Precision Diagnosis and Care for Families With Pulmonary Fibrosis in Ireland

This study aims to improve the understanding of how genes and the environment can influence and cause pulmonary fibrosis. By identifying the presence of genes and other factors that can put people at risk of developing pulmonary fibrosis, the influence these factors have on the progression of the disease can be studied.

Interstitial lung disease (ILD) is the medical term given to a group of lung diseases affecting the same part of the lung, the interstitium, each with similar symptoms. In some of these diseases, inflammation leads to lung scarring, known as fibrosis. Idiopathic Pulmonary Fibrosis (IPF) is one of these diseases; it has a particular pattern on computed tomography (CT) scans. IPF is 'idiopathic' as it is not yet fully understood why it happens. It has a poor prognosis. The average survival time is three to five years after diagnosis. While new antifibrotic drugs offer hope of slowing disease progression, lung transplant is the only cure, and it comes with its significant risks.

Although it is not fully understood what causes IPF, it is known that genetic factors significantly increase the risk of developing the disease. Up to a quarter (25%) of people with IPF with a family history appear to have a causative genetic variant. Familial-pulmonary-fibrosis (FPF), the term for people with at least one relative with IPF, may have worse disease when compared to those without a family history. However, this needs more research. Patients with specific genes, telomere-related gene variants, appear to have a greater risk of developing blood disorders from medications given to suppress the body's immune system after a lung transplant.

Progressive pulmonary fibrosis is pulmonary fibrosis where there is irreversible worsening of the disease, worsening of lung function, respiratory symptoms and even early death. It is of growing importance regardless of the cause, whether it be idiopathic, familial or secondary to a connective tissue disease. ILD is increasingly recognised as a complication of connective tissue diseases. It is the leading cause of death in people with systemic sclerosis. The new antifibrotic drugs slow the progression of CTD-ILD. People with progressive pulmonary fibrosis who have a greater than 10% drop over one year in a measure of their lung function, called the forced vital capacity, benefit most from antifibrotic therapy. Early identification of people with progressive disease would allow the commencement of treatment quicker. At-home spirometry may be a way of identifying those who are worsening early.

This study hypothesises that by improving knowledge of factors that affect disease behaviour and progression and assessing tools for the early identification of progressive disease, such as at-home spirometry and CT scan pattern determination by deep-learning analysis, we can provide 'precision' diagnosis and treatment. It is hoped that this improved understanding will help reduce the clinical risk for people with pulmonary fibrosis and their families.

This study aims to recruit 300 patients: 100 with IPF, 100 with FPF, and 100 with CTD ILD. Each participant will be followed for one year.

This observational study aims to help answer a number of questions:

1. What genetic variants cause people to develop ILD, and which increase a person's risk of developing ILD are present in the study population?
2. How does pulmonary fibrosis behave in people who have a family history of IPF compared to those who do not and in people with CTD-ILD?
3. Are different types of pulmonary fibrosis more progressive than others i.e. Is pulmonary fibrosis in those with a family history of pulmonary fibrosis more progressive than in those who do not have a family history?
4. Is the disease in those with a genetic variant known to cause ILD worse than in those who don't have a gene?
5. Can at-home spirometry help identify people at risk of progressive disease early?
6. Can deep-learning analysis (AI) be used to find CT scan patterns to predict when pulmonary fibrosis will worsen?


Eligibility Criteria:
Inclusion Criteria:

* Able and willing to give written informed consent.
* An MDT diagnosis of fibrotic ILD which fall into one of the following three catagories;

  1. Have a multidisciplinary team (MDT) diagnosis of a fibrotic interstitial lung disease, reporting one or more relatives with a fibrotic form of ILD
  2. Have a MDT diagnosis of IPF in accordance with consensus criteria, ATS, ERS, JRS, ALAT guidelines without a family history of pulmonary fibrosis.
  3. Meet the American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis, scleroderma, Sjogren's syndrome, idiopathic inflammatory myopathy and systemic lupus erythematosus.

Exclusion Criteria:

* Currently participating in an interventional clinic trial.
* Change in clinical phenotype from initial radiological diagnosis to screening.
* Acute or chronic hypersensitivity pneumonitis with consensus criteria (appropriate exposure history, radiological features ± avian and fungal precipitins).
* Asbestosis (appropriate occupational history and radiological evidence of asbestos exposure)
* Life expectancy for any disease, including ILD \<12 months (investigator assessment)
* Major extrapulmonary physiological restriction (e.g. chest wall abnormality, large pleural effusion)