Large Airways Research Articles

Neuroplasticity and neuroimmune interactions in fatal asthma.

Alteration of airway neuronal function and density and bidirectional interaction between immune cells and sensory peripheral nerves have been proposed to trigger and perpetuate inflammation that contribute to asthma severity. To date, few studies analysed neuroplasticity and neuroinflammation in tissue of asthmatic individuals. We hypothesized that the presence of these phenomena would be a pathological feature in fatal asthma. We have quantified the expression of the pan-neuronal marker PGP9.5 and the neuronal sensory-derived neuropeptide calcitonin gene-related peptide (CGRP) in the large airways of 12 individuals deceased due to an asthma attack and compared to 10 control lung samples. The proximity between nerve bundles to eosinophils, mast cells and CADM1+ cells was also quantified. We have additionally developed a hPSC-derived sensory neuron/mast cell co-culture model, from where mast cells were purified and differences in gene expression profile assessed. Fatal asthma patients presented a higher PGP9.5 and CGRP positive area in the airways, indicating sensory neuroplasticity. Eosinophils, mast cells and CADM1+ cells were observed in close contact or touching the airway nerve bundles, and this was found to be statistically higher in fatal asthma samples. Invitro co-culture model showed that human mast cells adhere to sensory neurons and develop a distinct gene expression profile characterized by upregulated expression of genes related to heterophilic adhesion, activation and differentiation markers, such as CADM4, PTGS2, C-KIT, GATA2, HDC, CPA3, ATXN1 and VCAM1. Our results support a significant role for neuroplasticity and neuroimmune interactions in fatal asthma, that could be implicated in the severity of the fatal attack. Accordingly, the presence of physical neuron and mast cell interaction leads to differential gene expression profile in the later cell type.

Neutrophilic inflammation in sputum or blood does not define a clinically distinct asthma phenotype in ATLANTIS

IntroductionNeutrophilic asthma has been suggested to be a clinically distinct phenotype characterized by more severe airflow obstruction and higher exacerbation risk. However, this has only been assessed in few and smaller studies, using different cut-offs to define neutrophilia, and with conflicting results.We used data from ATLANTIS, an observational longitudinal study including a large number of patients with asthma and healthy controls.AimTo examine if neutrophilic inflammation, either in sputum or blood, is more prevalent in asthma and whether it correlates with disease severity.MethodsATLANTIS included 773 asthma patients, with blood collected from 767 (99%) and sputum from 228 patients (30%). Data were available from 244 healthy controls, all providing blood and 126 (52%) providing sputum. Asthma patients were characterized including parameters of large and small airways disease at baseline and after 6- and 12-months follow-up. Sputum and blood neutrophilia were defined as values exceeding the upper quartile in asthma patients.ResultsThe prevalence of sputum neutrophilia did not differ between asthma patients and healthy controls. Asthma patients with sputum neutrophilia did not display more severe symptoms, large or small airways disease, or more frequent exacerbations. Blood neutrophilia was more common in asthma and associated with higher BMI, female sex, current smoking and systemic corticosteroid use. Patients with blood neutrophilia had a statistically significant, but small, increase in RV/TLC. Blood neutrophilia was not associated with large or small airways disease, or exacerbation risk.ConclusionSputum and blood neutrophilia do not define a distinct clinical phenotype in asthma.

The Impact of Lung Function on Sleep Monitoring in Obstructive Sleep Apnea Associated with Obstructive Lung Diseases: Insights from a Clinical Study.

Background/Objectives: Obstructive sleep apnea (OSA) and obstructive lung diseases (OLD) are common and interdependent respiratory disorders, where one condition may contribute to the development and worsening of the other (OLDOSA syndrome). The term OLDOSA syndrome includes two different conditions: Overlap syndrome (OVS: OSA + chronic obstructive pulmonary disease, COPD) and Alternative Overlap syndrome (aOVS: OSA + Asthma). Data on the interactions between lung function and respiratory monitoring during sleep in OLDOSA patients are few and controversial. Our study aims to evaluate the impact of lung function impairment on sleep breathing disorders, paying attention to the lack of literature about comparisons between OVS, aOVS, and the impact of small airways disease (SAD) in these patients. Methods: In total, 101 patients with a diagnosis of OSA and asthma or COPD underwent pulmonary function tests (PFTs) and nocturnal home sleep cardiorespiratory monitoring (HSCM). Exclusion criteria: Obesity hypoventilation syndrome (OHS) and other non-respiratory sleep disorders. Results: Sleep time with oxygen saturation below 90% (T90) was negatively correlated with forced expiratory volume in the first second, % of predicted (%FEV1), forced vital capacity, % of predicted (%FVC), forced expiratory flow at 25-75% of the pulmonary volume, % of predicted (%FEF25-75), and, after multivariable linear regression analysis, %FEF25-75 remained an independent factor for T90 with a negative correlation in mild and moderate OSA. Obstructive apnea index (oAI) and FEV1/FVC were negatively correlated in mild and moderate OSA. OVS presented with more severe OSA (higher AHI, oAI, and T90) and SAD (lower FEF25-75) compared to aOVS. Conclusions: This study highlights a possible interdependence between OLD and OSA; obstruction of the large and small airways at PFTs contributes to the worsening of these patients' nocturnal hypoxemia and obstructive events of the upper airway during sleep. Furthermore, this study shows that patients with OVS should be carefully monitored, as they present worse data at HSCM and have greater small airways involvement compared to aOVS.

New Brønsted–Lowry acid Co(II) complexes: Synthesis, characterization, and investigation of electrochemical application for sensing of salbutamol

In recent years, the employment of transition metal complexes for working electrode surface modification for sensor fabrication has become an area of research direction. Based on this, in this study, three Co(II) complexes: Co(phen)Cl2 (CoC12H8N2Cl2) (C1), and Brønsted–Lowry acids Co(phen)(HTA)Cl (CoC16H13N2O6Cl)(C2), and Co(phen)(HTA)2 (CoC20H18N2O12)(C3) were synthesized and characterized using various techniques such as UV–Vis, FT-IR, ICP OES, TGA, DTA, pXRD as well as electrolytic conductivity, and acid-base property analysis. C and C3 were found polycrystalline whose size falls within the nano range of 50 and 51 nm, respectively. The synthesis was intended to get materials for voltammetrically modifying glassy carbon electrodes for the determination of salbutamol. Salbutamolis a short-acting β2adrenergic receptor agonist that is applied for opening the medium and large airways in the lungs and eventually treats asthma among other problems. The electrochemical application of the synthesized materials was studied by fabricating through electropolymerization of C1, C2, and C3 on glassy carbon electrodes. The poly(C1)/GCE, poly(C2)/GCE, and poly(C3)/GCE) revealed effective surface area is 0.174 cm2, 0.183 cm2, and 0.281 cm2, respectively, and electrochemical catalysis of the materials increased with the number of the tartrate. The Rct values are 5686, 242, 216, and 185 Ω cm2, while the Cdl values are 9.93 × 10−8, 5.35 × 10−6, 1.25 × 10−5, and 2.72 × 10−5, for bare GCE, poly(C1)/GCE, poly(C2)/GCE and poly(C3)/GCE, respectively. Similarly, the rate of charge transfer (k°) increased significantly on the modified electrode compared to the bare GCE. Salbutamol demonstrated a single well-shaped irreversible oxidative peak at the modified electrodes in the ascending order of poly(C1)/GCE, poly(C2)/GCE, and poly(C3)/GCE when compared to a bare GCE.

Low-Dose Whole-Chest Dynamic CT for the Assessment of Large Airway Collapsibility in Patients with Suspected Tracheobronchial Instability.

Purpose To quantify tracheal collapsibility using low-dose four-dimensional (4D) CT and to compare visual and quantitative 4D CT-based assessments with assessments from paired inspiratory-expiratory CT, bronchoscopy, and spirometry. Materials and Methods The authors retrospectively analyzed 4D CT examinations (January 2016-December 2022) during shallow respiration in 52 patients (mean age, 66 years ± 12 [SD]; 27 female, 25 male), including 32 patients with chronic obstructive pulmonary disease (mean forced expiratory volume in 1 second percentage predicted [FEV1%], 50% ± 27), with suspected tracheal collapse. Paired CT data were available for 27 patients and bronchoscopy data for 46 patients. Images were reviewed by two radiologists in consensus, classifying patients into three groups: 50% or greater tracheal collapsibility, less than 50% collapsibility, or fixed stenosis. Changes in minimal tracheal lumen area, tracheal volume, and lung volume from inspiration to expiration were quantified using YACTA software. Tracheal collapsibility between groups was compared employing one-way analysis of variance (ANOVA). For related samples within one group, ANOVA with repeated measures was used. Spearman rank order correlation coefficient was calculated for collapsibility versus pulmonary function tests. Results At 4D CT, 25 of 52 (48%) patients had tracheal collapsibility of 50% or greater, 20 of 52 (38%) less than 50%, and seven of 52 (13%) had fixed stenosis. Visual assessment of 4D CT detected more patients with collapsibility of 50% or greater than paired CT, and concordance was 41% (P < .001). 4D CT helped identify more patients with tracheal collapsibility of 50% or greater than did bronchoscopy, and concordance was 74% (P = .39). Mean collapsibility of tracheal lumen area and volume at 4D CT were higher for 50% or greater visually assessed collapsibility (area: 53% ± 9 and lumen: 52% ± 10) compared with the less than 50% group (27% ± 9 and 26% ± 6, respectively) (P < .001), whereas both tracheal area and volume were stable for the fixed stenosis group (area: 16% ± 12 and lumen: 21% ± 11). Collapsibility of tracheal lumen area and volume did not correlate with FEV1% (rs = -0.002 to 0.01, P = .99-.96). Conclusion The study demonstrated that 4D CT is feasible and potentially more sensitive than paired CT for central airway collapse. Expectedly, FEV1% was not correlated with severity of tracheal collapsibility. Keywords: CT-Quantitative, Tracheobronchial Tree, Chronic Obstructive Pulmonary Disease, Imaging Postprocessing, Thorax Supplemental material is available for this article. © RSNA, 2024.

Covert airflow obstruction dominates the overt ones in interstitial lung disease: An appraisal.

Background & objectives The co-presence of non-emphysematous airflow obstruction in interstitial Lung disease (ILD) is not elaborated. The present study aims the job with spirometry. Methods ILD affected individuals with or without airflow obstruction (FEV1/FVC<0.7 or >0.7) on spirometry were compared in terms of FEV1 and FEF25-75 derived variables [FEF25-75 (%-predicted), FEV1-FEF25-75 distance, reversibility of FEV1 and FEF25-75 to salbutamol and change in FEV1 and FEF25-75 in %-predicted values]. Those showing significant difference (P=0.0001) suggesting obstruction were selected to draw respective receiver operating curve (ROC) curves to identify the best cut-off value for individual parameters. The efficacy of each surrogate was tested to identify airflow obstruction in both the initial 'overlap' as well as the 'unmixed' ILD affected individual for the presence of airflow obstruction. Results FEV1/FVC identified 30 overlap from 235 ILDs. The FEF25-75 (%-predicted), FEV1-FEF25-75 distance, FEF25-75 reversibility (in ml) and FEV1 (%-predicted) were significantly (P<0.0001) different between the two groups. Of these, the FEF25-75 (%-predicted) had high specificity and sensitivity (93.33 and 79.47%) to identify airflow limitation in the initial unmixed ILD-group. The surrogates with their cut off values identified 92 extra individuals making it 122/235 (51.91%) of ILD having airflow obstruction. The 'unmixed' group showed higher frequency and degree of FEV1 reversibility. Interpretation & conclusions The findings of this study suggest that the airflow obstruction in ILD involves both the intrathoracic large and small airways. Although seemingly parallel, their relative status (qualitative and quantitative) needs research especially in light of the a etio pathology and the extent of involvement of ILD.

Can lung anatomy predict the development of COVID-19 pneumonia in RT-PCR positive cases?

Purpose: The objective of this study was to investigate the relationship between Coronavirus disease 2019 (COVID-19) pneumonia and anatomical characteristics, including tracheobronchial and fissure variations, right/left main bronchus angle, carina angle, and large airway diameter, in patients who tested positive for the virus via reverse transcription-polymerase chain reaction (RT-PCR) at the outset of the pandemic. Materials and Methods: This cross-sectional study included 165 cases with positive RT-PCR tests who were admitted between March and June 2020 and subsequently scanned with thin-section unenhanced chest computed tomography (CT). They were divided into two groups according to the presence of pneumonia based on the chest CT images. Results: In our study, a total of 165 cases were analyzed, pneumonia was found in 35 of 76 (46.05%) female patients and 51 of 89 (57.30%) male patients. COVID-19 pneumonia was observed in older age groups. Anatomical variations and the presence of incomplete fissures were statistically higher in the pneumonia-positive group, while the difference was not statistically significant for accessory fissures. Mean tracheal area and right main bronchus angle were statistically higher in the pneumonia-positive group compared to the negative patients. The right lung was more involved than the left in terms of both zonal and total lung involvement. When the presence of comorbidity was assessed, 59 patients (35.75%) were found to have comorbidity. Hypertension, diabetes mellitus and cardiovascular disease were significantly higher among comorbidities in the pneumonia-positive group. The regression model showed that hypertension was associated with a 3.75-fold increase in COVID-19 pneumonia in test positive cases. Conclusion: Anatomical lung variations and incomplete fissures were observed more frequently in the COVID-19 pneumonia cases, independent of other comorbidities. We believe that there are anatomical variables that can be used to identify those predisposed to pneumonia in RT-PCR test positive cases.

The pH-sensitive translocation of V-ATPase in the small airway of cystic fibrosis pigs.

In contrast to pig large airways, the pH of airway surface liquid (ASL) in pig small airways is regulated by CFTR mediated HCO-3 secretion and the vacuolar-type H+ ATPase (V-ATPase) proton secretion. We hypothesized that in Cystic Fibrosis (CF), the ASL pH of small airways is acidic, and the V-ATPase is internalized. We quantified proton secretion during the addition of an alkaline test solutions by measuring changes in a pH dependent fluorescent dye generated by porcine small airway epithelia in the absence and presence of bafilomycin A1. The pH-dependent translocation of V-ATPase in ex vivo and in vivo preparations was measured using immunolocalization of V-ATPase. We found that bafilomycin sensitive proton secretion stopped when the ASL pH was less than 7.10. In non-CF pigs and mice, we found that V-ATPase was localized in the apical membrane, and internalized when the lungs were instilled with a pH 6.8 solution.Studies where we immediately fixed lungs from pigs revealed apical V-ATPase detection in non-CF piglets and less apical detection in CF piglets. Our data suggest that V-ATPase in small airways is internalized when the ASL pH is acidic. The decrease in apical localization of V-ATPase in CF pigs is consistent with an acidic ASL pH.

Quantitative assessment of chlorine gas inhalation injury based on endoscopic OCT and spectral encoded interferometric microscope imaging with deep learning.

Chlorine exposure can cause severe airway injuries. While the acute effects of chlorine inhalation are well-documented, the structural changes resulting from the post-acute, high-level chlorine exposure remain less understood. Airway sloughing is one of the standards for doctors to evaluate the lung function. Here, we report the application of a high-resolution swept-source optical coherence tomography system to investigate the progression of injury based on airway sloughing evaluation in a chlorine inhalation rabbit model. This system employs a 1.2mm diameter flexible fiberoptic endoscopic probe via an endotracheal tube to capture in vivo large airway anatomical changes before and as early as 30minafter acute chlorine exposure. We conducted an animal study using New Zealand white rabbits exposed to acute chlorine gas (800 ppm, 6min) during ventilation and monitored them using optical coherence tomography (OCT) for 6h. To measure the volume of airway sloughing induced by chlorine gas, we utilized deep learning for the segmentation task on OCT images. The results showed that the volume of chlorine induced epithelial sloughing on rabbit tracheal walls initially increased, peaked around 30min, and then decreased. Furthermore, we utilized a spectral encoded interferometric microscopy system to study ex vivo airway cilia beating dynamics based on Doppler shift, aiding in elucidating how chlorine gas affects cilia beating function. Cilia movability and beating frequency were decreased because of the epithelium damage. This quantitative approach has the potential to enhance the diagnosis and monitoring of injuries from toxic gas inhalation and to evaluate the efficacy of antidote treatments for these injuries.

Intermittent ozone inhalation during house dust mite-induced sensitization primes for adverse asthma phenotype

The ability of air pollution to induce acute exacerbation of asthma is well documented. However, the ability of ozone (O3), the most reactive gaseous component of air pollution, to function as a modulator during sensitization is not well established. C57BL/6 J male mice were intranasally sensitized to house dust mite (HDM) (40 μg/kg) for 3 weeks on alternate days in parallel with once-a-week O3 exposure (1 ppm). Mice were euthanized 24 h following the last HDM challenge. Lung lavage, histology, lung function (both forced oscillation and forced expiration-based), immune cell profiling, inflammation (pulmonary and systemic), and immunoglobulin production were assessed. Compared to HDM alone, HDM + O3 leads to a significant increase in peribronchial inflammation (p < 0.01), perivascular inflammation (p < 0.001) and methacholine-provoked large airway hyperreactivity (p < 0.05). Serum total IgG and IgE and HDM-specific IgG1 were 3–5 times greater in HDM + O3 co-exposure compared to PBS and O3-exposed groups. An increase in activated/mature lung total and monocyte-derived dendritic cells (p < 0.05) as well as T-activated, and T memory lymphocyte subset numbers (p < 0.05) were noted in the HDM + O3 group compared to HDM alone group. Concurrent O3 inhalation and HDM sensitization also caused significantly greater (p < 0.05) lung tissue interleukin-17 pathway gene expression and mediator levels in the serum. Redox imbalance was manifested by impaired lung antioxidant defense and increased oxidants. O3 inhalation during allergic sensitization coalesces in generating a significantly worse TH17 asthmatic phenotype.

Small airway inflammation in atypical asthma

BackgroundLess attention has been paid to the pathophysiological changes in atypical asthma such as cough variant asthma (CVA) and chest tightness variant asthma (CTVA). The obstruction of large and small airways is the important component in the development of asthma. We investigated whether small airway inflammation (SAI) induced small airway dysfunction (SAD) in these atypical asthmatics. MethodsSix hundred and eighty-six patients were enrolled and analyzed in the study. The partitioned airway inflammation was assessed by fractional exhaled nitric oxide (FeNO), such as FnNO, FeNO50, FeNO200, and calculated alveolar fraction of exhaled NO (CaNOdual). Correlations between exhaled NOs and SAD-related variables were assessed, whereas cell classification was evaluated by Spearman's rank tests. Classic asthma, CVA, and CTVA about potential risk were conducted using binary logistic regression models. ResultsThe whole airway inflammation increased in classic and atypical asthma than controls, whereas the central and peripheral airway inflammation in the CVA and CTVA groups increased compared with the classic asthma group. Smoking exposure was found to increase the central and peripheral airway inflammation in patients with asthma. The exhaled NO of FeNO50 and FeNO200 was associated with SAD in classic asthma, but not in CVA and CTVA. FeNO200 was the main risk (adjusted odds ratio [OR], 1.591; 95 % CI, 1.121–2.259; P = .009) in classic asthma and (adjusted OR, 1.456; 95 % CI, 1.247–1.700; P = .000) in CVA. The blood eosinophil levels were correlated with FeNO50 and FeNO200 in classic asthma and atypical asthma. ConclusionMore severe inflammatory process was present in central and peripheral airways in CVA and CTVA, which might reflect a pre-asthmatic state. SAI was the predominant risk factor in the development of asthma before SAD.

Factors influencing airway smooth muscle tone: a comprehensive review with a special emphasis on pulmonary surfactant.

A thin film of pulmonary surfactant lines the surface of the airways and alveoli, where it lowers the surface tension in the peripheral lungs, preventing collapse of the bronchioles and alveoli and reducing the work of breathing. It also possesses a barrier function for maintaining the blood-gas interface of the lungs and plays an important role in innate immunity. The surfactant film covers the epithelium lining both large and small airways, forming the first line of defense between toxic airborne particles/pathogens and the lungs. Furthermore, surfactant has been shown to relax airway smooth muscle (ASM) after exposure to ASM agonists, suggesting a more subtle function. Whether surfactant masks irritant sensory receptors or interacts with one of them is not known. The relaxant effect of surfactant on ASM is absent in bronchial tissues denuded of an epithelial layer. Blocking of prostanoid synthesis inhibits the relaxant function of surfactant, indicating that prostanoids might be involved. Another possibility for surfactant to be active, namely through ATP-dependent potassium channels and the cAMP-regulated epithelial chloride channels [cystic fibrosis transmembrane conductance regulators (CFTRs)], was tested but could not be confirmed. Hence, this review discusses the mechanisms of known and potential relaxant effects of pulmonary surfactant on ASM. This review summarizes what is known about the role of surfactant in smooth muscle physiology and explores the scientific questions and studies needed to fully understand how surfactant helps maintain the delicate balance between relaxant and constrictor needs.

Early diagnosis of small airway disease in asymptomatic polishing sector workers of a leather factory

Background: The leather industry stands as one of India’s burgeoning sectors, boasting significant manpower. Workers in the finishing sector, particularly those involved in polishing, face heightened risks due to exposure to formaldehyde, aniline, and resins, which can lead to respiratory complications. Aims and Objectives: The aims and objectives of the study are to determine the small airway obstruction in asymptomatic finishing sector workers of a leather factory. Materials and Methods: The current study was a cross-sectional study conducted in a leather factory located in Chennai, Tamil Nadu. A random sample of 60 workers was drawn from different sectors of a leather factory. Basic demographic details, smoking history, nature of work, exposure to irritants along with duration, and respiratory symptoms were collected. All workers were subjected to spirometry as per ATS guidelines and the results were analyzed. Association between length (years) of exposure, respiratory symptoms, and spirometry impairment among the workers were analysed. Results: Out of 60 samples, 38 were exposed to irritants and 22 were not exposed to irritants. Out of 38, 25 had small airway disease, seven had large airway obstruction, one had a restrictive pattern, and five had normal spirometry. 42.1% of them were asymptomatic. Conclusion: Small airway obstruction is notably prevalent, especially among asymptomatic workers in the polishing sector. Prolonged exposure is associated with the development of large airway obstructive disease. This study underscores the importance of continuous monitoring for airway diseases in occupationally exposed workers, advocating for timely preventive and protective measures to curb disease progression.

High comorbidity rates in congenital lobar emphysema and the effect on clinical presentation.

The presence of comorbidities (CM) in congenital lobar emphysema (CLE) has been previously described with varying rates. However, the clinical implication of CM on the clinical presentation and patient outcome in CLE is unclear. This was a retrospective cohort study between 2000 and 2022 in a single institution. The study included pediatric patients diagnosed with CLE. During the study period, 36 patients were identified with CLE. The presence of respiratory symptoms at diagnosis was documented in 69% (24/35) of the patients with 48% admitted to intensive care units. The presence of CM was documented in 14/36 (39%) of the patients, with cardiovascular anomalies as the most common (22%), followed by genitourinary anomalies (11%) and large airway anomalies (8%). When comparing the CM group (n = 14) vs the non-CM group (N = 22), there was no significant difference regarding gender, term birth, age of diagnosis, and the location of the lesion. The CM group had significantly higher rates of intensive care unit (ICU) admissions (75% vs 33%, p = 0.02), longer duration of admission (median 46days vs 9, p = 0.02), and need for pre-operative non-invasive respiratory support (50% vs 5%, p = 0.002).Conclusion: The presence of CM in CLE was associated with a more severe presentation as reflected with significantly higher rates of ICU admissions, prolonged admissions, and higher need for non-invasive respiratory support. Screening for CM, mostly for cardiac anomalies, is recommended at time of CLE diagnosis. What is Known: • Congenital lobar emphysema (CLE) is a developmental lung anomaly generally associated with other comorbidities; however, their clinical implication on presentation is unclear • The prevalence of comorbidities in CLE was previously reported around 15-20%, with cardiovascular anomalies as the most common What is New: • Comorbidities are very common (39%) in CLE, and their presence is related to a more severe clinical presentation and need for respiratory support • Screening for comorbidities is recommended in CLE, specifically for cardiovascular and genitourinary anomalies.

Worse pulmonary function in association with cumulative exposure to nanomaterials. Hints of a mediation effect via pulmonary inflammation

BackgroundToday, nanomaterials are broadly used in a wide range of industrial applications. Such large utilization and the limited knowledge on to the possible health effects have raised concerns about potential consequences on human health and safety, beyond the environmental burden. Given that inhalation is the main exposure route, workers exposed to nanomaterials might be at risk of occurrence of respiratory morbidity and/or reduced pulmonary function. However, epidemiological evidence regarding the association between cumulative exposure to nanomaterials and respiratory health is still scarce. This study focused on the association between cumulative exposure to nanomaterials and pulmonary function among 136 workers enrolled in the framework of the European multicentric NanoExplore project.ResultsOur findings suggest that, independently of lifelong tobacco smoking, ethnicity, age, sex, body mass index and physical activity habits, 10-year cumulative exposure to nanomaterials is associated to worse FEV1 and FEF25 − 75%, which might be consistent with the involvement of both large and small airway components and early signs of airflow obstruction. We further explored the hypothesis of a mediating effect via airway inflammation, assessed by interleukin (IL-)10, IL-1β and Tumor Necrosis Factor alpha (TNF-α), all quantified in the Exhaled Breath Condensate of workers. The mediation analysis results suggest that IL-10, TNF-α and their ratio (i.e., anti-pro inflammatory ratio) may fully mediate the negative association between cumulative exposure to nanomaterials and the FEV1/FVC ratio. This pattern was not observed for other pulmonary function parameters.ConclusionsSafeguarding the respiratory health of workers exposed to nanomaterials should be of primary importance. The observed association between cumulative exposure to nanomaterials and worse pulmonary function parameters underscores the importance of implementing adequate protective measures in the nanocomposite sector. The mitigation of harmful exposures may ensure that workers can continue to contribute productively to their workplaces while preserving their respiratory health over time.

Repeat treatment of organotypic airway cultures with ethyl methanesulfonate causes accumulation of somatic cell mutations without expansion of bronchial-carcinoma-specific cancer driver mutations

The human in vitro organotypic air-liquid-interface (ALI) airway tissue model is structurally and functionally similar to the human large airway epithelium and, as a result, is being used increasingly for studying the toxicity of inhaled substances. Our previous research demonstrated that DNA damage and mutagenesis can be detected in human airway tissue models under conditions used to assess general and respiratory toxicity endpoints. Expanding upon our previous proof-of-principle study, human airway epithelial tissue models were treated with 6.25–100 µg/mL ethyl methanesulfonate (EMS) for 28 days, followed by a 28-day recovery period. Mutagenesis was evaluated by Duplex Sequencing (DS), and clonal expansion of bronchial-cancer-specific cancer-driver mutations (CDMs) was investigated by CarcSeq to determine if both mutation-based endpoints can be assessed in the same system. Additionally, DNA damage and tissue-specific responses were analyzed during the treatment and following the recovery period. EMS exposure led to time-dependent increases in mutagenesis over the 28-day treatment period, without expansion of clones containing CDMs; the mutation frequencies remained elevated following the recovery. EMS also produced an increase in DNA damage measured by the CometChip and MultiFlow assays and the elevated levels of DNA damage were reduced (but not eliminated) following the recovery period. Cytotoxicity and most tissue-function changes induced by EMS treatment recovered to control levels, the exception being reduced proliferating cell frequency. Our results indicate that general, respiratory-tissue-specific and genotoxicity endpoints increased with repeat EMS dosing; expansion of CDM clones, however, was not detected using this repeat treatment protocol. DisclaimerThis article reflects the views of its authors and does not necessarily reflect those of the U.S. Food and Drug Administration. Any mention of commercial products is for clarification only and is not intended as approval, endorsement, or recommendation.

Sex differences in asthma control, lung function and exacerbations: the ATLANTIS study

BackgroundAsthma is a heterogeneous disease with a prevalence and severity that differs between male and female patients.QuestionWhat are differences between male and female patients with asthma with regard to asthma...

Biodegradable tracheal stents: our ten-year experience with adult patients

BackgroundBiodegradable (BD) stents made from polydioxanone have been used only in human airways. These stents combine the advantages of classical tracheal stents, and fewer side effects are expected due to their biocompatibility and their time-limited presence in airways. However, new clinical consequences have arisen. Here, the authors share their experiences with BD stents for tracheal indications, focusing on their safety and efficacy.MethodsThis was a retrospective review of a collected database of adult patients who underwent implantation of biodegradable tracheal stents between September 2013 and December 2022 at the Department of Respiratory Medicine of the 1st Faculty of Medicine in Prague and Thomayer University Hospital. The indications included functionally significant nonmalignant tracheal stenosis and tracheomalacia. Self-expandable, biodegradable, polydioxanone tracheal stents manufactured by ELLA-CS Ltd. (Hradec Kralove, Czech Republic) were implanted during rigid bronchoscopy under general anaesthesia. All patients were followed up in the department and were provided with the necessary care. The main efficacy and safety parameters and relationships were analysed using descriptive statistics and Fisher´s exact, Wilcoxon and Kruskal‒Wallis tests.ResultsA total of 65 stents were implanted in 47 adult patients. During the first two months after implantation, when adequate function was expected, the stent was found to be effective in 26 out of 39 patients who completed this period (66.7%). The clinical effectiveness reached 89.7%, as early restenoses were mostly mild and necessitated treatment in only 4 patients. The frequencies of significant mucostasis, migration and granulation tissue growth were 2.6%, 7.5% and 23.1%, respectively, during this period. Thirty-four participants completed the half-year follow-up period after the first or second stent insertion, and some were followed up beyond this period. Poor control of symptoms, the development of restenosis and the need for interventions were characteristic of this period as the stents degraded. Twenty-two patients who experienced remodelling or stabilization of the tracheal lumen achieved a stent-free state. Seven patients underwent subsequent surgical treatment.ConclusionsBD stents are safe and provide adequate tracheal support until they begin to degrade. The use of BD stents necessitates close monitoring of patients and accurate treatment of possible restenosis.Trial registrationBased on project NT14146 – Biodegradable stents in the management of the large airways (2013–2015, MZ0/NT), registered on May 1, 2013, in the Research and Development and Innovation Information System of the Czech Republic and at ClinicalTrials.gov (reg. no. NCT02620319, December 2, 2015).

An Ovine Model Yields Histology and Gene Expression Changes Consistent with Laryngotracheal Stenosis.

Animal models for laryngotracheal stenosis (LTS) are critical to understand underlying mechanisms and study new therapies. Current animal models for LTS are limited by small airway sizes compared to human. The objective of this study was to develop and validate a novel, large animal ovine model for LTS. Sheep underwent either bleomycin-coated polypropylene brush injury to the subglottis (n = 6) or airway stent placement (n = 2) via suspension microlaryngoscopy. Laryngotracheal complexes were harvested 4 weeks following injury or stent placement. For the airway injury group, biopsies (n = 3 at each site) were collected of tracheal scar and distal normal regions, and analyzed for fibrotic gene expression. Lamina propria (LP) thickness was compared between injured and normal areas of trachea. No mortality occurred in sheep undergoing airway injury or stent placement. There was no migration of tracheal stents. After protocol optimization, LP thickness was significantly increased in injured trachea (Sheep #3: 529.0 vs. 850.8 um; Sheep #4: 933.0 vs. 1693.2 um; Sheep #5: 743.7 vs. 1378.4 um; Sheep #6: 305.7 vs. 2257.6 um). A significant 62-fold, 20-fold, 16-fold, 16-fold, and 9-fold change of COL1, COL3, COL5, FN1, and TGFB1 was observed in injured scar specimen relative to unaffected airway, respectively. An ovine LTS model produces histologic and transcriptional changes consistent with fibrosis seen in human LTS. Airway stent placement in this model is safe and feasible. This large airway model is a reliable and reproducible method to assess the efficacy of novel LTS therapies prior to clinical translation. N/A Laryngoscope, 134:4239-4245, 2024.

The effect of telephone and short-message follow-ups on compliance and efficacy in asthmatic children treated with inhaled corticosteroid: A randomized controlled trial.

This study aims to evaluate the effect of telephone and short-message follow-ups on compliance and efficacy in asthmatic children treated with inhaled corticosteroids. A total of 120 children with moderate bronchial asthma who visited the Asthma Outpatient Department of the Affiliated Hospital of Qingdao University were enrolled in the study. They were divided randomly into 3 groups based on the type of follow-up given: a combined telephone and short-message service (Tel + SMS) group, a SMS group, and a control group. After being followed up for 12 weeks, each child's asthma control level was assessed and their lung function was measured. The compliance rates of children in the Tel + SMS group and SMS group were 86.49% and 56.25%, respectively. The total effective rates of these 2 groups (94.59% and 75.0%, respectively) were significantly higher than the rate of the control group (P < .01). The lung function indicators of the children in all 3 groups were better than those before treatment, although only the Tel + SMS group and SMS group improved significantly (P < .05). The lung function indicators of the large and small airways in the Tel + SMS group and the SMS group were also significantly better than those of the control group (P < .01). The results of the study suggest that 1 of the causes of poor compliance in asthmatic children is fear of an adverse reaction to inhaled corticosteroids. Telephone and short-message follow-ups can increase compliance with inhaled corticosteroid treatment and improve the asthma control levels and lung function of asthmatic children.