Interstitial lung disease (ILD) encompasses a heterogeneous group of respiratory disorders characterised by inflammation and/or fibrosis of the lung interstitium. Broadly speaking, ILD can be divided into four main groups. (1) Firstly, there are the Idiopathic Interstitial Pneumonias (IIPs) including Idiopathic Pulmonary Fibrosis (IPF), the most common IIP, along with idiopathic non-specific idiopathic pneumonia (NSIP), acute interstitial pneumonia (AIP) and respiratory bronchiolitis-associated ILD (RB-ILD), to name a few. ILD attributable to known causes such as connective tissue disease (CTD-ILD) or specific exposures; granulomatous ILD including sarcoidosis and hypersensitivity pneumonitis (HP); and rare forms of ILD such as lymphangioleiomyomatosis (LAM) or Langerhans cell histiocytosis (LCH) account for the remaining subgroups.
ILD includes a spectrum of clinical phenotypes. Delineating the specific ILD pattern and disease behaviour is now, more than ever, pertinent to management. Morbidity and mortality, as well as treatment options differ between subtypes. For example, the use of anti-fibrotic agents and avoidance of immunosuppression is paramount in IPF comparative to CTD-ILD where immunosuppression is often first line therapy. (2, 3, 4, 5) There is now also increasing recognition of the “progressive fibrotic” phenotype across disease subtypes, with recent publications highlighting a potential role for anti-fibrotics in these conditions in addition to standard therapy. (6, 7) To establish accurate diagnoses, guidelines mandate thorough clinical history and examination combined with high resolution CT imaging and autoimmune serology. These data should be presented to an ILD multi-disciplinary meeting (MDM) with consideration of lung biopsy in cases with persisting diagnostic uncertainty. (8) Discussing cases at an ILD MDM with sufficient subspecialty expertise can significantly improve diagnostic accuracy. (9)
There is now increasing momentum calling for improved epidemiological data. Whilst the availability of incidence and prevalence data in IPF has greatly improved over the years, little information is available for other ILDs. (10) A number of ILD advocacy groups have highlighted the need worldwide for ILD registries to provide critical real world data, aspiring to translate this knowledge into improved clinical care and patient outcomes. (11) Further rationale for this is highlighted by the lack of data to inform standardised diagnostic and treatment approaches, particularly for the rarer ILD subgroups.
A national (or international) ILD registry offers an opportunity to understand disease patterns, standardise care and provide relevant longitudinal data. The Australian IPF Registry (AIPFR) has been recruiting patients successfully since 2012. This internationally acclaimed registry has 817 participants recruited, to August 2019. Following the success in working across multiple centres in this nationally coordinated registry, we launched the Australasian ILD Registry (AILDR) inclusive of all ILD diagnoses in centres across Australia and New Zealand.
The Australasian Ild Registry Overview
AILDR is a bi-national prospective observational cohort registry designed to recruit patients attending ILD clinics at speciality centres around Australia and New Zealand (see Fig. 1.). The registry was launched in three anticipated phases; a pilot study of four sites, a second phase to recruit a further sixteen sites and the third phase to ensure ongoing prospective data collection and recruitment of both patients and additional centres. The four site pilot study is now complete (2016–2018) and the second phase of recruitment is underway. Ethical approval for the registry was granted by the Sydney Local Health District HREC on 1st September 2016 (HREC/16/RPAH/345) and the Western Australian South Metropolitan Health Service HREC on 5th May 2017 (RGS11/ILD1) with each site responsible for obtaining local governance approval.
The objectives of AILDR are to 1) establish the incidence and prevalence of ILD subtypes across Australasia; 2) to provide a clinically meaningful database allowing for audits of practice and identification of areas for clinical improvement (e.g. establishing bi-national diagnostic and treatment pathways); 3) to provide data on real world treatment practice; and 4) to enable collaborative research particularly of rare forms of ILD. Inclusion criteria are patients > 18 years of age, able to give informed consent and with a diagnosis of ILD, where applicable, according to American Thoracic Society/European Respiratory Society (ATS/ERS) criteria. Exclusion criteria are those < 18 years of age or those unable to give informed consent. All patients are provided with both verbal and written information and advised they can withdraw consent at any time, without affect ongoing clinical care. AILDR is designed as an opt-in registry therefore any centre with an ILD MDM that wishes to join is welcomed.
Lung Foundation Australia (LFA) provides registry governance, serving to support the purpose and strategic goals of the AILDR, provide oversight of the agreed protocols with appropriate ethics, provide qualified personnel and ensure that deliverable measures are in place. Individual sites have signed a memorandum of understanding with LFA prior to recruitment. A registry steering committee convenes quarterly with attendance expected from the Principle Investigator (PI) at each site.
Data Collection
For all participants, retrospective data is entered after consent at first clinic visit with prospective data entered after each subsequent clinic visit. Data is recorded on a secure server hosted by a leading international server hosting infrastructure company using third party database software FileMaker (initially version Pro15, subsequently updated to Pro17). Responsibility for data entry falls to the PI or nominated co-investigator(s) at each site. There is a project manager with overall access to the registry but only local individual data can be accessed by each site. No additional visits or investigations are performed for the sole purpose of the registry and the frequency of objective testing and clinic review is determined independently by each site.
A summary of core data recorded on the registry is demonstrated in Table 1. This includes basic demographic data such as sex, age and ethnicity. Clinical data includes detailed descriptions of presenting symptoms, clinical findings, occupational and environmental exposures, family history and co-morbid disease. Current and past medication lists are recorded including oxygen use. ILD diagnosis is chosen from a pre-specified drop-down list of diagnoses, reflecting the local ILD MDM consensus findings. Results of investigations performed as part of baseline and ongoing assessment are recorded, including serum blood markers, high resolution CT chest findings, blood gases, bronchoscopy +/- biopsy. Functional parameters include standardised pulmonary function tests (PFTs), and 6-minute walk test (6MWT). Participants are treated according to clinical practice at each site. Active and past treatments specific to any form of ILD are encouraged to be recorded, as is reporting of any adverse effects or incidents, although these are not mandatory. Mortality data is reviewed every 6 months with dates of death and lung transplantation recorded as determined by clinical records and/or death certificates.
Table 1
AILDR registry data headings including information collected
| Subgroups | Data Collected |
Patient Demographics | Demographics Physicians Consent Smoking status Family history Environmental exposures Trial participants | Gender, date of birth, ethnicity, postcode Vital status, mortality status, date of deceased Miscellaneous: Hospital number, lung transplant date General Practitioner, Referrer, treating Physician Date when obtained Current, ex (pack years), Never Pulmonary fibrosis, autoimmune disease Asbestos, metals, mineral dusts, moulds, birds, chemicals, compost/potting mix, farming, drugs within last 5 years, other (free text) Consent date and trial name/number |
Clinical Data | Symptoms at presentation Medical history Clinic visit details | Date of onset, dyspnoea and cough severity, connective tissue disease features Cardiac disease, liver disease, TB, Asthma/COPD, Lung cancer, Diabetes, Thromboembolic disease, Autoimmune disease, OSA, Surgery, Other medical issues (free text) Date of attendance, oxygen saturations, cardiovascular and respiratory examination |
Medications | Oxygen use Current medications Past medications Trial interventions | Date started, frequency, flow rate Name, dosing and frequency: Anti-fibrotics, immunosuppression, acid suppression agents, pulmonary hypertension medications, other (free text) Stop date and reason Trial name |
Investigations | Core data Blood tests (serology) HRCT Chest Six minute walk test Pulmonary function tests Arterial blood gases BAL/Biopsy Non-core data Echocardiogram Sleep studies Right heart catheterisation | Date and results |
ILD Diagnosis | Clinical diagnosis Radiology diagnosis Histopathology diagnosis | MDD Date MDD consensus diagnosis and management plan |
Supplementary | Patient reported outcome measures (Questionnaires) | Shortness of Breath Questionnaire St George Respiratory Questionnaire Hospital Anxiety and Depression Scale |
Abbreviations: ILD – Interstitial lung disease; TB – Tuberculosis; COPD – Chronic obstructive pulmonary disease; OSA – Obstructive sleep apnoea; BAL – Bronchoalveolar lavage; HRCT – High resolution computerised tomography; MDD – multi-disciplinary discussion |
Supplementary (or non-core) data includes tests such as echocardiogram, sleep studies and right heart catheterisation and is recorded at investigators’ discretion. Sites are also authorised to record any of the following approved questionnaires which were performed; Shortness of Breath Questionnaire (SOBQ- Australia/English Version 2011), St George Respiratory Questionnaire (SGRQ – UK/English original version) and Hospital Anxiety and Depression Scale (HADS – undated).