Airway Disease Research Articles

Small airways disease in chronic obstructive pulmonary disease.

Small airway disease (SAD) represents a common and critical feature of Chronic Obstructive Pulmonary Disease (COPD). Introduced in the '60s, SAD has gradually gained increasing interest as assessment methodologies have improved. Chronic exposure to smoking and noxious particles or gases induces inflammation and remodeling, leading to airway obstruction and SAD, eventually resulting in complete airway loss. A literature search up to June 2024 was performed in PubMed to identify articles on SAD and airway diseases mainly COPD, but also to the extent that it seemed relevant in the uncontrolled/severe asthma field, where SAD is better studied. We provide clinicians and translational scientists with a comprehensive analysis of the existing literature on SAD in COPD, concentrating on the underlying pathophysiological mechanisms, diagnostic techniques, and current pharmacological approaches targeting airflow obstruction in small airways. Small airways are the primary site for the onset and progression of airflow obstruction in patients with COPD, with significant clinical consequences associated with poor lung function, hyperinflation, and impaired quality of life. The early identification of individuals with subclinical SAD may allow us to prevent its further progress from airway loss and potential development of emphysema and choose the appropriate therapeutic approach.

ZFP36 family expression is suppressed by Th2 cells in asthma, leading to enhanced synthesis of inflammatory cytokines and cell surface molecules

Asthma is a chronic inflammatory airway disease, in which inflammatory cytokines play a pivotal role. The zinc finger binding protein 36 (ZFP36) family includes ZFP36, ZFP36L1, and ZFP36L2 and is among the RNA-binding proteins (RBPs) reported to cause inflammation. The present study aimed to clarify the roles of the ZFP36 family in asthma, particularly highlighting the relationship between the ZFP36 family and Th2 cells, which are key players in type 2 inflammation in asthma. Real-time PCR analysis revealed the preferential expression of ZFP36 family mRNAs in human white blood cells. Gene expression analysis using public datasets from the GEO database (https://www.ncbi.nlm.nih.gov/gds) showed significantly suppressed expression of ZFP36 family mRNAs in patients with asthma compared to that in healthy controls. Using multiple cytokine assays, Th2 cell transfection with ZFP36 family siRNAs enhanced the expression of inflammatory cytokines IL-8, IFN-γ, CCL3/MIP-1α, CCL4/MIP-1β, and TNF-α and cell surface molecules CCR4 (CD194) and PSGL-1 (CD162). Treatment with IL-2, 4, and 15 significantly suppressed, and corticosteroid significantly enhanced the expressions of ZFP36 family mRNAs by Th2 cells. In conclusion, the ZFP36 family expressed by Th2 cells was suppressed in patients with asthma, leading to the enhanced expression of cytokines and cell surface molecules. Suppressed ZFP36 expression in asthma may be involved in the enhancement of airway inflammation, and the ZFP36 family may be a therapeutic target for inflammatory diseases, including asthma.

Airway diseases in very low birth weight infants.

To identify the incidence and characteristics of airway diseases in very low birth weight infants (VLBWIs). A retrospective study of 214 inborn VLBWIs admitted to our NICU between April 2009 and March 2022 (approval no: 2023-0008). Neonatologists ourselves performed bronchoscopy to diagnose airway diseases. Symptomatic airway diseases were present in 36/214 (16.8%) of VLBWIs. Common airway diseases were tracheobronchomalacia (TBM) and pharyngomalacia. Infants with airway diseases had shorter gestational age, lower birth weight, more boys, and more moderate/severe bronchopulmonary dysplasia (BPD). Regarding treatment, more infants with airway diseases required intubation were intubated longer, used more dexamethasone, were on ventilators and oxygen longer, and were hospitalized longer. We found that VLBWIs were more frequently complicated with airway diseases, especially TBM. We also observed many pharyngeal lesions, which have not been previously reported. Intensity of prematurity, BPD, and the need for stronger respiratory management were risks for airway diseases. In VLBWIs, bronchoscopy should be actively performed because airway diseases are important complications.

Diagnostic criteria for eosinophilic chronic rhinosinusitis: Comparative analysis and novel scoring system.

Accurate identification of eosinophilic chronic rhinosinusitis is essentialg because its treatment and prognosis substantially differ from other subtypes. This retrospective observational study included 640 patients who underwent endoscopic sinus surgery for chronic rhinosinusitis in a single tertiary center from January 2021 to December 2022. Receiver operating characteristic curves were generated to compare accuracy, sensitivity, specificity of the novel scoring system, and previous diagnostic criteria (Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis, European Forum for Research and Education in Allergy and Airway Diseases, European Position Paper on Rhinosinusitis and Nasal Polyps, and Sakuma etal.) for predicting eosinophilic chronic rhinosinusitis (ECRS) by tissue eosinophil count ≥70 per high power field. Patients were randomly divided into estimation (n=430) and validation (n=210) groups. The area under the receiver operating characteristic curve for the novel score was 0.753 (95% confidence interval [CI], 0.670-0.835) in the estimation group, 0.729 (0.629-0.830) in the validation group, and 0.661 (0.584-0.738) in the 20-fold cross-validation with the entire dataset. We propose a novel scoring system that incorporates three key parameters: "novel score=blood eosinophil (%) + total Lund-Mackay score of anterior ethmoid sinuses + 2 if nasal polyp present" greater than 7 can be reliably used for diagnosing ECRS. This system can facilitate decision-making processes regarding the administration of oral steroids and biologics targeting type 2 inflammation prior to surgical intervention.

Novel approach for tracheal resection in Morquio a syndrome with end-stage critical airway obstruction: a UK case series

BackgroundMucopolysaccharidosis (MPS) type IVA is a rare lysosomal storage disorder caused by aberrations of the N-acetyl-galactosamine-6-sulfatase (GALNS) enzyme. MPS IVA is associated with a wide gamut of respiratory and airway disorders that manifest in a continuum of severity. In individuals exhibiting severe phenotypic expression, terminal stages of the disease frequently culminate in life-threatening, critical airway obstruction. These manifestations of end-stage disease are engendered by an insidious progression of multi-level airway pathologies, comprising of tracheomalacia, stenosis, tortuosity and 'buckling'. Historically, the management of end-stage airway disease has predominantly leaned towards palliative modalities. However, contemporary literature has posited that the potential benefits of tracheal resection with aortopexy, performed under cardiopulmonary bypass (CPB), may offer a promising therapeutic option. In this context, we report on outcomes from patients undergoing a novel approach to tracheal resection that is combined with manubrial resection, leading to improved airway calibre, obviating the requisition for CPB.ResultsIn this study, seven patients with severe MPS IVA exhibited clinical symptoms and radiological evidence indicative of advanced airway obstruction. All patients had a tracheal resection with a partial upper manubriectomy via transcervical approach, which did not require CPB. The surgical cohort consisted of 5 females and 2 males, the median age was 16 years (range 11-19) and the median height was 105.6cm (range 96.4-113.4). Postoperatively, significant improvements were seen in forced expiratory volume in 1 second (FEV1), with a mean increase of 0.68 litres (95% CI: 0.45-0.91; SD: 0.20). Notably, other spirometry variables also showed meaningful improvements, providing evidence of positive treatment effects. Furthermore, there were no major long-term complications, and the procedure resulted in a significant enhancement in patient-reported domains using PedsQL (version 4.0).ConclusionsThis study represents the largest case series to date, on tracheal resection in patients with severe MPS IVA. Our findings demonstrate the effectiveness of the transcervical approach with partial manubriectomy for improving respiratory function and quality of life for individuals with advanced airway obstruction. Tracheal resection presents a promising treatment modality for severe cases of MPS IVA. Successful outcomes rely on meticulous multidisciplinary assessment, judicious decision-making, and appropriate timing of tracheal surgery. Further research and long-term follow-up studies are warranted to validate the long-term efficacy and safety of this approach.

Airway specific deregulation of asthma-related serpins impairs tracheal architecture and oxygenation in D. melanogaster

Serine proteases are important regulators of airway epithelial homeostasis. Altered serum or cellular levels of two serpins, Scca1 and Spink5, have been described for airway diseases but their function beyond antiproteolytic activity is insufficiently understood. To close this gap, we generated fly lines with overexpression or knockdown for each gene in the airways. Overexpression of both fly homologues of Scca1 and Spink5 induced the growth of additional airway branches, with more variable results for the respective knockdowns. Dysregulation of Scca1 resulted in a general delay in fruit fly development, with increases in larval and pupal mortality following overexpression of this gene. In addition, the morphological changes in the airways were concomitant with lower tolerance to hypoxia. In conclusion, the observed structural changes of the airways evidently had a strong impact on the airway function in our model as they manifested in a lower physical fitness of the animals. We assume that this is due to insufficient tissue oxygenation. Future work will be directed at the identification of key molecular regulators following the airway-specific dysregulation of Scca1 and Spink5 expression.

Co-Occurrence of Equine Asthma and Pharyngeal Lymphoid Hyperplasia in Pleasure Horses

With the increasing awareness of the “united airway disease” theory, more horses, not only sport horses but also pleasure horses, undergo detailed examinations of the respiratory tract. Using endoscopy, equine asthma (EA) is most commonly diagnosed in the lower airway, while pharyngeal lymphoid hyperplasia (PLH) is common in the upper airway. Grading EA as mild–moderate (MEA) and severe (SEA), this study aims to compare the co-occurrence and investigate the possible relationship between the clinical symptoms and endoscopic signs of MEA/SEA and PLH in pleasure horses. In this retrospective study, 80 out of 93 pleasure horses suspected of EA were enrolled and underwent a standardized protocol for a complete airway examination, including resting endoscopy with mucus accumulation assessment and cytology. The obtained results were scored and analyzed. In the studied pleasure horses, PLH co-occurred more frequently in horses with EA than without (p < 0.0001) and more in horses with SEA than with MEA (p = 0.025). However, when EA and PLH co-occurred, the severity of the clinical symptoms of EA did not increase (p > 0.05). In both EA and PLH, the amount of tracheal and nasopharyngeal mucus increased with the severity of the disease; however, it was positively correlated (ρ = 0.33; p = 0.02) only in SEA horses. In conclusion, it is likely that EA is often accompanied by PLH; however, PLH did not play a role in increasing the severity of EA’s clinical symptoms. The role of the severity of accumulated mucus in the lower and upper airways when EA/PLH co-occur requires further research to confirm the morphological and functional unity of the respiratory tract, aligning with the concept of “united airways disease”.

Nasal epithelial gene expression identifies relevant asthma endotypes in the ATLANTIS study

IntroductionAsthma is an inflammatory airways disease encompassing multiple phenotypes and endotypes. Several studies suggested gene expression in nasal epithelium to serve as a proxy for bronchial epithelium, being a non-invasive...

Bronchodilator response in Post-COVID-19 patients undergoing pulmonary rehabilitation.

SARS-CoV-2 infections can result in a broad spectrum of symptoms from mild to life-threatening. Long-term consequences on lung function are not well understood yet. In our study, we have examined 134 post-COVID patients (aged 54.83±14.4 years) with dyspnea on exertion as a leading symptom 6 weeks to 24 months after a SARS-CoV-2 infection for bronchodilator responsiveness during their stay in our pulmonary rehabilitation clinic. Prior to bronchial dilation, six out of 134 patients (4.47%) presented an FEV1/FVC ratio below lower limit of normal (Z-score=-1.645) indicative of an obstructive airway disease. Following inhalation of a ß2-adrenergic agonist we measured a mean FEV1 increase of 181.5 mL in our cohort, which was significantly elevated compared to a historical control group (ΔFEV1 = 118 mL). 28.7% of the patients showed an increase greater than 200 mL and 12% displayed a significant bronchodilation response (>200 mL ΔFEV1 and >12% FEV1 increase). Interestingly, no significant difference in bronchial dilation effect was observed when comparing patients hospitalized and those non-hospitalized during the course of their SARS-CoV-2 infection. Our data provides evidence for increased prevalence of obstructive ventilatory defects and increased bronchodilator responsiveness in patients with persisting symptoms after COVID-19. Depending on the extent of this complication, post-COVID patients may benefit from an adapted ß2-inhalation therapy including subsequent reevaluation.

Evaluation of impact of adherence to inhaled therapy and critical mistakes in inhalation technique on clinical outcomes in patients with obstructive airway diseases in India

Evaluation of impact of adherence to inhaled therapy and critical mistakes in inhalation technique on clinical outcomes in patients with obstructive airway diseases in India

Evaluation of impact of adherence to inhaled therapy and critical mistakes in inhalation technique on clinical outcomes in patients with obstructive airway diseases in India

Adherence to inhaled therapy is more relevant in respiratory diseases because, to achieve therapeutic efficacy, it is necessary that the patient adhere to the recommended therapy as well as use their inhalers correctly with appropriate inhalation technique.This was a prospective, observational study that included 126 patients >18 years of age of all genders, diagnosed with an obstructive airway disease, and prescribed inhaler medication. Adherence was assessed using the Test of Adherence to Inhalers (TAI) questionnaire, and inhaler device technique was assessed every 3 months. At the end of one year, outcome data like the number of exacerbations, the number of admissions, including critical-care admissions, the number of days of hospitalization, adverse events, and their associations were analyzed.Poor adherence to inhaled therapy was found in 40.48% of patients, with the majority of patients (69.05%) having an unwitting or ignorant pattern of non- adherence. Out of 75 patients using MDI (Metered Dose Inhaler), 34.67% had critical mistakes in technique, and out of 51 patients using Rotahaler, 23.53% had critical mistakes in technique. There was no significant relationship between level of adherence and critical mistakes with gender, BMI category, or past history of smoking. Patients with poor adherence and those with critical mistakes in inhalation technique had poor health outcomes.This study highlights the role of adherence and identifies barriers responsible for non-adherence to inhaled therapy. Identifying the behaviors responsible for non-adherence and counseling the patients on the correct inhalation technique can improve the health outcomes of chronic respiratory diseases.

STRUCTURE-FUNCTION IN SMOKERS : WHEN A SMALL AIRWAYS TEST REALLY REFLECTS THE SMALL AIRWAYS.

INTRODUCTION: If Multiple Breath Washout (MBW) derived acinar ventilation heterogeneity (Sacin) really represents peripheral units, the N2 phase-III of the first MBW exhalation should be curvilinear. This is due to the superposed effect of gas diffusion and convection resulting in an equilibration of N2 concentrations between neighbouring lung units throughout exhalation. We investigated this in smokers with CT-proven functional small airway disease. METHODS: Instantaneous N2slopes were computed over 40ms intervals throughout phase-III and normalized by mean phase-III N2 concentration. N2phase-III (concave) curvilinearity was quantified as the rate at which the instantaneous N2 slope decreases past the phase-II peak over a 1s interval; for a linear N2phase-III unaffected by diffusion, this rate would amount to 0L-1/s. N2phase-III curvilinearity was obtained on the experimental curves and on existing model simulations of N2curves from a normal peripheral lung model and one with missing terminal bronchioles (either 50% or 30% TB left). RESULTS: In forty-six smokers (66 (+8) years; 49 (+26) packyears) with CT-evidence of peripheral lung destruction, instantaneous N2 slope decrease was compared between those with (fSAD+fEmphys)>20% (-0.26+0.14(SD) L-1/s;n=24) and those with (fSAD+fEmphys)<20% (-0.16+0.12(SD)L-1/s;n=22) (P=0.014). Experimental values fell in the range predicted by a realistic peripheral lung model with progressive reduction of terminal bronchioles: values of instantaneous N2-slope decrease obtained from model simulations were -0.09L-1/s (normal lung;100%TB left), -0.17L-1/s (normal lung 50%TB left) and -0.29L-1/s (30%TB left). DISCUSSION : In smokers with CT-based evidence of functional small airways alterations, it is possible to demonstrate that Sacin really does represent the most peripheral airspaces.

Validation of a computed tomography diagnostic model for differentiating fibrotic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis

BackgroundThe diagnosis of fibrotic hypersensitivity pneumonitis (fHP) from other interstitial lung diseases, particularly idiopathic pulmonary fibrosis (IPF), is often difficult. This study aimed to examine computed tomography (CT) findings that were useful for differentiating between fHP and IPF and to develop and validate a radiological diagnostic model. MethodsIn this study, 246 patients (fHP, n = 104; IPF, n = 142) from two institutions were included and randomly divided into the test (n = 164) and validation (n = 82) groups (at a 2:1 ratio). Three radiologists evaluated CT findings, such as pulmonary fibrosis, small airway disease, and predominant distribution, and compared them between fHP and IPF using binomial logistic regression and multivariate analysis. A prognostic model was developed from the test group and validated with the validation group. ResultsGround-glass opacity (GGO) with traction bronchiectasis (TB), honeycombing, hypoattenuation area, three-density pattern, diffuse craniocaudal distribution, peribronchovascular opacities in the upper lung, and random distribution were more common in fHP than in IPF. In multivariate analysis, GGO with TB, peribronchovascular opacities in the upper lung, and random distribution were significant features. The area under the curve of the fHP diagnostic model with the three aforementioned CT features was 0.733 (95% confidence interval [CI], 0.655–0.811, p < 0.001) in the test group and 0.630 (95% CI, 0.504–0.755, p < 0.047) in the validation group. ConclusionGGO with TB, peribronchovascular opacities in the upper lung, and random distribution were important CT features for differentiating fHP from IPF.

Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells

BackgroundCystic Fibrosis causing mutations in the gene CFTR, reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) has been well established. The CFTR modulatory compound, Ivacaftor (VX-770), potentiates channel activity of CFTR and certain CF-causing mutations and has been shown to ameliorate mucus obstruction and improve lung function in people harbouring these CF-causing mutations. A pilot trial of Ivacaftor supported its potential efficacy for the treatment of mucus obstruction in COPD. These findings prompted the search for CFTR potentiators that are more effective in ameliorating cigarette-smoke (CS) induced mucostasis.MethodsSmall molecule potentiators, previously identified in CFTR binding studies, were tested for activity in augmenting CFTR channel activity using patch clamp electrophysiology in HEK-293 cells, a fluorescence-based assay of membrane potential in Calu-3 cells and in Ussing chamber studies of primary bronchial epithelial cultures. Addition of cigarette smoke extract (CSE) to the solutions bathing the apical surface of Calu-3 cells and primary bronchial airway cultures was used to model COPD. Confocal studies of the velocity of fluorescent microsphere movement on the apical surface of CSE exposed airway epithelial cultures, were used to assess the effect of potentiators on CFTR-mediated mucociliary movement.ResultsWe showed that SK-POT1, like VX-770, was effective in augmenting the cyclic AMP-dependent channel activity of CFTR. SK-POT-1 enhanced CFTR channel activity in airway epithelial cells previously exposed to CSE and ameliorated mucostasis on the surface of primary airway cultures.ConclusionTogether, this evidence supports the further development of SK-POT1 as an intervention in the treatment of COPD.

Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells

BackgroundCystic Fibrosis causing mutations in the gene CFTR, reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) has been well established. The CFTR modulatory compound, Ivacaftor (VX-770), potentiates channel activity of CFTR and certain CF-causing mutations and has been shown to ameliorate mucus obstruction and improve lung function in people harbouring these CF-causing mutations. A pilot trial of Ivacaftor supported its potential efficacy for the treatment of mucus obstruction in COPD. These findings prompted the search for CFTR potentiators that are more effective in ameliorating cigarette-smoke (CS) induced mucostasis.MethodsSmall molecule potentiators, previously identified in CFTR binding studies, were tested for activity in augmenting CFTR channel activity using patch clamp electrophysiology in HEK-293 cells, a fluorescence-based assay of membrane potential in Calu-3 cells and in Ussing chamber studies of primary bronchial epithelial cultures. Addition of cigarette smoke extract (CSE) to the solutions bathing the apical surface of Calu-3 cells and primary bronchial airway cultures was used to model COPD. Confocal studies of the velocity of fluorescent microsphere movement on the apical surface of CSE exposed airway epithelial cultures, were used to assess the effect of potentiators on CFTR-mediated mucociliary movement.ResultsWe showed that SK-POT1, like VX-770, was effective in augmenting the cyclic AMP-dependent channel activity of CFTR. SK-POT-1 enhanced CFTR channel activity in airway epithelial cells previously exposed to CSE and ameliorated mucostasis on the surface of primary airway cultures.ConclusionTogether, this evidence supports the further development of SK-POT1 as an intervention in the treatment of COPD.

Asthma Inception: Epidemiologic Risk Factors and Natural History Across the Life-Course.

Asthma is a descriptive label for an obstructive, inflammatory disease in the lower airways manifesting with symptoms including breathlessness, cough, difficulty in breathing and wheezing. From a clinician's point of view, asthma symptoms can commence at any age although most asthma patients - regardless of their age of onset - seem to have had some form of airway problems during childhood. Asthma inception and related pathophysiologic processes are therefore very likely to occur early in life, further evidenced by recent lung physiologic and mechanistic research. Herein, we present state-of-the-art updates on the role of genetics and epigenetics, early viral and bacterial infections, immune response and pathophysiology as well as lifestyle and environmental exposures in asthma across the life-course. We conclude early environmental insults in genetically vulnerable individuals to induce an abnormal, pre-asthmatic airway response as key events in asthma inception and highlight disease heterogeneity - across ages - and the potential shortness of treating all patients with asthma using the same treatments. Although there are no interventions that, at present, can modify long-term outcomes, a precision-medicine approach should be implemented to optimize treatment and tailor follow-up for all patients with asthma.

Asthma Inception: Epidemiologic Risk Factors and Natural History Across the Life-Course.

Asthma is a descriptive label for an obstructive, inflammatory disease in the lower airways manifesting with symptoms including breathlessness, cough, difficulty in breathing and wheezing. From a clinician's point of view, asthma symptoms can commence at any age although most asthma patients - regardless of their age of onset - seem to have had some form of airway problems during childhood. Asthma inception and related pathophysiologic processes are therefore very likely to occur early in life, further evidenced by recent lung physiologic and mechanistic research. Herein, we present state-of-the-art updates on the role of genetics and epigenetics, early viral and bacterial infections, immune response and pathophysiology as well as lifestyle and environmental exposures in asthma across the life-course. We conclude early environmental insults in genetically vulnerable individuals to induce an abnormal, pre-asthmatic airway response as key events in asthma inception and highlight disease heterogeneity - across ages - and the potential shortness of treating all patients with asthma using the same treatments. Although there are no interventions that, at present, can modify long-term outcomes, a precision-medicine approach should be implemented to optimize treatment and tailor follow-up for all patients with asthma.

Non-invasive strategy: Developing a topical IL-4Rα-specific nanobody for the treatment of allergic airway diseases

Inhibiting IL-4 and IL-13 are critical cytokines that induce the pathogenic responses of allergic airway diseases. Currently, monoclonal antibodies targeting IL-4Rα are administered subcutaneously to treat eosinophilic rhinosinusitis and allergic asthma. However, these treatments have several drawbacks. To address these issues, we have developed a novel IL-4Rα-targeting nanobody designed for non-invasive delivery to local inflammatory sites in allergic airway diseases. H5, selected via the ribosomal display applied screening from synthetic nanobody library, underwent dimerization and in-silico affinity maturation using AlphaFold2 and GROMACS resulting in a substantial/dramatic enhancement of its binding affinity. H5 effectively controlled inflammatory markers such as MUC5AC, CCL26, and FOXJ1 in human nasal epithelial cells (HNECs) by inhibiting IL-4 and IL-13 signaling. The bivalent form of H5 showed efficacy in easily accessible cells, such as multi-ciliated cells, while the monovalent variant targeted hard-to-reach cells, such as basal cells of HNECs. In summary, we developed a nanobody that could effectively inhibit inflammatory signaling in HNECs via intranasal administration, showing promise as a non-invasive rhinitis treatment.

Association between triglyceride-glucose index and sarcopenia in patients with chronic inflammatory airway disease

ObjectiveThis research sought to explore the association between the triglyceride-glucose (TyG) index and the risk of sarcopenia in patients with chronic inflammatory airway disease (CIAD). MethodsData were obtained from the National Health and Nutrition Examination Survey 2011–2018. Grouping was performed using TyG index tertiles and multiple logistic regression was employed to assess the correlation between TyG levels and the risk of sarcopenia. The Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the prognostic value of the TyG index for sarcopenia. Linear regression analysis was utilized to elucidate the direct relationship between TyG index and sarcopenia. Additionally, the curve between the TyG and sarcopenia indices was examined using a generalized additive model. ResultsThe study included 981 individuals diagnosed with CIAD. After adjusting for potential confounders, a significant positive correlation was observed between TyG and sarcopenia (OR = 1.70, 95 % CI: 1.20–2.39, P = 0.002). Trend analysis using the chi-square test revealed an increase in sarcopenia prevalence concomitant with higher TyG levels (P < 0.05). Furthermore, linear regression analysis revealed a notable inverse linear association between the TyG and sarcopenia indices (β = −0.03; 95 % CI: −0.07–0.01; P = 0.020). The ROC curves corroborated the robust predictive capacity of TyG for sarcopenia among patients with CIAD, with an AUC of 0.685 (95 % CI: 0.636–0.735, P < 0.001). ConclusionOur research indicates a positive association between TyG and sarcopenia in CIAD patients. The TyG index may serve as a reliable marker for predicting sarcopenia risk in CIAD patients.

Efficacy of dupilumab for severe chronic rhinosinusitis with nasal polyps and asthma: A prospective study

Background: Dupilumab exerts clinical effects, including improved sinus opacification, olfactory function, and quality of life, in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). Meanwhile, only a few studies have reported its effects on nasal airway resistance and olfactory function, particularly in the Japanese population. Predictors of response remain unclear.Objective: In this prospective, observational study, we assessed the comprehensive efficacy and therapeutic response to dupilumab in severe CRSwNP patients with comorbid asthma.Methods: In 16 adult severe CRSwNP patients with comorbid asthma, the efficacy of 48-week dupilumab treatment, including olfactory function measured by a T&T olfactometer, nasal airway resistance measured by rhinomanometry, nasal polyp score, Lund-Mackay computed tomography score (LMS), and 22-item Sinonasal Outcome Test (SNOT-22), was assessed. Regarding asthma, the annualized rate of exacerbations, 7-item Asthma Control Questionnaire (ACQ-7), and spirometry were assessed. Treatment responsiveness was analyzed.Results: With 48-week dupilumab treatment, olfactory function, nasal airway resistance, nasal polyp score, LMS, and SNOT-22 scores improved significantly. Regarding comorbid asthma, the rate of exacerbations decreased, and ACQ-7 scores and lung function improved significantly. According to the European Position Paper on Rhinosinusitis and Nasal Polyps 2022/European Forum for Research and Education in Allergy and Airway Diseases criteria, 15 patients (94%) were moderate-to-excellent responders at 48 weeks of treatment. Patients with higher SNOT-22 scores, ACQ-7 scores, rates of asthma exacerbation in the previous year, and blood eosinophil counts benefited more from treatment.Conclusion: Dupilumab improved upper and lower airway outcomes especially in severe CRSwNP patients with comorbid, poorly controlled asthma.