This review examines asthma in older adults over the past decade, focusing on epidemiology, diagnostic challenges, and current management. It also explores why asthma remains underdiagnosed and undertreated in this population. Asthma prevalence is increasing among older adults worldwide, particularly in developed regions and Asia, yet underdiagnosis and undertreatment remain common. Diagnostic complexity is driven by atypical presentations, comorbidities, overlapping COPD features, and limitations of standard diagnostic criteria. Patient-related barriers include low health literacy, poor inhaler technique, symptom misattribution, psychological comorbidity, and limited social support. Access to biologic therapies remains uneven, and precision medicine approaches for older adults are lacking. Asthma in older adults is an important and underrecognized public health issue. Better awareness, age-adapted diagnostic protocols, improved inhaler education, and more integrated management of comorbidities are needed to improve outcomes and quality of life.
Human milk (HM) contains a diverse array of immunological, microbial, and metabolic bioactive factors that may influence early immune maturation and allergic disease susceptibility. This narrative review examines current evidence linking major HM bioactives with eczema, food allergy, and wheezing/asthma, integrating mechanistic findings with human observational and clinical data. Transforming growth factor-β (TGF-β), secretory IgA (sIgA), human milk oligosaccharides (HMOs), cytokines, fatty acids, short-chain fatty acids, the HM microbiome, and extracellular vesicles have all been implicated in pathways relevant to epithelial integrity, microbial colonization, and immune tolerance. However, associations with allergic outcomes are heterogeneous and frequently context dependent. Findings vary according to lactation stage, maternal characteristics, infant susceptibility, microbial exposures, and outcome definition. Mechanistic evidence is often stronger than prospective clinical evidence, and no individual HM component or bioactive profile has yet emerged as a reproducible predictor of allergy protection. Current evidence supports viewing HM as a dynamic maternal–milk–infant biological network rather than as a source of isolated protective factors. Future studies should integrate repeated HM sampling, rigorous allergic phenotyping, and multi-omic approaches to distinguish causal mediators from biomarkers of maternal or infant biology.
This review aims to summarize the established and potential targets of glucocorticoids (GCs) on mast cells, which are implicated in the pathophysiology of various allergic and inflammatory diseases including asthma, allergic rhinitis, and atopic dermatitis. We sought to answer the following questions: (1) How do glucocorticoids inhibit the release of mediators from mast cells? (2) What are the effects of glucocorticoids on mast cell signaling molecules? (3) By what mechanisms do glucocorticoids induce mast cell apoptosis? and (4) What are the genomic and non-genomic mechanisms underlying these effects? Evidence published since 2020 reinforces that glucocorticoid effects on mast cells are context dependent rather than uniform. Dexamethasone can directly suppress selected functions of human and murine mast cells, including in combination with inhibitory CD300a signaling [22]. Conversely, activated human lung mast cells can reduce corticosteroid responsiveness in neighboring airway smooth muscle cells by altering glucocorticoid-regulated transcription [23]. In patients with asthma, six weeks of inhaled budesonide reduced airway mast cell infiltration and improved airway hyperresponsiveness; importantly, associations differed according to mast cell phenotype, airway location, and inflammatory phenotype [25]. Single-cell studies now reveal multiple human mast cell transcriptional states across tissues [7, 8], while integrated RNA-seq and H3K27ac profiling in primary human mast cells demonstrates selective regulation of mast-cell identity genes and super-enhancer networks [92]. These findings place glucocorticoid responsiveness within a framework of mast cell state, tissue niche, species, glucocorticoid compound, and experimental context. Glucocorticoid-associated mast cell depletion may involve reduced stromal/fibroblast-derived SCF and, in IL-3-dependent murine models, reduced IL-3 receptor expression; these are mechanistically distinct effects. Glucocorticoids can target mast cells at several levels, including mediator synthesis and release, intracellular signaling, survival, and transcriptional regulation, but the magnitude and nature of these effects vary substantially among species, tissue compartments, mast cell phenotypes/states, glucocorticoid compounds, activation pathways, and experimental conditions. Classical GR-dependent transcription involves GRE-dependent regulation and interactions with transcription factors such as NF-κB and AP-1, yet mast-cell-specific GR-regulated gene and chromatin programs remain incompletely defined. Rapid effects on degranulation are also unresolved, with evidence for membrane-associated classical GR signaling as well as other rapid mechanisms. Contemporary human and single-cell data therefore argue against treating mast cells as a single uniformly corticosteroid-responsive population. Future studies should define the molecular basis of rapid glucocorticoid signaling and map GR-responsive transcriptional and chromatin programs across primary human mast cell states and tissue niches.
The prevalence of cannabis and nicotine vaporizer use appears to be increasing, but their effects on the respiratory system are incompletely elucidated. This review brings together clinical, pathologic, and molecular knowledge describing airway disease, acute lung injury syndromes, and structural lung injury resulting from nicotine and cannabis vaporizer use. We describe consistent epidemiologic associations of nicotine vaporizer use with obstructive lung disease, bronchitis, emphysema, and constrictive bronchiolitis; cannabis vaporizer use is more frequently associated with acute lung injury and airway disease symptoms. At a molecular level, nicotinic receptor activation drives collagen deposition, epithelial barrier dysfunction, and impaired mucociliary clearance; cannabinoid receptor activation has effects on airway inflammation, epithelial integrity, and immune cell function. Oxidative stress and mitochondrial dysfunction likely mediate effects of nicotine and cannabis vaporizer exposure through receptor-independent mechanisms. Use of nicotine and cannabis vaporizers affects clinical pulmonary disease through a variety of converging molecular and cellular mechanisms in the respiratory epithelium. Significant knowledge gaps remain, particularly with regard to molecular investigations of cannabis vaporizer use and dual nicotine-cannabis vaporizer use. Future investigations integrating molecular mechanisms of disease with clinical and histopathologic outcomes are necessary to better characterize the effects of these increasingly impactful public health risks.
Asthma and obesity are affecting children and teenagers at higher rates than previous generations. Epidemiological data link obesity during childhood with the subsequent development of asthma. In this review we describe developmental and inflammatory factors that contribute to asthma severity in children with obesity. Asthma driven by obesity is likely due to both structural and inflammatory changes. Excess weight places mechanical stress on the airway thereby reducing lung volumes. In addition, obesity is linked to chronic inflammation. Adipose tissue releases pro-inflammatory cytokines (IL-6 and TNF-α) which drives the airway towards hyperresponsiveness. This “obesity-related asthma” phenotype does not respond well to corticosteroids making these patients difficult to treat. In children and teenagers, treatment options are limited to currently approved asthma medications; however, improvement in asthma control has been observed in adults utilizing metformin and GLP-1 agonists. Children with obesity are more likely to develop asthma. Their asthma symptoms tend to be more frequent and harder to control. With the rate of obesity on the rise, it is paramount to identify the mechanisms underlying systemic inflammation in those with elevated BMIs. This will allow us to find better treatment options for “obesity-related asthma.”
