Though children with sickle cell anemia (SCA) possess an elevated risk for sleep-disordered breathing (SDB), progression of obstructive sleep apnea (OSA) across childhood and optimal screening approach remain unclear. Improved understanding of SDB symptomatology and relationship to OSA may simplify screening. This study longitudinally describes SDB symptom profile in children with SCA and examines how they evolve in relation to upper-airway anatomy.

Patients with SCA aged 2-18 years were prospectively recruited. Demographic data, clinical assessments, and upper airway examinations were obtained. OSA symptoms were compared to polysomnography (PSG) outcomes and anatomical features.

Habitual snoring was the most common symptom (n = 55/153;36%). Among PSG-qualifying participants (n = 92/153;60%), most exhibited overlapping symptoms (n = 54/92;58.7%), of which 78% co-occurred with habitual snoring. Remaining single qualifying SDB symptoms included habitual snoring (14.1%) vs others (27.2%). PSG performed in 49/92 (53.3%) children confirmed 23 OSA cases; 19 (82.6%) with habitual snoring, 3 (13%) mouth breathing, and 1 (4.3%) stroke. Habitual snoring but not other SDB symptoms was associated with OSA (p = 0.017). Tonsillar hypertrophy (p = 0.003) and higher Mallampati scores (p = 0.041) predicted habitual snoring. Although habitual snoring prevalence and mean upper-airway anatomical measures cross-sectionally appeared stable (p = 0.602), dynamic longitudinal interactions were observed. New-onset snoring among baseline non-snorers (27.9%) was associated with larger tonsils, whereas snoring resolution in habitual snorers (40.4%) was associated with lower Mallampati scores.

In SCA, habitual snoring as opposed to other symptoms is a practical clinical indicator for the preliminary assessment of OSA. Emergence and resolution of habitual snoring reflect dynamic upper-airway anatomical changes, underscoring importance of periodic reassessments.

Systemic corticosteroids (SCS) are widely prescribed for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), yet no strict guidelines standardize their use. While data-specific to CRSwNP remains limited, growing evidence from lower respiratory disease supports a dose-response relationship between SCS use and related adverse outcomes that begin at relatively low cumulative doses. Reporting on SCS use among patients with CRSwNP is crucial to better understand prescribing patterns and inform future assessments of potential risks.

This study investigates dispensing patterns of SCS among CRSwNP patients.

A population-based retrospective cohort study of community-based pharmacy claims data. The study period was between January 1, 2012 and December 31, 2022.

The province of British Columbia, Canada, home of approximately 5 million residents.

Insured residents diagnosed with CRSwNP and at least 2 years of data on dispenses.

SCS dispenses were identified for all cohort members.

Cumulative SCS doses were calculated. Dispensed SCS courses were characterized based on administration method, dose, course length, and prescriber specialties. Prednisone prescribing patterns were evaluated.

A total of 7000 patients diagnosed with CRSwNP were included in the cohort. Among them, 1527 (21.8%) received 1 gram or more of SCS, an exposure level that has been associated with an increased risk of adverse outcomes in studies of lower respiratory diseases. High cumulative SCS exposure was more common among patients residing in rural areas and those with comorbid respiratory conditions. The mean SCS per patient per year (PPPY) dose was 212.6 mg (SD: 438.2), lower than figures reported in other countries. General practitioners were the most frequent prescribers overall, including among patients without asthma. Otolaryngologists were the second most common prescribers and demonstrated inconsistent prednisone prescribing practices over the study period.

Population-based dispensing data showed unwarranted variation in SCS dispensing among CRSwNP patients, which may contribute to differential exposure to SCS-related adverse outcomes.

There is a need for clear clinical guidelines to standardize SCS exposure among CRSwNP patients, optimize treatment, and support more consistent and appropriate SCS use.

The nasal microbiome's role in predicting sublingual immunotherapy (SLIT) efficacy in children with allergic rhinitis (AR) remains unclear. Haemophilus, a Proteobacteria genus linked to respiratory inflammation, is a promising candidate biomarker.

To evaluate Haemophilus dynamics as a potential predictor of SLIT response in children with moderate-severe AR.

In this prospective cohort, 63 children with AR and 40 healthy controls (CG) were enrolled. AR patients were stratified by disease severity (mild [MAR] vs. moderate-severe [MSAR]), with MSAR patients receiving 1-year standardized house dust mite SLIT. Based on >20% reduction in Total Nasal Symptom Score (TNSS), patients were classified as responders (RG, n = 25) or non-responders (NRG, n = 15). Nasal microbiome was profiled via 16S rDNA sequencing.

Compared to CG, AR children showed increased alpha diversity (Chao1, p < .05; Shannon, p < .01) and enrichment of Staphylococcus. MSAR patients had significantly higher Proteobacteria abundance, particularly Haemophilus, compared to MAR (LDA score >4, p < .001). After SLIT, RG patients showed normalized microbial evenness (Pielou E index) to CG levels, driven by marked Haemophilus depletion (p < .001). In contrast, NRG patients maintained high Haemophilus abundance. Haemophilus and Moraxella showed strong positive correlation (r = .68, p < .001), with both decreasing in RG post-SLIT.

Elevated nasal Haemophilus is associated with AR severity, and its depletion correlates with SLIT efficacy. Haemophilus may serve as a clinically actionable microbial biomarker for monitoring SLIT response in pediatric AR, offering a novel precision medicine approach to allergen immunotherapy.

The Bronchiectasis Health Questionnaire (BHQ) was developed to assess the health-related quality of life (HRQOL) in patients with noncystic fibrosis (CF) bronchiectasis. This study aimed to translate, culturally adapt, and validate the BHQ for use among Chinese patients.

The traditional Chinese version of the BHQ (TC-BHQ) was created through a process of translation, cognitive debriefing interviews, and expert panel reviews. The psychometric evaluation of the TC-BHQ encompassed assessments of factor structure, convergent validity, known-group comparison, internal consistency, and test-retest reliability.

We recruited 150 non-CF bronchiectasis patients. Confirmatory factor analysis (CFA) supported the one-factor structure of the BHQ. In terms of concurrent validity, the TC-BHQ total score showed a significant correlation with the St. George's Respiratory Questionnaire (SGRQ) total score (r = -0.77,  p < 0.01). In addition, the TC-BHQ total score significantly correlated with all SGRQ subscale scores, including the symptom score (r = -0.62,  p < 0.01), activity score (r = -0.60,  p < 0.01), and impact score (r = -0.75,  p < 0.01). There was a statistically significant change in the total score between baseline and follow-up (p = 0.007). Both internal consistency and test-retest reliability of the TC-BHQ were acceptable.

TC-BHQ is a promising tool for assessing HRQOL in patients with non-CF bronchiectasis. It has the potential to be a useful instrument in both clinical and research settings.

Gut microbial dysbiosis has been observed in several diseases. Although causal links and direct effects on host cells remain unclear, bacteria-derived extracellular vesicles (BEVs) from the gut microbiota may regulate the host immune response. We examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the gut microbiome and BEVs release, and the effects of released BEVs on cytokine responses in monocyte-derived cell lines. Fecal samples from 17 patients with coronavirus disease 2019 (COVID-19) and 20 healthy individuals were collected to isolate bacterial and BEV fractions. Parental BEV-releasing bacteria were identified from vesicle-encapsulated bacterial DNA by 16S rRNA gene sequencing. Patients with COVID-19 exhibited altered gut microbiota composition and the profile of bacterial DNA-containing BEVs (dcBEVs) release compared to healthy controls. BEVs from patients, but not from healthy individuals, significantly changed cytokine levels in U937 monocyte cells. Following COVID-19 recovery, dcBEV profiles diverged into two distinct groups: those that retained the capacity to induce cytokines in monocytes and those that lost this functionality. BEVs from single bacterial cultures within families altered after COVID-19 onset affected the expression of genes in monocytes, primarily immune-response genes, notably chemokine ligands and G protein-coupled receptors. SARS-CoV-2-induced dysbiosis alters the profile of dcBEVs release, thereby modulating the host immune response and potentially contributing to COVID-19 pathogenesis.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of nucleic acid-based therapies in people with CF of any age and any genotype.

To identify serum lipid biomarkers for acute pulmonary embolism (APE) and evaluate their diagnostic value, and to investigate the impact of glycerol monolaurate (GML) and glycerol monooleate (GMO) on cytotoxic T cell function.

A total of 436 subjects, including APE, healthy controls, and patients with related diseases, were enrolled. Serum samples were subjected to pseudotargeted lipidomics to screen differential lipid species. Targeted LC-MS/MS analysis was used to validate the GML and GMO levels. Flow cytometry was used to assess cytotoxic T cell markers such as granzyme B, perforin, and granulysin. In vitro experiments examined the inhibitory effect of GML and GMO on Notch1 signaling and cytotoxic protein expression in T cells. ROC curve analyses were performed to evaluate the diagnostic performance of lipid biomarkers.

Pseudotargeted lipidomics identified 203 upregulated and 57 downregulated serum lipids in APE versus controls. Targeted LC-MS/MS confirmed significantly elevated serum GML and GMO in APE compared with healthy controls and other diseases. Serum GML and GMO were correlated with clinical risk stratification. ROC analyses showed high sensitivity and specificity for GML and GMO individually. Cytotoxic T cells from APE patients exhibited decreased granzyme B, perforin and granulysin. In vitro, GML and GMO reduced Notch1 and granzyme B expression in T cells.

Elevated serum GML and GMO could serve as effective diagnostic biomarkers for APE, correlating with disease severity. They were likely to impair cytotoxic T cell function by downregulating Notch1 signaling and cytotoxic proteins, suggesting their involvement in APE pathogenesis.

Eosinophils have traditionally been viewed as terminal effector cells in allergic rhinitis (AR), driving tissue damage through the release of cytotoxic granule proteins and pro-inflammatory mediators. However, accumulating evidence over the past two decades has challenged this paradigm, revealing that eosinophils harbor a substantial immunoregulatory repertoire. This Mini Review synthesizes emerging findings on four underappreciated dimensions of eosinophil immunoregulatory function in the context of AR: (i) the capacity of eosinophils to produce interleukin-10 (IL-10) and engage in functional crosstalk with Foxp3+ regulatory T cells (Tregs); (ii) the dual role of eosinophil-derived transforming growth factor-beta (TGF-β) in both tissue remodeling and mucosal tolerance; (iii) eosinophil lipid mediator class-switching from pro-inflammatory cysteinyl leukotrienes (CysLTs) to specialized pro-resolving mediators (SPMs); and (iv) the functional heterogeneity between tissue-resident and inflammatory eosinophil subsets. We further discuss the clinical implications of these findings, including the paradoxical outcomes of anti-IL-5 therapies in AR and the potential of immunoregulatory eosinophil markers as biomarkers for allergen-specific immunotherapy (AIT). A deeper understanding of the context-dependent immunoregulatory functions of eosinophils in the nasal mucosa may inform precision therapeutic strategies that selectively target pro-inflammatory eosinophil subsets while preserving their homeostatic and tolerogenic roles.

NFKB1 haploinsufficiency caused by monoallelic loss-of-function variants in NFKB1 results in a CVID-like phenotype or other forms of hypogammaglobulinemia.

This study aims to characterize the clinical and immunological profiles of 21 individuals from nine families with this disorder.

Gene panel sequence and/or whole exome sequence, followed by Sanger sequencing, were used to identify and confirm NFKB1 variants. Immunophenotyping were performed by flow cytometry. The type I interferon signature was determined by quantitative PCR.

Of the nine NFKB1 variants, seven novel heterozygous variants were identified in this study. Ten individuals were clinically asymptomatic, while 11 were symptomatic, resulting in clinical penetrance of 52%. However, immunologic abnormalities were observed in all asymptomatic family members tested (n=9). The main presenting symptoms in symptomatic individuals were respiratory tract infections (7/11) and autoimmune or autoinflammatory features (7/11). Interestingly, two patients had Moyamoya disease, and one patient was complicated by alopecia and rheumatoid arthritis. Immunological analyses were performed in 19 individuals, including 9 asymptomatic, and revealed that 58% had low absolute T cell counts and that 72% of individuals displayed inverted CD4/CD8 T-cell ratio. B-cell lymphopenia and decreased switch memory B cells were observed in 42% and 61% of individuals, respectively. A type I interferon signature was not observed.

In addition to hypogammaglobulinemia/CVID-like phenotype, NFKB1 variants have been associated with a wide range of manifestations, ranging from various organ involvements to autoimmunity. Autoinflammatory features have also been reported; however, the presence of type I interferon signatures was not specifically addressed in this study.

Neutrophilic asthma represents a distinct inflammatory phenotype characterized by sputum neutrophilia (≥61% neutrophils), glucocorticoid resistance, and more severe disease course compared to eosinophilic asthma. This review comprehensively examines the molecular mechanisms underlying neutrophilic asthma pathogenesis, focusing on the Th17/IL-17 axis, neutrophil extracellular traps (NETs), and NLRP3 inflammasome activation. We present a precision identification framework integrating molecular endotypes with clinical phenotypes and biomarker profiles to guide therapeutic decisions. Unlike eosinophilic asthma, neutrophilic asthma demonstrates intrinsic resistance to glucocorticoids due to impaired neutrophil apoptosis and persistent activation of pro-inflammatory pathways. Emerging therapeutic approaches targeting IL-17, NET formation, and inflammasome components show promise, with several agents in clinical development. The microbiome-neutrophil axis represents a novel therapeutic target, with evidence suggesting that airway dysbiosis perpetuates neutrophilic inflammation through pattern recognition receptor activation. This review provides a comprehensive framework for understanding neutrophilic asthma pathogenesis and outlines precision medicine approaches for this difficult-to-treat asthma phenotype.