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Toxics Sep 2023Smoking cessation is difficult but maintaining smoke-free without nicotine replacement therapy is even harder. During the last few years, several different alternative...
Smoking cessation is difficult but maintaining smoke-free without nicotine replacement therapy is even harder. During the last few years, several different alternative products, including heated tobacco products (HTP), have been introduced to the market. In this study, we investigated the acute effects of IQOS and glo (two HTP) consumption on small airway function and arterial stiffness in a head-to-head design, comparing them to combustible cigarettes, nicotine-free e-cigarettes and a sham smoking group. Seventeen healthy occasional smokers were included in a single-center, five-arm, crossover study. The parameters of small airway function and hemodynamics were collected at several time points before and after consumption using Mobil-O-Graph™ (I.E.M., Stolberg, Germany) and TremoFlo c-100 (THORASYS Thoracic Medical Systems Inc., Montreal, QC, Canada). Small airway obstruction and resistance were both significantly increased after the consumption of cigarettes and substitute products. All products containing nicotine led to similar significant increases in blood pressure and arterial stiffness. Hemodynamic parameters were also increased after the consumption of e-cigarettes without nicotine, but compared to nicotine-containing products, the increase was shorter and weaker. We conclude that, although it has yet to be determined why, HTP have acute harmful effects on small airway function, possibly even exceeding the effects of combustible cigarettes. Like other nicotine-containing products, HTP leads to a nicotine-related acute increase in arterial stiffness and cardiovascular stress, similar to combustible cigarettes, which associates these products with an increased cardiovascular risk.
PubMed: 37755768
DOI: 10.3390/toxics11090758 -
Children (Basel, Switzerland) Oct 2023Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are genetic respiratory diseases featured by chronic upper and lower airway inflammation and infection, mainly... (Review)
Review
Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are genetic respiratory diseases featured by chronic upper and lower airway inflammation and infection, mainly due to impaired mucociliary clearance due to genetic mutations. Sleep is crucial to healthy children's normal physical and psychological development and has an important value in chronic respiratory diseases. Impaired sleep quality, such as sleep deprivation or insufficient sleep during the night, and sleep respiratory disorders (SRDs) are common in 5% to 30% of the general population. Sleep disruption leads to attention deficits, daytime sleepiness, fatigue and mood disorders and correlates to a worsened quality of life. Furthermore, sleep respiratory disorders (SRSs) are under-recognized comorbidities in CF and PCD patients. SRSs include a spectrum of symptoms ranging from primary snoring through upper airway resistance to obstructive sleep apnea (OSA), nocturnal hypoventilation and hypoxemia occurring in people with moderate to severe lung disease and damaging the disease-related outcomes and quality of life. Effective screening during sleep with polysomnography is very important for the timely initiation of efficacious treatments and to prevent worsened respiratory, metabolic and cardiovascular outcomes. However, the impact of SRDs on health and quality of life is still underinvestigated.
PubMed: 37892370
DOI: 10.3390/children10101707 -
Radiology. Cardiothoracic Imaging Dec 2023Purpose To determine if proton (H) MRI-derived specific ventilation is responsive to bronchodilator (BD) therapy and associated with clinical biomarkers of type 2 airway...
Purpose To determine if proton (H) MRI-derived specific ventilation is responsive to bronchodilator (BD) therapy and associated with clinical biomarkers of type 2 airway inflammation and airways dysfunction in severe asthma. Materials and Methods In this prospective study, 27 participants with severe asthma (mean age, 52 years ± 9 [SD]; 17 female, 10 male) and seven healthy controls (mean age, 47 years ± 16; five female, two male), recruited between 2018 and 2021, underwent same-day spirometry, respiratory oscillometry, and tidal breathing H MRI. Participants with severe asthma underwent all assessments before and after BD therapy, and type 2 airway inflammatory biomarkers were determined (blood eosinophil count, sputum eosinophil percentage, sputum eosinophil-free granules, and fraction of exhaled nitric oxide) to generate a cumulative type 2 biomarker score. Specific ventilation was derived from tidal breathing H MRI and its response to BD therapy, and relationships with biomarkers of type 2 airway inflammation and airway dysfunction were evaluated. Results Mean MRI specific ventilation improved with BD inhalation (from 0.07 ± 0.04 to 0.11 ± 0.04, < .001). Post-BD MRI specific ventilation ( = .046) and post-BD change in MRI specific ventilation ( = .006) were greater in participants with asthma with type 2 low biomarkers compared with participants with type 2 high biomarkers of airway inflammation. Post-BD change in MRI specific ventilation was correlated with change in forced expiratory volume in 1 second ( = 0.40, = .04), resistance at 5 Hz ( = -0.50, = .01), resistance at 19 Hz ( = -0.42, = .01), reactance area ( = -0.54, < .01), and reactance at 5 Hz ( = 0.48, = .01). Conclusion Specific ventilation evaluated with tidal breathing H MRI was responsive to BD therapy and was associated with clinical biomarkers of airways disease in participants with severe asthma. MRI, Severe Asthma, Ventilation, Type 2 Inflammation © RSNA, 2023 See also the commentary by Moore and Chandarana in this issue.
Topics: Male; Humans; Female; Middle Aged; Protons; Prospective Studies; Asthma; Inflammation; Biomarkers; Magnetic Resonance Imaging
PubMed: 38166343
DOI: 10.1148/ryct.230054 -
Pediatric Pulmonology Nov 2023Mechanisms underlying lung dysfunction after preterm birth are poorly understood. Studying phenotypes of prematurity-associated lung disease may aid understanding of...
INTRODUCTION
Mechanisms underlying lung dysfunction after preterm birth are poorly understood. Studying phenotypes of prematurity-associated lung disease may aid understanding of underlying mechanisms. Preterm-born children with and without lung dysfunction and term controls were assessed using oscillometry before and after exercise, and after postexercise bronchodilation.
METHODS
Preterm-born children, born at gestation of 34 weeks or less, were classified into those with prematurity-associated obstructive lung disease (POLD; FEV < LLN, FEV /FVC < LLN), prematurity-associated preserved ratio of impaired spirometry (pPRISm; FEV < LLN, FEV /FVC ≥ LLN) and compared to preterm (FEV ≥ LLN) and term controls (%predicted FEV > 90%). All children underwent cardiopulmonary exercise, and oscillometry assessment at baseline, postexercise, and after postexercise bronchodilator administration.
RESULTS
From 241 participants aged 7-12 years, complete data were available from 179: 15 children with POLD and 11 with pPRISm were compared with 93 preterm and 60 term controls. POLD group, when compared to both control groups, had impaired impedance, greater resistance, more negative (greater magnitude) reactance at low frequencies, and also had decreased compliance. pPRISm group demonstrated impaired reactance and compliance compared to term controls. No differences were noted between the preterm and term controls. Exercise had little impact on oscillometry values, but children with POLD had greatest improvements after postexercise bronchodilator administration, with decreased resistance and decreased magnitude of reactance, particularly at low frequencies.
CONCLUSION
Preterm-born children with obstructive airway disease had the greatest oscillometry impairments and the largest improvements after postexercise bronchodilator compared to control groups. Oscillometry can potentially be used to identify preterm-born children with lung disease to institute treatment.
Topics: Child; Female; Humans; Infant, Newborn; Bronchodilator Agents; Oscillometry; Forced Expiratory Volume; Premature Birth; Lung; Lung Diseases; Lung Diseases, Obstructive; Spirometry; Infant, Newborn, Diseases
PubMed: 37701982
DOI: 10.1002/ppul.26658 -
Inflammation Apr 2024Interleukin-27 receptor (IL-27R) is expressed in a variety of immune cells and structural cells, including dendritic cells. The mechanism of IL-27 in asthma has not been...
Interleukin-27 receptor (IL-27R) is expressed in a variety of immune cells and structural cells, including dendritic cells. The mechanism of IL-27 in asthma has not been fully elucidated. This study aimed to examine whether IL-27 regulated the CD39/ATP axis of dendritic cells in asthma. Our results showed that in ovalbumin (OVA)-induced asthma mouse model, IL-27Rα asthmatic mice showed increased airway resistance, increased infiltration of inflammatory cells in lung tissue, proliferation of goblet cells, enhanced expression of Muc5 AC around airway epithelium, increased total number of cells and eosinophils, increased levels of total IgE, OVA-IgE, IL-4, IL-5, IL-13 and IL-17 A, and increased expression of transcription factors GATA-3 and RORγt in lung tissue. The expression of CD39 mRNA and protein in the lung tissue of IL-27Rα asthmatic mice decreased, and the expression of NLRP3, ASC and Caspase-1 in NLRP3 inflammasome components increased. The concentration of ATP was significantly increased compared with WT asthmatic mice. In vitro experiments showed that the expression of CD39 in lung dendritic cells of IL-27Rα asthmatic mice decreased, while the expression of NLRP3 inflammasome components NLRP3, ASC and Caspase-1 increased. These findings indicate that IL-27 directly and indirectly regulates immunoinflammatory responses in asthma by acting on dendritic cells CD39/ATP Axis.
Topics: Animals; Mice; Adenosine Triphosphate; Antigens, CD; Apyrase; Asthma; Dendritic Cells; Inflammation; Interleukins; Lung; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Receptors, Interleukin; Respiratory Hypersensitivity
PubMed: 38117410
DOI: 10.1007/s10753-023-01945-9 -
Physiological Reports Jul 2023The pathogenesis of asthma has been partially linked to lung and gut microbiome. We utilized a steroid-resistant chronic model of cockroach antigen-induced (CRA) asthma...
The pathogenesis of asthma has been partially linked to lung and gut microbiome. We utilized a steroid-resistant chronic model of cockroach antigen-induced (CRA) asthma with corticosteroid (fluticasone) treatment to examine lung and gut microbiome during disease. The pathophysiology assessment demonstrated that mucus and airway hyperresponsiveness were increased in the chronic CRA with no alteration in the fluticasone (Flut)-treated group, demonstrating steroid resistance. Analysis of mRNA from lungs showed no decrease of MUC5AC or Gob5 in the Flut-treated group. Furthermore, flow-cytometry in lung tissue showed eosinophils and neutrophils were not significantly reduced in the Flut-treated group compared to the chronic CRA group. When the microbiome profiles were assessed, data showed that only the Flut-treated animals were significantly different in the gut microbiome. Finally, a functional analysis of cecal microbiome metabolites using PiCRUSt showed several biosynthetic pathways were significantly enriched in the Flut-treated group, with tryptophan pathway verified by ELISA with increased kynurenine in homogenized cecum samples. While the implications of these data are unclear, they may suggest a significant impact of steroid treatment on future disease pathogenesis through microbiome and associated metabolite pathway changes.
Topics: Animals; Lung; Asthma; Allergens; Fluticasone; Microbiota; Cockroaches
PubMed: 37403414
DOI: 10.14814/phy2.15761 -
JCI Insight Feb 2024BACKGROUNDInformation about the size, airway location, and longitudinal behavior of mucus plugs in asthma is needed to understand their role in mechanisms of airflow...
BACKGROUNDInformation about the size, airway location, and longitudinal behavior of mucus plugs in asthma is needed to understand their role in mechanisms of airflow obstruction and to rationally design muco-active treatments.METHODSCT lung scans from 57 patients with asthma were analyzed to quantify mucus plug size and airway location, and paired CT scans obtained 3 years apart were analyzed to determine plug behavior over time. Radiologist annotations of mucus plugs were incorporated in an image-processing pipeline to generate size and location information that was related to measures of airflow.RESULTSThe length distribution of 778 annotated mucus plugs was multimodal, and a 12 mm length defined short ("stubby", ≤12 mm) and long ("stringy", >12 mm) plug phenotypes. High mucus plug burden was disproportionately attributable to stringy mucus plugs. Mucus plugs localized predominantly to airway generations 6-9, and 47% of plugs in baseline scans persisted in the same airway for 3 years and fluctuated in length and volume. Mucus plugs in larger proximal generations had greater effects on spirometry measures than plugs in smaller distal generations, and a model of airflow that estimates the increased airway resistance attributable to plugs predicted a greater effect for proximal generations and more numerous mucus plugs.CONCLUSIONPersistent mucus plugs in proximal airway generations occur in asthma and demonstrate a stochastic process of formation and resolution over time. Proximal airway mucus plugs are consequential for airflow and are in locations amenable to treatment by inhaled muco-active drugs or bronchoscopy.TRIAL REGISTRATIONClinicaltrials.gov; NCT01718197, NCT01606826, NCT01750411, NCT01761058, NCT01761630, NCT01716494, and NCT01760915.FUNDINGAstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi-Genzyme-Regeneron, and TEVA provided financial support for study activities at the Coordinating and Clinical Centers beyond the third year of patient follow-up. These companies had no role in study design or data analysis, and the only restriction on the funds was that they be used to support the SARP initiative.
Topics: Humans; Asthma; Bronchoscopy; Lung; Mucus; Tomography, X-Ray Computed
PubMed: 38127464
DOI: 10.1172/jci.insight.174124 -
Annals of Thoracic Medicine 2023Most interstitial lung diseases (ILDs) manifest with a restrictive ventilatory defect as the common physiologic abnormality. Low carbon monoxide diffusing capacity...
BACKGROUND
Most interstitial lung diseases (ILDs) manifest with a restrictive ventilatory defect as the common physiologic abnormality. Low carbon monoxide diffusing capacity (Dlco) is considered to be the earliest abnormality on pulmonary function tests (PFTs) in patients with ILD. However, its measurement requires complex and expensive equipment. Our study aimed to assess if high expiratory flows are the earliest PFT abnormality in patients with idiopathic pulmonary fibrosis (IPF) and ILD.
METHODS
In a real-world cohort of incident cases with ILD, we identified the initial PFTs on all patients newly diagnosed with ILD at Kingston Health Sciences Center (in Kingston, Ontario, Canada) between 2013 and 2017. The diagnosis of ILD, including IPF, was established as per current guidelines. Among patients with normal forced vital capacity (FVC), total lung capacity (TLC), and Dlco, we assessed the frequency of high expiratory flows defined as forced expiratory volume in 1 s (FEV)/FVC, FEF, FEF, FEF and peak expiratory flow > 95% confidence limit of normal. We adjusted for emphysema, increased airway resistance, and obesity.
RESULTS
We assessed PFTs of 289 patients with ILD; 88 (30%) of them had normal FVC, TLC, and Dlco. Among these, high FEV1/FVC was the most common abnormality in 37% of patients, in 43% of nonobese patients, and in 58% of those with no emphysema and normal airway resistance. Results were similar in the 88 patients with IPF.
CONCLUSIONS
High FEV1/FVC could allow identifying patients with ILD/IPF in the earliest stages of their disease with simple spirometry, leading to earlier diagnosis and treatment.
PubMed: 37663875
DOI: 10.4103/atm.atm_38_23 -
European Review For Medical and... Oct 2023Narrow maxilla occurring due to various congenital or acquired causes creates major orthodontic problems and complicates prosthetic dental rehabilitation. The etiologic...
OBJECTIVE
Narrow maxilla occurring due to various congenital or acquired causes creates major orthodontic problems and complicates prosthetic dental rehabilitation. The etiologic factors are mostly related to upper airway pathologies that restrict breathing and cause negative pressure at the base of the nose and nasopharynx. The upper and lower airway is a whole unit. Regional anomalies or acquired problems affect the entire system. This can lead to developmental issues and permanent disorders in childhood, which will last their real life. This study was planned to investigate the incidence of nasopharyngeal obstruction originating from allergic rhinitis, turbinate hypertrophy, septum deviation, and adenoid vegetation in children scheduled for orthodontic treatment due to maxillary stenosis.
PATIENTS AND METHODS
Our study group consists of one hundred children aged 12-16 years who applied to the orthodontist due to dental malalignment and were found to have a narrowing of the maxilla. After the orthodontic evaluation, the patients were referred for an ENT examination to evaluate the etiological factors originating from the upper respiratory tract. In the study group, nasal congestion and allergic rhinitis were first investigated. All symptoms were evaluated and scored. Then, an ENT physical examination was performed in all cases, and nasal cavities, nasopharynx, and oropharynx were assessed with a fiberoptic endoscope. Regarding etiological factors, allergic rhinitis, turbinate hypertrophy, nasal septum deviation, and adenoid vegetation that would prevent breathing were carefully investigated.
RESULTS
Firstly, deep palate, narrowed maxillary arch, V-shaped arch, adenoid face type, bilateral posterior crossbite, insufficient lip presence, maxillary incisor protrusion (upper forward thrust), skeletal class 2 division 1 malocclusion, and increased lower face height detected in patients primarily diagnoses were grouped according to their pathologies. Allergic rhinitis was found in 43 cases, turbinate hypertrophy in 30 instances, nasal septum deviation in 18 cases, and adenoid vegetation that prevented respiration in 61 patients.
CONCLUSIONS
It is known that increased nasal airway resistance due to allergic rhinitis, septal deviation, turbinate hypertrophy, or adenoid vegetation in the upper respiratory tract may lead to permanent orthodontic disorders in children and adolescents. A multidisciplinary approach, early diagnosis, and treatment should be the first step to prevent this situation. Secondly, it should be planned to correct the anatomical disorders that have occurred with appliances and, if necessary, surgical approaches. Taking precautions before permanent problems arise in childhood is also crucial in prosthetic dentistry.
Topics: Child; Adolescent; Humans; Maxilla; Nose; Nasopharynx; Rhinitis, Allergic; Hypertrophy
PubMed: 37869951
DOI: 10.26355/eurrev_202310_34073 -
Respiratory Research Apr 2024Airway remodelling plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) is a significant...
BACKGROUND
Airway remodelling plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) is a significant process during the occurrence of airway remodelling. Increasing evidence suggests that glucose transporter 3 (GLUT3) is involved in the epithelial mesenchymal transition (EMT) process of various diseases. However, the role of GLUT3 in EMT in the airway epithelial cells of COPD patients remains unclear.
METHODS
We detected the levels of GLUT3 in the peripheral lung tissue of COPD patients and cigarette smoke (CS)-exposed mice. Two Gene Expression Omnibus GEO datasets were utilised to analyse GLUT3 gene expression profiles in COPD. Western blot and immunofluorescence were used to detect GLUT3 expression. In addition, we used the AAV9-GLUT3 inhibitor to reduce GLUT3 expression in the mice model. Masson's staining and lung function measurement were used detect the collagen deposition and penh in the mice. A cell study was performed to confirm the regulatory effect of GLUT3. Inhibition of GLUT3 expression with siRNA, Western blot, and immunofluorescence were used to detect the expression of E-cadherin, N-cadherin, vimentin, p65, and ZEB1.
RESULTS
Based on the GEO data set analysis, GLUT3 expression in COPD patients was higher than in non-smokers. Moreover, GLUT3 was highly expressed in COPD patients, CS exposed mice, and BEAS-2B cells treated with CS extract (CSE). Further research revealed that down-regulation of GLUT3 significantly alleviated airway remodelling in vivo and in vitro. Lung function measurement showed that GLUT3 reduction reduced airway resistance in experimental COPD mice. Mechanistically, our study showed that reduction of GLUT3 inhibited CSE-induced EMT by down-regulating the NF-κB/ZEB1 pathway.
CONCLUSION
We demonstrate that CS enhances the expression of GLUT3 in COPD and further confirm that GLUT3 may regulate airway remodelling in COPD through the NF-κB/ZEB1 pathway; these findings have potential value in the diagnosis and treatment of COPD. The down-regulation of GLUT3 significantly alleviated airway remodelling and reduced airway resistance in vivo. Our observations uncover a key role of GLUT3 in modulating airway remodelling and shed light on the development of GLUT3-targeted therapeutics for COPD.
Topics: Humans; Mice; Animals; NF-kappa B; Airway Remodeling; Cigarette Smoking; Glucose Transporter Type 3; Pulmonary Disease, Chronic Obstructive; Epithelial-Mesenchymal Transition; Epithelial Cells; Zinc Finger E-box-Binding Homeobox 1
PubMed: 38594707
DOI: 10.1186/s12931-024-02785-3