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Pulmonary – Treatable traits
Published in Vibeke Backer, Peter G. Gibson, Ian D. Pavord, The Asthmas, 2023
Vibeke Backer, Peter G. Gibson, Ian D. Pavord
Dysphonia commonly occurs due to deposition of inhaled corticosteroid particles locally in the oropharynx, around the vocal cords, and local side effects such as oral candidiasis and hoarseness of voice may also develop. Use of a large volume spacer device and careful rinsing of the mouth after the use of inhaled corticosteroids reduces the risk of these local effects. Systemic side effects include bruising and atrophy of the skin, cataract formation, glaucoma and reduced bone mineral density. Suppression of the adrenocortical axis can occur with high-dose inhaled corticosteroids and specific advice on use of corticosteroid replacement therapy during intercurrent illness should be considered in patients who genuinely require long-term high-dose therapy. Systemic effects occur partly due to gastrointestinal absorption of swallowed particles and partly due to systemic absorption via the airways. The use of spacer devices, dry powder mechanisms and mouth rinsing after inhaler use minimise adverse effects. Another approach to minimise local side effects is to use Ciclesonide, a pro-drug which is activated by contact with the lower airway epithelium. Drugs with high first-pass metabolism in the liver such as budesonide and fluticasone have less systemic side effects than beclomethasone, but at high doses (>800–1,000 mcg daily of budesonide or >500 mcg daily of fluticasone) systemic absorption through the buccal and airway mucosa becomes increasingly important.
Ciclesonide
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
In the period 2009-2011, In Helsinki, Finland, 79 patients had undergone patch testing with a steroid series including ciclesonide 0.1% and 0.5% in pet. and 0.1% and 0.5% alcohol, mainly because of eczematous conditions and suspected contact allergy to topical corticosteroids. None of these patients had had previous treatment with inhalation pharmaceuticals containing ciclesonide. They were also tested with the commercial ciclesonide inhalation spray at 160 mg/dose 0.1% and 0.5% in alcohol and 0.1% and 0.5% in pet. Ten (13%) of the 79 patch tested patients showed positive reactions to inhaled ciclesonide; all were also positive to the other 4 ciclesonide test materials. Budesonide 0.1% in pet. gave a positive reaction in all four patients with positive patch tests to ciclesonide. Conversely, there were no patients with a positive reaction to budesonide but a negative reaction to ciclesonide. It was concluded that all reactions to ciclesonide were cross-reactions to budesonide (2).
Safety and efficacy of glucocorticoids in the treatment of COVID-19: A meta-analysis of randomized control trials
Published in Expert Review of Respiratory Medicine, 2023
Wenxiao Qiao, Lihong Meng, Ye Zhang, Dian Li, Jingjing Chen, Jinyun Wang, Di Xie, Xiaoming Xue
Based on subgroup analysis, the efficacy of glucocorticoids was related to the type of drug. Only dexamethasone administration had a significant effect on the reduction of patient mortality, consistent with a previous study [35]. Even though Edalatifard at al [24]. reported that high-dose methylprednisolone was beneficial in reducing mortality, there was no data from other RCTs to verify it. The dose of glucocorticoid affects the curative effect. The results of meta-analysis showed that low dose of glucocorticoid may be related to the reduction of all-cause mortality, but high dose of glucocorticoid has nothing to do with it. The efficacy of glucocorticoids may also be related to the dosage form and the severity of the disease. Both ciclesonide and budesonide are inhaled drugs, and the main purpose of treatment is to relieve the patient’s condition, such as cough, asthma, loss of sense of smell, etc. The results of this study show that the above two drugs are not beneficial to the relief of symptoms. Hence, it is not recommended to use inhaled drugs to relieve the clinical symptoms of mild and common patients. For severe patients, no RCT uses inhaled glucocorticoids, so it is regrettable that its efficacy for severe patients cannot be evaluated, and more RCT results are needed to verify.
Improving the risk-to-benefit ratio of inhaled corticosteroids through delivery and dose: current progress and future directions
Published in Expert Opinion on Drug Safety, 2022
Piotr Damiański, Grzegorz Kardas, Michał Panek, Piotr Kuna, Maciej Kupczyk
New molecules introduced into clinical practice, such as ciclesonide and mometasone furoate, present high potency with favorable safety profile due to low oral bioavailability and high serum protein binding. The exceptional feature of ciclesonide inhaled in its pro-drug form is on-site activation into the active form (des-ciclesonide) in the lungs. Other developments include combination of several molecules, namely ICS, long-acting β2-agonists, and long-acting anticholinergics in one inhaler. Several studies and our every-day clinical practice proved that this approach is optimal in regard to gaining control of the disease with the lowest doses of all drugs due to synergistic mechanisms and improved compliance. A good example gives the new, one daily combination of IND/MF or triple combination of IND/GLY/MF, with the latest showing higher efficacy in improvement in lung function and reduction of asthma exacerbations as compared with the standard treatment. An interesting path in ICS development shows fluticasone furoate, which in comparison to fluticasone propionate is characterized by higher receptor binding affinity and selectivity together with longer lung retention. This points how simple modification of a given molecule may result in optimization of its pharmacokinetic and pharmacodynamic properties. Preliminary reports on new, highly potent synthetic glucocorticosteroids and selective glucocorticoid receptor modulators give promising results; however, further studies in this field are needed.
The effect of inhaled corticosteroids on the outcomes of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials
Published in Expert Review of Clinical Pharmacology, 2022
Chao-Hsien Chen, Cheng-Yi Wang, Ya-Hui Wang, Ching-Yi Chen, Kuang-Hung Chen, Chih-Cheng Lai, Yu-Feng Wei, Pin-Kuei Fu
Systemic dexamethasone is a relatively inexpensive and widely available treatment that was shown to reduce mortality in severe and intensive care-related COVID-19 in two large-scale studies [21,22]. Therefore, systemic corticosteroid is recommended for ameliorating the exaggerated inflammation or cytokine in late COVID-19. However, it is not recommended in patients with early or mild COVID-19 due to the concern of its effect on suppressing the early immune response. Current evidence is insufficient to recommend either for or against the use of ICS for the treatment of COVID-19 [23]. Nevertheless, ICS treatment is simple, safe, low-cost, well studied, and widely used in patients with obstructive lung disease. Our meta-analysis showed that patients treated with ICS were associated with 21% and 12% improvements in symptom resolution at day 14 and day 28, respectively, and that they were associated with an 85% decreased risk of urgent medical visits or hospitalizations. These results provide evidence of the beneficial effect of ICS treatment for mild-to-moderate or non-hospitalized COVID-19 patients, which should be applicable to global health care systems, including developing and low-income countries. Subgroup analysis of our study showed that inhaled budesonide was associated with a 22% significant improvement in symptom resolution at day 14. However, inhaled ciclesonide was associated with a marginal improvement but did not reach statistical difference compared with the usual care group at day 14. This difference between inhaled ciclesonide and budesonide on symptom resolution may be due to the systemic bioactivity, in that ciclesonide does not exhibit systemic glucocorticoid effects, which is in contrast to budesonide, which exhibits systemic glucocorticoid activity as evidenced by 44% adrenal suppression at the dose of 1600 μg sued in the PRINPLE and STOIC trials [24]. Notably, two out of three studies that evaluated ciclesonide only used a half dose than the third study. Further comparisons of different classes or the dosage and potency of different ICS to treat SARS-CoV-2 patients are warranted in future studies.