FormalPara Key Messages

The incidence of idiopathic pulmonary fibrosis (IPF) increases with age; however, its symptoms—cough, dyspnoea and fatigue—are non-specific; thus, a careful history and investigation are required for accurate diagnosis.

New treatments (pirfenidone and nintedanib) that slow IPF disease progression have recently become available; however, the benefits of therapy must be weighed against potential toxicities.

Co-morbidities—including chronic obstructive pulmonary disease, gastroesophageal reflux disease, pulmonary hypertension and depression—are common in the elderly IPF population and are important targets for therapeutic intervention.

1 Introduction

Idiopathic pulmonary fibrosis (IPF) is a severe and progressive fibrosing interstitial lung disease (ILD), which ultimately results in respiratory failure and death. With a median age at diagnosis of 66 years and an incidence increasing with age [1], IPF is a disease that is now recognised to predominantly affect the elderly population. IPF is often difficult to diagnose, as its symptoms—cough, fatigue and dyspnoea on exertion—are non-specific. Making a confident diagnosis in elderly patients can be especially challenging, as these symptoms may often be attributed to other common co-morbid conditions, such as heart failure and chronic obstructive pulmonary disease (COPD), making the diagnosis of IPF even more elusive.

In this review, we highlight measures to improve recognition and accurate diagnosis of IPF, as well as co-morbidities that often affect the diagnosis and disease course. Differentiation of IPF from other ILDs is imperative, as new treatments that slow disease progression specifically in IPF have recently become available. As with all new treatments, caution must be advocated in the elderly, as these patients often lie outside the narrow clinical trial cohorts that are studied, and the benefits of therapy must be weighed against potential harms. We summarise the current recommendations for treatment of IPF, drawing particular attention to areas affecting the elderly.

2 Aetiology and Pathogenesis of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis is the most common of the idiopathic interstitial pneumonias (IIPs) but is only one of over 500 different types of ILD [2]. The categories of ILD are summarised in Fig. 1.

Fig. 1
figure 1

Classification of interstitial lung diseases (ILDs)

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While the aetiology of IPF is largely unknown, cigarette smoking and environmental exposures, as well as gastroesophageal reflux disease, have all been proposed to play a role in pathogenesis [3]. This is supported by epidemiological studies in which cigarette smoking (especially greater than 20 pack-years) and metal and wood dust exposure have been associated with an increased risk of IPF [4, 5]. Genetic factors are also likely to play a role in the pathogenesis of IPF; indeed, familial cases of pulmonary fibrosis have been documented. Genome-wide association studies show an increase in polymorphisms in the promoter region of the MUC5B (mucin 5B, oligomeric mucus/gel-forming) gene in both familial and sporadic IPF patients [6]. Mutations in telomerase enzymes (TERT [telomerase reverse transcriptase] and TERC [telomerase RNA component]), which result in premature shortening of telomere length and cell senescence, have also been found in familial and sporadic IPF [7, 8]. Interestingly, telomere length naturally decreases with aging; thus, it is unsurprising that IPF is a disease of the elderly, with IPF being virtually absent in patients younger than 50 years but increasing to a prevalence of 0.2 % in those aged over 75 years [1].

The pathogenesis of IPF is complex and incompletely understood. Significant progress in the understanding of this devastating disease has been made, with a recent shift in the pathogenic paradigm from inflammation-driven fibrosis to aberrant wound healing, a primary fibrotic process. According to this hypothesis, the alveolar epithelium accumulates clinically silent injuries over a prolonged period of time. Beyond a certain threshold, the alveolar epithelial cells become aberrantly activated [9, 10], in turn activating pro-fibrotic signalling pathways. This in turn leads to migration, proliferation and activation of mesenchymal cells, resulting in development of the hallmark fibroblastic foci and deposition of excess extracellular matrix seen on histopathology. There are, however, many other intricate signalling pathways. These involve a diversity of growth factors and chemokines that activate numerous effector cells, which are not yet fully appreciated [11]. It is hoped that greater understanding of this complex pathogenesis will lead to development of novel therapeutic targets in the future.

3 Natural History of Idiopathic Pulmonary Fibrosis

While the overall prognosis of IPF is poor, the clinical course is variable [12], ranging from rapid deterioration to slowly progressive disease or even periods of relative stability interposed with periods of acute deterioration (Fig. 2). Importantly, interstitial changes can also be found in asymptomatic elderly individuals who are unlikely to develop IPF. In a study by Copley et al. [13], high-resolution computed tomography (HRCT) was performed in two groups of patients (aged >75 years or <55 years) without respiratory symptoms. In the older age group, 60 % of patients had interstitial changes with a limited, predominantly subpleural, basal, reticular pattern, while no patients in the younger cohort had these features. The authors suggested that these changes on HRCT may represent the normal spectrum of morphology of the aging lung, rather than clinically relevant disease.

Fig. 2
figure 2

The variable clinical course described in idiopathic pulmonary fibrosis patients. A rapid deterioration. B relative stability with periods of acute deterioration. C, D slow progression. Reprinted with permission of the American Thoracic Society. Copyright © 2016 American Thoracic Society. Ley et al. [12]

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4 Diagnosis of Idiopathic Pulmonary Fibrosis

Accurate diagnosis of IPF poses significant challenges. The initial evaluation of a patient with suspected IPF should involve a detailed history, including environmental and occupational exposures, as well as careful examination for connective tissue disease. Pulmonary function testing will often demonstrate reduced lung volumes and impaired diffusion capacity. Interstitial infiltrates may be evident on chest radiography; however, these findings are not specific for IPF, and HRCT is warranted for evaluation. Serological testing to exclude autoimmune diseases that may present with interstitial lung involvement should also be considered.

A confident diagnosis of IPF requires exclusion of other known causes of ILD and the presence of a usual interstitial pneumonia (UIP) pattern on HRCT (Fig. 3) [3]. In cases where the HRCT is not definitive, a surgical lung biopsy is required to make a confident diagnosis (Table 1; Fig. 4).

Fig. 3
figure 3

High-resolution computed tomographic image of usual interstitial pneumonia, showing subpleural, basal honeycombing with reticulation and traction bronchiectasis

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Table 1 Features of usual interstitial pneumonia (UIP) on radiology and histopathology
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Fig. 4
figure 4

Histopathology of usual interstitial pneumonia. Top left patchy involvement by fibrosis with subpleural accentuation. Top right marked fibrosis with architectural distortion, including honeycomb change. Bottom left fibroblastic foci. Bottom right established subpleural fibrosis and smooth muscle proliferation

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While surgical lung biopsies can indeed clarify the diagnosis and hence alter management and prognosis [14], this procedure is not without risk. The mortality associated with this procedure ranges from 4.4 to 6.0 % over 60 to 90 days [15, 16], and morbidity (including prolonged hospital stays, need for mechanical ventilation and postoperative pneumonia) occurs in up to 19.1 % of patients [15]. While age was not associated with increased risk in these studies, the mean age of the patients in both studies was only 58 years [15, 16]. The question arises as to whether an elderly patient with possible IPF and an atypical HRCT should proceed to surgical lung biopsy. This is an important question, particularly in light of a recent study showing that increasing age is associated with increased probability of a diagnosis of IPF [17]. In that study, age above 75 years was associated with a 100 % predictive value of confirmation of IPF at surgical lung biopsy in patients without definitive UIP on HRCT, while age greater than 70 years had a predictive value of 95 %. With that important study in mind, it is vital to particularly consider whether there is a need to proceed to surgical lung biopsy in the elderly population.

Given the complexities of diagnosis, the gold standard for IPF diagnosis is a multidisciplinary meeting whereby respiratory clinicians, radiologists and histopathologists reach a consensus diagnosis after interactive discussion (Table 2) [18]. Accurate diagnosis of IPF is critically important, as there have been recent breakthroughs in the treatment of IPF, with the advent of new antifibrotic therapies that have been shown to slow IPF disease progression [19, 20]. At the same time, traditional immunosuppressive medications frequently used for the treatment of other ILDs, including connective tissue disease–related ILD and hypersensitivity pneumonitis, have been shown to be harmful in IPF patients [21]. When therapeutic intervention in the elderly IPF population is being considered, consideration also needs to be given to other co-morbidities and medications, as well as the overall outlook of the patients.

Table 2 Multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF)
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5 Determining Prognosis in Patients with Idiopathic Pulmonary Fibrosis

Determination of the likely prognosis of individuals diagnosed with IPF is important to guide management, including pharmacotherapy, symptom control and timely referral to transplant and palliative care services. Many clinical and physiological features, as well as biomarkers, have been studied, some giving important insights into the behaviour and natural progression of IPF.

5.1 Demographic Factors

Of the clinical predictors that have been investigated, older age has been associated with poorer survival. In one study, the median survival of patients over 70 years was 14.6 months, compared with 27.2 months in those aged 60–70 years, 62.8 months in those aged 50–60 years and 116.4 months in those younger than 50 years of age [1]. These survival data, however, reflected death from any cause and may not necessarily have reflected mortality associated with IPF. Also, while IPF is more common in males, Han et al. [22] specifically investigated sex differences and found that females had a survival advantage (hazard ratio [HR] 0.63; 95 % confidence interval [CI] 0.41–0.97), but other studies have reported inconsistent results [23–25].

5.2 Physiological Factors

Physiological markers have also been extensively investigated to assess the severity of IPF and to predict the disease course. Of the pulmonary function variables, reductions in the forced vital capacity (FVC), diffusion capacity for carbon monoxide (DLCO) and total lung capacity (TLC) have been consistently shown to be associated with a poorer prognosis [23, 24, 26–28]. Also, a composite physiological index (CPI) combining the FVC, DLCO and forced expiratory volume in 1 second (FEV1) has been developed to account for concomitant emphysema, which is sometimes seen in IPF and has been shown to correlate with disease extent and predict survival [29]. While these measures are useful in patients presenting with later, more severe disease, baseline measures still do not provide an adequate prediction of disease behaviour, especially in patients presenting with early and mild disease.

Changes in serial pulmonary function may improve predictive power, with several studies showing that a relative fall in the FVC of ≥10 % or in the DLCO of ≥15 % over 6–12 months is associated with an increased risk of death [30–32]. In other studies, marginal falls in the FVC of only 5–10 % have also been associated with increased mortality [33].

5.3 Imaging and Histopathology

High-resolution computed tomography is also increasingly being utilised to determine the prognosis of IPF patients. The overall extent of fibrosis, a composite of reticulation and honeycombing, is associated with disease severity as assessed on pulmonary function and has been consistently associated with survival [27, 28, 34, 35]. There is also evidence to suggest that patients who have a UIP pattern on radiology have a worse prognosis than those with an atypical HRCT [36], though other studies have shown that when UIP is present on histopathology, the prognosis is poor, regardless of HRCT findings [35]. While significant research is underway to find a biomarker that may also assist with diagnosis of IPF and assessment of prognosis [37–40], none are currently in routine use.

These physiological and radiological markers assist in predicting the IPF disease course, which is an important endeavour, as new therapies aim to slow disease progression. It must be noted, however, that elderly patients often have multiple co-morbidities, some of which have the potential to alter the IPF disease course and increase the risk of mortality. Recognition of these co-morbidities is vital, as specific treatment may assist in improving outcomes in this universally devastating disease.

6 Co-morbidities in the Elderly

Co-morbidities are common in the elderly, with 65 % of people aged 65–84 years having at least two chronic conditions, increasing to 80 % in those aged over 85 years [41]. Given that IPF is a disease affecting the elderly population, it is no surprise that co-morbidities are common in patients with IPF. Some common co-morbidities and their reported prevalence rates are outlined in Table 3 [42]. Depression is prevalent in both the elderly and the IPF population but is often under-recognised and may have important implications for disease management and quality of life. In determining the optimal treatment of elderly patients with IPF, it is important to assess them for co-morbidities that confer a worse prognosis or that have the potential for therapeutic intervention [43].

Table 3 Common co-morbidities in patients with idiopathic pulmonary fibrosis [42]
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6.1 Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease is common in the elderly, with a reported prevalence of 14.2 % in people aged over 65 years, compared with 8.2 % in those aged 40–64 years [44]. The reported prevalence of COPD in the IPF cohort varies between 6 and 67 %, with the highest reported prevalence occurring in Asia. Indeed, there appears to be a particular cohort of patients with both IPF and concomitant emphysema, who have a distinct syndrome termed ‘combined pulmonary fibrosis and emphysema’ (CPFE) [45]. This syndrome is more common in men with a heavy smoking history. These patients often have relatively preserved lung volumes with a decreased DLCO. The presence of emphysema has been associated with reduced survival in several studies [46, 47], as well as increased risks of lung cancer and pulmonary hypertension (PH). However, in one study, this link to increased mortality was not present following adjustment for the presence of PH [47].

6.2 Pulmonary Hypertension

Pulmonary hypertension is a common complication of advanced IPF, occurring in up to 86 % of patients immediately prior to lung transplantation [42], and has been associated with increased mortality [45, 48]. However, PH may develop at any stage of the IPF disease course, and there is a poor relationship between the presence or severity of PH and the extent of the underlying fibrosis. There is also uncertainty as to whether mild to moderate PH, as opposed to severe PH, has prognostic significance [48–53]. While there is no evidence to suggest that PH is more common in the elderly, the older population is more likely to suffer from conditions that predispose to PH, including congestive cardiac failure, thromboembolic disease and obstructive sleep apnoea (OSA). While a study of sildenafil (a phosphodiesterase-5 inhibitor) in a subset of IPF patients with right ventricular dysfunction showed a smaller decline in the 6-min walk distance in comparison with placebo [54], ambrisentan (an endothelin receptor antagonist) was associated with increased risks of disease progression and mortality [55]. Currently, pulmonary vasodilators lack evidence of efficacy in patients with IPF and are not recommended for use in this group [56–58].

6.3 Sleep Breathing Disorders

The incidence of OSA increases with age [59] and is associated with an increased risk of cardiovascular events [60]. Within the IPF population, the prevalence of OSA varies, but it appears to be more common in patients with a higher body mass index (BMI) [42]. Other factors that may predispose IPF patients to OSA include enhanced collapsibility of the upper airway, due to reduced caudal traction, as well as ventilatory control instability [61]. While there have been few studies examining the presence of OSA and mortality in IPF, it has been suggested that the severity of nocturnal desaturation, regardless of apnoeas, is related to survival. It is hypothesised that lower oxygen saturations promote development of PH and thus result in higher mortality. This theory is supported by a study by Kolilekas et al. [62], who showed that the lowest nocturnal oxygen saturations were associated with higher right ventricular pressures and death in their cohort of 31 IPF patients. Despite this association, the true impacts of OSA and nocturnal oxygen desaturation on IPF are unclear, and the beneficial effects of targeted treatment, such as continuous positive airway pressure (CPAP) or nocturnal oxygen therapy, on quality of life or mortality remain uncertain.

6.4 Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is common in the elderly [63], as well as in IPF, and has been observed on 24-h pH monitoring in up to 94 % of patients [64]. GERD has been proposed as having a potential role in the pathogenesis, with microaspiration contributing to subclinical pneumonitis, leading to development or exacerbation of IPF [65, 66]. Observational studies have shown a survival benefit in IPF patients receiving antacid therapy [67]. Also, in an aggregate analysis of placebo groups from three randomised, controlled IPF trials, patients receiving antacid therapy had significantly less disease progression and fewer acute exacerbations than those not taking antacid therapy, although there was no difference in all-cause mortality or hospitalisation [68]. Currently, given that GERD is common and that these studies have shown possible benefit, consideration of treatment with antacid therapy is recommended in all IPF patients [57].

6.5 Depression

Depression is an under-recognised co-morbidity in the elderly, with depressive symptoms occurring in up to 16 % of adults aged over 60 years [69]. In ILD, clinically significant depression has been reported to occur in 23–27 % of patients and has been associated with poorer quality of life [70, 71]. Dyspnoea, a symptom affecting up to 90 % of IPF patients at the time of diagnosis, has also been found to strongly correlate with depression in IPF patients, independent of the severity of lung function limitation (as measured by the FVC and DLCO) [70]. Given the high prevalence of depression in the elderly, as well as in IPF, routine screening and treatment of depression should be considered. Although there have been no studies addressing treatment of depression in the IPF population, improvements in mood may well equate to improvements in quality of life and should be considered. The cause of depression is likely to be multifactorial; therefore, treatment should be comprehensive and should include education and psychosocial support, as well as pulmonary rehabilitation and pharmacological therapy if required.

7 Antifibrotic Therapy: Considerations in the Elderly Patient with Idiopathic Pulmonary Fibrosis

Until just recently, an effective treatment for IPF was not available, and management was focused on palliation of symptoms and referral for lung transplantation. Medical therapies that have previously been considered included immunosuppressive medications such as corticosteroids and azathioprine [72], N-acetylcysteine [73] and anticoagulation [74]. While these therapies showed some early promising results, larger, randomised trials failed to show benefit and in some cases caused increased harm [21].

7.1 Pirfenidone

Pirfenidone is one of two new antifibrotic agents approved by the US Food and Drug Administration (FDA) in 2014 for use in IPF. It has been shown to reduce lung fibrosis in animal models by reducing fibroblast proliferation and collagen synthesis, and through its effect on pro-fibrotic and pro-inflammatory cytokine cascades. The ASCEND trial [19] was a randomised, double-blind, placebo-controlled trial and randomised 555 patients with IPF to receive either pirfenidone (2403 mg/day) or placebo. The inclusion criteria were relatively specific, with patients greater than 80 years of age specifically being excluded. Overall, of the 1562 patients who were screened, only 36 % were included. During the 52-week follow-up period, pirfenidone significantly reduced the proportion of patients who had a ≥10 % decline in the FVC (16.5 % in the pirfenidone treatment group versus 31.8 % of those in the placebo group). There was also almost a 50 % reduction in the FVC decline in the pirfenidone group (235 mL versus 428 mL in the placebo group). A pooled analysis [75] of 1247 patients from the ASCEND [19] and CAPACITY [76] studies confirmed these findings, with a 43.8 % reduction in the proportion of patients with a ≥10 % decline in the FVC or death at 1 year. Additionally, a subgroup analysis of FVC outcomes also showed a consistent treatment effect in all strata of demographic and baseline measures, including age over 75 years.

The main adverse effects were nausea, abdominal pain and a photosensitive rash. However, the drug was well tolerated overall, with only 14.4 % of patients discontinuing pirfenidone treatment, compared with 10.8 % in the placebo group.

7.2 Nintedanib

Nintedanib, a tyrosine kinase inhibitor, also gained approval for use in IPF in the USA in 2014 on the basis of INPULSIS 1 and 2, two replicate randomised, double-blind, placebo-controlled studies [20]. While these studies did not have an upper age limit, the mean age of participants was 66–67 years. In this group of 1066 patients followed for 52 weeks (with a 3:2 ratio for treatment with nintedanib 150 mg or placebo), there was a >50 % reduction in the adjusted annual FVC decline in the nintedanib group compared with the placebo group (114.7 mL in the nintedanib group versus 239.9 mL in the placebo group), with fewer patients treated with nintedanib experiencing a 10 % decline in the FVC (relative risk [RR] 1.16; 95 % CI 1.06–1.27).

A pooled analysis [77] of 1231 patients from the INPULSIS [20] and TOMORROW [78] studies also showed a reduced annual decline in the FVC with nintedanib, and while it also showed a reduced time to the first acute exacerbation (HR 0.53; 95 % CI 0.34–0.83), there was no significant effect on mortality (HR 0.70; 95 % CI 0.46–1.08). An analysis of prespecified subgroups [79] showed consistent effects of nintedanib across a range of IPF phenotypes, including those in the older age group (≥65 years).

Diarrhoea was the most common adverse event, occurring in over 60 % of the treatment group, compared with 18 % in the placebo group. Other common events included nausea and vomiting, but most events were mild to moderate, with few people discontinuing treatment (17–21 % in the nintedanib group versus 10–15 % in the placebo group). It should also be noted that there were more myocardial infarction occurred in the nintedanib group than in the placebo group; however, the numbers were small (<2 %), and the significance of this is currently unclear. The pharmacokinetic profile, interactions and adverse effects of both drugs are listed in Table 4.

Table 4 Properties of two new antifibrotic agents: pirfenidone and nintedanib
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7.3 Limitations of Randomised, Controlled Trials

While there were variations in the inclusion and exclusion criteria in the ASCEND and INPULSIS studies, both trials recruited patients with mild to moderate disease, with patients with an FVC <50 % or a DLCO <30 % being excluded from both trials. Patients with significant co-morbidities were also often excluded, though—unlike ASCEND, which excluded patients with an FEV1/FVC ratio of <80 %—INPULSIS 1 and 2 did include some patients with coexistent emphysema, with no difference in the efficacy of nintedanib in this group. These strict criteria, resulting in a fairly homogenous cohort—although useful for clinical trials—limited the data on the tolerability and safety of these medications, as well as the generalisability of efficacy, particularly in patients aged over 80 years.

Other limitations of these trials included their short durations, with both ASCEND and INPULSIS reporting outcomes only over 52 weeks. The use of these medications beyond this time period remains questionable; however, provisional data suggest that the benefit is sustained [80] and that continued use is safe [81]. Also, there are still no clear answers regarding management of patients who progress despite single antifibrotic therapy. Further trials in such patients, with either sequential or upfront combination therapy, are required. Finally, despite the advances in therapeutic interventions, it is important to remember that lung transplantation remains a viable option in IPF patients, with IPF patients who receive lung transplantation having favourable long term outcomes [82]. Also, while increasing age is often associated with co-morbidities, age alone should not be considered a contraindication to transplantation [83].

7.4 Polypharmacy

Polypharmacy is a common problem in the elderly, with patients aged over 65 years often receiving more than five medications per day [84], and it has the potential to alter the metabolism and effect of antifibrotic agents. Polypharmacy also has important consequences, including an increased risk of adverse drug reactions, decreased adherence and increased risks of morbidity and mortality. The risk of adverse drug reactions increases with increased medication use, with one study in hospitalised patients showing that the risk of adverse drug reactions was 2.65-fold higher in patients taking more than four drugs [85]. The number of drugs taken was also the most significant predictor of adverse drug-related emergency hospital admission, irrespective of co-morbidities, with patients taking three or more medicines having a 4.3-fold higher risk [86].

Polypharmacy also has the potential to reduce compliance and therefore the efficacy of prescribed medications. In the elderly, the need to take more than three medicines daily raises the likelihood of non-compliance in direct proportion to the number of different drugs that need to be taken [87]. Also, compliance declines significantly when medications need to be taken more frequently [88]. These issues regarding the pill burden are particularly important for consideration of pirfenidone, which requires three-times-daily treatment with 3–4 tablets.

7.5 Drug Interactions

While interactions of antifibrotics with other drugs appear to be minimal, it is particularly important to consider this potential issue in elderly patients, who may be less able to tolerate increased side effects from medications. As pirfenidone is mostly metabolised by cytochrome P450 (CYP) 1A2, inhibitors (fluvoxamine and ciprofloxacin) may increase the available drug, while inducers can reduce drug concentrations. Nintedanib, on the other hand, is metabolised by P-glycoprotein (P-gp) and to a minor extent by CYP3A4, with potential interactions with inhibitors (ketoconazole and erythromycin) and inducers (carbamazepine, phenytoin, rifampicin and St John’s wort). There is also a theoretical risk of increased bleeding with tyrosine kinase inhibitors, and, as such, it is not recommended to take nintedanib with anticoagulants or antiplatelet agents other than aspirin. Smoking reduces the systemic exposure to both nintedanib and pirfenidone; hence, patients should avoid smoking while on these medications (see Table 4). While there have been no studies looking at the efficacy of the combination of nintedanib and pirfenidone, Ogura et al. [89] showed in a randomised, double-blind, phase 2 study of 50 patients that the addition of nintedanib to pirfenidone resulted in lower concentrations of nintedanib, while pirfenidone was not significantly affected.

A comprehensive geriatric assessment evaluating the patient’s global prognosis and identifying diseases that take priority for treatment is important to reduce polypharmacy [90]. In this sense, the new antifibrotic medications aimed at slowing disease progression need to be considered in the context of the patient’s other co-morbidities. Consideration for the patient’s overall prognosis and burden of disease needs to be undertaken prior to the decision to initiate antifibrotic therapy, to balance the risks and benefits of this expensive but revolutionary therapy.

8 Palliation of Symptoms and End-of-Life Care

Disease-centred therapy for IPF is often the focus of many physicians and patients alike; however, it is important to remember that there is still no treatment that halts the disease. Symptoms including intractable dyspnoea, cough, weight loss and fatigue will become universally prevalent as the disease progresses, and the presence of these symptoms often leads to depression and reduced quality of life. The palliation of these symptoms is therefore a priority to improve quality of life, as are discussions that focus on end-of-life care. This requires advanced care planning, relief of physical and psychological burdens, and patient and carer education [91, 92].

8.1 End-of-Life Care

A number of studies in the past decade have identified lack of early integration of palliative care in patients with IPF. In a study of 277 patients with IPF, 57 % died in hospital (rather than in a community hospice or another place of their choice), 13.7 % had a formal palliative care referral and the majority (71 %) were referred within a month of their death [93]. Similar results were seen in a study done in the UK, where end-of-life preferences were poorly documented or implemented in patients with severe IPF, prior to their death [94]. The lack of early implementation of palliative care in these patients may be due to the sudden onset of a life-threatening acute exacerbation in a previously stable patient. Acute exacerbations of IPF are characterised by rapid deterioration—over days to weeks—in symptoms, lung function and radiological appearance, in the absence of some other identifiable cause (infection, pulmonary embolism heart failure, etc.). Supportive care is the mainstay of therapy; however, high-dose corticosteroids are commonly prescribed, despite a lack of controlled trials assessing their efficacy. Exacerbations are associated with poor outcomes; therefore, it is important to recognise this risk of rapid deterioration at any point throughout the disease course and, indeed, to discuss this with IPF patients. This allows for important education and discussions about end-of-life wishes to take place in a timely manner prior to any deterioration in the disease.

8.2 Symptom-Centred Management

8.2.1 Dyspnoea

As IPF progresses, dyspnoea increases and is in fact an important prognostic marker [26]. The cause is likely to be multifactorial, including respiratory failure from poor gas exchange, increased ventilatory demand and respiratory muscle weakness, as well as depression and anxiety. Dyspnoea is strongly correlated with depression and quality of life, independent of lung function [95]. Despite the frequency of dyspnoea in IPF, there are few data on its management in this disease. Evaluation and treatment of co-morbidities—such as heart failure, sleep disordered breathing and PH, which may contribute to dyspnoea—are important.

Pulmonary rehabilitation is a cornerstone of symptom-centred management in IPF and is associated with improvements in functional exercise capacity, as measured by improvement in the 6-min walk distance in patients with IPF [96]. It also results in improved quality of life and—most importantly—it is safe, at least over the short term [97]. Some studies have also shown improvement in dyspnoea with pulmonary rehabilitation [98]; thus, it is essential that all patients with IPF are considered for referral to a pulmonary rehabilitation programme. Supplemental oxygen for hypoxic patients is also beneficial, at least in the short term [99]. Palliation of dyspnoea with opioids can also be considered [100]; however, use of benzodiazepines remains controversial [101].

8.2.2 Cough

Chronic cough is also a common problem in IPF, which often results in a significant symptom burden. The precise mechanism is unknown but is likely to be multifactorial, with IPF possibly causing increased cough sensitivity and with the cough being exacerbated by GERD, asthma or upper airway cough syndrome. Unfortunately, it is a difficult symptom to palliate, but consideration of antitussives, such as codeine and other opioids, is warranted. Thalidomide has also shown promise, with Horton et al. [102] showing improvement of cough and respiratory quality of life in a small, single-centre study of 47 patients with IPF.

8.2.3 Fatigue

Fatigue is common in IPF and can be the dominant symptom in many patients. It often results in lower physical activity, even in patients with relatively preserved respiratory function [103]. This reduction in physical activity can lead to a cycle of deconditioning and increased fatigue, potentially increasing overall mortality [104]. Like all palliative measures, education and regular assessment are key, as is pulmonary rehabilitation.

9 Conclusion

Idiopathic pulmonary fibrosis, though rare, is more common in the elderly and presents some unique considerations. IPF diagnosis is often more difficult in the elderly, as the symptoms are non-specific and asymptomatic interstitial changes are relatively frequent. However, accurate diagnosis is imperative, as antifibrotic agents offer new hope in this devastating disease. While caution is advised, treating physicians should always endeavour to use these agents in appropriate patients, without age being a barrier to this approach. Treatment of the elderly IPF patient should also include diagnosis and treatment of co-morbidities that have the potential to alter the disease course. Lastly, it is important to remember that symptoms are common and burdensome, particularly in the later stages, and symptom-centred management is critical to the overall care of the IPF patient. We hope that improved awareness of the subtleties of IPF diagnosis and the diversity of management options improves patient outcomes in this fatal disease.