Abstract
Rationale The Relationship between asthma and abnormalities in cellular growth and neoplastic transformations has remained controversial due to contradictory population studies and the absence of a mechanistic understanding of such associations.
Objectives To identify the relationship between asthma and neoplasms.
Methods We used a large-scale observational administrative dataset from the state of Florida and “Causal Inference Using Composition of Transitions” (CICT) to produce multiple hypotheses on potential relationships between asthma-and neoplasms. Next, we used a similar dataset from the state of California to validate the initial findings. Nine case-control cohorts were created for patients exposed to subtypes of asthma and COPD and corresponding control groups matched on gender, age, race and history of tobacco abuse. In each cohort odds ratio analysis was conducted to measure the association of asthma and COPD with 26 different neoplasms. Bonferroni-Holm correction was applied to adjust for family-wise error.
Results A total of 234 individual studies were conducted between Asthma (N= 998,585, male= 33%, age=50) and COPD (N=715,971, male = 50%, age=69) patients and corresponding matched control groups (N=8,400,004, male= 42%, age= 47) of unexposed patients. Subtypes of COPD were strongly associated with bronchial and lung malignancies, with the strongest association for emphysema (OR: 9.94). Allergic asthma was associated with benign neoplasm of the meninges, salivary, pituitary, parathyroid, and thyroid glands ORs between 1.52 to 2.52, and malignant neoplasms of intrahepatic bile ducts, breast, hematopoietic, and lymphatic system with ORs between 1.45 to 2.05. Emphysema was strongly associated with malignancies of the lung, GI system, bladder and secondary malignancies. Allergic asthma diverged from COPD’s in the set of neoplasms associations. Associations of obstructive asthma was a blend of COPD and allergic asthma
Conclusions Our study identified novel associations between glandular neoplasms and allergic asthma in two large-scale US-based populations. Confirmation of previously known associations between COPD and malignancies in the same database supports the use of our approach for the identification of causal associations. Additional studies on the role of allergic inflammation neoplastic transformation of common structures of secretory organs including epithelial cells are required.
Authors Contribution
Abbas Shojaee designed the study, developed the methodology, performed analysis and wrote the manuscript, Geoffrey Chupp supervised the research and together with Naftali Kaminski and Jose Gomez verified the results and critically contributed to writing the manuscript, Seyedtaghi Takyar conceived the idea of the asthma-neoplasms relationship and contributed to the writing. Hongyu Zhao and Xiaochen Wang contributed to verifying methods and writing.
Footnotes
Disclosures: The authors declare that they have no relevant or material financial interests that relate to the research described in this paper.
At a Glance Commentary: Over the past three decades, consensus over the potential relationship between asthma-specific inflammation and abnormality in cellular growth and neoplasm has not been reached. The debate rises from controversial, population-level evidence that has emerged from different methods, data sources and cohorts and in the lack of sufficient molecular-level understanding of the association between allergic airway inflammation and malignant transformation.
The present study includes the most extensive cohort of patients with asthma or COPD. We used machine learning methods of causal inference combined with conventional epidemiological reasoning tools to identify potential associations between asthma and neoplasms. Our study reaffirms the well-known connections of COPD and lung cancer and reveals previously unknown relations between allergic asthma and benign neoplasms of various glands. Further, we identified the association between subtypes of COPD and hematological and lymphatic malignancies and confirmed this relation with allergic asthma. Our findings help to clarify the contradictory results from other large studies on asthma and its connection to lung cancer. Moreover, we show that the set of neoplasms in allergic asthma and COPD have significant differences, suggesting the involvement of various pathways.