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  1. AU="Heerfordt, Christian Kjer"
  2. AU="Arunachalam, Thilaka"
  3. AU="Alongi A."
  4. AU="Lou, Haifei"
  5. AU="Ourani, Sofia"
  6. AU="Ribichini, Flavio L"
  7. AU="Johnson, Christopher D"
  8. AU="Wang, YuMing"
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  21. AU="Khalfallah, Ali"
  22. AU="Kopecky, O."
  23. AU="Mueller, C L"
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  1. Article ; Online: Inhaled corticosteroids and risk of lower respiratory tract infection with

    Johnsen, Rikke Helin / Heerfordt, Christian Kjer / Boel, Jonas Bredtoft / Dessau, Ram Benny / Ostergaard, Christian / Sivapalan, Pradeesh / Eklöf, Josefin / Jensen, Jens-Ulrik Stæhr

    BMJ open respiratory research

    2023  Volume 10, Issue 1

    Abstract: Background: Use of inhaled corticosteroids (ICS) is common in patients with chronic obstructive pulmonary disease (COPD) and has been associated with an increased risk of pneumonia. : Objective: To investigate if accumulated ICS use in patients with ... ...

    Abstract Background: Use of inhaled corticosteroids (ICS) is common in patients with chronic obstructive pulmonary disease (COPD) and has been associated with an increased risk of pneumonia.
    Objective: To investigate if accumulated ICS use in patients with COPD, is associated with a dose-dependent risk of infection with
    Methods: This observational cohort study included 18 870 persons with COPD who were registered in The Danish Register of COPD. Linkage to several nationwide registries was performed.Exposure to ICS was determined by identifying all prescriptions for ICS, redeemed within 365 days prior to study entry. Main outcome was a lower respiratory tract sample positive for
    Results: We found an increased, dose-dependent, risk of a lower respiratory tract sample with
    Conclusion: Our study shows a dose-dependent increased risk of infection with
    MeSH term(s) Humans ; Moraxella catarrhalis ; Respiratory Tract Infections/epidemiology ; Patients ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Adrenal Cortex Hormones/adverse effects
    Chemical Substances Adrenal Cortex Hormones
    Language English
    Publishing date 2023-08-18
    Publishing country England
    Document type Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2736454-9
    ISSN 2052-4439 ; 2052-4439
    ISSN (online) 2052-4439
    ISSN 2052-4439
    DOI 10.1136/bmjresp-2023-001726
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Inhaled corticosteroids and

    Rønn, Christian / Kamstrup, Peter / Heerfordt, Christian Kjer / Sivapalan, Pradeesh / Eklöf, Josefin / Boel, Jonas Bredtoft / Ostergaard, Christian / Dessau, Ram Benny / Moberg, Mia / Janner, Julie / Ulrik, Charlotte Suppli / Jensen, Jens-Ulrik Stæhr

    BMJ open respiratory research

    2024  Volume 11, Issue 1

    Abstract: Objectives: Inhaled corticosteroids (ICS) are widely used in patients with chronic obstructive pulmonary disease (COPD). However, ICS are associated with an increased risk of adverse effects.We aimed to determine whether an association between a lower ... ...

    Abstract Objectives: Inhaled corticosteroids (ICS) are widely used in patients with chronic obstructive pulmonary disease (COPD). However, ICS are associated with an increased risk of adverse effects.We aimed to determine whether an association between a lower respiratory tract culture with
    Design: An observational cohort study of outpatients with COPD in Denmark between 2010 and 2018.ICS exposure was categorised into four groups based on average daily consumption 1 year prior to inclusion: no use, low ICS dose (≤400 µg), moderate ICS dose (400-800 µg) and high ICS dose (>800 µg). Dose-response relationship was investigated by a multivariable Cox proportional hazards regression.
    Results: Of the total 22 689 patients, 459 had lower respiratory tract cultures positive for
    Conclusions: We found that ICS was associated with a high, dose-dependent increased hazard of
    MeSH term(s) Humans ; Stenotrophomonas maltophilia ; Retrospective Studies ; Outpatients ; Administration, Inhalation ; Pulmonary Disease, Chronic Obstructive ; Adrenal Cortex Hormones ; Cohort Studies
    Chemical Substances Adrenal Cortex Hormones
    Language English
    Publishing date 2024-03-09
    Publishing country England
    Document type Observational Study ; Journal Article
    ZDB-ID 2736454-9
    ISSN 2052-4439 ; 2052-4439
    ISSN (online) 2052-4439
    ISSN 2052-4439
    DOI 10.1136/bmjresp-2023-001929
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Inhalation devices and inhaled corticosteroids particle size influence on severe pneumonia in patients with chronic obstructive pulmonary disease: a nationwide cohort study.

    Heerfordt, Christian Kjer / Rønn, Christian / Harboe, Zitta Barrella / Ingebrigtsen, Truls Sylvan / Svorre Jordan, Alexander / Wilcke, Jon Torgny / Bonnesen, Barbara / Biering-Sørensen, Tor / Sørensen, Rikke / Holler, Jon Gitz / Itenov, Theis Skovsgaard / Johansen, Helle Krogh / Sivapalan, Pradeesh / Eklöf, Josefin / Jensen, Jens-Ulrik Stæhr

    BMJ open respiratory research

    2023  Volume 10, Issue 1

    Abstract: Background: Inhaled corticosteroids (ICSs) are associated with an increased risk of pneumonia among patients with chronic obstructive pulmonary disease (COPD). The introduction of extrafine particle ICS has aimed to improve the distribution of medicine ... ...

    Abstract Background: Inhaled corticosteroids (ICSs) are associated with an increased risk of pneumonia among patients with chronic obstructive pulmonary disease (COPD). The introduction of extrafine particle ICS has aimed to improve the distribution of medicine in the airways by altering deposition within the lungs, potentially affecting efficacy and side effects. It remains unclear if extrafine particle ICS administration alters the risk of pneumonia compared with standard particle size ICS.
    Methods: An observational cohort study including all Danish COPD outpatients receiving ICS from 2010 to 2017. The primary outcome was pneumonia hospitalisation in the different ICS particle dosing regimens. The primary analysis was an adjusted Cox proportional hazards model. For sensitivity analysis, a subgroup analysis of patients receiving spray devices was done. Further, we created a propensity score matched cohort, in which we matched for the same covariates as adjusted for in the main analysis.
    Results: A total of 35 691 patients were included of whom 1471 received extrafine particle ICS. Among these patients, 4657 were hospitalised due to pneumonia. Patients with COPD receiving extrafine particle ICS had a lower risk of hospitalisation due to pneumonia compared with patients receiving standard particle size ICS in our primary analysis (HR 0.75; 95% CI 0.63 to 0.89; p=0.002), subgroup analysis (HR 0.54; 95% CI 0.45 to 0.65; p<0.0001) and the propensity-matched population (HR 0.72; 95% CI 0.60 to 0.87; p=0.0006).
    Interpretation: The use of extrafine particle ICS administration was associated with a lower risk of pneumonia hospitalisation in patients with COPD compared with those who received standard size treatment.
    MeSH term(s) Humans ; Cohort Studies ; Particle Size ; Administration, Inhalation ; Pulmonary Disease, Chronic Obstructive/complications ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Adrenal Cortex Hormones ; Pneumonia/epidemiology ; Pneumonia/etiology ; Nebulizers and Vaporizers
    Chemical Substances Adrenal Cortex Hormones
    Language English
    Publishing date 2023-09-29
    Publishing country England
    Document type Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2736454-9
    ISSN 2052-4439 ; 2052-4439
    ISSN (online) 2052-4439
    ISSN 2052-4439
    DOI 10.1136/bmjresp-2023-001814
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Renin-angiotensin-system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study.

    Vilstrup, Frida / Heerfordt, Christian Kjer / Kamstrup, Peter / Hedsund, Caroline / Biering-Sørensen, Tor / Sørensen, Rikke / Kolekar, Shailesh / Hilberg, Ole / Pedersen, Lars / Lund, Thomas Kromann / Klausen, Tobias Wirenfeldt / Skaarup, Kristoffer Grundtvig / Eklöf, Josefin / Sivapalan, Pradeesh / Jensen, Jens-Ulrik Stæhr

    BMJ open respiratory research

    2023  Volume 10, Issue 1

    Abstract: Objective: The renin-angiotensin system (RAS) has been shown to play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD) because of the inflammatory properties of the system. Many patients with COPD use RAS-inhibiting (RASi) ... ...

    Abstract Objective: The renin-angiotensin system (RAS) has been shown to play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD) because of the inflammatory properties of the system. Many patients with COPD use RAS-inhibiting (RASi) treatment. The aim was to determine the association between treatment with RASi and the risk of acute exacerbations and mortality in patients with severe COPD.
    Methods: Active comparator analysis by propensity-score matching. Data were collected in Danish national registries, containing complete information on health data, prescriptions, hospital admissions and outpatient clinic visits. Patients with COPD (n=38 862) were matched by propensity score on known predictors of the outcome. One group was exposed to RASi treatment (cases) and the other was exposed to bendroflumethiazide as an active comparator in the primary analysis.
    Results: The use of RASi was associated with a reduced risk of exacerbations or death in the active comparator analysis at 12 months follow-up (HR 0.86, 95% CI 0.78 to 0.95). Similar results were evident in a sensitivity analysis of the propensity-score-matched population (HR 0.89, 95% CI 0.83 to 0.94) and in an adjusted Cox proportional hazards model (HR 0.93, 95% CI 0.89 to 0.98).
    Conclusion: In the current study, we found that the use of RASi treatment was associated with a consistently lower risk of acute exacerbations and death in patients with COPD. Explanations to these findings include real effect, uncontrolled biases, and-less likely-chance findings.
    MeSH term(s) Humans ; Renin ; Registries ; Bendroflumethiazide ; Enzyme Inhibitors ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Pulmonary Disease, Chronic Obstructive/epidemiology ; Angiotensins
    Chemical Substances Renin (EC 3.4.23.15) ; Bendroflumethiazide (5Q52X6ICJI) ; Enzyme Inhibitors ; Angiotensins
    Language English
    Publishing date 2023-03-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2736454-9
    ISSN 2052-4439 ; 2052-4439
    ISSN (online) 2052-4439
    ISSN 2052-4439
    DOI 10.1136/bmjresp-2022-001428
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease and Risk of Acquiring

    Heerfordt, Christian Kjer / Eklöf, Josefin / Sivapalan, Pradeesh / Ingebrigtsen, Truls Sylvan / Biering-Sørensen, Tor / Harboe, Zitta Barrella / Koefod Petersen, Jesper / Andersen, Christian Østergaard / Boel, Jonas Bredtoft / Bock, Anne Kathrine / Mathioudakis, Alexander G / Hurst, John R / Kolekar, Shailesh / Johansson, Sofie Lock / Bangsborg, Jette Marie / Jarløv, Jens Otto / Dessau, Ram Benny / Laursen, Christian Borbjerg / Perch, Michael /
    Jensen, Jens-Ulrik Stæhr

    International journal of chronic obstructive pulmonary disease

    2023  Volume 18, Page(s) 373–384

    Abstract: Background: Inhaled corticosteroids (ICS) are associated with an increased risk of clinical pneumonia among patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the risk of microbiologically verified pneumonia such as ... ...

    Abstract Background: Inhaled corticosteroids (ICS) are associated with an increased risk of clinical pneumonia among patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the risk of microbiologically verified pneumonia such as pneumococcal pneumonia is increased in ICS users.
    Methods: The study population consists of all COPD patients followed in outpatient clinics in eastern Denmark during 2010-2017. ICS use was categorized into four categories based on accumulated use. A Cox proportional hazard regression model was used adjusting for age, body mass index, sex, airflow limitation, use of oral corticosteroids, smoking, and year of cohort entry. A propensity score matched analysis was performed for sensitivity analyses.
    Findings: A total of 21,438 patients were included. Five hundred and eighty-two (2.6%) patients acquired a positive lower airway tract sample with 
    Interpretation: Use of ICS in patients with severe COPD was associated with an increased and dose-dependent risk of acquiring
    MeSH term(s) Humans ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Pulmonary Disease, Chronic Obstructive/epidemiology ; Administration, Inhalation ; Pneumonia/chemically induced ; Adrenal Cortex Hormones/adverse effects ; Pneumococcal Infections/diagnosis ; Pneumococcal Infections/epidemiology ; Pneumococcal Infections/prevention & control ; Epidemiologic Studies
    Chemical Substances Adrenal Cortex Hormones
    Language English
    Publishing date 2023-03-21
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2212419-6
    ISSN 1178-2005 ; 1176-9106
    ISSN (online) 1178-2005
    ISSN 1176-9106
    DOI 10.2147/COPD.S386518
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Use of Inhaled Corticosteroids and Risk of Acquiring

    Mohsin, Raza Ul / Heerfordt, Christian Kjer / Eklöf, Josefin / Sivapalan, Pradeesh / Saeed, Mohamad Isam / Ingebrigtsen, Truls Sylvan / Nielsen, Susanne Dam / Harboe, Zitta Barrella / Iversen, Kasper Karmark / Bangsborg, Jette / Jarløv, Jens Otto / Boel, Jonas Bredtoft / Østergaard Andersen, Christian / Calum, Henrik Pierre / Dessau, Ram B / Jensen, Jens-Ulrik Stæhr

    Journal of clinical medicine

    2022  Volume 11, Issue 12

    Abstract: Background: Inhaled corticosteroids (ICS) are widely used in chronic obstructive pulmonary disease (COPD), despite the known risk of severe adverse effects including pulmonary infections. Research Question: Our study investigates the risk of acquiring a ... ...

    Abstract Background: Inhaled corticosteroids (ICS) are widely used in chronic obstructive pulmonary disease (COPD), despite the known risk of severe adverse effects including pulmonary infections. Research Question: Our study investigates the risk of acquiring a positive Haemophilus influenzae airway culture with use of ICS in outpatients with COPD. Study Design and Methods: We conducted an epidemiological cohort study using data from 1 January 2010 to 19 February 2018, including 21,218 outpatients with COPD in Denmark. ICS use 365 days prior to cohort entry was categorised into low, moderate, and high, based on cumulated ICS dose extracted from a national registry on reimbursed prescriptions. A Cox proportional hazards regression model was used to assess the future risk of acquiring H. Influenzae within 365 days from cohort entry, and sensitivity analyses were performed using propensity score matched models. Results: In total, 801 (3.8%) patients acquired H. Influenzae during follow-up. Use of ICS was associated with a dose-dependent increased risk of acquiring H. Influenzae with hazard ratio (HR) 1.2 (95% confidence interval (CI) 0.9−1.5, p value = 0.1) for low-dose ICS; HR 1.7 (95% CI 1.3−2.1, p value < 0.0001) for moderate dose; and HR 1.9 (95% CI 1.5−2.4, p value < 0.0001) for high-dose ICS compared to no ICS use. Results were confirmed in the propensity-matched model using the same categories. Conclusions: ICS use in outpatients with COPD was associated with a dose-dependent increase in risk of isolating H. Influenzae. This observation supports that high dose ICS should be used with caution.
    Language English
    Publishing date 2022-06-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm11123539
    Database MEDical Literature Analysis and Retrieval System OnLINE

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