Publications by authors named "Alicia B Mitchell"

Purpose Of Review: Lung transplantation presents a rescue therapy for those with end-stage lung disease. Survival in lung transplant patients remains limited due to chronic lung allograft dysfunction (CLAD), a range of pathologic manifestations leading to graft loss. The mechanisms underlying CLAD remain poorly understood, and the lung microbiome has been suggested as a potential contributor to this condition.

View Article and Find Full Text PDF

Background: Lung transplantation provides a unique opportunity to investigate the constituents and temporal dynamics of the human pulmonary microbiome after lung transplantation. For methodological reasons, prior studies using metagenomics have detected DNA viruses but not demonstrated the presence of RNA viruses, including those that are common community acquired. In this proof-of-concept study, we aimed to further characterize the pulmonary microbiome after lung transplantation by using metagenomic next-generation sequencing (mNGS), with a particular focus on the RNA virome.

View Article and Find Full Text PDF

and are gram-negative organisms that achieve colonization within the lungs of patients with cystic fibrosis, and are associated with accelerated pulmonary function decline. Multidrug resistance is a hallmark of these organisms, which makes eradication efforts difficult. Furthermore, the literature has outlined increased morbidity and mortality for lung transplant (LTx) recipients infected with these bacterial genera.

View Article and Find Full Text PDF

One of the great challenges of lung transplantation is to bridge the dichotomy between supply and demand of donor organs so that the maximum number of potential recipients achieve a meaningful benefit in improvements in survival and quality of life. To achieve this laudable goal is predicated on choosing candidates who are sufficiently unwell, in fact possessing a terminal respiratory illness, but otherwise fit and able to undergo major surgery and a prolonged recuperation and rehabilitation stage combined with ongoing adherence to complex medical therapies. The choice of potential candidate and the timing of that referral is at times perhaps more art than science, but there are a number of solid guidelines for specific illnesses to assist the interested clinician.

View Article and Find Full Text PDF
The lung microbiome and transplantation.

Curr Opin Organ Transplant

June 2019

Purpose Of Review: Lung transplantation survival is still limited compared with other solid organ transplant modalities, due to a range of factors that are continuing to be elucidated. However, new research is emerging which indicates that the microbiome of the lungs, and of other organs, may have important implications for immune response and mediating transplant outcomes. Pathogenic bacterial and viral species are known to have deleterious effects on the allograft, but taking a more global view, and considering the overall composition of the community of microbial species may undercover a greater understanding of the complex interplay involved in allograft dysfunction.

View Article and Find Full Text PDF

Background: Lung transplantation provides a unique opportunity to investigate the dynamics of the human pulmonary virome that is transplanted within the donor lungs. The pulmonary virome comprises both "resident" and "transient" viruses. In this study we aimed to analyze the dynamics of the "transient" members.

View Article and Find Full Text PDF

There have been great advances in the methodologies available for the detection of respiratory viruses. Accompanying this, our knowledge surrounding the impact of these viruses has also made a great leap forward. We have come a long way from the once commonly accepted belief that the lower respiratory tract was sterile and that the detection of any microbial species must represent a breach in host defence and likely be associated with symptomatic infection.

View Article and Find Full Text PDF

Background: Bronchiectasis is a chronic respiratory condition. Persistent bacterial colonisation in the stable state with increased and sometimes altered bacterial burden during exacerbations are accepted as key features in the pathophysiology. The extent to which respiratory viruses are present during stable periods and in exacerbations is less well understood.

View Article and Find Full Text PDF

Background: Respiratory viruses circulate constantly in the ambient air. The risk of opportunistic infection from these viruses can be increased in mechanically ventilated patients. The present study evaluates the feasibility of detecting airborne respiratory viruses in mechanically ventilated patients using a novel sample collection method involving ventilator filters.

View Article and Find Full Text PDF

Once considered a sterile site below the larynx, the tracheobronchial tree and parenchyma of the lungs are now known to harbor a rich diversity of microbial species including bacteria, viruses, fungi, and archaea. Many of these organisms, particularly the viruses which comprise the human respiratory virome, have not been identified, so their true role is unknown. It seems logical to conclude that a "healthy" respiratory microbiome exists which may be modified in disease states and perhaps by therapies such as antibiotics, antifungals, and antiviral treatments.

View Article and Find Full Text PDF

Respiratory viruses are very common in the community and contribute to the burden of illness for patients with chronic respiratory diseases, including acute exacerbations. Traditional sampling methods are invasive and problematic to repeat. Accordingly, we explored whether respiratory viruses could be isolated from disposable spirometry filters and whether detection of viruses in this context represented presence in the upper or lower respiratory tract.

View Article and Find Full Text PDF

Despite the dominant role of community-acquired respiratory viruses as etiological agents of disease, there has been little focus to date on the translation of rapidly developing diagnostic modalities, such as next-generation sequencing techniques in the examination of lower respiratory tract samples. When applied, these techniques should inform strategies to both understand the nexus between health and disease states of the respiratory virome, and drive a paradigm shift in how the practicing pulmonologist views the conceptual framework of respiratory infections. The lower respiratory tract was once thought to be a sanctuary site from microbiological colonization owing to the efficacy of upper airway-protective mechanisms and the host mucosal barrier function of the lower airways, combined with both innate and adaptive immune responses.

View Article and Find Full Text PDF