Editorial

4 pages, 232 KiB

Open AccessEditorial

Respiratory Immune Responses during Infection and Pollution Inhalation

by Cormac McCarthy and Patrick Geraghty

Medicina 2023, 59(2), 242; https://doi.org/10.3390/medicina59020242 - 27 Jan 2023

Viewed by 949

The COVID-19 pandemic highlighted the importance of lung immune responses to pathogens and environmental factors [...] Full article

(This article belongs to the Special Issue Respiratory Immune Responses during Infection and Pollution Inhalation)

Research

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11 pages, 547 KiB

Open AccessArticle

Procalcitonin Levels in COVID-19 Patients Are Strongly Associated with Mortality and ICU Acceptance in an Underserved, Inner City Population

by Theresa Feng, Alecia James, Kyra Doumlele, Seth White, Wendy Twardzik, Kanza Zahid, Zeeshan Sattar, Osato Ukponmwan, Mohamd Nakeshbandi, Lillian Chow and Robert Foronjy

Medicina 2021, 57(10), 1070; https://doi.org/10.3390/medicina57101070 - 07 Oct 2021

Cited by 6 | Viewed by 1831

Abstract

Background and Objectives: This study aimed to identify demographic and clinical factors at the time of critical care consultation associated with mortality or intensive care unit acceptance in a predominantly Afro-Caribbean population during the first wave of the COVID19 pandemic. Materials and [...] Read more.

Background and Objectives: This study aimed to identify demographic and clinical factors at the time of critical care consultation associated with mortality or intensive care unit acceptance in a predominantly Afro-Caribbean population during the first wave of the COVID19 pandemic. Materials and Methods: This retrospective, single-center observational cohort study included 271 COVID19 patients who received a critical care consult between March 11 and April 30, 2020 during the first wave of the COVID19 pandemic at State University of New York Downstate Health Sciences University. Results: Of the 271 patients with critical care consults, 33% survived and 67% expired. At the bivariate level, age, blood urea nitrogen, and blood neutrophil percentage were significantly associated with mortality (mean age: survivors, 61.62 ± 1.50 vs. non-survivors, 68.98 ± 0.85, p < 0.001). There was also a significant association between neutrophil% and mortality in the univariate logistic regression model (quartile 4 vs. quartile 1: odd ratio 2.73, 95% confidence interval (1.28–5.82), p trend = 0.044). In the multivariate analyses, increasing levels of procalcitonin and C-reactive protein were significantly associated with mortality, adjusting for age, sex, and race/ethnicity (for procalcitonin quartile 4 vs. quartile 1: odds ratio 5.65, 95% confidence interval (2.14–14.9), p trend < 0.001). In contrast, higher platelet levels correlated with significantly decreased odds of mortality (quartile 4 vs. quartile 1, odds ratio 0.47, 95% CI (0.22–0.998), p trend = 0.010). Of these factors, only elevated procalcitonin levels were associated with intensive care unit acceptance. Conclusions: Procalcitonin showed the greatest magnitude of association with both death and likelihood of intensive care unit acceptance at the bivariate level. Our data suggests that procalcitonin reflects pneumonia severity during COVID-19 infection. Thus, it may help the intensivist identify those COVID19 patients who require intensive care unit level care. Full article

(This article belongs to the Special Issue Respiratory Immune Responses during Infection and Pollution Inhalation)

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11 pages, 1310 KiB

Open AccessArticle

Alpha-1 Antitrypsin Augmentation Inhibits Proteolysis of Neutrophil Membrane Voltage-Gated Proton Channel-1 in Alpha-1 Deficient Individuals

by Padraig Hawkins, Julian Sya, Nee Kee Hup, Mark P. Murphy, Noel G. McElvaney and Emer P. Reeves

Medicina 2021, 57(8), 814; https://doi.org/10.3390/medicina57080814 - 10 Aug 2021

Cited by 2 | Viewed by 2529

Abstract

Background and Objectives: Alpha-1 antitrypsin is a serine protease inhibitor that demonstrates an array of immunomodulatory functions. Individuals with the genetic condition of alpha-1 antitrypsin deficiency (AATD) are at increased risk of early onset emphysematous lung disease. This lung disease is partly [...] Read more.

Background and Objectives: Alpha-1 antitrypsin is a serine protease inhibitor that demonstrates an array of immunomodulatory functions. Individuals with the genetic condition of alpha-1 antitrypsin deficiency (AATD) are at increased risk of early onset emphysematous lung disease. This lung disease is partly driven by neutrophil mediated lung destruction in an environment of low AAT. As peripheral neutrophil hyper-responsiveness in AATD leads to excessive degranulation and increased migration to the airways, we examined the expression of the membrane voltage-gated proton channel-1 (HVCN1), which is integrally linked to neutrophil function. The objectives of this study were to evaluate altered HVCN1 in AATD neutrophils, serine protease-dependent degradation of HVCN1, and to investigate the ability of serum AAT to control HVCN1 expression. Materials and Methods: Circulating neutrophils were purified from AATD patients (n = 20), AATD patients receiving AAT augmentation therapy (n = 3) and healthy controls (n = 20). HVCN1 neutrophil expression was assessed by flow cytometry and Western blot analysis. Neutrophil membrane bound elastase was measured by fluorescence resonance energy transfer. Results: In this study we demonstrated that HVCN1 protein is under-expressed in AATD neutrophils (p = 0.02), suggesting a link between reduced HVCN1 expression and AAT deficiency. We have demonstrated that HVCN1 undergoes significant proteolytic degradation in activated neutrophils (p < 0.0001), primarily due to neutrophil elastase activity (p = 0.0004). In addition, the treatment of AATD individuals with AAT augmentation therapy increased neutrophil plasma membrane HVCN1 expression (p = 0.01). Conclusions: Our results demonstrate reduced levels of HVCN1 in peripheral blood neutrophils that may influence the neutrophil-dominated immune response in the AATD airways and highlights the role of antiprotease treatment and specifically AAT augmentation therapy in protecting neutrophil membrane expression of HVCN1. Full article

(This article belongs to the Special Issue Respiratory Immune Responses during Infection and Pollution Inhalation)

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9 pages, 591 KiB

Open AccessEditor’s ChoiceArticle

Short-Term Effects of a Conditioning Telerehabilitation Program in Confined Patients Affected by COVID-19 in the Acute Phase. A Pilot Randomized Controlled Trial

by Cleofas Rodriguez-Blanco, Juan Jose Gonzalez-Gerez, Carlos Bernal-Utrera, Ernesto Anarte-Lazo, Manuel Perez-Ale and Manuel Saavedra-Hernandez

Medicina 2021, 57(7), 684; https://doi.org/10.3390/medicina57070684 - 03 Jul 2021

Cited by 45 | Viewed by 4967

Abstract

Background and objectives: The COVID-19 pandemic has become a challenge for health systems and, specifically, to physical therapists obligated to adapt their job and stop face-to-face consultations. In this situation, therapeutic exercise has been implemented in different COVID-19 patients. This study evaluated [...] Read more.

Background and objectives: The COVID-19 pandemic has become a challenge for health systems and, specifically, to physical therapists obligated to adapt their job and stop face-to-face consultations. In this situation, therapeutic exercise has been implemented in different COVID-19 patients. This study evaluated the feasibility and effectiveness of a novel therapeutic exercise program through telerehabilitation tools in COVID-19 patients with mild to moderate symptomatology in the acute stage. Materials and Methods: A total of 40 subjects were randomized an experimental group, based on muscle conditioning, and in a control group, who did not perform physical activity. Thirty-six subjects, 18 in each group, completed the one-week intervention. We measured the six-minute walking test, multidimensional dyspnoea-12, thirty seconds sit-to-stand test, and Borg Scale. Results: Both groups were comparable at baseline. Statistically significant improvement between groups (p < 0.05) in favor of the experimental group was obtained. No differences between gender were found (p > 0.05). Ninety percent adherence was found in our program. Conclusion: A one-week telerehabilitation program based on muscle toning exercise is effective, safe, and feasible in COVID-19 patients with mild to moderate symptomatology in the acute stage. Full article

(This article belongs to the Special Issue Respiratory Immune Responses during Infection and Pollution Inhalation)

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Review

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27 pages, 1518 KiB

Open AccessReview

Senescence: Pathogenic Driver in Chronic Obstructive Pulmonary Disease

by Melissa Rivas, Gayatri Gupta, Louis Costanzo, Huma Ahmed, Anne E. Wyman and Patrick Geraghty

Medicina 2022, 58(6), 817; https://doi.org/10.3390/medicina58060817 - 17 Jun 2022

Cited by 8 | Viewed by 4809

Abstract

Chronic obstructive pulmonary disease (COPD) is recognized as a disease of accelerated lung aging. Over the past two decades, mounting evidence suggests an accumulation of senescent cells within the lungs of patients with COPD that contributes to dysregulated tissue repair and the secretion [...] Read more.

Chronic obstructive pulmonary disease (COPD) is recognized as a disease of accelerated lung aging. Over the past two decades, mounting evidence suggests an accumulation of senescent cells within the lungs of patients with COPD that contributes to dysregulated tissue repair and the secretion of multiple inflammatory proteins, termed the senescence-associated secretory phenotype (SASP). Cellular senescence in COPD is linked to telomere dysfunction, DNA damage, and oxidative stress. This review gives an overview of the mechanistic contributions and pathologic consequences of cellular senescence in COPD and discusses potential therapeutic approaches targeting senescence-associated signaling in COPD. Full article

(This article belongs to the Special Issue Respiratory Immune Responses during Infection and Pollution Inhalation)

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19 pages, 1642 KiB

Open AccessReview

Vaping-Associated Lung Injury: A Review

by Marissa O'Callaghan, Niamh Boyle, Aurelie Fabre, Michael P. Keane and Cormac McCarthy

Medicina 2022, 58(3), 412; https://doi.org/10.3390/medicina58030412 - 10 Mar 2022

Cited by 8 | Viewed by 6914

Abstract

Since commercial development in 2003, the usage of modern electronic cigarette (e-cigarette) continues to increase amongst people who have never smoked, ex-smokers who have switched to e-cigarettes, and dual-users of both conventional cigarettes and e-cigarettes. With such an increase in use, knowledge of [...] Read more.

Since commercial development in 2003, the usage of modern electronic cigarette (e-cigarette) continues to increase amongst people who have never smoked, ex-smokers who have switched to e-cigarettes, and dual-users of both conventional cigarettes and e-cigarettes. With such an increase in use, knowledge of the irritative, toxic and potential carcinogenic effects on the lungs is increasing. This review article will discuss the background of e-cigarettes, vaping devices and explore their popularity. We will further summarise the available literature describing the mechanism of lung injury caused by e-cigarette or vaping use. Full article

(This article belongs to the Special Issue Respiratory Immune Responses during Infection and Pollution Inhalation)

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16 pages, 8329 KiB

Open AccessFeature PaperReview

Deciphering Respiratory-Virus-Associated Interferon Signaling in COPD Airway Epithelium

by Hong Guo-Parke, Dermot Linden, Sinéad Weldon, Joseph C. Kidney and Clifford C. Taggart

Medicina 2022, 58(1), 121; https://doi.org/10.3390/medicina58010121 - 13 Jan 2022

Cited by 8 | Viewed by 2548

Abstract

COPD is a chronic lung disorder characterized by a progressive and irreversible airflow obstruction, and persistent pulmonary inflammation. It has become a global epidemic affecting 10% of the population, and is the third leading cause of death worldwide. Respiratory viruses are a primary [...] Read more.

COPD is a chronic lung disorder characterized by a progressive and irreversible airflow obstruction, and persistent pulmonary inflammation. It has become a global epidemic affecting 10% of the population, and is the third leading cause of death worldwide. Respiratory viruses are a primary cause of COPD exacerbations, often leading to secondary bacterial infections in the lower respiratory tract. COPD patients are more susceptible to viral infections and associated severe disease, leading to accelerated lung function deterioration, hospitalization, and an increased risk of mortality. The airway epithelium plays an essential role in maintaining immune homeostasis, and orchestrates the innate and adaptive responses of the lung against inhaled and pathogen insults. A healthy airway epithelium acts as the first line of host defense by maintaining barrier integrity and the mucociliary escalator, secreting an array of inflammatory mediators, and initiating an antiviral state through the interferon (IFN) response. The airway epithelium is a major site of viral infection, and the interaction between respiratory viruses and airway epithelial cells activates host defense mechanisms, resulting in rapid virus clearance. As such, the production of IFNs and the activation of IFN signaling cascades directly contributes to host defense against viral infections and subsequent innate and adaptive immunity. However, the COPD airway epithelium exhibits an altered antiviral response, leading to enhanced susceptibility to severe disease and impaired IFN signaling. Despite decades of research, there is no effective antiviral therapy for COPD patients. Herein, we review current insights into understanding the mechanisms of viral evasion and host IFN antiviral defense signaling impairment in COPD airway epithelium. Understanding how antiviral mechanisms operate in COPD exacerbations will facilitate the discovery of potential therapeutic interventions to reduce COPD hospitalization and disease severity. Full article

(This article belongs to the Special Issue Respiratory Immune Responses during Infection and Pollution Inhalation)

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20 pages, 1634 KiB

Open AccessReview

The Upper Airway Microbiota, Environmental Exposures, Inflammation, and Disease

by Ziyad Elgamal, Pratyush Singh and Patrick Geraghty

Medicina 2021, 57(8), 823; https://doi.org/10.3390/medicina57080823 - 14 Aug 2021

Cited by 14 | Viewed by 4198

Abstract

Along with playing vital roles in pathogen exclusion and immune system priming, the upper airways (UAs) and their microbiota are essential for myriad physiological functions such as conditioning and transferring inhaled air. Dysbiosis, a microbial imbalance, is linked with various diseases and significantly [...] Read more.

Along with playing vital roles in pathogen exclusion and immune system priming, the upper airways (UAs) and their microbiota are essential for myriad physiological functions such as conditioning and transferring inhaled air. Dysbiosis, a microbial imbalance, is linked with various diseases and significantly impedes the quality of one’s life. Daily inhaled exposures and/or underlying conditions contribute to adverse changes to the UA microbiota. Such variations in the microbial community exacerbate UA and pulmonary disorders via modulating inflammatory and immune pathways. Hence, exploring the UA microbiota’s role in maintaining homeostasis is imperative. The microbial composition and subsequent relationship with airborne exposures, inflammation, and disease are crucial for strategizing innovating UA diagnostics and therapeutics. The development of a healthy UA microbiota early in life contributes to normal respiratory development and function in the succeeding years. Although different UA cavities present a unique microbial profile, geriatrics have similar microbes across their UAs. This lost community segregation may contribute to inflammation and disease, as it stimulates disadvantageous microbial–microbial and microbial–host interactions. Varying inflammatory profiles are associated with specific microbial compositions, while the same is true for many disease conditions and environmental exposures. A shift in the microbial composition is also detected upon the administration of numerous therapeutics, highlighting other beneficial and adverse side effects. This review examines the role of the UA microbiota in achieving homeostasis, and the impact on the UAs of environmental airborne pollutants, inflammation, and disease. Full article

(This article belongs to the Special Issue Respiratory Immune Responses during Infection and Pollution Inhalation)

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Other

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8 pages, 1728 KiB

Open AccessCase Report

The Use of Targeted Monoclonal Antibodies in the Treatment of ABPA—A Case Series

by Aoife O’Reilly and Eleanor Dunican

Medicina 2022, 58(1), 53; https://doi.org/10.3390/medicina58010053 - 29 Dec 2021

Cited by 6 | Viewed by 2092

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder occurring in response to Aspergillus fumigatus that can complicate the course of asthma and cystic fibrosis. Here we present a case of acute ABPA without central bronchiectasis, a case of chronic active ABPA with central [...] Read more.

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder occurring in response to Aspergillus fumigatus that can complicate the course of asthma and cystic fibrosis. Here we present a case of acute ABPA without central bronchiectasis, a case of chronic active ABPA with central bronchiectasis, and a case of severe relapsing ABPA with central bronchiectasis. All three were initially treated with corticosteroids and antifungal agents but had an incomplete response. These patients were then treated with anti-IgE therapy with omalizumab before being switched to the anti-IL5R agent benralizumab. They responded well to both agents. These case reports highlight the potential role of omalizumab and benralizumab in the treatment of ABPA, but further studies are required to evaluate the effectiveness of these medications. Longer follow-up periods and objective measurements of the impact of treatment are necessary. Full article

(This article belongs to the Special Issue Respiratory Immune Responses during Infection and Pollution Inhalation)

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