Phase angle as an indicator of sarcopenia and malnutrition in patients with chronic obstructive pulmonary disease.

BACKGROUND: Phase angle (PhA), which is measured using bioelectrical impedance analysis, is an indicator of muscle quality and malnutrition. PhA has been shown to be correlated with sarcopenia and malnutrition; however, studies on patients with chronic obstructive pulmonary disease (COPD) are limited. In this study, we investigated the correlation between PhA and sarcopenia and malnutrition and determined the cutoff values of PhA for those in patients with COPD. METHODS: This study included 105 male patients with COPD (mean age 75.7 ± 7.7 years, mean forced expiratory volume in 1s % predicted [%FEV1] 57.0 ± 20.1%) and 12 male controls (mean age 74.1 ± 3.8 years) who were outpatients between December 2019 and March 2024. PhA was measured using the InBody S10, and its correlation with sarcopenia and malnutrition was assessed. The cutoff PhA values for sarcopenia and malnutrition were determined using receiver operating characteristic curves. RESULTS: The prevalence rates of sarcopenia and malnutrition were 31% and 22%, respectively, in patients with COPD. PhA significantly correlated with sarcopenia- and malnutrition-related indicators. Multivariate logistic regression analysis independently correlated PhA with sarcopenia and malnutrition. The cutoff values of the PhA for sarcopenia and malnutrition were 4.75° (AUC = 0.78, 95% CI = 0.68-0.88) and 4.25° (AUC = 0.75, 95% CI = 0.63-0.86), respectively. CONCLUSIONS: PhA was significantly correlated with sarcopenia and malnutrition in Japanese patients with COPD and may be a useful diagnostic indicator.

Utility of the Shortness of Breath in Daily Activities Questionnaire (SOBDA-Q) to Detect Sedentary Behavior in Patients with Chronic Obstructive Pulmonary Disease (COPD).

Sedentary behavior has been shown to be an independent predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). However, physicians have difficulty ascertaining patients' activity levels because they tend to avoid shortness of breath. The reformed shortness of breath (SOB) in the daily activities questionnaire (SOBDA-Q) specifies the degree of SOB by measuring low-intensity activity behavior in everyday living. Therefore, we aimed to explore the utility of the SOBDA-Q in detecting sedentary COPD. We compared the modified Medical Research Council dyspnea scale (mMRC), COPD assessment test (CAT), and SOBDA-Q with physical activity levels (PAL) in 17 healthy patients, 32 non-sedentary COPD patients (PAL ≥ 1.5 METs·h), and 15 sedentary COPD patients (PAL < 1.5 METs·h) in this cross-sectional study. CAT and all domains of the SOBDA-Q in all patients are significantly correlated with PAL, even after adjusting for age. The dietary domain has the highest specificity, and the outdoor activity domain has the highest sensitivity for detecting sedentary COPD. Combining these domains helped determine patients with sedentary COPD (AUC = 0.829, sensitivity = 1.00, specificity = 0.55). The SOBDA-Q is associated with PAL and could be a useful tool for determining patients with sedentary COPD. Moreover, eating and outing inactivity claims reflect sedentary behavior in patients with COPD.

Metabolic and Epigenetic Regulation of SMAD7 by STC1 Ameliorates Lung Fibrosis.

As shown in our previous studies, the intratracheal-administration of STC1 (stanniocalcin-1) ameliorates pulmonary fibrosis by reducing oxidative and endoplasmic reticulum stress through the uncoupling of respiration in a bleomycin-treated mouse model. However, the overall effect of STC1 on metabolism was not examined. Therefore, we first conducted a comprehensive metabolomics analysis to screen the overall metabolic changes induced by STC1 in an alveolar epithelial cell line using capillary electrophoresis time-of-flight mass spectrometry. The results were subsequently validated in multiple alveolar epithelial and fibroblast cell lines by performing precise analyses of each substance. STC1 stimulated glycolysis, acetyl-CoA synthesis, and the methionine and cysteine-glutathione pathways, which are closely related to the uncoupling of respiration, modulation of epigenetics, and reduction in oxidative stress. These results are consistent with our previous study. Subsequently, we focused on the inhibitory factor SMAD7, which exerts an antifibrotic effect and is susceptible to epigenetic regulation. STC1 upregulates SMAD7 in an uncoupling protein 2-dependent manner, induces demethylation of the SMAD7 promoter region and acetylation of the SMAD7 protein in human alveolar epithelial and fibroblast cell lines and a bleomycin-treated mouse model, and subsequently attenuates fibrosis. The antifibrotic effects of STC1 may partially depend on the regulation of SMAD7. In the evaluation using lung tissue from patients with idiopathic pulmonary fibrosis, SMAD7 expression and acetylation were high in the alveolar structure-preserving region and low in the fibrotic region. The intratracheal administration of STC1 may prevent the development of pulmonary fibrosis by regulating the metabolism-mediated epigenetic modification of SMAD7 in patients.

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020.

The prevalence of sleep disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared in order to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Because sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021.

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020.

The prevalence of sleep-disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Since sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021.

Risk prediction for new-onset atrial fibrillation using the Minnesota code electrocardiography classification system.

BACKGROUND: Few risk models are available to predict future onset of atrial fibrillation (AF) in workers. We aimed to develop risk prediction models for new-onset AF, using annual health checkup (HC) data with electrocardiogram findings. METHODS AND RESULTS: We retrospectively included 56,288 factory or office workers (mean age = 51.5 years, 33.0% women) who underwent a HC at a medical center and fulfilled the following criteria; age ≥ 40 years, no history of AF, and greater than 1 annual follow-up HC in 2013-2016. Using Cox models with the Akaike information criterion, we developed and compared prediction models for new-onset AF with and without the Minnesota code information. We externally validated the discrimination accuracy of the models in a general Japanese population cohort, the Hisayama cohort. During the median 3.0-year follow-up, 209 (0.37%) workers developed AF. Age, sex, waist circumference, blood pressure, LDL cholesterol, and γ-GTP were associated with new-onset of AF. Using the Minnesota code information, the AUC significantly improved from 0.82 to 0.84 in the derivation cohort and numerically improved from 0.78 to 0.79 in the validation cohort, and from 0.77 to 0.79 in the Hisayama cohort. The NRI and IDI significantly improved in all and male subjects in both the derivation and validation cohorts, and in female subjects in both the validation and the Hisayama cohorts. CONCLUSIONS: We developed useful risk model with Minnesota code information for predicting new-onset AF from large worker population validated in the original and external cohorts, although study interpretation is limited by small improvement of AUC.

Respiratory resistance among adults in a population-based cohort study in Northern Japan.

BACKGROUND: Forced oscillation technique (FOT) is a noninvasive method used to measure respiratory system resistance (Rrs) and reactance (Xrs) during quiet breathing, which has been extensively studied in clinical settings. The distribution of measured FOT values was previously assessed in a community-based cohort study. In this study, we aimed to confirm the distribution of measured FOT values in a different cohort in order to investigate the relationship between these values and patient clinical and biological data. METHODS: We reviewed FOT data and relevant patient clinical and biological information collected from the Community-Based Cohort Study (CommCohort Study), carried out between 2013 to 2016 as a part of the Tohoku Medical Megabank project (TMM). In total, 16,231 adults were enrolled in the study (Male/Female: 4886/11,345). RESULTS: Significant gender differences were observed in distributions of Rrs and Xrs values at 5 Hz (termed R5 and X5, respectively). R5 values in males were lower than those in females, while X5 values in males were slightly less negative. High R5 values were strongly associated with high BMI, short height, smoking status in males, high serum IgE level, and high peripheral blood eosinophil count. CONCLUSION: The present distribution values and their relation to clinical and biological data should provide useful insights for clinical settings and serve as a helpful guide in implementing FOT. Forced oscillation technique, respiratory system resistance, respiratory system reactance, gender difference, obesity.

Combination of assist use of short-acting beta-2 agonists inhalation and guidance based on patient-specific restrictions in daily behavior: Impact on physical activity of Japanese patients with chronic obstructive pulmonary disease.

BACKGROUND: Assist use of inhaled short-acting beta 2 agonists (SABAs) is reportedly effective for preventing shortness of breath on exertion in chronic obstructive pulmonary disease (COPD) patients. However, it is unclear what strategy would be useful for improving physical activity in such patients. The aim is to investigate the effects of assisted use of SABA (procaterol) on physical activity in Japanese COPD patients targeting patient-specific restrictions in daily behavior. METHODS: Fourteen patients with stable COPD (age: 72.1±1.5, %FEV1: 55.6±4.5%) were asked to inhale 20 µg of procaterol 15 minutes before patient-specific daily physical activity that had been identified as limited by a questionnaire and document their usage in a diary. Physical activity was measured using a triaxial accelerometer and the results were collected every month for 2 months. In the first month, a clinician assessed whether inhalation of SABA was appropriate based on a usage diary and coached patients to conduct adequate assist use of SABA for limited physical activity. RESULTS: The strategy significantly improved the physical activity level, assessed using the values of the metabolic equivalents (METs) multiplied by physical activity endurance, at ≥3.0 METs (p<0.05), and physical activity endurance at ≥2.5 and ≥3.0 METs, (p<0.05, p<0.05, respectively). The degree of improvement of physical activity level was significantly positively correlated with the baseline %FVC and %FEV1 (p<0.05, p<0.05, respectively). CONCLUSIONS: Assist use of SABA targeting patient-specific restrictions, particularly when better lung function is still preserved, could be a useful approach for improving physical activity in patients with COPD.

The relationship between increased oxidative stress and visual field defect progression in glaucoma patients with sleep apnoea syndrome.

PURPOSE: Sleep apnoea syndrome (SAS) is often associated with glaucoma, and intermittent hypoxia, present in SAS, can contribute to glaucoma pathogenesis. However, the relationships between SAS, high systemic oxidative stress and the speed of glaucoma progression are unclear. Thus, we investigated these relationships in glaucoma patients with and without SAS. METHODS: Peripheral blood samples were collected from 166 eyes of 166 Japanese patients: 42 controls, 109 open-angle glaucoma (OAG) patients without SAS and 15 OAG patients with SAS. Prognostic factors for visual field defect progression were determined with logistic regression. Diacron reactive oxygen metabolites (dROM) and biological antioxidant potential (BAP) were measured with a free radical analyser. Clinical parameters were also recorded. Intergroup comparisons used the Mann-Whitney U test. RESULTS: Multiple regression analysis showed that SAS was a statistically significant contributing factor to fast visual field defect progression, defined as mean deviation (MD) slope ≤-2.0 dB/Y (SAS: odds ratio (OR) = 14.48; p = 0.002). The non-SAS and SAS groups had similar age, sex, intraocular pressure (IOP), axial length and antiglaucoma drug use. The SAS group had a significantly higher dROM level (p = 0.001), BAP level (p = 0.038) and steeper MD slope (p = 0.001) than the non-SAS group. CONCLUSION: Glaucoma patients with SAS have higher dROM, as well as steeper MD slope, than patients without SAS, suggesting that SAS may induce systemic oxidative stress and promote glaucomatous visual field defect progression.

Peripheral alveolar nitric oxide concentration reflects alveolar inflammation in autoimmune pulmonary alveolar proteinosis.

Nitric oxide and alveolar macrophage inflammation http://ow.ly/czCx30i12n8.

Fractional Exhaled Nitric Oxide (FeNO) and Spirometry as Indicators of Inhalation Exposure to Chemical Agents in Pathology Workers.

OBJECTIVE: The objective of this study was to examine whether fractional exhaled nitric oxide (FeNO) and spirometry can be used as indices to evaluate adverse health effects of low-concentrated chemical inhalation exposure, mainly to formaldehyde. METHODS: Thirty-three subjects (pathology technicians) and 30 controls (workers without handling any chemicals in the same hospitals) participated in this study. All participants underwent FeNO measurement and spirometry before and after 5 days of work. RESULTS: FeNO significantly increased in the subjects with a history of asthma (P < 0.05), whereas forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) decreased in the subjects (P < 0.05). Furthermore, work duration and pre-work levels of FEV1 in the subjects had a significant association. CONCLUSION: The results suggest that FeNO, FVC, and FEV1 represent effective health-effect indices of low-concentrated chemical inhalation exposure.

Sequential Granulocyte-Macrophage Colony-Stimulating Factor Inhalation after Whole-Lung Lavage for Pulmonary Alveolar Proteinosis. A Report of Five Intractable Cases.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by the excessive accumulation of surfactant proteins within the alveolar spaces and by higher titers of autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in the serum and bronchoalveolar lavage fluid. The antibodies inhibit the maturation and phagocytosis of alveolar macrophages. Although the standard therapy for aPAP has been whole-lung lavage (WLL), this procedure is invasive and needs to be repeated for several years. GM-CSF inhalation therapy is a new procedure for treating aPAP and can induce remission with less invasiveness, although it is generally less effective in severe cases. We evaluated five cases with remarkable improvement by using sequential GM-CSF inhalation therapy after WLL; however, the treatment failed when this therapy preceded WLL. Therefore, sequential GM-CSF inhalation after WLL may reinforce the efficiency of WLL in patients with severe aPAP.

End-Tidal CO2 Tension Is Predictive of Effective Nocturnal Oxygen Therapy in Patients with Chronic Heart Failure and Central Sleep Apnea.

Central sleep apnea (CSA) is characterized by recurring cycles of crescendo-decrescendo ventilation during sleep, and enhances sympathetic nerve activity. Thus CSA has a prognostic impact in patients with chronic heart failure (CHF). Although nocturnal oxygen (O2) therapy decreases frequency of CSA and improves functional exercise capacity, it is also known that some non-responders to the therapy exist. We thus aimed to identify predictors of responders to nocturnal O2 therapy in CHF patients with CSA. In 12 CHF patients with CSA hospitalized at our department, sleep study was performed at 2 consecutive nights. Patients nasally inhaled O2 at either the first or second night in a randomized manner. To predict the percentage reduction in apnea-hypopnea index (%ΔAHI) in response to the nocturnal O2 therapy, we performed multiple regression analysis with a stepwise method with variables including age, brain-natriuretic peptide, circulation time, baseline AHI, hypercapnic ventilatory response and end-tidal carbon dioxide tension (PETCO2). Nocturnal O2 therapy significantly decreased AHI (from 32 ± 13 /h to 12 ± 10 /h, P < 0.0001). Among the possible predictors, PETCO2 was the only variable that is predictive of % changes in AHI. Receiver operating characteristics analysis determined 4.25% as the optimal cutoff PETCO2 level to identify responder to nocturnal O2 therapy (> 50% reduction of AHI), with 88.9% of sensitivity and 66.7% of specificity. In conclusion, PETCO2 is useful to predict the efficacy of O2 therapy in CHF patients with CSA, providing important information to the current nocturnal O2 therapy.

Effect of Respiratory Therapy on the Prognosis of Chronic Heart Failure Patients Complicated With Sleep-Disordered Breathing　- A Pilot Efficacy Trial.

BACKGROUND: Sleep-disordered breathing (SDB) has been reported to influence mortality and occurrence of ventricular tachyarrhythmia in patients with chronic heart failure (CHF). It remains to be elucidated, however, whether respiratory therapy (RT) can affect the occurrence of fatal ventricular tachyarrhythmia in CHF patients with SDB. METHODS AND RESULTS: We prospectively examined whether the severity of SDB was associated with fatal cardiac events in CHF patients and, if so, whether RT for SDB improved prognosis. We enrolled 95 patients with stable CHF, in whom SDB was examined on overnight polygraphy. The severity of SDB was quantified using the apnea-hypopnea index (AHI). All patients with AHI ≥10 (n=42) at initial evaluation were recommended to have RT, such as home oxygen therapy and continuous positive airway pressure, and 24 agreed to this. During the follow-up period of 29±17 months, 8 ventricular tachyarrhythmias occurred and 14 of the 95 patients died. On multivariate proportional hazard analysis AHI ≥5 was a risk factor for fatal arrhythmic events (P=0.026). Although RT significantly reduced AHI, it did not significantly reduce the event rates, but 4 patients with AHI <5 on RT had no fatal arrhythmic events or death. CONCLUSIONS: SDB is an independent prognostic factor and thus an important therapeutic target in CHF patients.

Mesenchymal stem cells correct inappropriate epithelial-mesenchyme relation in pulmonary fibrosis using stanniocalcin-1.

Current hypotheses suggest that aberrant wound healing has a critical role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). In these hypotheses, continuous TGF-ß1 secretion by alveolar epithelial cells (AECs) in abnormal wound healing has a critical role in promoting fibroblast differentiation into myofibroblasts. Mesenchymal stem cells (MSCs) home to the injury site and reduce fibrosis by secreting multifunctional antifibrotic humoral factors in IPF. In this study, we show that MSCs can correct the inadequate-communication between epithelial and mesenchymal cells through STC1 (Stanniocalcin-1) secretion in a bleomycin-induced IPF model. Inhalation of recombinant STC1 shows the same effects as the injection of MSCs. Using STC1 plasmid, it was possible to enhance the ability of MSCs to ameliorate the fibrosis. MSCs secrete large amounts of STC1 in response to TGF-ß1 in comparison to AECs and fibroblasts. The antifibrotic effects of STC1 include reducing oxidative stress, endoplasmic reticulum (ER) stress, and TGF-ß1 production in AECs. The STC1 effects can be controlled by blocking uncoupling protein 2 (UCP2) and the secretion is affected by the PI3/AKT/mTORC1 inhibitors. Our findings suggest that STC1 tends to correct the inappropriate epithelial-mesenchymal relationships and that STC1 plasmid transfected to MSCs or STC1 inhalation could become promising treatments for IPF.

Myriad Functions of Stanniocalcin-1 (STC1) Cover Multiple Therapeutic Targets in the Complicated Pathogenesis of Idiopathic Pulmonary Fibrosis (IPF).

Idiopathic pulmonary fibrosis (IPF) is an intractable disease for which the pathological findings are characterized by temporal and spatial heterogeneity. The pathogenesis is composed of myriad factors, including repetitive injuries to epithelial cells, alterations in immunity, the formation of vascular leakage and coagulation, abnormal wound healing, fibrogenesis, and collagen accumulation. Therefore, the molecular target drugs that are used or attempted for treatment or clinical trials may not cover the myriad therapeutic targets of IPF. In addition, the complicated pathogenesis results in a lack of informative biomarkers to diagnose accurately the status of IPF. These facts point out the necessity of using a combination of drugs, that is, each single drug with molecular targets or a single drug with multiple therapeutic targets. In this review, we introduce a humoral factor, stanniocalcin-1 (STC1), which has myriad functions, including the maintenance of calcium homeostasis, the promotion of early wound healing, uncoupling respiration (aerobic glycolysis), reepithelialization in damaged tissues, the inhibition of vascular leakage, and the regulation of macrophage functions to keep epithelial and endothelial homeostasis, which may adequately cover the myriad therapeutic targets of IPF.

Relationship between sleep bruxism and sleep respiratory events in patients with obstructive sleep apnea syndrome.

PURPOSE: Both obstructive sleep apnea syndrome (OSAS) and sleep bruxism (SB) are commonly related to arousal events. In this study, we examined the effect of SB on the sleep architecture and investigated the relationship between SB and sleep respiratory events in patients with OSAS. METHODS: Patients with OSAS (n=67) in whom apnea/hypopnea occurred five or more times per hour were recruited to this study. Healthy volunteers (n=16) were recruited as controls. None of the healthy volunteers had any sleep disorders or medical disorders, nor had they taken any medication or alcohol. Data were collected by standard polysomnography during overnight sleep tests in a dark, quiet room. RESULTS: The frequency of SB was higher in the OSAS than in the control group. The risk of SB was significantly higher in the OSAS than in the control group (odds ratio, 3.96; 95% confidence interval, 1.03-15.20; P<0.05). Apnea/hypopnea and desaturation events occurred significantly more frequently in patients with than without SB. The frequency of the phasic type of SB correlated positively with that of obstructive apnea, micro-arousal, and oxygen desaturation. The frequency of SB events during micro-arousal events consequent on apnea/hypopnea events was significantly higher in the OSAS than in the control group. CONCLUSIONS: We found that patients with OSAS have a high risk of SB. In particular, this is the first report relating phasic-type SB to obstructive apnea events. This relationship suggests that improvement in OSAS might prevent exacerbations of SB.

Application of impulse oscillometry for within-breath analysis in patients with chronic obstructive pulmonary disease: pilot study.

BACKGROUND: The impulse oscillometry is increasingly used for assessing the oscillatory mechanics of the respiratory system. The within-breath behaviour of the oscillatory mechanics in chronic obstructive pulmonary disease (COPD) is a well-known physiological feature. The purpose of this study was to develop a new approach for assessing this feature using impulse oscillometry. METHODS: The oscillatory mechanics were assessed by a commercially available impulse oscillometry device. The respiratory system resistance (Rrs) and reactance (Xrs) were measured during tidal breathing in patients with COPD (n=39) and healthy subjects (n=5). Selected data, the Rrs at 5 Hz (R5), Rrs at 20 Hz (R20), Xrs at 5 Hz (X5), and resonant frequency of Xrs (Fres) every 0.2 s, were extracted from the device. These data were divided into eight time fractions during the respiratory cycle to form averaged respiratory phases. RESULTS: The time courses of the R5 and X5 were notably dependent on the respiratory cycles in patients with COPD, while there was little such dependency in healthy subjects. Irrespective of respiratory phase, R5 and Fres increased, and X5 fell to a more negative level in patients with COPD in a severity-dependent fashion. The increase in the R5 and negative level in the X5 were more prominent in the middle of the expiratory phase. The severity dependence in the R20 was relatively small compared with that in the R5. CONCLUSIONS: The results of this study suggest that impulse oscillometry can assess the within-breath behaviour of the oscillatory mechanics with high temporal resolution, which may be helpful for evaluating the severity of COPD. Further studies are needed to reveal which biomarkers obtained with this approach would be suitable for evaluating the airway obstruction.