Osteoporosis and fracture risk associated with ICS use among Swedish COPD patients: the ARCTIC study

The effect of inhaled corticosteroids (ICS) on the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to assess this risk in patients with COPD.Electronic medical record data linked to National Health Registries were collected from COPD patients and matched reference controls at 52 Swedish primary care centres (2000–2014). The outcomes analysed were the effect of ICS on all fractures, fractures typically related to osteoporosis, recorded osteoporosis diagnosis, prescriptions of drugs for osteoporosis and a combined measure of any-osteoporosis-related event. The COPD patients were stratified by the level of ICS exposure.A total of 9651 patients with COPD and 59 454 matched reference controls were analysed. During the follow-up, 19.9% of COPD patients had at least one osteoporosis-related event compared with 12.9% of reference controls (p<0.0001). Multivariate analysis in the COPD population demonstrated a dose-effect relationship, with high-dose ICS being significantly associated with any osteoporosis-related event (risk ratio [RR; 95% confidence interval] 1.52 [1.24–1.62]), while the corresponding estimate for low-dose ICS was 1.27 (1.13–1.56), compared with COPD patients not using ICS. A similar dose-related adverse effect was found for all four of the specific osteoporosis-related events: all fractures, fractures typically related to osteoporosis, prescriptions of drugs for osteoporosis and diagnosis of osteoporosis.We conclude that patients with COPD have a greater risk of bone fractures and osteoporosis and high-dose ICS use increased this risk further.

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Current opportunities of inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease

Russian Pulmonology ◽

10.18093/0869-0189-2021-31-1-75-87 ◽

2021 ◽

Vol 31 (1) ◽

pp. 75-87

Author(s):

I. V. Leshchenko ◽

A. S. Meshcheryakova

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Inhaled Corticosteroids ◽

Fixed Combination ◽

Chronic Obstructive ◽

Delivery Device ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Long Acting ◽

Blood Eosinophils

Chronic obstructive pulmonary disease (COPD) is the leading cause of death in the structure of respiratory diseases. The problem of rational pharmacotherapy of COPD have attracted attention of the medical scientific society for many years. The understanding of the pathogenesis of the disease has deepened and approaches to the therapy have changed. Some COPD patients need regular fixed-combination therapy: long-acting bronchodilators (LABD) and inhaled corticosteroids (ICS) in order to prevent exacerbations and reduce the severity of symptoms of the disease. Blood eosinophils count is one of criteria for choosing regular therapy. The appearance of fixed triple combinations of ICS/LABD increased the effectiveness of COPD therapy, and a new delivery device for fixed combination of budesonide/formoterol makes it possible to use ICS successfully in the most severe patients.

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Inhaled Corticosteroids and the Pneumonia Risk in Patients With Chronic Obstructive Pulmonary Disease: A Meta-analysis of Randomized Controlled Trials

Frontiers in Pharmacology ◽

10.3389/fphar.2021.691621 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hong Chen ◽

Jian Sun ◽

Qiang Huang ◽

Yongqi Liu ◽

Mengxin Yuan ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Inhaled Corticosteroids ◽

Chronic Obstructive ◽

Controlled Trials ◽

Response Relationship ◽

Dose Response Relationship ◽

Obstructive Pulmonary Disease ◽

Randomized Controlled ◽

Copd Patients ◽

Baseline Characteristics

Background: Whether all types of inhaled corticosteroids (ICSs) would increase the pneumonia risk in patients with chronic obstructive pulmonary disease (COPD) remains controversial. We aimed to assess the association between ICSs treatment and pneumonia risk in COPD patients, and the impact of medication details and baseline characteristics of patients on the association.Methods: Four databases (PubMed, Embase, Cochrane Library, and Clinical Trials.gov) were searched to identify eligible randomized controlled trials (RCTs) comparing ICSs treatment with non-ICSs treatment on the pneumonia risk in COPD patients. Pooled results were calculated using Peto odds ratios (Peto ORs) with corresponding 95% confidence intervals (CIs).Results: A total of 59 RCTs enrolling 103,477 patients were analyzed. All types of ICSs significantly increased the pneumonia risk (Peto OR, 1.43; 95% CI, 1.34–1.53). Subgroup analysis showed that there was a dose-response relationship between ICSs treatment and pneumonia risk (low-dose: Peto OR, 1.33; 95% CI, 1.22–1.45; medium-dose: Peto OR, 1.50; 95% CI, 1.28–1.76; and high-dose: Peto OR, 1.64; 95% CI, 1.45–1.85). Subgroup analyses based on treatment durations and baseline characteristics (severity, age, and body mass index) of patients were consistant with the above results. Subgroup analysis based on severity of pneumonia showed that fluticasone (Peto OR, 1.75; 95% CI, 1.44–2.14) increased the risk of serious pneumonia, while budesonide and beclomethasone did not.Conclusions: ICSs treatment significantly increased the risk of pneumonia in COPD patients. There was a dose-response relationship between ICSs treatment and pneumonia risk. The pneumonia risk was related with COPD severity.

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Association between inhaled corticosteroids and upper respiratory tract infection in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials

BMC Pulmonary Medicine ◽

10.1186/s12890-020-01315-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Hong Chen ◽

Yulin Feng ◽

Ke Wang ◽

Jing Yang ◽

Yuejun Du

Keyword(s):

Inhaled Corticosteroids ◽

Chronic Obstructive ◽

Controlled Trials ◽

High Dose ◽

Upper Respiratory Tract ◽

Short Term ◽

Obstructive Pulmonary Disease ◽

Randomized Controlled ◽

Upper Respiratory

Abstract Background We aimed to assess the association between inhaled corticosteroids (ICSs) and the risk of upper respiratory tract infection (URTI) in patients with chronic obstructive pulmonary disease (COPD). Methods PubMed, Embase, Cochrane Library and Clinical Trials.gov were searched from inception to October 2019. Randomized controlled trials (RCTs) of any ICSs vs control for COPD with reporting of URTI as an adverse event were included. The study was registered with PROSPERO prospectively (#CRD42020153134). Results Seventeen RCTs (20,478 patients) were included. ICSs significantly increased the risk of URTI in COPD patients (RR, 1.13; 95% CI 1.03–1.24; P = 0.01; heterogeneity: I2 = 7%). Futher subgroup analyses suggested that short-term use of ICSs increased the risk of URTI (RR, 1.29; 95% CI 1.06–1.56; P = 0.01; heterogeneity: I2 = 14%) but not for long-term use (RR, 1.08; 95% CI 0.97–1.2; P = 0.14; heterogeneity: I2 = 0%). Short-term use of high-dose fluticasone increased the risk of URTI (RR, 1.33; 95% CI 1.03–1.71; P = 0.03; heterogeneity: I2 = 0%) but not for long-term use (RR, 1.12; 95% CI 0.97–1.29; P = 0.13; heterogeneity: I2 = 50%). Medium-dose (RR, 0.97; 95% CI 0.71–1.32; P = 0.84; heterogeneity: I2 = 0%) and low-dose (RR, 1.39; 95% CI 0.92–2.1; P = 0.12; heterogeneity: I2 = 30%) fluticasone did not increase the risk of URTI regardless of duration. Neither mometasone (RR, 1.05; 95% CI 0.87–1.26; P = 0.61; heterogeneity: I2 = 0%) nor budesonide (RR, 1.08; 95% CI 0.77–1.5; P = 0.67; heterogeneity: I2 = 46%) increased the risk of URTI, regardless of dosage or duration. Conclusions Long-term use of ICSs does not increase the risk of URTI in patients with COPD. Short-term use of high-dose fluticasone increases the risk of URTI in patients with COPD, but not mometasone or budesonide.

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Reassessing the Role of Eosinophils as a Biomarker in Chronic Obstructive Pulmonary Disease

Journal of Clinical Medicine ◽

10.3390/jcm8070962 ◽

2019 ◽

Vol 8 (7) ◽

pp. 962 ◽

Cited By ~ 8

Author(s):

Tinè ◽

Biondini ◽

Semenzato ◽

Bazzan ◽

Cosio ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Inhaled Corticosteroids ◽

Real Life ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Exacerbation Risk ◽

Blood Eosinophils

Blood eosinophils measurement, as proxy for tissue eosinophils, has become an important biomarker for exacerbation risk and response to inhaled corticosteroids (ICS) in Chronic Obstructive Pulmonary Disease (COPD). Its use to determine the pharmacological approach is recommended in the latest COPD guidelines. The potential role of blood eosinophils is mainly based on data derived from post-hoc and retrospective analyses that showed an association between increased blood eosinophils and risk of exacerbations, as well as mitigation of this risk with ICS. Yet other publications, including studies in real life COPD, do not confirm these assumptions. Moreover, anti-eosinophil therapy targeting interleukin (IL)-5 failed to reduce exacerbations in COPD patients with high blood eosinophils, which casts significant doubts on the role of eosinophils in COPD. Furthermore, a reduction of eosinophils might be harmful since COPD patients with relatively high eosinophils have better pulmonary function, better life quality, less infections and longer survival. These effects are probably linked to the role of eosinophils in the immune response against pathogens. In conclusion, in COPD, high blood eosinophils are widely used as a biomarker for exacerbation risk and response to ICS. However, much is yet to be learned about the reasons for the high eosinophil counts, their variations and their controversial effects on the fate of COPD patients.

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Roflumilast succeeds where traditional therapy fails: a case report

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2013.30 ◽

2015 ◽

Vol 79 (3-4) ◽

Author(s):

Gabriella Guarnieri

Keyword(s):

Inhaled Corticosteroids ◽

Chronic Obstructive ◽

High Dose ◽

Welding Fumes ◽

Obstructive Pulmonary Disease ◽

Once Daily ◽

X Ray ◽

Clinical Control ◽

History Of ◽

Chest X Ray

The case of a 72-year-old man with a long history of chronic obstructive pulmonary disease (COPD, patient D according to Guidelines GOLD 2013) in a subject professionally exposed to welding fumes is presented. Diagnosis was based on symptoms and spirometry and confirmed by chest X-ray examination. Since 1997 the patient has been under different therapies, including high-dose inhaled corticosteroids and bronchodilators, with poor clinical control and frequent exacerbations. Roflumilast 500 μg once daily was started in January 2012 and patient’s respiratory symptoms, number of exacerbations and spirometry values have gradually improved since then. Roflumilast was an effective treatment in this case of difficult to treat severe COPD.

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Cost-Effectiveness of Combination Therapy for Chronic Obstructive Pulmonary Disease

Canadian Respiratory Journal ◽

10.1155/2008/257618 ◽

2008 ◽

Vol 15 (8) ◽

pp. 437-443 ◽

Cited By ~ 15

Author(s):

Anderson Chuck ◽

Philip Jacobs ◽

Irvin Mayers ◽

Darcy Marciniuk

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Cost Effectiveness ◽

Combination Therapy ◽

Pulmonary Disease ◽

Inhaled Corticosteroids ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Life Years

BACKGROUND: There is evidence that combination therapy (CT) in the form of long-acting beta2-agonists (LABAs) and inhaled corticosteroids can improve lung function for patients with chronic obstructive pulmonary disease (COPD).OBJECTIVE: To determine the cost-effectiveness of using CT in none, all or a selected group of COPD patients.METHODS: A Markov model was designed to compare four treatment strategies: no use of CT regardless of COPD severity (patients receive LABA only); use of CT in patients with stage 3 disease only (forced expiratory volume in 1 s [FEV1] less than 35% of predicted); use of CT in patients with stages 2 and 3 disease only (FEV1less than 50% of predicted); and use of CT in all patients regardless of severity of COPD. Estimates of mortality, exacerbation and disease progression rates, quality-adjusted life years (QALYs) and costs were derived from the literature. Three-year and lifetime time horizons were used. The analysis was conducted from a health systems perspective.RESULTS: CT was associated with a cost of $39,000 per QALY if given to patients with stage 3 disease, $47,500 per QALY if given to patients with stages 2 and 3 disease, and $450,333 per QALY if given to all COPD patients. Results were robust to various assumptions tested in a Monte Carlo simulation.CONCLUSION: Providing CT for COPD patients in stage 2 or 3 disease is cost-effective. The message to family physicians and specialists is that as FEV1worsens and reaches 50% of predicted values, CT is recommended.

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Biological Age in COPD Patients Reveals an Accelerated Lung Aging

10.21203/rs.3.rs-156651/v1 ◽

2021 ◽

Author(s):

Manuela Campisi ◽

Filippo Liviero ◽

Piero Maestrelli ◽

Gabriella Guarnieri ◽

Sofia Pavanello

Keyword(s):

Inhaled Corticosteroids ◽

Blood Parameters ◽

Biological Age ◽

Biological Aging ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

New Finding ◽

New Research ◽

Research Challenge

Abstract Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, shows striking clinical aging-associated features of lung. We tested the hypothesis that lung biological aging in COPD is accelerated. Biological aging was assessed by mitotic telomere length (TL) and non-mitotic age-dependent methylation changes in specific CpGs (DNAmAge) of lung cells, obtained from induced sputum, and peripheral blood leucocytes in 18 COPD patients (72.4±7.7 years; 50% males), clinically appraised by lung function and blood parameters. DNAmAge (67.4±5.80 vs 61.6±5.40 years; p=0.0003), AgeAcc (-4.5±5.02 vs -10.8±3.50 years; p=0.0003) and TL attrition (1.05±0.35 vs 1.48±0.21 T/S; p=0.0341) are higher in lung than blood in the same patients. Blood DNAmAge (r=0.927245; p=0.0026) and AgeAcc (r=0.916445; p=0.0037), but not TL, highly correlate with that of lung. Therefore, blood can be a proxy indicator of lung biological age. Multiple regression analyses show that both blood DNAmAge and AgeAcc decrease (i.e., younger) in patients with combined inhaled corticosteroids (ICS) therapy (p=0.0494 and p=0.0553) and FEV1% enhancement (p=0.0254; p=0.0296). In conclusion, the new finding, that lung of COPD patients is remarkably biologically older than blood, opens new research challenge on novel therapeutic approaches to counteract this key aspect of the disease.

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Maintenance inhaler therapy preferences of patients with asthma or chronic obstructive pulmonary disease: a discrete choice experiment

Thorax ◽

10.1136/thoraxjnl-2019-213974 ◽

2020 ◽

Vol 75 (9) ◽

pp. 735-743 ◽

Cited By ~ 5

Author(s):

Tommi Tervonen ◽

Natalia Hawken ◽

Nicola A Hanania ◽

Fernando J Martinez ◽

Sebastian Heidenreich ◽

...

Keyword(s):

Discrete Choice Experiment ◽

Discrete Choice ◽

Patient Preferences ◽

Choice Experiment ◽

Inhaled Corticosteroids ◽

Symptom Relief ◽

Chronic Obstructive ◽

Onset Of Action ◽

Obstructive Pulmonary Disease ◽

Copd Patients

BackgroundA variety of maintenance inhaler therapies are available to treat asthma and COPD. Patient-centric treatment choices require understanding patient preferences for the alternative therapies.MethodsA self-completed web-based discrete choice experiment was conducted to elicit patient preferences for inhaler device and medication attributes. Selection of attributes was informed by patient focus groups and literature review.ResultsThe discrete choice experiment was completed by 810 patients with asthma and 1147 patients with COPD. Patients with asthma most valued decreasing the onset of action from 30 to 5 min, followed by reducing yearly exacerbations from 3 to 1. Patients with COPD most and equally valued decreasing the onset of action from 30 to 5 min and reducing yearly exacerbations from 3 to 1. Both patients with asthma and patients with COPD were willing to accept an additional exacerbation in exchange for a 15 min decrease in onset of action and a longer onset of action in exchange for a lower risk of adverse effects from inhaled corticosteroids. Patients with asthma and COPD valued once-daily over twice-daily dosing, pressurised inhalers over dry powder inhalers and non-capsule priming over single-use capsules, although these attributes were not valued as highly as faster onset of action or reduced exacerbations.ConclusionsThe most important maintenance inhaler attributes for patients with asthma and COPD were fast onset of symptom relief and a lower rate of exacerbations. Concerns about safety of inhaled corticosteroids and device convenience also affected patient preferences but were less important.

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The pharmacogenomics of inhaled corticosteroids and lung function decline in COPD

European Respiratory Journal ◽

10.1183/13993003.00521-2019 ◽

2019 ◽

Vol 54 (6) ◽

pp. 1900521 ◽

Cited By ~ 1

Author(s):

Ma'en Obeidat ◽

Alen Faiz ◽

Xuan Li ◽

Maarten van den Berge ◽

Nadia N. Hansel ◽

...

Keyword(s):

Genome Wide Association Study ◽

Inhaled Corticosteroids ◽

Forced Expiratory Volume ◽

Health Study ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Dna Elements ◽

Steroid Responsiveness

Inhaled corticosteroids (ICS) are widely prescribed for patients with chronic obstructive pulmonary disease (COPD), yet have variable outcomes and adverse reactions, which may be genetically determined. The primary aim of the study was to identify the genetic determinants for forced expiratory volume in 1 s (FEV1) changes related to ICS therapy.In the Lung Health Study (LHS)-2, 1116 COPD patients were randomised to the ICS triamcinolone acetonide (n=559) or placebo (n=557) with spirometry performed every 6 months for 3 years. We performed a pharmacogenomic genome-wide association study for the genotype-by-ICS treatment effect on 3 years of FEV1 changes (estimated as slope) in 802 genotyped LHS-2 participants. Replication was performed in 199 COPD patients randomised to the ICS, fluticasone or placebo.A total of five loci showed genotype-by-ICS interaction at p<5×10−6; of these, single nucleotide polymorphism (SNP) rs111720447 on chromosome 7 was replicated (discovery p=4.8×10−6, replication p=5.9×10−5) with the same direction of interaction effect. ENCODE (Encyclopedia of DNA Elements) data revealed that in glucocorticoid-treated (dexamethasone) A549 alveolar cell line, glucocorticoid receptor binding sites were located near SNP rs111720447. In stratified analyses of LHS-2, genotype at SNP rs111720447 was significantly associated with rate of FEV1 decline in patients taking ICS (C allele β 56.36 mL·year−1, 95% CI 29.96–82.76 mL·year−1) and in patients who were assigned to placebo, although the relationship was weaker and in the opposite direction to that in the ICS group (C allele β −27.57 mL·year−1, 95% CI −53.27– −1.87 mL·year−1).The study uncovered genetic factors associated with FEV1 changes related to ICS in COPD patients, which may provide new insight on the potential biology of steroid responsiveness in COPD.

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Influence of COPD Assessment Text (CAT) evaluation and rehabilitation education guidance on the respiratory and motor functions of COPD patients

Open Medicine ◽

10.1515/med-2015-0062 ◽

2015 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Jing Liu ◽

Guangju Meng ◽

Yi Ma ◽

Xia Zhang ◽

Dongmei Chen ◽

...

Keyword(s):

Inhaled Corticosteroids ◽

Life Quality ◽

Control Group ◽

Chronic Obstructive ◽

Study Group ◽

Motor Functions ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Quality Of Life Scale ◽

Life Scale

Abstract The study aimed to evaluate the influence of the COPD Assessment Test (CAT) evaluation and rehabilitation education guidance on the respiratory and motor functions of patients with chronic obstructive pulmonary disease (COPD). Forty-five patients with COPD admitted from Nov. 2012 to Nov. 2013 were treated with combined bronchodilators and inhaled corticosteroids. Thirty-five patients admitted from Nov. 2012 to Nov. 2013 and classified as a study group received rehabilitation education guidance on the basis of the treatment of the control group to compare the quality-of-life-scale score, dyspnea index score, and motor function of the two groups of patients after 48 weeks of treatment. After treatment, the CAT score of both groups of patients was significantly lowered. After 48 weeks of treatment, the respiratory function of both groups was significantly improved, but the Medical Research Council (MRC) scale for the study group after treatment was significantly lower than that for the control group. After 48 weeks of rehabilitation exercises, the 6-minute walk test (6MWT) for patients with COPD was significantly prolonged, but the test results were significantly higher for the study group after treatment than for the control group. After receiving CAT rehabilitation education, COPD patients had significantly improved life quality and significantly enhanced exercise tolerance. The treatment mode may be gradually introduced in future clinic and nursing work.

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