Ethical Issues in Using Bronchial Biopsies for Asthma Research

Introduction

Asthma is a major health concern in all countries regardless of their level of economic development. According to the World Health Organization (WHO), there are currently 235 million people suffering from asthma worldwide.⁴⁶ Despite the current available standard treatments, asthma prevalence in adults and children has been increasing, and 1 in 250 deaths worldwide is thought to have resulted from this disease.¹ To date, the reasons for such prevalence are not completely understood and this may be attributed to the inadequate understanding of the asthma pathophysiology. This article stresses that research on asthmatic airways is crucial to finding better treatments for the disease, but that, importantly, requires the analysis of bronchial biopsies from asthmatic patients. To do so, we discuss the means available and implications of taking biopsies for asthma research in a study currently being undertaken at the Lung Disease Research Laboratory, National University of Singapore (NUS), in collaboration with the National University Hospital (NUH), Singapore.

Background: A Study to Investigate the Molecular Mechanism(s) of Airway Wall Remodelling in Asthma

Research into the molecular mechanism(s) of asthma in patients is essential towards the improvement of our basic understanding of the disease progression, and eventually may lead to optimal clinical management.² Non-invasive methods, such as the measurement of exhaled nitric oxide and tidal forced expirations as assessments of asthma pathology, have contributed hugely towards asthma research.³, ⁴ However, non-invasive methods may not allow a definitive diagnosis to be made. Different phenotypes of asthma seem to exist. For example: 1) persistent symptoms without airway inflammation; 2) high dose steroid dependent eosinophilic inflammation; and 3) persistent eosinophilic inflammation even with high dose of oral prednisolone accompanied by airway wall remodelling.⁵–⁹ These asthma phenotypes are unlikely to be addressed by the non-invasive methods. Asthmatic patients who respond poorly to corticosteroid, the first line treatment of asthma, should be considered to undergo bronchial biopsy (invasive method). This allows direct inspection of the airways to understand the underlying asthma pathophysiology and thus, better disease management. Invasive techniques on the airways of asthmatic patients are thus required for basic asthma research and to validate the assessment results of the non-invasive methods.¹⁰ Since there is limited progress in disease treatment, research biopsies may potentially widen our knowledge and thereby advance the treatment of asthma by: 1) the identification of biomarkers for the disease: 2) gaining insight into how our treatments actually work: and 3) assessing biological pathways responsible for asthma.¹⁰ The ultimate goal for the use of research biopsies is to investigate the root cause of asthma, and armed with that knowledge, perhaps make asthma a curable disease in the future.

In asthma airway research, biopsy samples are often taken from asthmatic participants with an existing co-morbidity, such as lung cancer. In these patients, one can obtain the asthmatic biopsy samples from the second-to-fourth generation of the main bronchus after lung resection surgery. Samples can also be acquired from the macroscopically healthy segments of the bronchus from patients with lung cancer (without asthma condition), which is non-tumorigenic, and such (non-asthmatic) control biopsy samples may be used for comparison. These procedures are routine in our Lung Disease Research laboratory and they are approved by the NUS Human Research Ethics Board (NUS-IRB). Patients are selected based on certain criteria (not pregnant, no children, etc.) and with informed consent obtained voluntarily from the patients. This approach is justified because an area of bronchus of the resected specimens in the lung resection surgery (tissue primarily dissected to remove tumours) not related to the pathology, in this case cancer, is used by our laboratory to obtain biopsy samples for asthma research.

In other asthma research laboratories, the biopsy samples may be obtained directly from the airways of the asthmatic patients and healthy volunteers for comparison. These are achieved via three different techniques using the flexible bronchoscope: transbronchial biopsy, endobronchial biopsy and brush biopsy.¹¹ During transbronchial biopsy, samples are obtained using a bronchoscope...