Individualized lung function trends in alpha-1-antitrypsin deficiency: a need for patience in order to provide patient centered management?

Figures & data

Table 1 Characteristics of the patients with and without COPD

Characteristics	Non-COPD n=87				COPD n=395				P-value
	N	%	Mean	SD	N	%	Mean	SD
Never smokers	59	67.8%			82	20.8%			<0.0001
Index patient	38	43.7%			353	89.4%			<0.0001
Female	56	64.4%			153	38.7%			<0.0001
Age	87		44.8	13.2	395		52.9	9.3	<0.0001
FEV1 % predicted	87		113.4	15.7	395		53.1	21.9	<0.0001
FVC % predicted	87		115.5	16.6	395		109.4	22.4	0.002
FEV1/FVC	87		82.9	7.2	395		39.0	12.7	<0.0001
TLco % predicted	47		87.1	21.6	247		61.4	18.1	<0.0001
Kco % predicted	87		89.4	18.4	394		62.8	18.0	<0.0001
RV % predicted	87		88.8	21.4	385		128.1	39.3	<0.0001
TLC % predicted	86		106.8	13.6	385		117.1	15.2	<0.0001
RV/TLC	86		27.4	8.6	385		36.5	8.7	<0.0001
FEV1 % slope per year	87		−0.12	2.3	395		−1.14	1.8	<0.0001
Kco % slope per year	87		−1.06	2.1	377		−1.41	2.0	0.145
Distribution within FEV1 decline groups
FEV1 group 1	50	57.5%			93	23.5%			<0.0001
FEV1 group 2	5	5.7%			42	10.6%
FEV1 group 3	10	11.5%			59	14.9%
FEV1 group 4	22	25.3%			201	50.9%
Distribution within Kco decline groups
Kco group 1	25	28.7%			72	19.1%			0.259
Kco group 2	6	6.9%			30	8.0%
Kco group 3	13	14.9%			60	15.9%
Kco group 4	43	49.4%			215	57.0%

Notes: TLco is overall gas transfer; Kco is gas transfer corrected for alveolar ventilation. % values indicate the proportion of each group with individual categorical characteristics. Significant P-values are given in bold.

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expired volume in 1 second; FVC, forced vital capacity; SD, standard deviation; RV, residual volume; TLC, total lung capacity

Table 2 Characteristics of patients without COPD substratified by FEV₁ decline

Demographics for FEV1 decline groups non-COPD
FEV1 decline group	Group 1 n=50				Group 2 n=5				Group 3 n=10				Group 4 n=22				Across all groups	Statistic groups 1 and 4
	No decline (decline of <−0.1% predicted per year)				Decline of −0.1 to <−0.5				Decline of −0.5 to <−1.0				Decline of at least −1.0
	N	%	Mean	SD	N	%	Mean	SD	N	%	Mean	SD	N	%	Mean	SD	P-value	P-value
Never smokers	34	48.0%			3	60.0%			6	60.0%			16	72.7%			0.882	0.688
Index patient	24	48.0%			2	40.0%			1	10.0%			11	50.0%			0.146	0.876
Female	33	66.0%			3	60.0%			6	60.0%			14	63.6%			0.980	0.846
Age	50		42.8	12.9	5		34.4	12.4	10		46.7	14.2	22		50.7	11.7	0.031	0.140
FEV1 % predicted	50		110.0	15.6	5		118.6	10.2	10		117.9	17.1	22		117.8	15.4	0.344	0.142
FVC % predicted	50		110.4	16.9	5		115.6	11.8	10		122.2	17.8	22		123.9	12.2	0.012	0.002
FEV1/FVC	50		84.4	7.4	5		87.8	5.7	10		81.0	5.8	22		79.2	5.8	0.006	0.003
TLco % predicted	27		92.0	21.8	2		89.1	21.5	3		76.0	13.8	15		80.2	21.7	0.315	0.145
Kco % predicted	50		93.3	18.1	5		84.8	12.8	10		91.6	21.4	22		80.5	16.3	0.031	0.004
RV % predicted	50		85.3	17.7	5		108.0	31.1	10		93.2	14.8	22		90.4	27.0	0.253	0.557
TLC % predicted	50		104.0	12.7	5		115.5	19.7	10		111.8	13.0	21		109.2	13.4	0.126	0.107
RV/TLC	50		26.2	6.7	5		26.8	8.9	10		27.4	6.4	21		30.5	12.6	0.543	0.153
FEV1 slope mL/year	50		−28.2	31.6	5		−37.0	30.3	10		−43.9	16.2	21		−105.1	49.5	N/A	N/A
FEV1 % slope per year	50		1.3	1.3	5		−0.3	0.1	10		−0.70	0.1	22		−3.1	2.0	N/A	N/A
Kco % slope per year	50		−0.9	2.0	5		−1.4	1.1	10		−1.47	2.5	22		−1.1	2.4	0.956	0.883
Distribution within Kco decline groups
Kco group 1	15	30.0%			0	0.0%			2	20.0%			8	36.4%			0.166	0.799
Kco group 2	2	4.0%			2	40.0%			1	10.0%			1	4.5%
Kco group 3	9	18.0%			0	0.0%			2	20.0%			2	9.1%
Kco group 4	24	48.0%			3	60.0%			5	50.0%			11	50.0%

Notes: TLco is overall gas transfer; Kco is gas transfer corrected for alveolar ventilation. % values indicate the proportion of each group with individual categorical characteristics. Significant P-values are given in bold.

Abbreviations: COPD, chronic obstructive pulmonary disease; FVC, forced vital capacity; FEV₁, forced expired volume in 1 second; N/A, not available; SD, standard deviation; RV, residual volume; TLC, total lung capacity.

Table 3 Characteristics of patients with COPD substratified by FEV₁ decline

Demographics for FEV1 Decline Groups COPD
FEV1 decline group	Group 1 n=93				Group 2 n=42				Group 3 n=59				Group 4 n=201				Across all groups	Statistic between groups 1 and 4
	No decline (decline of <−0.1% predicted per year)				Decline of −0.1 to <−0.5				Decline of −0.5 to <−1.0				Decline of at least −1.0
	N	%	Mean	SD	N	%	Mean	SD	N	%	Mean	SD	N	%	Mean	SD	P-value	P-value
Never smokers	19	20.4%			2	4.8%			9	15.3%			52	25.9%			0.013	0.311
Index patient	85	91.4%			40	95.2%			53	89.8%			175	87.1%			0.382	0.280
Female	43	46.2%			14	33.3%			20	33.9%			76	37.8%			0.337	0.171
Age	93		54.1	8.6	42		50.6	8.0	59		52.5	8.4	201		53.0	10.0	0.193	0.456
FEV1 % predicted	93		50.5	24.8	42		41.5	17.2	59		47.8	19.1	201		58.3	20.8	<0.0001	<0.0001
FVC % predicted	93		107.1	24.1	42		98.1	18.4	59		104.0	20.6	201		114.5	21.6	<0.0001	0.004
FEV1/FVC	93		37.7	13.8	42		34.3	11.6	59		36.9	12.1	201		41.2	12.1	0.001	0.017
DLco % predicted	61		61.3	19.7	20		57.1	20.5	37		62.6	17.9	132		61.8	17.3	0.722	0.788
Kco % predicted	92		64.6	19.2	42		62.4	19.0	59		66.2	19.1	201		61.2	16.8	0.265	0.203
RV % predicted	89		126.4	39.4	42		147.9	48.1	57		137.5	34.5	199		121.9	37.1	0.001	0.295
TLC % predicted	89		116.2	14.8	42		119.2	17.7	57		117.2	12.7	199		117.1	15.7	0.852	0.822
RV/TLC	89		37.2	8.8	42		40.3	10.1	57		38.8	7.1	199		34.7	8.4	<0.0001	0.010
FEV1 slope mL/year	93		11.2	32.3	42		−22.4	10.6	59		−36.3	8.2	201		−86.2	54.7	N/A	N/A
FEV1 % slope per year	93		0.9	1.2	42		−0.3	0.1	59		−0.8	0.1	201		−2.4	1.4	N/A	N/A
Kco % slope per year	89		−1.3	1.8	41		−1.2	1.5	58		−1.58	1.8	189		−1.5	2.2	0.709	0.730
Distribution within Kco decline groups
Kco Group 1	16	18.0%			10	24.4%			8	13.8%			38	20.1%			0.633	0.789
Kco Group 2	8	9.0%			5	12.2%			5	8.6%			12	6.3%
Kco Group 3	14	15.7%			5	12.2%			6	10.3%			35	18.5%
Kco Group 4	51	57.3%			21	51.2%			39	67.2%			104	55.0%

Notes: TLco is overall gas transfer; Kco is gas transfer corrected for alveolar ventilation. % values indicate the proportion of each group with individual categorical characteristics. Significant P-values are given in bold.

Abbreviations: COPD, chronic obstructive pulmonary disease; FVC, forced vital capacity; FEV₁, forced expired volume in 1 second; N/A, not available; SD, standard deviation; RV, residual volume; TLC, total lung capacity.

Figure 1 The proportion of patients who are ex-smokers.

Notes: The bar chart shows the proportion of those without COPD and those with different severity stages of COPD as defined by GOLD⁹ who are ex-smokers.

Abbreviations: COPD, chronic obstructive pulmonary disease; GOLD, Global initiative for chronic Obstructive Lung Disease.

Figure 2 The proportion of subjects showing no decline or rapid decline in FEV₁.

Notes: The bar chart shows the degree of decline in FEV₁, categorized as no decline or rapid decline, in those without COPD and those with different severity stages of COPD.
Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expired volume in 1 second.

Figure 3 The relationship between the decline in FEV₁ and Kco.

Notes: The figure substratifies correlations between FEV₁ and Kco values in individual patients without (A) and with (B) established COPD. The correlation coefficient (r) is shown for both the groups with its significance (P). In both the graphs, the horizontal axis goes through the point of no decline in FEV₁, such that those points lying below the line have worsening FEV₁, while those above it have shown an improvement. Similarly the vertical axis passes through the point of no decline in Kco, such that those points lying to the left are deteriorating, while those to the right are not. The four quadrants therefore represent decline in both FEV₁ and Kco (bottom left), decline in Kco alone (upper left), decline in FEV₁ alone (bottom right), and decline in neither measure (upper right). Kco is gas transfer corrected for alveolar ventilation.
Abbreviations: % pred, % predicted; COPD, chronic obstructive pulmonary disease; FEV₁, forced expired volume in 1 second.

Figure 4 The decline in FEV₁ for individual patients without COPD.

Notes: Representative patients have been chosen to demonstrate the pattern of FEV₁ decline in (A and B) slow/no decline and (C and D) rapid decline. The similarity of the slope in patients followed over prolonged periods (B and D) to those followed over shorter periods (A and B) demonstrates that decline is linear in an individual over time, such that shorter periods might be used to determine longer-term prognosis.

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expired volume in 1 second.

Figure 5 Decline in FEV₁ for individual patients with COPD.

Notes: This figure demonstrates the pattern of slow decline (A and B) and rapid decline (C and D) in patients with COPD. A linear pattern in any given individual was seen.
Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expired volume in 1 second.

Figure 6 The degree of agreement between measures of FEV₁ decline.

Notes: The decline in FEV₁ determined by linear regression analysis is shown for patients in whom both four and eleven annual data points were available. The horizontal and vertical lines indicate the threshold of 1% predicted decline used here to delineate the rapid decliners. The regression equation and r² value is shown; there is a good relationship indicating that four data points may be adequate to determine longer-term prognosis.
Abbreviation: FEV₁, forced expired volume in 1 second.

StockleyRAProteases and Antiproteases in Chronic Obstructive Pulmonary Disease: Pathogenesis to TreatmentChadwickDGoodeJAWileyChichester, UK2001189204

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