Pulmonary fibrosis (PF) is a progressive lung disease characterised by fibrosis or scarring of the lung tissue. As the disease progresses the build-up of fibrotic tissue causes the lungs to stiffen, limiting their ability to expand and contract, resulting in declines in lung function. By far the most common type of PF is idiopathic pulmonary fibrosis (IPF), which describes PF cases for which no cause has been established. According to recent estimates, there may be around 30,000 people in the UK currently living with IPF [1].
Some common symptoms of IPF include a dry persistent cough, shortness of breath, fatigue, loss of appetite, unexplained weight loss and clubbing of the fingers and toes. IPF patients may also experience sudden worsening of respiratory symptoms, termed acute exacerbations, from which many never fully recover. Additionally, IPF patients are at an increased risk of complications including infections, heart failure and pulmonary hypertension. As a result of these factors, the average life expectancy following a diagnosis of IPF is 2 to 5 years [2].
Undoubtedly, significant advances need to be made in the care of patients suffering from IPF to improve patient outcomes. This article will provide an overview of current challenges surrounding the diagnosis, treatment and management of IPF.
Diagnosing IPF
Many IPF patients experience significant diagnostic delays from the onset of symptoms to receiving an accurate diagnosis [3]. These delays come from patients not presenting early, when their symptoms are relatively mild and easily attributable to other causes. IPF can also be difficult to diagnose because many of its symptoms overlap with other common respiratory conditions e.g. asthma or COPD. Consequently, more than half of IPF patients receive at least one incorrect diagnosis [4]. These delays represent a missed opportunity to intervene early and slow disease progression and can negatively impact patient quality of life and survival [5,6].
The diagnosis of IPF also often requires the use of invasive diagnostic procedures. According to current guidelines, a diagnosis of IPF can be made based on the presence of usual interstitial pneumonia (UIP) patterns observable through chest CT imaging [5,6]. However, in patients where UIP patterns are not identifiable a surgical lung biopsy (SLB) is required [5,6]. As many as 30-60% of patients may undergo a surgical lung biopsy for confirmation of IPF [7]. The risk of performing an SLB should always be weighed against the benefits of obtaining a confirmed diagnosis, particularly in those with physiological impairments and comorbidities and should align with patient preferences [5,6].
Treating IPF
Despite extensive clinical trials in this area, available pharmacological treatments for IPF are limited to two agents, nintedanib, and pirfenidone. Nintedanib, an inhibitor of multiple tyrosine kinases blocks signalling pathways involved in fibroblast proliferation and scar tissue formation [8]. While pirfenidone exhibits both antifibrotic and anti-inflammatory activities through a variety of different mechanisms [9]. However, while these drugs can impact disease progression neither can reverse lung fibrosis and consequently cure IPF.
With limited pharmacologic options, treatment of IPF relies heavily on non-pharmacologic interventions such as pulmonary rehabilitation, oxygen therapy and lung transplantation. Lung transplantation is generally only considered for patients with end-stage disease. Lung transplants have been shown to improve survival in IPF patients however the benefits are often modest with two-thirds of transplant recipients living 3 years, and just over half living 5 years [10]. The transplant criteria are also strict with those over 70 years of age considered unsuitable due to the increase in comorbid conditions and reduced chances of transplant success [11]. The waiting list for lung transplants is also long due to the scarcity of suitable donor organs [11].
Managing IPF
The management of IPF relies on patients attending regular clinic appointments to monitor disease progression and treatment responses, the frequency which will depend on disease severity. These appointments typically involve repeat pulmonary function testing (PFT) specifically diffusing capacity for carbon dioxide and spirometry measurement of forced vital capacity [12]. However, many patients with advanced IPF report challenges in travelling to and attending clinic appointments and performing PFTs [13]. A lack of regular follow-ups can have a significant impact on treatment optimisation and negatively affect patient outcomes.
The management of IPF acute exacerbations involves the use of reactive treatment approaches. IPF patients experiencing exacerbations often require hospitalisation, treatment with high-dose corticosteroids and antibiotics and in severe cases ventilatory support. IPF exacerbations may account for more than 40% of deaths in IPF patients [14]. An inability to detect IPF exacerbations early prevents the use of more preventative treatment approaches with the potential to improve patient survival.
IPF continues to present multiple challenges in terms of its diagnosis, treatment and management as a result of its insidious onset, overlapping symptoms and the current lack of curative treatments. These challenges will undoubtedly be helped by advances in our understanding of the molecular basis of IPF, the identification of novel diagnostic and prognostic biomarkers for IPF and the development digital technologies for remote patient monitoring.
References
[1] The British Thoracic Society. BTS ILD Registry Annual Report 2020: a summary of the UK IPF Registry for the general public. 2020.
[2] Ley B, Collard HR, King TE. Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2011;183:431–440.
[3] Hewson T, McKeever TM, Gibson JE, et al. Timing of onset of symptoms in people with idiopathic pulmonary fibrosis. Thorax. 2018;73:683–685.
[4] Cosgrove GP, Bianchi P, Danese S, et al. Barriers to timely diagnosis of interstitial lung disease in the real world: the INTENSITY survey. BMC Pulm Med. 2018;18:9.
[5] Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2022;205:e18–e47.
[6] Raghu G, Collard HR, Egan JJ, et al. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med. 2011;183:788–824.
[7] Kaarteenaho R. The current position of surgical lung biopsy in the diagnosis of idiopathic pulmonary fibrosis. Respir Res. 2013;14:43.
[8] Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. New England Journal of Medicine. 2019;381:1718–1727.
[9] Antar SA, Saleh MA, Al-Karmalawy AA. Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and/or anti-SARS-CoV-2. Life Sci. 2022;309:121048.
[10] Lederer DJ, Martinez FJ. Idiopathic Pulmonary Fibrosis. New England Journal of Medicine. 2018;378:1811–1823.
[11] Balestro E, Cocconcelli E, Tinè M, et al. Idiopathic Pulmonary Fibrosis and Lung Transplantation: When it is Feasible. Medicina (B Aires). 2019;55:702.
[12] Robbie H, Daccord C, Chua F, et al. Evaluating disease severity in idiopathic pulmonary fibrosis. European Respiratory Review. 2017;26:170051.
[13] Kumar D. Assessment and follow-up of interstitial lung disease. Indian J Rheumatol. 2021;16:69.
[14] Natsuizaka M, Chiba H, Kuronuma K, et al. Epidemiologic Survey of Japanese Patients with Idiopathic Pulmonary Fibrosis and Investigation of Ethnic Differences. Am J Respir Crit Care Med. 2014;190:773–779.
