scholarly journals Effects of azithromycin on bronchial remodeling in the natural model of severe neutrophilic asthma in horses

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Sophie Mainguy-Seers ◽  
Roxane Boivin ◽  
Sheila Pourali Dogaheh ◽  
Francis Beaudry ◽  
Pierre Hélie ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Inhaled Corticosteroids ◽  
Steroid Resistance ◽  
Endobronchial Ultrasound ◽  
Clinical Effects ◽  
Exacerbation Rate ◽  
Beneficial Effects ◽  
Peripheral Airways

AbstractSteroid resistance in asthma has been associated with neutrophilic inflammation and severe manifestations of the disease. Macrolide add-on therapy can improve the quality of life and the exacerbation rate in refractory cases, possibly with greater effectiveness in neutrophilic phenotypes. The mechanisms leading to these beneficial effects are incompletely understood and whether macrolides potentiate the modulation of bronchial remodeling induced by inhaled corticosteroids (ICS) is unknown. The objective of this study was to determine if adding azithromycin to ICS leads to further improvement of lung function, airway inflammation and bronchial remodeling in severe asthma. The combination of azithromycin (10 mg/kg q48h PO) and inhaled fluticasone (2500 µg q12h) was compared to the sole administration of fluticasone for five months in a randomized blind trial where the lung function, airway inflammation and bronchial remodeling (histomorphometry of central and peripheral airways and endobronchial ultrasound) of horses with severe neutrophilic asthma were assessed. Although the proportional reduction of airway neutrophilia was significantly larger in the group receiving azithromycin, the lung function and the peripheral and central airway smooth muscle mass decreased similarly in both groups. Despite a better control of airway neutrophilia, azithromycin did not potentiate the other clinical effects of fluticasone.

scholarly journals Impact of smoking status on the efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review

BMJ Open ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. e037509
Author(s):  
Kimberley Sonnex ◽  
Hanna Alleemudder ◽  
Roger Knaggs
Keyword(s):  
Systematic Review ◽  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Smoking Status ◽  
Steroid Resistance ◽  
Cochrane Library ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

ObjectivesInhaled corticosteroids (ICS) reduce exacerbation rates and the decline in lung function in people with chronic obstructive pulmonary disease (COPD). There is evidence that smoking causes ‘steroid resistance’ and thus reduces the effect of ICS. This systematic review aimed to investigate the effect of smoking on efficacy of ICS in COPD in terms of lung function and exacerbation rates.DesignSystematic review.Data sourcesAn electronic database search of PubMed, Ovid MEDLINE, Ovid Embase and Cochrane Library (January 2000 to January 2020).Eligibility criteriaFully published randomised controlled trials (RCTs), in the English language, evaluating the use of ICS in COPD adults that stratified the participants by smoking status. Trials that included participants with asthma, lung cancer and pneumonia were excluded. The primary outcome measures were changes in lung function and yearly exacerbation rates.Data extraction and synthesisTwo independent reviewers extracted data and assessed risk of bias using the Cochrane Collaboration’s tool.ResultsSeven studies were identified. Four trials (17 892 participants) recorded change in forced expiratory volume in one second (FEV1) from baseline to up to 30 months after starting treatment. Heavier smokers (>36 pack years) using ICS had a greater decline in FEV1that ranged from −22 mL to −75 mL in comparison to lighter smokers. Smokers using ICS had mixed results in FEV1change: −8 mL to +77 mL in comparison to ex-smokers. Four trials (21 270 participants) recorded difference in COPD exacerbation rates at 52 weeks. The rate ratios favoured more exacerbations in ICS users who were current or heavier smokers than those who were ex-smokers or lighter smokers (0.81 to 0.99 vs 0.92 to 1.29).ConclusionsIn COPD, heavier or current smokers do not gain the same benefit from ICS use on lung function and exacerbation rates as lighter or ex-smokers do, however effects may not be clinically important.PROSPERO registration numberCRD42019121833

scholarly journals Pro: Inhaled corticosteroids for chronic obstructive pulmonary disease

2019 ◽  
Vol 2 (1) ◽  
pp. 35-40
Author(s):  
Donald A. Mahler
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Mechanisms Of Action ◽  
Phase Iii ◽  
Chronic Obstructive ◽  
Exacerbation Rate ◽  
Obstructive Pulmonary Disease ◽  
Long Acting

Background: Controversy exists about the use of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD). Although ICS are not approved as monotherapy for COPD, four ICS molecules, beclomethasone, budesonide, fluticasone furoate, and fluticasone propionate, are used widely in combination with long-acting bronchodilators to treat patients with this disease. Objectives: (1) To review the mechanisms of action of ICS therapy that contribute to the clinical benefits in COPD; and (2) to describe improvements in lung function, relief of dyspnea, increase in exercise tolerance, and the reduction in exacerbations with ICS use in COPD. Methods: A critical review of phase III and IV randomized clinical trials that evaluated ICS therapy in patients with COPD. Results: ICS have two major mechanisms of action in human airways: a reduction in edema and inflammation, and a decrease in airway hyperresponsiveness. ICS monotherapy significantly increases the morning peak expiratory flow rate and forced expiratory volume in 1 second (peak and trough) as early as the first day of treatment. Discontinuation of ICS therapy leads to deterioration in lung function. Treatment with ICS, alone and in combination with a long-acting bronchodilator, reduces dyspnea related to daily activities, whereas withdrawal increases breathing difficulty. Patients with COPD exhibit a significant increase in exercise duration with ICS therapy. The combination of ICS with one or more bronchodilators significantly reduces the exacerbation rate compared with bronchodilator therapy alone. The major serious adverse effect is an increased risk of pneumonia. Conclusion: Randomized controlled trials demonstrate that ICS therapy improves both physiologic and clinical outcomes in patients with COPD. These benefits are enhanced when ICS molecules are combined with one or more long-acting bronchodilators.

scholarly journals Extrafine HFA-beclomethasone-formoterol vs. nonextrafine combination of an inhaled corticosteroid and a long acting β2-agonist in patients with persistent asthma: A systematic review and meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257075
Author(s):  
Ting Liu ◽  
Dan Yang ◽  
Chuntao Liu
Keyword(s):  
Symptom Control ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Clinical Effects ◽  
Inhaled Corticosteroid ◽  
Exacerbation Rate ◽  
Peripheral Airways ◽  
Expiratory Flow ◽  
Long Acting ◽  
Β2 Agonist

Objective Airway inflammation in asthma involves not only the central airways but extends to peripheral airways. Lung deposition may be key for an appropriate treatment of asthma. We compared the clinical effects of extrafine hydrofluoroalkane (HFA)-beclomethasone-formoterol (BDP-F) versus equipotent doses of nonextrafine combination of an inhaled corticosteroid and a long acting β2-agonist (ICS-LABA) in asthma. Methods We identified eligible studies by a comprehensive literature search of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). Data analysis was performed with the Review Manager 5.3.5 software (Cochrane IMS, 2014). Results A total of 2326 patients with asthma from ten published randomized controlled trials (RCTs) were enrolled for analysis. Change from baseline in morning pre-dose peak expiratory flow (PEF), evening pre-dose PEF and forced expiratory volume in one second (FEV1) were detected no significant differences between extrafine HFA-BDP-F and nonextrafine ICS-LABAs (p = 0.23, p = 0.99 and p = 0.23, respectively). Extrafine HFA-BDP-F did not show any greater benefit in forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%), the parameter concerning peripheral airways (MD 0.03L/s, p = 0.65; n = 877). There were no substantial differences between interventions in fractional exhaled nitric oxide (FeNO) levels or in its alveolar fraction. The overall analysis showed no significant benefit of extrafine HFA-BDP-F over nonextrafine ICS-LABA in improving Asthma Control Test (ACT) score (p = 0.30) or decreasing the number of puffs of rescue medication use (p = 0.16). Extrafine HFA-BDP-F did not lead to less exacerbations than nonextrafine ICS-LABA (RR 0.61, 95% CI: 0.31 to 1.20; I2 = 0; p = 0.15). Conclusion Enrolled RCTs of extrafine HFA-BDP-F have demonstrated no significant advantages over the equivalent combination of nonextrafine ICS-LABA in improving pulmonary function concerning central airways or peripheral airways, improving asthma symptom control or reducing exacerbation rate.

Lung emphysema treated successfully using volume reduction with lung sealant (AeriSeal®)

Open Medicine ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. 648-651
Author(s):  
Roger Fei ◽  
Hermann Ingerl ◽  
Martin Kohlhäufl ◽  
Keyword(s):  
Lung Function ◽  
Lung Volume ◽  
Volume Reduction ◽  
Secondary Outcome ◽  
Lung Volume Reduction ◽  
Peripheral Airways ◽  
Lung Emphysema ◽  
Before And After ◽  
Valve Implantation

AbstractEmphysema is a progressive and irreversible disease for which there is no cure to date. Endoscopic lung volume reduction with valve implantation or using lung sealant is a treatment option for patients with severe emphysema. A 60-year-old ex-smoker (80 pack years) referred to our center because of severe lung emphysema with progressive worsening of the obstructive ventilator pattern and clinical condition. By our patient we detected collateral channels by using the Chartis system®, which allow airflow into the target lobe and prevent atelectasis and significant lung volume reduction. Thus, we decided to treat the advanced emphysema of our patient with endoscopic volume reduction using lung sealant (AeriSeal®). The foam of lung sealant AeriSeal® is instilled into the peripheral airways and alveoli where it polymerizes and functions as tissue glue, forming a film of material on the lung surface that seals the target region to cause durable absorption atelectasis. Over a period of 16 weeks, the air within the sealed region was absorbed. The follow- up evaluation of this patient showed improved lung function (increased FEV 1, and a reduction of TLC and RV) with improved quality of life. Correlation between changes in primary and secondary outcome measures in the lung function parameters and 6- minute-walking test before and after the application of AeriSealant revealed significant reduction of hyperinflation and improvement both in the flow rates and physical capacity of our patient.

scholarly journals Airway inflammation in COPD after long-term withdrawal of inhaled corticosteroids

2016 ◽  
Vol 49 (1) ◽  
pp. 1600839 ◽  
Author(s):  
Lisette I.Z. Kunz ◽  
Nick H.T. ten Hacken ◽  
Thérèse S. Lapperre ◽  
Wim Timens ◽  
Huib A.M. Kerstjens ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Inhaled Corticosteroids ◽  
Term Treatment ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Cell Counts ◽  
Long Term Treatment ◽  
Severe Copd

Long-term treatment with inhaled corticosteroids (ICS) might attenuate lung function decline and decrease airway inflammation in a subset of patients with chronic obstructive pulmonary disease (COPD), and discontinuing ICS treatment could result in further lung function decline. We hypothesised that airway inflammation increases after ICS withdrawal following long-term ICS treatment in COPD.In the GLUCOLD-1 study (GL1), 114 patients with moderate-severe COPD were randomised to 6-month or 30-month treatment with fluticasone propionate (500 µg twice daily), 30-month treatment with fluticasone/salmeterol (500/50 µg twice daily) or placebo. During the 5-year follow-up study (GL2), patients were followed prospectively while being treated by their physician. Bronchial biopsies and induced sputum were collected at baseline, at 30 months (end of GL1) and at 7.5 years (end of GL2) to assess inflammatory cell counts. Data were analysed using linear mixed-effects models.In patients using ICS during GL1 and using ICS 0–50% of the time during GL2 (n=61/85), there were significant increases in GL2 bronchial CD3+ (fold change per year calculated as GL2 minus GL1 2.68, 95% CI 1.87–3.84), CD4+ (1.91, 95% CI 1.33–2.75) and CD8+ cells (1.71, 95% CI 1.15–2.53), and mast cells (1.91, 95% CI 1.36–2.68). The sputum total cell counts increased significantly in GL2 (1.90, 95% CI 1.42–2.54), as did counts of macrophages (2.10, 95% CI 1.55–2.86), neutrophils (1.92, 95% CI 1.39–2.65) and lymphocytes (2.01, 95% CI 1.46–2.78).ICS discontinuation increases airway inflammation in patients with moderate-severe COPD, suggesting that the anti-inflammatory effects of ICS in COPD are not maintained after ICS discontinuation.

scholarly journals Variability in airway inflammation, symptoms, lung function and reliever use in asthma: anti-inflammatory reliever hypothesis and STIFLE study design

2020 ◽  
Vol 6 (2) ◽  
pp. 00333-2019
Author(s):  
Tim Harrison ◽  
Ian D. Pavord ◽  
James D. Chalmers ◽  
Glenn Whelan ◽  
Malin Fagerås ◽  
...  
Keyword(s):  
Lung Function ◽  
Maintenance Therapy ◽  
Airway Inflammation ◽  
Temporal Dynamics ◽  
Inhaled Corticosteroids ◽  
Dry Powder Inhaler ◽  
Airway Disease ◽  
Open Label ◽  
Asthma Symptoms ◽  
Anti Inflammatory

Asthma is a chronic inflammatory airway disease. Increase in airway inflammation is hypothesised to contribute to worsening of asthma symptoms and deterioration in lung function, resulting in the use of reliever medication. Short-acting β2-agonists only treat the symptoms, whereas an anti-inflammatory reliever is believed to treat both symptoms and the underlying inflammation, thereby arresting the progression to an exacerbation. As-needed budesonide/formoterol as an anti-inflammatory reliever reduces the risk of severe exacerbations. However, supporting mechanistic evidence has not yet been described, specifically the temporal dynamics of parameters including airway inflammation, over time and during asthma worsening.The STIFLE study aims to characterise daily variability in airway inflammation, symptoms, lung function and reliever use in people with asthma. This phase IV, open-label, parallel-group, multicentre, exploratory study will enrol 60–80 adult patients with asthma receiving low- or medium-dose inhaled corticosteroids/long-acting β2-agonists (EudraCT identifier number 2018-003467-64). Participants will be randomised 1:1 to either as-needed budesonide/formoterol dry-powder inhaler or salbutamol reliever for 24 weeks, in addition to their maintenance therapy. Daily data will be captured for fractional exhaled nitric oxide, spirometry, asthma symptoms and medication use using devices connected to a smartphone via the STIFLE application. STIFLE will thereby enable not only characterisation of the variability of airway inflammation and clinical outcomes in relation to asthma worsening, but also elucidate the effect of as-needed budesonide/formoterol on airway inflammation against a background of daily maintenance therapy.

scholarly journals Increased Ratio of Matrix Metalloproteinase-9 (MMP-9)/Tissue Inhibitor Metalloproteinase-1 from Alveolar Macrophages in Chronic Asthma with a Fast Decline in FEV1 at 5-Year Follow-up

2019 ◽  
Vol 8 (9) ◽  
pp. 1451 ◽  
Author(s):  
Fu-Tsai Chung ◽  
Hung-Yu Huang ◽  
Chun-Yu Lo ◽  
Yu-Chen Huang ◽  
Chang-Wei Lin ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Alveolar Macrophages ◽  
Inhaled Corticosteroids ◽  
Airway Remodeling ◽  
Bronchial Biopsy ◽  
Chronic Asthma ◽  
Tissue Inhibitor ◽  
Fev1 Decline

Chronic asthma is associated with progressive airway remodeling, which may contribute to declining lung function. An increase in matrix metalloproteinases-9 (MMP-9)/tissue inhibitor metalloproteinase-1 (TIMP-1) may indicate airway inflammation and bronchial injury. Bronchial biopsy specimens and alveolar macrophages (AMs) were obtained from patients with asthma under regular treatment with inhaled corticosteroids or combination therapy and normal subjects (n = 10). Asthmatics included those with a slow forced expiratory volume in one second (FEV1) decline (<30 mL/year, n = 13) and those with a fast FEV1 decline (≥30 mL/year, n = 8) in 5-year follow-up. Immunostaining expression of MMP-9 and TIMP-1 was detected in airway tissues. MMP-9 and TIMP-1 was measured from AMs cultured for 24 h. After the 5-year treatment, the methacholine airway hyperresponsiveness of the slow FEV1 decline group was decreased, but that of the fast FEV1 decline group was increased (PC20, provocative concentration causing a 20% decrease in FEV1, 3.12 ± 1.10 to 1.14 ± 0.34 mg/dL, p < 0.05). AMs of asthma with a fast FEV1 decline released a higher level of MMP-9 (8.52 ± 3.53 pg/mL, p < 0.05) than those of a slow FEV1 decline (0.99 ± 0.20 pg/mL). The MMP-9/TIMP ratio in the fast FEV1 decline group (0.089 ± 0.032) was higher than that of the slow FEV1 decline group (0.007 ± 0.001, p < 0.01). The annual FEV1 decline in 5 years was proportional to the level of MMP-9 (r = 57, p < 0.01) and MMP-9/TIMP-1 ratio (r = 0.58, p < 0.01). The airways of asthma with greater yearly decline in FEV1 showed an increased thickness of submucosa and strong expression of MMP-9. An increase in MMP-9 and MMP-9/TIMP-1 in airways or AMs could be indicators of chronic airway inflammation and contribute to a greater decline in lung function of patients with chronic asthma.

Violence-related distress and lung function in two longitudinal studies of youth

2021 ◽  
pp. 2102329
Author(s):  
Kristina Gaietto ◽  
Yueh-Ying Han ◽  
Erick Forno ◽  
Leonard B. Bacharier ◽  
Wanda Phipatanakul ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Function ◽  
Prospective Study ◽  
Puerto Rican ◽  
Asthma Control ◽  
Low Dose ◽  
Inhaled Corticosteroids ◽  
Related Quality ◽  
Over Time

Increasing violence-related distress over time was associated with worse lung function and worse asthma-related quality of life in youth with asthma despite treatment with low-dose inhaled corticosteroids.Exposure to violence has been associated with lower lung function in cross-sectional studies. We examined whether increasing violence-related distress over time is associated with worse lung function and worse asthma control or quality of life in a secondary analysis of a 48-week randomized clinical trial in 98 youth with asthma (ages 9–16 years) treated with low-dose inhaled corticosteroids (the Vitamin D Kids Asthma Study [VDKA]). We then replicated our findings for lung function in a prospective study of 232 Puerto Rican youth followed for an average of 5·4 years. Violence-related distress was assessed using the Checklist of Children's Distress Symptoms (CCDS) scale. Our outcomes of interest were percent predicted (%pred) lung function measures and (in VDKA only) asthma control (assessed using the Asthma Control Test) and asthma-related quality of life (assessed using the Pediatric Asthma Quality of Life questionnaire). In a multivariable analysis in VDKA, each 1-point increment in the CCDS score was associated with decrements of 3.27% in %predFEV1 (95% confidence interval [CI]=−6.44% to −0.22%, p=0.04) and a 2.65% decrement in percent predicted FVC (95% CI=−4.86% to −0.45%, p=0.02), and 0.30 points in the overall PAQLQ score (95% CI=−0.50 to −0.10, p<0.01). Similar findings for FEV1 and FVC were obtained in the prospective study of Puerto Rican youth. Our findings suggest that violence-related distress may worsen lung function and quality of life in youth with asthma (even those treated with low-dose inhaled corticosteroids) and further support policies to reduce exposure to violence among children in the U.S. and Puerto Rico.

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