Journal of Respiration

Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological function in vitro and in vivo. A thorough investigation of therapeutic effects of EVs in asthma has not been conducted. Therefore, this systematic review is designed to synthesize recent literature on the therapeutic effects of EVs on physiological and biological outcomes of asthma in pre-clinical studies. An electronic search of Web of Science, EMBASE, MEDLINE, and Scopus will be conducted on manuscripts published in the last five years that adhere to standardized guidelines for EV research. Grey literature will also be included. Two reviewers will independently screen the selected studies for title and abstract, and full text based on the eligibility criteria. Data will be extracted, narratively synthesized and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will summarize the current knowledge from preclinical studies investigating the therapeutic effects of EVs on asthma. The results will delineate whether EVs can mitigate biological hallmarks of asthma, and if so, describe the underlying mechanisms involved in the process. This insight is crucial for identifying key pathways that can be targeted to alleviate the burden of asthma. The data will also reveal the origin, dosage and biophysical characteristics of beneficial EVs. Overall, our results will provide a scaffold for future intervention and translational studies on asthma treatment. Full article

Spontaneous pneumothorax can be divided into two categories: primary and secondary. The management of each one depends on resource availability, physician preference, and procedural capability, and is broadly based on guidelines that are over a decade old. Emerging evidence from three recent randomized controlled trials on ambulatory pneumothorax pathways are exciting and herald a new era for management of spontaneous pneumothorax. These three trials and their implications are discussed. Full article

Air pollution, particularly fine and ultrafine particulate matter aerosols, underlies a wide range of communicable and non-communicable disease affecting many systems including the cardiopulmonary and immune systems, and arises primarily from transportation and industry. A number of air pollution driven diseases also are Covid19 comorbidities. Thus, a number of studies on air pollution exposure, particularly particulate matter, strongly indicate air pollution is an important underlying factor in Covid19 transmission, severity, and mortality. This suggests that air pollution from natural sources, particularly wildfires, could play a role in the Covid19 pandemic. We tested this hypothesis on three wildfire smoke events in Orange County, CA, each of which was followed by Covid19 case increases after an approximately one-week lag. This lag was consistent with combined incubation time and testing/reporting times. Moreover, the three events suggest a dose dependency. The wildfire comorbidity hypothesis implies that at-risk-populations should reduce smoke exposure from wildfires, as well as indoors from biomass burning for heating, cooking, and aesthetic purposes. Full article

The safety of electronic cigarettes (e-cigarettes) is a major topic of discussion. The key goals of this study were to examine the contents of e-cigarette vapor and determine if nicotine altered inflammatory responses against respiratory syncytial virus (RSV) infection. E-cigarette vapor was passed through a hollow 3D-model of an adult lung, and gas chromatography detected over 50 compounds passed through the 3D model, including nicotine, propylene glycol (PG), ethanol, methanol, and diacetyl. The murine alveolar macrophage cell line MH-S cells were exposed to nicotine and e-cigarette vapor with and without nicotine. Nicotine significantly induced the expression of matrix metalloprotease (Mmp) 12 and reduced expression of Ifnβ and Tnfα. To examine the role of nicotine in lung defense against RSV infection, A/J mice were exposed to PBS, e-cigarette vapor with and without nicotine for 2 months before RSV infection. E-cigarette vapor did not influence RSV infection-induced animal weight loss, RSV infectivity, airway hyperresponsiveness during methacholine challenge, or immune cell infiltration into the lungs. However, e-cigarette vapor containing nicotine enhanced obstruction and induced secretion of MMP12 and reduced levels of Ifnβ and TNFα. In conclusion, nicotine in vaping products modulates immune responses that may impact the lungs during a respiratory infection. Full article

The Coronavirus Disease-2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has claimed 1.2 million people globally since December 2019. Although the host factors underpinning COVID-19 pathology are not fully understood, type I interferon (IFN-I) response is considered crucial for SARS-CoV-2 pathogenesis. Perturbations in IFN-I signaling and associated interferon-inducible genes (ISG) are among the primary disease severity indicators in COVID-19. Consequently, IFN-I therapy, either alone or in- combination with existing antiviral or anti-inflammatory drugs, is tested in many ongoing clinical trials to reduce COVID-19 mortality. Since signaling by the IFN-I family of molecules regulates host immune response to other infectious and non-infectious diseases, any imbalance in this family of cytokines would impact the clinical outcome of COVID-19, as well as other co-existing diseases. Therefore, it is imperative to evaluate the beneficial-versus-detrimental effects of IFN-I immunotherapy for COVID-19 patients with divergent disease severity and other co-existing conditions. This review article summarizes the role of IFN-I signaling in infectious and non-infectious diseases of humans. It highlights the precautionary measures to be considered before administering IFN-I to COVID-19 patients having other co-existing disorders. Finally, suggestions are proposed to improve IFN-I immunotherapy to COVID-19. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the current pandemic of coronavirus disease 2019 (COVID-19), and COVID-19 vaccines focus on its spike protein. However, in addition to facilitating the membrane fusion and viral entry, the SARS-CoV-2 spike protein promotes cell growth signaling in human lung vascular cells, and patients who have died of COVID-19 have thickened pulmonary vascular walls, linking the spike protein to a fatal disease, pulmonary arterial hypertension (PAH). In addition to SARS-CoV spike proteins, gp120, the viral membrane fusion protein of human immunodeficiency virus (HIV), has been reported to promote cell signaling, and long-term surviving HIV-positive patients have a high incidence of developing PAH. This article describes the findings of the SARS-CoV-2 spike protein affecting lung vascular cells and explains how the spike protein possibly increases the incidence of PAH. Since the SARS-CoV-2 spike protein will be administered to millions of people as COVID-19 vaccines, it is critical to understand the biological effects of this protein on human cells to ensure that it does not promote long-term adverse health consequences. Full article

Tau, a microtubule-associated protein, plays a critical role in the pathophysiology of neurons. However, whether tau protein is expressed in smooth muscle cells is unknown. Thus, we tested the hypothesis that tau protein is expressed in the primary cultures of smooth muscle cells. Here, we report that tau protein is expressed and constitutively phosphorylated at threonine 181 in various smooth muscle cell types, including human pulmonary artery smooth muscle cells, bronchial airway smooth muscle cells, and cerebral artery smooth muscle cells. Immunofluorescence staining revealed that phosphorylated tau at threonine 181 is more organized in the cell than is total tau protein. A protein phosphatase inhibitor, calyculin A, induced the formation of higher molecular weight species of phosphorylated tau, as visualized by Western blotting, indicating the occurrence of tau aggregation. Immunofluorescence analysis also showed that calyculin A caused the aggregation of phosphorylated tau and disrupted the cytoskeletal organization. These results demonstrate the existence of tau protein in smooth muscle cells, and that smooth muscle tau is susceptible to protein phosphorylation and aggregation. Lung smooth muscle tau may therefore play an important role in pulmonary pathophysiology. Full article

Airway obstruction with chronic inflammation and infection are major contributors to the lung damage and mortality of cystic fibrosis (CF). A better understanding of the congested milieu of CF airways will aid in improving therapeutic strategies. This article retrospectively reports our observations, and discusses insights gained in the handling and analysis of CF sputa. CF and non-CF mucus samples were surveyed for morphological features by electron microscopy and analyzed for the macromolecular dry weight (MDW), total protein, lipid, carbohydrate, and DNA. Mucus character was investigated with chemical solubilization time as a comparative tool. CF mucus appeared distinctly thick, viscous, and heterogeneous, with neutrophils as the dominant immune cell. CF sputum DNA content varied markedly for and between individuals (~1–10% MDW), as did solubilization times (~1–20 h). CF Sputum DNA up to 7.1% MDW correlated positively with solubilization time, whereas DNA >7.1% MDW correlated negatively. 3D analysis of CF sputa DNA, GP, and solubilization times revealed a dynamic and predictive relationship. Reflecting on the heterogeneous content and character of CF mucus, and the possible interplay in space and time in the respiratory tract of polymeric DNA and mucous glycoproteins, we highlight it’s potential to affect infection-related airway pathologies and the success of therapeutic interventions. Full article

Objective: To evaluate the clinical effect of omalizumab therapy on the symptoms of patients with chronic rhinosinusitis (CRS). Methods: This cross-sectional study evaluated CRS major symptom improvement in patients with CRS on omalizumab therapy and patients who met omalizumab therapy indications, but could not access coverage for omalizumab. Changes in overall chronic rhinosinusitis symptom burden and each of the major symptoms of CRS were rated on a 10 cm visual analogue scale (VAS). The Mann–Whitney test was used to compare the symptom improvement between groups. Results: Omalizumab therapy provided a mean overall symptom improvement of 69.5% (individual symptom improvement: facial pain 78.5%, nasal obstruction 69.8%, rhinorrhea 56.2%, and olfaction 55.8%). For the control group, mean overall symptom improvement since omalizumab screening was 16.8% (individual symptom improvement: rhinorrhea 16.4%, nasal obstruction 15.3%, no improvement in facial pain or olfaction). Overall, and for each major symptom, improvement was significantly greater for omalizumab treated patients (p < 0.05). Conclusion: Omalizumab treatment provided significant improvement in every major clinical symptom of CRS in the treated cohort of patients with recalcitrant CRS, in comparison to the control cohort. A well-designed randomized clinical trial is needed to further assess the efficacy and safety of omalizumab treatment for CRS. Full article