Welcome to ERS 2022
ERS Committee members, Richard Costello, Dublin, Ireland, and Christopher Brightling, Leicester, UK, welcomed 15,000 delegates from across the world to share knowledge and best practice in the field of respiratory medicine. For the first time, delegates could participate either in person or online. As outgoing Science Council Chair, Prof. Brightling recognised some of the key achievements of the council, including the publication of a ‘living guideline’ on the management of hospitalised adults with COVID-19, so-called because it is updated as soon as new evidence appears. The council also responded to the need for more educational tools, launching the ERS Respiratory Channel, which offers a range of online content.
“Over the last few years, even though our clinical work has been plagued by COVID, there’s been so much innovation happening”
- Richard Costello, ERS Committee Member
Holistic management and rehabilitation of fibrosing interstitial lung diseases (f-ILDs)
This session on the holistic management and rehabilitation of f-ILDs to discuss the latest 
non-pharmacological interventions in clinical practice and consider the ‘new normal’ in the context of the pandemic. As an introduction, the audience listened to a short video prepared by Steve Jones, Chair of Trustees for Action for Pulmonary Fibrosis. He presented a traffic light summary of issues faced by patients across 18 countries. Common problems were lack of information and support for idiopathic pulmonary fibrosis (IPF) self-management, reimbursement for oxygen, access to respiratory nurses and pulmonary rehabilitation (PR), and cumbersome oxygen equipment. While many patients really value the remote consultations and data monitoring that came with the pandemic, for others the balance has shifted too far and they have lost important face-to-face contact.
Marlies Wijsendbeek, 
Rotterdam, Netherlands, presented data that supported Steve Jones’s assertion of a global increase in digital care during the pandemic but also showed that ~50% of patients still have no access to eHealth.
The feedback from 286 physicians and specialist nurses from 54 countries has been overwhelmingly positive with almost 100% believing that eHealth improved their patients’ quality of care. Home spirometry techniques are advancing and good correlation to hospital assessments has been shown.
Home monitoring also tended to improve psychological well-being in patients with IPF. There is potential to use digital support at all stages from pre-diagnosis through to palliative care (PC).
Elisabetta Renzoni, London, UK, discussed supportive care pathways for patients with f-ILDs and how these have been impacted by the pandemic. There are a number of barriers to the provision of PC, including a lack of local access, uncertainty over when to refer, and insufficient collaboration between respiratory and PC teams. To attend a PC consultation in person, patients have to overcome challenges of severe breathlessness and high supplemental oxygen requirements. A pilot programme to introduce a telemedicine option for PC at the University of California San Francisco was well received by patients and caregivers who reported improved symptom management, better understanding of illness and completion of advance care planning. This option allowed seriously ill and symptomatic patients to access speciality PC. Insufficient information throughout the course of the disease is another area of concern. Specialist ILD nurses are perceived by patients and carers as a key resource, enabling them to access help on practical management and triggering medical intervention when required. All IPF patients should have access to an ILD specialist nurse.
Supportive care of patients with f-ILDs can include PR and its sustained benefit was demonstrated for the first time in a recent Cochrane analysis. 
Anne Holland, Melbourne, Australia, described an immediate, significant improvement in dyspnoea with PR that was sustained for up to 12 months along with improved six-minute walk distance (6MWD). Although PR for IPF/ILD is recommended by multiple guidelines, national referral rates are low, e.g. 4.5% in Germany. However, access to remote PR has increased markedly as a result of the pandemic and was offered by 86.5% of programmes in the UK in 2021 according to the UK National Audit. Technology allows remote delivery via videoconferencing while monitoring pulse and oxygen saturation levels. Remote PR is just as effective as centre-based PR. From their experience during the pandemic, Prof. Holland found that 20% of patients were unsuitable for remote training for reasons including the risk of falls, high oxygen requirements and preference to exercise with other people. She concluded that the key to successful implementation is optimal patient selection.
“Our challenge for remote delivery options is making sure we get the right model of rehabilitation, to the right patient, at the right time”
- Anne Holland, Australia
Hypoxaemia on exertion occurs in about 40% of patients at diagnosis of ILD and is associated with a worsened prognosis. Magnus Ekström, Lund, Sweden, considered whether ambulatory oxygen should be prescribed to these patients. 
Dyspnoea results from a mismatch between the central ventilatory drive and the afferent signals from multiple systems throughout the body so oxygenation is only part of the bigger picture. In ILDs it is important to remember that patients suffer from serious mechanical insufficiencies and this cannot be solved by oxygenation. Ambulatory oxygen therapy may be helpful in some patients to slow the fall in oxygenation that occurs with exertion and delay the onset of dyspnoea. The American Thoracic Society (ATS) suggests using ambulatory oxygen in selective patients who have severe exertional hypoxaemia.
Trends, controversies and open questions in ILD
Cormac McCarthy, Dublin, Ireland, discussed new trends in diffuse cystic lung disease (DCLD) 
which includes lymphangioleiomyomatosis (LAM), pulmonary langerhans cell histiocytosis (PLCH) and Birt-Hogg-Dubé syndrome (BHD). These rare conditions often present as pneumothorax and it is important to accurately diagnose the type of DCLC in order to optimise treatment. New data has led to the development of guidelines, improved prognostication and a better understanding of the pathways than might underlie a common pathogenesis.
Acute exacerbations (AEs) occur with an annual incidence of 5–20% in patients with f-ILDs. Because effective treatment is a major gap in this field, AE-IPF patients have a poor prognosis of 2.2 months’ median survival time and 90% mortality within a year. ATS guidelines make only a weak recommendation to treat with steroids and make no recommendations for further therapies or adaption of antifibrotics. 
Michael Kreuter, Heidelberg, Germany, shared data from his recent survey on the real-life management of AE-IPF, which showed that almost all clinicians were treating with steroids. Almost a fifth of clinicians were treating with cyclophosphamide, an immunosuppressant, which has now been shown to worsen survival. Clinicians must beware of treatments that are only supported by retrospective, uncontrolled data.
“The use of steroids based on no evidence is being used by the majority of us”
- Michael Kreuter, Germany
Elisabeth Bendstrup, Aarhus, Denmark, reviewed the latest evidence for treatment options in pulmonary manifestations of autoimmune diseases, including systemic sclerosis (SSc)-ILD and rheumatoid arthritis (RA)-ILD. The first treatment choice for progressive disease is made according to whether the disease type is inflammatory or fibrotic 
When treating SSc-ILD, there is a well-defined treatment pathway based on good quality evidence. In patients with early inflammatory SSc-ILD, randomised, controlled trials (RCTs) of immunosuppressants have shown sustained benefit on forced vital capacity (FVC) for up to 2 years, with mycophenolate being better tolerated than cyclophosphamide. Other recent RCTs demonstrated improvements in lung function in SSc-ILD patients who were treated with tocilizumab for skin involvement and with nintedanib. In contrast, there are no RCTs at all to guide treatment in RA-ILD. Treatment pathways in RA-ILD are based on observational data only and suggest that abatacept and rituximab may stabilise lung function in the majority of patients. The latest retrospective data with methotrexate suggest that treatment may delay onset of ILD in RA patients.
The final presentation of the session was given by Philippe Camus, Dijon, France, founder of the drug-induced lung diseases website, Pneumotox.com. Set up in 1997, Pneumotox is a database for healthcare professionals offering free, quick access to literature and case study data to help them diagnose any drug-induced respiratory disorder. He paid tribute to mentors, colleagues, and authors as he gave a whistlestop tour of key cases that have led to the understanding of drug-induced respiratory pathologies since Sir William Osler published a report on morphia poisoning in 1880 right up to modern day cases associated with COVID vaccination, vaping and the ‘fat burner’ dinitrophenol.
ILD in connective tissue diseases: patient’s journey from diagnosis and new treatment strategies to transplantation
Genetic testing is valued by patients with ILDs but that knowledge brings stress, uncertainty and questions around data reliability and confidentiality. Antoine Froidure, Brussels, Belgium, discussed evidence to show the association between various genetic variants and connective tissue disease (CTD)-ILDs.
An analysis from the Finnish biobank showed that carrying the MUC5B gene increased lifelong risk in RA patients for developing RA-ILD. Also, higher levels of telomere-related gene (TRG) mutations were observed in patients who were diagnosed with RA-ILD at a younger age. Could either of these genetic factors have a role in diagnosis in clinical practice? Testing for TRG var-iants could be considered in patients with familial fibrosis or if they show any other clinical features of short telomere syndrome. Recent studies show that there may be value in including screening for MUC5B promoter variant in clinical practice but it’s currently used only in a research capacity.
“The best way to tackle patient concerns around genetic testing will be to provide expertise in a multidisciplinary fashion”
- Antoine Froidure, Belgium
Bruno Crestani, Paris, France, reviewed new developments in diagnosis and treatment strategies. High-resolution computed tomography (HRCT) is currently the gold standard for the diagnosis of ILD in CTD patients but it exposes patients to radiation. An alternative approach would be to give all RA patients lung ultrasound and to screen for serum KL-6, an indicator of disease activity in PF. Only patients who show an abnormality in these two parameters would need HRCT.
“Treatment pathways will be more complicated but more patient-focussed”
- Bruno Crestani, France
CTDs are considered a risk factor in lung transplantation but recent data have reported reasonable short- and long-term outcomes in patients with CTD compared with other lung fibrosis patients. Jose Manuel Cifrian Martinez, Santender, Spain, explained that patient selection is key and described extrapulmonary conditions that should be considered before transplantation.
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In the final presentation, Ingrid Lundberg, a rheumatologist from Stockholm, Sweden, introduced the new way to categorise myositis. To date, 16 autoantibodies have been identified that are specific to myositis and are not found in other autoimmune diseases. The largest subgroup is the anti-synthetase antibodies and it is these, along with anti-MDA5, that are associated with ILD. Patients with myositis and an ILD-associated anti-synthetase antibody may initially present with symptoms from the lungs, joints or muscle but lung pathology ultimately occurs in up to 90% of cases. Patients categorised in the anti-MDA5 subgroup usually present with a skin rash and carry a very high risk of developing rapidly progressive ILD. In terms of treatment, there are no RCTs in myositis and ILDs but pulmonary function of these patients may improve during immunosuppression. Treatment should be started immediately and stepped up as needed. Patients with rapidly progressive ILD should be treated aggressively and lung transplant considered early. The speaker encouraged the audience to use the MyoNet registry, an international database of longitudinal data from more than 6000 myositis cases for research on genetics, clinical and laboratory data, serology and muscle biopsy data.
“The most important message is that these are complicated cases and we need to manage them in a multidisciplinary team”
- Ingrid Lundberg, Sweden
Challenges in imaging of ILDs
IPF is well defined with respect to disease course, management guidelines, risk factors, and clinical, functional and radiological characterisation. However, other ILDs are less well characterised and are often challenging for the multidisciplinary team to diagnose. The pathways of disease progression are also different depending on the category of ILD, e.g. idiopathic interstitial pneumonia (IIP), autoimmune, or exposure-related. Veronika Müller, Budapest, Hungary, considered how to assess disease progression in a 75-year-old female with systemic sclerosis (SSc). An audience poll recommended clinical and functional assessment of this patient every 4–6 months, which was supported by the latest society guidelines and the speaker. HRCT should be used to detect increased extent of fibrosis, such as increased coarseness of reticular abnormality or lobar volume loss. Computer-based quantitative CT can be helpful to provide a more objective and reproducible measure of progression. Lung function assessment should include composite values of FVC, diffusing capacity for carbon monoxide (DLCO) and total lung capacity.
The requirement for follow up will vary between patients according to the different progression rates of diseases. For example, the audience agreed that annual clinical and functional assessment would be appropriate in the case study of a 70-year-old female with connective tissue disease ILD (CTD-ILD) and RA, who presented with dry cough and showed only minor changes on chest CT, provided she did not experience any substantial changes in function.
“In ILD diagnosis and follow up, the multidisciplinary discussion is really key”
- Veronika Müller, Hungary
Helmut Prosch, Vienna, Austria, explained how septal lines in the pulmonary lobes may be caused by engorged lobular veins or lymphatics, or thickened septal walls. Categorisation into acute or chronic, and aspects of their appearance can help with differential diagnosis. 
Prof. Prosch presented the case of a patient with pulmonary veno-occlusive disease, which is a rare cause of pulmonary hypertension caused by an occlusion of the postcapilliary venous root. The chest CT showed signs of pulmonary hypertension, smoothly thickened interlobular septa and ground glass opacities. One of the key challenges in diagnosis of ILDs is the high degree of variability between observers when describing CT pattern. New artificial intelligence-based software can be used to extract the key parenchymal abnormalities to reduce variability. This system can also retrieve casespecific resources online to reduce the diagnostic process time by 31%.
What is hot in ILD?
This abstract session featured new data in the field of ILD, including clinical trials, registries and risk factors that predict outcomes. It was chaired by Wim Wuyts, Leuven, Belgium, and Fernanda Ines Hernandez Gonzalez, Barcelona, Spain.
Novel treatment approaches
Luca Richeldi, Rome, Italy, presented a post-hoc analysis of a phase 2 study of BI 1015550, an oral preferential inhibitor of PDE4B, versus placebo (n=147). 
The analysis investigated whether BI 1015550 has an additive effect when given in combination with background antifibrotics. They found that BI 1015550 may have a more pronounced clinical benefit when taken with nintedanib but not pirfenidone. The adjusted mean change in FVC at Week 12 in the BI 1015550 arm was +23.4 mL with nintedanib compared with -18.8 mL with pirfenidone. Treatment emergent adverse events were more common in the BI 1015550 group with diarrhoea being the most frequently reported.
Toby Maher, London, UK, presented two abstracts from his research group, both interim analyses from ongoing trials. Early data from an open-label, single arm, phase 2 trial in patients with IPF (n=21) suggested a promising effect of angiotensin II type 2 receptor agonist, C21, on lung function. 
This drug was well tolerated, causing no gastro-intestinal toxicity. His team also reported the first effective therapy to treat daytime cough in patients with IPF, which is a ma-jor cause of morbidity in this disease. Interim data from a randomised, controlled, placebo-controlled, crossover, phase 2 study suggested a benefit of nalbuphine, a dual-acting κ opioid receptor agonist/µ opioid receptor antagonist. Patients (n=26) with a mean baseline daytime cough frequency of 31 coughs per hour were treated with nalbuphine or placebo for 22 days, separated by a 2-week washout. Treatment with nalbuphine achieved a 77.3% reduction in hourly cough frequency compared with a 25.7% reduction with placebo (p<0.0001). This highly significant and consistent reduction in chronic cough associated with IPF supports proof of concept.
Genetic factors
Tinne Goos, Leuven, Belgium, reported that patients with familial IPF (f-IPF) showed a faster decline in lung function compared with patients with sporadic IPF (s-IPF). f-IPF was defined by the presence of at least two relatives with ILD in one family and was met by 14.4% of their hospital database of 400 ILD patients. It is valuable to carry out a comprehensive family history in order to inform patients about the likely evolution of their disease. It would also be beneficial to screen relatives of f-IPF patients to help early detection and treatment.
A protective benefit in IPF patients who were at least 56 years old at their diagnosis was identified by Joanne van der Vis, Nieuwegein, Netherlands, who had studied the impact of the minor T-allele of the MUC5B promoter polymorphism rs35705950 in a real-world European IPF population (n=1751). The group found that the percentage of MUC5B allele carriers increased significantly with age at diagnosis from 44% in patients below 56 years to 63% in those over 65. Patients with two copies of the allele had a median survival of 49 months compared with 45 months in heterozygous patients and 31 months in non-carriers.
This association was independent of age, sex, lung function, HRCT pattern, smoking status and treatment with antifibrotic drugs. The MUC5B genotype had no survival benefit among IPF patients who were diagnosed younger than 56.
Risk factors predicting outcome
Matthew Randall, Basel, Switzerland identified MMP-7 as a prognostic blood biomarker of IPF disease progression in clinical trials ISABELA 1 and 2. Patients with an annual decline in FVC of 10% or more had higher MMP-7 at baseline (p<0.005). Those with baseline MMP-7 of above 5.18 µg had a greater probability for disease progression (p<0.0001). Iris van der Sar, Rotterdam, Netherlands, demonstrated that technology that can diagnose ILD from exhaled volatile organic compounds can be used to predict response. In this study, an eNose predicted a ≥5% improvement in FVC to immunosuppressive or antifibrotic treatment. The survival impact of nocturnal hypoxaemia (NH) and obstructive sleep apnoea (OSA) among patients (n=102) with f-ILD was reported by Katherine Myall, London, UK. Mean survival was significantly worse in those with NH (691 days vs 998 days without; p=0.002). Disease-related quality of life was also worse in the NH but not the OSA patients. Trials of nocturnal oxygen may be warranted. Finally, Michael Kreuter, Heidelberg, Germany, reported on the difference in outcomes of ILD patients managed in specialised compared to non-specialised centres based on data from the largest German health insurance fund. Outcomes were better among patients treated in the specialised centres as evidenced by lower mortality and all-cause hospitalisation. Respiratory-related costs were higher in this group compared with those treated in non-specialised centres but overall costs were similar.
Lungs on fire: ILD
This popular format puts an expert panel on the spot to discuss real-life challenging clinical cases that they have never seen before. This year’s cases were presented by Paolo Spagno, Padua, Italy, and Maria Molina Molina, Barcelona, Spain on behalf of the contributors. Experts on the panel were Katerina Antoniou, Crete, Greece, Sergio Harari, Arezzo, Italy, and Michael Kreuter, Heidelberg, Germany.
-------------------------------------------- Presentation and history -------------------------------------------------
- 69-year-old male, former smoker
- History of myocardial ischaemia
- Presented to GP with fatigue and weight loss
- Blood and urine tests showed high erythrocyte sedimentation rate and severe proteinuria
- Thorax CT scan showed diffuse centrilobular emphysema and reticular thickening with peripheral predominance (more pronounced at the upper lobes)
- Further tests by the pulmonologist reported bibasilar crackles, restrictive ventilatory pattern and very severe reduction of DLCO
- 8-year-old male
- Previously diagnosed with LHC at 6 years
- Cough and respiratory distress
- Imaging suggested mediastinal and abdominal lymphadenopathy with diffuse cystic lung disease
- Enlarged liver and spleen
- Open lung biopsy revealed multiple foci of nodular lymphoid aggregates and granulomas leading to suspected GLILD (a pulmonary complication of CVID), but inconsistent with normal immunoglobulin levels
--------------------------------------------- Treatment and outcome ------------------------------------------------
- 45-day oral corticosteroid cycle did not improve symptoms and patient reported shortness and peripheral oedema
- Antibodies panel identified ANA 1/160, and cardiac evaluation showed ischaemic dilated heart disease
- Suspected amyloidosis requires further testing (e.g. typing of amyloid deposits, sequencing of transthyretin gene) to identify underlying cause
- There is no cure for amyloidosis and support therapy varies depending on the cause
- Investigations ongoing to differentiate between LCH, sarcoidosis and GLILD
- Oral prednisolone and weaned off oxygen over 3 months
--------------------------------------------------- Key Learnings ------------------------------------------------------
- Amyloidosis is an ultra-rare disease that may involve different organs including the lungs, with wide spectrum of clinical-radiological features and common delay in diagnosis
- Look for extrapulmonary typical signs such as proteinuria, hypoalbuminaemia, and increased serum kappa-levels
- HRCT may show different radiological images. Diagnosis confirmation requires Red Congo staining
ANA, antinuclear antibodies; CT, computed tomography; DLCO, diffuisng capacity for carbon monoxide; GP, general practitioner; HRCT, high-resolution computed tomography
- Granulomatous lung disease is a highly heterogeneous group of disorders with a wide spectrum of pathologies, clinical manifestations and outcomes
- Differential diagnosis is challenging and includes both infectious and non-infectious diseases
- A multidisciplinary approach is essential
CVID, common variable immunodeficiency; GLILD, granulomatous-lymphocytic interstitial lung disease; LHC, Langerhans Cell Histiocytosis
-------------------------------------------- Presentation and history --------------------------------------------------
- 33-year-old female, obese, never-smoker
- Progressive dyspnoea over 4 years, bilateral basal crackles and episodes of thick yellow sputum
- Diagnosed with CVID with severe IG-deficiency syndrome 3 years previously
- Presented with further deterioration of lung function
- Bronchoscopy and EBUS with BAL showed extensive hiliar and mediastinal lymphadenopathy, and moderate lymphocytic alveolitis/pneumonia
- 27-year-old male, ex-smoker
- Hospitalised repeatedly over past 2 years for haemoptysis, dyspnoea and night sweats
- Chest CT showed extensive fluid in lung (hydrothorax), compressive atelectasis, ground glass opacities, parapleural lymphostasis, mediastinal oedema and lymphadenopathy
- Histopathological features identified AFOP
--------------------------------------------- Treatment and outcome ------------------------------------------------
- Rituximab improved lung function
- Methylprednisolone dose was reduced
- Methylprednisolone successfully treated AFOP but hydrothorax progressed
- Sirolimus (mTOR inhibitor) for 3 months improved radiological features and dyspnoea but not lung function. Symptoms returned within 6 months with widespread fluid retention
- Echocardiography and cardiac MRI showed constrictive pericarditis
- Review of histological samples and CT scans by international experts led to diagnosis of DPL
- Thoracotomy with bilateral pleural and pericardial drainage
- Talc pleurodesis worsened symptoms and sirolimus was restarted
- Medical treatment did not have a long-term effect because of constrictive pericarditis leading to heart failure
-------------------------------------------------- Key Learnings -----------------------------------------------------
- GLILD or CVID-associated ILD is difficult to diagnose and should be suspected in young patients with predominant nodular interstitial pattern on HRCT scan
- Other granulomatous diseases should be excluded
- Immunodeficiency and frequent infections are common in GLILD
- Treatment should balance immunomodulation with risk of infection
EBUS, endobronchial ultrasound AL, bronchoalveolar lavage; EBUS, endobronchial ultrasound
- DPL is a rare condition that is difficult to diagnose and has no consensus guidelines
- Consider a combination of medical and surgical treatments
- Many medications (interferon-alfa 2b, glucocorticoids, bisphosphates, propranolol, bevacizumab, sirolimus and thalidomide) and interventional procedures (sclerotherapy, surgery, radiotherapy, lung transplantation) have been tried to treat DPL
- Risks of deterioration may outweigh benefits of talc pleurodesis in patients with pleural adhesions
- AFOP, acute fibrinous organising pneumonia;
- DPL, diffuse pulmonary lymphangiomatosis; MRI, magnetic resonance imaging
- MRI, magnetic resonance imaging
Congress wrap-up