Journal of Clinical Medicine

Editorial

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7 pages, 238 KiB

Open AccessEditorial

Therapeutic Modalities for Asthma, COPD, and Pathogenesis of COVID-19: Insights from the Special Issue

by Sukhwinder Singh Sohal

J. Clin. Med. 2022, 11(15), 4525; https://doi.org/10.3390/jcm11154525 - 3 Aug 2022

Cited by 1 | Viewed by 2246

Abstract

The human lung is a vital organ, which is vulnerable to outside insults and injuries [...] Full article

(This article belongs to the Special Issue Pharmacology and Therapeutic of Asthma and COPD)

Research

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14 pages, 1228 KiB

Open AccessArticle

Benralizumab in Patients with Severe Eosinophilic Asthma: A Multicentre Real-Life Experience

by Giulia Scioscia, Pasquale Tondo, Santi Nolasco, Corrado Pelaia, Giovanna Elisiana Carpagnano, Maria Filomena Caiaffa, Giuseppe Valenti, Angelantonio Maglio, Francesco Papia, Massimo Triggiani, Nunzio Crimi, Girolamo Pelaia, Alessandro Vatrella, Maria Pia Foschino Barbaro and Claudia Crimi

J. Clin. Med. 2023, 12(13), 4362; https://doi.org/10.3390/jcm12134362 - 28 Jun 2023

Cited by 2 | Viewed by 2137

Abstract

Background: Mepolizumab and benralizumab are monoclonal antibodies directed against anti-IL-5 and anti-IL5R, respectively, and their use reduces the exacerbation rate and maintains oral corticosteroid requirements in severe eosinophilic asthma. Previous studies have tested the therapeutic switch between two biologics with excellent results, further [...] Read more.

Background: Mepolizumab and benralizumab are monoclonal antibodies directed against anti-IL-5 and anti-IL5R, respectively, and their use reduces the exacerbation rate and maintains oral corticosteroid requirements in severe eosinophilic asthma. Previous studies have tested the therapeutic switch between two biologics with excellent results, further demonstrating the heterogeneity of asthmatic disease and the complexity of the therapeutic choice. It remains unclear if such patients may improve following a switch from mepolizumab to benralizumab. Aims: Within a multicentre real-life setting, we decided to evaluate the potential effectiveness of a therapeutic switch to benralizumab in patients with severe eosinophilic asthma initially treated with mepolizumab, who experienced sub-optimal responses. The secondary aim was to identify the clinical factors associated with a better response to benralizumab. Methods: We retrospectively assessed patients with severe eosinophilic asthma treated at six Italian specialist centres, who were switched from mepolizumab to benralizumab following a sub-optimal response, defined as a partial or total lack of clinical remission (i.e., frequent severe exacerbations and/or poorly controlled symptoms and/or higher OCS daily use in patients with a poor or moderate response in the global evaluation of treatment effectiveness scale), after at least 12 months of treatment. Results: Twenty-five patients were included in the analysis (mean age 56.76 ± 11.97 years, 65% female). At 6 months of treatment with benralizumab, the ACT score was significantly higher than the ACT score with mepolizumab (20.24 ± 3.38 vs. 16.77 ± 3.48, p < 0.0001); the mean number of daily SABA inhalations was significantly lower after 6 months and 12 months of treatment with benralizumab than that after treatment with mepolizumab; OCS intake and the prednisone median dosage at 6 months of treatment with benralizumab were significantly lower than those with mepolizumab. Benralizumab treatment resulted in a marked improvement in asthma control, suppressed blood eosinophil levels and reduction in the number of exacerbations in the subgroup of patients with severe eosinophilic asthma and nasal polyposis. Conclusions: Patients diagnosed with severe eosinophilic asthma who experience a partial response to mepolizumab could benefit from switching to benralizumab, and even more those who have nasal polyposis. Full article

(This article belongs to the Special Issue Pharmacology and Therapeutic of Asthma and COPD)

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15 pages, 750 KiB

Open AccessArticle

Can Leukotriene Receptor Antagonist Therapy Improve the Control of Patients with Severe Asthma on Biological Therapy and Coexisting Bronchiectasis? A Pilot Study

by Vitaliano Nicola Quaranta, Silvano Dragonieri, Nunzio Crimi, Claudia Crimi, Pierachille Santus, Francesco Menzella, Corrado Pelaia, Giulia Scioscia, Cristiano Caruso, Elena Bargagli, Konstantinos Kostikas, Christos Kyriakopoulos, Nicola Scichilone and Giovanna Elisiana Carpagnano

J. Clin. Med. 2022, 11(16), 4702; https://doi.org/10.3390/jcm11164702 - 11 Aug 2022

Cited by 6 | Viewed by 2045

Abstract

Introduction: Asthma and bronchiectasis appear to be two related diseases and in their complex inflammatory interaction, the cysteinyl leukotriene/cysteinyl leukotriene receptor 1 (cysLT/cysLTR1) axis appears to play an important role given its involvement also in the neutrophilic pathway. To our knowledge, few studies [...] Read more.

Introduction: Asthma and bronchiectasis appear to be two related diseases and in their complex inflammatory interaction, the cysteinyl leukotriene/cysteinyl leukotriene receptor 1 (cysLT/cysLTR1) axis appears to play an important role given its involvement also in the neutrophilic pathway. To our knowledge, few studies have been conducted so far to evaluate the role of the leukotriene cysLT/cysLTr1 axis in the management of clinical and inflammatory outcomes within a population of patients with severe asthma and bronchiectasis. The aim of our study was to verify in this population the effect of leukotriene receptor antagonist (LTRA) therapy in clinical and inflammatory control before and after 6 months of introduction of biologic therapy. Methods: We retrospectively enrolled, from eight different severe asthma centers’ outpatients, 36 atopic patients with the simultaneous presence of non-cystic fibrosis (non-CF) and non-allergic bronchopulmonary aspergillosis (non-ABPA) bronchiectasis and severe asthma. The first biological injection was performed at baseline (T0 time). Patients who were already taking LTRA therapy at time T0 were recorded, and no new prescriptions were made. We observed our population over a 6-month period (T1 time). At the baseline we collected the following data: baseline characteristics, clinical history, high resolution computed tomography and bronchiectasis-related parameters and skin prick test. At both times T0 and T1 we collected the following data: asthma control test (ACT), asthma control questionnaire (ACQ), immunoglobulin E (IgE) level, blood count, fractional exhaled nitric oxide 50 (FeNO 50) and flow-volume spirometry. The study was retrospectively registered. Results: Our population had a mean age of 59.08 ± 11.09 and 50% were female. At T1, patients on LTRA therapy had a significantly lower FeNO value (33.03 ± 23.61 vs. 88.92 ± 77.96; p = 0.012). We assessed that the value of ΔFeNO (FeNO 50 T1 − FeNO 50 T0) and the number of unplanned specialist visits allowed a discrimination of 66.7% in the presence of LTRA therapy. We also verified how low FeNO values at time T1 were statistically significant predictors of LTRA therapy (ODD = 9.96 (0.94–0.99); p = 0.032). Conclusion: The presence of LTRA in therapy in a population of severe asthmatics with coexisting non-ASBPA bronchiectasis and non-cystic fibrosis, acting simultaneously on the T helper type 2 (TH2) pathway and probably on the neutrophilic component of bronchiectasis, would allow a further amplification of the beneficial effects of biological therapy, leading to a reduction in the number of unplanned visits to specialists. Full article

(This article belongs to the Special Issue Pharmacology and Therapeutic of Asthma and COPD)

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11 pages, 715 KiB

Open AccessArticle

Effect of a New Tele-Rehabilitation Program versus Standard Rehabilitation in Patients with Chronic Obstructive Pulmonary Disease

by Jose Cerdán-de-las-Heras, Fernanda Balbino, Anders Løkke, Daniel Catalán-Matamoros, Ole Hilberg and Elisabeth Bendstrup

J. Clin. Med. 2022, 11(1), 11; https://doi.org/10.3390/jcm11010011 - 21 Dec 2021

Cited by 23 | Viewed by 5909

Abstract

In chronic obstructive pulmonary disease (COPD), rehabilitation is recommended, but attendance rates are low. Tele-rehabilitation may be key. We evaluate the effect of a tele-rehabilitation program vs. standard rehabilitation on COPD. A randomized, non-inferiority study comparing eight weeks of tele-rehabilitation (physiotherapist video/chat-consultations and [...] Read more.

In chronic obstructive pulmonary disease (COPD), rehabilitation is recommended, but attendance rates are low. Tele-rehabilitation may be key. We evaluate the effect of a tele-rehabilitation program vs. standard rehabilitation on COPD. A randomized, non-inferiority study comparing eight weeks of tele-rehabilitation (physiotherapist video/chat-consultations and workout sessions with a virtual-autonomous-physiotherapist-agent (VAPA)) and standard rehabilitation in stable patients with COPD. At baseline, after 8 weeks and 3 and 6 months of follow-up, 6 min walk test distance (6MWTD), 7-day pedometry, quality of life, exercise tolerance, adherence, patient satisfaction and safety were assessed. Fifty-four patients (70 ± 9 years, male 57%, FEV1% 34.53 ± 11.67, FVC% 68.8 ± 18.81, 6MWT 376.23 ± 92.02) were included. Twenty-seven patients were randomized to tele-rehabilitation. Non-inferiority in Δ6MWTD at 8 weeks (47.4 ± 31.4), and at 3 (56.0 ± 38.0) and 6 (95.2 ± 47.1) months follow-up, was observed. No significant difference was observed in 7-day pedometry or quality of life. In the intervention group, 6MWTD increased by 25% and 66% at 3 and 6 months, respectively; adherence was 81%; and patient satisfaction was 4.27 ± 0.77 (Likert scale 0–5). Non-inferiority between groups and high adherence, patient satisfaction and safety in the intervention group were found after rehabilitation and at 3 and 6 months of follow-up. Tele-rehabilitation with VAPA seems to be a promising alternative. Full article

(This article belongs to the Special Issue Pharmacology and Therapeutic of Asthma and COPD)

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12 pages, 1140 KiB

Open AccessArticle

The Effects of Previous Asthma and COPD on the Susceptibility to and Severity of COVID-19: A Nationwide Cohort Study in South Korea

by Younghee Jung, Jee Hye Wee, Joo-Hee Kim and Hyo Geun Choi

J. Clin. Med. 2021, 10(20), 4626; https://doi.org/10.3390/jcm10204626 - 9 Oct 2021

Cited by 12 | Viewed by 2696

Abstract

Background: There is controversial evidence of the associations of asthma and chronic obstructive pulmonary disease (COPD) with the risk and outcomes of Coronavirus Disease 2019 (COVID-19). We aimed to evaluate the effects of asthma and COPD on the susceptibility to and severity of [...] Read more.

Background: There is controversial evidence of the associations of asthma and chronic obstructive pulmonary disease (COPD) with the risk and outcomes of Coronavirus Disease 2019 (COVID-19). We aimed to evaluate the effects of asthma and COPD on the susceptibility to and severity of COVID-19. Methods: Data from a nationwide COVID-19 cohort database by the Korea National Health Insurance Corporation were utilized. A total of 4066 COVID-19 patients (1 January 2020 through 4 June 2020) were 1:4 matched with 16,264 controls with regard to age, sex, and income. Asthma and COPD were defined as diagnostic codes (ICD-10) and medication claim codes. Conditional and unconditional multivariate logistic regression were applied to analyze the susceptibility to and severity of COVID-19 associated with asthma and COPD. Results: The prevalence of mild and severe asthma/COPD did not differ between the COVID-19 and control patients in the multivariate analyses. Among the total 4066 COVID-19 patients, 343 (8.4%) had severe COVID-19, of whom 132 (3.2% of the total COVID-19 patients) died. Regarding the outcomes of COVID-19, neither mild nor severe asthma were associated with the severity or mortality of COVID-19 after adjusting for other variables. However, severe COPD was a significant risk factor for severe COVID-19 (odds ratio (OR) = 2.23, 95% confidence intervals (CI): 1.08–4.60, p = 0.030) and the mortality of COVID-19 in the multivariate analyses (OR = 3.06, 95% CI: 1.14–8.2, p = 0.026). Conclusions: In a Korean nationwide cohort, neither asthma nor COPD were associated with COVID-19, but severe COPD was associated with the severity and mortality of COVID-19. Full article

(This article belongs to the Special Issue Pharmacology and Therapeutic of Asthma and COPD)

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18 pages, 13334 KiB

Open AccessArticle

Electronic Cigarette Aerosol Is Cytotoxic and Increases ACE2 Expression on Human Airway Epithelial Cells: Implications for SARS-CoV-2 (COVID-19)

by Kielan Darcy McAlinden, Wenying Lu, Parisa Vahidi Ferdowsi, Stephen Myers, James Markos, Josie Larby, Collin Chia, Heinrich C. Weber, Greg Haug, Mathew Suji Eapen and Sukhwinder Singh Sohal

J. Clin. Med. 2021, 10(5), 1028; https://doi.org/10.3390/jcm10051028 - 3 Mar 2021

Cited by 29 | Viewed by 5196

Abstract

Tobacco smoking has emerged as a risk factor for increasing the susceptibility to infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via increased expression of angiotensin-converting enzyme-2 (ACE2) in the lung, linked to coronavirus disease 2019 (COVID-19) development. Given the modifiable nature [...] Read more.

Tobacco smoking has emerged as a risk factor for increasing the susceptibility to infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via increased expression of angiotensin-converting enzyme-2 (ACE2) in the lung, linked to coronavirus disease 2019 (COVID-19) development. Given the modifiable nature of electronic cigarettes and the delivery of high concentrations of nicotine, we investigate whether electronic cigarette vaping has the potential to increase susceptibility to SARS-CoV-2 infection. We exposed BEAS-2B cells (bronchial epithelium transformed with Ad12-SV40 2B) and primary small airway epithelial cells (SAECs) to electronic cigarette aerosol condensates produced from propylene glycol/vegetable glycerin or commercially bought e-liquid (±added nicotine) and cigarette smoke extract to investigate if electronic cigarette exposure, like cigarette smoke, increases the expression of ACE2 in lung epithelial cells. In BEAS-2B cells, cytotoxicity (CCK-8), membrane integrity (LDH), and ACE2 protein expression (immunofluorescence) were measured for both 4- and 24 h treatments in BEAS-2B cells and 4 h in SAECs; ACE2 gene expression was measured using quantitative polymerase chain reaction (qPCR) for 4 h treatment in BEAS-2B cells. Nicotine-free condensates and higher concentrations of nicotine-containing condensates were cytotoxic to BEAS-2B cells. Higher LDH release and reduced membrane integrity were seen in BEAS-2B cells treated for 24 h with higher concentrations of nicotine-containing condensates. ACE2 protein expression was observably increased in all treatments compared to cell controls, particularly for 24 h exposures. ACE2 gene expression was significantly increased in cells exposed to the locally bought e-liquid condensate with high nicotine concentration and cigarette smoke extract compared with cell controls. Our study suggests that vaping alone and smoking alone can result in an increase in lung ACE2 expression. Vaping and smoking are avoidable risk factors for COVID-19, which, if avoided, could help reduce the number of COVID-19 cases and the severity of the disease. This is the first study to utilize electronic cigarette aerosol condensates, novel and developed in our laboratory, for investigating ACE2 expression in human airway epithelial cells. Full article

(This article belongs to the Special Issue Pharmacology and Therapeutic of Asthma and COPD)

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11 pages, 2161 KiB

Open AccessArticle

The Long-Term Effectiveness of Omalizumab in Adult Patients with Severe Allergic Asthma: Continuous Treatment Versus Boosting Treatment

by Wei-Chang Huang, Pin-Kuei Fu, Ming-Cheng Chan, Chun-Shih Chin, Wen-Nan Huang, Kuo-Lung Lai, Jiun-Long Wang, Wei-Ting Hung, Yi-Da Wu, Chia-Wei Hsieh, Ming-Feng Wu, Yi-Hsing Chen and Jeng-Yuan Hsu

J. Clin. Med. 2021, 10(4), 707; https://doi.org/10.3390/jcm10040707 - 11 Feb 2021

Cited by 9 | Viewed by 3205

Abstract

The implications of boosting Omalizumab treatment (OT) in patients with severe allergic asthma (SAA) remain unclear. The study aimed to explore and compare the 12-month effectiveness between continuous, at least 10-month OT (continuation group) and four-month boost of Omalizumab (boost group) in adult [...] Read more.

The implications of boosting Omalizumab treatment (OT) in patients with severe allergic asthma (SAA) remain unclear. The study aimed to explore and compare the 12-month effectiveness between continuous, at least 10-month OT (continuation group) and four-month boost of Omalizumab (boost group) in adult patients with SAA. In this retrospective cohort study, clinical data were collected for further analysis. Of all participants (n = 124), a significant reduction in annual exacerbations (baseline = 0.8 ± 1.5, follow-up = 0.5 ± 1.0, p = 0.047 *) and improvement in small airway ventilation as evaluated by forced expiratory flow at 25–75% (baseline = 55.1 ± 11.1%, follow-up = 59.4 ± 8.4%, p < 0.001 *) were found in the continuation group (n = 110). By contrast, the boost group (n = 14) had significantly increased annual exacerbations (baseline = 0.7 ± 1.4, follow-up = 2.9 ± 3.6, p = 0.031 *) and impaired small airway function (baseline = 55.3 ± 12.9, follow-up = 52.1 ± 12.5, p = 0.026 *). Furthermore, the continuation group rather than the boost group had significant decreases in the frequency of oral corticosteroid (OCS) use as controllers (baseline = 32.7%, follow-up = 20.0%, p = 0.047 *; baseline = 50.0%, follow-up = 21.4%, p = 0.237, respectively) and OCS maintenance dose (mg/month) (baseline = 85.9 ± 180.8, follow-up = 45.8 ± 106.6, p = 0.020 *; baseline = 171.4 ± 221.5, follow-up = 50.0 ± 104.3, p = 0.064, respectively), and increases in asthma control test scores (baseline = 16.0 ± 3.0, follow-up = 19.8 ± 4.4, p < 0.001 *; baseline = 14.6 ± 3.8, follow-up = 19.7 ± 4.7, p = 0.050, respectively). Continuous OT would be beneficial for adult patients with SAA, while boost of Omalizumab would worsen their long-term outcomes. Full article

(This article belongs to the Special Issue Pharmacology and Therapeutic of Asthma and COPD)

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Review

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11 pages, 255 KiB

Open AccessReview

Considerations for and Mechanisms of Adjunct Therapy in COPD

by Rachana Mandru, Christine Y. Zhou, Rachel Pauley and Robert M. Burkes

J. Clin. Med. 2021, 10(6), 1225; https://doi.org/10.3390/jcm10061225 - 16 Mar 2021

Cited by 6 | Viewed by 3037

Abstract

Inhaled bronchodilators and corticosteroids, when indicated, form the backbone of COPD therapy. However, over the last decade there has been an emergence of adjunct therapies in oral or inhaled form that are now part of the therapeutic approach to COPD. While these therapies [...] Read more.

Inhaled bronchodilators and corticosteroids, when indicated, form the backbone of COPD therapy. However, over the last decade there has been an emergence of adjunct therapies in oral or inhaled form that are now part of the therapeutic approach to COPD. While these therapies have shown to be beneficial when used in the appropriate instances, there are particular considerations that need to be minded when using these therapies. This review article discussed the mechanism of roflumilast, macrolide antibiotics, other chronic antibiotic regimens, vitamin D supplementation, oral corticosteroids, n-acetylcysteine, and nebulized hypertonic saline, the clinical data behind each of these therapies, adverse events associated with therapy, and the expert recommendations for their utilization. Our goal is to provide a brief but informative and clinically useful review of commonly encountered therapies used in advanced COPD. Full article

(This article belongs to the Special Issue Pharmacology and Therapeutic of Asthma and COPD)

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