Browsing by Subject "Administration, Inhalation"

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Open Access
Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine.
(Drug Des Devel Ther, 2013) Noveck, Robert J; Douglas, Pamela S; Chow, Shein-Chung; Mangum, Barry; Kori, Shashidhar; Kellerman, Donald J
OBJECTIVE: MAP0004 is an investigational product which delivers dihydroergotamine (DHE) through the lung via a breath-synchronized metered dose inhaler. The objective of this study was to compare the acute effects of orally inhaled and intravenous (IV) DHE to placebo on maximum change and area under the curve for pulmonary arterial systolic pressure (PASP). RESEARCH DESIGN AND METHODS: A randomized, double-blind, placebo-controlled, 3-period, crossover study of 24 health adults. Trial registration NCT01089062. Study assessments included pharmacokinetics, electrocardiograms (ECG), and validated echocardiographic (Doppler)-derived measures of PASP by echocardiogram. The primary endpoint was the absolute change in calculated PASP using area under the curve, 0 to 2 hours (AUC(0-2h)). RESULTS: The change in PASP with IV DHE was significantly different than MAP0004 and placebo (AUC(0-2h)2857, 2624, and 2453 mmHg*min, respectively). After a second dose of MAP0004, AUC(0-4h) remained lower with MAP0004 than with a single dose of IV DHE. Adverse events were more common with IV DHE than with MAP0004 or placebo. None of the treatments produced clinically significant changes in PASP or other cardiac parameters. Changes in PASP were significantly smaller with MAP0004 compared with IV DHE. CONCLUSION: These results indicate the effects 1 mg of orally inhaled DHE on the cardiovascular system are less than with 1 mg of IV DHE, and that serial echocardiography can be a useful noninvasive means of assessing acute systemic effects.
Open Access
Donor pretreatment with nebulized complement C3a receptor antagonist mitigates brain-death induced immunological injury post-lung transplant.
(American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2018-10) Cheng, Qi; Patel, Kunal; Lei, Biao; Rucker, Lindsay; Allen, D Patterson; Zhu, Peng; Vasu, Chentha; Martins, Paulo N; Goddard, Martin; Nadig, Satish N; Atkinson, Carl
Donor brain death (BD) is an inherent part of lung transplantation (LTx) and a key contributor to ischemia-reperfusion injury (IRI). Complement activation occurs as a consequence of BD in other solid organ Tx and exacerbates IRI, but the role of complement in LTx has not been investigated. Here, we investigate the utility of delivering nebulized C3a receptor antagonist (C3aRA) pretransplant to BD donor lungs in order to reduce post-LTx IRI. BD was induced in Balb/c donors, and lungs nebulized with C3aRA or vehicle 30 minutes prior to lung procurement. Lungs were then cold stored for 18 hours before transplantation into C57Bl/6 recipients. Donor lungs from living donors (LD) were removed and similarly stored. At 6 hours and 5 days post-LTx, recipients of BD donor lungs had exacerbated IRI and acute rejection (AR), respectively, compared to recipients receiving LD lungs, as determined by increased histopathological injury, immune cells, and cytokine levels. A single pretransplant nebulized dose of C3aRA to the donor significantly reduced IRI as compared to vehicle-treated BD donors, and returned IRI and AR grades to that seen following LD LTx. These data demonstrate a role for complement inhibition in the amelioration of IRI post-LTx in the context of donor BD.
Open Access
Epithelial injury and interstitial fibrosis in the proximal alveolar regions of rats chronically exposed to a simulated pattern of urban ambient ozone.
(Toxicology and applied pharmacology, 1992-08) Chang, LY; Huang, Y; Stockstill, BL; Graham, JA; Grose, EC; Menache, MG; Miller, FJ; Costa, DL; Crapo, JD
Electron microscopic morphometry was used to study the development of lung injury during and after chronic (78 weeks) exposure to a pattern of ozone (O3) designed to simulate high urban ambient concentrations that occur in some environments. The daily exposure regimen consisted of a 13-hr background of 0.06 ppm, an exposure peak that rose from 0.06 to 0.25 ppm, and returned to the background level over a 9-hr period, and 2-hr downtime for maintenance. Rats were exposed for 1, 3, 13, and 78 weeks. Additional groups of rats exposed for 13 or 78 weeks were allowed to recover in filtered clean air for 6 or 17 weeks, respectively. Rats exposed to filtered air for the same lengths of time were used as controls. Samples from proximal alveolar regions and terminal bronchioles were obtained by microdissection. Analysis of the proximal alveolar region revealed a biphasic response. Acute tissue reactions after 1 week of exposure included epithelial inflammation, interstitial edema, interstitial cell hypertrophy, and influx of macrophages. These responses subsided after 3 weeks of exposure. Progressive epithelial and interstitial tissue responses developed with prolonged exposure and included epithelial hyperplasia, fibroblast proliferation, and interstitial matrix accumulation. The epithelial responses involved both type I and type II epithelial cells. Alveolar type I cells increased in number, became thicker, and covered a smaller average surface area. These changes persisted throughout the entire exposure and did not change during the recovery period, indicating the sensitivity of these cells to injury. The main response of type II epithelial cells was cell proliferation. The accumulation of interstitial matrix after chronic exposure consisted of deposition of both increased amounts of basement membrane and collagen fibers. Interstitial matrix accumulation underwent partial recovery during follow-up periods in air; however, the thickening of the basement membrane did not resolve. Analysis of terminal bronchioles showed that short-term exposure to O3 caused a loss of ciliated cells and differentiation of preciliated and Clara cells. The bronchiolar cell population stabilized on continued exposure; however, chronic exposure resulted in structural changes, suggesting injury to both ciliated and Clara cells. We conclude that chronic exposure to low levels of O3 causes epithelial inflammation and interstitial fibrosis in the proximal alveolar region and bronchiolar epithelial cell injury.
Open Access
High prevalence of substance use disorders among adolescents who use marijuana and inhalants.
(Drug and alcohol dependence, 2005-04) Wu, Li-Tzy; Pilowsky, Daniel J; Schlenger, William E
BACKGROUND: We examined the association between the use of inhalants, marijuana, and other drugs and recent DSM-IV substance use disorders among adolescents aged 12-17 years. METHODS: Data were drawn from 2000 to 2001 National Household Surveys on Drug Abuse. Adolescents aged 12-17 years who reported having ever used an illicit drug in their lifetime were categorized into four mutually exclusive groups: inhalant users (16%), marijuana users (53%), inhalant and marijuana users (16%), and other drug users (15%). Logistic regression models were used to estimate associations with recent substance use diagnoses among lifetime adolescent drug users (N=10,180). RESULTS: We found that 31% of lifetime drug users reported having never used marijuana. One half of these atypical drug users were predominantly nonmedical users of pain relievers. Adolescents who used inhalants or other drugs but not marijuana were least likely to report multidrug use. Adolescents who reported using both inhalants and marijuana were most likely to use three or more classes of drugs (73%) and to receive a diagnosis of past year alcohol (35%) and drug (39%) abuse or dependence. CONCLUSIONS: Our study findings suggest that among lifetime adolescent drug users, those who use both inhalants and marijuana are at very high risk for alcohol and drug use disorders.
Open Access
Inhalant abuse and dependence among adolescents in the United States.
(Journal of the American Academy of Child and Adolescent Psychiatry, 2004-10) Wu, Li-Tzy; Pilowsky, Daniel J; Schlenger, William E
To examine the patterns of inhalant use and correlates of the progression from inhalant use to abuse and dependence among adolescents aged 12 to 17.Study data were drawn from the 2000 and 2001 National Household Surveys on Drug Abuse. Multinominal logistic regression was used to identify the characteristics associated with progression to inhalant abuse and dependence.Inhalant use was common among the studied adolescents. Among adolescents aged 12 to 17, 0.4% met DSM-IV inhalant abuse or dependence criteria in the past year. Inhalant abuse and dependence affected adolescents regardless of gender, age, race/ethnicity, and family income. The progression from inhalant use to abuse or dependence was related to early first use, use of multiple inhalants, and weekly inhalant use. Adolescents with inhalant use disorders reported coexisting multiple drug abuse and dependence, mental health treatment, and delinquent behaviors.Adolescents with an inhalant use disorder may represent a subgroup of highly troubled youths with multiple vulnerabilities. Because early use is associated with progression to abuse and dependence, prevention programs should target elementary school-age children.
Open Access
Inhalant use and disorders among adults in the United States.
(Drug and alcohol dependence, 2006-10) Wu, Li-Tzy; Ringwalt, Christopher L
To examine the patterns of adult inhalant use and correlates of inhalant use disorder.We drew study data from the 2002 and 2003 National Surveys on Drug Use and Health (NSDUH). We used logistic regression to identify the characteristics associated both with inhalant use and inhalant use disorder.One in 10 of all adults had used an inhalant at least once in their lives, and 0.5% used one in the past year. Among all past year inhalant users, 8% met the criteria for an inhalant use disorder (i.e., 6.6% for abuse and 1.1% for dependence) within that period. We found an increased prevalence of past year inhalant use among young adults aged 18-25 years, Asians, past year alcohol abusers and dependents, lifetime drug users, white women, and men reporting symptoms of serious mental illness. Inhalant-using adults who met the criteria for an inhalant use disorder were predominantly adults aged 35-49 years and were less educated, had received recent professional treatment for emotional or psychological problems, used inhalants weekly, and had a coexisting alcohol use disorder.The patterns and consequences of adult inhalant use differ from those of adolescents. Compared with adolescent inhalant users, adult users tend not to initiate inhalant use until adulthood, use inhalants less frequently, use fewer inhalants, and are less likely to engage in criminal activities.
Open Access
Inhaled Nitric Oxide (iNO) and Inhaled Epoprostenol (iPGI2) Use in Cardiothoracic Surgical Patients: Is there Sufficient Evidence for Evidence-Based Recommendations?
(Journal of cardiothoracic and vascular anesthesia, 2018-06) Rao, Vidya; Ghadimi, Kamrouz; Keeyapaj, Worasak; Parsons, Cody A; Cheung, Albert T
Open Access
Inhaled Pulmonary Vasodilator Therapy in Adult Lung Transplant: A Randomized Clinical Trial.
(JAMA surgery, 2022-01) Ghadimi, Kamrouz; Cappiello, Jhaymie; Cooter-Wright, Mary; Haney, John C; Reynolds, John M; Bottiger, Brandi A; Klapper, Jacob A; Levy, Jerrold H; Hartwig, Matthew G; INSPIRE-FLO Investigators
Importance
Inhaled nitric oxide (iNO) is commonly administered for selectively inhaled pulmonary vasodilation and prevention of oxidative injury after lung transplant (LT). Inhaled epoprostenol (iEPO) has been introduced worldwide as a cost-saving alternative to iNO without high-grade evidence for this indication.
Objective
To investigate whether the use of iEPO will lead to similar rates of severe/grade 3 primary graft dysfunction (PGD-3) after adult LT when compared with use of iNO.
Design, setting, and participants
This health system-funded, randomized, blinded (to participants, clinicians, data managers, and the statistician), parallel-designed, equivalence clinical trial included 201 adult patients who underwent single or bilateral LT between May 30, 2017, and March 21, 2020. Patients were grouped into 5 strata according to key prognostic clinical features and randomized per stratum to receive either iNO or iEPO at the time of LT via 1:1 treatment allocation.
Interventions
Treatment with iNO or iEPO initiated in the operating room before lung allograft reperfusion and administered continously until cessation criteria met in the intensive care unit (ICU).
Main outcomes and measures
The primary outcome was PGD-3 development at 24, 48, or 72 hours after LT. The primary analysis was for equivalence using a two one-sided test (TOST) procedure (90% CI) with a margin of 19% for between-group PGD-3 risk difference. Secondary outcomes included duration of mechanical ventilation, hospital and ICU lengths of stay, incidence and severity of acute kidney injury, postoperative tracheostomy placement, and in-hospital, 30-day, and 90-day mortality rates. An intention-to-treat analysis was performed for the primary and secondary outcomes, supplemented by per-protocol analysis for the primary outcome.
Results
A total of 201 randomized patients met eligibility criteria at the time of LT (129 men [64.2%]). In the intention-to-treat population, 103 patients received iEPO and 98 received iNO. The primary outcome occurred in 46 of 103 patients (44.7%) in the iEPO group and 39 of 98 (39.8%) in the iNO group, leading to a risk difference of 4.9% (TOST 90% CI, -6.4% to 16.2%; P = .02 for equivalence). There were no significant between-group differences for secondary outcomes.
Conclusions and relevance
Among patients undergoing LT, use of iEPO was associated with similar risks for PGD-3 development and other postoperative outcomes compared with the use of iNO.
Trial registration
ClinicalTrials.gov identifier: NCT03081052.
Unknown
Is inhalant use a risk factor for heroin and injection drug use among adolescents in the United States?
(Addictive behaviors, 2007-02) Wu, Li-Tzy; Howard, Matthew O
We examined whether inhalant use was associated with heroin and injection drug use (IDU) among adolescents aged 12 to 17 in the United States.Data were drawn from the 2002/2003 administrations of the National Survey on Drug Use and Health (NSDUH). We conducted logistic regression analyses to estimate associations of inhalant use with heroin use, heroin injection, and IDU, respectively, among adolescent drug users (N=8161).Approximately 30.9% of adolescents had ever used at least one illicit drug. More than one-fifth (22.2%) of adolescents were past-year or recent drug users. Among past-year adolescent drug users, 1.4% had progressed to heroin use and 1.2% reported IDU. Adolescents who had used inhalants and marijuana were 2.8 and 2.9 times as likely as adolescents who had used marijuana but not inhalants to report heroin use and any IDU, respectively. Adolescents who had used inhalants or other drugs but not marijuana were unlikely to use heroin. However, inhalant users, irrespective of their marijuana use histories, had greater odds of IDU than drug users who had not used inhalants. Adolescent drug users who were females, school dropouts, whites, or delinquents had significantly increased odds of heroin use and IDU. Cigarette smoking before the age of 15 was strongly associated with heroin use, and a history of foster care placement was associated with IDU.This national study of American adolescents identifies several subgroups of recent drug users, such as females, school dropouts, and youth who have used inhalants and marijuana, which have substantially increased odds of heroin use and IDU. Screening, prevention, and treatment interventions targeted to these groups might reduce medical and social complications of heroin use and IDU.
Open Access
Pharmacologically augmented S-nitrosylated hemoglobin improves recovery from murine subarachnoid hemorrhage.
(Stroke, 2011-02) Sheng, H; Reynolds, JD; Auten, RL; Demchenko, IT; Piantadosi, CA; Stamler, JS; Warner, DS
Background and purpose
S-nitrosylated hemoglobin (S-nitrosohemoglobin) has been implicated in the delivery of O(2) to tissues through the regulation of microvascular blood flow. This study tested the hypothesis that enhancement of S-nitrosylated hemoglobin by ethyl nitrite inhalation improves outcome after experimental subarachnoid hemorrhage (SAH).
Methods
A preliminary dosing study identified 20 ppm ethyl nitrite as a concentration that produced a 4-fold increase in S-nitrosylated hemoglobin concentration with no increase in methemoglobin. Mice were subjected to endovascular perforation of the right anterior cerebral artery and were treated with 20 ppm ethyl nitrite in air, or air alone for 72 hours, after which neurologic function, cerebral vessel diameter, brain water content, cortical tissue Po(2), and parenchymal red blood cell flow velocity were measured.
Results
At 72 hours after hemorrhage, air- and ethyl nitrite-exposed mice had similarly sized blood clots. Ethyl nitrite improved neurologic score and rotarod performance; abated SAH-induced constrictions in the ipsilateral anterior, middle cerebral, and internal carotid arteries; and prevented an increase in ipsilateral brain water content. Ethyl nitrite inhalation increased red blood cell flow velocity and cortical tissue Po(2) in the ipsilateral cortex with no effect on systemic blood pressure.
Conclusions
Targeted S-nitrosylation of hemoglobin improved outcome parameters, including vessel diameter, tissue blood flow, cortical tissue Po(2), and neurologic function in a murine SAH model. Augmenting endogenous Po(2)-dependent delivery of NO bioactivity to selectively dilate the compromised cerebral vasculature has significant clinical potential in the treatment of SAH.
Open Access
PINOT NOIR: pulmonic insufficiency improvement with nitric oxide inhalational response.
(J Cardiovasc Magn Reson, 2013-09-04) Hart, Stephen A; Devendra, Ganesh P; Kim, Yuli Y; Flamm, Scott D; Kalahasti, Vidyasagar; Arruda, Janine; Walker, Esteban; Boonyasirinant, Thananya; Bolen, Michael; Setser, Randolph; Krasuski, Richard A
BACKGROUND: Tetralogy of Fallot (TOF) repair and pulmonary valvotomy for pulmonary stenosis (PS) lead to progressive pulmonary insufficiency (PI), right ventricular enlargement and dysfunction. This study assessed whether pulmonary regurgitant fraction measured by cardiovascular magnetic resonance (CMR) could be reduced with inhaled nitric oxide (iNO). METHODS: Patients with at least moderate PI by echocardiography undergoing clinically indicated CMR were prospectively enrolled. Patients with residual hemodynamic lesions were excluded. Ventricular volume and blood flow sequences were obtained at baseline and during administration of 40 ppm iNO. RESULTS: Sixteen patients (11 with repaired TOF and 5 with repaired PS) completed the protocol with adequate data for analysis. The median age [range] was 35 [19-46] years, BMI was 26 ± 5 kg/m(2) (mean ± SD), 50% were women and 75% were in NYHA class I. Right ventricular end diastolic volume index for the cohort was 157 ± 33 mL/m(2), end systolic volume index was 93 ± 20 mL/m(2) and right ventricular ejection fraction was 40 ± 6%. Baseline pulmonary regurgitant volume was 45 ± 25 mL/beat and regurgitant fraction was 35 ± 16%. During administration of iNO, regurgitant volume was reduced by an average of 6 ± 9% (p=0.01) and regurgitant fraction was reduced by an average of 5 ± 8% (p=0.02). No significant changes were observed in ventricular indices for either the left or right ventricle. CONCLUSION: iNO was successfully administered during CMR acquisition and appears to reduce regurgitant fraction in patients with at least moderate PI suggesting a potential role for selective pulmonary vasodilator therapy in these patients. TRIALS REGISTRATION: ClinicalTrials.gov, NCT00543933.
Open Access
Psychiatric disorders in inhalant users: results from The National Epidemiologic Survey on Alcohol and Related Conditions.
(Drug and alcohol dependence, 2007-05) Wu, Li-Tzy; Howard, Matthew Owen
To examine the prevalence and correlates of mood, anxiety, and personality disorders among lifetime inhalant users.Statistical analyses were based on data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative survey of adults in the United States.Inhalant users (N=664) had high lifetime prevalences of DSM-IV mood (48%), anxiety (36%), and personality (45%) disorders. Of all inhalant users, 70% met criteria for at least one lifetime mood, anxiety, or personality disorder and 38% experienced a mood or anxiety disorder in the past year. Prevalences of comorbid psychiatric disorders varied by gender. Compared with male inhalant users, female inhalant users had higher prevalences of lifetime dysthymia (24% versus 16%), any anxiety disorder (53% versus 30%), panic disorder without agoraphobia (25% versus 11%), and specific phobia (28% versus 14%), but a lower prevalence of antisocial personality disorder (22% versus 36%). Female inhalant users also were more likely than male inhalant users to meet criteria for three or more mood or anxiety disorders (15% versus 8%) in the past year. Among inhalant users with comorbid disorders, those who developed social or specific phobia typically experienced onset of these disorders prior to initiation of inhalant use; all other mood and anxiety disorders usually developed following the onset of inhalant use. Inhalant users who were women, poor, less educated, with early onset of inhalant use, family histories of psychopathology, and personal histories of substance abuse treatment had increased odds of psychiatric disorders.Psychiatric disorders are highly prevalent among inhalant users nationally and female inhalant users are more likely than male inhalant users to experience multiple psychiatric disorders. Inhalant use and its consequences among females warrant greater research attention.
Open Access
Regional Gas Exchange Measured by ¹²⁹ Xe Magnetic Resonance Imaging Before and After Combination Bronchodilators Treatment in Chronic Obstructive Pulmonary Disease.
(Journal of magnetic resonance imaging : JMRI, 2021-09) Mummy, David G; Coleman, Erika M; Wang, Ziyi; Bier, Elianna A; Lu, Junlan; Driehuys, Bastiaan; Huang, Yuh-Chin
Background
Hyperpolarized ¹²⁹ Xe magnetic resonance imaging (MRI) provides a non-invasive assessment of regional pulmonary gas exchange function. This technique has demonstrated that chronic obstructive pulmonary disease (COPD) patients exhibit ventilation defects, reduced interstitial barrier tissue uptake, and poor transfer to capillary red blood cells (RBCs). However, the behavior of these measurements following therapeutic intervention is unknown.
Purpose
To characterize changes in ¹²⁹ Xe gas transfer function following administration of an inhaled long-acting beta-agonist/long-acting muscarinic receptor antagonist (LABA/LAMA) bronchodilator.
Study type
Prospective.
Population
Seventeen COPD subjects (GOLD II/III classification per Global Initiative for Chronic Obstructive Lung Disease criteria) were imaged before and after 2 weeks of LABA/LAMA therapy.
Field strength/sequences
Dedicated ventilation imaging used a multi-slice 2D gradient echo sequence. Three-dimensional images of ventilation, barrier uptake, and RBC transfer used an interleaved, radial, 1-point Dixon sequence. Imaging was acquired at 3 T.
Assessment
¹²⁹ Xe measurements were quantified before and after LABA/LAMA treatment by ventilation defect + low percent (ven_{def + low} ) and by barrier uptake and RBC transfer relative to a healthy reference population (bar_%ref and RBC_%ref ). Pulmonary function tests, including diffusing capacity of the lung for carbon monoxide (DL_CO ), were also performed before and after treatment.
Statistical tests
Paired t-test, Pearson correlation coefficient (r).
Results
Baseline ven_{def + low} was 57.8 ± 8.4%, bar_%ref was 73.2 ± 19.6%, and RBC_%ref was 36.5 ± 13.6%. Following treatment, ven_{def + low} decreased to 52.5 ± 10.6% (P < 0.05), and improved in 14/17 (82.4%) of subjects. However, RBC_%ref decreased in 10/17 (58.8%) of subjects. Baseline measurements of bar_%ref and DL_CO were correlated with the degree of post-treatment change in ven_{def + low} (r = -0.49, P < 0.05 and r = -0.52, P < 0.05, respectively).
Conclusion
LABA/LAMA therapy tended to preferentially improve ventilation in subjects whose ¹²⁹ Xe barrier uptake and DL_CO were relatively preserved. However, newly ventilated regions often revealed RBC transfer defects, an aspect of lung function opaque to spirometry. These microvasculature abnormalities must be accounted for when assessing the effects of LABA/LAMA therapy.
Level of evidence
1 TECHNICAL EFFICACY STAGE: 4.
Open Access
Use of nitrite inhalants ("poppers") among American youth.
(The Journal of adolescent health : official publication of the Society for Adolescent Medicine, 2005-07) Wu, Li-Tzy; Schlenger, William E; Ringwalt, Chris L
PURPOSE: We examined the patterns and correlates of nitrite inhalant use among adolescents aged 12 to 17 years. METHODS: Study data were drawn from the 2000 and 2001 National Household Surveys on Drug Abuse. Logistic regression was used to identify the characteristics associated with nitrite inhalant use. RESULTS: Among adolescents aged 12 to 17 years, 1.5% reported any lifetime use of nitrite inhalants. The prevalence of lifetime nitrite inhalant use increased to 12% and 14% among adolescents who were dependent on alcohol and any drug in the past year, respectively. Many nitrite inhalant users used at least three other types of inhalants (68%) and also met the criteria for alcohol (33%) and drug (35%) abuse or dependence. Increased odds of nitrite inhalant use were associated with residing in nonmetropolitan areas, recent utilization of mental health services, delinquent behaviors, past year alcohol and drug abuse and dependence, and multi-drug use. CONCLUSIONS: Adolescents who had used nitrite inhalants at least once in their lifetime tend to engage in delinquent activities and report co-occurring multiple drug abuse and mental health problems in the past year.
Open Access
Wood smoke particle exposure in mice reduces the severity of influenza infection.
(Toxicology and applied pharmacology, 2021-09) Vose, Aaron; McCravy, Matthew; Birukova, Anastasiya; Yang, Zhonghui; Hollingsworth, John W; Que, Loretta G; Tighe, Robert M
Elevated ambient temperatures and extreme weather events have increased the incidence of wildfires world-wide resulting in increased wood smoke particle (WSP). Epidemiologic data suggests that WSP exposure associates with exacerbations of respiratory diseases, and with increased respiratory viral infections. To assess the impact of WSP exposure on host response to viral pneumonia, we performed WSP exposures in rodents followed by infection with mouse adapted influenza (HINI-PR8). C57BL/6 male mice aged 6-8 weeks were challenged with WSP or PBS by oropharyngeal aspiration in acute (single dose) or sub-acute exposures (day 1, 3, 5, 7 and 10). Additional groups underwent sub-acute exposure followed by infection by influenza or heat-inactivated (HI) virus. Following exposures/infection, bronchoalveolar lavage (BAL) was performed to assess for total cell counts/differentials, total protein, protein carbonyls and hyaluronan. Lung tissue was assessed for viral counts by real time PCR. When compared to PBS, acute WSP exposure associated with an increase in airspace macrophages. Alternatively, sub-acute exposure resulted in a dose dependent increase in airspace neutrophils. Sub-acute WSP exposure followed by influenza infection was associated with improved respiratory viral outcomes including reduced weight loss and increased blood oxygen saturation, and decreased protein carbonyls and viral titers. Flow cytometry demonstrated dynamic changes in pulmonary macrophage and T cell subsets based on challenge with WSP and influenza. This data suggests that sub-acute WSP exposure can improve host response to acute influenza infection.

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