Inhalation Volume Research Articles

THE “MASS” PRODUCTION OF MARIJUANA

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Marijuana smoking is associated with various forms of acute and chronic lung injury with radiological findings ranging from diffuse alveolar hemorrhage to paraseptal emphysema.[1] These effects may be attributed to marijuana usage habits which include increased inhalation volumes, depths of inhalation, and breath-holding times.[1] Such maneuvers have increased risk of subpleural blebs and emphysematous changes compared to tobacco inhalation alone.[1] We report the finding of post traumatic hemorrhage into paraseptal emphysema in a chronic marijuana smoker mimicking a mass. CASE PRESENTATION: A 41-year-old male patient with history of extensive marijuana smoking presented complaining of cough. Two weeks prior, patient was in a motorbike accident. He was found to have bilateral pneumothoraces, multifocal pulmonary contusions, renal lacerations with perirenal hematoma, and multiple rib fractures requiring bilateral chest tubes. Chest radiograph 2 weeks later showed multiple lung masses. CT chest confirmed multiple lobular, soft tissue density masses in the periphery of the left lung. DISCUSSION: Inhalational marijuana use has a wide spectrum of presentation in the acute and chronic setting. Marijuana usage is associated with increased cough, sputum production, dyspnea, and wheezing.[1] Chronic use can result in emphysema, subpleural blebs, and lung cancer[1,2] The risk of lung cancer increases 8% for each joint year of cannabis smoking after adjusting for confounding variables including cigarette smoking.[2] The blebs and bullous disease from marijuana smoking may result in spontaneous pneumothoraces, pneumomediastinum, and alveolar hemorrhage in the acute setting.[1] In our case, mass-like lesions presented a broad differential diagnosis which included septic emboli, lung cancer (primary or metastatic), and infectious nodules. However, these masses were confirmed to have an acute onset and were not present on imaging from two weeks prior making lung cancer less likely. The masses also have the density of blood suggesting blood-filled bullae. These bullae could also be post-traumatic pneumatoceles, which have thin walls with fully circumferential lung parenchyma.[3] However, the bullae in this patient did not have surrounding lung parenchyma, favoring emphysematous changes secondary to marijuana. Overall, these findings are consistent with paraseptal hemorrhage into marijuana-induced emphysematous blebs. CONCLUSIONS: The occurrence of these unusual masquerading “masses” should be considered a deleterious structural effect of chronic marijuana smoking on pulmonary parenchyma. With the increasing popularity of marijuana as a result of its legalization, it is important that clinicians stay up to date with the pulmonary sequelae of inhalational marijuana use. Reference #1: Golwala, H. (2012). Marijuana abuse and bullous emphysema. Lung India, 29(1), 56-58. https://doi.org/10.4103/0970-2113.92365 Reference #2: Aldington, S., Harwood, M., Cox, B., Weatherall, M., Beckert, L., Hansell, A., . . . Respiratory Disease Research, G. (2008). Cannabis use and risk of lung cancer: a case-control study. Eur Respir J, 31(2), 280-286. https://doi.org/10.1183/09031936.00065707 Reference #3: Quigley, M. J., & Fraser, R. S. (1988). Pulmonary pneumatocele: pathology and pathogenesis. AJR Am J Roentgenol, 150(6), 1275-1277. https://doi.org/10.2214/ajr.150.6.1275 DISCLOSURES: No relevant relationships by Crystal Duran, source=Web Response No relevant relationships by Corey Garvin, source=Web Response No relevant relationships by jayanth keshavamurthy, source=Web Response No relevant relationships by Yasasvi Tadavarthi, source=Web Response No relevant relationships by Varsha Taskar, source=Web Response

Determination of emitted particle characteristics and upper airway deposition of Symbicort® Turbuhaler® dry powder inhaler

The mass median aerodynamic diameter (MMAD) of the particle ensemble released from Symbicort® Turbuhaler® dry powder inhaler and the aerosol particle volume size distribution in a realistic upper airway was studied experimentally, assuming different inhalation waveforms. The idealized waveforms were determined from the breathing parameters of 25 healthy voluntary adults who inhaled through a not activated Turbuhaler® device.The amount of particles available for lung deposition was quantified by numerical simulations with the help of the stochastic lung deposition model (SLDM). It was calculated that approximately 30% of the particles released from the DPI are deposited in the upper airway. The lung deposition of the drug from the DPI was calculated to be between 16% and 59% of the nominal dose. The peak inhalation flow and the inhalation volume were found to be the main factors affecting the efficiency of the deposition, the inhalation time has also a small effect on it.

Effect of Static Respiratory Volume on the Waveform of Cardiac-induced Sternal Vibrations.

Cardio-respiratory activity originating in the chest creates vibrations that diffuse through the organs to the thoracic wall. The vibrational waves were detected in all six degrees of freedom by an inertial motion sensor at the xiphoid process of the sternum. Vibrational cardiography (VCG) combines the detection of vibrations via acceleration, termed as seismocardiography, and gyration, termed as gyrocardiography. The objective of this study was to determine the effect of static respiration volume on the morphology of cardiac-induced waveforms in the VCG signal. In this study, 24 subjects were tested while holding breath at peak inhalation, and at peak exhalation. Ensemble averages of the waveforms showed larger variations in the signal when the lungs were inhaled for both the primary and secondary heart sounds. Inter-subject variability was accounted for by averaging all waveforms and calculating the root mean squared value over a sliding window of 60 milliseconds. The peak amplitudes of both heart sounds were consistently larger for high lung volumes. However, the ratio of primary to the secondary heart sound was found to be inversely proportional to lung volume. These opposing effects offer a strong analysis tool for the determination of relative inhalation volume using VCG morphology alone.

Inhaled salbutamol from aerolizer and diskus at different inhalation flows, inhalation volume and number of inhalations in both healthy subjects and COPD patients

The aim of the present study was to demonstrate the effect of inhalation-flow, inhalation-volume and number of inhalations on aerosol-delivery of inhaled-salbutamol from two different dry powder inhalers (DPIs) in both healthy-subjects and chronic obstructive pulmonary disease (COPD) patients. Relative pulmonary-bioavailability and systemic-bioavailability of inhaled-salbutamol, delivered by Diskus and Aerolizer, was determined in 24-COPD patients and 24-healthy subjects. The healthy-subjects and the COPD-patients participated in the study for 7 days in which they received 4 study doses of 200 μg salbutamol (one slow-inhalation, two slow-inhalations, one fast-inhalation, and two fast-inhalations) in four alternative days with 24 hr washout period after each dose. Two urine-samples were collected from each study subjects. The first was provided 30 min post inhalation (USAL0.5), as an index of relative pulmonary-bioavailability, and the second was pooled to 24 hr post inhalation (USAL24), as an index of systemic-bioavailability. Fast-inhalation resulted in significantly higher USAL0.5 and USAL24 than slow-inhalation (p < 0.05) after one-inhalation in both healthy-subjects and COPD-patients but there was no significant difference between slow and fast-inhalation after two-inhalations. One-inhalation resulted in significantly higher USAL0.5 and USAL24 in healthy-subjects compared to COPD-patient at both slow and fast-inhalation (p < 0.05) except USAL0.5 with Diskus at slow-inhalation there was no significant difference. Also, two-inhalations resulted in significantly higher USAL0.5 and USAL24 compared to one-inhalation at slow-inhalation only (p < 0.05). No significant difference was found between Aerolizer and Diskus except in USAL0.5 of one slow-inhalation in both health-subjects and COPD-patients (p = 0.048 and 0.047, respectively). Device-formula relation is present at low inhalation-flow since Diskus resulted in significantly higher USAL0.5 and USAL24 in healthy-subjects compared to COPD-patient at slow inhalation than Aerolizer. It is essential to inhale-twice and as hard and deep as possible from each dose when using DPI especially with COPD-patients having poor inspiratory efforts such as elderly patients and children.

What to consider before prescribing inhaled medications: a pragmatic approach for evaluating the current inhaler landscape.

Inhaled therapies are the cornerstone of treatment in asthma and chronic obstructive pulmonary disease, and there are a multitude of devices available. There is, however, a distinct lack of evidence-based guidance for healthcare providers on how to choose an appropriate inhaler. This review aims to summarise recent updates on topics related to inhaler choice, and to offer practical considerations for healthcare providers regarding currently marketed devices. The importance of choosing the right inhaler for the right patient is discussed, and the relative merits of dry powder inhalers, pressurised metered dose inhalers, breath-actuated pressurised metered dose inhalers, spacers and soft mist inhalers are considered. Compiling the latest studies in the devices therapy area, this review focuses on the most common types of handling errors, as well as the comparative rates of incorrect inhalation technique between devices. The impact of device-specific handling errors on inhaler performance is also discussed, and the characteristics that can impair optimal drug delivery, such as inhalation flow rate, inhalation volume and particle size, are compared between devices. The impact of patient perceptions, behaviours and problems with inhalation technique is analysed, and the need for appropriate patient education is also highlighted. The continued development of technology in inhaler design and the need to standardise study assessment, endpoints and patient populations are identified as future research needs.The reviews of this paper are available via the supplemental material section.

Effect of Human Error, Inhalation Flow, and Inhalation Volume on Dose Delivery from Ellipta® Dry-Powder Inhaler

Ellipta® is a new dry-powder inhaler (DPI), with medium flow resistance. The present study aimed to evaluate Ellipta® dose preparation and inhalation technique and determine the effect of human factor, inhalation flow, and inhalation volume on total emitted dose (TED). Two-hundred obstructive lung disease patients were asked to load Ellipta® dose and inhale from placebo Ellipta®, without receiving counseling (first attempt). They were divided into patients who previously used DPI (100 patients) and others who never used DPI before (100 patients). Secondly, TED of single-loaded dose from Relvar-Ellipta® was determined at different inhalation flows (20, 40, and 60 L/min) and inhalation volumes (2 and 4 L). TED was also determined after loading the dose twice at inhalation flows of 40 and 60 L/min and inhalation volume of 4 L. Doses were prepared while Ellipta® is in upright and horizontal positions. The number of handling errors performed by patients who previously used DPI was lower compared to others who never used DPI before. No significant difference was found between TEDs of 40 and 60 L/min inhalation flow at 2 or 4 L inhalation volume when loading Ellipta®, once or twice, in an upright or horizontal position. TED at inhalation flow of 20 L/min was significantly lower than at 40 and 60 L/min (p < 0.001). A 4-L inhalation volume significantly increased TED than 2 L/min only at inhalation flow of 20 L/min (p = 0.001). Ellipta® is a consistent DPI. It can be used to deliver inhaled medication at a flow of ≥ 40 L/min without fear of not receiving the needed dose. It does not allow delivering double dosing.

Metal emissions from e-cigarettes: a risk assessment analysis of a recently-published study

Introduction: A recent study reported levels of metal emissions in e-cigarette (EC) aerosol. Herein we present a risk assessment analysis of the published findings using total daily exposure limits.Methods: Median and 75th percentile metal concentrations in EC aerosols were used to determine the level of daily liquid consumption (g/d) that would exceed the permissible daily exposures (PDEs) defined for inhalation medications (cadmium, chromium, copper, nickel, lead, antimony and tin). For metals not having PDEs, minimal risk levels (manganese) or risk exposure levels (aluminum, iron and zinc) were converted into total daily exposure using an inhalation volume of 20 m3 (for 24 h) and 6.7 m3 (for 8 h) respectively.Results: The lowest amount of liquid consumption exceeding safety limits was found for nickel (73 g/day for median and 17 g/day for 75th percentile levels). The consumption corresponding to the 75th percentile could be associated with realistic use, although this would represent an extreme rather than average consumption. For chromium, the respective levels were 358 and 68 g/day and for lead 338 and 135 g/day. For all other metals, liquid consumption would need to be orders of magnitude higher, reaching to 1.5 million grams for aluminum.Conclusion: EC emissions contain trace levels of metals. For almost all metals, unrealistically high levels of liquid need to be consumed in order for total daily exposure to exceed established limits.

Total emitted dose of salbutamol sulphate at different inhalation flows and inhalation volumes through different types of dry powder inhalers

The aim of the present study was to compare the performance of two different dry powder inhalers (DPIs) at different inhalations volumes and inhalation flows.Ventolin Diskus contain blisters of 200µg salbutamol. To test the TED from Aerolizer, salbutamol in Diskus blister was emptied and placed in size 3 capsules suitable for use with Aerolizer.Total emitted dose (TED) delivered by Diskus and Aerolizer was determined using DPI sampling apparatus after one and two inhalations from the same dose. 10-60L/min inhalation flows at 2 and 4L inhalation volume were used in the determination. At inhalation flow ≤30L/min, two inhalations resulted in higher TED than one inhalation (p < 0.05) and Diskus resulted in higher TED than Aerolizer (p < 0.05).The highest TED was at inhalation flow 40L/min above which the effect of the second inhalation and formula device relation were negligible.Device formula relation is present at low inhalation flow but at flow >30L/min Diskus drug formula can be delivered by Aerolizer with no significant difference in TED produced. For the best TED patients are required to inhale as fast as possible (a minimum of 40L/min). At lower inhalation flow two inhalations results in better emitted dose than one inhalation for both DPIs. So, we recommend patients with poor inspiratory efforts to inhale twice and as hard and deep as possible from each dose as they may not receive much benefit from one inhalation even when using DPI with low resistance (Aerolizer) or medium resistance (Diskus). However, further in-vivo study are required to validate this recommendtation.

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler\xae150 and 300\xa0\u03bcg

Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose.

Hydrodynamics of viscous inhalant flows.

Inhalant flows draw fluid into an orifice from a reservoir and are ubiquitous in engineering and biology. Surprisingly, there is a lack of quantitative information on viscous inhalant flows. We consider here laminar flows (Reynolds number Re≤100) developing after impulsive inhalation begins. We implement finite element simulations of flows with varying Re and extraction height h (orifice height above a bottom bed). Numerical results are experimentally validated using particle image velocimetry measurements in a physical model for a representative flow case in the middle of the Re-h parameter space. We use two metrics to characterize the flow in space and time: regions of influence (ROIs), which describe the spatial extent of the flow field, and inhalation volumes, which describe the initial distribution of inhaled fluid. The transient response for all Re features an inviscid sinklike component at early times followed by a viscous diffusive component. At lower Re, diffusion entrains an increasing volume of fluid over time, enlarging the ROI indefinitely. In some geometries, these flows spatially bifurcate, with some fluid being inhaled through the orifice and some bypassing into recirculation. At higher Re, inward advection dominates outward viscous diffusion and the flow remains trapped in a sinklike state. Both ROIs and inhalation volumes are strongly dependent on Re and extraction height, suggesting that organisms or engineers could tune these parameters to achieve specific inhalation criteria.

Erratum to: Impact of Inhalation Flow, Inhalation Volume and Critical Handling Errors on Delivered Budesonide/Formoterol Dose in Different Inhalers: An In Vitro Study

Inhaled drugs are essential for treatment of asthma and chronic obstructive pulmonary disease, but drug delivery via the respiratory tract is complex. Correct inhaler use is challenging as inhalers differ and inhaler technique errors are common. This in vitro study examined impact of inhalation flow, volume, and shaking of commonly used budesonide/formoterol (BUD/FORM) dry powder inhalers (DPIs). Two strengths of each included BUD/FORM DPI, Turbuhaler, Easyhaler and Spiromax, were examined. Fine particle dose (FPD) was measured using the Next Generation Impactor, at fixed pressure drops of 2, 4 and 6 kPa. Delivered dose (DD) for inhalation volume and shaking tests was performed at an airflow rate equivalent to a 4-kPa pressure drop, collected on Respirgard II, 303EU filters. FPD flow rate dependence was similar for all inhalers and strengths. BUD/FORM Turbuhaler and Easyhaler were unaffected by inhalation volume, whereas Spiromax showed significant inhalation volume dependence with about 50% decrease for both inhaler strengths. For a BUD/FORM Turbuhaler 160/4.5-µg/dose, there were no differences in the DD between shaking and no shaking, whereas the higher strength showed a 10% decrease after shaking. BUD/FORM Easyhaler DD decreased with about 50% for both strengths when the device was not shaken, while Spiromax decreased with 20% for the lower strength and 80% for the higher strength when shaken. This study revealed significant differences in inhaler performance after testing at different inhalation flow and volume and following exposure to potential pre-inhalation handling errors, which may lead to decreased drug delivery to the lungs. AstraZeneca

Impact of Inhalation Flow, Inhalation Volume and Critical Handling Errors on Delivered Budesonide/Formoterol Dose in Different Inhalers: An In Vitro Study

Inhaled drugs are essential for treatment of asthma and chronic obstructive pulmonary disease, but drug delivery via the respiratory tract is complex. Correct inhaler use is challenging as inhalers differ and inhaler technique errors are common. This in vitro study examined impact of inhalation flow, volume, and shaking of commonly used budesonide/formoterol (BUD/FORM) dry powder inhalers (DPIs). Two strengths of each included BUD/FORM DPI, Turbuhaler, Easyhaler and Spiromax, were examined. Fine particle dose (FPD) was measured using the Next Generation Impactor, at fixed pressure drops of 2, 4 and 6 kPa. Delivered dose (DD) for inhalation volume and shaking tests was performed at an airflow rate equivalent to a 4-kPa pressure drop, collected on Respirgard II, 303EU filters. FPD flow rate dependence was similar for all inhalers and strengths. BUD/FORM Turbuhaler and Easyhaler were unaffected by inhalation volume, whereas Spiromax showed significant inhalation volume dependence with about 50% decrease for both inhaler strengths. For a BUD/FORM Turbuhaler 160/4.5-µg/dose, there were no differences in the DD between shaking and no shaking, whereas the higher strength showed a 10% decrease after shaking. BUD/FORM Easyhaler DD decreased with about 50% for both strengths when the device was not shaken, while Spiromax decreased with 20% for the lower strength and 80% for the higher strength when shaken. This study revealed significant differences in inhaler performance after testing at different inhalation flow and volume and following exposure to potential pre-inhalation handling errors, which may lead to decreased drug delivery to the lungs. AstraZeneca

Appropriate use of a dry powder inhaler based on inhalation flow pattern

BackgroundAn optimal inhalation flow pattern is essential for effective use of a dry powder inhaler (DPI). We wondered whether DPI instructors inhale from a DPI with an appropriate pattern, and if not, whether self-training with visual feedback is effective.MethodsSubjects were 14 pharmacists regularly engaged in instruction in DPI use. A newly designed handy inhalation flow visualizer (Visual Trainer: VT) was used to assess inhalation profiles and to assist in self-training. With a peak inhalation flow rate (PIFR) > 50 L/min, time reaching PIFR (TPF) < 0.4 s, inhalation volume (VI) > 1 L, and flow at 0.3 s after the onset of inhalation (F0.3) > 50 L/min, the pattern was considered optimal.ResultsUsing Diskus or Turbuhaler 12 and 10 subjects respectively inhaled with a suitable PIFR. Those with a satisfactory F0.3 were 10 and 7 respectively. The TPF was short enough in only 1 and 2 respectively. All 14 subjects inhaled deeply (VI) through Diskus, and 10 did so through Turbuhaler. In the self-training session, only 3 subjects satisfied all three variables at the first trial, while 2 or 3 trials were required in other subjects. Among the three variables, optimal TPF was the most difficult to attain. Once a satisfactory inhalation pattern was achieved using one DPI, eleven out of 12 subjects inhaled with a satisfactory pattern through the other DPI.ConclusionVisualization of the inhalation flow pattern facilitates the learning of proper inhalation technique through a DPI.

Effect of Flow Rate on In Vitro Aerodynamic Performance of NEXThaler® in Comparison with Diskus® and Turbohaler® Dry Powder Inhalers

Background: European and United States Pharmacopoeia compendial procedures for assessing the in vitro emitted dose and aerodynamic size distribution of a dry powder inhaler require that 4.0 L of air at a pressure drop of 4 kPa be drawn through the inhaler. However, the product performance should be investigated using conditions more representative of what is achievable by the patient population. This work compares the delivered dose and the drug deposition profile at different flow rates (30, 40, 60, and 90 L/min) of Foster NEXThaler® (beclomethasone dipropionate/formoterol fumarate), Seretide® Diskus® (fluticasone propionate/salmeterol xinafoate), and Symbicort® Turbohaler® (budesonide/formoterol fumarate).Methods: The delivered dose uniformity was tested using a dose unit sampling apparatus (DUSA) at inhalation volumes either 2.0 or 4.0 L and flow rates 30, 40, 60, or 90 L/min. The aerodynamic assessment was carried out using a Next Generation Impactor by discharging each inhaler at 30, 40, 60, or 90 L/min for a time sufficient to obtain an air volume of 4 L.Results: Foster® NEXThaler® and Seretide® Diskus® showed a consistent dose delivery for both the drugs included in the formulation, independently of the applied flow rate. Contrary, Symbicort® Turbohaler® showed a high decrease of the emitted dose for both budesonide and formoterol fumarate when the device was operated at airflow rate lower that 60 L/min. The aerosolizing performance of NEXThaler® and Diskus® was unaffected by the flow rate applied. Turbohaler® proved to be the inhaler most sensitive to changes in flow rate in terms of fine particle fraction (FPF) for both components. Among the combinations tested, Foster NEXThaler® was the only one capable to deliver around 50% of extra-fine particles relative to delivered dose.Conclusions: NEXThaler® and Diskus® were substantially unaffected by flow rate through the inhaler in terms of both delivered dose and fine particle mass.

Transient measurement of the effective particle density of cigarette smoke

The real-time effective particle density of cigarette smoke was determined using a Centrifugal Particle Mass Analyzer (CPMA) and Differential Mobility Spectrometer (DMS). A Puff Inhale Exhale (PIE) simulator was used to produce the smoke from various research and commercial cigarettes following the International Standard Organization (ISO) puffing parameters (35ml puff of 2s duration, every 60s) or the Health Canada Intense (HCI) puffing parameters (55ml puff of 2s duration, every 30s). The impact of modifying parameters, such as smoke mass, cigarette format, filter type, inhalation volume and mouth hold period, on the effective particle density was also investigated. All of the effective density functions were found to be independent of particle size within the bias uncertainty of the measurement system, indicating that the cigarette smoke particles likely had a spherical morphology. Trends in the average effective particle densities were observed for the different cigarettes and puffing parameters. While all of these shifts were within the bias uncertainty of the CPMA–DMS system, two-sample t-tests and the Tukey method were used to identify where the shifts were statistically probable. However due to the complexity of cigarette smoke, the aerosol mechanisms behind most of these shifts were unknown and require further investigation. For all of the tested cases the average effective particle density, considering puffs 3–6, varied from 1090 to 1518kg/m3, with a majority (9 out of 16 cases) falling within 1300 to 1394kg/m3. The Tukey method identified no statistical change in the effective particle density over the duration of an ISO puff, but it did identify significant differences between effective densities produced by different cigarettes.

Development and Characterisation of a Smoking Behaviour Measurement System

Summary Respiratory deposition from smoking articles is influenced by particle or droplet properties (such as diameter), puffing parameters (such as draw effort or pressure drop, flow rate, duration), mouth losses, and post-puff inhalation dynamics (determined by inhalation depth, volume and breath hold duration). The Smoking Behaviour System (SBS) described herein is a novel system with regard to its capability to measure flow and duration characteristics of typical smoking cycles, which may consist of puffing, mouth hold, post-puff inhalation, breath hold and exhalation. It combines two analysers: the first measures the puffing topography and optical obscuration from puffed aerosol, while the second measures the respiratory topography and optical obscuration from exhaled aerosol. The puffing and respiratory analysers were calibrated and operated between flow rates of 0-7 L.min-1 and 0-50 L.min-1, respectively, as typically encountered during the human smoking cycle. The volumes measured by the puffing and respiratory analysers met the design specification and tolerance limits of ± 2% and ± 5%, respectively. The optical obscuration measurements showed no statistical difference among the three units tested or in day-to-day variation, verifying the robustness of the SBS for use in optical measurements of smoke when combined with topography measurements. In conclusion, the SBS is a validated technology that provides a means to measure the real-time flow and duration profile of puffing, mouth hold, post-puff inhalation, breath hold

Effect of cigarette design on biomarkers of exposure, puffing topography and respiratory parameters

Despite the lack of evidence, many reports exist which have implied that smokers inhale low-yield cigarette smoke more deeply than that of high-yield cigarettes. The objective of this study was to investigate the effect of short-term switching between smoker’s own brand and test cigarettes with different smoke yields on puffing topography, respiratory parameters and biomarkers of exposure. Participants were randomly assigned to smoke either a Test Cigarette-High Tar (TCH), for two days, and then switched to a Test Cigarette-Low Tar (TCL), for two days or the reverse order (n = 10 each sequence). Puffing topography (CReSS microdevice), respiratory parameters (inductive plethysmography) and biomarkers of exposure (BOE, urinary nicotine equivalents – NE and blood carboxyhemoglobin – COHb) were measured at baseline and on days 2 and 4. The average puffs per cigarette, puff volume and puff durations were statistically significantly lower, and inter-puff interval was significantly longer for the TCH compared to the TCL groups. Respiratory parameters were not statistically significantly different between the TCH and TCL groups. Post-baseline NE and COHb were statistically significantly lower in the TCL compared to the TCH groups. Under the conditions of this study, we found no indication of changes in respiratory parameters, particularly inhalation time and volume, between study participants smoking lower versus higher yield cigarettes. Likewise, the BOE provides no indication of deeper inhalation when smoking low- versus high-yield cigarettes. These findings are consistent with the published literature indicating smoking low-yield cigarettes does not increase the depth of inhalation.

Nicotine and cotinine exposure from electronic cigarettes: a population approach.

Electronic cigarettes (e-cigarettes) are a recent technology that has gained rapid acceptance. Still, little is known about them in terms of safety and effectiveness. A basic question is how effectively they deliver nicotine; however, the literature is surprisingly unclear on this point. Here, a population pharmacokinetic model was developed for nicotine and its major metabolite cotinine with the aim to provide a reliable framework for the simulation of nicotine and cotinine concentrations over time, based solely on inhalation airflow recordings and individual covariates [i.e., weight and breath carbon monoxide (CO) levels]. This study included ten adults self-identified as heavy smokers (at least one pack of cigarettes per day). Plasma nicotine and cotinine concentrations were measured at regular 10-min intervals for 90 min while human subjects inhaled nicotine vapor from a modified e-cigarette. Airflow measurements were recorded every 200 ms throughout the session. A population pharmacokinetic model for nicotine and cotinine was developed based on previously published pharmacokinetic parameters and the airflow recordings. All of the analyses were performed with the non-linear mixed-effect modeling software NONMEM(®) version 7.2. The results show that e-cigarettes deliver nicotine effectively, although the pharmacokinetic profiles are lower than those achieved with regular cigarettes. Our pharmacokinetic model effectively predicts plasma nicotine and cotinine concentrations from the inhalation volume, and initial breath CO. E-cigarettes are effective at delivering nicotine. This new pharmacokinetic model of e-cigarette usage might be used for pharmacodynamic analysis where the pharmacokinetic profiles are not available.

Breathing simulator of workers for respirator performance test.

Breathing machines are widely used to evaluate respirator performance but they are capable of generating only limited air flow patterns, such as, sine, triangular and square waves. In order to evaluate the respirator performance in practical use, it is desirable to test the respirator using the actual breathing patterns of wearers. However, it has been a difficult task for a breathing machine to generate such complicated flow patterns, since the human respiratory volume changes depending on the human activities and workload. In this study, we have developed an electromechanical breathing simulator and a respiration sampling device to record and reproduce worker’s respiration. It is capable of generating various flow patterns by inputting breathing pattern signals recorded by a computer, as well as the fixed air flow patterns. The device is equipped with a self-control program to compensate the difference in inhalation and exhalation volume and the measurement errors on the breathing flow rate. The system was successfully applied to record the breathing patterns of workers engaging in welding and reproduced the breathing patterns.

Cross‐sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study

Increased delta-9-tetrahydrocannabinol (THC) concentrations in cannabis may lead to higher THC exposure, cannabis dependence and treatment need, but users may also adapt the actual intake of THC through reduced inhalation of THC containing smoke (titration). We investigated whether consumers of stronger cannabis use less cannabis per joint or inhale less smoke than those using less potent cannabis and whether these factors predict cannabis dependence severity. Heavy cannabis users (n = 98) brought their own cannabis, rolled a joint and smoked it ad libitum in a naturalistic setting. We analysed the content of the joint, its association with smoking behaviour and the cross-sectional and prospective (1.5-year follow-up) relations between smoking behaviour and cannabis dependence severity (total number of DSM-IV dependence symptoms). THC concentration in cannabis (range 1.10-24.70%) was correlated positively with cannabis dose per joint (b = 0.008, P = 0.01), but the resulting THC concentration per joint (range 0.24-15.72%) was associated negatively with inhalation volume (b = -0.05, P = 0.03). Smoking behaviour measures (number of puffs, inhaled volume, reduction of puff volume and puff duration while smoking) predicted follow-up dependence severity, independently of baseline dependence severity and monthly THC dose (number of joints × cannabis dose × cannabis THC concentration). Monthly THC dose only predicted follow-up dependence severity when unadjusted for baseline severity. Cannabis users titrate their delta-9-tetrahydrocannabinol intake by inhaling lower volumes of smoke when smoking strong joints, but this does not fully compensate for the higher cannabis doses per joint when using strong cannabis. Thus, users of more potent cannabis are generally exposed to more delta-9-tetrahydrocannabinol. Smoking behaviour appears to be a stronger predictor for cannabis dependence severity than monthly delta-9-tetrahydrocannabinol dose.