In COPD, chronic inflammation and exposure to irritants, such as cigarette smoke, lead to the thickening of bronchial walls. This results from increased deposition of collagen and other extracellular matrix components, contributing to the narrowing of airways. Nevertheless, it is widely recognized that COPD is an inflammatory disorder marked by partially reversible airflow limitation wherein genetic factors interact with the environment. In recent years, numerous investigations have substantiated the correlation between gene polymorphisms and COPD. SUMF1 has been implicated in diverse cellular processes, including lysosomal function and extracellular matrix maintenance, both of which play pivotal roles in respiratory health. The genetic variations in SUMF1 could lead to an imbalanced sulfation in the extracellular matrix of lung tissue, potentially playing a role in the onset of COPD. Recent studies have uncovered a potential link between dysregulation of SUMF1 and COPD progression, shedding light on its involvement in the abnormal sulfatase activity observed in COPD patients. Through a comprehensive review of current literature and experimental findings, this article aims to contribute to the growing body of knowledge surrounding the genetic intricacies concerning sulfation of airway remodeling and possible pharmacological applications in COPD and asthma management.

Variations in the Sulfatase Modifying Factor-1 (SUMF1) gene have been linked to an elevated susceptibility to COPD. Moreover, different SUMF1 single nucleotide polymorphisms (SNPs) were found to have differential impact on the disease affecting SUMF1 mRNA expression levels in lung tissue and associated with lung function. The aim of this study was to investigate the association of two common SNPs (rs11915920 and rs793391) in the SUMF1 gene with lung function characteristics, COPD progression and response to treatment with inhaled corticosteroids (ICS). A total of 165 COPD patients, GOLD stage B-D, subjects of the HISTORIC study (Stolz et al, 2023), a randomized, placebo-controlled, double-blind, investigator-initiated trial were genotyped for rs11915920 and rs793391, SUMF1 common SNPs. Heterozygous patients for the rs11915920 variance allele (CT) presented with lower airway smooth muscle cells (ASMCs) in endobronchial biopsies (p=0.015) and higher blood neutrophils (p=0.0130), at baseline. Homozygous patients (TT) had higher DLCOc values, after bronchodilation. Furthermore, there were significant (p<0.0001) differences in response to ICS among different rs11915920 genotypes (CC, TT, TT) (Fig.1). At baseline, homozygous patients for the rs793391 reference allele (TT) presented with higher N2-washout values (p=0.0009) and homozygous for the alternative allele (GG) had higher blood eosinophils (p=0.050). These results indicate that studied SUMF1 polymorphisms are associated with COPD progression and response to ICS and may be helpful in personalized treatment in COPD.