Marked Deterioration in the Quality of Life of Patients With Idiopathic Pulmonary Fibrosis During the Last Two Years of Life

K. Rajala; J. T. Lehto; E. Sutinen; H. Kautiainen; M. Myllärniemi; T. Saarto


BMC Pulm Med. 2018;18(172) 

In This Article

Materials and Methods

Study Population

The FinnishIPF study is a national prospective clinical registry of IPF patients that was established in 2012. IPF diagnosis is based on the ATS/ERS 2011/2015 criteria.[1,6] Nearly all Finnish IPF patients are initially evaluated at public university and central hospitals. Patients from these specialist centres with informed consent are included in the FinnishIPF registry, which consists of approximately 76% of all Finnish IPF patients.[2] Currently, the registry contains data from over 700 IPF patients.

All 300 patients registered in the FinnishIPF study in April 2015 were asked to participate in this substudy by sending an informed consent form together with the questionnaires. Those who did not respond within two weeks were called and reminded. Of the 300 registered patients, 247 (82%) provided informed consent for this substudy, answered the first questionnaire and were included in this study. Subsequently, the same questionnaire was sent to the patients five times at six months intervals until August 2017.

Data Collection and Questionnaires

Disease and sociodemographic characteristics were collected from patient records and with a separate questionnaire (Additional file 1). These included the date of birth, sex, age, marital status, education, living conditions, physical activity level, the need for assistance in daily activities, the date of IPF diagnosis, smoking status, and comorbidities. Patients were asked the frequency of leisure time physical exercise that causes breathlessness and sweating for a minimum 30 min during the preceding six months. Death certificates were acquired from the "National Authority for Collecting and Compiling Statistics on Various Fields of Society and Economy".

The questionnaires regarding HRQOL and symptoms were the RAND 36-Item Health Survey (RAND-36), the Modified Medical Research Council Dyspnea Scale (MMRC), and the modified Edmonton Symptom Assessment Scale (ESAS).

RAND-36[29] is a general QOL measurement tool with existing Finnish general population reference values.[30] RAND-36 is similar to the previously IPF-validated short-Form-36.[30–32] RAND-36 is divided into eight health concepts.[29,30] Concepts are scored on a scale from 1 to 100, where a lower score indicates a worse HRQOL during the past four weeks.[29,30] The concepts are as follows: "general health" (five questions), "vitality" (four questions regarding energy level and tiredness), "bodily pain" (two questions), "physical functioning" (ten questions regarding the ability to take care of personal hygiene and the ability to move and exercise), "physical role" (four questions regarding role limitations due to physical health), "mental health" (five questions regarding mood, depression and anxiety), "emotional role" (three questions regarding role limitations due to emotional problems), and "social functioning" (two questions).[29,30]

The self-rated MMRC measures the degree of disability that breathlessness causes during day-to-day activities on a scale from 0 to 4, in which 0 indicates no breathlessness except during strenuous exercise, 1 indicates shortness of breath when walking up a slight hill or hurrying on a level, 2 indicates walking slower than people of same age on a level because of breathlessness or needing to stop to for breath when walking at one's own pace on a level, 3 indicates needing to stop for breath after a few minutes when walking on a level or after walking approximately 100 m, and 4 indicates that the patient is too breathless to leave the house or is breathless when dressing or undressing.[33,34]

The ESAS is a numeric self-rating symptom-based scale that was originally developed to assess the symptoms of cancer patients.[35,36] Different symptoms are measured on Numeric Rating Scale (NRS) from 0 (no symptoms) to 10 (the worst possible symptoms).[36–38] In this study, we used a version including 12 symptoms (pain at rest, pain with movement, tiredness, nausea, depression, anxiety, insomnia, loss of appetite, shortness of breath, cough, constipation, dry mouth, and overall wellbeing). There is a lack of evidence to recommend cut-off points for the ESAS. However, an NRS score ≥ 4 is commonly used as a trigger for more comprehensive symptom assessment in clinical practice.[39]

Statistics and Ethical Aspects

The study population characteristics are presented as the means with standard deviations (SD) or as counts with percentages. Patients' answers were grouped, according the time they answered from the aspect of death. The Kaplan-Meier method was used to estimate the cumulative mortality after the diagnosis. We used restricted cubic splines to detect a possible non-linear dependency. A nonlinear relationship between the RAND-36 domains, symptom severity, the MMRC and time before death were assessed by using 5-knot-restricted cubic spline random-effects regression models with appropriate distribution and link functions. Models included age and gender (only main effects) as covariates. A test of interaction between independent variables was performed through the MFPIgen command. The length of the distribution (months before death) of knots was located at the 5th, 27.5, 50th, 72.5, and 95th percentiles, which correspond to time before death of − 22, − 15, − 9, − 5 and − 1. The locations of the knots were determined by the percentiles recommended in Harrell's publication.[40] The normality of the variables was tested by using the Shapiro-Wilk test. The Finnish general population values for the eight Rand-36 domains were weighted to match the gender and age distribution of the study population, statistical analysis between our population and general population was not performed.[30] The Stata 15.0[41] statistical package was used for the analysis.

The ethics committee of Helsinki University Central Hospital approved this study (381/13/03/01/2014). The Finnish National Institute for Health and Welfare (Dnro THL/1161/5.05.01/2012) approved the screening of hospital registries for patients with IPF. All participating patients provided written informed consent to participate to this specific study.