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Asthma is a disorder characterized by the inflammation of the airways. Common symptoms include wheezing, shortness of breath, chest tightness and coughing. Many environmental triggers such as exercise, animals and dust have all been well-established as initiators of asthmatic symptoms. However, recently certain cancer patients have been shown to be developing asthma after chemotherapy for breast cancer. While pulmonary toxicity is one of the most frequent non-hematologic toxicity associated with chemotherapy, with a reported incidence of 39%, a role of chemotherapy in the development of asthma has yet to be fully established.
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Evidence Suggest a Possible Curative Effect of Chemotherapy in Asthma Patients
While there is little scientific evidence highlighting the advantages and disadvantages of chemotherapy in asthma, a few cast reports in asthmatic children suggest that chemotherapy may play a role in the treatment of asthmatic symptoms. One example is an 8-year-old asthmatic boy diagnosed with a parameningeal myxoid sarcoma. He received 15 months of systemic chemotherapy (vincristine, cyclophosphamide and actinomycin D) and radiation therapy to the primary tumor site. Prior to his diagnosis of cancer, the boy was admitted to the hospital with bronchiolitis at the age of 6 months and with asthma at the age of 4 years. His asthmatic symptoms were controlled by regular inhalation treatment with 400 mg per day of budesonide. During the 15 months of systemic chemotherapy, the boy became completely wheeze free. However, 14 months following the discontinuation of all chemotherapy, he began to again have mild episodic asthma and requirement treatment for respiratory infections. It is important to note that his asthmatic symptoms were not severe enough to warrant therapy with inhaled steroids. Together, findings from this case study demonstrated that the boy had reduced asthmatic symptoms during chemotherapy and a decrease response to multiple triggers 14 months after chemotherapy was discontinued. However, airway inflammatory symptoms returned in the absence of chemotherapy.
A curative effect of chemotherapy in asthmatic children was demonstrated in another study which evaluated the role of maintenance chemotherapy (50 mg/m2 of purine antagonists daily and 50 mg/m2 MTX weekly or biweekly) in 43 children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Of the 43 children, 3 suffered from asthmatic symptoms prior to cancer diagnosis. Throughout the treatment, neither of the 3 asthmatic patients nor the other 40 children showed any signs of obstructive airway disease or asthma. A full recovery was observed in the 3 asthmatic patients and asthma therapy was discontinued in these patients.
Together, these case reports suggest that chemotherapy may play a curative role in asthmatic children. However, little is known of the effects of chemotherapy on asthmatic symptoms in the adult population.
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A Possible Link Between Tamoxifen and Asthma
While there have yet to be any official studies investigating the possibility of developing asthma after chemotherapy for breast cancer, there have been a few reports of unexplained asthma symptoms in patients receiving Tamoxifen for the treatment of breast cancer. Tamoxifen is an antagonist of the estrogen receptor. Some breast cancer cells require estrogen to grow and Tamoxifen has been shown to compete with endogenous estrogen for the estrogen receptor and block the estrogen-dependent growth of breast tissue. In certain sensitive patients, it has been reported that Tamoxifen can act as a trigger for an asthmatic attack. Moreover, preclinical studies using animal models demonstrated that estrogen plays a pro-inflammatory role in the allergic lung response. Furthermore, Tamoxifen has also been shown to enhance airway inflammation. However, until today no concrete evidence is available that has shown a direct link between Tamoxifen and developing asthma after chemotherapy for breast cancer.
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Chap L et al. Pulmonary toxicity of high-dose chemotherapy for breast cancer: a non-invasive approach to diagnosis and treatment. Bone Marrow Transplantation 1997; 20:1063–1067.
Jones PD et al. Chemotherapy for Malignancy Induces a Remission in Asthma Symptoms and Airway Inflammation but Not Airway Hyperresponsiveness. Pediatric Pulmonology 1998; 25:74–77.
Weigel S et al. Intensive chemotherapeutic regimens against acute leukemia transiently suppress asthma symptoms but do not lead to long-term relief. Pediatric Hematology and Oncology 2000;17:656-665.
Ligeiro de Oliveira AP et al. Regulation of allergic lung inflammation in rats: interaction between estradiol and corticosterone. Neuroimmunomodulation. 2004;11:20-7.
Smith RP, Dewar JA, Winter JH. Tamoxifen-induced asthma. Lancet. 1993;341:772.