Measurement of respiratory sensation in patients referred for lung transplantation

Introduction

The Medical University of Silesia is the only centre in Poland where lung transplantations (LT) are performed. Patients are referred for lung transplantation to the Dpt. of Lung Diseases and Tuberculosis in Zabrze. The selection of patients for lung transplants involves the estimation of disease progress. Dyspnoea is the cardinal symptom of the failing lung that significantly affects all elements of quality of life (QL). The main goal of LT, instead of increase of life expectancy, is improvement of quality of life (QL). Each patient when being referred for LT has accurate estimation of QL performed. Tests specific for end-stage, advanced lung diseases have not been invented yet. Among the available tests, the SF-36 questionnaire assesses both physical and mental conditions. Saint Georges Respiratory Questionnaire (SGRQ), specific to chronic lung diseases, evaluates quality of life in three domains: symptoms, activity and impact on life. The aim of the study was to determine a relationship between quality of life and dyspnoea in patients awaiting lung transplantation, and to assess whether they are related to the clinical data in the examined group.

Material and methods

Study population





86 patients, all of them qualified for LT in 2005-2010 and fulfilling ISHLT criteria for lung transplantation [1, 2] were evaluated. The study group consisted of 18 females and 68 males of average age of 52 ±10 years and BMI 24 ±6. Thirty patients were diagnosed with idiopathic pulmonary fibrosis (IPF), 22 with COPD and 34 with a form of idiopathic interstitial pneumonia other than IPF (IIP). To avoid the potential influence of medication on the ratings of dyspnoea, only patients free of exacerbations of the disease for at least 48 hours were included. The study was approved by the Medical University of Silesia’s Review Board, and informed consent was obtained.





Rating of dyspnoea



Four different clinical methods were used for rating dyspnoea at a point in time: a modification of the Medical Research Council questionnaire (MRC) [4], Oxygen-Cost Diagram (OCD) [5], Baseline Dyspnoea Index (BDI) [5] and Borg’s scale [6].

MRC is a 5-grade scale that grades the degree of breathlessness related to activities. In our study, each patient was instructed to read the descriptive statements and then select the number which best fitted his shortness of breath. For descriptive and statistical reasons MRC was modified so that lack of breathlessness except for strenuous exercise was marked as grade 1; the maximal level of dyspnoea, when too breathless to leave the house or breathless when dressing or undressing was marked as grade 5. OCD is a visual-analogue scale consisting of a 100 mm long line with descriptions of different activities causing dyspnoea. The top of the vertical line represents “no breathlessness – brisk walking uphill” (grade 1), while the bottom of the line reflects “the greatest breathlessness – even when sleeping” (grade 5). The patient was instructed to “mark the line at a point above which you would become breathless”. The distance from the bottom of the scale to the patient’s mark was measured in millimetres and provided a quantification of the subject’s dyspnoea.

The BDI describes dyspnoea in five grades for each of three categories: disability of everyday activities (FI, functional impairment), difficulties in performing tasks (MT, magnitude of task), and difficulties in undertaking an effort (ME, magnitude of effort). This scale enables differentiation of extra-pulmonary causes of dyspnoea; e.g. osteoarthritis pain, chest pain, and situations where it is not possible to define the causes of dyspnoea. In such cases, the patient marks a relevant answer that is not classified in dyspnoea estimation. Visual Borg Scale rates patients’ dyspnoea from 0 (rest) to 10, where 10 is the maximum dyspnoea ever.

Physiologic measurements

Physiologic testing was completed on the same day when dyspnoea was graded. Lung function tests and mobility, patient’s age, BMI and duration of symptoms (years) were taken into consideration.

Spirometry was performed using Jaeger-Masterlab (Erich Jaeger GmbH, Wurzburg, Germany). Two lung function parameters were measured: forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), and were normalized to the reference values proposed by the European Community for Coal and Steel and presented as a percentage of predicted (% pred.). Mobility was presented as a distance in 6 minute walking tests (6MWT). The test was performed according to the guidelines of the American Thoracic Society [7].





Quality of life



In estimation of Quality of Life the SF-36 questionnaire [8] – generally describing Quality of Life and St. George Respiratory Questionnaire [9] – characteristic of chronic lung diseases were used. The SF-36 questionnaire consists of 36 questions, which cover basic domains describing the condition of health: 1) Physical Functioning (PF), 2) Role Physical (RP), 3) Bodily Pain (BP), 4) General Health (GH), 5) Vitality (VT), 6) Social Functioning (SF), 7) Role Emotional (RE), 8) Mental Health (MH). In SF-36 scoring, the higher scores meant better general health status. Methodical rules and the analysis of data by SF-36 questionnaire had been earlier described in the previous paper [10].

St. George Respiratory Questionnaire composed of 50

questions, is grouped in 3 subscales: symptoms, activity and influence on life. Each scale responds to an experimentally set number of points. The points are pooled together in each subscale and divided by the maximal number of points in each subscale. The received score varies between 0 (minimum handicap) and 100 (maximum handicap). Simultaneously a global outcome of the questionnaire was calculated. The agreement of Prof. Jones, the author of SGRQ was obtained before the research program started.





Statistical analysis



Results are expressed as mean ± SD. Spearman’s rank correlation coefficient was used to measure statistical dependence. A correlation between results of dyspnoea tests and physiologic testing, spirometric data, mobility, and quality of life questionnaires’ domains were determined. Analysis was performed using the Statistica programme. Statistical significance was defined as p < 0.05.

Results

Patient characteristics Anthropometric data and results of lung function and mobility are presented in Table I. Gender was comparable in study groups. Oldest patients were in COPD group (without statistical difference). In COPD group, the disease duration was the longest (nearly 19 yr.) and BMI was the lowest (22.7, without statistical significance in comparison to IPF or IIP). Patients with IPF and IIP exhibited significantly highest (p < 0.05) levels of FEV1 compared to COPD patients. Mean results of FVC and walking ability (6 MWT) were similar in all study subgroups (COPD, IPF and IIP), and under the level of 50% of predicted values (FVC, 6 MWT).



Dyspnoea evaluation





The mean values for the clinical rating of breathlessness were in the upper limit in all clinical ratings of dyspnoea (Table II). Values obtained by the clinical rating methods of breathlessness were highly interrelated (MRC vs. OCD, r = 0.85; MRC vs. BDI, r = 0.87; MRC vs. Borg’s scale, r = 0.78; BDI vs. OCD, r = 0.88; BDI vs. Borg’s scale, r = 0.86). There were no statistically significant differences in perception of dyspnoea between COPD, IPF and IIP in all clinical ratings. Nevertheless, the highest perception of breathlessness was observed in IIP in all scales (Table II); in those groups the highest values of min and max scores were observed, too. Instead of FI, COPD patients presented mean values of dyspnoea below mean values observed in the total study population. IPF patients presented the lowest perception of dyspnoea in FI and ME of BDI in comparison to COPD and IIP and mean total values (without statistically significance), as well. In remaining descriptors of breathlessness for IPF, mean values were similar to mean values observed in the total study population.



Quality of life evaluation





In SGRQ most impaired quality of life domain was activity (76.29 ±14.25) whereas the least affected domain was symptoms (64.49 ±18.36). The global score indicates the poorest quality of life in COPD patients (72.84 ±11.19), the best score was achieved in a group of patients diagnosed with IPF (68.09 ± 13.86) (Table III). No statistically significant differences were found in SGRQ domains between patients with different diagnosis. Quality of life evaluated with SF-36 questionnaire is most

impaired in RP domain (16.17 ±22.55), least in BP domain (48.77 ±22.14). Basing on cumulative scores, the smallest PCS impairment was discovered in COPD patients (25.09 ±8.34), the biggest (25.95 ±6.39) in IIP patients. Mental cumulative health score was the highest in IPF patients (42.44 ±14.24), and the lowest in COPD patients (37.83 ±15.27) (Table III). No statistically significant differences were found in SGRQ domains between patients with different diagnosis.



Dyspnoea and quality of life





In the study group, there was a statistically significant correlation between dyspnoea and quality of life (Table IV). Domains: Activities and Impact of SGRQ correlate significantly with all clinical ratings of dyspnoea of our study (MRC, OCD, BDI and Borg’s scale). In most cases the correlation was very strong (p < 0.001). No relations were found between symptoms of SGRQ and clinical ratings of dyspnoea. Correlations between clinical ratings of dyspnoea and domains of SF-36 questionnaire were noticed, too. They were most wide between BDI and GH, Vit, SF and PCS. With the exception of Borg’s scale, correlations were observed between the clinical rating of dyspnoea and PCS. No correlations were observed between MCS and clinical ratings of dyspnoea.

Depending on the diagnosis, the strongest correlation in IIP patients was found between OCD and activity (r = 0.62), in COPD patients between BDI and impact (r = 0.79) and in IPF patients between BDI and PF (r = 0.60).

There was no correlation between BMI and dyspnoea and quality of life questionnaires’ domains.



Ratings of dyspnoea and physiologic measurements



There was no correlation found between gender, age, disease duration, BMI and clinical ratings of dyspnoea (MRC, OCD, BDI, Borg). However, there was a correlation between mobility, lung function tests and rating of dyspnoea. Most often correlations were seen between dyspnoea domains and distance in 6 MWT (Fig. 1). It was observed not only in whole populations, but also in patients with COPD (6 MW vs. MRC: r = –0.70, 6 MW vs. OCD: r = –0.51, 6 MW vs. BDI: r = –0.68, 6 MW vs. Borg’s scale: r = –0.46) and IPF. In IPF patients, a strong correlation was observed between rating of dyspnoea and lung function tests (FVC, FVC%pred., FEV1, FEV1%pred, FEV1%VC), too. In COPD patients, correlations were observed between rating of dyspnoea and FEV1 and FEV1%VC, instead of 6 MW. No correlations were observed between dyspnoea and lung function tests in patients

with IIP.

Discussion

The results of this study are preliminary, being limited by the small number of patients in the sample of groups with different lung diseases referred for LT. Nonetheless, we noticed that patients with advanced lung diseases on the waiting list for LT showed great impairments in their rating of dyspnoea. We believe that the clinical measurement of dyspnoea is important in patients referred for LT for several reasons. First, breathlessness is frequently the patient’s major complaint in advanced lung diseases. By quantifying dyspnoea, the physician can assess its severity and impact on the person’s health status. It is most important in patients referred for LT when accurate estimation of health status plays a crucial role on placing lung recipients on the waiting list. Second, as a symptom, breathlessness represents the summation of physiologic factors which collectively provide a distressing signal to the patients. And finally, grading the dyspnoea is an important consideration for establishing efficiency of treatment. At present, except for oxygen, lung transplantation is the only one objective evidence that may benefit in length of life and quality of life. So accurate rating of dyspnoea in patients waiting for LT seems be very important in the future, when the benefit of LT is being estimated in every patient. Dyspnoea scores from all four methods were significantly correlated between each other in our study. It was previously reported by authors describing in detail clinical methods for rating dyspnoea [11-13]. However, in our opinion BDI provides more quantitative information which is complementary to physiologic testing and assessing quality of life. BDI, which includes the components of functional impairment and magnitude of effort affecting breathlessness along with magnitude of task, for each of these three components demonstrate differences. In our study those differences were not statistically significant, but from the clinical point of view, they are very important. For example, a patient may require extraordinary effort to accomplish a relatively easy task, and the corresponding ratings for these components of the BDI would be distinctly different. Also, the demands of an individual task may have totally different consequences depending on a person’s activities at work or home. For these reasons, measurement of specific components affecting dyspnoea appears to be important. Such scales as MRC, OCD and Borg’s scale, which could be used as visual scales are useful for rating dyspnoea in documenting changes in breathlessness. Because the MRC scale, which contains only five grades, may be too coarse to demonstrate distinct changes, we believe that a visual scale, such as OCD or Borg’s scale is most appropriate for statistical comparisons of changes in perceptions of breathlessness. In our study all of these clinical ratings of dyspnoea demonstrate clinical utility confirmed by significant correlations with quality of life and results of lung function test and mobility. Health-related quality of life is a measure of decrease of physical, mental and social well-being as a result of an illness. Dyspnoea could significantly affect all three elements of health. Those relationships were first time demonstrated by Siafakas et al. [14]. In his study, he noticed that dyspnoea was the main determinant of the overall health status in patients with airway diseases. Dyspnoea correlates with such domains of general health as anxiety, depression, optimism, stigma, sleep and activities of daily living [15]. In our study, in SF-36 questionnaire, which assesses general health status and is focused on the basic values relevant for health, we noticed that domains related to physical and functional alterations presented greater impairment. High scores for vitality, social functioning, role emotional, and mental health could indicate that these patients, even though weak physically, feel sheltered and involved by those around them, such as family members, friends and health care staff. Their expectations were strengthened by the possibility of a lung transplantation. Similar results are presented in a study of Feltrim et al. [16], where physical functioning is the most affected among patients referred for LT. In SGRQ, which is recommended to be used for patients with chronic lung diseases, the questions are geared to symptoms, activities and emotional impact related to the disease. All domains were seriously affected. It was obvious because in our study patients were in the end stage of lung diseases, referred for lung transplantation. All patients displayed dyspnoea as the common symptom of diseases, followed by cough in COPD and IPF. The COPD and IIP groups were the most affected in performing their activities and emotional impact, which were limited due to the complaint of serious dyspnoea. The IPF group reported the least impact of the disease on their quality of life. In our opinion, it could be connected with a relatively short duration of the disease in this group. Activities and emotional impact – domains of SGRQ – correlate positively with all clinical ratings of dyspnoea (MRC, OCD, BDI, Borg’s scale). No correlations were found between symptoms and rating of dyspnoea. Lack of correlations could be explained by the fact that with the exception of dyspnoea, different symptoms were declared in groups with restrictive and obstructive diseases. Dyspnoea scores investigated in our study correlated significantly with mobility, presented as a distance in 6-minute walking test. In our opinion, it is a very important observation.

6 MWT is a well noticed predictive factor when referring patients for LT. In our study, in 2005 we concluded for the first time that 6 MWT defines survival in patients with IPF referred for this procedure [17]. Three years later Martinu

et al. [18] confirmed utility of 6 MWT in predicting survival in lung transplant candidates. So adding accurate estimation grade of dyspnoea in lung transplant candidates to physiologic measurements as a 6 MWT or lung function test could help in accurate estimation of indications for referral for LT.

We believe that the clinical measurement of dyspnoea in lung transplant candidates has wide potential application in the practice. The measurement process is reproducible and can be completed in less than five minutes. The cost is minimal, and a nurse, respiratory therapist or physician can grade easily the severity of a patient’s breathlessness. The measurement of dyspnoea can be useful in referring patients for LT and in the treatment of even seriously

affected patients.



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