Orla O'Carroll June'20.pdf (2.92 MB)
Reproducibility of the Respiratory Microbiome in Asthmatic Patients
thesisposted on 2021-12-13, 16:23 authored by Orla O'Carroll
Contrary to classical teaching, the lungs are not sterile. In fact they play host to thousands of diverse microbes including bacteria, viruses, fungi, and protozoa. The collective term for the genetic material of these microbial components is the microbiome. Since the discovery of the respiratory microbiome some ten years ago, there has been much interest in the study of this topic across a range of respiratory conditions. It has been shown that the respiratory microbiome is significantly altered in asthmatics, though the functional impact of these alterations remains unknown. Alterations in the microbiome of the skin and gut have been implicated in the development of asthma. Studies involving concurrent assessment of all these microbial compartments are rare and it is not known how these communities interact with each other. It is also unknown whether the microbiome interacts with the intrinsic differences in airway physiology which define asthma. Furthermore the response of the asthmatic microbiome to treatments such as antibiotics is largely unknown. We aimed to assess whether airway physiology and the bacterial density of the oropharynx, lung, skin and gut change significantly after an asthmatic patient is exposed to an antibiotic.
Patients were included if they demonstrated either reversible airflow limitation or clinically significant bronchial hyperresponsiveness combined with clinically relevant symptoms of asthma. Skin swabs, throat swabs, faecal samples, and bronchoscopy lung brush samples were obtained in thirteen asthmatic patients. Subjects were asked to take oral levofloxacin for 10 days. Repeated skin swabs, throat swabs, and faecal samples were collected at regular intervals until airway physiology measurement and bronchoscopy were repeated 8 weeks later. Biological samples underwent qPCR assessment of bacterial burden. Data were analysed using a combination of paired T-test and Friedman testing.
There were no significant differences in airway physiology measures including fraction of exhaled nitric oxide, end tidal carbon dioxide, and skin prick allergy testing, post exposure to antibiotic. Bacterial counts in faecal samples (n=37), skin swabs (n=52), throat swabs (n=49) and lung brushes (n=88) did not change significantly over the study period. When patients were stratified by eosinophil count (elevated >0.4x109) there were no significant changes in bacterial count, p=0.24. When patients were stratified by disease severity (according to GINA guidelines) there were similarly no significant changes in bacterial count, p=0.53. Streptococcus-specific qPCR was assessed for faecal samples and there were no significant changes in bacterial counts at the various time points, p=0.37.
Airway physiology and the bacterial density of faeces, skin, throat, and lung samples do not change meaningfully after an asthmatic patient is exposed to an antibiotic. Sequence data will be key to further assess for community compositional changes in response to antibiotics.
First SupervisorConor Burke
Second SupervisorLiam Cormican
CommentsSubmitted for the Award of Doctor of Medicine to the Royal College of Surgeons in Ireland, 2020
Published CitationO'Carroll O,. Reproducibility of the Respiratory Microbiome in Asthmatic Patients [PhD Thesis] Dublin: Royal College of Surgeons in Ireland; 2020
- Doctor of Medicine (MD)
Date of award2020-05-31
- Doctor of Medicine (MD)