Peak Inspiratory Flow Research Articles

Clinically Important Deterioration Among Patients with Chronic Obstructive Pulmonary Disease (COPD) Treated with Nebulized Glycopyrrolate: A Post Hoc Analysis of Pooled Data from Two Randomized, Double-Blind, Placebo-Controlled Studies.

PurposeUsing a composite endpoint, pooled data from two 12-week Phase III placebo-controlled trials (GOLDEN 3, NCT02347761; GOLDEN 4, NCT02347774) were analyzed to determine whether glycopyrrolate inhalation solution (25 mcg and 50 mcg) administered twice daily (BID) via the eFlow® Closed System nebulizer (GLY) reduced the risk of clinically important deterioration (CID) in patients with moderate-to-very-severe COPD.MethodsCID was defined as ≥100-mL decrease from baseline in post-bronchodilator trough forced expiratory volume in one second (FEV1), or ≥4-unit increase in baseline St. George’s Respiratory Questionnaire (SGRQ) total score, or moderate/severe exacerbation. The relative treatment effect of GLY versus placebo on the odds of CID (any and by component endpoints) was expressed as the odds ratio (OR) and 95% confidence interval (CI). Subgroups categorized by age (<65/≥65 years), sex, smoking status (current/former), long-acting beta agonist (LABA) use, FEV1 (<50%/≥50%), and peak inspiratory flow rate (PIFR) (<60 L/min/≥60 L/min) were analyzed.ResultsCompared to placebo, GLY 25 mcg and 50 mcg BID over 12 weeks significantly reduced the risk of CID by 50% (OR: 0.50 [0.37–0.68]) and 40% (OR: 0.60 [0.44–0.80]), respectively. Subjects treated with GLY 25 mcg BID were 59% less likely to experience CID in FEV1 (OR: 0.41 [0.27–0.62]) and 48% less likely to perceive CID in health status (OR: 0.52 [0.37–0.73]). Statistically significant reductions were also observed at the higher dose. The incidence of moderate/severe exacerbations was low and comparable among the cohorts. GLY 25 mcg BID was significantly more effective than placebo (p<0.05) in preventing CID irrespective of age, smoking status, LABA use, COPD severity, or PIFR. Subjects <65 years (OR 0.45 [0.29–0.68]) and those with PIFR <60 L/min (OR 0.36 [0.20–0.67]) exhibited the largest benefit.ConclusionNebulized GLY over 12 weeks significantly reduced the risk of CID and provided greater short-term stability in patients with moderate-to-very-severe COPD.

In Vitro Effect of Different Airflow Rates on the Aerosol Properties of Nebulized Glycopyrrolate in the eFlow® Closed System and Tiotropium Delivered in the HandiHaler®.

IntroductionPersonalized therapy for patients with COPD requires appropriate choice of drug and delivery device. Inhalers and nebulizers vary in their drug delivery characteristics, particularly the need for passive or active patient inhalation for appropriate drug dispersal and delivery. In this in vitro analysis, we assessed the aerosol performance and drug delivery of two long-acting muscarinic antagonists, glycopyrrolate (GLY; 25 µg solution; 1 ml) and tiotropium (TIO; 18 µg powder) through their respective delivery systems: the eFlow® Closed System (CS) vibrating membrane nebulizer and the HandiHaler® dry-powder inhaler (DPI).MethodsThe aerosol performances of the eFlow® CS nebulizer and the HandiHaler® were determined using the Next Generation cascade Impactor. The delivered dose of GLY and TIO was determined using different breathing patterns, which varied in tidal volume and peak inspiratory flow rate, respectively, to simulate breathing conditions ranging from normal to severe obstruction.ResultsAerodynamic particle analysis showed generally similar mass median aerodynamic diameter (MMAD, range, 3.6–4.6 µm) and fine particle fraction (FPF, range, 48.2%–63.7%) with GLY delivered using the eFlow® CS nebulizer under all breathing patterns tested. TIO, delivered via the HandiHaler®, showed variations in MMAD (range, 3.8–5.8 µm) and FPF (range, 16.1%–32.4%) under different inspiratory flow rates. The majority of GLY was deposited in stages 2–5 of the impactor, which corresponds with particle sizes in the respirable range (< 5 µm), whereas a large proportion of TIO was deposited in the throat/mouthpiece pre-separator, irrespective of test conditions. The median residual dose of GLY with eFlow® CS was notably lower compared to that of TIO with HandiHaler® (2.4%–4.4% vs. 40%–67%, respectively).ConclusionsThese simulation results highlight the different deposition patterns generated by a DPI device and a vibrating membrane nebulizer, which may help inform device selection and treatment decision in COPD management.

Respiratory pathology in the Optn-/- mouse model of Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder that results in death due to respiratory failure. Many genetic defects are associated with ALS; one such defect is a mutation in the gene encoding optineurin (OPTN). Using an optineurin null mouse (Optn-/-), we sought to characterize the impact of optineurin deficiency on respiratory neurodegeneration. Respiratory function was assessed at 6 and 12 mo of age using whole body plethysmography at baseline during normoxia (FiO2: 0.21; N2 balance) and during a respiratory challenge with hypoxia and hypercapnia (FiCO2: 0.07, FiO2: 0.10; N2 balance). Histological analyses to assess motor neuron viability and respiratory nerve integrity were performed in the medulla, cervical spinal cord, hypoglossal nerve, and phrenic nerve. Minute ventilation, peak inspiratory flow, and peak expiratory flow are significantly reduced during a respiratory challenge in 6 mo Optn-/-mice. By 12 mo, tidal volume is also significantly reduced in Optn-/- mice. Furthermore, 12mo Optn-/- mice exhibit hypoglossal motor neuron loss, phrenic and hypoglossal dysmyelination, and accumulated mitochondria in the hypoglossal nerve axons. Overall, these data indicate that Optn-/- mice display neurodegenerative respiratory dysfunction and are a useful model to study the impact of novel therapies on respiratory function for optineurin-deficient ALS patients.

A Novel Endoscopic Arytenoid Medialization for Unilateral Vocal Fold Paralysis.

Arytenoid adduction (AA) has been indicated for unilateral vocal fold paralysis (UVFP) patients with vertical vocal fold height mismatch and/or large posterior glottic gaps that are unable to be adequately addressed by anterior medialization techniques. Although AA offers several advantages over other methods, it is technically challenging and involves significant laryngeal manipulation of the cricoarytenoid joint. A novel, minimally invasive endoscopic arytenoid medialization technique is presented for the closure of the posterior commissure. Prospective case series. Seventeen consecutive patients were diagnosed and treated with unilateral endoscopic arytenoid medialization (EAM) combined with injection laryngoplasty because of unilateral vocal fold paralysis. Jitter, shimmer, harmonics-to-noise ratio (HNR), maximum phonation time (MPT), fundamental frequency (F0 ), Voice Handicap Index (VHI), peak inspiratory flow (PIF), and quality of life (QoL) were evaluated preoperatively, 1 month, and 1 year after EAM. Jitter, shimmer, HNR, and MPT significantly improved and remained stable 1 year after the intervention. F0 and PIF remained unchanged. Significant improvements in VHI and QoL demonstrated patient satisfaction with voicing and respiratory functions. Endoscopic arytenoid medialization is a quick, minimally invasive solution for unilateral vocal fold paralysis. With simultaneous augmentation of the vocal fold, it provides a complete glottic closure along the entire vocal fold in UVFP patients. 4 Laryngoscope, 131:E903-E910, 2021.

Rhinitis in patients with acquired hypothyroidism.

Our aim was to evaluate the rhinological changes during hypothyroid and euthyroid periods in patients with acquired hypothyroidism. The newly diagnosed 40 adult patients with hypothyroidism who presented to the Endocrinology clinic at a tertiary hospital were enrolled in the study. Patients having blood thyroid-stimulating hormone levels greater than 4.95IU/dl were consulted to the ENT clinic. Nasal Obstruction Symptom Evaluation scores, Peak Nasal Inspiratory Flow rates and nasalmucociliary clearancetime of patients were noted before and 4months after the oral levothyroxine sodium tablet treatment. Of the patients included in the study, 34 (85%) were females and 6 (15%) were males. The mean thyroid-stimulating hormone values before the treatment was 10.01 ± 3.31IU/dl and 4.03 ± 2.45IU/dl at the end of the treatment. The difference in values was statistically significant (p < 0.001). The mean mucociliary clearancetime before treatment was 8.03 ± 3.29min and 7.35 ± 2.87min at the end of treatment. The decrease in mucociliary clearancetime was statistically significant (p = 0.001). We did not detect any significant difference between pre- and posttreatment values of nasal obstruction symptom evaluation scores and peak nasal inspiratory flow rates. The patients with hypothyroidism have prolonged mucociliary clearance time in hypothyroid period of the disease. Regarding to this data, we may recommend clinicians to follow-up these patients more closely for respiratory tract diseases and sinonasal infections.

Glabridin attenuates airway inflammation and hyperresponsiveness in a mice model of ovalbumin-induced asthma

Asthma is an inflammatory disease of the airways of the lungs, which is characterized by airflow obstruction and bronchospasms. Glabridin is a major flavonoid, especially found in root of Glycyrrhiza glabra, and has several pharmacological activities, including antioxidant and anti-inflammatory effects. The anti-asthmatic effect and possible mechanism of glabridin, however, have not been revealed so far.The aim of this study is to investigate the effects and possible mechanisms of glabridin against ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) and inflammation in mice.In male BALB/c mice, asthma was induced by intraperitoneal (i.p) injection of OVA mixed with 2 mg aluminium hydroxide on days 0, 14 and boosted with OVA aerosol challenge on days 21, 22, and 23. Mice were either treated with dexamethasone (i.p, 1 mg/kg) or glabridin (10, 20, and 30 mg/kg) from days 18–23. Pulmonary function parameters such as peak inspiratory flow, peak expiratory flow, tidal volume, expiratory volume, the frequency of breathing, enhanced pause values were evaluated by using whole-body plethysmography. Measurements were performed at baseline and following methacholine (50 mg/mL) challenges. In addition, white blood cells (WBC) count, total protein, and IgE levels were measured in bronchial alveolar lavage fluid (BALF), lung, and serum, respectively.Glabridin (20 or 30 mg/kg) significantly attenuated (p < 0.05) OVA-induced alteration in respiratory parameters. Elevated counts of total WBC, differential WBC (neutrophils, lymphocytes, monocytes, and eosinophils) in BALF and the total protein in lungs and BALF were significantly decreased (p < 0.05) by glabridin (20 or 30 mg/kg). It also significantly attenuated the increased serum IgE levels (p < 0.05).As glabridin reduces the level of serum IgE, the total protein and the count of WBC and improves respiratory function, it may be a novel therapeutic agent in asthma.

Cigarette smoke extract triggers neoplastic change in lungs and impairs locomotor activity through wnt3a-β-catenin signaling in aged COPD rodent model

Background Chronic cigarette smoking primes immense decline in lung functions and retardation of motor functions with increase in age. This raise the question of whether age status overwhelm the susceptibility to smoking induced lung inflammatory diseases and neuro-motor dysfunctions. Methods To study the hypothesis 11–12 month old aged wistar rats (n = 6) were administered cigarette smoke extract (CSE) through intraperitoneal route (0.5 ml/rat) twice a week for 2 months. Respiratory lung functions were measured through whole body plethysmography. Lung histopathological evaluation and neuronal degeneration were observed by using H&E, picrosirius red and nissl staining respectively. Motor function tests were done through panel of neuro-behavioral tests and protein expressions were performed in lung and brain tissue homogenates through western blotting. Results Sub-chronic CSE exposure worsened the lung functions including decreased tidal volume (p < 0.05), peak inspiratory flow (p < 0.05) and enhanced pause (p < 0.05). Grossly, solid neoplastic lesions were visible on the supra-lateral surface of the lungs of the CSE treated animals. Histopathological examination revealed immune cell infiltration, dominated with macrophages and alveolar type II cells stained positive for PCNA. Increased expression of BAX, PCNA, Wnt-3a, p-β-catenin (p < 0.05) was seen in the lungs of CSE treated aged animals. Elevated expression of inflammatory markers including NF-ϏB, TNF-α, TNF-R1, p-AKT was found in CSE treated lung tissues. Moreover, our result showed increased MCP-1, VEGF and IL-6 levels in BALF and plasma (p < 0.01) which might lead to neo-vascularization and excessive cell proliferation in lungs of CSE induced rats. Sub-chronic cigarette smoke exposure retarded the motor activity with suppression of D1 and D2 receptor expression in brain tissues. Brain tissue revealed the abundance of hyperchromatic and pyknotic nuclei suggesting neuronal degeneration. Conclusion So in conclusion, chronic cigarette smoking in old age creates susceptibility to fast onset of lung inflammatory diseases and neuro-motor retardation than their nonsmoker counterparts.

Effect of physical training on gender difference in trained personal

Many controlled studies and neurological studies demonstrate that men and women are physically and mentally different. The purpose of this study is to find out whether there is any gender difference in respiratory capacity between trained athletes of both gender. This study was conducted at Kolkata (Serampore area), West Bengal, India. The subject was trained table tennis players of age group was 14 – 17 years. Significant differences have been found in height (cm), W/H ratio and PIF (l/s) between male and female lawn tennis players and all these values are significantly higher (P&lt;0.05) in male than female players. Greater mean height in trained male than female tennis player of same age range is advantageous for male. This might be due to their own growth pattern under the influences of different specific hormones which is not considered in this study. Higher centrally located fats in trained male than female tennis player in this age range might be due to less affectivity of physical training in male. Higher central fat distribution may hinder different lung capacities by influencing abdominal cavity. Higher peak inspiratory flow in trained male than female tennis player indicates inspiratory muscles are more powerful in male player of this age range. So, it can be concluded from this study that gender differences in lung capacities can be minimized by proper training load in female trained player at least in 14-17 years age range. This study also claimed that stature is not only the decisive factor for differences in lung capacities in male and female trained tennis player of 14-17 years age range. Body composition, central fat distribution, active inspiratory muscles and proper physical training have definite role in improving lung capacities of trained male and female tennis player.

Korean Modification of the Nasal Provocation Test With House Dust Mite Antigen Following the EAACI Guidelines.

ObjectivesWe evaluated the usefulness of the standardized nasal provocation test (NPT) protocol recently published by the European Academy of Allergy and Clinical Immunology (EAACI) and compared the utility of several parameters for diagnosing allergic rhinitis (AR) caused by house dust mites (HDM). Subjective parameters were nasal and ocular symptoms measured using a visual analog scale (VAS), and objective parameters were peak nasal inspiratory flow (PNIF), minimal cross-sectional area (MCA), and total nasal volume (TNV).MethodsBefore and after spraying Dermatophagoides pteronyssinus (DP) allergen (1,000 AU/mL, 100 μL) into both nostrils of 13 patients with AR (AR group) and 22 patients with non-AR (NAR group), we used VAS scores to measure nasal symptoms (nasal obstruction, rhinorrhea, sneezing, and itching) and ocular symptoms and assessed PNIF, MCA, and TNV.ResultsThe AR group had significantly worse symptoms than the NAR group 15 minutes after DP challenge (P<0.001). After 30 minutes, nasal obstruction and rhinorrhea remained worse in the AR group (P<0.001); a similar but less marked difference was seen for sneezing (P=0.012) and itching (P=0.039). Ocular symptoms, PNIF, MCA, and TNV differed between groups after both 15 and 30 minutes (P<0.05). The area under the receiver operating characteristic curve was higher for nasal obstruction (0.977), rhinorrhea (0.906), and TNV (0.979) than for sneezing (0.755), itching (0.673), and MCA (0.836).ConclusionNPT performed according to the EAACI guidelines could help diagnose AR caused by HDM. TNV and VAS changes in nasal obstruction and rhinorrhea had higher diagnostic accuracy than other parameters.

Nebulized Therapies in COPD: Past, Present, and the Future.

Current guidelines recommend inhalation therapy as the preferred route of drug administration for treating patients with chronic obstructive pulmonary disease (COPD). Inhalation devices consist of nebulizers and handheld inhalers, such as dry-powder inhalers (DPIs), pressurized metered-dose inhalers (pMDIs), and soft mist inhalers (SMIs). Although pMDIs, DPIs and SMIs may be appropriate for most patients with COPD, certain patient populations may have challenges with these devices. Patients who have cognitive, neuromuscular, or ventilatory impairments (and receive limited assistance from caregivers), as well as those with suboptimal peak inspiratory flow may not derive the full benefit from handheld inhalers. A considerable number of patients are not capable of producing a peak inspiratory flow rate to overcome the internal resistance of DPIs. Furthermore, patients may have difficulty coordinating inhalation with device actuation, which is required for pMDIs and SMIs. However, inhalation devices such as spacers and valved holding chambers can be used with pMDIs to increase the efficiency of aerosol delivery. Nebulized treatment provides patients with COPD an alternative administration route that avoids the need for inspiratory flow, manual dexterity, or complex hand-breath coordination. The recent approval of two nebulized long-acting muscarinic antagonists has added to the extensive range of nebulized therapies in COPD. Furthermore, with the availability of quieter and more portable nebulizer devices, nebulization may be a useful treatment option in the management of certain patient populations with COPD. The aim of this narrative review was to highlight recent updates and the treatment landscape in nebulized therapy and COPD. We first discuss the pathophysiology of patients with COPD and inhalation device considerations. Second, we review the updates on recently approved and newly marketed nebulized treatments, nebulized treatments currently in development, and technological advances in nebulizer devices. Finally, we discuss the current applications of nebulized therapy in patients with COPD.

Associations of soluble metals and lung and liver toxicity in mice induced by fine particulate matter originating from a petrochemical complex.

Adverse health effects have been observed in nearby residents due to exposure to petrochemical-derived chemicals. The objective of this study was to examine associations of soluble metals with lung and liver toxicity in fine particulate matter (PM2.5) in the vicinity of a petrochemical complex. PM2.5 was collected in the vicinity of a petrochemical complex of Mailiao Township (Yunlin County, Taiwan) to investigate lung and liver toxicity in BALB/c mice. The PM2.5 concentration was 30.2 ± 11.2μg/m3, and the PM2.5 was clustered in major local emissions (19.1μg/m3) and minor local emissions (14.1μg/m3) using a k-means clustering model. The PM2.5 (50 and 150μg/kg) and PM2.5-equivalent soluble nickel (Ni), vanadium (V), and lead (Pb) concentrations were intratracheally instilled into BALB/c mice. PM2.5 and V significantly decreased the tidal volume after exposure (p< 0.05). The peak expiratory flow (PEF) and peak inspiratory flow (PIF)/PEF ratio were significantly altered by 150μg/kgV (p< 0.05). V and Pb significantly increased total protein and lactate dehydrogenase (LDH) levels in bronchoalveolar lavage fluid (BALF) (p< 0.05). Interleukin (IL)-6 in BALF significantly increased after exposure to Pb (p< 0.05) accompanied by lung inflammatory infiltration. PM2.5 and Pb significantly increased levels of 8-isoprostane (p< 0.05). The level of caspase-3 activity significantly increased after exposure to Pb (p< 0.05). LDH in the liver was significantly increased by PM2.5 (p< 0.05). 8-Isoprostane in the liver was significantly increased by PM2.5 and Pb (p< 0.05). IL-6 in the liver was significantly increased by PM2.5, Ni, V, and Pb after exposure (p< 0.05), accompanied by liver inflammatory infiltration. Our results demonstrated that V in PM2.5 was associated with an increase in 8-isoprostane for all emissions and major local petrochemical emissions. In conclusion, V contributes to in vivo liver toxicity induced by PM2.5 in the vicinity of a petrochemical complex.

Expiratory airflow obstruction due to tracheostomy tube: A spirometric study in 50 patients

Tracheostomy is commonly used in intensive care units and in head and neck departments. Airway obstruction due to occluded cuffless tracheostomy tubes themselves remains unknown, although capping trials are commonly used before decannulation. The aim of this study was to evaluate the extent to which airway obstruction can be caused by occluded cuffless tubes in patients who underwent head and neck surgery. Prospective Research Outcome. University teaching hospital. Fifty patients requiring transient tracheostomy after head and neck surgery. A flow-volume loop (FVL) through the mouth using a portable spirometer, with the occluded fenestrated cuffless tube, was measured before and immediately after decannulation, by obstructing the orifice of tracheostomy tube. The measurement of FVL recorded the forced vital capacity (FVC), forced expiratory volume in 1second (FEV1 ), peak expiratory flow (PEF), forced expiratory flow at 50% of FVC, peak inspiratory flow (PIF) and forced inspiratory flow at 50% of FVC. A statistically significant difference between all spirometric parameters was found. Mean PEF and PIF, respectively, increased from 2.8 to 4.5L/s (P<.0001) and 2.3 to 2.7L/s (P<.01) before and after decannulation, with a strong positive correlation (r=0.7; P<.05). A mean expiratory (34%) and inspiratory (9%) airflow reduction was observed due to cannula. Occluded cuffless tracheostomy tubes cause a dramatic airflow obstruction, mainly in the expiratory phase of FVL. This should be taken into account during capping trials.

Nasal Peak Inspiratory Flow in Healthy and Obstructed Patients: Systematic Review and Meta-Analysis.

Nasal peak inspiratory flow (NPIF) is a practical and affordable tool that measures maximum inspiratory flow rate through both nostrils. Although NPIF values for healthy controls and patients appear to differ considerably, a generally expected value for populations with and without nasal obstruction has yet to be established. The aim of this systematic review and meta-analysis was to determine the mean NPIF value in populations with and without nasal obstruction. Medline (1946-) and Embase (1947-) were searched until July 1, 2017. A search strategy was used to identify studies that reported NPIF values for defined healthy or disease states. All studies providing original data were included. The study population was defined as having either normal nasal breathing or nasal obstruction. A meta-analysis of the mean data was presented in forest plots, and data were presented as mean (95% confidence interval [CI]). The search yielded 1,526 studies, of which 29 were included. The included studies involved 1,634 subjects with normal nasal breathing and 817 subjects with nasal obstruction. The mean NPIF value for populations with normal nasal breathing was 138.4 (95% CI: 127.9-148.8) L/min. The mean value for populations with nasal obstruction was 97.5 (95% CI: 86.1-108.8) L/min. Current evidence confirms a difference between mean NPIF values of populations with and without nasal obstruction. The mean value of subjects with no nasal obstruction is 138.4 L/min, and the mean value of nasally obstructed populations is 97.5 L/min. Prospective studies adopting a standardized procedure are required to further assess normative NPIF values. Laryngoscope, 131:260-267, 2021.

Inappropriate Peak Inspiratory Flow Rate with Dry Powder Inhaler in Chronic Obstructive Pulmonary Disease

Optimal peak inspiratory flow rate (PIFR) is crucial for optimizing dry powder inhaler (DPI) effectiveness for chronic obstructive pulmonary disease (COPD). This study provide an insight that there was a substantial proportion of improper PIFRs (not only insufficient but also excessive) among COPD patients using DPIs. We enrolled 138 COPD patients from a medical center in Taiwan and measured PIFRs against different internal resistances of DPIs. Proportion of excessive, optimal, suboptimal, and insufficient PIFRs were 2%, 54%, 41%, 3%, respectively, against medium-high resistance; 2%, 77%, 20%, 1%, respectively, against medium resistance; 27%, 63%, 9%, 1%, respectively, against medium-low resistance; and 42%, 57%, 1%, 0%, respectively, against low resistance (p < 0.01). Although most PIFRs against medium-high (54%), medium (77%), medium-low (63%) and low (57%) resistance were optimal, a substantial proportion of PIFRs against low resistance were excessive (42%, p < 0.01), irrespective of age, body-mass index, dyspnea severity score, and COPD severity. Insufficient PIFRs were infrequent, but suboptimal/insufficient PIFRs were most prevalent in patients older than 75 years than in younger patients (36% vs. 56%, p = 0.036) against medium-high resistance. Regularly monitoring PIFRs against the specific resistance of the DPIs and instructing patients to employ a proper inspiration effort may help to optimize the effects of DPIs.

Peak Inspiratory Flows: Defining Repeatability Limits and a Predictive Equation for Different Inhalers

Peak inspiratory flow (PIF) has been proposed as a measure to assess a patient's ability to use dry powder inhalers (DPIs). However, robust quality criteria to determine a repeatability limit for measuring PIF are lacking. What are the repeatability limits for measuring PIF? What is therelationship between PIF measured using the In-Check DIAL device at Diskus (GlaxoSmithKline; PIFD) and HandiHaler (Boehringer Ingelheim; PIFHH) resistances? Data from a randomized, controlled, phase 3 trial (study 0149; see Clinical Trial Registration data) were used to define repeatability limits for PIF. In addition, a model to characterize the relationship between PIF measured with the In-Check DIAL device at PIFD and PIFHH was defined using data from two randomized, controlled, phase 3 trials (studies 0128 and 0149). In study 0128, the mean values (SD) for PIF at zero resistance and PIFHH were 84.6 (33.4) and 57.3 (26.1) L/min, respectively. In study 0149, the mean values (SD) for PIFD and PIFHH were 42.4 (11.2) and 29.0 (8.3) L/min, respectively. At the mean level, the mean difference between measurement attempts for PIFD and PIFHH was small,< 5 and< 3 L/min, respectively. The repeatability limit was determined as 10 and 5 L/min for PIFD and PIFHH, respectively. Modeling the relationship between PIFD and PIFHH, after controlling for significant covariates, demonstrated that a PIFD value of 60 L/min was approximately equivalent to PIFHH of 40 L/min. This analysis demonstrated that the two highest values of PIF using the In-Check DIAL device among three inspiratory efforts, met the repeatability limit. Altogether, these data provide guidance for measuring PIF against the simulated resistance of a specific DPI in clinical practice and research studies. ClinicalTrials.gov; Nos.: NCT02518139 (study 0128) and NCT03095456 (study 0149); URL: www.clinicaltrials.gov.

An assessment of a simple clinical technique to estimate pharyngeal collapsibility in people with obstructive sleep apnea.

Quantification of upper airway collapsibility in obstructive sleep apnea (OSA) could help inform targeted therapy decisions. However, current techniques are clinically impractical. The primary aim of this study was to assess if a simple, novel technique could be implemented as part of a continuous positive airway pressure (CPAP) titration study to assess pharyngeal collapsibility. A total of 35 participants (15 female) with OSA (mean ± SD apnea-hypopnea index = 35 ± 19 events/h) were studied. Participants first completed a simple clinical intervention during a routine CPAP titration, where CPAP was transiently turned off from the therapeutic pressure for ≤5 breaths/efforts on ≥5 occasions during stable non-rapid eye movement (non-REM) sleep for quantitative assessment of airflow responses (%peak inspiratory flow [PIF] from preceding 5 breaths). Participants then underwent an overnight physiology study to determine the pharyngeal critical closing pressure (Pcrit) and repeat transient drops to zero CPAP to assess airflow response reproducibility. Mean PIF of breaths 3-5 during zero CPAP on the simple clinical intervention versus the physiology night were similar (34 ± 29% vs. 28 ± 30% on therapeutic CPAP, p = 0.2; range 0%-90% vs. 0%-95%). Pcrit was -1.0 ± 2.5 cmH2O (range -6 to 5 cmH2O). Mean PIF during zero CPAP on the simple clinical intervention and the physiology night correlated with Pcrit (r = -0.7 and -0.9, respectively, p < 0.0001). Receiver operating characteristic curve analysis indicated significant diagnostic utility for the simple intervention to predict Pcrit < -2 and < 0 cmH2O (AUC = 0.81 and 0.92), respectively. A simple CPAP intervention can successfully discriminate between patients with and without mild to moderately collapsible pharyngeal airways. This scalable approach may help select individuals most likely to respond to non-CPAP therapies.

Body plethysmography for measuring airway resistance in patients with bilateral vocal fold immobility

ObjectiveThis study investigated the reliability of body plethysmography in comparison to spirometry in objectively measuring upper airway functions. MethodsThe study population consisted of 53 participants, 23 patients with BVFI after endolaryngeal laser posterior cordectomy and 30 healthy volunteers. All of them had body plethysmography (airway resistance, Raw), spirometry (ratio of forced expiratory flow at 50% to forced inspiratory flow at 50%, FEF50/FIF50 and peak inspiratory flow, PIF), 6 min-walking-test (6MWT) and Medical Research Council (MRC) dyspnea scale measurements. The tests were repeated and reliability was evaluated using intraclass correlation (ICC) and Spearman correlation. ResultsThe reliability of Raw was high with ICC of 0.92, comparable to the spirometry measurements: FEF50/FIF50(ICC = 0.72) and PIF (ICC = 0.97). The mean of Raw was significantly higher in patient group. A strong significant correlation between Raw and MRC dyspnea scale (r = 0.79; p<0.05) and a moderate negative correlation between Raw and 6MWT (r = 0.4; p<0.05) was demonstrated. ConclusionBody plethysmography (Raw) is a reliable tool in objective measurement of upper airway resistance that reflects the patient's perception of breathlessness. A larger number of participants are necessary to confirm this finding.

Motor Neuron Pathology Leads to Respiratory Deficiency in Optn−/− Mice

Amyotrophic Lateral Sclerosis (ALS) is a devastating and fatal neurodegenerative disease with no current cure. Respiratory failure is the leading cause of death in ALS. Death occurs3–5 years after diagnosis when patients with ALS ultimately succumb to inadequate ventilation, hypoxia, and respiratory failure. Several genes are associated with ALS. One of these genes encodes optineurin (OPTN) which is associated with neurodegeneration in both ALS and glaucoma. Optineurin has multiple roles in various biochemical pathways such as regulation of inflammation and autophagy. However, the exact mechanism by which loss of OPTN results in progressive neural degeneration and respiratory failure in ALS is still unclear.In order to understand the impact of OPTN deficiency on respiratory function, our goal was to study the respiratory pathophysiology in the Optn−/− mouse. The hypothesis driving this work is that the Optn−/− mouse has respiratory insufficiency due to degeneration of the respiratory motor unit – motor neuron, nerve, neuromuscular junction and muscle. Physiological, histological and molecular outcome measures were used to assess the impact of OPTN on the respiratory system. We used whole body plethysmography (WBP) to assess breathing at baseline and during a respiratory challenge with hypercapnic and hypoxic conditions (FiCO2: 0.07, FiO2: 0.10; nitrogen balance). During the respiratory challenge, compared to the WT mice, Optn−/− mice had significantly lower tidal volume, minute ventilation, peak inspiratory flow, and peak expiratory flow starting at 6 months of age indicating weakened muscle strength. Furthermore, throughout the challenge period Optn−/− mice spent a greater amount of time in apnea indicating pathology in the respiratory control centers. The weakness and pathology in control of breathing during the respiratory challenge progresses as the mice age. At 1 year of age, Optn−/− mice have stunted growth accompanied by reduced diaphragm size compared to WT mice. Postmortem immunohistochemical studies of the medulla reveal Optn−/− mice have fewer hypoglossal motor neurons. Finally, the hypoglossal (XII) nerves of Optn−/− mice had significantly reduced g‐ratio which indicates pathology and decompaction of myelin sheaths. Within the XII nerve, there are an increase in both the number of mitochondria and area of mitochondria. These along with elevated levels of LC3‐II to LC3‐I indicate reduced mitophagy. In conclusion, the Optn−/− ALS mouse model displays motor neuron pathology, increased nerve demyelination and aberrant control of breathing leading to respiratory insufficiency.

Respiratory Dysfunction in a Mouse Model of Spinocerebellar Ataxia 7

Spinocerebellar ataxia type 7 (SCA‐7) is a neurodegenerative polyglutamine disease within the family of spinocerebellar ataxias. Classically SCA7 is a disease of ataxia and vision loss. However, patients with SCA also have difficulty breathing, swallowing, coughing and maintaining a stable open airway which often result in fatal respiratory failure. While respiratory measures have been reported in other SCA mouse models, ventilation in a SCA‐7 mouse has not yet been studied. Using the SCA‐7 mouse model (Atxn7266Q/+) we sought to characterize the respiratory pathology of SCA‐7.Whole body plethysmography (WBP) was used to assess respiratory dysfunction in the Atxn7266Q/+ mouse both at baseline breathing (FiO2: 0.21; nitrogen balance) and during a hypercapnic and hypoxic challenge (Fi:CO2: 0.07, FiO2: 0.10; nitrogen balance). Neurobehavioral testing and strength was assessed using the inverted screen test and the grip strength test. Post mortem histological analysis was performed on the phrenic and hypoglossal motor neurons and nerves.At 4 weeks of age, the SCA‐7 mice are indistinguishable from their unaffected littermates. However, by 8 weeks of age, SCA‐7 mice perform poorly on both neurobehavioral and strength tests as compared to their WT littermates. 50% of the SCA‐7 mice died by 9 weeks, while littermate controls thrived. SCA‐7 mice have elevated respiratory rate at baseline, as well as reduced tidal volume, minute ventilation, peak inspiratory flow, peak expiratory flow, and inspiratory time during the respiratory challenge. These results indicate that the SCA‐7 mice have respiratory dysfunction. To understand the respiratory deficits, ongoing studies are histologically analyzing the diaphragm neuromuscular junction, phrenic and hypoglossal nerves, as well as phrenic and hypoglossal motor nuclei. Preliminary nerve analysis of the hypoglossal and phrenic nerves reveals significant axonal pathology. In conclusion, WBP analysis and preliminary histological nerve data reveals respiratory dysfunction in the Atxn7266Q/+ mouse model.Support or Funding Information Funding: R01 HD099486‐01; 1R21NS098131‐01

Barrier Protection Measures for the Management of Allergic Rhinitis: A Systematic Review and Meta-analysis

Pharmacotherapy for allergic rhinitis (AR) still remains unsatisfying regarding its effect and safety. Barrier protection measures may be a good choice for the patients with AR. To assess the efficacy and safety of barrier protection measures in the treatment of AR. We selected relevant randomized controlled trials published between January 1, 1990, and February 20, 2019, by searching Embase, PubMed, Cochrane, Web of Knowledge, and ClinicalTrials.gov. The primary outcome for this analysis was rhinitis symptom scores, overall quality of life, nasal peak inspiratory flow (NPIF), and adverse events. Differences were expressed as weighted mean difference (WMD) with 95% confidence intervals (CIs) for continuous outcomes. Statistical heterogeneity across trials was assessed with the statistic (P < .1) and the I2 statistic. Fifteen RCTs (with data for 1154 participants) satisfied our inclusion criteria. The types of barrier protection measures comprised cellulose, pollen blocker cream, microemulsion, and nasal filter. To reduce the potential risk of bias and heterogeneity, we carried out subgroup analysis according to different types of barrier protection measures (cellulose: WMD = -2.18, 95% CI, -3.01 to -1.35, P < .00001; pollen blocker cream: WMD = -4.55, 95% CI, -6.10 to -3.00, P < .00001; microemulsion: WMD = -0.22, 95% CI, -0.42 to -0.03, P = .03). Findings from our meta-analysis show that, compared with placebo, barrier protection measures can yield improved symptomatic control for AR, with no increase in adverse events. Furthermore, barrier protection measures can improve the quality of life and NPIF. Although further studies are still needed, our findings clearly lend support to barrier protection measures as a safe and efficacious option for the treatment of AR patients.