Early Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis: A Narrative Review

Pulm Ther https://doi.org/10.1007/s41030-023-00216-0 REVIEW Early Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis: A Narrative Review Hana Alsomali . Evelyn Palmer . Avinash Aujayeb . Wendy Funston Received: November 23, 2022 / Accepted: January 19, 2023 Ó The Author(s) 2023 ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease of unknown aetiology. Patients typically present with symptoms of chronic dyspnoea and cough over a period of months to years. IPF has a poor prognosis, with an average life expectancy of 3–5 years from diagnosis if left untreated. Two anti-fibrotic medications (nintedanib and pirfenidone) have been approved for the treatment of IPF. These drugs slow disease progression by reducing decline in lung function. Early diag- H. Alsomali
W. Funston Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK E. Palmer (&)
W. Funston Department of Respiratory Medicine, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne NE1 4LP, UK e-mail: A. Aujayeb Department of Respiratory Medicine, Northumbria Healthcare NHS Trust, Northumbria Way, Cramlington NE23 6NZ, UK nosis is crucial to ensure timely treatment selection and improve outcomes. High-resolution computed tomography (HRCT) plays a major role in the diagnosis of IPF. In this narrative review, we discuss the importance of early diagnosis, awareness among primary care physicians, lung cancer screening programmes and early IPF detection, and barriers to accessing anti-fibrotic medications. Keywords: Idiopathic pulmonary fibrosis; Early diagnosis; Anti-fibrotic medications Pulm Ther Key Summary Points Idiopathic pulmonary fibrosis (IPF) is a rare disease, often diagnosed late due to the overlap of symptoms with other respiratory conditions. Anti-fibrotic medications slow the decline in lung function in patients with IPF. There is a growing body of evidence suggesting that anti-fibrotic medications reduce the risk of acute deteriorations in lung function and improve life expectancy in IPF. Early diagnosis of IPF is crucial to ensure timely treatment selection and improve outcomes. Early diagnosis can be enhanced by improving awareness among primary care physicians, lung cancer screening programmes and the use of artificial intelligence (AI) systems to analyse computed tomography (CT) images and pulmonary function test results. In the USA and Europe, prescription of anti-fibrotic medications for patients with confirmed IPF is reported to be between 58% and 70%. Barriers to the prescription of anti-fibrotic medications include delayed referral to specialist centres, restriction in the prescription based on percentage predicted of forced vital capacity (%FVC) targets, ‘watch and wait’ approach adopted by patients and clinicians, and the side-effect profile of the medications. Treatment access could be improved by education of non-respiratory clinicians about the presenting symptoms of IPF, utilising computer-aided informatics, streamlining referral pathways and planned changes to the %FVC requirement for people to start antifibrotic medications. INTRODUCTION What is Idiopathic Pulmonary Fibrosis? Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease (ILD) of unknown cause [1]. It is characterised by irreversible loss of lung function due to lung fibrosis and typically presents with symptoms of chronic exertional dyspnoea and dry cough over a period of months to years[1, 2]. IPF remains a rare disease with worldwide incidence recently reported as 0.09–1.30 and prevalence of 0.33–4.51 per 10,000 of the population [3]. The prevalence of IPF appears to be increasing, though it is unclear whether this reflects increased recognition or a true increase in incidence [2]. The prognosis for people living with IPF remains poor, with a median life expectancy of 3–5 years from diagnosis if left untreated [4]. Despite the development of antifibrotic medications to slow disease progression, IPF can ultimately be a fatal lung disease. Early diagnosis is crucial to ensure timely treatment selection such as consideration of anti-fibrotic medications, supportive and palliative therapies, and, if appropriate, referral for lung transplantation [5, 6]. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. EARLY-STAGE DIAGNOSIS IN IPF Clinical Presentation IPF is usually diagnosed in the sixth or seventh decade of life and is uncommon below the age of 50 years [7, 8]. Risk factors for IPF include older age, male sex and a history of cigarette smoking [9]. Typically, IPF presents with exertional dyspnoea, dry cough, fatigue and a gradual decline in ability to undertake activities of daily living. Symptoms can be present for many months to years. Bibasal ‘velcro-like’ midto-end inspiratory crackles on chest auscultation and nail clubbing are common physical Pulm Ther examination findings. Resting hypoxaemia or exertional desaturation are also commonly observed in clinical investigations. When radiological features are identified incidentally in patients without any prior suspicion of ILD, they are called interstitial lung abnormalities (ILAs) [10]. Patients with ILAs might be asymptomatic but may eventually progress and be diagnosed as IPF [10]. Pulmonary Function Tests Pulmonary function tests provide a non-invasive quantitative measure of the severity of IPF, and repeated testing to monitor disease course has become the cornerstone of current practice [11]. In patients with suspected IPF, lung function studies typically identify a reduced forced vital capacity (FVC), reduced total lung capacity (TLC) and a reduction in the diffusing capacity of the lung for carbon monoxide (DLCO) [2]. Patients with early IPF may have normal or only mildly impaired lung function parameters [12]. Moreover, the course of IPF can be highly unpredictable, with significant variation across individuals ranging from patients who have gradual worsening of lung function over years to those who decline rapidly from disease onset [13, 14]. Baseline lung function alone is therefore a poor predictor of mortality in IPF [15] and composite scoring systems such as the Gender–Age–Physiology (GAP) index may offer better prognostic accuracy [16] [see ‘High-resolution computed tomography (HRCT)’]. A recent analysis from the Australian IPF registry found that patients with IPF with mild physiological impairment (FVC C 80%) had better survival than patients with moderate-tosevere disease (FVC \ 80%). However, the overall rate of disease progression was comparable, thus suggesting that better survival in early disease simply reflects an earlier point on the natural history of IPF [12]. Similarly, posthoc analyses of major clinical drug trials in IPF have found that the rate of FVC decline is simi (...truncated)