ophen and asthma hypothesis 10 years on: a case to answer. J Allergy. Clin Immunol 2009;124:649â651. From the Authors: We thank Chang and colleagues for ...
Correspondence
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GAIL DAVEY, M.D. Addis Ababa University Addis Ababa, Ethiopia
rhinoconjunctivitis and eczema in adolescents: ISAAC phase three. Am J Respir Crit Care Med 2011;183:171–178. 2. Farquhar H, Stewart A, Mitchell E, Crane J, Eyers S, Weatherall M, Beasley R. The role of paracetamol in the pathogenesis of asthma. Clin Exp Allergy 2010;40:32–41. 3. Farquhar H, Crane J, Mitchell EA, Eyers S, Beasley R. The acetaminophen and asthma hypothesis 10 years on: a case to answer. J Allergy Clin Immunol 2009;124:649–651.
JOHN BRITTON, M.D. ANDREA VENN, PH.D. University of Nottingham Nottingham, United Kingdom
From the Authors:
We thank Chang and colleagues for their interest in our study. In responding to their comments, and as discussed in detail in the article (1), our study reports an adverse effect of frequent acetaminophen use in the first year on the incidence of wheeze between 1 and 3 years. As Chang and colleagues mention, reverse causation is an intrinsic weakness in cross-sectional studies (2, 3); however, our longitudinal analysis was based on those children who had never reported wheeze up to the age of 1 year (when exposure to acetaminophen was measured), and the outcome was defined as reported wheeze between 1 and 3 years. Unlike Beasley’s cross-sectional study in children (2), our study was not biased by recall, as we used a birth cohort to make very early measurements of acetaminophen exposure. Moreover, we were able to account for the impact of further controlling for infantile respiratory tract infections, and unlike the previous study by Lowe and colleagues (4), our wheeze association remained statistically significant. Therefore, reverse causation and/or confounding by indication is an unlikely explanation for our observed association (1). The contraindication to using aspirin in asthma that is widely recognized in developed countries is not a major concern in our developing country population. We have previously shown in the same setting that only 1% of the population in the study area reported avoidance of aspirin due to asthma risk, and only 4% of those with wheeze/asthma were taking any asthma medication (5). Awareness of the risks of aspirin (including Reye’s syndrome) are extremely low in this community, even among prescribers and dispensers (6). Moreover, as discussed in detail in the article, nonsteroidal anti-inflammatory drugs (NSAIDs) that may be linked to asthma and allergic diseases are not readily available or affordable in this rural community. Together these alternative explanations are unlikely to play a role in our study. However, we agree with Chang and colleagues that the consistently reported adverse role of acetaminophen in the pathogenesis of asthma merits further research. One clinical trial from the United States compared acetaminophen and ibuprofen in children with asthma and showed increased risk in the acetaminophen group, but lacked a placebo arm (7). Another trial from India reported that 15-day treatment with 2 g of acetaminophen increased total airway resistance, but this trial enrolled small number of subjects and only had short-term outcomes (8). These observations, therefore, call for a wellpowered placebo-controlled randomized trial with long-term outcome measures to generate evidence on which to base recommendations concerning acetaminophen use in children. Author Disclosure: A.A. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. G.D. has received a grant from Asthma UK. J.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. A.V.’s institution has received grants from Asthma UK and Wellcome Trust.
ALEMAYEHU AMBERBIR, B.SC., M.P.H. Addis Ababa University Addis Ababa, Ethiopia and University of Nottingham Nottingham, United Kingdom
References 1. Amberbir A, Medhin G, Alem A, Britton J, Davey G, Venn A. The Role of acetaminophen and geohelminth infection on the incidence of wheeze and eczema: a longitudinal birth-cohort study. Am J Respir Crit Care Med 2011;183:165–170. 2. Beasley R, Clayton T, Crane J, von Mutius E, Lai CKW, Montefort SR, Stewart A. Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6–7 years: analysis from Phase Three of the ISAAC program. Lancet 2008;372:1039–1048. 3. Beasley R, Clayton T, Crane J, Lai CKW, Montefort SR, von Mutius E, Stewart A; ISAAC Phase Three Study Group. Acetaminophen use and risk of asthma, rhinoconjunctivitis and eczema in adolescents: ISAAC Phase Three. Am J Respir Crit Care Med 2011;183:171–178. 4. Lowe AJ, Carlin JB, Bennett CM, Hosking CS, Allen KJ, Robertson CF, Axelrad C, Abramson MJ, Hill DJ, Dharmage SC. Paracetamol use in early life and asthma: prospective birth cohort study. BMJ 2010;341:c4616. 5. Davey G, Berhane Y, Duncan P, Aref-Adib G, Britton J, Venn A. Use of acetaminophen and the risk of self-reported allergic symptoms and skin sensitization in Butajira, Ethiopia. J Allergy Clin Immunol 2005; 116:863–868. 6. Duncan P, Aref-Adib G, Venn A, Britton J, Davey G. Use and misuse of aspirin in rural Ethiopia. East Afr Med J 2006;83:31–36. 7. Lesko SM, Louik C, Vezina RM, Mitchell AA. Asthma morbidity after the short-term use of ibuprofen in children. Pediatrics 2002;109:e20. 8. Kodgule R, Kapoor S, Pawar R, Vanjare N, Gaikwad K, Salvi S, Brashier B. Paracetamol increases airway resistance in stable asthmatics: a double blind, randomized, placebo controlled study [abstract]. Eur Respir J 2010;36:A3872.
Possible Relationship between Asbestos Exposure and Bronchial Asthma: A Need for Clarification To the Editor:
We read with interest the recent article by Amellie and coworkers (1). They concluded that there is no relationship between asbestos exposure alone and airway obstruction. However, one study has reported that asbestos exposure could cause asthmatic symptoms, although the subjects were also exposed to dusts other than asbestos (2). In addition, serum immunoglobulin E (IgE) elevation has been reported in asbestos-exposed workers (3, 4), and asbestos exposure may cause an atopic condition (5). We suspect that asbestos exposure itself is a risk factor for the development of bronchial asthma. Bronchial asthma might develop by asbestos exposure independent of dose. Previous studies of nonmalignant respiratory disease caused by asbestos exposure lack appropriate examinations of allergic status, such as sputum eosinophil population, fractional exhaled nitric oxide concentration, bronchial hyperresponsiveness, serum IgE levels, and radioallergosorbent testing. Asbestos exposure may cause airway obstruction by inducing bronchial asthma, even if confirmed asbestosis is absent. To clarify this hypothesis, further investigation will be needed. Author Disclosure: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
MIKIO TOYOSHIMA, M.D., PH.D. Hamamatsu University School of Medicine Hamamatsu, Japan
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and Hamamatsu Rosai Hospital Hamamatsu, Japan
JACQUES AMEILLE, M.D. AP-HP, Hoˆpital Raymond Poincare´ Garches, France MARC LETOURNEUX, M.D. INSERM ERI No. 3 Caen, France
MASAKI SATO, M.D., PH.D. Hamamatsu Rosai Hospital Hamamatsu, Japan
CHRISTOPHE PARIS, PH.D. INSERM U954 Nancy, France PATRICK BROCHARD, PH.D. University Hospital Bordeaux, France
References
From the Authors:
We thank Dr. Toyoshima and coworkers for suggesting the possibility that asbestos exposure may contribute to asthma. To support this hypothesis, they quote the article by Eagan and colleagues (1). In this study that examined the incidence of respiratory symptoms and asthma in an 11-year Norwegian community cohort of 2,819 subjects, asbestos exposure (positive response to the question ‘‘have you been exposed to asbestos dust in your work?’’) was associated with a higher risk of attacks of dyspnea and wheezing (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.0–3.6). However, while of the same order of magnitude, the risk of physician-diagnosed asthma was not significantly increased (OR, 2.0; 95% CI, 0.95–4.1). In the discussion, the authors indicate that questions on quartz and asbestos can be interpreted as indicators of an unhealthy working environment and that inferences of a causal relationship between asbestos and asthma must therefore be drawn with caution. More recently, in a population-based cohort (52,325 Singaporean subjects), information on occupational exposures was collected at enrolment (1993–1998) and respiratory outcomes were obtained via follow-up interviews in 1999–2004 (2). Persons exposed to mineral dusts, including asbestos, had not significantly higher odds of adult-onset asthma compared with those without exposure to these dusts (OR, 1.16; 95% CI, 0.95–1.43). Consequently, to our knowledge the link between asbestos exposure and asthma has not been thoroughly evaluated, but the available information does not convincingly support such an association. It should also be stressed that our study, devoted to obstructive ventilatory disorders independently of any data on the severity of bronchial reactivity, was not qualified to assess a possible association between asbestos exposure and asthma (3). Author Disclosure: J.A., M.L., and P.B. do not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. C.P.’s institution has received grants from INSERM, and travel support from the
2011
European Respiratory Society Congress. J.C.P.’s institution received grants from The National Health Insurance and the French Ministry of Labor and Health.
KINGO CHIDA, M.D., PH.D. TAKAFUMI SUDA, M.D., PH.D. Hamamatsu University School of Medicine Hamamatsu, Japan
1. Ameille J, Letourneux M, Paris C, Brochard P, Stoufflet A, Schorle E, Gislard A, Laurent F, Conso F, Pairon JC. Does asbestos exposure cause airway obstruction, in the absence of confirmed asbestos? Am J Respir Crit Care Med 2010;182:526–530. 2. Eagan TM, Gulsvik A, Eide GE, Bakke PS. Occupational airborne exposure and the incidence of respiratory symptoms and asthma. Am J Respir Crit Care Med 2002;166:933–938. 3. Rosenthal GJ, Simeonova P, Corsini E. Asbestos toxicity: an immunologic perspective. Rev Environ Health 1999;14:11–20. 4. Ilavska´ S, Jahnova´ E, Tulinska´ J, Horva´thova´ M, Dusinska´ M, Wsolova´ L, Kyrtopoulos SA, Fuortes L. Immunological monitoring in workers occupationally exposed to asbestos. Toxicol 2005;206: 299–308. 5. Toyoshima M, Chida K, Kono M, Kaida Y, Nakamura Y, Suda T, Sugimura H. IgG4-related lung disease in a worker occupationally exposed to asbestos. Intern Med 2010;49:1175–1178.
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JEAN-CLAUDE PAIRON, PH.D. INSERM U955 Cre´teil, France References 1. Eagan TML, Gubsvik A, Eide GE, Bakke PS. Occupational airborne exposure and the incidence of respiratory symptoms and asthma. Am J Respir Crit Care Med 2002;166:933–938. 2. LeVan TD, Koh WP, Lee HP, Koh D, Yu MC, London HJ. Vapor, dust, and smoke exposure in relation to adult-onset asthma and chronic respiratory symptoms: the Singapore Chinese Health Study. Am J Epidemiol 2006;163:1118–1128. 3. Ameille J, Letourneux M, Paris C, Brochard P, Stoufflet A, Schorle´ E, Gislard A, Laurent F, Conso F, Pairon JC. Does asbestos exposure cause airway obstruction in the absence of confirmed asbestosis? Am J Respir Crit Care Med 2010;182:526–530.
Early-Stage Lung Cancer Mimicking Pulmonary Arteriovenous Malformation To the Editor:
With the growing use of computed tomography (CT), the number of nodules detected incidentally increased and the sizes of the nodules detected are smaller than those in the chest X-ray era (1). These solitary pulmonary nodules (SPNs) may reflect a variety of disorders, including neoplasm, infection, inflammation, and vascular abnormality (2). During the assessment of SPNs, the goal is thus to especially discriminate between benign causes and malignant lesions. However, various morphologies or atypical findings of lung cancer on CT may often lead to misdiagnosis. A 55-year-old male was admitted to our hospital for evaluation of an SPN that was detected through a medical check-up. A contrast-enhanced CT scan of chest showed a 0.8 3 0.5 cm–sized nodule in the left lower lobe (Figures 1A–1C). The nodule was connected with linear structures suggestive of feeding artery and draining vein. On contrast-enhanced CT images, the SPN was well enhanced with 144 Hounsfield units (HU). In addition, a round low-density area was also detected within the nodule; thus, the radiologic impression was a pulmonary arteriovenous malformation (PAVM) with thrombus formation. On pulmonary angiography there was no definitive evidence of PAVM. The patient was recommended to undergo surgical resection of the nodule for diagnostic and therapeutic purposes, but he refused, discharged, and did not follow-up. On chest CT obtained 5 years later, the pulmonary nodule was markedly increased to 5.8 3 2.8 cm, which was heterogeneously enhanced and associated with mediastinal lymphadenopathy
