The Prevalence of Alpha-1 Antitrypsin Deficiency Among Patients Found to Have Airflow Obstruction

Figures & data

Table 1.  Recruitment by clinical center

Clinical Center	Enrollment
Atlanta VA Medical Center	64
Cleveland Clinic	128
Cleveland Clinic Florida	178
Emory Crawford Long Hospital	9
Emory University	35
Hospital Municipal de San Juan	80
Mayo Clinic	766
Medical University of South Carolina	365
Miami VA Medical Center	189
National Jewish Medical and Research	463
Oregon Health and Science University	50
St. Luke-Roosevelt Hospital Center	184
University of California Los Angeles	60
University of Chicago	268
University of Florida (Gainesville)	167
University of Florida (Jacksonville)	18
University of Miami	43
University of North Carolina	132
University of Texas	258
Total	3457

Figure 1.  Consort Diagram of the Study.

Table 2.  Characteristics of participating subjects

	Normal (MM)	Mild (MS,MZ,SS)	Severe (SZ,ZZ)	p-Value
	N = 2780	N = 352	N = 20
Age (Mean (SD))	63.8 (12.3)	64.5 (11.2)	58.0 (10.3)	0.6515
Female (%)	44.2	41.2	20.0	0.1202
Race (%)				<.0001
Caucasian	78.4	88.6	95.0
African American	14.5	4.3	0.0
Asian	0.5	0.0	0.0
Other	6.6	7.1	5.0
Smoke Ever (%) (N = 3141)	81.2	86.3	80.0	0.0284
Smoke Now (%) (N = 2606)	26.1	23.5	11.1	0.1955
Avg Cig Packs Per Day * Years Smoked (Median (Q1, Q3)) (N = 2501)	43 (27, 64)	44 (27, 63)	31 (20, 50)	0.7739
PreFEV (Mean (SD))	1.3 (0.6)	1.3 (0.5)	1.4 (.6)	0.6458
Pre FVC	2.6 (0.9)	2.7 (0.9)	3.0 (1.0)	0.3454
Pre FEV1/FVC	0.50 (0.1)	0.49 (0.1)	0.45 (0.1)	0.0313
Pre TLC	6.3 (1.6)	6.7 (1.6)	7.7 (1.9)	0.0002
Pre RV	3.5 (1.3)	3.8 (1.4)	3.9 (1.7)	0.006
Pre RV/TLC	0.6 (0.1)	0.6 (0.1)	0.5 (0.2)	0.9232
Pre DLCO	56.6 (22.9)	52.9 (22.9)	54.5 (31.1)	0.1046
Post FEV	1.5 (0.6)	1.4 (0.5)	1.5 (0.5)	0.7478
Post FVC	2.8 (0.9)	2.9 (0.9)	3.2 (0.9)	0.1303
Post FEV1/FVC	0.51(0.1)	0.50 (0.1)	0.46 (0.1)	0.0187

Abbreviations: Pre = Pre bronchodilator; Post = Post Bronchodilator; DLCO = Carbon Monoxide Diffusing Capacity; FEV1 = Forced Expiratory Volume in 1 second; FVC = Forced Vital Capacity; GOLD = The Global Initiative for Chronic Obstructive Lung Disease; PFT = Pulmonary Function Test; RV = Residual Volume; TLC = Total Lung Capacity.

Table 3.  Alpha-1 Antitrypsin Genotype Distribution by COPD GOLD Stage

GOLD Class	Genotype
Frequency Percent Row% Col%	1-Normal(MM)	2-Mild (MS,MZ,SS)	3-Severe(SZ,ZZ)	Total%
II	1506	175	8	1689
	47.78	5.55	0.25	53.59
	89.17	10.36	0.47
	54.17	49.72	40.00
III	972	136	9	1117
	30.84	4.31	0.29	35.44
	87.02	12.18	0.81
	34.96	38.64	45.00
IV	302	41	3	346
	9.58	1.30	0.10	10.98
	87.28	11.85	0.87
	10.86	11.65	15.00
Total%	2780	352	20	3152
	88.20	11.17	0.63	100.00

Table 4.  Summary of previous AATD detection efforts

First Author	Detection Strategy	Number of Patients	Prevalence of Specific AAT Phenotype (%)
			PI*ZZ	PI*SZ	PI*MZ	PI*SS	PI*MS	Other
Targeted detection (other than by Spirometric Criteria)
Bals (19)	Case-finding linked to an AATD awareness program	2696 (Germany)	9.9	2.0	18.1		3.6	Rare phenotype 0.5
Luisetti (23)	Case-finding (missing or reduced α1 globulin band, early onset emphysema, familial cluster, first degree relative of subjects with ascertained AATD or MZ heterozygosity)	2127 (Italy)	7.3	1.9	17.9	0.05	6.6	Null Null 0.4
Ferrarotti (33)								Z null 0.2
								Rare variants 0.2
Lieberman (4)	Case-finding (Patients with advanced COPD admitted for carotid body surgery)	965 (US)	1.9	0.3	7.7	0.3	10.1
Corda (21)	Case-finding (Emphysema without risk factors or of early-onset, spontaneous pneumothorax, cervical artery dissection, PAS positive bodies in liver, isolated transaminase elevation, ANCA positive, or low alpha-1 proteins on protein electrophoresis)	285 (Italy)	12	8	62		14	PI*ZI 0.35, PI*ZM malton 0.35 PI*MM malton 2.1
Detection in Patients with Obstructive Diseases
Brantly (22)	Case-finding (Targeted detection in COPD with education program and free testing)	969 (Florida)	3.2	0.4	11
de la Roza (20)	Case-finding (Patients with COPD)	2137 (Spain)	0.37	0.14		0.14
Wencker (18)	Targeted detection (Patients with COPD, emphysema, asthma, or bronchiectasis)	1060 (Germany)	0	0.2	3.7	0.09	3.4	PI*M Null 0.09
Matzen (25)	Case-finding (Individuals with abnormal PFTs)	225 (US)	0		2.7		7.1	PI*FF 0.4
Rahaghi (26)	Case-finding in GOLD II-IV sent for Spirometry tested after alert addended to reports	29 (US)	0		1
Rahaghi (current study)	Case-finding in GOLD II-IV sent for Spirometry- excluded previously tested patients	3152 (US)	0.32	0.32	3.87	0.25	7.01