Anti-inflammatory effects of medications used for viral infection-induced respiratory diseases.

Respiratory viruses like rhinovirus, influenza virus, respiratory syncytial virus, and coronavirus cause several respiratory diseases, such as bronchitis, pneumonia, pulmonary fibrosis, and coronavirus disease 2019, and exacerbate bronchial asthma, chronic obstructive pulmonary disease, bronchiectasis, and diffuse panbronchiolitis. The production of inflammatory mediators and mucin and the accumulation of inflammatory cells have been reported in patients with viral infection-induced respiratory diseases. Interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, and regulated on activation normal T-cell expressed and secreted are produced in the cells, including human airway and alveolar epithelial cells, partly through the activation of toll-like receptors, nuclear factor kappa B and p44/42 mitogen-activated protein kinase. These mediators are associated with the development of viral infection-induced respiratory diseases through the induction of inflammation and injury in the airway and lung, airway remodeling and hyperresponsiveness, and mucus secretion. Medications used to treat respiratory diseases, including corticosteroids, long-acting ß2-agonists, long-acting muscarinic antagonists, mucolytic agents, antiviral drugs for severe acute respiratory syndrome coronavirus 2 and influenza virus, macrolides, and Kampo medicines, reduce the production of viral infection-induced mediators, including cytokines and mucin, as determined in clinical, in vivo, or in vitro studies. These results suggest that the anti-inflammatory effects of these medications on viral infection-induced respiratory diseases may be associated with clinical benefits, such as improvements in symptoms, quality of life, and mortality rate, and can prevent hospitalization and the exacerbation of chronic obstructive pulmonary disease, bronchial asthma, bronchiectasis, and diffuse panbronchiolitis.

The association between inhaled corticosteroid and the risks of SARS-COV-2 infection: A systematic review and meta-analysis.

BACKGROUND: The effect of inhaled corticosteroid (ICS) on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection is unclear. METHODS: We performed a systematic review and meta-analysis of clinical studies that assessed the association between the use of ICS and the risk of SARS-COV-2 infection. PubMed, Web of Science, Scopus, Cochrane Library and Google Scholar were searched to January 1st, 2023. ROBINS-I was used to assess risk of bias of included studies. The outcome of interest was the risk of SARS-COV-2 infection in patients and odds ratio (OR) with 95% confidence interval (95% CI) were calculated using Comprehensive Meta-analysis software version 3. RESULTS: Twelve studies involving seven observational cohort studies, three case-control studies, and two cross-sectional studies were included in this meta-analysis. Overall, compared to non-ICS use, the pooled odds ratio (OR) of the risk of SARS-COV-2 infection was 0.997 (95% confidence interval [CI] 0.664-1.499; p = 0.987) for patients with ICS use. Subgroup analyses demonstrated no statistical significance in the increased risk of SARS-COV-2 infection in patients with ICS monotherapy or in combination with bronchodilators (pooled OR=1.408; 95% CI=0.693-2.858; p = 0.344 in ICS monotherapy, and pooled OR=1.225; 95% CI=0.533-2.815; p = 0.633 in ICS combination, respectively). In addition, no significant association was observed between ICS use and the risk of SARS-COV-2 infection for patients with COPD (pooled OR=0.715; 95% CI=0.415-1.230; p = 0.225) and asthma (pooled OR=1.081; 95% CI=0.970-1.206; p = 0.160). CONCLUSIONS: The use of ICS, either monotherapy or in combination with bronchodilators, does not have impact on the risk of SARS-COV-2 infection.

Use of inhaled corticosteroids in preschool children and variability among pediatricians: a real-world analysis before and during the SARS-CoV-2 pandemic.

BACKGROUND: In Italy, inhaled corticosteroids (ICSs) are inappropriately prescribed to provide relief in URTI symptoms. Extreme variation in ICS prescribing has been described at regional and sub-regional level. During 2020, extraordinary containment measures were implemented in attempt to halt Coronavirus, such as social distancing, lockdown, and the use of mask. Our objectives were to evaluate the indirect impact of the SARS-CoV-2 pandemic on prescribing patterns of ICSs in preschool children and to estimate the prescribing variability among pediatricians before and during the pandemic. METHODS: In this real-world study, we enrolled all children residing in the Lazio region (Italy), aged 5 years or less during the period 2017-2020. The main outcome measures were the annual ICS prescription prevalence, and the variability in ICS prescribing, for each study year. Variability was expressed as Median Odds Ratios (MORs). If the MOR is 1.00, there is no variation between clusters (e.g., pediatricians). If there is considerable between-cluster variation, the MOR will be large. RESULTS: The study population consisted of 210,996 children, cared by 738 pediatricians located in the 46 local health districts (LHDs). Before the pandemic, the percentage of children exposed to ICS was almost stable, ranging from 27.3 to 29.1%. During the SARS-CoV-2 pandemic, the ICS prescription prevalence dropped to 17.0% (p < 0.001). In each study year, a relevant (p < 0.001) variability was detected among both LHDs and pediatricians working in the same LHD. However, the variability among individual pediatricians was always higher. In 2020, the MOR among pediatricians was 1.77 (95% CI: 1.71-1.83) whereas the MOR among LHDs was 1.29 (1.21-1.40). Furthermore, MORs remained stable over time, and no differences were detected in ICS prescription variability before and after pandemic outbreak. CONCLUSIONS: If on one hand the SARS-CoV-2 pandemic indirectly caused the reduction in ICS prescriptions, on the other the variability in ICS prescribing habits among both LHDs and pediatricians remained stable over the whole study time span (2017-2020), showing no differences between pre- pandemic and pandemic periods. The intra-regional drug prescribing variability underlines the lack of shared guidelines for appropriate ICS therapy in preschool children, and raises equity issues in access to optimal care.

Clinical benefits of inhaled ciclesonide for hospitalized patients with COVID-19 infection: a retrospective study.

BACKGROUND: The successful management of patients infected with coronavirus disease 2019 (COVID-19) with inhaled ciclesonide has been reported, however few studies have investigated its application among hospitalized patients. METHODS: This retrospective cohort study enrolled all adult patients admitted to our hospital with confirmed COVID-19 infection from May to June 2021. Critical patients who received mechanical ventilation within 24 h after admission and those who started ciclesonide more than 14 days after symptom onset were excluded. The in-hospital mortality rate was compared between those who did and did not receive inhaled ciclesonide. RESULTS: A total of 269 patients were enrolled, of whom 184 received inhaled ciclesonide and 85 did not. The use of ciclesonide was associated with lower in-hospital mortality (7.6% vs. 23.5%, p = 0.0003) and a trend of shorter hospital stay (12.0 (10.0-18.0) days vs. 13.0 (10.0-25.3) days, p = 0.0577). In subgroup analysis, the use of inhaled ciclesonide significantly reduced mortality in the patients with severe COVID-19 infection (6.8% vs. 50.0%, p < 0.0001) and in those with a high risk of mortality (16.4% vs. 43.2%, p = 0.0037). The use of inhaled ciclesonide also reduced the likelihood of receiving mechanical ventilation in the patients with severe COVID-19 infection. After multivariate analysis, inhaled ciclesonide remained positively correlated with a lower risk of in-hospital mortality (odds ratio: 0.2724, 95% confidence interval: 0.087-0.8763, p = 0.0291). CONCLUSIONS: The use of inhaled ciclesonide in hospitalized patients with COVID-19 infection can reduce in-hospital mortality. Further randomized studies in patients with moderate to severe COVID-19 infection are urgently needed.

Inhaled corticosteroids do not affect the antibody titer against the SARS-CoV-2 spike protein in BNT162b2 mRNA vaccinated patients.

OBJECTIVES: Oral corticosteroids reduce the antibody titer of the BNT162b2 mRNA vaccine against SARS-CoV-2. To date, the effect of inhaled corticosteroids on antibody titers is unknown. STUDY DESIGN: The design of this study is retrospective study. METHODS: We analyzed the relationship between the clinical features and total antibody titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in 320 subjects who had never been infected with Coronavirus disease 2019 (COVID-19) and were vaccinated the second time with the BNT162b2 mRNA vaccine between October 1 to December 28, 2021. RESULTS: Of the 320 subjects, 205 were treated with inhaled corticosteroids. The median antibody titer of patients treated with inhaled corticosteroids was 572 U/mL, which was significantly higher than that of patients treated without inhaled corticosteroids (454U/mL, P = 0.00258). The median antibody titers of smokers, men, and patients aged 65 years and over, were 315.5 U/mL, 385 U/mL, and 425.5 U/mL, respectively. These results are significantly lower than those of patients who never smoked, women, and patients aged less than 64 years (582 U/mL [P < 0.0001], 682.5 U/mL [P < 0.0001], and 717 U/mL [P < 0.0001], respectively). The multivariate analysis revealed that females and age were independent antibody titer-reducing factors (P = 0.0001 and P < 0.0001, respectively). CONCLUSIONS: The use of inhaled corticosteroids did not reduce the antibody titer against SARS-CoV-2 spike protein. Clinicians should continue treatment with inhaled corticosteroids if indicated.

Clinical Application of Inhaled Ciclesonide and Enoxaparin for COVID-19 Pneumonia

The novel coronavirus disease 2019 (COVID-19) pandemic is a threat to global public health. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and characterized by high transmission, high mortality, lack of effective treatment, and prolonged hospitalization. Currently, there is no clear management strategy for COVID-19 infection. Some clinical evidence suggests that the use of inhaled ciclesonide and enoxaparin subcutaneous injection maybe helpful for disease treatment. In this article, we report the successful treatment of a 65-year-old male with COVID-19 pneumonia with Inhaled corticosteroid and enoxaparin subcutaneously, which also shortened the course of the disease without significant complications. Copyright (C) 2022, Taiwan Society of Geriatric Emergency & Critical Care Medicine.

Lung function before and after COVID-19 in young adults: A population-based study.

Background: There is limited evidence on the long-term impact of mild-to-moderate coronavirus disease 2019 (COVID-19) on lung function among young adults. Objectives: We aimed to assess whether COVID-19 has a negative impact on lung function in young adults and whether asthma, allergic sensitization, or use of inhaled corticosteroids (ICSs) modifies a potential association. Methods: Participants from the population-based BAMSE (Barn, Allergi, Miljö, Stockholm, Epidemiologi) cohort with spirometry assessed before (2016-2019) and after onset of the COVID-19 pandemic (2020-2021) were included. Serum levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain-specific IgG, IgM, and/or IgA (determined with ELISA) defined seropositivity. Mean change in lung function (ie, change in FEV1, forced vital capacity [FVC], and FEV1/FVC ratio expressed as percent of predicted [pp]) from before to after onset of the pandemic were compared between the seronegative and seropositive participants. In seropositive participants, change in lung function was assessed in relation to allergic sensitization and self-reported ICS use. Results: Of the 853 included participants, 29% (n = 243) were seropositive. There were no differences in change in lung function between the seronegative and seropositive participants (for mean change in FEV1 pp [SD], seropositivity = 0.87% [4.79%] and seronegativity = 1.03% (4.76%) [P = .66] for difference using a t test; FVC pp (SD), seropositivity = 1.34% (4.44%) and seronegativity = 1.29% (4.27%) [P = .87]; and for FEV1/FVC pp (SD), seropositivity = -0.25% (3.13%) and seronegativity = -0.13% (3.15%) [P = .61]). Similar results were observed among participants with asthma (n = 147 [17%]). Among seropositive participants, allergic sensitization or ICS use did not influence lung function. Conclusion: We found no evidence of mild-to-moderate COVID-19 affecting lung function long term in a population-based cohort of young adults. Moreover, neither asthma nor allergic sensitization nor ICS use affected the results.

Infection with SARS-CoV-2 among children with asthma: evidence from Global Asthma Network.

BACKGROUND: Clinical presentations of coronavirus disease 2019 (COVID-19) among children with asthma have rarely been investigated. This study aimed to assess clinical manifestations and outcome of COVID-19 among children with asthma, and whether the use of asthma medications was associated with outcomes of interest. METHODS: The Global Asthma Network (GAN) conducted a global survey among GAN centers. Data collection was between November 2020 and April 2021. RESULTS: Fourteen GAN centers from 10 countries provided data on 169 children with asthma infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was asymptomatic in 58 (34.3%), mild in 93 (55.0%), moderate in 14 (8.3%), and severe/critical in 4 (2.4%). Thirty-eight (22.5%) patients had exacerbation of asthma and 21 (12.4%) were hospitalized for a median of 7 days (interquartile range 3-16). Those who had moderate or more severe COVID-19 were significantly more likely to have exacerbation of asthma as compared to those who were asymptomatic or had mild COVID-19 (adjusted odds ratio (adjOR) 3.97, 95% CI 1.23-12.84). Those who used inhaled bronchodilators were significantly more likely to have a change of asthma medications (adjOR 2.39, 95% CI 1.02-5.63) compared to those who did not. Children who used inhaled corticosteroids (ICS) did not differ from those who did not use ICS with regard to being symptomatic, severity of COVID-19, asthma exacerbation, and hospitalization. CONCLUSIONS: Over dependence on inhaled bronchodilator may be inappropriate. Use of ICS may be safe and should be continued in children with asthma during the pandemic of COVID-19.

Association between Inhaled Corticosteroid Use and SARS-CoV-2 Infection: A Nationwide Population-Based Study in South Korea.

BACKGROUND: Although it is known that inhaled corticosteroid (ICS) use may increase the risk of respiratory infection, its influence on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Thus, the aim of this study was to investigate the association between ICS use and the positivity of SARS-CoV-2 infection among patients with chronic respiratory diseases. METHODS: Nationwide data of 44,968 individuals with chronic respiratory diseases tested for SARS-CoV-2 until May 15, 2021 were obtained from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea. The positivity of SARS-CoV-2 infection was retrospectively analysed according to the prescription, type, and dose of ICS taken one year before SARS-CoV-2 test. RESULTS: Among 44,968 individuals tested, 931 (2.1%) were positive for SARS-CoV-2. A total of 7,019 patients (15.6%) were prescribed ICS one year prior to being tested for SARS-CoV-2. Low, medium, and high doses of ICS were prescribed in 7.5%, 1.6%, and 6.5% of total cases, respectively. Among types of ICS, budesonide, fluticasone, beclomethasone, and ciclesonide were prescribed in 3.7%, 8.9%, 2.3%, and 0.6% of total cases, respectively. A multivariate analysis showed no significant increase in infection with ICS use (odds ratio, 0.84; 95% confidence interval, 0.66-1.03). Moreover, there were no associations between the positivity of infection and the dose or type of ICS prescribed. CONCLUSION: Prior ICS use did not increase the positivity for SARS-CoV-2 infection. Moreover, different doses or types of ICS did not affect this positivity.

Inhaled corticosteroid is not associated with a poor prognosis in COVID-19.

Inhaled corticosteroid is not associated with a poor prognosis in COVID-19.

Severity of COVID-19 in hospitalized patients with and without atopic disease.

BACKGROUND: Data from the 2009 influenza pandemic suggested asthma might protect from severe disease in hospitalized patients. Asthma does not appear to increase risk for hospitalization or mortality with COVID-19. OBJECTIVE: This study was undertaken to see if atopy actually protected those hospitalized with COVID-19. METHODS: Retrospective chart review on all patients testing positive for SARS-CoV-2 over 2 months at a major adult and pediatric tertiary referral center hospital. Charts were evaluated for history of atopic disease, as were the need for ICU admission, requirement for supplemental oxygen and/or intubation, and in hospital mortality. RESULTS: No significant differences in outcomes for patients (n = 275) based on atopic disease were noted: ICU admission, 43% versus 44.7% (atopic versus no atopic disease, respectively; p = 0.84); supplemental oxygen use, 79.1% versus 73.6% (p = 0.36); intubation rate, 35.8% versus 36.5% (p = 0.92); and mortality rate, 13.4% versus 20.7% (p = 0.19). More patients with atopic disease had COPD listed as a diagnosis in their chart (38.8% versus 17.3%, p < 0.001). COPD was associated with an increased rate of ICU admission (aOR = 2.22 (1.15, 4.30) p = 0.02) and intubation (aOR = 2.05 (1.07, 3.92) p = 0.03). After adjusting for COPD, patients with atopic disease had a trend for reduced mortality (aOR 0.55 (0.23, 1.28), p = 0.16), but those with asthma did not (p > 0.2). CONCLUSION: Severity of COVID-19 in hospitalized patients does not differ based on atopic status. However, adjusting for presence of COPD led to a suggestion of possible reduced severity in patients with atopy but not asthma.

Use of corticosteroids in asthma and COPD patients with or without COVID-19.

The potential detrimental effects of steroids on the immune system to fight viral infections had always been a concern for patients on long term steroids in chronic conditions. A recent warning from WHO on systemic corticosteroid use amid COVID-19 raised suspicion among public and healthcare professionals regarding the safety of steroid use during the SARS-CoV-2 pandemic. The corticosteroids (inhaled and oral) are commonly prescribed in the management of asthma and COPD patients and any unsolicited changes in medications use may lead to potentially severe exacerbations and may risk patient lives. This article provides a critical review of clinical evidence and offers a detailed discussion on the safety and efficacy of corticosteroids in asthma and COPD patients, both with and without COVID-19.