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The Journal of Allergy and Clinical... Mar 2018Airway obstruction is a physiologic feature of asthma, and IL-15 might have an important role in asthma pathogenesis.
BACKGROUND
Airway obstruction is a physiologic feature of asthma, and IL-15 might have an important role in asthma pathogenesis.
OBJECTIVE
We tested the hypothesis that regulation of IL-15 is critical for preservation of allergen-induced airway hyperresponsiveness (AHR), airway resistance, and compliance in response to methacholine.
METHODS
Airway inflammation, AHR, resistance, and compliance were assessed in Il15 gene-deficient mice and IL-15-overexpressing mice in an allergen-induced murine model of asthma. We assessed eosinophil numbers by using anti-major basic protein immunostaining, goblet cell hyperplasia by using periodic acid-Schiff staining, and cytokine and chemokine levels by performing quantitative PCR and ELISA.
RESULTS
We made a novel observation that IL-15 deficiency promotes baseline airway resistance in naive mice. Moreover, rIL-15 delivery to the lung downregulates expression of proinflammatory cytokines and improves allergen-induced AHR, airway resistance, and compliance. These observations were further validated in doxycycline-inducible CC10-IL-15 bitransgenic mice. Doxycycline-exposed, Aspergillus species extract-challenged CC10-IL-15 bitransgenic mice exhibited significantly reduced levels of proinflammatory cytokines (IL-4, IL-5, and IL-13) and decreased goblet cell hyperplasia. Airway obstruction, including AHR and airway resistance, was diminished in allergen-challenged doxycycline-exposed compared with non-doxycycline-exposed CC10-IL-15 bitransgenic mice. Mechanistically, we observed that IL-15-mediated protection of airway obstruction is associated with induced IFN-γ- and IL-10-producing regulatory CD4CD25 forkhead box p3 (Foxp3) T cells. Additionally, we found that a human IL-15 agonist (ALT-803) improved airway resistance and compliance in an experimental asthma model.
CONCLUSION
We report our novel finding that IL-15 has a potent inhibitory effect on the airway obstruction that occurs in response to environmental allergens.
Topics: Allergens; Animals; Asthma; Bronchial Hyperreactivity; Disease Models, Animal; Eosinophils; Goblet Cells; Interferon-gamma; Interleukin-10; Interleukin-15; Lung; Mice; Mice, Inbred BALB C; Mice, Knockout; Uteroglobin
PubMed: 28606589
DOI: 10.1016/j.jaci.2017.05.025 -
Laryngoscope Investigative... Oct 2023Anterior active rhinomanometry (AAR) is widely used in Swedish routine clinical practice to decide if septoplasty is necessary. The scientific basis for the method needs...
OBJECTIVES
Anterior active rhinomanometry (AAR) is widely used in Swedish routine clinical practice to decide if septoplasty is necessary. The scientific basis for the method needs to be strengthened. Therefore, the aims were to evaluate nasal airway resistance (NAR), paradoxical reactions to pharmacological decongestion, and test-retest characteristics of the Rhino-Comp® AAR in healthy subjects.
METHODS
A prospective longitudinal design was used. AAR was performed before and after decongestion at baseline and after ≥6 months on 60 healthy volunteers. The relationships between NAR, height, weight, BMI, sex, and allergic rhinitis were evaluated by regression analyses. Descriptive statistics were used to evaluate paradoxical reactions. Test-retest and repeatability characteristics were evaluated with intra-class coefficients (ICC), Cronbach's α, and standard error of measurement.
RESULTS
No statistically significant differences were found between genders or nasal cavity sides. NAR was statistically significantly related to height. Short- and long-term test-retest characteristics were good with ICC and Cronbach's > .75. The minimal significant difference in NAR Log10V2 values between the two measurements was 0.11 and 0.09 (long- and short-term). Paradoxical reactions to pharmacological decongestion were rare, mostly weak, and not evidently reproducible.
CONCLUSION
In this study, we report reference data for healthy subjects, test-retest capabilities, and the minimal relevant difference between two measurements for the Rhino-Comp® AAR, information that is vital and necessary for the appropriate use of AAR in clinical practice. An effective method for pharmacological decongestion is described and recommended for future studies and clinical practice. Paradoxical reactions to pharmacological decongestants exist but maybe without clinical significance.
LEVEL OF EVIDENCE
NA.
PubMed: 37899860
DOI: 10.1002/lio2.1157 -
Comparative evaluation of expiratory airflow limitation between patients with COPD and BE using IOS.Scientific Reports Feb 2021Impulse oscillometry (IOS) allows evaluation of the compartmentalized resistance and reactance of the respiratory system, distinguishing central and peripheral... (Comparative Study)
Comparative Study
Impulse oscillometry (IOS) allows evaluation of the compartmentalized resistance and reactance of the respiratory system, distinguishing central and peripheral obstruction. The IOS measurements are getting attention in the diagnosis and differentiation of chronic respiratory diseases. However, no data are available in the literature to differentiate between COPD and BE using IOS parameters. We aimed to evaluate the feasibility of IOS in the diagnosis of bronchiectasis non-cystic fibrosis (BE) in comparison to COPD. Whole breath, inspiration, expiration, and inspiratory-expiratory difference (Δ) were evaluated based on the IOS parameters: total resistance (R5), central airway resistance (R20), peripheral airway resistance (R5-R20), reactance (X5), reactance area (AX), and resonance frequency (Fres). Fifty-nine subjects (21 Healthy, 19 BE, and 19 COPD) participated in this study. It was observed a significant difference in the comparison of healthy and pulmonary disease groups (BE and COPD) for total breathing (R5-R20, X5, AX, and Fres), inspiratory phase (R5 and R5-R5), and expiratory phase (R5-R20 and X5). The comparison between BE and COPD groups showed significant difference in the expiratory phase for resistance at 5 and 20 Hz and, ΔR5 and ΔR20. The IOS evidenced an increase of R5, R20 and R5-R20 in patients with BE and COPD when compared to healthy subjects. Expiratory measures of IOS revealed increased airway resistance in COPD compared to BE patients who had similar FEV1 measured by spirometry, however, further studies are needed to confirm these differences.
Topics: Aged; Airway Resistance; Bronchiectasis; Case-Control Studies; Disease Management; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Oscillometry; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Respiratory Function Tests; Spirometry
PubMed: 33633234
DOI: 10.1038/s41598-021-84028-9 -
Science Translational Medicine Sep 2018The elevation of carbon dioxide (CO) in tissues and the bloodstream (hypercapnia) occurs in patients with severe lung diseases, including chronic obstructive pulmonary...
The elevation of carbon dioxide (CO) in tissues and the bloodstream (hypercapnia) occurs in patients with severe lung diseases, including chronic obstructive pulmonary disease (COPD). Whereas hypercapnia has been recognized as a marker of COPD severity, a role for hypercapnia in disease pathogenesis remains unclear. We provide evidence that CO acts as a signaling molecule in mouse and human airway smooth muscle cells. High CO activated calcium-calpain signaling and consequent smooth muscle cell contraction in mouse airway smooth muscle cells. The signaling was mediated by caspase-7-induced down-regulation of the microRNA-133a (miR-133a) and consequent up-regulation of Ras homolog family member A and myosin light-chain phosphorylation. Exposure of wild-type, but not caspase-7-null, mice to hypercapnia increased airway contraction and resistance. Deletion of the gene prevented hypercapnia-induced airway contractility, which was restored by lentiviral transfection of a miR-133a antagonist. In a cohort of patients with severe COPD, hypercapnic patients had higher airway resistance, which improved after correction of hypercapnia. Our data suggest a specific molecular mechanism by which the development of hypercapnia may drive COPD pathogenesis and progression.
Topics: Acetylcholine; Aged; Aged, 80 and over; Airway Resistance; Animals; Calcium; Calpain; Carbon Dioxide; Caspase 7; Chronic Disease; Down-Regulation; Enzyme Activation; Female; Humans; Hypercapnia; MEF2 Transcription Factors; Male; Mice, Inbred C57BL; MicroRNAs; Middle Aged; Muscle Contraction; Muscle, Smooth; Myocytes, Smooth Muscle; Pulmonary Disease, Chronic Obstructive; Signal Transduction; rhoA GTP-Binding Protein
PubMed: 30185650
DOI: 10.1126/scitranslmed.aat1662 -
BMC Pulmonary Medicine May 2024Assessing mechanical properties of the respiratory system (C) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an...
BACKGROUND
Assessing mechanical properties of the respiratory system (C) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals.
METHODS
A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (V) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RC).
RESULTS
During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of C and airway resistance (R) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of C and an overestimation of R were observed in the severe obstruction model.
CONCLUSION
Using the modified dynamic signal analysis approach, respiratory system properties (C and R) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.
Topics: Humans; Airway Resistance; Pulmonary Disease, Chronic Obstructive; Respiration, Artificial; Respiratory Distress Syndrome; Tidal Volume; Respiratory Mechanics; Lung; Lung Compliance; Models, Biological; Adult
PubMed: 38769572
DOI: 10.1186/s12890-024-03061-2 -
Lasers in Surgery and Medicine Feb 2019Adenotonsillectomy (AT) is commonly used to treat upper airway obstruction in children, but selection of patients who will benefit most from AT is challenging. The need...
OBJECTIVES
Adenotonsillectomy (AT) is commonly used to treat upper airway obstruction in children, but selection of patients who will benefit most from AT is challenging. The need for diagnostic evaluation tools without sedation, radiation, or high costs has motivated the development of long-range optical coherence tomography (LR-OCT), providing real-time cross-sectional airway imaging during endoscopy. Since the endoscope channel location is not tracked in conventional LR-OCT, airway curvature must be estimated and may affect predicted airway resistance. The study objective was to assess effects of three realistic airway curvatures on predicted airway resistance using computational fluid dynamics (CFD) in LR-OCT reconstructions of the upper airways of pediatric patients, before and after AT.
METHODS
Eight subjects (five males, three females, aged 4-9 years) were imaged using LR-OCT before and after AT during sedated endoscopy. Three-dimensional (3D) airway reconstructions included three airway curvatures. Steady-state, inspiratory airflow simulations were conducted under laminar conditions, along with turbulent simulations for one subject using the k-ω turbulence model. Airway resistance (pressure drop/flow) was compared using two-tailed Wilcoxon signed rank tests.
RESULTS
Regardless of the airway curvatures, CFD findings corroborate a surgical end-goal with computed post-operative airway resistance significantly less than pre-operative (P < 0.01). The individual resistances did not vary significantly for different airway curvatures (P > 0.25). Resistances computed using turbulent simulations differed from laminar results by less than ∼5%.
CONCLUSIONS
The results suggest that reconstruction of the upper airways from LR-OCT imaging data may not need to account for airway curvature to be predictive of surgical effects on airway resistance. Lasers Surg. Med. 51:150-160, 2019. © 2018 Wiley Periodicals, Inc.
Topics: Adenoids; Airway Obstruction; Airway Resistance; Child; Child, Preschool; Computer Simulation; Esophagoscopy; Female; Humans; Hydrodynamics; Hypertrophy; Male; Palatine Tonsil; Plastic Surgery Procedures; Tomography, Optical Coherence
PubMed: 30051633
DOI: 10.1002/lsm.23005 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Jul 2021Structural nasal obstruction(SNO) is a series of diseases caused by congenital or acquired structural anatomical abnormalities of nasal airway and its surrounding...
Structural nasal obstruction(SNO) is a series of diseases caused by congenital or acquired structural anatomical abnormalities of nasal airway and its surrounding tissues, which leads to increased nasal ventilation resistance. The effect of medication drugs for SNO is poor and surgical intervention is often needed. However, the abnormal structure of nasal airway is very complex, including the periphery of nasal airway, internal nasal airway, the front and rear of nasal airway and complex factors. These abnormal structures may interfere with the nasal airflow mechanics by changing the nasal ventilation volume and disrupting the symmetry of the bilateral nasal cavity, and finally lead to subjective feeling of nasal obstruction. In addition, the structure of nasal airway has plasticity. After the abnormal structure appears, the corresponding compensation of nasal airway can occur to ensure normal nasal ventilation and bilateral nasal cavity symmetry. Therefore, the SNO is the result of the failure of nasal airway remodeling after the appearance of abnormal structures. The etiology of SNO is complex, involving original structural abnormalities, nasal symmetry changing and nasal airway structure remodeling. Therefore, accurate identification of the main factors leading to SNO is the vitalpremise of making personalized nasal ventilation surgery.
Topics: Airway Resistance; Humans; Nasal Cavity; Nasal Obstruction; Nose
PubMed: 34304503
DOI: 10.13201/j.issn.2096-7993.2021.07.021 -
Frontiers in Medicine 2023Aerobika oscillating positive expiratory pressure (OPEP) device promotes airway clearance in many respiratory diseases. However, studies have yet to focus on its...
Impact of Aerobika oscillating positive expiratory pressure in improving small airway resistance, lung function, symptoms and exercise capacity in chronic obstructive pulmonary disease.
BACKGROUND
Aerobika oscillating positive expiratory pressure (OPEP) device promotes airway clearance in many respiratory diseases. However, studies have yet to focus on its effectiveness in improving small airway resistance impulse oscillometry (IOS) measurement in COPD subjects. We aim to evaluate the improvement of small airway resistance ( IOS), lung function (spirometry), exercise capacity [ 6-min walking test (6MWT)], symptoms [COPD assessment test (CAT)] and severe exacerbation events among COPD subjects using Aerobika OPEP.
METHODS
This was a prospective, single-arm interventional study among COPD subjects with small airway disease. Subjects were instructed to use twice daily Aerobika OPEP (10 min each session); for 24 weeks; as an additional to standard therapy. IOS, spirometry, 6MWT, CAT score and severe exacerbation events were evaluated at baseline, 12 weeks and 24 weeks.
RESULTS
Fifty-three subjects completed the study. Aerobika usage showed improvement of IOS parameters; e.g. measurement of airway resistance at 5 Hz (R5), cmH20/L/s, (12-week = 0.008, 24-week < 0.001), R5% predicted (12-week = 0.007, 24-week < 0.001) and small airway resistance (R5-R20), cmH20/L/s, (12-week 0.021, 24-week < 0.001). There were improvement of lung function; e.g. FEV, L (12-week = 0.018, 24-week = 0.001), FEV% predicted (12-week = 0.025, 24-week = 0.001), FEF, L (12-week = 0.023, 24-week = 0.002), and FEF% predicted (12-week = 0.024, 24-week < 0.001). CAT score improved at 12 weeks ( < 0.001) and 24 weeks ( < 0.001). Subjects had improved exercise capacity (6MWT, metres) after 24 weeks ( = 0.016). However, there was no significant difference in severe exacerbation events 24 weeks before and after Aerobika usage.
CONCLUSION
Aerobika OPEP demonstrated significant improvement in small airway resistance as early as 12 weeks of usage, with sustained improvement at 24 weeks. Aerobika OPEP administration had significantly improved lung function, 6MWT, and CAT scores over 24 weeks. There was no difference in severe exacerbation events.
PubMed: 37332765
DOI: 10.3389/fmed.2023.1202380 -
Respiratory Care May 2018Impulse oscillometry is a method of airway assessment and diagnosis that provides data on lung mechanics. In the literature, studies have used different types of...
BACKGROUND
Impulse oscillometry is a method of airway assessment and diagnosis that provides data on lung mechanics. In the literature, studies have used different types of mouthpieces or did not describe the model used for the tests. We sought to compare the 3 most commonly described mouthpieces in terms of test results, comfort, and subject preference.
METHODS
Thirty-nine healthy volunteers were evaluated with spirometry and impulse oscillometry, assessing the resistance at 5 Hz and 20 Hz (R5 and R20, respectively), reactance at 5 Hz (X5), reactance area, and resonant frequency. A filter heat exchanger with a circular mouthpiece (B1), a filter heat exchanger with an oval mouthpiece (B2), and a filter heat exchanger with a circular mouthpiece coupled with a free-flow piece (B3) were compared using an acceptability and tolerance scale, and subjects noted their preference.
RESULTS
Statistical analysis showed differences between all the mouthpieces and the predicted values for R5, R20, and X5. The mouthpiece comparison showed differences in R5 between a filter heat exchanger with an oval mouthpiece (B2) and a circular mouthpiece coupled with a free-flow piece (B3) ( = .007); resonant frequency between a filter heat exchanger with a circular mouthpiece (B1) and a filter heat exchanger with an oval mouthpiece (B2) ( = .004) and between a filter heat exchanger with a circular mouthpiece (B1) and a circular mouthpiece coupled with a free-flow piece (B3) ( = .003); and reactance area between a filter heat exchanger with a circular mouthpiece (B1) and a circular mouthpiece coupled with a free-flow piece (B3) ( = .01). In the subjective evaluation, acceptability and tolerance differences were found in the ease of carrying out the evaluation, and no difference was found with regard to the degree of discomfort. Ten subjects preferred a filter heat exchanger with a circular mouthpiece (B1), 15 preferred a filter heat exchanger with an oval mouthpiece (B2), and 14 preferred a circular mouthpiece coupled with a free-flow piece (B3).
CONCLUSIONS
A circular mouthpiece coupled with a free-flow piece (B3) appeared to be the most suitable mouthpiece for the impulse oscillometry tests. It assured smaller impedance values for the respiratory system, and subjects expressed the most confidence in using this mouthpiece.
Topics: Adult; Airway Resistance; Equipment Design; Female; Healthy Volunteers; Humans; Lung; Male; Oscillometry; Respiratory Function Tests; Respiratory Mechanics
PubMed: 29487095
DOI: 10.4187/respcare.05471 -
Annals of the American Thoracic Society Jan 2022Inspiratory flow limitation (IFL), characterized by flattening of individual breaths on the airflow/time tracing, is a noninvasive indicator of elevated upper airway...
Inspiratory flow limitation (IFL), characterized by flattening of individual breaths on the airflow/time tracing, is a noninvasive indicator of elevated upper airway resistance. An IFL "event" in isolation has not been defined, nor has the ability to reproducibly identify event occurrence been tested. IFL events and their association with immediate physiological responses-as well as the impact of characteristics such as age, sex, sleep stage, sleepiness, and event duration on their association with such outcomes-have not been studied. Symptomatic patients with a normal to mildly abnormal apnea-hypopnea index who have predominant IFL on their polysomnography may benefit from treatment. To test the reproducibility of identifying IFL events and their termination and to determine the frequency of the immediate physiological response to their occurrence, including desaturation, electroencephalography (EEG) arousal, and increased heart rate (HR). Fifty-eight patients with obstructive sleep apnea (OSA) underwent full diagnostic polysomnography. IFL events and their termination were identified manually using predefined rules from the unscored nasal cannula flow channel alone and were evaluated for responses such as EEG arousal, oxygen desaturation of ⩾3%, and HR increase. Interscorer reliability was acceptable, with an average percent agreement for occurrence of 82% ± 3%. Of all IFL events, 24% (regardless of the definition) were not associated with an EEG arousal, an increase in HR, or O desaturation. Of all IFL events scored, 25% caused O desaturation, 40% were associated with an EEG arousal, and 55% were associated with an increase in HR; 67% caused either an EEG arousal and/or an increase in HR. Responses were observed to occur either in isolation or in combination. IFL events that terminated with at least two non-IFL breaths, one of which had a 200% increase in amplitude, were significantly associated with O desaturation, EEG arousal, and increase in HR compared with events that ended in one non-IFL breath. IFL events that had a >50% reduction in flow amplitude compared with baseline were significantly associated with O desaturation compared with events that had a 30% reduction or less. Most IFL events resulted in immediate physiological responses, and no single consequence reliably occurred after every event. We propose a framework that can incorporate the scoring of IFL events into assessing the diagnosis and severity of OSA and suggest that no single consequence be used to define IFL as a respiratory event. The relationship of IFL events to OSA outcomes remains to be tested.
Topics: Airway Resistance; Humans; Lung; Polysomnography; Reproducibility of Results; Sleep Apnea, Obstructive
PubMed: 34347573
DOI: 10.1513/AnnalsATS.202001-004OC