Measurement Of Airway Resistance Research Articles

Protective effects of Parkin knockout on asthma-induced changes in juvenile mice: inflammation, airway resistance, and oxidative stress

Objective This study aimed to explore the effects of Parkin (Prkn) knockout in a juvenile mouse model of asthma. Methods Prkn knockout (KO) and wild type (WT) mice were utilized to establish a juvenile mouse asthma model. The asthma model involved exposure to hyperoxia/ovalbumin (OVA), encompassing hyperoxia from postnatal day 1 (P1) to P7, sensitization on P21 and P28, and challenge from P36 to P42. Room air/phosphate-buffered saline (PBS) served as the control condition. Following airway resistance measurement, bronchoalveolar lavage fluid (BALF) was collected for cellular analysis, and lung tissues were subjected to histological examination and oxidative stress assessment. Serum levels of ovalbumin-specific immunoglobulin E (IgE), total IgE, interleukin-4 (IL-4), IL-5, and IL-13 were quantified using enzyme-linked immunosorbent assay (ELISA). Results WT mice exposed to hyperoxia/OVA showed decreased body weight and increased airway resistance compared to those exposed to control condition. Conversely, KO mice exhibited increased body weight under asthma conditions. KO mice with asthma had reduced total cell counts, along with lower levels of lymphocytes, eosinophils, and neutrophils, compared to WT asthma mice. Histological assessment showed attenuated inflammation and reduced collagen deposition in KO mice relative to WT mice, with lower serum levels of inflammatory markers and improved lung oxidative stress profiles. No significant differences were observed between KO and WT mice under room air/PBS conditions. Conclusions Parkin knockout in juvenile mice mitigates asthma-related alterations in airway resistance, histopathological changes, inflammation status, and oxidative stress. These findings highlight a protective role of Parkin deficiency against asthma-associated pathologies.

Effect of Cholinergic Receptor Antagonists on the Potentiation of the Effect of Adenosine Receptor Blockers in People with Bronchial Asthma

Background: The interaction between adenosine receptor blockers and anticholinergic substances in the treatment of bronchial asthma is an area of interest. The efficacy of such combinations in managing bronchial asthma and bronchial hypersensitivity needs to be explored further. Understanding lung function parameters such as airway resistance and intrathoracic gas volume is crucial for evaluating the effects of these medications. Objective: This study aimed to investigate the effect of combining the adenosine receptor blocker, bamifylline, with the anticholinergic substance, ipratropium bromide spray, in patients with bronchial asthma. Specifically, the study sought to assess changes in lung function parameters, including airway resistance and intrathoracic gas volume, after administering ipratropium bromide alone and in combination with bamifylline. Methods: Sixteen patients with bronchial asthma were enrolled in the study. Lung function was evaluated using body plethysmography, with measurements of airway resistance (Raw), intrathoracic gas volume (ITGV), airway specific resistance (SRaw), and airway specific conductance (SGaw). Patients initially received ipratropium bromide inhalation (2 inhalations x 20µg), followed by Raw and ITGV measurements at intervals (5, 30, 60, and 120 minutes). Subsequently, patients received bamifylline (2 x 600 mg) daily for seven days at home. On the eighth day, they were administered ipratropium bromide spray (2 inhalations x 20µg), and lung function parameters were assessed similarly. Results: Administration of ipratropium bromide alone led to a significant reduction in airway resistance (p<0.05). However, the combination of ipratropium bromide with bamifylline did not significantly enhance the effects of adenosine receptor blockade (p<0.05). Specifically, there were no significant changes in Raw, ITGV, SRaw, or SGaw after combining ipratropium bromide with bamifylline. Conclusion: The study findings suggest that the addition of anticholinergic substances did not potentiate the action of adenosine receptor blockers in patients with bronchial asthma. Therefore, the anti-inflammatory effects of xanthines, such as bamifylline, were not augmented by anticholinergic substances in this study. These results highlight the need for further research to explore alternative therapeutic approaches in the management of bronchial asthma.

Vandetanib as a prospective anti-inflammatory and anti-contractile agent in asthma.

Background: Vandetanib is a small-molecule tyrosine kinase inhibitor. It exerts its therapeutic effects primarily in a range of lung cancers by inhibiting the vascular endothelial growth factor receptor 2. However, it remains unclear whether vandetanib has therapeutic benefits in other lung diseases, particularly asthma. The present study investigated the pioneering use of vandetanib in the treatment of asthma. Methods: In vivo experiments including establishment of an asthma model, measurement of airway resistance measurement and histological analysis were used primarily to confirm the anticontractile and anti-inflammatory effects of vandetanib, while in vitro experiments, including measurement of muscle tension and whole-cell patch-clamp recording, were used to explore the underlying molecular mechanism. Results: In vivo experiments in an asthmatic mouse model showed that vandetanib could significantly alleviate systemic inflammation and a range of airway pathological changes including hypersensitivity, hypersecretion and remodeling. Subsequent in vitro experiments showed that vandetanib was able to relax the precontracted rings of the mouse trachea via calcium mobilization which was regulated by specific ion channels including VDLCC, NSCC, NCX and K+ channels. Conclusions: Taken together, our study demonstrated that vandetanib has both anticontractile and anti-inflammatory properties in the treatment of asthma, which also suggests the feasibility of using vandetanib in the treatment of asthma by reducing abnormal airway contraction and systemic inflammation.

Managing Small Airway Disease in Patients with Severe Asthma: Transitioning from the "Silent Zone" to Achieving "Quiet Asthma".

Background/Objectives: Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABA) therapy in the treatment of severe asthma. Aim and objectives: To demonstrate that treating Small Airways Disease (SAD) in severe asthma patients who are candidates for biologics can improve respiratory symptoms, lung function, and airways inflammation, potentially avoiding or delaying the use of biological therapy. Methods: Thirty-two severe asthma patients with SAD were transitioned from separate inhalers for ICS/LABA and LAMA to extrafine single-inhaler beclomethasone, formoterol, and glycopyrronium. None of these patients underwent biological therapy before the study. Follow-up evaluations were conducted at baseline (T0) and three months after initiation (T3). Assessments included clinical evaluations, spirometry, oscillometry, and inflammation markers. Results: Transitioning to single-inhaler triple therapy from T0 to T3 resulted in significant improvements in Asthma Control Test (ACT) and SAD parameters, including increased Forced Expiratory Volume in the mid-range of lung capacity and improved airway resistance and reactance measurements using impulse oscillometry. A significant reduction in airway inflammation was evidenced by lower levels of Fractional Exhaled Nitric Oxide 350 (FeNO 350) (p < 0.001 for all). Conclusions: Adopting a single-inhaler triple therapy notably enhanced clinical control and small airway function in patients with severe asthma and SAD, supporting the positive impact of target-therapy for the achievement of a stable state termed "Quiet Asthma".

Changes in lung mechanics and ventilation-perfusion match: comparison of pulmonary air- and thromboembolism in rats

BackgroundPulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism.MethodsAnesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO2 concentration (ETCO2), shape factors, and dead space parameters by volumetric capnography.ResultsIn the presence of a uniform decrease in ETCO2 in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO2, and PaCO2, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting.ConclusionsOur findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO2 elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.

Total airway mechanics and fractional exhaled nitric oxide levels of children living in banjihas (semi-basements).

The ISAAC phase III study in Korea found a higher incidence of wheezing illnesses among residents in basements or semi-basements. This study investigates the link between living in banjihas (semi-basements) and airway resistance and Th2 airway inflammation in Korean children, compared to those on higher floors. We assessed 575 fifth- and sixth-grade students (aged 10-12) in an inner-city area of South Korea. The study utilized impulse oscillometry to measure small and total airway resistance (Rrs20-5 and Rrs0, respectively) and Fractional Exhaled Nitric Oxide (FeNO) measurements to evaluate airway inflammation. We also considered a range of biological and environmental factors, including allergen sensitization, serum 25-hydroxyvitamin D levels, and urinary metabolites like VOCs, bisphenol, and triclosan. Participants were categorized by living floors: banjihas, first-fifth floors, and sixth floors or higher. Twenty-five children (4.3%) lived in banjihas, 311 (54.1%) on the first to fifth floor, and 239 (41.6%) on the sixth floor or above. Despite similar levels of allergen sensitization and urinary pollutant metabolite levels across all groups, banjiha dwellers showed significantly higher total airway resistance (adjusted &1: 0.633, 95%CI: 0.156, 1.109; P = 0.009) and a greater prevalence of elevated FeNO levels (> 35 ppb) (P = 0.033). These findings persisted after adjusting for critical factors like height, gender, BMI z-score, and birth conditions. Children in banjihas exhibit elevated airway resistance and FeNO levels independently of allergen sensitization or pollution exposure, underscoring the necessity for enhanced focus on their respiratory health in such living conditions.

Reproducibility and responsiveness of airway impedance measures derived from the forced oscillation technique across different operating lung volumes

BackgroundThe forced oscillation technique (FOT) enables non-invasive measurement of respiratory system impedance. Limited data exists on how changes in operating lung volume (OLV) impact FOT-derived measures of airway resistance (Rrs) and reactance (Xrs). ObjectivesThis study examined the reproducibility and responsiveness of FOT-derived measures of Rrs and Xrs during simulated changes in OLV. MethodsParticipants simulated breathing at six OLVs: total lung capacity (TLC), ∼50% of inspiratory reserve volume (IRV50), ∼two-times tidal volume (VT2), tidal volume (VT), ∼50% of expiratory reserve volume (ERV50), and residual volume (RV), on a commercially available FOT device. Each simulated OLV manuever was performed in triplicate and in random order. Total Rrs and Xrs were recorded at 5, 11, and 19 Hz. ResultsTwelve healthy participants (2 female) completed the study (weight: 76.5 ± 13.6 kg, height: 178.6 ± 9.7 cm, body mass index: 23.9 ± 3.1 kg/m2). Reproducibility of Rrs and Xrs at VT, VT2 and IRV50 was good to excellent (Range: ICC: 0.89–0.98, 95% confidence interval (CI): 0.70–0.98), while reproducibility at TLC, RV, and ERV50 was poor to excellent (Range: ICC: 0.60–0.98, 95% CI: 0.36–0.97). Rrs and Xrs were not different between VT and VT2 at any frequency (P > .05). With lung hyperinflation from VT to TLC, Rrs and Xrs decreased at all three frequencies (e.g., At 5 Hz Rrs: mean difference (MD): − 0.89, 95%CI: − 0.03 to − 1.75, P = .04; Xrs: MD: − 0.56, 95%CI: − 0.25 to − 0.86, P < .01). With lung hypoinflated from VT to RV, Rrs increased, and Xrs decreased for all frequencies (e.g., MD at 5 Hz, Rrs: MD: 2.31, 95%CI: 0.94–3.67, P < .01; Xrs: MD: −2.53, 95%CI: −4.02 to −1.04, P < .01). ConclusionFOT-derived measures of airway Rrs and Xrs are reproducible across a range of OLV’s, and are responsive to hyper- and hypo-inflation of the lung. To further understand the impact of lung hyper- and hypo-inflation on FOT-derived airway impedance additional study is required in individuals with pathological variations in operating lung volume.

Investigation of the Methodology of Specific Airway Resistance Measurements in COPD.

Specific resistance (SRaw) measurements in Chronic Obstructive Pulmonary Disease (COPD) patients may be performed by panting or tidal breathing. The aim of this study was to compare how breathing frequency affected SRaw in COPD and compare different tangent plotting methods. Fifteen COPD patients participated. Three protocols were performed: tidal 1 - spontaneous tidal breathing; tidal 2 - tidal breathing with a flow of ±1 L/sec; panting - 60 breaths per min. Effective (SReff), total (SRtot), ±0.5 L/s (SR0.5), and mid (SRmid) specific resistance were assessed. The tidal breathing protocols provided similar results. Panting resulted in higher SReff (p = 0.0002) and SRtot (p < 0.0001) versus tidal breathing, but not SR0.5 or SRmid. Breathing frequency did not affect intra-test variance. SReff and SRtot measurements were similar, and were higher than SR0.5, during tidal breathing (p = 0.0014 and p < 0.0001 respectively) and panting (p = 0.0179 and p < 0.0001 respectively). SRtot was higher than SRmid during tidal breathing (p < 0.0001) and panting (p < 0.0001). Intra-test variance of SReff and SRtot were similar and showed the lowest percent coefficient of variation during both tidal breathing and panting. Panting and tidal breathing manoeuvres are not interchangeable in COPD patients. Panting widens the clubbing in the SRaw loop. SR0.5 and SRmid may underestimate abnormal physiology in COPD.

Role of histamine H4 receptor in the anti-inflammatory pathway of glucocorticoid-induced leucin zipper (GILZ) in a model of lung fibrosis

IntroductionThis study investigates the interactions between histaminergic system and glucocorticoid-induced leucin zipper (GILZ) in the inflammatory process and glucocorticoid modulation in lung fibrosis.MethodsWild-type (WT) and GILZ Knock-Out (KO) mice were treated with bleomycin (0.05 IU) or saline, delivered by intra-tracheal injection. After surgery, mice received a continuous infusion of JNJ7777120 (JNJ, 2 mg/kg b.wt.) or vehicle for 21 days. Lung function was studied by measuring airway resistance to air insufflation through the analysis of pressure at airway opening (PAO). Lung samples were collected to evaluate the expression of histamine H4R, Anx-A1, and p65-NF-kB, the activity of myeloperoxidase (MPO), and the production of pro-inflammatory cytokines.ResultsAirway fibrosis and remodeling were assessed by measuring TGF-β production and α-SMA deposition. JNJ reduces PAO in WT but not in GILZ KO mice (from 22 ± 1 mm to 15 ± 0.5 and from 24 ± 1.5 to 19 ± 0.5 respectively), MPO activity (from 204 ± 3.13 pmol/mg to 73.88 ± 2.63 in WT and from 221 ± 4.46 pmol/mg to 107 ± 5.54 in GILZ KO), the inflammatory response, TGF-β production, and α-SMA deposition in comparison to WT and GILZ KO vehicle groups.ConclusionIn conclusion, the role of H4R and GILZ in relation to glucocorticoids could pave the way for innovative therapies to counteract pulmonary fibrosis.

A Longitudinal Study of Respiratory Mechanics in Pregnant Women with Obesity and Overweight.

Respiratory mechanics and the role of sex hormones in pregnancy are not well elucidated. We examined longitudinal and positional changes in lung mechanics in pregnancy and investigated the role of sex hormones. A longitudinal study enrolled 135 women with obesity in early pregnancy. Fifty-nine percent of women identified as White; median body mass index at enrollment was 34.4kg/m2. Women with respiratory disease were excluded. We obtained measurements of airway resistance and respiratory system reactance in various positions using impedance oscillometry and sex hormones in early and late pregnancy. With pregnancy progression, there was a significant increase in resonant frequency (Fres) (p = 0.012), integrated area of low frequency reactance (AX) (p = 0.0012) and R5-R20Hz (p = 0.038) in the seated position,and a significant increase in R5Hz (p = 0.000), Fres (p = 0.001), AX (p < 0.001 = 0.000), and R5-R20Hz (p = 0.014) in the supine position. Compared to the seated position, the supine position was associated with a significant increase in R5Hz, R20Hz, X5Hz, Fres, and AX in early (p-values < 0.026) and late pregnancy (p-values ≤ 0.001). Changes in progesterone levels between early and late pregnancy predicted the change in R5, Fres, and AX (p-values ≤ 0.043). Resistive and elastic loads increase with pregnancy progression and a change in body position from seated to supine increases resistive and elastic loads in both early and late pregnancies. The increase in airway resistance is primarily related to an increase in peripheral rather than central airways resistance. There was an association between the change in progesterone levels and airway resistance.

Impact of Aerobika® oscillating positive expiratory pressure in improving small airway resistance, lung function, symptoms and exercise capacity in chronic obstructive pulmonary disease.

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 via impulse oscillometry (IOS) measurement in COPD subjects. We aim to evaluate the improvement of small airway resistance (via IOS), lung function (spirometry), exercise capacity [via 6-min walking test (6MWT)], symptoms [COPD assessment test (CAT)] and severe exacerbation events among COPD subjects using Aerobika® OPEP. 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. 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 p = 0.008, 24-week p < 0.001), R5% predicted (12-week p = 0.007, 24-week p < 0.001) and small airway resistance (R5-R20), cmH20/L/s, (12-week p = 0.021, 24-week p < 0.001). There were improvement of lung function; e.g. FEV1, L (12-week p = 0.018, 24-week p = 0.001), FEV1% predicted (12-week p = 0.025, 24-week p = 0.001), FEF25-75, L (12-week p = 0.023, 24-week p = 0.002), and FEF25-75% predicted (12-week p = 0.024, 24-week p < 0.001). CAT score improved at 12 weeks (p < 0.001) and 24 weeks (p < 0.001). Subjects had improved exercise capacity (6MWT, metres) after 24 weeks (p = 0.016). However, there was no significant difference in severe exacerbation events 24 weeks before and after Aerobika® usage. 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.

Airway Resistance and Respiratory Distress in Laryngeal Cancer: A Computational Fluid Dynamics Study.

Obstructive upper airway pathologies are a great clinical challenge for the airway surgeon. Protection against acute obstruction is critical, but avoidance of unnecessary tracheostomy must also be considered. Decision-making regarding airway, although supported by some objective findings, is largely guided by subjective experience and training. This investigation aims to study the relationship between clinical respiratory distress and objective measures of airway resistance in laryngeal cancer as determined by computational fluid dynamic (CFD) and morphometric analysis. Retrospective CT and clinical data were obtained for series of 20 cases, defined as newly diagnosed laryngeal cancer patients who required admission or urgent airway surgery, and 20 controls. Cases and controls were matched based on T-staging. Image segmentation and morphometric analysis were first performed. Computational models based on the lattice Boltzmann method were then created and used to quantify the continuous mass flow, rigid wall, and constant static pressure inlet boundary conditions. The analysis demonstrated a significant relationship between airway resistance and acute obstruction (OR 1.018, 95% CI 1.001-1.045). Morphometric analysis similarly demonstrated a significant relationship when relating measurements based on the minimum cross-section, but not on length of stenosis. Morphometric measurements also showed significance in predicting CFD results, and their relationship demonstrated that airway pressures increase exponentially below 2.5 mm. Tumor subsite did not show a significant difference, although the glottic subgroup tended to have higher resistances. Airway resistance analysis from CFD computation correlated with presence of acute distress requiring emergent management. Morphometric analysis showed a similar correlation, demonstrating a radiologic airway assessment technique on which future risk estimation could be performed. 4 (case-control study) Laryngoscope, 133:2734-2741, 2023.

Comparative analysis of pulmonary function in children born preterm and full-term at 6-9 years of age.

Objective:To compare pulmonary function parameters and the prevalence of altered pulmonary function in children born preterm and full-term, using the Global Lung Initiative reference values.Methods:This is a cross-sectional study with 6–9-year-old children submitted to measurement of airway resistance (Rint) and spirometry according to the American Thoracic Society and European Respiratory Society Technical Statement. The inclusion criteria were, among the preterm group: gestational age <37 weeks and birth weight <2000g; among the full-term group: schoolchildren born full-term with birth weight >2500g, recruited at two public schools in São Paulo, Brazil, matched by sex and age with the preterm group. As exclusion criteria, congenital malformations, cognitive deficit, and respiratory problems in the past 15 days were considered.Results:A total of 112 children were included in each group. Preterm children had gestational age of 30.8±2.8 weeks and birth weight of 1349±334g. Among them, 46.6% were boys, 46.4% presented respiratory distress syndrome, 19.6% bronchopulmonary dysplasia, and 65.2% were submitted to mechanical ventilation in the neonatal unit. At study entry, both groups were similar in age and anthropometric parameters. Parameters of pulmonary function (Z scores) in preterm and full-term groups were: Rint (0.13±2.24 vs. -1.02±1.29; p<0.001); forced vital capacity (FVC) (-0.39±1.27 vs. -0.15±1.03; p=0.106), forced expiratory volume in one second (FEV1)/FVC (-0.23±1.22 vs. 0.14±1.11; p=0.003), FEV1 (-0.48±1.29 vs. -0.04±1.08; p=0.071), and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) (1.16±1.37 vs. 2.08±1.26; p=0.005), respectively. The prevalence values of altered airway resistance (16.1 vs. 1.8%; p<0.001) and spirometry (26.8 vs. 13.4%, p=0.012) were higher in preterm infants than in full-term ones.Conclusions:Preterm children had higher prevalence of altered pulmonary function, higher Z scores of airway resistance, and lower Z scores of FEV1/FVC and FEF25-75 compared with those born full-term.

Differences in respiratory oscillometry measurements using mouthpiece, mouth, and nasal mask in healthy adults.

Airway resistance measurements using oscillometry provide a potential alternative to spirometry in assessing airway obstruction and dynamics due to measurements taken during tidal breathing. Oscillometry typically requires participants to form a tight seal around a mouthpiece that can prove challenging for some people. To address this challenge, we conducted a prospective study to evaluate the effect of different interfaces like mouthpiece, mouth mask, and nasal mask on respiratory impedance results from oscillometry in a cohort of healthy adults. Ten healthy adults [7 females; mean age: 38.9 yr (SD ±15.5)] underwent oscillometry using each of the three interfaces. We measured resistance at 5 Hz (Rrs5), frequency dependence of resistance at 5-20 Hz (Rrs5-20), and reactance area (Ax). Rrs5 was not different when using the mouthpiece compared with the mouth mask [mean 2.98 cmH2O/L/s (SD ±0.68) vs. mean 3.2 cmH2O/L/s (SD ±0.81); P = 0.92; 95% CI -0.82 to +0.38], respectively. Nasal mask Rrs5 measurements were significantly higher than mouthpiece measurements (mean 7.31 cmH2O/L/s; SD ±2.62; P < 0.01; 95%CI -6.91 to -1.75). With Ax5, we found a mean of 4.01 cmH2O/L (SD ±2.04) with the mouth mask compared with a mean of 4.02 cmH2O/L (SD ±1.87; P = 1.0 95% CI -1.86 to +1.87) for the mouthpiece, however, we found a significant difference between the mouthpiece and nasal mask for Ax (mean = 10.71; SD ±7.0 H2O/L; P = 0.04, 95% CI -12.96 to -0.43). Our findings show that oscillometry using a mouth mask may be just as effective as using a mouthpiece in assessing airway dynamics and resistance.NEW & NOTEWORTHY This is the first study to compare the use of different interfaces: mouthpiece, mouth mask, and nasal mask, for oscillometry in an adult population. We report that using a mouth mask in oscillometry may provide a valid alternative to a mouthpiece in cohorts who may struggle to form the required tight seal that is typically required in oscillometry or spirometry.

Alteration of glycosphingolipid metabolism by ozone is associated with exacerbation of allergic asthma characteristics in mice.

Asthma is a common chronic respiratory disease exacerbated by multiple environmental factors. Acute ozone exposure has previously been implicated in airway inflammation, airway hyperreactivity, and other characteristics of asthma, which may be attributable to altered sphingolipid metabolism. This study tested the hypothesis that acute ozone exposure alters sphingolipid metabolism within the lung, which contributes to exacerbations in characteristics of asthma in allergen-sensitized mice. Adult male and female BALB/c mice were sensitized intranasally to house dust mite (HDM) allergen on days 1, 3, and 5 and challenged on days 12-14. Mice were exposed to ozone following each HDM challenge for 6 h/day. Bronchoalveolar lavage, lung lobes, and microdissected lung airways were collected for metabolomics analysis (N = 8/sex/group). Another subset of mice underwent methacholine challenge using a forced oscillation technique to measure airway resistance (N = 6/sex/group). Combined HDM and ozone exposure in male mice synergistically increased airway hyperreactivity that was not observed in females and was accompanied by increased airway inflammation and eosinophilia relative to control mice. Importantly, glycosphingolipids were significantly increased following combined HDM and ozone exposure relative to controls in both male and female airways, which was also associated with both airway resistance and eosinophilia. However, 15 glycosphingolipid species were increased in females compared with only 6 in males, which was concomitant with significant associations between glycosphingolipids and airway resistance that ranged from R2 = 0.33-0.51 for females and R2 = 0.20-0.34 in male mice. These observed sex differences demonstrate that glycosphingolipids potentially serve to mitigate exacerbations in characteristics of allergic asthma.

Mechanical effects of obesity on central and peripheral airway resistance in nonasthmatic early pubescent children.

In children, obesity typically reduces functional residual capacity (FRC), which reduces airway caliber and increases airway resistance. Whether these obesity-related changes in respiratory function can alter bronchodilator responsiveness is unknown. To investigate bronchodilator responsiveness in nonasthmatic children with and without obesity. Seventy nonasthmatic children, 8-12 years old, without (n = 19) and with (n = 51) obesity, completed spirometry, impulse oscillometry, and airway resistance measurements through plethysmography pre/post 360 µg of inhaled albuterol. FRC was assessed pre albuterol. A two-way analysis of variance determined the effects of obesity (group) and inhaled albuterol (pre-post) on outcome measures. FRC (%total lung capacity) was 16% lower in children with obesity compared with those without obesity. There was no significant group by pre-post albuterol interaction on any outcome variables. Albuterol inhalation reduced total, central and peripheral airway resistance and increased airway reactance (i.e., less negative) to a similar degree in children with and without obesity. In children with obesity, airway resistance was increased whether measured by impulse oscillometry or plethysmography. However, once airway resistance was adjusted for lung volumes (i.e., specific airway resistance or sRaw ), there were no differences between children with and without obesity. In addition, significant but moderate associations were detected between chest mass and FRC (r = -0.566; p < 0.001), FRC and total airway resistance (i.e., Raw ; r = -0.445; p < 0.001). In nonasthmatic early pubescent children, obesity increases total, central, and peripheral respiratory system resistance. However, the added respiratory system resistance and low lung volume breathing with obesity are not sufficient to reduce bronchodilator responsiveness.

Analysis of Upper Airway Flow Dynamics in Robin Sequence Infants Using 4-D Computed Tomography and Computational Fluid Dynamics.

Robin Sequence (RS) is a potentially fatal craniofacial condition characterized by undersized jaw, posteriorly displaced tongue, and resultant upper airway obstruction (UAO). Accurate assessment of UAO severity is crucial for management and diagnosis of RS, yet current evaluation modalities have significant limitations and no quantitative measures of airway resistance exist. In this study, we combine 4-dimensional computed tomography and computational fluid dynamics (CFD) to assess, for the first time, UAO severity using fluid dynamic metrics in RS patients. Dramatic intrapopulation differences are found, with the ratio between most and least severe patients in breathing resistance, energy loss, and peak velocity equal to 40:1, 20:1, and 6:1, respectively. Analysis of local airflow dynamics characterized patients as presenting with primary obstructions either at the location of the tongue base, or at the larynx, with tongue base obstructions resulting in a more energetic stenotic jet and greater breathing resistance. Finally, CFD-derived flow metrics are found to correlate with the level of clinical respiratory support. Our results highlight the large intrapopulation variability, both in quantitative metrics of UAO severity (resistance, energy loss, velocity) and in the location and intensity of stenotic jets for RS patients. These results suggest that computed airflow metrics may significantly improve our understanding of UAO and its management in RS.

Aromatic ointments for the common cold: what does the science say?

BackgroundUpper respiratory tract infections occur with an annual incidence of 17.2 billion cases globally. The negative impact that symptoms have on sleep is thought to slow the recovery process. Plant-derived aromatics have been used since ancient times to treat respiratory illnesses. In this narrative review, we summarize the use of aromatics for the symptomatic relief of upper respiratory tract infections and how this affects sleep quality.MethodsLiterature searches were conducted using a series of search terms and results were screened for relevance. Additional references were included according to the expert knowledge of the authors.DiscussionMultiple studies have observed that essential oil mixtures of aromatics enhance symptom relief for upper respiratory tract infections and their inhalation has been reported to have antitussive effects. Clinical trials assessing the efficacy of an ointment containing menthol, eucalyptus and camphor found patients to experience faster nasal cooling and decongestion times. Treatment with the same ointment also resulted in significant improvements in reported sleep quality. Aromatic treatment did not improve objective nasal airway measures in any of the studies.ConclusionWhilst not affecting objective measures of nasal airway resistance, the use of aromatics leads to improvements in a number of subjective sensations associated with the common cold. Such benefits result in better sleep, which likely aids recovery. Therefore, aromatics remain a well tolerated and effective option for the symptomatic relief of upper respiratory tract infections.

Beneficial short-term effect of autogenic drainage on peripheral resistance in childhood cystic fibrosis disease

BackgroundAirway clearance techniques are supposed to be a necessary adjunct for the enhancement of impaired peripheral clearance in cystic fibrosis (CF). The objective was to assess the effect of one physiotherapy session (autogenic drainage: AD) on mucus clearance (sputum wet weight) and impulse oscillometry system (IOS) indices, including those obtained from extended Resistance-Inertance-Compliance (eRIC) modelling, considering the degree of bronchial congestion.MethodsThirty children with CF (median age: 12.7 years) in a stable condition prospectively underwent IOS measurements at baseline and after AD. They were divided in two groups: with (visual analog scale of bronchial congestion by the physiotherapist ≥ 5/10) and without (scale < 5/10) bronchial congestion. Paired-comparison of the effects of AD on airway resistance measurements was done with Wilcoxon test.ResultsThe congestion scale correlated with the wet weight of sputum production during the session (Pearson test: p < 0.0001, R = 0.66). Ten children had bronchial congestion and 20 were without congestion. In the whole group, R5–20 Hz significantly decreased after AD (P = 0.049), which was related to a decrease in the children with congestion (P = 0.025), whereas it was not significantly modified in the children without congestion (P = 0.327). The eRIC model allowed the calculation of the peripheral resistance of the respiratory system, which also decreased in the children with congestion (P = 0.037), however, not modified in the children without congestion (P = 0.390).ConclusionOne session of autogenic drainage has the ability to decrease peripheral resistance obtained from IOS measurements, more specifically in children with CF with moderate to severe bronchial congestion.Trial registrationClinicalTrials.gov Identifier: NCT04094441.

Small Airway Dysfunction Measured by Impulse Oscillometry and Fractional Exhaled Nitric Oxide Is Associated With Asthma Control in Children.

BackgroundImpulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO) are sensitive and non-invasive methods to measure airway resistance and inflammation, although there are limited population-based studies using IOS and FeNO to predict asthma control.ObjectiveThis study aimed to investigate the utility of IOS and FeNO for assessing childhood asthma control in terms of small airway dysfunction and airway inflammation.MethodsThis prospective observational cohort study enrolled 5,018 school children (aged 6–12 years), including 560 asthmatic children and 140 normal participants. FeNO, spirometry, IOS, bronchial dilation test, total IgE, and childhood asthma control test (C-ACT) were measured. FeNO, IOS, spirometry, and C-ACT results were correlated with childhood asthma with and without control.ResultsUncontrolled asthmatic children had abnormal FeNO, IOS, and spirometric values compared with control subjects (P < 0.05). IOS parameters with R5, R5-R20, X5, Ax, △R5, and FeNO can predict lower C-ACT scales by the areas under receiver operating characteristic curves (AUCs) (0.616, 0.625, 0.609, 0.622, 0.625, and 0.714). A combination of FeNO (>20 ppb) with IOS measure significantly increased the specificity for predicting uncontrolled asthma patients compared with FeNO alone (P < 0.01). A multiple regression model showed that small airway parameter (R5-R20) was the strongest risk factor [OR (95% CI): 87.26 (7.67–993.31)] for uncontrolled asthma patients. Poor control with lower C-ACT scales correlated with high FeNO (r = −0.394), R5 (r = −0.106), and R5-R20 (r = −0.129) in asthmatic children (P < 0.05).ConclusionA combined use of FeNO and IOS measurements strongly predicts childhood asthma with or without control.