Decades of research in animal models have provided abundant evidence to show that IL-13 is a key TH 2 cytokine that directs many of the important features of airway inflammation and remodeling in ...patients with allergic asthma. Several promising focused therapies for asthma that target the IL-13/IL-4/signal transducer and activator of transcription 6 pathway are in development, including anti–IL-13 mAbs and IL-4 receptor antagonists. The efficacy of these new potential asthma therapies depends on the responsiveness of patients. However, an understanding of how IL-13–directed therapies might benefit asthmatic patients is confounded by the complex heterogeneity of the disease. Recent efforts to classify subphenotypes of asthma have focused on sputum cellular inflammation profiles, as well as cluster analyses of clinical variables and molecular and genetic signatures. Researchers and clinicians can now evaluate biomarkers of TH 2-driven airway inflammation in asthmatic patients, such as serum IgE levels, sputum eosinophil counts, fraction of exhaled nitric oxide levels, and serum periostin levels, to aid decision making in clinical trials and drug development and to identify subsets of patients who might benefit from therapies. Although it is unlikely that these therapies will benefit all asthmatic patients with this heterogeneous disease, advances in understanding asthma subphenotypes in relation to clinical variables and TH 2 cytokine responses offer the opportunity to improve the efficacy and safety of proposed therapies for asthma.
Mounting evidence suggests that obesity, parameters of metabolic syndrome, and asthma are significantly associated. Interestingly, these conditions are also associated with microbiome dysbiosis, ...notably in the airway microbiome for patients with asthma and in the gut microbiome for patients with obesity and/or metabolic syndrome. Considering that improvements in asthma control, lung function, and airway hyperresponsiveness are often reported after bariatric surgery, this review investigated the potential role of bacterial gut and airway microbiome changes after bariatric surgery in ameliorating asthma symptoms. Rapid and persistent gut microbiota alterations were reported following surgery, some of which can be sustained for years. The gut microbiome is thought to modulate airway cellular responses via short‐chain fatty acids and inflammatory mediators, such that increased propionate and butyrate levels following surgery may aid in reducing asthma symptoms. In addition, increased prevalence of Akkermansia muciniphila after Roux‐en‐Y gastric bypass and sleeve gastrectomy may confer protection against airway hyperreactivity and inflammation. Metabolic syndrome parameters also improved following bariatric surgery, and whether weight‐loss‐independent metabolic changes affect airway processes and asthma pathobiology merits further research. Fulfilling knowledge gaps outlined in this review could facilitate the development of new therapeutic options for patients with obesity and asthma.
McCravy and Ingram discuss the study by Zhang and colleagues on the development of squamous epithelium in the tracheobronchial tree. The authors begin by identifying patches of squamous-appearing ...cells in samples taken from the posterior trachea of healthy subjects. These areas are confirmed to be squamous epithelium by positive staining for KRT13 and lack of staining for lineage markers of ciliated and goblet cells. Importantly, they examined tracheal sections from other species commonly used in translational studies (mouse, rabbit, and pig) to confirm that this phenomenon is conserved across species.
A majority of children admitted to a single hospital in late 2021–early 2022 with acute hepatitis of unknown cause tested positive for adenovirus. This report describes the children’s illnesses and ...outcomes.
Over 20 million adults and 6 million children in the United States (US) have asthma, a chronic respiratory disease characterized by airway inflammation, bronchoconstriction, and mucus hypersecretion. ...Obesity, another highly prevalent disease in the US, is a major risk factor for asthma and a significant cause of diminished asthma control, increased submucosal eosinophilia, and reduced quality of life. A large subgroup of these patients experiences severe symptoms and recurrent exacerbations despite maximal dosage of standard asthma therapies. In the past two decades, the development of biological therapies has revolutionized the field and advanced our understanding of type 2 inflammatory biomarkers. However, patients with obesity and comorbid asthma are not principally considered in clinical trials of biologics. Large landmark cluster analyses of patients with asthma have consistently identified specific asthma phenotypes that associate with obesity but may be differentiated by age of asthma onset and inflammatory cell profiles in sputum. These patterns suggest that biologic processes driving asthma pathology are heterogenous among patients with obesity. The biological mechanisms driving pathology in patients with asthma and comorbid obesity are not well understood and likely multifactorial. Future research needs to be done to elicit the cellular and metabolic functions in the relationship of obesity and asthma to yield the best treatment options for this multiplex condition. In this review, we explore the key features of type 2 inflammation in asthma and discuss the effectiveness, safety profile, and research gaps regarding the currently approved biological therapies in asthma patients with obesity.
Persistent ill health after acute COVID-19-referred to as long COVID, the post-acute COVID-19 syndrome, or the post-COVID-19 condition-has emerged as a major concern. We undertook an international ...consensus exercise to identify research priorities with the aim of understanding the long-term effects of acute COVID-19, with a focus on people with pre-existing airways disease and the occurrence of new-onset airways disease and associated symptoms. 202 international experts were invited to submit a minimum of three research ideas. After a two-phase internal review process, a final list of 98 research topics was scored by 48 experts. Patients with pre-existing or post-COVID-19 airways disease contributed to the exercise by weighting selected criteria. The highest-ranked research idea focused on investigation of the relationship between prognostic scores at hospital admission and morbidity at 3 months and 12 months after hospital discharge in patients with and without pre-existing airways disease. High priority was also assigned to comparisons of the prevalence and severity of post-COVID-19 fatigue, sarcopenia, anxiety, depression, and risk of future cardiovascular complications in patients with and without pre-existing airways disease. Our approach has enabled development of a set of priorities that could inform future research studies and funding decisions. This prioritisation process could also be adapted to other, non-respiratory aspects of long COVID.
During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon admission. In November 2021, hospital ...clinicians, the Alabama Department of Public Health, the Jefferson County Department of Health, and CDC began an investigation. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Airway remodelling is a feature of asthma that contributes to loss of lung function. One of the central components of airway remodelling is subepithelial fibrosis. Interleukin (IL)-13 is a key ...T-helper 2 cytokine and is believed to be the central mediator of allergic asthma including remodelling, but the mechanism driving the latter has not been elucidated in human asthma. We hypothesised that IL-13 stimulates collagen type-1 production by the airway fibroblast in a matrix metalloproteinase (MMP)- and transforming growth factor (TGF)-β1-dependent manner in human asthma as compared to healthy controls. Fibroblasts were cultured from endobronchial biopsies in 14 subjects with mild asthma and 13 normal controls that underwent bronchoscopy. Airway fibroblasts were treated with various mediators including IL-13 and specific MMP-inhibitors. IL-13 significantly stimulated collagen type-1 production in asthma compared to normal controls. Inhibitors of MMP-2 significantly attenuated collagen production in asthma but had no effect in normal controls. IL-13 significantly increased total and active forms of TGF-β1, and this activation was blocked using an MMP-2 inhibitor. IL-13 activated endogenous MMP-2 in asthma patients as compared to normal controls. In an ex vivo model, IL-13 potentiates airway remodelling through a mechanism involving TGF-β1 and MMP-2. These effects provide insights into the mechanism involved in IL-13-directed airway remodelling in asthma.
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