Palliative Care Support Improves Quality of Life of Patients with Fibrotic Interstitial Lung Disease

Background

Fibrotic interstitial lung disease (fILD) is frequently progressive and unpredictable.^1–3 The main features of fILD are declining pulmonary function, worsening symptoms (cough, severe dyspnea, anxiety, panic, and depression) and health-related quality of life (HRQoL), and early mortality.^4–6 Patients with fILD may have the same symptom burden and need of medical care as terminal cancer patients. ⁷ There are several palliative interventions that can mitigate the impact of end-stage lung disease to improve symptoms and quality of life (QoL), with mortality benefit also observed in some populations such as terminal cancer. ⁸ However, evidence supporting the pharmacological and nonpharmacological interventions provided by the palliative care team is limited, with inconsistent results particularly for patients with fibrotic ILD. ⁹ The aim of this study was therefore to analyze the impact of a palliative bundle of care in patients with fILD. We hypothetized that the interventions suggested by the palliative care team would improve symptoms and HRQoL in patients with fILD.

Methods

Results

Sample demographic and clinical characteristics

We included 14 patients during the study period, with all patients being followed up at 30 and 90 days (Table 1). Median age was 63 years (54–71), and 85% were female. The most frequent etiology associated with fILD was connective tissue disease (64%), with 44% of these having rheumatoid arthritis. Only 14% of patients had a diagnosis of IPF. The median Karnofsky index was 65 (50–70), reflecting the requirement of occasional assistance but with the ability to self-manage most personal needs. Lung function was severely reduced with the median FVC of 44%, (33–47) and a 6-minute walk distance of 328 meters (283–360). All patients reported cough, dyspnea, and fatigue at baseline.

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Table 1.

General Characteristics of the Population under Study (n = 14)

Variable	Median (IQR)
Age (years)	63 (54–71)
Female	12 (85%)
Weight (kg)	58 (53–68)
Size (meters)	1.47 (1.41–1.53)
BMI (kg/m2)	27.8 (23.8–31.7)
Charlson’s Index	2 (2–3)
Baseline functional capacity
Karnofsky	65 (50–70)
LVEF through TTE (%)	61 (59–65)
FVC (%p)	44 (33–47)
6-minute walk (meters)	328 (283–360)
Baseline symptoms
Cough	14 (100%)
Shortness of breath	14 (100%)
Pain (unspecified)	10 (71.4%)
Fatigue	14 (100%)
Nausea	6 (42.9%)
Depression	12 (85.7%)
Anxiety	8 (57.1%)
Sleepiness	9 (64.3%)
Loss of appetite	8 (57.1%)
Difficulty sleeping	11 (78.6%)

Data are presented as frequencies with percentages and medians with interquartile range.

BMI, body mass index; ILD, interstitial lung disease; RA, rheumatoid arthritis; IPF, idiopathic pulmonary fibrosis; NSIP, nonspecific interstitial pneumonia; HP, hypersensitivity pneumonitis; LVEF, left ventricular ejection fraction; TTE, transthoracic echocardiogram; FVC, forced vital capacity.

Change in symptoms and quality of life

There was statistically significant improvement in all symptoms at days 30 and 90 (Table 2). The improvements were seen over time in dyspnea (mMRC scale, p < 0.001) and cough (p < 0.001). The ESAS questionnaire also showed improvement in tiredness/fatigue (p = 0.002), appetite (p < 0.001), difficulty sleeping (p = 0.015), and sleepiness (p = 0.041) (Fig. 1). There was improvement in QoL and well-being at 30 and 90 days, particularly in the SGRQ-1 (p = 0.001), which improved by 20 points from baseline to 90-day follow-up (91.2 points, IQR 84.3–96 vs. 71.3 points, IQR 55.9–75.6, p = 0.006) (Fig. 2).

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FIG. 1.

Changes in symptom perception at follow-up with palliative care intervention.

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FIG. 2.

Quality of life evaluation, perceived by the patients through the SGRQ-1 (Saint-George Respiratory Questionnaire-1).

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Table 2.

Change in Symptoms and Quality of Life over Time

Variable	Baseline	30-day evaluation	90-day evaluation	p Value
mMRC dyspnea	3 (3–4)	2 (2–3)	2 (1–2)	<0.001
Cough (VAS)	9 (8–10)	5 (4–7)	4.5 (2–5)	<0.001
ESAS
Pain	4.5 (0–8)	2 (0–4)	0 (0–2)	0.092
Tiredness	5 (3–5)	6 (5–7)	5 (3–5)	0.002
Nausea	1.5 (0–5)	0 (0-0)	0 (0-0)	0.052
Sleepiness	7 (0–8)	5.5 (0–7)	2 (0–4)	0.041
Loss of appetite	7.5 (5–9)	5 (0–6)	0 (0–5)	<0.001
Difficulty sleeping	5 (3–6)	2.5 (2–5)	1.5 (0–3)	0.015
EQ-5d	0.29 (0.08–0.65)	0.60 (0.23–0.71)	0.63 (0.34–0.74)	0.082
SGRQ-1	91.2 (84.3–96)	80.9 (66.2–88)	71.3 (55.9–75.6)	0.001*

Data are presented as medians with an interquartile range.

p Value using Kruskal-Wallis test. ^*Post-hoc 90-day evaluation versus. Baseline, p = 0.006 (Chi-square test).

mMRC, modified medical research council; VAS, Visual Analogue Scale; ESAS, Edmonton Symptom Assessment System; EQ-5D, EuroQol-5D; SGRQ-1, Saint-George Respiratory Questionnaire-1.

Discussion

Fibrotic ILD has a substantial impact on symptoms, QoL, and survival.^3,4,6 Palliative care has potential to mitigate the consequences of severe fILD; however, this intervention is rarely implemented in patients with fILD, in part due to limited and inconsistent results in the previous literature. In this study, we show a consistent and clinically meaningful benefit of common palliative care interventions on symptoms and QoL in patients with fILD.

Early comprehensive palliative support and management of refractory dyspnea significantly improved the perception of symptoms in a previous study of 105 patients, including 19 with ILD. Similar to our study, this previous study employed a multidisciplinary team approach that included multiple potential interventions directed by experts in respiratory physiotherapy, occupational therapy, and palliative care. This multidisciplinary team evaluated and treated the physical, emotional or psychological, and spiritual aspects in what was essentially a bundle of care. Like the present study, it is unclear what components of care were most helpful. ⁸ In contrast, another study of 36 patients with fILD did not find a benefit of morphine on dyspnea; however, this endpoint was assessed only after seven days of treatment. ¹³

We demonstrated that implementing palliative care and particularly considering the addition of morphine is associated with improved dyspnea and HRQoL in patients with fILD. ¹⁴ This benefit was sustained at 30- and 90-day follow-ups. There did not appear to be implications in the respiratory function of the patients, which is a frequent concern that often limits prescription of opioids in clinical practice. Our findings are also consistent with previous evidence showing that opioids improve the severity of cough, dyspnea, and anxiety without increasing the risk of respiratory impairment in patients with advanced respiratory disease.^15–17 Beyond the improvement in dyspnea, we also observed improvements in sleep quality and anxiety, which is similar to previous studies.^16,18

The optimal timing of referral to PC is unclear; however, the sustained benefits we observed at 30 and 90 days of follow-up suggest early referral has limited downside. Early referral to PC would also support better establishment of a trustful relationship and better ability for patients and caregivers to participate in critical decision-making. ¹⁹ Early referral also provides greater potential for benefit given the need to titrate some potential medications to effect. Despite the likely benefit, before dying, only 13.7% of the patients with a non-cancer disease have received palliative care, and rarely being offered to patients with fILD. Unfortunately, the lack of palliative care support remains as high as 70% even in the 30 days before death. ²⁰

This analysis is limited by the small sample size; however, this is countered by the statistically significant benefits suggesting adequate power, including the sustained benefit of the intervention over three months of follow-up. We did not repeat pulmonary function measurements to understand whether symptom improvement was independent of any potential increase in pulmonary function; however, the progressive nature of fILD makes this an unlikely possibility. The absence of a placebo group is similarly mitigated by the large and persistent benefits in the context of what is almost universally a progressive disease. Finally, the doses and types of drugs were adjusted based on patient needs as assessed by the treating physicians without a standardized protocol, resulting in some lack of certainty as to what components of care are most beneficial.

In conclusion, implementing a bundle of palliative care in patients with fILD was associated with a decrease in symptoms and improvement in HRQoL. The sustained benefits over 90 days of follow-up suggest early intervention may be appropriate to yield the greatest patient benefit. Additional studies with a larger sample size and greater standardization of interventions are necessary to confirm and expand upon the benefit observed in the present study.

Authors’ Contributions

The author(s) meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).

Ethical Approval and Informed Consent Statements

The research and ethics committees from the hospital approved the protocol (number 2019-018). All the patients provided informed consent.

Data Availability Statement

The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.

Disclaimers

The authors declare that the views expressed in the present article are their own without any representations for an official position of an institution or funder.