Evaluation Of HHIP Polymorphisms And Their Relationship With Chronic Obstructive Pulmonary Disease Phenotypes

Figures & data

Table 1 Characteristics Considered For Dividing Patients Into The Three Different Phenotypes

Phenotype	History Of Atopy	Number of Exacerbations In The Previous 12 Months	Bronchodilation Post Salbutamol Spray 400 mcg	DLCO % Predicted	TLC% Predicted	RV% Predicted
FE	Negative	≥ 2	Negative	> 75	< 130	< 125
ACO	Positive	< 2	Positive	> 75	< 130	< 125
Emphysema- hyperinflation	Negative	< 2	Negative	< 75	> 130	> 125

Abbreviations: ACO, asthma/COPD overlap; FE, frequent exacerbator; bronchodilator test was considered positive when an increment ≥ 12% FEV1% predicted was associated to 200 mL of the absolute baseline FEV₁, DLCO, carbon monoxide diffusion capacity; TLC%, total lung capacity % predicted; RV%, residual volume % predicted.

Table 2 Subjects’ Demographic And Functional Characteristics

	FE	ACO	Emphysema Hyperinflation	P-Value
Age (years, mean ± SD)	67.0 ±7.8	60.7 ± 7.8	67.0 ± 7.8	0.06
Male gender (n/total)	15/21	7/14	13/26	0.99
Smoking load	46.7 ± 24.5	60.2 ± 27.6	48.5±30.2	0.33
FEV1% (mean ± SD)	58.4 ± 20.7	68.3 ± 15.3*	52.3 ± 16.3*	0.03
FVC% (mean ± SD)	92.0 ± 25.1	100.0 ± 19.0	91.3 ± 18.5	0.41

Notes: Used ANOVA for categorical numbers and chi-square for gender. *Multiple comparison showed difference between ACO and emphysema/hyperinflation groups (p=0.02). Bold text indicates statistical significance.

Abbreviations: ACO, asthma/COPD overlap; FE, frequent exacerbator; FEV1%, forced expiratory volume in the first second % predicted; FVC%, forced vital capacity % predicted.

Figure 1 Recruitment flowchart.

Abbreviations: COPD, chronic obstructive lung disease; ACO, asthma/COPD overlap; FE, frequent exacerbator, pulmonary comorbidities included, tuberculosis sequelae, pulmonary fibrosis and lung cancer.

Table 3 Genotypic Frequency In The Phenotypes Studied

Polymorphism	FE (n/%)	ACO (n/%)	Emphysema-Hyperinflation (n/%)	p-Value
HHIP rs 1828591
AA	6 (28.5)	3 (21.4)	11 (42.4)	0.552
AG	11 (34.3)	8 (57.1)	13 (50.0)
GG	4 (19.0)	3 (21.4)	2 (7.6)
HHIP rs 13118928
AA	8 (38.1)	4 (28.5)	16 (61.5)	0.058
AG	9 (32.1)	9 (42.8)	10 (35.7)
GG	4 1(9.0)	1 (7.1)	0 (0.0)
HHIP rs 6537296
AA	5 (23.8)	5 (35.7)	12 (46.1)	0.296
AG	13 (61.9)	6 (42.8)	13 (50.0)
GG	3 (14.2)	3 (21.4)	1 (3.8)

Abbreviations: ACO, asthma/COPD overlap; FE, frequent exacerbator; HHIP, Hedgehog interaction protein.

Table 4 Allelic And Genotypic Frequency In 2 × 2 Comparisons With The Rs 13118928 HHIP Gene Polymorphism

Polymorphism	Allele A (n/%)	A (p-Value)	Allele G (n/%)	G (p-Value)	AA x AG x GG (n)	AA x AG x GG (p-Value)
FE	17 (80.9)	0.019	13 (61.9)	0.1	AA 8/AG 9/GG 4	0.1
Emphysema-hyperinflation	26 (100.0)		10 (38.4)		AA 16/AG 10/GG 0
FE	17 (80.9)	0.32	13 (61.9)	0.5	AA 8/AG 9/GG 4	0.4
ACO	13 (92.8)		10 (71.4)		AA 4/AG 9/GG 1
ACO	13 (92.8)	0.16	10 (71.4)	0.04	AA 4/AG 9/GG 1	0.04
Emphysema-hyperinflation	26 (100.0)		10 (38.4)		AA 16/AG 10/GG 0

Note: Bold text indicates statistical significance.

Abbreviations: ACO, asthma/COPD overlap; FE, frequent exacerbator; HHIP, Hedgehog interaction protein.