18 minute read
IRISH THORACIC SOCIETY
AUTHOR:
James Fogarty
IRISH THORACIC SOCIETY, ANNUAL SCIENTIFIC MEETING, KILLASHEE HOTEL, NAAS, 1-3 DECEMBER 2022
ITS meeting hears about changing nature of asthma therapy
The therapeutic face of asthma has changed remarkably for clinicians over the decades, the Irish Thoracic Society Annual Scientific Meeting 2022 was informed during a series of oral presentations.
The meeting took place from 1-3 December 2022 at Killashee Hotel, Naas, Co Kildare. It was the Society’s first inperson meeting since 2019.
In one oral presentation, the meeting heard about the Inhaler Adherence in Severe Unstable Asthma (INCA-Sun) randomised clinical trial.
Presenting on behalf of the trial’s research group, Prof Richard Costello from Beaumont Hospital, Dublin, delivered a talk entitled ‘Use of digital measurement of medication adherence and lung function to guide the management of uncontrolled asthma’.
Prof Costello said a number of members of the Society had taken part in the multicentre study. The study was carried out in 10 centres in Ireland and the UK. Patients older than 18-years-old were enrolled in the 32week single-blind randomised clinical trial, with an eight-week education period and three treatment adjustment phases.
Treatment decisions guided by the digitally acquired data on adherence, inhaler technique and peak flow were compared with current methods. Prof Richard Costello
Prof Costello said that since he started in clinical practice the area of asthma “at least therapeutically” has changed “remarkably”.
He recalled the “massive change” that occurred with the introduction of inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) therapy and then the “dramatic” transformation brought by the introduction of monoclonal therapies.
“Despite these amazing drugs, there are a number of really important practical aspects of asthma management that need to be considered by us. And the first one is, many patients with asthma don’t take their treatment,” Prof Costello said, stating this figure was estimated to be about 50 per cent.
“The other problem is patients don’t tell you that they have been non-adherent. This means that you are liable to increase the treatment for someone when in fact you’d be better to address their adherence.”
Furthermore, inhaler technique was also poor for many people, which meant that “people can be adherent, but [are] not effectively getting the drug”. Another important factor was that asthma symptoms can be very non-specific.
“Think of the asthma patient who during the pandemic gained some weight and has started to reflux. They are going to have increased breathlessness, intermittent cough, particularly at night, and that is going to sound like asthma, unless you objectively assess and show that they have asthma,” Prof Costello said. “So there are a lot of practical problems with how we implement the treatment of asthma.”
He highlighted the INCA device, which records when and how the inhaler was taken. Each time the inhaler is opened and taken, an audio file is created, which can then be analysed and used to improve adherence.
Prof Costello said that a clinical decision tool has been developed, which encodes the decision for treatment adjustment, and he praised its creators.
“It formed the basis for this trial,” he said. “If you digitally assess adherence, if you digitally measure low function, and you then make the decisions objectively using
a digital clinical decision-making tool, will you get a difference in outcome in poorly controlled severe asthmatics?”
In the study, the active group had personalised biofeedback on inhaler adherence, technique, and peak expiratory flow (PEF). Treatment decisions were informed by digital data. The control group had adherence coaching, inhaler training, and an action plan. Treatment was adjusted base on pharmacy refill rates, asthma control, and risk exacerbations. Both groups used a digitally-enabled inhaler and PEF.
Of the 220 patients that consented to participate, 213 were randomised, with 105 in the control group and 108 into the active group. Some 200 completed the 32-week study. The mean age was 47 years; 137 women participated. They had experienced high levels of exacerbations in the previous year.
At week 32, 11 of the active and 21 members of the control group required add-on biologic therapy. Some 16 per cent of the active group and 44 per cent of the control group who initiated fluticasone propionate (FP) 500mcg per day, had their dose increased to 1,0000mcg/day. Some 26 of the 83 (31 per cent) in the active group and 13 of the 73 (18 per cent) control patients were reduced to FP 500mcg/day.
The study found that, despite a lower treatment burden, there were differences in asthma control, lung function, T2 inflammation, nor exacerbations between the two groups. It also meant that by not escalating treatment in non-adherent patients, there were no increased sideeffects, increased exacerbations, and loss of asthma control.
It concluded that evidence-based care informed by digital data safely led to a significantly lower treatment burden.
“Patients were 58 per cent less likely to be prescribed a biologic if you use the digital system,” said Prof Costello. “If you used the digital system you were 75 per cent less likely to have your ICS dose increased from a medium dose. And you were twice as likely to have your dose down escalated. About 40 per cent of patients were affected in a positive way by the digital system in terms of less treatment burden as opposed to increased treatment burden.”
In terms of cost-effectiveness, this led to a €3,000 per person savings for severe asthma cases. “We enrolled 200 patients, the overall study saved €500,000, if you did it as a direct cost model.”
Responding to questions from the floor, the number of people with “truly refractory asthma is really very small”, Prof Costello said.
“What this system allows us to do is rapidly identify who has the refractory asthma, so we can get them to a biologic treatment quicker.”
Speaking on de-escalation, he cited a paper by Dr Vincent Brennan et al, “which indicated how dangerous high-dose inhaled cortical steroids are.”
“Some 20 per cent of people on highdose inhaled cortical steroids, that’s 500[mcg] BD, had adrenal insufficiency…. That is someone who has been taking 500 twice a day for a long time is extraordinarily, potentially harmful.
“One of the things that came out of the study is that if you make people adherent to high-dose inhaled steroids, and asthma isn’t the cause of their problem, you sure as hell are giving them a huge risk of adrenal insufficiency.”
Referencing COPD patients on a ward round who may have been on inhaled steroids for a long time, Prof Costello said “you look at the co-morbidities, cataracts, diabetes, and osteoporosis, and you start thinking they look like steroid-related side-effects”.
The outcomes of pulmonary arterial hypertension (PAH) patients in Ireland are comparable with those in other European centres, the Irish Thoracic Society Annual Scientific Meeting 2022 was told.
During the meeting’s oral presentations, a study on the incidence and outcomes of PAH in the Republic of Ireland by Dr Sarah Cullivan of St James’s Hospital, Dublin, was delivered.
Dr Cullivan, who won the prize for best oral presentation, was presenting on behalf of the national pulmonary hypertension unit (NPHU) at the Mater Misericordiae University Hospital, Dublin.
Pulmonary hypertension (PH) is a progressive disease of the pulmonary vasculature, which is characterised by premature morbidity and mortality. The study defined the characteristics of PH in the NPHU. The main objective was to examine PAH, which is a subgroup of pulmonary hypertension characterised by an elevated mean pulmonary artery pressure and elevated pulmonary vascular resistance.
Cases of PH, which were referred to the NPHU between 2010 and 2020, were included in the study. PH was defined as a mean pulmonary artery pressure >25mmHg at right heart catheterisation.
Dr Cullivan said PH had an estimated prevalence in 1 per cent of the global population.
“PAH is a rare and progressive disease of the pulmonary circulation. The global incidence is estimated to be about six
cases per million of the adult cases,” Dr Cullivan said.
“It was often considered a disease of young females, but as we know the demographics are changing. It’s increasingly diagnosed in older persons. There’s often equal sex distribution when patients are older and they often have concomitant co-morbidities.”
There were currently three main treatment pathways and double combination therapy was considered the standard of care for patients without significant cardiopulmonary comorbidities, she said.
“Outcomes were originally quite poor. The median survival… was 2.8 years in the 1980s, but this has improved in recent decades.”
She said that the retrospective study’s objective was to “address the paucity of data regarding the characteristics of PAH in Ireland” and it used the 2015 PAH definition by the European Society of Cardiology (ESC) and European Respiratory Society (ERS).
Some 415 cases of PH were identified by the study. Group 1 was made up of PAH patients and accounted for 39 per cent (n=163) of cases, with a calculated annual incidence of 3.11 per million population (95 per cent CI, 1.53-4.70).
“If you focus on the group as a whole you can see there was a female predominance at 77 per cent and a mean age of 56. Haemodynamics were quite severe…. The mean DLCO [diffusing capacity for carbon monoxide] was 49. The one, three, and five-year survival was 89, 75, and 65 per cent,” she said.
“In our cohort, the leading subgroup was PAH associated with connective tissue disease at 49 per cent or 80 cases. This was followed by IPAH [idiopathic pulmonary arterial hypertension] at 20 per cent or 33 cases, and then congenital heart disease-associated PAH.
“PAH associated with connective tissue disease, showed female predominance at 90 per cent, the mean age of diagnosis 64. Patients typically presented with quite symptomatic disease and haemodynamics were quite severe.
“Between 56 and 18 per cent of patients received double or triple combination therapies in the first 12 months following diagnosis.”
She said that there were a number of important points for discussion, including that there was a marked female predominance in this cohort and the mean age of diagnosis in this cohort was quite young at 56.
“This could suggest that we might be missing the older cases of PAH in male cases,” said Dr Cullivan.
“We also see that patients typically present with quite advanced and symptomatic disease. This could suggest the need to improve disease awareness and case recognition at an earlier stage of the disease trajectory. This is once again reinforced by the incidence, which appears to be quite low relative to global estimates.”
She highlighted, from a treatment perspective, the revised ECS/ERS guidelines have recommended upfront double combination therapies “so in that sense we are ahead of the game”.
“Outcomes are quite good when we are compared to other European centres. It is widely accepted that the outcomes for those with systemic sclerosisassociated PAH are quite poor and certainly this requires additional research and exploration,” she said.
In terms of limitations, she said that the study was retrospective and there was missing data.
“Furthermore, not all cases of congenital heart disease associated with PAH were referred to the unit as they are often managed by cardiology, which could mean the incidence of that cohort, and also the entire cohort, is underestimated,” Dr Cullivan said.
“In conclusion, this study highlights the outcomes of PAH in Ireland is comparable in other European centres; however, the incidence appears low.”
There was also the need to improve disease awareness and its evolving phenotype.
“Increasing access to diagnostics, which includes right heart [catheterisation], and a perspective national registry are important ways to address this,” she said.
She was asked from the floor what she thought about echocardiography as a tool to identify PH in this group.
“I know we had the detect algorithm for patients with systemic sclerosis…. But I think this data would suggest that we are not using that screening tool. That’s supposed to be done in asymptomatic patients and these patients are typically presenting with functional class 3 or 4 symptoms. Greater awareness of the high prevalence of PAH in that cohort by the rheumatologists who are managing those patients would be incredibly important."
Prof Marcus Kennedy and Dr Sarah Cullivan
THE DEBATE – ‘E-CIGARETTES DO MORE HARM THAN GOOD’
Adebate on the pros and cons of e-cigarettes was one of the centerpieces of the Irish Thoracic Society Annual Scientific Meeting 2022.
Prof Luke Clancy of the Tobacco Free Research Institute chaired the debate, which proposed that ‘e-cigarettes are more harm than good’.
Prof Des Cox of Children’s Health Ireland spoke in favour of the motion, while Dr Emer Kelly of St Vincent’s University Hospital, Dublin, opposed it.
At the start of the debate, Prof Clancy asked for a show of hands on who agreed with the motion, which he described as a “nice contentious issue for debating”.
The majority of the attendees signaled they supported the motion.
Supporting the motion
Prof Cox said that a 2021 Health Research Board (HRB) systematic meta-analysis presented an overview from a number of studies, which had examined outcomes for nicotine replacement therapies (NRTs) versus e-cigarettes.
“They couldn’t find any effect from the time point of six months; in other words e-cigarettes weren’t that effective at helping people quit at the point of six months,” he said.
Bupropion has been shown to be very effective at smoking cessation, he said.
Prof Cox cited a Cochrane Review that using bupropion made it between 52to-77 per cent more likely that a person would stop smoking.
“There is conflicting evidence as to whether e-cigarettes are any good for tobacco cessation, but at best they are no better than NRT.”
Explaining why he believed e-cigarettes should not be used in smoking cessation, Prof Cox highlighted that a common phrase used by ‘provaping lobbyists’ was that e-cigarettes were 95 per cent less harmful than tobacco cigarettes.
“That is one of the worst ‘factoids’ out there about this,” he said. “Where this statement came from was a 2013 paper from a group of 13 tobacco control experts looking at all the different products and how harmful they were compared with tobacco cigarettes. Actually, in the study itself, the authors said a ‘limitation of this study is the lack of hard evidence for the harms of most products on most of the criteria’. So even in the paper they said there was no hard evidence for what they were suggesting.”
In terms of the long-term impacts, Prof Cox cited research published earlier this year in the New England Journal of Medicine on ex-smokers who used e-cigarettes over a couple of years. Airway biopsies were taken from the ex-smokers and found areas of constricted bronchiolitis.
“They also found that when people stopped vaping, this regressed,” he said. “It is possible that this is what we might see in the next 20 years in the airways of people who chronically vape.”
He also highlighted that an ingredient of e-cigarettes, diacetyl, had been linked with bronchiolitis.
Citing a study ‘The association between e-cigarette use and asthma among combustible cigarette smokers’, which had 3,000 participants, Prof Cox said it found a 39 per cent greater risk of asthma in the people who vaped who had never previously smoked.
“So again, there is an association with a chronic condition.”
In the European School Survey Project on Alcohol and Other Drugs (ESPAD) survey, which looked at 2019 data, 39 per cent of teenagers in the 15-to-16 age group had previously used e-cigarettes.
“A smaller proportion, about 14 per cent, were using them on a regular basis; this is a significant increase from the previous ESPAD survey in 2015. There is a rising incidence of the use of e-cigarettes among adolescents,” said Prof Cox.
Discussing e-cigarettes as a gateway to tobacco products, a HRB review published in 2020 found an over four-fold increased risk in teenagers, who vaped, of moving on to using tobacco products.
He concluded that e-cigarettes were not an effective tobacco cessation tool and that doctors should be promoting well known and proven smoking cessation products. He added its chronic use was likely to be damaging to the airways.
“There is experimental evidence of that. There are case reports coming through that there are harmful effects on the airways,” he said.
Against the motion
Opposing the motion, Dr Kelly, whose main research interest is chronic obstructive pulmonary disease (COPD), acknowledged that she had an “uphill battle”.
“Us humans have a very complex
relationship with nicotine,” she said.
“It was in 1956 that the surgeon general report in the US stated a clear association with lung cancer and cigarettes. But in 2022 cigarettes are still freely available.”
She said that doctors detested cigarettes and they wished the product had never been invented.
“But they were and there are over a billion smokers in the world. There are six million deaths a year from smoking. We know that it is the single leading preventable cause of mortality. Aiding smoking cessation is the most valuable preventive medicine intervention that we can do.”
The majority of patients, 70 per cent, say they wished to quit and many seek medical advice on trying to quit, Dr Kelly said.
“So we need to keep our minds open, we need to at least consider e-cigarettes, if they can help at all.”
She said that “no matter what we do” about 9 per cent of pregnant women still smoke at the time of their delivery. Regarding teenage smoking, it was a multi-factorial issue, which included risk-taking behaviour, the meeting heard.
She said given it must be the case that many parents smoke given that approximately 20 per cent of adults are smokers.
“That means that kids, CF [cystic fibrosis] and asthma patients, they are being exposed to cigarette smoke,” Dr Kelly said. “We know for a fact that exposure to cigarette smoke is going to change lung development in a young lung, that it predisposes to obstructive lung disease and to cancer.”
She argued that anything that helped smoking cessation had to be good.
“There is literature about 800 smokers, half of them are put on nicotine replacement therapy, and half are put on e-cigarettes. About 10 per cent of those on nicotine replacement stopped and about 18 per cent of those on e-cigarettes stopped,” Dr Kelly said.
Dr Kelly also cited a 2021 Cochrane Review, ‘Electronic cigarettes for smoking cessation,’ which found that people were more likely to stop smoking for at least six months using nicotine e-cigarettes than using nicotine replacement therapy.
“For every 100 people using e-cigarettes to stop smoking, nine-to-14 might successfully stop, compared with only six of 100 people using nicotine replacement therapy.”
She said there was a need to change the thinking in addressing smoking as a public health problem.
“We need to challenge our thinking in this. Smoking has become concentrated in the poorest sections of society. These people need our attention,” she said. “Also what we have to offer smokers has become reduced.”
She said that there was good data regarding varenicline (Champix), “but has anyone tried prescribing it recently?”
“It is not available since April of last year. I rang a pharmacy before I gave this talk and it is not going to be available for a while yet.”
In the UK, in November of last year, the National Institute for Health and Care Excellence guidelines brought out a “comprehensive document” on prevention and promoting quitting, “and discussing the vaping products with our patients.”
In his rebuttal, Prof Cox said Dr Kelly’s data came from the UK, which was an outlier internationally.
“Very few countries have taken such a pro-vaping tack as the UK,” he said. He continued that neither the World Health Organisation nor the European Respiratory Society supported the use of e-cigarettes as a cessation tool. He also said there had been no dramatic decrease in smoking rates in the UK. He highlighted that many e-cigarette users were also smoking, and that there was a slight uptake in the number of adolescent smokers, and there was a strong association with e-cigarette usage with this increase.
Dr Kelly said while she took Prof Cox’s point on the UK information, “that doesn’t change the fact that it’s good information.” She added that bupropion was a “tough sell to patients with a sideeffect profile”, she said.
“Although Champix is a good option, it is just not out there.... The reality is in adult medicine our patients are smoking, and if they want to try e-cigarettes and if it works for them, we at least have to be the doctor that listens to them and brings them along that path,” Dr Kelly said.
During questions from the floor, the environmental impact of single-use, plastic e-cigarettes was highlighted.
“They are really bad for the environment,” Prof Cox agreed. “There’s been an upsurge in disposable vapes in the past year or two.”
As well as being single-use and plastic, they also had a lithium battery, Prof Cox said. “I think it’s certainly an argument for disposable vapes to be banned.”
Dr Kelly said she agreed that e-cigarettes should be regulated and that she does speak about both nicotine replacement therapy and e-cigarettes in her practice.
She cited one patient who was an inpatient in a psychiatric facility who was trying to give up smoking.
“He is not going to go cold turkey. He’s tried nicotine replacement before, so it is better for him than the 40 cigarettes a day he’s smoking. So I do discuss e-cigarettes with him, otherwise, we are ignoring the elephant in the room.”
Another question asked if there was any data on the length of time people vaped. Prof Clancy said that qualitative data from young adults found that users reported that a “big ‘advantage’” of e-cigarettes was they could be used any time and continuously.
“There is evidence that they are continuously using it and the levels of nicotine are quite high.”
Responding to another question, Prof Cox said that as far as he was aware there was very little evidence that there is a carcinogenic effect of e-cigarettes.
