations can be found in patients with other
conditions, such as herpes infections, systemic lupus erythematosus with renal
disease, burns, and in those who exercise vigorously.22
If, indeed, formaldehyde has caused a mild immunosuppressive state,
it would seem plausible that it can lead to an overgrowth of various microorganisms.
Yoskovitch and Cantrell23 reported the first
case of cytomegalovirus associated with nasal polyps in patients with the
acquired immunodeficiency syndrome. Sanchez-Segura et al7
demonstrated a predominance of CD8+ suppressor cells in the immunohistochemical
analysis of the nasal polyps. Thus, variable degrees of immunosuppression
(local and/or systemic) could be the common denominator leading to changes
in nitric oxide concentrations in the nasal mucosa, with subsequent overgrowth
of microorganisms in certain forms of nasal polyposis. More epidemiological
and immunopathologic studies would, therefore, be of interest to examine specifically
the relationship of formaldehyde and other noxious environmental pollutants
in the development of nasal polyposis. Furthermore, the etiopathogenesis of
nasal polyposis can be classified into 2 components: (1) internal (immunologic)
and (2) external (environmental).
There are some limitations of this study. First, the airtightness of
the woodstoves and homes, reflecting the pollutant levels in question, was
not ascertained in either group.13, 18
Also, the level of occupational exposures to noxious environmental pollutants
was not measured either. It is difficult in general to quantify the level
of exposures to the environmental pollutants in question.
As in any case-control study, there is a possibility of recall bias.
However, the fact that patients were only told that it was a "study on nasal
polyps," that it inquired about several agents, and that there was no prior
awareness of any associations are likely to have minimized these concerns.
Finally, the fact that one of us (J.K.) was also the one who conducted
the interviews could be construed as lack of blinding. However, at the beginning
of the study, this author (J.K.) was unaware of any association between woodstoves
and nasal polyps. The question being studied was the role of environmental
pollutants in the workplace or at home and the development of nasal polyps.
Woodstoves were included among the exposures because of the high prevalence
of woodstove use in this rural community—much higher than in metropolitan
cities. Only near the end of the study did the author (J.K.) recognize a pattern
in the responses, making blinding more difficult.
In conclusion, this study found a strong association between the use
of woodstoves as a principal source of heating and nasal polyposis. To our
knowledge, such an association has not been previously reported. There was
also a strong association between occupational exposures to noxious inhalant
compounds (other than tobacco smoke) and the development of nasal polyposis.
These findings merit further investigation.
AUTHOR INFORMATION
Accepted for publication November 2, 2001.
Corresponding author and reprints: Julie Kim, MD, FRCSC, Polyclinique
de l'oreille, 2113, Boulevard Casavant Ouest, St-Hyacinthe, Quebec, Canada
J2S 8B8 (e-mail: juliek{at}total.net).
From the Centre Hospitalier l'Hotel Dieu de Gaspé, Gaspé
(Dr Kim), and the Department of Epidemiology and Biostatistics, McGill University,
Montreal (Dr Hanley), Quebec. Dr Kim is now with the Department of Otolaryngology,
Reseau Sante Richelieu-Yamaska, St-Hyacinthe, Quebec.
REFERENCES
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1. Teran LM, Park HS, Djukanovic R, Roberts K, Holgate S. Cultured nasal polyps from nonatopic and atopic patients release RANTES
spontaneously and after stimulation with phytohemagglutinin. J Allergy Clin Immunol. 1997;100:499-504.
FULL TEXT
|
ISI
| PUBMED
2. Lee CH, Lee KS, Rhee CS, Lee SO, Min YG. Distribution of RANTES and interleukin-5 in allergic nasal mucosa and
nasal polyps. Ann Otol Rhinol Laryngol. 1999;108:594-598.
ISI
| PUBMED
3. Dellacono FR, Eisma R, Lafreniere D, Leonard G, Kreutzer D. Interferon gamma expression in human nasal polyps. Laryngoscope. 1997;107:626-630.
FULL TEXT
|
ISI
| PUBMED
4. Tingsgaard PK, Larsen PL, Bock T, Lange Vejlsgaard G, Tos M. Expression of intercellular adhesion molecule-1 on the vascular endothelium
in nasal polyps before, during and after topical glucocorticoid treatment. Acta Otolaryngol. 1998;118:404-408.
FULL TEXT
| PUBMED
5. Pinto S, Gallo O, Polli G, et al. Cyclooxygenase and lipoxygenase metabolite generation in nasal polyps. Prostaglandins Leukot Essent Fatty Acids. 1997;57:533-537.
FULL TEXT
|
ISI
| PUBMED
6. Larsen K, de Maat MP, Jespersen J. Plasminogen activators in human nasal polyps and mucosa. Rhinology. 1997;35:175-177.
PUBMED
7. Sanchez-Segura A, Brieva JA, Rodriguez C. T lymphocytes that infiltrate nasal polyps have a specialized phenotype
and produce a mixed TH1/TH2 pattern of cytokines. J Allergy Clin Immunol. 1998;102:953-960.
FULL TEXT
|
ISI
| PUBMED
8. Pasto M, Serrano E, Urocoste E, et al. Nasal polyp–derived superoxide anion: dose-dependent inhibition
by nitric oxide and pathophysiologic implications. Am J Respir Crit Care Med. 2001;163:145-151.
FREE FULL TEXT
9. Norlander T, Bronnegard M, Stierna P. The relationship of nasal polyps, infection, and inflammation. Am J Rhinol. 1999;13:349-355.
ISI
| PUBMED
10. Ponikau JU, Sherris DA, Kern EB. The diagnosis and incidence of allergic fungal sinusitis. Mayo Clin Proc. 1999;74:877-884.
ISI
| PUBMED
11. Morpeth JF, Rupp NT, Dolen WK, Bent JP, Kuhn FA. Fungal sinusitis: an update. Ann Allergy Asthma Immunol. 1996;76:128-139.
ISI
| PUBMED
12. Tuthill RW. Woodstoves, formaldehyde, and respiratory disease. Am J Epidemiol. 1984;120:952-955.
FREE FULL TEXT
13. Samet JM, Marbury MC, Spengler JD. Health effects and sources of indoor air pollution: part I. Am Rev Respir Dis. 1987;136:1486-1508.
ISI
| PUBMED
14. Daigler GE, Markello SJ, Cummings KM. The effect of indoor air pollutants on otitis media and asthma in children. Laryngoscope. 1991;101:293-296.
ISI
| PUBMED
15. Samet JM, Marbury MC, Spengler JD. Health effects and sources of indoor air pollution: part II. Am Rev Respir Dis. 1988;137:221-242.
ISI
| PUBMED
16. Levin L, Purdom PW. A review of the health effects of energy conserving materials. Am J Public Health. 1983;73:683-690.
FREE FULL TEXT
17. Honicky RE, Osborne III JS, Akpom CA. Symptoms of respiratory illness in young children and the use of wood-burning
stoves for indoor heating. Pediatrics. 1985;75:587-593.
FREE FULL TEXT
18. Honicky RE, Osborne III JS. Respiratory effects of wood heat: clinical observations and epidemiologic
assessment. Environ Health Perspect. 1991;95:105-109.
ISI
| PUBMED
19. Moloney JR. Nasal polyps, nasal polypectomy, asthma, and aspirin sensitivity: their
association in 445 cases of nasal polyps. J Laryngol Otol. 1977;91:837-846.
ISI
| PUBMED
20. Sin A, Terzioglu E, Kokuludag A, et al. Allergy as an etiologic factor in nasal polyposis. J Investig Allergol Clin Immunol. 1997;7:234-237.
ISI
| PUBMED
21. Pimentel JC. 92 cases of allergic-type nasal polyp: a methodology for its etiological
characterization. Acta Med Port. 1995;8:379-384.
PUBMED
22. Pross HF, Day JH, Clark RH, Lees RE. Immunologic studies of subjects with asthma exposed to formaldehyde
and urea-formaldehyde foam insulation (UFFI) off products. J Allergy Clin Immunol. 1987;79:797-810.
FULL TEXT
|
ISI
| PUBMED
23. Yoskovitch A, Cantrell H. Cytomegalovirus infection presenting as chronic sinusitis and nasal
polyposis: a case report. Ear Nose Throat J. 1998;77:35-38.
PUBMED
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