Continuous estimation of respiratory system compliance and airway resistance during pressure-controlled ventilation without end-inspiration occlusion.

BACKGROUND: Assessing mechanical properties of the respiratory system (Cst) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals. METHODS: A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (VT) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RCexp). RESULTS: During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of Crs and airway resistance (Raw) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of Crs and an overestimation of Raw were observed in the severe obstruction model. CONCLUSION: Using the modified dynamic signal analysis approach, respiratory system properties (Crs and Raw) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.

Effects of adenoid hypertrophy on nasopharyngeal airway ventilation: A computational fluid dynamics study.

OBJECTIVES: Adenoid hypertrophy causes impaired nasopharyngeal airways (NA) ventilation. However, it is difficult to evaluate the ventilatory conditions of NA. Therefore, this study aimed to analyze the nasopharyngeal airway resistance (NARES) based on computational fluid dynamics simulations and the nasopharyngeal airway depth (NAD) and adenoid hypertrophy grade measured on cephalometric cone-beam computed tomography images and determine the relationship between NAD and grade and NARES to ultimately assess using cephalometric measurements whether NA has airway obstruction defects. METHODS: Cephalogram images were generated from cone-beam computed tomography data of 102 children (41 boys; mean age: 9.14 ± 1.43 years) who received orthodontic examinations at an orthodontic clinic from September 2012 to March 2023, and NAD and adenoid grade and NARES values were measured based on computational fluid dynamics analyses using a 3D NA model. Nonlinear regression analyses were used to evaluate the relationship between NARES and NAD and correlation coefficients to evaluate the relationship between grade and NARES. RESULTS: NARES was inversely proportional to the cube of NAD (R2 = 0.786, P < 0.001), indicating a significant relationship between these variables. The resistance NARES increased substantially when the distance NAD was less than 5 mm. However, adenoid Grade 4 (75 % hypertrophy) was widely distributed. CONCLUSIONS: These study findings demonstrate that the ventilatory conditions of NA can be determined based on a simple evaluation of cephalogram images. An NAD of less than 5 mm on cephalometric images results in NA obstruction with substantially increased airflow resistance.

Impact of palatopharyngeal sizes changing on pharyngeal airflow fluctuation and airway vibration in a pediatric airway.

Snoring is common in children and is associated with many adverse consequences. One must study the relationships between pharyngeal morphology and snoring physics to understand snoring progression. Although some model studies have provided fluid-structure interaction dynamic descriptions for the correlation between airway size and snoring physics, the descriptions still need to be further investigated in patient-specific airway models. Fluid-structure interaction studies using patient-specific airway structures complement the above model studies. Based on reported cephalometric measurement methods, this study quantified and preset the size of the palatopharynx airway in a patient-specific airway and investigated how the palatopharynx size affects the pharyngeal airflow fluctuation, soft palate vibration, and glossopharynx vibration with the help of a verified FSI method. The results showed that the stenosis anterior airway of the soft palate increased airway resistance and airway resistance fluctuations, which can lead to increased sleep effort and frequent snoring. Widening of the anterior airway can reduce airflow resistance and avoid obstructing the anterior airway by the soft palate vibration. The pharyngeal airflow resistance, mouth inflow proportion, and soft palate apex displacement have components at the same frequencies in all airway models, and the glossopharynx vibration and instantaneous inflow rate have components at the same frequencies, too. The mechanism of this same frequency fluctuation phenomenon can be explained by the fluid-structure interaction dynamics of an ideal coupled model consisting of a flexible plate model and a collapsible tube model. The results of this study demonstrate the potential of FSI in studying snoring physics and clarify to some degree the mechanism of airway morphology affecting airway vibration physics.

Impact of posture and CPAP on nasal airflow.

Obstructive sleep apnea (OSA) patients who use continuous positive airway pressure (CPAP) often complain of nasal dryness and nasal obstruction as side effects of CPAP. The physiological mechanisms by which CPAP may cause nasal dryness and nasal obstruction remain poorly understood. It has been hypothesized that CPAP interferes with the nasal cycle, abolishing the resting phase of the cycle and leading to nasal dryness. We performed rhinomanometry measurements in 31 OSA patients sitting, laid supine, and supine after 10 min of CPAP at 10 cmH2O. A posture change from sitting to supine led to more symmetric airflow partitioning between the left and right nostrils in the supine position. CPAP did not have a significant impact on nasal resistance, unilateral airflows, or airflow partitioning. Our results suggest that airflow partitioning becomes more symmetric immediately after changing to a supine position, while CPAP had no effect on nasal airflow, thus preserving the nearly symmetric airflow partitioning achieved after the posture change.

The Effect of Laser-Resistant Endotracheal Tube Design on Airflow Dynamics: A Benchtop and Clinical Study.

OBJECTIVE: Compare ventilation pressures of 2 endotracheal tube designs used in laser airway surgery in clinical practice and with a benchtop model to elucidate differences and understand the design elements that impact airflow dynamics. METHODS: Ventilatory and aerodynamic characteristics of the laser resistant stainless-steel endotracheal tube (LRSS-ET) design and the laser resistant aluminum-wrapped silicone endotracheal tube (LRAS-ET) design were compared. Ventilatory parameters were collected for 32 patients undergoing laser-assisted airway surgery through retrospective chart review. An in vitro benchtop simulation measured average resistance and centerline turbulence intensity of both designs at various diameters and physiological frequencies. RESULTS: Baseline patient characteristics did not differ between the 2 groups. Clinically, the median LRAS-ET peak inspiratory pressure (PIP; 21.00 cm H2O) was significantly decreased compared to LRSS-ET PIP (34.67 cm H2O). In benchtop simulation, the average PIP of the LRAS-ET was significantly lower at all sizes and frequencies. The LRSS-ET consistently demonstrated an increased resistance, although no patterns were observed in turbulence intensity data between both designs. CONCLUSION: The benchtop model demonstrated increased resistance in the LRSS-ET compared to the LRAS-ET at all comparable sizes. This finding is supported by retrospective ventilatory pressures during laser airway surgery, which show significantly increased PIPs when comparing identically sized inner diameters. Given the equivocal turbulence intensity data, these differences in resistance and pressures are likely caused by wall roughness and intraluminal presence of tubing, not inlet or outlet geometries. The decreased PIPs of the LRAS-ET should assist in following lung protective ventilator management strategies and reduce risk of pulmonary injury and hemodynamic instability to the patient.

Algorithm for Nasal Breathing Impairment Evaluation.

Assessing patients with complaints of nasal obstruction has traditionally been done by evaluation of the nasal airway looking for fixed or dynamic obstructive locations that could impair nasal airflow. Not infrequently, however, symptoms of nasal obstruction do not match the clinical examination of the nasal airway. Addressing this subset of patients may be a challenge to the surgeon. Evaluation of patients with symptoms of nasal obstruction should include a combination of a patient-reported assessment of nasal breathing and at least one objective method for measuring nasal airflow or nasal airway resistance or dimensions. This will allow distinction between patients with symptoms of nasal obstruction and low airflow or high nasal airway resistance and patients with similar symptoms but whose objective evaluation demonstrates normal nasal airflow or normal airway dimensions or resistance. Patients with low nasal airflow or high nasal airway resistance will require treatment to increase nasal airflow as a necessary step to improve symptoms, whereas patients with normal nasal airflow or nasal airway resistance will require a multidimensional assessment looking for less obvious causes of impaired nasal breathing sensation.

Overview of Nasal Airway and Nasal Breathing Evaluation.

Several methods are available for evaluating nasal breathing and nasal airflow, as this evaluation may be made from several different perspectives.Physiologic methods for nasal airway evaluation directly measure nasal airflow or nasal airway resistance, while anatomical methods measure nasal airway dimensions. Subjective methods evaluate nasal breathing through several validated patient-reported scales assessing nasal breathing. Computational fluid dynamics evaluates nasal airflow through the analysis of several physics' variables of the nasal airway.Being familiar to these methods is of utmost importance for the nasal surgeon to be able to understand data provided by the different methods and to be able to choose the combination of evaluation methods that will provide the information most relevant to each clinical situation.

Impulse oscillometry assessment of respiratory function in pediatric patients with a history of COVID-19.

OBJECTIVE: While coronavirus disease 2019 (COVID-19) is generally considered to exhibit a less severe clinical course in children than in adults, studies have demonstrated that respiratory symptoms can endure for more than 3 months following infection in at least one-third of pediatric cases. The present study evaluates the respiratory functions of children aged 3-15 years within 3-6 months of their recovery from COVID-19 using impulse oscillometry (IOS) and compares them with the values of healthy children. METHODS: Included in this prospective cross-sectional study were 63 patients (patient group) aged 3-15 years who contracted COVID-19 between December 2021 and May 2022, as well as 57 healthy children as a control group, matched for age and sex. The demographic, clinical, and laboratory data of the patients were recorded, and respiratory function was assessed based on airway resistance (zR5, zR20, R5-20) and reactance (zX5, zX20, reactance area [AX], resonant frequency [Fres]) using an IOS device. RESULTS: There were no significant differences in the age, weight, height, and body weight z score values of the two groups (p > .05). While the zR5 and R5-20 levels of the patient group were higher (p = .008 and p < .001, respectively) than those of the controls, the zR20, AX, and Fres values did not differ significantly between the groups (p > .05). The parameters indicating the reactance, including zX5 and zX20, were significantly lower in the patient group than in the control group (p = .028 and p < .001, respectively). CONCLUSION: Total and peripheral airway resistances were found to be elevated in children who had recovered from COVID-19 in the preceding 3-6 months.

Nasal Obstruction: Overview of Pathophysiology and Presentation of a Clinically Relevant Preoperative Plan for Rhino(Septo)plasty.

Impairment of nasal breathing is a highly prevalent and bothersome symptom that affects daily functioning and/or sleep quality. Those surgeons dealing with patients seeking rhinoplasty need to carefully analyze the preoperative nasal breathing capacity and predict the positive or even negative impact of rhino(septo)plasty on nasal breathing. Given the lack of correlation between the subjective feeling of suboptimal nasal breathing and the objective measurements of nasal flow and nasal resistance, a critical and mainly clinical evaluation of all anatomical, mucosal, and sensory mechanisms involved in nasal obstruction is mandatory. Indeed, thermo-, mechano-, and chemosensory receptors on the nasal mucosa, airflow, and respiratory dynamics might all contribute to the overall perception of nasal breathing capacity. In this review, we provide an overview of the factors determining suboptimal nasal breathing including different diagnostic and experimental tests that can be performed to evaluate nasal flow and nasal resistance and current limitations in our understanding of the problem of nasal breathing in an individual patient. An algorithm for the preoperative or diagnostic workup for nasal obstruction is included that might be useful as a guide for clinicians dealing with patients seeking nose surgery.

Household Air Pollution and Child Lung Function: The Ghana Randomized Air Pollution and Health Study.

Rationale: The impact of a household air pollution (HAP) stove intervention on child lung function has been poorly described. Objectives: To assess the effect of a HAP stove intervention for infants prenatally to age 1 on, and exposure-response associations with, lung function at child age 4. Methods: The Ghana Randomized Air Pollution and Health Study randomized pregnant women to liquefied petroleum gas (LPG), improved biomass, or open-fire (control) stove conditions through child age 1. We quantified HAP exposure by repeated maternal and child personal carbon monoxide (CO) exposure measurements. Children performed oscillometry, an effort-independent lung function measurement, at age 4. We examined associations between Ghana Randomized Air Pollution and Health Study stove assignment and prenatal and infant CO measurements and oscillometry using generalized linear regression models. We used reverse distributed lag models to examine time-varying associations between prenatal CO and oscillometry. Measurements and Main Results: The primary oscillometry measure was reactance at 5 Hz, X5, a measure of elastic and inertial lung properties. Secondary measures included total, large airway, and small airway resistance at 5 Hz, 20 Hz, and the difference in resistance at 5 Hz and 20 Hz (R5, R20, and R5-20, respectively); area of reactance (AX); and resonant frequency. Of the 683 children who attended the lung function visit, 567 (83%) performed acceptable oscillometry. A total of 221, 106, and 240 children were from the LPG, improved biomass, and control arms, respectively. Compared with control, the improved biomass stove condition was associated with lower reactance at 5 Hz (X5 z-score: ß = -0.25; 95% confidence interval [CI] = -0.39, -0.11), higher large airway resistance (R20 z-score: ß = 0.34; 95% CI = 0.23, 0.44), and higher AX (AX z-score: ß = 0.16; 95% CI = 0.06, 0.26), which is suggestive of overall worse lung function. The LPG stove condition was associated with higher X5 (X5 score: ß = 0.16; 95% CI = 0.01, 0.31) and lower small airway resistance (R5-20 z-score: ß = -0.15; 95% CI = -0.30, 0.0), which is suggestive of better small airway function. Higher average prenatal CO exposure was associated with higher R5 and R20, and distributed lag models identified sensitive windows of exposure between CO and X5, R5, R20, and R5-20. Conclusions: These data support the importance of prenatal HAP exposure on child lung function. Clinical trial registered with www.clinicaltrials.gov (NCT01335490).

Peak Nasal Inspiratory Flow (PNIF) for Nasal Breathing Evaluation.

Measuring nasal airflow and nasal breathing has been a major goal of rhinology. Many objective methods for measuring nasal airflow or nasal airway resistance or dimensions provide valuable data but are time-consuming and require expensive equipment and trained technicians, thus making these methods less practical for clinical practice. Peak nasal inspiratory flow (PNIF) measurement is fast, unexpensive, noninvasive, and able to provide an objective evaluation of nasal airflow in real-time. Unilateral PNIF measurements allow separated evaluation of each side of the nasal airway and may prove particularly useful when clinical assessment detects significant asymmetry between both nasal cavities.PNIF measurements are most useful for assessing changes in nasal airflow achieved by any form of therapy, including surgical treatment of the nasal airway. These measurements generally correlate with other objective methods for nasal airway evaluation, but not unequivocally with patient-reported evaluation of nasal breathing. Nevertheless, as low PNIF values prevent the sensation of a suitable nasal breathing, PNIF measurement may also prove useful to optimize the decision of how to best address patients with complaints of nasal airway obstruction.

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

Introduction: 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. 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. Results: 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. Conclusion: 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.

Window of opportunity for respiratory oscillometry: A review of recent research.

Oscillometry has been around for almost 70 years, but there are still many unknowns. The test is performed during tidal breathing and is therefore free from patient-dependent factors that could influence the results. The Forced Oscillation Technique (FOT), which requires minimal patient cooperation, is gaining ground, particularly with elderly patients and children. In pulmonology, it is a valuable tool for assessing obstructive conditions (with a distinction between central and peripheral obstruction) and restrictive disorders (intrapulmonary and extrapulmonary). Its sensitivity allows the assessment of bronchodilator and bronchoconstrictor responses. Different lung diseases show different patterns of changes in FOT, especially studied in asthma and chronic obstructive pulmonary disease. Because of these differences, many studies have analysed the usefulness of this technique in different areas of medicine. In this paper, the authors would like to present the basics of oscillometry with the areas of its most recent clinical applications.

Peripheral Airway Dysfunction in Obesity and Obese Asthma.

BACKGROUND: The purpose of this study was to investigate physiological phenotypes of asthma in obesity. RESEARCH QUESTION: Do physiological responses during bronchoconstriction distinguish different groups of asthma in people with obesity, and also differentiate from responses simply related to obesity? STUDY DESIGN AND METHODS: Cross-sectional study of people with obesity (31 with asthma and 22 without lung disease). Participants underwent methacholine challenge testing with measurement of spirometry and respiratory system impedance by oscillometry. RESULTS: Participants had class III obesity (BMI, 46.7 ± 6.6 kg/m2 in control subjects and 47.2 ± 8.2 kg/m2 in people with asthma). Most participants had significant changes in peripheral airway impedance in response to methacholine: in control subjects, resistance at 5 Hz measured by oscillometry increased by 45% ± 27% and area under the reactance curve (AX) by 268% ± 236% in response to 16 mg/mL methacholine; in people with asthma, resistance at 5 Hz measured by oscillometry increased by 52% ± 38% and AX by 361% ± 295% in response to provocation concentration producing a 20% fall in FEV1 dose of methacholine. These responses suggest that obesity predisposes to peripheral airway reactivity. Two distinct groups of asthma emerged based on respiratory system impedance: one with lower reactance (baseline AX, 11.8; interquartile range, 9.9-23.4 cm H2O/L) and more concordant bronchoconstriction in central and peripheral airways; the other with high reactance (baseline AX, 46.7; interquartile range, 23.2-53.7 cm H2O/L) and discordant bronchoconstriction responses in central and peripheral airways. The high reactance asthma group included only women, and reported significantly more gastroesophageal reflux disease, worse chest tightness, more wheeze, and more asthma exacerbations than the low reactance group. INTERPRETATION: Peripheral airway reactivity detected by oscillometry is common in obese control subjects and obese people with asthma. There is a subgroup of obese asthma characterized by significant peripheral airway dysfunction by oscillometry out of proportion to spirometric airway dysfunction. This peripheral dysfunction represents clinically significant respiratory disease not readily assessed by spirometry.

An identifiable model of lung mechanics to diagnose and monitor COPD.

BACKGROUND: Current methods to diagnose and monitor COPD employ spirometry as the gold standard to identify lung function reduction with reduced forced expiratory volume (FEV1)/vital capacity (VC) ratio. Current methods utilise linear assumptions regarding airway resistance, where nonlinear resistance modelling may provide rapid insight into patient specific condition and disease progression. This study examines model-based expiratory resistance in healthy lungs and those with progressively more severe COPD. METHODS: Healthy and COPD pressure (P)[cmH2O] and flow (Q)[L/s] data is obtained from the literature, and 5 intermediate levels of COPD and responses are created to simulate COPD progression and assess model-based metric resolution. Linear and nonlinear single compartment models are used to identify changes in inspiratory (R1,insp) and linear (R1,exp)/nonlinear (R2Φ) expiratory resistance with disease severity and over the course of expiration. RESULTS: R1,insp increases from 2.1 to 7.3 cmH2O/L/s, R1,exp increases from 2.4 to 10.0 cmH2O/L/s with COPD severity. Nonlinear R2Φ increases (mean R2Φ: 2.5 cmH2O/L/s (healthy) to 24.4 cmH2O/L/s (COPD)), with increasing end-expiratory nonlinearity as COPD severity increases. CONCLUSION: Expiratory resistance is increasingly highly nonlinear with COPD severity. These results show a simple, nonlinear model can capture fundamental COPD dynamics and progression from regular breathing data, and such an approach may be useful for patient-specific diagnosis and monitoring.

Parameterisation of Respiratory Impedance in Lung Cancer Patients From Forced Oscillation Lung Function Test.

OBJECTIVE: This study aims to analyze the contribution and application of forced oscillation technique (FOT) devices in lung cancer assessment. Two devices and corresponding methods can be feasible to distinguish among various degrees of lung tissue heterogeneity. METHODS: The outcome respiratory impedance Zrs (in terms of resistance Rrs and reactance Xrs) is calculated for FOT and is interpreted in physiological terms by being fitted with a fractional-order impedance mathematical model (FOIM). The non-parametric data obtained from the measured signals of pressure and flow is correlated with an analogous electrical model to the respiratory system resistance, compliance, and elastance. The mechanical properties of the lung can be captured through Gr to define the damping properties and Hr to describe the elastance of the lung tissue, their ratio representing tissue heterogeneity ηr. RESULTS: We validated our hypotheses and methods in 17 lung cancer patients where we showed that FOT is suitable for non-invasively measuring their respiratory impedance. FOIM models are efficient in capturing frequency-dependent impedance value variations. Increased heterogeneity and structural changes in the lungs have been observed. The results present inter- and intra-patient variability for the performed measurements. CONCLUSION: The proposed methods and assessment of the respiratory impedance with FOT have been demonstrated useful for characterizing mechanical properties in lung cancer patients. SIGNIFICANCE: This correlation analysis between the measured clinical data motivates the use of the FOT devices in lung cancer patients for diagnosis of lung properties and follow-up of the respiratory function modified due to the applied radiotherapy treatment.

The cumulative effect of methacholine on large and small airways when deep inspirations are avoided.

BACKGROUND AND OBJECTIVE: The effect of serial incremental concentrations of methacholine is only slightly cumulative when assessed by spirometry. This limited cumulative effect may be attributed to the bronchodilator effect of deep inspirations that are required between concentrations to measure lung function. Using oscillometry, the response to methacholine can be measured without deep inspirations. Conveniently, oscillometry can also dissociate the contribution of large versus small airways. Herein, oscillometry was used to assess the cumulative effect of methacholine in the absence of deep inspirations on large and small airways. METHODS: Healthy and asthmatic volunteers underwent a multiple-concentration methacholine challenge on visit 1 and a single-concentration challenge on visit 2 using the highest concentration of visit 1. The maximal response was compared between visits to assess the cumulative effect of methacholine. The lung volume was also measured after the final concentration to assess hyperinflation. RESULTS: In both healthy and asthmatic subjects, increases in resistance at 19 Hz (Rrs19 ), reflecting large airway narrowing, did not differ between the multiple- and the single-concentration challenge. However, increases in resistance at 5 Hz (Rrs5 ) minus Rrs19 , reflecting small airway narrowing, were 117 and 270% greater in the multiple- than the single-concentration challenge in healthy (p = 0.006) and asthmatic (p < 0.0001) subjects, respectively. Hyperinflation occurred with both challenges and was greater in the multiple- than the single-concentration challenge in both groups. CONCLUSION: Without deep inspirations, the effect of methacholine is cumulative on small airways but not on large airways. Lung hyperinflation and derecruitment may partially explain these different responses.

Oscillatory Mechanics Response to Inhaled Bronchodilators in Very Preterm Infants: A Retrospective Study.

OBJECTIVES: To identify short-term repeatability of forced oscillation technique (FOT) measurement of lung function, assess the lung function response to bronchodilators (BDs) by FOT, and prove the concept that only some very preterm infants manifest a change in lung mechanics in response to BD. STUDY DESIGN: We retrospectively analyzed respiratory system resistance and respiratory system reactance measured by FOT (Fabian HFOi). The measurement short-term repeatability was assessed in 43 patients on 60 occasions; BD responsiveness was assessed using a different data set, including 38 measurements in 18 infants. The coefficient of repeatability was calculated as twice the SD of differences between measurements performed 15 minutes apart. We assessed BD responsiveness by measuring respiratory system resistance and respiratory system reactance before and 15 minutes after administering 200 mcg/kg of nebulized salbutamol. A positive response was defined as an improvement in respiratory system resistance or respiratory system reactance greater than the identified coefficient of repeatability. RESULTS: The coefficient of repeatability was 7.5 cmH2O∗s/L (21%) for respiratory system resistance and 6.3 cmH2O∗s/L (21%) for respiratory system reactance. On average, respiratory system resistance did not change significantly following BD administration, though respiratory system reactance increased significantly (from -32.0 [-50.2, -24.4] to -27.9 [-38.1, -22.0] cmH2O∗s/L, P < .001). Changes in respiratory system resistance or respiratory system reactance after BD were greater than the identified coefficient of repeatability in 8 infants (44%) on 13 (34%) occasions. CONCLUSIONS: We identified a threshold to assess BD responsiveness by FOT in preterm infants. We speculate that FOT could be used to assess and personalize treatment with BD.

Role of hyperpnea in the relaxant effect of inspired CO2 on methacholine-induced bronchoconstriction.

Inhaling carbon dioxide (CO2) in humans is known to cause inconsistent effects on airway function. These could be due to direct effects of CO2 on airway smooth muscle or to changes in minute ventilation (V̇e). To address this issue, we examined the responses of the respiratory system to inhaled methacholine in healthy subjects and subjects with mild asthma while breathing air or gas mixtures containing 2% or 4% CO2. Respiratory mechanics were measured by a forced oscillation technique at 5 Hz during tidal breathing. At baseline, respiratory resistance (R5) was significantly higher in subjects with asthma (2.53 ± 0.38 cmH2O·L-1·s) than healthy subjects (2.11 ± 0.42 cmH2O·L-1·s) (P = 0.008) with room air. Similar values were observed with CO2 2% or 4% in the two groups. V̇e, tidal volume (VT), and breathing frequency (BF) significantly increased with CO2-containing mixtures (P < 0.001) with insignificant differences between groups. After methacholine, the increase in R5 and the decrease in respiratory reactance (X5) were significantly attenuated up to about 50% with CO2-containing mixtures instead of room air in both asthmatic (P < 0.001) and controls (P < 0.001). Mediation analysis showed that the attenuation of methacholine-induced changes in respiratory mechanics by CO2 was due to the increase in V̇e (P = 0.006 for R5 and P = 0.014 for X5) independently of the increase in VT or BF, rather than a direct effect of CO2. These findings suggest that the increased stretching of airway smooth muscle by the CO2-induced increase in V̇e is a mechanism through which hypercapnia can attenuate bronchoconstrictor responses in healthy subjects and subjects with mild asthma.NEW & NOTEWORTHY The main results of the present study are as follows: 1) breathing gas mixtures containing 2% or 4% CO2 significantly attenuated bronchoconstrictor responses to methacholine, not differently in healthy subjects and subjects with mild asthma, and 2) the causal inhibitory effect of CO2 was significantly mediated via an indirect effect of the increment of V̇e in response to intrapulmonary hypercapnia.

Lung resistance and elastance are different in ex vivo sheep lungs ventilated by positive and negative pressures.

Lung resistance (RL) and elastance (EL) can be measured during positive or negative pressure ventilation. Whether the different modes of ventilation produce different RL and EL is still being debated. Although negative pressure ventilation (NPV) is more physiological, positive pressure ventilation (PPV) is more commonly used for treating respiratory failure. In the present study, we measured lung volume, airway diameter, and airway volume, as well as RL and EL with PPV and NPV in explanted sheep lungs. We found that lung volume under a static pressure, either positive or negative, was not different. However, RL and EL were significantly higher in NPV at high inflation pressures. Interestingly, diameters of smaller airways (diameters <3.5 mm) and total airway volume were significantly greater at high negative inflation pressures compared with those at high positive inflation pressures. This suggests that NPV is more effective in distending the peripheral airways, likely due to the fact that negative pressure is applied through the pleural membrane and reaches the central airways via the peripheral airways, whereas positive pressure is applied in the opposite direction. More distension of lung periphery could explain why RL is higher in NPV (vs. PPV), because the peripheral parenchyma is a major source of tissue resistance, which is a part of the RL that increases with pressure. This explanation is consistent with the finding that during high frequency ventilation (>1 Hz, where RL reflects airway resistance more than tissue resistance), the difference in RL between NPV and PPV disappeared.