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Respiratory Research Oct 2023Deep inspiration (DI) has been shown to induce bronchodilation and bronchoprotection in bronchochallenged healthy subjects, but not in asthmatics. Strain-induced... (Review)
Review
BACKGROUND
Deep inspiration (DI) has been shown to induce bronchodilation and bronchoprotection in bronchochallenged healthy subjects, but not in asthmatics. Strain-induced relaxation of airway smooth muscle (ASM) is considered one of the factors responsible for these effects. Other factors include the release or redistribution of pulmonary surfactant, alteration in mucus plugs, and changes in airway heterogeneity.
MAIN BODY
The present review is focused on the DI effect on ASM function, based on recent findings from ex vivo sheep lung experiments showing a large change in airway diameter during a DI. The amount of stretch on the airways, when applied to isolated airway rings in vitro, caused a substantial decrease in ASM contractility that takes many minutes to recover. When challenged with a bronchoconstrictor, the increase in pulmonary resistance in the ex vivo ovine lungs is mostly due to the increase in airway resistance.
CONCLUSIONS
Although non-ASM related factors cannot be excluded, the large strain on the airways associated with a DI substantially reduces ASM contractility and thus can account for most of the bronchodilatory and bronchoprotective effects of DI.
Topics: Humans; Animals; Sheep; Bronchi; Lung; Asthma; Inhalation; Muscle, Smooth
PubMed: 37853472
DOI: 10.1186/s12931-023-02538-8 -
Cell Reports. Medicine Jan 2024Antibiotics and cystic fibrosis transmembrane conductance regulator (CFTR) modulators play a pivotal role in cystic fibrosis (CF) treatment, but both have limitations.... (Review)
Review
Antibiotics and cystic fibrosis transmembrane conductance regulator (CFTR) modulators play a pivotal role in cystic fibrosis (CF) treatment, but both have limitations. Antibiotics are linked to antibiotic resistance and disruption of the airway microbiome, while CFTR modulators are not widely accessible, and structural lung damage and pathogen overgrowth still occur. Complementary strategies that can beneficially modulate the airway microbiome in a preventive way are highly needed. This could be mediated via oral probiotics, which have shown some improvement of lung function and reduction of airway infections and exacerbations, as a cost-effective approach. However, recent data suggest that specific and locally administered probiotics in the respiratory tract might be a more targeted approach to prevent pathogen outgrowth in the lower airways. This review aims to summarize the current knowledge on the CF airway microbiome and possibilities of microbiome treatments to prevent bacterial and/or viral infections and position them in the context of current CF therapies.
Topics: Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Microbiota; Lung; Anti-Bacterial Agents
PubMed: 38232705
DOI: 10.1016/j.xcrm.2023.101371 -
Respiratory Research Nov 2023The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults...
The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus-predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis.
Topics: Adult; Humans; Haemophilus; Pseudomonas; Longitudinal Studies; Bronchiectasis; Respiratory System; Anti-Bacterial Agents
PubMed: 37919749
DOI: 10.1186/s12931-023-02562-8 -
BMC Oral Health Sep 2023This study is to evaluate and compare the improvement of upper airway morphology and hyoid bone position in children with Class II mandibular retrusion treated with...
BACKGROUND
This study is to evaluate and compare the improvement of upper airway morphology and hyoid bone position in children with Class II mandibular retrusion treated with Invisalign mandibular advancement (MA) and Twin-Block (TB) appliances, utilizing cone beam computed tomography (CBCT).
METHODS
32 children aged between 8 and 11.5 years old were included in this study, with an average age of 10.2 years old. These children were divided into two groups, MA and TB, with 16 children in each group. Changes in upper airway morphology and hyoid bone position before and after treatment were analyzed using CBCT.
RESULTS
(1) Changes in upper airway before and after treatment: the oropharynx volume (Or-V), the oropharynx minimum cross-sectional area (Or-mCSA), the hypopharynx volume (Hy-V), and the hypopharynx minimum cross-sectional area (Hy-mCSA) in both the MA and TB groups increased after treatment, and the differences were statistically significant (P < 0.05) compared to pre-treatment status. (2) Changes in hyoid bone position before and after treatment: The distances between H point and third cervical vertebra (H-C3), H point and pogonion (H-RGN), H point and mandibular plane (H-MP), H point and Frankfort horizontal plane (H-FH), H and S point (H-S), and H point and palatal plane (H-PP) in both the MA and TB groups increased after treatment, and the differences were statistically significant (P < 0.05).
CONCLUSION
Both MA and TB appliances effectively improved the structural narrowness of the upper airway and reduced respiratory resistance, thus improving breath quality. However, MA showed more effectiveness in improving the narrowest part of the hypopharynx compared to TB. Both appliances also promoted anterior downward movement of the hyoid bone, which opens the upper airway of the oropharynx and hypopharynx and helps the upper airway morphology return to normal range.
Topics: Child; Humans; Retrospective Studies; Mandibular Advancement; Hyoid Bone; Nose; Orthodontic Appliances, Removable
PubMed: 37705022
DOI: 10.1186/s12903-023-03295-2 -
American Journal of Respiratory and... Feb 2024Respiratory resistance (Rrs) and reactance (Xrs) as measured by oscillometry and their intrabreath changes have emerged as sensitive parameters for detecting early...
Respiratory resistance (Rrs) and reactance (Xrs) as measured by oscillometry and their intrabreath changes have emerged as sensitive parameters for detecting early pathological impairments during tidal breathing. This study evaluates the prevalence and association of abnormal oscillometry parameters with respiratory symptoms and respiratory diseases in a general adult population. A total of 7,560 subjects in the Austrian LEAD (Lung, hEart, sociAl, boDy) Study with oscillometry measurements (computed with the Resmon Pro FULL; Restech Srl) were included in this study. The presence of respiratory symptoms and doctor-diagnosed respiratory diseases was assessed using an interview-based questionnaire. Rrs and Xrs at 5 Hz, their inspiratory and expiratory components, the area above the Xrs curve, and the presence of tidal expiratory flow limitation were analyzed. Normality ranges for oscillometry parameters were defined. The overall prevalence of abnormal oscillometry parameters was 20%. The incidence of abnormal oscillometry increased in the presence of symptoms or diagnoses: 17% (16-18%) versus 27% (25-29%), < 0.0001. All abnormal oscillometry parameters except Rrs at 5 Hz were significantly associated with respiratory symptoms/diseases. Significant associations were found, even in subjects with normal spirometry, with abnormal oscillometry incidence rates increasing by 6% (4-8%; < 0.0001) in subjects with symptoms or diagnoses. Abnormal oscillometry parameters are present in one-fifth of this adult population and are significantly associated with respiratory symptoms and disease. Our findings underscore the potential of oscillometry as a tool for detecting and evaluating respiratory impairments, even in individuals with normal spirometry.
Topics: Adult; Humans; Oscillometry; Lung; Respiration; Exhalation; Respiratory Tract Diseases; Spirometry; Forced Expiratory Volume; Airway Resistance
PubMed: 37972230
DOI: 10.1164/rccm.202306-0975OC -
Biomedicines Feb 2024Evidence from large epidemiological studies has shown that obesity may predispose to increased Th2 inflammation and increase the odds of developing asthma. On the other... (Review)
Review
Evidence from large epidemiological studies has shown that obesity may predispose to increased Th2 inflammation and increase the odds of developing asthma. On the other hand, there is growing evidence suggesting that metabolic dysregulation that occurs with obesity, and more specifically hyperglycemia and insulin resistance, may modify immune cell function and in some degree systemic inflammation. Insulin resistance seldom occurs on its own, and in most cases constitutes a clinical component of metabolic syndrome, along with central obesity and dyslipidemia. Despite that, in some cases, hyperinsulinemia associated with insulin resistance has proven to be a stronger risk factor than body mass in developing asthma. This finding has been supported by recent experimental studies showing that insulin resistance may contribute to airway remodeling, promotion of airway smooth muscle (ASM) contractility and proliferation, increase of airway hyper-responsiveness and release of pro-inflammatory mediators from adipose tissue. All these effects indicate the potential impact of hyperinsulinemia on airway structure and function, suggesting the presence of a specific asthma phenotype with insulin resistance. Epidemiologic studies have found that individuals with severe and uncontrolled asthma have a higher prevalence of glycemic dysfunction, whereas longitudinal studies have linked glycemic dysfunction to an increased risk of asthma exacerbations. Since the components of metabolic syndrome interact with one another so much, it is challenging to identify each one's specific role in asthma. This is why, over the last decade, additional studies have been conducted to determine whether treatment of type 2 diabetes mellitus affects comorbid asthma as shown by the incidence of asthma, asthma control and asthma-related exacerbations. The purpose of this review is to present the mechanism of action, and existing preclinical and clinical data, regarding the effect of insulin resistance in asthma.
PubMed: 38398039
DOI: 10.3390/biomedicines12020437 -
Heliyon Nov 2023Gastroesophageal reflux (GER) occurs in most cystic fibrosis (CF) patients and is the primary source of bile aspiration in the airway tract of CF individuals. Aspirated... (Review)
Review
Gastroesophageal reflux (GER) occurs in most cystic fibrosis (CF) patients and is the primary source of bile aspiration in the airway tract of CF individuals. Aspirated bile is associated with the severity of lung diseases and chronic inflammation caused by as the most common pathogen of CF respiratory tract infections. is equipped with several mechanisms to facilitate the infection process, including but not limited to the expression of virulence factors, biofilm formation, and antimicrobial resistance, all of which are under the strong regulation of quorum sensing (QS) mechanism. By increasing the expression of , and , bile exposure directly impacts the QS network. An increase in expression and pyocyanin production can promote biofilm formation. Along with the loss of flagella and reduced swarming motility, GER-derived bile can repress the expression of genes involved in creating an acute infection, such as expression of Type Three Secretion (T3SS), hydrogen cyanide (), amidase (), and phenazine (). Inversely, to cause persistent infection, bile exposure can increase the Type Six Secretion System (T6SS) and efflux pump expression, which can trigger resistance to antibiotics such as colistin, polymyxin B, and erythromycin. This review will discuss the influence of aspirated bile on the pathogenesis, resistance, and persistence of in CF patients.
PubMed: 38034726
DOI: 10.1016/j.heliyon.2023.e22111 -
Journal of Veterinary Internal Medicine 2023Pulmonary hypertension (PH) secondary to respiratory disease is caused by pulmonary vascular remodeling and hypoxia. Severe PH can induce various clinical signs,...
BACKGROUND
Pulmonary hypertension (PH) secondary to respiratory disease is caused by pulmonary vascular remodeling and hypoxia. Severe PH can induce various clinical signs, including syncope and right-sided heart failure.
HYPOTHESIS/OBJECTIVES
To investigate the echocardiographic characteristics in dogs with PH secondary to respiratory diseases.
ANIMALS
Thirty-one dogs with respiratory diseases with or without PH and 15 healthy dogs.
METHODS
Prospective cross-sectional study. Dogs were classified according to respiratory disease (obstructive airway/lung disease [OALD] or restrictive lung disease [RLD]) and PH-relevant signs. The association between echocardiographic variables and PH (classified by respiratory disease and PH-relevant signs) was investigated.
RESULTS
Twenty-one dogs were diagnosed with PH; of these, 11 showed PH-related signs (OALD, n = 2; RLD, n = 9), 14 had right ventricular hypertrophy, and 19 had pulmonary arterial enlargement. Right ventricular dysfunction and dilatation were observed only in dogs with PH-related signs (n = 10). Left and right ventricular stroke volumes were significantly lower in dogs with PH (median [interquartile range]: 17.2 [12.4-20.8] and 16.8 [15.3-29.5] mL/m , respectively). Dogs with RLD had higher echocardiography-estimated pulmonary vascular resistance than those with OALD (median [interquartile range]: 3.1 [1.9-3.3] and 1.6 [1.3-2.2], respectively).
CONCLUSIONS AND CLINICAL IMPORTANCE
Pulmonary arterial enlargement was the most common echocardiographic finding in dogs with PH secondary to respiratory diseases. Right ventricular dysfunction, dilatation, and decreased left and right ventricular stroke volume were significantly associated with the PH-related signs, indicating that comprehensive echocardiography is recommended in dogs with respiratory disease. Restricted lung disease might induce more severe PH than OALD.
Topics: Dogs; Animals; Hypertension, Pulmonary; Ventricular Dysfunction, Right; Prospective Studies; Cross-Sectional Studies; Echocardiography; Lung Diseases; Dog Diseases
PubMed: 37593765
DOI: 10.1111/jvim.16836 -
Alcohol, Clinical & Experimental... Oct 2023Chronic alcohol ingestion predisposes to lung injury and disrepair during sepsis. Our previous studies outlined roles for transforming growth factor-beta 1 (TGFβ1) and...
BACKGROUND
Chronic alcohol ingestion predisposes to lung injury and disrepair during sepsis. Our previous studies outlined roles for transforming growth factor-beta 1 (TGFβ1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in epithelial barrier homeostasis and how alcohol perturbs their expression and signaling. Here we hypothesize that ethanol-exposed lung fibroblasts (LF) are a source of dysregulated TGFβ1 and GM-CSF and thereby alter airway epithelial barrier function.
METHODS
Human or rat LF were cultured ± ethanol for 2 weeks and then co-cultured with human or rat airway epithelial cells (AEC) seeded on Transwell permeable supports. In selected groups, a TGFβ1 receptor type 1 (TGFβR1) inhibitor (SB431542) or a TGFβ1 neutralizing antibody was applied. Transepithelial electrical resistance (TER) was measured prior to co-culture and on day 5 of co-culture. AEC were then analyzed for the expression of selected tight junction and mesenchymal proteins, and transwell membranes were analyzed by immunofluorescence microscopy for ZO-1 expression and localization. TGFβ1 and GM-CSF levels in conditioned media from the co-cultures were quantified by ELISA.
RESULTS
AEC co-cultured with ethanol-exposed LF (ELF) showed a significant reduction in TER and corresponding decreases in ZO-1 expression, whereas collagen type 1A1 and α-smooth muscle actin protein expression were increased. In parallel, in conditioned media from the ELF + AEC co-cultures, activated TGFβ1 levels increased and GM-CSF levels decreased. Notably, all the effects of ELF on the AEC were prevented by blocking TGFβ1 activity.
CONCLUSIONS
Prior ethanol exposure to LF induces barrier dysfunction in naive AEC in a paracrine fashion through activation of TGFβ1 signaling and suppression of GM-CSF. These experimental findings provide a potential mechanism by which chronic alcohol ingestion impairs airway epithelial integrity and renders individuals susceptible to lung injury.
PubMed: 37864530
DOI: 10.1111/acer.15174 -
Sleep Oct 2023Obesity is a chronic disease affecting over 670 million adults globally, with multiple complications including obstructive sleep apnea (OSA). Substantial weight loss in...
Obesity is a chronic disease affecting over 670 million adults globally, with multiple complications including obstructive sleep apnea (OSA). Substantial weight loss in patients with obesity-related OSA can reduce or even eliminate OSA as well as reduce sleepiness and improve cardio-metabolic health. Evidence suggests that these improvements exceed those that occur with device-based OSA therapies like continuous positive airway pressure which continue to be the first-line of therapy. Resistance to weight management as a first-line strategy to combat OSA could arise from the complexities in delivering and maintaining adequate weight management, particularly in sleep clinic settings. Recently, incretin-based pharmacotherapies including glucagon-like peptide 1 (GLP-1) receptor agonists alone or combined with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have been developed to target glycemic control in type 2 diabetes. These medications also slow gastric emptying and reduce energy intake. In randomized, placebo-controlled trials of these medications in diabetic and non-diabetic populations with obesity, participants on active medication lost up to 20% of their body weight, with corresponding improvements in blood pressure, lipid levels, physical functioning, and fat mass loss. Their adverse effects are predominantly gastrointestinal-related, mild, and transient. There are trials currently underway within individuals with obesity-related OSA, with a focus on reduction in weight, OSA severity, and cardio-metabolic outcomes. These medications have the potential to substantially disrupt the management of OSA. Pending coming data, we will need to consider pharmacological weight loss as a first-line therapy and how that influences training and management guidelines.
Topics: Adult; Humans; Incretins; Diabetes Mellitus, Type 2; Obesity; Weight Loss; Sleep Apnea, Obstructive
PubMed: 37668448
DOI: 10.1093/sleep/zsad224