Patients' perceptions and patient-reported outcomes in progressive-fibrosing interstitial lung diseases

Patients' perspectives on diagnosis

Unfortunately, the emotional toll paid by patients diagnosed with PF-ILD typically begins long before the diagnosis is confirmed. Published data reveal, after coming to medical attention, it takes patients with IPF (on average) longer than a year and multiple visits to physicians to be diagnosed [4].

Having to wait a long time before a diagnosis is made and living that time without a name to explain the cause of their symptoms (leaving patients unaware of what they are up against), generates anxiety for patients who feel they are unable to prepare themselves for what living with the disease entails [5, 6]. Collard et al. [7] administered surveys to 1448 patients with IPF, nearly two-thirds of whom (63.5%) reported being ill-informed about disease management. Patients have also expressed frustrations about a lack of patient-friendly, readily-available, easily-accessible information on IPF at the time of their diagnosis. Similarly, all-comers with connective tissue disease related-ILD, or cohorts of patients with rheumatoid arthritis- or systemic sclerosis-related (SSc)-ILD have expressed confusion around their diagnoses and recognised a need for improved patient–doctor communication [8, 9]. In IPF, the past couple of years have witnessed progress toward answering the call for more educational resources. Such tools are critical to helping patients better prepare themselves for what can be an uncertain future living with the disease. Part of this preparation involves learning healthy coping strategies to deal with negative thoughts and feelings. The involvement of practitioners, including experienced nurses or behavioural health experts, who are trained to help patients navigate the emotional effects of living with a progressive, chronic illness assures adequate support in selected cases.

Day-to-day life

Cough and activity-limiting dyspnoea have immense impact on the everyday lives of patients with IPF and other ILDs [2, 10–12]. Cough can affect sleep, willingness to participate in social activities [9] and thus, physical and emotional well-being. Fatigue can be equally debilitating and lead to decreased social participation, physical deconditioning, low mood and isolation [2, 10, 12, 13].

In patients with PF-ILD, dyspnoea limits physical activity in many ways [8, 9]. Some patients avoid certain activities altogether, because the dyspnoea those activities induce is overwhelming; many patients describe having to slow down or stop and rest (perhaps multiple times) to complete an activity. For patients with IPF, this is frustrating and compounds the burden of facing an uncertain future that will probably include worsening health, the need for supplemental oxygen and shortened survival [10].

As the disease progresses, patients' declining physical functioning limits their ability to look after themselves, forcing them to rely on others (most often a spouse) for help [2]. In the latter stages of IPF, performing basic tasks, such as showering or simple household chores, becomes a struggle [2, 10].

Besides posing a substantial threat to patients' physical well-being, PF-ILD can negatively impact patients' mental well-being. Patients may suffer from bouts of anxiety and/or depression and develop feelings of grief and anger [9, 12]. Living with, and coming to terms with a terminal illness, is remarkably difficult [6]. Patients with IPF struggle to cope with the loss of independence and grieve the loss of the lives they once enjoyed [2, 14]. Patients can also feel disconnected with family, as they are unable to participate in family life and care for others [9, 10].

Patients' expectations of treatment

An ideal treatment would prolong survival, improve QoL and functional status, and reduce the frequency and severity of symptoms [10]. Currently, there are no “cures” for PF-ILD. There are no approved treatment options for PF-ILDs, although corticosteroids and immunosuppressive therapies are sometimes used. While the antifibrotic medications, recently approved to treat IPF (pirfenidone and nintedanib), may slow disease progression, neither was associated with consistent, beneficial effects on symptoms or QoL across phase II and III trials, and neither are approved for the treatment of other PF-ILDs. Specific treatments for fibrosing ILDs that may present a progressive phenotype are covered in more detail by Richeldi et al. [15].

Oxygen therapy is commonly given to alleviate dyspnoea in IPF [14]. This treatment relies on access to oxygen, and requires patients to carry, push or pull tanks and to wear a cannula or have a catheter to breathe in the oxygen. Having to use oxygen can leave patients housebound [10]. The idea of being connected to a machine or tank to receive oxygen is unpleasant, and IPF patients would welcome more convenient oxygen delivery systems that would enable them to be more physically mobile and to travel [10].

The authors recognise that the treatments themselves (taking antifibrotics and/or using supplemental oxygen) can be sources of stress and anxiety for patients. Practitioners aware of this possibility, and able to deal with it if it occurs, are likely to help patients remain adherent to therapeutic interventions.

PROs used in clinical trials

The vast majority of ILD-related clinical trials have focused on IPF and generally used lung function and/or mortality as primary end-points. PROs could easily be used in clinical trials to evaluate symptoms, the effectiveness of a drug and progression of disease [16]. However, few interventional trials have been focused on patient well-being [11, 17] and, when used in these studies, PROs have mainly been regarded as lower-tier end-points [3, 11, 12, 14].

PROs that have been used in studies include dyspnoea indices, cough questionnaires, health status instruments, health-related QoL (HRQoL) measures, depression or anxiety questionnaires and sleep surveys [3]. St. George's Respiratory Questionnaire (SGRQ) has been used in IPF and other PF-ILD trials to assess respiratory health status [11, 18]. Dyspnoea-specific PROs have also been used to evaluate treatment response [11, 19]. The Medical Outcome Study short-form 36 (SF-36) and the EuroQoL-5D are questionnaires that have been used to assess health status and HRQoL [11, 20, 21]. Anxiety and depression have been quantified using the Hospital Anxiety and Depression Scale and the Generalised Anxiety Disorder Questionnaire – 7 item [22]. An overview of the most widely used PROs in IPF are summarised in tables 1 and 2 [14].

ILD-specific PROs

To date, the PROs most commonly used in IPF trials were originally intended for other uses, including assessing outcomes in patients with other respiratory diseases [37, 38]. PROs developed for chronic obstructive pulmonary disease (COPD), including the SGRQ and COPD assessment tests, have been studied in patients with IPF [12, 14]. Despite some items lacking face validity for IPF, the SGRQ appears to perform reasonably well (particularly its Activities domain) as a measure of health status and symptom severity in patients with IPF. A modified version of the SGRQ has been developed particularly for patients with IPF [12]. The reliability and validity of this PRO is comparable with the original SGRQ as demonstrated by certain psychometric parameters (e.g. internal consistency) and correlation with relevant disease severity measures. However, longitudinal response data are needed to further assess its performance in IPF [14].

A questionnaire specifically developed for ILDs is the King's Brief ILD (K-BILD) health status questionnaire [14, 25]. The K-BILD requires longitudinal evaluation in PF-ILD [11].

Symptom-specific PROs that have been used to assess outcomes in patients with ILDs are summarised in table 2. These include the University of California San Diego Shortness of Breath Questionnaire, the modified Medical Research Council (mMRC) scale, the Mahler Baseline and Transition Dyspnoea indexes and the Borg scale [11, 14]. Recently, the Functional Assessment of Chronic Illness Therapy-Dyspnoea has been shown to possess validity for assessing dyspnoea in patients with SSc [39]. The mMRC score has been shown to predict survival in patients with IPF [40], but has not been verified for use in patients with SSc-ILD [11].

Although cough is a common symptom of many ILDs, questionnaires have not been developed to assess cough severity or impacts specifically for patients with PF-ILD [14]. In the authors' opinion, characterisation of this potentially debilitating symptom would be beneficial. The Leicester Cough Questionnaire is currently considered suitable for use in clinical trials (particularly in IPF) [11, 14], but the utility of the Cough QoL Questionnaire in other ILDs that may present a progressive-fibrosing phenotype remains to be elucidated [11].

While fatigue is an important symptom, to date, no specific fatigue questionnaires for IPF exist. As with cough, such a tool may or may not be needed. The Fatigue Assessment Scale, originally developed for sarcoidosis, has been used [14]. The Functional Assessment of Chronic Illness Therapy Fatigue Scale has been validated for use in SSc-ILD [11].

An IPF-specific PRO is currently being developed with the input of a multidisciplinary team of patients and carers [41]. An IPF-specific QoL instrument, A Tool to Assess Quality of Life in IPF, and its modified variant, the living with IPF questionnaire [14] have been developed and are in the late stages of US Food and Drug Administration qualification.

Relevance of existing PROs for assessing HRQoL

Using disease-specific and validated PROs in the clinical arena could improve quality of care by alerting practitioners to effects of disease that may otherwise go unrecognised. In the research arena, PROs allow measurement of disease-specific effects not captured by other outcomes. Widely used PROs fail to address certain aspects deemed important by patients [11, 12]. For example, in IPF, patients generally experience a non-productive cough; however, some patients report a productive “hacking cough”, which is not captured in current PROs [10, 13]. Some language in the SGRQ, such as “attack” or “attacks of the chest”, do not resonate with IPF patients, as they feel that this does not correctly describe their disease experience [13]. A “sometimes” response option would be useful to capture IPF patients' perceptions on some true/false items on the SGRQ more accurately [13]. A category missing from HRQoL questionnaires is one that includes items addressing the impact of supplemental oxygen on QoL [13]. Because many patients with PF-ILDs will need supplemental oxygen, it is imperative that the impact of this treatment on patient's lives is captured [13].

For any PRO to be useful as a research tool, its basic psychometric properties must be confirmed to fall within the acceptable ranges. For PROs that have been used in IPF research, some of these properties remain to be determined [13]. For a PRO to be used as an end-point in longitudinal research, data to support its longitudinal validity must be generated. For tools currently under development, such data are accruing [13].