Dyspnea (breathlessness) in amyotrophic lateral sclerosis/motor neuron disease: prevalence, progression, severity, and correlates

Figures & data

Figure 1. Dyspnea-12 item threshold map ordered by difficulty.

Table 1. Fit to the Rasch model.

Sample/domain	Fit residuals		Chi-square interaction fit			Reliability		Unidimensionality % t values (LCI)	DIF	ECV	Analysis level
	Items	Persons	Total	df	p	PSI	α
Training total LD clusters	1.164	0.701	33.6	27	0.178	0.69	0.86	1.3	None	0.90	2
Validation total LD clusters	1.342	1.006	3.48	27	0.293	0.74	0.87	3.0	None	0.90	2
Total sample item set LD clusters	1.763	0.858	46.9	27	0.010	0.72	0.87	4.1	None	0.90	2
Training physical	0.884	0.987	91.6	63	0.011	0.85	0.95	4.0	None	–	1
Validation physical	1.965	1.165	79.3	63	0.080	0.87	0.96	5.1 (2.9)	None	–	1
Total physical sample LD clusters	2.225	0.829	47.6	27	0.009	0.79	0.91	3.2	None	–	2
Training affective	0.517	1.165	28.2	35	0.787	0.60	0.95	5.6 (2.9)	None	–	1
Validation affective LD clusters	0.736	1.275	42.1	28	0.034	0.68	0.92	4.0	None	0.96	2
Total affective sample	1.038	1.214	55.6	35	0.015	0.68	0.95	4.3	None	–	1

df: degrees of freedom; PSI: Person Separation Index; α: Cronbach’s alpha; LCI: Latent Correlation Index; DIF: differential item functioning; ECV: expected common variance; LD: local dependency.

N = 880.

Table 2. Transformation table converting Dypnea-12 total raw score to interval level for total, physical, and affective scales.

Raw score	Dyspnea-12 Total	Dyspnea-12 Physical	Dyspnea-12 Affective
0	0.0	0.0	0.0
1	4.5	2.0	1.4
2	7.8	3.7	2.5
3	10.2	4.9	3.5
4	12.2	6.0	4.4
5	13.9	7.1	5.3
6	15.4	8.0	6.2
7	16.6	8.8	7.1
8	17.6	9.6	7.9
9	18.4	10.4	8.8
10	19.2	11.3	9.8
11	19.8	12.1	10.8
12	20.4	13.0	11.7
13	21.0	13.8	12.6
14	21.6	14.6	13.7
15	22.1	15.3	15.0
16	22.6	15.9
17	23.0	16.6
18	23.5	17.3
19	23.9	18.1
20	24.2	19.3
21	24.5	21.0
22	24.8
23	25.1
24	25.4
25	25.6
26	25.9
27	26.1
28	26.4
29	26.7
30	27.0
31	27.4
32	28.0
33	28.7
34	29.9
35	32.1
36	36.0

Instructions for use of the transformation table. Providing the respondent has answered all the items, take the raw score and look across to the interval scale estimate for the relevant (sub)scale. For example, if you are converting the total Dyspnea-12, a raw score of 20 would give a standardized metric of 24.2. A raw Dyspnea-12 Physical of 20 gives a standardized metric of 19.3.

Table 3. Baseline trajectory characteristics.

Characteristic	Group 1	Group 2	Group 3	Total	Range
Demographic
Age (years)	65.1	62.9	65.2	64.9*	16–90
% Female	41.5	28.1	40.2	39.6	0–100
% Married	76.3	84.4	77.6	77.7*	0–100
Clinical
Duration (months)	25.5	19.6	19.0	21.8	0.3–295.7
Subtype %
Bulbar	20.9	20.8	34.3	27.3	0–100
Limb	78.6	79.2	61.5	70.5	0–100
Respiratory	0.5	0.0	4.2	2.2	0–100
% King’s stage ≥3	38.5	45.8	73.1	55.8	0–100
Symptoms
Breathlessness (Dyspnea-12)	0.0	3.0	15.4	7.6	0–36^a
Fatigue (NFI-MND)	11.5	12.4	14.6	13.1	0–24^a
% bothered by
Fasciculation	16.6	21.1	20.8	19.0*	0–100
Muscle cramps	24.1	28.4	36.5	30.4	0–100
Head drop	6.8	9.5	23.1	14.9	0–100
Drooling	11.0	9.4	23.7	16.9	0–100
Choking	9.9	17.9	33.5	22.0	0–100
Emotional lability	14.4	20.8	22.0	18.6	0–100
Functioning
ALSFRS-R	36.6	37.2	29.2	33.0	0–48
Bulbar	9.7	9.6	7.6	8.6	0–12
Limb	15.6	16.4	13.0	14.4	0–24
Respiratory	11.5	11.1	8.5	10.0	0–12
Disability (WHODAS 2.0)	51.9	49.9	64.8	57.9	0–128^a
Perceived health
Health status (EQ5D)	0.648	0.682	0.530	0.545	−0.27 to 1.0
Quality of life
QOL (WHOQOL-Bref)	49.5	49.4	41.6	45.7	0–96
Personal factors
Anxiety (M-HADS-A)	5.1	5.5	6.7	5.9	0–18^a
Stigma (SSCI-8)	8.1	8.1	10.1	9.0	0–32^a
Social withdrawal (MND SWS)	29.9	29.2	33.6	31.6	0–60^a
Self-efficacy (GSES)	17.6	17.3	15.3	16.5	0–30
Worry (Penn State)	26.1	27.0	27.6	26.9*	0–64^a
N	434	96	490	1020

NFI-MND: Neurological Fatigue Index-MND; ALSFRS-R: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised; WHODAS: World Health Organization Disability Assessment Schedule; WHOQOL-Bref: World Health Organization Quality of Life-Bref; M-HADS-A: Modified Anxiety Subscale of Hospital Anxiety and Depression Scale; SSCI: Stigma Scale for Chronic Illness; MND SWS: MND Social Withdrawal Scale; GSES: General Self-Efficacy Scale.

N = 1020. All group comparisons are significant (Chi-square; ANOVA) except those marked with *. All PROMs measures except ALSFRS-R are metric.

^a Higher scores are worse.

Figure 2. Dyspnea-12 trajectories. Fine dashed lines indicate 95% confidence limits.

Table 4. Logistic regression for group 3 against group 1 as the reference.

	Odds ratio	Std. err	t-value	p Value	95% confidence interval		Sig.
Demographics
Age	0.998	0.008	−0.20	0.839	0.982	1.015
Gender: base, male
Female	0.948	0.17	−0.30	0.766	0.667	1.347
Marital status: base, married
Other	1.031	0.207	0.15	0.878	0.696	1.529
Clinical
Onset type: base, bulbar
Limb	0.561	0.137	−2.37	0.018	0.347	0.905	**
Respiratory	6.179	5.078	2.22	0.027	1.234	30.932	**
Duration	0.993	0.002	−3.07	0.002	0.988	0.997	***
King’s stage ≥3	2.855	0.533	5.62	0.000	1.98	4.118	***
Symptoms: independent items, base, absent
Fasciculation
Present, but not bothering	0.804	0.18	−0.98	0.328	0.518	1.246
Bothering	0.526	0.165	−2.05	0.041	0.285	0.973	**
Muscle cramps
Present, but not bothering	1.032	0.212	0.15	0.877	0.691	1.542
Bothering	1.767	0.446	2.25	0.024	1.077	2.899	**
Head drop
Present, but not bothering	1.551	0.484	1.41	0.159	0.842	2.859
Bothering	2.017	0.541	2.61	0.009	1.192	3.414	***
Drooling
Present, but not bothering	1.052	0.251	0.21	0.830	0.66	1.679
Bothering	0.658	0.202	−1.37	0.172	0.36	1.2
Choking
Present, but not bothering	1.962	0.462	2.86	0.004	1.237	3.114	***
Bothering	4.005	1.111	5.00	0.000	2.326	6.899	***
Emotional lability
Present, but not bothering	1.163	0.264	0.67	0.506	0.745	1.816
Bothering	0.709	0.179	−1.36	0.173	0.432	1.162
PROM-based symptoms
Fatigue (NFI-MND)	1.078	0.021	3.77	0.000	1.037	1.12	***
Anxiety (M-HADS-A)	1.073	0.028	2.76	0.006	1.021	1.129	***
Personal
Smoker: base, never
Past smoker	1.53	0.318	2.04	0.041	1.018	2.301	**
Current smoker	1.22	0.502	0.48	0.628	0.545	2.733
Unknown	1.007	0.206	0.04	0.971	0.675	1.503
Religious: base, no
Yes	0.598	0.102	−3.01	0.003	0.427	0.836	***
Constant	0.233	0.158	−2.15	0.031	0.062	0.878	**

N = 1015.

Std. err: standard error; PROM: patient reported outcome measure; NFI-MND: Neurological Fatigue Index-MND; M-HADS-A: Modified Anxiety Subscale of Hospital Anxiety and Depression Scale; McKelvey & Zavoina’s R2: 0.392.

*p < 0.1.

**p < 0.05.

***p < 0.01.

Figure 3. Dyspnea-12 trajectories in inception group (for whom duration since diagnosis ≤ 6 months). Fine dashed lines indicate 95% confidence limits.

Data availability statement

Data supporting this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Walton Center NHS Trust. Please contact [email protected].