Colonic Mucosal Immune Activation in Mice with Ovalbumin-Induced Allergic Airway Disease: Association between Allergic Airway Disease and Irritable Bowel Syndrome

Recent studies on the pathophysiology of irritable bowel syndrome (IBS) have focused on the role of mast cells (MCs) in intestinal mucosal immunity. A link between allergic airway diseases (AADs) and IBS has been suggested because both diseases have similar pathophysiology. We aimed to investigate whether the induction of AAD in mice could lead to inflammation of the colonic mucosa, similar to IBS. We also evaluated whether this inflammatory response could be suppressed by administering a therapeutic agent. Mice were divided into three groups: control, AAD-induced, and salbutamol-treated. An AAD mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin. Mice with AAD were intranasally administered salbutamol. Analyses of cytokine levels, MC count, and tryptase levels in the intestinal mucosa were performed to compare the changes in inflammatory responses among the three groups. Inflammation was observed in the intestinal mucosa of mice in the AAD group. This inflammation in AAD mice was suppressed after salbutamol treatment. Our study demonstrates that AAD induces an inflammatory response similar to that in IBS, suggesting a possible association between IBS and AADs. In patients with IBS with such allergic components, salbutamol may have the potential to alleviate the inflammatory response.

Systemic and local cytokine profile and risk factors for persistent allergic airway inflammation in patients sensitised to house dust mite allergens

Objective To evaluate cytokine profile, vitamin D status, symptom score and quality of life in patients with persistent allergic airway diseases sensitised to house dust mites (HDM) in comparison with healthy individuals. Material and methods Patients sensitized to HDM with persistent AR and having symptoms for at least 2 years with or without AA were involved into the study. Measurements of vitamin D level in serum and IL-10, IL-13, IL-17, IL-22, IL-33 and IFN-gamma in serum and nasal lavage were performed by ELISA. Results Eighty-one subjects were involved into the study. Serum IL-10 concentration was higher in patients with AR than in patients with AR and AA (6.71 ± 1.73 vs. 1.98 ± 0.24, p < 0.05). IFN-gamma level in nasal lavage was higher in patients with AR and AA than in patients with AR (p < 0.01) and healthy individuals (p < 0.05) (7.50 ± 0.37 vs. 6.80 ± 0.99 vs. 6.50 ± 0.22). Serum IL-22 negatively correlated with IL-22 in nasal lavage, whereas serum IFN-gamma positively correlated with IFN-gamma in nasal lavage. Positive correlation between serum IL-17 and total IgE and negative correlation between IL-17 in nasal lavage and eosinophils in nasal smear were found in patients with AR and AA. Serum IFN-gamma decreased the risk of AR for healthy individuals. Serum IL-10 and vitamin D decreased risk for development of AA for patients with AR. IL-22 in serum and IL-10 and IL-33 in nasal lavage increased this risk. Conclusion Novel cytokines such as IL-22, IL-17 and IL-33 and vitamin D may be involved in pathogenesis of persistent airway inflammation in patients sensitized to HDM.

The use of treatable traits to address COPD complexity and heterogeneity and to inform the care

COPD is complex and heterogeneous with respect to its aetiology, clinical presentation, phenotypes and biological mechanisms. Despite this, COPD is still diagnosed and treated according to simple clinical measures, including airflow limitation, symptoms and exacerbation frequency, leading to failure to recognise the disease's heterogeneity and/or to provide targeted interventions. COPD continues to have a very large burden of disease with suboptimal outcomes for people with the disease, including frequent hospitalisation with exacerbations, rapid lung function decline, multimorbidity and death from respiratory failure. In light of this, there have been increasing calls for a renewed taxonomy with better characterisation of COPD phenotypes and endotypes. This would allow the unravelling of COPD's complexity and heterogeneity, the implementation of targeted interventions and improved patient outcomes. The treatable traits strategy is a proposed vehicle for the implementation of precision medicine in chronic airway diseases. In this review, in addition to summarising the key knowledge on the heterogeneity of COPD, we refer to the existing evidence pertaining to the treatable traits strategy as applied in COPD and discuss implementation in different settings.

Decreased eosinophil counts and elevated lactate dehydrogenase predict severe COVID-19 in patients with underlying chronic airway diseases

BackgroundSeveral predictors of COVID-19 severity have been reported. However, chronic airway inflammation characterised by accumulated lymphocytes or eosinophils may affect the pathogenesis of COVID-19.MethodsIn this retrospective cohort study, we reviewed the medical records of all patients with laboratory-confirmed COVID-19 with chronic bronchitis, chronic obstructive pulmonary disease (COPD) and asthma admitted to the Sino-French New City Branch of Tongji Hospital, a large regional hospital in Wuhan, China, from 26 January to 3 April. The Tongji Hospital Ethics Committee approved this study.ResultsThere were 59 patients with chronic bronchitis, COPD and asthma. When compared with non-severe patients, severe patients were more likely to have decreased lymphocyte counts (0.6×10⁹/L vs 1.1×10⁹/L, p<0.001), eosinopaenia (<0.02×10⁹/L; 73% vs 24%, p<0.001), increased lactate dehydrogenase (LDH) (471.0 U/L vs 230.0 U/L, p<0.001) and elevated interleukin 6 level (47.4 pg/mL vs 5.7 pg/mL, p=0.002) on admission. Eosinopaenia and elevated LDH were significantly associated with disease severity in both univariate and multivariate regression models including the above variables. Moreover, eosinophil count and LDH level tended to return to normal range over time in both groups after treatment and severe patients recovered slower than non-severe patients, especially in eosinophil count.ConclusionsEosinopaenia and elevated LDH are potential predictors of disease severity in patients with COVID-19 with underlying chronic airway diseases. In addition, they could indicate disease progression and treatment effectiveness.

Influence of SARS-CoV-2 on airway mucus production: A review and proposed model

Coronavirus disease 2019 (COVID-19) is a worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has affected millions of lives. Individuals who survive severe COVID-19 can experience sustained respiratory symptoms that persist for months after initial infection. In other airway diseases, abnormal airway mucus contributes to sustained airway symptoms. However, the impact of SARS-CoV-2 on airway mucus has received limited attention. In the current review, we assess literature describing the impact of SARS-CoV-2 on airway pathophysiology with specific emphasis on mucus production. Accumulating evidence suggests that the 2 major secreted airway mucin glycoproteins, MUC5AC and MUC5B, are abnormal in some patients with COVID-19. Aberrations in MUC5AC or MUC5B in response to SARS-CoV-2 infection are likely due to inflammation, though the responsible mechanisms have yet to be determined. Thus, we also provide a proposed model highlighting mechanisms that can contribute to acute and sustained mucus abnormalities in SARS-CoV-2, with an emphasis on inflammatory cells and mediators, including mast cells and histamine. Last, we bring to light the challenges of studying abnormal mucus production in SARS-CoV-2 infections and discuss the strengths and limitations of model systems commonly used to study COVID-19. The evidence to date suggests that ferrets, nonhuman primates, and cats may have advantages over other models to investigate mucus in COVID-19.