Center law mesothelioma support

To the Editor.

The Ad Hoc Statement Committee submits that the American Thoracic Society currently recognizes no confounding by cigarette smoking in the radiographic presentation of asbestosis (1). This challenges the current state of science in this field. Small, irregular opacities are recognized to be present on the poster-oanterior chest X-ray in a significant number of individuals (~ 5%) without any prior history of exposure to either particles or fibers. There is voluminous investigation defining the capacity of cigarette smoking to result in such a profusion of irregular opacities (summarized in Reference 2). This association between cigarette smoking and chest X-ray findings of an interstitial lung injury is also supported by computed tomography that similarly demonstrates these opacities (3). Furthermore, there are pathologic data delineating the relationship between collagen deposition and fibrosis in the human lung and cigarette smoking (4). This manifests as microscopic foci of fibrosis in areas of emphysematous destruction, peribronchiolar fibrosis as an aspect of small airway disease, or the more generalized fibrosis observed with respiratory bronchiolitis-associated interstitial lung disease. Finally, there is postulated to be a shared mechanism of injury between cigarette smoking and fiber inhalation. Exposures to all particles and fibers can present as an oxidative stress in the lung and effect a fibrotic injury to the respiratory tract. Those particles associated with cigarette smoking are comparable to other particles and fibers in that oxidant generation follows in vitro and in vivo exposures (summarized in Reference 5). Such free radical production has been proposed as the common avenue for fibrosis in a tissue exposed to either cigarette smoke or asbestos.

Decades of investigation have provided the insight that cigarette smoking can confound the diagnosis of asbestosis. To disregard this evidence discredits the American Thoracic Society as a scientific body and contradicts the Society's recognition of interstitial lung disease associated with cigarette smoking (6).

Conflict of Interest Statement: A.J.G. earns $10,000 annually in providing opinions to both plaintiff and defense law firms and functioning as an expert witness for both plaintiff and defense law firms; V.L.R. earns approximately $100,000 per year as an expert in asbestos litigation and this comes from both plaintiff and defense attorneys and involves numerous law firms and is about equally divided between plaintiff and defense firms.

ANDREW J. GHIO

United States Environmental Protection Agency

Chapel Hill, North Carolina

VICTOR L. ROGGLI

Duke University Medical Center

Durham, North Carolina

References

1. American Thoracic Society. Diagnosis and initial management of nonmalignant diseases related to asbestos. Am J Respir Crit Care Med 2004; 170:691-715.

2. Meyer JD, Islam SS, Ducatman AM, McCunney RJ. Prevalence of small lung opacities in populations unexposed to dusts. Chest 1997;111:404-410.

3. Mastora I, Remy-Jardin M, Sobaszek A, Boulenguez C, Remy J, Edme JL. Thin-section CT finding in 250 volunteers: assessment of the relationship of CT findings with smoking history and pulmonary function test results. Radiology 2001;218:695-702.

4. Adesina AM, Vallyathan V, McQuillen EN, Weaver SO, Craighead JE. Bronchiolar inflammation and fibrosis associated with smoking. A morphologic cross-seclional population analysis. Am Rev Respir Dis 1991;143:144-149.

5. Rahman I, MacNee W. Role of oxidants/antioxidants in smoking-induced lung diseases. Free Radic Biol Med 1996;21:669-681.

6. American Thoracic Society/European Respiratory Society. American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopalhic interstitial pneumonias. Am J Respir Crit Care Med 2002;165:277-304.

To the Editor:

The American Thoracic Society (ATS) publishes official statements with the expectation that these statements will be balanced, scientifically rigorous, and reflect a comprehensive review of the medical literature. In our opinion, the recent ATS Statement, "Diagnosis and initial management of nonmalignant diseases related to asbestos" (1), did not fully consider alternative points of view and all of the available literature in several important areas.

Since space does not permit a point-by-point rebuttal of the Statement, we have elected to briefly consider examples of the Committee's treatment of two high-impact asbestos-related issues: the question of benign pleural thickening as a risk factor for future malignancy, and whether clinically relevant chronic obstructive pulmonary disease is a likely consequence of asbestos exposure. In the case of the former, the Committee's citing of evidence is selective, and with the latter, there are internal inconsistencies that are likely to leave readers confused and unable to independently draw their own evidence-based conclusions.

With regard to pleural plaques being associated with increased malignancy risk, the authors state, "The presence of plaques is associated with a greater risk of mesothelioma and of lung cancer compared with subjects with comparable histories of asbestos exposure who do not have plaques.... Therefore, the presence of pleural plaques should be interpreted as a marker for elevated risk of malignancy, which may be higher than the occupational history alone might suggest." To support this point, two studies were cited (2, 3). Weaknesses of these studies have been pointed out in a more recent publication (4). In addition, other (one could argue, more powerful) data were not included in the Statement. For instance, in a longitudinal study of asbestos cement workers, the presence of pleural plaques (in the absence of asbestosis) was not associated with an increased lung cancer risk (5). The strength of this study was its prospective cohort design in which radiographie and exposure data were available in a large at-risk population subsequently followed for cause-specific mortality. Additionally, a meta-analysis by Weiss (6) concluded that the weight of the evidence favors the position that persons with asbestos-related pleural plaques do not have an increased risk of lung cancer in the absence of asbestosis. This viewpoint is not considered in the Statement. Further, although risk of malignancy is considered in relation to pleural plaques, the question of whether asbestosis is required to attribute lung cancer to asbestos exposure is not addressed. Given that the most persuasive scientific evidence (5, 7, 8), extensively reviewed by Weiss (9), supports the hypothesis that asbestosis is required to assign causation of lung cancer to asbestos, it is a glaring omission that this document chose not to review this area of the literature. Instead, the document addressed only the unproven association between pleural plaques and malignancy.

In the section on chronic airway obstruction, the Statement implies that clinically significant chronic airway disease can be caused by asbestos exposure alone. However, the studies cited are unable to support that conclusion given their lack of dose-response information and failure to control for other factors (e.g., smoking, radiographic abnormalities, and age) that impact lung function. Despite this, the Committee reached conclusions that are contradictory and that were not based on a comprehensive review of the available literature. As an example of the former, the Committee states, "In general, the magnitude of the asbestos effect on airway function is relatively small. This effect, by itself, is unlikely to result in functional impairment or the usual symptoms and signs of chronic obstructive pulmonary disease." We agree. However, in the next paragraph, the Committee states, "Asbestos exposure independently contributes to accelerated decline in airflow over time, whether or not exposure ceases...." Finally, in the concluding paragraph of the airway disease section, the claim is made that "[t]he association between airway obstruction and exposure to asbestos has been well demonstrated in nonsmokers...." However, when excluding non-smoking patients with radiographic evidence of asbestos-related lung disease and when adhering to the definition of COPD (reduced FEV^sub 1^/FVC ratio) as put forth by the GOLD initiative (10), there is no evidence of an association between clinically significant airway obstruction and asbestos exposure alone. Comments made by the Committee to the contrary are misleading and are not based on the published data.