Alpha-1 Antitrypsin Deficiency and Tobacco Smoking: Exploring Risk Factors and Smoking Cessation in a Registry Population

Figures & data

Table 1. Characteristics of respondents, presented by AATD genotype.

	MZ	SZ	ZZ/Rare	p Value
n	91	72	130
Age (years)	58.0 [46.0, 65.0]	57 [44.8, 65.3]	58 [51.3, 65.0]	0.648
Male sex (%)	36 (39.6)	37 (51.4)	70 (53.8)	0.099
Educational level	2.73 (1.31)	2.78 (1.24)	2.44 (1.17)	0.099
Age at AATD diagnosis	50.0 [41.5, 59.0]	50.0 [34.0, 58.2]	46.0 [38.0, 54.5]	0.136
Reason for AATD diagnosis (%)				<0.001
Lung disease	30 (32.9)	20 (27.8)	77 (59.2)
Pediatric liver disease	5 (5.5)	3 (4.2)	4 (3.1)
Adult liver disease	3 (3.3)	7 (9.7)	5 (3.9)
Family screening	33 (36.3)	23 (31.9)	39 (30.2)
Other	14 (15.4)	6.3 (6.4)	4 (3.1)
Unaware of diagnosis	6 (6.59)	6 (8.3)	1 (0.8)
GOLD (%)				<0.001
0	48 (52.7)	39 (54.2)	33 (25.4)
1	22 (24.2)	17 (23.6)	19 (14.6)
2	13 (14.3)	11 (15.3)	36 (27.7)
3	5 (5.5)	2 (2.8)	28 (21.5)
4	3 (3.3)	3 (4.2)	14 (10.8)
Ever-smoker (%)	49 (53.8)	41 (56.9)	80 (61.5)	0.510
Pack-years (ever-smokers)	15.8 [6.0, 27.8]	25.0 [8.5, 46.3]	17.1 [7.9, 26.5]	0.018
Parental smoking exposure (%)	69 (75.8)	50 (69.4)	84 (64.6)	0.206
Parental smoking related disease (%)	44 (53.0)	37 (51.4)	49 (38.6)	0.071
Awareness of AAT type (%)	30 (33)	42 (58.3)	88 (67.7)	<0.001

Respondents with ZZ AATD were more likely to have been diagnosed with AATD due to lung disease, demonstrated worse airflow obstruction, and were significantly more likely to be aware of their genotype than MZ or SZ individuals (p < 0.001 for all). Data presented as mean +/– SD for parametric tests, median + [IQR] for non-parametric tests or n= and (%) for categorical.

Figure 1. Univariate analysis of the association of parental smoking with cumulative tobacco consumption (pack-years; top) and quit attempts (bottom) prior to successful cessation among former-smokers (n = 153). Parental smoking was associated with significantly greater tobacco consumption (+8.7 pack-year, p = 0.005) and quit attempts (+2.63 quit attempts, p = 0.007).

Table 2. Adjusted odds of ever-smoker status for demographic and social factors.

Predictor	OR	95% CI	p Value
Parental smoking	1.84	1.09 to 3.06	0.018
Educational level (increase)	0.84	0.69 to 1.02	0.09
Male sex	1.17	0.73 to 1.88	0.51

Multivariate binomial logistic regression analysis for outcome of ever-smoker.

Method: glm binomial logistic regression.

Parental smoking was found to significantly increase the odds of ever smoking in respondents.

Table 3. Characteristics of ever-smoking respondents presented by former- vs. current-smokers.

	Former-smoker	Current-smoker	p Value
n	153	17
Age	58.0 [49.0, 65.0]	49 [27.0, 59.5]	0.004
Male (%)	78 (51.0)	8 (47.1)	0.959
Educational level	2.46 (1.19)	2.76 (1.39)	0.321
Genotype (%)			0.009
MZ	41 (26.8)	8 (47.1)
SZ	34 (22.2)	7 (41.2)
ZZ/Rare	78 (51.0)	2 (11.8)
Age at AAT diagnosis	46.0 [40.0, 55.3]	26.0 [21.5, 50.0]	0.019
Pack-years smoked	17.0 [7.0, 30.0]	27 [14.0, 33.0]	0.133
Awareness of AAT type (%)	86 (56.2)	7 (41.2)	0.355
Age started smoking	16.0 [15.0, 18.0]	16.0 [15.0, 21.0]	0.323
Physician-diagnosed lung disease (%)	99 (64.7)	12 (70.6)	0.830
GOLD (%)			0.242
0	43 (28.1)	7 (41.2)
1	26 (17.0)	5 (29.4)
2	42 (27.5)	4 (23.5)
3	26 (17.0)	0 (0.0)
4	16 (10.5)	1 (5.9)
Quit attempts	3.0 [1.0, 6.0]	3.0 [3.0, 10.0]	0.137
Parental smoking (%)	116 (75.8)	12 (70.6)	0.859
No cessation aids (%)	91 (59.5)	5 (29.4)	0.035
Nicotine (%)	47 (30.7)	8 (47.1)	0.274
E-cigarettes/Vaping (%)	17 (11.1)	11 (64.7)	<0.001
Varenicline (%)	7 (4.6)	1 (5.9)	1.000
Hypnosis (%)	7 (4.6)	0 (0.0)	0.797
Acupuncture (%)	8 (5.2)	0 (0.0)	0.717
Other (%)	9 (5.9)	1 (5.9)	1.000

Current-smokers are seen to be younger at time of diagnosis and study participation, with less severe airflow obstruction and more commonly of the MZ or SZ genotypes. Data presented as mean +/– SD for parametric tests, median + [IQR] for non-parametric tests or n= and (%) for categorical.

Table 4. Adjusted odds of current-smoker (vs. former-smoker) status for patient factors.

Predictor	OR	95% CI	p Value
Age (per year increase)	0.91	0.86 to 0.96	<0.001
SZ (vs. MZ)	0.58	0.16 to 2.17	0.421
ZZ/Rare (vs. MZ)	0.15	0.03 to 0.78	0.025
Male sex	0.65	0.20 to 2.10	0.477
Parental smoking	0.95	0.24 to 3.76	0.939
Pack-years	1.04	1.01 to 1.08	0.018

Multivariate binomial logistic regression analysis for outcome of current-smoker.

Method: glm binomial logistic regression.

Older age and ZZ genotype were associated with lower odds of current smoking. No significant effect was seen for SZ genotype (vs. MZ) or parental smoking.

Figure 2. Representation of the double-hit hypothesis for COPD risk in AATD families. A single AAT deficient parent (in this example one heterozygous MZ individual) is sufficient to pass on a deficient Z allele in 50% of children. This inheritance of MZ AATD is not associated with an increase in the risk of COPD without the addition of tobacco smoking. The presence of smoking at a parental level (red arrow) will increase the likelihood of smoking in progeny compared to those born to nonsmoking parents (blue arrow). With the addition of cigarette smoking, MZ progeny will have a significantly increased risk of COPD compared to smoking MM siblings.

Data availability

Data from this study will not be publicly available due to the terms of the patient consent to participation.