Development of a patient-specific dyspnoea questionnaire in motor neurone disease (MND): the MND dyspnoea rating scale (MDRS)

Journal of the Neurological Sciences 180 (2000) 86–93 www.elsevier.com / locate / jns

Development of a patient-specific dyspnoea questionnaire in motor neurone disease (MND): the MND dyspnoea rating scale (MDRS) a b b a, C.F. Dougan , Claire O. Connell , E. Thornton , C.A. Young * a

Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazakerley, Liverpool L9 7 LJ, UK b Department of Psychology, University of Liverpool, Liverpool, UK

Abstract Motor neurone disease (MND) is a progressive, unremitting and fatal disease. Respiratory dysfunction is common and a significant cause of morbidity. The relationship between subjective dyspnoea and objective measures of lung function have been unexplored in MND. Increasing interest in the specific treatment of respiratory symptoms in MND has highlighted the need for simple, reliable and valid measures to quantify the degree of dyspnoea in this condition. Several generic questionnaires have been developed to rate subjective breathlessness but are inappropriate for use in MND patients as they often assess dyspnoea by exercise-limitation. As yet, there are no published disease-specific measures to assess dyspnoea in MND. In order to accurately and reproducibly measure the subjective experience of dyspnoea in this patient group, we have developed and validated a novel patient-specific dyspnoea questionnaire, the MND dyspnoea rating scale (MDRS). It comprises three domains covering dyspnoea, emotion and mastery and is valid for use in MND patients at all stages of disease progression. In our cohort of 40 unselected patients with MND we have shown that the patients subjective experience of dyspnoea is closely related to emotion and psychological control over the disease. Dyspnoea is not related to objective measures of lung function such as vital capacity, irrespective of limb or bulbar presentation. In conclusion, vital capacity, although useful prognostically, is only one aspect of respiratory function in MND. The MDRS is a reliable and valid tool to rate subjective dyspnoea in MND.  2000 Elsevier Science B.V. All rights reserved. Keywords: Motor neurone disease; Amyotrophic lateral sclerosis; Dyspnoea; Questionnaire; Vital capacity

1. Introduction Dyspnoea, the unpleasant sensation of breathlessness, is a distressing symptom which may adversely affect quality of life of people with motor neurone disease (MND). The mechanism by which the individual experiences breathlessness is complex with integration of both physical and psychological components. Despite the frequent involvement of the respiratory system in MND [1,2] the relationship between dyspnoea, physiological measures and functional state remain unexplored. Dyspnoea is significant in contributing to poor quality of life in other disease states and several questionnaires have

*Corresponding author. E-mail address: [email protected] (C.A. Young).

been developed to assess the degree of dyspnoea [3–5]. However, existing measures such as the Medical Research Council (MRC) dyspnoea scale [5] are inappropriate for MND as the dyspnoea is graded on exercise tolerance which cannot be applied to a patient with exercise-limiting limb weakness. There are no published disease-specific measures for dyspnoea in MND. The primary aim of this study was to develop a dyspnoea questionnaire for MND patients which would be easy to easy to administer and applicable to patients at all stages of disease progression and all levels of disability. Psychometric properties of the questionnaire were tested to establish validity, internal consistency and reliability. Secondary outcomes were to examine the relationship between subjective experience of dyspnoea and a more objective measure of lung function and to investigate the relationships between dyspnoea, fatigue, emotion and mastery.

0022-510X / 00 / $ – see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S0022-510X( 00 )00415-9

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2. Methods

2.1. Development of the MND dyspnoea rating scale ( MDRS) After review of the literature, we modelled the dyspnoea domain of our questionnaire on the chronic respiratory disease questionnaire (CRDQ) by Guyatt et al. [3]. The dyspnoea domain is generated by the patient identifying five activities of daily living which may make them feel breathless. The patient then rates the degree of dyspnoea on a five-point Likert scale which quantifies the severity. In this way the patient can personalise the questionnaire and it can be applied to all patients irrespective of their physical limitations. A pilot study was conducted and included open interview with patients, their carers and MND experts to generate the remaining items important to this group of individuals. The questionnaire was extensively modified and reworded for clarity. Reflecting the importance of both the physical and psychological contributors to dyspnoea, the remainder of the questionnaire examined emotion, fatigue and mastery. The final questionnaire that emerged consisted of 16 questions each rated on a five-point likert scale 0–4, the MDRS (see Appendix A). Low scores indicated minimal symptoms; high scores indicated maximal symptoms. The questionnaire was worded so it could be self-administered or answered with the assistance of a carer or health professional and requires approximately 10 min to administer. To examine the test–retest reliability of the MDRS, 10 stable patients completed the MDRS and had their vital capacity measured 7 days after the initial data collection by the same researcher.

2.2. Recruitment of patients and data collected 2.2.1. Patient group Patients were recruited from the Walton Centre MND database, and clinics at three teaching hospitals in the North–West of England. All patients had a diagnosis of MND confirmed by their consultant neurologist. After consultation with the patient’s general practitioner, patients in the community were approached initially by explanatory letter or at their usual clinic visit. Ethical approval was obtained for each centre and informed consent from each participant. Data was collected in specialist clinics or at home in those patients too unwell to visit hospital. 2.2.2. Demographics Data collected included age, duration of disease as defined by date of onset of first symptom, mode of onset and presence of bulbar symptoms at the time of study.

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2.2.3. Lung function Vital capacity was used to measure lung function as it is the only test of lung function that has been shown to have prognostic value in MND [2,6]. Sitting slow vital capacity was measured using a hand held spirometer with a modified mouthpiece for those patients with orofacial weakness. The best of three attempts was recorded. Height was measured and used to predict expected vital capacity using standardised tables [7]. 2.2.4. Subjective measures To test the validity of the MDRS compared to existing dyspnoea scales, each patient completed two further scales; the Borg scale and a visual analogue scale. Borg [4] developed an interval scale which has been used widely in clinical and research practice to measure dyspnoea in patients with chronic lung disease. The Borg scale grades the severity of dyspnoea between one and 10 with written cues beside each number. The visual analogue scale [8,9] is a widely used psychometric measure which is reliable and responsive [10] and has been used to measure breathlessness both in normal controls and patients with lung disease. The patient simply marks on a horizontal line their symptom severity between two extremes of no breathlessness and worst breathlessness ever. The point at which respondents mark represents their perception of breathlessness on this continuum. 2.2.5. Functional status The ALSFRS [11,12] was administered to assess the level of functional impairment. It is a valid, reliable and sensitive disease-specific measure comprising 10 questions enquiring about how swallowing, breathing, and limb function affects activities of daily living. It as an ordered categorical scale with each question graded between 0 and 4. High score indicate good function; low scores indicate poor function. 2.2.6. Anxiety and depression The Hospital Anxiety and Depression scale [13] was completed. It is a screening questionnaire for assessing the presence or absence of anxiety and depression. The scale consists of 14 items divided equally into depression and anxiety subscales. Ratings by patients are made on fourpoint scales which represent degree of symptoms. Items are summed; high scores indicate presence of clinically significant anxiety or depression. 2.3. Statistical analysis SPSS for Windows version 9.0 was used for statistical analysis [14]. Non-parametric tests were used as the data did not conform to a normal distribution. Principal components factor analysis [15] was performed to examine the underlying structure of the MDRS. This is a statistical model rearranges a large set of

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variables (or items) into smaller groups (or factors) of related items. Internal consistency was examined using Cronbach’s a. Test–retest reliability was assessed by comparing the average and mean difference in paired scores [16,17]. Relationships between variables were explored using Spearman’s correlation co-efficient. Mann–Whitney U-test was used to explore differences between limb and bulbar patients.

3. Results

3.1. Descriptives of the MND patients (see Table 1) Forty patients were recruited (25 male, 15 female). Median age of onset of MND was 60 years (range, 34–80) with the median duration of the disease being 31 months (range, 7–99). The median percent predicted vital capacity was 56.9 (range, 4–96%). There was no difference between males and females for any variable so they were treated as a group. This was a representative group of all stages of MND with a wide range of functional abilities demonstrated by the ALSFRS (median, 24 of 40; range, 5–37).

3.2. The MDRS evaluation 3.2.1. Validity by factor analysis ( Table 2) Three factors (domains) were extracted to explain a total of 68% of the variance. The factor loading or correlation of each item on the three extracted factors enabled us to define which items belonged to each domain. The three domains were best described as emotion, dyspnoea and mastery. Fatigue had only a weak factor loading onto the emotion domain and did not form a separate dimension. The final questionnaire that emerged was named the MDRS and is shown in Appendix A with scoring. Table 1 Descriptives and baseline measures Measure

Number of patients

Median

Range

Age (years)

40

60

34–80

Gender Male Female

25 15

Type of onset Limb Bulbar

28 12

Bulbar symptoms at time of study Duration (months) Percent predicted vital capacity ALSFRS

Table 2 Rotated factor loadings Item number a

Factor 1 emotion

Factor 2 dyspnoea

Factor 3 mastery

14, satisfied 11, relaxed 13, depressed 9, upset, worried 6, frustration 8, confident 16, tense 12, fatigue 2, dyspnoea 3, dyspnoea 4, dyspnoea 1, dyspnoea 5, dyspnoea 15, fear 7, panic 10, control

0.89 0.78 0.77 0.72 0.67 0.60 0.58 0.45 0.24 0.00 0.26 0.15 0.25 0.27 0.31 0.33

0.00 0.19 0.32 0.24 0.35 0.22 0.34 0.41 0.81 0.67 0.67 0.66 0.60 0.43 0.37 0.27

0.22 0.41 0.39 0.22 0.21 0.52 0.44 20.21 0.18 0.30 0.23 0.23 0.34 0.80 0.77 0.67

a The word next to the item number is a brief cue. The full question corresponding to each item number is given in full in Appendix A. Bold type indicates the strongest factor loadings for each domain.

3.2.2. Internal consistency Cronbach’s a was 0.84 showing a high degree of internal consistency. This increased to 0.93 when the dyspnoea domain was extracted, suggesting that the dyspnoea domain is measuring a separate sensation to the remaining items. 3.2.3. Test–retest reliability (see Fig. 1 a,b) There was no significant change in respiratory symptoms or vital capacity over 7 days confirming the stability of this group. The average difference in the total MDRS score over this time was 21 (S.D. 5.9) confirming a high degree of stability. The dyspnoea domain scores were more variable but still reliable with an average difference of 3.22 (S.D. 3.01) between the two scores. 3.2.4. Validity Validity of the dyspnoea domain was confirmed by strong correlation with both measures of subjective breathlessness. There was a highly significant correlation with both the Borg scale (Spearman correlation co-efficient, r50.66, P50.0001) and the visual analogue scale (r5 0.72, P50.0001). 3.3. Relationships between dyspnoea and other psychological measures

24 40 40

34 57

7–99 4–96

40

24

5–37

3.3.1. Subject dyspnoea rating versus lung function There was no correlation between percent predicted vital capacity and any of the three measures of subjective dyspnoea although vital capacity did correlate weakly with the total ALSFRS (r50.41, P50.01) and the bulbar domain of the ALSFRS (r50.36, P50.03).

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Fig. 1. (a) Test–retest reliability: difference in MDRS scores over 7 days plotted against their average. (b) Reliability: difference between MDRS dyspnoea domain scores plotted against their average.

3.3.2. Dyspnoea rating versus anxiety and depression The dyspnoea domain was significantly correlated with the hospital anxiety and depression scale (r50.41, P5 0.01). Looking at anxiety and depression separately, anxiety was highly significantly correlated with the dyspnoea domain (r50.42, P50.009); in contrast depression was not correlated with the dyspnoea domain (r5 0.27, P50.19). The Borg and VAS scales were also significantly associated with anxiety although the relation-

ships were weaker (Borg: r50.33, P50.05; VAS: r50.37, P50.03).

3.3.3. Dyspnoea rating versus fatigue, emotion and mastery Subjective dyspnoea rated by the MDRS dyspnoea domain was highly significantly associated with emotion (r50.47, P50.003) and mastery (r50.5, P50.002) but

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was not correlated with fatigue question of the emotion domain (r50.28, P50.09).

3.3.4. Dyspnoea rating versus functional status There was no relationship between subjective dyspnoea and functional status (r520.22, P50.18). 3.4. Comparison of limb and bulbar groups Patients were grouped into limb or bulbar onset by their first symptom. There was a significant difference in the duration of illness between the two groups with limb patients having a median duration of 20 months and bulbar patients a shorter duration of 13 months (Mann–Whitney U-test, two-tailed significance, P50.04). When corrected for differences in duration of MND, the vital capacity was significantly lower in the bulbar group compared to the limb group (median vital capacity, 42 and 63% predicted, respectively, P50.03). Interestingly, despite this marked difference in vital capacity in each group, there was no significant difference between the two groups with respect to their perception of breathlessness.

4. Discussion This study shows that dyspnoea is an important and common symptom in MND patients regardless of whether they have bulbar involvement or not. We have developed a novel disease-specific questionnaire which appears to be a valid, reliable measure to quantify dyspnoea in MND. The perception of breathlessness in MND is not related to disease duration, level of disability or vital capacity. This study also demonstrates that mastery of breathlessness and anxiety are important psychological components to the patient’s perception of dyspnoea. Previous measures to quantify breathlessness have been developed for use in lung and cardiac disease [3–5] but these often rate breathlessness according to exercise capacity which is clearly not applicable in many MND patients. Guyatt et al. [3] developed the chronic respiratory disease questionnaire to assess the impact of dyspnoea on the quality of life. The dimensions of this questionnaire were dyspnoea, fatigue, emotion and mastery. It appears that fatigue is not so important to MND patients as patients with chronic lung disease. This may be because MND patients are more disabled physically and are likely to have reduced levels of activity compared to patients with pure lung disease. The Borg [4] and visual analogue scales [8,9] are global rating scales and only give limited information about the factors contributing to breathlessness. In contrast, the MDRS dyspnoea domain is patient-specific and allows the patient to quantify how dyspnoea affects their daily life.

Dyspnoea is a complex sensation resulting from the integration of physical and psychological input under higher cortical control [18] so it is not surprising that this study has demonstrated no association between awareness of breathlessness and objective measures of vital capacity or fatigue or physical functioning. This lack of association between dyspnoea ratings and pulmonary function has been found by several studies in lung disease [19–21] and in MND [22]. The BDNF study group found no strong association between the respiratory subscale of the ALSFR-R and percent predicted forced vital capacity (Spearman’s correlation co-efficient 0.33). This supports the assertion that subjective reports of dyspnoea are not just a reflection of lung function but a result of the integration of numerous neuroanatomical pathways. These include input from peripheral sensory receptors (mechanoreceptors, irritant, stretch and C-fibre receptors), chemoreceptors, effort, work load, psychological input and higher cortical control [18]. Recognition of the multifactorial nature of breathlessness has important implications clinically in that it emphasises that assessment of respiratory system by vital capacity alone is inadequate and may overlook more sensitive markers of respiratory function. The finding that there is no difference in perception of dyspnoea between limb and bulbar groups is initially surprising as intuitively one would expect bulbar patients to perceive more breathlessness due to dys-coordination of bulbar muscles which is important to breathing during speech and eating. Again this reflects the complex pathways involved in the perception of dyspnoea. Fallat et al. [2] observed that reduction in vital capacity to as low as 50% in patients with neuromuscular disease was commonly overlooked by clinicians so there is a clear need for early markers of respiratory system involvement. The development of breathlessness is an important phase in the natural history of MND. Specific treatments of breathlessness by have been explored in lung disease [23–25] and are being developed to manage respiratory failure in MND [26,27]. However, studies on simple treatment of this potentially distressing symptom are lacking in MND. Future research will establish the ability of the MDRS to demonstrate responsiveness to change and its role as an outcome measure evaluating response to specific treatment of dyspnoea in this condition.

Acknowledgements We are indebted to Mary O. Brien and Professor D. Mitchell, Royal Preston Hospital and Dr. Schady, Manchester Royal Infirmary for helping with data collection. Sister Dott Marshall and Dave Watling, Walton Centre for Neurology and Neurosurgery who assisted with clinics and vital capacity measurement.

C.F. Dougan et al. / Journal of the Neurological Sciences 180 (2000) 86 – 93

Appendix A A.1. The MND dyspnoea rating scale ( MDRS) We would be grateful if you could take time to complete this questionnaire. Please attempt to answer all of the questions. We are interested in your answers even if you do not have a problem with breathlessness. If you have any problems with completing the questionnaire we can help you complete it at the clinic visit. (A) I would like you to think of the activities that you have done during the last 2 weeks that may have made you feel short of breath. These should be activities which you do frequently and which are important in your day to day life. Please list as many activities as you can that you have done during the last 2 weeks that have made you feel short of breath.

chosen to be the most important to rate the amount of breathlessness, if any, that you have experienced. I would now like you to describe how much shortness of breath you have experienced during the last 2 weeks while doing the five most important activities you have selected. Please circle one number from 0 to 4 which best describes the degree of breathlessness during the five selected activities:

(1) Activity 1: . . . Extremely short of breath

Very short of breath

4

3

Moderate shortness of breath 2

Slight shortness of breath 1

Not at all short of breath 0

(2) Activity 2: . . . Extremely short of breath

1. 2. 3. 4. 5.

91

Very short of breath

4

3

Moderate shortness of breath 2

Slight shortness of breath 1

Not at all short of breath 0

(3) Activity 3: . . .

(B) Below is a checklist of activities which make some people feel short of breath. Please read through the list and circle any activities that may have made you short of breath during the past two weeks. The activities are: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

Talking Eating Dressing Preparing meals Carrying such as carrying groceries Playing with children / grandchildren Walking Moving around your own home (aided or unaided) Having a bath or shower (aided or unaided) Bending Being angry or upset Lying flat While trying to sleep

(C) From your answers to questions A and B, please choose the five most important to you in your day to day life and list below. 1. 2. 3. 4. 5.

Extremely short of breath

Very short of breath

4

3

Moderate shortness of breath 2

Slight shortness of breath 1

Not at all short of breath 0

(4) Activity 4: . . . Extremely short of breath

Very short of breath

4

3

Moderate shortness of breath 2

Slight shortness of breath 1

Not at all short of breath 0

(5) Activity 5: . . . Extremely short of breath 4

Very short of breath 3

Moderate shortness of breath 2

Slight shortness of breath 1

Not at all short of breath 0

(6) In general, how much of the time during the last 2 weeks have you felt frustrated or impatient? All of the time 4

Most of the time

Some of the time

Hardly any of the time

None of the time

3

2

1

0

(7) How often during the past 2 weeks did you have a feeling of fear or panic when you had difficulty getting your breath? All of the time 4

Most of the time

Some of the time

Hardly any of the time

None of the time

3

2

1

0

(8) In the last 2 weeks, how much of the time did you feel very confident and sure that you could deal with your illness? All of the time

The next section uses the five activities which you have

4

Most of the time

Some of the time

Hardly any of the time

None of the time

3

2

1

0

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(9) In general, how much of the time did you feel upset, worried, or depressed during the last 2 weeks? All of the time 4

Most of the time

Some of the time

Hardly any of the time

None of the time

3

2

1

0

(10) How often during the last 2 weeks did you feel you had complete control of your breathing problems with shortness of breath and tiredness? All of the time 4

Most of the time

Some of the time

Hardly any of the time

None of the time

3

2

1

0

(11) How much of the time during the last 2 weeks did you feel relaxed and free of tension? All of the time 4

Most of the time

Some of the time

Hardly any of the time

None of the time

3

2

1

0

(12) How often during the last 2 weeks have you felt low in energy? All of the time 4

Most of the time

Some of the time

Hardly any of the time

None of the time

3

2

1

0

(13) In general, how often during the last 2 weeks have you felt discouraged or down in the dumps? All of the time 4

Most of the time

Some of the time

Hardly any of the time

None of the time

3

2

1

0

(14) How happy, satisfied, or pleased have you been with your personal life during the last 2 weeks? All of the time 4

Most of the time

Some of the time

Hardly any of the time

None of the time

3

2

1

0

(15) How often during the last 2 weeks did you feel upset or scared when you had difficulty getting your breath? All of the time 4

Most of the time

Some of the time

Hardly any of the time

None of the time

3

2

1

0

(16) In general, how often during the last 2 weeks have you felt restless, tense or uptight: All of the time 4

Most of the time

Some of the time

Hardly any of the time

None of the time

3

2

1

0

Scoring of the MDRS MDRS-dyspnoea. Questions 1–5 quantify dyspnoea. Low scores indicate less breathlessness, high scores indicate more breathlessness. Possible range 0–20. MDRS-emotion. Questions 6, 8, 9, 11, 12, 13, 14 and 16 assess emotional function. Low score indicates low per-

ceived emotional disturbance, high score indicates high perceived detrimental emotional disturbance. Possible scores range from 0 to 32. MDRS-mastery. Questions 7, 10, and 15 assess mastery / control over the disease. Low score indicates low perceived detrimental affect on mastery and control over the disease, high score indicates high perceived detrimental affect over mastery / control over the disease. Possible scores range from 0 to 12. Total MDRS score 0–64.

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