Interstitial Lung Disease Exacerbations Study

Idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (PF-ILDs) are increasingly common fatal disorders with a median life expectancy from diagnosis of 3-5 years. Fibrotic interstitial lung disease (fILD) is a general term for a group of conditions that involve scarring of the lung (fibrosis) with or without evidence of inflammation. While different ILDs are associated with different aetiological factors and disease courses, there is considerable overlap in the characteristics of these conditions. In general, fILDs usually progress in terms of symptoms, lung function, and radiological features, resulting in increasing symptoms and respiratory failure.

In addition to the gradual progression that is typical of fILD, these conditions can become acutely worse during episodes of acute exacerbation (AE-fILD). An AE can be defined as an acute (less than one month) deterioration in symptoms associated with new ground glass changes on CT chest and not explained by other pathology such as pulmonary embolus, pneumothorax, or cardiac failure (adapted from the definition by Collard et al for AE-IPF). The prognosis of acute exacerbations of idiopathic pulmonary fibrosis (IPF), the commonest form of fILD, is very poor (over 90% in-hospital mortality in some reports). However, there has been very little research on AEs in non-IPF fILD.

Furthermore, there is currently no treatment guideline or established standard of care for the management of patients with AE-fILD. Other significant gaps in the literature in this area, include:

• What is the typical clinical course and outcome of acute exacerbations in non-IPF fILD?
• What features predict the risk of in-hospital and post-discharge mortality from AE-fILD (e.g. age, sex, baseline diagnosis)?
• Are currently used treatments for AE-fILD effective? How should AE-fILD be managed (steroids, oxygen therapy etc)?
• How well are aspects of care that patients find important (e.g. provision of specialist palliative care, opportunities to discuss advanced care planning, and oxygen therapy) delivered to patients with AE-fILD?

There are significant gaps in the literature in the field of AE-fILD. Much of the current practice in AE-fILD management is based on clinical judgement, and adequately powered randomised controlled trials to identify appropriate treatment approaches have not been performed. This has led to significant heterogeneity in the approach to AE-fILD between clinicians and centres, an issue illustrated by the fact that only one of seven NHS trusts in the East Midlands has a treatment guideline specific for the management of AE-fILD (unpublished data). This lack of consistency in approach poses a significant challenge to the design of randomised control trials, as heterogeneity within a standard care control arm can obscure any specific signals. Furthermore, in the absence of RCTs, there is the potential that clinicians may unintentionally use interventions that are harmful.

The study is an observational cohort study of patients admitted to hospital with AE-fILD to answer the questions listed above. These data will help to clarify research priorities in this area, and identify areas where care could improve and allow us to make recommendations for clinical care. The study will also use these data to inform and generate hypotheses for future clinical trials.

Inclusion criteria

• Patients admitted to an acute NHS trust during study period 1st September 2022-31st August 2023 with an underlying or new diagnosis of an ILD (defined by ICD-10 codes in Table 1) with a fibrotic phenotype (established fibrosis on current or previous radiological imaging) AND
• Increasing pulmonary symptoms AND
• No extra-parenchymal cause identified as primary cause of admission

• Segmental or larger pulmonary embolus as main discharge diagnosis in absence of acute exacerbation features on imaging
• Pleural effusion as main discharge diagnosis
• Pneumothorax as main discharge diagnosis in absence of acute exacerbation features on imaging
• Left sided heart failure or volume overload

Exclusion criteria

• No underlying or new diagnosis of ILD with a fibrotic phenotype
• Acute presentation of pneumonitis/ILD without evidence of fibrosis (Table 2)
• Non-respiratory related hospital admission (no increasing pulmonary symptoms)
• Respiratory related hospital admission due to extra-parenchymal cause

• Segmental or larger pulmonary embolus as main discharge diagnosis in absence of acute exacerbation features on imaging
• Pleural effusion as main discharge diagnosis
• Pneumothorax as main discharge diagnosis in absence of acute exacerbation features on imaging
• Left sided heart failure or volume overload
• Participant signatory to NHS National Data Opt Out
• Elective/non-emergency admission
• Admission under non-medical specialty
• In cases where there are >=1 eligible admissions only the first (index) admission shall be included