-
American Journal of Physiology. Lung... Oct 2007Endothelin-1 (ET) induces increases in intracellular Ca(2+) concentration ([Ca(2+)](i)), Ca(2+) sensitization, and contraction of both bronchiole and pulmonary arteriole...
Endothelin-1 (ET) induces increases in intracellular Ca(2+) concentration ([Ca(2+)](i)), Ca(2+) sensitization, and contraction of both bronchiole and pulmonary arteriole smooth muscle cells (SMCs) and may play an important role in the pathophysiology of asthma and pulmonary hypertension. However, because it remains unclear how changes in [Ca(2+)](i) and the Ca(2+) sensitivity regulate SMC contraction, we have studied mouse lung slices with phase-contrast and confocal microscopy to correlate the ET-induced contraction with the changes in [Ca(2+)](i) and Ca(2+) sensitivity of bronchiole and arteriole SMCs. In comparison with acetylcholine (ACh) or serotonin (5-HT), ET induced a stronger and long-lasting contraction of both bronchioles and arterioles. This ET-induced contraction was associated with prominent asynchronous Ca(2+) oscillations that were propagated as Ca(2+) waves along the SMCs. These Ca(2+) oscillations were mediated by cyclic intracellular Ca(2+) release and required external Ca(2+) for their maintenance. Importantly, as the frequency of the Ca(2+) oscillations increased, the extent of contraction increased. ET-induced contraction was also associated with an increase in Ca(2+) sensitivity. In "model" slices in which the [Ca(2+)](i) was constantly maintained at an elevated level by pretreatment of slices with caffeine and ryanodine, the addition of ET increased bronchiole and arteriole contraction. These results indicate that ET-induced contraction of bronchiole and arteriole SMCs is regulated by the frequency of Ca(2+) oscillations and by increasing the sensitivity of the contractile machinery to Ca(2+).
Topics: Acetylcholine; Animals; Arterioles; Bronchi; Calcium; Calcium Signaling; Dose-Response Relationship, Drug; Endothelin-1; Extracellular Fluid; In Vitro Techniques; Intracellular Membranes; Lung; Mice; Mice, Inbred BALB C; Muscle Contraction; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Oscillometry; Osmolar Concentration; Receptors, Endothelin; Serotonin; Vasoconstriction
PubMed: 17616645
DOI: 10.1152/ajplung.00184.2007 -
Chest Jun 2017During the past decade, there has been increasing evidence that the small airways (ie, airways < 2 mm in internal diameter) contribute substantially to the... (Review)
Review
During the past decade, there has been increasing evidence that the small airways (ie, airways < 2 mm in internal diameter) contribute substantially to the pathophysiologic and clinical expression of asthma and COPD. The increased interest in small airways is, at least in part, a result of innovation in small-particle aerosol formulations that better target the distal lung and also advanced physiologic methods of assessing small airway responses. Increasing the precision of drug deposition may improve targeting of specific diseases or receptor locations, decrease airway drug exposure and adverse effects, and thereby increase the efficiency and effectiveness of inhaled drug delivery. The availability of small-particle aerosols of corticosteroids, bronchodilators, or their combination enables a higher total lung deposition and better peripheral lung penetration and provides added clinical benefit, compared with large-particle aerosol treatment. However, a number of questions remain unanswered about the pragmatic approach relevant for clinicians to consider the role of small airways directed therapy in the day-to-day management of asthma and COPD. We thus have tried to clarify the dilemmas, confusion, and misconceptions related to small airways directed therapy. To this end, we have reviewed all studies on small-particle aerosol therapy systematically to address the dilemmas, confusion, and misconceptions related to small airways directed therapy.
Topics: Administration, Inhalation; Asthma; Beclomethasone; Bronchioles; Bronchodilator Agents; Disease Management; Drug Combinations; Dry Powder Inhalers; Equipment Design; Fluocinolone Acetonide; Formoterol Fumarate; Glucocorticoids; Humans; Inhalation Spacers; Metered Dose Inhalers; Nebulizers and Vaporizers; Particle Size; Pregnenediones; Pressure; Pulmonary Disease, Chronic Obstructive
PubMed: 27522955
DOI: 10.1016/j.chest.2016.07.035 -
Tuberculosis (Edinburgh, Scotland) Jan 2021Symptoms of infectious respiratory illnesses are often assumed to drive transmission. However, production and release of Mycobacterium tuberculosis (Mtb) bioaerosols is...
BACKGROUND
Symptoms of infectious respiratory illnesses are often assumed to drive transmission. However, production and release of Mycobacterium tuberculosis (Mtb) bioaerosols is poorly understood. We report quantitation of Mtb exhaled during specific respiratory manoeuvres.
METHODS
Direct capture of nascent bioaerosol particles and indirect collection of aged particles was performed in 10 healthy subjects. Indirect and direct capture of exhaled viable Mtb bacilli was compared in 38 PTB patients and directly captured viable Mtb during cough and bronchiole-burst manoeuvres in 27 of the PTB patients.
RESULTS
Direct sampling of healthy subjects captured larger bioaerosol volumes with higher proportions of 2-5 μm particles than indirect sampling. Indirect sampling identified viable Mtb in 92.1% (35 of 38) of PTB patients during 60-min relaxed breathing, median bacillary count 7.5 (IQR: 3.25-19). Direct sampling for 10-min identified Mtb in 97.4% (37 of 38) of PTB patients with higher bacilli counts (p < 0.001), median 24.5 (IQR:11.25-37.5). A short 5-min sampling regimen of 10 coughs or 10 bronchiole-burst manoeuvres yielded a median of 11 (IQR: 4-17) and 11 (IQR: 7-17.5) Mtb bacilli, respectively (p = 0.53).
CONCLUSIONS
Peripheral lung bioaerosol released through deep exhalations alone contained viable Mtb suggesting non-cough transmission is possible in PTB.
Topics: Adult; Aerosols; Aged; Cough; Female; Humans; Lung; Male; Middle Aged; Mycobacterium tuberculosis; Specimen Handling; Tuberculosis, Pulmonary
PubMed: 33316737
DOI: 10.1016/j.tube.2020.102038 -
Physiology (Bethesda, Md.) Sep 2017The small airways of the lungs are under constant assault from the pathogens and debris in the air that they must conduct to alveoli. Although hygiene is of paramount... (Review)
Review
The small airways of the lungs are under constant assault from the pathogens and debris in the air that they must conduct to alveoli. Although hygiene is of paramount importance for respiratory health, the underlying principles of airway clearance have not been well integrated or established. Newly emerging concepts of simultaneous absorption and secretion of airway surface liquid (ASL) and the role of [Formula: see text] in the maturation of mucins have advanced from experimental evidence as well as observations from the congenital disease cystic fibrosis (CF) to present a novel model that integrates microanatomy with organ physiology to meet the constant challenge of cleaning small airways.
Topics: Animals; Bronchioles; Cystic Fibrosis; Humans; Mucins; Respiratory Mucosa
PubMed: 28814498
DOI: 10.1152/physiol.00013.2017 -
PloS One 2020This study aimed to evaluate the visualization of peripheral bronchioles in normal lungs via quarter-detector computed tomography (QDCT). Visualization of bronchioles...
This study aimed to evaluate the visualization of peripheral bronchioles in normal lungs via quarter-detector computed tomography (QDCT). Visualization of bronchioles within 10 mm from the pleura is considered a sign of bronchiectasis. However, it is not known peripheral bronchioles how close to the pleura in normal lungs can be tracked using QDCT. This study included 228 parts in 76 lungs from 38 consecutive patients who underwent QDCT. Reconstruction was performed with different thicknesses, increments, and matrix sizes: 0.5-mm thickness and increment with 512 and 1024 matrixes (Group5 and Group10, respectively) and 0.25-mm thickness and increment with 1024 matrix (Group10Thin). The distance between the most peripheral bronchiole visible and the pleura was determined in the three groups. The distance between the peripheral bronchial duct ends and the nearest pleural surface were significantly shorter in the order of Group10Thin, Group10, and Group5, and the mean distances from the pleura in Group10Thin and Group10 were shorter than 10 mm. These findings suggest the visualization of peripheral bronchioles in QDCT was better with a 1024 axial matrix than with a 512 matrix, and with a 0.25-mm slice thickness/increment than with a 0.5-mm slice thickness/increment. Our study also indicates bronchioles within 10 mm of the pleura do not necessarily indicate pathology.
Topics: Adult; Aged; Aged, 80 and over; Bronchiectasis; Bronchioles; Female; Humans; Lung; Male; Middle Aged; Pleura; Radiographic Image Interpretation, Computer-Assisted; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 32946530
DOI: 10.1371/journal.pone.0239459 -
Respiration; International Review of... 2023Several studies have shown the importance of the complement and coagulation systems in the pathogenesis of asthma.
BACKGROUND
Several studies have shown the importance of the complement and coagulation systems in the pathogenesis of asthma.
OBJECTIVES
We explored whether we could detect differentially abundant complement and coagulation proteins in the samples obtained from the small airway lining fluid by collection of exhaled particles in patients with asthma and whether these proteins are associated with small airway dysfunction and asthma control.
METHOD
Exhaled particles were obtained from 20 subjects with asthma and 10 healthy controls (HC) with the PExA method and analysed with the SOMAscan proteomics platform. Lung function was assessed by nitrogen multiple breath washout test and spirometry.
RESULTS
53 proteins associated with the complement and coagulation systems were included in the analysis. Nine of those proteins were differentially abundant in subjects with asthma as compared to HC, and C3 was significantly higher in inadequately controlled asthma as compared to well-controlled asthma. Several proteins were associated with physiological tests assessing small airways.
CONCLUSIONS
The study highlights the role of the local activation of the complement and coagulation systems in the small airway lining fluid in asthma and their association with both asthma control and small airway dysfunction. The findings highlight the potential of complement factors as biomarkers to identify different sub-groups among patients with asthma that could potentially benefit from a therapeutic approach targeting the complement system.
Topics: Complement Activation; Blood Coagulation; Asthma; Humans; Male; Female; Middle Aged; Pulmonary Alveoli; Bronchioles
PubMed: 37423212
DOI: 10.1159/000531374 -
The Journal of International Medical... Jul 2020The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 infection is a serious global concern. Increased morbidity and... (Review)
Review
The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 infection is a serious global concern. Increased morbidity and mortality is associated with older age, male gender, cardiovascular disease, diabetes, and smoking. As COVID-19 spreads from coastal borders, both state to state and country to country, our understanding of its pathophysiology has evolved. Age and type 2 diabetes mellitus (T2DM) play especially important roles in COVID-19 progression. T2DM is an age-related disease associated with metabolic syndrome, obesity, insulin resistance (hyperinsulinemia), hyperlipidemia, hypertension, hyperglycemia, and endothelial activation and dysfunction. This review evaluates the relationships and intersection between endothelial cell activation and dysfunction in T2DM and COVID-19. COVID-19 induces multiple injuries of the terminal bronchioles and alveolar blood-gas barrier and associated ultrastructural tissue remodeling. COVID-19 may unmask multiple vulnerabilities associated with T2DM including damage to the endothelial glycocalyx and multiple end-organ macro and microvascular diseases. Unmasking existing vulnerabilities in diabetic patients with COVID-19 is important. Globally, we must come together to better understand why T2DM is associated with increased COVID-19 morbidity and mortality.
Topics: Animals; Betacoronavirus; Blood-Air Barrier; Bronchioles; COVID-19; Comorbidity; Coronavirus Infections; Diabetes Mellitus, Type 2; Drug Repositioning; Endothelial Cells; Humans; Metabolic Syndrome; Models, Biological; Pandemics; Pneumonia, Viral; Pulmonary Alveoli; Rats; SARS-CoV-2; Wound Healing
PubMed: 32722979
DOI: 10.1177/0300060520939746 -
Folia Histochemica Et Cytobiologica 2007Lung cancer is the leading cause of cancer deaths for people of both sexes worldwide. Early diagnosis of precancer lesions may be of crucial significance to lowering... (Review)
Review
Lung cancer is the leading cause of cancer deaths for people of both sexes worldwide. Early diagnosis of precancer lesions may be of crucial significance to lowering lung cancer mortality. The World Health Organization has defined three preneoplastic lesions of the bronchial epithelium: squamous dysplasia and carcinoma in situ, atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. These lesions are believed to progress to squamous cell carcinoma, adenocarcinoma and carcinoid tumors, respectively. Apart from WHO classification, two other lesions such as bronchiolization and bronchiolar columnar cell dysplasia (BCCD) can be observed and thought to be preneoplastic lesions leading to adenocarcinoma. In this review we summarize the data of morphological and cell cycle related proteins changes in both central and peripheral compartments of lung. Many molecular changes, which accompany the multistep process of the development of invasive types of cancer, may be observed thanks to the application of immunohistochemical markers. A deeper knowledge of molecular and genetic changes accompanying pre-cancer states may show new directions of early diagnostics of cancer development.
Topics: Animals; Biomarkers, Tumor; Disease Progression; Humans; Immunohistochemistry; Lung; Lung Neoplasms; Precancerous Conditions
PubMed: 17597018
DOI: No ID Found -
Nature Communications Nov 2017We inhale respiratory pathogens continuously, and the subsequent signaling events between host and microbe are complex, ultimately resulting in clearance of the microbe,...
We inhale respiratory pathogens continuously, and the subsequent signaling events between host and microbe are complex, ultimately resulting in clearance of the microbe, stable colonization of the host, or active disease. Traditional in vitro methods are ill-equipped to study these critical events in the context of the lung microenvironment. Here we introduce a microscale organotypic model of the human bronchiole for studying pulmonary infection. By leveraging microscale techniques, the model is designed to approximate the structure of the human bronchiole, containing airway, vascular, and extracellular matrix compartments. To complement direct infection of the organotypic bronchiole, we present a clickable extension that facilitates volatile compound communication between microbial populations and the host model. Using Aspergillus fumigatus, a respiratory pathogen, we characterize the inflammatory response of the organotypic bronchiole to infection. Finally, we demonstrate multikingdom, volatile-mediated communication between the organotypic bronchiole and cultures of Aspergillus fumigatus and Pseudomonas aeruginosa.
Topics: Aspergillosis; Aspergillus fumigatus; Bronchioles; Cytokines; Host-Pathogen Interactions; Humans; Lung Diseases; Models, Biological; Pseudomonas Infections; Pseudomonas aeruginosa; Volatile Organic Compounds
PubMed: 29176665
DOI: 10.1038/s41467-017-01985-4