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Bacterial infection plays an extremely important role in COPD exacerbations, according to Prof Sanjay Sethi, Professor of Medicine and Assistant Vice President for Health Sciences at the University at Buffalo, State University of New York, US.
Prof Sethi, who delivered one of the key guest lectures at the Irish Thoracic Society 2015 Annual Scientific Meeting, which took place in Cork on 13 and 14 November, said that the majority of exacerbations are in fact infectious in origin and that chronic infection, or “colonisation”, is likely to contribute to COPD progression.
“There are many more people who now recognise that there are bacterial exacerbations and that chronic infection plays a role in a certain proportion of patients,” Prof Sethi told the Medical Independent (MI).
“So there is quite a change in the way that people think about it. Our work and the work of other people has shown this. It is a combination of different things coming together; it is data-driven. It is being driven by research explaining how exacerbations happen, and showing that chronic colonisation is inflammatory.”
Prof Sethi described how chronic infection can lead to a “vicious cycle”, as the inflammatory response trying to clear the infection is often damaging to the immune mechanism.
“If you have a lot of neutrophils, the neutrophils release proteases,” he explained.
“Proteases themselves can damage your antimicrobial peptides and they are contributing to the whole cycle. That is why we call it the ‘vicious cycle’, because you can’t get out of it.”
Unreported exacerbations, which could be bacterial or viral in origin, are a significant problem.
“Patient have these episodes and they never report it,” he said.
“And then we miss these episodes. So I think these are episodes of increased inflammation of the lungs that could be driven by virus, bacteria, even could be non-infectious and could be the result of other inflammatory mechanisms. The problem is that because we are so struck with our definition of requiring therapy and requiring them to be seen by a healthcare practitioner, we haven’t paid sufficient attention to these unreported episodes and I think we need to, because they must be having consequences. People have already shown that they have worse quality life and they are also likely to lead to worsening of the disease over time.”
The clinical implications of understanding the link between bacterial infection and COPD include that antibiotics have a role to play in treatment exacerbations and that antibiotic prophylaxis can be used in certain patients.
Prof Sethi also said that understanding the host-pathogen interaction will lead to new interventions in the future and that the application of “prudent” microbiome techniques may have a role.
Also, he said that enhancing aspects of innate immunity and enhancing adaptive immunity through vaccines may also be used in the future in terms of managing COPD.
‘DOTS programme should be strengthened to reduce TB detentions under Health Act’
Research presented at the Irish Thoracic Society Annual Scientific Meeting in Cork has sought to raise awareness of people who are detained as a result of TB infection.
Researchers from Departments of Respiratory Medicine in the Mercy University Hospital (MUH), Cork, and St James’s Hospital, Dublin, described four cases of patients in MUH and two patients in St James’s who were detained under Section 38 of the Health Act 1947.
The first case involved a patient who was diagnosed with cavitary pulmonary TB and was monitored by the directly observed treatment short-course (DOTS) programme, but was not compliant with treatment and failed to follow up in the outpatients department.
The second case involved a female patient with a medical history of HIV who had multi-drug-resistant tuberculosis (MDR-TB) and refused to comply with further treatment and refused tests, while the third case involved a man with pulmonary TB with resected renal cell carcinoma who was not compliant with treatment on the DOTS programme.
Finally, the fourth case was a man with a history of TB in 1998 who was detained previously for non-compliance, moved to Cork for work, developed symptoms and was diagnosed with TB again but refused treatment.
All of the above cases were from MUH.
According to the researchers, compliance with treatment for TB and protecting the public from the spread of TB have assumed greater importance over the past decade, since the wider recognition of MDR-TB and XDR-TB and recognisable TB alliance with HIV, as well as the international measures to improve treatment adherence and completion.
Registrar in MUH Dr Lana Khorseed told the MI that the purpose of the study was to raise awareness of these issues in order to prevent detentions in the future.
“We are hoping that this will enlighten people and for them to focus more on this issue,” Dr Khorseed said.
While Dr Khorseed explained the researchers were not calling for the TB detention legislation to be amended, she did suggest that the DOTS programme could be strengthened.
“If this is stronger and made into a complete and powerful body in the community, it might reduce the need for patients to be detained in hospital,” she said.
Another study from the cystic fibrosis unit in St Vincent’s University Hospital, Dublin, presented during the meeting, focused on identifying predicators of frequent hospitalisations in cystic fibrosis.
Frequent hospitalisations were seen in 22 per cent of those studied. Risk factors predicting frequent admissions were lower FEV1 percentage predicted, chronic pseudomonas, and a previous history of frequent exacerbations.
“The presence of these risk factors identify a group of patients that may benefit from more intensive monitoring and treatment to prevent the adverse outcomes associated with frequent hospitalisations,” according to the authors.
Asthma patients and treatments ‘need to be stratified’
The use of corticosteroids needs to be better targeted in the management of severe asthma, delegates at the Irish Thoracic Society Annual Scientific Meeting heard.
Prof Liam Heaney, Professor of Respiratory Medicine in Queen’s University Belfast, provided details of the Medical Research Council UK Refractory Stratification Programme (RASP-UK), which will be rolled-out early next year to stratify the treatment of asthma for patients with severe forms of the condition.
The Programme, which Prof Heaney is leading, will deliver early ‘proof of concept’ studies in stratified phenotypes of patients with severe asthma.
In his presentation, Prof Heaney stressed that a “one-size-fits-all” approach does not work in the treatment of asthma, particularly in relation to steroids.
“There are a number of divisions and that is what happens with stratifications — you make different divisions,” Prof Heaney told MI.
“The key division at the start is steroid responsiveness and we know if you have a certain pattern of asthma, which is characterised by eosinophils in the airway, it tends to be steroid-responsive. However, we now know that whilst that pattern is often steroid responsive, in older patients other immune mechanisms come in that make them less responsive to the steroids and we often have to use high-dose steroids, including steroid tablets, which have great side-effects and problems for the patient. But we are fortunate, as there are a number of new drugs that are coming in that pattern of the disease, which we will have over the next five-to-10 years.”
Prof Heaney said that one of the major challenges in the area is the treatment of non-eosinophilic asthma.
“We have taken our eye off the ball a bit there,” according to Prof Heaney.
“There are undoubtedly aspects of the disease that don’t respond to steroids and will not respond to these new drugs and those are the patients that we need to concentrate our research efforts on now. We don’t completely understand the mechanisms behind this; it is called T2 low or Type 2 low or non-eosinophilic; all of these terms broadly mean the same thing. The mechanisms behind that, even what those patients completely look like… we have a lot to learn there and that is an important part of this programme. It is confounded too by the fact that we have given all of these patients all of the same treatments. So we are starting to see effects that are caused by the treatment, particularly the treatment that may not have been appropriate in the first, or may not have been appropriate to escalate to the levels it is at. So a lot of work needs to be done to target the currently-available treatments better to try and understand where the gaps are.”
UCD Conway Institute researchers among ITS 2015 award winners
Dr Sinead Walsh, UCD Conway Institute and St Vincent’s University Hospital, Dublin, won the award for Best Oral Presentation at the Irish Thoracic Society Annual Scientific Meeting.
Dr Walsh received the award for her presentation, which was entitled ‘Is Gremlin causing havoc in idiopathic pulmonary fibrosis?’
Pulmonary fibrosis was also the subject of the winner of the Best Poster Presentation Award. Dr Katherine Gaynor and Dr Noelle Murphy of the Conway Institute, UCD, and St Vincent’s University Hospital, Dublin, won the award for their presentation ‘Altered expression of bone morphogenetic protein accessory proteins in pulmonary fibrosis’.
The runner-up award went to Dr Michelle White, RCSI and Beaumont Hospital, Dublin, for her presentation ‘Antitrypsin augmentation therapy corrects neutrophil membrane structure cell activity’.
Dr Dermot Linden, Royal Victoria Hospital Belfast, won the Best Case Presentation for describing an interesting case of septic shock, while Dr Nicola Ronan from Cork University Hospital won the Best Case Study Poster award. Best Oral Presentation in the Paediatric Forum went to Dr JJ Fitzpatrick of Our Lady’s Children’s Hospital, Crumlin.
His presentation described how a need for oxygen on admission is associated with longer length of stay in paediatric pleural empyema.