Plethysmographic assessment of tidal expiratory flow limitation.

Chronic obstructive pulmonary disease (COPD) patients often experience tidal expiratory flow-limitation (tEFL), a condition causing respiratory and cardiovascular detrimental effects. As the appearance of tEFL should increase expiratory (Rexp) relative to inspiratory (Rins) resistance, we hypothesized that Rexp/Rins can be used to detect tEFL. Rexp/Rins was measured with a commercial plethysmograph in 109 healthy subjects and, before and after bronchodilation (BD), in 64 COPD patients, 36 with and 28 without tEFL according to the NEP technique. Before BD, the median (interquartile range) of Rexp/Rins was significantly greater (P < 0.001) in COPD patients with tEFL (2.47(3.06;7.07)) than in COPD patients without tEFL (1.63(1.44;1.82)) and in healthy subjects (1.52(1.35;1.62)). In COPD patients Rexp/Rins above 1.98 predicted the presence of tEFL with 96 % specificity and 92 % sensitivity, Rexp2/Rins performing even better. After BD the predictive ability of Rexp/Rins slightly declined, but remained elevated. The non-invasive measurement of Rexp/Rins is an easy, inexpensive, routinely usable method to detect tEFL in spontaneously breathing COPD subjects.

Modelling aerosol-based exposure to SARS-CoV-2 by an agent based Monte Carlo method: Risk estimates in a shop and bar.

Present day risk assessment on the spreading of airborne viruses is often based on the classical Wells-Riley model assuming immediate mixing of the aerosol into the studied environment. Here, we improve on this approach and the underlying assumptions by modeling the space-time dependency of the aerosol concentration via a transport equation with a dynamic source term introduced by the infected individual(s). In the present agent-based methodology, we study the viral aerosol inhalation exposure risk in two scenarios including a low/high risk scenario of a "supermarket"/"bar". The model takes into account typical behavioral patterns for determining the rules of motion for the agents. We solve a diffusion model for aerosol concentration in the prescribed environments in order to account for local exposure to aerosol inhalation. We assess the infection risk using the Wells-Riley model formula using a space-time dependent aerosol concentration. The results are compared against the classical Wells-Riley model. The results indicate features that explain individual cases of high risk with repeated sampling of a heterogeneous environment occupied by non-equilibrium concentration clouds. An example is the relative frequency of cases that might be called superspreading events depending on the model parameters. A simple interpretation is that averages of infection risk are often misleading. They also point out and explain the qualitative and quantitative difference between the two cases-shopping is typically safer for a single individual person.

A new approach to improve the hemodynamic assessment of cardiac function independent of respiratory influence.

Cardiovascular and respiratory systems are anatomically and functionally linked; inspiration produces negative intrathoracic pressures that act on the heart and alter cardiac function. Inspiratory pressures increase with heart failure and can exceed the magnitude of ventricular pressure during diastole. Accordingly, respiratory pressures may be a confounding factor to assessing cardiac function. While the interaction between respiration and the heart is well characterized, the extent to which systolic and diastolic indices are affected by inspiration is unknown. Our objective was to understand how inspiratory pressure affects the hemodynamic assessment of cardiac function. To do this, we developed custom software to assess and separate indices of systolic and diastolic function into inspiratory, early expiratory, and late expiratory phases of respiration. We then compared cardiac parameters during normal breathing and with various respiratory loads. Variations in inspiratory pressure had a small impact on systolic pressure and function. Conversely, diastolic pressure strongly correlated with negative inspiratory pressure. Cardiac pressures were less affected by respiration during expiration; late expiration was the most stable respiratory phase. In conclusion, inspiration is a large confounding influence on diastolic pressure, but minimally affects systolic pressure. Performing cardiac hemodynamic analysis by accounting for respiratory phase yields more accuracy and analytic confidence to the assessment of diastolic function.

Assessing Young Adults' ENDS Use via Ecological Momentary Assessment and a Smart Bluetooth Enabled ENDS Device.

INTRODUCTION: The assessment of electronic nicotine delivery systems (ENDS) use poses unique challenges that go beyond established assessment methods for tobacco cigarettes. Recent studies have proposed using ecological momentary assessment (EMA), a method to collect self-reported data on mobile devices, or data passively collected by "smart" Bluetooth enabled ENDS to assess use. The current study sought to compare ENDS use data using EMA and puff counts collected from a smart device. AIMS AND METHODS: We recruited 18 young adult ENDS users (age M = 23.33; 44.4% female) from the San Francisco Bay Area. For a total of 30 days, participants completed daily diaries by EMA and used a second-generation smart Bluetooth enabled ENDS that collected puff data. Repeated measures correlations, multilevel regressions, and paired t tests assessed concordance of EMA reports and ENDS data. A subset of four highly compliant participants were selected for sensitivity analyses. RESULTS: Among all 18 participants, completion of EMA daily diaries was high (77.4%). The ENDS device collected approximately twice as many puffs per day as participants reported. Compared with self-reported number of sessions and amount of e-liquid used, self-reported puff counts had the highest correlation with device-collected puff counts (rrm = 0.49; p < .001). Correlations between self-reported and device-collected puff counts improved among the subset of four highly compliant participants (rrm = 0.59; p < .001). CONCLUSIONS: Self-reports potentially underestimate use of ENDS. Puff counts appear to be the best self-reported measure to assess ENDS use compared with number of sessions or liquid volume. IMPLICATIONS: The comparison of EMA self-reports and passively collected ENDS device data can inform future efforts to assess ENDS use. Self-reported puff counts are preferable over number of sessions or amount of liquid used, but compared with objective usage data, self-reported puff counts may still underestimate actual use. ENDS use behavior is likely higher than users estimate and report. Future research on improved measures of ENDS use is needed.

Early Inspiratory Effort Assessment by Esophageal Manometry Predicts Noninvasive Ventilation Outcome in De Novo Respiratory Failure. A Pilot Study.

Rationale: The role of inspiratory effort still has to be determined as a potential predictor of noninvasive mechanical ventilation (NIV) failure in acute hypoxic de novo respiratory failure.Objectives: To explore the hypothesis that inspiratory effort might be a major determinant of NIV failure in these patients.Methods: Thirty consecutive patients with acute hypoxic de novo respiratory failure admitted to a single center and candidates for a 24-hour NIV trial were enrolled. Clinical features, tidal change in esophageal pressure (ΔPes), tidal change in dynamic transpulmonary pressure (ΔPl), expiratory Vt, and respiratory rate were recorded on admission and 2-4 to 12-24 hours after NIV start and were tested for correlation with outcomes.Measurements and Main Results: ΔPes and ΔPes/ΔPl ratio were significantly lower 2 hours after NIV start in patients who successfully completed the NIV trial (n = 18) compared with those who needed endotracheal intubation (n = 12) (median [interquartile range], 11 [8-15] cm H2O vs. 31.5 [30-36] cm H2O; P < 0.0001), whereas other variables differed later. ΔPes was not related to other predictors of NIV failure at baseline. NIV-induced reduction in ΔPes of 10 cm H2O or more after 2 hours of treatment was strongly associated with avoidance of intubation and represented the most accurate predictor of treatment success (odds ratio, 15; 95% confidence interval, 2.8-110; P = 0.001 and area under the curve, 0.97; 95% confidence interval, 0.91-1; P < 0.0001).Conclusions: The magnitude of inspiratory effort relief as assessed by ΔPes variation within the first 2 hours of NIV was an early and accurate predictor of NIV outcome at 24 hours.Clinical trial registered with www.clinicaltrials.gov (NCT03826797).

Low-cost, easy-to-build noninvasive pressure support ventilator for under-resourced regions: open source hardware description, performance and feasibility testing.

AIM: Current pricing of commercial mechanical ventilators in low-/middle-income countries (LMICs) markedly restricts their availability, and consequently a considerable number of patients with acute/chronic respiratory failure cannot be adequately treated. Our aim was to design and test an affordable and easy-to-build noninvasive bilevel pressure ventilator to allow a reduction in the serious shortage of ventilators in LMICs. METHODS: The ventilator was built using off-the-shelf materials available via e-commerce and was based on a high-pressure blower, two pressure transducers and an Arduino Nano controller with a digital display (total retail cost <75 USD), with construction details provided open source for free replication. The ventilator was evaluated, and compared with a commercially available device (Lumis 150 ventilator; Resmed, San Diego, CA, USA): 1) in the bench setting using an actively breathing patient simulator mimicking a range of obstructive/restrictive diseases; and b) in 12 healthy volunteers wearing high airway resistance and thoracic/abdominal bands to mimic obstructive/restrictive patients. RESULTS: The designed ventilator provided inspiratory/expiratory pressures up to 20/10 cmH2O, respectively, with no faulty triggering or cycling; both in the bench test and in volunteers. The breathing difficulty score rated (1-10 scale) by the loaded breathing subjects was significantly (p<0.005) decreased from 5.45±1.68 without support to 2.83±1.66 when using the prototype ventilator, which showed no difference with the commercial device (2.80±1.48; p=1.000). CONCLUSION: The low-cost, easy-to-build noninvasive ventilator performs similarly to a high-quality commercial device, with its open-source hardware description, which will allow for free replication and use in LMICs, facilitating application of this life-saving therapy to patients who otherwise could not be treated.

Fluoroscopic and radiographic assessment of variations in tracheal height during inspiration and expiration in healthy adult small-breed dogs.

The objective of this study was to document tidal variations in tracheal height during normal respiration in 19 healthy adult (> 1 y old) small-breed dogs (< 10 kg) using fluoroscopy and radiography. Each dog underwent tracheal fluoroscopic examination on inspiration and expiration while in a standing position (F-S) and in right lateral recumbency (F-RL), followed by radiographic projections obtained in right lateral recumbency. The percent variation in tracheal height during maximal inspiration and expiration was determined at 3 different locations [cervical region (CR), thoracic inlet (TI), and intrathoracic (IT) region]. When all imaging procedures and sites of measurement were considered, tracheal height varied during physiologic inspiration and expiration from 0% to 21.1%, with a mean of 4.5%. The mean percent variation in tracheal height was not significantly different among imaging modalities (F-S versus F-RL versus radiography) (P = 0.16) or measurement sites (CR versus TI versus IT) (P = 0.89). The body condition score (BCS) (P = 0.96), age (P = 0.95), and breed (P = 0.19) did not significantly influence the mean percent variation in tracheal height. The average variation in tracheal height during maximal physiological inspiration and expiration is small (< 6%) in most healthy adult small-breed dogs as assessed by fluoroscopy and radiography, although tracheal height may vary by as much as 21.1% in some healthy individuals. Inspiratory and expiratory radiographs acquired in right lateral recumbency provide an accurate assessment of tracheal height as an alternative to fluoroscopy.

L'objectif de la présente étude était de documenter les variations de la hauteur de la trachée durant la respiration normale chez 19 chiens adulte en santé (> 1 an) de petites races (< 10 kg) à l'aide de la fluoroscopie et de la radiographie. Chaque chien a été soumis à un examen fluoroscopique de la trachée lors de l'inspiration et de l'expiration alors qu'il était en position debout (F-S) et en décubitus latéral droit (F-RL), suivi d'images radiographiques obtenues en décubitus latéral droit. Le pourcentage de variation de la hauteur de la trachée durant l'inspiration et l'expiration maximales fut déterminé à trois endroits différents [région cervicale (CR), l'entrée thoracique (TI), et la région intrathoracique (IT)]. Lorsque toutes les procédures d'imagerie et les sites de mesure étaient considérés, la hauteur de la trachée variait durant l'inspiration et l'expiration physiologique de 0 % à 21,1 %, avec une moyenne de 4,5 %. Le pourcentage de variation moyen de la hauteur de la trachée n'était pas significativement différent parmi les différentes modalités d'imagerie (F-S versus F-RL versus radiographie) (P = 0,16) ou les sites de mesure (CR versus TI versus IT) (P = 0,89). Le score de condition corporelle (BCS) (P = 0,96), l'âge (P = 0,95), et la race (P = 0,19) n'influençaient pas significativement le pourcentage de variation moyen de la hauteur de la trachée. La variation moyenne de la hauteur de la trachée durant l'inspiration et l'expiration physiologique maximale est petite (< 6 %) chez la plupart des chiens adultes de petites races en santé telle qu'évalué par fluoroscopie et radiographie, bien que la hauteur de la trachée puisse varier jusqu'à 21,1 % chez certains individus en santé. Les radiographies à l'inspiration et à l'expiration obtenues en décubitus latéral droit fournissent une évaluation précise de la hauteur de la trachée comme alternative à la fluoroscopie.(Traduit par Docteur Serge Messier).

Ultrashort Echo-Time MRI for the Assessment of Tracheomalacia in Neonates.

BACKGROUND: Bronchoscopy is the gold standard for evaluating tracheomalacia; however, reliance on an invasive procedure limits understanding of normal airway dynamics. Self-gated ultrashort echo-time MRI (UTE MRI) can assess tracheal dynamics but has not been rigorously evaluated. METHODS: This study was a validation of UTE MRI diagnosis of tracheomalacia in neonates using bronchoscopy as the gold standard. Bronchoscopies were reviewed for the severity and location of tracheomalacia based on standardized criteria. The percent change in cross-sectional area (CSA) of the trachea between end-inspiration and end-expiration was determined by UTE MRI, and receiver-operating curves were used to determine the optimal cutoff values to predict tracheomalacia and determine positive and negative predictive values. RESULTS: Airway segments with tracheomalacia based on bronchoscopy had a more than threefold change in CSA measured from UTE MRI (54.4 ± 56.1% vs 14.8 ± 19.5%; P < .0001). UTE MRI correlated moderately with bronchoscopy for tracheomalacia severity (ρ = 0.39; P = .0001). Receiver-operating curves, however, showed very good ability of UTE MRI to identify tracheomalacia (area under the curve, 0.78). A "loose" definition (> 20% change in CSA) of tracheomalacia had good sensitivity (80%) but low specificity (64%) for identifying tracheomalacia based on UTE MRI, whereas a "strict" definition (> 40% change in CSA) was poorly sensitive (48%) but highly specific (93%). CONCLUSIONS: Self-gated UTE MRI can noninvasively assess tracheomalacia in neonates without sedation, ionizing radiation, or increased risk. This technique overcomes major limitations of other diagnostic modalities and may be suitable for longitudinal population studies of tracheal dynamics.

Quality of life, anxiety and depression in head and neck cancer patients: a randomized clinical trial / Calidad de vida, ansiedad y depresión de pacientes con cáncer de cabeza y cuello: estudio clínico randomizado / Qualidade de vida, ansiedade e depressão de pacientes com câncer de cabeça e pescoço: estudo clínico randomizado

Abstract OBJECTIVE To evaluate an educational program based on the principles of self-management with a conventional educational program through quality of life, anxiety and depression instruments within 12 months of starting cancer treatment. METHOD An experimental, randomized, controlled study conducted with head and neck cancer patients treated at a university hospital in the city of São Paulo, Brazil. Patients were randomly divided into two groups: the control group submitted to the conventional educational plan, and the experimental group submitted to the educational plan for self-management. Descriptive and analytical statistics were used for the analyzes using the t-test, Fischer's exact test and Repeated Measures ANOVA. RESULTS Twenty (20) patients were selected. Most participants were male, in advanced stages of disease and undergoing three therapeutic modalities. The control group showed a gradual decrease in quality of life scores during treatment, while the experimental group progressively increased. The correlation was significant between the presence of anxiety and depression symptoms and poor quality of life. Patients in the control group had a significant worsening in social/family well-being (P = 0.02) and the prevalence of additional head and neck cancer-related additional concerns (P = 0.01), while the experimental group had reduced anxiety symptoms (P = 0.001) and improved emotional well-being (P = 0.01). CONCLUSION The educational intervention based on building self-management skills favored quality of life and reduced anxiety and depression. Brazilian Registry of Clinical Trials (RBR 2q53ct).

Resumen OBJETIVO Evaluar un programa educativo basado en los principios de la autogestión con programa educativo convencional, mediante instrumentos de calidad de vida, ansiedad y depresión en período de 12 meses transcurridos desde el inicio del tratamiento. MÉTODO Estudio experimental, randomizado controlado, llevado a cabo con pacientes con cáncer de cabeza y cuello, tratados en hospital universitario del municipio de São Paulo. Los pacientes fueron divididos aleatoriamente en dos grupos: grupo control, sometido al plan educativo convencional, y grupo experimento, sometido al plan educativo para la autogestión. Para los análisis se empleó estadística descriptiva y analítica, utilizándose la prueba t, la prueba exacta de Fischer y ANOVA de Medidas Repetidas. RESULTADOS Fueron seleccionados 20 pacientes. La mayoría de los participantes fue del sexo masculino, en estadíos avanzados de enfermedad y sometidos a tres modalidades terapéuticas. El grupo control presentó caída gradual de los scores de calidad de vida en el trascurso del tratamiento, mientras que el grupo experimento incrementó progresivamente. La correlación fue significativa entre la presencia de síntomas de ansiedad y depresión y la baja calidad de vida. Pacientes del grupo control presentaron empeoramiento significativo del bienestar social/familiar (P = 0,02) y de la prevalencia de preocupaciones adicionales relacionadas con el cáncer de cabeza y cuello (P = 0,01), mientras que el grupo experimento presentó reducción de los síntomas de ansiedad (P = 0,001) y mejora del bienestar emotivo (P = 0,01). CONCLUSIÓN La intervención educativa basada en la construcción de habilidades para la autogestión favoreció la calidad de vida y redujo la ansiedad y la depresión. Registro Brasileño de Ensayos Clínicos (RBR 2q53ct).

Resumo OBJETIVO Avaliar um programa educativo baseado nos princípios do autogerenciamento com programa educativo convencional, por meio de instrumentos de qualidade de vida, ansiedade e depressão em período de 12 meses transcorridos do início do tratamento. MÉTODO Estudo experimental, randomizado, controlado, realizado com pacientes com câncer de cabeça e pescoço, tratados em hospital universitário do município de São Paulo. Os pacientes foram divididos aleatoriamente em dois grupos: grupo controle, submetido ao plano educativo convencional, e grupo experimento, submetido ao plano educativo para o autogerenciamento. Para as análises empregaram-se estatísticas descritiva e analítica, utilizando-se o teste t, o teste exato de Fischer e ANOVA de Medidas Repetidas. RESULTADOS Foram selecionados 20 pacientes. A maioria dos participantes foi do sexo masculino, em estádios avançados de doença e submetidos a três modalidades terapêuticas. O grupo controle apresentou queda gradual dos escores de qualidade de vida no transcorrer do tratamento, enquanto o grupo experimento aumentou progressivamente. A correlação foi significativa entre a presença de sintomas de ansiedade e depressão e baixa qualidade de vida. Pacientes do grupo controle apresentaram piora significativa do bem-estar social/familiar (P = 0,02) e da prevalência de preocupações adicionais relacionadas ao câncer de cabeça e pescoço (P = 0,01), enquanto o grupo experimento apresentou redução dos sintomas de ansiedade (P = 0,001) e melhora do bem-estar emocional (P = 0,01). CONCLUSÃO A intervenção educativa pautada na construção de habilidades para o autogerenciamento favoreceu a qualidade de vida e reduziu a ansiedade e a depressão. Registro Brasileiro de Ensaios Clínicos (RBR 2q53ct).

Assessment of Central Drive to the Diaphragm by Twitch Interpolation: Normal Values, Theoretical Considerations, and Future Directions.

BACKGROUND: The twitch interpolation technique is a promising tool for assessing central drive to the diaphragm. It is used to quantify the degree of voluntary diaphragm activation during predefined breathing maneuvers. OBJECTIVES: This study was designed to (a) determine reference values for the level of voluntary activation of the diaphragm using the twitch occlusion technique in healthy adults and (b) explore the association between central drive to the diaphragm and volitional tests of respiratory muscle strength. METHODS: Twenty-seven healthy volunteers aged 26 ± 14 years (18 male) were enrolled. Twitch transdiaphragmatic pressure (Pdi) was determined at relaxed functional residual capacity in response to cervical magnetic stimulation (CMS) of the phrenic nerves. The subjects were then instructed to gradually increase voluntary activation of the diaphragm, and the effects of superimposed magnetic stimuli on voluntary Pdi were assessed. RESULTS: The twitch Pdi amplitude following CMS linearly decreased with increasing inspiratory effort. The resulting diaphragm voluntary activation index (DVAI) during maximal voluntary contraction was 75 ± 15% irrespective of gender or age. Twitch duration, half relaxation time, and area under the curve of superimposed Pdi deflections did not show a linear but an exponential association with increasing voluntary activation of the diaphragm. More than 2/3 of the decrease in the above values was evident after 1/3 of voluntary diaphragm contraction. Forced vital capacity (FVC) was inversely correlated with the DVAI. CONCLUSIONS: Twitch interpolation allows for assessment of central drive to the diaphragm. The maximum DVAI is independent of gender or age, and significantly related to FVC but not to maximum inspiratory pressure or Pdi as direct measures of diaphragm strength.

Beyond inspiratory muscle strength: Clinical utility of single-breath work capacity assessment in veterans with COPD.

BACKGROUND: Inspiratory muscle function in COPD has been traditionally described in terms of maximal inspiratory pressure (MIP). Arguably, however, is the day-to-day relevance of MIP, given that individuals rarely need maximal inspiratory forces to perform general tasks, but rather repeated breathing muscle contractions which demand endurance. The sustained maximal inspiratory pressure (SMIP) reflects the ability of the respiratory muscles to maintain force over time (i.e. single-breath work capacity). We investigated the relationships between SMIP and COPD-related clinical outcomes, hypothesizing that SMIP would have superior correlational and discriminatory value when compared to MIP. METHODS: 61 males with mild-to-very severe airflow obstruction underwent measures of spirometry, whole-body plethysmography, symptomatology, comorbidity, quality of life, exacerbations and mental health. MIP and SMIP were obtained via the Test of Incremental Respiratory Endurance. RESULTS: The mean ±â€¯SD MIP and SMIP were 77.2 ±â€¯22.9 cmH2O and 407.9 ±â€¯122.8 PTU. Both MIP and SMIP positively correlated with pulmonary function, with SMIP displaying the highest correlations. We found significant differences in spirometry, hyperinflation, symptomatology, exacerbation frequency, comorbidity, quality of life and anxiety in subjects grouped as having reduced or normal single-breath work capacity. Finally, significantly lower SMIP values were found in individuals with an IC/TLC ratio ≤25%. CONCLUSIONS: The assessment of SMIP appears to have superior clinical value than MIP in COPD. Our analyses revealed that subjects whose SMIP was reduced experienced more severe airflow obstruction, greater hyperinflation, as well as worse health and mental status with increased symptomatology and impaired quality of life.

Assessment of Maximum Dynamic Inspiratory Pressure.

BACKGROUND: Inspiratory muscle strength has been considered an important marker of ventilatory capacity and a predictor of global performance. A new tool has become available for dynamically evaluating the maximum inspiratory pressure (the S-Index). However, the proper assessment of this parameter needs to be determined. Thus, the aim of the present study was to investigate the number of inspiratory maneuvers necessary to reach a maximum and reliable S-Index and the influence of inspiratory muscle warm-up on this assessment. METHOD: We performed a retrospective study from the database of 432 healthy subjects who underwent S-Index tests and inspiratory muscle warm-up or sham. The effect of repeated maneuvers on the S-Index and the impact of inspiratory muscle warm-up were analyzed by using the intraclass correlation coefficient and unpaired t test. RESULTS: We analyzed 81 subjects, (55% men), mean ± SD age 38.1 ± 9.6 y, 43 subjects in the inspiratory muscle warm-up group. Maximum and reliable S-Indexes were reached at the eighth maneuver in both groups preceding inspiratory muscle warm-up or sham, 102 cm H2O (95% CI 95-109 cm H2O); intraclass correlation coefficient 0.96; P < .001. Only the inspiratory muscle warm-up group presented a significant increase in the S-Index after warm-up, 13.5 cm H2O (95% CI 10-17), P < .001. CONCLUSIONS: Eight maneuvers were necessary to reach maximum and reliable values of the S-Index preceding inspiratory muscle warm-up or sham. Moreover, inspiratory muscle warm-up preceding S-Index assessment improved inspiratory muscle performance.

Assessment of the Power Required for Optimal Use of Current Inhalation Devices.

Background: Inhalation of medications is the cornerstone in the treatment of patients with lung diseases. A variety of inhalation devices exists and each device has specific requirements to achieve optimum inhalation of the drug. The goal of this study was to establish a clear overview on performance requirements of standard inhalation devices that should be met by the patient's breathing power and to develop a new method to measure the individual performance data. Materials and Methods: An optimum and still acceptable required breathing power (P in watts) was calculated for each device with the aid of individual device flow rates (determined by a literature search) and the flow resistances (by measuring the pressure drop over the different inhalation devices). For the in vivo part of the study, peak inspiratory flow and peak inspiratory pressure drop were measured in 21 adult patients with asthma or chronic obstructive pulmonary disease and healthy volunteers and the peak inspiratory power (PIPO in watts) was calculated. Results: Nearly no power is needed to achieve optimum results when using pressurized metered dose inhalers. For dry powder inhalers, the required power depends on the specific inhalation device. Conclusions: Inhalation devices impose differing demands on the inspiratory breathing power of patients. To ensure adequate use of the different devices, a cheap and simple assessment of patients' PIPO may be one option.

Cost-utility analysis of an intervention designed to reduce the critical handling error of insufficient inspiratory effort.

OBJECTIVES: Up to 70-80% of patients use inhalers incorrectly. Dry-powder inhalers (DPIs) require forceful inhalation for optimal delivery, and approximately 40% of Global Initiative for Asthma (GINA)-defined Step-3+ patients inhale corticosteroid and long-acting beta-agonist through DPIs. The CRITIKAL study (Price et al. in J Allergy Clin Immunol Pract 5:1071-e9-1081-e9, 2017) found a statistically significant association between 'insufficient inspiratory effort' error and increased risk of uncontrolled asthma and hospitalisation-requiring exacerbations. This paper explores the cost-effectiveness of an error-targeted intervention. METHODS: A probabilistic Markov cost-utility model simulated patients transitioning between controlled and uncontrolled health states over one year. Odds ratios (ORs, from the CRITIKAL study) of a patient having uncontrolled asthma conditional on making the error were applied to baseline transition probabilities sourced from the literature, both indirectly via an adjustment formula (Zhang et al. in JAMA 280:1690-1691, 1998) and directly by assuming OR approximates relative risk (RR). The analysis explored complete/partial eradication of the error when the intervention was priced to match comparators, as well as impact of indirect costs based on lost/reduced productivity. RESULTS: The intervention dominated both DPI comparators over one year, with direct cost savings of £45/£86 with 0.0053/0.0102 additional quality-adjusted life years (QALYs), and had the highest probability of being cost-effective at a £20,000/QALY threshold. Key factors driving variance were weekly utilities per state and RR of moving to an uncontrolled state. CONCLUSION: The analysis demonstrated the economic and societal costs of 'insufficient inspiratory effort' and potential economic benefits of introducing an effective intervention to reduce/eradicate this error. Further research should assess the economic impact of other handling errors.

Bronchiolitis obliterans murine model induced by nitric acid aerosol inhalation: An economical and reproducible model.

PURPOSE: Bronchiolitis obliterans (BO) is a highly debilitative and fatal syndrome associated with a series of severe lower airway disorders. The pathogenesis of BO is complicated and not entirely understood. An appropriate animal model of BO may aid research into its pathogenesis. Here, we establish a mouse model of BO to provide insight into this disease. MATERIALS AND METHODS: 6-8 week old BABL/c mice were exposed to 5% nitric acid (NA) aerosol through a nebulizer for 3 hours, and controls were exposed to distilled water instead. Symptoms, airway resistance and pathological process were observed dynamically. The levels of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), 8-isoprostane and myeloperoxidase (MPO) in lung tissue and bronchoalveolar lavage fluids (BLAF) were determined by ELISA on day 3, 7, 14, 28 and 56 after the aerosol nebulization. RESULTS: Typical BO lesions were observed in NA nebulized mice characterized histologically by initial necrotizing bronchiolitis and final airway fibrosis at day 28 after the aerosol nebulization. NA nebulized mice also exhibited labored breathing and significantly increased airway resistance. Expression of MMP-2, MMP-9, TIMP-1, 8-isoprostane and MPO were significantly elevated in NA nebulized mice in different time frame. CONCLUSION: A murine BO model was established by NA aerosol inhalation. It provides an easy, economic, and reproducible mice model for BO research.

Health Risk Assessment on Hazardous Ingredients in Household Deodorizing Products.

The inhalation of a water aerosol from a humidifier containing disinfectants has led to serious lung injuries in Korea. To promote the safe use of products, the Korean government enacted regulations on the chemicals in various consumer products that could have adverse health effects. Given the concern over the potential health risks associated with the hazardous ingredients in deodorizing consumer products, 17 ingredients were analyzed and assessed according to their health risk on 3 groups by the application type in 47 deodorizing products. The risk assessment study followed a stepwise procedure (e.g., collecting toxicological information, hazard identification/exposure assessment, and screening and detailed assessment for inhalation and dermal routes). The worst-case scenario and maximum concentration determined by the product purpose and application type were used as the screening assessment. In a detailed assessment, the 75th exposure factor values were used to estimate the assumed reasonable exposure to ingredients. The exposed concentrations of seven ingredients were calculated. Due to limitation of toxicity information, butylated hydroxyl toluene for a consumer’s exposure via the dermal route only was conducted for a detailed assessment. This study showed that the assessed ingredients have no health risks at their maximum concentrations in deodorizing products. This approach can be used to establish guidelines for ingredients that may pose inhalation and dermal hazards.

A Device for the Quantification of Oxygen Consumption and Caloric Expenditure in the Neonatal Range.

BACKGROUND: The accurate measurement of oxygen consumption (VO2) and energy expenditure (EE) may be helpful to optimize the treatment of critically ill patients. However, current techniques are limited in their ability to accurately quantify these end points in infants due to a low VO2, low tidal volume, and rapid respiratory rate. This study describes and validates a new device intended to perform in this size range. METHODS: We created a customized device that quantifies inspiratory volume using a pneumotachometer and concentrations of oxygen and carbon dioxide gas in the inspiratory and expiratory limbs. We created a customized algorithm to achieve precise time alignment of these measures, incorporating bias flow and compliance factors. The device was validated in 3 ways. First, we infused a certified gas mixture (50% oxygen/50% carbon dioxide) into an artificial lung circuit, comparing measured with simulated VO2 and carbon dioxide production (VCO2) within a matrix of varying tidal volume (4-20 mL), respiratory rate (20-80 bpm), and fraction of inspired oxygen (0.21-0.8). Second, VO2, VCO2, and EE were measured in Sprague Dawley rats under mechanical ventilation and were compared to simultaneous Douglas bag collections. Third, the device was studied on n = 14 intubated, spontaneously breathing neonates and infants, comparing measured values to Douglas measurements. In all cases, we assessed for difference between the device and reference standard by linear regression and Bland-Altman analysis. RESULTS: In vitro, the mean ± standard deviation difference between the measured and reference standard VO2 was +0.04 ± 1.10 (95% limits of agreement, -2.11 to +2.20) mL/min and VCO2 was +0.26 ± 0.31 (-0.36 to +0.89) mL/min; differences were similar at each respiratory rate and tidal volume measured, but higher at fraction of inspired oxygen of 0.8 than at 0.7 or lower. In rodents, the mean difference was -0.20 ± 0.55 (-1.28 to +0.89) mL/min for VO2, +0.16 ± 0.25 (-0.32 to +0.65) mL/min for VCO2, and -0.84 ± 3.29 (-7.30 to +5.61) kcal/d for EE. In infants, the mean VO2 was 9.0 ± 2.5 mL/kg/min by Douglas method and was accurately measured by the device (bias, +0.22 ± 0.87 [-1.49 to +1.93] mL/kg/min). The average VCO2 was 8.1 ± 2.3 mL/kg/min, and the device exhibited a bias of +0.33 ± 0.82 (-1.27 to +1.94) mL/kg/min. Mean bias was +2.56% ± 11.60% of the reading for VO2 and +4.25% ± 11.20% of the reading for VCO2; among 56 replicates, 6 measurements fell outside of the 20% error range, and no patient had >1 of 4 replicates with a >20% error in either VO2 or VCO2. CONCLUSIONS: This device can measure VO2, VCO2, and EE with sufficient accuracy for clinical decision-making within the neonatal and pediatric size range, including in the setting of tachypnea or hyperoxia.

Assessment of inhalation flow patterns of soft mist inhaler co-prescribed with dry powder inhaler using inspiratory flow meter for multi inhalation devices.

The patients' inhalation flow pattern is one of the significant determinants for clinical performance of inhalation therapy. However, the development of inhalation flow meters for various inhalation devices has been unable to keep up with the increasing number of newly launched inhalation devices. In the present study, we developed simple attachment orifices for the inhalation flow pattern monitoring system, which are suitable for all commercial inhalers, and investigated the efficacy of the system on the clinical inhalation instruction for patients co-prescribed dry powder inhaler (DPI) and soft mist inhaler (SMI). First, we constructed simple attachment orifices that were adjusted for 13 commercial inhalers, and examined the correlation between orifice and inhalation device. Second, the inhalation flow patterns (peak inspiratory flow rate, PIFR; inhalation duration time, DT) of patients prescribed a combination of DPI and SMI were monitored before and after inhalation instruction. The inhalation resistance of commercial inhalers are listed in the following order; Twincaps® > Handihaler® > Swinghaler® = Clickhaler® > Twisthaler® > Turbuhaler® > Jenuair® > Diskus® = Ellipta® > Diskhaler® > Breezhaler® > Respimat® = pMDI. The pressure drop via orifice was significantly correlated with that via the commercial inhaler. For the confirmation, all participants achieved the DPI criterion of PIFR. On the other hand, 4 participants (6 clinical visits) of 10 experimented participants could not achieve the essential criterion of DT (> 1.5 sec) for SMI, but all participants improved their duration time after inhalation instruction by pharmacists (P<0.05). In the present study, we successfully developed simple attachment orifice suitable for 13 commercial inhalation devices. These data suggested that our simple attachment orifices for the inhalation flow pattern monitoring system can detect patients with inadequate inhalation patterns via SMI.