A proposal to account for the stimulus, the mechanism, and the mediators released in exercise-induced bronchoconstriction.

Exercise induced bronchoconstriction (EIB) describes the transient narrowing of the airways that follows vigorous exercise. It commonly occurs in children and adults who have asthma and in elite athletes. The primary stimulus is proposed to be loss of water, by evaporation, from the airway surface due to conditioning inspired air. The mechanism, whereby this evaporative loss of water provokes contraction of the bronchial smooth muscle, is thought to be an increase in osmolarity of the airway surface liquid. The increase in osmolarity causes mast cells to release histamines, prostaglandins, and leukotrienes. It is these mediators that contract smooth muscle causing the airways to narrow.

Host phylogeny shapes viral transmission networks in an island ecosystem.

Virus transmission between host species underpins disease emergence. Both host phylogenetic relatedness and aspects of their ecology, such as species interactions and predator-prey relationships, may govern rates and patterns of cross-species virus transmission and hence zoonotic risk. To address the impact of host phylogeny and ecology on virus diversity and evolution, we characterized the virome structure of a relatively isolated island ecological community in Fiordland, New Zealand, that are linked through a food web. We show that phylogenetic barriers that inhibited cross-species virus transmission occurred at the level of host phyla (between the Chordata, Arthropoda and Streptophyta) as well as at lower taxonomic levels. By contrast, host ecology, manifest as predator-prey interactions and diet, had a smaller influence on virome composition, especially at higher taxonomic levels. The virus-host community comprised a 'small world' network, in which hosts with a high diversity of viruses were more likely to acquire new viruses, and generalist viruses that infect multiple hosts were more likely to infect additional species compared to host specialist viruses. Such a highly connected ecological community increases the likelihood of cross-species virus transmission, particularly among closely related species, and suggests that host generalist viruses present the greatest risk of disease emergence.

Development and acceptability of a mobile health application integrated with the electronic heath record for treatment of chronic insomnia disorder.

STUDY OBJECTIVES: To describe the development and feasibility of a cognitive behavioral therapy for insomnia (CBT-I) program delivered via personal digital devices and fully integrated with the electronic health record (EHR). METHODS: A multidisciplinary team of clinicians and members of our Center for Digital Health collaborated to develop a Chronic Insomnia Interactive Care Plan (ChI-ICP), an application that provides personalized and just in time education and promotes self-management using CBT-I concepts, and is activated from and fully integrated into the EHR. Following development, we evaluated patient engagement and workflows, assessed changes to provider workload, and examined outcomes on measures of insomnia during a pilot deployment of the application. RESULTS: A total of 222 patients were enrolled and 179 engaged with the plan during the 3-month pilot program. Enrolled patients generated an average of 3.9 ± 2.3 In Basket messages, most being automated notifications related to noncompletion of assigned tasks, while only a few were related to patients requesting additional training or help with insomnia. Sleep efficiency improved from baseline until the completion of the program from 74.5% ± 16.7% to 87.6% ± 10.8% (P = .001), and the Insomnia Severity Index improved from 14.9 ± 5.22 to 11.6 ± 4.80 (P = .006). CONCLUSIONS: In this pilot implementation of an integrated ChI-ICP, patient engagement was favorable, workflows and workload were not significantly burdensome for the care teams, and initial evaluation of efficacy was favorable. This provides evidence for an application that is a scalable method to assist patients with chronic insomnia and future work should assess its efficacy in controlled trials. CITATION: Morgenthaler TI, Kolla BP, Anderson SE, et al. Development and acceptability of a mobile health application integrated with the electronic heath record for treatment of chronic insomnia disorder. J Clin Sleep Med. 2022;18(12):2785-2792.

Evaluating the success of functional restoration after reintroduction of a lost avian pollinator.

Conservation translocation is a common method for species recovery, for which one increasingly frequent objective is restoring lost ecological functions to promote ecosystem recovery. However, few conservation translocation programs explicitly state or monitor function as an objective, limiting the ability to test assumptions, learn from past efforts, and improve management. We evaluated whether translocations of hihi (Notiomystis cincta), a threatened New Zealand passerine, achieved their implicit objective of restoring lost pollination function. Through a pollinator-exclusion experiment, we quantified, with log response ratios (lnR), the effects of birds on fruit set and seed quality in hangehange (Geniostoma ligustrifolium), a native flowering shrub. We isolated the contributions of hihi by making comparisons across sites with and without hihi. Birds improved fruit set more at sites without hihi (lnR = 1.27) than sites with hihi (lnR = 0.50), suggesting other avian pollinators compensated for and even exceeded hihi contributions to fruit set. Although birds improved seed germination only at hihi sites (lnR = 0.22-0.41), plants at sites without hihi had germination rates similar to hihi sites because they produced 26% more filled seeds, regardless of pollination condition. Therefore, although our results showed hihi improved seed quality, they also highlighted the complexity of ecological functions. When an important species is lost, ecosystems may be able to achieve similar function through different means. Our results underscore the importance of stating and monitoring the ecological benefits of conservation translocations when functional restoration is a motivation to ensure these programs are achieving their objectives.

Evaluación del Éxito de la Restauración Funcional Posterior a la Reintroducción de un Ave Polinizadora Desaparecida Resumen La reubicación para la conservación es un método común para la recuperación de especies en el cual un objetivo cada vez más frecuente es la restauración de las funciones ecológicas que se perdieron para promover la recuperación del ecosistema. Sin embargo, pocos programas de reubicación para la conservación establecen o monitorean explícitamente a la función como un objetivo, lo que limita la posibilidad de comprobar suposiciones, aprender de esfuerzos anteriores y mejorar la gestión. Analizamos si las reubicaciones de hihi (Notiomystis cincta), un ave paseriforme amenazada de Nueva Zelanda, lograron el objetivo implícito de restaurar la desaparecida función de polinización. Mediante un experimento de exclusión del polinizador, cuantificamos con relaciones de respuesta logarítmica (lnR) los efectos de las aves sobre el conjunto de frutos y la calidad de la semilla del arbusto floral nativo Geniostoma ligustrifolium. Aislamos las contribuciones del hihi cuando comparamos entre sitios con y sin su presencia. Las aves favorecieron más al conjunto de frutos en sitios sin hihi (lnR = 1.27) que en los sitios con hihi (lnR = 0.50), lo que sugiere que otras aves polinizadoras compensaron y excedieron las contribuciones del hihi al conjunto de frutos. Aunque las aves aumentaron la germinación de semillas sólo en sitios con hihi (lnR = 0.22-0.41), las plantas en los sitios sin hihi tuvieron tasas de germinación similares a los sitios con hihi porque produjeron 26% más de semillas completas sin importar la condición de la polinización. Por lo tanto, aunque nuestros resultados mostraron mejoras en la calidad de la semilla a causa del hihi, también resaltaron la complejidad de las funciones ecológicas. Cuando desaparece una especie importante, puede que los ecosistemas logren una función similar por medio de diferentes métodos. Nuestros resultados hacen hincapié en la importancia que tiene establecer y monitorear los beneficios ecológicos de las reubicaciones para la conservación cuando la restauración es motivo para asegurar que estos programas están logrando sus objetivos.

Inhaled Medicines: Past, Present, and Future.

The purpose of this review is to summarize essential pharmacological, pharmaceutical, and clinical aspects in the field of orally inhaled therapies that may help scientists seeking to develop new products. After general comments on the rationale for inhaled therapies for respiratory disease, the focus is on products approved approximately over the last half a century. The organization of these sections reflects the key pharmacological categories. Products for asthma and chronic obstructive pulmonary disease include ß -2 receptor agonists, muscarinic acetylcholine receptor antagonists, glucocorticosteroids, and cromones as well as their combinations. The antiviral and antibacterial inhaled products to treat respiratory tract infections are then presented. Two "mucoactive" products-dornase α and mannitol, which are both approved for patients with cystic fibrosis-are reviewed. These are followed by sections on inhaled prostacyclins for pulmonary arterial hypertension and the challenging field of aerosol surfactant inhalation delivery, especially for prematurely born infants on ventilation support. The approved products for systemic delivery via the lungs for diseases of the central nervous system and insulin for diabetes are also discussed. New technologies for drug delivery by inhalation are analyzed, with the emphasis on those that would likely yield significant improvements over the technologies in current use or would expand the range of drugs and diseases treatable by this route of administration. SIGNIFICANCE STATEMENT: This review of the key aspects of approved orally inhaled drug products for a variety of respiratory diseases and for systemic administration should be helpful in making judicious decisions about the development of new or improved inhaled drugs. These aspects include the choices of the active ingredients, formulations, delivery systems suitable for the target patient populations, and, to some extent, meaningful safety and efficacy endpoints in clinical trials.

Rapid response to medical device recalls: an organized patient-centered team effort.

As more patients depend upon mechanical or electronic technologies for treatment, medical device recalls-like the recent recall of common positive airway pressure treatment devices-impact millions of patients, often causing significant anxiety, extra costs, and interruption of care for patients. When recalls require health care and/durable medical equipment providers to be part of the solution, the burden on practices and businesses can be significant, creating strains on access for new patients and on limited medical supplies. We have observed that having an established and well-organized medical device recall plan in place allows for a rapid response, decreased practice burden, and reduced provider stress. Coupling the organized response with proactive, empathic, and clear communication with patients reduces their anxiety, provides clear directions for how to address the issue constructively, and reduces reactive communications. We share what we believe are key components of a medical device and produce recall procedure as we describe our institutions response in hopes that others can build on these basics as they design their own response plans. CITATION: Morgenthaler TI, Linginfelter EA, Gay PC, et al. Rapid response to medical device recalls: an organized patient-centered team effort. J Clin Sleep Med. 2022;18(2):663-667.

Repurposing drugs as inhaled therapies in asthma.

For the first 40 years of the 20th century treatment for asthma occurred in response to an asthma attack. The treatments were given by injection or orally and included the adrenergic agonists adrenalin/epinephrine and ephedrine and a phosphodiesterase inhibitor theophylline. Epinephrine became available as an aerosol in 1930. After 1945, isoprenaline, a non-selective beta agonist, became available for oral use but it was most widely used by inhalation. Isoprenaline was short-acting with unwanted cardiac effects. More selective beta agonists, with a longer duration of action and fewer side-effects became available, including orciprenaline in 1967, salbutamol in 1969 and terbutaline in 1970. The inhaled steroid beclomethasone was available by 1972 and budesonide by 1982. Spirometry alone and in response to exercise was used to assess efficacy and duration of action of these drugs for the acute benefits of beta2 agonists and the chronic benefits of corticosteroids. Early studies comparing oral and aerosol beta2 agonists found equivalence in bronchodilator effect but the aerosol treatment was superior in preventing exercise-induced bronchoconstriction. Inhaled drugs are now widely used including the long-acting beta2 agonists, salmeterol and formoterol, and the corticosteroids, fluticasone, ciclesonide, mometasone and triamcinolone, that act locally and have low systemic bio-availability. Repurposing drugs as inhaled therapies permitted direct delivery of low doses of drug to the site of action reducing the incidence of unwanted side-effects and permitting the prophylactic treatment of asthma.

Mechanisms and Biomarkers of Exercise-Induced Bronchoconstriction.

Exercise is a common trigger of bronchoconstriction. In recent years, there has been increased understanding of the pathophysiology of exercise-induced bronchoconstriction. Although evaporative water loss and thermal changes have been recognized stimuli for exercise-induced bronchoconstriction, accumulating evidence points toward a pivotal role for the airway epithelium in orchestrating the inflammatory response linked to exercise-induced bronchoconstriction. Overproduction of inflammatory mediators, underproduction of protective lipid mediators, and infiltration of the airways with eosinophils and mast cells are all established contributors to exercise-induced bronchoconstriction. Sensory nerve activation and release of neuropeptides maybe important in exercise-induced bronchoconstriction, but further research is warranted.

Repurposing excipients as active inhalation agents: The mannitol story.

The story of how we came to use inhaled mannitol to diagnose asthma and to treat cystic fibrosis began when we were looking for a surrogate for exercise as a stimulus to identify asthma. We had proposed that exercise-induced asthma was caused by an increase in osmolarity of the periciliary fluid. We found hypertonic saline to be a surrogate for exercise but an ultrasonic nebuliser was required. We produced a dry powder of sodium chloride but it proved unstable. We developed a spray dried preparation of mannitol and found that bronchial responsiveness to inhaling mannitol identified people with currently active asthma. We reasoned that mannitol had potential to replace the 'osmotic' benefits of exercise and could be used as a treatment to enhance mucociliary clearance in patients with cystic fibrosis. These discoveries were the start of a journey to develop several registered products that are in clinical use globally today.

'Indirect' challenges from science to clinical practice.

Indirect challenges act to provoke bronchoconstriction by causing the release of endogenous mediators and are used to identify airway hyper-responsiveness. This paper reviews the historical development of challenges, with exercise, eucapnic voluntary hyperpnoea (EVH) of dry air, wet hypertonic saline, and with dry powder mannitol, that preceded their use in clinical practice. The first challenge developed for clinical use was exercise. Physicians were keen for a standardized test to identify exercise-induced asthma (EIA) and to assess the effect of drugs such as disodium cromoglycate. EVH with dry air became a surrogate for exercise to increase ventilation to very high levels. A simple test was developed with EVH and used to identify EIA in defence force recruits and later in elite athletes. The research findings with different conditions of inspired air led to the conclusion that loss of water by evaporation from the airway surface was the stimulus to EIA. The proposal that water loss caused a transient increase in osmolarity led to the development of the hypertonic saline challenge. The wet aerosol challenge with 4.5% saline, provided a known osmotic stimulus, to which most asthmatics were sensitive. To simplify the osmotic challenge, a dry powder of mannitol was specially prepared and encapsulated. The test pack with different doses and an inhaler provided a common operating procedure that could be used at the point of care. All these challenge tests have a high specificity to identify currently active asthma. All have been used to assess the benefit of treatment with inhaled corticosteroids. Over the 50 years, the methods for testing became safer, less complex, and less expensive and all used forced expiratory volume in 1 sec to measure the response. Thus, they became practical to use routinely and were recommended in guidelines for use in clinical practice.

Evaluating a multigene environmental DNA approach for biodiversity assessment.

BACKGROUND: There is an increasing demand for rapid biodiversity assessment tools that have a broad taxonomic coverage. Here we evaluate a suite of environmental DNA (eDNA) markers coupled with next generation sequencing (NGS) that span the tree of life, comparing them with traditional biodiversity monitoring tools within ten 20×20 meter plots along a 700 meter elevational gradient. RESULTS: From six eDNA datasets (one from each of 16S, 18S, ITS, trnL and two from COI) we identified sequences from 109 NCBI taxonomy-defined phyla or equivalent, ranging from 31 to 60 for a given eDNA marker. Estimates of alpha and gamma diversity were sensitive to the number of sequence reads, whereas beta diversity estimates were less sensitive. The average within-plot beta diversity was lower than between plots for all markers. The soil beta diversity of COI and 18S markers showed the strongest response to the elevational variation of the eDNA markers (COI: r=0.49, p<0.001; 18S: r=0.48, p<0.001). Furthermore pairwise beta diversities for these two markers were strongly correlated with those calculated from traditional vegetation and invertebrate biodiversity measures. CONCLUSIONS: Using a soil-based eDNA approach, we demonstrate that standard phylogenetic markers are capable of recovering sequences from a broad diversity of eukaryotes, in addition to prokaryotes by 16S. The COI and 18S eDNA markers are the best proxies for aboveground biodiversity based on the high correlation between the pairwise beta diversities of these markers and those obtained using traditional methods.

The compounding effects of high pollen limitation, selfing rates and inbreeding depression leave a New Zealand tree with few viable offspring.

BACKGROUND AND AIMS: Interactions between species are especially sensitive to environmental changes. The interaction between plants and pollinators is of particular interest given the potential current global decline in pollinators. Reduced pollinator services can be compensated for in some plant species by self-pollination. However, if inbreeding depression is high, selfed progeny could die prior to reaching adulthood, leading to cryptic recruitment failure. METHODS: To examine this scenario, pollinator abundance, pollen limitation, selfing rates and inbreeding depression were examined in 12 populations of varying disturbance levels in Sophora microphylla (Fabaceae), an endemic New Zealand tree species. KEY RESULTS: High pollen limitation was found in all populations (average of 58 % reduction in seed production, nine populations), together with high selfing rates (61 % of offspring selfed, six populations) and high inbreeding depression (selfed offspring 86 % less fit, six populations). Pollen limitation was associated with lower visitation rates by the two endemic bird pollinators. CONCLUSIONS: The results suggest that for these populations, over half of the seeds produced are genetically doomed. This reduction in the fitness of progeny due to reduced pollinator service is probably important to population dynamics of other New Zealand species. More broadly, the results suggest that measures of seed production or seedling densities may be a gross overestimate of the effective offspring production. This could lead to cryptic recruitment failure, i.e. a decline in successful reproduction despite high progeny production. Given the global extent of pollinator declines, cryptic recruitment failure may be widespread.

Urinary excretion of lipid mediators in response to repeated eucapnic voluntary hyperpnea in asthmatic subjects.

Exercise-induced bronchoconstriction displays refractoriness manifested as a decreased response to repeated exercise challenge within hours. The refractoriness may be attenuated by inhibition of the biosynthesis of prostaglandins (PG). The aim of the study was to determine which PGs and other lipid mediators are excreted during the refractory period. First, 16 subjects with mild stable asthma performed two repeated 4-min challenges with eucapnic voluntary hyperpnea (EVH) 1 and 3 h apart. There was a similar degree of refractoriness in both protocols (∼15% protection). The 1-h interval was too short to study mediator excretion because the urinary levels did not return to baseline before the second challenge. With the 3-h protocol, there was increased urinary excretion of cysteinyl-leukotrienes and metabolites of the mast cell product PGD2 after both challenges. Next, another eight subjects performed two 6-min challenges with EVH 3 h apart, which produced a greater bronchoconstrictor response than the 4-min protocol (30.0 ± 5.4 vs. 17.7 ± 1.5%; P = 0.0029) and a greater degree of refractoriness (∼30%). Analysis by ultra-performance liquid chromatography triple quadrupole mass spectrometry confirmed excretion of the bronchoconstrictor cysteinyl-leukotrienes and PGD2 during both challenges. In addition, there was increased excretion of the bronchoprotective PGE2, and also of the main metabolite of PGI2. This is the first report of excretion of PGE2 and PGI2 during the refractory period to EVH challenge, suggesting that they may mediate the refractoriness. Maintained excretion of PGD2 and leukotriene E4 following the repeat challenge argues against mast cell mediator depletion as the mechanism of refractoriness.

An Apparatus to Deliver Mannitol Powder for Bronchial Provocation in Children Under Six Years Old.

BACKGROUND: Currently bronchial provocation testing (BPT) using mannitol powder cannot be performed in children under 6 years. A primary reason is it is challenging for children at this age to generate a consistent inspiratory effort to inhale mannitol efficiently from a dry powder inhaler. A prototype system, which does not require any inhalation training from the pediatric subject, is reported here. It uses an external source of compressed air to disperse mannitol powder into a commercial holding chamber. Then the subject uses tidal breathing to inhale the aerosol. METHOD: The setup consists of a commercially available powder disperser and Volumatic™ holding chamber. Taguchi experimental design was used to identify the effect of dispersion parameters (flow rate of compressed air, time compressed air is applied, mass of powder, and the time between dispersion and inhalation) on the fine particle dose (FPD). The prototype was tested in vitro using a USP throat connected to a next generation impactor. The aerosols from the holding chamber were drawn at 10 L/min. A scaling factor for estimating the provoking dose to induce a 15% reduction in forced expiratory volume in 1 second (FEV1) (PD15) was calculated using anatomical dimensions of the human respiratory tract at various ages combined with known dosing values from the adult BPT. RESULTS: Consistent and doubling FPDs were successfully generated based on the Taguchi experimental design. The FPD was reliable over a range of 0.8 (±0.09) mg to 14 (±0.94) mg. The calculated PD15 for children aged 1-6 years ranged from 7.1-30 mg. The FPDs generated from the proposed set up are lower than the calculated PD15 and therefore are not expected to cause sudden bronchoconstriction. CONCLUSION: A prototype aerosol delivery system has been developed that is consistently able to deliver doubling doses suitable for bronchial provocation testing in young children.

Air quality and temperature effects on exercise-induced bronchoconstriction.

Exercise-induced bronchoconstriction (EIB) is exaggerated constriction of the airways usually soon after cessation of exercise. This is most often a response to airway dehydration in the presence of airway inflammation in a person with a responsive bronchial smooth muscle. Severity is related to water content of inspired air and level of ventilation achieved and sustained. Repetitive hyperpnea of dry air during training is associated with airway inflammatory changes and remodeling. A response during exercise that is related to pollution or allergen is considered EIB. Ozone and particulate matter are the most widespread pollutants of concern for the exercising population; chronic exposure can lead to new-onset asthma and EIB. Freshly generated emissions particulate matter less than 100 nm is most harmful. Evidence for acute and long-term effects from exercise while inhaling high levels of ozone and/or particulate matter exists. Much evidence supports a relationship between development of airway disorders and exercise in the chlorinated pool. Swimmers typically do not respond in the pool; however, a large percentage responds to a dry air exercise challenge. Studies support oxidative stress mediated pathology for pollutants and a more severe acute response occurs in the asthmatic. Winter sport athletes and swimmers have a higher prevalence of EIB, asthma and airway remodeling than other athletes and the general population. Because of fossil fuel powered ice resurfacers in ice rinks, ice rink athletes have shown high rates of EIB and asthma. For the athlete training in the urban environment, training during low traffic hours and in low traffic areas is suggested.

Calciphylaxis: an unusual case with an unusual outcome.

OVERVIEW: Calciphylaxis is most common in patients with end-stage renal disease, and hyperparathyroidism is often present as well. But several cases in patients with normal renal and parathyroid function have been reported; this article describes one such case. The etiology and pathophysiology of calciphylaxis aren't well understood. There are many risk factors, and the reported median survival time is 2.6 months after diagnosis. The condition is characterized by isolated or multiple lesions that progress to firm, nonulcerated plaques and then to ischemic skin necrosis and ulceration. In August 2010, a female patient arrived at the hospital with multiple deep, painful necrotic wounds. Given this patient's presentation on admission, the nurses kept expecting the physicians to initiate end-of-life discussions with her and were surprised when this did not happen. After five days, the patient was diagnosed with calciphylaxis in the unusual presentation of normal renal and parathyroid function, and the team realized that her chances for survival were greater than expected. The nursing staff was crucial in developing and implementing an intensive treatment plan. The patient survived and made a full recovery.

Inspiratory flows and volumes in subjects with cystic fibrosis using a new dry powder inhaler device.

INTRODUCTION: Drug inhalation via a dry-powder inhaler (DPI) is a convenient, time efficient alternative to nebulizers in the treatment of cystic fibrosis (CF). Efficient drug administration via DPIs depends on the device resistance and adequate (≥ 45L/min) inspiratory flows and volumes generated by individuals. Dry-powder mannitol is delivered using a RS01 breath-actuated device developed by Plastiape, for Pharmaxis. The study aim was to determine in vivo if CF patients' inspiratory flows and volumes are adequate to use the RS01 DPI device. MATERIALS AND METHODOLOGY: An open, non-interventional study; enrolled 25 CF subjects, aged ≥ 6 years with FEV1 ≥ 30 to < 90‰ predicted. Inspiratory flows and volumes were measured when subjects inhaled in a controlled manner through the RS01 device in series with a spirometer. RESULTS: The mean inspiratory volume (IV) of CF subjects was 1.83L ± 0.97. Their achieved mean ± SD peak inspiratory flow (PIF) was 75.5 ± 27.2L/min. Twenty-three subjects (92%) achieved PIF of > 45L/min with the inhaler device; eighteen of those subjects (78%) had a baseline FEV1 of > 1L. CONCLUSION: Use of the RS01 DPI device allowed adequate inspiratory flow and volume for dispersion of dry-powder mannitol in CF patients.

Inspiratory Flows and Volumes in Subjects with Non-CF Bronchiectasis Using a New Dry Powder Inhaler Device.

INTRODUCTION: Drug inhalation via a dry-powder inhaler (DPI) is a convenient, time efficient alternative to nebulizers in the treatment of cystic fibrosis (CF) or non-CF bronchiectasis. Efficient drug administration via DPIs depends on the device resistance and adequate (≥45L/min) inspiratory flows and volumes generated by individuals. Drypowder mannitol is delivered using a RS01 breath-actuated device developed by Plastiape, for Pharmaxis. The study aim was to determine in vivo if non-CF bronchiectasis patients' inspiratory flows and volumes are adequate to use the RS01 DPI device. MATERIALS AND METHODOLOGY: An open, non-interventional study; enrolled 17 subjects with non-CF bronchiectasis, 18 to 80 years, with baseline FEV1 ≥1.0L and ≥50‰ predicted. Inspiratory flows and volumes were measured when subjects inhaled in a controlled manner through the RS01 device in series with a spirometer. RESULTS: The mean inspiratory volume (IV) of non-CF bronchiectasis subjects was 2.08 ± 0.5L and achieved a mean PIF of 78.6 ± 11.2L/min with the inhaler device. CONCLUSION: Use of the RS01 DPI device allowed adequate inspiratory flow and volume for dispersion of dry-powder mannitol in non-CF bronchiectasis patients.