Background: Vitamin K is a cofactor necessary for the biological activity of proteins like Matrix Gla Protein (MGP), which reduce calcification and help preserve lung function. This study aims to determine, first, whether low vitamin K status is associated with chronic obstructive pulmonary disease (COPD), and secondary, whether the level of vitamin K is associated with COPD severity, smoking exposure, or mortality. Methods: The plasma concentration of dephosphorylated uncarboxylated (dp-uc) MGP was used as an inverse biomarker for vitamin K in 98 COPD patients from the CODEX-P COPD study and 986 controls from the DanFunD study. Low vitamin K status was defined as the upper quartile of dp-ucMGP (>589 pmol/L). Using a logistic regression model, we examined whether low vs. high/moderate vitamin K status increased the odds ratio (OR) of having COPD. Secondary analyses, in the COPD cohort only, examined the association between low vitamin K status and COPD severity, smoking exposure in packyears and all-cause mortality, using a Welch’s t-test and log-rank test, respectively. Results: Low vitamin K status was associated with increased odds of having COPD, OR 9.7 (95% CI [5.5 to 17.5], p < 0.001). We found no associations between low vitamin K and COPD severity (est. −0.03, p = 0.7; 95% CI [−0.2 to 0.1]), smoking exposure (p = 0.7), or all-cause mortality (p = 0.5). Conclusions: Low vitamin K status was associated with substantially higher odds of having COPD compared to high/moderate vitamin K status. No association was found between low vitamin K status and COPD severity, smoking exposure, or all-cause mortality. Further studies are needed to determine if vitamin K plays a role in the pathophysiology of COPD and whether supplement therapy is indicated.

Background: Non-cystic fibrosis bronchiectasis (BE) is a chronic lung condition characterized by irreversible bronchial dilation and presented with persistent respiratory symptoms, recurrent respiratory infections, and decreased quality of life. Inhaled corticosteroids (ICSs) are frequently prescribed in patients with bronchiectasis, despite limited evidence supporting their clinical efficacy. Inhaled corticosteroids have been associated with increased risk of respiratory infection with Haemophilus influenzae (H. influenzae) in other groups of lung diseases. We aimed to evaluate the association between ICS use and the risk of isolating H. influenzae from lower respiratory tract samples in patients with bronchiectasis. Methods: A retrospective cohort study was conducted using data from 2010 to 2018, encompassing all patients diagnosed with bronchiectasis in outpatient clinics in Eastern Denmark. ICS use was standardized in budesonide equivalent doses and categorized in tertiles: low (<210 μg/day), moderate (211–625 μg/day), and high (≥626 μg/day) based on cumulative budesonide equivalent doses redeemed in the 12 months before cohort entry. The primary outcome was the first isolation of H. influenzae from lower respiratory tract samples post-cohort entry. Cox proportional hazards models, adjusted for relevant confounders, estimated hazard ratios (HRs), and inverse probability-of-treatment weighting (IPTW) was used in sensitivity analyses. Results: Among 3663 patients (mean age 66 years; 61% female), 2175 (59.4%) did not use ICS, while 484 (13.2%), 508 (13.9%), and 496 (13.5%) were in the low-, moderate-, and high-dose ICS groups, respectively. Furthermore, 594 (16.22%) patients had a lower respiratory tract culture positive for H. influenzae during follow-up. High-dose ICS use was associated with an increased risk of H. influenzae; HR 1.63 (95% Cl, 1.19 to 2.12, p < 0.005) compared with no ICS use. No association for low or moderate ICS use was found: low-dose ICS HR 0.75 (95% Cl, 0.52 to 1.07, p = 0.11) and moderate-dose ICS HR 1.27 (95% Cl, 0.93 to 1.72, p = 0.12). IPTW analysis confirmed the main finding. Conclusions: High-dose ICS use in patients with bronchiectasis was associated with an increased risk of acquiring H. influenzae in the lower respiratory tract. Hence, patients with bronchiectasis should be cautiously prescribed high-dose ICS.

Background/Objectives: Inhaled corticosteroids (ICS) increase the risk of pneumonia caused by various pathogens in patients with chronic obstructive pulmonary disease (COPD). Treatment may also increase the risk of infection with non-tuberculous mycobacteria (NTM), although evidence remains limited. The aim of this study was to assess the association between ICS treatment and the risk of NTM isolation among patients with COPD. Methods: This retrospective register-based cohort study included patients with a specialist-verified COPD diagnosis between 2008 and 2021. ICS exposure was based on redeemed prescriptions during the year preceding the index date. Exposure was calculated as the mean daily budesonide-equivalent dose and categorized as none, low, medium, or high. A cause-specific Cox proportional hazards regression model with death as a competing risk was applied, adjusted for potential confounders. Sensitivity analyses included, among others, an inverse probability of treatment weighted model, and a time-dependent Cox regression model. Results: A total of 120,006 patients were included, with a median follow-up time of 4.9 years. During follow-up, 378 (0.32%) patients reached the primary endpoint. Medium- and high-dose ICS were associated with an increased hazard of NTM isolation, with hazard ratios of 1.39 (95% CI 1.06–1.88, p = 0.020) and 1.52 (95% CI 1.14–2.04, p = 0.005), respectively. This association remained significant for high-dose ICS across all sensitivity analyses. Conclusions: In patients with COPD, ICS treatment was associated with an increased and dose-dependent hazard of NTM isolation, particularly at high doses. High-dose ICS should, therefore, be prescribed with caution.

Objectives: Non-cystic fibrosis bronchiectasis (BE) is a chronic airway disease with increasing prevalence, reduced quality of life, and increased mortality. Inhaled corticosteroids (ICS) are used in BE despite limited evidence of effect on lung function parameters. ICS may increase the risk of Staphylococcus aureus (S. aureus) infections in patients with BE, but this is unexplored. We examined the association between ICS use prior to BE diagnosis at different doses and the risk of S. aureus isolation in patients with BE. Methods: We conducted a national register-based cohort study including Danish patients with a BE diagnosis code between 2001 and 2018 with a 1-year follow-up time from the date of diagnosis. ICS exposure was categorized based on accumulated prescriptions redeemed 365 days before BE diagnosis and divided into none, low, moderate, or high use based on clinically relevant doses. A cause-specific Cox proportional hazards regression model was used to estimate the risk of S. aureus isolation. A sensitivity analysis, an inverse probability of treatment weighted model (IPTW), was performed. Results: A total of 5093 patients were included in this study. S. aureus was isolated in 156 patients (3.1%). High-dose ICS was associated with an increased risk of S. aureus isolation, HR 3.81 (95% CI 2.51; 5.79). No association for low or moderate use was found, low-dose HR 1.22 (95% CI 0.77; 1.93), and moderate-dose HR 1.24 (95% CI 0.72; 2.16). IPTW analysis yielded similar results. Conclusions: High-dose ICS use in patients with BE was associated with an increased risk of S. aureus isolation. ICS should be used cautiously in patients with BE.