Idiopathic pulmonary fibrosis is a heterogeneous disease, with a highly variable disease course (10, 11). Additionally, different phenotypes of IPF exist. Most patients have a slow disease progression, while some patients display relative stable periods followed by acute exacerbations and a small group of patients experiences a rapid decline in lung function (12). Uncertainty about the disease course and prognosis can cause emotional distress and anxiety, and, as a result, IPF has a major impact on most patients’ health-related quality of life (HRQOL). HRQOL can be defined as a patient’s perceived well-being affected by disease and treatment of the disease (13). IPF affects patients in almost every domain of life; hence, the burden of the disease is high, not just for patients but also for their partners and families. Patients often struggle with loss of independence because of functional limitations and deteriorating symptoms. Not only can breathlessness, cough, and fatigue diminish QOL, but also other symptoms such as sleep disorders, loss of appetite, and psychological problems can (14–18).

Most clinical trials in IPF that have been performed so far, have shown no convincing improvement of patient HRQOL (5, 6, 19). To date, the main focus in research has been to stabilize or improve physiological outcomes rather than HRQOL. Physiological parameters, such as lung function, do not correlate well with HRQOL measurements (20, 21). To our knowledge for parameters as imaging and biomarkers, relationships with HRQOL have not yet been established. Thus, decline in lung function does not adequately reflect the perceived impact of the disease on patients’ lives.

Every person has a different lifestyle, personal circumstances, and coping strategies. These factors can play an important role in how a disease manifests itself; hence, the same disease affects each person in a different way (16, 22, 23). Medication may show promising results at group level in randomized controlled trials, but still in some individual patients, treatment may fail (22). For example, the side effects of medication may outweigh the positive effects of medication in daily practice, or the burden of treatment might be too high for patients. To improve and personalize treatment of IPF, we should also include patient perspectives and QOL.

Personalized, stratified, or precision medicine is a broad term which can be referred to as “delivering the right treatment to the right patient at the right time” (24). Personalized medicine has gained increasing attention during the past decade (22, 25). However, the concept is not new; Hippocrates already mentioned the importance of a personalized approach to diagnosis and treatment in the fifth century BC, stating that “individuality of human beings affects predisposition to disease and response to treatment,” and also noting that “not all patients are able to drink the same therapeutic drinks” (1, 26). His concepts already include the notion that experiences with treatment differ among patients. This idea is also acknowledged by Britten et al., who suggest that because individuals are more than their genetic profile, the main concept of stratified medicine is too limited at the moment (22). Personalized treatment comprises not only “biology,” but should also focus on patient perspectives, needs, experiences, personality, environment, lifestyle, and other personal circumstances (Figure 1) (9, 22). Accordingly, the term “personomics” has been introduced to capture a patient’s life circumstances that may alter disease behavior and response to treatment (23). Below we will briefly touch on the role of biology and other aspects of personalized medicine as shown in Figure 1, but the focus will be on patient perspectives.

In other fields, especially oncology, personalized medicine has dramatically changed clinical practice during the last few years. Biomarkers have been used to develop targeted therapy and allocate patients to individual treatment plans (27–29).

Currently, the diagnosis of IPF is based on clinical, radiological, and pathological findings (3). The exact etiology of IPF is, however, incompletely understood. One of the proposed hypotheses is the concept of dysfunctional wound healing: repeated epithelial injury and dysfunctional regeneration possibly in combination with a dysregulated immune system normally facilitating wound healing leads to fibrogenesis and, as a consequence, excessive scarring of the lung tissue (11, 30). Epithelial injury might be caused by risk factors such as cigarette smoking, micro-aspiration of gastric content, and lead to development of IPF in susceptible individuals (11). At present, it is assumed that multiple biological pathways and complex interactions between genetic, molecular, and environmental factors are involved in the pathogenesis of IPF. Improved understanding of the pathogenesis of IPF has led to the identification of potential molecular biomarkers (7, 11, 31–33). Genome-wide association studies found genetic mutations that correlate with disease risk and possibly also disease progression (34–37); subsequently, the first examples of drug–gene interactions in IPF were found (38). To date, the value of biomarkers in IPF has not been fully clarified, and, therefore biomarkers or genetic endotyping are not yet used in clinical practice (7, 33).

Novel studies in IPF suggest that the “respiratory microbiome” is also involved in IPF pathogenesis, disease progression, and mortality (39–41). Patients with IPF have a higher bacterial burden and abundance of specific pathogens in the lung microbiome than the normal population. Furthermore, interactions have been found between specific gene expression and an altered lung microbiome in IPF, which is the first evidence for host-environmental interactions in IPF (42, 43). The lung microbiome may serve as a prognostic factor in the future, and clinical trials aimed at altering the microbiome of patients with IPF have already started (44).

A detailed description of (molecular) biology and its current role and potential in the IPF field is beyond the scope of this review.

The importance of engaging patients in IPF care has gained increasing attention during the last several years (45). Recent qualitative studies have reported a need for better education about IPF, information about specific treatment options and palliative care, and access to specialist centers and specialist nurses. Additionally, more support for caregivers is warranted (16, 17, 46–48). These recommendations underscore the idea that not only pharmacological treatment but also non-pharmacological treatment options such as oxygen therapy, pulmonary rehabilitation, psychological support, and palliative care, are an important part of personalized management. With regard to pharmacological treatment, it is important to assess the needs and perspectives of patients before starting treatment, thereby enhancing shared decision-making. For instance, some side effects of disease-modifying drugs might have a devastating impact on one patient, but be far less bothersome to other patients (22). At the moment, over-use and under-use of medication, compliance problems, and waste of medication are not unusual in IPF (22, 49, 50). Non-adherence to medication could therefore be prevented when patients’ preferences and lifestyle are taken into account (9). Since patient preferences and needs may change because of disease progression or personal circumstances, an important aspect of disease management is iterative evaluation of the situation of individual patients (16, 46, 51). Only in this way can “holistic” personalized care be given in IPF.

Holistic care also means looking further than the lungs. IPF is associated with a number of pulmonary and extra-pulmonary comorbidities, such as pulmonary hypertension, respiratory infection, cardiovascular disease, emphysema, lung cancer, diabetes mellitus, venous thromboembolism, and gastroesophageal reflux (52–56). Comorbidities are more prevalent in patients with IPF than in the normal population and have a negative influence on QOL and survival (54, 56–58). Hence, early identification and treatment of comorbid conditions have the potential to improve QOL, functional outcomes, and survival for patients with IPF (53). Kreuter et al. (54) proposed the “IPF comorbidome,” which visually displays prevalence of comorbidities and their strength of association with mortality in patients with IPF. This comorbidome could be used to predict prognosis for individual patients with IPF, and thus enhance personalized treatment.

Moreover, extra attention should be paid to the frail, elderly patients who have multiple comorbidities and functional impairment (55). As a consequence, these patients might have a higher risk of harmful side effects of disease-modifying medication and should be closely monitored during treatment. Besides, polypharmacy may play an important role in this group of patients. It is generally known that polypharmacy decreases medication compliance, increases risk of adverse drug events, and might lead to impaired functional status and cognitive impairment in elderly patients (59). Furthermore, co-medication can also interfere with disease-modifying medication, and subsequently increase side effects or reduce treatment efficacy (60). Accordingly, co-medication could play an important role in the choice of pharmacological treatment in IPF. Expected risk–benefit ratio, comorbidities, and co-medication should be taken into account before pharmacological treatment is started in individual patients.

A PRO is defined as “any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else” (61). Patient-reported outcome measures (PROMs) can be used to measure (HR)QOL, assess symptoms, and evaluate disease progression. There is a difference between generic and disease-specific PROMs. Disease-specific PROMs are developed to assess symptoms and (HR)QOL in a specific disease, whereas generic PROMs address more general questions and can be used in the whole population (62). One of the most commonly used generic PROMs in IPF trials are the short-form 36 and the Euroqol-5D, which is also a widely accepted instrument for economic evaluation in healthcare (63, 64). An overview of the most widely used PROMs in IPF is given in Table 1.

PROs could be very helpful to enhance personalized treatment in IPF (Figure 2). Until now, PROMs have been mainly used for research purposes, as a secondary endpoint in clinical trials. The most used primary endpoint in IPF trials is forced vital capacity, which is accepted as a surrogate measure for mortality (85). One study showed that HRQOL, assessed with the SGRQ, is also an independent prognostic factor for mortality in IPF (86). PROMs probably reflect another dimension of disease compared with traditional physiological parameters (86). In the future, PROMs could possibly be used to predict treatment success in IPF.

PROM uses in daily practice can allow healthcare providers and patients to gain more insight into the individual disease and patient behavior. In a study of Sampson et al. (46), most patients were uncertain about their own disease course and progression and had difficulties interpreting objective hospital-based parameters. PROMs could allow both patients and healthcare providers to keep track of symptoms and disease progression easily. PRO results can even be used as a simple tool to communicate with patients, educate them, promote self-management, and aid shared decision making during the course of the disease (19, 87). A systematic review in oncology has shown strong evidence that routine collecting of PROs improved patient-centered care, patient satisfaction, and detection of unrecognized problems (88).

Optimal treatment requires close monitoring of the balance between the effects and side effects of disease-modifying drugs. Nonetheless, to our knowledge, a reliable measure to assess patient experiences with medication in IPF is not yet available in clinical practice. For this reason, a consortium of doctors, scientists, and patient representatives has joined forces to develop the patient experiences and satisfaction with medications (PESaM) questionnaire, which has a generic module and a disease-specific part for IPF (84). The PESaM questionnaire focuses on perceived effectiveness, side effects, and ease of use of medication and its impact on patients’ lives. This patient-reported experience measure (PREM) could not only be used in future clinical trials, but also in clinical practice to help with better detection of side effects and adjustment of medication. Moreover, Russell and colleagues, together with patients, are currently developing the “IPF-PREM.” This is a measure to assess patient experiences with healthcare and can possibly be used to improve the quality of care for patients (69).

Ideally, for a better tailored treatment, frequent monitoring with a low burden for the patient is needed. In the last decade, the use of e-health in chronic diseases has been growing, and shows mostly promising results (89–91). E-health involves the exchange of data between a patient and a healthcare provider using information and communication technologies (92). By using e-health tools, patients may better understand their health condition and become actively involved in the management of their own disease. It allows frequent monitoring in between regular visits and collection of PROs at home (93). Recently, a study showed that daily home spirometry in a population of patients with IPF was highly feasible and informative (94). Home-based spirometry predicts disease decline and mortality better than hospital-based measurements. Routine home spirometry could be very helpful to identify patients with rapid decline in lung function and to evaluate response to treatment. The authors suggest that daily home spirometry will allow for more individualized patient care. The feasibility of home-based spirometry in IPF was confirmed by Johannson et al. (95), who additionally showed that home spirometry might reduce sample size as well as the length of future clinical trials. Another promising example of home monitoring in IPF is the longitudinal follow-up of physical activity with activity trackers worn by patients at home (96). Decline in physical activity can provide reliable, objective data on disease progression and could be integrated into a home monitoring program. A comprehensive home monitoring program, consisting of an e-health tool combined with home spirometry and online collecting of PROs, has the potential to enhance trial design, stimulate self-management, allow for early treatment adaption to minimize side effects, prevent hospital admissions, and subsequently improve personalized management and QOL for patients with IPF.