Impact case study database

Bronchiectasis is described by the President of the European Respiratory Society (2018-19) as a “neglected disease with a high morbidity and mortality” [E1]. Historically, poor awareness of the condition and a lack of research meant there was uncertainty about the underlying causes of bronchiectasis and the effectiveness of treatments, further compounded by poorly developed services.

Chalmers’ work has provided much-needed evidence for the investigation and management of bronchiectasis, shifting the clinical approach from reactive symptom control to proactive management based on an understanding of disease aetiology. His work has informed the first international guidelines for the management of bronchiectasis, raised global awareness of the disease and supported the establishment of a patient registry and patient-focussed approaches.

Development of international guidelines

Prior to 2017 there were no international treatment guidelines for bronchiectasis; management of the condition focused primarily on alleviating symptoms. Chalmers (with co-chair Polverino) directed the development of the 2017 European Respiratory Society (ERS) guidelines [E2]. The guidelines draw on Chalmers’ work, prioritising the prevention of exacerbations using mucoactive medications and antibiotics [R2]. According to the President of the ERS, the guidelines:

have been instrumental, as the first international guidelines published for this condition, in driving improvements in care including increased use of diagnostic testing [E1].

Following publication of the ERS guidelines, adoption of evidence-based interventions has increased. A comparison of three-year periods immediately before and after September 2017 reveals, among patients in the registry, increases in appropriate diagnostic testing from 44.7% to 51.8% (p<0.0001), airway clearance use from 47.0% to 57.4% (p<0.0001) and use of prophylactic antibiotic treatment from 28.6% to 32.2% (p=0.009) [E3].

Chalmers was also part of the British Thoracic Society Bronchiectasis in Adults Guideline Development Group [E4]. The resulting (2019) guideline recommends use of the BSI [R2] at baseline/diagnosis in all patients for evaluation and to support treatment planning.

Improving disease management and raising awareness worldwide

The impact of the research is evident beyond Europe. EMBARC (co-chaired by Chalmers) has driven improvements to bronchiectasis services across Europe as well as in Israel and India [E5].

In 2014, EMBARC partnered with the Respiratory Research Network of India to establish the Indian Bronchiectasis Registry. The Registry operates across 31 centres in India; it was the first prospective multicentre bronchiectasis registry established in a lower middle-income country [E6] and according to the Chair of the Respiratory Research Network of India, “by far the largest study into this orphan disease in an Asian country” [E7].

The research identified key differences with European studies including a distinct aetiology (the commonest underlying cause was tuberculosis) and characterisation (typified by early onset, extensive lung damage and severe symptomatology). The findings enabled physicians to identify how management of the condition could be improved, leading to an increased use of diagnostic testing for bronchiectasis patients and improved guideline adherence [E7]. Additionally the registry provided evidence of the underutilisation of macrolide antibiotics for frequently exacerbating patients, thus informing the development of evidence-based consensus recommendations aimed at increasing the use of macrolide antibiotics in bronchiectasis and other respiratory conditions (submitted January 2019, accepted September 2020; final publication March 2021 was delayed due to COVID) [E8].

The work of EMBARC is credited with raising awareness of the condition worldwide, leading to greater public and professional awareness of the disease and ensuring that the disease is now firmly established as a regular core topic at major international meetings [E1] [E7]:

Prior to 2015 there were no specific European meetings on bronchiectasis and the topic was rarely discussed at international society events… Bronchiectasis has now become a core topic, addressed at all international meetings such as the ERS and the American Thoracic Society annual meetings… [E1]

Promoting evidence-based interventions

Until recently, no licensed therapies for bronchiectasis were available and clinical trial findings were inconsistent, possibly because specific treatment-responsive endotypes of bronchiectasis had not yet been identified [E5]. The BSI [R2] is now used to characterise patients for randomised clinical trials and has been used in 12 clinical trials between its publication in March 2014 and the end of 2020. It was, for example, used in a 24-week Phase 2 trial led by Chalmers which tested the effectiveness of Brensocatib, a selective, orally active inhibitor of dipeptidyl peptidase I. This enzyme activates elastase during neutrophil maturation [E9]. The overall risk of exacerbation during the treatment period was 40% less than with placebo, demonstrating the benefits of an evidence-based approach to treatment. Brensocatib entered Phase 3 trials in December 2020, led by Chalmers (NCT04594369).

Championing a patient-focussed approach

Before the establishment of EMBARC, there was no formal patient organisation, charity or advocacy group for bronchiectasis. From the outset, EMBARC has been patient-focussed and, where appropriate, patient-led.

The EMBARC Roadmap Study Group including Chalmers and four “expert patients” set out to identify the challenges faced by bronchiectasis patients, their families and friends. A questionnaire asking what changes would most improve quality of life for people with bronchiectasis was published online in 12 languages, eliciting 1086 responses from 22 countries. The results were used to set priorities and develop an EMBARC consensus statement [E10].

Three members of the Patient Advisory Group established as a result of these efforts participated in the EMBARC steering group and were full members of the 2017 Guidelines Task Force [E11], the first-time patients had played such a role “….the patients’ perspective often differed from those of guideline panellists….[they]….made an important contribution in modifying the ultimate guideline recommendations” [E11].

Patients also led the development of the comprehensive “Patient Priorities: Bronchiectasis” online resources. The website holds a range of resources including factsheets in 21 languages, alongside videos and lay summaries of guidelines in multiple languages to support patients to understand and self-manage their bronchiectasis [E12]. In summary, according to the President of the European Respiratory Society 2018-19 [E1]:

There is no doubt that EMBARC and the collaborative European research that Professor Chalmers has led has been a major contributor.…It is no exaggeration to say that this research has transformed this previously neglected disease and is improving the lives of patients worldwide.