Inhalation Patterns Research Articles

Squamous Carcinoma of the Lung: Still a Long and Winding Road to Successful Treatment

Lung cancer is the leading cause of cancer-related death worldwide, accounting for approximately 1.4 million deaths in 2010 in the USA, according to the SEER d atabase [1]. Approximately 85% of newly diagnosed lung tumors are non-small-cell lung cancer (NSCLC) and, among them, 20–30% are squamous cell lung cancer (SQCLC). The incidence of this subtype has now been surpassed by adenocarcinoma, reflecting trends in reduced tobacco exposure with the introduction of filtered and low-tar content cigarettes, as well as changes in cigarette smoke inhalation patterns [2]. The diagnosis of SQCLC is currently performed by light microscopy and relies on the presence of keratinization and/or intracellular bridges. With the increasing need of a correct histological diagnosis in order to choose the right therapeutic regimen, the dichotomy between small-cell lung cancer and NSCLC became obsolete. For such reasons when in poorly differentiated lung carcinomas there is no clear-cut cellular differentiation at light microscopy, which account for 20–30% of cases, a panel of immunohistochemistry (IHC) markers has been shown to increase the likelihood of an appropriate subtyping. This panel includes at least cytokeratin CK7, CK5, TTF-1 and p63, as demonstrated by a retrospective study performed on fine-needle aspiration cytology cell blocks [3]. Another marker, p40, an antibody that recognizes the ΔNp63-a p63 isoform, is equivalent to p63 in sensitivity but markedly superior to p63 in specificity, which eliminates the potential pitfall of misinterpreting a p63-positive adenocarcinoma or unsuspected lymphoma as a SCC [4]. Current available treatment options for advanced SQCLC rely only on systemic cytotoxic chemotherapy. Patients with a good performance status (Eastern Cooperative Oncology Group performance status 0–1) should receive a platinum agent, cisplatin (preferentially) or carboplatin, plus a third-generation drug (taxanes,

Performance of Dry Powder Inhalers with Single Dosed Capsules in Preschool Children and Adults Using Improved Upper Airway Models

The pulmonary administration of pharmaceutical aerosols to patients is affected by age-dependent variations in the anatomy of the upper airways and the inhalation pattern. Considering this aspect, different upper airway models, representing the geometries of adults and preschool children, and a conventional induction port according to the European Pharmacopeia were used for in vitro testing of dry powder inhalers with single dosed capsules (Cyclohaler®, Handihaler® and Spinhaler®). Deposition measurements were performed using steady flow rates of 30 and 60 L/min for the Handihaler®/Spinhaler® and 30, 60 and 75 L/min for the Cyclohaler®. The inhalation volume was set at 1 L. For the Cyclohaler®, the in vitro testing was supplemented by a pediatric inhalation profile. Slight differences of pulmonary deposition between the idealized adult (11%–15%) and pediatric (9%–11%) upper airway model were observed for the Cyclohaler®. The applied pediatric inhalation profile resulted in a reduction of pulmonary deposition by 5% compared to steady conditions and indicated the influence of the inhalation pattern on the amount of pulmonary deposited particles. The comparison of two pediatric upper airway models showed no differences. The performance of the Handihaler® was similar to the Cyclohaler®. The Spinhaler® showed an insufficient performance and limited reproducibility in our investigations.

PAST AND PRESENT TRENDS OF DRY POWDER INHALER DEVICES: A REVIEW

Administration of dry powder inhalers (DPIs) for to the management of respiratory diseases has improved significantly in modern lifetime. Currently there is a vast margin of available DPIs that differ not only in the design-plan, effective operational techniques that are requisite, output features and the delivery of drug across an assortment of inhalation pattern. Diverse patient population possibly make choice of individual types of DPI as it is precisely easier to use when in comparison to the other types and preferring the right DPI which shall fulfil a particular requirement for patient will certainly enhance the patient compliance along with the therapy. For instance some DPIs are found to put forth a greater resistance against inspirational flow rate contrast to others which undoubtedly affects the total emitted dose (TED) and also the fine particle fraction (FPF) of aerosol that has been released. As a consequence an individual patient may receive different doses of drug while inhaling from the different DPIs. For that reason, it is essential that the prescriber should be in complete knowledge of the characteristics of different types of DPI, in order to prescribe the device which is most appropriate to the individual patient’s needs. The present study sights the features of currently accessible DPIs, evaluates their effectiveness, usage, patient acceptability, drugs administered by that inhaler. The variation in output characteristics, availability and patient’s selection between the available devices has revealed to have an effect on treatment efficacy and patient compliance through therapy. Altering the DPI that has been prescribed to the patient to a cost effective or a generic device may consequently affect disease control and thereby amplify the cost of treatment.

A Wearable Sensor System for Monitoring Cigarette Smoking

Available methods of smoking assessment (e.g., self-report, portable puff-topography instruments) do not permit the collection of accurate measures of smoking behavior while minimizing reactivity to the assessment procedure. This article suggests a new method for monitoring cigarette smoking based on a wearable sensor system (Personal Automatic Cigarette Tracker [PACT]) that is completely transparent to the end user and does not require any conscious effort to achieve reliable monitoring of smoking in free-living individuals. The proposed sensor system consists of a respiratory inductance plethysmograph for monitoring of breathing and a hand gesture sensor for detecting a cigarette at the mouth. The wearable sensor system was tested in a laboratory study of 20 individuals who performed 12 different activities including cigarette smoking. Signal processing was applied to evaluate the uniqueness of breathing patterns and their correlation with hand gestures. The results indicate that smoking manifests unique breathing patterns that are highly correlated with hand-to-mouth cigarette gestures and suggest that these signals can potentially be used to identify and characterize individual smoke inhalations. With the future development of signal processing and pattern-recognition methods, PACT can be used to automatically assess the frequency of smoking and inhalation patterns (such as depth of inhalation and smoke holding) throughout the day and provide an objective method of assessing the effectiveness of behavioral and pharmacological smoking interventions.

Marijuana’s dose-dependent effects in daily marijuana smokers.

Active marijuana produces significant subjective, psychomotor, and physiological effects relative to inactive marijuana, yet demonstrating that these effects are dose-dependent has proven difficult. This within-subject, double-blind study was designed to develop a smoking procedure to obtain a marijuana dose-response function. In four outpatient laboratory sessions, daily marijuana smokers (N = 17 males, 1 female) smoked six 5-s puffs from 3 marijuana cigarettes (2 puffs/cigarette). The number of puffs from active (≥5.5% Δ⁹-tetrahydrocannabinol/THC) and inactive (0.0% THC) marijuana varied according to condition (0, 2, 4, or 6 active puffs); active puffs were always smoked before inactive puffs. Subjective, physiological, and performance effects were assessed prior to and at set time points after marijuana administration. Active marijuana dose-dependently increased heart rate and decreased marijuana craving, despite evidence (carbon monoxide expiration, weight of marijuana cigarettes post-smoking) that participants inhaled less of each active marijuana cigarette than inactive cigarettes. Subjective ratings of marijuana "strength," "high," "liking," "good effect," and "take again" were increased by active marijuana compared with inactive marijuana, but these effects were not dose-dependent. Active marijuana also produced modest, non-dose-dependent deficits in attention, psychomotor function, and recall relative to the inactive condition. In summary, although changes in inhalation patterns as a function of marijuana strength likely minimized the difference between dose conditions, dose-dependent differences in marijuana's cardiovascular effects and ratings of craving were observed, whereas subjective ratings of marijuana effects did not significantly vary as a function of dose.

Deep inhalation bronchoprotection

When methacholine is inhaled with total lung capacity inhalations, which is the recommended inhalation pattern for the 5-breath dosimeter method, [1] Crapo R.O. Casaburi R. Coates A.L. et al. Guidelines for methacholine and exercise challenge testing-1999. Am J Respir Crit Care Med. 2000; 161: 309-329 Crossref PubMed Scopus (2176) Google Scholar as many as a quarter of asthmatic patients can have a false-negative test result. [2] Cockcroft D.W. Davis B.E. The bronchoprotective effect of inhaling methacholine by using total lung capacity inspirations has a marked influence on the interpretation of the test results. J Allergy Clin Immunol. 2006; 117: 1244-1248 Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar It has been suggested to us that high forced expiratory volume in 1 second (FEV1) could explain negative (dosimeter) methacholine test results in patients with asthma. We therefore decided to perform additional analyses on previously published data in 55 asthmatic patients comparing the 2 American Thoracic Society (ATS) methacholine methods. [2] Cockcroft D.W. Davis B.E. The bronchoprotective effect of inhaling methacholine by using total lung capacity inspirations has a marked influence on the interpretation of the test results. J Allergy Clin Immunol. 2006; 117: 1244-1248 Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar

Development of Dry Salbutamol Sulfate Powder with High Inhalation Performance Independent of Inhalation Patterns

While dry powder inhalations are commonly used to treat pulmonary diseases, their clinical performance depends on patient inspiratory flow patterns. The purpose of this study was to develop a new powder with high and stable therapeutic performance for various patients. We applied the supercritical antisolvent (SCF) method to salbutamol sulfate (SS) to prepare a bulky SS particle (SS-SCF). Tests of in vitro inhalation performance with a human inspiratory flow simulator revealed SS-SCF to be less susceptible to inspiratory flow patterns than milled SS. When inspired, the unique structure seemed to be broken resulting in small fragments that could be delivered to the lungs. However, stability tests under physical stress showed tolerance for transportation and handling. In addition, optimization of the concentration of the SS solution applied to SCF method improved the in vitro inhalation performance of SS-SCF. These results indicated that a unique bulky SS powder prepared by the SCF method was useful for dry powder inhalation.

Size-change and deposition of conventional and composite cigarette smoke particles during inhalation in a subject-specific airway model

In light of the established health risks of cigarette smoking, less harmful cigarettes (or potential reduced exposure products (PREPs)) have been marketed. Thus, it is of interest to analyze and compare the inhaled droplet dynamics of conventional and new composite cigarette smoke particles (CSPs). Inhalation pattern, hygroscopic growth and deposition of different composite cigarette smoke particles (CSPs) have been simulated numerically in a subject-specific human respiratory airway model from the mouth to generation G9. The validated computer model has been developed to consider the interaction of different deposition mechanisms, including impaction, sedimentation, diffusion, hygroscopic growth, coagulation, as well as possible cloud motion under different exposure and steady breathing conditions (e.g., puffing, post-puffing and two-step inhalation). The computer simulation results are consistent with numerous in-vivo and in-vitro studies as well as whole-lung modeling for deposition of conventional CSPs including hygroscopic growth and cloud motion. It is demonstrated that changes in cigarette composition significantly influence the hygroscopic growth of CSPs. In general, the growth rate of new composite CSPs is larger than the conventional one if the initial water mole-fraction is lower in the droplet. Hygroscopic growth of the new composite CSPs is not a significant mechanism leading to elevated deposition in the oral and tracheobronchial (TB) airways, provided that the relative humidity in the lungs does not exceed 99.5% and the droplet size does not exceed 3μm; however, enhanced deposition may occur if the particles can grow over 3μm. In this case, the deposition patterns of CSPs may be controlled by changing the primary composition, especially the initial ratio of water and glycerol. The simulation data with cloud diameters of 0.15–0.2cm in the oral cavity and 0.5–0.6cm in the trachea closely match the in-vivo lung deposition measurements of highly dense (conventional) CSPs. Specifically, preferred deposition occurs in the upper airway region, i.e., from the oral cavity to the second bifurcation, with deposition fractions of about 13–22% from the oral cavity to the larynx and 40–57% in the TB airways. This study is helpful for quantitatively evaluating the dose-exposure and subsequent health effects of both conventional and potentially less-harmful cigarettes.

Study on gas/solid flow in an obstructed pulmonary airway with transient flow based on CFD–DPM approach

A comprehensive three-dimensional numerical model was developed to study the gas/solid flow behaviors in a pulmonary airway affected by chronic obstructive pulmonary disease (COPD), a high morbidity lung disease and the patients of which suffer from respiratory difficulty caused by narrowed airway. The gas phase was modeled with laminar computational fluid dynamics (CFD) model and the particle phase was modeled with discrete phase model (DPM). Computational gas–solid flow behaviors in a three-generation airway were validated with experiment. After that gas/solid flow characteristics in an obstructed four-generation model were investigated by simulations. The air flow patterns and flow rates changing along the time series of transient inhalation and particle deposition patterns and efficiencies of the obstructed tube and adjacent generations under real inhalation condition were compared with the steady inlet results. It is found that air flow rates of the obstruction and its downstream generations reduce due to the stagnation and recirculation zones development with unsteady inhalation. Deposition area could enlarge and become more scattered than steady inlet. Secondary flow may contribute to the particle deposition in the inflamed airway for real inhalation. The deposition efficiency outcomes of the constricted tube indicate that transient inhalation condition may be more appropriate for COPD or similar obstructed airway simulation than steady inlet condition.

Cigarette smoking and lung cancer in women: Results of the French ICARE case–control study

BackgroundThe incidence of female lung cancer in developed countries has been increasing since 1950. In order to have recent and reliable data on the association between cigarette smoking and the risk of lung cancer in women, we analysed cases from a French population-based case–control study. MethodsThe ICARE study is a multicenter case–control study on respiratory cancers (lung and UADT cancers), set up in 10 départements that include a general cancer registry. We included 648 women lung cancer cases up to 76 years of age, with a histologically confirmed primary lung cancer. The 775 controls were randomly selected from the general population and frequency-matched with cases by age and département. ResultsOverall, smoking cigarettes at some time was associated with a 8-fold increase in lung cancer risk (OR=8.2, 95% CI 6.0–11.4). A dose–response relationship was observed as a function of duration, intensity and pack-years. Using restricted splines cubic models, we have shown that intensity dose-response departed significantly from linearity while the risk increased linearly with duration and decreased linearly with time since cessation. The following characteristics were associated with a higher relative risk: smoke inhalation, smoking non-filter cigarettes, smoking dark tobacco cigarettes and starting at a young age. In addition, duration, intensity and time since cessation was significantly related with histological type. This was not the case for characteristics such as the use of a filter or not, the inhalation pattern, or the type of tobacco smoked. The proportion of lung cancer cases attributable to cigarette smoking was 55% (95% CI: [47–63%]). ConclusionsOur results confirm that cigarette smoking is by far the most important cause of the current epidemic of lung cancer among French women and that the most important smoking-related variables for varying the risk of lung cancer are the duration, the intensity and the time since cessation.

Inhalation heterogeneity from subresidual volumes in elite divers

Punctate reopening of the lung from subresidual volumes (sub-RV) is commonly observed in excised lung preparations, either degassed or collapsed to zero transpulmonary pressure, and in the course of reinflation of human lungs when the chest is open, secondary to traumatic or surgical pneumothoraxes. In the course of physiological studies on two elite breath-hold divers, who are able to achieve lung volumes well below traditional RV with glossopharyngeal exsufflation, we used MRI lung imaging with inhaled hyperpolarized (129)Xe to visualize ventilatory patterns. We observed strikingly inhomogeneous inhalation patterns with small inhalation volumes from sub-RV, consistent with reopening of frankly closed airways. On the other hand, two age-matched and two older controls, inhaling from just above RV, showed a much more homogeneous pattern. Our results demonstrate the concept of frank airway closure below RV in young healthy adults with an intact chest wall.

Regional lung deposition of aged and diluted sidestream tobacco smoke

Since aged and diluted smoke particles are in general smaller and more stable than mainstream tobacco smoke, it should be possible to model their deposition on the basis of their measured particle diameters. However in practice, measured deposition values are consistently greater than those predicted by deposition models. Thus the primary objective of this study was to compare theoretical predictions obtained by the Monte Carlo code IDEAL with two human deposition studies to attempt to reconcile these differences. In the first study, male and female volunteers inhaled aged and diluted sidestream tobacco smoke at two steady-state concentrations under normal tidal breathing conditions. In the second study, male volunteers inhaled aged and diluted sidestream smoke labelled with 212Pb to fixed inhalation patterns. Median particle diameters in the two studies were 125 nm (CMD) and 210 nm (AMD), respectively. Experimental data on total deposition were consistently higher than the corresponding theoretical predictions, exhibiting significant inter-subject variations. However, measured and calculated regional deposition data are quite similar to each other, except for the extra-thoracic region. This discrepancy suggests that either the initial particle diameter decreases upon inspiration and/or additional deposition mechanisms are operating in the case of tobacco smoke particles.

Tobacco industry research and efforts to manipulate smoke particle size: implications for product regulation.

Over the past half-century of cigarette design, tobacco manufacturers have prioritized efficiency of delivery alongside ease of inhalation and use. As a result, the modern cigarette is uniquely effective at facilitating the absorption of nicotine as well as carcinogens and other toxins. The present study draws on internal tobacco company documents to assess industry consideration of the role of smoke particle size as a potentially controllable influence over inhalation patterns and lung exposure. Tobacco manufacturers evaluated particle size manipulation both as a means of controlling physical and sensory product attributes and as a possible approach to reducing health hazards related to exposure. Industry scientists concluded that the smoke aerosol particle distribution of conventional cigarettes, constructed within common parameters, falls within a narrow and effective inhalation range. However, the internal findings suggest that differences in smoke particle size distribution are possible through less conventional approaches to product design. We propose that particle size be included among the many design features to be considered in emerging tobacco product regulation. However, the present review does not address whether particle size regulation would be a plausible means of substantially reducing addictiveness or harmfulness of cigarettes, and therefore we do not propose it as a high-priority target for regulation.

Advanced Nebulizer Designs Employing Vibrating Mesh/Aperture Plate Technologies for Aerosol Generation

Recent technological advances and improved nebulizer designs have overcome many limitations of jet nebulizers. Newer devices employ a vibrating mesh or aperture plate (VM/AP) for the generation of therapeutic aerosols with consistent, increased efficiency, predominant aerosol fine particle fractions, low residuals, and the ability to nebulize even microliter volumes. These enhancements are achieved through several different design features and include improvements that promote patient compliance, such as compact design, portability, shorter treatment durations, and quiet operation. Current VM/AP devices in clinical use are the Omron MicroAir, the Nektar Aeroneb, and the Pari eFlow. However, some devices are only approved for use with specific medications. Development of "smart nebulizers" such as the Respironics I-neb couple VM technologies with coordinated delivery and optimized inhalation patterns to enhance inhaled drug delivery of specialized, expensive formulations. Ongoing development of advanced aerosol technologies should improve clinical outcomes and continue to expand therapeutic options as newer inhaled drugs become available.

Tobacco smoking and risk of bladder cancer

Tobacco smoking is the main known cause of urinary bladder cancer in humans. In most populations, over half of cases in men and a sizeable proportion in women are attributable to this habit. Epidemiological studies conducted in different populations have shown a linear relationship between intensity and duration of smoking and risk. Quitting smoking reduces the risk of bladder cancer. Smoking black (air-cured) cigarettes results in a higher risk than smoking blond (flue-cured) tobacco cigarettes; results on inhalation patterns and use of filter are not consistent. Cigar and pipe smoking also increases the risk of bladder cancer; data on other tobacco products are limited. The evidence for non-transitional bladder carcinoma is limited, but consistent with an increased risk. The available evidence does not point towards a different carcinogenic effect of tobacco smoking in men and women or in whites and blacks. Data on involuntary smoke and use of smokeless tobacco products are limited, but do not suggest an increased risk of bladder cancer.

Ultrafine particle emissions from waterpipes

Objectives:Ultrafine particle emissions from waterpipes and their impact on human health have not been extensively studied. The aim of this study was to characterise the inhalation pattern of waterpipe smokers,...

Microspheres containing lipid/chitosan nanoparticles complexes for pulmonary delivery of therapeutic proteins

Chitosan/tripolyphosphate nanoparticles have already been demonstrated to promote peptide absorption through several mucosal surfaces. We have recently developed a new drug delivery system consisting of complexes formed between preformed chitosan/tripolyphosphate nanoparticles and phospholipids, named as lipid/chitosan nanoparticles (L/CS-NP) complexes. The aim of this work was to microencapsulate these protein-loaded L/CS-NP complexes by spray-drying, using mannitol as excipient to produce microspheres with adequate properties for pulmonary delivery. Results show that the obtained microspheres are spherical and present appropriate aerodynamic characteristics for lung delivery (aerodynamic diameters around 2-3 microm and low apparent tap density of 0.4-0.5 g/cm3). The physicochemical properties of the L/CS-NP complexes are affected by the phospholipids composition. Phospholipids provide a controlled release of the encapsulated protein (insulin), which was successfully associated to the system (68%). The complexes can be easily recovered from the mannitol microspheres upon incubation in aqueous medium, maintaining their morphology and physicochemical characteristics. Therefore, this work demonstrates that protein-loaded L/CS-NP complexes can be efficiently microencapsulated, resulting in microspheres with adequate properties to provide a deep inhalation pattern. Furthermore, they are expected to release their payload (the complexes and, consequently, the encapsulated macromolecule) after contacting with the lung aqueous environment.

Respiratory retention of nicotine and urinary excretion of nicotine and its five major metabolites in adult male smokers

Urinary excretion of nicotine and its five major metabolites (nicotine- N-glucuronide, cotinine, cotinine- N-glucuronide, trans-3′-hydroxycotinine, and trans-3′-hydroxycotinine- O-glucuronide), expressed as nicotine equivalents (NE), has been used as a biomarker of smoking-related nicotine exposure. In this open-label, single center study, we investigated the relationship between nicotine retention from smoking and urinary excretion of NE in adult smokers. After a 4-day washout period, 16 adult male smokers smoked 6 cigarettes per day for four consecutive days according to three predefined smoking patterns: no inhalation (Pattern A), normal inhalation (Pattern B), and deep inhalation (Pattern C). The amount of nicotine retained in the respiratory tract during smoking was estimated from the difference between the amounts of nicotine delivered and exhaled. The daily excretion of urinary NE was measured in 24 h urine samples by LC–MS/MS. The mean (±S.D.) amount of nicotine retained was 0.126 ± 0.167, 0.960 ± 0.214, and 1.070 ± 0.223 mg/cig for Patterns A, B, and C, respectively. The mean (±S.D.) relative retention (the amount retained relative to the amount delivered) was 11.2 ± 14.7%, 98.0 ± 1.6%, and 99.6 ± 0.3% for Patterns A, B, and C, respectively. On the fourth day of smoking, an average of 86 ± 20% of the total daily amount of retained nicotine was recovered as NE in 24 h urine. Nicotine equivalents was treated as a single component and the data was described by a first-order elimination pharmacokinetic model which assumed instantaneous input and distribution. Based on this model, the elimination half-life of NE was 19.4 ± 2.6 h, and the NE excretion had reached ∼96% of the steady state levels by Day 4. Our results suggest that most of the nicotine inhaled from a cigarette is retained (≥98%) in the lung, and at steady state, daily urine NE excretion reflects ∼90% of the retained nicotine dose from cigarette smoking.

The Diskus: a review of its position among dry powder inhaler devices.

The use of dry powder inhalers (DPIs) to administer treatments for respiratory diseases has increased significantly in recent years. There is now a wide range of DPIs available that vary considerably in design, required operational techniques, output characteristics and drug delivery across a range of inhalation patterns. Different patient populations may find individual types of DPI easier to use correctly than others and selecting the right DPI for particular patient requirements will improve compliance with therapy. For example, some DPIs offer a greater resistance against inspirational flow rate than others which affects the total emitted dose and also fine particle mass of the aerosol released. An individual patient may therefore receive different amounts of drug when inhaling from different DPIs. Therefore, it is important that the prescriber is fully aware of the characteristics of the different types of DPI, so that he or she can prescribe the device that is most appropriate to an individual patient's needs. This review explores the characteristics of currently available DPIs and evaluates their efficacy and patient acceptability. The differences in output characteristics, ease of use and patient preferences between available devices is shown to affect treatment efficacy and patient compliance with therapy. Changing the DPI prescribed to a patient to a cheaper or generic device may therefore adversely affect disease control and thereby increase the cost of treatment.

A New Method for Estimating the Retention of Selected Smoke Constituents in the Respiratory Tract of Smokers During Cigarette Smoking

This report describes a new method for estimating the retention of selected mainstream smoke constituents in the respiratory tract of adult smokers during cigarette smoking. Both particulate-phase (PP) constituents including nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N′-nitrosonornicotine (NNN), two tobacco-specific nitrosamines (TSNA), and gas-vapor-phase (GVP) constituents including carbon monoxide (CO), isoprene (IP), acetaldehyde (AA), and ethylene, were studied. To estimate the amounts of smoke constituents delivered during smoking, we used predetermined linear relationships between the measured cigarette filter solanesol content and machine-generated mainstream deliveries of these selected compounds. To determine the amounts of smoke constituents exhaled, the expired breath was directed through a Cambridge filter pad (CFP) attached to an infrared spectrometer. PP compounds were trapped on the CFP for later analysis and GVP compounds were analyzed in near real time. The smokers' respiratory parameters during smoking, such as inhalation/exhalation volume and time, were monitored using LifeShirt®, a respiratory inductive plethysmography (RIP) device. The retention of each smoke constituent, expressed as a percentage, was then calculated as the difference between the amount delivered (estimated) and the amount exhaled relative to the amount delivered. We studied 16 adult male smokers who smoked cigarettes according to 3 predefined smoking patterns: no inhalation (pattern A), normal inhalation (pattern B), and deep inhalation (pattern C). For the three PP constituents, the mean retentions for pattern A ranged between 10 and 20%; and while the mean retentions of the two TSNAs were significantly higher for pattern C (84% for NNK and 97% for NNN) than those for pattern B (63% for NNK and 84% for NNN), the mean retentions of nicotine were basically the same between patterns B and C, which were both greater than 98%. For the GVP constituents, the retentions were similar between pattern B and pattern C, although different constituents were retained to different degrees (average values of 33%, 52%, 79%, and 99% for ethylene, IP, CO, and AA, respectively). The differences in the retention between different constituents could be interpreted in terms of each constituent's physical properties such as volatility and solubility. In conclusion, the method described is suitable for studying the retention of selected mainstream smoke constituents in the respiratory tract of smokers.