Autonomous Metabolic Oscillations Robustly Gate the Early and Late Cell Cycle.

Eukaryotic cell division is known to be controlled by the cyclin/cyclin dependent kinase (CDK) machinery. However, eukaryotes have evolved prior to CDKs, and cells can divide in the absence of major cyclin/CDK components. We hypothesized that an autonomous metabolic oscillator provides dynamic triggers for cell-cycle initiation and progression. Using microfluidics, cell-cycle reporters, and single-cell metabolite measurements, we found that metabolism of budding yeast is a CDK-independent oscillator that oscillates across different growth conditions, both in synchrony with and also in the absence of the cell cycle. Using environmental perturbations and dynamic single-protein depletion experiments, we found that the metabolic oscillator and the cell cycle form a system of coupled oscillators, with the metabolic oscillator separately gating and maintaining synchrony with the early and late cell cycle. Establishing metabolism as a dynamic component within the cell-cycle network opens new avenues for cell-cycle research and therapeutic interventions for proliferative disorders.

Diagnostic Potential of Oscillometry: A Population-based Approach.

Rationale: Respiratory resistance (Rrs) and reactance (Xrs) as measured by oscillometry and their intrabreath changes have emerged as sensitive parameters for detecting early pathological impairments during tidal breathing. Objectives: This study evaluates the prevalence and association of abnormal oscillometry parameters with respiratory symptoms and respiratory diseases in a general adult population. Methods: A total of 7,560 subjects in the Austrian LEAD (Lung, hEart, sociAl, boDy) Study with oscillometry measurements (computed with the Resmon Pro FULL; Restech Srl) were included in this study. The presence of respiratory symptoms and doctor-diagnosed respiratory diseases was assessed using an interview-based questionnaire. Rrs and Xrs at 5 Hz, their inspiratory and expiratory components, the area above the Xrs curve, and the presence of tidal expiratory flow limitation were analyzed. Normality ranges for oscillometry parameters were defined. Measurements and Main Results: The overall prevalence of abnormal oscillometry parameters was 20%. The incidence of abnormal oscillometry increased in the presence of symptoms or diagnoses: 17% (16-18%) versus 27% (25-29%), P < 0.0001. All abnormal oscillometry parameters except Rrs at 5 Hz were significantly associated with respiratory symptoms/diseases. Significant associations were found, even in subjects with normal spirometry, with abnormal oscillometry incidence rates increasing by 6% (4-8%; P < 0.0001) in subjects with symptoms or diagnoses. Conclusions: Abnormal oscillometry parameters are present in one-fifth of this adult population and are significantly associated with respiratory symptoms and disease. Our findings underscore the potential of oscillometry as a tool for detecting and evaluating respiratory impairments, even in individuals with normal spirometry.

Preschool impulse oscillometry predicts active asthma and impaired lung function at school age.

BACKGROUND: Asthmatic symptoms often start during early childhood. Impulse oscillometry (IOS) is feasible in preschool children who may be unable to reliably perform spirometry measurements. OBJECTIVE: We sought to evaluate the use of IOS in a multicenter, multiethnic high-risk asthma cohort titled the Vitamin D Antenatal Asthma Reduction Trial. METHODS: The trial recruited pregnant women whose children were followed from birth to age 8 years. Lung function was assessed with IOS at ages 4, 5, and 6 years and spirometry at ages 5, 6, 7, and 8 years. Asthma status, respiratory symptoms, and medication use were assessed with repeated questionnaires from birth to age 8 years. RESULTS: In total, 220 children were included in this secondary analysis. Recent respiratory symptoms and short-acting ß2-agonist use were associated with increased respiratory resistance at 5 Hz at age 4 years (ß = 2.6; 95% CI, 1.0 to 4.4; P = .002 and ß = 3.4; 95% CI, 0.7 to 6.2; P = .015, respectively). Increased respiratory resistance at 5 Hz at age 4 years was also associated with decreased lung function from ages 5 to 8 years (ß = -0.3; 95% CI, -0.5 to -0.1; P < .001 for FEV1 at 8 years) and active asthma at age 8 years (ß = 2.0; 95% CI, 0.2 to 3.8; P = .029). CONCLUSIONS: Increased respiratory resistance in preschool IOS is associated with frequent respiratory symptoms as well as school-age asthma and lung function impairment. Our findings suggest that IOS may serve as a potential objective measure for early identification of children who are at high risk of respiratory morbidity.

Oscillometry for personalizing continuous distending pressure maneuvers: an observational study in extremely preterm infants.

RATIONALE: Lung recruitment and continuous distending pressure (CDP) titration are critical for assuring the efficacy of high-frequency ventilation (HFOV) in preterm infants. The limitation of oxygenation (peripheral oxygen saturation, SpO2) in optimizing CDP calls for evaluating other non-invasive bedside measurements. Respiratory reactance (Xrs) at 10 Hz measured by oscillometry reflects lung volume recruitment and tissue strain. In particular, lung volume recruitment and decreased tissue strain result in increased Xrs values. OBJECTIVES: In extremely preterm infants treated with HFOV as first intention, we aimed to measure the relationship between CDP and Xrs during SpO2-driven CDP optimization. METHODS: In this prospective observational study, extremely preterm infants born before 28 weeks of gestation undergoing SpO2-guided lung recruitment maneuvers were included in the study. SpO2 and Xrs were recorded at each CDP step. The optimal CDP identified by oxygenation (CDPOpt_SpO2) was compared to the CDP providing maximal Xrs on the deflation limb of the recruitment maneuver (CDPXrs). RESULTS: We studied 40 infants (gestational age at birth = 22+ 6-27+ 5 wk; postnatal age = 1-23 days). Measurements were well tolerated and provided reliable results in 96% of cases. On average, Xrs decreased during the inflation limb and increased during the deflation limb. Xrs changes were heterogeneous among the infants for the amount of decrease with increasing CDP, the decrease at the lowest CDP of the deflation limb, and the hysteresis of the Xrs vs. CDP curve. In all but five infants, the hysteresis of the Xrs vs. CDP curve suggested effective lung recruitment. CDPOpt_SpO2 and CDPXrs were highly correlated (ρ = 0.71, p < 0.001) and not statistically different (median difference [range] = -1 [-3; 9] cmH2O). However, CDPXrs were equal to CDPOpt_SpO2 in only 6 infants, greater than CDPOpt_SpO2 in 10, and lower in 24 infants. CONCLUSIONS: The Xrs changes described provide complementary information to oxygenation. Further investigation is warranted to refine recruitment maneuvers and CPD settings in preterm infants.

Clinical characterization and outcomes of impulse oscillometry-defined bronchodilator response: an ECOPD cohort-based study.

BACKGROUND: The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR. METHODS: Participants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ - 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ - 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model. RESULTS: This study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up. CONCLUSIONS: The participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

The role of oscillometry in asthma.

PURPOSE OF REVIEW: Oscillometry is a noninvasive pulmonary function test that has gained significant interest in the evaluation of lung disease. Currently, oscillometry is primarily a research tool, but there is a growing body of evidence supporting its clinical use. This review describes the recent work evaluating the role of oscillometry in the diagnosis and treatment of asthma. RECENT FINDINGS: A large body of observational data supports the ability of oscillometry to distinguish healthy individuals from those with respiratory symptoms or lung disease. Oscillometry may not be as useful as an isolated diagnostic test in asthma, but the combination with other pulmonary function tests may improve its diagnostic ability. Oscillometry can detect peripheral airways dysfunction in asthma, which is associated with symptoms and the risk for exacerbations. To help guide future research, minimal clinically important differences for specific oscillometry variables have been developed. Oscillometry may be useful in monitoring the response to biological therapy and has potential for personalizing treatment for individual patients. Oscillometry also has potential in uncovering unique aspects of the pathophysiology of asthma in obesity. SUMMARY: Oscillometry is a promising tool in the diagnosis and management of asthma. More research is needed to support its routine clinical use.

Adding oscillometry to spirometry in guidelines better identifies uncontrolled asthma, future exacerbations, and potential targeted therapy.

The objective of this review is to provide new advances in our understanding of the clinical importance of establishing peripheral airway impairment (PAI) by impulse oscillometry (IOS) and targeted therapy, which could result in better asthma outcomes. Data sources include PubMed and Google search, limited to English language and human disease, with key words IOS and asthma. Key findings include PAI being consistently associated with uncontrolled asthma across ethnicities, using IOS reference equations factoring Hispanic and White reference algorithms. It is noted that PAI is common even in patients considered well-controlled by asthma guidelines. In a large longitudinal analysis (Assessment of Small Airways Involved in Asthma or ATLANTIS study), a composite of R5-R20, AX, and X5 ordinal scores were independently predictive of asthma control and exacerbation in a multivariate analysis, but forced expiratory volume in 1 second was not significantly predictive of morbidities. However, combining forced expiratory volume in 1 second less than 80% with PAI resulted in greater odds of identifying uncontrolled asthma and exacerbations, than either alone. Applying an external validation method in children with asthma offers the clinician the IOS reference equations best fit for their own specific population. Several clinical phenotypes can also identify PAI with high probability, useful when IOS is not available. Poor asthma outcomes for obese patients with asthma are associated with dysanapsis and PAI, not obesity alone. Extrafine inhaled corticosteroids achieve better asthma control and improve peripheral airway function with fewer exacerbations at lower dosages than nonextrafine inhaled corticosteroid aerosols. In conclusion, these data support the benefit of adding IOS to spirometry in future asthma guidelines and suggest the potential benefit from targeted therapy.

Associations of personal urinary volatile organic compounds and lung function in children.

BACKGROUND: We investigated the correlation between urine VOC metabolites and airway function in children exposed to anthropogenic volatile organic compounds (VOCs), notable pollutants impacting respiratory health. METHODS: Out of 157 respondents, 141 completed skin prick tests, spirometry, IOS, and provided urine samples following the International Study of Asthma and Allergies in Childhood (ISAAC)-related questions. Allergic sensitization was assessed through skin prick tests, and airway functions were evaluated using spirometry and impulse oscillometry (IOS). Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) was recorded and FEV1/FVC ratio was calculated. Airway mechanics parameters including respiratory resistance at 5 Hz (Rrs5) mean respiratory resistance between 5 Hz and 20 Hz (Rrs5-20), were also recorded. Urine concentrations of metabolites of benzene, ethylbenzene, toluene, xylene, styrene, formaldehyde, carbon-disulfide were analyzed by gas chromatography/tandem mass spectroscopy. RESULTS: The median age at study participation was 7.1 (SD 0.3) years. Muconic acid (benzene metabolites) and o-methyl-hippuric acid (xylene metabolites) above medians were associated with a significant increase in Rrs5 (muconic acid: aß = 0.150, p = .002; o-methyl-hippuric acid: aß = 0.143, p = .023) and a decrease in FEV1/FVC (o-methyl-hippuric acid: aß = 0.054, p = .028) compared to those below median. No associations were observed for Rrs5-20 and FEV1 between the groups categorized as above and below the median (all parameter p values > .05). CONCLUSIONS: Elevated levels of benzene and xylene metabolites were associated with a significant increase in Rrs5 and a decrease in FEV1/FVC, related to increased resistance and restrictive lung conditions compared to individuals with concentrations below the median.

The impact of respiratory reactance in oscillometry on survival in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Pulmonary function tests (PFTs) aid in evaluating the disease status of IPF. The clinical significance of oscillometry measurements in interstitial lung diseases has recently been reported. Our previous study showed that respiratory reactance (Xrs) measured by oscillometry reflected disease severity and predicted subsequent lung capacity decline in patients with IPF. However, the direct impact of Xrs on survival needs to be determined, and there are currently no reference values in oscillometry to predict prognosis. Therefore, this study aimed to investigate the association between oscillometry measurements, particularly Xrs, and survival in patients with IPF and to determine the cutoff values of Xrs that predict 3-year survival. METHODS: We analyzed the relationship between the measured values of PFT and oscillometry derived from 178 patients with IPF. Univariate and multivariate Cox proportional hazards analyses were performed to investigate the relationships between clinical indices at the time of the first oscillometry and survival. We performed the time-dependent receiver operating characteristic (ROC) curve analysis to set the optimized cutoff values of Xrs for 3-year survival prediction. We examined the discriminating power of cutoff values of Xrs on survival using the Kaplan-Meier method and the log-rank test. RESULTS: Xrs components, especially in the inspiratory phase (In), significantly correlated with the PFT values. In the multivariate analyses, Xrs (all of reactance at 5 Hz [X5], resonant frequency [Fres], and low-frequency reactance area [ALX] in the inspiratory phase) had a significant impact on survival (X5, p = 0.003; Fres, p = 0.016; ALX, p = 0.003) independent of age, sex, and other prognostic factors derived from the univariate analysis. The area under the ROC curve was 0.765, 0.759, and 0.766 for X5 In, Fres In, and ALX In, with cutoff values determined at - 0.98, 10.67, and 5.32, respectively. We found significant differences in survival after dividing patients using each of the cutoff values of Xrs. CONCLUSIONS: In patients with IPF, Xrs measured by oscillometry significantly impacted survival. We also determined the cutoff values of Xrs to discriminate patients with poor prognoses.

Childhood severe asthma: relationship among asthma control scores, FeNO, spirometry and impulse oscillometry.

INTRODUCTION: The evaluation of the asthmatic patient is usually based on clinical and functional parameters that do not necessarily evidence the degree of airway inflammation. The aim of this study was to analyze whether clinical scores (CS) correlate with spirometry (S), impulse oscillometry (IO) and FeNO, in severe asthmatic children. MATERIAL AND METHODS: A multicentric, prospective, cross-sectional study was conducted over a 12-month period. All SA patients (6-18 years old) followed-up in the Pulmonology Department were recruited. CS, FeNO measurements, IO and S were consecutively performed on the same day. Asthma control was ascertained using ACT and GINAq. A cut-off value of ≥ 25 parts per billion (ppb) was used to define airway inflammation. RESULTS: Eighty-one patients were included. ACT: 75% (n 61) were controlled; GINAq: 44.5% (n 36) were controlled; 39.5% (n 32) were partly controlled, and 16% (n 13) were uncontrolled. FeNO had a median value of 24 ppb (IQR 14-41); FeNO ≥ 25 ppb was observed in 49% of patients (n 39). ROC AUC for FeNO vs. ACT was 0.71 (95%CI 0.57-0.86), PPV 0.47, NPV 0.87, SE 0.61, SP 0.80; FeNO vs. GINAq was ROC AUC 0.69 (95%CI 0.54-0.85), PPV 0.34, NPV 0.91, SE 0.62, SP 0.77; Youden cut-off FeNO > 39 ppb for both CS. CONCLUSION: In severe asthmatic children, current symptoms control as evidenced by ACT and GINA correlates with low FeNO values. Clinical scores showed good correlation with airway inflammation.

Accuracy of oscillometric noninvasive blood pressure at the ankle in the lateral position during general anesthesia.

BACKGROUND: This study aimed to evaluate the accuracy of ankle blood pressure measurements in relation to invasive blood pressure in the lateral position. METHODS: This prospective observational study included adult patients scheduled for elective non-cardiac surgery under general anesthesia in the lateral position. Paired radial artery invasive and ankle noninvasive blood pressure readings were recorded in the lateral position using GE Carescape B650 monitor. The primary outcome was the ability of ankle mean arterial pressure (MAP) to detect hypotension (MAP < 70 mmHg) using area under the receiver operating characteristic curve (AUC) analysis. The secondary outcomes were the ability of ankle systolic blood pressure (SBP) to detect hypertension (SBP > 140 mmHg) as well as bias (invasive measurement - noninvasive measurement), and agreement between the two methods using the Bland-Altman analysis. RESULTS: We analyzed 415 paired readings from 30 patients. The AUC (95% confidence interval [CI]) of ankle MAP for detecting hypotension was 0.88 (0.83-0.93). An ankle MAP of ≤ 86 mmHg had negative and positive predictive values (95% CI) of 99 (97-100)% and 21 (15-29)%, respectively, for detecting hypotension. The AUC (95% CI) of ankle SBP to detect hypertension was 0.83 (0.79-0.86) with negative and positive predictive values (95% CI) of 95 (92-97)% and 36 (26-46)%, respectively, at a cutoff value of > 144 mmHg. The mean bias between the two methods was - 12 ± 17, 3 ± 12, and - 1 ± 11 mmHg for the SBP, diastolic blood pressure, and MAP, respectively. CONCLUSION: In patients under general anesthesia in the lateral position, ankle blood pressure measurements are not interchangeable with the corresponding invasive measurements. However, an ankle MAP > 86 mmHg can exclude hypotension with 99% accuracy, and an ankle SBP < 144 mmHg can exclude hypertension with 95% accuracy.

Impulse oscillometry in the diagnosis of cough variant asthma in children.

BACKGROUND: Cough variant asthma (CVA) is one of the most common causes of chronic cough in children worldwide. The diagnosis of CVA in children remains challenging. This study aimed to assess the diagnostic utility of impulse oscillometry (IOS) pulmonary function in children with CVA. METHODS: This study included children aged 4 to 12 years diagnosed with CVA who underwent IOS pulmonary function and bronchodilation (BD) tests. A control group of healthy children was matched. Pre- and post-BD IOS parameters were recorded and presented as mean ± standard deviation or median. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to evaluate the discriminatory potential of the IOS parameters for diagnosing CVA. RESULTS: A total of 180 patients with CVA and 65 control subjects were included. The baseline IOS parameters in the CVA group, except X5%pred, were significantly greater compared to the control group. After inhalation of salbutamol sulfate, all IOS parameters improved significantly in the CVA group. However, Z5%pred, R5%pred, and R20%pred remained greater in the CVA group compared to the control group. The improvement rates of IOS parameters in the CVA group significantly surpassed those in the control group. The ROC curve results for pre-BD IOS parameters and the improvement rate during the BD test showed that the combinations of pre-Z5%pred+△Z5% and pre-R5%pred+△R5% achieved the highest AUC value of 0.920 and 0.898, respectively. The AUC values of these combined parameters surpassed those of individual ones. CONCLUSIONS: This study highlights that children with CVA exhibit greater IOS parameters compared to healthy children. The changes in IOS parameters during the BD test provided valuable diagnostic information for CVA, and the combination of various parameters can help pediatricians accurately identify CVA in children.

One size does not fit all: universal cuff overestimates oscillometric blood pressure in persons with large arm circumference.

OBJECTIVE: Some brachial cuffs for oscillometric blood pressure (BP) measurement are claimed to cover a wide range of upper-arm circumferences; however, their validation is rarely conducted. Our aim was to compare oscillometric BP measurements obtained with a universal cuff with those obtained with an appropriately sized cuff. METHODS: We utilised the Microlife B6 Connect monitor, conducting oscillometric BP measurements in a random sequence with both a universal cuff (recommended for arm circumferences from 22 to 42 cm) and an appropriately sized cuff (medium for circumference 22-32 cm and large for 32-42 cm). We included 91 individuals with an arm circumference of 22-32 cm and 64 individuals with an arm circumference of 32-42 cm. RESULTS: For arm circumferences > 32 cm, systolic and diastolic BP measured with the universal cuff was higher than that measured with the large cuff (systolic 6.4 mmHg, 95% confidence interval [CI]). 3.9-8.8, diastolic 2.4 mmHg, 95%CI, 1.2-3.7, p < 0.001 for both). Overestimation of BP with the universal cuff was statistically significant after correcting for the sequence of measurements. No statistical difference was found between the universal cuff and medium cuff for circumferences in the 22-32 cm range. The bladder size in the universal cuff matched the dimensions of the medium-sized cuff; however, the cuff was larger. CONCLUSION: Overestimation of BP measured with a universal cuff in persons with large arm circumferences is clinically important. It poses the risk of unnecessary initiation or intensification of antihypertensive medication in persons using the universal cuff.

What is the context?Clinical guidelines recommend individualisation of the size of the cuff used for blood pressure measurement according to the circumference of the upper arm.Many blood pressure monitors are sold with a single "universal" cuff claimed to cover a wide range of upper arm sizes.We compared blood pressure obtained with the Microlife B6 Connect monitor and a "universal" cuff with the results obtained with individual sized cuffs (medium size for arm circumference between 22 and 32 cm and large size for arm circumference between 32 and 42 cm).What is new?In persons with large upper arm circumference is the systolic blood pressure 6.4 mmHg higher and the diastolic blood pressure 2.4 mmHg higher with the universal cuff than with the individual-sized large cuff.What is the impact?The universal cuff overestimates blood pressure in persons with large arm circumference.

Correlation between impulse oscillometry parameters and test for respiratory and asthma control in kids (TRACK) in asthma control of preschoolers with asthma.

BACKGROUND: Little research has been conducted to evaluate the correlation between impulse oscillometry (IOS), Childhood Asthma Control Test (C-ACT), and Test for Respiratory and Asthma Control in Kids (TRACK). METHODS: This study was conducted at China Medical University Hospital between September 1, 2019, and March 31, 2021. Children aged 2-6 years who had been diagnosed with asthma with acute exacerbation were enrolled and followed-up until the end of the study. Correlations between the parameters of IOS, C-ACT and TRACK were assessed. The validity and reliability of TRACK were verified. RESULTS: A total of 114 children with asthma and acute exacerbations were recruited. Their mean age was 4.1 ± 1.1 years, and 60.5% were males. After a year of treatment, the change of R5-R20 from baseline 0.64 ± 0.38 kPa/L/s to 12th month 0.48 ± 0.2 kPa/L/s (p = 0.022). TRACK and C-ACT scores were significantly correlated during the observation period. R5-R20 in IOS at baseline and at the 12th month of follow-up as well as the change in IOS parameters were significantly associated with C-ACT (p = 0.003, 0.015, and 0.001, respectively). R5% and R5-R20 changes in IOS were associated with TRACK (p = 0.04 and 0.025, respectively). Sensitivity and specificity of TRACK were 80.8% (67.5-90.4) and 100% (94.1-100), respectively, with cut-off points >95 and AUC 93.8%. CONCLUSION: TRACK score appears to have a stronger association with the IOS parameter than C-ACT score. Our findings indicate that TRACK is a valid tool for assessing asthma control in preschool children.

Comparison of Forced Oscillation Technique, Lung Volumes by Body Plethysmography, and Spirometry in Moderate Persistent Adult Asthma.

BACKGROUND: Spirometry is used extensively, but airway oscillometry is gaining acceptance for evaluating obstructive airway disorders. Moderate persistent asthma requires daily treatment with inhaled corticosteroids (ICS). MATERIALS AND METHODS: We aimed to examine the relationship between airway oscillometry and lung volumes, which are the markers of lung physiology in obstructive airway disease and spirometry in the real-world clinical setting. A total of 72 adults with moderate persistent asthma followed up in our outpatient department from November 2021 to August 2022, and their clinical details and tests of spirometry, forced oscillation technique (FOT), and lung volumes by body plethysmography (BP) performed before and after bronchodilator administration were analyzed. RESULTS: The mean age of the study population was 40 years, and the majority (57%) were females. FOT detected airflow limitation in 12 of the 31 patients with normal spirometry. BP detected abnormalities in more patients than both spirometry and FOT (91.6 vs 73.6%, p < 0.001). Respiratory resistance 5 (R5) had a negative correlation with functional residual capacity (FRC) and total lung capacity (TLC). Reactance 5 (X5) correlated positively with inspiratory capacity (IC) and TLC and negatively with reserve volume (RV)/TLC ratio. A positive correlation was found between IC/TLC% and postbronchodilator X5 and between R5 and 19 and RV/TLC. R5 had a negative and X5 had a positive correlation with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, and maximal mid expiratory flow rates (MMEF). ∇X5 had a negative correlation with FEV1, MMEF, and FEV1/FVC. Spirometry detected postbronchodilator responsiveness in more patients than FOT when only the R5 criterion was used and in a comparable number when the X5 criterion was added. ∇X5 and R5-R19/R5 declined significantly after bronchodilators. CONCLUSION: We concluded that there is a moderate correlation between FOT and spirometry and lung volumes by BP. FOT and spirometry should be used together to identify airflow obstruction and postbronchodilator responsiveness in asthma. Lung volumes by BP identify more abnormalities in adults with asthma than both spirometry and FOT. Thresholds to define postbronchodilator responsiveness (PBDR) for ∇X5 and R5-R19 need to be defined.

Evaluation of rheological properties of soft lining materials with different composition under various temperatures.

PURPOSE: The aim of this in vitro study was to evaluate the changes the rheological properties of some soft lining materials, to compare the rheological properties and viscoelastic behaviour at different temperatures. MATERIALS AND METHODS: Five soft lining materials (acrylic and silicone based) were used. the storage modulus (G'), loss modulus (G"), tan delta (tan δ) and complex viscosity (η') were chosen and for each material, measurements were repeated at 23, 33 and 37  °C, using an oscillating rheometer. All data were statistically analyzed using the Mann Whitney U test, Kruskal Wallis test and Conover's Multiple Comparison test at the significance level of 0.05. RESULTS: Soft lining materials had different viscoelastic properties and most of the materials showed different rheological behavior at 23, 33 and 37  °C. At the end of the test (t¹5), at all the temperatures, Sofreliner Tough M had the highest storage modulus values while Visco Gel had the highest loss Tan delta values. CONCLUSIONS: There were significant changes in the rheological parameters of all the materials. Also temperature affected the initial rheological properties, and polymerization reaction of all the materials, depending on temperature increase. CLINICAL IMPLICATIONS: Temperature affected the initial rheological properties, and polymerization reaction of soft denture liner materials, and clinical inferences should be drawn from such studies conducted. It can be recommended to utilize viscoelastic acrylic-based temporary soft lining materials with lower storage modulus, higher tan delta value, and high viscosity in situations where pain complaint persists and tissue stress is extremely significant, provided that they are replaced often.

Lower Arginine Bioavailability, Increased FeNO Levels, and Airway Resistance on Impulse Oscillometry Are Characteristics of Asthma in Children and Young Adults with Sickle Cell Disease.

Background and Objectives: Data on characteristics of asthma in children with sickle cell disease (SCD) is conflicting. Recently, the L-arginine pathway has gained attention in the pathogenesis of asthma and SCD. This study aimed to determine the distinctive clinical and laboratory features and the role of arginine metabolism in asthmatic children with SCD. Materials and Methods: A total of 52 children and adolescents with SCD, including 24 with asthma (SCD-A) and 28 without asthma (SCD-NA), and 40 healthy controls were included. A questionnaire, atopy tests, fractional exhaled nitric oxide (FeNO), and lung function tests were employed. Serum metabolites of the arginine pathway were measured. The results of the three groups were compared. Results: The demographic characteristics and atopy markers of the three groups were similar. FEV1%, FEV1/FVC, MMEF%, and total lung capacity (TLC%) values of SCD-A patients were not significantly different from the SCD-NA group, but they were significantly lower than the values measured in the controls. FeNO values greater than 35 ppb were present only in the SCD-A group. In impulse oscillometry, median resistance values at 5 Hz (R5)% were higher in both SCD subgroups than in healthy controls (p = 0.001). The (R5-20/R5)% values were higher in the SCD-A group (p = 0.028). Serum arginine levels and arginine bioavailability indices were significantly lower in the SCD-A group than in the SCD-NA group and healthy controls (p = 0.003 and p < 0.001). Conclusions: Asthma in children with SCD was not associated with atopy or low FEV1/FVC levels. However, lower arginine bioavailability and higher FeNO levels differentiated asthma in patients with SCD. High R5% and (R5-20/R5)% values indicated increased airway resistance in SCD, with a predominance of small airway disease in asthmatics.

Correlation between impulse oscillometry with bronchodilator reversibility in asthmatic population in a tertiary referral centre.

INTRODUCTION: Spirometry is considered as a 'gold standard' for diagnosis of asthma. Impulse oscillometry (IOS) is an alternative diagnostic tool which requires less cooperation by the participants. We performed a study to determine the correlation of IOS with bronchodilator reversibility from spirometry in asthmatic participants. We studied the correlation between forced expiratory flow (FEF25%-75%) and differences between the resistance at 5Hz and 20Hz (R5-R20) in small airway disease (SAD) and the proportion of SAD diagnosed using IOS. MATERIALS AND METHODS: This was a cross-sectional study involving 82 asthmatic participants in Hospital Canselor Tuanku Muhriz (HCTM), Universiti Kebangsaan Malaysia (UKM) conducted between December 2020 till January 2022. Participants performed pre- and post-bronchodilator IOS and spirometry within the same day. Correlation between spirometry and IOS parameters and FEF25%-75% with IOS were determined and analysed. RESULTS: The change of forced expiratory volume in 1 second (FEV1) was statistically correlated with a change of R5 in IOS. A decrement of 14.5% in R5 can be correlated with positive bronchodilator response (BDR) with a sensitivity of 63.9% and specificity of 60.9%, p=0.007. Pre-bronchodilator FEF25%-75% correlated with all parameters of SAD in IOS, e.g., R5-R20, reactance at 5Hz (X5) and area of reactance (AX), p < 0.05. IOS detection for SAD is higher compared to FEF25%-75% in the BDR negative group (91.3% vs 58.7%). CONCLUSION: IOS detected both bronchodilator reversibility and SAD hence can be considered as an alternative tool to spirometry for diagnosis of asthma in adults. IOS detected SAD more than FEF25%-75%, especially in BDR-negative group.

[Research on portable airway impedance monitoring device based on expiratory oscillation].

Monitoring airway impedance has significant clinical value in accurately assessing and diagnosing pulmonary function diseases at an early stage. To address the issue of large oscillator size and high power consumption in current pulmonary function devices, this study adopts a new strategy of expiration-driven oscillation. A lightweight and low-power airway impedance monitoring system with integrated sensing, control circuitry, and dynamic feedback system, providing visual feedback on the system's status, was developed. The respiratory impedance measurement experiments and statistical comparisons indicated that the system could achieve stable measurement of airway impedance at 5 Hz. The frequency spectrum curves of respiratory impedance ( R and X) showed consistent trends with those obtained from the clinical pulmonary function instrument, specifically the impulse oscillometry system (IOS). The differences between them were all less than 1.1 cm H 2O·s/L. Additionally, there was a significant statistical difference in the respiratory impedance R5 between the exercise and rest groups, which suggests that the system can measure the variability of airway resistance parameters during exercise. Therefore, the impedance monitoring system developed in this study supports subjects in performing handheld, continuous measurements of dynamic changes in airway impedance over an extended period of time. This research provides a foundation for further developing low-power, portable, and even wearable devices for dynamic monitoring of pulmonary function.

Oscillatory expression of Hes1 regulates cell proliferation and neuronal differentiation in the embryonic brain.

The expression of the transcriptional repressor Hes1 oscillates in many cell types, including neural progenitor cells (NPCs), but the significance of Hes1 oscillations in development is not fully understood. To examine the effect of altered oscillatory dynamics of Hes1, we generated two types of Hes1 knock-in mice, a shortened (type-1) and an elongated (type-2) Hes1 gene, and examined their phenotypes focusing on neural development. Although both mutations affected Hes1 oscillations, the type-1 mutation dampened Hes1 oscillations more severely, resulting in much lower amplitudes. The average levels of Hes1 expression in type-1 mutant NPCs were also lower than in wild-type NPCs but similar to or slightly higher than those in Hes1 heterozygous mutant mice, which exhibit no apparent defects. Whereas type-2 mutant mice were apparently normal, type-1 mutant mice displayed smaller brains than wild-type mice and upregulated proneural gene expression. Furthermore, proliferation of NPCs decreased and cell death increased in type-1 mutant embryos. When Hes3 and Hes5 were additionally deleted, neuronal differentiation was also accelerated, leading to microcephaly. Thus, robust Hes1 oscillations are required for maintenance and proliferation of NPCs and the normal timing of neurogenesis, thereby regulating brain morphogenesis.