An update on pulmonary fibrosis

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Reference: April 2025 | Issue 4 | Vol 11 | Page 31

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Interstitial lung disease (ILD) is a heterogeneous group of lung diseases affecting the lung parenchyma. The most common type, idiopathic pulmonary fibrosis (IPF), is a devastating fibrosing ILD of unknown cause which affects, conservatively, 1,000 people in Ireland. Approximately 400 new cases of IPF are diagnosed in Ireland each year.¹ Chronic inflammation and abnormal tissue repair lead to scarring of the lung parenchyma.

Patients typically present with progressive dyspnoea and/or a non-productive cough. The prognosis is poor. IPF has a median survival of two to five years, which is worse than many cancers, including lymphoma, breast, and colon cancer.² Although antifibrotic agents such as nintedanib and pirfenidone slow down disease progression, lung transplant remains the only curative treatment.

While the exact cause of IPF remains unknown, several risk factors have been identified. These include cigarette smoke exposure, environmental factors such as pollution, viral infections, family history and genetic factors.^3,4 IPF predominantly affects older men. In recent UK registry data, 77.8per cent of cases were male (68% in Irish 2018 registry data), and the mean registry age was 74+/-8.1 years.⁵

Unfortunately, the majority of IPF patients have a smoking history and a significant number continue to smoke.¹ Smoking is known to increase a person’s risk of pulmonary fibrosis and this risk appears to increase the higher the number of pack-years smoked.⁶ Air pollution is associated with worse outcomes, including worse lung function, disease progression, an increased number of acute exacerbations, increased mortality, and a higher incidence of ILD.⁷

In Ireland, approximately one in five patients with IPF has a relative who also has fibrotic ILD.¹ This is a much higher rate than the 6.2 per cent reported by the UK ILD registry.⁵ These cases are now commonly called familial pulmonary fibrosis (FPF). There is a significant genetic contribution to FPF, with between 25 and 40 per cent of cases thought to have a monogenic cause, ie, a single causative gene.^8,9 Two main groups of monogenic causes have been identified: Telomere-related genes and surfactant-related genes.

Apart from monogenic causes, other genetic risks have been identified that contribute to a person’s risk of developing pulmonary fibrosis, such as single nucleotide polymorphisms. The single nucleotide polymorphism (SNP) rs35705950 in the Mucin 5B (MUC5B) gene promotor is associated with an increased risk of IPF, FPF, and rheumatoid arthritis-associated ILD (RA-ILD).^10,11 Conversely, it has been associated with increased survival time after diagnosis.¹²

Diagnosis

The diagnosis of IPF involves the exclusion of other forms of fibrotic-ILD, in particular, autoimmune disease-associated ILD such as RA-ILD, scleroderma-related ILD or myositis. This involves blood tests such as an extended myosotis panel, anti-cyclic citrullinated peptide (anti-CCP) antibody levels, and rheumatoid factor. Clinical examination for signs of connective tissue disease and a detailed exposure history remain integral to the diagnosis.

Examination of an IPF patient often reveals bibasilar fine crepitations on auscultation, and patients may have finger clubbing. Pulmonary function testing is also important for diagnosing and monitoring IPF, with a reduced forced vital capacity (FVC), diffusion capacity, and a restrictive pattern associated with the disease. Imaging of the chest is also an essential part of the workup.

A high-resolution computed tomography (CT) scan is required to diagnose ILD. In IPF, the identification of a specific pattern on CT, usual interstitial pneumonia (UIP), is essential for diagnosis.

Delivering an accurate and timely diagnosis of ILD is the first and most essential component of care for patients. A review of cases at an ILD multidisciplinary meeting (MDM) remains integral to diagnosis. At the ILD MDM, a member of the patient’s medical team presents a summary of the patient’s case. The history and relevant test results are then discussed by a team of physicians, including respiratory physicians, ILD physicians, rheumatologists, thoracic surgeons, and radiologists with a special interest in ILD. A consensus diagnosis is made based on all the evidence presented.

Usually, in less than 5 per cent of cases, a biopsy, either a surgical lung biopsy (SLB) or a transbronchial lung cryobiopsy, may be recommended if the diagnosis is still unclear following discussion. SLBs and cryobiopsies are carried out at specialist centres, with Cork University Hospital being the only centre currently performing cryobiopsy in Ireland. Centre expertise, availability, and patient factors will inform the decision on the recommended biopsy type.

Managing FPF has some extra challenges beyond those of IPF. Cases often have added complexity, and a multidisciplinary team with experience in pulmonary fibrosis and genetics is needed to deliver the best care for these patients. The Centre for Familial Pulmonary Fibrosis in Beaumont Hospital receives referrals for patients with a family history of ILD. At this specialist clinic, complex familial cases are considered, and genetic testing and counselling are provided in line with the American College of Medical Genetics Guidelines.¹³ The centre also runs clinical and translational research studies for patients.

Treatment

Two antifibrotics are currently approved for use in Ireland: Pirfenidone for the treatment of IPF and nintedanib for IPF, chronic-progressive fibrosing ILDs, and systemic sclerosis-associated ILD. Clinical trials have demonstrated that both medications slow the decline in FVC and reduce exacerbation rates.^14-17 There is no established superiority of either antifibrotic agent in IPF management.

Treatment selection often depends on patient-specific factors, including preference, tolerance of side-effects, and potential drug interactions. Both medications can cause gastrointestinal disturbances, with nintedanib predominantly associated with diarrhoea and pirfenidone with nausea. Additionally, pirfenidone can induce photosensitivity reactions, making it potentially unsuitable for patients who spend considerable time outdoors. Patients must have their liver function monitored regularly to ensure no hepatotoxicity.

No specific treatment is currently available for FPF. Antifibrotics are prescribed according to guidance for IPF and those patients with progressive pulmonary fibrosis. Although there remains no curative treatment, awareness of familial variants can allow physicians to screen for genetic variants and evidence of clinical disease and start treatment earlier in affected family members.

The multi-disciplinary team can also advise against risk behaviours such as smoking and alcohol use. It is thought that monogenic pulmonary fibrosis may affect a younger cohort and may have a more progressive disease course than sporadic cases of pulmonary fibrosis.¹⁸ This should initiate consideration for earlier referral to the National Transplant Service in the Mater Hospital.

Patients can undertake many preventative behaviours to reduce their risk of exacerbations. Encouraging patients to quit smoking and providing them with information about local smoking cessation support services remains an important part of care.

As acute infections contribute to the risk of an acute exacerbation, IPF patients should ensure they have up-to-date vaccinations for Covid-19, flu, and pneumococcal pneumonia. Patients should also seek treatment early for respiratory infections. Patients should check with their ILD specialist or GP when starting new medications or considering any procedures or surgeries. Patients should also check with their doctor before flying, particularly if they are on oxygen. A flight assessment might be required.

The care of the patient with pulmonary fibrosis requires a multidisciplinary team. IPF patients in Ireland need timely access to all services provided by all multidisciplinary team members. The psychological support, education and clinical care provided by ILD clinical nurse specialists and advanced nurse practitioners are crucial for patients. Having a regular point of care in the hospital outside the clinic is invaluable. The Irish Lung Fibrosis Association, a charitable organisation, also provides support, education and advocacy for people with IPF and other ILDs.

Physiotherapists provide oxygen assessment, pulmonary rehabilitation, and breathing exercises, all of which are vital to the clinical care of patients. Pulmonary rehabilitation improves exercise capacity and is thought to improve quality of life and dyspnoea.^19,20 When IPF progresses, oxygen therapy may be prescribed to allow patients to continue their everyday activities. Physiotherapists can assess the amount of oxygen a patient requires and the method of administration. Oxygen therapy can also help prevent the development of pulmonary hypertension.

Palliative care services remain a critical resource for people with this life-limiting disease. As well as end-of-life and hospice care, palliative care services provide symptomatic treatment for cough and breathlessness. Palliative measures range from offering advice and strategies to manage breathlessness to the use of opioids and anxiolytics.

Referral to a dietician can aid if weight loss is an issue or if anorexia or gastrointestinal symptoms from antifibrotics become problematic.

Progress

Despite our increasing knowledge of pulmonary fibrosis, treatment options remain few. Access to lung transplant is limited and only select patients are suitable. Several promising therapeutic advances and possible new therapeutic options are on the horizon. The recognition of the role of genetics is expanding our knowledge and opening up new and exciting research areas, internationally and in Ireland.

In Beaumont Hospital and the Royal College of Surgeons in Ireland, the Living Lung Lab is generating patient-derived induced pluripotent stem cells from samples from patients with FPF. This will allow further understanding of the disease and hopefully lead to improved, precision care for pulmonary fibrosis patients in the future.

Multiple clinical trials are underway in the area of IPF. One promising medication is nerandomilast, a phosphodiesterase 4B (PDE4B) inhibitor. PDE4B inhibitors help prevent the degradation of cAMP, a secondary messenger that regulates fibrotic and inflammatory pathways. FIBRONEER-IPF and FIBRONEER-ILD met their primary endpoint of an absolute change from baseline in FVC at 52 weeks. The results from the trial were better when nerandomilast was combined with nintedanib or pirfenidone.

Further analysis and applications are underway to bring this medication to the market. Research into whether combination therapy with nintedanib and pirfenidone offers additional benefits over single-drug treatment is ongoing. Combination therapy is safely tolerated in the majority of patients.²¹ However, whether this combination therapy offers clinical advantages over single-drug treatment has not been determined.

Good outpatient access to all members of the multidisciplinary team is vital to the care of IPF patients. Specialist clinics in tertiary centres are working on improving patient care in Ireland. There are many new developments in the care of IPF, including the possibility of new pharmacological therapies. There is increasing knowledge and recognition of the disease by healthcare practitioners and the Irish public. The Irish Government has provided €0.5 million in funding for pulmonary fibrosis in the 2025 Budget. This is a positive step forward and will help towards improving care and support for patients with pulmonary fibrosis and their families.  

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