The Distribution of Alpha-1 Antitrypsin Genotypes Between Patients with COPD/Emphysema, Asthma and Bronchiectasis

Figures & data

Table 1 Baseline Characteristics of Probands

	All	COPD/ Emphysema	Asthma	Bronchiectasis	p-value
N	18736	12283	4041	285
Age [Median (IQR)]	62.72 (51.2–71.76)	64.78 (56.13–74.03)	48.59 (30.17–60.52)	59.85 (42.72–70.46)	^### ^§§§ ***
Male Female	47% 52.2%	55.2% 43.8%	46.5% 53%	38.2% 60%	^## ^§§§ ***
Smokers Past-smokers Non-smokers	25.7% 40.4% 33.9%	29.6% 44.7% 20.7%	12.2% 20.4% 61.8%	7.7% 19.6% 62.5%	^## ^§§§ ***
Augmentation therapy	1%	1.1%	0.3%	0.7%	***

Notes: Table 1 displays the baseline characteristics of patients according to the chronic respiratory diseases. Patients with asthma were of the youngest age (median 48.59 years) when compared to patients with bronchiectasis (59.85 years) and COPD/emphysema (64.78 years). Patients with bronchiectasis or asthma were predominantly female (60% and 53%), whereas more patients with COPD/emphysema were men (55.2%). Smoking habits were different among the three groups, too: Patients with bronchiectasis or asthma were mainly non-smokers (62.5% and 61.8%) in contrast to COPD/emphysema patients, who had a history of smoking in 44.7% and were currently smoking in 29.6%. Patients with COPD/emphysema received augmentation therapy most frequently (1.1%) when compared to patients with bronchiectasis or asthma (0.7% and 0.3%); ^###p<0.001, ^##p<0.01 significant between bronchiectasis and asthma; ^§§§p<0.001 significant between bronchiectasis and COPD/emphysema; ***p<0.001 significant between asthma and COPD/emphysema.

Figure 1 Frequency of 18,736 patients among chronic respiratory disorders without consideration on AATD. A three-way Venn diagram was plotted to investigate the relationship between patients of COPD/Emphysema, asthma and bronchiectasis and their overlaps. COPD/Emphysema only: 12,283 (65.56%); asthma only: 4,041 (21.57%); bronchiectasis only: 285 (1.52%); COPD/Emphysema and asthma overlap: 1,592 (8.50%); COPD/Emphysema and bronchiectasis overlap: 345 (1.84%); asthma and bronchiectasis overlap: 92 (0.49%); COPD/Emphysema and asthma and bronchiectasis overlap: 98 (0.52%). BioVenn – a web application for the comparison and visualization of biological lists using area-proportional Venn diagrams. T. Hulsen, J. de Vlieg and W. Alkema, BMC Genomics 2008, 9 (1): 488.

Figure 2 Frequency of symptoms among the chronic respiratory diseases: COPD/emphysema, asthma and bronchiectasis. Figure 2 displays the frequency of clinical symptoms (dyspnea, dyspnea attacks, cough, phlegm, wheezing, acute bronchitis and chronic bronchitis) among the chronic respiratory diseases (COPD/emphysema, asthma and bronchiectasis). Chi-square test was used for statistical analyses. This information has been evaluated on the basis of the information on the AlphaKits®. Dyspnea appeared most frequently in patients with COPD/emphysema, whereas dyspnea attacks were more often in patients with asthma. Cough and phlegm could be observed most frequently in patients with bronchiectasis. Acute and chronic bronchitis occurred more often in patients with asthma or bronchiectasis than in patients with COPD/emphysema. ^###p<0.001 significant between bronchiectasis and asthma; ^§§§p<0.001, ^§p<0.05 significant between bronchiectasis and COPD/emphysema; ***p<0.001, **p<0.01 significant between asthma and COPD/emphysema.

Figure 3 Distribution of the AAT alleles.

Table 2 Distribution of the AAT Alleles Among Patients with COPD/Emphysema or Asthma, or Bronchiectasis

	COPD/Emphysema	Asthma	Bronchiectasis
Pi*MM	7,154 (58.24%)	2,215 (54.81%)	169 (59.3%)
Pi*MS	557 (4.53%)	261 (6.46%)	14 (4.91%)
Pi*MZ	2,704 (22.01%)	1,238 (30.64%)	61 (21.4%)
Pi*SS	33 (0.27%)	12 (0.3%)	2 (0.7%)
Pi*SZ	306 (2.49%)	81 (2%)	8 (2.81%)
Pi*ZZ	1,120 (9.12%)	112 (2.77%)	20 (7.02%)
Pi*M/Rare	142 (1.16%)	76 (1.88%)	6 (2.11%)
Pi*S/Rare	31 (0.25%)	10 (0.25%)	2 (0.7%)
Pi*Z/Rare	202 (1.64)	32 (0.79%)	1 (0.35%)
Pi*Rare/Rare	34 (0.28%)	4 (0.1%)	2 (0.7%)

Figure 4 Distribution of AAT alleles among the chronic respiratory diseases: COPD/emphysema, asthma and bronchiectasis. Figure 4 displays the distribution of AAT alleles among the chronic respiratory diseases bronchiectasis, asthma and COPD/emphysema. The distribution of the wild type (Pi*MM) was roughly comparable between the three groups (significant only between asthma and COPD/emphysema). The same applied to the distribution of the genotypes Pi*MS, Pi*M/rare and Pi*Z/rare, while the genotypes Pi*SS, Pi*SZ and Pi*S/rare were not distributed significantly different. A higher percentage of asthma patients exhibited the Pi*MZ genotype, whereas more COPD/emphysema and bronchiectasis patients exhibited the Pi*ZZ genotype when compared to asthma patients. ^###p<0.001, ^##p<0.01 significant between bronchiectasis and asthma; ***p<0.001, *p<0.05 significant between asthma and COPD/emphysema.

Table 3 Distribution of AAT Alleles Among Different Combinations of the Three Diagnostic Groups

	COPD/Emphysema and Asthma	COPD/Emphysema and Bronchiectasis	COPD/Emphysema and Bronchiectasis and Asthma	Asthma and Bronchiectasis
Pi*MM	986 (61.93%)	184 (53.33%)	56 (57.14%)	65 (70.65%)
Pi*MS	84 (5.28%)	19 (5.51%)	4 (4.08%)	5 (5.43%)
Pi*MZ	321 (20.16%)	72 (20.87%)	23 (23.47%)	18 (19.57%)
Pi*SS	1 (0.06%)	1 (0.29%)	0 (%)	0 (0%)
Pi*SZ	33 (2.07%)	4 (1.16%)	0 (0%)	0 (0%)
Pi*ZZ	114 (7.16%)	51 (14.78%)	13 (13.27%)	2 (2.17%)
Pi*M/Rare	24 (1.51%)	2 (0.58%)	1 (1.02%)	2 (2.17%)
Pi*S/Rare	3 (0.19%)	1 (0.29%)	0 (0%)	0 (0%)
Pi*Z/Rare	25 (1.57%)	7 (2.03%)	1 (1.02%)	0 (0%)
Pi*Rare/Rare	1 (0.06%)	4 (1.16%)	0 (0%)	0 (0%)

Figure 5 Detection rate of patients with COPD/emphysema, bronchiectasis, asthma.