Pulmonary function decline in amyotrophic lateral sclerosis

Figures & data

Figure 1 Median overall decline in pulmonary functions over time. This figure demonstrates the decline from origin at time 0 and measured in absolute change in % over time. Note the most rapid decline occurs in the MEP followed by the laying FVC and inspiratory pressures (supine SNIP and MIP). This suggests that pressure measurements should be part of clinical assessments of respiratory function and both be used for determining initiation of NIV.

Table 1 Baseline demographics and disease characteristics for patients with ≥3 visits.

Variable	Overall	Group 1	Group 2
	(n = 65)	(n = 42)	(n = 23)
Age (years)	58.19 (35.83, 82.03)	55.69 (35.83, 82.03)	63.71 (40.58, 77.58)
Gender, N (%)
F	23 (35.38%)	14 (33.33%)	9 (39.13%)
M	42 (64.62%)	28 (66.67%)	14 (60.87%)
BMI	26.07 (18.83, 40.26)	26.75 (18.83, 38.77)	25.94 (20.66, 40.26)
Site of Onset, N (%)
Bulbar	12 (18.5%)	6 (14.3%)	6 (26.1%)
Extremity	53 (81.5%)	36 (85.7%)	17 (73.9%)
Sitting FVC % Predicted	82.0 (47.00, 96.0)	89.0 (74.0, 96.0)	61.0 (47.0, 76.0)
Laying FVC % Predicted	69.5 (28.0, 102.0; n = 56)	80.0 (33.0, 102.0; n = 37)	48.0 (28.0, 69.0; n = 19)
MIP cm H2O	39.0 (4.0, 86.0, n = 59)	43.0 (17.0, 86.0; n = 39)	22.0 (4.0, 86.0; n = 20)
Sitting SNIP cm H2O	46.0 (10.0, 102.0; n = 59)	55.5 (10.0, 100.0; n = 38)	30.0 (19.0, 102.0, n = 21)
Laying SNIP cm H2O	46.0 (3.0, 114.0; n = 55)	56.0 (15.0, 102.0; n = 36)	34.0 (3.0, 114.0; n = 19)
MEP cm H2O	53.0 (9.0, 141.0; n = 59)	60.0 (9.0, 141.0; n = 39)	33.5 (16.0, 98.0; n = 20)
SMVV L/min	53.3 (4.8, 172.9; n = 55)	63.2 (29.9, 172.9; n = 36)	36.6 (4.8, 95.0; n = 19)
ALS FRS	35.5 (15.0, 45.0; n = 64)	36.0 (22.0, 45.0; N = 41)	35.0 (15.0, 43.0; n = 23)
Follow up (days)	336 (73, 371)	336 (120, 371)	284 (73, 347)
Number of Study Visits,( N)	65	42	23
Mean (SD)	6.51 (1.56)	6.81 (1.44)	5.96 (1.66)
Median (IQR)	7.00 (5.00, 7.00)	7.00 (6.00, 8.00)	6.00 (5.00, 7.00)
Median (Range)	7 (3, 10)	7 (4, 9)	6 (3, 10)

Table entries are median (range) or count (%); data was obtained on all subjects except where n is indicated.Group 1 subjects were >80-95% FVC on study entry and Group 2 were those subjects with FVCs 50-79%. Abbrev SSNIP refers to SNIP in the sitting position and LSNIP in the labing position.

Table 2 Rate of decline per month in PFTs and ALS FRS scores overall and by group^a.

Variable	Overall	Group 1	Group 2	p-Value
	(n = 65)	(n = 42)	(n = 23)	Group 1 vs. 2
SFVC Max	−2.01 (−10.85, 2.28)	−1.97 (−8.91, 2.28)	−2.32 (−10.85, 0.34)	0.84
LVFVC Max	−2.02 (−11.27, 2.15) n = 55	−2.03 (−7.26, 1.96) n = 38	−1.83 (−11.27, 2.15)	0.67
MEP Max	−2.60 (−9.89, 3.81) n = 64	−2.70 (−9.89, 3.81)	−2.44 (−7.64, 1.52) n = 22	0.23
MIP Max	−1.59 (−8.36, 2.25) n = 64	−2.27 (−8.36, 2.25)	−0.88 (−6.07, 0.92) n = 22	0.21
SSNIP Max	−1.25 (−7.23, 5.49) n = 64	−1.09 (−7.23, 5.49)	−1.39 (−4.13, 0.98) n = 22	0.99
LSNIP Max	−1.42 (−6.77, 1.56) n = 54	−1.36 (−6.67, 1.56) n = 38	−1.56 (−6.77, 0.40) n = 16	0.63
SMVV	−1.62 (−10.92, 5.32) n = 58	−2.48 (−10.92, 5.32) n = 40	−0.47 (−6.98, 0.62) n = 18	0.06
ALS FRS	−1.13 (−2.54, 0.20) n = 51	−1.13 (−2.35, 0.20) n = 36	−1.13 (−2.54, −0.30) n = 15	0.47
ALS FRS Respiratory Domains	−0.27 (−0.89, 0.12), n = 51	−0.21 (−0.89, 0.12) n = 36	−0.50 (−0.74, −0.02) n = 15	0.09

^aTable entry = median slope (range) of decline on a monthly basis (range), where ≥3 values for a measure were not available on all subjects within a category, the number of subjects (n) with available measures is indicated. These declines are based on %drop from baseline. For the Overall Group all the values were significantly different from 0 (p<0.01). Declines were not significantly different between Groups 1 and 2 (p-value Group 1 vs. 2 column).

Table 3 Overall correlations among baseline values of pulmonary functions. Spearman Correlation Coefficients Prob > |r| under H0: Rho=0 Number of Observations

	SFVC	LFVC	MIP	SSNIP	LSNIP	MEP	SMVV
SFVC	1.00000	0.83	0.45	0.34	0.41	0.32	0.401
	–	<.0001	0.0003	0.009	0.002	0.01	0.002
	65	56	59	59	55	59	55
LFVC	0.83	1.00	0.43	0.41	0.47	0.23005	0.278
	<0.0001	–	0.001	0.002	0.0003	0.088	0.047
	56	56	56	55	55	56	55
MIP	0.45	0.43	1.00	0.76	0.74	0.59	0.56
	0.0003	0.0009	–	<0.0001	<0.0001	<0.0001	<0.0001
	59	56	59	58	55	59	55
SSNIP	0.34	0.41	0.76	1.00	0.89	0.52	0.46
	0.009	0.002	<.0001	–	<.0001	<.0001	0.0004
	59	55	58	59	55	58	55
LSNIP	0.41	0.47	0.74	0.89	1.00	0.48	0.440
	0.002	0.0003	<.0001	<.0001	–	0.0002	0.0008
	55	55	55	55	55	55	55
MEP	0.32	0.23	0.59	0.52	0.48	1.00	0.53
	0.01	0.09	<.0001	<.0001	0.0002	–	<.0001
	59	56	59	58	55	59	55
SMVV	0.40	0.27	0.56	0.46	0.44	0.53	1.00
	0.002	0.047	<.0001	0.0004	0.0008	<.0001	–
	55	55	55	55	55	55	55

Table 4 Overall correlations between baseline values of pulmonary functions and ALS FRS score with rates of their decline over time. Spearman Correlation Coefficients Prob > |r| under H0: Rho=0 Number of Observations

	SFVC	LFVC	MIP_	SSNIP	LSNIP	MEP	SMVV	FRS_Total
Slope_SFVC	−0.01	−0.06	−0.03	0.02	0.04	0.04	−0.04	0.29
	0.946	0.635	0.820	0.878	0.792	0.763	0.749	0.018
	65	56	59	59	55	59	55	64
Slope_LFVC	−0.05	−0.19	0.035	−0.03	−0.03	0.09	0.07398	0.25
	0.704	0.191	0.810	0.827	0.864	0.547	0.613	0.072
	55	50	50	50	49	50	49	54
Slope_MIP	−0.11	−0.10	−0.57	−0.42	−0.39	−0.41	−0.20	0.08
	0.371	0.463	<.0001	0.0008	0.004	0.001	0.13555	0.558
	64	56	59	59	55	59	–	63
Slope_SSNIP	0.17	0.11	−0.12	−0.28	−0.13	−0.20	−0.06	0.32
	0.18	0.414	0.351	0.030	0.336	0.129	0.669	0.012
	64	56	59	59	55	59	55	63
Slope_LSNIP	0.01	−0.03	−0.25	−0.24	−0.46	−0.19	−0.16	0.02
	0.925	0.841	0.077	0.092	0.001	0.192	0.274	0.864
	54	50	50	50	49	50	49	53
Slope_MEP	−0.10	−0.034	−0.46	−0.34	−0.31	−0.61	−0.31	0.11
	0.419	0.787	0.0002	0.009	0.02	<.0001	0.021	0.413
	64	56	59	59	55	59	55	63
Slope_SMVV	−0.13	−0.12	−0.20	−0.17	−0.24	−0.23	−0.51	0.17
	0.333	0.383	0.140	0.213	0.084	0.086	<0.0001	0.193
	58	54	55	54	53	55	53	57
Slope_ALSFRS_	0.12	0.07	−0.08	0.002	0.03	−0.07	0.01	0.02
	0.402	0.660	0.572	0.990	0.824	0.659	0.923	0.872
	51	47	48	47	46	48	46	50

Values are bolded because they reached statistical significance of p < 0.05.

Table 5 Correlations among the rates of decline for PFTS and ALS FRS with each other over time. Spearman Correlation Coefficients Prob > |r| under H0: Rho=0 Number of Observations

	Slope_SFVC	Slope_LFVC	Slope_MIP_	Slope_SSNIP	Slope_LSNIP	Slope_MEP_	Slope_SMVV	Slope_ALSFRS
Slope_SFVC	1.00	0.68	0.48	0.65	0.58	0.35	0.59	0.78
	–	<0.0001	<0.0001	<0.0001	<0.0001	0.0044	<0.0001	<0.0001
	65	55	64	64	54	64	58	51
Slope_LFVC	0.68	1.00	0.38	0.58	0.44	0.25	0.42	0.67
	<0.0001	–	0.004	<0.0001	0.001	0.065	0.002	<0.0001
	55	55	55	55	54	55	53	48
Slope_MIP	0.48	0.38	1.00	0.55	0.47	0.66	0.48	0.57
	<0.0001	0.0044	–	<0.0001	0.0003	<.0001	0.0001	<0.0001
	64	55	64	64	54	64	58	51
Slope_SSNIP	0.65	0.58	0.55	1.00	0.65	0.57	0.44	0.64
	<0.0001	<0.0001	<0.0001	–	<0.0001	<0.0001	0.001	<0.0001
	64	55	64	64	54	64	58	51
Slope_LSNIP	0.58	0.44	0.47	0.65	1.00	0.56	0.42	0.51
	<0.0001	0.0009	0.0003	<0.0001	–	<0.0001	0.002	0.0002
	54	54	54	54	54	54	53	48
Slope_MEP	0.35	0.25	0.66	0.57	0.56	1.00	0.41	0.43
	0.004	0.065	<0.0001	<0.0001	<0.0001	–	0.002	0.002
	64	55	64	64	54	64	58	51
Slope_SMVV	0.59	0.42	0.48	0.44	0.42	0.41	1.0	0.59
	<0.0001	0.002	0.0001	0.001	0.002	0.002	–	<.0001
	58	53	58	58	53	58	58	50
Slope_ALSFRS	0.78	0.67	0.57	0.64	0.51	0.43	0.59	1.00
	<0.0001	<0.0001	<0.0001	<0.0001	0.0002	0.002	<0.0001	–
	51	48	51	51	48	51	50	51