Normal Tidal Breathing Research Articles

Oscillometry defined small airways dysfunction as a treatable trait in asthma.

The small airways, also referred to as the lung's silent zone, are closely associated with poor symptom control and more frequent asthma exacerbations. The oscillometry technique superimposes sound or airwaves onto normal tidal breathing and provides information on resistance and reactance, that is, obstacles to airflow occurring inside and outside of the bronchi. More recently, a management paradigm based on so-called 'treatable traits' has been proposed to personalize and improve asthma care for individuals by proactively identifying and targeting modifiable pulmonary, extra-pulmonary, and behavioral traits affecting asthma control. In this review article we examine the literature on small airways dysfunction as a potential treatable trait in persistent asthma. Pointedly, we discuss whole- and intra-breath oscillometry as well as the impact of extrafine inhaled corticosteroids and systemic biologics on the peripheral airways.

Biophysical impact of lubricating base oil aerosols on natural pulmonary surfactant film

Lubricating base oils have been extensively employed for producing various industrial and consumer products. Therefore, their environmental and health impacts should be carefully evaluated. Although there have been many reports on pulmonary cytotoxicity and inflammatory responses of inhaled lubricating base oils, their potential influences on pulmonary surfactant (PS) films that play an essential role in maintaining respiratory mechanics and pulmonary immunity remains largely unknown. Here a systematic study on the interactions between an animal-derived natural PS and aerosols of water and representative mineral and vegetable base oils is performed using a novel biophysical assessing technique called constrained drop surfactometry capable of providing in vitro simulations of normal tidal breathing and physiologically relevant temperature and humidity in the lung. It was found that the mineral oil aerosols can impose strong inhibitions to the biophysical property of PS film, while the airborne vegetable oils and water show negligible adverse effects within the studied concentration range. The inhibitory effect is originated from the strong hydrophobicity of mineral oil, which makes it able to disrupt the interfacial molecular ordering of both phospholipid and protein compositions and consequently suppress the formation of condensed phase and multilayer scaffolds in a PS film. Environmental ImplicationUnderstanding the biophysical influence of airborne lubricating base oils on pulmonary surfactant (PS) films can provide new insights into the environmental impacts and health concerns of various industrial lubricant products. Here a comparative study on interactions between an animal-derived natural PS film and the aerosols of water and representative mineral and vegetable base oils under the true physiological conditions was conducted in situ using constrained drop surfactometry. We show that the most frequently used mineral base oil can cause strong inhibitions to the PS film by disrupting the molecular ordering of saturated phospholipids and surfactant-associated proteins at the interface.

Constrained drop surfactometry for studying adsorbed pulmonary surfactant at physiologically relevant high concentrations.

Exogenous surfactant therapy has been used as a standard clinical intervention for treating premature newborns with respiratory distress syndrome. The phospholipid concentrations of exogenous surfactants used in clinical practice are consistently higher than 25 mg/mL; while it was estimated that the phospholipid concentration of endogenous surfactant is approximately in the range between 15 and 50 mg/mL. However, most in vitro biophysical simulations of pulmonary surfactants were only capable of studying surfactant concentrations up to 3 mg/mL, one order of magnitude lower than the physiologically relevant concentration. Using a new in vitro biophysical model, called constrained drop surfactometry, in conjunction with atomic force microscopy and other technological advances, we have investigated the biophysical properties, ultrastructure, and topography of the pulmonary surfactant film adsorbed from the subphase at physiologically relevant high surfactant concentrations of 10-35 mg/mL. It was found that the effect of surfactant concentration on the dynamic surface activity of the surfactant film was only important when the surface area of the surfactant film varied no more than 15%, mimicking normal tidal breathing. The adsorbed surfactant film depicts a multilayer conformation consisting of a layer-by-layer assembly of stacked bilayers with the height of the multilayers proportional to the surfactant concentration. Our experimental data suggest that the biophysical function of these multilayer structures formed after de novo adsorption is to act as a buffer zone to store surface-active materials ejected from the interfacial monolayer under extreme conditions such as deep breathing.NEW & NOTEWORTHY An in vitro biophysical model, called constrained drop surfactometry, was developed to study the biophysical properties, ultrastructure, and topography of the pulmonary surfactant film adsorbed from the subphase at physiologically relevant high surfactant concentrations of 10-35 mg/mL. These results suggest that the biophysical function of multilayers formed after de novo adsorption is to act as a buffer zone to store surface-active materials ejected from the interfacial monolayer under extreme conditions such as deep breathing.

Measuring Expiratory Diaphragm Activity: An Electrifying Tool to Guide Positive End-Expiratory Pressure Strategy in Critically Ill Children?

Measuring Expiratory Diaphragm Activity: An Electrifying Tool to Guide Positive End-Expiratory Pressure Strategy in Critically Ill Children?

Multiple breath washout: measuring early manifestations of lung pathology.

The multiple breath washout (MBW) test measures the efficiency of gas mixing in the lungs and has gained significant interest over the past 20 years. MBW outcomes detect early lung function impairment and peripheral airway pathology, through its main outcome measure lung clearance index (LCI). LCI measures the number of lung turnovers required to washout an inert tracer gas. MBW is performed during normal (tidal) breathing, making it particularly suitable for young children or those who have trouble performing forced manoeuvres. Additionally, research in chronic respiratory disease populations has shown that MBW can detect acute clinically relevant changes before conventional lung function tests, such as spirometry, thus enabling early intervention. The development of technical standards for MBW and commercial devices have allowed MBW to be implemented in clinical research and potentially routine clinical practice. Although studies have summarised clinimetric properties of MBW indices, additional research is required to establish the clinical utility of MBW and, if possible, shorten testing time. Sensitive, feasible measures of early lung function decline will play an important role in early intervention for people living with respiratory diseases.Educational aimTo describe the multiple breath washout test, its applications to lung pathology and respiratory disease, as well as directions for future research.

Abstracts from The International Society for Aerosols in Medicine 23rd ISAM Congress Boise, Idaho May 22–26, 2021

Abstracts from The International Society for Aerosols in Medicine 23rd ISAM Congress Boise, Idaho May 22–26, 2021

Inhaled nasopharyngeal nitric oxide concentrations during unilateral nostril breathing – A pilot study

The yogic pranayama technique of unilateral nostril breathing (UNB) has previously demonstrated improvements in language and anxiety in stroke sufferers, as well as reduced blood pressure and increased heart rate in normal healthy adults. The nose typically passes different amounts of air through each nostril with the greater amount of air passing through the ‘patent’ side, and a lesser amount through the ‘congested’ side. Each side of the nose periodically takes turns at carrying the dominant tidal air flow in what is termed the’ nasal cycle’. The nasal sinuses are a rich source of inhaled nitric oxide, a colourless and odourless gas that acts as a bronchodilator, vasodilator, and neurotransmitter. Nasal derived nitric oxide (NO) may contribute to the benefits attributed to UNB. This investigation seeks to assess the influence the nasal cycle has on inhaled nasopharyngeal NO concentrations during UNB by comparing unobstructed bilateral nostril breathing to patent-side and congested-side UNB in healthy individuals demonstrating a nasal cycle.After determining the patent and congested nasal sides in healthy adult volunteers, and sampling air at both nostrils, nasopharyngeal inhaled NO concentrations were then assessed during normal nasal at-rest tidal breathing during three different nasal breathing states: first both nostrils, then allocated in randomised order, patent side only, and congested side with only UNB.Nasopharyngeal NO concentrations were found to be consistently higher on both exhalation and inhalation during congested side UNB, when compared with either unilateral patent side UNB or breathing through both nostrils.

Pulmonary Function Testing in the Coronavirus Disease Era: Lessons and Opportunities.

Pulmonary Function Testing in the Coronavirus Disease Era: Lessons and Opportunities.

Fabrication, characterization and optimization of nanostructured lipid carrier formulations using Beclomethasone dipropionate for pulmonary drug delivery via medical nebulizers

Aerosolization is a non-invasive approach in drug delivery for localized and systemic effect. Nanostructured lipid carriers (NLCs) are new generation versatile carriers, which offer protection from degradation and enhance bioavailability of poorly water soluble drugs. The aim of this study was to develop and optimize NLC formulations in combination with optimized airflow rates (i.e. 60 and 15 L/min) and choice of medical nebulizers including Air jet, Vibrating mesh and Ultrasonic nebulizer for superior aerosolization performance, assessed via a next generation impactor (NGI). Novel composition and combination of NLC formulations (F1 – F15) were prepared via ultrasonication method, employing five solid lipids (glycerol trimyristate (GTM), glycerol trilaurate (GTL), cetyl palmitate (CP), glycerol monostearate (GMS) and stearic acid (SA)); and three liquid lipids (glyceryl tributyrate (GTB), propylene glycol dicaprylate/dicaprate (PGD) and isopropyl palmitate (IPP)) in 1:3 w/w ratios (i.e. combination of one solid and one liquid lipid), with Beclomethasone dipropionate (BDP) incorporated as the model drug. Out of fifteen BDP-NLC formulations, the physicochemical properties of formulations F7, F8 and F10 exhibited desirable stability (one week at 25 °C), with associated particle size of ~241 nm, and >91% of drug entrapment. Post aerosolization, F10 was observed to deposit notably smaller sized particles (from 198 to 136 nm, 283 to 135 nm and 239 to 157 nm for Air jet, Vibrating mesh and Ultrasonic nebulizers, respectively) in all stages (i.e. from stage 1 to 8) of the NGI, when compared to F7 and F8 formulations. Six week stability studies conducted at 4, 25 and 45 °C, demonstrated F10 formulation stability in terms of particle size, irrespective of temperature conditions. Nebulizer performance study using the NGI for F10 identified the Air jet to be the most efficient nebulizer, depositing lower concentrations of BDP in the earlier stages (1–3) and higher (circa 82 and 85%) in the lateral stages (4–8) using 60 and 15 L/min airflow rates, when compared to the Vibrating mesh and Ultrasonic nebulizers. Moreover, at both airflow rates, the Air jet nebulizer elicited a longer nebulization time of ~42 min, facilitating aerosol inhalation for prophylaxis of asthma with normal tidal breathing. Based on characterization and nebulizer performance employing both 60 and 15 L/min airflow rates, the Air jet nebulizer offered enhanced performance, exhibiting a higher fine particle dose (FPD) (90 and 69 µg), fine particle fraction (FPF) (70 and 54%), respirable fraction (RF) (92 and 69%), and lower mass median aerodynamic diameter (MMAD) (1.15 and 1.62 µm); in addition to demonstrating higher drug deposition in the lateral parts of the NGI, when compared to its counterpart nebulizers. The F10 formulation used with the Air jet nebulizer was identified as being the most suitable combination for delivery of BDP-NLC formulations.

Current COVID-19 guidelines for respiratory protection of health care workers are inadequate.

Current COVID-19 guidelines for respiratory protection of health care workers are inadequate.

Deep anaesthesia: The Thailand cave rescue and its implications for management of the unconscious diver underwater.

In 2018 12 children and one adult were anaesthetised before being extricated through over a kilometre of flooded cave in Thailand. Full face dive masks (FFMs) putatively capable of maintaining constant positive airway pressure (CPAP) were employed. Here we describe the anaesthetic intervention and investigate the CPAP capability of the FFM. Pressure was measured inside and outside the Interspiro Divator FFM during 10 tidal and 10 vital capacity breaths in divers at the surface and submerged with the mask deployed on open-circuit scuba (10 divers); and a closed-circuit rebreather (five divers). Relative in-mask pressure was calculated as the difference between inside and outside pressures. We also measured the in-mask pressure generated by activation of the second stage regulator purge valve in open-circuit mode. When submerged in open-circuit mode the mean relative in-mask pressure remained positive in normal tidal breathing (inhalation 0.6 kPa [95% CI 0.3-0.9]; exhalation 1.1 [0.8-1.4]) and vital capacity breathing (inhalation 0.8 [0.4-1.1]; exhalation 1.2 [0.9-1.4]). As expected, the relative in-mask pressure was predominantly negative when used on closed-circuit with back mounted counter-lungs due to a negative static lung load. Mean in-mask pressure during purge valve operation was 3.99 kPa (approximately equal to 40 cmH2O) (range: 2.56 to 5.3 kPa). The CPAP function of the Interspiro Divator FFM works well configured with open-circuit scuba. This may have contributed to the success of the Thailand cave rescue. Caution is required in generalising this success to other diving scenarios.

Comparative Study between Ultrasound-Guided Serratus Anterior Plane Block versus Thoracic Epidural Analgesia for Post-Thoracotomy Pain: A Prospective, Randomized, Clinical Trial

Objectives and Aim: Thoracotomies are widely recognized to cause acute pain which is associated with many complications. The target study aimed to assess the safety and efficacy of SAPB compared to TEA for relieving severe thoracotomy pain. Patients and Methods: Forty patients scheduled for thoracotomy randomly allocated either to receive SAPB or thoracic epidural (TEA). Visual analogue pain score (VAS) at rest and coughing every 6 hrs. Postoperative, hemodynamic parameters (heart rate and MAP), pain rescue analgesic consumption in the first 24 hrs., complications, and duration of hospital stay recorded. Results: In our study, we found that the recently described SAPB, while maintaining stable blood pressure, provided excellent analgesia comparable to that offered by TEA for acute post-thoracotomy pain. Hypotension was more noteworthy in those who had epidurals than those with serratus anterior plane (SAP) catheters. Morphine rescue analgesia, as well as Visual Analogue Scale (VAS) pain scores during normal tidal breathing, were like in both groups. Conclusion: We recommend that the Serratus anterior plane block appears to be a safe and effective alternative for postoperative analgesia after thoracotomy.

Impact of lung volume changes on perfusion estimates derived by Electrical Impedance Tomography

Abstract Electrical Impedance Tomography (EIT), an imaging technique which operates non-invasively and without radiation exposure, provides information about ventilation- and cardiac-synchronous (pulsatile) changes in the lung. It is well known, that perfusion within the thorax is influenced by lung volume or intrathoracic pressure. In this observational study, it shall be investigated if this phenomenon can be monitored by EIT. Therefore, the impact of the amount of air within the lung on the pulsatile EIT signal was evaluated by carrying out EIT measurements with a spontaneously breathing lung healthy subject holding the breath at three different inspiratory and three various expiratory volume levels during normal tidal breathing. For EIT data analysis, a region of interest was defined by including lung tissue and excluding the heart region. The EIT data revealed, that the shape and the amplitude of the pulsatile EIT signal (evaluated per heartbeat) during the phases of breath holding were dependent on the enclosed lung volume. For lung volumes > 4 L, the amplitude of the pulsatile EIT signal increased with rising inspiratory level and the shape remained almost unchanged. For lung volumes < 4 L, a change in shape was visible but the amplitude remained more or less the same with decreasing expiratory level. Since the results of this observational study show that the pulsatile EIT signal is influenced by the lung volume, it might be used in future to draw conclusions of cardiacpulmonary interactions or intrathoracic pressure states, benefitting the treatment of intensive care patients.

Impulse Oscillometry

Pulmonary function testing involves a battery of tests from the simple pulse oximetry to the cardiopulmonary exercise testing. Impulse oscillometry (IOS) is one of the newly described pulmonary function tests. It is based on the old principle of forced oscillatory technique modified and refined as per research and advances. It involves the use of sound waves during normal tidal breathing, which gives information on oscillatory pressure-flow relationships and eventually resistance and reactance. The resistance at 20 Hz (R20) represents the resistance of the large airways. The resistance at 5 Hz (R5) means the total airway resistance. (R5-R20) reflects resistance in the small airways. The reactance at 5 Hz (X5) indicates the elastic recoil of the peripheral airways. Resonant frequency and area of reactance are also measured. IOS has major uses in diagnosis and control of asthma in children and the elderly, where spirometry is otherwise normal. IOS has been studied in other respiratory diseases like COPD, ILD and supraglottic stenosis.

I Say IOS You Say AOS: Comparative Bias in Respiratory Impedance Measurements

BackgroundThe forced oscillation technique (FOT) measures respiratory impedance during normal tidal breathing and requires minimal patient cooperation.ObjectiveTo compare IOS and AOS devices in patients with asthma and COPD.MethodsWe compared two different FOT devices, namely impulse oscillometry using a loudspeaker (IOS: Jaeger Masterscreen) and airwave oscillometry using a vibrating mesh (AOS: Thorasys Tremoflo) for pre- and post-bronchodilator measurements in 84 patients with asthma and COPD.ResultsThe overall pattern of measurement bias was for higher resistance with IOS and higher reactance with AOS, this being the case in asthma and COPD separately. There were small but significantly higher values using IOS for resistance at 5 Hz (R5) and 20(19) Hz (R20(19)). In converse, values for reactance at 5 Hz (X5), reactance area (AX) and resonant frequency (Fres) were significantly higher using AOS but to a much larger extent. The difference in AX between devices was more pronounced in COPD than in asthma. Salbutamol reversibility as % change was greater in asthma than COPD patients with AX but not FEV1.ConclusionOur study showed evidence of better agreement for resistance than reactance when comparing IOS and AOS, perhaps inferring that AOS may be more sensitive at measuring reactance in patients with airflow obstruction.

Effect of changes in tidal volume on multiple breath washout outcomes.

The lung clearance index (LCI), measured by multiple breath washout (MBW), reflects global ventilation inhomogeneity and is a sensitive marker of early obstructive airway disease. For the MBW test to accurately reflect a subject’s gas mixing within the lungs, the breathing pattern should represent physiologically appropriate tidal volumes (VT) and respiratory rate (RR). We aimed to assess whether changes in VT impact MBW outcome measures with a series of prospective and retrospective studies. MBW testing was performed using the Exhalyzer ® D (EcoMedics AG, Switzerland). Healthy adult subjects performed MBW with uninstructed tidal breathing and a series of instructed tidal breathing tests, designed to isolate specific features of the breathing pattern. In addition, we retrospectively analyzed MBW data from two pediatric multi-centre interventional studies of cystic fibrosis (CF) subjects to determine the range of VT observed during uninstructed breathing, and whether breathing outside this range impacted results. The LCI was lower, but not significantly different between deep breathing at 20 ml/kg body weight and uninstructed tidal breathing; whereas LCI was significantly higher during shallow breathing compared with normal tidal breathing. For the majority of subjects with CF (80%), VT ranged from 9-15mL/kg. Within the observed VT range, LCI was similar in trials with mean VT /kg below this range compared to trials with VT /kg within the range. If subjects breathe naturally and are not instructed to use specific targets, the range of VT is within physiologically appropriate limits and normal variations observed do not impact MBW outcomes.

MRI Assessment of Global and Regional Diaphragmatic Motion in Critically Ill Patients Following Prolonged Ventilator Weaning.

Introduction: diaphragmatic dysfunction is a common cause of slow weaning in mechanically ventilated patients. Diaphragmatic dysfunction in ventilated patients can be global or regional. The aim of our study was to evaluate the motion of the entire diaphragm in patients who were ventilated for a protracted period in comparison with healthy controls by using Magnetic Resonance Imaging (MRI). Methods: Intensive care patients who had a prolonged ventilator wean and required tracheostomies were enrolled based on extensive exclusion criteria. MRI dynamic sequence and subtraction images were used to measure vertical displacement at five different points on each hemi-diaphragm during normal tidal breathing. Tidal displacement of each point on the right and left hemi-diaphragms of the patients were compared to the precise respective points on the right and left hemi-diaphragms of enrolled controls. Results: Eight intensive care patients and eight controls were enrolled. There were observed significant differences in the displacements of the left hemi-diaphragm between the two groups (median 6.4 mm [Interquartile range (IQR), 4.6–12.5]) vs. 11.6 mm [IQR, 9.5–14.5], p = 0.02). There were also observed significant differences in the displacements at five evaluated study points on the left hemi-diaphragms of the patients when compared to the precise respective points in controls, especially at the dome (median 6.7 mm [IQR, 5.0–11.4] vs. 13.5 mm [IQR 11.5-18], p value = 0.005) and the anterior zone of apposition (median 5.0 mm [IQR, 3.3–7.1] vs. 7.8mm [IQR, 7.1–10.5], p value = 0.01). The intensive care patients showed lower minimal and maximal values of displacement of right hemi-diaphragms compared to the controls, suggesting that the differences in the displacement of right hemi-diaphragm are possible; however, the differences in the mean values of displacement of right hemi-diaphragm between the intensive care patient group and the control group (median 9.8 mm [IQR (Interquartile range), 5.0–12.3] vs. 10.1 mm [IQR 8.3–18.5], p = 0.12) did not reach the level of significance. Conclusion: Although frequently global, diaphragm dysfunction in ventilated patients after prolonged ventilation can also be regional or focal when assessed by MRI dynamic sequence. The vertical displacement of both right and left hemi-diaphragms at various anatomical locations had different values in both controls, and patients. There were significant focal variations in the movement of diaphragm in patients with ventilator-induced diaphragmatic dysfunction.

Pulmonary blood mass dynamics on 4DCT during tidal breathing

We previously reported that apparent lung mass varies across the phases of 4D computed tomography (4DCT) images. We hypothesize that these variations correspond to the physiologic changes in pulmonary perfusion induced during normal tidal breathing, and should therefore be present in every breathing patient. In this study, we characterize and quantify the respiratory induced variation in pulmonary blood mass (▵PBM) on 89 patients treated with stereotactic body radiotherapy. ▵PBM was computed from the treatment planning helical 4DCT images of each patient. Conversion from Hounsfield Units (HU) to density and mass per voxel was made using the density calibration curve, applied to the lung parenchyma volume within each phase. A difference in the lung mass with breathing was found for all cases, as was a substantial individual variation in lung volume. We found that the ▵PBM increased during inhalation, and decreased during exhalation. A significant correlation between the individual ▵PBM and tidal volume was observed; ▵PBM increased with tidal volume. We further evaluated the anatomic distribution of ▵PBM variation comparing the central versus peripheral lung, cranial versus caudal, dependent versus non-dependent lung. Our observations regarding spatial distribution of the ▵PBM agree with previously reported differences among similar regions for the supine patient. These results show that a variation in pulmonary mass during respiration is apparent on 4DCT and suggest that these variations reflect respiratory induced changes in the pulmonary perfusion. Therefore, the 4DCT derived respiratory induced ▵PBM signal can provide further insight into the pulmonary circulation and advance the overall understanding and diagnosis of human health and disease.

Effect of Holding Chamber as an Add-on Device on Aerosol Delivery and Fugitive Aerosol from Different Jet Nebulizers

A new Circulaire II (holding chamber) was designed to be used with VixOne nebulizer to increase the inhalable doses reaching the patient. The aim of this study was to evaluate the efficacy of this holding chamber with VixOne nebulizer and determine its usability with other nebulizers. The aerodynamic characteristics of emitted dose of 2 ml salbutamol solution, 5000 μg/ml, were evaluated using cooled Andersen cascade impactor at inhalation flow 15 L/min. The respirable solutions were nebulized using 3JN (VixOne, NebuTech, and En full Kit) with both holding chamber and T-piece. To evaluate the pulmonary and systemic bioavailability, 12 non-smoking health subjects (6 females), > 18 years, with an average(SD) FEV1 > 90% of predicted, inhaled nebulized aerosol of 1 ml respirable solution (5000 μg salbutamol), diluted to 2 ml total volume using normal saline through the same nebulizer setting described above using normal tidal breathing. Subjects provided urine samples 30 min post-dosing (USAL0.5) as an index of pulmonary bioavailability and cumulatively collected their urine for 24 h (USAL24) as an index of systemic bioavailability. To determine the amount that would reach the patients (aerosol-emitted), subjects again inhaled 1 ml salbutamol-diluted respirable solution through the same nebulizer setting described above but with filters to capture salbutamol-emitted. Amount of salbutamol deposited in the holding chamber was significantly higher than in T-piece among all nebulizers (p < 0.001). The fine particle fraction (FPF), < 3 μm, of VixOne with holding chamber, was significantly higher (p < 0.001) and the mass median aerodynamic diameter (MMAD) was significantly lower (p = 0.022) than that with T-piece. The NebuTech and Kit had lower FPF and higher MMAD with holding chamber compared to T-piece (p < 0.05). There was no significant difference in the USAL24 and the emitted aerosol between the 3JNs with holding chamber or T-piece. Holding chamber did not significantly increase the emitted aerosol or USAL24 responsible for the side effect but improved the FPF < 3 μm and MMAD, responsible for lung deposition, with VixOne-JN only. Holding chamber, or similar add-on device, can be used with other nebulizers other than the VixOne, not to increase the inhaled dose but as a fugitive aerosol saver.

Is small airways dysfunction related to asthma control and type 2 inflammation?

Small airways dysfunction (SAD) in adults with persistent asthma and preserved forced expiratory volume in 1 second (FEV1) is related to worse asthma control. [1] Manoharan A Anderson WJ Lipworth J Ibrahim I Lipworth BJ Small airway dysfunction is associated with poorer asthma control. Eur Respir J. 2014; 44: 1353-1355 Crossref PubMed Scopus (46) Google Scholar Impulse oscillometry (IOS) is an effort-independent test used to phenotype SAD, which involves normal quiet tidal breathing. [2] Galant SP Komarow HD Shin HW Siddiqui S Lipworth BJ The case for impulse oscillometry in the management of asthma in children and adults. Ann Allergy Asthma Immunol. 2017; 118: 664-671 Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar Peripheral airways resistance can be derived from the difference between resistance at 5 Hz and 20 Hz (R5-R20), whereas the area under the reactance curve (AX) reflects peripheral lung compliance. [3] Lipworth B Manoharan A Anderson W Unlocking the quiet zone: the small airway asthma phenotype. Lancet Respir Med. 2014; 2: 497-506 Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar In patients with moderate to severe persistent asthma, R5-R20 and AX, but not spirometry, were closely related to asthma control, as assessed by the Asthma Control Questionnaire (ACQ). [4] Jabbal S Manoharan A Lipworth J Lipworth B Utility of impulse oscillometry in patients with moderate to severe persistent asthma. J Allergy Clin Immunol. 2016; 138: 601-603 Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar Type 2 inflammation plays a central role in asthma disease pathophysiology by determining downstream airway hyperresponsiveness and remodeling. Widely used clinical type 2 airway inflammatory biomarkers (T2) include fractional exhaled nitric oxide (FeNO), serum immunoglobulin E (IgE), and blood eosinophils (Eos). [5] Robinson D Humbert M Buhl R et al. Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy. 2017; 47: 161-175 Crossref PubMed Scopus (247) Google Scholar