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Pharmacology & Therapeutics Jul 2021Asthma is a highly prevalent disorder characterized by chronic lung inflammation and reversible airways obstruction. Pathophysiological features of asthma include... (Review)
Review
Asthma is a highly prevalent disorder characterized by chronic lung inflammation and reversible airways obstruction. Pathophysiological features of asthma include episodic and reversible airway narrowing due to increased bronchial smooth muscle shortening in response to external and host-derived mediators, excessive mucus secretion into the airway lumen, and airway remodeling. The aberrant airway smooth muscle (ASM) phenotype observed in asthma manifests as increased sensitivity to contractile mediators (EC) and an increase in the magnitude of contraction (E); collectively these attributes have been termed "airways hyper-responsiveness" (AHR). This defining feature of asthma can be promoted by environmental factors including airborne allergens, viruses, and air pollution and other irritants. AHR reduces airway caliber and obstructs airflow, evoking clinical symptoms such as cough, wheezing and shortness of breath. G-protein-coupled receptors (GPCRs) have a central function in asthma through their impact on ASM and airway inflammation. Many but not all treatments for asthma target GPCRs mediating ASM contraction or relaxation. Here we discuss the roles of specific GPCRs, G proteins, and their associated signaling pathways, in asthma, with an emphasis on endogenous mechanisms of GPCR regulation of ASM tone and lung inflammation including regulators of G-protein signaling (RGS) proteins, G-protein coupled receptor kinases (GRKs), and β-arrestin.
Topics: Asthma; G-Protein-Coupled Receptor Kinases; GTP-Binding Proteins; Humans; RGS Proteins; Receptors, G-Protein-Coupled; Signal Transduction; beta-Arrestins
PubMed: 33600853
DOI: 10.1016/j.pharmthera.2021.107818 -
Respiratory Medicine Mar 2019The exercise challenge is the gold standard for diagnosing exercise-induced bronchoconstriction (EIB). Airway obstructions appear up to 30 min after the challenge,... (Comparative Study)
Comparative Study
BACKGROUND
The exercise challenge is the gold standard for diagnosing exercise-induced bronchoconstriction (EIB). Airway obstructions appear up to 30 min after the challenge, with a maximum decrease in spirometry and a maximum increase in airway resistance. There is evidence that changes in body plethysmography parameters are more sensitive to the exercise challenge and precede those in spirometry.
PURPOSE
To compare changes in body plethysmography and spirometry parameters after exercise challenges and to verify the cut-off values of sReff in EIB.
PROCEDURES
In 82 subjects with suspected EIB, a total of 473 lung function tests were measured at baseline and at 5, 10, 15, and 30 min after exercise challenges at different stages of bronchial obstruction.
FINDINGS
The maximum changes in the body plethysmography parameter sReff significantly preceded the maximum changes in the spirometry parameter FEV (sReff: 12.2 min ±8.8, FEV: 15.2 min ±9.3, p < 0.005). The parameters of sReff and FEV had a strong negative correlation (r = -0.63, p < 0.0001) with a nonlinear, polynomial relationship. Furthermore, sReff and Reff had a strong linear correlation (r = 0.86, p < 0.001), and Reff and Rtot had a perfect linear correlation (r = 0.99, p < 0.001). Based on baseline values and on quantile regression, an increase of 0.25 kPa s in sReff was defined as significant. Using this cut-off value, FEV and sReff almost equally detected EIB.
CONCLUSION
The changes in sReff were more sensitive and better indicated lung impairment than did the changes in FEV, which underestimated the degree of hyperinflation.
Topics: Adolescent; Adult; Airway Obstruction; Airway Resistance; Asthma, Exercise-Induced; Bronchial Provocation Tests; Child; Female; Forced Expiratory Volume; Humans; Male; Plethysmography, Whole Body; Spirometry; Young Adult
PubMed: 30827475
DOI: 10.1016/j.rmed.2019.01.011 -
Treatment of patients with COPD and recurrent exacerbations: the role of infection and inflammation.International Journal of Chronic... 2016Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a... (Review)
Review
Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations.
Topics: Bacterial Infections; Clinical Decision-Making; Clinical Trials as Topic; Disease Management; Disease Progression; Humans; Inflammation; Practice Guidelines as Topic; Pulmonary Disease, Chronic Obstructive; Risk Factors; Secondary Prevention; Severity of Illness Index; Symptom Flare Up; Virus Diseases
PubMed: 27042040
DOI: 10.2147/COPD.S98333 -
Frontiers in Medicine 2023Respiratory insufficiency is a leading cause of death in individuals with osteogenesis imperfecta (OI). However, evaluating pulmonary function in OI presents challenges....
INTRODUCTION
Respiratory insufficiency is a leading cause of death in individuals with osteogenesis imperfecta (OI). However, evaluating pulmonary function in OI presents challenges. Commonly used pulmonary function tests such as spirometry and body plethysmography are sometimes difficult to perform for OI patients, and reference intervals are not always applicable. The forced oscillation technique (FOT) is a patient-friendly method for detecting respiratory abnormalities that requires no effort from the patient.
OBJECTIVE
This study investigates the feasibility of FOT in the evaluation of respiratory function in the clinical management of OI patients.
METHODS
Twelve OI patients, comprising eight with Sillence OI I, two with OI IV, and two with OI III, underwent spirometry, body plethysmography, and FOT, both pre-and post-administration of salbutamol.
RESULTS
FOT measurements exhibited consistent trends that aligned with spirometry and body plethysmography findings. The resistance at 8 Hz decreased after the administration of salbutamol, indicating that FOT is able to detect bronchial obstruction and its alleviation by medication ( < 0.05). The resonant frequency during expiration was higher than during inspiration in nearly all patients, suggesting obstructive disease. The technique gives insight into both inspiratory and expiratory impairment of pulmonary ventilation. The main FOT parameters showed a relatively high repeatability in duplicate measurements.
CONCLUSION
Bronchial obstruction can be detected by FOT in patients with OI during quiet breathing, making it an easily executable alternative to other lung function measurements. The technique can detect the bronchodilator effect of sympathomimetic medication. It has the potential to provide information on expiratory flow limitation, pulmonary restriction, and reduced lung compliance.
PubMed: 38179272
DOI: 10.3389/fmed.2023.1301873 -
Respiration; International Review of... 2018In patients with bronchial obstruction estimating the location of the maximal obstruction is crucial for guiding interventional bronchoscopy. However, flow-volume curves... (Clinical Trial)
Clinical Trial
BACKGROUND
In patients with bronchial obstruction estimating the location of the maximal obstruction is crucial for guiding interventional bronchoscopy. However, flow-volume curves cannot discriminate between the right and left lungs.
OBJECTIVES
The aim of this study was to physiologically evaluate bronchial obstruction during interventional bronchoscopy.
METHODS
We prospectively measured lateral airway pressure (Plat) at either side of the obstruction using a double-lumen catheter (pressure-pressure [P-P] curve) simultaneously to assess the degree of bronchial obstruction in 22 patients. The shape of the P-P curve was assessed to confirm the site of maximal obstruction.
RESULTS
In the experimental study, Plat was uniform between both bronchi in the normal model. For the unilateral and bilateral obstruction models, a phase shift was only seen for the more obstructed side. In healthy subjects, the angle of the P-P curve was close to 45° and linear in shape. In patients with bronchial obstruction, the angle was much smaller but approached 45° after the bronchoscopic procedure. The degree of bronchial obstruction was significantly correlated with the angle of the P-P curve (r = -0.51, p < 0.01). Dyspnea significantly increased when the airway lumen was obstructed by more than 60% (p < 0.0001), and when the P-P curve appeared loop-shaped (p < 0.01).
CONCLUSIONS
The shape of the P-P curve could be used to detect the site of maximal obstruction for the optimal positioning of the stent and assess the need for additional procedures in real time in patients with bronchial obstruction.
Topics: Adult; Aged; Aged, 80 and over; Airway Obstruction; Bronchial Diseases; Bronchoscopy; Feasibility Studies; Female; Humans; Male; Middle Aged; Pressure
PubMed: 29190612
DOI: 10.1159/000481572 -
Journal of Visualized Surgery 2017Congenital bronchial atresia (CBA) is a rare congenital malformation consisting in an interruption of a lobar or-more frequently-of a segmental bronchus. It leads to... (Review)
Review
Congenital bronchial atresia (CBA) is a rare congenital malformation consisting in an interruption of a lobar or-more frequently-of a segmental bronchus. It leads to mucus impaction and hyperinflation of the obstructed lung segment. It causes infectious complications and, in the long term, destruction of the adjacent lung parenchyma. Thus, a surgical resection is usually indicated, even in asymptomatic patients.
PubMed: 29302450
DOI: 10.21037/jovs.2017.10.15 -
International Journal of Molecular... Jan 2016Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early... (Review)
Review
Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours. Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary. It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy. Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease. As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve.
Topics: Aged; Airway Obstruction; Bronchoscopy; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Combined Modality Therapy; Humans; Lung Neoplasms; Male; Mesothelioma; Photochemotherapy; Photosensitizing Agents; Pleural Neoplasms; Thoracic Neoplasms; Treatment Outcome
PubMed: 26805818
DOI: 10.3390/ijms17010135 -
Annals of the Rheumatic Diseases Aug 1994To investigate the prevalence of airways obstruction and bronchial reactivity to inhaled methacholine in rheumatoid arthritis patients and unselected controls. The...
OBJECTIVES
To investigate the prevalence of airways obstruction and bronchial reactivity to inhaled methacholine in rheumatoid arthritis patients and unselected controls. The control population consisted of patients attending the rheumatology department for minor degenerative joint problems.
METHODS
One hundred patients with rheumatoid arthritis (RA) [72 (72%) women, 28 (28%) men; mean (SD) age 58 (10) years] and fifty controls [30 (60%) women, 20 (40%) men; mean (SD) age 56 (9) years] were studied. Detailed medical, smoking and drug histories were taken; skin prick tests were performed to assess atopy and chest and hand radiographs were performed. Spirometry, flow volume loops and gas transfer factor measurement were performed to detect airflow obstruction and methacholine inhalation tests were carried out to assess bronchial reactivity.
RESULTS
There was no significant difference between rheumatoid arthritis patients and the controls in age, sex, smoking status and atopy on skin prick testing (p < 0.05). A significantly higher number of patients with RA had a history of wheeze compared with the controls (18% v 4%, p < 0.05). FEV1, FVC, FEV1/FVC, FEF25-75%, FEF25%, FEF50% and FEF75% were all significantly lower in the rheumatoid arthritis group (p < 0.05). A significantly higher number of patients with RA compared with controls showed bronchial reactivity to inhaled methacholine [55 (55%) v 8 (16%), p < 0.05]. FEV1, FVC, FEV1/FVC, FEF25-75%, FEF25%, FEF50% and FEF75% were all significantly lower among the patients with RA achieving PD20 FEV1 to inhaled methacholine (p < 0.05).
CONCLUSION
In unselected rheumatoid arthritis patients both airflow obstruction and bronchial reactivity are significantly increased compared with controls.
Topics: Adult; Aged; Arthritis, Rheumatoid; Bronchial Hyperreactivity; Female; Forced Expiratory Volume; Humans; Hypersensitivity, Immediate; Lung; Lung Diseases, Obstructive; Male; Methacholine Chloride; Middle Aged; Prospective Studies; Respiratory Function Tests; Smoking
PubMed: 7944635
DOI: 10.1136/ard.53.8.511 -
Journal of Investigational Allergology... 2018The rising frequency of obstructive respiratory diseases during recent years, in particular allergic asthma, can be partially explained by changes in the environment,... (Review)
Review
The rising frequency of obstructive respiratory diseases during recent years, in particular allergic asthma, can be partially explained by changes in the environment, with the increasing presence in the atmosphere of chemical triggers (particulate matter and gaseous components such as nitrogen dioxide and ozone) and biologic triggers (aeroallergens). In allergic individuals, aeroallergens stimulate airway sensitization and thus induce symptoms of bronchial asthma. Over the last 50 years, the earth's temperature has risen markedly, likely because of growing concentrations of anthropogenic greenhouse gas. Major atmospheric and climatic changes, including global warming induced by human activity, have a considerable impact on the biosphere and on the human environment. Urbanization and high levels of vehicle emissions induce symptoms of bronchial obstruction (in particular bronchial asthma), more so in people living in urban areas compared than in those who live in rural areas. Measures need to be taken to mitigate the future impact of climate change and global warming. However, while global emissions continue to rise, we must learn to adapt to climate variability.
Topics: Air Pollutants; Air Pollution; Allergens; Animals; Asthma; Climate Change; Humans; Hypersensitivity; Pollen; Vehicle Emissions
PubMed: 29345235
DOI: 10.18176/jiaci.0228 -
Journal of the American Veterinary... Jun 2022To assess the prevalence of bronchial wall thickening (BWT) and collapse in brachycephalic dogs with and without brachycephalic obstructive airway syndrome (BOAS) and in...
OBJECTIVE
To assess the prevalence of bronchial wall thickening (BWT) and collapse in brachycephalic dogs with and without brachycephalic obstructive airway syndrome (BOAS) and in nonbrachycephalic dogs.
ANIMALS
85 dogs with no history of lower respiratory tract disease that underwent CT of the thorax.
PROCEDURES
Electronical medical records for March 2011 through August 2019 were reviewed to identify brachycephalic dogs with BOAS (BOAS group) and brachycephalic dogs without BOAS (BDWB group) that did not have any evidence of lower respiratory tract disease and had undergone thoracic CT. A population of nonbrachycephalic dogs of similar weight (control dogs) was also retrospectively recruited.
RESULTS
BWT was identified in 28 of 30 (93.3%; 95% CI, 80.3% to 98.6%) dogs in the BOAS group, 15 of 26 (57.7%; 95% CI, 38.7% to 75.0%) dogs in the BDWB group, and 10 of 28 (35.7%; 95% CI, 20.1% to 54.2%) control dogs. On multivariable analysis, only brachycephalic conformation (P < 0.01) and body weight (P = 0.02) were significantly associated with the presence of BWT. Bronchial collapse was identified in 17 of 30 (56.7%; 95% CI, 39.0% to 73.1%) dogs in the BOAS group, 17 of 26 (65.4%; 95% CI, 46.3% to 81.3%) dogs in the BDWB group, and 3 of 28 (10.7%; 95% CI, 3.1% to 25.9%) control dogs. On multivariable analysis, only brachycephalic conformation was significantly (P < 0.01) associated with the presence of bronchial collapse.
CLINICAL RELEVANCE
A relationship between brachycephalic conformation and body weight with BWT was established, with heavier dogs having thicker bronchial walls. However, further studies are required to investigate the cause. Bronchial collapse was also more common in dogs with brachycephalic conformation, which is in agreement with the previously published literature.
Topics: Dogs; Animals; Retrospective Studies; Prevalence; Dog Diseases; Craniosynostoses; Airway Obstruction; Syndrome; Body Weight
PubMed: 35905164
DOI: 10.2460/javma.21.10.0448