Respiratory Airway Inflammation Research Articles

A smart mask for exhaled breath condensate harvesting and analysis.

Recent respiratory outbreaks have garnered substantial attention, yet most respiratory monitoring remains confined to physical signals. Exhaled breath condensate (EBC) harbors rich molecular information that could unveil diverse insights into an individual's health. Unfortunately, challenges related to sample collection and the lack of on-site analytical tools impede the widespread adoption of EBC analysis. Here, we introduce EBCare, a mask-based device for real-time in situ monitoring of EBC biomarkers. Using a tandem cooling strategy, automated microfluidics, highly selective electrochemical biosensors, and a wireless reading circuit, EBCare enables continuous multimodal monitoring of EBC analytes across real-life indoor and outdoor activities. We validated EBCare's usability in assessing metabolic conditions and respiratory airway inflammation in healthy participants, patients with chronic obstructive pulmonary disease or asthma, and patients after COVID-19 infection.

A potent MAPK13-14 inhibitor prevents airway inflammation and mucus production.

Common respiratory diseases continue to represent a major public health problem, and much of the morbidity and mortality is due to airway inflammation and mucus production. Previous studies indicated a role for mitogen-activated protein kinase 14 (MAPK14) in this type of disease, but clinical trials are unsuccessful to date. Our previous work identified a related but distinct kinase known as MAPK13 that is activated in respiratory airway diseases and is required for mucus production in human cell-culture models. Support for MAPK13 function in these models came from effectiveness of MAPK13 versus MAPK14 gene-knockdown and from first-generation MAPK13-14 inhibitors. However, these first-generation inhibitors were incompletely optimized for blocking activity and were untested in vivo. Here we report the next generation and selection of a potent MAPK13-14 inhibitor (designated NuP-3) that more effectively downregulates type-2 cytokine-stimulated mucus production in air-liquid interface and organoid cultures of human airway epithelial cells. We also show that NuP-3 treatment prevents respiratory airway inflammation and mucus production in new minipig models of airway disease triggered by type-2 cytokine challenge or respiratory viral infection. The results thereby provide the next advance in developing a small-molecule kinase inhibitor to address key features of respiratory disease.NEW & NOTEWORTHY This study describes the discovery of a potent mitogen-activated protein kinase 13-14 (MAPK13-14) inhibitor and its effectiveness in models of respiratory airway disease. The findings thereby provide a scheme for pathogenesis and therapy of lung diseases [e.g., asthma, chronic obstructive pulmonary disease (COPD), Covid-19, postviral, and allergic respiratory disease] and related conditions that implicate MAPK13-14 function. The findings also refine a hypothesis for epithelial and immune cell functions in respiratory disease that features MAPK13 as a possible component of this disease process.

Role of Inflammatory Risk Factors in the Pathogenesis of Streptococcus pneumoniae.

Streptococcus pneumoniae (Spn) is a colonizer of the human nasopharynx (NP), causing a variety of infections in humans including otitis media, pneumonia, sepsis, and meningitis. The NP is an immune permissive site which allows for the persistence of commensal bacteria. Acute or chronic respiratory airway inflammation constitutes a significant risk factor for the manifestation of Spn infections. The inflammatory conditions caused by an upper respiratory viral infection or respiratory conditions such as allergic asthma and chronic obstructive pulmonary disorders (COPDs) are implicated in the dysregulation of airway inflammation and tissue damage, which compromise the respiratory barrier integrity. These immune events promote bacterial outgrowth leading to Spn dissemination and invasion into the bloodstream. Therefore, suppression of inflammation and restoration of respiratory barrier integrity could contain Spn infections manifesting in the backdrop of an inflammatory disease condition. The gained knowledge could be harnessed in the design of novel therapeutic interventions to circumvent Spn bacterial infections.

Psoriasis and Respiratory Comorbidities: The Added Value of Fraction of Exhaled Nitric Oxide as a New Method to Detect, Evaluate, and Monitor Psoriatic Systemic Involvement and Therapeutic Efficacy.

Psoriasis is a chronic inflammatory systemic disease characterized by a wide range of comorbidities. Respiratory comorbidities are currently poorly characterized and with discordant results. The systemic state of inflammation caused by psoriasis acts de novo on respiratory tissues and amplifies preexisting inflammation from asthma or chronic obstructive pulmonary disease. Because the lungs act as a gas exchanger between the internal and external environment, the impact of chronic psoriasis inflammation may be easily assessed through the analysis of exhaled breath. The fraction of exhaled nitric oxide test (FeNO) is a potential noninvasive solution that can provide quantitative and qualitative indices of respiratory airway inflammation. FeNO is routinely used to screen and manage asthmatic patients. Recent pilot studies contain encouraging data that underscore its possible use with systemic inflammatory nonpulmonary diseases, such as psoriasis. FeNO may therefore be a useful tool to evaluate underestimated airway inflammation and at the same time globally evaluate the impact of systemically antipsoriatic therapies.

Reliability Study Of The Technique To Assess Upper Respiratory Airway Inflammation In A Polluted Environment

Reliability Study Of The Technique To Assess Upper Respiratory Airway Inflammation In A Polluted Environment

Hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium induced by endotoxin.

To elucidate the mechanisms of epithelial mucus hypersecretion in upper respiratory airway inflammation, we produced hypertrophic and metaplastic changes of goblet cells in rat nasal respiratory epithelium by intranasal instillation of endotoxin. Significant increase of hypertrophic goblet cells was induced in the septal epithelium transversely sectioned at the level of incisive papilla at 24 h after the intranasal instillation of 0.1 mg of endotoxin. This change was completed after 3 d of endotoxin instillations and recovered by normal epithelium 7 d after the last instillation. Total cell number and the number of basal and ciliated cells counted over 2 mm of basal lamina did not change; however, the number of goblet cells increased and that of nongranulated secretory cells decreased time-dependently after endotoxin instillations. Mitotic rates examined after a 6-h colchicine metaphase blockade were very low at any time point studied, and cell division did not play a major role in this process. These results indicate that endotoxin induces hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium rather than a hyperplastic change, and this metaplasia is produced by direct conversion of nongranulated secretory cells into the goblet cells. Histochemical examination of this epithelium revealed that most of the mucus produced by these goblet cells was sulfomucin. Intraperitoneal injection of antirat neutrophil antiserum or cyclophosphamide depleted circulating blood neutrophils. Endotoxin-induced changes of goblet cells were significantly inhibited in these neutrophil-depleted rats, and intranasal instillation of elastase also induced hypertrophic and metaplastic changes of goblet cells.

Effects of Transient Neutrophil Influx on the Ultrastructural Morphology of Secretory Cells and Intraepithelial Mucosubstances in Canine Bronchi

Respiratory airway inflammation is often characterized by increased production and secretion of mucus from surface epithelium and by infiltration of airway lumens by inflammatory leukocytes (i.e. neutrophils). Both inflammatory exudation and hypersecretion of airway mucus are thought to be important factors in the pathogenesis of several obstructive pulmonary diseases, including chronic bronchitis and cystic fibrosis. To better understand the pathogenesis of inflammatory airway disorders, it is important to determine what changes in the mucus-secretory apparatus are due to the induced inflammatory process and what changes are due to the inhaled bacteria, toxicant, or other etiologic agent. We previously demonstrated that transepithelial migration of neutrophils elicits a transient depletion of mucosubstances stored in the nasal respiratory epithelium of the rat. This result suggested that neutrophil migration stimulates hypersecretion of mucus from nasal airway secretory cells. The purpose of the present study was to determine whether a transient neutrophi1-influx in the distal intrapulmonary bronchi will elicit a similar hypersecretory response of airway mucus.

Plasma high sensitivity c-reactive protein level in children with asthma seen at Aminu Kano teaching hospital, Kano

Background: Exact pathogenesis of asthma is unknown, however the hallmark of asthma is airway inflammation and bronchoconstriction. C-reactive protein (CRP) participates in the systemic response to inflammation and is useful in assessing airway inflammation and asthma severity. Objectives: To measure the plasma levels of high sensitivity-CRP (hs-CRP) in asthmatic and nonasthmatic children, to assess the association between demographic parameters and peak expiratory flow rate with a high level of hs-CRP and also to determine if hs-CRP is a predictor of asthma severity. Materials and Methods: A case-control study in asthmatics and nonasthmatics aged 4-15 years at Aminu Kano Teaching Hospital, Kano. Controls were age and gender matched; without asthma or other atopic conditions. The plasma level of hs-CRP was determined by particle enhanced turbidimetric method. Statistical Analysis: Appropriate statistical tests for quantitative and categorical variables were determined using SPSS. A P value < 0.05 was considered statistically significant. Results: Of the 70 stable asthmatics and 70 controls recruited, 50 (71%) were males and 20 (29%) females. The male to female ratio in both groups was 2.5:1. Fifteen of the asthmatics had attack during the study period. Twenty-five (35.7%) stable asthmatics and 12 (17.1%) of the controls had high-plasma level of hs-CRP. All 15 (100%) asthmatics that presented with an attack had high-plasma level of hs-CRP. Mean ± standard deviation hs-CRP of asthmatics with attack was 21.67 ± 6.57 mg/L which was significantly higher than that of stable asthmatics (9.68 ± 6.85 mg/L, P < 0.0001) and control group (6.96 ± 4.30 mg/L, P < 0.0001). Conclusion: Mean plasma hs-CRP levels was significantly higher (P < 0.001) in asthmatics with attack than stable asthmatics and controls. Plasma levels of hs-CRP may be a good indicator of respiratory airway inflammation.