The latest ERS congress report

Wednesday morning, a much-changed Milan and ERS appeared: the temperature had dropped, there was light rain, the city smelled of flowers and green grass, and a scarcity of people in the huge conference convention. All the voices, faces, queues and noise of the hard-working ventilation – soon just a memory.

COVID-19 – a fading memory?

The International Respiratory Coalition (IRC) presented its work, and we were reminded that the world suffered from the COVID-19 pandemic just two years ago, but even that memory seems to be fading. The political area lost the knowledge of the pandemia, says Tobias Welte, Hannover, Germany. The next pandemic will, no doubt, come at some point in time, and we must not miss the chance to be better prepared. The IRC was initiated to develop ways to tackle hazards for health care in the respiratory field.

While during the COVID-19 pandemic an increased life expectancy in people living with chronic respi- ratory conditions was observed¹, re-prioritisation of health care resources also reduced the chances of survival in case of hospital admissions². Hospital mortality of an acute COPD exacerbation, Welte reminds the audience, is 5%, while 30% of persons experiencing an acute exacerbation of their COPD will be re-admitted to hospital. This comprises huge consequences for people and healthcare. Moreover, during the pandemic, more people died due to de-prioritised or delayed care of conditions like lung cancer, cardiovascular diseases or other comorbidities³. Exacerbation rates in COPD became higher than before⁴.

COPD: cheaper to stick to guidelines

Marc Miravitlles, Spain, showed numbers on the financial impact of low adherence to treatment guidelines in COPD^5,6, underlining the societal costs related to exacerbations. One COPD exacerbation has been shown to be a prognosticator for the next exacerbation⁷. Susceptibility to exacerbations in defined groups of persons and prognostics risk factors are known, thus, Dr. Miravitlles concludes: “We know whom we shall concentrate our efforts on in the first place”.

Wildfires, a burning health topic

More threats to global lung health: Christine Jenkins, Sydney, Australia, shows scientific evidence of the devastating impacts of wildfires on health: wildfire smoke is recognised for its toxicity, partly caused by the immense amount of respirable particulate matter. The frequency of wildfires increases after periods of dryness, and as we remember from pictures in the newspapers during summer 2023, wildfires are not limited to Australia or America, but occur in Europe. This gives rise to short and long-term consequences for lung health⁸:
Again, persons living with respiratory conditions are extra vulnerable in such environments, as shown by the increased need for oral corticosteroids⁹. Wildfires release greenhouse gases also contributes to global warming.

So, what can be done NOW to be better prepared for the future?

HEPA filters: For the threats caused by wildfires, use of HEPA filters as well as recommendations for vulnerable groups (children, pregnant women, elderly, and persons living with asthma and/or COPD) to wear face masks and assure valid rescue medication at home were discussed during the presentation.

Vaccinate: The importance of preventive vaccinations cannot be overemphasised, as it has been shown to both reduce morbidity and mortality10. Furthermore, there is still a need to improve diagnosis of COPD, primarily using spirometry, and with this, to identify persons with increased health risks.

Communicate: In the capacity as representative of GAAPP, an international coalition of 108 patient advocacy groups, Tonya Winders, Hendersonville, USA, emphasised the patient ́s perspective:
we were presented with a clear communication on what matters for patients with respiratory conditions.

We need to look at the person, not just the patient or the diseased organ, says Winders.

Moreover, mortality, morbidity, knowledge of risk factors, and communication matters to patients. She expands the point of the importance of communication and demands information in native languages, taking cultural adaptations into account, and the use of lay language. “Talk as if you were addressing a ten-year old.” As parts of the world are challenged in literacy, reliable digital health information is important, eg. collaborations with YouTube Health or the use of chatbots to manage chronic disease.

What can YOU yourself do?

Educate yourself: More suggested actions can be found in the paper “Climate change and respiratory disease: clinical guidance for healthcare” (see recommended reading).

Organize. If existing channels/organizations can be used to create more impact, use your voice. The IRC is welcoming actions to prepare healthcare for future challenges, but the IRC does not (yet) have national committees in the Nordic region. However, the IRC offers help and support to form one. Go to https://international-respiratory-coalition.org and find the “Join us” form.

Recommended reading:

IRC manifesto:

https://international-respiratory-coalition.org/ wp-content/uploads/2023/06/IRC-Manifesto-Final.pdf

Andersen ZJ, Vicedo-Cabrera AM, Hoffmann B, Melén E. Climate change and respiratory disease: clinical guidance for healthcare professionals. Breathe (Sheff). 2023 Jun;19(2):220222. doi: 10.1183/20734735.0222-2022. Epub 2023 Jul 11. PMID: 37492343; PMCID: PMC10365076.

The ability to monitor certain aspects of patients’ health from their home has become an increasingly popular telehealth option that have been accelerated by the COVID-19 pandemic¹. Generally, telehealth spans from simple video calls between patients and doctors replacing routine visits to complex remote monitoring of general health or specific disease related parameters. Interestingly, telehealth as such have been shown to cut down on patients’ travel costs² and infection risk at hospitals or in the GPs office³. But the overall health benefits are debated and a recent review of 29 studies utilizing remote monitoring in COPD care concluded that no important benefits for patients were obtained, neither looking at symptoms nor quality of life⁴. However, people who were monitored through telehealth technology and usual care had some reduction in risk of hospital re-admission⁴.

In COPD and asthma care, remote monitoring can largely be categorized based on the purpose of the monitoring:

1. To predict or foresee flare ups by collecting health and disease parameters. This kind of monitoring is usually associated with simple monitoring such as QoL questionaries and health parameters as body temperature which is report digitally and monitored by nurses or potentially AI.
2. To improve patient awareness of changes in symptoms by recording in digital diaries or mobile applications and thus realize potential triggers, which may lead to improved self-management.
3. To improve care by increasing treatment adherence and or compliance, which usually involves the use of smart inhalers or add-on modules in connection with a mobile application displaying the data for the patient.

Despite the development of various digital tools such as mobile applications, smart inhalers, and smart add-on modules, a general implementation of these remains a challenge due to complexities in the use and the relative high cost that patients are reluctant to pay⁵. The cost related to remote monitoring and associated increased workload of analysing reports need to be studied to show that the use of these is cost effective, providing better disease control and improved quality of life for patients⁵.

Thus, having the purpose in mind when trying to identify patients where remote monitoring can add value seems to be key –when it comes to remote monitoring of patients there is no one size fits all!

Reference to presentation: Current challenges in airways disease management – Evolution in GOLD: we cannot ‘see’ ‘C’ anymore and LABA/ICS are gone. Helpful or a hindrance?

Speaker: Antonio Anzueto, USA

When the first GOLD guideline document was released in 2001, the assumption was that poorer lung function led to poorer outcome. The best strategy was therefore thought to be a step-up approach where more pharmacotherapy was added depending on the severity of the lung function reduction.

By 2015, data had accumulated showing that there was no association between the severity by lung function and symptoms evolution, risk of exacerbations or even outcomes. Data also clearly showed that there were means to prevent exacerbations and reduce symptoms. The GOLD committee decided to divide patients into four groups, ABCD (2015 Global Initiative for Chronic Obstructive Lung Disease).

Exacerbations – not just about lungs

It was not fully understood until recent years that exacerbations changes disease progression. It is now recognized that exacerbations are bad and should be prevented. They trigger more inflammations, accelerate decline in lung function, increase worsening of comorbidities¹. Patients who are hospitalised due to exacerbation are significantly

at risk for cardiac events within the next 30 days. Exacerbations should be viewed in the light of the intimate interaction between lungs and the cardiovascular system.

There is strong data evidence to justify replacing the CD category with just E for Exacerbation prone patients, irrespective of symptoms. Whatever interventions done, they must address exacerbation risk.

State of the art COPD treatment – according to GOLD 2023

Based on the large amount of data gained in recent years to understand the role of bronchodilators, the committee decided to make following changes in GOLD 2023 guideline:

– “Initial therapy should consist of a LAMA+LABA combination…”

– “Consider LAMA+LABA+ICS combination if eos >300 cells/μL (practical recommendation…”

– “We do not encourage the use of LABA+ICS combination in COPD…”

– “If patients have COPD and concomitant asthma, they should be treated like patients with asthma…”

Gold 2023:

There are several publications showing that fixed LAMA/LABAs are better than ICS/LABA in lung function and reducing exacerbations.^2,3,4

Use of ICS

Safety issues: Patients on ICS based medications that are still not getting any clinical benefit, may have increased risk for pneumonia due to the change of the airway microbiome⁵. Eosinophils may serve as biomarkers to indicate risk of pneumonia: a very low eosinophil count (<100 cells/μL) marks an increased risk.⁶

Place in therapy: ICS, together with bronchodilators, are intended to give maximum bronchodilation and anti-inflammation. Programs including thousands of patients in registration studies have demonstrated that these medications decrease exacerbations⁷. Exacerbations are known to be key drivers for mortality in COPD⁸.

The importance and relevance of learnings from longitudinal studies was a topic in our previous issue of ERS congress report, and you can read more about the COPDGene and U-BIOPRED cohorts there. But because of its importance we wish to stay just a little longer on the subject.

The ATLANTIS¹ study, aiming to assess the involvement of small airways in asthma, presented by Monika Kraft (NY, USA), collected data from mild to moderate asthmatics for 8 years. Already in 1996, Dr. Kraft demonstrated that inflammation exists throughout the whole branch of the lungs. The study shows that the distal lung can no longer be referred to as the silent zone. ATLANTIS was the first study to collect data in a bigger sample size (n=773 individuals). Over 90% of study subjects were shown to have at least one sign of small airway dysfunction amongst all different measures performed². Physiological, but not CT measurements, are drivers for exacerbations, and oscillometry measurements are of value³. The ATLANTIS investigators hope to develop a single question-tool to be provided to clinicians that would allow identification of small airways dysfunction and with this, identifying who is at risk of exacerbations. Moreover, data from persons living with COPD is required.

A study cohort collecting real world evidence from asthma, COPD or combination of both, Alberto Papi (Cona, Ferrara, Italy) presented the 3 year long NOVELTY study⁴. The study starts from real life and physician’s diagnosis of disease, to thereafter break down the learnings into disease mechanisms⁵ and treatable traits.⁶ They are now starting to dig deeper into the molecular and underlying pathways and are hoping to present more insights characterizing new clinical endotypes within asthma and/or COPD. It will be exciting to see the future results of the study.

A session exploring how real-life research may aid decision-making and guideline development and complement RCT for better assessment of interventions.

Bias, both in randomised controlled trials (RCT) and Real-world evidence (RWE) is important to minimize, as pointed out by Dr Giorgio Walter Canonica (Milan, Italy). RCTs, on one hand might target a very narrow treatment group to mitigate confounding factors, whereas in RWEs, subpopulation results might get lost in the heterogeneity of the real world. While evidence of efficacy is the strongest with RCT, the evidence of effectiveness, i.e. how well a treatment works in practice in a broader population, is better shown with RWE¹. And thus, they complement each other, and both are needed.

Better use of real-world data

Aiming to raise the profile of real-life research, the Respiratory Effectiveness Group (REG) was formed. Together with EACCI (the European Academy of Allergy and Clinical Immunology), certain quality standards have been implemented. One point of action is to establish more registries for more systematic capture of real-world data².

The REG and EAACI also organized a workshop in March this year to discuss integration of RWE and EBM (Evidence Based Medicine) into next generation guidelines, in which regulatory bodies such as the FDA and EMA participated, as well as patient organizations. A second workshop in October will finalize the outcomes of the first workshop.

mHealth – getting more health data from mobile devices

The WHO (world health organization) defines mHealth as medical and public health practice supported by mobile devices, (e.g. mobile phones or personal digital assistants)³. With the huge collection of data, big data processing and artificial

intelligence (AI) algorithms can be used for future evidence generation⁴, says Dr Hilary Pinnock (Edinburgh, UK). Still, only a minority of mHealth is embedded in routine healthcare⁵, although an increase has been seen from 2010 and accelerated by the COVID pandemic. While traditional healthcare data collects data at visits, mHealth has the potential to capture so much more data over the course of an illness and/or a lifetime. EAACI lists a number of areas, e.g. epidemiology, health economics, public health, where mHealth can be of help.

Do mHealth data represent everyone in the real world?

There is a risk that patient tools might attract a specific “type” of patient. In a study to demonstrate pollen and wildfire impact on asthma symptoms, predominantly white, male colleague students with high income signed up – however women over 40 were more likely to keep reporting data. Out of 7593 enrolled, only 64 and 37 respectively, logged persistent data throughout the study period.⁶ So what happens, if we use biased limited data to train AI?

Use of automated feedback, like wearable devices may provide data that is more generalizable. Integration of these systems into routine practice is also a task for policy makers and administrators. We have a long way to go, concludes Dr Pinnock, before we are generating data evidence well from mobile devices and mHealth tools.

Even the tobacco industry acknowledges the harm in smoking and claims to make efforts to transform by reducing health impacts of its products. The solution – as proposed by tobacco companies is not to end nicotine use but switching users to e-cigarettes. The e-cigarette market is growing rapidly but more typically from attracting new users than switching old smokers. Vaping is also where the industry sees its future growth, especially if combined with cannabis. Several of the biggest tobacco companies are investing in the cannabis industry – both medical and recreational use.

Vaping is not harmless. Combustible cigarettes and e-cigarettes, with or without nicotine, increases the resistance of small airways and decreases small airway function1. Sven-Erik Jordt, USA, presented findings from Duke University, that most of the available e-liquid products contain synthetic cooling agents. Addition of menthol is regulated in many markets since its cooling and pleasant sensory effects facilitate smoking and tobacco product initiation. However, since these derivates are without flavor, these may bypass regulatory limits on menthol content in tobacco products as they may not qualify as “characterizing flavor”. This is a potential regulatory loophole that should be considered, especially since health effects of inhaling these compounds are not fully known.

Environmental burden

Beyond the direct health impact cigarettes have on consumers, the lifecycle impacts on the environment are considerable: from deforestation for agriculture of the sensitive tobacco plant that requires heavy use of fertilizers and pesticides, and burning biomass for tobacco curing, to the post-consumer waste with cigarette butts ending up in the oceans, poisoning water.

Greenwashing the industry

To counteract the bad PR and divert attention from the harm done both from manufacturing and consumption of cigarettes, several tobacco companies are establishing an ESG concept (environmental, social and governance for sustainable development) to appear “green” and ethical. They are playing the game to keep investors and succeeding at it. For instance, Philip Morris Industry managed to get a high score on the Dow Jones Sustainability index. The tobacco companies also portray themselves as socially conscious, making charitable contributions, especially in LMIC (low-middle income countries). Labelling tobacco companies as philanthropists: That’s rich coming from an industry that sells a product that kills half of its long-time users, says Elif Dagly (Turkey).

The prevalence of smoking tobacco has unfortunately not been a positive development: The number of smokers globally increased from 0.99 billion in 1990 to 1.14 billion in 2019, most of them coming from LMIC countries. Globally in 2019, smoking tobacco use accounted for 7.69 million deaths and 200 million disability adjusted life years.²

In the final comment on the global burden of tobacco use, Om Prakash Kurmi of the Coventry University, UK concluded that the smoking epidemic is far from over.

The good news, however, is that health benefits come quickly on smoking cessation and life expectancy is increased – it is never too late to stop smoking.

There is a difference between weather and climate, but still, one cannot help wondering if the current temperatures in Milan around 30 degrees is not to underline what a hot topic global warming is. The congress theme is Pollution, climate change and sustainable developments and the aim has been to integrate these themes as broadly as possible. The interconnection between planet health and respiratory health is becoming more and more evident. Pollutants are not only a health hazard, but many pollutants are also sources of high CO₂ emissions¹. Use of fossil fuels causes both particulate matter and CO₂. We breathe climate change, and addressing emissions will benefit both planet and human health.

At the Sunday session “Targeting treatable traits in severe chronic obstructive pulmonary disease: a nonpharmacological approach”, we got an update on ‘treatable traits’ for advanced COPD patients beyond ‘regular care’. There was a consensus throughout the session that we should regard the COPD patients as more than the diseased lung. Evidence evolved during the past decade shows that severe COPD patients benefit a lot from pulmonary rehabilitation programs. Frits M.E. Franssen from the Netherlands provided us with up-to-date insights on how to rehabilitate a severe COPD patient.

Franssen presented the definition of pulmonary rehabilitation as a comprehensive intervention based on a thorough patient assessment followed by patient tailored therapies. The aim of pulmonary rehabilitation is to improve the physical and psychological condition of patients, not only with COPD but also with other chronic respiratory diseases, as well as to promote a healthy lifestyle. There is an ongoing international debate about the core components of pulmonary rehabilitation. It is important to remember, says Franssen, that pulmonary rehabilitation is more than exercise training and education. If we look at the needs of individual patients, interventions like nutritional support, psychological support, lifestyle interventions, optimization of pharmacotherapies and adherence to medication and advanced care planning are also components with potentially large benefits. Looking closer at the benefits, most evidence is on improvement of exercise tolerance, reduction in shortness of breath and improvement in quality of life¹. 

However, studies also show that other important outcomes of pulmonary rehabilitation include improvement in body composition, reduction in psychological symptoms and reduction in mortality and re-admissions. Looking further into patient groups, hyperinflation is associated with dyspnoea, therefore patients with severe hyperinflation could be prevented from exercising to a sufficient level. Interestingly, when targeting specifically at this group of patients, Vanfleteren and colleagues (Vanfleteren et al., Arch Phys Med Rehabil 2018) demonstrated that static lung hyperinflation does not prevent patients from benefiting from pulmonary rehabilitation.  

Severe exacerbations in patients with chronic obstructive pulmonary disease (COPD) is a challenge for both patient and health care system. Methods to prevent exacerbations are therefore needed. 

To evaluate whether a primary care integrated disease program (IDM) can reduce health service utilisation, patients with severe COPD were studied in a real-world setting. All individuals managed by the Best Care program (2011-2019, Ontario Canada) with a clinical diagnosis of COPD were included (N=2451, mean age 67 years, female rate 48.3). Primary endpoint was COPD-related hospital admissions and COPD related ED visits, and the secondary endpoint was all cause hospitalizations and admissions and all-cause ED visits.

Through an interrupted time series analysis of retrospective administrative data, the study assessed the number of COPD-related and all-cause hospital admissions and emergency department (ED) visits 36 month pre- and post IDM program initiation. IDM program patients were linked to administrative health databases in the study amassing 13,000 person years of follow-up. In the year prior to commencing IDM, 9.2% of individuals experienced a total of 383 COPD related hospitalisations, and 20.4% individuals generated 809 COPD-related ED visits.

The study found that the monthly rate of COPD related hospitalisation and ED-visits in 1000 individuals 12 month after program initiation was decrease by 9.1 and 19.0 respectively, corresponding to a relative reduction of 56% and 46%. After 36 months, monthly rate of events per 1000 individuals almost halved.

Kian Fan Chung (London, UK) shared insights from the U-BIOPRED cohort, investigating Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes. 

Here, system biology was applied to reveal mechanisms of severe asthma. This resulted in the definition of several clusters, each comprising a distinct phenotype of the disease. One of the discovered clusters of biomarkers include the combination of blood eosinophils and fraction of exhaled nitric oxide, FeNO to be able to detect the IL-13 Type2 hi phenotype¹. Other clusters of biomarker combination define phenotypes of disease including “T2 low/non-T2”, which can either involve inflammasomes, Interferons and tumor-necrosis factor, or show signs of oxidative stress and aging, while being paucigranulocytic.

• Most persons living a life with COPD have at least one additional, clinically relevant chronic disease
• Many chronic diseases have shared risk factors, e.g. aging, smoking, pollution, physical inactivity, and poverty
• Co-occurring diseases potentially share pathobiological mechanisms
• The term “syndemic” is used to describe the co-occurrence of diseases with shared mechanisms and risk factors
• Approaching syndemic diseases including COPD in the multimorbid stage clinically could lead to more patient-centric rather than a single-disease approach to therapy